REGISTRATION REPORT Part A. Risk Management. COUNTRY: Germany Central Zone Zonal Rapporteur Member State: Germany NATIONAL ASSESSMENT

Transcription

1 Part A National Assessment Germany GF-2463 Central Zone Page 1 of 25 REGISTRATION REPORT Part A Risk Management Product code: Active Substances: GF-2463 Clopyralid 300 g/l Florasulam 25 g/l COUNTRY: Germany Central Zone Zonal Rapporteur Member State: Germany NATIONAL ASSESSMENT GmbH Date: 16/07/2013 Applicant Date Dow AgroSciences GmbH 16/07/2013

2 Part A National Assessment Germany GF-2463 Central Zone Page 2 of 25 Table of Contents PART A Risk Management 4 1 Details of the application Application background Annex I inclusion Regulatory approach Data protection claims Letters of Access 6 2 Details of the authorisation Product identity Classification and labelling Classification and labelling under Directive 99/45/EC Classification and labelling according to Regulation 1272/ R and S phrases under Directive 2003/82/EC (Annex IV and V) Other phrases (Safety phrases for use instructions) Restrictions linked to the PPP 7 Labelling phrases for IPM/sustainable use Specific restrictions linked to the intended uses Product uses 9 3 Risk management Reasoned statement of the overall conclusions taken in accordance with the Uniform Principles Physical and chemical properties (Part B, Section 1, Points 2 and 4) Methods of analysis (Part B, Section 2, Point 5) Analytical method for the formulation (Part B, Section 2, Point 5.2) Analytical methods for residues (Part B, Section 2, Points ) Acute Toxicity (Part B, Section 3, Point 7.1) Operator, Worker, Bystander, and Resident Exposure (Part B, Section 3, Point ) Operator Exposure (Part B, Section 3, Point 7.4) Worker Exposure (Part B, Section 3, Point 7.4) Bystander and Resident Exposure (Part B, Section 3, Point 7.4) Residues and Consumer Exposure (Part B, Section 4, Point 8) Residues (Part B, Section 4, Points 8.3 and 8.7) Consumer exposure (Part B, Section 4, Point 8.10) 14 Applicant Date Dow AgroSciences GmbH 16/07/2013

3 Part A National Assessment Germany GF-2463 Central Zone Page 3 of Ecotoxicology (Part B, Section 6, Point 10) Effects on Terrestrial Vertebrates (Part B, Section 6, Points 10.1 and 10.3) Effects on Aquatic Species (Part B, Section 6, Point 10.2) Effects on Bees and Other Arthropod Species (Part B, Section 6, Points 10.4 and 10.5) Effects on Earthworms and Other Soil Marco-organisms (Part B, Section 6, Point 10.6) Effects on organic matter breakdown (Part B, Section 6, Point 10.6) Effects on Soil Non-target Micro-organisms (Part B, Section 6, Point 10.7) Assessment of Potential for Effects on Other Non-target Organisms (Flora and Fauna) (Part B, Section 6, Point 10.8) Efficacy (Part B, Section 7, Point 8) Conclusions Further information to permit a decision to be made or to support a review of the conditions and restrictions associated with the authorisation 23 Appendix 1 Copy of the product authorisation 25 Appendix 2 Copy of the product label 25 Appendix 3 Letter of Access 25 Applicant Date Dow AgroSciences GmbH 16/07/2013

4 Part A National Assessment Germany GF-2463 Central Zone Page 4 of 25 PART A Risk Management This document describes the acceptable use conditions required for the registration of GF-2463 containing 25g as/l of florasulam and 300g as/l of clopyralid in Germany. The risk assessment conclusions are based on the information, data and assessments provided in, Part B Sections 1-7 and Part C and where appropriate the addendum for Germany. The information, data and assessments provided in, Parts B includes assessment of further data or information as required at national registration. It also includes assessment of data and information relating to GF-2463 where that data has not been considered in the EU review. Otherwise assessments for the safe use of GF-2463 have been made using endpoints agreed in the EU review of florasulam and clopyralid. This document describes the specific conditions of use and labelling required for Germany for the registration of GF Appendix 1 of this document provides a copy of the final product authorisation Germany. Appendix 2 of this document is a copy of the approved product label for Germany. The submitted draft product label has been checked by the competent authority. The applicant is requested to amend the product label in accordance with the decisions made by the competent authority. The final version of the label has to fulfil the requirements according to Article 16 of Directive 91/414/EEC. Appendix 3 of this document contains copies of the letters of access to the protected data / third party data that was needed for evaluation of the formulation. No letters of access are provided as the clopyralid and florasulam are Dow AgroSciences molecules. 1 Details of the application 1.1 Application background This application is submitted by Dow AgroSciences Germany in September The application is for approval of GF-2463 a Suspension Concentrate (SC) containing 300g as/l of clopyralid and 25 g as/l of florasulam active substances for use as herbicide in cereals (winter and spring wheat, winter and spring barley, winter triticale, winter rye, spelt wheat, spring oats and durum wheat). 1.2 Annex I inclusion Florasulam and Clopyralid were respectively included on Annex I of Directive 91/414/EEC on 10/01/2002 under Inclusion Directive 02/64/EC (florasulam) and on 01/01/2007 under Inclusion Directive 06/64/EC (clopyralid). Applicant Date Dow AgroSciences GmbH 16/07/2013

5 Part A National Assessment Germany GF-2463 Central Zone Page 5 of 25 The Annex I Inclusion Directive for Florasulam (02/64/EC) and for Clopyralid (06/64/EC) provides specific provisions under Part B which need to be considered by the applicant in the preparation of their submission and by the MS prior to granting an authorisation. Only uses as herbicide may be authorised. In assessing applications to authorise plant protection products containing clopyralid for uses other than spring applications, Member States shall pay particular attention to the criteria in Article 4(1)(b), and shall ensure that any necessary data and information is provided before such an authorisation is granted. The concerned Member States shall request the submission of further studies to confirm the results on animal metabolism. They shall ensure that the notifiers at whose request clopyralid has been included in this Annex provide such studies to the Commission within two years from the entry into force. For the implementation of the uniform principles of Annex VI, the conclusions of the review report on the Florasulam and Clopyralid active substances, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 (florasulam) and 4 April 2006 (clopyralid), shall be taken into account. In this overall assessment: For Clopyralid, Member States must pay particular attention to the protection of non target plants and groundwater under vulnerable conditions. Conditions of authorisation should include risk mitigation measures and monitoring programmes should be initiated to verify potential groundwater contamination in vulnerable zones, where appropriate. These concerns have been addressed within the current submission. For Florasulam, Member States should pay particular attention to the potential for groundwater contamination, when the active substance is applied in regions with vulnerable soil and/or climatic conditions. Conditions of authorisation must include risk-mitigation measures, where appropriate. These concerns have been addressed within the current submission. 1.3 Regulatory approach To obtain approval the product GF-2463 must meet the conditions of Annex I inclusion and be supported by dossiers satisfying the requirements of Annex II and Annex III, with an assessment to Uniform Principles, using Annex I agreed end-points. This application was submitted in order to allow the first approval of this product/use in Germany in accordance with the above. 1.4 Data protection claims Where protection for data is being claimed for information supporting registration of GF-2463, it is indicated in the reference lists in Appendix 1 of the, Part B, sections 1-7 and Part C. Applicant Date Dow AgroSciences GmbH 16/07/2013

6 Part A National Assessment Germany GF-2463 Central Zone Page 6 of Letters of Access No letters of access are provided as the clopyralid and florasulam are Dow AgroSciences molecules. 2 Details of the authorisation 2.1 Product identity Product Name Authorization Number (for re-registration) Function Applicant Composition Formulation type Packaging GF /00 herbicide Dow AgroSciences GmbH 300 g/l Clopyralid and 25 g/l Florasulam Suspension concentrate [Code: SC] 0,25 L to 20 L HDPE or PET bottles 2.2 Classification and labelling Due to a review of the concentration of a relevant non-active component of the product an updated classification an labelling was necessary. Therefore the valid proposal as listed below differs from the respective chapter in Part B, Section Classification and labelling under Directive 99/45/EC The following is proposed in accordance with Directive 99/45/EC in combination with the latest classification and labelling guidance under Directive 67/548/EEC (i.e. in the 18th ATP published as Directive 93/21/EEC): Hazard symbol(s): Indication(s) of danger: Risk phrases: N Dangerous for the environment R 50/53: Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment Safety phrases: S 35: This material and its container must be disposed of in a safe way. S 57: Use appropriate container to avoid environmental contamination. Labelling texts and restrictions: SP001: To avoid risks to man and the environment, comply with the instructions for use Classification and labelling according to Regulation 1272/2008 The following is proposed in accordance with Regulation 1272/2008: Hazard symbol(s): Signal word Hazard statement GHS09 Dangerous for the environment H400 Very toxic to aquatic life. H410 Very toxic to aquatic life with long lasting effects. Applicant Date Dow AgroSciences GmbH 16/07/2013

7 Part A National Assessment Germany GF-2463 Central Zone Page 7 of R and S phrases under Directive 2003/82/EC (Annex IV and V) Risk Phrases: None. Safety Phrases: None Other phrases (Safety phrases for use instructions) Restrictions linked to the PPP Safety phrases for instructions for use SB001 1 SB010 2 SF Avoid any unnecessary contact with the product. Misuse can lead to health damage. Keep out of the reach of children. Treated areas/crops may not be entered until the spray coating has dried. Labelling phrases for ecosystem protection NW 262 NW265 NW468 The product is toxic for algae The product is toxic for higher aquatic plants. Fluids left over from application and their remains, products and their remains, empty containers and packaging, and cleansing and rinsing fluids must not be dumped in water. This also applies to indirect entry via the urban or agrarian drainage system and to rainwater and sewage canals Labelling phrases for IPM/sustainable use WMB Mode of Action (HRAC-Group): B WMO Mode of Action (HRAC-Group): O WH951 The risk of resistance has to be indicated on the package and in the instructions for use. Particularly measures for an appropriate risk management have to be declared. NN1001 The product is classified as non-harmful for populations of relevant beneficial insects. NN1002 The product is classified as non-harmful for populations of relevant beneficial predatory mites and spiders. NB6641 The product is classified as non-hazardous to bees, even when the maximum application rate, or concentration if no application rate is stipulated, as stated for authorisation is applied. (B4) Specific restrictions linked to the intended uses Some of the authorized uses are linked to the following conditions (mandatory labelling): See 2.3 (Product uses) 1 ) Mandatory for plant protection products 2 ) With regard to preventive health protection and good agricultural practice Applicant Date Dow AgroSciences GmbH 16/07/2013

8 Part A National Assessment Germany GF-2463 Central Zone Page 8 of 25 NW609-1 NT103 When applying the product on areas adjacent to surface waters - except only occasionally but including periodically water-bearing surface waters - the product must be applied observing the minimum buffer zone stated below. It is not necessary to observe this buffer zone if the product is applied using equipment which is registered in the index of 'Loss Reducing Equipment' of 14 October 1993 (Federal Gazette No 205, p. 9780) as amended. Irrespective of this, in addition to the minimum buffer zone from surface waters stipulated by state law, the ban on application in or in the immediate vicinity of waters must be observed at all times. Violations may be punished by fines of up to EUR. (5 m) In a strip at least 20 m wide which is adjacent to other areas, the product must be applied using loss reducing equipment which is registered in the index of 'Loss Reducing Equipment' of 14 October 1993 (Federal Gazette No 205, p. 9780) as amended, and be registered in at least drift reducing class 90 % (except agriculturally or horticulturally used areas, roads, paths and public places). Loss reducing equipment is not required if the product is applied with portable plant protection equipment or if adjacent areas (field boundaries, hedges, groups of woody plants) are less than 3 m wide or the product is applied in an area which has been declared by the Biologische Bundesanstalt in the "Index of regional proportions of ecotones" of 7 February 2002 (Federal Gazette no. 70 a of 13 April 2002), as amended, as agrarian landscape with a sufficient proportion of natural and semi-natural structures. WH9161 The instructions for use must include a summary of weeds which can be controlled well, less well and insufficiently by the product, as well as a list of species and/or varieties showing which crops are tolerant of the intended application rate and which are not. WP711 Damage is possible to replanted dicotyledonous intermediate crops. Applicant Date Dow AgroSciences GmbH 16/07/2013

9 Part A National Assessment - Germany GF-2463 Central Zone Page 9 of Product uses GAP rev. (1), date: PPP (product name/code) active substance 1 active substance 2 GF-2463 florasulam clopyralid Formulation type: Conc. of as 1: Conc. of as 2: SC 25 g/l 300 g/l Applicant: Zone(s): Dow AgroSciences Central Zone professional use non professional use Verified by MS: yes Use- No. Member state(s) Crop and/ or situation (crop destination / purpose of crop) 001 Germany TRZAW Winter soft wheat, HORVW Winter barley, SECCW Winter rye, TRZSP Spelt, TTLWI Winter triticale 002 Germany TRZAS Spring soft wheat, TRZDS Spring durum wheat, F G or I F F Pests or Group of pests controlled (additionally: developmental stages of the pest or pest group) TTTDS Annual dicotyledonous weeds TTTDS Annual dicotyledonous weeds Method / Kind Application Timing / Growth stage of crop & season spraying BBCH 13-32; After emergence, spring, after emergence of weeds spraying BBCH 13-30; After emergence, spring, after emergence of Max. number (min. interval between applications) a) per use b) per crop/ season L product / ha a) max. rate per appl. b) max. total rate per crop/season Application rate kg as/ha a) max. rate per appl. b) max. total rate per crop/season 1; 1 0.2; 0.2 florasulam 0.005; clopyralid 0.06; ; 1 0.2; 0.2 florasulam 0.005; clopyralid 0.06; 0.06 Water L/ha min / max PHI (days) Remarks: e.g. safener/synergist per ha e.g. recommended or mandatory tank mixtures F WH9161; WP711 NW609-1 NT F WH9161; WP711 NW609-1 NT103 Applicant Date Dow AgroSciences GmbH 16/07/2013

10 Part A National Assessment - Germany GF-2463 Central Zone Page 10 of 25 HORVS weeds Spring barley, AVESS Oats General remarks/explanations: The GAP-Sheet should indicate if the displayed information was provided by the applicant OR was revised by the zrms (due to the product label and Annex III data). The zrms has to verify the presented information and to ask (the applicant) for clarification of missing details (e.g. BBCH stages, EC-codes of crops). All abbreviations in the GAP-Sheet used must be explained. Use separate worksheet for each product. Make use of existing standards like EPPO and BBCH. Product: Please indicate the specific variant of the active substance if relevant. If additional components have to be added to the applied product (tankmixtures), all relevant information must be provided in the column remarks. As the product usually will be determined either for professional or non professional use, this information should be given here. Otherwise to be indicated in column 4 of the GAP-sheet (conditions/location of use). Formulation: Type: e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) Refer to: GCPF Codes - GIFAP Technical Monograph No 2, (1989), 6 th Edition Revised May 2008 Catalogue of pesticide formulation types and international coding system. Technical Monograph n 2, 6th Edition - Revised May Catalogue of pesticide formulation types and international coding system (CropLife International) 1). Conc. of as: g/kg or g/l In case the plant protection product contains more than one active substance the amount applied for each active substance occurs in the same order as the substances are mentioned in the heading. Safener/Synergist: Since safeners and synergists are in scope of REG 1107/2009, information about safeners/synergists should be included in the GAP table as well. Zone(s): All relevant zone(s) should be indicated. For interzonal uses (e.g. greenhouse, seed treatment, etc.) EU should be chosen. Explanations to the particular columns: No.: Numeration would be important when references are necessary e. g. to the dossier or to the authorisation certificate. Member state(s):for a better general view of the valid uses for the particular zones/ms it would be helpful to mention both (the zone as well as the MS) in the column. However, to keep the table clearly arranged it seems dispensable to cite the zone; each MS is distinctly allocated to one zone; moreover the zone(s) are cited in the head of the table. Desirably MS are put in order accordant to the zone they belong. Crop and/or situation: The common name(s) of the crop and the EC (EPPO)-Codes or at least the scientific name(s) [EU and Codex classifications (both)] should be used; where relevant, the situation should be described (e.g. fumigation of a structure). In case of crop groups all single crops belonging to that group should be mentioned, (either in the respective table element or in case of a very extensive crop group - at least in a footnote). If it is not possible to mention all single crops belonging to a crop group (e.g. for horticulture), it should be referred to appropriate crop lists (e.g. EPPO, residue (codex). It would be desirable to have a joint list of crop groups for the zones. Exceptions of specific crops/products/objects or groups of these and restrictions to certain uses (e.g. only for seed production, fodder) must be indicated. This column should also include when indicated information concerning crop destination or purpose of crop and which part of plants will be used / processed (e. g. for medicinal crops roots or leaves or seeds). Conditions / location of use: Outdoor or field use (F), glasshouse application (G) or indoor application (I) Glasshouse indicates that the respective trials are acceptable for all zones. As results achieved in compartments without controlled conditions (temperature, light exposure), e.g. simple plastic tunnels [for those GAPs field trials have to be conducted in the respective zone the use is applied for], are not considered to be applicable for use in other zones the kind of glasshouse should be clearly indicated. [Remark: Greenhouse definitions are at the moment under evaluation]. Conditions include also information concerning the substrate (natural soil, artificial substrate). Pests or Group of pests controlled: Scientific names and EPPO-Codes of target pests/diseases/ weeds or when relevant the common names of the pest groups (e.g. biting and suckling insects, soil born insects, foliar fungi, weeds) and the developmental stages of the pests and pest groups at the moment of application must be named. If necessary in case of pest groups - exceptions (e.g. sucking insects excluding scale insects) should be indicated. In some cases, the set of pests concerned for a given crop may vary in different parts of the EU region (where appropriate the pests should be specified individually). If the product is used as growth regulator the target organism is the specific crop, whose development should be influenced; the aim could also be e.g. an empty room for treatment. Application details: Method / Kind: Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench, drilling, high precision drilling (with or without pneumatic systems). Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plant - type of equipment used (e.g. ultra low volume equipment (ULVA) or low volume equipment (LVA)) should be indicated if relevant. Timing of Application / Growth stage of crop & season: Time(s), period, first and last treatment, e.g. autumn or spring pre- or post-emergence, at sufficient pest density or begin of infection, including restrictions (e.g. not during flowering). Applicant Date Dow AgroSciences GmbH 16/07/2013

11 Part A National Assessment - Germany GF-2463 Central Zone Page 11 of 25 Growth stage of crop (BBCH-code) period, first and last treatment. Since the BBCH-codes are accomplished in the individual member states at different time periods the month(s) of application should be indicated in addition. BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN It seems sensible to constrain specifications in this column only to the crop, - information concerning the pest should be dealt in column pest or group of Pests controlled. In certain circumstances it might be helpful to give information about the expected rate of interception related to the BBCH codes. In many minor crops no BBCH/interception rate scenarios have been specified so far. This could also simplify grouping for the envelope approach. Number of applications and interval between applications a) Maximum number of applications per growing season used for the named crop/pest combination possible under practical conditions of use. b) The proposed maximum number in the crop including applications on all pests/targets on the same crop in a growing season should be given. It should be clearly indicated whether the displayed number of applications is per season, per crop cycle or per pest generation. Minimum interval (in days) between applications of the same product. The figure for the interval between the applications is to be set in brackets. Application rate: Application rate of the product per ha: a) (Maximum) product rate per treatment (usually kg or L product / ha). For specific uses other specifications might be possible, e.g.: g/m³ in case of fumigation of empty rooms or pallox (= big box used for storage potatoes, fruits, roots). b) Maximum product rate per growing season (especially if limited) or per crop cycle should be cited. Especially in three dimensional crops other dose expressions (kg/l per m² leaf wall area or kg/l per ha per meter crown (canopy) height) should be given additionally. For seed treatment also the load of product (l/g, kg) per kg, 100 kg or unit treated seed should be stated beside the application rate per hectare. The number of seeds per (seed) unit is to be given. The maximum seed drilling rate (=number of seed sown/maximum seed volume) per row and ha should be indicated. Information concerning the sowing method (precision drilling, ) would be advantageous. See also EPPO-Guideline PP 1/239 Dose expression for plant protection products (please note, additional EPPO-guidelines may be developed). Application rate of the active substance per ha: a) (Maximum) as rate per treatment (usually kg active substance / ha). For specific uses other specifications might be possible, e.g.: g/m³ in case of fumigation of empty rooms or pallox (= big box used for storage potatoes, fruits, roots). b) Maximum as rate per growing season (especially if limited) or per crop cycle should be cited. The dimension (g, kg) must be clearly specified. (Maximum) dose of a.s. per treatment (usually g, kg active substance / ha). In case the plant protection product contains more than one active substance the amount applied for each active substance occurs in the same order as the substances are mentioned in the heading. Water L/ha: It should be clearly indicated if a stated water volume range depends upon the developmental stage of the crop (low volume early crops stage, high volume late crop stage) which causes a consistent concentration of the spray solution, or if a water volume range indicates different spray solution concentrations. In the last mentioned case extremely low water volumes (indicating high concentrated spray solutions) need to be covered within selectivity trials. If water volume range depends on application equipments (e.g. ULVA or LVA) it should be mentioned under application: method/kind. PHI (days) minimum pre harvest interval: PHI - minimum pre-harvest interval For some crop situations a specific PHI may not be relevant. If so an explanation (e. g. the PHI is covered by the time remaining between application and harvest.) should be given in the remarks column (e.g. crop harvest at maturity or specific growth stages). Remarks: Remarks may include: amount of safener/synergist per ha or extent of use/economic importance/restrictions, e.g. limiting the number of uses per crop and season, if several target pests/diseases are controlled with the same product. If additional components (other ppp or adjuvant) should be used with the applied product (tankmixtures), all relevant information must be provided in the column remarks. In addition, it should be mentioned as well those mixtures are recommended or mandatory. Applicant Date Dow AgroSciences GmbH 16/07/2013

12 Part A National Assessment Germany GF-2463 Central Zone Page 12 of 25 3 Risk management 3.1 Reasoned statement of the overall conclusions taken in accordance with the Uniform Principles Physical and chemical properties (Part B, Section 1, Points 2 and 4) Overall Summary: The product GF-2463 is a suspension concentrate (SC). All studies have been performed in accordance with the current requirements, the critical GAP and the results are deemed to be acceptable. The appearance of the product is that of tan liquid, with an aromatic odour. It is not explosive, has no oxidising properties, and no self ignition temperature below 400 C. In aqueous solution, it has a ph value around 4.4. The stability at 54 C is acceptable for active ingredient and physical properties. The shelf life study for two years at ambient temperature will be finalised in March The technical characteristics are acceptable for a suspension concentrate (SC) formulation. Implications for labelling: none Compliance with FAO specifications: There are no FAO specifications for clopyralid or florasulam. Compliance with FAO guidelines: The product GF-2463 complies with the general requirements stated in the FAO/WHO manual (2010). Compatibility of mixtures: No report regarding physical and chemical compatibility of tank mixes has been submitted. Nature and characteristics of the packaging: Information with regard to type, dimensions, capacity, size of opening, type of closure, strength, leakproofness, resistance to normal transport & handling, have been submitted, evaluated and is considered to be acceptable. Nature and characteristics of the protective clothing and equipment: Information regarding the required protective clothing and equipment for the safe handling of GF-2463 has been provided and is considered to be acceptable Methods of analysis (Part B, Section 2, Point 5) Analytical method for the formulation (Part B, Section 2, Point 5.2) The active substances of GF-2463 can be quantified using the analytical HPLC method DAS-AM-G There are no relevant impurities in the formulation GF Therefore, no analytical method is required Analytical methods for residues (Part B, Section 2, Points ) Adequate analytical methods are available to monitor all compounds given in the respective residue definition, i.e. clopyralid in food of plant and animal origin, soil, water and air, florasulam in food of Applicant Date Dow AgroSciences GmbH 16/07/2013

13 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 13 of 25 plant material and air, and florasulam and 5-OH florasulam in soil and water. No residue definition in food of animal origin exists for florasulam. New studies on residue analytics were submitted by the applicant and were found to be acceptably validated. Clopyralid residues can be monitored in food of plant and animal origin by GC-MS, GC/ECD and LC- MS/MS methods, respectively. GC-MS methods are available for soil, water and air. Florasulam residues can be monitored in food of plant origin, soil and water by LC-MS/MS and by HPLC/UV in air. Furthermore, HPLC/UV methods are available for water. Methods for body fluids and tissues are not required since clopyralid and florasulam are not classified as toxic or highly toxic Mammalian Toxicology (Part B, Section 3, Point 7) Acute Toxicity (Part B, Section 3, Point 7.1) Acute toxicity studies for GF-2463 were not evaluated as part of the EU review of the clopyralid and florasulam. Therefore, all relevant data were provided and are considered adequate. GF-2463, containing 300 g/kg clopyralid and 25 g/kg florasulam, has a low toxicity in respect to acute oral and dermal toxicity and is not irritating to the rabbit skin and eye and is not a skin sensitiser to the mouse. Taking into account all submitted data and the labelling of the clopyralid, florasulam and additives concerning their concentrations, GF-2463 is not necessary to be labelled with a hazard symbol and a R-phrase Operator, Worker, Bystander, and Resident Exposure (Part B, Section 3, Point ) Operator Exposure (Part B, Section 3, Point 7.4) Operator exposure to GF-2463 was not evaluated as part of the EU review of clopyralid and florasulam for this submitted rate/crop. Therefore all relevant data and risk assessments have been provided and are considered to be adequate. Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of operator exposure was not necessary and was therefore not performed. The risk assessment has shown that the estimated exposure towards clopyralid and florasulam in GF-2463 will not exceed the systemic AOEL for operators, workers, bystanders and residents. No specific PPE is necessary for operators or for workers. If used properly and according to the intended conditions of use, adverse health effects for operators, workers, bystanders and residents will not be expected Worker Exposure (Part B, Section 3, Point 7.4) See under Bystander and Resident Exposure (Part B, Section 3, Point 7.4) See under Implications for labelling resulting from operator, worker, bystander assessments: Hazard Symbol: - Indication of danger: - Applicant Date Dow AgroSciences GmbH 16/07/2013

14 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 14 of 25 Risk Phrases: - Safety Phrases: - R and S phrases under Directive 2003/82/EC (Annex IV and V): - Other phrases: Residues and Consumer Exposure (Part B, Section 4, Point 8) The available data is considered sufficient for risk assessment. The chronic and the short-term intake of clopyralid and florasulam residues are unlikely to present a public health concern. As far as consumer health protection is concerned, DE agrees with the authorization of the intended uses Residues (Part B, Section 4, Points 8.3 and 8.7) Subsequent to the EU review of clopyralid and florasulam an evaluation of all uses has been made to establish EU MRLs. This evaluation reviewed all the data relevant to establishing MRLs for all supported uses and considered the dietary risk assessments appropriate for all EU member states utilising the EFSA model. The MRLs for clopyralid and florasulam are published in Annex III of Regulation (EC) No 396/2005. The proposed uses of GF-2463 are within those supported for the EU MRL assessment, therefore no further evaluation is required for national re-registration/registration. Application for additional crops or uses should be made by the appropriate process to establish an EU MRL and any additional risk assessment necessary to support additional uses should be submitted via relevant national label extension processes Consumer exposure (Part B, Section 4, Point 8.10) Long term exposure The chronic consumer risk assessment was carried out using the EFSA PRIMo model (TMDI calculation) and the German NVS II model (NTMDI calculation). Clopyralid: The TMDI was found to utilise the ADI of 0.15 mg/kg bw/day by 27.6 % based on Danish children. The NTMDI was calculated resulting in 22.1 % of the ADI based on German children aged 2-4 years. Florasulam: The TMDI was found to utilise the ADI of 0.05 mg/kg bw/day by 1.4 % based on UK toddlers. The NTMDI was calculated resulting in 0.9 % of the ADI based on German children aged 2-4 years. Short term exposure Based on the low acute toxicity of both active substances no ARfD has been allocated. An acute risk assessment is therefore not required. Based on the calculations made to estimate the risk for consumers through diet and other means it can be concluded that the use of product CHA 1270 does not lead to unacceptable risk for consumers when applied according to the recommendations. Therefore, both chronic and short-term intake of clopyralid and florasulam residues is unlikely to present a public health concern. As far as consumer health protection is concerned, Germany agrees with the authorization of the intended uses Environmental fate and behaviour (Part B, Section 5, Point 9) A full exposure assessment for the plant protection product GF-2463 in its intended uses in spring and winter cereals is documented in detail in the core assessment of the plant protection product GF-2463 Applicant Date Dow AgroSciences GmbH 16/07/2013

15 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 15 of 25 dated from the 07/11/2012 performed by Germany. The following chapters summarises specific exposure assessment for soil and surface water and the specific risk assessment for groundwater for the authorization of GF-2463 in Germany according to its intended use in spring and winter cereals ( Use No and ). Metabolites of clopyralid No new study on the fate and behaviour of clopyralid or has been performed. For the active substance clopyralid, no potentially relevant metabolites were observed. Hence, no metabolites need to be considered in the risk assessment. Metabolites of florasulam No new study on the fate and behaviour of florasulam or has been performed. Hence no potentially new metabolites need to be considered for environmental risk assessment. The risk assessment for the metabolites of florasulam has already been performed for EU approval (see DAR/ EFSA conclusion). The metabolites are considered ecotoxicologically not relevant. Therefore no new risk assessment hence no exposure assessment for these metabolites is necessary. However, the risk assessment for groundwater by direct leaching after application of the plant protection product in its intended uses includes the soil metabolites 5-OH, DFP-ASTCA and ASTCA of florasulam. Additionally, the soil metabolites 5-OH, DFP-ASTCA and ASTCA of florasulam were included in the groundwater risk assessment considering the entry path surface run-off and drainage with subsequent bank filtration Predicted Environmental Concentration in Soil (PEC soil ) (Part B, Section 5, Points 9.4 and 9.5) For the intended use of the plant protection product in spring and winter cereals according to use no and , PECsoil was calculated for the active substances clopyralid and florasulam considering a soil depth of 2.5 cm. Due to the fast degradation of the active substances clopyralid and florasulam in soil the accumulation potential of clopyralid and florasulam was not considered. Therefore PECsoil used for risk assessment comprises background concentration in soil (PECaccu) considering a tillage depth of 20 cm (arable crop) or 5 cm (permanent crops) and the maximum annual soil concentration PECact considering the relevant soil depth of 2.5 cm or 1.0 cm, respectively. The results for PEC soil for the active substances and their metabolites were used for the ecotoxicological risk assessment Predicted Environmental Concentration in Ground Water (PEC GW ) (Part B, Section 5, Point 9.6) 1. Direct leaching into groundwater Results of modelling with FocusPelmo show that the active substances clopyralid and florasulam are not expected to leach into groundwater at concentrations in concentrations 0.1µg/L in the intended uses of in spring and winter cereals. According to the modeling results with Focus Pelmo 4.4.3, concentrations of 0.1µg/L in the groundwater via leaching can also be excluded for the metabolites 5-OH and DFP-ASTCA of florasulam. For the metabolite ASTCA of florasulam concentrations of 0.1µg/L in groundwater cannot be excluded. However an assessment of this metabolite has already been performed for EU approval of florasulam. The metabolite ASTCA is classified as not relevant for groundwater. Consequences for authorization: None Applicant Date Dow AgroSciences GmbH 16/07/2013

16 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 16 of Ground water contamination by bank filtration due to surface water exposure via run-off and drainage Groundwater contaminations 0.1 µg/l of the active substance clopyralid, florasulam and its soil metabolites 5-OH, DFP-ASTCA and ASTCA via surface run-off and drainage into the adjacent ditch with subsequent bank filtration estimated by the model EXPOSIT 3.0 is not expected. Consequences for authorization: None Predicted Environmental Concentration in Surface Water (PEC SW ) (Part B, Section 5, Points 9.7 and 9.8) For the intended use of the plant protection product in spring and winter cereals according to use no and , PECsw was calculated for the active substances clopyralid and florasulam considering the two routes of entry (i) spraydrift and volatilisation with subsequent deposition and (ii) run-off, drainage separately. The calculation of concentrations in surface water was based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 C of the active substance clopyralid is > 10-4 Pa. Hence the active substance clopyralid is regarded as volatile (volatilization from soil and plant surfaces). Therefore exposure of surface water by the active substance clopyralid due to deposition following volatilization was considered. The vapour pressure at 20 C of the active substance florasulam is < 10-5 Pa. Hence the active substance florasulam is regarded as non-volatile. Therefore, exposure of surface water by the active substance florasulam due to deposition following volatilization was not considered. The concentration of the active substances clopyralid and florasulam in adjacent ditch due to surface runoff and drainage was calculated using the model EXPOSIT 3.0. The results for PEC surface water for the active substance and its metabolites were used for the ecotoxicological risk assessment Predicted Environmental Concentration in Air (PEC Air ) (Part B, Section 5, Point 9.9) Volatilisation of clopyralid has to be considered in risk assessment (vapour pressure 20 C > 10-4 Pa, experimental data from plant surfaces < 4 % in 24 h and from soil surfaces < 2 % in 24 h). Implications for labelling resulting from environmental fate assessment: Based on the data on the active substance clopyralid and florasulam, the plant protection product Primus Perfect is considered to be not readily degradable (Phrase R53 should be added to the label). Applicant Date Dow AgroSciences GmbH 16/07/2013

17 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 17 of Ecotoxicology (Part B, Section 6, Point 10) A full risk assessment according to Uniform Principles for the plant protection product GF-2463 in its intended uses in cereals is documented in detail in the core assessment of the plant protection product GF dated from 07/11/2012 performed by RMS Germany. The intended use of in Germany is generally covered by the uses evaluated in the course of the core assessment by Primus Perfect. The following chapters summarises specific risk assessment for non-target organisms and hence risk mitigation measures for the authorization of in Germany according to its intended use in cereals (use no. 001 and 002). Only information relevant for the prescription of national labelling and environmental restrictions are mentioned in the following chapters Effects on Terrestrial Vertebrates (Part B, Section 6, Points 10.1 and 10.3) The risk assessment for effects on birds and other terrestrial vertebrates was carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA Journal 2009; 7(12): 1438). Avian and mammalian acute oral and long-term reproduction studies have been carried out with florasulam and clopyralid. Full details of avian and mammalian toxicity studies are provided in the respective EU DAR. The studies with the relevant acute and long-term endpoints were agreed during EU review process and are used for the risk assessment. Based on the presumptions of the screening step and Tier 1, the calculated TER values for the acute and long-term risk resulting from an exposure of birds to the active substance clopyralid and florasulam according to the intended use of the formulation in cereals achieve the acceptability criteria TER 10 and TER 5, respectively, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point The results of the assessment indicate an acceptable risk for birds. The risk assessment for effects on birds and other terrestrial vertebrates was carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA Journal 2009; 7(12): 1438). Birds Effects on birds for were not evaluated as part of the EU review of either clopyralid or florasulam. However, the provision of further data on the formulation is not considered essential as the available data on clopyralid and florasulam are deemed to be sufficient to assess the risk of birds exposed to. Based on the presumptions of the screening step and Tier 1, the calculated TER values for the acute and long-term risk resulting from an exposure of birds to the active substance clopyralid and florasulam according to the intended use of the formulation in cereals achieve the acceptability criteria TER 10 and TER 5, respectively, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point The results of the assessment indicate an acceptable risk for birds. Terrestrial vertebrates (other than birds) Effects on mammals for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for GF-2463 SC with the proposed use pattern are provided here and are considered adequate. Applicant Date Dow AgroSciences GmbH 16/07/2013

18 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 18 of 25 Based on the highly conservative presumptions of the screening step, the acute and long-term risk of exposure of terrestrial vertebrates other than birds to florasulam and clopyralid as well as the formulation in cereals achieves the acceptability criteria TER 10 and TER 5, respectively, according to directive 1107/2009 (EG), Annex IV, uniform principles, point for acute and longterm effects. Therefore, no further risk assessment is necessary Effects on Aquatic Species (Part B, Section 6, Point 10.2) Effects on aquatic organisms for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here. Results of aquatic risk assessment for the intended for uses of in cereals based on Surface Water PEC values is presented in the core assessment, Part B, Section 6, Point 6.4. For authorization in Germany, exposure assessment of surface water considers the two routes of entry (i) spraydrift and volatilisation with subsequent deposition and (ii) run-off, drainage separately in order to allow risk mitigation measures separately for each entry route. 1. Exposure by spraydrift and deposition following volatilization The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressures at 20 C of the active substances clopyralid and florasulam are < 10-5 Pa. Therefore, exposure of surface water by the active substances clopyralid and florasulam due to deposition following volatilization was not considered. Based on the relevant toxicity of (EC50 = 0.02 mg/l; Lemna gibba) the calculated TER values for the risk to aquatic organism resulting from an exposure of surface water by spraydrift to Primus Perfect according to the use No and 002 only achieve the acceptability criteria of TER 10, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point if appropriate risk mitigation measures (5 m buffer strip or drift reducing technique) are applied. 2. Exposure by surface run-off and drainage The concentration of the active substances clopyralid and florasulam in adjacent ditch due to surface runoff and drainage was calculated using the model EXPOSIT 3. The calculated TER values for the risk to aquatic organism resulting from an exposure of surface water by the active substances clopyralid and florasulam due to runoff an drainage according to the use no 001 and 002 achieve the acceptability criteria of TER 100 or 10 respectively, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point Risk mitigation measures do not need to be applied. Consequences for authorization: Based on the intrinsic properties of the active substances florasulam and clopyralid, following national labelling and environmental restrictions are prescribed as mandatory: Risk mitigation measures: All uses NW 468: Fluids left over from application and their remains, products and their remains, empty containers and packaging, and cleansing and rinsing fluids must not be dumped in water. This also applies to indirect entry via the urban or agrarian drainage system and to rainwater and sewage canals. All uses NW609-1: Applicant Date Dow AgroSciences GmbH 16/07/2013

19 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 19 of 25 When applying the product on areas adjacent to surface waters - except only occasionally but including periodically water-bearing surface waters - the product must be applied observing the minimum buffer zone stated below. It is not necessary to observe this buffer zone if the product is applied using equipment which is registered in the index of 'Loss Reducing Equipment' of 14 October 1993 (Federal Gazette No 205, p. 9780) as amended. Irrespective of this, in addition to the minimum buffer zone from surface waters stipulated by state law, the ban on application in or in the immediate vicinity of waters must be observed at all times. Violations may be punished by fines of up to EUR. (5 m) Labelling: Because of the toxicity of the active ingredients as well as the formulation following labels must be given: NW262: The product is toxic for algae. NW265: The product is toxic for higher aquatic plants. Studies of the toxicity of GF-2463 for algae [EC 50 Florasulam = 8.94 µg/l, NOEC Florasulam = µg/l (S. capricornutum); EC 50GF-2463 = 84 µg/l (P. subcapitata)] and aquatic plants [EyC 50 GF-2463 = 20 µg/l, NOEC GF-2463 = 5.2 µg/l (L. gibba)] showed that this product should be labelled as toxic for aquatic organisms Effects on Bees and Other Arthropod Species (Part B, Section 6, Points 10.4 and 10.5) Bees Exposure The recommended use pattern for includes application in cereals at a maximum application rate of up to 0.2 L/ha. This maximum single application rate is equivalent to 232 g/ha based on a nominal formulation density of 1.16 g/ml. Bees may be exposed to formulated by direct spraying, through contact with fresh or dried residues or by oral uptake of contaminated pollen, nectar and honey dew. Hazard quotients Hazard quotients for oral and contact exposure according to EPPO (2003) Environmental risk assessment scheme for plant protection products (Chapter 10: Honeybees (PP 3/10(2)). Bulletin OEPP/EPPO Bulletin 33: ) were calculated as follows: Hazard Quotient = max. application rate [g test substance/ha] / LD 50 [µg test substance/bee] Table Hazard quotients for honeybees Test substance Exposure route LD 50 Max. single application rate Hazard quotient (HQ) HQ assessment trigger GF-2463 oral > µg product/bee 232 g < 1.1 contact > 200 µg product/bee product/ha < Risk Assessment Applicant Date Dow AgroSciences GmbH 16/07/2013

20 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 20 of 25 Due to the results of laboratory tests Promus Perfect and its active substances are considered to be practically non toxic to bees. All hazard quotients are clearly below the trigger of 50, indicating that the intended use of poses a low risk to bees in the field. Bee brood testing is not required since GF-2463 is not an IGR. Overall conclusion It is concluded that will not adversely affect bees or bee colonies when used as recommended. No special labeling is necessary. Label NB6641 will be applied. Other non-target arthropods Effects on arthropods other than bees for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here and are considered adequate. The risk assessment for effects on non-target terrestrial arthropods was carried out according to the Guidance Document on Terrestrial Ecotoxicology under Directive 91/414/EEC; SANCO/10329/2002 rev 2 final. Based on laboratory test endpoints (Typhlodromus pyri: ER 50 > 800 ml product/ha), the calculated TER values for the risk resulting from an exposure of non-target terrestrial arthropods to, the active substances clopyralid and florasulam or its metabolites according to the intended use of the formulation in cereals achieve the acceptability criteria TER 10, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point The results of the assessment indicate an acceptable risk for non-target terrestrial arthropods Effects on Earthworms and Other Soil Marco-organisms (Part B, Section 6, Point 10.6) Effects on earthworms and other soil non-target macro-organisms for were not evaluated as part of the EU review of either clopyralid or florasulam. Therefore, all relevant study data for this risk assessment are provided here and are considered valid and acceptable by the ZRMS. The risk assessment for effects on earthworms and other soil organisms was carried out according to the Guidance Document on Terrestrial Ecotoxicology under Directive 91/414/EEC; SANCO/10329/2002 rev 2 final. Based on acute and chronic endpoints, the calculated TER values for the acute and long-term risk resulting from an exposure of earthworms and other soil organisms to GF-2463, the active substances clopyralid and florasulam or its metabolites according to the intended use of the formulation GF-2463 in cereals achieve the acceptability criteria TER 10 and TER 5, respectively, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point The results of the assessment indicate an acceptable risk for earthworms and other soil organisms. Effects on other soil non-target macro-organisms No risk management measures are required for the protection of earthworms and other soil macroorganisms for the intended use pattern. Applicant Date Dow AgroSciences GmbH 16/07/2013

21 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 21 of Effects on organic matter breakdown (Part B, Section 6, Point 10.6) Since no risk was identified for soil fauna, soil micro-organism and non-target arthropods from the use of in cereals data on the effects on organic matter breakdown (litterbag) is not required although the florasulam metabolites 5-OH-florasulam, DFP-ASTCA, and STCA meet the trigger on degradation in soil Effects on Soil Non-target Micro-organisms (Part B, Section 6, Point 10.7) Based on data for GF-1374, a formulation containing clopyralid (80 g/l), florasulam (2.5 g/l) and the additional active substance fluroxypyr at g a.i./l.,, the active substances clopyralid and florasulam and the metabolite ASTCA the risk to soil microbial processes following exposure to the active substances clopyralid and florasulam and their metabiolites in cereals according to the GAP of the formulation is considered to be acceptable according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point No risk management measures are required for the protection of non-target soil micro-organisms for the intended use pattern Assessment of Potential for Effects on Other Non-target Organisms (Flora and Fauna) (Part B, Section 6, Point 10.8) Non-Target Plants Effects on terrestrial non-target plants for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here and are considered adequate. Based on data for (ER 50 = 5.22 ml prod./ha; Lactuca sativa, vegetative vigour), the risk to soil non-target terrestrial plants following exposure to the active substances clopyralid and florasulam and their metabolites in cereals according to the GAP of the formulation is considered to be acceptable according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point only of risk mitigation measures are used. Risk mitigation drift reduction technique of at least 50 % in combination with a buffer of 5 m is necessary. Alternatively, it must be used drift reduction technique of at least 90 % at 1 m buffer zone. Consequences for authorization: For the authorization of the plant protection product following labeling and conditions of use are mandatory: Risk mitigation measures: All uses NT103: In a strip at least 20 m wide which is adjacent to other areas, the product must be applied using loss reducing equipment which is registered in the index of 'Loss Reducing Equipment' of 14 October 1993 (Federal Gazette No 205, p. 9780) as amended, and be registered in at least drift reducing class 90 % (except agriculturally or horticulturally used areas, roads, paths and public places). Loss reducing equipment is not required if the product is applied with portable plant protection equipment or if adjacent areas (field boundaries, hedges, groups of woody plants) are less than 3 m wide or the product is Applicant Date Dow AgroSciences GmbH 16/07/2013

22 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 22 of 25 applied in an area which has been declared by the Biologische Bundesanstalt in the "Index of regional proportions of ecotones" of 7 February 2002 (Federal Gazette no. 70 a of 13 April 2002), as amended, as agrarian landscape with a sufficient proportion of natural and semi-natural structures. Other non-target species (Flora and Fauna) Tests on other non-target species are not required. Implications for labelling resulting from ecotoxicological assessment: Relevant toxicity data for classification and labelling of the formulation GF-2463 (DOW H-0-SC): GF-2463 ErC 50 = mg/l (Lemna gibba) Classification & Labelling according to directives 67/548/EEC, 78/631/EEC and 1999/45/EEC Hazard Symbol: Indication of danger: N Risk Phrases: R50/53 Safety Phrases: S35, S57 Classification & Labelling according to directive 1272/2008 Danger Symbol: GHS09 Hazard Statements: H400; H410 Other phrases: for the PPP: NW468 NW262 NW265 for all uses: NW609-1 (5 m) NT Efficacy (Part B, Section 7, Point 8) Clopyralid (3,6-Dichlorpyridin-2-carbonsäure) belongs to the chemical group of pyridine carboxylic acids and works as such as a synthetic auxin. Site of action (HRAC-group): O. When applied in postemergence, clopyralid will mainly be absorbed through green leaves. Uptake through roots is of much less importance. Acropetal translocation of clopyralid in xylem into young meristems and youngest leaves as well as basipetal transport in phloem into roots is possible. It has been shown that clopyralid is being accumulated in meristematic tissue and influencing cell division, cell elongation and cell extension as well as RNA synthesis. Florasulam belongs to the chemical group of triazolpyrimidine sulfonanilides. Florasulam is taken up by roots or by foliage and redistributes throughout the plant. Due to a rapid degradation in soils, only a small soil effect is expected. Translocation pattern are consistent with mobility in both the xylem and the phloem. Accumulation of florasulam occurs at primary and axillary meristems, which are primary locations for the action of sulfonanilide herbicides. Florasulam is known to inhibit the plant enzyme Applicant Date Dow AgroSciences GmbH 16/07/2013

23 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 23 of 25 acetolactate synthase enzyme (ALS) which is essential for the creation of amino acids with branched chain such as valine, leucine or isoleucine. Site of action (HRAC-group): B. Therefore florasulam affect the formation of protein and the plants die. The product should be labelled HRAC-group B for florasulam as well HRAC-group O for clopyralid for resistance management purposes. The data provided support the proposed label recommendations for the use of GF-2463 as postemergence herbicide to control annual dicotyledonous weeds when applied in spring at the rate of 0.2 L/ha in winter wheat, winter barley, winter triticale, winter rye and spelt from BBCH 13 growth stage (three leaves) to BBCH 32 stage (second node), and to spring wheat, spring barley, spring oats and durum wheat from BBCH 13 growth stage (three leaves) to BBCH 30 stage (end of tillering). However, the following label phrases will be applied: WH9161 and WP711. The evaluation indicates a medium to high inherent and agronomic risk of resistance development for GF for use in cereals. This is mainly due to the inherent properties of florasulam and the worldwide resistance situation regarding ALS inhibitors. The resistance risk of Stellaria media, Papaver rhoeas and Matricaria spp. for florasulam has to be classified as high Label phrase applied: WH 951 In laboratory studies conducted with the two indicator species (Aphidius rhopalosiphi and Typhlodromus pyri) on inert substrate, the test product GF-2463 showed no mortality rates or effects on reproduction > 30% up to 4-fold the proposed rate. Therefore the product is labelled NN1001 and NN1002. All the data regarding the efficacy of the product have been submitted. These data demonstrate that GF fulfils all criteria for the authorization of preparations described in Directive 97/57/EC (Uniform Principles, Annex VI to Directive 91/414/EEC). 3.2 Conclusions With respect to identity, physical, chemical and technical properties as well to analytical methods for the formulation an authorisation can be granted. With respect to analytical methods for residues an authorisation can be granted. With respect to efficacy and sustainable use/ipm an authorisation can be granted. Regarding compliance with MRLs set according to Reg. (EC) No 396/2005, health protection of operators, workers, bystanders, and residents following the intended use of GF-2463 an authorisation can be granted. With respect to fate and ecotoxicology an authorisation can be granted. An authorisation can be granted. 3.3 Further information to permit a decision to be made or to support a review of the conditions and restrictions associated with the authorisation The applicant needs to submit following confirmatory data : Applicant Date Dow AgroSciences GmbH 16/07/2013

24 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 24 of 25 AnnexIII point Data A shelf life study to demonstrate the stability of the formulation over two years at ambient temperature. The storage should be conducted in containers made of HDPE (and) PET. Applicant Date Dow AgroSciences GmbH 16/07/2013

25 Part A National Assessment Germany GF-2463 Registration Repor Central Zone Page 25 of 25 Appendix 1 Copy of the product authorisation See below. Appendix 2 Copy of the product label See above. Appendix 3 Letter of Access See above. Applicant Date Dow AgroSciences GmbH 16/07/2013

26 Bundesamt für Verbraucherschutz und Lebensmittelsicherheit Dienstsitz Braunschweig Postfach Braunschweig Dr. Dietmar Gottschild Referent Einschreiben mit Rückschein Dow AgroSciences GmbH Truderinger Str München TELEFON TELEFAX INTERNET IHR ZEICHEN IHRE NACHRICHT VOM +49 (0) (0) AKTENZEICHEN (bitte bei Antwort angeben) / DATUM 2. August 2013 ZV /00 Zulassungsverfahren für Pflanzenschutzmittel Bescheid Das oben genannte Pflanzenschutzmittel mit den Wirkstoffen: 300 g/l Clopyralid 25 g/l Florasulam Zulassungsnummer: Versuchsbezeichnung: DOW H-0-SC Antrag vom: 29. September 2011 wird auf der Grundlage von Art. 29 der Verordnung (EG) Nr. 1107/2009 des Europäischen Parlaments und des Rates vom 21. Oktober 2009 über das Inverkehrbringen von Pflanzenschutzmitteln und zur Aufhebung der Richtlinien 79/117/EWG und 91/414/EWG des Rates (ABl. L 309 vom , S. 1), wie folgt zugelassen: Zulassungsende BVL_FO_05_2437_200_V1.1 Die Zulassung endet am 31. Dezember Dienstsitz Braunschweig Bundesallee 50, Geb Braunschweig Abt. Pflanzenschutzmittel Messeweg 11/ Braunschweig Dienststelle Berlin Mauerstraße Berlin Referatsgr. Untersuchungen Diedersdorfer Weg Berlin Tel: +49 (0) Tel: +49 (0) Tel: +49 (0) Tel: +49 (0) Fax: +49 (0) Fax: +49 (0) Fax: +49 (0) Fax: +49 (0)

27 SEITE 2 VON 12 Festgesetzte Anwendungsgebiete bzw. Anwendungen Es werden folgende Anwendungsgebiete bzw. Anwendungen festgesetzt (siehe Anlage 1): Anwendungsnummer Zweckbestimmung Schadorganismus/ / Einjährige zweikeimblättrige Unkräuter / Einjährige zweikeimblättrige Unkräuter Pflanzen/-erzeugnisse/ Objekte Sommerweichweizen, Sommerhartweizen, Sommergerste, Hafer Winterweichweizen, Wintergerste, Winterroggen, Dinkel, Wintertriticale Verwendungszweck Festgesetzte Anwendungsbestimmungen Es werden folgende Anwendungsbestimmungen gemäß 36 Abs. 1 S. 1 des Gesetzes zum Schutz der Kulturpflanzen (Pflanzenschutzgesetz - PflSchG) vom 6. Februar 2012 (BGBl. I S. 148, 1281) festgesetzt: BVL_FO_05_2437_200_V1.1 (NW468) Anwendungsflüssigkeiten und deren Reste, Mittel und dessen Reste, entleerte Behältnisse oder Packungen sowie Reinigungs- und Spülflüssigkeiten nicht in Gewässer gelangen lassen. Dies gilt auch für indirekte Einträge über die Kanalisation, Hof- und Straßenabläufe sowie Regen- und Abwasserkanäle. Begründung: Aufgrund der Auswirkungen der Wirkstoffe Florasulam (EC50 = 0,00118 mg/l Lemna gibba) und Clopyralid (NOEC = 10,8 mg/l Pimephales promelas) gegenüber aquatischen Organismen besitzt das o.g. Pflanzenschutzmittel einen den Naturhaushalt schädigenden Charakter, so dass jeder weitergehende, d.h. den als Folge der sachgerechten und bestimmungsgemäßen Anwendung des Pflanzenschutzmittels "" übersteigende Eintrag von Rückständen in Gewässer zu einer erheblichen Gefährdung des Naturhaushaltes führen würde. Angesichts der Umstände, dass ein erheblicher Anteil an Pflanzenschutzmittelfrachten im einzelnen Gewässer auf Einträge aus kommunalen Kläranlagen zurückzuführen ist (vgl. Umweltpolitik - Wasserwirtschaft in Deutschland, Pestizide, S. 156 ff., BMU, Februar 1998 und Fischer, Bach, Frede: Abschlussbericht zum DBU-Projekt 09931, April 1998), ist es unverzichtbar, der Gefahr, die eine Verbringung von Pflanzenschutzmitteln in Gewässer mit sich bringt, durch die bußgeldbewehrte Anwendungsbestimmung im Sinne der Zweckbestimmung des Pflanzenschutzgesetzes durchsetzbar zu begegnen.

28 SEITE 3 VON 12 Siehe anwendungsbezogene Anwendungsbestimmungen in Anlage 1, jeweils unter Nr. 3. Verpackungen Gemäß 36 Abs. 1 S. 2 Nr. 1 PflSchG sind für das Pflanzenschutzmittel die nachfolgend näher beschriebenen Verpackungen für den beruflichen Anwender zugelassen: Verpackungsarmaterial Verpackungs- Anzahl Inhalt von bis von bis Einheit Flasche HDPE 1 0,25 20,00 l Flasche PET 1 0,25 20,00 l Die Verpackungen für den beruflichen Anwender sind wie folgt zu kennzeichnen: Anwendung nur durch berufliche Anwender zulässig. Auflagen Die Zulassung wird mit folgenden Auflagen gemäß 36 Abs. 3 S. 1 PflSchG verbunden: Kennzeichnungsauflagen: (NW262) Das Mittel ist giftig für Algen. (NW265) Das Mittel ist giftig für höhere Wasserpflanzen. (SB001) Jeden unnötigen Kontakt mit dem Mittel vermeiden. Missbrauch kann zu Gesundheitsschäden führen. (SB010) Für Kinder unzugänglich aufbewahren. (SF245-01) Behandelte Flächen/Kulturen erst nach dem Abtrocknen des Spritzbelages wieder betreten. (WMB) Wirkungsmechanismus (HRAC-Gruppe): B BVL_FO_05_2437_200_V1.1 (WMO) Wirkungsmechanismus (HRAC-Gruppe): O

29 SEITE 4 VON 12 Siehe anwendungsbezogene Kennzeichnungsauflagen in Anlage 1, jeweils unter Nr. 2. Sonstige Auflagen: (WH951) Auf der Verpackung und in der Gebrauchsanleitung ist auf das Resistenzrisiko hinzuweisen. Insbesondere sind Maßnahmen für ein geeignetes Resistenzmanagement anzugeben. Vorbehalt Dieser Bescheid wird mit dem Vorbehalt der nachträglichen Aufnahme, Änderung oder Ergänzung von Anwendungsbestimmungen und Auflagen verbunden. Angaben zur Einstufung und Kennzeichnung gemäß 4 Gefahrstoffverordnung Gefahrensymbole: Gefahrenbezeichnungen: N Umweltgefährlich Gefahrenhinweise (R-Sätze): R 50/53: Sehr giftig für Wasserorganismen, kann in Gewässern längerfristig schädliche Wirkungen haben. Sicherheitshinweise (S-Sätze): S 35: Abfälle und Behälter müssen in gesicherter Weise beseitigt werden S 57 : Zur Vermeidung einer Kontamination der Umwelt geeigneten Behälter verwenden Zur Vermeidung von Risiken für Mensch und Umwelt ist die Gebrauchsanleitung einzuhalten. Angaben zur Einstufung und Kennzeichnung gemäß Verordnung (EG) Nr. 1272/2008 Signalwort: - keine - Gefahrenpiktogramme: (GHS09) Umwelt BVL_FO_05_2437_200_V1.1 Gefahrenhinweise (H-Sätze): (EUH 401) Zur Vermeidung von Risiken für Mensch und Umwelt die Gebrauchsanleitung einhalten.

30 SEITE 5 VON 12 (H400) Sehr giftig für Wasserorganismen. (H410) Sehr giftig für Wasserorganismen mit langfristiger Wirkung. Sicherheitshinweise (P-Sätze): - keine - Abgelehnte Anwendungsgebiete bzw. Anwendungen Für folgende Anwendungsgebiete bzw. Anwendungen lehne ich Ihren Antrag ab (siehe Anlage 2): - keine - Hinweise Auf dem Etikett und in der Gebrauchsanleitung kann angegeben werden: (NB6641) Das Mittel wird bis zu der höchsten durch die Zulassung festgelegten Aufwandmenge oder Anwendungskonzentration, falls eine Aufwandmenge nicht vorgesehen ist, als nicht bienengefährlich eingestuft (B4). (NN1001) Das Mittel wird als nicht schädigend für Populationen relevanter Nutzinsekten eingestuft. (NN1002) Das Mittel wird als nicht schädigend für Populationen relevanter Raubmilben und Spinnen eingestuft. Weitere Hinweise und Bemerkungen Momentan gibt es seitens des BVL keinen Vorschlag für P-Sätze gemäß Verordnung (EG) Nr. 1272/2008 (CLP-Verordnung). BVL_FO_05_2437_200_V1.1 Zu KIIIA : Hinweis und Begründung für die Kennzeichnungsauflage zum Wirkungsmechanismus (WMO: Clopyralid und WMB: Florasulam): Die HRAC-Klassifizierung ist als neutrale Information direkt jedem einzelnen Wirkstoff (hier: Clopyralid und Florasulam) zuzuordnen. Die Kennzeichnung erleichtert der Praxis die Bestimmung des Wirkungsmechanismus von Herbiziden und ermöglicht so ein gezieltes Wirkstoffmanagement.

31 SEITE 6 VON 12 Vorsorglich weise ich darauf hin, dass bisher mitgeteilte Forderungen bestehen bleiben, soweit sie noch nicht erfüllt sind. Unterbleibt eine Beanstandung der vorgelegten Gebrauchsanleitung, so ist daraus nicht zu schließen, dass sie als ordnungsgemäß angesehen wird. Die Verantwortung des Zulassungsinhabers für die Übereinstimmung mit dem Zulassungsbescheid bleibt bestehen. Hinsichtlich der Gebühren erhalten Sie einen gesonderten Bescheid. Rechtsbehelfsbelehrung Gegen diesen Bescheid kann innerhalb eines Monats nach Bekanntgabe Widerspruch erhoben werden. Der Widerspruch ist bei dem Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Messeweg 11/12, Braunschweig, schriftlich oder zur Niederschrift einzulegen. Mit freundlichen Grüßen im Auftrag gez. Dr. Johannes Siebers Dieses Schreiben wurde maschinell erstellt und ist daher ohne Unterschrift gültig. Anlage BVL_FO_05_2437_200_V1.1

32 SEITE 7 VON 12 Anlage 1 zugelassene Anwendung: / Anwendungsgebiet Schadorganismus/Zweckbestimmung: Einjährige zweikeimblättrige Unkräuter Pflanzen/-erzeugnisse/Objekte: Verwendungszweck: 2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung Einsatzgebiet: Anwendungsbereich: - Erläuterungen: Anwendung im Haus- und Kleingartenbereich: Erläuterung zum Schadorganismus: Stadium des Schadorganismus: - Erläuterungen: Erläuterung zur Kultur: Winterweichweizen, Wintergerste, Winterroggen, Dinkel, Wintertriticale Ackerbau Freiland Nein Stadium der Kultur: 13 bis 32 - Erläuterungen: Anwendungszeitpunkt: - Erläuterungen: Maximale Zahl der Behandlungen - in dieser Anwendung: 1 - für die Kultur bzw. je Jahr: 1 - Abstand: - Erläuterungen Anzahl Behandlungen: Mischungspartner: - Erläuterungen: Anwendungstechnik: - Erläuterungen: Aufwand: Nach dem Auflaufen, Frühjahr, nach dem Auflaufen der Unkräuter spritzen - 0,2 l/ha in 200 bis 400 l Wasser/ha BVL_FO_05_2437_200_V1.1 - Erläuterungen: Sonstige Ergänzungen und Hinweise: - keine -

33 SEITE 8 VON Sonstige Kennzeichnungsauflagen (WH9161) In die Gebrauchsanleitung ist eine Zusammenstellung der Unkräuter aufzunehmen, die durch die Anwendung des Mittels gut, weniger gut und nicht ausreichend bekämpft werden, sowie eine Arten- und/oder Sortenliste der Kulturpflanzen, für die der vorgesehene Mittelaufwand verträglich oder unverträglich ist. (WP711) Schäden an nachgebauten zweikeimblättrigen Zwischenfrüchten möglich. 2.3 Wartezeiten (F) Freiland: Winterweichweizen Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. (F) Freiland: Wintergerste Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. (F) Freiland: Winterroggen Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. (F) Freiland: Dinkel Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. BVL_FO_05_2437_200_V1.1 (F) Freiland: Wintertriticale Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich.

34 SEITE 9 VON 12 3 Anwendungsbezogene Anwendungsbestimmungen (NT103) Die Anwendung des Mittels muss in einer Breite von mindestens 20 m zu angrenzenden Flächen (ausgenommen landwirtschaftlich oder gärtnerisch genutzte Flächen, Straßen, Wege und Plätze) mit einem verlustmindernden Gerät erfolgen, das in das Verzeichnis "Verlustmindernde Geräte" vom 14. Oktober 1993 (Bundesanzeiger Nr. 205, S. 9780) in der jeweils geltenden Fassung, mindestens in die Abdriftminderungsklasse 90 % eingetragen ist. Bei der Anwendung des Mittels ist der Einsatz verlustmindernder Technik nicht erforderlich, wenn die Anwendung mit tragbaren Pflanzenschutzgeräten erfolgt oder angrenzende Flächen (z. B. Feldraine, Hecken, Gehölzinseln) weniger als 3 m breit sind oder die Anwendung des Mittels in einem Gebiet erfolgt, das von der Biologischen Bundesanstalt im "Verzeichnis der regionalisierten Kleinstrukturanteile" vom 7. Februar 2002 (Bundesanzeiger Nr. 70a vom 13. April 2002) in der jeweils geltenden Fassung, als Agrarlandschaft mit einem ausreichenden Anteil an Kleinstrukturen ausgewiesen worden ist. Begründung: Das o.g. Pflanzenschutzmittel weist ein hohes Gefährdungspotenzial für terrestrische Nichtzielpflanzen auf. Bewertungsbestimmend ist hier die ER50 von 5,22 ml Präparat/ha für Lactuca sativa im Vegetative Vigour Test. Ausgehend von den geltenden Modellen zur Abdrift und einem Sicherheitsfaktor von 5 ist nach dem Stand der wissenschaftlichen Erkenntnisse die o.g. Anwendungsbestimmung erforderlich, um einen ausreichenden Schutz von terrestrischen Nichtzielpflanzen in Saumbiotopen zu gewährleisten. Weitere Informationen hierzu sind dem nationalen Addendum zum Part B des Draft zu entnehmen. BVL_FO_05_2437_200_V1.1 (NW609-1) Die Anwendung des Mittels auf Flächen in Nachbarschaft von Oberflächengewässern - ausgenommen nur gelegentlich wasserführende, aber einschließlich periodisch wasserführender Oberflächengewässer - muss mindestens mit unten genanntem Abstand erfolgen. Dieser Abstand muss nicht eingehalten werden, wenn die Anwendung mit einem Gerät erfolgt, das in das Verzeichnis "Verlustmindernde Geräte" vom 14. Oktober 1993 (Bundesanzeiger Nr. 205, S. 9780) in der jeweils geltenden Fassung eingetragen ist. Unabhängig davon ist, neben dem gemäß Länderrecht verbindlich vorgegebenen Mindestabstand zu Oberflächengewässern, das Verbot der Anwendung in oder unmittelbar an Gewässern in jedem Fall zu beachten. Zuwiderhandlungen können mit einem Bußgeld bis zu Euro geahndet werden. 5 m Begründung: Das o.g. Pflanzenschutzmittel bzw. der darin enthaltene Wirkstoff Florasulam weist ein hohes Gefährdungspotenzial für aquatische Organismen, insbesondere aquatische höhere Pflanzen auf. Bewertungsbestimmend ist hier die EC50 für Lemna gibba von 20 µg/l mit dem Präparat. Ausgehend von den geltenden Modellen zur Abdrift und einem Sicherheitsfaktor von 10 ist nach dem Stand der wissenschaftlichen Erkenntnisse die o.g. Anwendungsbestimmung erforderlich, um einen ausreichenden Schutz von Gewässerorganismen zu gewährleisten. Weitere Informationen hierzu sind dem nationalen Addendum zum Part B des Draft zu entnehmen.

35 SEITE 10 VON 12 Anlage 1 zugelassene Anwendung: / Anwendungsgebiet Schadorganismus/Zweckbestimmung: Einjährige zweikeimblättrige Unkräuter Pflanzen/-erzeugnisse/Objekte: Verwendungszweck: 2 Kennzeichnungsauflagen 2.1 Angaben zur sachgerechten Anwendung Einsatzgebiet: Anwendungsbereich: - Erläuterungen: Anwendung im Haus- und Kleingartenbereich: Erläuterung zum Schadorganismus: Stadium des Schadorganismus: - Erläuterungen: Erläuterung zur Kultur: Sommerweichweizen, Sommerhartweizen, Sommergerste, Hafer Ackerbau Freiland Nein Stadium der Kultur: 13 bis 30 - Erläuterungen: Anwendungszeitpunkt: - Erläuterungen: Maximale Zahl der Behandlungen - in dieser Anwendung: 1 - für die Kultur bzw. je Jahr: 1 - Abstand: - Erläuterungen Anzahl Behandlungen: Mischungspartner: - Erläuterungen: Anwendungstechnik: - Erläuterungen: Aufwand: Nach dem Auflaufen, Frühjahr, nach dem Auflaufen der Unkräuter spritzen - 0,2 l/ha in 200 bis 400 l Wasser/ha BVL_FO_05_2437_200_V1.1 - Erläuterungen: Sonstige Ergänzungen und Hinweise: - keine -

36 SEITE 11 VON Sonstige Kennzeichnungsauflagen (WH9161) In die Gebrauchsanleitung ist eine Zusammenstellung der Unkräuter aufzunehmen, die durch die Anwendung des Mittels gut, weniger gut und nicht ausreichend bekämpft werden, sowie eine Arten- und/oder Sortenliste der Kulturpflanzen, für die der vorgesehene Mittelaufwand verträglich oder unverträglich ist. (WP711) Schäden an nachgebauten zweikeimblättrigen Zwischenfrüchten möglich. 2.3 Wartezeiten (F) Freiland: Sommerweichweizen Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. (F) (F) Freiland: Sommerhartweizen Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. Freiland: Sommergerste Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. (F) Freiland: Hafer Die Wartezeit ist durch die Anwendungsbedingungen und/oder die Vegetationszeit abgedeckt, die zwischen Anwendung und Nutzung (z. B. Ernte) verbleibt bzw. die Festsetzung einer Wartezeit in Tagen ist nicht erforderlich. 3 Anwendungsbezogene Anwendungsbestimmungen BVL_FO_05_2437_200_V1.1 (NT103) Die Anwendung des Mittels muss in einer Breite von mindestens 20 m zu angrenzenden Flächen (ausgenommen landwirtschaftlich oder gärtnerisch genutzte Flächen, Straßen, Wege und Plätze) mit einem verlustmindernden Gerät erfolgen, das in das Verzeichnis "Verlustmindernde Geräte" vom 14. Oktober 1993 (Bundesanzeiger Nr. 205, S. 9780) in der jeweils gel-

37 SEITE 12 VON 12 tenden Fassung, mindestens in die Abdriftminderungsklasse 90 % eingetragen ist. Bei der Anwendung des Mittels ist der Einsatz verlustmindernder Technik nicht erforderlich, wenn die Anwendung mit tragbaren Pflanzenschutzgeräten erfolgt oder angrenzende Flächen (z. B. Feldraine, Hecken, Gehölzinseln) weniger als 3 m breit sind oder die Anwendung des Mittels in einem Gebiet erfolgt, das von der Biologischen Bundesanstalt im "Verzeichnis der regionalisierten Kleinstrukturanteile" vom 7. Februar 2002 (Bundesanzeiger Nr. 70a vom 13. April 2002) in der jeweils geltenden Fassung, als Agrarlandschaft mit einem ausreichenden Anteil an Kleinstrukturen ausgewiesen worden ist. Begründung: Das o.g. Pflanzenschutzmittel weist ein hohes Gefährdungspotenzial für terrestrische Nichtzielpflanzen auf. Bewertungsbestimmend ist hier die ER50 von 5,22 ml Präparat/ha für Lactuca sativa im Vegetative Vigour Test. Ausgehend von den geltenden Modellen zur Abdrift und einem Sicherheitsfaktor von 5 ist nach dem Stand der wissenschaftlichen Erkenntnisse die o.g. Anwendungsbestimmung erforderlich, um einen ausreichenden Schutz von terrestrischen Nichtzielpflanzen in Saumbiotopen zu gewährleisten. Weitere Informationen hierzu sind dem nationalen Addendum zum Part B des Draft zu entnehmen. (NW609-1) Die Anwendung des Mittels auf Flächen in Nachbarschaft von Oberflächengewässern - ausgenommen nur gelegentlich wasserführende, aber einschließlich periodisch wasserführender Oberflächengewässer - muss mindestens mit unten genanntem Abstand erfolgen. Dieser Abstand muss nicht eingehalten werden, wenn die Anwendung mit einem Gerät erfolgt, das in das Verzeichnis "Verlustmindernde Geräte" vom 14. Oktober 1993 (Bundesanzeiger Nr. 205, S. 9780) in der jeweils geltenden Fassung eingetragen ist. Unabhängig davon ist, neben dem gemäß Länderrecht verbindlich vorgegebenen Mindestabstand zu Oberflächengewässern, das Verbot der Anwendung in oder unmittelbar an Gewässern in jedem Fall zu beachten. Zuwiderhandlungen können mit einem Bußgeld bis zu Euro geahndet werden. 5 m Begründung: Das o.g. Pflanzenschutzmittel bzw. der darin enthaltene Wirkstoff Florasulam weist ein hohes Gefährdungspotenzial für aquatische Organismen, insbesondere aquatische höhere Pflanzen auf. Bewertungsbestimmend ist hier die EC50 für Lemna gibba von 20 µg/l mit dem Präparat. Ausgehend von den geltenden Modellen zur Abdrift und einem Sicherheitsfaktor von 10 ist nach dem Stand der wissenschaftlichen Erkenntnisse die o.g. Anwendungsbestimmung erforderlich, um einen ausreichenden Schutz von Gewässerorganismen zu gewährleisten. Weitere Informationen hierzu sind dem nationalen Addendum zum Part B des Draft zu entnehmen. BVL_FO_05_2437_200_V1.1

38 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 1 of 32 REGISTRATION REPORT Part B Section 1: Identity, physical and chemical properties, other information Detailed summary of the risk assessment Product code: GF-2463 Active Substances: Clopyralid Florasulam 300 g/l 25 g/l Central Zone Rapporteur Member State: Germany CORE ASSESSMENT GmbH Submission Date: September 2011 Evaluator: BVL / DE Date: June 2013

39 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 2 of 32 Table of Contents IIIA 1 IDENTITY OF THE PLANT PROTECTION PRODUCT... 8 IIIA 1.1 Applicant... 8 IIIA 1.2 Manufacturer of the Preparation, Manufacturer and Purity of the Active Substance(s)... 8 IIIA Manufacturer(s) of the preparation... 8 IIIA Manufacturer(s) of the active substance(s)... 8 IIIA Statement of purity (and detailed information on impurities) of the active substance(s)... 8 IIIA 1.3 Trade Names and Manufacturer s Code Numbers for the Preparation... 8 IIIA 1.4 Detailed Quantitative and Qualitative Information on the Composition of the Preparation... 8 IIIA Content of active substance and formulants... 8 IIIA Certified limits of each component... 9 IIIA Common names and code numbers for the active substance(s)... 9 IIIA Co-formulant details: identity, structure, codes, trade name, specification and function... 9 IIIA Formulation process IIIA Description of formulation process IIIA Discussion of the formation of impurities of toxicological concern IIIA 1.5 Type of Preparation and Code IIIA 1.6 Function IIIA 1.7 Other/Special Studies IIIA 2 PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE PLANT PROTECTION PRODUCT IIIA 2.16 Summary and Evaluation of Data Presented Under Points 2.1 to Evaluator: BVL / DE Date: June 2013

40 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 3 of 32 IIIA 3 DATA ON APPLICATION OF THE PLANT PROTECTION PRODUCT IIIA 3.1 Field of Use IIIA 3.2 Nature of the Effects on Harmful Organisms IIIA 3.3 Details of Intended Use IIIA Details of existing and intended uses IIIA Details of harmful organisms against which protection is afforded IIIA Effects achieved IIIA 3.4 Proposed Application Rates (Active Substance and Preparation) IIIA 3.5 Concentration of the Active Substance in the Material Used IIIA 3.6 IIIA 3.7 Method of Application, Type of Equipment Used and Volume of Diluent Number and Timings of Applications, Timing, Growth Stages (of Crop and Harmful Organism) and Duration of Protection IIIA Maximum number of applications and their timings IIIA Growth stages of crops or plants to be protected IIIA Development stages of the harmful organism concerned IIIA Duration of protection afforded by each application IIIA IIIA 3.8 IIIA Duration of protection afforded by the maximum number of applications Necessary Waiting Periods or Other Precautions to Avoid Phytotoxic Effects on Succeeding Crops Minimum waiting periods or other precautions between last application and sowing or planting succeeding crops IIIA Limitations on choice of succeeding crops IIIA Description of damage to rotational crops IIIA 3.9 Proposed Instructions for Use as Printed on Labels IIIA 3.10 Other/Special Studies Evaluator: BVL / DE Date: June 2013

41 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 4 of 32 IIIA 4 FURTHER INFORMATION ON THE PLANT PROTECTION PRODUCT IIIA 4.1 Packaging and Compatibility with the Preparation IIIA Description and specification of the packaging IIIA Suitability of the packaging and closures IIIA Resistance of the packaging material to its contents IIIA 4.2 Procedures for Cleaning Application Equipment IIIA Procedures for cleaning application equipment and protective clothing IIIA Effectiveness of the cleaning procedures IIIA 4.3 IIIA IIIA IIIA IIIA IIIA IIIA IIIA IIIA 4.4 Re-entry Periods to Protect Man, Livestock and the EnvironmentFehler! Textmarke nicht Pre-harvest interval (in days) for each relevant cropfehler! Textmarke nicht definiert. Re-entry period (in days) for livestock, to areas to be grazedfehler! Textmarke nicht defini Re-entry period (in hours or days) for man to crops, buildings or spaces treated...fehler! Textmarke nicht definiert. Withholding period (in days) for animal feeding stuffsfehler! Textmarke nicht definiert. Waiting period (in days) between application and handling of treated products...fehler! Textmarke nicht definiert. Waiting period (in days) between last application and sowing or planting succeeding crops...fehler! Textmarke nicht definiert. Information on specific conditions under which the preparation may or may not be used...fehler! Textmarke nicht definiert. Statement of the Risks Arising and the Recommended Methods and Precautions and Handling Procedures to Minimise Those Risks IIIA Warehouse storage IIIA User level storage IIIA Transport IIIA Fire IIIA Nature of protective clothing proposed IIIA Characteristics of protective clothing proposed Evaluator: BVL / DE Date: June 2013

42 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 5 of 32 IIIA Suitability and effectiveness of protective clothing and equipment IIIA Procedures to minimise the generation of waste IIIA Combustion products likely to be generated in the event of fire IIIA 4.5 Detailed Procedures for Use in the Event of an Accident During Transport, Storage or Use IIIA Containment of spillages IIIA Decontamination of areas, vehicles and buildings IIIA Disposal of damaged packaging, adsorbents and other materials IIIA Protection of emergency workers and bystanders IIIA First aid measures IIIA 4.6 Neutralisation Procedure for Use in the Event of Accidental Spillage IIIA Details of proposed procedures for small quantities IIIA Evaluation of products of neutralization (small quantities) IIIA Procedures for disposal of small quantities of neutralized waste IIIA Details of proposed procedures for large quantities IIIA Evaluation of products of neutralization (large quantities) IIIA Procedures for disposal of large quantities of neutralized waste IIIA 4.7 Pyrolytic Behaviour of the Active Substance IIIA 4.8 Disposal Procedures for the Plant Protection Product IIIA Detailed instructions for safe disposal of product and its packaging IIIA Methods other than controlled incineration for disposal IIIA 4.9 Other/Special Studies IIIA 11 FURTHER INFORMATION IIIA 11.1 Information of Authorisations in Other Countries IIIA 11.2 Information on Established Maximum Residue Limits (MRL) in Other Countries IIIA 11.3 Justified Proposals for Classification and Labelling Evaluator: BVL / DE Date: June 2013

43 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 6 of 32 IIIA 11.4 Proposals for Risk and Safety Phrases IIIA 11.5 Proposed Label IIIA 11.6 Specimens of Proposed Packaging Appendix 1: List of data used in support of the evaluation Appendix 2: Critical Uses justification and GAP tables Appendix 3: Experimental testing of the product's physico-chemical and technical characteristics: Evaluator: BVL / DE Date: June 2013

44 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 7 of 32 Introduction This document summarises the information related to the identity, the physical and chemical properties, the data on application, further information and the classification for the product GF-2463 containing the active substances clopyralid and florasulam which were included into Annex I of Directive 91/414. This product was not the representative formulation. The product has not been previously evaluated according to Uniform Principles. Where appropriate this document refers to the conclusions of the EU review of clopyralid and florasulam. This will be where: the active substance data are relied upon in the risk assessment of the formulation; or when the EU review concluded that additional data/information should be considered at national reregistration. This Part B document only reviews data (Annex II or Annex III) and additional information that has not previously been considered within the EU review process, as part of the Annex I inclusion decision. The following table provides the EU endpoints to be used in the evaluation. Agreed EU End-points End-Point Clopyralid (06/64/EC) Florasulam (02/64/EC) Purity of active substance min 950 g/kg min 970 g/kg The Annex I Inclusion Directives for Clopyralid (06/64/EC)and Florasulam (02/64/EC) provide specific provisions under Part B which need to be considered by the applicant in the preparation of their submission and by the MS prior to granting an authorisation (see Part A of this submission). However, these provisions do not pertain the information given for the product GF-2463 in this section. Appendix 1 of this document contains the list of references included in this document for support of the evaluation. Appendix 2 of this document is the table of intended uses for GF Information on the detailed composition of GF-2463 can be found in the confidential dossier of this submission ( - Part C). Evaluator: BVL / DE Date: June 2013

45 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 8 of 32 IIIA 1 IIIA 1.1 IDENTITY OF THE PLANT PROTECTION PRODUCT Applicant Dow AgroSciences GmbH Truderinger Straße München Germany Contact person: Tel.No.: XXXXXXX XXXXXXXXX XXXXXXXXX IIIA 1.2 Manufacturer of the Preparation, Manufacturer and Purity of the Active Substance(s) IIIA Manufacturer(s) of the preparation Confidential information - data provided separately (Part C). IIIA Manufacturer(s) of the active substance(s) Confidential information - data provided separately (Part C). IIIA Statement of purity (and detailed information on impurities) of the active substance(s) Clopyralid: minimum 950 g/kg Florasulam: minimum 970 g/kg Further information/justification is provided in Part C. IIIA 1.3 Trade name: Trade Names and Manufacturer s Code Numbers for the Preparation GF-2463 Company code number: GF-2463 SC IIIA 1.4 Detailed Quantitative and Qualitative Information on the Composition of the Preparation IIIA Content of active substance and formulants The formulation was not the representative formulation for Annex I inclusion. Evaluator: BVL / DE Date: June 2013

46 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 9 of 32 Pure active substance: content of pure clopyralid: content of pure clopyralid olamine: limits clopyralid: 300 g/l g/l g/l content of pure florasulam: limits florasulam (as stated by applicant): limits florasulam (according to FAO/WHO manual) 25 g/l g/l g/l Technical active substance: content of technical clopyralid at minimum purity (95 %): content of technical florasulam: at minimum purity (97 %): g/l (27.20 % w/w) 25.8 g/l (2.22 % w/w) Clopyralid is present in the formulation in the form of the olamine- (monoethanolamine-) salt. Further information on the active substances and on the certified limits of formulants is considered confidential and is provided separately (Part C). IIIA Certified limits of each component This is not an EC data requirement. IIIA Common names and code numbers for the active substance(s) Data Type Name/Code Number Point ISO common name Clopyralid Florasulam CAS No EINECS No CIPAC No ELINCS Salt, ester anion or cation present IIIA Co-formulant details: identity, structure, codes, trade name, specification and function. CONFIDENTIAL information - data provided separately (Part C). Evaluator: BVL / DE Date: June 2013

47 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 10 of 32 IIIA Formulation process IIIA Description of formulation process This is not an EC data requirement. IIIA Discussion of the formation of impurities of toxicological concern Clopyralid does not contain any impurities of toxicological or ecotoxicological concern. Florasulam does not contain any impurities of toxicological or ecotoxicological concern. IIIA 1.5 Type of Preparation and Code Type : Suspension Concentrate Code : SC IIIA 1.6 Function The product will be used as herbicide. IIIA 1.7 None. Other/Special Studies Evaluator: BVL / DE Date: June 2013

48 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 11 of 32 IIIA 2 PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF THE PLANT PROTECTION PRODUCT All studies have been performed in accordance with the current requirements and the results are deemed to be acceptable for a SC formulation. The shelf life study is still ongoing and must be submitted after finalisation in March Table 1: Summary of the physical, chemical and technical properties of the plant protection product Test or study & Annex point Colour, odour and physical state (IIIA 2.1) Method used / deviations OPPTS (visually) OPPTS (olfactory) OPPTS (visually) Explosive properties (IIIA 2.2.1) EEC A 14 Oxidizing properties (IIIA 2.2.2) Flash point (IIIA 2.3.1) EEC A 21 OPPTS (ASTM D ) Flammability - - Test material purity and specification TSN % clopyralid 2.05 % florasulam TSN g/l clopyralid 27 g/l florasulam TSN g/l clopyralid 27 g/l florasulam TSN % clopyralid 2.05 % florasulam Findings Tan liquid at 23.5 C with an aromatic odor not explosive non oxidising > 100 C no flash point was observed up to 100 C not applicable GLP Y/N Y Y Y Y Reference Acceptability / comments Rozniak, M., 2011, (NAFST-11-27) Turner, B., 2011, (NAFST-11-21) Turner, B., 2011, (NAFST-11-21) Rozniak, M., 2011, (NAFST-11-27) Acceptable Acceptable Formulation has no explosive properties. Acceptable Formulation has no oxidising properties. Acceptable - - Acceptable Evaluator: BVL / DE Date: June 2013

49 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 12 of 32 Test or study & Annex point (IIIA 2.3.2) Auto-flammability (IIIA 2.3.3) Acidity or alkalinity and ph (IIIA 2.4.1) ph of a 1% aqueous dilution, emulsion or dispersion (IIIA 2.4.2) Method used / deviations EEC A 15 Test material purity and specification TSN g/l clopyralid 27 g/l florasulam Findings none below 400 C - - The test was not conducted, because the ph value of the product was between 4 and 10. OPPTS CIPAC MT 75.3 TSN % clopyralid 2.05 % florasulam TSN g/l clopyralidolamine 27 g/l florasulam 4.42 at 22 C Y before storage: 4.44 after storage: 4.49 GLP Y/N Y Reference Acceptability / comments Turner, B., 2011, (NAFST-11-21) - - open Y Rozniak, M., 2011, (NAFST-11-27) Thirugnanam, 2011, (NAFST ), Acceptable According to the applicant, the ph of the neat formulation is 6.13, as determined in interim report after 12 month storage (NAFST ), but the report was not submitted yet. Acceptable Acceptable Kinematic viscosity (IIIA 2.5.1) - - Formulation is not for Ultra Low Volume use (ULV). - - Acceptable Evaluator: BVL / DE Date: June 2013

50 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 13 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments Dynamic viscosity (IIIA 2.5.2) OPPTS (OECD 114) TSN % clopyralid 2.05 % florasulam non-newtonian behaviour : 677 mpa s (19.9 C, 4 rpm) 281 mpa s (40.0 C, 10 rpm) Y Rozniak, M., 2011, (NAFST-11-27) Acceptable Surface tension (IIIA 2.5.3) EEC A 5 TSN g/l clopyralid 27 g/l florasulam 58.0 mn/m (0.05 %, 20 C) 46.5 mn/m (0.2 %, 20 C) Y Turner, B., 2011, (NAFST-11-21) Acceptable. Relative density (IIIA 2.6.1) OPPTS TSN % clopyralid 2.05 % florasulam g/ml at 20 C Y Rozniak, M., 2011, (NAFST-11-27) Acceptable Bulk or tap density (IIIA 2.6.2) Storage Stability after 14 days at 54º C (IIIA 2.7.1) - - not relevant; formulation is a liquid CIPAC MT 46.3 TSN g/l clopyralidolamine 27 g/l florasulam storage in glass bottles: Active Ingredients were stable after storage (clopyralid 1.7 %, florasulam 0.9 %), no significant physical changes, and all performance properties remained within acceptable limits. Y Thirugnanam, 2011, (NAFST ) Acceptable Evaluator: BVL / DE Date: June 2013

51 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 14 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments Stability after storage for other periods and/or temperatures (IIIA 2.7.2) CIPAC MT 46.3 storage conditions: 8 weeks at 40 C study in grogress NAFST Not considered necessary, for the formulation is stable at 54 C Minimum content after heat stability testing (IIIA 2.7.3) Effect of low temperatures on stability (IIIA 2.7.4) - - Not necessary, since the decrease of the active substance did not exceed 5 %. CIPAC MT 39.3 TSN g/l clopyralidolamine 27 g/l florasulam Active Ingredients were stable after storage, no significant physical changes, all performance properties remained within acceptable limits. - - Acceptable Y Thirugnanam, 2011, (NAFST ) Acceptable Ambient temperature shelf life (IIIA 2.7.5) - TSN g/l clopyralid 27 g/l florasulam in progress; will be finalised in March An interim report after 12 month demonstrates the compatibility with HDPE and PET packaging, but this report was not submitted yet. Y NAFST Not acceptable; study must be submitted after finalisation. Shelf life in months (if less than 2 years) (IIIA 2.7.6) - TSN g/l clopyralid 27 g/l florasulam in progress Y NAFST Acceptable Wettability (IIIA 2.8.1) - - not relevant; formulation is a liquid - - Acceptable Evaluator: BVL / DE Date: June 2013

52 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 15 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments Persistence of foaming (IIIA 2.8.2) CIPAC MT 47.2 TSN g/l clopyralidolamine 27 g/l florasulam 1 % in CIPAC water D, in ml: storage interval 10s 1 min 3 min 12 min Y Thirugnanam, 2011, (NAFST ) Acceptable Initial weeks, 54 C Suspensibility (IIIA ) CIPAC MT 184 TSN g/l clopyralidolamine 27 g/l florasulam 0.2 % in CIPAC water D, in %: storage interval clopyralid florasulam Y Thirugnanam, 2011, (NAFST ) Acceptable Initial weeks, 54 C d, 0 C % in CIPAC water D, in %: storage interval clopyralid florasulam Initial weeks, Evaluator: BVL / DE Date: June 2013

53 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 16 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments 54 C 7 d, 0 C Spontaneity of dispersion (IIIA ) CIPAC MT 160 TSN g/l clopyralidolamine 27 g/l florasulam before storage: > % after storage: > % Y Thirugnanam, 2011, (NAFST ) Acceptable Dilution stability (IIIA 2.8.4) Dry sieve test (IIIA ) Wet sieve test (IIIA ) Particle size distribution (IIIA ) Nominal size range of granules (IIIA ) Dust content (IIIA ) - - not relevant - - Acceptable - - not relevant: formulation is a liquid - - Acceptable CIPAC MT 185 TSN g/l clopyralidolamine 27 g/l florasulam residue on 75 m sieve: initial: % 14 d at 54 C: % 7 d at 0 C: % Y Thirugnanam, 2011, (NAFST ) Acceptable - - see IIIA Acceptable - - Not applicable - - Acceptable - - Not applicable - - Acceptable Evaluator: BVL / DE Date: June 2013

54 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 17 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments Particle size of dust (IIIA ) Friability and attrition (IIIA ) Emulsifiability (IIIA ) Dispersibility (IIIA ) Flowability (IIIA ) Pourability (including rinsed residue) (IIIA ) Dustability following accelerated storage (IIIA ) - - Not applicable - - Acceptable - - Not applicable - - Acceptable - - Not applicable - - Acceptable - - Not applicable - - Acceptable - - Not applicable - - Acceptable CIPAC MT 148 TSN g/l clopyralidolamine 27 g/l florasulam initial: residue: 2.37 % residue after rinsing: 0.17 % 14 d at 54 C: residue: 2.17 % residue after rinsing: 0.17 % Y Thirugnanam, 2011, (NAFST ) Acceptable - - Not applicable - - Acceptable Physical compatibility of tank mixes (IIIA 2.9.1) - - not relevant, no tank mixes recommended Evaluator: BVL / DE Date: June 2013

55 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 18 of 32 Test or study & Annex point Method used / deviations Test material purity and specification Findings GLP Y/N Reference Acceptability / comments Chemical compatibility of tank mixes (IIIA 2.9.2) Adhesion to seeds (IIIA ) Distribution to seed (IIIA ) - - not relevant, no tank mixes recommended - - not relevant; formulation not for seed treatment - - not relevant; formulation not for seed treatment Miscibility (IIIA 2.11) Dielectric breakdown (IIIA 2.12) Corrosion characteristics (IIIA 2.13) Container material (IIIA 2.14) Other/special studies (IIIA 2.15) - - no data requirement no data requirement no data requirement no data requirement no data requirement Evaluator: BVL / DE Date: June 2013

56 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 19 of 32 IIIA 2.16 Summary and Evaluation of Data Presented Under Points 2.1 to 2.15 The product GF-2463 is a suspension concentrate (SC). All studies have been performed in accordance with the current requirements, the critical GAP and the results are deemed to be acceptable. The appearance of the product is that of tan liquid, with an aromatic odour. It is not explosive, has no oxidising properties, and no self ignition temperature below 400 C. In aqueous solution, it has a ph value around 4.4. The stability at 54 C is acceptable for active ingredient and physical properties. The shelf life study for two years at ambient temperature will be finalised in March The technical characteristics are acceptable for a suspension concentrate (SC) formulation. Experimental testing of the product's physico-chemical and technical characteristics: See Appendix 3 Implications for labelling: No labelling necessary due to physical or chemical properties. IIIA 3 DATA ON APPLICATION OF THE PLANT PROTECTION PRODUCT IIIA 3.1 Field of Use GF-2463 is intended as herbicide for post-emergence applications in spring, in spring and winter cereals to control annual dicotyledonous weeds.. IIIA 3.2 Nature of the Effects on Harmful Organisms Clopyralid (3,6-Dichlorpyridin-2-carbonsäure) belongs to the chemical group of pyridine carboxylic acids and works as such as a synthetic auxin. When applied in post-emergence, clopyralid will mainly be absorbed through green leaves. Uptake through roots is of much less importance. Acropetal translocation of clopyralid in xylem into young meristems and youngest leaves as well as basipetal transport in phloem into roots is possible. It has been shown that clopyralid is being accumulated in meristematic tissue and influencing cell division, cell elongation and cell extension as well as RNA synthesis. Consequently, meristematic tissue dies off. Site of action (HRAC-group): O Florasulam belongs to the chemical group of triazolpyrimidine sulfonanilides. Florasulam is taken up by roots or by foliage and redistributes throughout the plant. Due to a rapid degradation in soils, only a small soil effect is expected. Translocation pattern are consistent with mobility in both the xylem and the phloem. Accumulation of florasulam occurs at primary and axillary meristems, which are primary locations for the action of sulfonanilide herbicides. Florasulam is known to inhibit the plant enzyme acetolactate synthase enzyme (ALS) which is essential for the creation of amino acids with branched chain such as valine, leucine or isoleucine. Therefore florasulam affect the formation of protein and the plants die. Site of action (HRAC-group): B IIIA 3.3 Details of Intended Use IIIA Details of existing and intended uses Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. Evaluator: BVL / DE Date: June 2013

57 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 20 of 32 IIIA Details of harmful organisms against which protection is afforded GF-2463 is intended as herbicide for post-emergence use in spring in cereals to control annual dicotyledonous weeds. Primary target weeds in Central Zone are: IIIA Galium aparine (GALAP) Matricaria species (MATCH, MATIN) Cruciferous weeds (BRSNW, CAPBP, SINAR,THLAR) Stellaria media (STEME) Centaurea cyanus (CENCY) Polygonum species (POLCO, POLPE, POLAV). Effects achieved Winter cereals (use 001): Efficacy data to support the label claims in winter cereals were generated in a total of 26 efficacy trials carried out during the period in Germany (24 trials) and UK (2 trials). One spring application of GF-2463 at a use rate of 0.2 L/ha controls Galium aparine, Centaurea cyanus, Matricaria sp., Stellaria media, Polygonum convolvulus, volunteer oil seed rape and smaller stages of Capsella bursa-pastoris. Cirsium arvense is being controlled (suppressed) sufficiently in the year of treatment. Other weeds such as Geranium sp., Veronica sp., Viola arvensis and volunteer potatoes will not be controlled at a commercially acceptable level (for further details please refer to Part B Section 7). Spring cereals (use 002): Efficacy data to support the label claims in spring cereals were generated in a total of 17 efficacy trials carried out during the period in Germany. One spring application of GF-2463 at a use rate of 0.2 L/ha controls volunteer oilseed rape, Capsella bursa-pastoris, Galium aparine, Centaurea cyanus, Matricaria sp., Stellaria media, Polygonum convolvulus, P. persicaria, Raphanus raphanistrum, Sinapis arvense, and Solanum nigrum. Cirsium arvense is being controlled (suppressed) sufficiently in the year of treatment. Other weeds such as Veronica species, Lamium amplexicaule, Chenopodium species, Thlaspi arvense and Viola arvensis will not be controlled at a commercially acceptable level (for further details please refer to Part B Section 7). IIIA 3.4 Proposed Application Rates (Active Substance and Preparation) Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA 3.5 Concentration of the Active Substance in the Material Used Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA 3.6 Method of Application, Type of Equipment Used and Volume of Diluent Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA 3.7 IIIA Number and Timings of Applications, Timing, Growth Stages (of Crop and Harmful Organism) and Duration of Protection Maximum number of applications and their timings Evaluator: BVL / DE Date: June 2013

58 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 21 of 32 Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA Growth stages of crops or plants to be protected Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA Development stages of the harmful organism concerned Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA Duration of protection afforded by each application Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA Duration of protection afforded by the maximum number of applications Please refer to Appendix 2: Critical Uses justification and GAP tables. For further details please refer to Part B Section 7. IIIA 3.8 Necessary Waiting Periods or Other Precautions to Avoid Phytotoxic Effects on Succeeding Crops IIIA Minimum waiting periods or other precautions between last application and sowing or planting succeeding crops EC 10 -values are only available for both active substances but not for the herbicide GF The PEC calculation submitted by the applicant is based on an interception of 25%. Since GF-2463 can be applied at an early growth stage at BBCH 13 the realistic interception rate is probably much lower. Based on an interception of 0% and on a low degradation (DT 50 maximum values provided by the applicant), there is a theoretical risk of damage for oilseed rape and phacelia when sown in autumn of the same year. For further details please refer to Part B Section 7. IIIA Please refer to IIIA IIIA Please refer to IIIA IIIA 3.9 Limitations on choice of succeeding crops Description of damage to rotational crops Proposed Instructions for Use as Printed on Labels Please refer to Part A, Appendix 2 for the relevant country. IIIA 3.10 Other/Special Studies This is not an EC data requirement/ not required by Directive 91/414/EEC. Evaluator: BVL / DE Date: June 2013

59 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 22 of 32 IIIA 4 FURTHER INFORMATION ON THE PLANT PROTECTION PRODUCT IIIA 4.1 Packaging and Compatibility with the Preparation Packaging Summary Information with regard to type, dimensions, capacity, size of opening, type of closure, strength, leakproofness, resistance to normal transport & handling, resistance to & compatibility with the contents of the packaging, have been submitted, evaluated and is considered to be acceptable. IIIA Description and specification of the packaging GF-2463 is to be marketed in high-density polyethylene (HDPE) or PET bottles L to 20 L bottles: material: HDPE shape/size: - opening: - closure / seal: 1-2 L: 50 mm screw cap with inductiuon seal 3-10 L: 63 mm screw cap with inductionseal 20 L: 61 mm screw cap with compression foam wad L to 20 L bottles: material: PET shape/size: - opening: - closure / seal: L: 45 mm screw cap with inductiuon seal 3-10 L: 63 mm screw cap with induction seal 20 L: 63 mm screw cap with compression foam wad or bore seal. IIIA Suitability of the packaging and closures The packaging complies with ADR regulations having been tested using the ADR test methods appropriate to the pack type and material and classification of the contents and an appropriate UN certificate issued. IIIA Resistance of the packaging material to its contents A packaging storage stability study has been carried out on GF-2463 for 2 weeks at 54 C, but only in glass. HDPE bottles and PET bottles are proposed primary sales packages for GF A shelf life study in these package materials is not finalised yet. IIIA 4.2 Procedures for Cleaning Application Equipment Evaluator: BVL / DE Date: June 2013

60 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 23 of 32 IIIA Procedures for cleaning application equipment and protective clothing To avoid subsequent injury to crops, all spraying equipment must be thoroughly cleaned both inside and outside: Immediately after spraying, drain tank completely. Any contamination on the outside of the spraying equipment should be removed by washing with clean water. Rinse inside of tank with clean water and flush through booms and hoses using at least one tenth of the spray tank volume. Drain tank completely. Half fill tank with clean water and add a Cleaning Agent (e.g. All Clear Extra) at the recommended rate. Agitate and then briefly flush the boom and hoses with the cleaning solution. Top up with water making sure the tank is completely full and allow to stand for 15 minutes with agitation. Flush the boom and hoses and drain tank completely. Nozzles and filters should be removed and cleaned separately with Cleaning Agent solution. Rinse the tank with clean water and flush through the boom and hoses using al east one tenth of the spray tank volume. Drain tank completely. For disposal of washings, follow Code of Practice for the Safe Use of Pesticides on Farms and holdings. Do not spray onto sensitive crop or land intended for cropping with sensitive crop. Note: If it is not possible to drain the tank completely, step 3 must be repeated before going onto step 4. No specific protective clothing is recommended for cleaning application equipment. IIIA Effectiveness of the cleaning procedures Water is recommended in Europe for clopyralid containing formulations. Cleaning agents like All Clear Extra have proven in field trials to be efficacious for cleaning out florasulam containing formulations. For GF-2463, containing both clopyralid and florasulam, cleaning agents like All Clear Extra are efficacious for cleaning of the tank. Beside this more general description no study has been submitted by the applicant. IIIA 4.3 IIIA Re-entry Periods to Protect Man, Livestock and the Environment Pre-harvest interval (in days) for each relevant crop Due to application early in the growing season (BBCH 13-32), no specific pre-harvest interval (PHI) needs to be set ( F ). It is covered by the time elapsing between treatment and commercial harvest. IIIA Not relevant. Re-entry period (in days) for livestock, to areas to be grazed IIIA Re-entry period (in hours or days) for man to crops, buildings or spaces treated Evaluator: BVL / DE Date: June 2013

61 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 24 of 32 The following safety instruction applies: Treated areas/crops may not be entered until the spray coating has dried (BVL code SF245-01). IIIA Withholding period (in days) for animal feeding stuffs Please refer to - Part B Section 4, IIIA IIIA Waiting period (in days) between application and handling of treated products Please refer to - Part B Section 4. IIIA Not relevant. IIIA 4.4 Waiting period (in days) between last application and sowing or planting succeeding crops Statement of the Risks Arising and the Recommended Methods and Precautions and Handling Procedures to Minimise Those Risks The safety data sheet complies with actual EEC regulations and is based on the present state of knowledge. IIIA Warehouse storage Refer to safety data sheet of GF IIIA User level storage Refer to safety data sheet of GF IIIA Transport Refer to safety data sheet of GF IIIA Fire Refer to safety data sheet of GF IIIA Nature of protective clothing proposed Refer to safety data sheet of GF IIIA Characteristics of protective clothing proposed Refer to safety data sheet of GF Evaluator: BVL / DE Date: June 2013

62 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 25 of 32 IIIA Suitability and effectiveness of protective clothing and equipment Refer to safety data sheet of GF IIIA Procedures to minimise the generation of waste Refer to safety data sheet of GF IIIA Combustion products likely to be generated in the event of fire Refer to safety data sheet of GF IIIA 4.5 Detailed Procedures for Use in the Event of an Accident During Transport, Storage or Use IIIA Containment of spillages Refer to safety data sheet of GF IIIA Decontamination of areas, vehicles and buildings Refer to safety data sheet of GF IIIA Disposal of damaged packaging, adsorbents and other materials Refer to safety data sheet of GF IIIA Protection of emergency workers and bystanders Refer to safety data sheet of GF IIIA First aid measures Refer to safety data sheet of GF IIIA 4.6 Neutralisation Procedure for Use in the Event of Accidental Spillage GF-2463 does not require specific neutralisation. Any spilt material should be absorbed onto dry, inert material (e.g. sand) and swept up into labelled containers for disposal IIIA Details of proposed procedures for small quantities Not applicable, no neutralization procedures are proposed. Evaluator: BVL / DE Date: June 2013

63 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 26 of 32 IIIA Evaluation of products of neutralization (small quantities) Not applicable, no neutralization procedures are proposed. IIIA Procedures for disposal of small quantities of neutralized waste Not applicable, no neutralization procedures are proposed. IIIA Details of proposed procedures for large quantities Not applicable, no neutralization procedures are proposed. IIIA Evaluation of products of neutralization (large quantities) Not applicable, no neutralization procedures are proposed. IIIA Procedures for disposal of large quantities of neutralized waste Not applicable, no neutralization procedures are proposed. IIIA 4.7 Pyrolytic Behaviour of the Active Substance As the halogen content of GF2463 is less than 60 %, there is no need for a pyrolysis study. IIIA 4.8 Disposal Procedures for the Plant Protection Product IIIA Detailed instructions for safe disposal of product and its packaging If destruction is necessary then incineration is recommended, however contact with the supplier should be made to evaluate the return of excess material before destruction is undertaken. Incineration (minimum 1220 C for 2 seconds) must take place in a facility approved to handle chemical waste. As the halogen content is < 60 % there is no need for a pyrolysis study. Container and washings must be disposed of safely and in accordance with applicable regulations. The preferred options are to send to a licensed reclaimer or to permitted incinerators. Do not re-use the container for any purpose. No other data is available to assess the safety and effectiveness of these procedures. IIIA Methods other than controlled incineration for disposal No additional disposal methods are recommended. IIIA 4.9 Other/Special Studies No additional studies were performed. Evaluator: BVL / DE Date: June 2013

64 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 27 of 32 IIIA 11 FURTHER INFORMATION IIIA 11.1 Information of Authorisations in Other Countries For details please refer to Section 7: Efficacy Data and Information. IIIA 11.2 Information on Established Maximum Residue Limits (MRL) in Other Countries MRLs set at European Level are stated in the Regulation (EC) No 396/2005 (see: EU Pesticides database, as published on June 8, 2010, Internet: index.cfm). IIIA 11.3 Justified Proposals for Classification and Labelling Proposals for classification and labelling of GF-2463 in accordance with the EC Directive on dangerous preparations 1999/45/EC and Directive 2001/59/EC (as amended) are presented below: Physico - chemical properties Table Physico-chemical properties Study Type Findings Reference (triggered risk phrase) Explosivity Not explosive (-). Oxidizing Not oxidizing (-) properties Flammability Not flammable (flash point > 100 C). Toxicology Table Toxicology Study Type Results Reference (triggered risk phrase) Acute oral LD 50 = >2000 mg/kg bw/day, rat Dalal, V., 2010 (OECD 423) Acute dermal LD 50 = >2000 mg/kg bw/day, rat (OECD 402) Dalal, V., 2010 Acute inhalation Not submitted, not necessary (vapour pressure of active substances: clopyralid 1.36 x 10-3 Pa, 25 C; florasulam 1 x 10-5 Pa, 25 C (below 10-2 Pa); no respirable droplets, not confirmed Skin irritation Non-irritatant, rabbit (OECD 404) Dalal, V., 2010 Eye irritation Non-irritant (OECD 405) Dalal, V., 2010 Skin sensitisation Non-sensitising (OECD 429, LLNA) Tiwari, V. K., 2011 Ecotoxicology/Environment Evaluator: BVL / DE Date: June 2013

65 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 28 of 32 Table Study Type (duration) Lemna gibba (7 d, semistatic) Biodegradation Ecotoxicology/Environment Results Reference (triggered risk phrase) E r C 50 = 0,036 mg/l (R 50) Porch, J. et al., 2011 The product contains the active substances clopyralid and florasulam, which are not readily biodegradable (R 53) Jenkins, W.R. 1991; Jenkins, W.R. 1994; IIIA 11.4 Proposals for Risk and Safety Phrases Table Hazard symbol(s) Classification proposed N Indications of danger Dangerous for the environment Risk phrases R 50/53 Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment Safety phrases S 35 This material and its container must be disposed of in a safe way. S 57 Use appropriate container to avoid environmental contamination Labelling texts and restrictions To avoid risks to man and the environment, comply with the instructions for use. Table Labelling proposed Hazard symbol(s): N Indications of danger: Dangerous for the environment Risk phrases: R 50/53 Safety phrases: S IIIA 11.5 Proposed Label Please refer to Part A. IIIA 11.6 Specimens of Proposed Packaging Specimens of the packaging were not provided as there was no request. Evaluator: BVL / DE Date: June 2013

66 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 29 of 32 Appendix 1: List of data used in support of the evaluation Annex point/ reference No KIIIA KIIIA KIIIA Author(s) Year Title Source (where different from company) Report-No. GLP or GEP status (where relevant), Published or not Authority registration No M. Rozniak 2011 Determination of color, odor, physical state, oxidizing and reducing action, flashpoint, ph, viscosity and density of GF- 2463, an End Use Product containing clopyralid and florasulam under GLP; Dow AgroSciences LLC DAS no. NAFST GLP: yes Unpublished B. Turner 2011 Determination of surface tension, explosive properties, auto-ignition temperature (liquids and gases) and oxidizing properties (liquids) for GF Dow AgroSciences LLC DAS no. NAFST GLP: Yes Unpublished P.E. Thirugnana m 2011 GF-2463: Laboratory study of accelerated storage stability at 54 C and stability at 0 C. Dow AgroSciences LLC DAS no. NAFST GLP: Yes Unpublished Data protection claimed Owner Y DAS 1 Y DAS 1 Y DAS 1 How considered in drr Study-Status / Usage * * 1 accepted (study valid and considered for evaluation) 2 not accepted (study not valid and not considered for evaluation) 3 not considered (study not relevant for evaluation) 4 not submitted but necessary (study not submitted by applicant but necessary for evaluation) 5 supplemental (additional information, alone not sufficient to fulfil a data requirement, considered for evaluation) Evaluator: BVL / DE Date: June 2013

67 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 30 of 32 Appendix 2: Critical Uses justification and GAP tables PPP (product name/code) GF-2463 active substance 1 florasulam active substance 2 clopyralid Applicant: Dow AgroSciences Zone(s): Central Zone Verified by MS: yes Formulation type: Conc. of as 1: Conc. of as 2: professional use non professional use GAP rev. (1), date: SC 25 g/l 300 g/l Member Crop and/ Pests or Group of Application Application rate PHI Remarks: state(s) or situation pests controlled (days) Use- No. (crop destination / purpose of crop) 001 Germany TRZAW Winter soft wheat, HORVW Winter barley, SECCW Winter rye, TRZSP Spelt, TTLWI Winter triticale 002 Germany TRZAS Spring soft wheat, F G or I F F (additionally: developmental stages of the pest or pest group) TTTDS Annual dicotyledonous weeds TTTDS Annual Method / Kind Timing / Growth stage of crop & season spraying BBCH 13-32; After emergence, spring, after emergence of weeds spraying BBCH 13-30; After Max. number (min. interval between applications) a) per use b) per crop/ season L product / ha a) max. rate per appl. b) max. total rate per crop/season kg as/ha a) max. rate per appl. b) max. total rate per crop/season 1; 1 0.2; 0.2 florasulam 0.005; clopyralid 0.06; ; 1 0.2; 0.2 florasulam 0.005; Water L/ha min / max e.g. safener/synergist per ha e.g. recommended or mandatory tank mixtures F WH9161; WP F WH9161; WP711 Evaluator: BVL / DE Date: June 2013

68 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 31 of 32 TRZDS Spring durum wheat, HORVS Spring barley, AVESS Oats dicotyledonous weeds emergence, spring, after emergence of weeds clopyralid 0.06; 0.06 Evaluator: BVL / DE Date: June 2013

69 Part B Section 1 Core Assessment Germany GF-2463 Central Zone Page 32 of 32 Appendix 3: Experimental testing of the product's physico-chemical and technical characteristics: The following physical, chemical and technical properties of the plant protection product were experimentally tested: density, colour, ph, surface tension, storage stability at high temperatures (14 d at 54 C) and low temperature stability (7 d at 0 C), persistent foaming, suspensibility, particle size distribution (laser diffraction) and pourability incl. rinsed residue. No significant deviations from the data submitted by the applicant were detected. The formulation complies with the chemical, physical and technical criteria which are stated for this type of formulation in the FAO/WHO manual (2010). Evaluator: BVL / DE Date: June 2013

70 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 1 of 40 REGISTRATION REPORT Part B Section 2 Analytical Methods Detailed summary of the risk assessment Product code: GF-2463 Active Substance: Clopyralid 300 g/l Florasulam 25 g/l Central Zone Rapporteur Member State: Germany CORE ASSESSMENT Submission Date: September 2011 Evaluator: BVL, BfR / DE Date: June 2013

71 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 2 of 40 Table of Contents IIIA 5 METHODS OF ANALYSIS...3 IIIA 5.1 Analytical Standards and Samples...3 IIIA Samples of the preparation...3 IIIA Analytical standards for the pure active substance...3 IIIA IIIA IIIA IIIA 5.2 IIIA IIIA Samples of the active substance as manufactured...3 Analytical standards for relevant metabolites and all other components included in the residue definition...3 Samples of reference substances for relevant impurities...3 Methods for the Analysis of the Plant Protection Product...3 Description of the analytical methods for the determination of the active substance in the plant protection product...4 For preparations containing more than one active substance, description of method for determining each in the presence of the other...4 IIIA Applicability of existing CIPAC methods...6 IIIA Description of analytical methods for the determination of relevant impurities...6 IIIA Description of analytical methods for the determination of formulants...6 IIIA 5.3 Description of Analytical Methods for the Determination of Residues...7 IIIA Evaluation of Clopyralid...7 IIIA Evaluation of florasulam...13 IIIA 5.4 Conclusion on the availability of analytical methods for the determination of residues...18 Appendix 1 List of data submitted in support of the evaluation...19 Appendix 2 Detailed evaluation of the additional studies relied upon...25 A 1.1 Analytical methods for clopyralid...25 A 1.2 Analytical methods for the active substance B: florasulam...33 Evaluator: BVL, BfR / DE Date: June 2013

72 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 3 of 40 IIIA 5 METHODS OF ANALYSIS This document summarises the information related to the analytical methods for the product GF-2463 with the active substances clopyralid and florasulam which were approved according to Regulation (EC) No 1107/2009. This product was not the representative formulation. The product has not been previously evaluated according to Uniform Principles. Where appropriate this document refers to the conclusions of the EU review of clopyralid and florasulam. This will be where: the active substance data are relied upon in the risk assessment of the formulation; or when the EU review concluded that additional data/information should be considered at national re-registration. This Part B document only reviews data and additional information that has not previously been considered within the EU review process, as part of the Annex I inclusion decision. The Annex I Inclusion Directive for clopyralid and florasulam provides specific provisions under Part B which need to be considered by the applicant in the preparation of their submission and by the MS prior to granting an authorisation. Appendix 1 of this document contains the list of references included in this document for support of the evaluation. Information on the detailed composition of GF-2463 can be found in the confidential dossier of this submission ( - Part C). IIIA 5.1 Analytical Standards and Samples IIIA Samples of the preparation A sample of the preparation was provided by the applicant. IIIA Analytical standards for the pure active substance Analytical standards of clopyralid and florasulam were not provided because there was no request. IIIA Samples of the active substance as manufactured No samples were provided because there was no request. IIIA Analytical standards for relevant metabolites and all other components included in the residue definition No samples were provided because there was no request. IIIA Samples of reference substances for relevant impurities There are no relevant impurities in clopyralid or florasulam as manufactured. IIIA 5.2 Methods for the Analysis of the Plant Protection Product Evaluator: BVL, BfR / DE Date: June 2013

73 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 4 of 40 Analytical methods for the determination of clopyralid and florasulam and their impurities and relevance of CIPAC methods were not evaluated as part in the EU review. IIIA Description of the analytical methods for the determination of the active substance in the plant protection product Please refer to chapter as GF-2463 contains two active substances. IIIA For preparations containing more than one active substance, description of method for determining each in the presence of the other The following analytical method for the determination of the active substances in the plant protection product GF-2463 has not previously been reviewed. Report: 5.2.2/01, Cathie, 2011 Title: Extension to Analytical Method DAS-AM for the Determination of Florasulam and Clopyralid in GF-2463 Document No: DAS-AM-G Guidelines: EPA OPPTS & EEC Guidelines SANCO/3030/99 rev. 4 GLP Yes Method description The active substances are determined by HPLC on a reverse phase ZORBAX SB-phenyl column (250 x 4.6 mm, dp = 5 µm) at ambient temperature, using internal calibration. Injection volume is 10 µl. The separation is achieved by using gradient flow (acetonitrile / water) for the detection and quantification of the actives (1.5 ml/min). Detection is performed with a DAD UV detector at 260 nm. Method validation It was with respect to precision, accuracy, linearity and specificity proved that the method is suitable for the determination of clopyralid and florasulam in the SC-formulation GF The method is sufficiently validated according to SANCO/3030/99 rev. 4. It must be noted that technical clopyralid from one out of three suppliers showed a peak at the retention time of florasulam equivalent to 3 % of the peak area in the calibration solution. So according to the applicant the method is not suitable for analysis of GF-2463 prepared with technical clopyralid manufactured at this supplier without first screening the technical to ensure the absence of interfering peaks. Evaluator: BVL, BfR / DE Date: June 2013

74 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 5 of 40 Table containing the methods and validation of the methods (formulation GF-2463) Analyte Linearity n = 8 (clopyralid) n = 5 (florasulam) Accuracy n = 7 Mean [%] Repeatability n = 10 [% RSD] Specificity/Inteferences clopyralid florasulam mg/l % r 2 = (this result was obtained during validation of method DAS-AM ; the required range is identical) mg/l % r 2 = % ( %) % ( %) 0.2 % (RSDr = 1.6 %) 0.2 % (RSDr = 2.4 %) Method used for the analysis of suspensibility / spontaneity of dispersion: No interferences were detected between solvent blank, formulation blank, internal standard and technical active substances. Chromatograms of formulation with and without active substances were submitted. No interferences were noted. Chromatograms of formulation with and without active substances were submitted. Report: 5.2.2/01, Thirugnanam, 2011 Title: Validation of the Analytical Method for the Determination of Active Ingredient in GF-2463 Suspensibility and Spontaneity samples Document No: NAFST Guidelines: EPA OPPTS & EEC Guidelines SANCO/3030/99 rev. 4 GLP Yes Method description The method is identical to the method DAS-AM-G described above. Method validation The method is applicable to the assay of florasulam and clopyralid in GF-2463 formulation at 0.2 % v/v (low use rate) and 1.0 % v/v (high use rate) for suspensibility and 5 % v/v for spontaneity rate. Based on a signal to noise ratio > 10:1 a LOQ of 2 mg/l for clopyralid and of 1 mg/l for florasulam was determined. Evaluator: BVL, BfR / DE Date: June 2013

75 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 6 of 40 Table containing the methods and validation of the methods (formulation GF-2463) Analyte Linearity n = 5 Specificity/Inteferences clopyralid florasulam mg/l r 2 = mg/l r 2 = mg/l r 2 = mg/l r 2 = Accuracy n = 5 Mean [%] % (LOQ level fortification) 98.2 % (at 0.2 % v/v) 99.6 % (at 1 % v/v) 100.6% (LOQ level fortification) % (at 0.2 % v/v) % (at 1 % v/v) Repeatability n = 10 [% RSD] 0.74 % (LOQ level fortification) 0.03 % (at 0.2 % v/v) 0.92 % (at 1 % v/v) 1.63 % (LOQ level fortification) 0.44 % (at 0.2 % v/v) 0.65 % (at 1 % v/v) no interference no interference Summary The active substances of GF-2463 can be quantified using the analytical HPLC method DAS-AM-G IIIA Applicability of existing CIPAC methods There are no CIPAC method available for the determination of clopyralid or florasulam in formulations. IIIA Description of analytical methods for the determination of relevant impurities There are no relevant impurities in the formulation GF Therefore, no analytical method is required. IIIA Description of analytical methods for the determination of formulants No formulants with toxicological or ecotoxicological relevant compounds are present in the formulation. Therefore, no analytical methods for the determination of formulants are necessary. Evaluator: BVL, BfR / DE Date: June 2013

76 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 7 of 40 IIIA 5.3 IIIA Description of Analytical Methods for the Determination of Residues Evaluation of Clopyralid The conclusion regarding the peer review of the analytical methods for residues of clopyralid are summarized in SANCO/10012/2006 (ASB ) and in EFSA Scientific Report (2005) 50, 1-65 (ASB ). Table IIIA 5.3-1: Information on the active substance clopyralid Name of component of residue definiton substance code IUPAC name formula clopyralid 3,6-Dichloropyridine-2-carboxylic acid C 6 H 3 Cl 2 NO 2 Structural formula Cl Cl N COOH IIIA Overview of residue definitions and levels for which compliance is required Compared to the residue definition proposed in the Draft Assessment Report (incl. its addenda, ASB ) the current legal residue definition is different. Table IIIA 5.3-2: Relevant residue definitions Matrix Relevant residue definition Reference Remarks plant material Clopyralid Regulation (EU) No 322/2012, annex III part A clopyralid, its salts and conjugates, expressed as clopyralid EFSA Scientific Report (2005) 50, 1-65 foodstuff of animal origin Clopyralid Regulation (EU) No 322/2012, annex III part A clopyralid, its salts and conjugates, expressed as clopyralid EFSA Scientific Report (2005) 50, 1-65 soil ecotoxicology clopyralid and its salts EFSA Scientific Report (2005) 50, 1-65 water ecotoxicology clopyralid and its salts EFSA Scientific Report (2005) 50, 1-65 human toxicology clopyralid and its salts EFSA Scientific Report (2005) 50, 1-65 air clopyralid and its salts EFSA Scientific Report (2005) 50, 1-65 body fluids/tissue not required not classified as T / T+ Evaluator: BVL, BfR / DE Date: June 2013

77 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 8 of 40 Table IIIA 5.3-3: Levels for which compliance is required Matrix MRL Reference for MRL/level Remarks Plant, high water content 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A Plant, acidic commodities 0.5 mg/kg Regulation (EU) No 322/2012, annex III part A Plant, dry commodities 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A Plant, high oil content 0.5 mg/kg Regulation (EU) No 322/2012, annex III part A Plant, difficult matrices (spices, tea) 0.5 mg/kg Regulation (EU) No 322/2012, annex III part A meat 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A milk 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A eggs 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A fat 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A liver, kidney 0.05 mg/kg Regulation (EU) No 322/2012, annex III part A soil 0.05 mg/kg common limit drinking water 0.1 µg/l general limit for drinking water surface water µg/l NOEC Pimephales promelas, EFSA Scientific Report (2005) 50, 1-65 air 300 µg/m 3 AOEL sys.: 1.0 mg/kg bw/d tissue (meat or liver) not required not classified as T / T+ body fluids not required not classified as T / T+ IIIA Description of Analytical Methods for the Determination of Residues of clopyralid in Plant Matrices (OECD KIII A 5.3.1) An overview of the acceptable methods and possible data gaps for analysis of clopyralid in plant matrices is given in the following tables. For the detailed evaluation of additional studies refer to Appendix 2. Evaluator: BVL, BfR / DE Date: June 2013

78 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 9 of 40 Table IIIA 5.3-4: Overview of independently validated methods and confirmatory methods for food and feed of plant origin (always required for first 4 matrix types) Matrix type Primary method ILV Confirmatory method high water content Hastings, 2002a * Rawle, 2002 * Wood, 1994 * acidic Hastings, 2002a * not necessary not necessary ** fatty Hastings, 2002a * not necessary Hastings, 2003 * dry Hastings, 2002a * Rawle, 2002 * Clements, Harrington, 1997 difficult not required for the intended GAP not required for the intended GAP *EU agreed method (see Draft Assessment Report) ** Confirmatory method for high water content commodities uses alkaline extraction. not required for the intended GAP Table IIIA 5.3-5: Statement on extraction efficiency Method for products of plant origin Required, available from: DAR, vol. 3, chapter B & B.7.1.2, Chapelo, Caley, 2002a; Chapelo, Caley, 2002b Table IIIA 5.3-6: Author(s), year Hastings, 2002a MET Rawle, 2002 MET Wood, 1994 MET Hastings, 2003 MET Clements, Harrington, 1997 MET Methods suitable for the determination of residues (enforcement) in products of plant origin Matrix group high water content, acidic, dry, fatty high water content, dry high water content high water content, fatty Method LOQ Principle of method 0.01 mg/kg GC-MS with NCI, HP-5MS, m/z 233, 235 (as propyl ester) 0.01 mg/kg GC-MS with NCI, HP-5MS, m/z 233, 235 (as propyl ester) Comment no confirmation no confirmation, ILV of Hastings, 2002a Evaluated in section B of DAR section B of DAR 0.01 mg/kg GC-ECD, DB-5 no confirmation section B of DAR 0.01 mg/kg GC-MS with NCI, DB-5, m/z 205, 207 (as methyl ester) dry 0.05 mg/kg GC-MS, Ultra-2, m/z 310 (as butyl ester) no confirmation no confirmation section B of Addendum 1 additional study, see appendix 2 IIIA Description of Analytical Methods for the Determination of Residues of clopyralid in Animal Matrices (OECD KIII A 5.3.1) An overview of the acceptable methods and possible data gaps for analysis of clopyralid in animal matrices is given in the following tables. For the detailed evaluation of additional studies refer to Appendix 2. Evaluator: BVL, BfR / DE Date: June 2013

79 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 10 of 40 Table IIIA 5.3-7: Overview of independently validated methods and confirmatory methods for food and feed of animal origin (if appropriate) Matrix type Primary method ILV Confirmatory method milk Shaffer, 2012 Gemrot, 2012 Shaffer, 2012 eggs Shaffer, 2012 Gemrot, 2012 Shaffer, 2012 meat Shaffer, 2012 Gemrot, 2012 Shaffer, 2012 fat Shaffer, 2012 Gemrot, 2012 Shaffer, 2012 kidney, liver Shaffer, 2012 Gemrot, 2012 Shaffer, 2012 Table IIIA 5.3-8: Statement on extraction efficiency Required, available from: Method for products of animal origin DAR, vol. 3, chapter B7.2.1; Bauriedel, 1983 (RIP ) In the study of Bauriedel, 1983 the suitability of the extraction procedure of the proposed monitoring method for animal matrices is proven. It is shown that extraction procedure using alkaline hydrolysis is suitable for clopyralid. Table IIIA 5.3-9: Methods suitable for the determination of residues (enforcement) in products of animal origin Author(s), year Matrix Method LOQ Principle of method Shaffer, 2012 ASB Gemrot, 2012 ASB milk, eggs, meat, fat, liver, kidney milk, eggs, meat, liver 0.01 mg/kg LC-MS/MS, phenyl-hexyl, ESI-, m/z , mg/kg LC-MS/MS, phenyl-hexyl, ESI-, m/z , Comment confirmation included confirmation included, ILV of Shaffer, 2012 Evaluated in additional study, see appendix 2 additional study, see appendix 2 IIIA Description of Methods for the Analysis of clopyralid in Soil (OECD KIII A 5.4) An overview of the acceptable methods and possible data gaps for analysis of clopyralid in soil is given in the following tables. New studies have not been provided. Table IIIA : Overview of suitable primary and confirmatory methods for soil Component(s) of residue definition Primary method Confirmatory method clopyralid and its salts Hastings, Schauermann, 2001a Butler et al., 2000 Evaluator: BVL, BfR / DE Date: June 2013

80 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 11 of 40 Table IIIA : Methods for soil Author(s), year Method LOQ Principle of method Comment Evaluated in Hastings, Schauermann, 2001a MET Butler et al., 2000 MET mg/kg GC-MS with NCI, HP-5MS, m/z 233, 235 (as propyl ester) mg/kg GC-MS, Ultra-2, m/z 174 no confirmation section B of DAR no confirmation section B of DAR IIIA Description of Methods for the Analysis of clopyralid in Water (OECD KIII A 5.6) An overview of the acceptable methods and possible data gaps for analysis of clopyralid in surface and drinking water is given in the following table. For the detailed evaluation of additional studies refer to Appendix 2. Table IIIA : Overview of suitable primary and confirmatory methods for water Component(s) of residue definition clopyralid and its salts Matrix Primary method Confirmatory method drinking water, surface water Hastings, Schauermann, 2001b Clements, Wicks, 1996 Table IIIA : Methods for drinking water and surface water Author(s), year Method LOQ Principle of method Comment Evaluated in Hastings, Schauermann, 2001b MET Clements, Wicks, 1996 MET µg/l (drinking water) 5 µg/l (surface water) 0.05 µg/l (drinking water) 5 µg/l (surface water) GC-MS with NCI, HP-5MS, m/z 233, 235 (as propyl ester) GC-ECD, HP-5 no confirmation section B of DAR no confirmation additional study, see appendix 2 IIIA Description of Methods for the Analysis of clopyralid in Air (OECD KIII A 5.7) An overview of the acceptable methods and possible data gaps for analysis of clopyralid in air is given in the following table. New studies have not been provided. Table IIIA : Overview of suitable primary and confirmatory methods for air Component(s) of residue definition Primary method Confirmatory method clopyralid and its salts Devine, Rawle, 2002 not required Table IIIA : Methods for air Author(s), year Method LOQ Principle of method Comment Evaluated in Devine, Rawle, 2002 MET µg/m 3 GC-MS, HP-5MS, m/z 174 (as propyl ester) no confirmation section B of DAR Evaluator: BVL, BfR / DE Date: June 2013

81 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 12 of 40 IIIA Description of Methods for the Analysis of clopyralid in Body Fluids and Tissues (OECD KIII A 5.8) Methods for body fluids and tissues are not required, because clopyralid is not considered to be toxic or very toxic (T / T+) nor is it classified according to GHS as follows: Acute toxicity (cat. 1-3), CMR (cat. 1) or STOT (cat. 1). IIIA none Other Studies/ Information Evaluator: BVL, BfR / DE Date: June 2013

82 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 13 of 40 IIIA Evaluation of florasulam The conclusion regarding the peer review of the analytical methods for residues of florasulam are summarized in SANCO/1406/2001 (ASB ). Table IIIA : Information on the active substance florasulam Name of component of residue definiton substance code IUPAC name formula Structural formula florasulam XDE-570, XR-570, DE-570 2,6,8-Trifluor-5-methoxy-[1,2,4]-triazolo[1,5- c]pyrimidin-2-sulfonanilid C 12 H 8 F 3 N 5 O 3 S F F NH O S O N N N OMe F N 5-OH florasulam N-(2,6, 8-Trifluor-5-hydroxy-(1,2,4)-triazolo- [1,5c]-pyrimidin-2-sulfonamide C 11 H 6 F 3 N 5 O 3 S F F NH O S O N N N OH F N IIIA Overview of residue definitions and levels for which compliance is required Compared to the residue definition proposed in the Draft Assessment Report (incl. its addenda, ASB ) the current legal residue definition is the same except for foodstuff of animal origin. While in the DAR a residue definition of florasulam was proposed, the conclusive evaluation showed that a residue definition for foodstuff of animal origin is not necessary because residues in feeding stuff are not expected. Table IIIA : Relevant residue definitions Matrix Relevant residue definition Reference Remarks plant material florasulam Regulation (EC) No 149/2008, annex II, annex III part B foodstuff of animal origin not defined Regulation (EC) No 149/2008, annex II, annex III part B soil ecotoxicology florasulam, 5-OH florasulam DAR, Vol. 1, section water ecotoxicology florasulam, 5-OH florasulam DAR, Vol. 1, section human toxicology florasulam minimal requirement for drinking water air florasulam generally defined body fluids/tissue not required not classified as T / T+ Evaluator: BVL, BfR / DE Date: June 2013

83 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 14 of 40 Table IIIA : Levels for which compliance is required Matrix MRL Reference for MRL/level Remarks Plant, high water content 0.01 mg/kg Regulation (EC) No 149/2008, annex II, annex III part B Plant, acidic commodities 0.01 mg/kg Regulation (EC) No 149/2008, annex II, annex III part B Plant, dry commodities 0.01 mg/kg Regulation (EC) No 149/2008, annex II, annex III part B Plant, high oil content 0.01 mg/kg Regulation (EC) No 149/2008, annex II, annex III part B Plant, difficult matrices (hops, spices, tea) 0.1 mg/kg Regulation (EC) No 149/2008, annex II, annex III part B foodstuff of animal origin MRLs do not exist Regulation (EC) No 149/2008, annex II, annex III part B soil 0.05 mg/kg common limit drinking water 0.1 µg/l general limit for drinking water surface water 1.2 µg/l (florasulam) µg/l (5-OH florasulam) EC 50 Lemna gibba, EC 50 Pseudokirchneriella subcapitata; DAR, Vol. 1, List of end points air 15 µg/m 3 AOEL sys: 0.05 mg/kg bw/d tissue (meat or liver) not required not classified as T / T+ body fluids not required not classified as T / T+ IIIA Description of Analytical Methods for the Determination of Residues of florasulam in Plant Matrices (OECD KIII A 5.3.1) An overview of the acceptable methods and possible data gaps for analysis of florasulam in plant matrices is given in the following tables. For the detailed evaluation of additional studies refer to Appendix 2. Table IIIA : Overview of independently validated methods and confirmatory methods for food and feed of plant origin (always required for first 4 matrix types) Matrix type Primary method ILV Confirmatory method high water content Shackelford, 2004 Class, 2005 Class, 2005 acidic Shackelford, 2004 not necessary not required ** fatty Shackelford, 2004 not necessary Rodrigues, 2011 dry Butcher et al., 1996 * Shackelford, 2004 difficult not required for the intended GAP Butcher, 1996 * Class, 2005 not required for the intended GAP *EU agreed method (see Draft Assessment Report) ** Confirmatory method for high water content commodities uses acidic extraction. Class, 2005 not required for the intended GAP Evaluator: BVL, BfR / DE Date: June 2013

84 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 15 of 40 Table IIIA : Statement on extraction efficiency Required, available from: Not required, because: not necessary Method for products of plant origin no residues above 0.01 mg/kg expected in plant materials Table IIIA : Methods suitable for the determination of residues (enforcement) in products of plant origin Author(s), year Butcher et al., 1996 MET Butcher, 1996 MET Shackelford, 2004 ASB Class, 2005 ASB Rodrigues, 2011 ASB Matrix group Method LOQ Principle of method dry 0.01 mg/kg HPLC-UV, C18, 260 nm (methyl derivative) dry 0.01 mg/kg HPLC-UV, C18, 260 nm (methyl derivative) high water content, acidic, dry, fatty high water content, dry high water content, acidic, dry, fatty 0.01 mg/kg LC-MS/MS, C8, ESI+, m/z mg/kg LC-MS/MS, C8, ESI+, m/z mg/kg LC-MS/MS, C8, ESI+, m/z , m/z Comment no confirmation no confirmation, ILV of Butcher et al., 1996 no confirmation confirmation by ESI-, m/z included, ILV of Shackelford, 2004 confirmation by ion ratio included Evaluated in section B of DAR section B of DAR additional study, see appendix 2 additional study, see appendix 2 Additional study, see appendix 2 IIIA Description of Analytical Methods for the Determination of Residues of florsulam in Animal Matrices (OECD KIII A 5.3.1) An overview of the acceptable methods and possible data gaps for analysis of florasulam in animal matrices is given in the following tables. New studies have not been provided. Table IIIA : Overview of independently validated methods and confirmatory methods for food and feed of animal origin (if appropriate) Matrix type Primary method ILV Confirmatory method milk not necessary not necessary not necessary eggs not necessary not necessary not necessary meat not necessary not necessary not necessary fat not necessary not necessary not necessary kidney, liver not necessary not necessary not necessary Evaluator: BVL, BfR / DE Date: June 2013

85 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 16 of 40 Table IIIA : Statement on extraction efficiency Required, available from: Not required, because: not required no MRLs Method for products of animal origin Table IIIA : Methods suitable for the determination of residues (enforcement) in products of animal origin Author(s), year Matrix Method LOQ Principle of method Comment no methods submitted and not required because no MRLs are set Evaluated in IIIA Description of Methods for the Analysis of florasulam in Soil (OECD KIII A 5.4) An overview of the acceptable methods and possible data gaps for analysis of florasulam in soil is given in the following tables. New studies have not been provided. Table IIIA : Overview of suitable primary and confirmatory methods for soil Component(s) of residue definition Primary method Confirmatory method florasulam Butcher et al., 1997 Butcher et al., OH florasulam Butcher et al., 1997 Butcher et al., 1996 Table IIIA : Methods for soil Author(s), year Method LOQ Principle of method Comment Evaluated in Butcher et al., 1997 MET Butcher et al., 1996 MET mg/kg LC-MS/MS, C18, ESI+, m/z (florasulam), (5-OH florasulam) mg/kg LC-MS, C8, ESI-, m/z 358 (florasulam), 344 (5-OH florasulam) no confirmation section B of DAR no confirmation section B of DAR IIIA Description of Methods for the Analysis of florasulam in Water (OECD KIII A 5.6) An overview of the acceptable methods and possible data gaps for analysis of florasulam in surface and drinking water is given in the following table. For the detailed evaluation of additional studies refer to Appendix 2. Table IIIA : Overview of suitable primary and confirmatory methods for water Component(s) of residue definition Matrix Primary method Confirmatory method florasulam drinking water Butcher, 1995 Gibson, Butcher, 1996a florasulam surface water Gibson, Butcher, 1996b Maycock et al., 1997a 5-OH florasulam surface water Gibson, Butcher, 1996b Hastings, 2008 Evaluator: BVL, BfR / DE Date: June 2013

86 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 17 of 40 Table IIIA : Methods for drinking water and surface water Author(s), year Method LOQ Principle of method Comment Evaluated in Butcher, 1995 MET Gibson, Butcher, 1996a MET Gibson, Butcher, 1996b MET Maycock et al., 1997a MET Hastings, 2008 ASB µg/l HPLC-UV, C18, 260 mn (as methyl derivative) 0.05 µg/l (florasulam) 0.1 µg/l (5-OH florasulam) 0.05 µg/l (florasulam) 0.2 µg/l (5-OH florasulam) HPLC-UV, C18, 260 mn HPLC-UV, C18, 260 mn no confirmation, only florasulam 0.1 µg/l ELISA only for confirmation, only florasulam 0.05 µg/l (per analyte) LC-MS/MS, C8, ESI-, m/z , (florasulam), , (5-OH florasulam) section B of DAR no confirmation section B of DAR no confirmation section B of DAR confirmation included section B of DAR additional study, see appendix 2 IIIA Description of Methods for the Analysis of florasulam in Air (OECD KIII A 5.7) An overview of the acceptable methods and possible data gaps for analysis of florasulam in air is given in the following table. New studies have not been provided. Table IIIA : Overview of suitable primary and confirmatory methods for air Component(s) of residue definition Primary method Confirmatory method florasulam Bolton, 1998 not required Table IIIA : Methods for air Author(s), year Method LOQ Principle of method Comment Evaluated in Bolton, 1998 MET µg/m 3 HPLC-UV, C8, 260 mn (as methyl derivative) no confirmation section B of DAR IIIA Description of Methods for the Analysis of florasulam in Body Fluids and Tissues (OECD KIII A 5.8) Methods for body fluids and tissues are not required, because florasulam is not considered to be toxic or very toxic (T / T+) nor is it classified according to GHS as follows: Acute toxicity (cat. 1-3), CMR (cat. 1) or STOT (cat. 1). IIIA none Other Studies/ Information Evaluator: BVL, BfR / DE Date: June 2013

87 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 18 of 40 IIIA 5.4 Conclusion on the availability of analytical methods for the determination of residues - Sufficient analytical methods for the determination of residues of florasulam and clopyralid are available. Evaluator: BVL, BfR / DE Date: June 2013

88 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 19 of 40 Appendix 1 List of data submitted in support of the evaluation Annex point/ reference No Author(s) Year Title Report-No. Authority registration No KIIIA /01 C.A. Cathie 2004 Validation of a method for the determination of clopyralid and florasulam in Radicape herbicide, Gf Dow AgroSciences DAS-AM GLP: Yes Unpublished KIIIA /01 C.A. Cathie 2011 Extension to Analytical method DAS- AM for the determination of florasulam and clopyralid in GF Dow AgroSciences DAS-AM-G GLP: Yes Unpublished KIIIA /01 P.E. Thirugnanam 2011 Validation of the Analytical Method for the Determination of Active Ingredient in GF-2463 Suspensibility and Spontaneity samples. Dow AgroSciences DAS No. NAFST GLP : Yes Unpublished all Anon Review report for the active substance florasulam SANCO/1406/2001-final ASB all Anon Conclusion regarding the peer review of the pesticide risk assessment of the active substance clopyralid ASB all Anon Review report for the active substance clopyralid SANCO/10012/ rev. 3 ASB all Belgium 1999 Florasulam: (Monograph) Vol. 1-3 ASB all Finland 2003 Clopyralid: (Draft Assessment Report) Vol. 1-4 ASB OECD: KIIA 4.3 Class, T Independent laboratory validation of Dow AgroSciences LLC method GRM Determination of residues of florasulam in agricultural commodities by high performance liquid chromatography with tandem mass spectrometric detection ! BVL , BVL , ASB OECD: KIIA 4.3 Clements, B.; Harrington, R Determination of residues of MCPA, Clopyralid and Fluroxypyr in grass and cereal grain and straw; ERC 97.10! O47! BVL , BVL , BVL , MET OECD: KIIA 4.3 Hastings, M. J 2003 Determination of residues of Clopyralid and Picloram in canola by gas chromatography with negative-ion chemical ionization mass spectrometry ! O45! BVL , BVL , BVL , MET Data protection claimed Owner Y DAS N Y DAS Y Y DAS Y How considered in RR * Add Add Add Add Add Add Add Add Evaluator: BVL, BfR / DE Date: June 2013

89 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 20 of 40 Annex point/ reference No Author(s) Year Title Report-No. Authority registration No OECD: KIIA 4.3 Shackelford, D. D Validation report for method grm determination of residues of florasulam in agricultural commodities by high performance liquid chromatography with tandem mass spectrometry detection ! BVL , BVL , ASB OECD: KIIA 4.5 Clements, B.; Wicks, D Determination of Clopyralid residues in drinking water ERC BVL , MET OECD: KIIA 4.5 Hastings, M. J Method validation report for the determination of residues of florasulam and its 5-OH metabolite in waters by liquid chromatography with tandem mass spectrometry detection using Dow AgroSciences method GRM ! BVL , BVL , ASB OECD: KIIA 4.3 Almond, R. H The determination of residues of Clopyralid in sugar beet molasses GHE-P-1334 BVL , MET OECD: KIIA 4.3 Butcher, S Independent validation of DowElanco analytical method ERC 95.6 for the determination of XDE-570 residues in wheat and barley GHE-P-5036 BVL , MET OECD: KIIA 4.3 Butcher, S.; Gibson, R.; Hastings, M.; Rickard, G Determination of XDE-570 residues in wheat and barley ERC 95.6 BVL , MET OECD: KIIA 4.3 Clements, B.; Class, T Clopyralid: Assessment of multi-residue enforcement method(s) for the PTRL Europe Assessment No. B 579/2 O93! B579/2! BVL , MET OECD: KIIA 4.3 Clements, B.; Rawle, N Independent laboratory validation of a method for the determination of Clopyralid residues in crops O95! GHE-P-9567! CEMR-1671! BVL , MET OECD: KIIA 4.3 Duebelbeis, D. O Residue method validation report for the determination of DE-570 (Florasulam) in cereal crop commodities: Forage and immature green; grain; hay and immature dried; and straw by capillary gas chromatography with mass selective detection GRM 98.01! GH-C 4832! RES98071 BVL , MET OECD: KIIA 4.3 Freemann, J. M. H Determination of Clopyralid residues in maize corn, cobs and forage ERC 83.9 BVL , BVL , ASB OECD: KIIA 4.3 Freeman, J. M. H.; Smith, D. W Determination of Clopyralid residues in wheat grain and straw ERC 83.23! 085! BVL , MET Data protection claimed Owner How considered in RR * Add Add Add N Y Y N Y N N N Evaluator: BVL, BfR / DE Date: June 2013

90 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 21 of 40 Annex point/ reference No Author(s) Year Title Report-No. Authority registration No OECD: KIIA 4.3 Gemrot, F Independent laboratory validation of an analytical method for the determination of Clopyralid in animal matrices ! S BVL , ASB OECD: KIIA 4.3 Hastings, M. J Determination of residues of Clopyralid in animal tissues by gas chromatography with negative-ion chemical ionization mass Spectrometry ! GRM 02.14! 0446 BVL , ASB OECD: KIIA 4.3 Hastings, M. J Determination of residues of Clopyralid on agricultural crops by gas chromatography with negative-ion chemical ionization mass spectrometry O97! GRM 01.16! ! GH-C 5439 BVL , MET OECD: KIIA 4.3 Hastings, M.; Schmidt, F Examination of the applicability of DFG method S 19 for the determination of XDE-570: analytical preliminaries GHE-P-6427! REV BVL , MET OECD: KIIA 4.3 Jones, E. M Determination of 3,6-Dichlorpicolinic acid (DOWCO 290) in rape seed, oil, cake and straw by gas chromatography ERC 75.3! BVL , MET OECD: KIIA 4.3 Jones, E. M Determination of 3,6-Dichloropicolinic acid (DOWCO 290) in wheat and barley grain and straw by gas chromatography O23! ERC 75.1! BVL , MET OECD: KIIA 4.3 Jones, E. M Determination of 3,6-Dichlorpicolinic acid (Dowco 290) in sugarbeet by gas chromatography ERC 77.4! BVL , MET OECD: KIIA 4.3 Kubitschek, C. E.; Kyle, J. A. OECD: KIIA 4.3, OECD: KIIA 4.8 OECD: KIIA 4.3, OECD: KIIA 4.8 OECD: KIIA 4.3, OECD: KIIA Determination of Clopyralid in sugar beets and sugar beet processed products by capillary gas chromatography/mass spectroscopy O102! 22053! GRM 94.04! GH-C 3308! RES93143 BVL , ASB Kuper, A. W Determination of residues of 3,6- Dichloropicolinic acid in chicken tissues and eggs by gas chromatography ACR 74.2! BVL , BVL , MET Kuper, A. W Determination of residues of 3,6- Dichloropicolinic acid in bovine tissues by gas chromatography ACR 74.9! BVL , BVL , MET Kuper, A. W Determination of residues of 3,6- Dichloropicolinic acid in chicken tissues and eggs by gas chromatography ACR 75.2! BVL , BVL , MET OECD: KIIA 4.3 Kutschinski, A. H Determination of residues of DOWCO 290 (3,6-Dichloropicolinic acid) in milk and cream by gas chromatography ACR 74.3! BVL , MET Data protection claimed Owner How considered in RR * Y N Y N N N N N N N N N Evaluator: BVL, BfR / DE Date: June 2013

91 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 22 of 40 Annex point/ reference No Author(s) Year Title Report-No. Authority registration No OECD: KIIA 4.3 Kutschinski, A. H Determination of residues of 3,6- Dichloropicolinic acid and 2,4-D in barley and wheat by gas chromatography O38! ACR79.5! BVL , MET OECD: KIIA 4.3 Reed, R. L Independent Laboratory Validation of Dow AgroSciences LLC residue analytical method GRM Determination of residues of Clopyralid in animal tissues by gas chromatography with Negative-ion chemical ionization mass spectrometry ! DN ! GRM 02.14! ! BVL , ASB OECD: KIIA 4.3 Shaffer, S Method validation study for the determination of residues of Clopyralid in bovine and poultry matrices by liquid chromatography with tandem mass spectrometry detection ! BVL , ASB OECD: KIIA 4.3 Teasdale, R Determination of Clopyralid residues in sugar beet molasses ERC 88.1! DOWN DE89A! BVL , MET OECD: KIIA 4.3 Teasdale, R. J Determination of Clopyralid residues in strawberries ERC 93.9 BVL , BVL , ASB OECD: KIIA 4.3 Teasdale, R. J Independent method validation of DowElanco analytical method ERC 83.9: Determination of Clopyralid residues in maize cobs and forage GHE-P-3110 BVL , BVL , ASB OECD: KIIA 4.3 Teasdale, R. J.; Coombe, N.; Bolton, A Independent method validation of DowElanco analytical method ERC 93.9: Determination of Clopyralid residues in strawberries GHE-P-3393 BVL , BVL , ASB OECD: KIIA 4.3 Wood, S. J Determination of residues of Clopyralid in grass O47! ERC94.8! BVL , MET OECD: KIIA 4.3 Rodriguez, A Residue method validation for the determination of Florasulam in agricultural commodities BVL , BVL , BVL , ASB OECD: KIIA 4.4 OECD: KIIA 4.4 Butcher, S.; Gibson, R.; Ghosh, D. Butcher, S.; Wright, D. R.; Bratby, B.; Abrar, M Determination of the residues of XDE- 570 and its 5-hydroxy metabolite in soil ERC BVL , MET Determination of residues of XDE-570 and 5-hydroxy XDE-570 in soil using organic extraction ERC BVL , MET Data protection claimed Owner How considered in RR * N Y Y N N N N Y Add Y Y Evaluator: BVL, BfR / DE Date: June 2013

92 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 23 of 40 Annex point/ reference No Author(s) Year Title Report-No. Authority registration No OECD: KIIA 4.4 Butler, R. E Determination of residues of Clopyralid in soil O90! ERC 98.18! BVL , MET OECD: KIIA 4.4 OECD: KIIA 4.4 OECD: KIIA 4.4 OECD: KIIA 4.4 OECD: KIIA 4.4 Gambie, A.; McLaughlin, E. Ghosh, D.; Maycock, R.; Todd, M.; Brewin, S.; Abrar, M. Ghosh, D.; Maycock, R.; Wright, D. R.; Bratby, B.; Abrar, M. Hastings, M.; Schauerman, M. Maycock, R.; Gibson, R.; Roberts, R Determination of residues of DE-570 in soil ERC BVL , MET Determination of residues of XDE-570 and 5-hydroxy XDE-570 in soil using organic extraction ERC 95.1 BVL , MET Determination of residues of XDE-570 and 5-hydroxy XDE-570 in soil using aqueous extraction ERC 95.2 BVL , MET Determination of Clopyralid and Picloram residues in soil by gas chromatography with mass selective detection GRM 00.18! 81291! O55! 092 BVL , MET Validation of analytical method ERC Determination of bioavailable residues of DE-570 in soil using a magnetic particle-based immunoassay test kit GHE-P-6355! RV BVL , MET OECD: KIIA 4.4 Maycock, R.; Roberts, R A comparison of three analytical methods (immunochemical, LC/MS-MS and bioassay) to determine the bioavailable residues of DE-570 from field derived soils GHE-P-6365! R BVL , MET OECD: KIIA 4.4 Roberts, R.; Maycock, R.; Gibson, R Determination of bioavailable residues of DE-570 in soil using a magnetic particle-based immunoassay test kit ERC BVL , MET OECD: KIIA 4.5 Butcher, S Determination of XDE-570 residues in drinking water ERC BVL , MET OECD: KIIA 4.5 Gibson, R.; Butcher, S Determination of the residues of XDE- 570 and its 5-hydroxy metabolite in drinking water ERC BVL , MET OECD: KIIA 4.5 Gibson, R.; Butcher, S Determination of the residues of XDE- 570 and its 5-hydroxy metabolite in surface water ERC BVL , MET OECD: KIIA 4.5 Hastings, M.; Schauerman, M Determination of residues of Clopyralid and Picloram in waters (drinking water, surface water and ground water) by gas chromatography with mass selective detection O91! GRM 00.17! BVL , MET Data protection claimed Owner How considered in RR * Y N N N Y Y N N Y N Y Y Evaluator: BVL, BfR / DE Date: June 2013

93 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 24 of 40 Annex point/ reference No OECD: KIIA 4.5 Author(s) Year Title Report-No. Authority registration No Maycock, R.; Gibson, R.; Roberts, R Determination of residues of XDE-570 in ground, surface and drinking water using a magnetic particle-based immunoassay test kit GHE-P-5534! RV BVL , MET OECD: KIIA 4.5 Roberts, R Independent laboratory validation of an analytical method for the determination of residues of XDE-570 in drinking water GHE-P-4781! REV BVL , MET OECD: KIIA 4.5 Roberts, R Determination of XDE-570 concentrations in drinking water using both LC/UV and immunoassay methods GHE-P-4774! R BVL , MET OECD: KIIA 4.7 Bolton, A Determination of DE-570 residues in air samples ERC BVL , MET OECD: KIIA 4.7 Devine, H. C.; Rawle, N. W Determination of Clopyralid in air by capillary gas chromatography with mass spectrometric detection O103! GRM 02.06! BVL , MET OECD: KIIA 4.7 Long, T.; Balluf, M Development and validation of a low level air monitoring method for Clopyralid GHE-P-3716! R BVL , MET OECD: KIIA 4.8 Nicholson, A.; Marshall, D.E Determination of DE-570 residues in human plasma and urine ERC BVL , MET OECD: KIIA Bauriedel, W. R The metabolic fate of 14C-3,6- Dichloropicolinic acid (DOWCO 290) fed to lactating goats GH-C 1600! BVL , RIP * Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted by applicant but necessary for evaluation Data protection claimed Owner How considered in RR * Y N N Y Y N N Y Evaluator: BVL, BfR / DE Date: June 2013

94 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 25 of 40 Appendix 2 Detailed evaluation of the additional studies relied upon A 1.1 Analytical methods for clopyralid Methods for enforcement of residues in food and feed of plant origin Analytical method 1 Reference: OECD KIIA 4.3 Report Guideline(s): Deviations: GLP: Acceptability: Determination of Residues of MCPA, Clopyralid and Fluroxypyr in Grass and Cereal Grain and Straw; Clements, B., Harrington R.; 1997; method ERC 97.10; MET not stated not applicable Yes Yes (but only for dry commodities) Materials and methods Clopyralid is extracted from grass, grain and straw by macerating with caustic methanol. Ana aliquot is acidified and the analyte is partitioned into methyl tertiary butyl ether (MTBE) then into aqueous sodium bicarbonate, which is acidified and the analyte is extracted back into MTBE. The organic phase is evaporated to dryness and the residuum treated with 4 % concentrated sulphuric acid/n-butanol to form the butyl ester of clopyralid. Following the addition of water, the clopyralid butyl ester is partitioned into hexane. The hexane extract is then analysed by GC-MS (HP-Ultra 2 column, m/z 310) using external calibration. Results and discussions Table A 1: Recovery results from method validation of grass, grain and straw using the analytical method. Standards were prepared in hexane Matrix grass grain Fortification level (mg/kg) No of samples per fortification level Mean recovery straw RSD (%) Comments Evaluator: BVL, BfR / DE Date: June 2013

95 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 26 of Table A 2: Characteristics for the analytical method used for the quantitation of clopyralid residues in grass, grain and straw clopyralid butyl ester Calibration function y = x R 2 = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) Assessment of matrix effects is presented (yes/no) no Interference >30% of LOQ in blank sample is absent (yes/no) µg/ml mg/kg (samples with higher amounts were diluted with hexane) yes yes Conclusion The method was sufficiently validated for the determination of residues of clopyralid in grass, grain and straw with an LOQ of 0.05 mg/kg (grain) respectively 0.2 mg/kg (grass, straw). The validated LOQ of grass and straw is not appropriate for monitoring of the existing MRLs in the respective commodity groups. Therefore, the method is accepted for grain (dry commodity) only. The method does not include a confirmatory technique. Comments of zrms: Acceptable for the determination of residues of clopyralid in dry commodities; used for evaluation. Methods for enforcement of residues in food and feed of animal origin Analytical method 1 Reference: OECD KIIA 4.3 Report Guideline(s): Deviations: Method validation study for the determination of residues of Clopyralid in bovine and poultry matrices by liquid chromatography with tandem mass spectrometry detection; Shaffer, S.; 2012; study ; ASB Yes (SANCO/825/00 rev. 8.1; SANCO/3029/99 rev. 4; EPA Guideline OPPTS ; PMRA Residue Chemistry Guidelines as Regulatory Directive Dir98-02) No Evaluator: BVL, BfR / DE Date: June 2013

96 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 27 of 40 GLP: Acceptability: Yes Yes Materials and methods Residues of clopyralid were extracted by heating with a 2.5 N sodium hydroxide solution at 105 C for two hours. An aliquot was acidified with hydrochloric acid and submitted to a polymeric reversed-phase SPE column. Elution was performed with dichloromethane. The eluate was evaporated to dryness and the residues were reconstituted in acetonitrile/0.1 % formic acid (10:90; v/v). After filtration through PTFE, the extract was analyzed by LC-MS/MS with negative electrospray ionization (phenyl-hexyl column, m/z , ) using external calibration. Sample concentration at 1 mg/kg level was g/ml, at all other levels sample concentration was 0.15 g/ml. Results and discussions Table A 3: Recovery results from method validation of animal matrices using the analytical method. Standards were prepared in acetonitrile/0.1 % formic acid (10:90; v/v) Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments bovine muscle m/z bovine fat m/z bovine liver m/z bovine kidney m/z milk m/z poultry muscle m/z poultry fat m/z poultry liver m/z eggs m/z bovine muscle m/z bovine fat m/z bovine liver m/z bovine kidney m/z Evaluator: BVL, BfR / DE Date: June 2013

97 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 28 of 40 milk m/z poultry muscle m/z poultry fat m/z poultry liver m/z eggs m/z Table A 4: Characteristics for the analytical method used for the quantitation of clopyralid residues in animal matrices m/z Calibration function y = 4.53e+004x r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) m/z y = 2.98e+004x r = ng/ml ng/ml mg/kg (different dilutions) yes Assessment of matrix effects is presented (yes/no) yes Interference >30% of LOQ in blank sample is absent (yes/no) yes mg/kg (different dilutions) yes yes yes Conclusion The method was sufficiently validated for the determination of residues of clopyralid in milk, eggs, meat, fat, liver and kidney with a LOQ of 0.01 mg/kg. It is also suitable for confirmatory purposes. Comments of zrms: Acceptable for the determination of residues of clopyralid in milk, eggs, meat, fat, liver and kidney. Independent laboratory validation Reference: OECD KIIA 4.3 Report Guideline(s): Independent laboratory validation of an analytical method for the determination of Clopyralid in animal matrices; Gemrot, F.; 2012; study ; ASB Yes (SANCO/825/00 rev. 8.1; SANCO/3029/99 rev. 4; EPA Guideline OPPTS ; PMRA Residue Chemistry Guidelines as Regulatory Directive Dir98-02) Evaluator: BVL, BfR / DE Date: June 2013

98 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 29 of 40 Deviations: GLP: Acceptability: No Yes Yes Materials and methods Residues of clopyralid were extracted by heating with a 2.5 N sodium hydroxide solution at 105 C for two hours. An aliquot was acidified with hydrochloric acid and submitted to a polymeric reversed-phase SPE column. Elution was performed with dichloromethane. The eluate was evaporated to dryness and the residues were reconstituted in acetonitrile/0.1 % formic acid (10:90; v/v). After filtration through PTFE, the extract was analyzed by LC-MS/MS with negative electrospray ionization (phenyl-hexyl column, m/z , ) using external calibration. Sample concentration was 0.15 g/ml. Results and discussions Table A 5: Recovery results from the independent laboratory validation of animal matrices using the analytical method. Standards were prepared in matrix Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments bovine muscle m/z milk m/z poultry liver m/z eggs m/z bovine muscle m/z milk m/z poultry liver m/z eggs m/z Table A 6: Characteristics for the analytical method used for the independent laboratory validation of clopyralid residues in muscle m/z Calibration function y = 92643x r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) m/z y = 62436x r = ng/ml ng/ml Corresponding calibration range in mass ratio mg/kg mg/kg Evaluator: BVL, BfR / DE Date: June 2013

99 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 30 of 40 units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) yes Assessment of matrix effects is presented (yes/no) yes Interference >30% of LOQ in blank sample is absent (yes/no) yes yes yes yes Table A 7: Characteristics for the analytical method used for the independent laboratory validation of clopyralid residues in milk m/z Calibration function y = 96842x r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) m/z y = 66075x r = ng/ml ng/ml mg/kg mg/kg yes Assessment of matrix effects is presented (yes/no) yes Interference >30% of LOQ in blank sample is absent (yes/no) yes yes yes yes Table A 8: Characteristics for the analytical method used for the independent laboratory validation of clopyralid residues in liver m/z Calibration function y = x 5796 r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) m/z y = 76481x r = ng/ml ng/ml mg/kg mg/kg yes Assessment of matrix effects is presented (yes/no) yes Interference >30% of LOQ in blank sample is absent (yes/no) yes yes yes yes Table A 9: Characteristics for the analytical method used for the independent laboratory validation of clopyralid residues in eggs m/z Calibration function y = x r = m/z y = 78345x r = Evaluator: BVL, BfR / DE Date: June 2013

100 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 31 of 40 Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) ng/ml ng/ml mg/kg mg/kg yes Assessment of matrix effects is presented (yes/no) yes Interference >30% of LOQ in blank sample is absent (yes/no) yes Conclusion The method was sufficiently validated for the determination of residues of clopyralid in milk, eggs, meat and liver with a LOQ of 0.01 mg/kg. It is also suitable for confirmatory purposes. The study independently validated the method of Shaffer, Comments of zrms: Acceptable as ILV of Shaffer, 2012, for the determination of residues of clopyralid in milk, eggs, meat and liver. Description of Methods for the Analysis of Soil no additional data yes yes yes Description of Methods for the Analysis of Water Analytical method 1 Reference: OECD KIIA 4.5 Report Guideline(s): Deviations: GLP: Acceptability: Determination of Clopyralid residues in drinking water; Clements, B., Wicks, D.; 1996; method ERC 95.23; MET not stated not applicable Yes Yes Materials and methods Following acidification of the drinking water, clopyralid is partitioned into methyl-tertiary-butyl ether (MTBE). The organic phase is evaporated to dryness and the residuum treated with 4 % (v/v) concentrated sulphuric acid/n-butanol to form butyl ester of clopyralid. Following the addition of water, clopyralid butyl ester is partitioned into hexane. The hexane extract is purified using a silica solid phase extraction cartridge eluting with 95/5 (v/v) hexane/diethyl ether. The eluate is diluted to volume and analysed by GC-ECD (HP-5 column) using external calibration. Evaluator: BVL, BfR / DE Date: June 2013

101 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 32 of 40 Results and discussions Table A 10: Recovery results from method validation of drinking water using the analytical method. Standards were prepared in hexane Matrix Fortification level (µg/l) No of samples per fortification level Mean recovery RSD (%) Comments drinking water Table A 11: Characteristics for the analytical method used for the quantitation of clopyralid residues in drinking water clopyralid butyl ester Calibration function y = x r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? Assessment of matrix effects is presented (yes/no) no Interference >30% of LOQ in blank sample is absent (yes/no) µg/ml µg/l (samples with higher amounts were diluted with hexane) yes yes Conclusion The method was sufficiently validated for the determination of residues of clopyralid in drinking water with an LOQ of 0.05 µg/l. It can also be accepted for surface water with an LOQ 100 times higher than that for drinking water, i.e. 5 µg/l. The method does not include a confirmatory technique. Comments of zrms: Acceptable for the determination of residues of clopyralid in drinking and surface water; used for evaluation. Description of Methods for the Analysis of Air no additional data Description of Methods for the Analysis of Body Fluids and Tissues not required Extraction efficiency of enforcement methods for foodstuff no additional data Other Studies/ Information Evaluator: BVL, BfR / DE Date: June 2013

102 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 33 of 40 none A 1.2 Analytical methods for the active substance B: florasulam Methods for enforcement of residues in food and feed of plant origin Analytical method 1 Reference: OECD KIIA 4.3 Report Guideline(s): Deviations: GLP: Acceptability: Validation report for method GRM Determination of residues of florasulam in agricultural commodities by high performance liquid chromatography with tandem mass spectrometry detection; Shackelford, D.D.; 2004; method GRM 04.13; study ; ASB Yes (OPPTS , SANCO/825/00 rev. 7, PMRA Dir98-02) No Yes Yes Materials and methods Residues of florasulam are extracted by homogenizing and shaking with acetone/water/acetic acid (80:19:1; v/v/v). An aliquot of the extract is diluted with HPLC grade water and is applied to a polymeric sorbent solid phase extraction plate. The plate is dried and washed twice with isooctane. After further drying, florasulam is eluted from the plate with a solution of 1-chlorobutane/ethyl acetate (70:30; v/v). The eluate is evaporated to dryness and the residues are reconstituted acetonitrile/methanol/water/acetic acid (25:25:49.9:0.1; v/v/v/v). The final solution is analyzed by LC-MS/MS with positive ESI (C8 column, m/z ) using external calibration. Results and discussions Table A 12: Recovery results from method validation of different matrices from all commodity groups using the analytical method. Standards were prepared in acetonitrile/methanol/water/acetic acid (25:25:49.9:0.1; v/v/v/v) Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments high water content sum of 6 crops acidic sum of 5 crops dry sum of 9 crops fatty sum of 5 crops Evaluator: BVL, BfR / DE Date: June 2013

103 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 34 of 40 Table A 13: Characteristics for the analytical method used for the quantitation of florasulam residues in different matrices from all commodity groups florasulam Calibration function y = x + 42 r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) Assessment of matrix effects is presented (yes/no) no Interference >30% of LOQ in blank sample is absent (yes/no) µg/ml mg/kg yes yes Conclusion The method was sufficiently validated for the determination of residues of florasulam in the four relevant commodity groups with an LOQ of 0.01 mg/kg. Chromatograms were shown only for example commodities of each commodity group instead of all validated commodities which is not in accordance with SANCO/825/00 but can be accepted. Comments of zrms: Acceptable for the determination of residues of florasulam in all commodity groups; used for evaluation. Independent laboratory validation Reference: OECD KIIA 4.3 Report Independent laboratory validation of Dow AgroSciences LLC method GRM Determination of residues of florasulam in agricultural commodities by high performance liquid chromatography with tandem mass spectrometric detection; Class, T.; 2005; method GRM 04.13; study ; ASB Guideline(s): Yes (SANCO/825/00 rev. 7, OPPTS (c), PR Notice 96-1) Deviations: GLP: Acceptability: No Yes Yes Materials and methods Residues of florasulam are extracted by homogenizing and shaking with acetone/water/acetic acid (80:19:1; v/v/v). An aliquot of the extract is diluted with HPLC grade water and is applied to a polymeric Evaluator: BVL, BfR / DE Date: June 2013

104 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 35 of 40 sorbent solid phase extraction plate. The plate is dried and washed twice with isooctane. After further drying, florasulam is eluted from the plate with a solution of 1-chlorobutane/ethyl acetate (70:30; v/v). The eluate is evaporated to dryness and the residues are reconstituted acetonitrile/methanol/water/acetic acid (25:25:49.9:0.1; v/v/v/v). The final solution is analyzed by LC-MS/MS with positive ESI (C8 column, m/z ), respectively negative ESI (m/z ) for confirmation, using external calibration. Results and discussions Table A 14: Recovery results from the independent laboratory validation of tomato and wheat grain using the analytical method. Standards were prepared in acetonitrile/methanol/water/acetic acid (25:25:49.9:0.1; v/v/v/v) Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments tomato primary transition tomato confirmatory transition wheat grain primary transition wheat grain confirmatory transition Table A 15: Characteristics for the analytical method used for the independent laboratory validation of florasulam residues in tomato and wheat grain florasulam Calibration function y = 2.95e+3x r = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) Assessment of matrix effects is presented (yes/no) no Interference >30% of LOQ in blank sample is absent (yes/no) µg/ml mg/kg yes yes Conclusion The method was sufficiently validated for the determination of residues of florasulam in commodities with high water content and in dry commodities with an LOQ of 0.01 mg/kg. A confirmatory method is included by a second mass transition. The method confirms the applicability of the method of Shackelford (2004) in an independent laboratory. Comments of zrms: Acceptable for the determination of residues of florasulam in high water content and dry commodities; ILV of Shackelford (2004); used for evaluation. Evaluator: BVL, BfR / DE Date: June 2013

105 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 36 of 40 Confirmatory method Reference: OECD KIIA 4.3 Report Guideline(s): Deviations: GLP: Acceptability: Residue method validation for the determination of florasulam in agricultural commodities; Rodrigues, A.; 2011, report no ; ASB Yes (EPA OPPTS ; SANCO/3029/99 rev. 4, SANCO/825/00 rev. 8.1; PMRA Dir 98-02) No Yes Yes Materials and methods The sample extraction and cleanup follows the same principle as described in the method of Shackelford, 2004; (method GRM 04.13). Final quantification is done by LC-MS/MS using a C8 column and monitoring two MS/MS transitions m/z , after electrospray ionisation in positive mode. For confirmation the peak area ratio of the 1 st and the 2 nd transition is calculated for each sample and each standard. The difference of the peak area ratio of the sample and the standard expressed in percent is given as confirmation ratio (see column 6 of table A.5) Results and discussions Table A 16: Recovery results from the confirmatory method validation of florasulam in dry crops, acidic matrices, fatty matrices and high water content matrices using the confirmatory method. Standards were prepared in acetonitrile/water/acetic acid (25/25/49.9/0.1, v/v/v) Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Difference, min-max (%) 1 Apple Potato Tomato Orange Corn grain Wheat gain Evaluator: BVL, BfR / DE Date: June 2013

106 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 37 of Canola seed Soybean seed confirmation ratio= peak area /peak area ; % difference=1- (confirmation ratio sample / confirmation ratio mean standard )* Table A 17: Characteristics for the confirmatory method used for the quantitation of florasulam residues in dry crops, acidic matrices, fatty matrices and high water content matrices florasulam Calibration function Y=5.08*10 7 *X +615, R=0.9998; X: concentration in µg/ml; Y: peak area in counts Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) ng/ml mg/kg Yes Assessment of matrix effects is presented (yes/no) Yes (3-17 % suppression) Interference >30% of LOQ in blank sample is absent (yes/no) Yes Conclusion The study of Rodriguez, 2011 is acceptable for the quantification of florasulam residues in dry crops, high water content matrices, acidic matrices and fatty matrices. The study included data and chromatograms for a second transition which is acceptable for confirmation. Comments of zrms: acceptable Methods for enforcement of residues in food and feed of animal origin not required Description of Methods for the Analysis of Soil no additional data Description of Methods for the Analysis of Water Analytical method 1 Reference: OECD KIIA 4.5 Evaluator: BVL, BfR / DE Date: June 2013

107 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 38 of 40 Report Method validation report for the determination of residues of florasulam and its 5-OH metabolite in waters by liquid chromatography with tandem mass spectrometry detection using Dow AgroSciences method GRM 07.23; Hastings, M.J.; 2008; method GRM 07.23; study ; ASB Guideline(s): Yes (SANCO/3029/99 rev. 4, SANCO/825/00 rev. 7, OPPTS , PMRA Dir 98-02) Deviations: GLP: Acceptability: No Yes Yes Materials and methods Residues of florasulam and its 5-OH florasulam metabolite are extracted from acidified water and purified using a polymeric sorbent solid phase extraction cartridge. The SPE cartridge is washed with a water/methanol (90:10; v/v) solution and eluted with acetonitrile containing 0.1 % formic acid. The eluate is evaporated to dryness, reconstituted in water/acetonitrile/methanol/acetic acid (90:5:5:0.1; v/v/v/v) and analyzed by LC-MS/MS, with negative ESI (C8 column, m/z , for florasulam and m/z , for 5-OH florasulam) using external calibration. Results and discussions Table A 18: Recovery results from method validation of drinking water, ground water and surface water using the analytical method. Standards were prepared in water/acetonitrile/methanol (90:5:5; v/v/v) Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments drinking water florasulam, primary transition florasulam, confirmatory transition ground water florasulam, primary transition florasulam, confirmatory transition surface water florasulam, primary transition florasulam, confirmatory transition drinking water OH florasulam, primary transition OH florasulam, confirmatory transition Evaluator: BVL, BfR / DE Date: June 2013

108 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 39 of 40 Matrix Fortification level (mg/kg) No of samples per fortification level Mean recovery RSD (%) Comments ground water OH florasulam, primary transition OH florasulam, confirmatory transition surface water OH florasulam, primary transition OH florasulam, confirmatory transition Table A 19: Characteristics for the analytical method used for the quantitation of florasulam residues in drinking water, ground water and surface water Calibration function florasulam primary transition: y = 78223x 1628 r 2 = OH florasulam primary transition: y = 28971x 959 r 2 = Accepted calibration range in concentration units (e.g. in μg/ml or ng/μl) Corresponding calibration range in mass ratio units for the sample (e.g.in mg/kg or μg/l) Does the calibration consist of at least 3 levels (duplicated points) or 5 levels (single points)? (yes/ no) Assessment of matrix effects is presented (yes/no) no Interference >30% of LOQ in blank sample is absent (yes/no) confirmatory transition: y = 6815x 129 r 2 = confirmatory transition: y = 6073x + 54 r 2 = ng/ml ng/ml µg/l µg/l yes yes yes no yes Conclusion The method was sufficiently validated for the determination of residues of florasulam (including its metabolite 5-OH florasulam) in drinking water, ground water and surface water with an LOQ of 0.05 µg/l. A confirmatory method is included by a second mass transition. Comments of zrms: Acceptable for the determination of residues of florasulam in drinking water, ground water and surface water; used for evaluation. Description of Methods for the Analysis of Air no additional data Description of Methods for the Analysis of Body Fluids and Tissues not required Evaluator: BVL, BfR / DE Date: June 2013

109 Part B Section 2 Core Assessment Germany GF-2463 Central Zone Page 40 of 40 Extraction efficiency of enforcement methods for foodstuff not required Other Studies/ Information none Evaluator: BVL, BfR / DE Date: June 2013

110 GF /00 Part B Section 3 - Core Assessment zrms version REGISTRATION REPORT Part B Section 3: Mammalian Toxicology Detailed summary of the risk assessment Product code: GF-2463 Active Substances: 300 g/l Clopyralid 25 g/l Florasulam Central Zone Zonal Rapporteur Member State: Germany CORE ASSESSMENT Applicant: DOW AGROSCIENCES Date: March 2012 Page 1 / 44

111 GF /00 Part B Section 3 - Core Assessment zrms version Table of Contents IIIA 7 Mammalian Toxicology...4 IIIA 7.1 Toxicological Evaluation of Active Substances...4 IIIA Clopyralid...4 IIIA Florasulam...4 IIIA 7.2 Toxicological Evaluation of Pesticide...5 IIIA 7.3 Dermal Absorption...6 IIIA 7.4 Safety Assessment of Pesticide Application...7 IIIA Selection of critical use(s) and justification...7 IIIA Evaluation of the Active Substance Clopyralid...9 IIIA Operator exposure and risk assessment...9 IIIA Worker exposure and risk assessment...10 IIIA Bystander and resident exposure and risk assessment...10 IIIA Evaluation of the active substance florasulam...11 IIIA Operator exposure and risk assessment...11 IIIA Worker exposure and risk assessment...12 IIIA Bystander and resident exposure and risk assessment...13 IIIA Conclusion of exposure estimation and risk assessment...13 IIIA 7.5 Justified Proposals for Classification and Labelling and Safety Instructions...14 Appendix 1 List of Data Submitted in Support of the Evaluation...15 Appendix 2 Detailed Evaluation of the Studies Relied Upon...16 A 2.1 Acute Oral Toxicity...16 A 2.2 Acute Percutaneous (Dermal) Toxicity...17 A 2.3 Acute Inhalation Toxicity...18 A 2.4 Skin Irritation...18 A 2.5 Eye Irritation...19 A 2.6 Skin Sensitisation...21 A 2.7 Supplementary Studies for Combinations of Plant Protection Products...22 A 2.8 Short-Term Toxicity Studies...22 A 2.9 Data on Formulants...22 A Material safety data sheet for each formulant...22 A Available toxicological data for each formulant...22 A 2.10 Studies on Dermal Absorption...23 A Dermal absorption of Florasulam, in vivo in the rat...23 A Comparative dermal absorption, in vitro, using rat and human skin...26 A 2.11 Other/Special Studies...30 Page 2 / 44

112 GF /00 Part B Section 3 - Core Assessment zrms version Appendix 3 Exposure Calculations...31 A 3.1 Exposure Calculations for the Active Substance Clopyralid...31 A Operator exposure calculations using the German model...31 A Operator exposure calculations using the UK POEM...33 A Worker exposure calculations...35 A Bystander and resident exposure calculations...35 A 3.2 Exposure Calculations for the Active Substance Florasulam...37 A Operator exposure calculations using the German model...37 A Operator exposure calculations using the UK POEM...39 A Worker exposure calculations...41 A Bystander and resident exposure calculations...42 Page 3 / 44

113 GF /00 Part B Section 3 - Core Assessment zrms version IIIA 7 IIIA 7.1 Mammalian Toxicology Toxicological Evaluation of Active Substances IIIA Clopyralid Table IIIA 7.1-1: General information on clopyralid Common Name Clopyralid CAS-No Table IIIA 7.1-2: Agreed EU endpoints Value Reference ADI 0.15 mg/kg bw EFSA Scientific Report (2005) 50, 1 65 AOEL systemic 1 mg/kg bw/d EFSA Scientific Report (2005) 50, 1 65 ARfD (acute reference dose) n.n. EFSA Scientific Report (2005) 50, 1 65 Table IIIA 7.1-3: Classification and proposed labelling for clopyralid with regard to toxicological data (according to the criteria in Dir. 67/548/EEC) with regard to toxicological data (according to the criteria in Reg. 1272/2008) Regulation (EC) No 1272/2008 (Table 3.2): Xi - Irritant R41 - Risk of serious damage to eyes Additional proposal: none additional Regulation (EC) No 1272/2008 (Table 3.1): Serious eye damage, cat. 1 H318 - Causes serious eye damage Additional proposal: none additional IIIA Florasulam Table IIIA 7.1-4: General information on florasulam Common Name Florasulam CAS-No Table IIIA 7.1-5: Agreed EU endpoints Value Reference ADI 0.05 mg/kg bw SANCO/1406/ final ( ) AOEL systemic 0.05 mg/kg bw/d SANCO/1406/ final ( ) ARfD (acute reference dose) n.n. SANCO/1406/ final ( ) Page 4 / 44

114 GF /00 Part B Section 3 - Core Assessment zrms version Table IIIA 7.1-6: Classification and proposed labelling for florasulam with regard to toxicological data (according to the criteria in Dir. 67/548/EEC) with regard to toxicological data (according to the criteria in Reg. 1272/2008) Regulation (EC) No 1272/2008 (Table 3.2): no classification necessary Additional proposal: none Regulation (EC) No 1272/2008 (Table 3.1): no classification necessary Additional proposal: none IIIA 7.2 Toxicological Evaluation of Pesticide Table IIIA 7.2-1: General information on GF-2463 Product name and code Formulation type Active substances (incl. content) Category Statement as to whether the product was already evaluated as the representative formulation during the Annex I inclusion or has been previously evaluated in an other MS according to Uniform Principles GF-2463 (DOW H-0-SC) SC Clopyralid, 300 g/l and florasulam, 25 g/l Herbicide Information on the detailed composition of GF-2463 can be found in the confidential dossier of this submission ( - Part C). A summary of the toxicological evaluation for GF-2463 is given in Table IIIA Full summaries of studies on the product GF-2463 are presented in Appendix 2. No Table IIIA 7.2-2: Summary of evaluation of the studies on acute toxicity including irritancy and skin sensitisation for GF-2463 Type of test, species (Guideline) Result Acceptability Classification (acc. to the criteria in Dir. 67/548/EEC) Classification (acc. to the criteria in Reg. 1272/2008) Reference LD 50 oral, rat (OECD 423) LD 50 dermal, rat (OECD 402) LC 50 inhalation, rat Skin irritation, rabbit (OECD 404) Eye irritation, rabbit (OECD 405) Skin sensitisation, mouse (OECD 429, LLNA) > 2000 mg/kg bw/day > 2000 mg/kg bw/day Yes None None XXXXX 2010 Yes None None XXXXX 2010 Not submitted, not necessary (vapour pressure of active substances: clopyralid 1.36 x 10-3 Pa, 25 C; florasulam 1 x 10-5 Pa, 25 C (below 10-2 Pa); no respirable droplets, not confirmed, ref.: ASB ) Non-irritant Yes None None XXXXX 2010 Non-irritant Yes None None XXXXX 2010 Non-sensitising Yes None None XXXXX 2011 Page 5 / 44

115 GF /00 Part B Section 3 - Core Assessment zrms version Supplementary studies for combinations of plant protection products No data not required Table IIIA 7.2-3: Additional relevant 1) toxicological information Type of test, species (Guideline) Substance (Concentration in product, % w/w) Classification of the substance (acc. to the criteria in Dir. 67/548/EEC and/or in Reg. 1272/2008) Reference Classification of GF (acc. to the criteria in Dir. 67/548/EEC, in Dir. 1999/45/EC and/or in Reg. 1272/2008) Short-term toxicity studies No data not required Toxicological data on active substances (not tested with the preparation) Clopyralid (25.8 % (w/w)) None None Florasulam (2.2 % (w/w)) None None Toxicological data on non-active substances (not tested with the preparation) Ethanolamine (CAS-No , 9.1 % (w/w)) 2) C; R34, 5 % R37 necessary Xn; R20 ( 25 %) 3) H314, 5 % H335 necessary H332 5) Reg. (EC) No 1272/2008 R37 n. n. 4) H335 n. n. 4) Further relevant toxicological information No data not required 1) only toxicological endpoints mentioned that were not investigated by the studies summarised in the table above 2) Actually, ethanolamine is supposed to react with clopyralid to form the respective salt but, on the other hand there is no information about the concentration of remaining free ethanolamine in the product available. 3) acc. to Dir. 1999/45/EC 4) n. n.: not necessary 5) acc. to the principle of additivity described within Reg. (EC) No 1272/2008 An overview of the classification and labelling of the preparation is given in paragraph IIIA 7.5. IIIA 7.3 Dermal Absorption Dermal absorption to GF-2463 was not evaluated as part of the EU review of florasulam or clopyralid. Therefore, all relevant data and risk assessments are provided here and are considered adequate. A specific dermal absorption study using GF-2463 has not been conducted. A dermal absorption study on florasulam from a suspension concentrate formulation (EF-1343) has been undertaken. In accordance with SANCO/1406/2001 final 18 September 2002a dermal absorption of 12% is propsed for florasulam for the concentrate and the dilution. For clopyralid a dermal absorption study from a soluble liquid formulation (EF-1136) has been undertaken. Based on the study results, the appropriate dermal absorption value for clopyralid is 4% for the concentrate and dilutions. Full summaries of the studies on the dermal absorption for florasulam and clopyralid are described in detail in Appendix 2. Page 6 / 44

116 GF /00 Part B Section 3 - Core Assessment zrms version The dermal absorption values used for risk assessment are summarised in Table Table IIIA 7.3-1: Dermal absorption end-points for GF-2463 Test % Absorption of applied dose Concentrate Spray dilution Florasulam (50 g/l SC formulation) Reference In vivo (rat) XXXXX (1997) TOX Clopyralid (100 g ae/l SL formulation) In vitro (human skin) 4 4 XXXXX (2007) ASB IIIA 7.4 Safety Assessment of Pesticide Application Table IIIA 7.4-1: Product information and toxicological reference values used for safety assessment of pesticide application Product name and code Formulation type Active substances (incl. content) Category Container sizes, short description Statement as to whether the product was already evaluated as the representative formulation during the Annex I inclusion AOEL systemic GF-2463 (DOW H-0-SC) SC Clopyralid, 300 g/l and florasulam, 25 g/l Herbicide HDPE bottle 1 20 L, PET bottle 1 20 L, both types with mm screw caps The safety of the application of GF-2463 was not evaluated as part of the EU review of neither of the active substances. Clopyralid: 1 mg/kg bw/d Florasulam: 0.05 mg/kg bw/d Oral absorption Clopyralid: 100 % Florasulam: 100 % Inhalative absorption Clopyralid: 100 % Florasulam: 100 % Dermal absorption Clopyralid: Concentrate: 4 %, Dilution: 4 % (based on an SL formulation containing 100 g/l clopyralid) Florasulam: Concentrate: 12 %, Dilution: 12 % (based on an SC formulation containing 50 g/l florasulam) IIIA Selection of critical use(s) and justification The GAPs used for the safety assessment of pesticide application are presented in Table IIIA Page 7 / 44

117 GF /00 Part B Section 3 - Core Assessment zrms version Table IIIA 7.4-2: Critical uses according to Art. 51 VO 1107/2009 (worst case) for safety assessment of pesticide application Use- Member Crop and/ F Pests or Group of pests Application Application rate per treatment PHI Remarks: No. state(s) or situation G controlled Method / Timing / Growth Max. number L product / ha kg as/ha Water (days) or Kind stage of crop & L/ha e.g. safener/synergist per ha I season (additionally: developmental stages of the pest or pest group) (a) (b) (c) (d-f) (g) (h) (i) (j) 1 * DE Winter soft wheat, winter F Annual dicotyledonous Tractor BBCH ; clopyralid: barley, winter rye, spelt, weeds mounted post-emergence, 0.06, winter triticale spraying spring, after emergence florasulam: of weeds * DE Spring soft wheat, spring F Annual dicotyledonous Tractor BBCH ; clopyralid: durum wheat, spring weeds mounted post-emergence, 0.06, barley, oats spraying spring, after emergence florasulam: of weeds *Critical GAPs for Operator Exposure (German model and UK POEM), Worker Exposure, Bystander Exposure and Resident Exposure Remarks: (a) For crops, the EU and Codex classifications (both) should be used; where relevant, (g) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, the use situation should be described (e.g. fumigation of a structure) Blackwell, ISBN ), including where relevant, information on season at (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) time of application (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds (h) The minimum and maximum number of application possible under practical conditions (d) All abbreviations used must be explained of use must be provided (e) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, (i) PHI - minimum pre-harvest interval drench (j) Remarks may include: Extent of use/economic importance/restrictions (f) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated per crop/ season max. total rate per crop/season max. total rate per crop/season min / max e.g. recommended or mandatory tank mixtures Page 8 / 44

118 GF /00 Part B Section 3 - Core Assessment zrms version IIIA IIIA Evaluation of the Active Substance Clopyralid Operator exposure and risk assessment Estimation of operator exposure and risk assessment Table IIIA 7.4-3: Critical use(s) Model(s) Critical use(s) Model(s) Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) German model (available on [Uniform Principles for Safeguarding the Health of Applicators of Plant Protection Products (Uniform Principles for Operator Protection), Mitteilungen aus der Biologischen Bundesanstalt für Land-und Forstwirtschaft, Berlin-Dahlem, Heft 277, 1992] Various cereals (max. 1 x 0.2 L GF-2463/ha) Revised UK-POEM, (available on [Estimation of Exposure and Absorption of Pesticides by Spray Operators, Scientific subcommittee on Pesticides and British Agrochemical Association Joint Medical Panel Report (UK MAFF), 1986 and the Predictive Operator Exposure Model (POEM) V 1.0, (UK MAFF), 1992] Table IIIA 7.4-4: Estimated operator exposure towards clopyralid Model data Level of PPE Total absorbed dose (mg/kg bw/day) % of systemic AOEL 1) 2) 3) 4) Tractor mounted boom spray application outdoors to low crops Application rate: 0.06 kg a.s./ha German Model Body weight: 70 kg UK POEM Application volume: 200 L/ha Container: 10 L, 45 mm closure Body weight: 60 kg no PPE 1) with PPE 2) no PPE 3) with PPE 4) no PPE: Operator wearing T-shirt and shorts with PPE: gloves during mixing/loading (PPE acc. to the Federal Office of Consumer Protection and Food Safety (BVL); 2006; Personal protective equipment for handling plant protection products - Guidelines for requirements concerning personal protective equipment in plant protection no PPE: Operator wearing long sleeved shirt, long trousers ( permeable ) but no gloves with PPE: gloves during mixing/loading For the detailed calculations it is referred to Appendix 3 (see A 3.1). Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of operator exposure was not necessary and was therefore not performed. Page 9 / 44

119 GF /00 Part B Section 3 - Core Assessment zrms version IIIA Worker exposure and risk assessment Estimation of worker exposure and risk assessment Table IIIA 7.4-5: Critical use(s) Model Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) German re-entry model, Krebs et al. (2000) (available on [Uniform Principles for Safeguarding the Health of Workers Re-entering Crop Growing Areas after Application of Plant Protection Products, Nachrichtenbl. Deut. Pflanzenschutzdienst., 52(1), p. 5-9] Table IIIA 7.4-6: Estimated worker exposure towards clopyralid Model data Level of PPE Total absorbed dose (mg/kg bw/day) % of systemic AOEL Number of applications and application rate: 1 x 0.06 kg a.s./ha 2 hours/day 1), no PPE 3) TC: 1500 cm 2 /person/h 2) Body weight: 60 kg with PPE 4) ) 2) 3) 4) 2 h/day for professional applications for maintenance, inspection or irrigation activities etc. US-EPA policy paper [EPA, Science Advisory Council for Exposure; 2000; Agricultural Default Transfer Coefficients, Policy # 003.1, May revised 7 August 2000] no PPE: Worker wearing long sleeved shirt, long trousers ( permeable ) but no gloves with PPE: see 'Instructions for use' For the detailed calculations it is referred to Appendix 3 (see A 3.1.3). Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of worker exposure was not necessary and was therefore not performed. IIIA Bystander and resident exposure and risk assessment Estimation of bystander and resident exposure and risk assessment Table IIIA 7.4-7: Critical use(s) Model Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) Martin S. et al. (2008) (available on [Guidance for Exposure and Risk Evaluation for Bystanders and Residents Exposed to Plant Protection Products During and After Application; J. Verbr. Lebensm. 3 (2008): Birkhäuser Verlag Basel and Bundesanzeiger (BAnz), 06 January 2012, Issue No. 4, pp ] Page 10 / 44

120 GF /00 Part B Section 3 - Core Assessment zrms version Table IIIA 7.4-8: Estimated bystander and resident exposure towards clopyralid Model data Total absorbed dose (mg/kg bw/day) % of systemic AOEL Tractor mounted boom spray application outdoors to low crops Application rate: 0.06 kg a.s./ha Bystanders (adult) Drift rate: 2.77 % (1 m) Body weight: 60 kg Bystanders (children) Drift rate: 2.77 % (1 m) Body weight: kg Residents (adult) Drift rate: 2.77 % (1 m) Body weight: 60 kg Residents (children) Drift rate: 2.77 % (1 m) Body weight:16.15 kg For the detailed calculations it is referred to Appendix 3 (see A 3.1.4) Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of bystander or resident exposure was not necessary and was therefore not performed. IIIA IIIA Evaluation of the active substance florasulam Operator exposure and risk assessment Estimation of operator exposure and risk assessment Table IIIA 7.4-9: Critical use(s) Model(s) Critical use(s) Model(s) Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) German model (available on [Uniform Principles for Safeguarding the Health of Applicators of Plant Protection Products (Uniform Principles for Operator Protection), Mitteilungen aus der Biologischen Bundesanstalt für Land-und Forstwirtschaft, Berlin-Dahlem, Heft 277, 1992] Various cereals (max. 1 x 0.2 L GF-2463/ha) Revised UK-POEM, (available on [Estimation of Exposure and Absorption of Pesticides by Spray Operators, Scientific subcommittee on Pesticides and British Agrochemical Association Joint Medical Panel Report (UK MAFF), 1986 and the Predictive Operator Exposure Model (POEM) V 1.0, (UK MAFF), 1992] Page 11 / 44

121 GF /00 Part B Section 3 - Core Assessment zrms version Table IIIA : Estimated operator exposure towards florasulam Model data Level of PPE Total absorbed dose (mg/kg bw/day) % of systemic AOEL 1) 2) 3) 4) Tractor mounted boom spray application outdoors to low crops Application rate: kg a.s./ha German Model Body weight: 70 kg UK POEM Application volume: 200 L/ha Container: 10 L, 45 mm closure Body weight: 60 kg no PPE 1) with PPE 2) no PPE 3) with PPE 4) no PPE: Operator wearing T-shirt and shorts with PPE: gloves during mixing/loading (PPE acc. to the Federal Office of Consumer Protection and Food Safety (BVL); 2006; Personal protective equipment for handling plant protection products - Guidelines for requirements concerning personal protective equipment in plant protection no PPE: Operator wearing long sleeved shirt, long trousers ( permeable ) but no gloves with PPE: gloves during mixing/loading For the detailed calculations it is referred to Appendix 3 (see A 3.2). Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of operator exposure was not necessary and was therefore not performed. IIIA Worker exposure and risk assessment Estimation of worker exposure and risk assessment Table IIIA : Critical use(s) Model Table IIIA : Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) German re-entry model, Krebs et al. (2000) (available on [Uniform Principles for Safeguarding the Health of Workers Re-entering Crop Growing Areas after Application of Plant Protection Products, Nachrichtenbl. Deut. Pflanzenschutzdienst., 52(1), p. 5-9] Estimated worker exposure towards florasulam Model data Level of PPE Total absorbed dose (mg/kg bw/day) % of systemic AOEL Number of applications and application rate: 1 x kg a.s./ha 2 hours/day 1), no PPE 3) TC: 1500 cm 2 /person/h 2) Body weight: 60 kg with PPE 4) ) 2) 3) 4) 2 h/day for professional applications for maintenance, inspection or irrigation activities etc. US-EPA policy paper [EPA, Science Advisory Council for Exposure; 2000; Agricultural Default Transfer Coefficients, Policy # 003.1, May revised 7 August 2000] no PPE: Worker wearing long sleeved shirt, long trousers ( permeable ) but no gloves with PPE: see 'Instructions for use' Page 12 / 44

122 GF /00 Part B Section 3 - Core Assessment zrms version For the detailed calculations it is referred to Appendix 3 (see A 3.2.3). Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of worker exposure was not necessary and was therefore not performed. IIIA Bystander and resident exposure and risk assessment Estimation of bystander and resident exposure and risk assessment Table IIIA : Critical use(s) Model Exposure models for intended uses Various cereals (max. 1 x 0.2 L GF-2463/ha) Martin S. et al. (2008) (available on [Guidance for Exposure and Risk Evaluation for Bystanders and Residents Exposed to Plant Protection Products During and After Application; J. Verbr. Lebensm. 3 (2008): Birkhäuser Verlag Basel and Bundesanzeiger (BAnz), 06 January 2012, Issue No. 4, pp ] Table IIIA : Estimated bystander and resident exposure towards florasulam Model data Total absorbed dose (mg/kg bw/day) % of systemic AOEL Tractor mounted boom spray application outdoors to low crops Application rate: kg a.s./ha Bystanders (adult) Drift rate: 2.77 % (1 m) Body weight: 60 kg Bystanders (children) Drift rate: 2.77 % (1 m) Body weight: kg Residents (adult) Drift rate: 2.77 % (1 m) Body weight: 60 kg Residents (children) Drift rate: 2.77 % (1 m) Body weight:16.15 kg For the detailed calculations it is referred to Appendix 3 (see A 3.2.4) Since the exposure estimations carried out indicated that the acceptable operator exposure level (AOEL) will not be exceeded under conditions of intended uses, a study to provide measurements of bystander or resident exposure was not necessary and was therefore not performed. IIIA Conclusion of exposure estimation and risk assessment The risk assessment has shown that the estimated exposure towards clopyralid and florasulam in GF-2463 will not exceed the systemic AOEL for operators, workers, bystanders and residents. No specific PPE is necessary for operators or for workers. If used properly and according to the intended conditions of use, adverse health effects for operators, Page 13 / 44

123 GF /00 Part B Section 3 - Core Assessment zrms version workers, bystanders and residents will not be expected. IIIA 7.5 Justified Proposals for Classification and Labelling and Safety Instructions Justified proposals for classification and labelling In accordance with Directives 67/548/EEC and 1999/45/EC the following classification and labelling with regard to toxicological data is proposed for the preparation: Table IIIA 7.5-1: Classification and labelling according to Directives 67/548/EEC and 1999/45/EC Hazard symbol: Indication of danger: Risk phrases: Xi Irritating R37 Safety phrases: 2-23 Labelling texts and restrictions: To avoid risks to man and the environment, comply with the instructions for use. According to the criteria given in Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, the following classification for toxicological hazards of the preparation according to GHS would be proposed: Table IIIA 7.5-2: Classification and labelling according to Regulation (EC) No 1272/2008 Hazard class, category: STOT Single Exp. 3 Signal word: Hazard statement: Labelling texts and restrictions: Warning H335 To avoid risks to man and the environment, comply with the instructions for use. Safety instructions Table IIIA 7.5-3: Safety phrases for use instructions Safety instructions (codes according to BVL * ) Justification ** SB001 Avoid any unnecessary contact with the product. Misuse can lead to health damage. 1 SF Treated areas/crops may not be entered until the spray coating has dried. 2 * EN.pdf? blob=publicationfile&v=6 ** Justification: 1 Mandatory for plant protection products 2 With regard to preventive health protection and good agricultural practice Page 14 / 44

124 GF /00 Part B Section 3 - Core Assessment zrms version Appendix 1 List of Data Submitted in Support of the Evaluation Table A 1: List of data submitted in support of the evaluation Annex point/ reference No Author(s) Year Title Report-No. Authority registration No Data protection claimed Owner How considered in drr* * OECD: KIIIA OECD: KIIIA OECD: KIIIA OECD: KIIIA OECD: KIIIA OECD KIIIA OECD KIIIA XXXXX 2010 Acute oral toxicity study of GF-2463 in rats. XXXXX GLP: Yes Unpublished ASB XXXXX 2010 Acute dermal toxicity study of GF-2463 in rats. XXXXX GLP: Yes Unpublished ASB XXXXX 2010 GF-2463: acute dermal irritation study of GF-2463 in rabbits. Report file number: DR XXXXX GLP: Yes Unpublished ASB XXXXX 2010 GF-2463: acute eye irritation study of GF-2463 in rabbits. Report file number: DR XXXXX GLP: Yes Unpublished ASB XXXXX 2011 GF-2463: skin sensitization study of GF-2463 by local lymph node assay in mice. Report file number: DR XXXXX. GLP: Yes Unpublished ASB XXXXX Dermal absorption of [14C]-XDE-570 in male Fischer 344 rats following exposure to undiluted EF-1343 and a spray solution TOX XXXXX 2006 XXXXX In vitro percutaneous absorption of [14C]-Clopyralid formulated as EF and field dilution through human skin membranes using flow-through diffusion cells * Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted by applicant but necessary for evaluation DOW DOW DOW DOW DOW DOW DOW Y Y Y Y Y Y Y Page 15 / 44

125 GF /00 Part B Section 3 - Core Assessment zrms version Appendix 2 Detailed Evaluation of the Studies Relied Upon A 2.1 Acute Oral Toxicity Reference: KIIIA Report Acute Oral Toxicity Study of GF-2463 in Rats XXXXX 2010, study XXXXX ASB Guideline(s): OECD 423 Deviations: No GLP: Yes Acceptability: Yes Materials and methods The acute oral toxicity of GF-2463 (Lot/Batch #: 199/199-A), opaque liquid which contains 26.2 % w/w (305 g/l) clopyralid (a.i.), 2.05 % w/w (24 g/l) florasulam (a.i.) as the active ingredients) was evaluated in two sets of 3 female Wistar rats (RCCHan:WIST). Following an overnight fast, rats were given a single dose of GF-2463 (2000 mg/kg/body weight) by gavage, then observed daily for mortality, signs of gross toxicity, and behavioral changes and weighed weekly for 14 days. Survivors were sacrificed and a necropsy was performed. Results and discussions No clinical signs or deaths were observed during the study (see Table A 2). There were no effects on body weight gain resulting from treatment. No abnormalities were observed during necropsy examination. Table A 2: Dose (mg/kg bw) Female rats Results of acute oral toxicity study of GF-2463 in rats Toxicological results * Duration of signs Time of death LD 50 (mg/kg bw) (14-days) /0/6 n. a. n. a. > 2000 * number of animals that died/number of animals with clinical signs/number of animals used n. a.: not applicable Conclusion Under the experimental conditions, the oral LD 50 of GF-2463 is > 2000 mg/kg bw in rats and thus, GF is not classified for acute oral toxicity according to Dir. 67/548/EEC or Reg. 1272/2008/EC. Comments of zrms: Acceptable, no deviations from above mentioned test guideline, used for evaluation Page 16 / 44

126 GF /00 Part B Section 3 - Core Assessment zrms version A 2.2 Acute Percutaneous (Dermal) Toxicity Reference: KIIIA Report Acute Dermal Toxicity Study of GF-2463 in Rats XXXXX 2010, study XXXXX, ASB Guideline(s): OECD 402 Deviations: No GLP: Yes Acceptability: Yes Materials and methods The acute dermal toxicity of GF-2463 (Lot/Batch #: 199/199-A), opaque liquid which contains 26.2 % w/w (305 g/l) clopyralid (a.i.), 2.05 % w/w (24 g/l) florasulam (a.i.) as the active ingredients) was evaluated in 5 female and 5 male Wistar rats (RCCHan:WIST). Rats were given a single dermal limit dose of neat GF-2463 (2000 mg/kg body weight) corresponding to approximately 10 % of the body surface area (equivalent to 0.37 to 0.53 ml). The fur at this site was clipped off cautiously 24 h prior to application. After application the test area was covered with a porous dressing for 24 hours, after which residual test material was removed with distilled water. The animals were observed daily for mortality, signs of gross toxicity, and behavioural changes and weighed weekly for 14 days. Survivors were sacrificed and a necropsy was performed. Results and discussions No clinical signs or deaths were observed during the study (see Table A 3). There were no effects on body weight gain resulting from treatment. No abnormalities were observed during necropsy examination. Table A 3: Dose (mg/kg bw) Female rats Results of acute dermal toxicity study of GF-2463 in rats Toxicological results * Duration of signs Time of death LD 50 (mg/kg bw) (14-days) /0/5 n. a. n. a. > 2000 Male rats /0/5 n. a. n. a. > 2000 * number of animals that died/number of animals with clinical signs/number of animals used n. a.: not applicable Conclusion Under the experimental conditions, the dermal LD 50 of GF-2463 is >2000 mg/kg bw in rats and thus, GF is not classified for acute dermal toxicity according to Dir. 67/548/EEC or Reg. 1272/2008/EC. Comments of zrms: Acceptable, no deviations from above mentioned test guideline, used for evaluation Page 17 / 44

127 GF /00 Part B Section 3 - Core Assessment zrms version A 2.3 Acute Inhalation Toxicity No inhalation study has been conducted on GF According to Dir. 91/414/EEC this is mandatory if the plant protection product is: - a gas or liquified gas GF-2463 is a SC liquid formulation - is a smoke-generating formulation GF-2463 is a SC liquid formulation or fumigant - is a vapour releasing preparation GF-2463 is a SC liquid formulation - is used with fogging equipment GF-2463 is a SC liquid formulation - is an aerosol GF-2463 is a SC liquid formulation - contains an active substance with a vapour pressure > 1 x 10-2 Pa and is to be used in enclosed spaces such as warehouses or glasshouses - is a powder containing a significant proportion of particles of diameter < 50 m (> 1 % on a weight basis) - is to be applied from aircraft in cases where inhalation exposure is relevant - is to be applied in a manner which generates a significant proportion of particles or droplets of diameter < 50 m (> 1 % on a weight basis) The vapour pressure of clopyralid is 1.36 x 10-3 Pa at 25 C, that of florasulam is 1 x 10-5 Pa at 25C and GF-2463 is not intended to be used in enclosed spaces. GF-2463 is a liquid formulation Application of GF-2463 via aircraft is not intended Virtually all droplets produced by conventional field sprayers are too large to be inhaled into the lung (i.e., > 30 m). The majority of the droplets, if not all are, breathed into the mouth will impact the nasopharyngeal region and will be swallowed, not inhaled. Comments of zrms: Justification for waiving of the study acceptable, but no particular data confirming the above made statement concerning droplet size in spray produced by conventional field sprayers provided A 2.4 Skin Irritation Reference: KIIIA Report Acute Dermal Irritation Study of GF-2463 in Rabbits XXXXX 2010, study XXXXX, ASB Guideline(s): OECD 404 Deviations: No GLP: Yes Acceptability: Yes Materials and methods The skin irritation potential of GF-2463 (Lot/Batch #: 199/199-A), opaque liquid which contains 26.2 % w/w (305 g/l) clopyralid (a.i.), 2.05 % w/w (24 g/l) florasulam (a.i.) as the active ingredients) was evaluated in 3 healthy male New Zealand white rabbits. The rabbits were given a single dermal application of 0.5 ml GF-2463 (undiluted) that was distributed over approximately 6 cm 2 of shaved skin. The area was covered by a gauze patch and residual test material was removed with distilled water after 4 hours of treatment. An opposing skin area was treated Page 18 / 44

128 GF /00 Part B Section 3 - Core Assessment zrms version with 0.5 ml of distilled water and served as a control. Skin reactions were observed at 1, 24, 48 and 72 h after patch removal. Results and discussions At 1 h after patch removal, very slight erythema was observed for all three rabbits (see Table A 4). At 24 h and 48 h after patch removal, very slight erythema was observed on rabbit No 1, whereas rabbit No 2 and 3 had completely recovered within 24 hours and appeared normal. At 72 h after termination of the treatment, rabbit No 1 no longer showed any skin reactions. At no point in time oedema could be detected. The control skin area of all rabbits was without any findings throughout the experimental period. The mean scores of erythema (0.0 to 0.67) and oedema (0.0) resulting from 24, 48 and 72 hour readings were non-significant in all treated rabbits. There were no treatment related clinical signs or changes in body weight. Table A 4: Results of skin irritation study of GF-2463 Animal No. Scores after treatment * 1 h 24 h 48 h 72 h Mean scores (24-72 h) Reversible [day] 1 Erythema Oedema Erythema Oedema Erythema Oedema * scores in the range of 0 to 4 Clinical signs: No Conclusion Under the experimental conditions, GF-2463 is not a skin irritant acc. to Dir. 67/548/EEC or Reg. 1272/2008/EC. Therefore, no classification is necessary. Comments of zrms: Acceptable, no deviations from above mentioned test guideline, used for evaluation A 2.5 Eye Irritation Reference: KIIIA Report Acute Eye Irritation Study of GF-2463 in Rabbits XXXXX 2010, study XXXXX, ASB Guideline(s): OECD 405 Deviations: No GLP: Yes Acceptability: Yes Page 19 / 44

129 GF /00 Part B Section 3 - Core Assessment zrms version Materials and methods The eye irritation potential of GF-2463 (Lot/Batch #: 199/199-A), opaque liquid which contains 26.2 % w/w (305 g/l) clopyralid (a.i.), 2.05 % w/w (24 g/l) florasulam (a.i.) as the active ingredients) was evaluated in 3 healthy female New Zealand white rabbits. After having initially tested one rabbit, an aliquot of 0.1 ml of neat test substance was instilled into the conjunctival sac of one eye of the two additional rabbits after gently pulling the lower eyelid away from the eyeball. The eyelids were then gently held together for one second in order to prevent loss of test substance. The contralateral eye of each rabbit served as a control and was simultaneously instilled with 0.1 ml of 0.9% (w/v) normal saline. At 24 h after instillation of the test substance, the treated as well as the control eye were gently washed using 0.9 % saline. After instillation (day 0), the eyes of all rabbits were observed for signs of ocular irritation at 1, 24, 48 and 72 hours. Results and discussions At 1 h post-instillation, the treated eyes revealed conjunctival redness [some blood vessels hyperaemic (injected)] in all three rabbits (see Table A 5). At 24 h post-instillation, the treated eye revealed conjunctival redness [some blood vessels hyperaemic (injected)] in rabbit No 1 whereas rabbit No 2 and 3 had recovered completely and appeared normal. Examination with fluorescein dye and cobalt blue filter at 24 h post-instillation detected no corneal opacity (area) in all three rabbits. At 48 and 72 h postinstillation, the treated eye of rabbit No 1 had recovered completely and appeared normal. Corneal opacity, iritis and conjunctival chemosis were not observed in any of the three rabbits throughout the experimental phase. Therefore, the mean scores observed for corneal opacity, iritis and chemosis were 0.0, whereas the mean scores for conjunctival redness were 0.0 to 0.33 following grading at 24, 48 and 72 hours after instillation of GF There were no treatment related clinical signs or changes in body weight. Table A 5: Results of eye irritation study of GF-2463 Animal No. Scores after treatment * 1 h 24 h 48 h 72 h Mean scores (24-72 h) Reversible [day] 1 Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae 2 Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae 3 Corneal opacity Iritis Redness conjunctivae Chemosis conjunctivae * scores in the range of 0 to 4 (cornea opacity and chemosis), 0 to 3 (conjunctivae) or 0 to 2 (iris) Clinical signs: No Conclusion Under the experimental conditions, GF-2463 is not an eye irritant acc. to Dir. 67/548/EEC or Reg. 1272/2008/EC. Therefore, no classification is necessary. Page 20 / 44

130 GF /00 Part B Section 3 - Core Assessment zrms version Comments of zrms: Acceptable, no deviations from above mentioned test guideline, used for evaluation A 2.6 Skin Sensitisation Reference: KIIIA Report GF-2463: Skin Sensitization Study of GF-2463 by Local Lymph Node Assay in Mice XXXXX 2011, XXXXX, ASB Guideline(s): OECD 429 Deviations: No GLP: Yes Acceptability: Yes Materials and methods The skin sensitisation potential of GF-2463 (Lot/Batch #: 199/199-A), opaque liquid which contains 26.2 % w/w (305 g/l) clopyralid (a.i.), 2.05 % w/w (24 g/l) florasulam (a.i.) as the active ingredients) was evaluated in mice (female CBA/J). To assess the irritant potential of the test item, a preliminary test was carried out in which ear thickness increase in the treated mice was determined and the application sites were checked for erythema. Since no erythema was observed at any dose concentrations tested (25 %, 50 %, 75 % or 100 % (v/v) of GF-2463 in 1 % aqueous solution of Pluronic L 92) and earthickness increase did not exceed 25 % compared to the control, concentrations of 25 %, 50 % and 100 % (v/v) GF-2463 were chosen for the main study. Three groups (G2 to G4, made up of 5 mice each) were treated topically with GF-2463 at concentrations of 25 %, 50 % and 100 % (v/v) in 1 % aqueous Pluronic L 92 on three consecutive days (days 0, 1 and 2) on the dorsal surface of both ears (25 µl/ear) using calibrated micropipettes. 5 vehicle control mice (G1, 1 % aqueous solution of Pluronic L 92) and 5 positive control mice (G5, using 25 % (v/v) α- Hexylcinnamaldehyde in the above mentioned vehicle) were treated in a similar manner. On day 5 (approximately 72 hours after the last treatment), all mice from all groups were injected 250 μl of sterile phosphate buffered saline (PBS) containing 20 μci (7.4 x 10 5 Bq) of 3 H-methyl thymidine via the tail vein. Every individual animal was checked for clinical signs, local irritation at the site of application and systemic toxicity once every day (d 0 d 5). Body weights were recorded on the first day of dosing (day 0) and prior to administration of 3 H-methyl thymidine (day 5). Local irritation responses were recorded according to the criteria described in OECD 429, 2010; Section 22. On day 5, 5 hours after administration of 3 H-methyl thymidine, all mice from all groups were sacrificed by means of CO2 asphyxiation. The draining auricular lymph nodes of each mouse were excised and collected in phosphate buffered saline. Incorporation of 3 H-methyl thymidine was measured by β-scintillation counting (disintegrations per minute, DPM) separately for each mouse. Results and discussions No clinical signs were observed in any of the mice from the control groups or groups treated with GF No erythema was detected in vehicle control mice as well as in groups treated with GF-2463 on days 0 to 5. Very slight (barely perceptible) erythema (days 1 and 4) and well-defined erythema (days 2 and 3) were observed in all mice treated with α-hexylcinnamaldehyde (positive control). 3 H-methyl thymidine incorporation, considered as an indicator for cell proliferation is presented as the Page 21 / 44

131 GF /00 Part B Section 3 - Core Assessment zrms version mean group DPM value in Table A 6. Stimulation index (SI) values calculated for the groups treated with GF-2463 were found not to exceed 1.85 (100 % GF-2463) whereas the SI was > 10 in the case of the mice treated with α-hexylcinnamaldehyde. Since the SI values are < 3 for all concentrations of GF-2463 tested in this LLNA, the test item is not considered to be a skin sensitiser. Table A 6: Results of skin sensitisation study of GF-2463 No. of animals Concentration [%] Mean group DPM ± Standard Deviation Stimulation index (SI) * Vehicle control (Pluronic L 92) ± GF-2463 Positive control (α-hexylcinnamaldehyde) ± ± ± ± * mean DPM of test group divided by mean DPM of vehicle control group Clinical signs: No Conclusion Under the experimental conditions, GF-2463 is not a skin sensitiser. Therefore, no classification is necessary. Comments of zrms: Acceptable, no deviations from above mentioned test guideline, used for evaluation A 2.7 Supplementary Studies for Combinations of Plant Protection Products Not available, not necessary. A 2.8 Short-Term Toxicity Studies This is not an EC data requirement / not required by Regulation (EC) No 1107/2009. A 2.9 Data on Formulants A Material safety data sheet for each formulant Material safety data sheets of the formulants can be found in the confidential dossier of this submission ( - Part C). A Available toxicological data for each formulant Available toxicological data for each formulant can be found in the confidential dossier of this Page 22 / 44

132 GF /00 Part B Section 3 - Core Assessment zrms version submission ( - Part C). A 2.10 A Studies on Dermal Absorption Dermal absorption of Florasulam, in vivo in the rat Report: KIIIA /01, XXXXX (1997) Title: DE-570: Dermal absorption of [ 14 C] DE-570 in male Fischer 344 rats following exposure to undiluted EF-1343 and a spray solution Document No: XXXXX (Ref. M19) Guidelines: OECD 417, 1984 OECD draft Percutaneous absorption: in vivo method June 1996 GLP BfR Document No. Yes TOX The absorption of [ 14 C]-DE-570 (florasulam) was assessed in vivo in male Fischer 344 rats following a single topical application of either undiluted EF-1343 (53 g DE-570/L) or a spray dilution (0.09 g DE-570/L), chosen to represent concentrations that will be applied to field crops. EF-1343 is a suspension concentrate formulation containing a nominal 50 g DE-570/L. Both test substances were applied at a rate of 10 µl/cm 2 to the clipped dorsal area of the male rats. The dose remained in contact with the skin for 24 hours and then the application site was washed with soap solution to remove any dose remaining on the skin. Each test substance was administered to a group of 12 animals. Four animals per group were killed at 24, 48 and 72 hours after dosing. Radioactivity was determined in urine, faeces, cage wash, untreated skin, liver, kidneys, carcass, whole blood (~0.5 ml sample), treated skin, saddle and dressings ( gauze wash ), skin swabs and tape strips, by liquid scintillation spectrometry (counting). The overall total recoveries were % for all six groups of animals. Following a single topical application of undiluted [ 14 C] EF-1343 formulation containing [ 14 C]-DE-570 very little radioactivity was absorbed after 24, 48 and 72 hours (mean <0.5%). The levels of radioactivity in whole blood, carcass, liver, kidneys and faeces for the majority of samples taken at 24, 48 and 72 hours were below the limit of detection. Low levels of radioactivity were detected in the untreated skin of all animals in the 24 hour dose group, and because the levels are so low, this constituted 0.27/0.39= 69% of the absorbed dose. In the 48 hour and 72 hour group, only one rat in 8 had an amount greater than 0.02 %, and this single value 0.6 in the 48 hour sample skewed both the mean % dose in the treated skin and the absorbed dose. The absence of the any significant residue in the untreated skin at 48 and 72 hours indicated that the 24hour values may be an artefact. This explains the apparent decrease in absorbed dose over the sampling times. Table A 7. A very small proportion of dose (mean <0.15%) was excreted in the urine, and similar levels were found in the cage wash samples, and in two animals a very small proportion of dose was also detected in the faeces (mean <0.05%). The proportion of dose recovered from washes of the gauzes and saddles was between 1.4% and 4.8% (group means). The majority of dose (approximately 88%) was removed at the 24 hour skin swab, and Page 23 / 44

133 GF /00 Part B Section 3 - Core Assessment zrms version approximately 10% remained in the treated skin up to 72 hours after dosing. These results are summarised below in Table A 7. Table A 7:: Percentage of radiochemical material and mg equivalents of DE-570 absorbed, remaining in the treated skin and removed from the application site following a single topical application of radiolabelled EF-1343 formulation (approximately 0.53 mg DE-570/cm2) Time Absorbed* Treated skin (application site) Skin swab/gauze wash/tape strip Total h % mg % Mg % mg % (0.06)** *= urine, faeces, cage wash, carcass, tissues and untreated skin ** excluding outlier Further detailed analysis of the absorbed dose is summarised in Table A 8, which shows the percentage of radiochemical material of DE-570 excreted in each 24 hour period and systemically available during comparable periods following a single topical application of radiolabelled EF-1343 formulation (approximately 0.53 mg DE-570/cm 2 ). Table A 8:: Percentage of radiochemical material of DE-570 excreted in each 24 hour period (for the 72 hour time point) following a single topical application of radiolabelled EF-1343 formulation (approximately 0.53 mg DE-570/cm2) Time Urine Faeces (hr) ND ND ND* *ND, ND, ND, the single positive could be associated with material dislodged from the skin These data combined with the lack of movement from the application site, clearly indicate that absorption has ceased and the application site can be excluded. Based on the most conservative dataset, i.e. at 24 hours, a dermal absorption of 0.4% is applicable. Following a single topical application of diluted EF-1343 spray solution to the clipped dorsal area of the male rat, the levels of radioactivity in blood, untreated skin, carcass, liver, kidneys, faeces and cage wash at 24, 48 and 72 hours were all below the limits of detection. The absorbed dose was therefore equivalent to the levels excreted in the urine. The proportion of dose recovered from washes of the gauzes and saddles was between 2.5 and 7.3% (group means). The majority of dose (group means 71-85%) was removed at the 24 hour skin swabbing, and between 12 and 22% remained in the treated skin up to 72 hours after dosing. These results are summarised below in Table A 9: Table A 9:: Percentage of radiochemical material and mg equivalents of DE-570 absorbed, remaining in the treated skin and removed from the application site following a single topical application of radiolabelled diluted EF-1343 spray solution (approximately mg DE-570/cm 2 ) Time Absorbed* Treated skin Skin swab/gauze wash/tape strip Total Page 24 / 44

134 GF /00 Part B Section 3 - Core Assessment zrms version h % mg % mg % mg % * = urine, faeces, cage wash, carcass, tissues and untreated skin This data clearly indicates that there was no significant absorption has occurred over the period hours and therefore the amount at the application site can be excluded. The HSE review has quantified this approach by the following rationale:- If 75% of the absorption occurs within half of the duration, the total study duration should cover 4 halftimes. Four half-times will cover over 93% of the potential absorption, under normal exponential conditions. The bioavailability of the material remaining at the application site is considered to be minimal i.e absorption =excreta + CO2 / volatiles + carcass In this study, there is no sampling at 50% duration i.e. 36 hours, however the approach outlined in the HSE rationale can be represented graphically (Figure A 1) and a best fit equation generated to allow estimation of the theoretical % absorption for anytime point. Figure A 1: Absorption as a percentage of study duration For the 48 hour time point, the % absorption using the best fit equation would equate to 83% at 48 hours. The experimental data at 48 hours and at the end of the study (72 hours) were 0.26% and 0.29% respectively, which equates to 90% completion of absorption at 48 hours. Therefore, the application site can be excluded and a dermal absorption value of 0.3% is applicable. Conclusions/end-points (compulsory) In the absence of any value being already assigned for the absorption of florasulam from GF-2463 the study for EF-1343 has been evaluated in terms of the most recent review supplied to the EFSA PPR panel. Scientific report - Proposal for a Revision of the Guidance on Dermal absorption April The Notifier proposes a single value of 0.4% dermal absorption is appropriate for the absorption of florasulam from GF-2463 and the associated spray solution. Page 25 / 44

135 GF /00 Part B Section 3 - Core Assessment zrms version Comments of zrms The study is accepted for the assessment of the dermal absorption. The results of the study have been reported correctly and completely. Based on the study results, the appropriate dermal absorption values for exposure to the formulation and spray dilution are 12%. Percentage of radiochemical material remaining in the treated skin is included. This is in accordance with the evaluation of the EU (Florasulam SANCO/1406/2001 final 18 September 2002) A Comparative dermal absorption, in vitro, using rat and human skin Report: KIIIA /01, XXXXX (2007) Title: Document No: In Vitro Percutaneous Absorption of [14C]clopyralid Formulated as EF and Field Dilutions Through Human Skin Membranes Using Flow- Through Diffusion Cells XXXXX Report No. XXXXX, dated 1 March 2007 (unpublished) Guidelines: OECD 428 (adopted 13 th April 2004) Deviations from guideline: None GLP BfR Document No. Yes ASB The dermal absorption of clopyralid formulated as a soluble concentrate (EF-1136) was determined using an in vitro percutaneous study with [14C] clopyralid and human skin membrane. The percutaneous absorption was determined for the concentrated formulation, 97.5 g/l (group A), and at two concentrations g/l (group B), g/l (group C), recommended for use in the field. These concentrations equate to a skin surface dose of µg/cm, µg/cm and µg/cm, respectively. The objective of the study was to elucidate the extent of percutaneous absorption of clopyralid defined as compound-related radioactivity. The contact time was 8 hours, i.e. a normal working day and the postexposure time was 16 hours. In addition to the amount of [14C] clopyralid in the receptor fluid, the residues remaining in/on the skin membranes and in the stratum corneum (16 h post exposure) were determined. The study was performed in flow-through diffusion cells. Human skin membranes were prepared from three separate donors. After thawing of the skin, human skin was dermatomed using a Dermatome 25 mm (Nouvag GmbH, Germany). The thickness of the skin membranes were measured with a digimatic micrometer (Mitutoyo Corporatio, Japan). The mean thickness of the skin membranes that were assessed for skin integrity was found to be 0.606±0.096 mm. The solubility of clopyralid in the receptor fluid (saline containing 6% polyoxyethylene 20-oleyl ether (w/v)) is considered to meet the requirements of the OECD guideline. The water solubility of clopyralid is ca. 100 g/l, while the highest dose of Clopyralid is 640 µg; 100% absorption of the test compound over 24h would mean 640 µg clopyralid in 36 ml of receptor fluid, i.e mg/l. The integrity of the skin membranes was assessed using tritiated water. Only skin membranes with a permeability coefficient (Kp) of less than 2.5 x 10-3 cm/h were used. The percutaneous absorption of clopyralid was assessed using the test groups shown in the Table A 10. Page 26 / 44

136 GF /00 Part B Section 3 - Core Assessment zrms version Table A 10: Summary of dermal absorption following application of formulation and spray dilution of EF-1136 to human skin Test group Species Group size Nominal concentration Dose * Exposure time Sampling of receptor fluid A Human g.l µg.cm h 0-24 h B Human g.l µg.cm h 0-24 h C Human g.l µg.cm h 0-24 h * 6.4 µl of the solution was applied on each skin membrane (0.64 cm 2 ) The exposure time was 8 hours (i.e. equivalent to a normal working day) and the post-exposure time was 16 hours. Eight hours after application, skin was rinsed with 3% Teepol followed by 6 cotton swabs. After the 24 h sample, each skin membrane was dried with two additional dry cotton swabs. Each skin membrane was tape-stripped using D-squame (Monoderm, Monaco) tape. The first two tape strips were collected and counted separately and subsequent tape strips were collected and pooled in groups of three until the epidermis was reached or to a maximum of 20 tape strips. The last tape strip was counted separately. The remaining skin was digested in 5 ml of a 1.5 M KOH solution containing 20% ethanol. The flow cells were dismantled and washed with ethanol. All samples were analysed by liquid scintillation counting to determine the amount of clopyralid present and the overall study mass balance. The mean total absorption expressed as the percentage of the applied dose can be summarized as in Tables A 11 and A 12. A summary of the dermal absorption is provided in Table A 13. Table A 11: Results expressed as percentage of the applied dose Mean percentage (plus SD) of applied dose at termination of the study: Receptor fluid + receptor compartment 1.67 (1.36) 0.69 (0.24) 0.61 (0.20) wash Donor compartment 0.35 (0.38) 0.61 (0.95) 0.26 (0.05) Tape strips (excl. tape strip 1 and 2) 0.96 (0.98) 1.60 (1.20) 1.36 (0.60) Cotton swabs + tape strip 1 and (4.29) (4.11) (8.71) Skin 0.69 (0.36) 2.09 (1.75) 0.87 (0.71) Total recovery 90.0 (3.2) 90.0 (1.5) 97.9 (8.7) Total absorption * 2.36 (1.47) 2.78 (1.91) 1.48 (0.87) * Total absorption defined as amount in receptor fluid and skin membrane, excluding tape-strips Page 27 / 44

137 GF /00 Part B Section 3 - Core Assessment zrms version Table A 12: Results expressed as percentage of the applied dose Dose [µg/cm 2 ] Potential absorption ** [%] ** Potential absorption defined as amount in receptor fluid, tape strips (excl. tape strip 1 and 2) and skin membrane Table A 13: Summary of dermal absorption following application of formulation and spray dilution of EF-1136 to human skin Group A B C Concentration [g.l -1 ] Dose [µg.cm -2 ] n Penetration into the receptor fluid after 24 h % of dose µg.cm - 2 % of dose µg.cm - 2 % of dose µg.cm Maximum flux [µg.cm -2.h -1 ] Lag time [h] Actual total absorption * [% of dose] * Total absorption defined as amount in receptor fluid and skin membrane, excluding tape-strips The mean maximum fluxes for the absorption of clopyralid through human skin were µg/cm/h (group A), µg/cm/h (group B) and µg/cm/h (group C). Extrapolation of the maximum flux over 24 hours would result in predicted dermal absorption values of 3.67% for the concentrated formulation and 2.51% and 2.33% for the spray dilution. However, the mean total absorption, expressed as the radioactivity present in the receptor fluid, the receptor compartment wash and the skin (excluding tape strips), was 2.36% for the concentrated formulation and 2.78% and 1.48% for the spray dilution. The absorption profiles are presented in the following figures A 2 A 4 and indicate that the rate of absorption had decreased significantly after ca. 12 hours and, in some cases, had ceased. Figure A 2: Cumulative penetration of Clopyralid (950.2 µg.cm -2 ) through human skin (group A, 97.5 mg.ml -1 ) Cumulative absorption (µg/cm 2 ) Time (h) A1 A2 A3 A4 A5 A6 Page 28 / 44

138 GF /00 Part B Section 3 - Core Assessment zrms version Figure A 3: Cumulative penetration of Clopyralid (24.10 µg.cm -2 ) through human skin (group B, mg.ml -1 ) Cumulative absorption (µg/cm 2 ) Time (h) B1 B2 B3 B4 B5 B6 Figure A 4: Cumulative penetration of Clopyralid (2.235 µg.cm -2 ) through human skin (group C, mg.ml -1 ) Cumulative absorption (µg/cm 2 ) C1 C C C C C Time (h) The residue remaining in the stratum corneum (tape strip fraction) has been excluded from the amount absorbed on the basis of the opinion of the Scientific Committee on Plants (2002). Moreover, results of this present study suggest that most of the residue present in the stratum corneum will be lost by desquamation in the real life situation. The amount of radioactivity recovered from the tape strips generally decreased in each preparation from the surface to the interface with the skin (epidermis). The percentage of radioactivity recovered from the last tape strip ranged from 0.01 to 0.15% of the applied dose (group A), from 0.03 to 0.16% of the applied dose (group B) and from 0.02 to 0.30% of the last dose (group C). It is striking that 16 hours after removal of the test compound, the percentage of test compound in the stratum corneum is in the same order of magnitude as the percentage of test compound found in the rest of the skin membrane. This suggests high affinity of the test compound for the stratum corneum, and therefore only minimal relocation of the test compound from the stratum corneum to the deeper skin layers. In conclusion, the measured dermal absorption, based on the amount of clopyralid found in the receptor fluid and the skin (excluding tape strips) was found to be 2.36% (group A), 2.78% (group B) and 1.48% (group C). The notifier proposes values of 2.4 % for the formulation and 2.8% for spray dilutions. These values are considered appropriate as GF-2463 contains a higher concentration of clopyralid that EF-1136 and therefore, as % absorption is inversely related to concentration, this value is conservative. Similarly a lower concentration of clopyralid spray solution was examined for EF-1136 compared to the higher spray solution concentrations for the use of GF Page 29 / 44

139 GF /00 Part B Section 3 - Core Assessment zrms version Comments of zrms The study is accepted for the assessment of the dermal absorption. The results of the study have been reported correctly and completely. Based on the study results, the appropriate dermal absorption value for exposure to the formulation and spray dilution is 4% for the concentrate and dilutions (applied dose appr µg/cm 2 ). Percentage of radiochemical material remaining in the treated skin is included because the absorption was not essentially complete at the end of the study in all cases. Absorption is defined as amount in receptor fluid, tape strips (excl. tape strip 1 and 2) and skin membrane (Table A 12). Furthermore, results of absorption were not consistent concerning the applied doses. Hence, a rounded value for dermal absorption is considered to be an appropriate value for the dermal absorption of Clopyralid. A 2.11 Other/Special Studies Not available, not necessary. Page 30 / 44

140 GF /00 Part B Section 3 - Core Assessment zrms version Appendix 3 Exposure Calculations A 3.1 A Exposure Calculations for the Active Substance Clopyralid Operator exposure calculations using the German model Input parameters considered for the estimation of operator exposure: Formulation type: Liquid Application Field Crops, Tractor Application rate (AR): 0.06 kg a.s./ha technique: Mounted (FCTM) Area treated per day (A): 20 ha Dermal hands m/l 2.4 mg/person/kg (D M(H) ): a.s. Dermal absorption (DA): 4 % (concentr.) Dermal hands appl mg/person/kg (D A(H) ): a.s. 4 % (dilution) Dermal body appl. 1.6 mg/person/kg (D A(B) ): a.s. Inhalation absorption (IA): 100 % Dermal head appl mg/person/kg (D A(C) ): a.s. Body weight (BW): 70 kg/person Inhalation m/l (I M ): mg/person/kg AOEL 1 mg/kg bw/d Inhalation appl. (I A ): a.s mg/person/kg a.s. Operator exposure towards clopyralid Without PPE With PPE Operators: Systemic dermal exposure after application in various cereals Dermal exposure during mixing/loading Hands Hands SDE OM(H) = (D M(H) x AR x A x DA) / BW SDE OM(H) = (D M(H) x AR x A x PPE 1) x DA) / BW (2.4 x 0.06 x 20 x 4%) / 70 (2.4 x 0.06 x 20 x 0.01 x 4%) / 70 External dermal exposure 2.88 mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Dermal exposure during application Hands Hands SDE OA(H) = (D A(H) x AR x A x DA) / BW SDE OA(H) = (D A(H) x AR x A x PPE x DA) / BW (0.38 x 0.06 x 20 x 4%) / 70 (0.38 x 0.06 x 20 x 1 x 4%) / 70 External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Body Body SDE OA(B) = (D A(B) x AR x A x DA) / BW SDE OA(B) = (D A(B) x AR x A x PPE x DA) / BW (1.6 x 0.06 x 20 x 4%) / 70 (1.6 x 0.06 x 20 x 1 x 4%) / 70 External dermal exposure 1.92 mg/person External dermal exposure 1.92 mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Page 31 / 44

141 GF /00 Part B Section 3 - Core Assessment zrms version Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Head Head SDE OA(C) = (D A(C) x AR x A x DA) / BW SDE OA(C) = (D A(C) x AR x A x PPE x DA) / BW (0.06 x 0.06 x 20 x 4%) / 70 (0.06 x 0.06 x 20 x 1 x 4%) / 70 External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Total systemic dermal exposure: SDE O = SDE OM(H) + SDE OA(H) + SDE OA(B) + SDE OA(C) Total systemic dermal exposure: SDE O = SDE OM(H) + SDE OA(H) + SDE OA(B) + SDE OA(C) Total external dermal exposure Total external dermal exposure mg/person mg/kg bw/d Total external dermal exposure Total external dermal exposure mg/person mg/kg bw/d Total systemic dermal exposure mg/kg bw/d Total systemic dermal exposure mg/kg bw/d Operators: Systemic inhalation exposure after application in various cereals Inhalation exposure during mixing/loading SIE OM = (I M x AR x A x IA) / BW SIE OM = (I M x AR x A x PPE x IA) / BW ( x 0.06 x 20 x 100%) / 70 ( x 0.06 x 20 x 1 x 100%) / 70 External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Inhalation exposure during application SIE OA = (I A x AR x A x IA) / BW SIE OA = (I A x AR x A x PPE x IA) / BW (0.001 x 0.06 x 20 x 100%) / 70 (0.001 x 0.06 x 20 x 1 x 100%) / 70 External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Total systemic inhalation exposure: SIE O = SIE OM + SIE OA Total systemic inhalation exposure: SIE O = SIE OM + SIE OA Total external inhalation exposure mg/person Total external inhalation exposure mg/person Total external inhalation exposure Total systemic inhalation exposure mg/kg bw/d mg/kg bw/d Total external inhalation exposure Total systemic inhalation exposure mg/kg bw/d mg/kg bw/d Total systemic exposure: SE O = SDE O + SIE O Total systemic exposure: SE O = SDE O + SIE O Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 0.3 % % of AOEL 0.1 % 1) reduction factor for gloves is 0.01 (professional appl.) Page 32 / 44

142 GF /00 Part B Section 3 - Core Assessment zrms version A Operator exposure calculations using the UK POEM Without PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance Clopyralid Product GF-2463 Formulation type water-based Concentration of a.s. 300 mg/ml Dose 0.2 L preparation/ha (0.06 kg a.s./ha) Application volume 200 L/ha Application method Tractor-mounted/trailed boom sprayer: hydraulic nozzles Container 10 litres 45 mm closure Work rate/day 50 ha Duration of spraying 6 h PPE during mix./loading None PPE during application None Dermal absorption from product 4 % Dermal absorption from spray 4 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0.1 ml Application dose 0.2 Litres product/ha Work rate 50 ha/day Number of operations 1 /day Hand contamination 0.10 ml/day Protective clothing None Transmission to skin 100 % Dermal exposure to formulation 0.10 ml/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed boom sprayer: hydraulic nozzles Application volume 200 L spray/ha Volume of surface contamination 10 ml/h Distribution Hands Trunk Legs 65% 10% 25% Clothing None Permeable Permeable Penetration 100% 5% 15% Dermal exposure ml/h Duration of exposure 6 h Total dermal exposure to spray ml/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure 0.10 ml/day ml/day Concen. of a.s. product or spray mg/ml 0.30 mg/ml Dermal exposure to a.s mg/day mg/day Percent absorbed 4 % 4 % Absorbed dose 1.20 mg/day mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 ml/h Duration of exposure 6 h Concentration of a.s. in spray mg/ml Inhalation exposure to a.s mg/day Percent absorbed 100 % Absorbed dose mg/day PREDICTED EXPOSURE Total absorbed dose mg/day Page 33 / 44

143 GF /00 Part B Section 3 - Core Assessment zrms version Operator body weight 60 kg Operator exposure mg/kg bw/day Amount of AOEL 2.9 % With PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance Clopyralid Product GF-2463 Formulation type water-based Concentration of a.s. 300 mg/ml Dose 0.2 L preparation/ha (0.06 kg a.s./ha) Application volume 200 L/ha Application method Tractor-mounted/trailed boom sprayer: hydraulic nozzles Container 10 litres 45 mm closure Work rate/day 50 ha Duration of spraying 6 h PPE during mix./loading Gloves PPE during application None Dermal absorption from product 4 % Dermal absorption from spray 4 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0.1 ml Application dose 0.2 Litres product/ha Work rate 50 ha/day Number of operations 1 /day Hand contamination 0.10 ml/day Protective clothing Gloves Transmission to skin 5 % Dermal exposure to formulation ml/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed boom sprayer: hydraulic nozzles Application volume 200 L spray/ha Volume of surface contamination 10 ml/h Distribution Hands Trunk Legs 65% 10% 25% Clothing None Permeable Permeable Penetration 100% 5% 15% Dermal exposure ml/h Duration of exposure 6 h Total dermal exposure to spray ml/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure ml/day ml/day Concen. of a.s. product or spray mg/ml 0.30 mg/ml Dermal exposure to a.s mg/day mg/day Percent absorbed 4 % 4 % Absorbed dose 0.06 mg/day mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 ml/h Duration of exposure 6 h Concentration of a.s. in spray 0.30 mg/ml Inhalation exposure to a.s mg/day Percent absorbed 100 % Absorbed dose mg/day PREDICTED EXPOSURE Page 34 / 44

144 GF /00 Part B Section 3 - Core Assessment zrms version Total absorbed dose mg/day Operator body weight 60 kg Operator exposure mg/kg bw/day Amount of AOEL 1.0 % A Worker exposure calculations Input parameters considered for the estimation of worker exposure: Dislodgeable foliar residues 1 µg/cm 2 /kg Intended use(s): various cereals (DFR): a.s. Application rate (AR): 0.06 kg a.s./ha Transfer coefficient (TC): 1500 cm 2 /person/h Number of applications (NA): 1 Work rate per day (WR): 2 h/d Body weight (BW): 60 kg/person PPE 5 % Dermal absorption (DA): 4 % ('worst case') AOEL 1 mg/kg bw/d Worker exposure towards clopyralid Without PPE Worker (re-entry): Systemic dermal exposure after application in var. cereals SDE W = (DFR x TC x WR x AR x NA x DA) / BW With PPE SDE W = (DFR x TC x WR x AR x NA x PPE x DA) / BW (1 x 1500 x 2 x 0.06 x 1 x 4%) / 60 (1 x 1500 x 2 x 0.06 x 1 x 5% x 4%) / 60 External dermal exposure 0.18 mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL % % of AOEL % A Bystander and resident exposure calculations Estimation of bystander exposure towards clopyralid during/after application in Field Crops, Tractor Mounted (FCTM) Input parameters considered for the estimation of bystander exposure: Intended use(s): various cereals Drift (D): 2.77 % (FC, 1 m) 0.06 kg a.s./ha Exposed body surface 1 m² (adults) Application rate (AR): 6 mg/m 2 area (BSA): 0.21 m² (children) Body weight (BW): 60 kg/person (adults) kg/person (children) Dermal absorption (DA): 4 % ('worst case') Inhalation absorption (IA): 100 % AOEL: Bystander exposure towards clopyralid 1 mg/kg bw/d Specific Inhalation Exposure (I* A ): Area Treated (A): Exposure duration (T): mg/kg a.s. (6 h, adults) mg/kg a.s. (6 h, children) ha/d (based on 20 FCTM) 5 min Page 35 / 44

145 GF /00 Part B Section 3 - Core Assessment zrms version Adults Children Bystander: Systemic dermal exposure during/after application in (via spray drift) SDE B = (AR x D x BSA x DA) / BW SDE B = (AR x D x BSA x DA) / BW (6 x 2.77 % x 1 x 4 %) / 60 (6 x 2.77 % x 0.21 x 4 %) / External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Bystander: Systemic inhalation exposure during/after application in var. cereals (via spray drift) SIE B = (I* A x AR x A x T x IA) / BW SIE B = (I* A x AR x A x T x IA) / BW (0.001 / 360 x 0.06 x 20 x 5 x 100%) / 60 ( / 360 x 0.06 x 20 x 5 x 100%) / External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Total systemic exposure: SE B = SDE B + SIE B Total systemic exposure: SE B = SDE B + SIE B Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL % % of AOEL % Estimation of resident exposure towards clopyralid during/after application in Field Crops, Tractor Mounted (FCTM) Input parameters considered for the estimation of resident exposure: Intended use(s): various cereals Drift (D): 2.77 % (FC, 1 m) Application rate (AR): 0.06 kg a.s./ha 7300 cm 2 /h (adults) Transfer coefficient mg/cm 2 (TC): 2600 cm2 /h (children) Number of applications (NA): 1 Turf Transferable Residues (TTR): 5 % 60 kg/person Exposure Duration (adults) (H): 2 h Body weight (BW): kg/person Airborne Concentration of (children) Vapour (ACV): mg/m 3 Dermal absorption (DA): 4 % ('worst case') m 3 /d (adults) Inhalation Rate (IR): Inhalation absorption (IA): 100 % 8.31 m 3 /d (children) Oral absorption (OA): 100 % AOEL: 1 mg/kg bw/d Saliva Extraction Factor (SE): Surface Area of Hands (SA): Frequency of Hand to Mouth (Freq): Dislodgeable foliar residues (DFR): Ingestion Rate for Mouthing of Grass/Day (IgR): 50 % 20 cm 2 20 events/h 20 % 25 cm 2 /d Page 36 / 44

146 GF /00 Part B Section 3 - Core Assessment zrms version Resident exposure towards clopyralid Adults Children Residents: Systemic dermal exposure after application in var. cereals (via deposits caused by spray drift) SDE R = (AR x NA x D x TTR x TC x H x DA) / BW SDE R = (AR x NA x D x TTR x TC x H x DA) / BW ( x 1 x 2.77 % x 5% x 7300 x 2 x 4%) / 60 ( x 1 x 2.77 % x 5% x 2600 x 2 x 4%) / External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Residents: Systemic inhalation exposure after application in var. cereals (via vapour) SIE R = (AC V x IR x IA) / BW SIE R = (AC V x IR x IA) / BW (0.001 x x 100%) / 60 (0.001 x 8.31 x 100%) / External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Residents: Systemic oral exposure (hand-to-mouth transfer) SOE R(H) = (AR x NA x D x TTR x SE x SA x Freq x H x OA) / BW ( x 1 x 2.77 % x 5 % x 50 % x 20 x 20 x 2 x 100 %) / External oral exposure mg/person External oral exposure mg/kg bw/d Systemic oral exposure mg/kg bw/d Residents: Systemic oral exposure (object-tomouth transfer) SOE R(O) = (AR x NA x D x DFR x IgR x OA) / BW ( x 1 x 2.77 % x 20 % x 25 x 100 %) / External oral exposure mg/person External oral exposure mg/kg bw/d Systemic oral exposure mg/kg bw/d Total systemic exposure: SE R = SDE R + SIE R Total systemic exposure: SE R = SDE R + SIE R + SOE R(H) + SOE R(O) Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 0.03 % % of AOEL 0.06 % A 3.2 A Exposure Calculations for the Active Substance Florasulam Operator exposure calculations using the German model Input parameters considered for the estimation of operator exposure: Formulation type: Liquid Application Field Crops, Tractor Page 37 / 44

147 GF /00 Part B Section 3 - Core Assessment zrms version Application rate (AR): kg a.s./ha technique: Mounted (FCTM) Dermal hands m/l Area treated per day (A): 20 ha 2.4 mg/person/kg (D M(H) ): a.s. Dermal hands appl. 12 % (concentr.) 0.38 mg/person/kg (D A(H) ): a.s. Dermal absorption (DA): Dermal body appl. 12 % (dilution) 1.6 mg/person/kg (D A(B) ): a.s. Dermal head appl. Inhalation absorption (IA): 100 % 0.06 mg/person/kg (D A(C) ): a.s. Body weight (BW): 70 kg/person Inhalation m/l (I M ): mg/person/kg a.s. Inhalation appl. AOEL 0.05 mg/kg bw/d mg/person/kg (I A ): a.s. Operator exposure towards florasulam Without PPE With PPE Operators: Systemic dermal exposure after application in various cereals Dermal exposure during mixing/loading Hands Hands SDE OM(H) = (D M(H) x AR x A x DA) / BW SDE OM(H) = (D M(H) x AR x A x PPE 1) x DA) / BW (2.4 x x 20 x 12 %) / 70 (2.4 x x 20 x 0.01 x 12 %) / 70 External dermal exposure 0.24 mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Dermal exposure during application Hands Hands SDE OA(H) = (D A(H) x AR x A x DA) / BW SDE OA(H) = (D A(H) x AR x A x PPE x DA) / BW (0.38 x x 20 x 12 %) / 70 (0.38 x x 20 x 1 x 12 %) / 70 External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Body Body SDE OA(B) = (D A(B) x AR x A x DA) / BW SDE OA(B) = (D A(B) x AR x A x PPE x DA) / BW (1.6 x x 20 x 12 %) / 70 (1.6 x x 20 x 1 x 12 %) / 70 External dermal exposure 0.16 mg/person External dermal exposure 0.16 mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Head Head SDE OA(C) = (D A(C) x AR x A x DA) / BW SDE OA(C) = (D A(C) x AR x A x PPE x DA) / BW (0.06 x x 20 x 12 %) / 70 (0.06 x x 20 x 1 x 12 %) / 70 External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Page 38 / 44

148 GF /00 Part B Section 3 - Core Assessment zrms version Total systemic dermal exposure: SDE O = SDE OM(H) + SDE OA(H) + SDE OA(B) + SDE OA(C) Total external dermal exposure Total external dermal exposure mg/person mg/kg bw/d Total systemic dermal exposure: SDE O = SDE OM(H) + SDE OA(H) + SDE OA(B) + SDE OA(C) Total external dermal exposure Total external dermal exposure mg/person mg/kg bw/d Total systemic dermal exposure mg/kg bw/d Total systemic dermal exposure mg/kg bw/d Operators: Systemic inhalation exposure after application in various cereals Inhalation exposure during mixing/loading SIE OM = (I M x AR x A x IA) / BW SIE OM = (I M x AR x A x PPE x IA) / BW ( x x 20 x 100%) / 70 ( x x 20 x 1 x 100%) / 70 External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Inhalation exposure during application SIE OA = (I A x AR x A x IA) / BW SIE OA = (I A x AR x A x PPE x IA) / BW (0.001 x x 20 x 100%) / 70 (0.001 x x 20 x 1 x 100%) / 70 External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Total systemic inhalation exposure: SIE O = SIE OM + SIE OA Total systemic inhalation exposure: SIE O = SIE OM + SIE OA Total external inhalation exposure mg/person Total external inhalation exposure mg/person Total external inhalation exposure Total systemic inhalation exposure mg/kg bw/d mg/kg bw/d Total external inhalation exposure Total systemic inhalation exposure mg/kg bw/d mg/kg bw/d Total systemic exposure: SE O = SDE O + SIE O Total systemic exposure: SE O = SDE O + SIE O Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 1.5 % % of AOEL 0.7 % 1) reduction factor for gloves is 0.01 (professional appl.) A Operator exposure calculations using the UK POEM Without PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance Florasulam Product GF-2463 Formulation type water-based Concentration of a.s. 25 mg/ml Page 39 / 44

149 GF /00 Part B Section 3 - Core Assessment zrms version Dose 0.2 L preparation/ha (0.005 kg a.s./ha) Application volume 200 L/ha Application method Tractor-mounted/trailed boom sprayer: hydraulic nozzles Container 10 litres 45 mm closure Work rate/day 50 ha Duration of spraying 6 h PPE during mix./loading None PPE during application None Dermal absorption from product 12 % Dermal absorption from spray 12 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0.1 ml Application dose 0.2 Litres product/ha Work rate 50 ha/day Number of operations 1 /day Hand contamination 0.10 ml/day Protective clothing None Transmission to skin 100 % Dermal exposure to formulation 0.10 ml/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed boom sprayer: hydraulic nozzles Application volume 200 L spray/ha Volume of surface contamination 10 ml/h Distribution Hands Trunk Legs 65% 10% 25% Clothing None Permeable Permeable Penetration 100% 5% 15% Dermal exposure ml/h Duration of exposure 6 h Total dermal exposure to spray ml/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure 0.10 ml/day ml/day Concen. of a.s. product or spray mg/ml mg/ml Dermal exposure to a.s mg/day mg/day Percent absorbed 12 % 12 % Absorbed dose 0.3 mg/day mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 ml/h Duration of exposure 6 h Concentration of a.s. in spray mg/ml Inhalation exposure to a.s mg/day Percent absorbed 100 % Absorbed dose mg/day PREDICTED EXPOSURE Total absorbed dose mg/day Operator body weight 60 kg Operator exposure mg/kg bw/day Amount of AOEL 14.2 % With PPE THE UK PREDICTIVE OPERATOR EXPOSURE MODEL (POEM) Active substance Florasulam Product GF-2463 Formulation type water-based Page 40 / 44

150 GF /00 Part B Section 3 - Core Assessment zrms version Concentration of a.s. 25 mg/ml Dose 0.2 L preparation/ha (0.005 kg a.s./ha) Application volume 200 L/ha Application method Tractor-mounted/trailed boom sprayer: hydraulic nozzles Container 10 litres 45 mm closure Work rate/day 50 ha Duration of spraying 6 h PPE during mix./loading Gloves PPE during application None Dermal absorption from product 12 % Dermal absorption from spray 12 % EXPOSURE DURING MIXING AND LOADING Container size 10 Litres Hand contamination/operation 0.1 ml Application dose 0.2 Litres product/ha Work rate 50 ha/day Number of operations 1 /day Hand contamination 0.10 ml/day Protective clothing Gloves Transmission to skin 5 % Dermal exposure to formulation ml/day DERMAL EXPOSURE DURING SPRAY APPLICATION Application technique Tractor-mounted/trailed boom sprayer: hydraulic nozzles Application volume 200 L spray/ha Volume of surface contamination 10 ml/h Distribution Hands Trunk Legs 65% 10% 25% Clothing None Permeable Permeable Penetration 100% 5% 15% Dermal exposure ml/h Duration of exposure 6 h Total dermal exposure to spray ml/day ABSORBED DERMAL DOSE Mix/load Application Dermal exposure ml/day ml/day Concen. of a.s. product or spray mg/ml mg/ml Dermal exposure to a.s mg/day mg/day Percent absorbed 12 % 12 % Absorbed dose mg/day mg/day INHALATION EXPOSURE DURING SPRAYING Inhalation exposure 0.01 ml/h Duration of exposure 6 h Concentration of a.s. in spray mg/ml Inhalation exposure to a.s mg/day Percent absorbed 100 % Absorbed dose mg/day PREDICTED EXPOSURE Total absorbed dose mg/day Operator body weight 60 kg Operator exposure mg/kg bw/day Amount of AOEL 4.7 % A Worker exposure calculations Input parameters considered for the estimation of worker exposure: Page 41 / 44

151 GF /00 Part B Section 3 - Core Assessment zrms version Intended use(s): various cereals Dislodgeable foliar residues (DFR): 1 µg/cm 2 /kg a.s. Application rate (AR): kg a.s./ha Transfer coefficient (TC): 1500 cm 2 /person/h Number of applications (NA): 1 Work rate per day (WR): 2 h/d Body weight (BW): 60 kg/person PPE 5 % Dermal absorption (DA): 12 % ('worst case') AOEL 0.05 mg/kg bw/d Worker exposure towards florasulam Without PPE With PPE Worker (re-entry): Systemic dermal exposure after application in var. cereals SDE W = (DFR x TC x WR x AR x NA x DA) / BW SDE W = (DFR x TC x WR x AR x NA x PPE x DA) / BW (1 x 1500 x 2 x x 1 x 12 %) / 60 (1 x 1500 x 2 x x 1 x 5 % x 12 %) / 60 External dermal exposure 0.02 mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 0.06 % % of AOEL % A Bystander and resident exposure calculations Estimation of bystander exposure towards florasulam during/after application in Field Crops, Tractor Mounted (FCTM) Input parameters considered for the estimation of bystander exposure: Intended use(s): various cereals Drift (D): 2.77 % (FC, 1 m) kg a.s./ha Exposed body surface 1 m² (adults) Application rate (AR): 6 mg/m 2 area (BSA): 0.21 m² (children) Body weight (BW): 60 kg/person (adults) kg/person (children) Dermal absorption (DA): 12 % ('worst case') Inhalation absorption (IA): 100 % AOEL: Bystander exposure towards florasulam Adults 0.05 mg/kg bw/d Specific Inhalation Exposure (I* A ): Area Treated (A): Exposure duration (T): Children mg/kg a.s. (6 h, adults) mg/kg a.s. (6 h, children) ha/d (based on 20 FCTM) 5 min Bystander: Systemic dermal exposure during/after application in (via spray drift) SDE B = (AR x D x BSA x DA) / BW SDE B = (AR x D x BSA x DA) / BW (0.5 x 2.77 % x 1 x 12 %) / 60 (0.5 x 2.77 % x 0.21 x 12 %) / External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Page 42 / 44

152 GF /00 Part B Section 3 - Core Assessment zrms version Bystander: Systemic inhalation exposure during/after application in var. cereals (via spray drift) SIE B = (I* A x AR x A x T x IA) / BW SIE B = (I* A x AR x A x T x IA) / BW (0.001 / 360 x x 20 x 5 x 100 %) / 60 ( / 360 x x 20 x 5 x 100%) / External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Total systemic exposure: SE B = SDE B + SIE B Total systemic exposure: SE B = SDE B + SIE B Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 0.06 % % of AOEL 0.04 % Estimation of resident exposure towards florasulam during/after application in Field Crops, Tractor Mounted (FCTM) Input parameters considered for the estimation of resident exposure: Intended use(s): various cereals Drift (D): 2.77 % (FC, 1 m) Application rate (AR): kg a.s./ha 7300 cm 2 /h (adults) Transfer coefficient mg/cm 2 (TC): 2600 cm2 /h (children) Number of applications (NA): 1 Turf Transferable Residues (TTR): 5 % 60 kg/person Exposure Duration (adults) (H): 2 h Body weight (BW): kg/person Airborne Concentration of (children) Vapour (ACV): mg/m 3 Dermal absorption (DA): 12 % ('worst case') m 3 /d (adults) Inhalation Rate (IR): Inhalation absorption (IA): 100 % 8.31 m 3 /d (children) Oral absorption (OA): 100 % AOEL: 0.05 mg/kg bw/d Saliva Extraction Factor (SE): Surface Area of Hands (SA): Frequency of Hand to Mouth (Freq): Dislodgeable foliar residues (DFR): Ingestion Rate for Mouthing of Grass/Day (IgR): 50 % 20 cm 2 20 events/h 20 % 25 cm 2 /d Resident exposure towards florasulam Adults Children Residents: Systemic dermal exposure after application in var. cereals (via deposits caused by spray drift) SDE R = (AR x NA x D x TTR x TC x H x DA) / BW SDE R = (AR x NA x D x TTR x TC x H x DA) / BW ( x 1 x 2.77 % x 5 % x 7300 x 2 x 12 %) / 60 ( x 1 x 2.77 % x 5 % x 2600 x 2 x 12 %) / External dermal exposure mg/person External dermal exposure mg/person External dermal exposure mg/kg bw/d External dermal mg/kg bw/d Page 43 / 44

153 GF /00 Part B Section 3 - Core Assessment zrms version exposure Systemic dermal exposure mg/kg bw/d Systemic dermal exposure mg/kg bw/d Residents: Systemic inhalation exposure after application in var. cereals (via vapour) SIE R = (AC V x IR x IA) / BW SIE R = (AC V x IR x IA) / BW (0.001 x x 100%) / 60 (0.001 x 8.31 x 100%) / External inhalation exposure mg/person External inhalation exposure mg/person External inhalation exposure mg/kg bw/d External inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Systemic inhalation exposure mg/kg bw/d Residents: Systemic oral exposure (hand-to-mouth transfer) SOE R(H) = (AR x NA x D x TTR x SE x SA x Freq x H x OA) / BW ( x 1 x 2.77 % x 5% x 50% x 20 x 20 x 2 x 100%) / External oral exposure mg/person External oral exposure mg/kg bw/d Systemic oral exposure mg/kg bw/d Residents: Systemic oral exposure (object-tomouth transfer) SOE R(O) = (AR x NA x D x DFR x IgR x OA) / BW ( x 1 x 2.77 % x 20% x 25 x 100%) / External oral exposure mg/person External oral exposure mg/kg bw/d Systemic oral exposure mg/kg bw/d Total systemic exposure: SE R = SDE R + SIE R Total systemic exposure: SE R = SDE R + SIE R + SOE R(H) + SOE R(O) Total systemic exposure mg/person Total systemic exposure mg/person Total systemic exposure mg/kg bw/d Total systemic exposure mg/kg bw/d % of AOEL 0.56 % % of AOEL 1.04 % Page 44 / 44

154 GF /00 Part B Section 4 - Core Assessment zrms version REGISTRATION REPORT Part B Section 4: Metabolism and Residues Detailed summary of the risk assessment Product code: GF-2463 Clopyralid: Florasulam: 300 g/kg 25 g/kg Central Zone Zonal Rapporteur Member State: Germany CORE ASSESSMENT Applicant: DOW Agroscience Date: October 2012 Page 1 / 17

155 GF /00 Part B Section 4 - Core Assessment zrms version Table of Contents IIIA 8 METABOLISM AND RESIDUES DATA...3 IIIA 8.1 Evaluation of the active substances...3 IIIA Clopyralid...3 IIIA Storage stability...3 IIIA Metabolism in plants and plant residue definition(s)...3 IIIA Metabolism in livestock and animal residue definition(s)...4 IIIA Residues in rotational crops...5 IIIA Residues in livestock...5 IIIA Florasulam...6 IIIA Storage stability...6 IIIA Metabolism in plants and plant residue definition(s)...6 IIIA Metabolism in livestock and animal residue definition(s)...7 IIIA Residues in rotational crops...8 IIIA Residues in livestock...8 IIIA 8.2 Evaluation of the intended use(s)...8 IIIA Selection of critical use and justification...8 IIIA Cereals...10 IIIA Residues in primary crops...10 IIIA Distribution of the residue in peel/pulp...10 IIIA Residues in processed commodities...11 IIIA Proposed pre-harvest intervals, withholding periods...11 IIIA 8.3 Consumer intake and risk assessment...11 IIIA Clopyralid...11 IIIA Florasulam...11 IIIA 8.4 Proposed maximum residue levels (MRLs)...12 IIIA 8.5 Conclusion...12 Appendix 1 List of data submitted in support of the evaluation...13 Appendix 2 Detailed evaluation of the additional studies relied upon...15 A 2.1 Storage stability...15 A 2.2 Residues in primary crops...15 A 2.3 Residues in processed commodities...15 A 2.4 Residues in rotational crops...15 A 2.5 Residues in livestock...15 A 2.6 Other studies/information...15 Appendix 3 Pesticide Residue Intake Model (PRIMo)...16 Page 2 / 17

156 GF /00 Part B Section 4 - Core Assessment zrms version IIIA 8 IIIA 8.1 METABOLISM AND RESIDUES DATA Evaluation of the active substances IIIA Clopyralid Table IIIA 8.1-1: Identity of the active substance Structural formula Cl Cl N COOH Common Name Clopyralid CAS number IIIA Storage stability A brief summary of the storage stability data on clopyralid is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR by Finland (ASB ) and the EFSA Conclusion on the peer review of clopyralid (ASB ). Table IIIA 8.1-2: Stability of residues (Annex IIA, point 6.1) Stability of clopyralid Maize fodder, grain and forage (RIP ): stable for 12 months Pasture (RIP ): stable for 18 months According to the EFSA conclusion on the peer review (ASB ), clopyralid was also stable in oil containing plant materials for 18 months. IIIA Metabolism in plants and plant residue definition(s) A brief summary of the metabolism of clopyralid in plants is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR by Finland (ASB ) and the EFSA Conclusion on the peer review of clopyralid (ASB ). Table IIIA 8.1-3: Metabolism in plants (Annex IIA, point 6.2.1; 6.5.1, 6.5.2, and 6.7.1) Plant groups covered Foliar spray applications to sugar beet (300 g as/ha, RIP ), oilseed rape (300 g as/ha, BBCH 36, RIP ) and cabbage (420 g as/ha, BBCH 18-20, RIP ) No extensive metabolism occurred in the crops studied and clopyralid (including its anionic form) was the major component of the residue. Conjugated clopyralid was present at low levels in beet shoots (ca 1% TRR), but at levels of 18-30% TRR in oilseed rape matrices. All clopyralid fractions together accounted for % of TRR with free clopyralid as major component. No significant metabolites were detected. Page 3 / 17

157 GF /00 Part B Section 4 - Core Assessment zrms version Rotational crops Metabolism in rotational crops similar to metabolism in primary crops? (yes/no) Distribution of the residue in peel/ pulp Processed commodities (nature of residue) Residue pattern in raw and processed commodities similar? (yes/no) Plant residue definition for monitoring Wheat, soybeans and sugar beet were planted as rotational crops following wheat which received an application of 2x 0.91 kg as/ha (RIP ). At harvest residues in all matrices of rotational crops were < 0.01 mg as-eq/kg. The same result was obtained in a further study with the rotational crops witloof and broad beans being planted after sugar beet (RIP ). yes Not applicable A nature of the residue study under typical processing conditions was not available. 14 C-clopyralid was stable to hydrolysis during 5 days at 50 C in natural water and at ph 4, 7 and 9 in buffered systems (see DAR, ASB ). yes Regulation (EC) No 396/2005 and BfR proposal: clopyralid Plant residue definition for risk assessment Conversion factor(s) (monitoring to risk assessment) none Outcome of the peer review according to 91/414/EEC: clopyralid including its salts and conjugates, expressed as clopyralid clopyralid including its salts and conjugates, expressed as clopyralid IIIA Metabolism in livestock and animal residue definition(s) A brief summary of the metabolism of clopyralid in livestock is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR by Finland (ASB ) and the EFSA Conclusion on the peer review of clopyralid (ASB ). Table IIIA 8.1-4: Metabolism in livestock (Annex IIA, point to and 6.7.1) Animals covered Time needed to reach a plateau concentration in milk and eggs Animal residue definition for monitoring Lactating goats, 7 days, 69 and 230 mg/kg feed, RIP Laying hens: 5-6 days, 100 mg/kg feed, RIP Large parts of the applied dose were excreted. Residues in goat milk consisted of equal amounts of clopyralid and its glycine conjugate. In goat tissues conjugate levels were low or undetectable. The residues in hen tissues and eggs were identified as unchanged clopyralid. Milk: 4-5 days Eggs: not quantified Reg. (EC) No 396/2005 and BfR proposal: clopyralid Outcome of the peer review according to 91/414/EEC: clopyralid including its salts and conjugates, expressed as clopyralid Page 4 / 17

158 GF /00 Part B Section 4 - Core Assessment zrms version Animal residue definition for risk assessment Conversion factor(s) (monitoring to risk assessment) none Metabolism in rat and ruminant similar (yes/no) Fat soluble residue: (yes/no) clopyralid including its salts and conjugates, expressed as clopyralid yes No; log Pow = 2.65 (ph 7, 20 C) IIIA Residues in rotational crops No field rotational crop studies on clopyralid are available. Table IIIA 8.1-5: Residues in rotational crops (Annex IIA, point 6.6.3) Field studies Field studies are not available and not required when taking into account the results of the confined studies. IIIA Residues in livestock An actual calculation of the dietary burden is provided in the following table. Table IIIA 8.1-6: Calculation of the dietary burden (based on all relevant uses authorized in Germany) Feedstuff % DM Percent of daily livestock diet (dry feed basis) Chicken 1,9 kg bw daily maximum feed (DM) 120 g Dairy cattle 550 kg bw daily maximum feed (DM) 20 kg Beef cattle Pig 350 kg bw 75 kg bw daily daily maximum feed maximum (DM) 15 kg feed (DM) 3 kg Residue (mg/kg) Intake (mg/kg, dry feed basis) Chicken Dairy cattle Beef cattle Pig Grasses a Sugar beet leaves and tops b Cereal grains except maize c Sugar and fodder Beet d Oil seed e Intake (mg/kg dry weight feed) Intake (mg/kg bw/d) Intake (mg/animal/d) a HR, based on the following cgap: 1x 2.4 kg as/ha, PHI: 7 d b HR, based on the following cgap: 2x 0.12 kg as/ha, PHI: 90 d c STMR, based on the following cgap: 1x 0.2 kg as/ha, PHI: not specified (based on DAR) d HR, based on the following cgap: 2x 0.12 kg as/ha, PHI: 90 d e STMR, based on the following cgap: 1x 0.12 kg as/ha, PHI: F Table IIIA 8.1-7: Conditions of requirement of livestock feeding studies on clopyralid Expected intakes by livestock 0.1 mg/kg diet (dry weight basis) (yes/no If yes, specify the level) Ruminant: Poultry: Pig: Potential for accumulation (yes/no): no no no Metabolism studies indicate potential level of residues 0.01 mg/kg in edible tissues (yes/no) yes 27 yes 1.5 yes 4.3 yes yes yes A brief summary of the available livestock feeding studies is given in the following table. Data has previously been evaluated at EU level and is described in detail in the corresponding DAR by Finland (ASB ) and the EFSA Conclusion on the peer review of clopyralid (ASB ). Page 5 / 17

159 GF /00 Part B Section 4 - Core Assessment zrms version Table IIIA 8.1-8: Results of livestock feeding studies (Annex IIA, point 6.4) Feeding levels (mg/kg feed dry matter) in feeding studies Ruminant: Poultry: Pig: Lact. cows: 10; 30; 100; 300; 1000 (RIP ) Calves: 3; 10; 30; 100; 300; 1000 (RIP ) Hens: 1; 3; 10 (RIP ) Relevant dosing levels in feeding study: 30 1, 3 30 Pigs: 30; 100; 300 (RIP ) Expected residue levels in animal matrices (mg/kg): Muscle <0.05 <0.05 <0.05 Liver <0.05 <0.05 <0.05 Kidney 0.3 no data <0.05 Fat <0.05 <0.05 <0.05 Milk <0.05 Eggs <0.05 IIIA Florasulam Table IIIA 8.1-9: Identity of the active substance Structural formula F H N S O F O N N N OMe F N Common Name Florasulam CAS number IIIA Storage stability A brief summary of the storage stability data on florasulam is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR by Belgium (ASB ). Table IIIA : Stability of residues (Annex IIA, point 6.1) Stability of florasulam Florasulam residues are stable for at least 562 to 683 days in wheat matrices (whole plant, straw, grain). IIIA Metabolism in plants and plant residue definition(s) A brief summary of the metabolism of florasulam in plants is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR (ASB ). Page 6 / 17

160 GF /00 Part B Section 4 - Core Assessment zrms version Table IIIA : Metabolism in plants (Annex IIA, point 6.2.1; 6.5.1, 6.5.2, and 6.7.1) Plant groups covered Wheat (RIP ), 14 C-phenyl and 14 C-triazole label, 50 g as/has, BBCH Rotational crops After 30 days 30 % TRR was parent compound, % 4-hydroxyphenyl-florasulam (conjugated with glucose). At harvest residues were too low for characterization ( mg/kg). Carrot, sunflower, white cabbage, summer wheat (RIP ), application of 7.5 g as/ha to bare soil, PBI 30 days Metabolism in rotational crops similar to metabolism in primary crops? (yes/no) Distribution of the residue in peel/ pulp Processed commodities (nature of residue) Residue pattern in raw and processed commodities similar? (yes/no) Plant residue definition for monitoring Plant residue definition for risk assessment Residues were far below 0.01 mg/kg in all commodities at harvest. yes Conversion factor(s) (monitoring to risk assessment) none Not applicable No data available and none required Not applicable Florasulam This is in line with Reg. (EC) No 396/2005. Florasulam IIIA Metabolism in livestock and animal residue definition(s) A brief summary of the metabolism of florasulam in livestock is given in the following table. Data has been previously evaluated at EU level and is described in detail in the corresponding DAR (ASB ). Table IIIA : Metabolism in livestock (Annex IIA, point to and 6.7.1) Animals covered Lactating goats (RIP ): 14 C-phenyl and 14 C- triazole label, 11 mg/kg feed DM, 5 days Main residue was unchanged parent (97 % TRR in milk, 15 % TRR in liver, 95 % TRR in kidney), while metabolite 5-OH-florasulam was only detected in traces. Laying hens (RIP ): 14 C-phenyl and 14 C-triazole label, 11 mg/kg feed DM, 5 days Main residue was unchanged parent (95 % TRR in eggs, 15 % TRR in liver, % TRR in skin). Total residue levels were negligible (<0.01 mg/kg). The metabolism in lactating goats and laying hens indicated a slight metabolization of Florasulam. Quantifiable levels of radioactivity in edible tissues were found in goat milk, liver and kidney and in hen eggs and skin. The major constituant of the total residues was the parent molecule in excreta, milk, eggs and edible tissues. Unknown metabolites were also observed in goats and Page 7 / 17

161 GF /00 Part B Section 4 - Core Assessment zrms version Time needed to reach a plateau concentration in milk and eggs Animal residue definition for monitoring Animal residue definition for risk assessment Conversion factor(s) (monitoring to risk assessment) none Metabolism in rat and ruminant similar (yes/no) hens but their amounts were too low for further characterization. There was no major difference between the results from the study with the phenyl and the triazole label. Therefore, the sulphonamide bridge cleavage did not seem to occur to any significant extent. not concluded Not required Florasulam Fat soluble residue: (yes/no) no (log P ow = 1.00, 1.22 and 2.06 at PH 4, 7 & 10, respectively at 20 C) yes IIIA Residues in rotational crops No field rotational crop studies on florasulam are available. This is commented on in the following table. Table IIIA : Residues in rotational crops (Annex IIA, point 6.6.3) Field studies Significant residues are not expected in food and feed commodities obtained from succeeding crops (consequent to uses in compliance with cgap). IIIA Residues in livestock A calculation of the dietary burden was not required, since no residues are expected in feed items. Table IIIA : Conditions of requirement of livestock feeding studies on florasulam Expected intakes by livestock 0.1 mg/kg diet (dry weight basis) (yes/no If yes, specify the level) Ruminant: Poultry: Pig: no no no Potential for accumulation (yes/no): no no no Metabolism studies indicate potential level of residues 0.01 mg/kg in edible tissues (yes/no) Yes, but at a largely exaggerated dose Livestock feeding studies for florasulam were not submitted. no See ruminant IIIA 8.2 Evaluation of the intended use(s) IIIA Selection of critical use and justification The GAPs reported for cereals for the Central Zone are presented in the table below. Page 8 / 17

162 GF /00 Part B Section 4 - Core Assessment zrms version Table IIIA 8.2-1: Critical Use (worst case) used for consumer intake and risk assessment Use- No. Member state(s) Crop and/ or situation (crop destination / purpose of crop) (a) F G or I (b) Pests or Group of pests controlled (additionally: developmental stages of the pest or pest group) (c) Application Method / Kind (d-f) Timing / Growth stage of crop & season (g) Max. number (min. interval between applications) a) per use b) per crop/ season (h) Application rate kg, L product / ha a) max. rate per appl. b) max. total rate per crop/season kg as/ha a) max. rate per appl. b) max. total rate per crop/season Water L/ha min / max PHI (days) (i) Remarks: e.g. safener/synergist per ha e.g. recommended or mandatory tank mixtures (j) 1 DE Winter soft wheat, Winter barley, Winter rye, Spelt, Winter triticale F Annual dicotyledonous weeds spraying BBCH 13-32, after emergence, in spring, after emergence of weeds a) 1 b) 1 a) 0.2 b) 0.2 a) 0.06 (clopyralid), (florasulam) b) see a) F 2 DE Spring soft wheat, Spring durum wheat, Spring barley, Oats F Annual dicotyledonous weeds spraying BBCH 13-30, after emergence, in spring, after emergence of weeds a) 1 b) 1 a) 0.2 b) 0.2 a) 0.06 (clopyralid), (florasulam) b) see a) F Remarks: (a) For crops, the EU and Codex classifications (both) should be used; where relevant, the use situation should be described (e.g. fumigation of a structure) (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) (c) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds (d) All abbreviations used must be explained (e) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (f) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated (g) (h) (i) (j) Growth stage at last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN ), including where relevant, information on season at time of application The minimum and maximum number of application possible under practical conditions of use must be provided PHI - minimum pre-harvest interval Remarks may include: Extent of use/economic importance/restrictions Page 9 / 17

163 GF /00 Part B Section 4 - Core Assessment zrms version IIIA Cereals IIIA Residues in primary crops The following tables give a short overview of the supervised residue trials selected for the assessment of clopyralid and florasulam residues in cereals. Data which has been previously evaluated at EU level is described in detail in the DAR of clopyralid (ASB ) and the corresponding EFSA Conclusion (ASB ), and for florasulam in the DAR (ASB ). No additional studies were submitted. Due to early application, residue trials data can be extrapolated among wheat, barley, oats, rye and triticale. Table IIIA 8.2-2: Overview of the selected supervised residue trials for clopyralid in cereals based on the results presented in the EFSA Conclusion (ASB ) Commodity Region (a) Outdoor/ Indoor Individual trial results (mg/kg) Enforcement (clopyralid) Risk assessment (clopyralid) STMR (mg/kg) (b) HR (mg/kg) (c) Median CF (d) Barley NEU outdoor 0.14, 0.24, 0.34, 0.37, 0.38, 0.47, 0.61, 0.82, 0.95 Barley straw NEU outdoor 0.17, 0.28, 0.31, 0.4, 0.5, 0.87, 1.05, 1.08 Wheat NEU outdoor 0.07, 0.23, 0.73, 0.79, 0.93, 1.06, 1.11, , 0.24, 0.34, 0.37, 0.38, 0.47, 0.61, 0.82, , 0.28, 0.31, 0.4, 0.5, 0.87, 1.05, , 0.23, 0.73, 0.79, 0.93, 1.06, 1.11, (e) not relevant not relevant - Wheat straw NEU outdoor 0.26, 0.59, 0.79, 0.93, 1.06, 1.11, , 0.59, 0.79, 0.93, 1.06, 1.11, Underline median value from trial results (based on DoR for risk assessment) (a): NEU, SEU, EU or Import (country code). (b): Median value of the individual trial results according to the risk assessment residue definition. (c): Highest value of the individual trial results according to the risk assessment residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residues trial. (e): Extrapolated from wheat Table IIIA 8.2-3: Overview of the selected supervised residue trials for florasulam in cereals based on the results presented in the DAR (ASB ) Commodity Region (a) Outdoor/ Indoor Individual trial results (mg/kg) Enforcement (florasulam) Risk assessment (florasulam) STMR (mg/kg) (b) HR (mg/kg) (c) Median CF (d) Barley NEU outdoor <0.002(6) <0.002(6) <0.002 not relevant - Barley straw NEU outdoor <0.01(6) <0.01(6) <0.01 < Wheat NEU outdoor <0.002(11) <0.002(11) <0.002 not relevant - Wheat straw NEU outdoor <0.01(11) <0.01(11) <0.01 < Underline median value from trial results (based on DoR for risk assessment) (a): NEU, SEU, EU or Import (country code). (b): Median value of the individual trial results according to the risk assessment residue definition. (c): Highest value of the individual trial results according to the risk assessment residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residues trial. IIIA Distribution of the residue in peel/pulp Not relevant for the uses under consideration. Page 10 / 17

164 GF /00 Part B Section 4 - Core Assessment zrms version IIIA Residues in processed commodities Clopyralid: No information was available in the DAR. Considering the low utilization of the ADI value no further information on processing of cereals grains is required. Florasulam: Due to a no residue situation in grain at harvest, no processing studies are required. IIIA Proposed pre-harvest intervals, withholding periods The PHI is covered by the normal growth period of the crops ( F ). IIIA 8.3 Consumer intake and risk assessment IIIA Clopyralid The consumer intake and risk assessment is based on the appropriate input values given in Table IIIA and the toxicological reference values stated in Table IIIA For the detailed calculation results it is referred to Appendix 3. Table IIIA 8.3-1: Residue input values for the consumer risk assessment Commodity Chronic risk assessment Input value Comment (mg/kg) Acute risk assessment Input value (mg/kg) Comment all commodities various MRL -- no ARfD allocated Table IIIA 8.3-2: Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8) ADI TMDI (% ADI) according to EFSA PRIMo NTMDI (% ADI) according to German NVS IImodel IEDI (% ADI) according to EFSA PRIMo NEDI (% ADI) according to German NVS II-model Factors included in IEDI and NEDI ARfD IESTI (% ADI) according to EFSA PRIMo NESTI (% ARfD) according to German NVS IImodel Factors included in IESTI and NESTI 0.15 mg/kg bw 27.6 % (based on diet of DK children) 22.1 % (based on diet of German children, aged 2-4 years) not necessary not necessary none not allocated due to low toxicity Not applicable Not applicable Not applicable IIIA Florasulam The consumer intake and risk assessment is based on the input values given in Table IIIA and the toxicological reference values stated in Table IIIA For the detailed calculation results it is referred to Appendix 3. Page 11 / 17

165 GF /00 Part B Section 4 - Core Assessment zrms version Table IIIA 8.3-3: Residue input values for the consumer risk assessment Commodity Chronic risk assessment Input value Comment (mg/kg) Acute risk assessment Input value (mg/kg) Comment all commodities various MRL not necessary no ARfD necessary Table IIIA 8.3-4: Consumer risk assessment (Annex IIA, point 6.9, Annex IIIA, point 8.8) ADI TMDI (% ADI) according to EFSA PRIMo NTMDI (% ADI) according to German NVS IImodel IEDI (% ADI) according to EFSA PRIMo NEDI (% ADI) according to German NVS II-model Factors included in IEDI and NEDI ARfD IESTI (% ADI) according to EFSA PRIMo NESTI (% ARfD) according to German NVS IImodel Factors included in IESTI and NESTI 0.05 mg/kg bw 1.4 % (based on UK toddlers) 0.9 % (based on 2-4 years old DE children) not required not required none not allocated due to low toxicity Not applicable Not applicable Not applicable IIIA 8.4 Proposed maximum residue levels (MRLs) No new MRLs are required. An exceedance of the current MRLs of 2 mg/kg for clopyralid and of 0.01* mg/kg for florasulam in cereal grains as laid down in Reg. (EC) 396/2005 is not expected from the uses under consideration. IIIA 8.5 Conclusion The available data is considered sufficient for risk assessment. The chronic and the short-term intake of clopyralid and florasulam residues are unlikely to present a public health concern. As far as consumer health protection is concerned, DE/BfR agrees with the authorization of the intended uses. Page 12 / 17

166 GF /00 Part B Section 4 - Core Assessment zrms version Appendix 1 List of data submitted in support of the evaluation Table A 1: List of data submitted in support of the evaluation Annex point/ reference No Author(s) Year Title Report-No. Authority registration No Belgium 1999 Florasulam: (Monograph) Vol. 1-3 ASB EFSA 2005 Conclusion regarding the peer review of the pesticide risk assessment of the active substance clopyralid ASB Finland 2003 Clopyralid: (Draft Assessment Report) Vol. 1-4 ASB OECD: KIIA Clements, B.; Bolton, A Determination of the stability of Clopyralid residues in pasture under frozen storage conditions GHE-P-5350! N138 BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA Foster, D. R.; Blakeslee, B. A.; Rutherford, B. S Frozen storage stability of Clopyralid, 2,4-D in corn grain, forage and fodder RES ! GH-C 3779! N136 BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA Chapelo, S.; Caley, C The metabolism of [14C]-Clopyralid in sugar beet 19293! L10! ! GHE-P-9939 BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA Chapelo, S.; Caley, C The metabolism of [14C]-Clopyralid in oilseed rape ! L09! ! GHE-P-9938 BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA Guo, C Metabolism of 14C-Clopyralid in cabbage RES95095! GH-C 4289 BVL , RIP OECD: KIIA Pillar, F The metabolism of XDE-570 in winter wheat - Final report GHE-P-5729! BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1994 Nature of the residue of [14C]XDE-570 in laying hens MET94018! GH-C 3481 BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1974 Fate of 14C-DOWCO 290 in laying hens GH-C 740! H05! BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1994 Nature of the residue of [14C]XDE-570 in lactating goats MET94017! GH-C 3478 BVL , BVL , BVL , BVL , BVL , BVL , RIP Data protection claimed Owner How considered in drr * Add Add Add Y Y Y Y Y Y Y Y Y Page 13 / 17

167 GF /00 Part B Section 4 - Core Assessment zrms version Annex point/ reference No Author(s) Year Title Report-No. Authority registration No OECD: KIIA XXXXX 1975 Residues of DOWCO 290 (3,6- dichloropicolinic acid) in tissues of chicken fed the herbicide GH-C 819! BVL , BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1983 The metabolic fate of 14C-3,6- Dichloropicolinic acid (DOWCO 290) fed to lactating goats GH-C 1600! BVL , BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1975 Residues of DOWCO 290 (3,6- dichloropicolinic acid) in bovine tissues from calves fed the herbicide GH-C 811! BVL , BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1974 Residues of DOWCO 290 (3,6- Dichloropicolinic acid) in milk and cream from cows fed the herbicide GH-C 745! BVL , BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA XXXXX 1975 Residues of DOWCO 290 (3,6- Dichloropicolinic Acid) in tissues of swine fed the herbicide GH-C 874! BVL , BVL , BVL , BVL , BVL , BVL , BVL , RIP OECD: KIIA OECD: KIIA Bauriedel, W.R. and Miller, J.H. Freeman, J.M.H. and Walker, S.M A Rotational Crop Study Following the Application of DOWCO 290 to Spring Wheat GH-C 892 RIP Determination of Residues of 3,6- Dichloropicolinic Acid (DOWCO* 290) in Chicory and Tick Beans Following Soil Incorporation of Sugar Beet Tops Treated with LONTREL* 100 RIP OECD: KIIA Macdonald, A. M. G The uptake of XDE-570 into four succeeding crops GHE-P-4889! BVL , BVL , BVL , BVL , BVL , BVL , RIP * Y: Yes, relied on N: No, not relied on Add: Relied on, study not submitted by applicant but necessary for evaluation Data protection claimed Owner How considered in drr * Y Y Y Y Y Y Y Y Page 14 / 17

168 GF /00 Part B Section 4 - Core Assessment zrms version Appendix 2 Detailed evaluation of the additional studies relied upon A 2.1 Storage stability No further study on storage stability submitted/needed. A 2.2 Residues in primary crops No further study on primary crops submitted/needed. A 2.3 Residues in processed commodities No further study on residues in processed commodities submitted/needed. A 2.4 Residues in rotational crops No further study on residues in rotational crops submitted/needed. A 2.5 Residues in livestock No further study on residues in livestock submitted/needed. A 2.6 None Other studies/information Page 15 / 17

169 GF /00 Part B Section 4 - Core Assessment zrms version Appendix 3 Pesticide Residue Intake Model (PRIMo) Page 16 / 17

170 GF /00 Part B Section 4 - Core Assessment zrms version Page 17 / 17

171 Part B Section 5 Core Assessment Central Zone Page 1 of 48 REGISTRATION REPORT Part B Section 5 Environmental Fate Detailed summary of the risk assessment Product code: Active Substance(s): Clopyralid Florasulam 300 g/l 25 g/l Central Zone Zonal Rapporteur Member State: Germany CORE ASSESSMENT Applicant: DOW AGROSCIENCES Date: April 2013 Evaluator ZRMS Germany Date: April 2013

172 Part B Section 5 Core Assessment Central Zone Page 2 of 48 Table of Contents SEC 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) GENERAL INFORMATION ON THE FORMULATION PROPOSED USE PATTERN INFORMATION ON THE ACTIVE SUBSTANCE CLOPYRALID Identity, further information of clopyralid Physical and chemical properties of clopyralid Metabolites of clopyralid INFORMATION ON THE ACTIVE SUBSTANCES FLORASULAM Identity, further information of florasulam Physical and chemical properties of florasulam Metabolites of florasulam SUMMARY ON INPUTPARAMETER FOR ENVIRONMENTAL EXPOSURE ASSESSMENT Rate of degradation in soil- laboratory studies Rate of degradation in soil- field studies Adsorption/desorption Rate of degradation in water ESTIMATION OF CONCENTRATIONS IN SOIL (KIIIA1 9.4) ESTIMATION OF CONCENTRATIONS IN SURFACE WATER AND SEDIMENT (KIIIA1 9.7) ESTIMATION OF CONCENTRATIONS IN GROUNDWATER (KIIIA1 9.6) PEC gw calculation for active substance and its metabolites (Tier 1) Higher tier leaching assessment Summary Estimation of concentrations in groundwater APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION...27 APPENDIX 2 TABLE OF INTENDED USES, GAP AND JUSTIFICATION FOR THE RISK ENVELOPE 28 APPENDIX 3 DETAILED EVALUATION OF STUDIES RELIED UPON...29 KIIA 7 FATE AND BEHAVIOR OF THE ACTIVE SUBSTANCES IN THE ENVIRONMENT KIIIA1 9 STUDIES ON THE FATE AND BEHAVIOUR OF THE FORMULATION IN THE ENVIRONMENT Evaluator ZRMS Germany Date: April 2013

173 Part B Section 5 Core Assessment Central Zone Page 3 of 48 Sec 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) This document comprises the risk assessment for groundwater and the exposure assessment of surface water and soil for the plant protection product containing the active substances Clopyralid and Florasulam in their intended uses in Winter/ Spring wheat, Winter/ Spring barley, Winter triticale, Winter rye, Spelt wheat, Spring oats, and Durum wheat according to Part B, Section 1, Appendix 2. National Addenda are included containing country specific assessments for some annex points. 5.1 General Information on the formulation Table 5.1-1: General information on the formulation Code - plant protection product applicant Dow Agrosciences date of application September 2011 Formulation type (WP, EC, SC, ; density) active substance clopyralid florasulam Concentration of as 300g/L 25g/L codes of as SC - DE-570 XDE Proposed use pattern The GAPs classified according to the soil effective application rate (cumulative, disregarding degradation in soil) are presented in Table A list of all intended uses within the Central Zone is given in Appendix 2 of this document. Table 5.2-1: Classification of uses regarding soil effective concentration Group Crop/growth stage Season of application A Winter wheat, Winter barley, Winter triticale, Winter rye, Spelt wheat, Spring wheat, Spring barley, Spring oats, Durum wheat (BBCH 13) Spring Application rate (crop interception) (g/ha) 0.2 L/ha Primus Perfect (eq. 232 g/ha Primus Perfect) containing 60 g as/ha clopyralid & 5 g as/ha florasulam, 25% crop interception Soil effective application rate cumulative, disregarding degradation in soil 174 g Primus Perfect/ha with 45 g as/ha clopyralid and 3.75 g as/ha florasulam Evaluator ZRMS Germany Date: April 2013

174 Part B Section 5 Core Assessment Central Zone Page 4 of Information on the active substance clopyralid Identity, further information of clopyralid Table 5.3-1: Identity, further information on clopyralid Active substance (ISO common name) IUPAC Function (e.g. fungicide) Status under Reg. (EC) No 1107/2009 clopyralid 3,6-Dichlorpyridin-2-carbonsäure Herbicide approved Date of approval 01/01/2007 Conditions of approval Confirmatory data In assessing applications to authorise plant protection products containing clopyralid for uses other than spring applications, Member States shall pay particular attention to the criteria in Article 4(3) of Regulation (EC) No 1107/2009, and shall ensure that any necessary data and information is provided before such an authorisation is granted. For the implementation of the uniform principles as referred to in Article 29(6) of Regulation (EC) No 1107/2009, the conclusions of the review report on clopyralid, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 4 April 2006 shall be taken into account. In this overall assessment Member States must pay particular attention to: - the protection of non target plants and groundwater under vulnerable conditions. Conditions of authorisation should include risk mitigation measures and monitoring programmes should be initiated to verify potential groundwater contamination in vulnerable zones, where appropriate. The concerned Member States shall request the submission of further studies to confirm the results on animal metabolism. They shall ensure that the notifiers at whose request clopyralid has been included in this Annex provide such studies to the Commission within two years from the approval. The concerned Member States shall request the submission of further studies to confirm the results on animal metabolism. They shall ensure that the notifiers at whose request clopyralid has been included in the Annex I of Directive 91/414/EEC provide such studies to the Commission within 2 years from the entry into force of the Directive of inclusion. RMS Minimum purity of the active substance as manufactured (g/kg) Some other endpoints, however, require the generation or submission of additional studies to be submitted to the Member States in order to ensure authorisations for use. The list of studies to be generated, still ongoing or available but not peer reviewed can be found in the relevant part of the EFSA Scientific report (page 26) Germany 950 Molecular formula C 6 H 3 Cl 2 NO 2 Evaluator ZRMS Germany Date: April 2013

175 Part B Section 5 Core Assessment Central Zone Page 5 of 48 Molecular mass Structural formula mol/l Physical and chemical properties of clopyralid Physical and chemical properties of clopyralid as agreed at EU level (see SANCO /10012/2006-rev.3) and considered relevant for the exposure assessment are listed in Table Table 5.3-2: EU agreed physical chemical properties of clopyralid relevant for exposure assessment Parameter Value Reference Melting point ( C) LoEP Vapour pressure (Pa) Henry s law constant (Pa m ³ mol -1 ) Solubility in water (mg/l) Partition co-efficient, log K OW 1.36 x 10-3 Pa (extrapolated from o C) Unbuffered: 3.3 x Pa m 3 /mol ph5: 2.2 x Pa m 3 /mol ph7: 1.8 x Pa m 3 /mol ph9: 1.6 x Pa m 3 /mol Unbuffered: 7.85 g/l ph5: 118 g/l ph7: 135 g/l ph9: 157 g/l ph 5: at 20 o C ph 7: at 20 o C ph 9: at 20 o C log P ow = Estimation by the Leo-Hansch method. LoEP LoEP LoEP / registration report LoEP Dissociation constant, pka 2.01 at 25 o C LoEP Hydrolytic stability ph 4-9: stable LoEP Direct photolysis in water Stability in the air, indirect photolysis DT 50 = 261 d (ph 7, natural sunlight) DT 50 = 20 d (12h-day) k = x cm 3 s 1 (OH-Radical-Conc. 1,5 x 10 6 cm 3 ) LoEP DAR Metabolites of clopyralid According to the results of the assessment of clopyralid for EU approval, no major metabolites of clopyralid occur in the environment. No new studies on the fate and behavior of clopyralid have been performed. Hence, no potentially new metabolites need to be considered. Evaluator ZRMS Germany Date: April 2013

176 Part B Section 5 Core Assessment Central Zone Page 6 of Information on the Active Substances florasulam Identity, further information of florasulam Table 5.4-1: Identity, further information on florasulam Active substance (ISO common name) IUPAC Function (e.g. fungicide) Status under Reg. (EC) No 1107/2009 Florasulam 2,6,8 -Trifluor-5-methoxy-[1,2,4]-triazolo[1,5-c]pyrimidin-2- sulfonanilid Herbicide approved Date of approval 01/10/2002 Conditions of approval Confirmatory data RMS Minimum purity of the active substance as manufactured (g/kg) Molecular formula Only uses as herbicide may be authorised. For the implementation of the uniform principles as referred to in Article 29(6) of Regulation (EC) No 1107/2009, the conclusions of the review report on florasulam, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 shall be taken into account. In this overall assessment Member States: should pay particular attention to the potential for ground water contamination, when the active substance is applied in regions with vulnerable soil and/or climatic conditions. Conditions of authorisation must include risk mitigation measures, where appropriate. None Belgium 970 Molecular mass 359,3 Structural formula C12H8F3N5O3S F NH SO 2 F MeO N N N N F Physical and chemical properties of florasulam Physical and chemical properties of florasulam as agreed at EU level (see SANCO/1406/2001-final) and considered relevant for the exposure assessment are listed in Table Table 5.4-2: EU agreed physical chemical properties of florasulam relevant for exposure assessment Parameter Value Reference Melting point ( C) to C with decomposition Appendix 1 (LoEP) of SANCO/1406/2001-final Vapour pressure (Pa) 1 x 10-5 Pa at 25 C Appendix 1 (LoEP) of Evaluator ZRMS Germany Date: April 2013

177 Part B Section 5 Core Assessment Central Zone Page 7 of 48 SANCO/1406/ x 10-6 Pa at 20 C Henry s law constant (Pa m ³ mol -1 ) 3.29 x 10-5 Pa.m3/mol (ph 5) at 20 C 4.35 x 10-7 Pa.m3/mol (ph 7) at 20 C 2.94 x 10-8 Pa.m3/mol (ph 9) at 20 C Solubility in water (mg/l) solubility in : purified water (ph ) : g/l ph 5.0 buffer : g/l ph 7.0 buffer : 6.36 g/l ph 9.0 buffer : 94.2 g/l Partition co-efficient, log K OW ph 4.0: log P ow = 1.00 ph 7.0: log P ow = ph 10.0: log P ow = Dissociation constant, pka pka = 4.54 (determined at C) Hydrolytic stability 50 C: ph 4 and 7: less than 5% degradation after 7d 50 C: ph 9: k = d -1 ;t 1/2 = 2 d (triazole-label) 25 C:pH 5: no degradation observed after 30 d 25 C:pH 7: no degradation observed after 30 d 25 C:pH 9: k = d -1 ; t 1/2 = 100 d (phenyllabel) k = d -1 ; t 1/2 = 98 d (triazole-label) extrapolated from ZRMS Appendix 1 (LoEP) of SANCO/1406/2001 Appendix 1 (LoEP) of SANCO/1406/2001 Appendix 1 (LoEP) of SANCO/1406/2001 Appendix 1 (LoEP) of SANCO/1406/2001 Appendix 1 (LoEP) of SANCO/1406/2001 Direct photolysis in water Stability in the air, indirect photolysis ph 5, 25 C, natural sunlight 40 N, June and May; t 1/2 = d DT50 = 1.82 h k = 70.4 x cm 3 s -1 (OH-Radikal-Konz.: 1.5 x 10 6 cm -3 ) Appendix 1 (LoEP) of SANCO/1406/2001 DAR Metabolites of florasulam Environmental occurring metabolites of florasulam according to the results of the assessment of florasulam on for EU approval are summarized in Table No new studies on the fate and behaviour of florasulam have been performed. Hence no potentially new metabolites need to be considered. The risk assessment of the potentially ecotoxicologically relevant metabolites 5-OH-XDE-570, DFP- ASTCA, and ASTCA of florasulam has already been performed on EU approval (for details see DAR/ EFSA conclusion). The metabolites are regarded as not relevant but persistence of the metabolites 5- OH-XDE-570, DFP-ASTCA, and ASTCA in soil was not considered. Therefore, the metabolites of Evaluator ZRMS Germany Date: April 2013

178 Part B Section 5 Core Assessment Central Zone Page 8 of 48 florasulam will be considered further in the risk assessment for Earthworms and other Non-target Soil Organisms in this core assessment (see RR CA Part B, Section 6.7). However, the leaching potential into groundwater of the soil metabolites 5-OH, DFP-ASTCA and ASTCA will be assessed for the application of the plant protection product and its intended uses. Table 5.4-3: Metabolites of florasulam considered in the exposure assessment (> 10% of as or > 5% of as in 2 sequential measurements or > 5% of as and maximum of formation not yet reached at the end of the study) Metabolite 5-OH-XDE- 570 (XDE hydroxy) N-(2,6- difluorophenyl) -8-fluoro-5- hydroxyl (1,2,4) triazolo(1,5c) pyrimidine-2- sulphonamide Structural formula/molecular weight F F N O S O N N M = g/mol N OH F N Maximum occurence in compartements Soil, aerob: max % after 3 d Water of water/sediment study: max. 64 % after 60 d Sediment of water/sediment study: max. 35 % after 60 d (Soil photolysis: 60%) Ecotoxicologically relevant (see DAR/ EFSA conclusion) Aquatic organism: Water: not relevant Sediment: not relevant Terrestrial organism: not relevant Groundwater: not relevant (Step 2) 1) DFP-ASTCA (M3) N-(2,6- difluorophenyl) -5- aminosulphony l-1h- 1,2,4)triazole- 3-carboxylic acid F F N H O S O H N N M = g/mol N COOH Soil, aerob: max % after 28 d Water of water/sediment study: max. 15 % after 100 d Sediment of water/sediment study: max % after 182 d Aquatic organism: Water: not relevant Sediment: not relevant Terrestrial organism: not relevant Groundwater: not relevant (Step 2) 1) ASTCA (M4) 5- (aminosulphon yl)-1h-1,2,4- triazole-3- carboxylic acid 1) O N H H 2 N S N O N COOH M = g/mol Soil, aerob: max % after 59 d Aquatic organism: Water: not relevant Sediment: not relevant Terrestrial organism: not relevant Groundwater: not relevant (Step 3-4) 1) According to Guidance Document on the assessment of the relevance of metabolites in groundwater of substances regulated under council directive 91/414/EEC (SANCO/221/2000 rev.10- final - 25 February 2003) Evaluator ZRMS Germany Date: April 2013

179 Part B Section 5 Core Assessment Central Zone Page 9 of Summary on Inputparameter for environmental exposure assessment Rate of degradation in soil- laboratory studies Clopyralid A new study (Wardrope, 2009) on the soil degradation of clopyralid has been submitted. A detailed evaluation of this study is presented in Appendix 2. The DT 50 values of the new study together with the DT 50 values from the EU assessment are summarized in Table Table 5.5-1: Summary of aerobic degradation rates for clopyralid - laboratory studies Soil type ph DT 50 (d) 20 C pf2/10kpa Method of calculation Reference Marshall County Silt loam SFO Skinner (1995) Parabraunerde, Silty Loam SFO Marcham, Sandy loam SFO Castle Rising, Sandy loam SFO Speyer 2.1, Sand SFO Speyer 2.2, Loamy sand SFO A: Sandy loam (Warwickshire, UK) B: Clay loam (Chapel Farm, UK) C: Clay loam (Farditch Farm, UK) D: Loam (Pas de Calais, France) Geomean 15.0 median SFO SFO SFO SFO Baloch und Grant (1991) Wardrope (2009) Florasulam No new study on the soil degradation of florasulam has been submitted. However, a new study containing re-evalulations of the degradation kinetics of florasulam for the study Jackson and Gosh, 1997 already evaluated in the EU assessment together with temperature and moisture normalizations for the recalculated DT 50 values has been submitted (Jackson, 2010). A detailed evaluation of this study is presented in Appendix 2 of this document. Additionally, DT 50 values of the studies Pillar, 1997a and b already evaluated in the EU assessment were temperature and moisture normalized for this assessment according to guidance of the FOCUS groundwater scenarios workgroup [FOCUS, 2000, FOCUS, 2002]. The recalculated and/or normalized DT 50 values for florasulam are summarized in Table No new studies on the soil degradation of the florasulam soil metabolites 5-OH-XDE-570, DFP- ASTCA, and ASTCA have been submitted. However, the newly submitted study from Jackson, 2010 on the degradation of florasulam contains also re-evalulations of the degradation kinetics of 5-OH- XDE-570, DFP-ASTCA, and ASTCA from the study Jackson and Gosh, 1997 together with temperature and moisture normalizations for the recalculated DT 50 values. Additionally, degradation kinetics of DFP-ASTCA, and ASTCA were re-evaluated for the also in the EU assessment evaluated Evaluator ZRMS Germany Date: April 2013

180 Part B Section 5 Core Assessment Central Zone Page 10 of 48 soil degradation study for these metabolites from the Jackson and Massart, 1998 again with subsequent DT 50 temperature and moisture normalization. Besides, DT 50 values for 5-OH-XDE-570 from the studies Pillar, 1997a and b were temperature and moisture normalized for this assessment according to guidance of the FOCUS groundwater scenarios workgroup [FOCUS, 2000, FOCUS, 2002]. The recalculated and/or normalized DT 50 values for the florasulam soil metabolites 5-OH- XDE-570, DFP-ASTCA, and ASTCA are summarized in Table 5.5-3, Table 5.5-4, and Table Table 5.5-2: Soil type Speyer 2.2 loamy sand Summary of aerobic degradation rates for florasulam laboratory studies ph (H 2 O) T ( o C) % MWHC moisture DT 50 (d) DT 90 (d) DT 50 (d) 20 C pf2/10kpa Method of calculatio n FOMC SFO* Reference Jackson and Gosh, 1997/ Jackson, 2010 Marcham sandy clay loam % MWHC FOMC SFO* Kenslow, humus silt loam Andover, silt loam Marcham, Sandy clay loam % MWHC % MWHC SFO SFO % st order MWHC ** 25 5, st order Pillar 1997a 20 pf st order Pillar 1997b Cuckney, sand % st order MWHC ** st order Pillar 1997a 20 pf st order Pillar 1997b Aggregated DT 50 (n=6) * DT 90 FOMC/3.32 ** Geomean Coefficient of variation (%) 90 Geomean (d) 2.2 Geomean neutral and alkaline 2.49 soils (ph>7.0) Median (d) percentile (d) 6.3 Evaluator ZRMS Germany Date: April 2013

181 Part B Section 5 Core Assessment Central Zone Page 11 of 48 Table 5.5-3: Summary of aerobic degradation rates for the metabolite 5-OH-XDE laboratory studies Soil type Speyer 2.2, loamy sand Marcham, sandy clay loam Kenslow, humus silt loam Andover, silt loam Marcham, Sandy clay loam ph (H 2 O) T ( o C) % MWHC % MWHC % MWHC % MWHC 8.8 Moisture DT 50 / DT 90 (d) 14.1/ / / / % 42/ MWHC x 25 f.f. DT 50 (d) 20 C pf2/10kpa SFO SFO SFO SFO Method of calculation n.c st order ** 18/ n.c st order 59.8 x 20 pf2 36/ 120 x n.c. 36 Reference Jackson and Gosh, 1997/ Jackson, 2010 Pillar 1997a 1 st order Pillar 1997b Cuckney, sand % 33/ n.c st order MWHC x ** 25 21/ n.c st order 69.8 x 20 pf2 42/ 139 x n.c. 42 Pillar 1997a 1 st order Pillar 1997b Aggregated DT 50 (n=6) Coefficient of variation (%) 41 Geomean (d) 19.7 Median (d) th perzentil 30.5 Formation Fraction Arithmetic mean from florasulam 5- OH (n=4) Maximum ** Geomean n.c.: not calculated x DT 90 value estimated by ZRMS using the DT 50 value Table 5.5-4: Summary of aerobic degradation rates for the metabolite DFP-ASTCA - laboratory studies Soil type Speyer 2.2, loamy sand Marcham, sandy clay loam Andover, silt loam ph (H 2 O) T ( o C) % MWHC % MWHC % MWHC Moisture DT 50 / DT 90 (d) 44.6/ 149 f.f. DT 50 (d) 20 C pf2/10kpa SFO 12/ SFO 11.3/ SFO Method of calculation Reference Jackson and Gosh, 1997/ Jackson, 2010 Evaluator ZRMS Germany Date: April 2013

182 Part B Section 5 Core Assessment Central Zone Page 12 of 48 Cuckney, sand % MWHC Marcham, sandy clay loam Aggregated DT 50 (n=5) % MWHC 16.1/ / Coefficient of variation (%) 95 Geomean (d) 12.4 Median (d) th perzentil 33.0 Formation Fraction Arithmetic mean from 5-OH DFP- ASTCA (n=3) Maximum n.c SFO n.c. 4.2 SFO Jackson and Massart, 1998/ Jackson, 2010 Table 5.5-5: Soil type Cuckney, Sand, treated with DFP-ASTCA Cuckney, Sand, treated with ASTCA Marcham, sandy clay loam, treated with DFP- ASTCA Marcham, sandy clay loam, treated with ASTCA Summary of aerobic degradation rates for the metabolite ASTCA - laboratory studies ph (H2O) Aggregated DT 50 (n=2) T (oc) % MWHC % MWHC Moisture DT 50 / DT 90 (d) 122/ / 1601 f.f. DT 50 (d) 20 C pf2/10kpa SFO n.c. 465 Method of calculation SFO 214/ SFO 711 x 7 141/ n.c x Coefficient of variation (%) 21 Geomean (d) Median (d) Maximum 234 Formation Fraction Arithmetic mean from DFP-ASTCA ASTCA (n=2) Maximum x DT 90 value estimated by ZRMS using the DT 50 value SFO Reference Jackson and Massart, 1998/ Jackson, Rate of degradation in soil- field studies Clopyralid A new evaluation (Reeves, 2010) on the soil degradation of clopyralid under field conditions has been submitted. A detailed evaluation of this study is presented in Appendix 2. The DT 50 values of the new study together with the DT 50 values from the EU assessment are summarized in Table Evaluator ZRMS Germany Date: April 2013

183 Part B Section 5 Core Assessment Central Zone Page 13 of 48 Table 5.5-6: soil / location ph depth (cm) Summary of aerobic degradation rates for clopyralid - field studies DT 50 (d) not standa rdised DT 90 (d) DT 50 (d) 20 C, pf 2 standardise d Fit (Chi 2 ) Kinetic source Spalding. UK. Clay Loam * 30.8 % SFO Rawle und Yon (2002) Middlefart. Denmark. Sandy Clay * 12.6 % SFO 11.7 % SFO Rawle und Yon (2002) Reeves (2010) loam Ansonville. N. France. Silty Clay Loam * 18.9 % SFO 13.5 % Pseudo Rawle und Yon (2002) Reeves (2010) SFO Mainbervilliers. N. France. Clay Loam * 12.5 % SFO 12.5 % SFO Rawle und Yon (2002) Reeves (2010) Oederquart. Germany % SFO Rawle und Yon (2002) Silty Clay Loam 6.1* 12.6 % SFO Reeves (2010) geomean *(n=5) (new evaluations were considered, 3.2 only) median 2.7 Florasulam No new studies have been submitted on the soil degradation of florasulam and its metabolite 5-OH- XDE-570 under field conditions. However, the DT 50 values from the field studies, that were agreed upon during the EU assessment, were calculated using the Timme/Frehse model, which is not considered valid anymore. Thus, an attempt was made for this risk and exposure assessment to recalculate the DT 50 values according to FOCUS Degradation Kinetics, Unfortunately, no valid DT 50 values could be derived from the field studies for florasulam and 5-OH-XDE-570 due to the fast dissipation rates of florasulam under field conditions and the high variability of the data points. The risk and exposure assessment for the plant protection product is therefore based solely on the degradation rates measured under laboratory conditions Adsorption/desorption Clopyralid No new studies have been submitted regarding the adsorption/desorption of clopyralid in soil. The exposure modeling is based K foc values of the EU assessment as summarized in Table Table 5.5-7: Kf, Kfoc and 1/n (Freundlich exponent) values of clopyralid Soil Type OC [%] ph [-] Kf [ml g-1] Kfoc [ml g-1] 1/n [-] Reference Kalkasa, Sand Woodburn Evaluator ZRMS Germany Date: April 2013

184 Part B Section 5 Core Assessment Central Zone Page 14 of 48 Commerce, Loam (1987) Tama, Silt Loam Kenyon, Clay Loam Merzenhausen, Silt loam Kaldenkirchen, Loamy sand Reeves (2002) Lanna, Clay loam Overhetfeld, Loamy sand Arithmetic mean Florasulam No new studies have been submitted regarding the adsorption/desorption of florasulam and its soil metabolites 5-OH-XDE-570, DFP-ASTCA, and ASTCA in soil. Thus, the exposure assessment is based on the K foc and 1/n values or where not available the K d values agreed in the EU assessment as summarized in Table 5.5-8, Table 5.5-9, Table , and Table Table 5.5-8: Soil Type Kf, Kfoc and 1/n (Freundlich exponent) values for florasulam OC [%] ph (H 2 O) * K f [ml g -1 ] K foc [ml g -1 ] ** Catlin,Silty clay loam , ,88 Hanford, Sandy loam , ,86 Pewamo, clay , ,92 Fuquay, sand , ,00 Kenslow, Silt loam , ,94 Speyer, Sandy loam ,13 3 0,95 Arithmetic mean th percentile 12 n.c. *calculated from measured ph values in KCl **calculated from K f values and oc-content of the soil n.c: not calculated 1/n [-] Reference Ostrander, 1996 Table 5.5-9: Soil Type Kf, Kfoc and 1/n (Freundlich exponent) values for the metabolite 5-OH-XDE-570 OC [%] ph (H 2 O) * K f [ml g -1 ] K foc [ml g -1 ] ** Catlin,Silty clay loam Hanford, Sandy loam Pewamo, clay Fuquay, sand Kenslow, Silt loam Speyer, Sandy loam /n [-] Reference Ostrander, 1996 Evaluator ZRMS Germany Date: April 2013

185 Part B Section 5 Core Assessment Central Zone Page 15 of 48 Arithmetic mean th percentile 10 n.c. *calculated from measured ph values in KCl **calculated from K f values and oc-content of the soil n.c: not calculated Table : Kf, Kfoc and 1/n (Freundlich exponent) values for the metabolite DFP-ASTCA Soil Type OC [%] ph (H 2 O) K d [ml g -1 ] K doc [ml g -1 ] ** Marcham, Sandy clay n.a. loam Cuckney, Sand n.a. Sutton, Sandy clay loam n.a. Thessaloniki, Sandy silt n.a. loam Elvedon, Sand n.a. Toulouse, Clay n.a. Tours, Silty clay n.a. Wetterfeld, Silty clay n.a. loam Catlin, Silty loam n.a. Hanford, Sandy loam n.a. Arithmetic mean **calculated from K f values and oc-content of the soil default values for 1/n, in case where no attempt has been made to obtain Kf and 1/n values n.a.: not available 1/n [-] Reference Jackson & Massart, 1999 Table : Kf, Kfoc and 1/n (Freundlich exponent) values for the metabolite ASTCA Soil Type OC [%] ph (H 2 O) K d [ml g -1 ] K doc [ml g -1 ] ** Marcham, Sandy clay ,65 49 n.a. loam Cuckney, Sand ,42 28 n.a. Sutton, Sandy clay loam ,87 89 n.a. Thessaloniki, Sandy silt , n.a. loam Elvedon, Sand ,30 27 n.a. Toulouse, Clay ,89 74 n.a. Tours, Silty clay , n.a. Wetterfeld, Silty clay ,60 50 n.a. loam Catlin, Silty loam ,62 95 n.a. Hanford, Sandy loam , n.a. Arithmetic mean **calculated from K f values and oc-content of the soil default values for 1/n, in case where no attempt has been made to obtain Kf and 1/n values n.a.: not available 1/n [-] Reference Jackson & Massart, 1999 Evaluator ZRMS Germany Date: April 2013

186 Part B Section 5 Core Assessment Central Zone Page 16 of Rate of degradation in water Clopyralid No new water/sediment study has been submitted. The exposure modeling is based on the results of the the water/sediment study of clopyralid reviewed in the DAR/AR/Addendum. However, since no DT50 values for the whole system were available as required for deriving PECsw values for clopyralid, they were calculated for this assessment according to FOCUS degradation kinetics. The recalculation of the DT 50 values is described in detail in Appendix 2. The DT 50 values from the water/sediment study for clopyralid are summarized in Table Table : Degradation in water/sediment of clopyralid Water / DegT 50 Kinetic/ Fit DissT 50 / Kinetic/ Fit DissT 50 / Kinetic/ Reference sediment whole DegT 50 DegT 50 Fit system system water sed. Loamy Sand 688* SFO, chi 2 : DissT 50 : r 2 : no data - Hall (2002) 2,47%* 167 Swiss Lake Chatsworth DegT UK 50 : Sandy Silt Loam Rivalta sul Mincio, Lombardy, Italien Geomean * SFO, chi 2 : 1,04% No data DissT 50 : 128 DegT 50 : No data r 2 : no data - Hall (2002) * recalculated for this assessment according to FOCUS Degradation Kinetics, 2006 Florasulam No new study on the degradation of florasulam in water/sediment systems has been submitted. The exposure modeling is based on the results of the water/sediment study of florasulam reviewed in the DAR/AR/Addendum. The DT 50 values for florasulam and its metabolite 5-OH-XDE-570 from the water/sediment study are summarized in Table and Table Table : Degradation in water/sediment of florasulam Water / sediment system Brown Carrick Hill, sandy loam system Auchingilsie, clay loam system DegT 50 whole system Kinetic/ Fit DissT 50 / DegT 50 water 8.7* 1 st order r 2 : & 0.991** 17.3* 1 st order r 2 : & 0.991* Geomean Kinetic/ Fit DissT 50 / DegT 50 sed. -/8.7*** 1 st order r 2 : & 0.991*** -/17,3*** 1 st order r 2 : & 0.991*** n.c. n.c. Kinetic/ Fit n.c. n.c. Reference Phillips, 1997 *geomean of DT 50 values of water/sediment study phenyl- and triazol-labelled florasulam **r 2 for fit of water/sediment study with phenyl- and triazol-labelled florasulam *** DegT 50 water is equal to DegT 50 of the whole system, since <10% TAR of the active substance was measured in the sediment of both systems n.c. not calculated Evaluator ZRMS Germany Date: April 2013

187 Part B Section 5 Core Assessment Central Zone Page 17 of 48 Table : Degradation in water/sediment of the metabolite 5-OH-XDE 570 Water / sediment system Brown Carrick Hill, sandy loam system Auchingilsie, clay loam system DegT 50 whole system Kinetic/ Fit DegT 50 water * 1 st order r 2 : & 0.969** Kinetic/ Fit DegT 50 sed. n.c. n.c. n.c. n.c. n.c. n.c. n.c. n.c. n.c. n.c. *geomean of DT 50 values of water/sediment study phenyl- and triazol-labelled florasulam **r 2 for fit of water/sediment study with phenyl- and triazol-labelled florasulam n.c. not calculated Kinetic/ Fit Reference Phillips, Estimation of concentrations in soil (KIIIA1 9.4) PEC soil calculations are based on the recommendations of the FOCUS workgroup on degradation kinetics. A soil bulk density of 1.5 g/cm -3, a soil depth of 5 cm and a tillage depth of 20 cm (arable crop)/5 cm (permanent crops) were assumed. The maximum PECsoil values for the florasulam metabolites were calculated by assuming a direct application of the metabolites to the soil. The application rate was calculated from the maximum concentration of each metabolite observed in aerobic soil corrected for their molecular weight. The PEC soil calculations were performed with ESCAPE 2.0. The input parameters for clopyralid and florasulam are presented in Table and Table The input parameter for the metabolites 5-OH, DFP-ASTCA and ASTCA of florasulam as presented in Table Table 5.6-1: Input parameters for clopyralid for PEC soil calculations Parameter Remarks/Reference molecular mass 192 LoEP DT 50 in soil (d) 24 SFO. Maximum. Field studies; not standardised see Table Table 5.6-2: Input parameters for florasulam for PEC soil calculations Parameter Remarks/Reference molecular mass LoEP DT 50 in soil (d) 24 d SFO, Maximum, laboratory studies, normalised to 20 C and pf2 see Table Table 5.6-3: Input parameters for the metabolites 5-OH, DFP-ASTCA and ATSCA of florasulam for PEC soil calculations Metabolite 5-OH Parameter Remarks/Reference molecular mass LoEP Evaluator ZRMS Germany Date: April 2013

188 Part B Section 5 Core Assessment Central Zone Page 18 of 48 DT 50 in soil (d) 30.8 SFO, Maximum, laboratory studies, normalised to 20 C and pf2 see Table Maximum occurrence in soil (%) 71.6 Metabolite Parameter DFP-ASTCA LoEP molecular mass LoEP Remarks/Reference DT 50 in soil (d) 44.6 d SFO, Maximum, laboratory studies, normalised to 20 C and pf2 see Table Maximum occurrence in soil (%) 17.8 Metabolite Parameter ASTCA LoEP molecular mass LoEP Remarks/Reference DT 50 in soil (d) 234 SFO, Maximum, laboratory studies, normalised to 20 C and pf2 see Table Maximum occurrence in soil (%) 40 LoEP Due to the fast degradation of clopyralid and florasulam and its metabolites 5-OH and DFP-ASTCA in soil (DT 90 < 365 d, Kinetic, laboratory/field data) the accumulation potential of clopyralid and florasulam and its metabolites 5-OH and DFP-ASTCA does not need to be considered. Due to the slow degradation of the metabolite ASTCA in soil (DT 90 > 365 d, Kinetic, laboratory data) the accumulation potential of ASTCA needs to be considered. Therefore an accumulated soil concentration (PEC accu ) used for risk assessment that comprises background concentration in soil (PEC bkgd ) considering a tillage depth of 20 cm (arable crop) or 5 cm (permanent crops) and the maximum annual soil concentration PEC act for a soil depth of 5 cm. PEC act values together with PEC twa, 21 d values for clopyralid and for florasulam and its metabolites 5- OH, DFP-ASTCA and ASTCA are given for risk assessment in Table Table 5.6-4: Results of PEC soil calculation (soil bulk density 1.5 g/cm -3, soil depth 5 cm) plant protection product: use: Number of applications/intervall 1 application rate: winter and spring cereals crop interception: 25% (BBCH 13) active substance/preparati on soil relevant application rate (g/ha) 0.2 L /ha equivalent to 60 g/ha clopyralid and 5 g/ha florasulam: PEC act (mg/kg) PEC twa 21 d (mg/kg) tillage depth (cm) PEC bkgd (mg/kg) clopyralid < florasulam < OH < DFP-ASTCA < PEC accu = PEC act + PEC bkgd (mg/kg) Evaluator ZRMS Germany Date: April 2013

189 Part B Section 5 Core Assessment Central Zone Page 19 of 48 ASTCA Estimation of concentrations in surface water and sediment (KIIIA1 9.7) PEC sw and PEC sed calculations are provided according to the recommendations of the FOCUS working group on surface water scenarios in a stepwise approach considering the pathways drainage and runoff. Only FOCUS Step 1 and 2 calculations are documented here. Further calculations with FOCUS Step 3 or 4 were not performed as authorization of is only sought for Germany. National specific exposure/risk assessment is documented in the national addendum for Germany. The relevant input parameters for clopyralid and for florasulam used for PEC calculation are summarized in Table and Table Table 5.7-1: Input parameters for clopyralid for PEC sw/sed calculations Parameter Endpoint used for PEC sw/sed calculation Values in accordance to EU endpoint in LoEP Remarks Active substance clopyralid Water solubility [mg/l] 7850 not used* DT 50.soil [d] 3.2 not used* Geomean field studies, normalized to 20 C and pf2 (see Table 5.5-6) DT 50.whole system [d] 590 d No Geomean DT 50, whole system (see Table ) DT 50.water [d] No valid data, DT 50, wholesystem used No Geomean DT 50, wholesystem (see Table ) DT 50.sed [d] No valid data, DT 50, wholesystem used No Geomean DT 50, wholesystem (see Table ) K f.oc [ml g -1 ] 2.93 not used* arithm. Mean (see Table 5.5-7) * calculations for the EU assessment were not performed with FOCUS SW, thus certain endpoints weren t used Table 5.7-2: Input parameters for florasulam for PEC sw/sed calculations Parameter Endpoint used for PECsw/sed calculation Values in accordance to EU endpoint in LoEP Remarks Active substance florasulam Molecular mass yes LoEP Water solubility [mg/l] 121 not used* LoEP DT 50.soil [d] 2.2 no Geomean, laboratory data, standardized to 20 C and pf2 (see Table 5.5-2) DT 50.whole system [d] no Geomean (see Table ) Evaluator ZRMS Germany Date: April 2013

190 Part B Section 5 Core Assessment Central Zone Page 20 of 48 DT 50.water [d] no Geomean DT 50, water (see Table ) DT 50.sed [d] 1000 no Geomean DT50, whole system (Step 2) DT 50, crop [d] 10 not used* default K f.oc [ml g not used* Arithmetic mean (see ] Table 5.5-8) * calculations for the EU assessment were not performed with FOCUS SW, thus certain endpoints weren t used Results of FOCUS SW calculations for the worst-case application scenario of for the active substances clopyralid and florasulam are summarized in Table Additionally to PECact also PEC twa, 21d is given as it is necessary for risk assessment for birds and mammals. Table 5.7-3: Summary of highest global maximum FOCUS surface water PECsw and PECsed values Plant protection product: Use No evaluated , Crop Application method (-) Growth stage at first application (BBCH) Application time Winter cereals Spray 13 1st of March Crop interception: 25% (minimal crop cover in Step 2) Number of applications/intervall 1 Application rate: Active Substance FOCUS STEP 2 Scenario 60 g/ha clopyralid and 5 g/ha florasulam Clopyralid PEC SW (µg/l) PEC SED (µg/kg) Actual, 0 h TWA, 21 d Actual, 0 h Northern Europe, Mar.-May Southern Europe, Mar.-May Active Substance Florasulam PEC SED FOCUS STEP 2 (µg/kg) Scenario Actual, 0 h TWA, 21 d Actual, 0 h Northern Europe, Mar.-May Southern Europe, Mar.-May Estimation of concentrations in groundwater (KIIIA1 9.6) PEC gw calculation for active substance and its metabolites (Tier 1) Groundwater contamination by direct leaching of the active substance and its metabolites, degradation or reaction products through soil is generally assessed by groundwater model calculations. Evaluator ZRMS Germany Date: April 2013

191 Part B Section 5 Core Assessment Central Zone Page 21 of 48 The PEC of clopyralid and florasulam and their metabolites in ground water have been assessed with standard FOCUS scenarios to obtain outputs from the FOCUS PELMO The FOCUS calculation was performed by UBA. Clopyralid Table 5.8-1: Input parameters related to application for PEC gw modelling use no application rate (kg as/ha) 0.06 crop (crop rotation) winter cereals spring cereals date of application 1 st March interception (%) 25 soil moisture Q10-factor 2.58 moisture exponent 0.7 plant uptake 0 simulation period (years) % FC Table 5.8-2: Input parameters related to active substance for PEC gw modelling Parent clopyralid Remarks/Reference molecular mass 192 LoEP DT 50 in soil (d) 15 geometr. mean; 10 pf2 standardised laboratory values (see Table 5.5-1) K foc 2.93 arithmet. mean (see Table 5.5-7) 1/n arithmet. mean (see Table 5.5-7) Table 5.8-3: Use No /crop Winter cereals PEC GW at 1 m soil depth for clopyralid Szenario 80 th Percentile PEC GW at 1 m Soil Depth ( g L -1 ) groundwater model: FOCUS PELMO Clopyralid Châteaudun Hamburg <0.001 Jokioinen <0.001 Kremsmünster <0.001 Okehampton <0.001 Piacenza (no irrigation) <0.001 Sevilla no irrigation <0.001 Thiva no irrigation <0.001 Porto. no irrigation <0.001 Evaluator ZRMS Germany Date: April 2013

192 Part B Section 5 Core Assessment Central Zone Page 22 of 48 Spring cereals Châteaudun Hamburg <0.001 Kremsmünster <0.001 Okehampton <0.001 Porto. no irrigation <0.001 Jokioinen <0.001 According to the PECgw modelling with FocusPelmo a groundwater contamination of the active substance clopyralid at a concentration of 0.1 µg/l is not expected. Florasulam Table 5.8-4: Input parameters related to application for PECgw modelling use no application rate (kg as/ha) crop (crop rotation) date of application interception (%) 25 soil moisture Q10-factor 2.58 moisture exponent 0.7 plant uptake 0 simulation period (years) 10 Spring cereals/ winter cereals 1st of March 100 % FC Table 5.8-5: Input parameters related to the active substance for PEC gw modelling Parent florasulam Remarks/Reference molecular mass LoEP DT 50 in soil (d) 2.2 Geomean (see Table 5.5-2) K foc 37 Arithmetic mean (see Table 5.5-8) 1/n Arithmetic mean (see Table 5.5-8) Table 5.8-6: Input parameters related to the metabolites of florasulam for PEC GW modelling Metabolite 1 5-OH-XDE-570 Remarks/Reference molecular mass LoEP Formation fraction (Florasulam 5-OH) Arithmetic mean (see Table 5.5-3) DT 50 in soil (d) 19.7 Geomean (see Table 5.5-3) K foc 31 Arithmetic mean (Table 5.5-9) 1/n Arithmetic mean (Table 5.5-9) Evaluator ZRMS Germany Date: April 2013

193 Part B Section 5 Core Assessment Central Zone Page 23 of 48 Metabolite 2 DFP-ASTCA Remarks/Reference molecular mass LoEP Formation fraction (5-OH DFP-ASTCA) Arithmetic mean (see Table 5.5-4) DT 50 in soil (d) 12.4 Geomean (see Table 5.5-4) K foc 53 Arithmetic mean (see Table ) 1/n 1.0 Default (see Table ) Metabolite 3 ASTCA Remarks/Reference molecular mass LoEP Formation fraction (DFP-ASTCA ASTCA) Maximum (see Table 5.5-5) DT 50 in soil (d) 234 Maximum (see Table 5.5-5) K foc 83 Arithmetic mean (see Table ) 1/n 1.0 Default (see Table ) Table 5.8-7: Use No (crop) Winter cereals Spring cereals PEC GW at 1 m soil depth of florasulam and its metabolites Szenario Châteaudun, no irrigation 80 th Percentile PEC GW at 1 m Soil Depth ( g L -1 ) Florasulam Metabolit 5-OH Metabolit DFP-ASTCA Metabolit ASTCA < Hamburg < Jokoinen < Kremsmünster < Okehampton < Piacenza (no irrigation) Sevilla no irrigation Thiva no irrigation Porto. no irrigation Châteaudun, no irrigation < <0.001 <0.001 < <0.001 <0.001 < < < Hamburg < Jokoinen < Kremsmünster < Okehampton < Porto, no irrigation < Evaluator ZRMS Germany Date: April 2013

194 Part B Section 5 Core Assessment Central Zone Page 24 of 48 According to the PECgw modelling with FOCUS PELMO 4.4.3, a groundwater contamination of the active substance florasulam at a concentration of 0.1 µg/l is not expected. For the metabolites 5-OH and DFP-ASTCA, a groundwater concentration of 0.1 µg/l can also be excluded. For the metabolite ASTCA, groundwater concentration of 0.1 µg/l cannot be excluded for all scenarios. In addition to the tier 1 PEC GW modeling, a higher tier leaching assessment using experimental data from lysimeter studies with the active substances clopyralid and florasulam has been performed Higher tier leaching assessment Clopyralid In addition to the tier 1 PECgw modelling lysimeter studies for the active substance clopyralid were performed for the crops oil seed rape, sugar beet and winter wheat (crop rotation). active substance Clopyralid author: Reeves, G. und Schnöder, F. report: [ 14 C]Clopyralid: Leaching In Outdoor Lysimeters Following Spring Application to Oil Seed Rape Final Report study date 26. Juli 2004 study code reference see DAR for a detailed description of the study active substance author: Clopyralid Jackson, R. und Dust, M report: Degradation and leaching of clopyralid after post-emergence application to winter oilseed rape in German lysimeters study date 29/08/1994 study code GEHE-P-4037 reference see DAR for a detailed description of the study active substance Clopyralid author: Brumhard, B., Baloch, R. und Fuhr, F. report: Behaviour of [2,6-14 C] clopyralid (LONTREL) in a sandy pseudogley braunerde after post-emergence application to sugar beet. study date Mai 1993 study code GHE-P-2908 reference see DAR for a detailed description of the study The experimental data on the leaching behaviour of the active substance clopyralid show that the active substance clopyralid is not expected to leach into groundwater at concentrations of 0.1µg/L in the intended uses. Evaluator ZRMS Germany Date: April 2013

195 Part B Section 5 Core Assessment Central Zone Page 25 of 48 Florasulam In case of the active substance florasulam exposure assessment is based additionally on results of a lysimeter study. active substance Florasulam author: Jackson, R. and Paterson, G. report: The dissipation of XDE-570 in soil and crops using field lysimeters study date 17/12/1997 study code reference GHE-P-6751 see DAR for a detailed description of the study The experimental data on the leaching behaviour of the active substance Florasulam show that florasulam and its metabolite 5-OH are not expected to penetrate into groundwater at concentrations of 0.1µg/L in the intended for uses in winter and spring cereals after application in spring at locations for which the climate conditions of the UK (51.5 N latitude) are considered a worst case scenario. However, the duration of the lysimeter study is not considered long enough to estimate groundwater entries of the relatively late occurring secondary and tertiary soil metabolites DFP-ASTCA and ASTCA. Additionally, a second lysimeter study was with florasulam (Pillar, 2001), which was not evaluated during the EU aassessment was available for this exposure assessment: active substance Florasulam author: Pillar, F. report: The dissipation of DE-570 in field lysimeters following autumn application study date study code GEH-P-9281 In the study, the leaching behaviour of florasulam was tested in the UK (51.5 N latitude) for a single application of only 4 g/ha to cereals in autumn at a location. Due to the smaller application rate, it is thus not considered relevant for estimating possible groundwater entries of the active substance florasulam and its metabolites for this exposure assessment. Thus, no detailed description of the study is presented here Summary Estimation of concentrations in groundwater Results of modelling with FocusPelmo as well as lysimeter studies show that the active substance clopyralid is not expected to leach into groundwater at concentrations of 0.1µg/L in the intended for uses in spring and winter cereals. Results of modelling with FocusPelmo as well as the lysimeter study (Jackson and Paterson, 1997) show that the active substance florasulam is not expected to penetrate into groundwater at concentrations of 0.1µg/L in the intended for uses in spring and winter cereals. Evaluator ZRMS Germany Date: April 2013

196 Part B Section 5 Core Assessment Central Zone Page 26 of 48 According to the modeling results with Focus Pelmo 4.4.3, concentrations of 0.1µg/L in groundwater can also be excluded for the metabolites 5-OH and DFP-ASTCA. For the metabolite ASTCA, concentrations of 0.1µg/L in groundwater cannot also be excluded for all FOCUS scenarios. An assessment of metabolite ASTCA regarding their relevance for groundwater is necessary. However an assessment of this metabolite has already been performed for EU approval of florasulam. The metabolite ASTCA is classified as not relevant for groundwater. Evaluator ZRMS Germany Date: April 2013

197 Part B Section 5 Core Assessment Central Zone Page 27 of 48 Appendix 1 List of data submitted in support of the evaluation Table A 1-1: Annex point/ reference No OECD: KIIA & KIIIA OECD: KIIIA OECD: KIIA List of data submitted in support of the evaluation Author(s) Year Title Source (where different from company) Report-No. GLP or GEP status (where relevant), Published or not Authority registration No Wardrope, L The Degradation of [14C]-Clopyralid in Soil Under Aerobic Conditions. report no BVL Doc. No & BVL Doc. No Jackson, R Re-Evaluation of the Degradation Kinetics of Florasulam and its Major Metabolites in European Soils According to FOCUS Guidance.. report no. GHE-P BVL Doc. No Reeves, G Modelling the field soil degradation kinetics of clopyralid using FOCUS methodology updated to address EU zonal RMS questions report no. GHE-P BVL Doc. No Data protection claimed Owner Y DAS 1) Y DAS 1) Y DAS 1) How considered in RR Study- Status/Usage* * 1) accepted (study valid and considered for evaluation) 2) not accepted (study not valid and not considered for evaluation) 3) not considered (study not relevant for evaluation) 4) not submitted but necessary (study not submitted by applicant but necessary for evaluation) 5) supplemental (additional information, alone not sufficient to fulfil a data requirement, considered for evaluation) Evaluator ZRMS Germany Date: April 2013

198 Part B Section 5 Core Assessment Central Zone Page 28 of 48 Appendix 2 Table of intended uses, GAP and justification for the risk envelope Introduction: This document summarises the information related to country GAPs supported and cgaps derived from the GAPs, followed by the rationale for the risk envelope used in the ecotoxicological and Environemental Fate & behaviour risk assessment. The formulation covered in this document is: Formulation Code Type Active Substance(s) SC Clopyralid; Florasulam Detailed GAP for uses: Crop and/ or situation Member State or Country Product Name F G or I Pests or Group of pests controlle d Formulation Application Application rate per treatment PHI (days ) Remarks: (a) (b) (c) Winter wheat, Winter barley Winter triticale, Winter rye Spelt wheat Spring wheat, Spring barley, Spring oats Durum wheat Germany florasulam + clopyralid Primus Perfect Germany florasulam + clopyralid Primus Perfect Type (d-f) Conc of as (i) method kind (f-h) F BLWs SC 325 Tractor mounted spray F BLWs SC 325 Tractor mounted spray Growth stage & season (j) BBCH Spring (March- May) BBCH Spring (March- June) number min max (k) interval between applicatio ns (min) g as/hl min max 1 NA to NA to water L/ha min max g as/ha min max (l) (m) NA 200 ml/ha use rate NA 200 ml/ha use rate Evaluator ZRMS Germany Date: April 2013

199 Part B Section 5 Core Assessment Central Zone Page 29 of 48 Appendix 3 Detailed evaluation of studies relied upon KIIA 7 Fate and Behavior of the active substances in the Environment KIIA 7.2 Rate of degradation of clopyralid and florasulam in soil laboratory studies Wardrope, 2009 Reference: KIIA and Report The Degradation of [ 14 C]-Clopyralid in Soil Under Aerobic Conditions Wardrope, L. (2009), report No 29902, report no , BVL Doc. No & BVL Doc. No Guideline(s): Deviations: GLP: Acceptability: Yes (OECD Guideline for the Testing of Chemicals. Guideline 307, Aerobic and Anaerobic Transformation in Soil (April 2002).) Yes Yes Yes Materials and Methods This study was designed to investigate the route/rate of degradation of 14 C-clopyralid in four EU agricultural soils (Table A 2-1) under aerobic conditions in the laboratory at 20 C. The study was scheduled to continue through to 120 days. However, since the study objectives were met at 90 days, the final scheduled sampling at 120 days did not occur, and the final report only contains the results from 0 to 90 days. The soil moisture was determined and adjusted to ca 43% WHC, and then allowed to acclimatize for seven days in the dark at 20 C prior to application. 14 C-Clopyralid (RCP ca 98%) was applied to the soil in water at a rate of µg/kg dry weight (0.2 kg/ha based on distribution in the top 5 cm of soil with bulk density 1.5 g/ml). The application of 14 C-clopyralid adjusted the soils to ca 45% WHC. The test system consisted of a flow through apparatus in the dark where the soils (50 g dry-weight) were incubated at 20 C in Erlenmeyer flasks connected to a series of individual traps containing ethanediol and NaOH, for the collection of non-specific 14 C-volatile organics and 14 CO 2, respectively. Single replicate samples were removed for each soil type at zero time (immediately following application), 1, 3, 7, 14, 21, 30, 60 and 90 days. Trap solutions were sampled at the time of sample termination, and sampled and replenished at 30 day intervals. At each sampling time, single samples for each soil were removed and extracted. Extractions were generally performed by adding a solution of acetonitrile:2m HCl (4:1 v/v, 100 ml) to each sample, shaking for ca 1 hour, followed by centrifugation (ca 3500 rpm; ca 15 min). The extract was decanted and the total volume measured (Extract 1). The procedure was repeated on up to four further occasions (Extracts 2 to 5) depending upon the timepoint. Extractable soil radioactivity was quantified using LSC. Radioactive components in soil extracts (after combining and concentrating to a small volume) were quantified using reverse-phase HPLC with on line radiochemical detection, with confirmatory TLC analysis on selected samples. Nonextractable 14 C-residues were quantified using LSC following combustion. Evaluator ZRMS Germany Date: April 2013

200 Part B Section 5 Core Assessment Central Zone Page 30 of 48 Table A 3-1: soil characterisation data Soil A B C D Location Ryton, UK Evesham, UK Buxton, UK Calais, France Sand (% w/w) Silt (% w/w) Clay (% w/w) ADAS Texture Class ADAS USDA sandy loam sandy loam clay clay loam clay loam clay loam Org. Carbon (% w/w) ph (water) ph (0.01M CaCl 2 ) clay loam loam Moisture Content (%) Max. WHC 0ax. WHC Content (%)mc \s 2 i CEC (meq/100g Soil) Bulk Density (g/ml) Results and discussions The overall radiochemical balance is presented in Tables A 3-2 to A 3-5. The amount of radioactivity in the soil extracts declined from quantitative levels at 0 days to 4.0, 3.6, 3.0 and 4.8% AR at 90 days for soils A, B, C and D, respectively, with generally low levels of NER (up to 32.9% AR). The major degradation product in all soils was 14 CO 2 ( % AR). The overall radioactive recovery ranged from 91.2 to 105.8% AR. Table A 3-2: Radiochemical balance- soil A Day % Applied Radioactivity Extr. 1 Extr. 2 Extr. 3 Extr. 4 Extr. 5 Total Volatiles CO 2 NER Total ns ns ns ns <LOQ ns <LOQ ns ns <LOQ ns ns ns ns <LOQ ns ns ns ns ns ns ns = no sample Evaluator ZRMS Germany Date: April 2013

201 Part B Section 5 Core Assessment Central Zone Page 31 of 48 Table A 3-3: Radiochemical balance- soil B Day % Applied Radioactivity Extr. 1 Extr. 2 Extr. 3 Extr. 4 Extr. 5 Total Volatiles CO 2 NER Total ns ns ns ns <LOQ ns ns <LOQ ns ns <LOQ ns ns <LOQ ns ns <LOQ ns ns <LOQ ns ns ns ns ns = no sample Table A 3-4: Radiochemical balance- soil C Day % Applied Radioactivity Extr. 1 Extr. 2 Extr. 3 Extr. 4 Extr. 5 Total Volatiles CO 2 NER Total ns ns ns ns <LOQ ns <LOQ ns ns <LOQ ns ns <LOQ ns ns 7.01 <LOQ ns ns 6.82 <LOQ ns ns 4.27 <LOQ ns ns 3.01 <LOQ ns = no sample Evaluator ZRMS Germany Date: April 2013

202 Part B Section 5 Core Assessment Central Zone Page 32 of 48 Table A 3-5: Radiochemical balance- soil D Day % Applied Radioactivity Extr. 1 Extr. 2 Extr. 3 Extr. 4 Extr. 5 Total Volatiles CO 2 NER Total ns ns <LOQ ns <LOQ ns <LOQ ns <LOQ ns <LOQ ns 8.23 <LOQ ns 5.72 <LOQ ns 4.83 <LOQ ns = no sample The distribution of clopyralid and any degradation products in the soil extracts, as determined by HPLC are summarized in Table A 3-6. Since the soil extracts all contained <5% AR at 90 days, only the samples up to 60 days were characterized. One minor but transient polar degradation product was observed in all soil types. However, it did not exceed approximately 3% AR in any of the soils and was observed at only one sampling interval in soils A and B, and two sampling intervals (but not consecutive) in soils C and D. This was also confirmed in selected samples by TLC analysis (Table A 2-7). Table A 3-6: Degradation profile of clopyralid and its metabolites by HPLC % Applied Radioactivity Soil A Soil B Soil C Soil D Day Unknown d known known known Clopyrali Un- Un- Un- Clopyralid Clopyralid Clopyralid nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd nd 7.01 nd nd nd nd 6.82 nd 8.23 nd nd = not detected Table A 3-7: Confirmatory TLC Analysis Day Soil % Applied Radioactivity HPLC TLC Clopyralid Unknown Clopyralid Unknown* 0 A nd A nd B nd B nd C nd Evaluator ZRMS Germany Date: April 2013

203 Part B Section 5 Core Assessment Central Zone Page 33 of C D nd D nd nd = not detected * Majority of unknown radioactivity attributable to the origin and therefore likely to have become bound to the origin. The DT 50 (lab) and DT 90 (lab) values for clopyralid in each soil were calculated using a single firstorder (SFO) model according to FOCUS kinetics guidance (2006) using the data to 60 days. The resulting kinetic parameters are summarized in Table A 3-8. In all soils, clopyralid was readily degraded with DT 50 (lab) values at 20 C of 16.6, 23.1, 4.9 and 10.0 days in soils A, B, C and D, respectively, with DT 90 (lab) values <77 days. For further use of the DT 50 (lab) in various fate models at Tier I, the resulting DT 50 (lab) values were normalized to a soil moisture (pf2) according to the FOCUS groundwater guidance, and the geomean was obtained for model input. This procedure is shown in Table A 3-9. For a number of soils, the actual soil moisture exceeded the FOCUS default gravimetric w/c at pf2 for that soil type and so no correction was made. However, factors below 1 were applied for the remaining soils. The resulting geomean from the normalized DT 50 (lab) values of all four soils is 10.7 days. Table A 3-8: First-order DT 50(lab) and DT 90(lab) Clopyralid Values Soil Texture Class (ADAS) SFO DT 50(lab) (days) SFO DT 90(lab) (days) Chi 2 error (%) A sandy loam B clay C clay loam D clay loam r 2 Table A 3-9: Normalised Clopyralid DT 50(lab) Values for Use in Modelling Soil Texture (ADAS) SFO DT 50(lab) (days) Actual Moisture (% w/w) Gravimetric w/c at pf2 (% w/w) + Temp. Correction Factor Moisture Correction Factor^ Corrected DT 50(lab) at 20 C/pF2 (days) A sandy loam * B clay * C clay loam * D clay loam * Geomean 10.7 * 45% WHC + FOCUS default for soil texture (ADAS) ^ (actual moisture/gravimetric w/c) 0.7 Conclusion The route and rate of degradation of clopyralid was determined in four EU agricultural soils under laboratory conditions at 20 C and 45% WHC. DT 50 values ranged from 4.9 to 16.6 d with DT 90 (lab) values <77 days. The geomean of the DT 50 values after normalization to pf2 is 10.7 d. No major metabolites were found. Comments of zrms The study was performed according to guideline and is considered acceptable by the ZRMS. The results are used in this exposure assessment. Evaluator ZRMS Germany Date: April 2013

204 Part B Section 5 Core Assessment Central Zone Page 34 of 48 Jackson, 2010 Reference: KIIIA 9.1.1/02 Report Re-Evaluation of the Degradation Kinetics of Florasulam and its Major Metabolites in European Soils According to FOCUS Guidance, Jackson, R., 2010, report no. GHE-P-12511, BVL Doc. No Guideline(s): Deviations: GLP: Acceptability: Guidance Document on Estimating Persistence and Degradation Kinetics from Environmental Fate Studies on Pesticides in EU Registration, Report of the FOCUS Work Group on Degradation Kinetics, EC Document Ref. Sanco/10058/2005 ver.1, 2005 Yes- the comments of ZRMS Not applicable no laboratory study Yes Materials and methods The degradation kinetics of florasulam and its three major aerobic soil metabolites (5-OH, DFP- ASTCA, ASTCA) have been re-evaluated according to the FOCUS kinetics guidance (2006). As input, the data from two laboratory aerobic soil studies with florasulam,jackson and Gosh, 1997 (Jackson, R. and Gosh, D., The aerobic degradation of XDE-570 in soil. report no. GHE-P- 4710), and its metabolites DFP-ASTCA and ASTCA, Jackson and Massart, 1998 (Jackson, R. and Massart, J., The degradation of DFP-ASTCA and ASTCA (tow metabolites of DR-570) in soil. Report no. GHE-P-7522), already evaluated during the EU assessment were used. The re-calculation of the kinetic parameters was performed with the kinetics modelling tool KinGUI (ver. 1.1) using single first-order (SFO) for florasulam and its metabolites and for florasulam also using first-order multiple compartment (FOMC) and bi-exponential (DFOP) models to determine the best fit. The data of the four soils (Andover, Kenslow, Marcham and Speyer soil) used in the study Jackson and Gosh, 1997, were fitted to the different kinetics model sequentially, starting with florasulam alone then adding the metabolites one at a time and optimising the model at each step. The following degradation scheme of florasulam was used in the model. Florasulam 5-OH DFP-ASTCA ASTCA The data of the 2 soils (Marcham and Cockney soil) used in the study Jackson and Massart, 1998 to investigate the degradation of the metabolites DFP-ASTCA and ASTCA were modeled for both metabolites together where DFP-ASTCA was applied to the soil and for the metabolite ASTCA alone where ASTCA was applied to the soil. Results and discussions The degradation of florasulam was best described with biphasic models in all for soils (good visual fits, chi 2 error <15%). However, for the degradation of florasulam in the Kenslow soil, the SFO model describes the degradation of florasulam also adequately (good visual fit, chi 2 error <15%). For the degradation in the Andover soil, the SFO model gave an acceptable fit (good visual fit, chi 2 error <15%) after the data point at day 3 was removed as an outlier. Additionally, the kinetic fit after removal of the data point at day 1 was tested. For the degradation of florasulam in the Marcham soil, the SFO model gave an acceptable statistical fit (chi 2 error <15%), however the visual fit of the data points was poor. The applicant choose the SFO model nevertheless with the arguments of that the Evaluator ZRMS Germany Date: April 2013

205 Part B Section 5 Core Assessment Central Zone Page 35 of 48 statistical fit was acceptable and that the SFO model describes the degradation in the first 7 days adequately, where 80% of florasulam is degraded. The kinetic parameters derived for the metabolites 5-OH and DFP-ASTCA, however, are based on the FOMC model for florasulam. For the Speyer soil, the FOMC model was chosen to describe the degradation of florasulam. Acceptable kinetic parameters could also be obtained for the formation and degradation of 5-OH in all four soils (good visual fits, chi 2 error <15%). Acceptable kinetic parameters could be obtained for DFP-ASTCA in the soils Andover and Speyer. For the soil Marchham, an acceptable fit could only be obtained when the concentrations of DFP-ASTCA were combined with the concentrations of the metabolite DFP-TSA, although the chi 2 error was with 17.2% slightly above the recommended 15%. It was not possible to obtain acceptable fits to describe the formation and degradation of the metabolite ASTCA in the four soils. The kinetic parameters, finally used to describe the degradation of florasulam and its metabolites 5- OH and DFP-ASTCA in the soils Andover, Kenslow, Marcham and Speyer, are presented in Table A 3-10, Table A 3-11, Table A 3-12 and Table A For the Andover and the Kenslow soil, the kinetic parameters of the SFO fit of the parent alone are also presented. For the Marcham soil, the kinetic parameters of the FOMC fit for florasulam was presented given. Table A 3-10: Optimised kinetic parameters for the degradation of florasulam and its metabolites 5-OH and DFP-ASTCA in the Andover soil (without data point at day 3) Substance Kinetic Parameter Value Lower CI Florasulam SFO (parent only) M 0 (%) k (d -1 ) Florasulam SFO M 0 (%) (parent & k (d -1 ) 5-OH metaboliltes) ff k (d -1 ) DFP- ff ASTCA k (d -1 ) Upper CI Prop>t e e e Visual fit DT 50 (d) Chi 2 error (%) good good good good Table A 3-11: Optimised kinetic parameters for the degradation of florasulam and its metabolite 5-OH in the Kenslow soil Substance Kinetic Parameter Value Lower CI Florasulam SFO (parent only) M 0 (%) k (d -1 ) Florasulam SFO M 0 (%) (parent & k (d -1 ) 5-OH metaboliltes) ff k (d -1 ) Upper CI Prop>t e e e-7 Visual fit DT 50 (d) Chi 2 error (%) good good good Table A 3-12: Optimised kinetic parameters for the degradation of florasulam and its metabolites 5-OH and DFP-ASTCA in the Marcham soil Substance Kinetic Paramet er Value Lower CI Upper CI Prop>t Visual fit DT 50 (d) Florasulam SFO M 0 (%) poor Chi 2 error (%) Evaluator ZRMS Germany Date: April 2013

206 Part B Section 5 Core Assessment Central Zone Page 36 of 48 (parent only) k (d -1 ) e-4 Florasulam FOMC M 0 (%) (parent) & SFO alpha beta e-7 8.5e-5 5-OH (metabolit ff es) k (d -1 ) DFP- ff ASTCA** k (d -1 ) *DT50 SFP= DT 90 FOMC/3.32 **combined concentrations of DFP-ASTCA and DFP-TSA good 5.0* 3.9 good good Table A 3-13: Optimised kinetic parameters for the degradation of florasulam and its metabolites 5-OH and DFP-ASTCA in the Speyer soil Substance Kinetic Paramete r Florasulam FOMC (parent) & SFO M 0 (%) alpha beta 5-OH (metabolite ff s) k (d -1 ) DFP- ff ASTCA k (d -1 ) *DT50 SFP= DT 90 FOMC/3.32 Value Lower CI Upper CI Prop>t 2.7e-8 9.3e e e-5 Visual fit DT 50 (d) Chi 2 error (%) good 1.7* 7.8 good good Acceptable kinetic parameters could be obtained for the SFO model for the two metabolites DFP-ASTCA and ASTCA (good visual fits, chi 2 error <15%), in the experiments where DFP-ASTCA was applied as test substance to the Marcham and the Cockney soil and for ASTCA also in the case, where ASTCA was applied as test substance. For deriving kinetic parameters, the measured DFP- ASTCA concentration were again combined with the measured concentrations for DFP-ASTCA. The kinetic parameters, finally used to describe the degradation DFP-ASTCA and ASTCA in the soils Cuckney and Marcham, are presented in Table A 3-14 and Table A Table A 3-14: Optimised kinetic parameters for the degradation of the metabolites DFP- ASTCA and ASTCA in the Cuckney soil Substance Kinetic Paramete r Value Lower CI DFP- ASTCA SFO M 0 (%) k (d -1 ) ASTCA* ff k (d -1 ) ASTCA** SFO M 0 (%) k (d -1 ) *soil treated with DFP-ASTCA, **soil treated with DFP-ASTCA Upper CI Prop>t Visual fit DT 50 (d) Chi 2 error (%) e-8 good good e-4 good Evaluator ZRMS Germany Date: April 2013

207 Part B Section 5 Core Assessment Central Zone Page 37 of 48 Table A 3-15: Optimised kinetic parameters for the degradation of the metabolites DFP- ASTCA and ASTCA in the Marcham soil Substance Kinetic Paramete r Value Lower CI Upper CI Prop>t e e Visual fit DT 50 (d) Chi 2 error (%) DFP- ASTCA SFO M 0 (%) k (d -1 ) ASTCA ff k (d -1 ) ASTCA SFO M 0 (%) k (d -1 ) acceptable good acceptable The DT 50( was adjusted to standard moisture (pf2) according to FOCUS guidance. No temperature adjustment was necessary since all studies were performed at 20 C. The moisture correction factors for the soils together with the corrected and uncorrected DT 50 values and the formation fractions for the metabolites are summarized in Table A Table A 3-16: Kinetic parameters for florasulam and its soil metabolites corrected for standard moisture Substance Soil Moisture correction factor Florasulam 5-OH DFP-ASTCA ASTCA Uncorrected DT 50 (d) Moisture Corrected DT 5 0 (d) Andover Kenslow Marcham Speyer Formation Fraction Andover Kenslow Marcham Speyer Andover Marcham 1) Speyer Cuckney 2) Marcham 2) Cuckney 2) Cuckney 3) Marcham 2) Marcham 3) ) florasulam applied to soil, 2) DFP-ASTCA applied to soil, 3) ASTCA applied to soil Conclusion Evaluator ZRMS Germany Date: April 2013

208 Part B Section 5 Core Assessment Central Zone Page 38 of 48 The degradation kinetics of florasulam and its major soil metabolites 5-Oh, DFP-ASTCA and ASTCA have been re-evaluated according to FOCUS degradation kinetics, The resulting DT 50 values were normalized to standard moisture conditions (pf2). The normalized DT 50 values for florasulam ranged from 0.9 to 2.3 d. The metabolite 5-OH degraded with normalized DT 50 values between 6.2 and 17.6 d, the metabolite DFP-ASTCA with normalized DT 50 values between 4.2 and 44.6 d and ASTCA with normalized DT50 values between 118 and 465 d. Comments of zrms For degradation of florasulam in the Andover soil, the data point at day 3 was removed as an outlier. The applicant gave no scientific judgment for removing this data point and it is not obvious from the data if the data point at day 1 or day 3 is the outlier. However, the applicant tested the kinetics without both data points and derived the better fit when removing the data point at day 3. As no acceptable fit could be obtained when using all data points, the approach is considered acceptable by the ZRMS. For degradation of florasulam in the Marcham soil, the SFO model was used although the visual fit was poor. This is not according to FOCUS degradation kinetics, 2006, and is not considered acceptable by the ZRMS since the FOMC model gave a good visual fit and was also used by the applicant when deriving kinetic parameters for the metabolites. Thus, the DT 50 value of 5 days (DT90 FOMC/3.32) derived from the FOMC model was moisture normalized from the ZRMS and used instead. Besides, it is not considered valid to use the two DT 50 values for ASTCA derived with different experimental conditions in the same soils as separate degradation parameters. Thus, the geomean of both DT 50 values were used by the ZRMS instead. The resulting final normalized DT 50 values for florasulam and its metabolites used for exposure assessment is summarized in Table A Table A 3-16: Normalized DT 50 values for florasulam and its soil metabolites used for exposure assessment Soil DT 50 (d) (SFO, at 20 C and pf2) Florasulam 5-OH DFP-ASTCA ASTCA Andover n.c. Kenslow n.c. n.c. Marcham 1) 4.2* n.c. Speyer * n.c. Cuckney n.a. n.a Marcham 2) n.a. n.a ) florasulam applied to soil, 2) DFP-ASTCA applied to soil *DT 90 FOMC/3.32 Evaluator ZRMS Germany Date: April 2013

209 Part B Section 5 Core Assessment Central Zone Page 39 of 48 KIIA 7.3 Reeves, 2010: Reference: Report Guideline(s): Deviations: GLP: Acceptability: Rate of degradation of clopyralid and florasulam in soil field studies (BVL) Modelling the field soil degradation kinetics of clopyralid using FOCUS methodology updated to address EU zonal RMS questions. Reeves, G., 2010, report No GHE-P-12244; ; ; G.Reeves (U766007) No kinetic re-evaluation, no guidelines available Not applicable Not applicable no laboratory study Yes Materials and methods Five Northern European field dissipation trials at bare soil sites were conducted in following May (UK and Denmark), November (France - two sites) and June (Germany) applications and these were considered to represent representative agro-climatic conditions for the use of clopyralid products. Details on the field dissipation trials can be found in the DAR for clopyralid. All sites apart from Middlefart provided daily average soil temperatures that can be used directly in the normalisation. To remedy this for Middlefart, weather station data were sourced in December 2009 from the Danish Meteorological Office to cover the study period. Average daily soil temperatures were obtained from the nearest weather station that recorded these data (Aarslev; 50 km from test site). For daily soil moisture, no data were available in the original dissipation reports. However, this information can be estimated using a suitable model, e.g. PERSIST, which requires daily maximum and minimum air temperatures and daily rainfall. The former were available for three sites (Spalding, Ansonville and Mainbervilliers) and the latter for all but Middlefart. To remedy the missing daily maximum and minimum air temperatures for Middlefart and Oederquart, data were sourced from the MARS data set for the study period. For Middlefart, information was taken from MARS grid point and for Oederquart from MARS grid point MARS data were used here because local weather station data recording this information were not readily available. Finally, to remedy the missing rainfall data for Middlefart, weather station data were sourced in December 2009 from the Danish Meteorological Office to cover the study period. Daily total rainfall data were obtained from the nearest weather station that recorded these data (station number 23297; 5 km from the test site). Therefore, sufficient data were available for a normalisation of the day lengths for temperature at 20 C and soil moisture at field capacity (pf2). In order to use a DT50(field) in modelling, it must be demonstrated that the decline is due to degradation and not to dissipation. For clopyralid this is justified as follows. Firstly, its low vapour pressure indicates minimal loss to air, as confirmed by a BBA wind tunnel study. Secondly, the dissipation trials sampled residues in the 0 10 cm and cm horizons, with analysis showing that clopyralid was confined to the 0 10 cm layer in the majority of samples through to 6 months, with many < LOD at cm depth. Finally, three relevant (i.e. BBA guideline or near BBA-compliant) lysimeter studies have been carried out where residues in the horizons (below 30 cm) of sandy soil cores were quantified. In these longer term (up to 3 years) studies, no significant movement of total radioactivity occurred out of the top soil horizon. Therefore, since neither of these dissipative processes are contributing to the decline of clopyralid under field conditions, then it is considered that the DT50(field) is due to degradation, and as such is suitable for model input. To achieve the normalization, a day-length adjustment method was followed which is described in the FOCUS kinetics guidance. The normalisation was carried out by reducing or increasing day lengths Evaluator ZRMS Germany Date: April 2013

210 Part B Section 5 Core Assessment Central Zone Page 40 of 48 depending on soil temperature and field moisture by means of correction factors identical to those used in the leaching models. For temperature correction, a Q10 of 2.58 was used. The adjusted day lengths were determined and the cumulative days after application obtained by addition for each sampling time. The amounts of clopyralid (mg/kg) at each of the various sampling times were taken from the dissipation reports. Data from the 0 10 cm and cm horizons were added and a total for the 0 20 cm layer obtained. This was carried out for completeness despite the fact that the majority of residues were in the 0 10 cm layer. The 0 20 cm concentrations were then assigned to the appropriate normalised cumulative day after application (Tables to ). For subsequent KinGUI (ver. 1.1) kinetic modelling, the first instance of a residue concentration being below the LOD (i.e. < mg/kg) was reported as ½ LOD (i.e mg/kg, but entered as mg/kg). Subsequent values, if still below the LOD, were ignored. This is in alignment with the recommendations of the FOCUS kinetics guidance. The parent DT50 may be single first order (SFO), first order multiple compartment (FOMC), hockey stick (HS) or double first order in parallel (DFOP), and these are described in detail in the FOCUS kinetics guidance. The last three models all use bi phasic kinetics where the degradation rate appears to change (usually slows down) later in the study. These bi phasic models can be considered if the SFO fit to the data is not acceptable. The data were prepared as text files and evaluated by KinGUI in a simple linear degradation scheme. In this scheme, the sink compartment is represented by CO2, bound residues and minor metabolites <5% AR. The fitting of the model to the field data followed a stepwise approach, beginning with the simplest kinetic representation (SFO) and then a more complex bi phasic model (FOMC) to investigate if an improvement to the model fit could be obtained. If required for the bi-phasic FOMC model, a conservative first order DT 50 (field) can be back calculated as DT 50 (field) = DT90(field)/3.32, as recommended by FOCUS for use in groundwater models. For SFO, the model derived DT50(field) can be used directly. Selection of the best fit model (SFO or FOMC) was based upon obtaining the lowest chi2 error in combination with a good visual fit (i.e. an estimated zero time concentration that was close to the measured value and with even distribution of the residuals around zero). The kinetic modelling of clopyralid field data described in this report supersedes previous work by using daily temperature and soil moisture values in the day-length normalisation procedure to derive a DT50(field) for use in higher tier fate modelling. This provided a more robust assessment compared to previous work which used (in some cases) surrogate temperature and moisture values. In 2006 the final report of the FOCUS workgroup on degradation kinetics was published, and so the data were reevaluated to derive clopyralid DT50(field) values based upon day-length normalisation to reference soil conditions (20 C and 10 KPa) as they are for a laboratory study, using a Q10 of Results and discussions Single first order (SFO) kinetics were appropriate for three sites (Middlefart, Mainbervilliers, Oederquart) due to the low chi2 error (<15%), randomness of the residuals and statistical t test (<0.05), and the fact that applying a bi phasic model (FOMC) generally worsened the visual and statistical fits. However, for a fourth site (Ansonville) where the degradation was very rapid, a bi phasic FOMC model was more appropriate and here a pseudo SFO DT 50 (field) was back calculated from the FOMC DT 90 (field)/3.32. For a fifth site (Spalding) the decline data showed a pattern that would not be ideally fitted by either the SFO or FOMC models, with chi2 values of ca 32% and confidence intervals that include zero. For this reason, this site was not included further in the Evaluator ZRMS Germany Date: April 2013

211 Part B Section 5 Core Assessment Central Zone Page 41 of 48 evaluation. The results from the kinetic analysis of the normalized data from the sites are summarised in Tables A 3-17 and A For groundwater modelling, a single DT 50 (field) is required by the models. As shown here, reliable normalised DT50(field) data (20 C/pF2) have been derived for clopyralid from four dissipation trials. These data were for a degradation pathway with SFO kinetics, which was considered to best fit the data. For this number of soils, it is acceptable to use a geomean of the data for model input, as recommended by the FOCUS kinetics guidance. The overall geomean DT50(field) obtained for use in higher tier groundwater modelling was 3.4 days, as can be seen in Table A Table A 3-17 SFO Model Output Summary Site Chi 2 of residuals and overall Randomness fit a Lower CI (k) Upper CI (k) t-test (k) DT 50(field) (d) b Spalding 32.6% Poor d 8 Middlefart 11.7% Good Ansonville 21.7% Fair Mainbervilliers 12.5% Good Oederquart 12.6% Good a Qualitative assessment by report author b Normalised to 20 C and soil moisture content at field capacity (pf2) c Unstandardised, as given in original dissipation reports d Data from Spalding site excluded from further assessment due to poor model fit Original DT 50(field) (d) c Table A 3-18 FOMC Model Output Summary Site Chi 2 of residuals Randomness and overall fit a Spalding 32.4% Poor Middlefart 17.4% Fair Ansonville 13.5% Good Mainbervilliers 13.9% Fair Oederquart 22.4% Fair Lower CI ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) a Qualitative assessment by report author b Normalised to 20 C and soil moisture content at field capacity (pf2) c From DT 90(field) /3.32 d Data from Spalding site excluded from further assessment due to poor model fit Upper CI ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) DT 50(field) (d) b,c 18.5 d Evaluator ZRMS Germany Date: April 2013

212 Part B Section 5 Core Assessment Central Zone Page 42 of 48 Table A 3-19 Overall DT 50(field) Summary From Four Valid Data Sets Site Chi 2 DT 50(field) (d) a Middlefart 11.7% 10.9 Ansonville 13.5% 0.84 Mainbervilliers 12.5% 2.3 Oederquart 12.6% 6.1 Average 12.6% Geomean 3.4 d a Normalised to 20 C and soil moisture content at field capacity (pf2) Conclusion The overall geomean standardised (20 C; 10kPa) DT50(field) for use in higher tier groundwater modelling is 3.4d. Comments of zrms Study is acceptable and can be used for higher tier exposure assessment. Evaluator ZRMS Germany Date: April 2013

213 Part B Section 5 Core Assessment Central Zone Page 43 of 48 KIIA 7.8 Re-evaluation of the Degradation Kinetics of clopyralid in the water/sediment system: In order derive modelling endpoints for PEC sw for this exposure assessment, the ZRMS performed a new kinetic modelling evaluation of data from the two water sediment systems performed with clopyralid from the study Hall et al, 2002 (Hall, B.E., Allan, J., Lowrie, C, The Aerobic Degradation of [14C]-Clopyralid in Natural waters and their Associated sediments, report no. GHE- P-9584) already evaluated during EU assessment to derive modelling endpoints for PEC sw. Materials and methods Applied Kinetic Models The kinetic evaluation of the data from the two water/sediment systems loamy sand sytem and Silt loam system (Hall et al, 2002) was performed using the computer program DegKinManager. DegKinManager which incorporates the programm ModelMaker 4.0 was developed to calculate additional statistic parameters for the kinetic fits derived by Model Maker 4.0 in order to estimate the statistic quality of the derived fits. Input data for the modeling study Data from the two water/sediment studies with clopyralid in % TAR were used as input for the kinetic modeling approach. The data are presented in Table A Table A 3-20 Concentration of clopyralid in the two water/sediment systems Loamy sand system Silt loam system DAT Water Sediment Total Water Sediment Total nd nd nd Results and discussions DegT 50 /DegT 90 values for the total system: Degradation of clopyralid in both water/sediment systems loamy sand system and Silt loam system followed SFO kinetics giving acceptable fits. The two resulting fitted curves together with the residuals plots and the results of the statistic evaluation are shown in Table A Evaluator ZRMS Germany Date: April 2013

214 Part B Section 5 Core Assessment Central Zone Page 44 of 48 Table A 3-21 Kinetic parameterfor the degradation of clopyralid in water/sediment systems (total system) Kinetic model SFO System Loamy sand system Silt loam system Parameter k M0 chi² k M0 chi² Estimation % Confidence % measured SFO measured SFO The resulting DegT 50 and DegT 90 values for both water/sediment systems are summarized in Table A Table A 3-22 DT50 and DT90 values for clopyralid in water/sediment systems (total system) Water/sediment system DT 50 [d] DT 90 [d] Total system Loamy Sand System Silt Loam System An attempt was also made to calculate DegT50 values for the water and the sediment. However, no valid degradation parameters could be derived for both water/sediment system. Evaluator ZRMS Germany Date: April 2013

215 Part B Section 5 Core Assessment Central Zone Page 45 of 48 Conclusion DT 50 values were derived for the degradation of clopyralid in the two water/sediment systems Loamy Sand System and Silt Loam System. The resulting DT 50 values of 688 and 505 d were used in this exposure assessment. KIIIA1 9 Studies on the Fate and Behaviour of the formulation in the Environment KIIIA 9.7 Predicted environmental concentrations in surface water (PEC sw ) for clopyralid and florasulam The following calculations of PECsw and PECsed for clopyralid and florasulam and the intended use of in spring and winter cereals were performed by the ZRMS. Materials and methods Applied scenarios and modeling input The worst-case application scenario considered for PECsw and PEC calculations for clopyralid and florasulam is given in Table A Table A 3-23 Application scenario for clopyralid and florasulam in considered for PECsw and PECsed calculations Plant protection product: Use No evaluated , Crop Application method (-) Growth stage at first application (BBCH) Application time Winter cereals Spray 13 Crop interception: 25% Number of applications/intervall 1 Application rate: 1 st of March 60 g/ha clopyralid and 5 g/ha florasulam Input parameters for clopyralid and florasulam The relevant input parameters for clopyralid and for florasulam used for PEC calculation are summarized in Table A 3-24 and Table A Table A 3-24 Input parameters for clopyralid for PEC sw/sed calculations Parameter Endpoint used for PEC sw/sed calculation Values in accordance to EU endpoint in LoEP Remarks Active substance clopyralid Water solubility [mg/l] 7850 not used* Evaluator ZRMS Germany Date: April 2013

216 Part B Section 5 Core Assessment Central Zone Page 46 of 48 DT 50.soil [d] 3.2 not used* Geomean field studies, normalized to 20 C and pf2 (see Table 5.5-6) DT 50.whole system [d] 590 d No Geomean DT 50, whole system (see Table ) DT 50.water [d] No valid data, DT 50, wholesystem used DT 50.sed [d] No valid data, DT 50, wholesystem used No No Geomean DT 50, wholesystem (see Table ) Geomean DT 50, wholesystem (see Table ) K f.oc [ml g -1 ] 2.93 not used* arithm. Mean (see Table 5.5-7) * calculations for the EU assessment were not performed with FOCUS SW, thus certain endpoints weren t used Table A 3-25 Input parameters for florasulam for PEC sw/sed calculations Parameter Active substance Endpoint used for PEC sw/sed calculation florasulam Values in accordance to EU endpoint in LoEP Remarks Water solubility [mg/l] 121 not used* LoEP DT 50.soil [d] 2.2 no Geomean, laboratory data, standardized to 20 C and pf2 (see Table 5.5-2) DT 50.whole system [d] no Geomean (see Table ) DT 50.water [d] No valid data, DT 50, wholesystem used DT 50.sed [d] No valid data, DT 50, wholesystem used Geomean DT 50, wholesystem (see Table ) Geomean DT 50, wholesystem (see Table ) K f.oc [ml g not used* Arithmetic mean (see Table 5.5- ] 8) * calculations for the EU assessment were not performed with FOCUS SW, thus certain endpoints weren t used FOCUS surface water models and scenarios At Step 1 and Step 2, the software STEPS1-2 in FOCUS (Surface water Tool for Exposure Predictions Step 1 and 2) is used for exposure calculation. The FOCUS version 1.1 was used, which is the most recent model version available at the time of report preparation. The model is described in detail in FOCUS [FOCUS, 2001]. Setup of FOCUS surface water runs In a first step, FOCUS Step 1 and 2 calculations were carried out for clopyralid and florasulam for the intended use of in winter and spring cereals. The selected crop input parameter for FOCUS Step 1 and 2 simulations with clopyralid and florasulam are summarized in Table A Evaluator ZRMS Germany Date: April 2013

217 Part B Section 5 Core Assessment Central Zone Page 47 of 48 Table A 3-26 Crop input parameter for FOCUS Step 1 and 2 simulations FOCUS sw parameter Input for FOCUS Step 1 and 2 FOCUS sw crop Crop interception in STEP1-2 Application period Region Cereals, winter Minimal crop cover March - May North Europe, South Europe Results and discussions The PEC sw,act and the PEC sw,twa for clopyralid calculated with FOCUS Step 1 and 2 are summarized in Table A The PEC sw,act and the PEC sw,twa for florasulam calculated with FOCUS Step 1 and 2 are summarized in Table A Table A 3-27 PEC sw,act and the PEC sw,twa for clopyralid following application of to winter cereals calculated with FOCUS Step 1 and Step 2 Time* [d] PEC sw,act [µg L -1 ] Step 1 PEC sw,twa [µg L -1 ] North Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] Step 2 South Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] * Time: days after maximum concentration (PEC sw,act ) or time interval (PEC sw,twa ) Table A 3-28 PEC sw,act and the PEC sw,twa for florasulam following application of to winter cereals calculated with FOCUS Step 1 and Step 2 Time* [d] PEC sw,act [µg L -1 ] Step 1 PEC sw,twa [µg L -1 ] North Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] Step 2 South Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] Evaluator ZRMS Germany Date: April 2013

218 Part B Section 5 Core Assessment Central Zone Page 48 of 48 Time* [d] PEC sw,act [µg L -1 ] Step 1 PEC sw,twa [µg L -1 ] North Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] Step 2 South Europe PEC sw,act [µg L -1 ] PEC sw,twa [µg L -1 ] * Time: days after maximum concentration (PEC sw,act ) or time interval (PEC sw,twa ) For the sediment, only the PEC sed,max calculated with FOCUS step 1 and 2 are presented here, which can be considered as worst-case estimates of short-term and long-term exposure. Table A 3-29 shows maximum PECsed for clopyralid and florasulam after application of Primus Perfect to winter cereals. Table A 3-29 PEC sed,act for clopyralid following application of to winter cereals calculated with FOCUS Step 1 and Step 2 Step 2 Step 1 Compound North Europe South Europe PEC sed,max [µg kg -1 ] PEC sed,max [µg kg -1 ] PEC sed,max [µg kg -1 ] Clopyralid Florasulam Evaluator ZRMS Germany Date: April 2013

219 Part B Section 5 National Addendum - Germany Central Zone Page 1 of 17 REGISTRATION REPORT Part B Section 5 Environmental Fate Detailed summary of the risk assessment Product code: Active Substance(s): Clopyralid Florasulam 300 g/l 25 g/l Central Zone Zonal Rapporteur Member State: Germany National Addendum - Germany Applicant: DOW AGROSCIENCES Date: November 2012 Evaluator UBA/ Germany Date: April 2013

220 Part B Section 5 National Addendum - Germany Central Zone Page 2 of 17 Table of Contents SEC 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) PROPOSED USE PATTERN ESTIMATION OF CONCENTRATIONS IN SOIL (KIIIA1 9.4) ESTIMATION OF CONCENTRATIONS IN SURFACE WATER AND SEDIMENT (KIIIA1 9.7) PEC SW after exposure by spraydrift and deposition following volatilization PEC SW after exposure by surface run-off and drainage ESTIMATION OF CONCENTRATIONS IN GROUNDWATER (KIIIA1 9.6) Groundwater concentrations via leaching Higher tier leaching assessment Summary of groundwater concentrations via leaching Groundwater concentration via bank filtration of ditch water Summary of groundwater concentrations via bank filtration of ditch water Evaluator UBA/ Germany Date: April 2013

221 Part B Section 5 National Addendum - Germany Central Zone Page 3 of 17 Sec 5 FATE AND BEHAVIOUR IN THE ENVIRONMENT (KIIIA 9) The exposure assessment of the plant protection product in its intended use on spring and winter cereals is described in detail in the core assessment of the plant protection product Primus Perfect dated from the November 2012 performed by Germany. This document contains the specific exposure assessment regarding PEC soil, PEC gw and PEC sw for authorisation of the plant protection product in Germany according to its intended use on spring and winter cereals based on the data and results presented in the core assessment of the plant protection product. Regarding PEC gw relevant risk mitigation measures, if necessary, are documented in this document. PECsoil, PECsw are used for risk assessment to derive specific risk mitigation measures if necessary (see Part B section 6 and Part A). 5.1 Proposed use pattern The gaps for Germany classified according to the soil effective application rate (cumulative, disregarding degradation in soil) are presented in Table A list of all intended uses within the Central Zone is given in Appendix 2 of section 1 of the core assessment. Table 5.1-1: Classification of uses regarding soil effective concentration Use-No. Crop/ growth stage Application date Application rate (crop interception) (g/ha) Winter wheat, Winter barley, Winter triticale, Winter rye, Spelt wheat, Spring wheat, Spring barley, Spring oats, Durum wheat (BBCH 13) Spring (1 st of March) 0.2 L/ha (eq. 232 g/ha Primus Perfect) containing 60 g as/ha clopyralid & 5 g as/ha florasulam 25% crop interception Soil effective application rate cumulative, disregarding degradation in soil 174 g/ha with 45 g as/ha clopyralid and 3.75 g as/ha florasulam 5.2 Estimation of concentrations in soil (KIIIA1 9.4) Results of PECsoil calculations for clopyralid and florasulam according to EU assessment considering 5 cm soil depth are given in Table of Part B, Section 5 of the core assessment. For Germany exposure assessment, the applied soil depth is based on experimental data (Fent, Löffler, Kubiak: Ermittlung der Eindringtiefe und Konzentrationsverteilung gesprühter Pflanzenschutzmittelwirkstoffe in den Boden zur Berechnung des PEC-Boden. Abschlussbericht zum Forschungsvorhaben FKZ , UBA, Berlin 1999). Generally, for active substances with a K f,oc < 500 (arithmetic mean) a soil depth of 2.5 cm is used whereas for active substances with a K f,oc > 500 (arithmetic mean) a soil depth of 1 cm is applied. A soil bulk density 1.5 g cm -3 is assumed. Evaluator UBA/ Germany Date: April 2013

222 Part B Section 5 National Addendum - Germany Central Zone Page 4 of 17 The maximum PECsoil values for the florasulam metabolites were calculated by assuming a direct application of the metabolites to the soil. The application rate was calculated from the maximum concentration of each metabolite observed in aerobic soil corrected for their molecular weight. Due to the fast degradation of the active substances clopyralid and florasulam and its metabolites 5- OH and DFP-ASTCA in soil (DT 90 < 365 d, SFO Kinetic, laboratory conditions), the accumulation potential of clopyralid and florasulam and its metabolites 5-OH and DFP-ASTCA does not need to be considered. For risk assessment the maximum annual soil concentration PEC act considering the relevant soil depth of 2.5 cm or 1.0 cm respectively is used., Due to the slow degradation of the metabolite ASTCA in soil (DT 90 > 365 d, Kinetic, laboratory data) the accumulation potential of ASTCA needs to be considered. Therefore an accumulated soil concentration (PEC accu ) used for risk assessment that comprises background concentration in soil (PEC bkgd ) considering a tillage depth of 20 cm (arable crop) or 5 cm (permanent crops) and the maximum annual soil concentration PEC act for a soil depth of 2.5 or 1 cm. For the input parameters for clopyralid and florasulam and its metabolites 5-OH, DFP-ASTCA and ASTCA used for PEC soil calculations see Table 5.6-1, Table and Table of the core assessment, Part B Section 5. PEC act values for clopyralid and for florasulam are given in Table Table 5.2-1: Results of PEC soil calculation (soil bulk density 1.5 g/cm -3, soil depth 5 cm) plant protection product: use: Number of applications/intervall 1 application rate: winter and spring cereals crop interception: 25% (BBCH 13) active substance/preparatio n soil relevant application rate (g/ha) 0.2 L /ha equivalent to 60 g/ha clopyralid and 5 g/ha florasulam: Soil depth act (cm) PEC act (mg/kg) tillage depth (cm) PEC bkgd (mg/kg) clopyralid < florasulam < OH < DFP-ASTCA < PEC accu = PEC act + PEC bkgd (mg/kg) ASTCA n.n.: not necessary 5.3 Estimation of concentrations in surface water and sediment (KIIIA1 9.7) Results of PECsw calculations of clopyralid and florasulam for their intended use of in spring and winter cereals using FOCUS Surface Water are given in Table of Part B, Section 5 of the core assessment. For the German authorization of the exposure assessment of surface water, the routes of entry (spraydrift and deposition following volatilasation; run-off, drainage) are considered separately in Evaluator UBA/ Germany Date: April 2013

223 Part B Section 5 National Addendum - Germany Central Zone Page 5 of 17 order to derive risk mitigation measures for each entry route. The German surface water exposure assessment is outlined in the following chapters PEC SW after exposure by spraydrift and deposition following volatilization Clopyralid The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 C of the active substance clopyralid is > 10-4 Pa. Hence the active substance clopyralid is regarded as volatile (volatilization from from soil and plant surfaces). Therefore exposure of surface water by the active substance clopyralid due to deposition following volatilization needs to be considered. Therefore, the calculation of PECsw for clopyralid after exposure via spraydrift and deposition following volatilization using the model EVA 2.1 is required. The input parameters of clopyralid used in the model EVA 2.1 are summarized in Table Table 5.3-1: Inputparameter for clopyralid for EVA 2.1 Parameter Remark/Reference vapour pressure at 20 C (Pa) 1.36 x 10-3 LoEP Solubility in water (mg/l) 7850 LoEP DissT 50 water (d) 167 Maximum, see Table of Section 6, Part B of the core assessment hydrolysis/photolysis 1000 Default Inetception 25 % BBCH The PEC sw values after exposure by spraydrift and deposition following volatilization calculated for the active substance clopyralid for the intended for use in spring and winter cereals (worst case application rate) are summarized in Table Table 5.3-2: PECsw values after exposure by spraydrift and deposition following volatilization for the active substance clopyralid use no: application rate (g/ha) 60 relevant PEC if applicable twa-interval scenario/percentile: PECact 90stes percentil, agriculture cereals distance (m) PECsw via drift PECsw via volatilisation PECsw (via drift and volatilisation) (µg/l) depending on application technique (drift reduction) (%) (µg/l) (%) (µg/l) common 90% red. 75% red. 50% red Evaluator UBA/ Germany Date: April 2013

224 Part B Section 5 National Addendum - Germany Central Zone Page 6 of 17 Florasulam The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure at 20 C of the active substance florasulam is < 10-5 Pa. Hence the active substance florasulam is regarded as non-volatile. Thus, only the calculation of PECsw after exposure via spraydrift using the model EVA 2.1 is florasulam required. The input parameter for florasulam used in the model EVA 2.1 are summarized in Table Table 5.3-3: Inputparameter for florasulam for EVA 2.1 Parameter Remark/Reference vapour pressure at 20 C (Pa) 1 x 10-6 Pa extrapolated from ZRMS, see Table of Part B, Section 5 of the core assessment Solubility in water (mg/l) 121 LoEP DissT 50 water (d) 17.3 Maximum, DegT 50 Water, see Table of Part B, Section 5 of the core assessment hydrolysis/photolysis 1000 Default The PECsw values for florasulam calculated after exposure by spraydrift and deposition following volatilization for the intended for use in spring and winter cereals are summarized in Table Table 5.3-4: PEC sw values after exposure via spraydrift for the active substance florasulam use no: application rate (g/ha) 5 relevant PEC if applicable twa-interval PECact scenario/percentile: 90stes percentil, agriculture cereals distance (m) PECsw via drift PECsw via volatilisation PECsw (via drift and volatilisation) (µg/l) depending on application technique (drift reduction) (%) (µg/l) (%) (µg/l) common 90% red. 75% red. 50% red PEC SW after exposure by surface run-off and drainage Clopyralid The concentration of the active substances clopyralid in adjacent ditch due to surface water runoff and drainage is calculated using den model EXPOSIT 3.0. The input parameters of clopyralid used in EXPOSIT 3.0 are summarized in Table Evaluator UBA/ Germany Date: April 2013

225 Part B Section 5 National Addendum - Germany Central Zone Page 7 of 17 Table 5.3-5: Input parameters of clopyralid for Exposit 3.0 Parameter Solubility in water (mg/l) 7850 LoEP Remark/ Reference DT 50 soil (d) 24 Maximum not normalized field studies, see Table of Part B, Section 5 of the core assessment K OC, Run-off Austrag 2.93 Arithmetic mean, see Table of Part B, Section 5 of the core assessment K OC, Gefährdungsklasse 2.93 Arithmetic mean, see Table of Part B, Section 5 of the core assessment The calculated PECsw values due to surface run-off and drainage are calculated for the active substance clopyralid for the intended for use in spring and winter cereals are given in Table Table 5.3-6: PECsw values for clopyralid after surface water run-off and drainage mobility class 3 use no: Application rate (g/ha) 60 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) Exposure by drainage Drainage time of application autuum/winter/early spring 0.13 Spring/summer 0.40 PECsw in adjacent ditch (µg/l) PECsw in adjacent ditch (µg/l) Florasulam The concentration of the active substances florasulam in adjacent ditch due to surface runoff and drainage is calculated using den model EXPOSIT 3.0. The input parameters of florasulam used in EXPOSIT 3.0 are summarized intable Table 5.3-7: Inputparameter of florasulam for Exposit 3.0 Parameter Solubility in water (mg/l) 121 LoEP Remark/ Reference DT 50 soil (d) percentile of laboratory studies, Evaluator UBA/ Germany Date: April 2013

226 Part B Section 5 National Addendum - Germany Central Zone Page 8 of 17 normalized to 20 C and pf2, see Table of Part B, Section 5 of the core assessment K OC, Run-off Austrag 37 Arithmetic mean, see Table of Part B, Section 5 of the core assessment K OC, Gefährdungsklasse percentile, see Table of Part B, Section 5 of the core assessment The calculated PECsw values due to surface run-off and drainage are calculated for the active substance florasulamfor the intended for use in spring and winter cereals are summarized in Table Table 5.3-8: PECsw values for florasulam after surface water run-off and drainage mobility class 4 use no: Application rate (g/ha) 5 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) Exposure by drainage Drainage time of application autuum/winter/early spring 0.01 Spring/summer 0.03 PECsw in adjacent ditch (µg/l) PECsw in adjacent ditch (µg/l) 5.4 Estimation of concentrations in groundwater (KIIIA1 9.6) Results of PECgw calculation of clopyralid and florasulam for the intended uses of in spring and winter cereals according to EU assessment are given in Part B, Section 5 of the core assessment. For authorization in Germany exposure assessment of groundwater considers two pathways, direct leaching through soil and indirect leaching via bank filtration after surface run-off and drainage of the active substances into the adjacent ditch. Direct leaching through soil is modelled with FOCUS PELMO after choosing the input parameter for degradation and adsorption of the active substances in soil with INPUT DECISION 3.1. Indirect leaching via bank filtration after surface runoff and drainage is modeled with EXPOSIT 3.0. Evaluator UBA/ Germany Date: April 2013

227 Part B Section 5 National Addendum - Germany Central Zone Page 9 of Groundwater concentrations via leaching Groundwater contamination via direct leaching of the active substance and its metabolites, degradation or reaction products through soil is generally assessed by groundwater model calculations. Clopyralid The input parameter for clopyralid regarding the application in its intended use in in spring and winter cereals together with model input parameter for FocusPelmo 4.4. are summarized in Table Input parameters for clopyralid regarding the degradation and adsorption behavior in soil according to INPUT DECION 3.1 are summarized Table Table 5.4-1: Input parameters related to application for PEC gw modelling use no application rate (kg as/ha) 0.06 crop (crop rotation) winter cereals spring cereals date of application 1 st March interception (%) 25 soil moisture Q10-factor 2.58 moisture exponent 0.7 plant uptake 0 simulation period (years) % FC Table 5.4-2: Input parameters according to INPUT DECISION 3.1 for active substance for PEC gw modelling Parent clopyralid Remarks/Reference molecular mass 192 LoEP DT 50 in soil (d) 15 geomean; 10 pf2 standardised laboratory values see Table of Part B, Section 5 of the core assessment K foc 2.93 arithmet. mean see Table of Part B, Section 5 of the core assessment 1/n arithmet. mean see Table of Part B, Section 5 of the core assessment None of the input parameters for clopyralid differ from the input parameters used for groundwater modeling according to EU assessment (see Table and Table of Part B, Section 5 of the core assessment). Thus, the PEC gw of the two FOCUSgw scenarios Hamburg and Kremsmünster, summarized in Table of Part B, Section 5 of the core assessment are considered representative for German exposure assessment and are therefore presented in Table Evaluator UBA/ Germany Date: April 2013

228 Part B Section 5 National Addendum - Germany Central Zone Page 10 of 17 Table 5.4-3: Use No /crop Winter cereals Spring cereals PEC GW at 1 m soil depth for clopyralid Szenario 80 th Percentile PEC GW at 1 m Soil Depth ( g L -1 ) groundwater model: FOCUS PELMO Clopyralid Hamburg <0.001 Kremsmünster <0.001 Hamburg <0.001 Kremsmünster <0.001 According to the PECgw modelling with FocusPelmo a groundwater contamination of the active substance clopyralid at a concentration of 0.1 µg/l is not expected. Florasulam The input parameter for florasulam and its metabolites regarding the application in its intended use in in spring and winter cereals together with model input parameter for FocusPelmo 4.4. are summarized in Table Input parameters according to INPUT DECISION 3.1 for florasulam and its metabolites regarding their degradation and adsorption behavior in soil are summarized in Table 5.4-5, and Table According to INPUT DECISION 3.1, florasulam degrades slower in alkaline soils than in acidic soils. Thus different input parameters were used for the szenario Hamburg (ph ) and the scenario Kremsmünster (ph ). Besides, for the active substance florasulam and the metabolite 5-OH, the variation coefficients of the measured K foc values were >60% and no correlation could be found between the K foc values and any of the soil parameters. In this case, the 10 th percentile of the K f values are used for the first three soil horizons of the model scenario Hamburg in FOCUS PELMO together with a default value of zero for the soil horizons 4-6. Table 5.4-4: Input parameters related to application for PECgw modelling use no application rate (kg as/ha) crop (crop rotation) date of application interception (%) 25 soil moisture Q10-factor 2.58 moisture exponent 0.7 plant uptake 0 simulation period (years) 10 winter cereals Spring cereals 1 st of March 100 % FC Evaluator UBA/ Germany Date: April 2013

229 Part B Section 5 National Addendum - Germany Central Zone Page 11 of 17 Table 5.4-5: Input parameters according to INPUT DECISION 3.1 for the active substance for PEC gw modelling Parent florasulam Remarks/Reference molecular mass LoEP DT 50 in soil (d) 2.2 Geomean, all soils for scenario Hamburg, see Table of Part B, Section 5 of the core assessment 2.49 K f Geomean, neutral and alkaline soils (ph>7)) for scenario Kremsmünster,, see Table of Part B, Section 5 of the core assessment 10 th percentile to be used for the 1.-3 rd soil horizon for szenario Hamburg (see Table of Part B, Section 5 of the core assessment) Default to be used for the 4.-6th soil horizon for szenario Hamburg (see Table of Part B, Section 5 of the core assessment) 37 Arithmetic mean for szenario Kremsmünster (see Table of Part B, Section 5 of the core assessment) 1/n Arithmetic mean (see Table Table of Part B, Section 5 of the core assessment) Table 5.4-6: Input parameters according to INPUT DECISION 3.1 for the metabolites of florasulam for PEC GW modelling Metabolite 1 5-OH-XDE-570 Remarks/Reference molecular mass LoEP Formation fraction (Florasulam 5-OH) Arithmetic mean (see Table of Part B, Section 5 of the core assessment) DT 50 in soil (d) 19.7 Geomean (see Table of Part B, Section 5 of the core assessment) K f th percentile to be used for the soil horizon for szenario Hamburg (see Table of Part B, Section 5 of the core assessment) 0 Default to be used for the 4.-6th soil horizon for szenario Hamburg (see Table of Part B, Section 5 of the core assessment) 31 Arithmetic mean for szenario Kremsmünster (see Table of Part B, Section 5 of the core assessment) 1/n Arithmetic mean (see Table of Part B, Section 5 of the core assessment) Metabolite 2 DFP-ASTCA Remarks/Reference Evaluator UBA/ Germany Date: April 2013

230 Part B Section 5 National Addendum - Germany Central Zone Page 12 of 17 molecular mass LoEP Formation fraction (5-OH DFP-ASTCA) Arithmetic mean (see Table of Part B, Section 5 of the core assessment) DT 50 in soil (d) 12.4 Geomean (see Table of Part B, Section 5 of the core assessment) K foc 53 Arithmetic mean (see Table of Part B, Section 5 of the core assessment) 1/n 1.0 Default value for substances when only Kdoc values have been determined (see Table of Part B, Section 5 of the core assessment) Metabolite 3 ASTCA Remarks/Reference molecular mass LoEP Formation fraction (DFP-ASTCA ASTCA) Maximum (see Table of Part B, Section 5 of the core assessment) DT 50 in soil (d) 234 Maximum (see Table of Part B, Section 5 of the core assessment) K foc 83 Arithmetic mean (see Table ) 1/n 1.0 Default value for substances when only Kdoc values have been determined (see Table of Part B, Section 5 of the core assessment) The modelled PEC gw values for the two FOCUSgw scenarios Hamburg and Kremsmünster which are considered representative for German exposure assessment, are summarized in Table Table 5.4-7: Use No (crop) Spring cereals Winter cereals PEC GW at 1 m soil depth of florasulam and its metabolites Szenario 80 th Percentile PEC GW at 1 m Soil Depth ( g L -1 ) Florasulam Metabolit 5-OH Metabolit DFP-ASTCA Metabolit ASTCA Hamburg < Kremsmünster < Hamburg < Kremsmünster < According to the PECgw modelling with FOCUS PELMO 4.4.3, a groundwater contamination of the active substance florasulam at a concentration of 0.1 µg/l is not expected. For the metabolites 5-OH and DFP-ASTCA, groundwater concentrations of 0.1 µg/l can also be excluded. For the metabolite ASTCA, groundwater concentrations of 0.1 µg/l cannot be excluded according to the results of the groundwater simulation with FOCUS-PELMO However, these Evaluator UBA/ Germany Date: April 2013

231 Part B Section 5 National Addendum - Germany Central Zone Page 13 of Higher tier leaching assessment Clopyralid Since a groundwater contamination of the active substance clopyralid at a concentration of 0.1 µg/l are not expected according to the PECgw modelling with FOCUS PELMO 4.4., higher tier leaching assessment is not required for the intended use of in spring and winter cereals. Florasulam Since groundwater contaminations of the active substance florasulam at a concentration of 0.1 µg/l is not expected according to the PECgw modelling with FOCUS PELMO 4.4., higher tier leaching assessment is not required for the intended use of in spring and winter cereals Summary of groundwater concentrations via leaching Results of modelling with FocusPelmo show that the active substances clopyralid and florasulam are not expected to leach into groundwater at concentrations in concentrations 0.1µg/L in the intended uses of in spring and winter cereals. According to the modeling results with Focus Pelmo 4.4.3, concentrations of 0.1µg/L in the groundwater via leaching can also be excluded for the metabolites 5-OH and DFP-ASTCA. For the metabolites ASTCA concentrations of 0.1µg/L in groundwater cannot be excluded. However an assessment of this metabolite has already been performed for EU approval of florasulam. The metabolite ASTCA is classified as not relevant for groundwater. Consequences for authorization: None Groundwater concentration via bank filtration of ditch water Clopyralid Groundwater contamination with the active substance clopyralid after surface water run-off and drainage of the active substance clopyralid into an adjacent ditch with subsequent bank filtration is estimated using the model EXPOSIT 3.0. The input parameters of clopyralid used in EXPOSIT 3.0 are summarized in Table The calculated concentrations of clopyralid in the groundwater after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration are given in Table Table 5.4-8: PECgw values for clopyralid after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration mobility class 3 elimination rate during bank filtration 90% use no: Application rate (g/ha) 60 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) PECgw (µg/l) Evaluator UBA/ Germany Date: April 2013

232 Part B Section 5 National Addendum - Germany Central Zone Page 14 of Exposure by drainage Drainage time of application autuum/winter/early spring Spring/summer PECgw (µg/l) Groundwater contaminations 0.1 µg/l of the active substance clopyralid via surface run-off and drainage into the adjacent ditch with subsequent bank filtration estimated by the model EXPOSIT 3.0 is not expected. Florasulam Groundwater contamination with the active substance florasulam after surface water run-off and drainage of the active substance florasulam into an adjacent ditch with subsequent bank filtration is estimated using the model EXPOSIT 3.0. The input parameters of florasulam used in EXPOSIT 3.0 are summarized in Table The input parameters of the soil metabolites 5-OH, DFP-ASTCA and ASTCA used in EXPOSIT 3.0 are summarized in Table Table 5.4-9: Inputparameter of the metabolites 5-OH, DFP-ASTCA and ASTCA for Exposit 3.0 Metabolit Parameter Molecular correction factor Maximum occurrence in soil (%) 5-OH Remark/ Reference 71.6 See Table of Part B, Section 5 of the core assessment DT 50 soil (d) percentile of laboratory studies, normalized to 20 C and pf2, see Table of Part B, Section 5 of the core assessment K OC, Run-off Austrag 31 Arithmetic mean, see Table of Part B, Section 5 of the core assessment K OC, Gefährdungsklasse percentile, see Table of Part B, Section 5 of the core assessment Metabolit Parameter Molecular correction factor Maximum occurrence in soil (%) DFP-ASTCA Remark/ Reference 17.8 See Table of Part B, Section 5 of the core assessment DT 50 soil (d) percentile of laboratory studies, normalized to 20 C and pf2, see Table Evaluator UBA/ Germany Date: April 2013

233 Part B Section 5 National Addendum - Germany Central Zone Page 15 of 17 of Part B, Section 5 of the core assessment K OC, Run-off Austrag 53 Arithmetic mean, see Table of Part B, Section 5 of the core assessment K OC, Gefährdungsklasse 53 Arithmetic mean, see Table of Part B, Section 5 of the core assessment Metabolit Parameter Molecular correction factor Maximum occurrence in soil (%) ASTCA Remark/ Reference 40 See Table of Part B, Section 5 of the core assessment DT 50 soil (d) 234 Maximum of laboratory studies, normalized to 20 C and pf2, see Table of Part B, Section 5 of the core assessment K OC, Run-off Austrag 83 Arithmetic mean, see Table of Part B, Section 5 of the core assessment K OC, Gefährdungsklasse 83 Arithmetic mean, see Table of Part B, Section 5 of the core assessment The calculated concentrations for florasulam in the groundwater after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration are given in Table The calculated concentrations for the metabolites 5-OH, DFP-ASTCA and ASTCA in the groundwater after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration are given in Table , Table , and Table Table : PECgw values for florasulam after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration mobility class 4 elimination rate during bank filtration 100% use no: Application rate (g/ha) 5 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) 0 < PECgw (µg/l) 5 < < < Exposure by drainage Drainage time of application PECgw (µg/l) autuum/winter/early spring < Evaluator UBA/ Germany Date: April 2013

234 Part B Section 5 National Addendum - Germany Central Zone Page 16 of 17 Spring/summer < Table : PECgw values for 5-OH after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration mobility class 3 elimination rate during bank filtration 90% use no: Application rate (g/ha) 3.4 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) 0 < PECgw (µg/l) 5 < < < Exposure by drainage Drainage time of application autuum/winter/early spring < Spring/summer < PECgw (µg/l) Table : PECgw values for DFP-ASTCA after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration mobility class 2 elimination rate during bank filtration 75% use no: Application rate (g/ha) 0.7 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) 0 < PECgw (µg/l) 5 < < < Exposure by drainage Drainage time of application PECgw (µg/l) Evaluator UBA/ Germany Date: April 2013

235 Part B Section 5 National Addendum - Germany Central Zone Page 17 of 17 autuum/winter/early spring < Spring/summer < Table : PECgw values for ASTCA after surface water run-off and drainage into an adjacent ditch with subsequent bank filtration mobility class 2 elimination rate during bank filtration 75% use no: Application rate (g/ha) 0.9 Interception (%) 25 Exposure by surface runoff vegetated buffer strip (m) 0 < PECgw (µg/l) 5 < < < Exposure by drainage Drainage time of application autuum/winter/early spring < Spring/summer < PECgw (µg/l) Groundwater entries of the active substance florasulam and its metabolites 5-OH, DFP-ASTCA and ASTCA in concentrations 0.1 µg/l via surface run-off and drainage into the adjacent ditch with subsequent bank filtration estimated by the model EXPOSIT 3.0 are not expected Summary of groundwater concentrations via bank filtration of ditch water Results of modeling results with EXPOSIT 3.0 show that the active substance florasulam and clopyralid are not expected to reach the groundwater at concentrations of 0.1µg/L via surface run-off and drainage into the adjacent ditch with subsequent bank filtration in the intended uses of Primus Perfect in spring and winter cereals. According to the modeling results of EXPOSIT 3.0, concentrations of 0.1µg/L in groundwater can also be excluded for the metabolites 5-OH, DFP-ASTCA and ASTCA. Consequences for authorization: None Evaluator UBA/ Germany Date: April 2013

236 Part B Section 6 Core Assessment Germany Central Zone Page 1 of 102 REGISTRATION REPORT Part B Section 6: Ecotoxicological Studies Detailed summary of the risk assessment Product code Active Substance Member State: Germany Central Zone CORE ASSESSMENT Florasulam 25 g/l Clopyralid 300 g/l Applicant Dow AgroSciences Date April 2013 Evaluator: Germany Date: April 2013

237 Part B Section 6 Core Assessment Germany Central Zone Page 2 of 102 SEC 6 Table of Contents ECOTOXICOLOGICAL STUDIES Proposed use pattern Consideration of metabolites EFFECTS ON BIRDS (IIIA1 10.2) Overall summary Toxicity to exposure ratio for birds (K III A ) Drinking water exposure Details on formulation type in proportion per item Acute toxicity of the formulation (IIIA ) Supervised cage or field trials (IIIA ) Acceptance of bait, granules or treated seeds (palatability testing) (IIIA ) Effects of secondary poisoning (IIIA ) EFFECTS ON TERRESTRIAL VERTEBRATES OTHER THAN BIRDS (IIIA1 10.3) Overall summary Toxicity exposure ratios (IIIA ) Drinking water exposure Details on formulation type in proportion per item EFFECTS ON AQUATIC ORGANISMS (IIIA1 10.2) Overview and summary Toxicity exposure ratios (IIIA ) Risk from metabolites Acute toxicity of the formulation (IIIA ) Chronic toxicity to fish (IIIA ) Chronic toxicity to aquatic invertebrates (IIIA ) Accumulation in aquatic non-target organisms (IIIA ) EFFECTS ON BEES (IIIA 10.4) EFFECTS ON ARTHROPODS OTHER THAN BEES (IIIA 10.5) Overall Summary Overall conclusion Risk Assessment for Arthropods other than Bees Using artificial substrates Extended laboratory studies (IIIA ) Semi-field tests (IIIA ) Field tests (IIIA ) EFFECTS ON EARTHWORMS AND OTHER SOIL NON-TARGET MACRO-ORGANISMS (IIIA 10.6) Overall summary Toxicity exposure ratios, TER A and TER LT (IIIA ) Acute toxicity (IIIA ) Sublethal effects (IIIA ) Field tests (IIIA ) Residue content of earthworms (IIIA ) Effects on other non-target macro-organisms (IIIA ) Effects on organic matter breakdown (IIIA ) EFFECTS ON SOIL MICROBIAL ACTIVITY (IIIA 10.7) Overall summary Laboratory testing (IIIA ) Additional testing (IIIA ) EFFECTS ON NON-TARGET PLANTS (IIIA 10.8) Terrestrial plants (IIIA ) Effects on non-target aquatic plants (IIIA ) OTHER NON-TARGET SPECIES (FLORA AND FAUNA) (IIIA 10.9) Available preliminary data on other non-target species (flora and fauna) (IIIA ) Critical assessment of relevance of preliminary test data (IIIA ) OTHER/SPECIAL STUDIES (IIIA 10.10) Laboratory studies (IIIA ) Field studies (IIIA ) Evaluator: Germany Date: April 2013

238 Part B Section 6 Core Assessment Germany Central Zone Page 3 of 102 APPENDIX 1: APPENDIX 1: LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION 45 APPENDIX 2: DETAILED EVALUATION OF STUDIES RELIED UPON...49 A2-1 ACTIVE SUBSTANCE AND ITS METABOLITES (GENERALLY ONLY RELEVANT IN THE CASE THAT NEW ANNEX II DATA IS PROVIDED AFTER FLORASULAM APPROVAL) A2-2 FORMULATION APPENDIX 3: TABLE OF INTENDED USES, GAP AND JUSTIFICATION FOR THE RISK ENVELOPE 100 INTRODUCTION RISK ENVELOPE RATIONALE FOR ENVIRONMENTAL FATE AND BEHAVIOUR ) Soil: ) Groundwater ) Surface water Evaluator: Germany Date: April 2013

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240 Part B Section 6 Core Assessment Germany Central Zone Page 5 of 102 Sec 6 ECOTOXICOLOGICAL STUDIES Introduction This document reviews the ecotoxicological effects of the product containing the active substances florasulam and clopyralid, which are currently approved under Reg. (EC) No 1107/2009 (repealing Directive 91/414/EEC) and fulfill the criteria according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Details of the active substances, the Annex I inclusion Directives and Commission Review Reports or EFSA Conclusions are provided in the following table: Table 6-1 Details for the active substances Active substance Annex I Inclusion Directive EFSA Conclusions or SANCO Review Report a Florasulam 2002/64/EC SANCO/1406/2001 Clopyralid 2006/64/CE EFSA Scientific Report (2005) 50, 1-65 a Only the document containing the EU agreed endpoints is listed. The Annex I Inclusion Directive for clopyralid and florasulam provide specific provisions under Part B which need to be considered by the applicant in the preparation of their submission and by the MS prior to granting an authorisation. For the implementation of the uniform principles of Annex VI, the conclusions of the SANCO Review Report on clopyralid and florasulam, and in particular Appendices I and II thereof, as finalised in the Standing Committee on the Food Chain and Animal Health on 19 April 2002 (florasulam) and on 4 April 2006 (clopyralid) shall be taken into account. For florasulam no specific provisions relevant to the ecotoxicological risk assessment is indicated. In the case of clopyralid, it is indicated that Member States must pay particular attention to the protection of non target plants. These concerns have been addressed within the current submission. was not the representative formulation considered in the EU review process as part of the approvals of florasulam and clopyralid. A full risk assessment according Commission Regulation (EU) No 546/2011 is provided. Addenda are included containing country specific assessments for some annex points. In those cases this document should be read in conjunction with the relevant addenda. Where appropriate, this document refers to the conclusions of the EFSA, especially when data on the active substance is relied upon in the risk assessment of the formulation. Each section will begin with a table providing the EU endpoints used in this evaluation. Appendix 1: of this document contains the list of references included in this document in support of the evaluation. Appendix 2: of this document reports the detailed evaluation of studies relied upon. Fehler! Verweisquelle konnte nicht gefunden werden. of this document is the table of intended uses for. Information on the detailed composition of can be found in the confidential dossier of this submission ( - Part C). Evaluator: Germany Date: April 2013

241 Part B Section 6 Core Assessment Germany Central Zone Page 6 of Proposed use pattern The critical GAP used for exposure assessment are presented in Table that reports also a classification of intended uses for (see also Section 5). A list of all intended uses within the Central Zone is given in Appendix 3. Table 6.2-1: Critical use pattern of Group/ use No Crop/growth stage Application method Drift scenario Number of applications, Minimum application interval, application time, interception Application rate, cumulative (g as/ha) Soil effective application rate (g as/ha) Winter wheat, Winter barley, Winter triticale, Winter rye, Spelt wheat, Spring wheat, Spring barley, Spring oats, Durum wheat (BBCH 13) spraying agriculture 1 x 0.2 L/ha Primus Perfect (eq. 232 g/ha Primus Perfect) containing 60 g as/ha clopyralid & 5 g as/ha florasulam 25% crop interception 0.2 L/ha Primus Perfect (eq. 232 g/ha ) containing 60 g as/ha clopyralid & 5 g as/ha florasulam 25% crop interception 174 g Primus Perfect/ha with 45 g as/ha clopyralid and 3.75 g as/ha florasulam Consideration of metabolites The occurrence and risk from potentially ecotoxicologically relevant metabolites have been considered in the EU review of clopyralid and florasulam. According to the results of the assessment of clopyralid for EU approval, no major metabolites of clopyralid occur in the environment. Environmental occurring metabolites of florasulam according to the results of the assessment of florasulam on for EU approval are summarized in Table The risk from the potentially ecotoxicologically relevant metabolites 5-OH- XDE-570, DFP-ASTCA, and ASTCA of florasulam has already been performed on EU approval. The metabolites have been regarded as ecotoxicologically not relevant but persistence of the metabolites 5- OH-XDE-570, DFP-ASTCA, and ASTCA in soil was not considered. Therefore, the metabolites of florasulam will be considered further in the risk assessment for earthworms and other non-target Soil Organisms in this core assessment (see RR CA Part B, Section 6.7). Additionally to the assessment within the EU review of florasulam, also the risk based on run-off events of the florasulam metabolites 5-OH- XDE-570, DFP-ASTCA, TSA, and ASTCA on aquatic organisms was assessed in this core assessment (see RR CA Part B, Section 6.3.3). Table 6.2-2: Metabolites of florasulam potentially relevant for exposure assessment (> 10% of as or > 5% of as in 2 sequential measurements or >5 % of as and maximum of formation not yet reached at the end of the study) Metabolite 5-OH-XDE OHflurasulam (XDE hydroxy) N-(2,6- difluorophenyl) Structural formula/molecular weight F F N O S O N N M = g/mol N OH F N Maximum occurence in compartements Soil, aerob: max % after 3 d Water of water/sediment study: max. 64 % after 60 d Sediment of water/sediment study: Ecotoxicologically relevant (see DAR/ EFSA conclusion) Aquatic organisms: Water: not relevant 2) Sediment: not relevant Terrestrial organisms: not relevant 2) Groundwater: not relevant (Step 2) 1) Evaluator: Germany Date: April 2013

242 Part B Section 6 Core Assessment Germany Central Zone Page 7 of fluoro-5- hydroxyl (1,2,4) triazolo(1,5c) pyrimidine-2- sulphonamide max. 35 % after 60 d (Soil photolysis: 60%) DFP-ASTCA (M3) N-(2,6- difluorophenyl) -5- aminosulphony l-1h- 1,2,4)triazole- 3-carboxylic acid F F N H O S O H N N M = g/mol N COOH Soil, aerob: max % after 28 d Water of water/sediment study: max. 15 % after 100 d Sediment of water/sediment study: max % after 182 d Aquatic organisms: Water: not relevant 2) Sediment: not relevant Terrestrial organisms: not relevant 2) Groundwater: not relevant (Step 2) 1) ASTCA (M4) 5- (aminosulphon yl)-1h-1,2,4- triazole-3- carboxylic acid O N H H 2 N S N O N COOH M = g/mol Soil, aerob: max % after 59 d Aquatic organisms: Water: not relevant 2) Sediment: not relevant Terrestrial organisms: not relevant 2) Groundwater: not relevant (Step 3-4) 1) 1) According to Guidance Document on the assessment of the relevance of metabolites in groundwater of substances regulated under council directive 91/414/EEC (SANCO/221/2000 rev.10- final - 25 February 2003) 2) Additionally, the risk for the persistent soil metabolites was assessed in this core assessment. 6.2 Effects on Birds (IIIA1 10.2) Overall summary Avian acute oral and long-term reproduction studies have been carried out with florasulam and clopyralid. Full details of avian toxicity studies are provided in the respective EU DAR. The studies with the relevant acute and long-term endpoints were agreed during EU review process and are used for the risk assessment. Effects on birds for were not evaluated as part of the EU review of either clopyralid or florasulam. However, the provision of further data on the formulation is not considered essential as the available data on clopyralid and florasulam are deemed to be sufficient to assess the risk of birds exposed to. The risk assessment for effects on birds and other terrestrial vertebrates is carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12): 1438). Evaluator: Germany Date: April 2013

243 Part B Section 6 Core Assessment Germany Central Zone Page 8 of Toxicity The studies with the relevant acute and long-term endpoints which are used in the risk assessment procedure are listed in the following table: Table 6.2-1: Toxicity of florasulam and clopyralid to birds with reference to agreed endpoints species substance expostition: duration system Coturnix japonica Colinus virginianus Anas platyrhynchos Anas platyrhynchos Florasulam (DE-570) Florasulam (DE-570) Clopyralid Clopyralid 1 d akute 147 d Reproduction 1 d akute 140 d Reproduction results: toxicity LD 50 = 1047 mg/kg bw 2) NOEC = 162 mg/kg bw 2) = 1500 mg ai/kg food; highest concentration tested LD 50 = 1465 mg/kg bw 1) NOEC = 118 mg/kg bw 1) 1) EFSA Scientific Report (2005) 50, 1-65: Conclusion on the peer review of clopyralid 2) SANCO/1406/2001-final (2002): Review report for the active substance florasulam Refence: Author Date code XXX XXX XXX 1980 GH-RC 164 XXX ICS-No As indicated above, studies with the formulated product have not been conducted. Consequently, the toxicity of has been assessed considering data generated on the individual active substances and assuming dose additivity of the single active substances in the formulation (see 'Mixture toxicity' chapter below) Exposure is an herbicide formulation containing florasulam and clopyralid as active substances. The product is formulated as a suspension concentrate (SC). According to the GAP, is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). It will be used against weeds (annual dicotyledonous plants) on cereals (winter and summer). Exposure to standard generic focal species was estimated according to the Guidance Document on Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12): 1438). DDD i i PD FIR i FIR bw i bw total RUD AR PT RUD AR PT DDD PDi FIRi bw Daily dietary dose (mg/kg bw/day) composition of diet obtained from treated area Food intake rate of indicator species i (g fresh weight/d) Bodyweight (g) Evaluator: Germany Date: April 2013

244 Part B Section 6 Core Assessment Germany Central Zone Page 9 of 102 RUD Residue per unit dose, bases on an application rate of 1 kg a.s./ha and assuming broadcast seedling AR Application rate (kg/ha) PT Proportion of diet obtained in the treated area (0 1) In a first approach (Tier 1 assessment), it is assumed that birds do not avoid contaminated food items and that they feed exclusively in the treated area and on a single food type. Factors PT and PD are therefore equal to 1. The risk assessment procedure follows a stepwise approach. A first screening step involves standard scenarios and default values for the exposure estimate, representing a reasonable worst case. If a potential risk is indicated in the screening step, then one or several refinement steps (Tier 1, Tier 2) may follow. According to the Guidance Document, no further assessment is required if all uses are safe in the screening step. Mixture toxicty According to Appendix B of the Guidance Document on the Risk assessment for birds and mammals (EFSA, 2009), the basic concept of the risk assessment is that animals are exposed to residues of the active substances in the environment. Thus, the assessment of is not an assessment of the formulation toxicity as such, but an assessment of the effects of an exposure to a mixture of active substances in the environment, resulting from the use of the formulation. Toxicity studies for birds with formulated products are typically not available. For the assessment of acute effects, a surrogate LD 50 is calculated. Sublethal effects and effects on reproduction are assessed on a case-by-case basis. A model often used to estimate the toxicity of mixtures is the assumption of dose/concentration additivity of toxicity (Finney approach of concentration additivity of toxicity; Finney, D.J., 1948 and 1971). The following formula is used to derive a surrogate LD 50 for the mixture of active substances with known toxicity assuming dose additivity:.. 1 X a s. i LD 50 mix 50. i LD a s i where: X( a.s.i) = fraction of active substance (i) in the mixture expressed as: X (Florasulam) = 25 g a.s./kg / (25 g florasulam/kg g clopyralid/kg) = 0,08 X( quinmerac) = 300 g a.s./kg / (25 g florasulam/kg g clopyralid/kg) = 0,92 LD 50(a.s.i) = acute toxicity value for active substance (i) Because of the direct proportionality of the - according to the guidance document calculated - TER to the LD 50, it is possible, to calculate a TER(mix) with the following formula: TER(mix) i 1 TER(a.s. i ) 1 With: TER (a.s.i) = calculated TER for the active substance i Evaluator: Germany Date: April 2013

245 Part B Section 6 Core Assessment Germany Central Zone Page 10 of Risk Assessment overall conclusions The results of the acute and reproductive risk assessments are summarized in the following table: Table 6.2-2: TERs for birds after uses of in cereals Substance Risk assessment level Indicator bird Timescale TER TER risk assessment trigger Clopyralid Screening Small omnivorous Acute Screening Small omnivorous Long-term 57 5 Florasulam Screening Small omnivorous Acute Screening Small omnivorous Long-term Screening Small omnivorous Acute 138* 10 Screening Small omnivorous Long-term 52* 5 TERs shown in bold fall below the relevant trigger. * calculated mixture toxicity Drinking water risk assessment Drinking water assessments are not required as the ratio of effective treatment rate to toxicological endpoint does not exceed the trigger. Food chain behaviour An assessment of the risk from secondary poisoning is not required due to log POW values below the trigger Toxicity to exposure ratio for birds (K III A ) Acute toxicity exposure ratio (TER A ) Screening step Indicator species are used in the screening step. These are no real species but by size and feeding habits are considered to have higher exposure than other species occurring in a specific crop at a particular time, representing a worst case scenario. The indicator species for the intended uses are listed in the following table: Table: Avian indicator species for the use of and shortcut values Scenario Crop Indicator species Shortcut value (90th percentile RUD BBCH cereals Small omnivorous bird The following equations were used: Daily dietary dose: DDD single application = application rate [kg/ha] shortcut value* * see section 4.1 of EFSA/2009/1438 Toxicity exposure ratio (acute): Evaluator: Germany Date: April 2013

246 Part B Section 6 Core Assessment Germany Central Zone Page 11 of 102 TER A LD50 (mg/kg bw/day) = Acute DDD (mg/kg bw/day) The resulting TER A values for florasulam and clopyralid as well as calculated mixture toxicity for Primus Perfect are summarised in the following table: Table 6.2-3: Acute screening risk assessment (TER A ) for birds from uses Substance Indicator bird App. rate (kg/ha) Primus Perfect Clopyralid Florasulam Small omnivorous Small omnivorous Small omnivorous Shortcut value (acute) MAF DDD (mg/kg bw) LD 50 (mg/kg bw) TER A N/A N/A a based on a use rate of 0.2 L/ha and a nominal formulation density of 1.16 g/ml. TERs shown in bold fall below the relevant trigger. Based on the highly conservative presumptions of the screening step, the acute risk of exposure of birds to florasulam and clopyralid at the submitted indications of the formulation achieves the acceptability criteria TER 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point for acute effects Short-term toxicity exposure ratios (TER ST ) (IIIA ) There is no requirement for the calculation of TER ST for birds under the EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) and, consequently, a risk assessment for short-term toxicity has not been conducted Long-term toxicity exposure ratio (TER LT ) (IIIA ) Screening step For the reproductive risk assessment, the calculation of the long-term toxicity exposure ratio (TER LT ) in principle follows the same procedure as for the acute risk assessment. However, the defined daily dose is obtained by multiplying the application rate with the mean short-cut values (based on mean RUD according to the new Guidance Document; EFSA, 2009) as summarized in the following table: Scenario Crop Indicator Species Shortcut value (mean RUD) BBCH Cereals Small omnivorous bird 64.8 In accordance with the guidance document, it is justified to apply a time-weighted average (TWA) factor of 0.53 based on the default observation interval of 21 days and a default DT 50 of 10 days for the calculation of the DDD (daily dietary dose): DDD single application = application rate [kg/ha] shortcut value TWA* * see section 4.3 of EFSA/2009/1438 Toxicity exposure ratio (longterm): Evaluator: Germany Date: April 2013

247 Part B Section 6 Core Assessment Germany Central Zone Page 12 of 102 NOEL(mg/kg bw/day) TER LT = Long - term DDD (mg/kg bw/day) Long-term toxicity exposure ratios (TER LT ) for clopyralid and florasulam following applications of were calculated and results are summarised in table Table 6.2-4: Long-term screening risk assessment (TER LT ) for birds from uses Substance Clopyralid Florasulam Primus Perfect Indicator bird Small omnivorous Small omnivorous Small omnivorous App. rate (kg/ha) Shortcut value (long-term) f TWA a MAF DDD (mg/kg bw/day) NOEC (mg/kg bw/day) N/A a N/A b 608 TER LT a NOEC value for clopyralid of 118 mg/kg bw. b Endpoint is the LD 50 for florasulam of 1046 mg/kg bw divided by 10. The resulting value is lower than the NOEC from the reproductive study for florasulam of >162 mg/kg bw and it is therefore used in the risk assessment. N/A not applicable. TERs shown in bold fall below the relevant trigger. *calculated mixture toxicity 52* Based on the highly conservative presumptions of the screening step, the long term risk of exposure of birds to florasulam and clopyralid at the submitted GAP of the formulation achieves the acceptability criteria TER 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point for long term effects Drinking water exposure In case of early post-emergence uses as intended for birds might be exposed via drinking water from puddles. According to the new Guidance Document (EFSA, 2009), no specific calculations of drinking water exposure and TER are necessary when the ratio of effective application rate (in g/ha) to the relevant endpoint (in mg/kg bw/d) does not exceed 50 in the case of less sorptive substances (Koc < 500 L/kg) or 3000 in the case of more sorptive substances (Koc 500 L/kg). This is due to the characteristics of the exposure scenario in connection with the standard assumptions for water uptake by birds (for further details please refer to chapter 5.5. of the Guidance Document). The puddle scenario has been taken into account to calculate the exposure concentration of formed on a field after rainfall. The ratios do not exceed the value of 50 for florasulam (Koc = 37 L/kg) and clopyralid (Koc = 2.93 L/kg), thus it is not necessary to conduct a drinking water risk assessment for birds Details on formulation type in proportion per item Baits: Concentration of active substance in bait in mg/kg (IIIA ) is not formulated as bait Pellets, granules, prills or treated seed (IIIA ) is not formulated as pellets, granules, prills or treated seeds. Evaluator: Germany Date: April 2013

248 Part B Section 6 Core Assessment Germany Central Zone Page 13 of 102 Amount of active substance in or on each item (IIIA ) Not applicable. Proportion of active substance LD 50 per 100 items and per gram of items (IIIA ) Not applicable. Size and shape of pellet, granule or prill (IIIA ) Not applicable Acute toxicity of the formulation (IIIA ) An acute oral study with the formulated product has not been conducted. Consequently, the toxicity of has been assessed considering data generated on the individual active substances and the estimated LD 50 value for assuming dose additivity of the single active substances in the formulation Supervised cage or field trials (IIIA ) The risk assessment above demonstrated that the proposed uses of pose no unacceptable acute or long-term risks to birds, and therefore further studies are not considered necessary Acceptance of bait, granules or treated seeds (palatability testing) (IIIA ) The information concerned is not relevant since is intended for use as a foliar spray Effects of secondary poisoning (IIIA ) The EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) states that a log K ow 3 is used to indicate that there might be a potential for bioaccumulation (see Section 5.6 Bioaccumulation and food chain behaviour). The log K ow of clopyralid and florasulam are and and so these active substances have a negligible potential to bioaccumulate in animal tissues. No formal risk assessment from secondary poisoning is therefore required. 6.3 Effects on Terrestrial Vertebrates Other Than Birds (IIIA1 10.3) Overall summary Effects on mammals for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for with the proposed use pattern are provided here and are considered adequate. The risk assessment for effects on mammals is carried out according to the European Food Safety Authority Guidance Document on Risk Assessment for Birds and Mammals on request from EFSA (EFSA Journal 2009; 7(12): 1438) Toxicity The studies with the relevant acute and long-term endpoints which are used in the risk assessment procedure are listed in the following table: Table 6.3-1: Toxicity of clopyralid, florasulam and to mammals species substance exposition: duratrion system Results: toxicity Reference: author date ICS-No. Evaluator: Germany Date: April 2013

249 Part B Section 6 Core Assessment Germany Central Zone Page 14 of 102 Mouse Rat XDE-570 tech. (Florasulam) Lontrel T (Clopyralid) Akute oral LD mg/kg bw 2) Acute oral LD 50 > 5000 mg/kg bw 1) Rat Akute oral LD mg/kg bw 3) Rat Florasulam Two-generation dietary reproduction Rat Dowco 290 (Clopyralid) NOEL = 100 mg/kg KG/d Parents 2) 2-year chronic NOAEL = 50 mg/kg bw reduction in bodyweight 1) code XXX ; DR XXX 1987 K A XXX ! XXX XXX 1977 n.b ) EFSA Scientific Report (2005): 50, 1-65: Conclusion on the peer review of clopyralid 2) SANCO/1406/2001-final (2002): Review report for the active substance florasulam 3) New study submitted by the applicant, detailed information in Annex 2 of this document Exposure is an herbicide formulation containing florasulam and clopyralid as active substances. The product is formulated as a suspension concentrate (SC). According to the GAP, is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). It will be used against weeds (annual dicotyledonous plants) on cereals. Exposure to standard generic indicator species was estimated according to the Guidance Document on Risk Assessment for Birds and Mammals (EFSA Journal 2009; 7(12): 1438; see chapter for detailed information of calculation of TER and mixture toxicity) Risk assessment - overall conclusions The resulting TERvalues are represented in the following table: Evaluator: Germany Date: April 2013

250 Part B Section 6 Core Assessment Germany Central Zone Page 15 of 102 Table 6.3-2: Minimum TERs for mammals after uses of in cereals Substance Risk assessment level Screening Indicator mammal Timescale TER TER risk assessment trigger Small herbivorous Acute > Long-term 31 5 Clopyralid Florasulam TERs shown in bold fall below the relevant trigger. Acute > Long-term Acute > Long-term Toxicity exposure ratios (IIIA ) Acute toxicity exposure ratio (TER A ) (IIIA ) Screening step Indicator species are used in the screening step. These are no real species but by size and feeding habits are considered to have higher exposure than other species occurring in a specific crop at a particular time. The indicator species for the intended uses are listed in the following table: Table 6.3-3: Indicator species according to the GAP Scenario Crop Indicator species Shortcut value (90th percentile RUD) BBCH Cereals Small herbivorous mammal 18.4 The following equations were used: Daily dietary dose: DDD single application = application rate [kg/ha] shortcut value* * see section 4.1 of EFSA/2009/1438 Toxicity exposure ratio (acute): TER A LD50 (mg/kg bw/day) = AcuteDDD(mg/kg bw/day) Table 6.3-4: Acute screening risk assessment (TER A ) for mammals from uses Substance Primus Perfect Clopyralid Indicator mammal Small herbivorous Small herbivorous App. rate (kg/ha) Shortcut value (acute) MAF DDD (mg/kg bw) LD 50 (mg/kg bw) TERA a N/A 27.5 >2000 > N/A 7.10 >5000 >704 Evaluator: Germany Date: April 2013

251 Part B Section 6 Core Assessment Germany Central Zone Page 16 of 102 Florasulam Small herbivorous N/A >5000 >8440 a based on a use rate of 0.2 L/ha and a nominal formulation density of 1.16 g/ml. N/A not applicable. TERs shown in bold fall below the relevant trigger. Based on the highly conservative presumptions of the screening step, the acute risk of exposure of terrestrial vertebrates other than birds to florasulam and clopyralid as well as the formulation Primus Perfect achieves the acceptability criteria TER 10, according to directive 1107/2009 (EG), Annex IV, uniform principles, point for acute effects. Therefore, no further risk assessment is necessary Short-term toxicity exposure ratio (TER ST ) (IIIA ) There is no requirement for the calculation of TER ST for mammals under the EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) and, consequently, a risk assessment for short-term toxicity has not been conducted Long-term toxicity exposure ratio (TER LT ) (IIIA ) Screening step For the reproductive risk assessment, the calculation of the long-term toxicity exposure ratio (TER LT ) in principle follows the same procedure as for the acute risk assessment. However, the defined daily dietary dose is obtained by multiplying the application rate with the mean short-cut value (based on the mean RUD according to the new Guidance Document; EFSA, 2009) as summarized in the following table: Table 6.3-5: Indicator species according to the GAP Szenario Crop Indicator species Shortcut value (90th percentile RUD BBCH cereals Small herbivorous mammal 48.3 The following equations were used: Daily dietary dose: DDD single application = application rate [kg/ha] shortcut value* TWA * * see section 4.1 of EFSA/2009/1438 Toxicity exposure ratio (acute): NOEL (mg/kg bw/day) TER LT = Long - term DDD (mg/kg bw/day) The resulting TER LT values for florasulam and clopyralid are summarised in the following table: Table 6.3-6: Long-term risk assessment (TER LT ) for mammals from uses Substance Clopyralid Indicator bird Small herbivorous App. rate (kg/ha) Shortcut value (long-term) f TWA a MAF DDD (mg/kg bw/day) NOEC (mg/kg bw/day) TER LT N/A Evaluator: Germany Date: April 2013

252 Part B Section 6 Core Assessment Germany Central Zone Page 17 of 102 Florasulam Primus Perfect Small herbivorous N/A not applicable. TERs shown in bold fall below the relevant trigger N/A Based on the highly conservative presumptions of the screening step, the long term risk of exposure of mammals to florasulam and clopyralid when applied according to the GAP as well as the calculated additive toxicity achieves the acceptability criteria TER 5, according to directive 1107/2009 (EG), Annex IV, uniform principles, point for long term effects. Therefore, refinements are not necessary Drinking water exposure In case of early post-emergence uses as intended for mammals might be exposed via drinking water from puddles. According to the new Guidance Document (EFSA, 2009), no specific calculations of drinking water exposure and TER are necessary when the ratio of effective application rate (in g/ha) to the relevant endpoint (in mg/kg bw/d) does not exceed 50 in the case of less sorptive substances (Koc < 500 L/kg) or 3000 in the case of more sorptive substances (Koc 500 L/kg). This is due to the characteristics of the exposure scenario in connection with the standard assumptions for water uptake by mammals (for further details please refer to chapter 5.5. of the Guidance Document). The puddle scenario has been taken into account to calculate the exposure concentration of formed on a field after rainfall. The ratios do not exceed the value of 50 for florasulam (Koc = 37 L/kg) and clopyralid (Koc = 2.93 L/kg), thus it is not necessary to conduct a drinking water risk assessment for birds Details on formulation type in proportion per item Baits: Concentration of active substance in bait in mg/kg (IIIA ) is not formulated as bait Pellets, granules, prills or treated seed (IIIA ) is not formulated as pellets, granules, prills or treated seeds. Amount of active substance in or on each item (IIIA ) Not applicable. Proportion of active substance LD 50 per 100 items and per gram of items (IIIA ) Not applicable. Size and shape of pellet, granule or prill (IIIA ) Not applicable Other studies (IIIA ) Acute oral toxicity of the preparation Please refer to Annex 2 of this document. Evaluator: Germany Date: April 2013

253 Part B Section 6 Core Assessment Germany Central Zone Page 18 of Supervised cage or field trials (IIIA ) Supervised cage/field trials with the formulation were not performed, since low risk to mammals indicates that further studies are not required Acceptance of bait, granules or treated seed (palatability testing) (IIIA ) is not formulated as bait, granule or as treated seeds and, consequently, studies to determine palatability are not applicable Effects of secondary poisoning (IIIA ) The EFSA birds and mammals guidance document (EFSA Journal 2009; 7(12): 1438) states that a log K ow 3 is used to indicate that there might be a potential for bioaccumulation (see Section 5.6 Bioaccumulation and food chain behaviour). The log K ow of clopyralid and florasulam are and and so these active substances have a negligible potential to bioaccumulate in animal tissues. No formal risk assessment from secondary poisoning is therefore required. 6.4 Effects on Aquatic Organisms (IIIA1 10.2) Overview and summary Effects on aquatic organisms for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here Toxicity The endpoints for aquatic organisms relevant for the risk assessment are indicated in the following table: Table 6.4-1: Ecotoxicological endpoints of clopyralid to aquatic species Species Substace exposition: duration system results: toxicity reference: author date code ICS-No. Fish, acute toxicity Oncorhynchus mykiss Florasulam (DE-570) 4 d Static LC 50 > 100 mg/l 2) XXX 1995 DECO-ES Oncorhynchus mykiss Florasulam- Metabolite (5- OH-XDE-570) 4 d Static LC 50 > 91 mg/l 2) XXX 1996 DECO-ES Oncorhynchus mykiss Clopyralid 4 d Static LC 50 > 100 mg/l 1) XXX ; J Oncorhynchus mykiss (Lontrel 100) 4 d Static LC 50 = 500 mg prep./l 3) XXX 1989 GHE-T-196; 5986; IRI Oncorhynchus mykiss 4 d Semi-static LC 50 > 100 mg prep./l 3) XXX ; Fish, long-term toxicity Evaluator: Germany Date: April 2013

254 Part B Section 6 Core Assessment Germany Central Zone Page 19 of 102 Oncorhynchus mykiss Florasulam (DE-570) 28 d Flow-through NOEC = 119 mg/l 2) Subletal effects; Mortality; Highest concentration tested XXX 1996 DECO-ES Pimephales promelas Clopyralid 34 d Flow-through NOEC = ) mg/l Development Growth Mortality XXX ; J Invertebrates, acute toxicity Daphnia magna Florasulam (DE- 570) 2 d Static EC 50 > 292 mg/l 2) Immobilisation Kirk, H.D.; Landre, A.M.; Massaro, L.M.; Hugo, J.M. and Stahl, D.C 1995 DECO-ES Daphnia magna Florasulam- Metabolite (5-OH- XDE-570) 2 d Static EC 50 > 96.7 mg/l 2) Immobilisation Kirk, H.D., Landre, A.M. and Hugo, J.M DECO-ES Daphnia magna STC ASTA TSA ASTCA DFP-ASTCA 2 d Static EC 50 > mg/l, each 3) Immobilisation Kirk, H.D., Marino, T.A ; Daphnia magna Clopyralid 2 d Static LC 50 > 100 mg/l 1) Mortality Marino, T.; McClymont, E. and Staley, J Daphnia magna GF 2463 (Lontrel 100) 48 h Static EC 50 = mg prep./l 3) Immobilisation Caley, C.Y., Cameron, B.D., Chapleo, S GHE-T-195; 5985; IRI Daphnia magna 48 h Static EC 50 > 100 mg prep./l 3) Immobilisation Rebstock, M ; Invertebrates, long-term toxicity Daphnia magna Florasulam (DE- 570) 21 d Semi-static NOEC = 38.9 mg/l 2) Length; Weight Kirk, H.D., Landre, A.M., Hugo, J.M. and Stahl, D.C DECO-ES Evaluator: Germany Date: April 2013

255 Part B Section 6 Core Assessment Germany Central Zone Page 20 of 102 Daphnia magna Clopyralid 21 d Semi-static Sediment dwelling organisms Chironomus riparius Chironomus riparius Algae Selenastrum capricornutum Selenastrum capricornutum Pseudokirchneriella subcapitata Pseudokirchneriella subcapitata Selenastrum capricornutum Selenastrum capricornutum Pseudokirchneriella subcapitata Aquatic higher plants Florasulam (DE- 570) Clopyralid Florasulam (DE- 570) Florasulam- Metabolit (5-OH- XDE-570) ASTCA DFP-ASTCA 28 d static 28 d Water /Sediment 3 d Static NOEC = 17 mg/l 1) Mortality Reproduction EC 50 > 10 mg/l 2) Highest concentration tested EC 50 > 97 mg/l NOEC = 50 mg/l 1) emergence EC 50 = mg/l 2) NOEC = mg/l (highest concentration tested) 4 d EbC 50 = mg/l 2) NOEC = 6.64 mg/l 3 d Static 3 d Static M3; M4, M6 3 d Static Clopyralid GF 2463 (Lontrel 100) 3 d Static 3 d Static EC 50 > 9.2 mg ai/l 3) Growth EC 50 > 97 mg ai/l 3) Growth EC 50 > Leaching sample of 50 µg florasulam/kg ds 2) Growth ErC 50 = 30 mg/l 1) NOEC = 24.8 mg/l EC 50 = mg prep./l 3) Growth Douglas, M.; Bell, G. and McDonald, I DWC 615/ Kelly, C GHE-T-838 Barrett, K DOS 161/ Milazzo, D.P.; Humbert, L.M.; Hugo, J.M. and Martin, M.D DECO-ES-2946 Milazzo, D.P.; Hugo, J.M. and McFadden, L ES-3115 Kirk, H.D., Gilles, M.M., Rick, D.L., McFadden, L.G ; Rebstock, M. 2011; ; Jenkins, C.A DWC828/ Kirk, H.; Gilles, M.; McClymont, E. and McFadden, L ; J51 Caley, C.Y., Cameron, B.D., Chapleo, S GHE-T-198; 7035; IRI Evaluator: Germany Date: April 2013

256 Part B Section 6 Core Assessment Germany Central Zone Page 21 of 102 Lemna gibba Florasulam (DE- 570) 14 d Static NOEC = mg/l EC 50 = mg/l 2) Fronds Milazzo, D.P.; Kirk, H.D.; Hugo, J.M and Martin, M.D ES Lemna gibba 5-OH-XDE 7 d static EyC 50 = mg/l 3) ErC 50 = mg/l Fronds Hancock, G.A., Arnold, B.H., Carr, M.S., Najar, J.R Lemna gibba ASTCA 7 d Static EC 50 > 10.2 mg ai/l 3) Fronds Kirk, H.D., Gilles, M.M., Rick, D.L., McFadden, L.G ; Lemna gibba DFP-ASTCA 7 d Static EC 50 > 100 mg ai/l 3) Fronds, biomass Rebstock, M. 2011; Study Number ; Lemna gibba Clopyralid 96.7% (Lontrel T) 14 d Static EC 50 = 89 mg/l 1) NOEC = 7.2 mg/l Fronds Cowgill, U.M., Milazzo, D.P., Potter, R.B ES-DR J Lemna gibba GF d Semi-static EyC 50 = ) mg/l ErC 50 = mg/l NOEC = mg/l Fronds 1) EFSA Scientific Report (2005): 50, 1-65: Conclusion on the peer review of clopyralid 2) SANCO/1406/2001-final (2002): Review report for the active substance florasulam 3) New study submitted by the applicant, detailed information in Annex 2 of this document. Porch, J., Kendall, T.Z., Krueger, H.O A-119A; The most sensitive endpoint for the active ingredient florasulam is EC 50 = 1.18 µg/l (Lemna gibba). Clopyralid is toxic against fish, the most sensitive endpoint is NOEC = 10.8 mg/l (O. mykiss). The most sensitive endpoint for is EyC 50 = ) mg/l (Lemna gibba) Exposure Florasulam forms four major metabolites in surface water: 5-OH-florasulam (64 %), DFP-ASTCA (15 %). Moreover, there are two major metabolites in soil: ASTCA (40 %) and TSA (15.9 %). Contamination via run-off and drainage cannot be excluded. The risk posed by these metabolites to aquatic organisms will be assessed. Clopyralid forms no major metabolite in surface water or soil. The GAPs and rationale for the risk envelope assessed for aquatic organisms are provided in Appendix 3 and the critical GAP is summarized in table Appendix 3-1. Table 6.4-2: Critical GAP to assess the risk of applications to aquatic organisms Crop Zone Time of application No. of applications per year Maximum rate per application Cereals Central BBCH March to June L /ha equivalent to Evaluator: Germany Date: April 2013

257 Part B Section 6 Core Assessment Germany Central Zone Page 22 of 102 florasulam: 5 g/ha clopyralid: 60 g/ha Calculations of PECsw and PEC sed were performed with Focus surface water. For details see CA Part B, Section 5.7 Table 6.4-3: Summary of highest global maximum FOCUS surface water PECsw and PECsed values Plant protection product: Use No evaluated , Crop Application method (-) Growth stage at first application (BBCH) Application time Winter cereals Spray 13 1 st of March Crop interception: 25 % (minimal crop cover in Step 2) Number of applications/interval 1 Application rate: Active Substance FOCUS STEP 2 Scenario 60 g/ha clopyralid and 5 g/ha florasulam Clopyralid PEC SW (µg/l) PEC SED (µg/kg) Actual, 0 h TWA, 21 d Actual, 0 h Northern Europe, Mar.-May Southern Europe, Mar.-May Active Substance Florasulam PEC SED FOCUS STEP 2 (µg/kg) Scenario Actual, 0 h TWA, 21 d Actual, 0 h Northern Europe, Mar.-May Southern Europe, Mar.-May The assessment of PEC SW according to FOCUS STEPS is specific to individual active substances. For ecotoxicological risk assessment, there may be differences between the toxicity of the formulation and the toxicity of the pure active substance. Exposure to the formulation may be relevant for assessing risks from spray-drift. In order to allow a simple comparison of PEC SW with formulation data, initial PEC values were calculated based on the standard 90 th percentile drift factor for field crops (Rautmann et al., 2001) in a 30 cm deep static water body. PEC SW (µg/l) = A (g/ha) 10 6 (µg/g) F (%) 10 4 (m 2 /ha) d (m) 10 3 (L/m 3 ) 100 (%) Where: A = Application rate Evaluator: Germany Date: April 2013

258 Part B Section 6 Core Assessment Germany Central Zone Page 23 of 102 F = Drift factor (from Rautmann et al., 2001) d = Depth of water body (0.3m ditch/stream, 1.0m pond) Based on the maximum application rate of 0.2 L/ha, a formulation density of 1.16 g/ml and the 90 th percentile drift factor (1 application in cereals) of 2.77% for 1 m distance and 0.27 for 5 m distance, the initial PECsw of was calculated to be µg/l and µg/l, respectively Overall conclusions The TER values for the most sensitive species, calculated with FOCUS STEP 2 are shown in the following tables. Table 6.4-4: Fish long-term TER values for clopyralid after applications of Scenario Critical endpoint (µg/l) Drift reducing nozzles PEC SW (µg/l) TER LT TER risk assessment trigger Northern Europe Southern Europe TERs shown in bold fall below the relevant trigger. Table 6.4-5: Scenario Aquatic higher plant TER values for florasualm after applications of Critical endpoint (µg/l) Drift reducing nozzles PEC SW (µg/l) TER LT TER risk assessment trigger Northern Europe Southern Europe TERs shown in bold fall below the relevant trigger. Table 6.4-6: Scenario Aquatic higher plant TER values for after applications of Primus Perfect Critical endpoint (µg/l) Drift reducing nozzles PEC SW (µg/l) TER LT TER risk assessment trigger 1 m m TERs shown in bold fall below the relevant trigger. With FOCUS STEP 2 the TER LT values for clopyralid are greater than the Annex VI trigger value of 10. For florasulam and further refinement is necessary Toxicity exposure ratios (IIIA ) The risk assessment for, clopyralid, florasulam and their metabolites was carried out following application according to the proposed use. The initial risk assessments were carried out by comparing the initial maximum PEC SW values with the acute and long-term toxicity endpoints. Based on all aquatic studies as well as the corresponding safety factors the relevant endpoint for the active ingredient clopyralid is NOEC = 10.8 mg/l (Pimephales promelas). For the active ingredient florasulam the relevant endpoint is EC 50 = mg/l (Lemna gibba). The most sensitive endpoint for Primus Perfect is EyC 50 = ) mg/l (Lemna gibba). Risk assessment is done only for those organisms because for the other organisms the ratio endpoints - corresponding safety factor are higher. Evaluator: Germany Date: April 2013

259 Part B Section 6 Core Assessment Germany Central Zone Page 24 of TER A for fish (IIIA ) See above point TER LT for fish (IIIA ) The long-term risk assessment for fish is summarised in the following table, considering the lowest relevant endpoints and the maximum PEC SW. Table 6.4-7: Fish long-term TER values for clopyralid after applications of Scenario Critical endpoint (µg/l) Drift reducing nozzles PEC SW (µg/l) TER LT TER risk assessment trigger Northern Europe Southern Europe TERs shown in bold fall below the relevant trigger. The TER LT values are greater than the Annex VI trigger value of 10. This indicates that the active substances clopyralid contained in pose low long-term risk to fish following application of at the proposed application rates TER A for Daphnia (IIIA ) See above point TER LT for Daphnia (IIIA ) See above point TER A for aquatic insect (IIIA ) See above point TER LT for aquatic insect (IIIA ) See above point TER A for aquatic crustacean (IIIA ) See above point TER LT for aquatic crustacean (IIIA ) See above point TER A for aquatic gastropod mollusc (IIIA ) See above point TER LT for aquatic gastropod mollusc (IIIA ) See above point TER LT for algae (IIIA ) See above point Evaluator: Germany Date: April 2013

260 Part B Section 6 Core Assessment Germany Central Zone Page 25 of TER LT for aquatic higher plant (IIIA ) The long-term risk assessment for aquatic higher plant is summarised in the following table, considering the lowest relevant endpoints and the maximum PEC SW. Table 6.4-8: Aquatic higher plant TER values for florasualm after applications of Scenario Critical endpoint (µg/l) Drift reducing nozzles PEC SW (µg/l) TER LT TER risk assessment trigger Northern Europe Southern Europe TERs shown in bold fall below the relevant trigger. With FOCUS STEP 2 the TER LT values are below than the Annex VI trigger value of 10. Further refinement is necessary on member state level Risk from metabolites Clopyralid There are no relevant metabolites occurring in surface water or sediment from the active ingredient clopyralid. Florasulam Florasulam forms two major metabolites in surface water: 5-OH-florasulam (64 %), DFP-ASTCA (15 %). 5-OH-florasulam is also formed in sediment (35 %). Moreover there are two major metabolites in soil: ASTCA (40 %) and TSA (15.9 %). Contamination via run-off and drainage cannot be excluded. Ecotoxicolocical studies are available for the metabolites 5-OH-florasulam (fish acute, daphnia acute, algae and Lemna, ASTCA (daphnia acute, algae and Lemna), DFP-ASTCA (daphnia acute, algae and Lemna) and TSA (daphnia acute). 5-OH-Florasulam: Because of the low toxicity against Daphnia it is not necessary to provide an additional study on sediment dwelling organisms. Comparison of the studies for the metabolite 5-OHflorasulam with the studies of the parent florasulam shows a higher sensitivity of aquatic organisms against the active ingredient florasulam. Therefore, there is no environmental risk of the metabolite 5- OH-florasulam. For the metabolite ASTCA (soil, 40 %), there are studies available for daphnia acute, algae and Lemna. Compared to the active ingredient, ASTCA is less toxic against aquatic organismes. Environmental risk to aquatic organisms can be excluded. For the metabolite DFP-ASTCA (water 15 % on day 100 and soil 17.8 % on day 28) studies on daphnia acute, algae and aquatic higher plants are available. Compared to the active ingredient, DFP-ASTCA is less toxic against the most sensitive aquatic organisms (algae, Lemna). Environmental risk to aquatic organisms can be excluded. For the metabolite TSA (15.9 % on day 100, soil) only studies on daphnia acute were submitted. TSA is classified as artefact of the degradation of ASTCA and DFP-ASTCA during the extraction process. Moreover the chemical structure of TSA is very similar to ASTCA and DFP-ASTCA. Therefore, additional aquatic studies for the metabolite TSA are not considered necessary for risk assessment. Evaluator: Germany Date: April 2013

261 Part B Section 6 Core Assessment Germany Central Zone Page 26 of Acute toxicity of the formulation (IIIA ) Fish (IIIA ) A study on the effects of in fish is not required because fish are not the most sensitive group of aquatic organisms for either active ingredient in (SANCO/3268/2001). Additionally, the applicant has provided a study with. Please refer to Appendix 2: of this document Aquatic invertebrates (Daphnia) (IIIA ) A study on the effects of in Daphnia is not required because aquatic invertebrates are not the most sensitive group of aquatic organisms for either active ingredient in (SANCO/3268/2001). Additionally, the applicant has provided a study with. Please refer to Appendix 2: of this document. Algae (IIIA ) Please refer to Appendix 2: of this document Marine or estuarine organisms (IIIA ) No studies are submitted as this is not an EC data requirement Marine sediment invertebrates (IIIA ) No studies are submitted as this is not an EC data requirement Microcosm or mesocosm study (IIIA ) Since all TER A and TER LT values exceed their respective Annex VI triggers, microcosm and/or mesocosm studies are not required Residue data in fish (IIIA ) The log K ow of clopyralid and florasulam are and and so these active substances have a negligible potential to bioaccumulate in animal tissues. Data to evaluate the residues of clopyralid and florasulam in fish have therefore not been generated. Use of in cereals is not expected to result in an accumulation in fish Chronic toxicity to fish (IIIA ) Chronic toxicity tests with the formulated product were considered to be unnecessary since there is no evidence from the existing acute data for non-target organisms to suggest that the chronic toxicity of the formulated product cannot be assessed on the basis of the active substance contents alone Chronic toxicity to aquatic invertebrates (IIIA ) Chronic toxicity tests with the formulated product were considered to be unnecessary since there is no evidence from the existing acute data for non-target organisms that the chronic toxicity of the formulated product cannot be assessed on the basis of the active substance contents alone Accumulation in aquatic non-target organisms (IIIA ) Bioaccumulation of any of the active substances under natural conditions is not expected to occur (refer to Section ), and a study is not necessary to determine bioaccumulation in aquatic non-target organisms. Evaluator: Germany Date: April 2013

262 Part B Section 6 Core Assessment Germany Central Zone Page 27 of Effects on Bees (IIIA 10.4) This chapter is amended by Julius-Kühn-Insititut. List of studies Table containing the studies performed and the key endpoints Risk assessment conclusions 6.6 Effects on Arthropods Other Than Bees (IIIA 10.5) Overall Summary Effects on arthropods other than bees for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here and are considered adequate Toxicity The critical endpoints employed in the risk assessment for non-target arthropods are indicated in the table below. Table 6.6-1: Toxicity of to arthropods other than bees Test item Test species Study type Results toxicity [ml/ha] Typhlodromus pyri Aphidius rhopalosiphi Laboratory study 7d Laboratory study 12d +2d * New study submitted by the applicant, detailed information in chapter Appendix 2. Reference: Author Date Report-No.) ICS-No. LR 50 > Schwarz, 2011 Study no * LR 50 > Moll, 2010 Study no * Detailed information on the non-target arthropod toxicity of the active substances can be found in the EU- Evaluation of clopyralid and florasulam. Detailed information on the toxicity to non-target arthropods of the active substances can be found in the Draft Assessment Report on clopyralid of November 2003 provided by the Rapporteur member Finland, the Draft Assessment Report on florasulam of November 1999 provided by the Rapporteur member Belgium, the EFSA Conclusion Report (EFSA Scientific Report (2005) 50, 1-65) on clopyralid of 2005 and the Review Report (SANCO/1406/ final) on florasulam of 18 September Exposure In-field Non-target arthropods inhabiting the crop can be exposed to residues from by direct exposure or through contact with residues on plants and soil or in food items. According to the GAP, is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). It will be used against weeds (annual dicotyledonous plants) on cereals (winter and summer; BBCH 13 32, March to June). Evaluator: Germany Date: April 2013

263 Part B Section 6 Core Assessment Germany Central Zone Page 28 of 102 As a worst-case assumption, the maximum in-field exposure (Predicted Environmental Rate, PER) to arthropods is therefore 200 ml formulation/ha, assuming 0% crop interception. The in-field exposure (predicted environmental rate, PER) is calculated according to ESCORT 2 using the following equation: PER in field Applicatio n rate (g a.s./ha) MAF Where: MAF is a generic multiple application factor, which is used to take into account the potential build-up of applied substances between applications based on the application interval, DT 50 value and number of applications. Default foliar and soil MAF values following multiple applications are given in the ESCORT 2 Guidance Document. Since is applied only once a season, the multiple application factor MAF, can be omitted. The maximum predicted environmental rate (PER) occurring within the field after application of Primus Perfect at the maximum application rate are presented in table the following table: Table 6.6-2: In-field PER values for application of Substance Application rate PER (foliar) PER (soil) 200 ml/ha 200 ml/ha 200 ml/ha Off-field The risk assessment for areas immediately surrounding the crop is considered important since these areas represent a natural reservoir for immigration, emigration and reproduction of arthropod populations and provide increased species diversity. Exposure of non-target arthropods living in off-field areas to Primus Perfect will mainly be due to spray drift from field applications. Off-field PER values were calculated from in-field PERs in conjunction with drift values published by the BBA (2000) as shown in the following equation: Off - field foliar PER Maximum in - field PER x (% drift/100) vegetation distributi on factor Vegetation distribution factor: The model used to estimate spray drift was developed for drift onto a twodimensional water surface and, as such, does not account for interception and dilution by threedimensional vegetation in off-crop areas. Therefore, a vegetation distribution or dilution factor is incorporated into the equation when calculating PERs to be used in conjunction with toxicity endpoints derived from two-dimensional (glass plate or leaf disc) studies. A dilution factor of 10 is recommended by ESCORT 2. For 3-dimensional studies, i.e. where spray treatment is applied onto whole plants, the dilution factor of 10 is not used, as any dilution over the 3-dimensional vegetation surface is accounted for in the study design. The ZRMS prefers a VdF of 5 for 2-demensional studies, based on experimental data (See although national addenda). 2-dimensional structures were used for application in the laboratory studies on Aphidius and Typhlodromus. Therefore, a vegetation distribution factor of 10 was used for the off-field assessment for these species. The drift value at 1 m distance is 2.77% of the application rate (90th percentile drift). The drift factor (% drift/100) is therefore 2.77/100 = The resulting PERoff-field value is shown in the following table: Table 6.6-3: Off-field PER values for application of Substance Maximum in-field PER Drift factor (% drift/100) Vdf Off-field PER (ml /ha) Evaluator: Germany Date: April 2013

264 Part B Section 6 Core Assessment Germany Central Zone Page 29 of 102 (ml /ha) 200 ml/ha ml/ha Overall conclusion The testing and risk assessment strategy used here follow the approach recommended in the ESCORT 2 guidance document (Candolfi et al. 2001) 1 and the EC Guidance Document on Terrestrial Ecotoxicology 2. According to the GAP, is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). The resulting Hazard Quotients for the in-field and off-field risk of non-target arthropods is summarized in the following table: Table 6.6-4: Effects on arthropod species other than bees after uses of in cereals Test substance Primus Perfect Use pattern / max. use rate [ml prod./ha] Species 200 Typhlodromus pyri 200 Aphidius rhopalosi phi Test type labor atory labor atory HQs shown in bold are above the relevant trigger. Endpoint ER 50 [ml prod./ha] Worstcase PER in-field [ml prod./ha] HQ Infield Worstcase PER offfield (1 m) [ml prod./ha ] HQ Offfield > < < > < < HQ risk assess ment trigger The in- and off-field HQ values for A. rhopalosiphi and T. pyri are below the trigger value, indicating that does not pose an unacceptable risk to non-target arthropods in in- and off-field areas Risk Assessment for Arthropods other than Bees The risk assessment for effects to non-target arthropods for is based on a single application at a maximum rate of 200 ml product/ha for non-target arthropod populations present in the in-field area. Another area of risk is to non-target arthropod populations present in the off-field area where these species are exposed to spray drift at the time of application. A risk assessment for these scenarios may be conducted using the Hazard Quotient approach in ESCORT 2 (Guidance Document on Terrestrial Ecotoxicology: SANCO/10329/2002). The HQ can be defined as below: application rate MAF In field HQ ; LR 50 1 Candolfi MP, Barrett KL, Campbell PJ, Forster R, Grandy N, Huet M-C, Lewis G, Oomen PA, Schmuck R, Vogt H (2000) Guidance Document on regulatory testing procedures for plant protection products with non-target arthropods From the workshop, European Standard Characteristics of Non-target Arthropod Regulatory Testing (ESCORT 2) March EC Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEC, SANCO/10329, 17 October Evaluator: Germany Date: April 2013

265 Part B Section 6 Core Assessment Germany Central Zone Page 30 of 102 application rate MAF drift Off field HQ LR 50 factor correction factor VDF where: application rate: maximum rate of application in same units (ml product/ha) as the LR 50. MAF: multiple application factor set to 1 for a single application of. drift factor: 90 th percentile of the in-field rate, at a given distance from the treated area. For broadcast applications, the drift listed for field crops in Rautmann et al. ( i.e. 2.77% at 1 m) can be used. correction factor: safety factor used to give adequate protection to off-field species where diversity is greater than in-field and sensitivities are unknown and may not be adequately protected by the Tier 1 indicator organisms. Default value in Tier 1 calculations is 10. VDF: vegetation distribution factor that adjusts the standard spray-drift values (based on measurements on flat, 2-dimensional surfaces) to take account of the 3-dimensional character of the vegetated off-field zone. Default value = 10. From the results in Table 6.6-1, the LR 50 values for to the indicator species T. pyri and A. rhopalosiphi, under laboratory conditions, were estimated to be both in excess of 800 ml/ha. These values will be taken to represent the realistic worst case end point for non-target arthropods for Primus Perfect. The risk assessment is presented in the table below. Table 6.6-5: Risk to non-target arthropods from applications of ESCORT 2 Scenario Species Exposure Correction VDF LR50 HQ (ml/ha) factor (ml/ha) In-field T. pyri 200 N/A N/A >800 <0.25 A. rhopalosiphi 200 N/A N/A >800 <0.25 Off-field, spray T. pyri >800 <0.007 drift at 1 m A. rhopalosiphi >800 <0.007 N/A: not applicable. Note: Correction factor of 10 is applied to off-field exposure in HQ calculation to account for unknown species of greater sensitivity (ESCORT 2). The HQ for all scenarios are less than the ESCORT 2 trigger value of 2, indicating that at rates up to 0.2 L/ha does not pose an unacceptable risk to terrestrial non-target arthropods both in-field and off-field. Additionally, in the worst-case laboratory studies with the indicator species Typhlodromus pyri and Aphidius rhopalosiphi no adverse effect on fecundity was noted at rates up to 800 ml Primus Perfect/ha, which is higher than the maximum recommended rate for this product. Thus, based on the laboratory effect data for, a low in-field and off-field risk to non-target arthropods is indicated without risk mitigation measures Using artificial substrates Please refer to Appendix 2: of this document. 3 Rautmann, D., Streloke, M., Winkler, R. (2001). New basic drift values in the authorisation procedure for plant protection products. In Forster, R., Streloke, M. Workshop on Risk Assessment and Risk Mitigation Measures in the Context of the Authorization of Plant Protection Products (WORMM). Mitt. Biol. Bundesanst. Land- Forstwirtsch. Berlin-Dahlem, Heft 381. Evaluator: Germany Date: April 2013

266 Part B Section 6 Core Assessment Germany Central Zone Page 31 of Extended laboratory studies (IIIA ) Acceptable risk to in- and off-field communities of non-target terrestrial arthropods was indicated in the risk assessment and consequently no extended laboratory testing is necessary Semi-field tests (IIIA ) Acceptable risk to in- and off-field communities of non-target terrestrial arthropods was indicated in the risk assessment and consequently no semi-field testing is necessary Field tests (IIIA ) Acceptable risk to in- and off-field communities of non-target terrestrial arthropods was indicated in the risk assessment and consequently no field testing is necessary. 6.7 Effects on Earthworms and Other Soil Non-target Macro-organisms (IIIA 10.6) Overall summary Effects on earthworms and other soil non-target macro-organisms for were not evaluated as part of the EU review of either clopyralid or florasulam. Therefore, all relevant study data for this risk assessment are provided here and are considered valid and acceptable by the ZRMS. Evaluator: Germany Date: April 2013

267 Part B Section 6 Core Assessment Germany Central Zone Page 32 of Toxicity Table 6.7-1: Studies on earthworms Test species Compound Exposition Testperiod Studytype Acute effects on earthworms Eisenia foetida Clopyralid 14 d Acute Eisenia foetida Florasulam 14 d Acute Eisenia foetida 14 d Acute Eisenia foetida DFP-ASTCA 14 d Acute Eisenia foetida ASTCA 14 d Acute Eisenia foetida Primus Perfect Chronic toxicity to earthworms Eisenia foetida Clopyralid (EF-1136, a 100 g/l formulation of clopyralid) 14 d Acute 56 d Reproduction Eisenia foetida ASTCA 56 d Reproduction Eisenia foetida Primus Perfect 56 d Reproduction 5-OHflorasulam Toxicity to non-target macro-organisms Folsomia 5-OHflorasulam candida Results toxicity* [mg/kg soil] Reference: Author Date Report-No. LC 50 > 1000 Hayward, J CEMR ) LC 50 > 1320 LC 50 > 1120 LC 50 > 0,1 Boeri, R.L.; Magazu, J.P.; Ward, T.J DO Ward, T.J.; Magazu, J.P.; Boeri, R.L DECO-ES-3120* Ward, T.J., Magazu, J.P., Boeri, R.L DO; (R); ) LC 50 >100 Lührs, U P 3) >2000 Witte, B ! ) NOEC 2.0 (equivalent to 15 L/ha ) Hayward & Mallett CEMR ) NOEC 1.0 Lührs, U ) NOEC 5.33 Witte, B ; ) ICS-No EU EU d NOEC = 2.5 Witte, B ; ) Folsomia DFP-ASTCA 28 d NOEC = 10 Lührs, U candida ; ) Folsomia ASTCA 28 d NOEC = 12.5 Witte, B Evaluator: Germany Date: April 2013

268 Part B Section 6 Core Assessment Germany Central Zone Page 33 of 102 candida ; Hypoaspis aculeifer Hypoaspis aculeifer Hypoaspis aculeifer 5-OHflorasulam ) 14 d NOEC = 1.25 Witte, B ; ) DFP-ASTCA 14 d NOEC = 10 Witte, B ; ) ASTCA 14 d NOEC = 100 Witte, B ; ) 1) EFSA Scientific Report (2005): 50, 1-65: Conclusion on the peer review of clopyralid 2) SANCO/1406/2001-final (2002): Review report for the active substance florasulam 3) New study submitted by the applicant, detailed information in Appendix The studies except the marked new studies represent the EU-Evaluation of the active substances clopyralid and florasulam. Detailed information on the toxicity to earthworms of the active substances can be found in the Draft Assessment Report on clopyralid of November 2003 provided by the Rapporteur member Finland, the Draft Assessment Report on florasulam of November 1999 provided by the Rapporteur member Belgium, the EFSA Conclusion Report (EFSA Scientific Report (2005) 50, 1-65) on clopyralid of 2005 and the Review Report (SANCO/1406/ final) on florasulam of 18 September New metabolite studies, submitted by the applicant The applicant provided new studies assessing the acute toxicity of the major soil metabolites of florasulam 5-OH-florasulam, DFP-ASTCA and ASTCA as well as a new study on the sublethal toxicity of the florasulam metabolite ASTCA to earthworms. These studies are considered in the risk assessment. Florasulam forms three major metabolites in soil: 5-OH-florasulam, DFP-ASTCA and ASTCA. The risk posed by these metabolites to soil organisms will be assessed. Clopyralid forms no major metabolite in soil Exposure According to the GAP, is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). It will be used against weeds (annual dicotyledonous plants) on cereals (winter and summer; BBCH 13 32, March to June). For PEC calculations reference is made to the environmental fate section (Part B, Section 5) of this submission. The resulting maximum PECsoil values for the active substances clopyralid and florasulam and the major soil degradation products are presented in Table Calculations considered the maximum application rate of (i.e. a single application at 0.2 L/ha) and a minimum of 25% foliar interception for applications to cereals at BBCH of at least 13. PEC values for the soil metabolites were calculated considering the maximum percentage of their formation observed in either the aerobic or anaerobic soil degradation studies and correcting for molecular weight. Calculations assumed an even distribution of the substances in the top 5 cm horizon with a soil bulk density of 1.5 g/ml. Table 6.7-2: Maximum PEC S for, clopyralid, florasulam and their major soil degradation products after applications of (expressed as a.s.) Substance Maximum instantaneous PECs (mg/kg), 25% foliar interception Clopyralid Evaluator: Germany Date: April 2013

269 Part B Section 6 Core Assessment Germany Central Zone Page 34 of 102 Substance Maximum instantaneous PECs (mg/kg), 25% foliar interception Florasulam OH-florasulam DFP-ASTCA ASTCA The florasulam metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA were formed in concentrations >10 % TAR at the end of the study in the soil (see although section 5, Part 9.1) Overall conclusion All acute and chronic TERs for the active substances and the major soil degradation products are above the respective trigger values indicating that the acute and chronic risk to earthworms and other soil nontarget macroorganisms following treatment with is low and acceptable at the intended worst-case uses. The risk assessment results are summarized in the following table: Table 6.7-3: Toxicity/exposure ratios for earthworms (Eisenia foetida) after applications of in cereals Test substance Worst-case use pattern Timescale Endpoint (mg/kg dw soil) PEC (mg/kg dw soil TER TER risk assessment trigger Table 6.7-4: Toxicity/exposure ratios for non-target macro-organisms (Folsomia candida and Hypoaspis aculeifer) after applications of in cereals Test substance Worst-case use pattern Organism Primus 0.2 L Primus Acute >2000 > Perfect Perfect/ha Long-term Clopyralid equivalent to Acute > > florasulam: 5 g/ha Long-term Florasulam clopyralid: 60 g/ha Acute > > OHflorasulam Acute > > DFP- Acute > > ASTCA ASTCA Acute > > Long-term TERs shown in bold fall below the relevant trigger. 5-OHflorasulam 0.2 L Primus Perfect/ha Hypoaspis aculeifer DFP- equivalent to Folsomia ASTCA florasulam: 5 g/ha candida ASTCA clopyralid: 60 g/ha Folsomia candida TERs shown in bold fall below the relevant trigger. Endpoint (mg/kg dw soil) PEC (mg/kg dw soil TER TER risk assessment trigger Evaluator: Germany Date: April 2013

270 Part B Section 6 Core Assessment Germany Central Zone Page 35 of Toxicity exposure ratios, TER A and TER LT (IIIA ) Acute risk The potential acute risk of, the active substances clopyralid and florasulam as well as their major soil degradation products was assessed by comparing the maximum instantaneous PECsoil with the 14-day LC 50 value to generate acute TER values. The TER A was calculated as follows: TER A LC = PEC 50 soil (mg/kg) (mg/kg) The resulting TER A values are shown in the following table, considering the highest initial PEC in soil (i.e. 25% interception during applications): Table 6.7-5: Acute TER values for earthworms following applications of Test substance Maximum initial Timescale LC 50 or NOEC TER PEC (mg/kg) (mg/kg) Acute >2000 >8620 Long-term Clopyralid Acute >1000 >16600 Long-term Florasulam Acute >1320 > OH-florasulam Acute >1120 > DFP-ASTCA Acute >0.1 >100 ASTCA Acute >100 > Long-term TERs shown in bold fall below the relevant trigger. Based on the worst case scenario, the acceptability criteria TER 10 for acute effects, according to Annex VI to directive 1107/2009 (EG), uniform principles, point is reached Long-term risk For a study on the reproduction of earthworms was submitted and the long term risk of is assessed. There is no need to address the long term risk of the active substances clopyralid and florasulam and its metabolites 5-OH and DFP-ASTCA for earthworms, because their degradation in soil (DT 90 < 365 d, Kinetic, laboratory/field data) is fast. The major soil metabolite ASTCA of florasulam degrades slowly with normalized DT 90 values > 365 d. Therefore, a long term risk assessment is necessary for this metabolite (see Section 5, chapter and 9.4.). TER LT NOEC (mg/kg) = PEC (mg/kg) soil The resulting TER lt values are shown in the following table, considering the highest initial PEC in soil (i.e. 25% interception during applications): Table 6.7-6: Long-term TER values for earthworms following applications of Test substance Maximum initial Timescale LC 50 or NOEC TER PEC (mg/kg) (mg/kg) Acute >2000 >8620 Long-term Clopyralid Acute >1000 >16600 Long-term Florasulam Acute >1320 > Evaluator: Germany Date: April 2013

271 Part B Section 6 Core Assessment Germany Central Zone Page 36 of OH-florasulam Acute >1120 > DFP-ASTCA Acute >0.1 >100 ASTCA Acute >100 > Long-term TERs shown in bold fall below the relevant trigger. Based on the worst case scenario, the acceptability criteria TER 5 for long term effects, according to directive 1107/2009 (EG), Annex VI, uniform principles, point is reached for the formulation as well as the relevant metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA Acute toxicity (IIIA ) Please refer to Appendix 2: of this document Sublethal effects (IIIA ) Please refer to Appendix 2: of this document Field tests (IIIA ) Since all TER A and TER LT values for the active substances, clopyralid and florasulam, the formulated product and metabolites exceed their respective Annex VI triggers, field test on earthworms are not required Residue content of earthworms (IIIA ) The log K ow values of clopyralid and florasulam are < 3 (-2.63 and -1.22, respectively). Thus, it is very unlikely for both active substances to bioaccumulate in earthworms, as indicated by their low log Pow value (less than 3) in combination with its low toxicity and extensive metabolism. Therefore, studies determining residue content of earthworms are not necessary Effects on other non-target macro-organisms (IIIA ) According to SANCO/10329/2002 rev2 final tests on other soil non-target organisms are triggered by breaching the soil persistence criteria (DT 90 > 365 d). DT 90f values for clopyralid (mean: 38 days, EFSA Scientific Report (2005) 50, 1-65) and florasulam (median: 40.5 days, SANCO/1406/2001) are less than 365 days and the Tier I HQs for non-target arthropods were not indicative of a high risk (Table 6.6-5). Nevertheless, the degradation studies of the active ingredients in soil indicate that DT 90 values of the relevant major soil metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA are above the trigger for the soil persistence criteria (DT 90 > 365 d) or need further investigation (100 d < DT 90 < 365d). The maximum DT 90 values derived from the degradation studies of the active ingredients in soil were 5-OHflorasulam (mean: 139 d), DFP-ASTCA (mean: 149 d), and ASTCA (mean: 1601 d). The applicant provided new studies assessing the toxicity of the major soil metabolites of florasulam 5- OH-florasulam, DFP-ASTCA and ASTCA to non-target macro-organisms. These studies are considered in the risk assessment. Please refer to Annex 2 of this document for details of the studies. Florasulam forms three major metabolites in soil: 5-OH-florasulam, DFP-ASTCA and ASTCA. The risk posed by these metabolites to soil organisms will be assessed. Clopyralid forms no major metabolite in soil. Please refer to chapter Effects on organic matter breakdown (IIIA ) According to SANCO/10329/2002 rev2 final a test for assessing effects on organic matter breakdown (litterbag) is required where: DT 90f > 365 days or Evaluator: Germany Date: April 2013

272 Part B Section 6 Core Assessment Germany Central Zone Page 37 of 102 DT 90f is between 100 and 365 days and Effects on soil microflora > 25 % or TER LT earthworm < 5 or Collembola TER LT < 5 None of these criteria is met for clopyralid (DT 90f mean: 38 days, EFSA Scientific Report (2005) 50, 1-65) and florasulam (DT 90f median: 40.5 days, SANCO/1406/2001). DT 90f values are less than 365 days and no risk was identified for earthworms, soil micro-organisms and non-target arthropods from the use of this product. Maximum DT 90 values calculated from the degradation studies (see Section 5 chapter 5.5.1) were 139 d (5-OH-florasulam), 149 d (DFP-ASTCA), and 1601 d (ASTCA). No soil litterbag study or studies on the chronic effects to soil macro-organisms were submitted for these metabolites or for. According to assessment scheme given in SANCO/10329/2002 rev2 final additional tests for assessing effects of the relevant soil metabolites of florasulam on organic matter breakdown (litterbag) are currently required. However, in the light of current scientific and technical knowledge this functional test has to be considered as not fully appropriate to address the risk for soil macro-organisms (especially with respect to structural diversity). This new state of knowledge is also reflected in the current proposal for the revised annex II and III where the functional endpoint from a litterbag test is not any more considered as data appropriate requirement. Tests with the species Folsomia candida or Hypoaspis aculeifer are proposed to address the risk to soil macro organisms instead. The zrms is of the opinion that according to Art. 29 (1)(e) the current state of scientific and technical knowledge should be considered in the product assessment and therefore prefers tests showing the effects of these three soil metabolites on soil macroorganisms such as collembola instead. Therefore, tests are required to address the risk of the metabolites on collembola. According to soil metabolism studies the metabolite 5-OH-florasulam is expected to be formed in soil quite fast (max 71.6 % after 3 days) and is metabolised further shortly after. The metabolite DFP-ASTCA (max 17.8 % after 28 days) is also formed in relevant amounts earlier and so its effect on collembola can also be seen when florasulam or the product is applied in the test. So the effects of these metabolites are also covered by tests performed with florasulam or the product. The metabolite ASTCA (max 40.0 % after 59 days) is formed later. Consequently, tests with the metabolite ASTCA are required for the risk assessment. Studies with the species Folsomia candida and Hypoaspis aculeifer have been provided for the metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA indicating acceptable risk for organic matter breakdown after application of. 6.8 Effects on Soil Microbial Activity (IIIA 10.7) Overall summary Effects on soil micro-organisms for were not evaluated as part of the EU review of either clopyralid or florasulam. Therefore, all relevant data and assessments are provided here and are considered adequate. Evaluator: Germany Date: April 2013

273 Part B Section 6 Core Assessment Germany Central Zone Page 38 of Toxicity Table 6.8-1: Relevant studies on soil microbial activity Species Compound Exposition System C-transformation N-transformation Clopyralid (applied as formulation EF-1136 containing) Clopyralid (applied as formulation 28 d Aerob 28 d aerob EF-1136 containing) C-transformation Florasulam 28 d Aerob N-transformation Florasulam 28 d aerob C-transformation ASTCA 28 d Aerob N-transformation ASTCA 28 d Aerob C-transformation GF 1374 (86 g Clopyralid/L, 2.5 g Florasulam/L; 142 g Fluroxypyr-meptyl/L) 28 d Aerob Results toxicity [mg/kg soil] Effect < 25% 1500 g ai/ha resp. 2.0 mg/kg soil a Effect < 25% 1500 g ai/ha (= 2.0 mg/kg soil) a Effect < 25% 0.05 mg/kg soil Effect < 25% 0.05 mg/kg soil Effect < 25% 1.0 mg/kg soil* Effect < 25% 1.0 mg/kg soil* Effect < 25% 10 L/ha (= 13.9 mg/kg soil), corresponding to 1.15 as clopyralid as florasulam b N-transformation GF d Effect < 25% (86 g Clopyralid/L, 2.5 Aerob 10 L/ha (= 13.9 mg/kg g Florasulam/L; 142 g soil, corresponding to Fluroxypyr-meptyl/L) 1.15 as clopyralid as florasulam) b *New studies, submitted by the applicant, detailed information in Annex 2 of this document. Reference: Author Date Report-No. Hayward, J.C. & Morgan, A.J CEMS-2007 Hayward, J.C. & Morgan, A.J CEMS-2007 Forster, J ELL/1186 Forster, J ELL/1186 Feil * Feil * Rix, S CEMR-2422* Rix, S CEMR-2422* a Converted to mg/kg soil from the endpoint of 1500 g/ha listed in the EFSA Scientific Report (2005) 50, 1-65 assuming a soil bulk density of 1.5 g/ml and distribution in 5 cm of soil. b GF-1374, a formulation containing clopyralid (86 g/l), florasulam (2.5 g/l) and an additional active substance: fluroxypyr (142 g /L). The results obtained for GF-1374 (i.e mg GF-1374/kg soil) have been expressed in terms of clopyralid and florasulam for use in the risk assessment considering the content of clopyralid (i.e. 8.27% w/w) and florasulam (i.e. 0.24% w/w) in the lot tested in the study (desity of GF-1374 = 1040 g/ml). The studies except the marked new studies represent the EU-Evaluation of the active substances clopyralid and florasulam. Detailed information on the toxicity to micro-organisms of the active substances can be found in the Draft Assessment Report on clopyralid of November 2003 provided by the Rapporteur member Finland, the Draft Assessment Report on florasulam of November 1999 provided by the Rapporteur member Belgium, the EFSA Conclusion Report (EFSA Scientific Report (2005) 50, 1-65) on clopyralid of 2005 and the Review Report (SANCO/1406/ final) on florasulam of 18 September However, as the actual preparation contains two active substances, the data on the formulated product are most relevant for the risk assessments. No data is available for and soil microflora. Data on the worst-case formulation for Primus Perfect, GF, are summarised in Table GF-1374 contains clopyralid and florasulam plus an additional active substance, fluroxypyr. The maximum tested concentrations in this study were mg/kg soil (florasulam) and 1.15 mg/kg soil (clopyralid), respectively. ICS- No Evaluator: Germany Date: April 2013

274 Part B Section 6 Core Assessment Germany Central Zone Page 39 of 102 Although the concentrations of both clopyralid and florasulam are lower in GF-1374 than in Primus Perfect, the ratio of clopyralid to florasulam is higher in GF-1374 than in. A summary of the active substances concentrations and ratios of the two substances of interest is provided in the following table. Table 6.8-2: Comparison of the active substances in and GF-1374 Active substance GF-1374 Clopyralid 300 g/l 86 g/l Florasulam 25 g/l 2.5 g/l Fluroxypyr g/l Ratio of clopyralid to florasulam In light of the compositions and clopyralid to florasulam ratios in the formulations, it is considered valid to use soil microflora data for GF-1374 as a surrogate for as it provides for a worst-case assessment of the latter. Florasulam forms three major metabolites in soil: 5-OH-florasulam (max % after 3 d), DFP-ASTCA (max % after 28 d) and ASTCA (max % after 59 d), the most persistent of which is ASTCA. The risk posed by ASTCA to soil micro-organisms will be assessed Exposure See section of this document for the PECsoil values Overall conclusion The risk assessment results are summarized in the following table: Table 6.8-3: Risk assessment for soil microflora functions Substance (< 25% effect at 28 d) PECS (mg/kg), 25% MoS foliar interception Clopyralid 2.0 a Florasulam ASTCA as clopyralid b as florasulam b a Converted to mg/kg soil from the endpoint of 1500 g/ha listed in the EFSA Scientific Report (2005) 50, 1-65 assuming a soil bulk density of 1.5 g/ml and distribution in 5 cm of soil. b Based on data for GF-1374, a formulation containing clopyralid (80 g/l), florasulam (2.5 g/l) and an additional active substance: fluroxypyr at g a.i./l. Up to 28 days no effect > 25 % on soil microbial activity was found for the product GF 1374 (containing clopyralid, florasulam and fluroxypyr-meptyl), the active substance florasulam, and its metabolite ASTCA. It is assumed that these tests also covers the effects of the metabolites 5-OH-florasulam (maximum formation in soil: 71.6 % after 3 days) and DFP-ASTCA (maximum formation in soil: 17.8 % after 28 days). Clopyralid forms no major metabolite in soil applied at the proposed worst-case use patterns does not pose an unacceptable risk to soil microorganisms Toxicity exposure ratios SANCO/10329/2002 rev 2-final states that testing soil micro-organisms is always required when contamination of the soil is possible. The Predicted Environmental Concentrations of the formulation, the two active substances and the major soil degradation product ASTCA are below the concentrations at which no unacceptable effects (< 25%) were observed after 28 days of exposure. The results of the Evaluator: Germany Date: April 2013

275 Part B Section 6 Core Assessment Germany Central Zone Page 40 of 102 comparison expressed as Margin of Safety (MoS) considering the highest initial PEC in soil (i.e. 25% interception during applications) is presented in the following table: Table 6.8-4: Risk assessment to soil micro-organisms following applications of Substance Test type Maximum initial Effects <25% MoS PEC (mg/kg) (mg/kg) a N transformation 1.15 as clopyralid 19.2 C transformation as clopyralid as florasulam as florasulam 1.15 as clopyralid as florasulam Clopyralid N transformation C transformation Florasulam N transformation C transformation ASTCA N transformation C transformation a Based on data for GF-1374, a formulation containing clopyralid (80 g/l), florasulam (2.5 g/l) and an additional active substance fluroxypyr (99.94 g /L). TERs shown in bold fall below the relevant trigger. For the active ingredients in, clopyralid and florasulam, and their metabolite ASTCA the soil concentrations which caused no deviations greater than 25% in the micro-organism studies are at least 10-times higher than the corresponding maximum PEC in soil. Considering concurrent exposure to both the active ingredients in at the time of application, a low risk to soil microflora is also concluded being concentrations causing no deviations greater than ±25% at least 6.7-times higher than the maximum PEC in soil. Since up to 28 days no effect > 25 % on soil microbial activity was found for the product GF 1374 (containing clopyralid, florasulam and fluroxypyr-meptyl), the active substance florasulam, and its metabolite ASTCA. It is assumed that this test also covers the effects of the metabolites 5-OH-florasulam (maximum formation in soil: 71.6 % after 3 days) and DFP-ASTCA (maximum formation in soil: 17.8 % after 28 days). Consequently, it may be concluded that there will be no unacceptable risk to soil micro-organisms following the use of. Based on the worst case scenario, the acceptability criteria according to directive 1107/2009 (EG), Annex VI, uniform principles, point is reached Laboratory testing (IIIA ) Please refer to Appendix 2: of this document Additional testing (IIIA ) Additional testing on soil micro-organisms is not necessary since the studies performed on a worst-case formulation for (i.e. GF-1374), the active substances in, clopyralid and florasulam, and their relevant soil metabolite ASTCA resulted in no effects greater than ± 25% even at treatment levels equivalent to at least 6.7-times the maximum concentrations expected in soil following applications of. Use of in cereals is not expected to pose a risk to soil micro-organisms. Evaluator: Germany Date: April 2013

276 Part B Section 6 Core Assessment Germany Central Zone Page 41 of Effects on Non-Target Plants (IIIA 10.8) Terrestrial plants (IIIA ) Overview and summary Effects on terrestrial non-target plants for were not evaluated as part of the EU review of either clopyralid or florasulam. Data on is evaluated here, and risk assessments for Primus Perfect with the proposed use pattern are provided here and are considered adequate. Toxicity Table 6.9-1: Relevant studies on the toxicity of to terrestrial non-target plants Species Substance Exposition System Seedling emergence Lactuca sativa (300 g/l Clopyralid + 25 g/l Florasulam) Vegetative vigour Lactuca sativa (300 g/l Clopyralid + 25 g/l Florasulam) Daucus carota Beta vulgaris Brassica napus Cyperus esculentus Allium cepa Avena sativa Glycine max EF-1343 (Florasulam 50 g/l SCformulation) Lontrel 100 (Clopyralidformulation) 21 d Seedling emergence 21 d Vegetative vigour 17 d Vegetative vigour 21 d Vegetative vigour *New studies, submitted by the applicant, detailed information in Appendix 2. Results toxicity ER 50 = 17.2 ml Prod./ha biomass ER 50 = 5.29 ml prod./ha biomass ER 50 = 2.1 g ai/ha freshweight ER 50 = 25.4 g ai/ha freshweight Referenece author date Code Brockmann, A., Teresiak, H.; ; AC/DOW/10/ 01* Brockmann, A., Teresiak, H.; ; AC/DOW/10/ 02* Paterson, E GHE-P-7957 Paterson, E GHE-P-9045 ICS No The studies except the marked new studies represent the EU-Evaluation of the active substances clopyralid and florasulam. Detailed information on the toxicity to terrestrial plants of the active substances can be found in the Draft Assessment Report on clopyralid of November 2003 provided by the Rapporteur member Finland, the Draft Assessment Report on florasulam of November 1999 provided by the Rapporteur member Belgium, the EFSA Conclusion Report (EFSA Scientific Report (2005) 50, 1-65) on clopyralid of 2005 and the Review Report (SANCO/1406/ final) on florasulam of 18 September However, the data on the formulated product are most relevant for the risk assessments. Exposure Effects on non-target plants are of concern in the off-field environment, where they may be exposed to spray drift. The amount of spray drift reaching off-crop habitats is calculated using the 90th percentile Evaluator: Germany Date: April 2013

277 Part B Section 6 Core Assessment Germany Central Zone Page 42 of 102 estimates derived by the BBA (2000) 4 from the spray-drift predictions of Ganzelmeier & Rautmann (2000) 5. Any dilution over the 3-dimensional vegetation surface is accounted for in the study design. Therefore, in contrast to the assessment of risks to arthropods from standard laboratory tests, no vegetation distribution factor is considered here. PECoff-field= Maximum in-field PER x (%DRIFT/100) The exposure assessment for the intended uses, due to the ground-directed application of, which is a herbicide, is most appropriately addressed by the drift values for field crops. The highest single application rate of is 0.2 L product/ha corresponding to 5 g florasulam /ha and 60 g clopyralid/ha. The resulting maximum off-field predicted environmental rate (PERoff-field) at 1 m distance to the field is given in the following table: Table 6.9-2: Maximum off-field predicted environmental rates of GF-1463 Maximum intended in-field rate Maximum PERoff-field at 1m Maximum PERoff-field at 5m (PECin-field) (2.77% drift) (0.57% drift) 200 ml product/ha 5.54 ml product/ha 1.14 ml product/ha Overall conclusion The risk assessment results are summarized in the following table: Table 6.9-3: Risk assessment for terrestrial non-target plants exposed to Effect endpoint Seedling emergence Effect rate [ml product/ha] (ER 50 ) 17.2 PERin-field [ml product/ha] 200 ml/ha Distance [m] Exposure TER PERoff-field [ml product/ha] Vegetative vigour TERs shown in bold fall below the relevant trigger. Based on the most sensitive endpoints for seedling emergence and vegetative vigour, treatment of Primus Perfect according to the proposed uses, poses high and unacceptable risk to terrestrial non-target plants without consideration further risk mitigation measures Toxicity exposure ratios For plant protection products exerting effects of more than 50% at the maximum application rate (common for herbicides as ) a quantitative second tier risk assessment based on doseresponse endpoints represented by ER 50 values is required according to the terrestrial guidance document. The risk assessment based on the overall lowest effect endpoint for seedling emergence and vegetative vigour for the actual formulation and the relevant predicted environmental rate in the offfield area after treatment with in accordance to the maximum proposed use rate of 0.2 L product/ha is presented in the following table: 4 BBA (2000) Bundesanzeiger Jg. 52 (Official Gazette), Nr 100, S ( ) Bekanntmachung über die Abtrifteckwerte, die bei der Prüfung und Zulassung von Pflanzenschutzmitteln herangezogen werden. Public domain. 5 Ganzelmeier H., Rautmann D. (2000) Drift, drift-reducing sprayers and sprayer testing. Aspects of Applied Biology 57, 2000, Pesticide Application. Public domain. Evaluator: Germany Date: April 2013

278 Part B Section 6 Core Assessment Germany Central Zone Page 43 of 102 Table 6.9-4: Substance Primus Perfect Risk assessment for terrestrial non-target plants after uses of in cereals Effect endpoint Seedling emergence Effect rate [ml product/ha] (ER 50 ) 17.2 Distance [m] Exposure PERoff-field [ml product/ha] TER TER risk assessment trigger Vegetative vigour TERs shown in bold fall below the relevant trigger. Based on the criteria harmonized in the EU for a risk assessment without mitigation measures like specific buffer zones or drift reducing nozzles, TER values based on the most sensitive species identified in the seedling emergence as well as in the vegetative vigour study for are below the proposed Annex VI trigger of 5 indicating an unacceptable risk Seed germination (IIIA ) This is not an EC data requirement / not required by Directive Nr 1107/2009 (EG) Vegetative vigour (IIIA ) Please refer to Appendix 2: of this document Seedling emergence (IIIA ) Please refer to Appendix 2: of this document Field testing (IIIA ) No study submitted. Data gap if no appropriate risk mitigation measures can be used in member states. Otherwise, terrestrial field testing is not required since a low risk to non-target terrestrial plants is expected without the need of specific buffer zones if 90% drift reducing nozzles are used during applications or at a distance of 5 m from the treated area if 50% drift reducing nozzles are used during applications or with a 10 m buffer zone and no drift reducing nozzle Effects on non-target aquatic plants (IIIA ) Please refer to Appendix 2: Lemna growth test (IIIA ) Please refer to Appendix 2: Field tests (IIIA ) Due to the acceptable risk at lower tier, no aquatic field tests are required. Evaluator: Germany Date: April 2013

279 Part B Section 6 Core Assessment Germany Central Zone Page 44 of Other Non-Target Species (Flora and Fauna) (IIIA 10.9) Not relevant Available preliminary data on other non-target species (flora and fauna) (IIIA ) No additional relevant data available Critical assessment of relevance of preliminary test data (IIIA ) Not applicable Other/Special Studies (IIIA 10.10) Please refer to Appendix 2: Laboratory studies (IIIA ) Please refer to Appendix 2: Field studies (IIIA ) Not required. Evaluator: Germany Date: April 2013

280 Part B Section 6 Core Assessment Germany Central Zone Page 45 of 102 Annex point Appendix 1: Appendix 1: List of data submitted in support of the evaluation Author Year Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished KIIA 8.4 Rebstock, M DFP-ASTCA metabolite of florasulam (X ): Growth inhibition test with the unicellular green alga, Pseudokirchneriella subcapitata Dow AgroSciences Study Number: KIIA 8.6 Rebstock, M DFP-ASTCA metabolite of florasulam (X ): Growth inhibition test with the Freshwater aquatic plant duckweed, Lemna gibba Dow AgroSciences Study Number: KIIA Witte, B Effects of 5-hydroxy-florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: KIIA Lührs, U Effects of DFP-ASTCA metabolite of florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: KIIA Witte, B Effects of ASTCA metabolite of florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: KIIA Witte, B Effects of 5-hydroxy-florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: KIIA Witte, B Effects of ASTCA metabolite of florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: KIIA Witte, B Effects of DFP-ASTCA metabolite of florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: KIIIA XXX 2011 : Acute toxicity to the rainbow trout, Oncorhynchus mykiss, determined under static renewal test condition XXX Study Number: Data protection claimed Y/N Y Y Y Y Y Y Y Y Y Owner Evaluator: Germany Date: April 2013

281 Part B Section 6 Core Assessment Germany Central Zone Page 46 of 102 Annex point KIIIA KIIIA /01 KIIIA /01 KIIIA /01 KIIIA /02 KIIIA /01 KIIIA /01 KIIIA /01 KIIIA /01 Author Year Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished Rebstock, M : Acute toxicity to the water flea Daphnia magna, determined under static test condition Dow AgroSciences Study Number: Porch, J.R., Kendall, T.Z., Krueger, H.O. 2011a : a 72-hour toxicity test with the freshwater alga (Pseudokirchneriella subcapitata). Dow AgroSciences Study Number: Schmitzer, S Effects of (acute contact and oral) on honey bees (Apis mellifera L.) in the laboratory. Dow AgroSciences Study Number: and Schwarz, A Effects of on the predatory mite Typhlodromus pyri in the laboratory (Tier I) dose response test. Dow AgroSciences Study Number: Moll, M Effects of on the parasitoid Aphidius rhopalosiphi in the laboratory (Tier I) dose response test. Dow AgroSciences Study Number: Witte, B. 2010a Acute toxicity (14 days) of to the earthworm Eisenia fetida in artificial soil. Dow AgroSciences Study Number: Witte, B b Effects of on reproduction and growth of earthworms Eisenia fetida in artificial soil. Dow AgroSciences Dow AgroSciences Study Number: Rix, S GF-1374: determination of effects on soil microflora activity Dow AgroSciences Dow AgroSciences Study Number: Brockmann, A., Korfmacher, R., Teresiak, H a Evaluation of the phytotoxicity of Primus Perfect (clopyralid 300 g as/l + florasulam 25 g as/l, SC) GLP vegetative vigour test terrestrial non target plants (based on OECD Guideline 227) Europe Dow AgroSciences Dow AgroSciences Study Number: Data protection claimed Y/N Y Y Y Y Y Y Y Y Y Owner DAS DAS DAS DAS DAS DAS DAS DAS Evaluator: Germany Date: April 2013

282 Part B Section 6 Core Assessment Germany Central Zone Page 47 of 102 Annex point KIIIA /01 KIIIA /01 KIIIA /01 KIIIA /02 KIIIA /03 KIIIA /04 KIIIA /05 KIIIA /06 KIIIA /07 Author Year Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished Brockmann, A., Teresiak, H. Porch, J.R., Kendall, T.Z., Krueger, H.O. Kirk, H.D., Marino, T.A. Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G. Ward, T.J., Magazu, J.P., Boeri, R.L b 2011 b Evaluation of the phytotoxicity of Primus Perfect (clopyralid, 300 g as/l + florasulam, 25 g as/l, SC) GLP seedling emergence and seedling growth test terrestrial non target plants (based on OECD Guideline 208) Europe Dow AgroSciences. Dow AgroSciences Study Number: : A 7-day static-renewal toxicity test with duckweed (Lemna gibba G3). Dow AgroSciences Study Number: Toxicity of metabolites of XDE-570 to Daphnia magna. Dow AgroSciences Study Number: (Aminosulfonyl)-1H-1,2,4-triazole-3- carboxylic acid (florasulam M4 metabolite): growth inhibition test with the freshwater green alga, Selenastrum capricornutum PRINTZ. Dow AgroSciences Study Number: Toxicity of metabolites of XDE-570 to the earthworm, Eisenia foetida Exposurebased screening investigation. Dow AgroSciences Study Number: Lührs, U Acute toxicity (14 days) of ASTCA metabolite of florasulam to the earthworm Eisenia fetida in artificial soil. Dow AgroSciences Study Number: Lührs, U Effects of ASTCA metabolite of florasulam on reproduction and growth of earthworms Eisenia fetida in artificial soil. Dow AgroSciences Study Number: Feil, N Effects of ASTCA metabolite of florasulam on the activity of the soil microflora in the laboratory. Dow AgroSciences Study Number: Hancock, G.A. Arnold, B.H., Carr, M.S., Najar, J.R Hydroxy-florasulam: growth inhibition test with the aquatic plant duckweed, Lemna gibba. Dow AgroSciences Study Number: Data protection claimed Y/N Y Y Y Y Y Y Y Y Owner DAS DAS DAS DAS DAS DAS DAS DAS Evaluator: Germany Date: April 2013

283 Part B Section 6 Core Assessment Germany Central Zone Page 48 of 102 Annex point KIIIA /08 Author Year Title Source (where different from company) Company, Report No. GLP or GEP status (where relevant) Published or Unpublished Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G (Aminosulfonyl)-1H-1,2,4-triazole-3- carboxylic acid (florasulam M4 metabolite): growth inhibition test with the freshwater aquatic plant, duckweed, Lemna gibba L. G-3. Dow AgroSciences Study Number: Data protection claimed Y/N Y Owner DAS * 1) accepted (study valid and considered for evaluation) 2) not accepted (study not valid and not considered for evaluation) 3) not considered (study not relevant for evaluation) 4) not submitted but necessary (study not submitted by applicant but necessary for evaluation) 5) supplemental (additional information, alone not sufficient to fulfil a data requirement, considered for evaluation) Evaluator: Germany Date: April 2013

284 Part B Section 6 Core Assessment Germany Central Zone Page 49 of 102 Appendix 2: Detailed evaluation of studies relied upon A2-1 Active substance and its metabolites (generally only relevant in the case that new annex II data is provided after florasulam approval) Reports only studies, which (a) have not previously been evaluated within a peer reviewed process at EU level (Annex I inclusion of active substance) or (b) have been evaluated in a peer reviewed process at EU level but where in exceptional cases derived endpoints have to be revised in the light of current scientific and technical knowledge. Studies evaluations are ordered according to OECD code numbers. KIIA 8.3.2/01 Kirk, H.D., Marino, T.A. (1998) Report: Kirk, H.D., Marino, T.A. (1998). Title: Toxicity of metabolites of XDE-570 to Daphnia magna. Document No: Dow AgroSciences Study Number: Guidelines: FIFRA72-2, EEC Method C.2, OECD 202 GLP Yes Test material Test items: The following metabolites of florasulam: DFP- ASTCA, ASTCA, TSA, STA, STCA Purity: DFP-ASTCA: 73% ASTCA: 54% TSA: 98.3% STA: 99% STCA: 99% Lot No./Batch No.: DFP-ASTCA: TSN ASTCA: TSN TSA: TSN STA: TSN STCA: TSN Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Duration of study: Test conditions: Parameters measured: Observation intervals: Water flea (Daphnia magna) Acute None 48-hours Static Mortality and immobility 0, 24 and 48 hours Evaluator: Germany Date: April 2013

285 Part B Section 6 Core Assessment Germany Central Zone Page 50 of 102 Age range of water fleas at test initiation: Test concentrations: <24 hours Nominal: 0 (Control), 3 and 30 µg/l for each of the metabolites. Analytical confirmation of test Not performed concentrations: Analytical reference substances: N/A Number of water fleas per dose group 20 Number of water fleas per control group: 20 Feeding: None Environmental conditions: Temperature: 21.7 C at test initiation 20.6 C at test termination Photoperiod: 16 hour light:8 hour dark Oxygen concentration: 89-94% at test initiation 92-94% at test termination ph: at test initiation at test termination Water alkalinity: 30 mg CaCO 3 /L Water hardness: 174 mg CaCO 3 /L Water conductivity: 421 µs Methodology A definitive test was performed at nominal concentrations of 0 (Control), 3 and 30 µg/l for each of the five metabolites. Five neonates (<24-hours old) were added to each of four test chambers per treatment at the start of the test. The daphnids were observed for mortality and immobility at approximately 24 and 48 hours after test initiation. Total hardness, total alkalinity, and conductivity were measured in the dilution water on Day 1. Temperature, dissolved oxygen concentration, and ph were measured in bulk solutions and all treatment replicates at test initiation and at termination, respectively. Table Appendix : Effect of florasulam metabolites on immobility of Daphnia magna Treatment Initial no. of Cumulative mortality (%) (µg/l) daphnids DFP-ASTCA ASTCA TSA STA STCA 24-h 48-h 24-h 48-h 24-h 48-h 24-h 48-h 24-h 48-h Control Conclusions There were no sub-lethal effects or mortality observed following 48 hours of exposure to any of the five metabolites of florasulam during the conduct of the study at concentrations up to 30 µg/l. Evaluator: Germany Date: April 2013

286 Part B Section 6 Core Assessment Germany Central Zone Page 51 of 102 The EC 50 values of the florasulam metabolites DFP-ASTCA, ASTCA, TSA, STA and STCA must therefore all lie above 30 µg/l, the highest test concentration. Comments of zrms [Commenting box] Study Comments: KIIA 8.3.2/01 Agreed Endpoints: KIIA 8.3.2/01 The study is acceptable. 48-h EC 50 >30 µg/l for DFP-ASTCA and ASTCA (nominal concentrations) KIIA 8.4/01 Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G. (2000) Report: Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G. (2000). Title: 5-(Aminosulfonyl)-1H-1,2,4-triazole-3-carboxylic acid (florasulam M4 metabolite): growth inhibition test with the freshwater green alga, Selenastrum capricornutum PRINTZ. Document No: Dow AgroSciences Study Number: Guidelines: OECD 201, EEC Method C.3, FIFRA Subdivision J GLP Yes Test material Test item: Purity: Description: Lot No./Batch No.: 5-(Aminosulfonyl)-1H-1,2,4-triazole-3-carboxylic acid (ASTCA) 54% a.e. Solid TSN Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Duration of study: Environmental conditions: Observation intervals: Age of inoculum: Acclimation period/conditions: Freshwater green alga (Pseudokirchneriella subcapitata) laboratory study assessing algal growth static None 96-hours Temperature (range): C Photoperiod: Continuous light. Light intensity (range): lux 0, 24, 48, 72, 96 hours 6 days old The prepared cultures were maintained in a temperature-controlled environmental chamber Evaluator: Germany Date: April 2013

287 Part B Section 6 Core Assessment Germany Central Zone Page 52 of 102 Initial cell density: Growth medium: Test concentrations: Method of test item added to the test medium: No. of control replicates: No. of test concentration replicates: Analytical verification: under continuous light. Weekly, new cultures were cloned from an existing culture derived from the parent stock. All cultures were maintained under the same conditions as those used for testing cells/ml Name: AAM ph with algae: ph without algae: 6.9 All test solutions were swirled on an orbital shaker table at 100 rpm throughout the test. Nominal: 0 (control) and 10.9 mg/l (limit test) Mean measured concentrations: 0 (control) and 9.2 mg/l The test item was dosed in the AAM medium to obtain the target test concentration prior to addition of the algal inoculum abiotic abiotic Method: HPLC/NESI/MS Samples taken: Test initiation and termination. Limit of Detection: Not determined. Limit of Quantitation: 5 mg/l. Methodology The exposure flasks were 250-mL Erlenmeyer flasks with Shimadzu closure containing 100 ml of test medium. The control and the ASTCA test concentrations were each replicated ten times. An additional replicate, containing 100 ml of the appropriate, was also prepared and used to evaluate the potential for incorporation of the test substance into the algal biomass (abiotic replicate). At test initiation, all biotic replicates were inoculated with approximately cells/ml. At approximately 24, 48, 72 and 96 hours, cell density was measured in all replicates of the control and test substance treatment electron particle counting using a Coulter Multisizer. The abiotic replicate was not inoculated with algae. Table : Effect of ASTCA on growth of Pseudokirchneriella subcapitata Treatment Density (cells/ml) (mg/l) Day 0 Day 1 Day 2 Day 3 Day 4 Mean measured Mean Mean Mean Mean % change Mean % change Control Conclusions Based on mean measured concentrations, the 72-h and 96-h EC 50, E b C 50 and E r C 50 values were all >9.2 mg/l. Evaluator: Germany Date: April 2013

288 Part B Section 6 Core Assessment Germany Central Zone Page 53 of 102 Comments of zrms [Commenting box] Study Comments: KIIA 8.4/01 Agreed Endpoints: KIIA 8.4/01 The study is acceptable. 72-h and 96-h EC 50, E b C 50 and E r C 50 > 9.2 mg/l (mean measured concentrations) KIIA 8.4/02 Rebstock, M. (2011a) Reference: KIIA 8.4 Report Guideline(s): Yes; OECD 201 Deviations: GLP: Acceptability: Study evaluation Rebstock, M.; 2011; DFP-ASTCA metabolite of florasulam (X ): Growth inhibition test with the unicellular green alga, Pseudokirchneriella subcapitata Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: DFP-ASTCA Metabolite of florasulam Test conditions: Test concentrations: Static Nominal: 0 (control); 6,3; 13; 25; 50 und 100 mg ai/l (nom.) Results and discussions Table : Effect of DFP-ASTCA on growth of Pseudokirchneriella subcapitata Effect (based on nominal concentr ations) 72 h 96 h Value (mg ai/l) 95% confidence Value (mg ai/l) limits (mg ai/l) 95% confidence limits (mg ai/l) EC 50 (cell > density) n.a. 50 ErC 50 > 100 (cell > 100 n.a. n.a. 50 density) EyC > 100 n.a. 50 Conclusion NOEC Evaluator: Germany Date: April 2013

289 Part B Section 6 Core Assessment Germany Central Zone Page 54 of 102 Based on mean nominal concentrations, the 72-h EC 50 value was 97 mg ai/l for DFP-ASTCA. Comments of zrms [Commenting box] Study Comments: KIIA 8.4/02 Agreed Endpoints: KIIA 8.4/02 The study is acceptable. 3d-EC 50 = 97 mg ai/l for DFP-ASTCA (nominal concentrations) KIIA 8.6/01 Hancock, G.A. Arnold, B.H., Carr, M.S., Najar, J.R. (2007) Report: Hancock, G.A. Arnold, B.H., Carr, M.S., Najar, J.R. (2007). Title: 5-Hydroxy-florasulam: growth inhibition test with the aquatic plant duckweed, Lemna gibba. Document No: Dow AgroSciences Study Number: Guidelines: OECD 221, OPPTS , FIFRA Subdivision J GLP Yes Test material Test item: 5-OH-florasulam Purity: 98.1% Description: Solid, white Lot No./Batch No.: TSN Test system Organism (Species): Duckweed (Lemna gibba) Study Type: 7 day duration Guideline deviations reported by Study Director: None Test conditions: Static renewal, renewals on days 3 and 5 Parameters measured: Growth and Yield (Number of fronds and biomass as dry weight) Observation intervals: Days 3, 5, 7 Age of fronds at test initiation: 14 days Initial number of fronds: 12 per replicate Test concentrations: Nominal: 0 (control), , , , 0.160, and 1.00 mg/l Mean measured concentrations: <LOQ (control), , , , 0.129, 0.315, and mg/l Evaluator: Germany Date: April 2013

290 Part B Section 6 Core Assessment Germany Central Zone Page 55 of 102 Analytical confirmation of test concentrations: Number of fronds per control group: Number of fronds per dose group: Environmental conditions: 0, 3, 5, and 7 days Method: LC/UV LOQ: mg/l 72 (6 replicates + 1 abiotic replicate) 36 (3 replicates + 1 abiotic replicate) Temperature (range): C Photoperiod: Continuous light. Light intensity (range): lux Growth medium: 20X AAM ph of fresh solutions: 7.6 to 7.8 as measured on days 0, 3, and 5 in bulk solutions ph of spent solutions: 8.2 to 8.8 as measured on days 3, 5, and 7 in replicates containing duckweed ph of spent solutions:7.7 to 8.0 as measured on days 3, 5, and 7 in replicates not containing duckweed Methodology A 7-day static renewal test with the freshwater aquatic plant, Lemna gibba was performed. Each test flask received three plants for a total of 12 fronds at test initiation. There were three replicates per test treatment and six replicates for the control, resulting in 36 and 72 fronds per test treatment and control, respectively. Frond observations and counts were made at 3, 5, and 7 days, with renewals at days 3 and 5. Temperature and ph were measured in all fresh parent solutions, on days 0, 3 and 5. On days 3, 5, and 7, temperature and ph were measured in a pooled sample of each of treatment spent solutions. Biomass (dry weight) measurements of each control and test substance treatment replicate were performed on day 7 (test termination). Table : Effect of 5-OH-florasulam on growth of Lemna gibba Treatment (mg/l) Mean measured Yield (Day 7) Growth rate (Days 0-7) Frond no. Dry weight (mg) Frond no. Dry weight (mg) Mean % inhibition Mean % inhibition Mean % inhibition Mean % inhibition Control Table : Results Endpoint (mg/l) Yield 7 day Growth rate 7 day Frond no. Dry weight Frond no. Dry weight Evaluator: Germany Date: April 2013

291 Part B Section 6 Core Assessment Germany Central Zone Page 56 of 102 NOEC EC >0.823 EC 50 95% C.I Conclusions The test acceptability criteria for control growth (i.e., frond doubling time < 2.5 days, greater than a seven-fold increase in the number of fronds, and minimum average specific growth rate of day -1 ) set by OECD 221 test guideline were met for this study. The doubling time for the control fronds was 1.8 days, corresponding to a 15-fold increase in the number of fronds, and the average specific growth rate was day -1. This study is classified as acceptable and satisfies the guideline requirement for a growth inhibition test with Lemna gibba. The lowest EC 50 derived in the study is that based on frond number yield, which was 37.8 μg/l. The NOEC for all parameters was 21 μg/l. Comments of zrms [Commenting box] Study Comments: KIIA 8.6/01 Agreed Endpoints: KIIA 8.6/01 The study is acceptable. 7-d E y C 50 = 37.8 µg/l for 5-OH-florasulam (mean measured concentrations) KIIA 8.6/02 Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G. (2000) Report: Kirk, H.D. Gilles, M.M., Rick, D.L., McFadden, L.G. (2000). Title: 5-(Aminosulfonyl)-1H-1,2,4-triazole-3-carboxylic acid (florasulam M4 metabolite): growth inhibition test with the freshwater aquatic plant, duckweed, Lemna gibba L. G-3 Document No: Dow AgroSciences Study Number: Guidelines: FIFRA Subdivision J GLP Yes Test material Test item: Purity: Description: Lot No./Batch No.: 5-(Aminosulfonyl)-1H-1,2,4-triazole-3-carboxylic acid (ASTCA) 54% a.e. Solid TSN Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Duckweed (Lemna gibba) 14 day duration None Evaluator: Germany Date: April 2013

292 Part B Section 6 Core Assessment Germany Central Zone Page 57 of 102 Test conditions: Static Parameters measured: Growth (Number of fronds) Observation intervals: Days 2, 5, 7, 10, 14 Age of fronds at test initiation: Not specified Initial number of fronds: 12 per replicate Test concentrations: Nominal: 0 (control) and 10.2 mg/l (limit test) Analytical confirmation of test concentrations: Number of fronds per control group: Number of fronds per dose group: Environmental conditions: Attempted on Days 0 and 14. Difficulties associated with the intrinsic physical properties of the test compound and sample matrix did not allow a quantitation of ASTCA using HPLC/NESI/MS (or several alternative analytical techniques that were attempted). 156 (13 replicates + 1 abiotic replicate) 156 (13 replicates + 1 abiotic replicate) Temperature (range): C Photoperiod: Continuous light. Light intensity (range): lux Growth medium: 20X AAM ph of fresh solutions: 8.2 to 8.3 ph of spent solutions: 8.5 to 9.2 as measured on days 2, 5, 7, 10 and 14 in replicates containing duckweed ph of spent solutions:8.1 to 8.7 as measured on days 2, 5, 7, 10 and 14 in replicates not containing duckweed Methodology A 14-day static test with the freshwater aquatic plant, Lemna gibba was performed. Each test flask received three plants for a total of 12 fronds at test initiation. There were 13 replicates per test treatment and control, resulting in 156 fronds. Frond observations and counts were made at 2, 5, 7, 10 and 14 days. Temperature and ph were measured in all fresh parent solutions. The ph was also determined in similar test solutions without duckweed on days 2,5, 7, 10, and 14. At the end of the study, temperature and ph were measured in all replicates. Table : Effect of ASTCA on growth of Lemna gibba Treatment (mg/l) Nominal Mean Frond no./vessel Day 0 Day 2 Day 5 Day 7 Day 10 Day 14 % inhibition Control % inhibition Evaluator: Germany Date: April 2013

293 Part B Section 6 Core Assessment Germany Central Zone Page 58 of 102 Conclusions Based on nominal concentrations, the 7- and 14-day EC 25, EC 50 values for the number of fronds were >10.2 mg ASTCA/L. Comments of zrms [Commenting box] Study Comments: KIIA 8.6/02 Agreed Endpoints: KIIA 8.6/02 The study is acceptable. 7-d and 14-d EC 50 > 10.2 µg/l for ASTCA (nominal concentrations) KIIA 8.6/03 Rebstock, M. (2011b) Reference: KIIA 8.6 Report Guideline(s): Yes; OECD 221 Deviations: GLP: Acceptability: Study evaluation Rebstock, M.; 2011; DFP-ASTCA metabolite of florasulam (X ): Growth inhibition test with the Freshwater aquatic plant duckweed, Lemna gibba Dow AgroSciences Study Number: Study Number ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test conditions: Test concentrations: DFP-ASTCA Metabolite of florasulam Semistatic Nominal: 0 (control); 6,3; 13; 25; 50 und 100 mg ai/l (nom.) Results and discussions Table : Effect of DFP-ASTCA on growth of Lemna gibba Effect (based on nominal concentrations) 7 d value (mg ai/l) 95% confidence limits (mg ai/l) NOEC EyC50 (fronds) > 100 n.a. 100 ErC50 (biomass) > 100 n.a. 100 EyC50 (fronds) > 100 n.a. 100 ErC50 (biomass) > 100 n.a. 100 Conclusion Based on mean nominal concentrations, the 7d EC 50 value was > 100 mg ai/l for DFP-ASTCA. Evaluator: Germany Date: April 2013

294 Part B Section 6 Core Assessment Germany Central Zone Page 59 of 102 Comments of zrms [Commenting box] Study Comments: KIIA 8.6/03 Agreed Endpoints: KIIA 8.6/03 The study is acceptable. 7d EC 50 value was > 100 mg DFP-ASTCA/L (nominal concentrations) KIIA 8../01 Ward, T.J., Magazu, J.P., Boeri, R.L. (1998) Report: Ward, T.J., Magazu, J.P., Boeri, R.L. (1998). Title: Toxicity of metabolites of XDE-570 to the earthworm, Eisenia foetida Exposure-based screening investigation. Document No: Dow AgroSciences Study Number: Guidelines: OECD 207 GLP Yes Test material Test item: The following metabolites of florasulam: DFP- ASTCA, ASTCA, TSA, STA, STCA Purity: DFP-ASTCA: 73% ASTCA: 54% TSA: 98.3% STA: 99% STCA: 99% Lot No./Batch No.: DFP-ASTCA: TSN ASTCA: TSN TSA: TSN STA: TSN STCA: TSN Test system Organism (Species): Earthworm (Eisenia foetida) Study Type: 14 day acute earthworm study Guideline deviations reported by Study Director: None Study design: Assessment of the survival, behaviour and weight change of worms. 4 replicates, consisting of 10 worms in each vessel per test concentration. Test concentrations: 0 (control), 10 and 100 µg/kg dry soil for each of the metabolites. Soil parameters: Artificial soil according to OECD 207: ph at initiation: Evaluator: Germany Date: April 2013

295 Part B Section 6 Core Assessment Germany Central Zone Page 60 of 102 ph at termination: Moisture content at initiation: 24-25% Moisture content at termination: 22-27% Environmental conditions: Temperature: C Feeding: None Reference item: 2-chloroacetamide (conducted as a separate study) Methodology 14-days exposure in treated artificial soil. Different concentrations of the test items were mixed homogeneously into the soils which were filled in glass vessels before the earthworms were introduced on top of the soil; two concentrations and one control for each metabolite; 4 replicates per concentration with 10 worms each. Assessment of worm mortality and behavioural effects after 7 and 14 days, measurement of weight change as sublethal parameter after 14 days. Table : Effect of florasulam metabolites on survival and biomass change of earthworms Treatment (µg/kg dry soil) Initial no. of worms 14-d mortality (M) and body weight change (BW) (%) DFP-ASTCA ASTCA TSA STA STCA M BW M BW M BW M BW M BW Control M: mortality; BW: body weight. Conclusions In 14-day toxicity studies with the florasulam metabolites DFP-ASTCA, ASTCA, TSA, STA and STCA to earthworms (Eisenia foetida), the 7- and 14-day LC50 values were each estimated to be >100 µg/kg soil. No significant differences between the average weight change of the controls and either concentration of the five metabolites occurred at the conclusion of the test. Surviving worms exposed to the control and both concentrations of the 5 metabolites burrowed into the soil within 10 minutes on days 0 and 7 and significant lethargy was noted only in the 100 µg/kg treatments of DFP-ASTCA, ASTCA, and TSA at the end of the test. Comments of zrms [Commenting box] Study Comments: KIIA 8.9./01 Agreed Endpoints: KIIA 8.9./01 The study is acceptable. 14-d LC 50 > 100 µg/kg dry soil for DFP-ASTCA KIIA 8.9/02 Lührs, U. (2008) Report: Lührs, U. (2008). Evaluator: Germany Date: April 2013

296 Part B Section 6 Core Assessment Germany Central Zone Page 61 of 102 Title: Acute toxicity (14 days) of ASTCA metabolite of florasulam to the earthworm Eisenia fetida in artificial soil Document No: Dow AgroSciences Study Number: Guidelines: OECD 207, ISO GLP Yes Test material Test item: ASTCA metabolite of florasulam Purity: 100% Lot No./Batch No.: V , TSN Test system Organism (Species): Earthworm (Eisenia foetida) Study Type: 14 day acute earthworm study Guideline deviations reported by Study Director: None Study design: Assessment of the survival, behaviour and weight change of worms. 4 replicates, consisting of 10 worms in each vessel per test concentration. Test concentrations: 0 (control), 6.25, 12.5, 25.0, 50.0 and 100 mg ASTCA/kg dry soil. Soil parameters: Artificial soil according to OECD 207: ph at initiation: ph at termination: Moisture content at initiation: % Moisture content at termination: % Environmental conditions: Temperature: C Feeding: None Reference item: 2-chloroacetamide (conducted as a separate study) Methodology 14-days exposure in treated artificial soil. Different concentrations of the test items were mixed homogeneously into the soils which were filled in glass vessels before the earthworms were introduced on top of the soil; five concentrations and one control; 4 replicates per concentration with 10 worms each. Assessment of worm mortality and behavioural effects after 7 and 14 days, measurement of weight change as sublethal parameter after 14 days. Table : Effect of ASTCA on survival and biomass change of earthworms Nominal test concentrations Mortality after Body weight change after 14 days Evaluator: Germany Date: April 2013

297 Part B Section 6 Core Assessment Germany Central Zone Page 62 of 102 (mg ASTCA/kg dry soil) 14 days (%) (%) Control * Toxic Reference 14 day LC 50: 27.0 mg 2-chloroacetamide/kg wet weight *: Significantly different from the control. Conclusions In a 14-day toxicity study with the florasulam metabolite ASTCA to earthworms (Eisenia foetida), the 14-day LC 50 value was estimated to be >100 mg/kg soil. At the end of the test, a significant difference between the average weight change of the controls and the ASTCA treatments was found only at the highest concentration tested. Comments of zrms [Commenting box] Study Comments: KIIA 8.9/02 Agreed Endpoints: KIIA 8.9/02 The study is acceptable. 14-d LC 50 > 100 mg/kg dry soil for ASTCA KIIA 8.9/03 Lührs, U. (2008) Report: Lührs, U. (2008). Title: Effects of ASTCA metabolite of florasulam on reproduction and growth of earthworms Eisenia fetida in artificial soil Document No: Dow AgroSciences Study Number: Guidelines: OECD 222 and ISO GLP Yes Test material Test item: ASTCA metabolite of florasulam Purity: 100% Lot No./Batch No.: V , TSN Test system Organism (Species): Study Type: Earthworm (Eisenia foetida) 56 day earthworm reproduction study Evaluator: Germany Date: April 2013

298 Part B Section 6 Core Assessment Germany Central Zone Page 63 of 102 Guideline deviations reported by Study Director: None Study design: Assessment of the survival, behaviour and weight change of worms after 28 days exposure. Assessment of the number of offspring 56 days after treatment. 4 replicates, consisting of 10 worms in each vessel per test concentration. 8 replicates, consisting of 10 worms in each vessel for the control. Test concentrations: 0 (control), , 0.125, 0.250, 0.5 and 1.0 mg ASTCA/kg dry soil. Soil parameters: Artificial soil according to OECD 222: ph at initiation: ph at termination: Water content at initiation: 27.6% to 30.2% (45.2% to 49.5% of the maximum water holding capacity) Water content at termination: 33.6% to 38.9% (55.1% to 63.8% of the maximum water holding capacity) Environmental conditions: Temperature: C Photoperiod: 16-h light: 8-h dark Light intensity: : 420 lux to 700 lux Feeding: Finely ground cattle manure was used as food and was added each week for the first 4 weeks of the experiment. Reference item: Brabant Carbendazim Flowable (Carbendazim, 500 g/l nominal). Methodology 56-day test in treated artificial soil according to OECD 222; different concentrations of the test item were incorporated into the soil; 6 treatment groups (5 test item concentrations, control); 4 replicates for the test item treatments, 8 replicates for the control, 10 worms each. Assessment of adult worm mortality, behavioural effects and biomass development were carried out after 28 days exposure of adult worms in treated artificial soil. Reproduction rate (number of offspring) was assessed after an additional 28 days (assessed 56 days after application). Table : Effect of ASTCA on survival, biomass change and reproduction of earthworms Treatment (mg / kg soil dw) 28-d % mortality Body weight change after 28-d (%) Juveniles after 56-d Mean No. Control % change Evaluator: Germany Date: April 2013

299 Part B Section 6 Core Assessment Germany Central Zone Page 64 of Conclusions In an earthworm reproduction and growth study with the florasulam metabolite ASTCA the LC 50 was determined to be >1.0 mg test item/kg soil dry weight. The no-observed-effect-concentration (NOEC) for mortality, growth and reproduction of the earthworm Eisenia foetida was determined to be 1.0 mg test item/kg soil dry weight, i.e. the highest concentration tested. Comments of zrms [Commenting box] Study Comments: KIIA 8.9/03 Agreed Endpoints: KIIA 8.9/03 The study is acceptable. 56-d NOEC = 1.0 mg/kg dry soil for ASTCA KIIA /01 Witte, B. (2010) Reference: KIIA /01 Report Guideline(s): Yes; OECD 232 Deviations: GLP: Acceptability: Study evaluation Witte, B.; 2010; Effects of 5-hydroxy-florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: 5-hydroxy-florasulam Test concentrations: 0 (control), 0.15; 0.31; 0.62; 1.25 and 2.5 mg ai/kg soil dry weight Results and discussions Table : Effect of 5-hydroxy-florasulam on survival and reproduction of Folsomia candida Treatment (mg / kg soil dw) 28-d % mortality Mean No of juveniles 28-d % reproduction Control * Evaluator: Germany Date: April 2013

300 Part B Section 6 Core Assessment Germany Central Zone Page 65 of *significantly different compared to control Conclusion For 5-hydroxy-florasulam the 28d NOEC value was 2.5 mg ai/kg soil dw, the highest concentration tested in this study. Comments of zrms [Commenting box] Study Comments: KIIA /01 Agreed Endpoints: KIIA /01 The study is acceptable. 28d NOEC = 2.5 mg ai/kg mg/kg dry soil for 5-hydroxy-florasulam. KIIA /02 Lührs, U. (2011) Reference: KIIA /02 Report Lührs, U.; 2011; Effects of DFP-ASTCA metabolite of florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number: ; Guideline(s): Yes; OECD 232 Deviations: GLP: Acceptability: Study evaluation No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test concentrations: DFP-ASTCA Metabolite of florasulam Nominal: 0 (control); 0.63; 1.25; 2.5; 5.0 and 10 mg ai/kg soil dry weight Results and discussions Table : Effect of DFP-ASTCA on survival and reproduction of Folsomia candida Treatment (mg / kg soil dw) 28-d % mortality Mean No of juveniles 28-d % reproduction Control Evaluator: Germany Date: April 2013

301 Part B Section 6 Core Assessment Germany Central Zone Page 66 of Conclusion For DFP-ASTCA the 28d NOEC value was 10 mg ai/kg soil dw, the highest concentration tested in this study. Comments of zrms [Commenting box] Study Comments: KIIA /02 Agreed Endpoints: KIIA /02 The study is acceptable. 28-d NOEC = 10 mg/kg dry soil for DFP-ASTCA KIIA /03 Witte, B. (2010) Reference: KIIA /03 Report Guideline(s): Yes; OECD 232 Deviations: GLP: Acceptability: Study evaluation Witte, B.; 2010; Effects of ASTCA metabolite of florasulam on reproduction of the collembola Folsomia candida in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test concentrations: ASTCA Metabolite of florasulam Nominal: 0 (control); 1.56; 3.13; 6.25; 12.5 and 25 mg ai/kg soil dry weight Results and discussions Table : Effect of ASTCA on survival and reproduction of Folsomia candida Treatment (mg / kg soil dw) 28-d % mortality Mean No of juveniles 28-d % reproduction Control Evaluator: Germany Date: April 2013

302 Part B Section 6 Core Assessment Germany Central Zone Page 67 of * *significantly different compared to control Conclusion For ASTCA the 28d NOEC value was 12.5 mg ai/kg soil dw. Comments of zrms [Commenting box] Study Comments: KIIA /03 Agreed Endpoints: KIIA /03 The study is acceptable. 28-d NOEC = 12.5 mg/kg dry soil for ASTCA (reproduction) KIIA /04 Witte, B. (2010) Reference: KIIA /04 Report Guideline(s): Yes; OECD 226 Deviations: GLP: Acceptability: Study evaluation Witte, B.; 2010; Effects of 5-hydroxy-florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test concentrations: 5-hydroxy-florasulam Nominal: 0 (control); 0.15; 0.31; 0.62; 1.25 and 2.5 mg ai/kg soil dry weight Results and discussions Table : Effect of 5-hydroxy-florasulam on survival and reproduction of Hypoaspis aculeifer Treatment (mg / kg soil dw) 28-d % mortality Mean No of juveniles 28-d % reproduction Control Evaluator: Germany Date: April 2013

303 Part B Section 6 Core Assessment Germany Central Zone Page 68 of * * *significantly different compared to control Conclusion For 5-hydroxy-florasulam the 14d NOEC value was 1.25 mg ai/kg soil dw. Comments of zrms [Commenting box] Study Comments: KIIA /04 Agreed Endpoints: KIIA /04 The study is acceptable. 14-d NOEC = 1.25 mg/kg dry soil for 5-hydroxy-florasulam KIIA /05 Witte, B. (2010) Reference: KIIA /05 Report Guideline(s): Yes; OECD 226 Deviations: GLP: Acceptability: Study evaluation Witte, B.; 2010; Effects of ASTCA metabolite of florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test concentrations: ASTCA Metabolite of florasulam Nominal: 0 (control); 6.25; 12.5; 25; 50 and 100 mg ai/kg soil dry weight Results and discussions Table : Effect of ASTCA on survival and reproduction of Hypoaspis aculeifer Treatment (mg / kg soil dw) 14-d % mortality Mean No of juveniles 14-d % reproduction Evaluator: Germany Date: April 2013

304 Part B Section 6 Core Assessment Germany Central Zone Page 69 of 102 Control Conclusion For ASTCA the 14d NOEC value was 100 mg ai/kg soil dw, the highest concentration tested in this study. Comments of zrms [Commenting box] Study Comments: KIIA /05 Agreed Endpoints: KIIA /05 The study is acceptable. 14-d NOEC = 100 mg/kg dry soil for ASTCA KIIA /06 Witte, B. (2011) Reference: KIIA /04/06 Report Guideline(s): Yes; OECD 226 Deviations: GLP: Acceptability: Study evaluation Witte, B.; 2011; Effects of DFP-ASTCA metabolite of florasulam on reproduction of the predatory mite Hypoaspis aculeifer in artificial soil with 5% peat Dow AgroSciences Study Number: Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: Test concentrations: DFP-ASTCA Metabolite of florasulam Nominal: 0 (control); 0.63; 1.25; 2.5; 5.0 and 10 mg ai/kg soil dry weight Results and discussions Table : Effect of DFP-ASTCA on survival and reproduction of Hypoaspis aculeifer Treatment 14-d % mortality Mean No of juveniles 14-d % reproduction Evaluator: Germany Date: April 2013

305 Part B Section 6 Core Assessment Germany Central Zone Page 70 of 102 (mg / kg soil dw) Control Conclusion For DFP-ASTCA the 14d NOEC value was 10 mg ai/kg soil dw, the highest concentration tested in this study. Comments of zrms [Commenting box] Study Comments: KIIA /06 Agreed Endpoints: KIIA /06 The study is acceptable. 14-d NOEC = 10 mg/kg dry soil for DFP-ASTCA KIIA 8.10/01 Feil, N. (2008) Report: Feil, N. (2008) Title: Effects of ASTCA metabolite of florasulam on the activity of the soil microflora in the laboratory. Document No: Dow AgroSciences Study Number: Guidelines: OECD 216 and OECD 217 GLP Yes Test material Test item: ASTCA metabolite of florasulam Purity: 100% Lot No./Batch No.: V , TSN Test system Organism (Species): Study Type: Soil micro organisms laboratory study with OECD guideline natural soil, assessed for: Nitrate formation Microbial respiration Evaluator: Germany Date: April 2013

306 Part B Section 6 Core Assessment Germany Central Zone Page 71 of 102 Guideline deviations reported by Study Director: Duration of study: Parameters measured: None 28 days Nitrogen transformation: analysis of nitrate, nitrite and ammonium in extracted soil samples, via ion chromatography; limits of quantification: NO 3 -N: mg/kg soil dry weight NO 2 -N: mg/kg soil dry weight NH 4 -N: mg/kg soil dry weight soil water content 47% to 49% ph 7.1 to 7.2 Observation intervals: Test concentrations: Toxic reference: Method of test item application: Environmental conditions: Microbial respiration: soil respiration rates after addition of glucose 4 g/kg soil water content 48% to 49% ph , 7, 14 and 28 days Low Dose: 0.1 mg/kg ASTCA soil dry weight (corresponding to the PEC soil ) High Dose: 1.0 mg/kg ASTCA soil dry weight (corresponding to 10 times the PEC soil ) Sodium chloride The inhibition of soil respiration and nitrogen transformation by sodium chloride at a concentration of 16 g/kg soil dry weight is determined at least once a year as a means of assuring that the laboratory test conditions are adequate and have not changed significantly. Incorporation into the soil Conducted in the dark Temperature: C ph: Soil moisture: 46 to 49% of its maximum water holding capacity. Evaluator: Germany Date: April 2013

307 Part B Section 6 Core Assessment Germany Central Zone Page 72 of 102 Soil properties: Soil source: The soil batch used in this study was according to the Guidelines and was taken from fallow grassland: District authority: Darmstadt-Dieburg Municipality: Rossdorf, Germany Geographical position: longitude:8 45' 28'' E latitude: 49 51' 53'' N Moisture content of soil at start: 46% - 47% of MWHC Moisture content of soil during test: 47% - 49% of MWHC Clay(%): 9.0 Silt (%): 31.7 Sand (%): 59.3 Organic Carbon(%):1.04 Textural classification: Loamy sand Methodology Determination of soil respiration in soil after addition of glucose. Comparison of test item treated soil with a non-treated soil. Three replicates per treatment and concentration. A BSB-Sensomat System was used to determine the CO 2 -production over a period of up to 24 hours at different sampling intervals. Determination of nitrogen-transformation (ammonium-, nitrite- and nitrate-nitrogen levels) in soil enriched with lucerne meal (concentration in soil 0.5%). Comparison of test item treated soil with a non-treated soil. Three replicates per treatment and concentration. NH 4 -, NO 2 - and NO 3 -nitrogen formed from the nitrification process were determined by means of a Dionex ion chromatography system (DX-120 IC, AS 50 autosampler, ECD and UVD 340S UV photometer). Table : Effect of ASTCA on soil microflora in the laboratory Treatment (mg ASTCA/kg d.s.) Nitrate formation rate (interval days 14-28) Soil respiration rates (day 28) mg/kg % deviation mg CO 2 /kg % deviation Control Conclusions The soil respiration rates were within the trigger value of ±25% set by OECD guideline 217 at day 28. The soil nitrate content was terminated on day 28 when the difference between the control and ASTCA treatments were below the 25% trigger value given by the OECD 216 guideline. Based on the results of this study, ASTCA has no impact on respiration activity, soil nitrate content and soil nitrate formation rate of soil microflora when formed in soil at concentrations up to and including 1.0 mg/kg soil dry weight. It can be concluded that the florasulam metabolite ASTCA will not have any long term influence on soil microflora. Comments of zrms [Commenting box] Evaluator: Germany Date: April 2013

308 Part B Section 6 Core Assessment Germany Central Zone Page 73 of 102 Study Comments: KIIA 8.10/01 Agreed Endpoints: KIIA 8.10/01 The study is acceptable. < 25% effects on nitrogen and carbon transformation for ASTCA: 1.0 mg/kg dry soil A2-2 Formulation KIIIA /01 XXX(2011) Reference: KIIIA /01 Report Guideline(s): Yes; OECD 203 Deviations: GLP: Acceptability: Study evaluation XXX 2011; : Acute toxicity to the rainbow trout, Oncorhynchus mykiss, determined under static renewal test condition XXX Study Number: Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: GF 2463 (26.2% clopyralid % florasulam) Test conditions: Test concentrations: Semistatic Nominal: 0 (control); 6,5; 13; 25; 50 und 100 mg ai/l (nom.) Conclusion Based on nominal concentrations, the 24-, 48-, 72- and 96-h LC 50 values were > 100 mg Primus Perfect/L. Comments of zrms [Commenting box] Study Comments: KIIIA /01 Agreed Endpoints: KIIIA /01 The study is acceptable. 96-h LC 50 > 100 mg /L (nominal concentrations) Evaluator: Germany Date: April 2013

309 Part B Section 6 Core Assessment Germany Central Zone Page 74 of 102 KIIIA /01 Rebstock, M. (2012) Reference: KIIIA Report Guideline(s): Yes; OECD 226 Deviations: GLP: Acceptability: Study evaluation Rebstock, M.; 2012; : Acute toxicity to the water flea Daphnia magna, determined under static test condition Dow AgroSciences Study Number: ; No Yes Yes Study evaluation by zrms Materials and methods Test material Test item: GF 2463 (26.2% clopyralid % florasulam) Test conditions: Test concentrations: Static Nominal: 0 (control) and 100 mg ai/l (nom.) Conclusion Based on nominal concentrations, the 2d EC 50 values was > 100 mg /L (immobilisation); the NOEC = 100 mg /L, the highest concentration tested. Comments of zrms [Commenting box] Study Comments: KIIIA /01 Agreed Endpoints: KIIIA /01 The study is acceptable. 2d EC 50 values was > 100 mg /L (immobilisation); (nominal concentration) KIIIA /01 Porch, J.R., Kendall, T.Z., Krueger, H.O. (2011a) Report: Title: Porch, J.R., Kendall, T.Z., Krueger, H.O. (2011a). : a 72-hour toxicity test with the freshwater alga (Pseudokirchneriella subcapitata). Document No: Dow AgroSciences Study Number: Guidelines: OECD Guideline 201, EU Method C.3 GLP Yes Evaluator: Germany Date: April 2013

310 Part B Section 6 Core Assessment Germany Central Zone Page 75 of 102 Test material Test item: Purity: Description: Lot No./Batch No.: 26.2% w/w clopyralid and 2.05%w/w florasulam liquid TSN , Lot No. 199/199-A Test system Organism (Species): Freshwater green algae, Pseudokircheriella subcapitata Study Type: laboratory study assessing algal growth Guideline deviations reported by Study Director: None Duration of study: 72-hr Test conditions: Static Parameters measured: Cell density, yield, and growth rate Observation intervals: 0, 24, 48, 72 hours Age of inoculum: 4 days since last culture transfer Acclimation period/conditions: Culture conditions: Photoperiod: 24/0 Temperature: 24 ± 2 C Light intensity: 6000 ± 900 lux Initial cell density: 5000 cells/ml Growth medium: Name: Freshwater Algal Medium ph at test initiation: ph at test termination: Constant stirring at 100 rpm on shaker table Test concentrations: Nominal: 0, 0.06, 0.13, 0.25, 0.50 and 1.00 mg /L Mean measured: <LOQ (control), 0.065, 0.14, 0.27, 0.53 and 1.1 mg /L Method of test item added to the test In culture medium medium: No. of control replicates: 6 No. of test concentration replicates: 3 Analytical confirmation of test concentrations: Method: measuring concentrations of clopyralid using HPLC Samples taken: 0 and 72 hrs Limit of Quantitation: mg/l of Primus Evaluator: Germany Date: April 2013

311 Part B Section 6 Core Assessment Germany Central Zone Page 76 of 102 Perfect Recoveries from QC fortifications: 91 to 107% Environmental conditions: Test solution ph (range): Temperature (range): C Photoperiod: continuous light Light intensity (range): lux Methodology The green alga, Pseudokirchneriella subcapitata, was exposed to five test concentrations and a negative control (culture medium) for 72 hours. Nominal test concentrations selected were 0.06, 0.13, 0.25, 0.50, and 1.0 mg./l. Measured concentrations were determined from samples of test medium collected from the treatment and control groups at 0 and 72 hours of the test. Three replicate test chambers were maintained in each treatment and six replicate test chambers in the control group. At test initiation, an inoculum of the algal cells was added to each test chamber to achieve a nominal concentration of approximately 5,000 cells/ml. Samples were collected from each replicate test chamber at approximately 24-hour intervals during the test to determine cell densities, yield, and growth rates. Cell densities, yield, and growth rates were used to calculate percent inhibition values relative to the controls over the 72-hour exposure period. EC 50, E y C 50, and E r C 50 values were calculated at 72-hours. No-observed-effect concentrations (NOEC) were determined at 72 hours through statistical evaluation of the cell densities, yield, and growth rates, as well as examination of the concentration-response pattern. Table : Effects of on growth of Pseudokirchneriella subcapitata Treatment (mg ) Nominal Cell density (cells 10 4 /ml) Yield (cells 10 4 /ml) Growth rate (cells/ml/hour) Mean at 72 hr % change Total mean at 72 hr % change Mean (0-72 hr) Control * * * * * * * * * * * * * * * -60 * Significant reduction of growth as compared to the control % change Table : Results Hour EC type EC value (mg /L) 72 95% confidence limits (mg /L) EC <0.06 E y C <0.06 E r C <0.06 NOEC (mg /L) Evaluator: Germany Date: April 2013

312 Part B Section 6 Core Assessment Germany Central Zone Page 77 of 102 Conclusions The freshwater green alga, Pseudokirchneriella subcapitata, was exposed to five nominal concentrations of ranging from 0.06 to 1.00 mg/l. Effects were evaluated based on cell density, yield, and growth rate. The calculated 72-hour EC 50 value was mg/l. The calculated 72-hour E y C 50 value was mg/l. The calculated E r C 50 value was 0.65 mg/l. The 72 hour NOEC for cell density, yield, and growth rate was below 0.06 mg/l. All validity criteria for the study were met. The mean cell density in the control replicates increased by a factor greater than 16 within three days (factor of 278); the coefficient of variation of average specific growth rates in the control replicates during the whole test period did not exceed 7% and was 1.8%; the mean percent coefficient of variation for section-by-section specific growth rates did not exceed 35% and was 10.6%. Comments of zrms [Commenting box] Study Comments: KIIIA /01 Agreed Endpoints: KIIIA /01 The study is acceptable. 72-h EC 50 and E y C 50 = mg /L (nominal concentrations) KIIIA 10.3/01 Report: XXX (2010) Title: Acute oral toxicity study of in rats. Document No: XXX Study Number: Guidelines: OECD 423 GLP Yes Comments of zrms [Commenting box] Study Comments: KIIIA 10.3/01 Agreed Endpoints: KIIIA 10.3/01 The study is acceptable. LD 50 > 2000 mg /kg bw KIIIA /01 Schmitzer, S. (2010) Report: Schmitzer, S. (2010) Title: Effects of (acute contact and oral) on honey bees (Apis mellifera L.) in the laboratory Document No: Dow AgroSciences Study Number: and Guidelines: OECD 213 and 214 GLP Yes Test material Test item: Evaluator: Germany Date: April 2013

313 Part B Section 6 Core Assessment Germany Central Zone Page 78 of 102 Purity: Description: Lot No./Batch No.: 26.2% w/w clopyralid and 2.05%w/w florasulam liquid TSN , Lot No. 199/199-A Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Study design: (No. of bees per replicate, observation intervals etc) Information on bee colony (health etc): Test concentrations: Amount of treated diet consumed: Honey bee (Apis mellifera L.) Acute oral and contact toxicity None Limit test; acute oral and contact toxicity test; duration 48 h; 5 replicates, each consisting of 10 bees in one cage per test concentration; assessment of mortality after 4, 24 and 48 hours; reference item: dimethoate 400 g/l (nominal). Female worker bees obtained from a healthy queenright colony, bred by IBACON, collected on the morning of use. Oral: 0, µg /bee; Contact: 0, µg /bee Consumption of the treated diets ranged from 216 to 225 µg /bee Feeding: Commercial ready-to-use syrup (Apiinvert; 30% sucrose, 31% glucose, 39% fructose) ad libitum; was given directly after treatment using syringes; no replacements of the food was necessary during the experimental time (48 h). Environmental conditions: Temperature: 25 C Relative humidity: 50-77% Photoperiod: 24 h darkness Reference substance (nominal): 0.30, 0.15, 0.08 and 0.05 µg Dimethoate per bee (oral test) 0.30, 0.20, 0.15 and 0.10 µg Dimethoate per bee (contact test) Solvent substance (if applicable): None Methodology Oral study: after mixing the test solutions with ready-to-use sugar syrup (composition of the sugar component: 30% sucrose, 31% glucose, 39% fructose) the final concentration of sugar syrup in the test item solution offered to the bees was 50%. For the controls water and sugar syrup was used at the same ratio (1 + 1). Evaluator: Germany Date: April 2013

314 Part B Section 6 Core Assessment Germany Central Zone Page 79 of 102 Contact study: a single 5 µl droplet of in an appropriate carrier (tap water + 0.5% Adhäsit) was placed on the dorsal bee thorax using a Burkard Applicator. For the control one 5 µl droplet of tap water containing 0.5% Adhäsit was used. Table : Toxicity of to honey bees in an oral toxicity test Treatment (µg /bee) Contact Test (48 h) Oral Test (48 h) Observation Period 24 h 48 h 24 h 48 h Treatment Mortality 0.0% 0.0% 0.0% 0.0% Control Mortality 0.0% 0.0% 2.0% 2.0% LD 50 >200.0 µg product/bee >219.6 µg product/bee The contact and oral LD 50 (24 h) values of the reference item (dimethoate) were calculated to be 0.17 and 0.13 µg a.i./bee, respectively. Conclusions The toxicity of was tested in both an acute contact and an oral toxicity test on honey bees. The LD 50 (48 h) was >200.0 µg product/bee in the contact toxicity test. The LD 50 (48 h) was >219.6 µg product/bee in the oral toxicity test. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. Oral LD 50 >200.0 µg /bee Contact LD 50 >219.6 µg /bee KIIIA Schwarz, A. (2011) Report: Schwarz, A. (2011) Title: Effects of on the predatory mite Typhlodromus pyri in the laboratory (Tier I) dose response test Document No: Dow AgroSciences Study Number: Guidelines: Blümel et al., 2000 GLP Yes Test material Test item: Purity: 26.2% w/w clopyralid (or 305 g/l) and 2.05%w/w florasulam (or 24 g/l) Description: liquid Lot No./Batch No.: TSN , Lot No. 199/199-A Evaluator: Germany Date: April 2013

315 Part B Section 6 Core Assessment Germany Central Zone Page 80 of 102 Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Study design: Test concentrations: Environmental conditions: Reference substance: Predatory mite (Typhlodromus pyri) Tier I laboratory study, glass plates for mortality and fecundity None Assessments of mortality measured 7 days after treatment and egg production 14 days after treatment. Three replicates, each consisting of 20 mites in one arena per treatment. 0 (control), 5.54, 100, 200, 400 and 800 ml product/ha. Temperature: C Relative Humidity: 67-78% Photoperiod: 16 h light : 8 h dark Light intensity: lux Feeding: A mixture of pine (Pinus nigra) and birch (Betula sp.) pollen (3: 1) ad libitum on the day of test start and on each assessment day except for the last one (i.e. at least every four days) or with an interval of maximum 4 days. Perfekthion (3.3 g dimethoate/ha) Methodology The study comprised 7 treatment groups (5 dose rates of the test item, control and reference item) with 3 replicates each containing 20 mites. The mites were exposed to fresh, dried residues on treated glass plates. Survival of the mites was assessed after 3 and 7 days. For the reproduction assessment surviving mites from the control and from all test item groups where there was less than 50% corrected mortality were sexed and the number of eggs per female was recorded on 3 assessment days within one week (days 10, 13 and 14 after treatment). Table : Effects of on the survival and reproduction capacity of Typhlodromus pyri Test concentrations Mortality (7 DAT) Number of eggs/female (7-14 DAT) (ml /ha) Mean % % corrected Mean % difference Control * Dimethoate (3.3 g/ha) * - - Evaluator: Germany Date: April 2013

316 Part B Section 6 Core Assessment Germany Central Zone Page 81 of 102 *: Significantly different from the control. Conclusions All the validity criteria for the study (i.e. <20% mortality and 4 eggs/female in the control and >50% mortality in the reference substance treatment) were met. Under worst case laboratory conditions the 7-day LR 50 of on Typhlodromus pyri is estimated to be greater than 800 ml product/ha in 200 L water/ha. Reproduction of T. pyri was assessed in the control and all dose rates. Reproduction was not significantly affected up to and including 800 ml product/ha. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. Typhlodromus pyri laboratory study LR 50 >800 ml /ha KIIIA /02 Moll, M. (2010) Report: Moll, M. (2010) Title: Effects of on the parasitoid Aphidius rhopalosiphi in the laboratory (Tier I) dose response test Document No: Dow AgroSciences Study Number: Guidelines: Mead-Briggs et al GLP Yes Test material Test item: Purity: 26.2% w/w clopyralid (or 305 g/l) and 2.05%w/w florasulam (or 24 g/l) Description: liquid Lot No./Batch No.: TSN , Lot No. 199/199-A Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Study design: Parasitic wasp (Aphidius rhopalosiphi) Tier I laboratory study, glass plates for mortality and barley plants for fecundity None Assessments of mortality measured 48 hrs after treatment and parasitisation days after treatment. Four replicates, each consisting of 10 wasps in one Evaluator: Germany Date: April 2013

317 Part B Section 6 Core Assessment Germany Central Zone Page 82 of 102 Test concentrations: Environmental conditions: Reference substance: arena per test concentration for mortality phase females wasps for each treatment (control and test item) taken through to the fecundity phase (20 were introduced, but in all treatment groups at least one wasp was dead or not found after 24 hours). 0 (control), 5.54, 100, 200, 400 and 800 ml product/ha. Temperature: C Relative Humidity: 66 78% (mortality phase); 80-84% (reproduction phase) Photoperiod: 16 h light: 8 h dark. Light intensity: lux (mortality phase), lux (reproduction phase). Feeding: A 10% fructose solution (mortality phase). Perfekthion (0.12 g dimethoate/ha) Methodology The study comprised 7 treatment groups (5 dose rates of the test item, control and reference item) with 4 replicates each containing 10 parasitoids. The parasitoids were exposed to fresh, dried residues on treated glass plates. Survival of the parasitoids was assessed after approximately 2, 24 and 48 hours. At 48 hours, for the three highest treatment groups where there was less than 50.0% corrected mortality, female wasps were removed and their reproductive capacity was assessed by confining them individually over untreated barley plants infested with the host cereal aphids, R. padi. The adult parasitoids were removed after 24 hours and the aphid-infested plants left for a further days before the numbers of aphid mummies that had developed were assessed. Table : Effects of on the survival and reproduction capacity of Aphidius rhopalosiphi Test concentrations (ml /ha) Mortality (48 hours) Number of mummies/female (2-15 DAT) Mean % % corrected Mean % difference Control Dimethoate (0.12 g/ha) * - - *: Significantly different from the control. Evaluator: Germany Date: April 2013

318 Part B Section 6 Core Assessment Germany Central Zone Page 83 of 102 Conclusions All the validity criteria for the study (i.e. <13% mortality in the control, 5 mummies/female in the control with no more than 2 parasitoids producing 0 mummies and >50% mortality in the reference substance treatment) were met. Under worst case laboratory conditions the 48-hour LR 50 of on Aphidius rhopalosiphi is estimated to be greater than 800 ml product/ha in 200 L water/ha. Reproduction was tested at all dose rates. As there was no statistically significant effect on the reproduction compared to the control and the effect on reproduction was below the trigger value of 50% at all dose rates, there were no effects on the reproduction (parasitisation efficiency) of surviving females up to and including a rate of 800 ml product/ha. Comments of zrms [Commenting box] Study Comments: IIIA /02 Agreed Endpoints: IIIA /02 The study is acceptable. Aphidius rhopalosiphi laboratory study LR 50 > 800 ml Primus Perfect/ha KIIIA /01 Witte, B. (2010a) Report: Title: KIIIA /01, Witte, B. (2010a) Acute toxicity (14 days) of to the earthworm Eisenia fetida in artificial soil. Document No: Dow AgroSciences Study Number: Guidelines: OECD 207 GLP Yes Test material Test item: Purity: 26.2% w/w clopyralid (or 305 g/l) and 2.05%w/w florasulam (or 24 g/l) Description: liquid Lot No./Batch No.: TSN , Lot No. 199/199-A Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Study design: Earthworm (Eisenia fetida) 14 day acute toxicity study None Assessment of the survival, behaviour and weight change of worms. Four replicates, consisting of 10 worms in each vessel per test concentration. Evaluator: Germany Date: April 2013

319 Part B Section 6 Core Assessment Germany Central Zone Page 84 of 102 Test concentrations: 0, 2000 mg test item/kg soil dry weight Soil parameters: Artificial soil according to OECD 207: ph: at initiation 5.9 at termination Water content at initiation: 32.2% to 32.3% (54.6% to 54.7% of the maximum water holding capacity) Water content at termination: 32.1% to 32.2% (54.4% to 54.6% of the maximum water holding capacity) Environmental conditions: Temperature: C Photoperiod: constant light (within the range of lux) Feeding: none Reference substance (nominal): 2-chloroacetamide (conducted and reported as a separate study) Methodology 14 days exposure to treated artificial soil. One concentration of the test item was mixed homogeneously into the soil and put into the test chambers before the earthworms were introduced to the soil surface, one concentration and one control, 4 replicates per concentration with 10 worms in each chamber. Assessment of worm mortality and behavioural effects after 7 and 14 days, measurement of weight change as sub-lethal parameter after 14 days. Table : Effects of on earthworm survival and biomass Nominal test concentrations (mg /kg dry soil) Mortality after 14 days (%) Control Toxic Reference Body weight change after 14 days (%) 14 day LC 50: 23.7 mg 2-chloroacetamide/kg wet weight Conclusions All the validity criteria for the study (i.e. <10% mortality) were met. In a 14-day toxicity study with to earthworms (Eisenia fetida) the 14-day LC 50 was estimated to be greater than 2000 mg /kg soil. The No Observed Effect Concentration (NOEC) for mortality and body weight was determined to be 2000 mg test item/kg soil. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. LC 50 >2000 mg /kg dry soil Evaluator: Germany Date: April 2013

320 Part B Section 6 Core Assessment KIIIA /01 Witte, B. (2010b) Germany Central Zone Page 85 of 102 Report: Title: KIIIA /01, Witte, B. (2010b) Effects of on reproduction and growth of earthworms Eisenia fetida in artificial soil. Document No: Dow AgroSciences Study Number: Guidelines: OECD 222 GLP Yes Test material Test item: Purity: 26.2% w/w clopyralid (or 305 g/l) and 2.05%w/w florasulam (or 24 g/l) Description: liquid Lot No./Batch No.: TSN , Lot No. 199/199-A Test system Organism (Species): Earthworm (Eisenia fetida) Study Type: 56 day reproductive toxicity study Guideline deviations reported by Study Director: None Study design: Assessment of the survival, behaviour and weight change of worms after 28 days exposure. Assessment of the number of offspring 56 days after treatment. Four replicates, consisting of 10 worms in each vessel per test concentration. 8 replicates, consisting of 10 worms in each vessel for the control. Test concentrations: 0, 0.33, 0.67, 1.33, 2.67 and 5.33 mg /kg soil dry weight Soil parameters: Artificial soil according to OECD 222: ph: at initiation 6.3 at termination Water content at initiation: 29.9% to 32.2% (50.6% to 54.6% of the maximum water holding capacity) Water content at termination: 33.2% to 35.0% (56.3% to 59.3% of the maximum water holding capacity) Environmental conditions: Temperature: within the range of C Photoperiod: 16 hours light and 8 hours dark Light intensity: within the range of lux Feeding: Finely ground cattle manure, once a week Evaluator: Germany Date: April 2013

321 Part B Section 6 Core Assessment Germany Central Zone Page 86 of 102 Reference substance (nominal): during first 28 days only carbendazim (conducted and reported as a separate study). ER 50 : 1.47 mg carbendazim/kg artificial soil dry weight. Methodology 56-day test in treated artificial soil according to OECD 222; different concentrations of the test item were incorporated into the soil; 6 treatment groups (5 test item concentrations, control); 4 replicates for the test item treatments, 8 replicates for the control, 10 worms each. Assessment of adult worm mortality, behavioural effects and biomass development was carried out after 28 days exposure of adult worms in treated artificial soil. Reproduction rate (number of offspring) was assessed after additional 28 days (assessed 56 days after application). Table : Effects of on earthworm survival, biomass and reproduction (mg/kg soil dry weight) % Mortality (day 28) % Weight change (day 28) Mean no. of juveniles (day 56) Control * Significantly different from the control. % change in numbers of juveniles produced relative to control (day 56) Conclusions All the validity criteria for the study (i.e. <10% mortality, 30 juveniles/container and <30% coefficient of variation for reproduction in the control) were met. In an earthworm reproduction and growth study with the LC 50 was estimated to be greater than 5.33 mg test item/kg soil. The no-observed-effect-concentration (NOEC) for mortality, growth and reproduction of the earthworm Eisenia fetida was determined to be 5.33 mg test item/kg soil, i.e. the highest concentration tested. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. NOEC = 5.33 mg /kg dry soil Evaluator: Germany Date: April 2013

322 Part B Section 6 Core Assessment KIIIA /01 Rix, S. (2005) Germany Central Zone Page 87 of 102 Report: Rix, S. (2005) Title: GF-1374: determination of effects on soil microflora activity Document No: Dow AgroSciences Study Number: Guidelines: OECD 216 and OECD 217 GLP Yes Test material Test item: Purity: Description: Lot No./Batch No.: GF g/l clopyralid 2.5 g/l florasulam 142 g/l fluroxypyr-meptyl Density: g/ml Straw coloured oily liquid 187/76-A Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Duration of study: Parameters measured: Soil micro organisms laboratory study with OECD guideline natural soil, assessed for: - Nitrate formation - Microbial respiration A minor mistake was made in the calculation of the required amount of dry weight lucerne during the study. Since the difference in the amount used in the study and that actually required was very small, this deviation is unlikely to have had impact on the outcome of the study. 28 days Nitrogen transformation: analysis of nitrate and ammonium in extracted soil samples, via Alpkem RFA. soil water content: 41% MWHC (maximum water holding capacity) at initiation % MWHC at termination Microbial respiration: Evaluator: Germany Date: April 2013

323 Part B Section 6 Core Assessment Germany Central Zone Page 88 of 102 soil respiration rates after addition of glucose soil water content: 41% MWHC (maximum water holding capacity) at initiation % MWHC at termination Observation intervals: Test concentrations: Toxic reference Method of test item application: Environmental conditions: Soil properties ph , 7, 14 and 28 days Low Dose: 2.77 mg GF-1374/kg soil dry weight (or mg/kg as clopyralid and mg/kg as florasulam) High Dose: 13.9 mg GF-1374/kg soil dry weight (or 1.15 mg/kg as clopyralid and mg/kg as florasulam) Dinoseb (1 and 10 mg/kg soil dry weight) evaluated as a separate study Incorporation into the soil Conducted in the dark. Temperature: 20 ± 2 C ph: Soil moisture: % MWHC. Soil source: The soil batch used in this study was a LUFA 2.3 soil: Moisture content of soil at start: 41% MWHC Moisture content of soil at end: % MWHC Clay (%): 9.1 Silt (%): 31.7 Sand (%): 59.1 Organic Carbon(%): 1.02 Textural classification: Sandy loam Methodology Determination of soil respiration in soil after addition of glucose. Comparison of test item treated soil with a non-treated soil. Three replicates per treatment and concentration. An infrared gas analyser was used to determine the CO 2 -production over a period longer than 12 hours at hourly sampling intervals. Determination of nitrogen-transformation in soil enriched with lucerne meal (concentration in soil 0.5%). Comparison of test item treated soil with a non-treated soil. Three replicates per treatment and concentration. NH 4 -, NO 2 - and NO 3 -nitrogen formed from the nitrification process were determined by means of Alpkem RFA. Evaluator: Germany Date: April 2013

324 Part B Section 6 Core Assessment Germany Central Zone Page 89 of 102 Table : Effects of GF-1374 on the activity of the soil microflora in the laboratory Treatment, nominal GF concentration (mg/kg d.s.) Nitrate formation rate (interval days 14-28) Soil respiration rates (day 28) mg/kg/d % deviation mg CO 2 /kg/h % deviation Control Conclusions The validity criteria for the study (i.e. <15% variability between control replicates) were met. The differences in soil respiration rates between the control and the GF-1374 treatments were within the trigger value of ±25% set by OECD guideline 217 at day 28. The soil nitrate content was terminated on day 28 when the difference between the control and GF-1374 treatments were below the 25% trigger value given by the OECD 216 guideline. Based on the results of this study, GF-1374 has no impact on respiration activity, soil nitrate content and soil nitrate formation rate of soil microflora when applied up to and including 13.9 mg/kg soil dry weight. It can be concluded that GF-1374 will not have any long term influence on soil microflora. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. <25% effects on nitrogen and carbon transformation: 13.9 mg GF-1374/kg dry soil, equivalent to 1.15 mg/kg clopyralid and mg/kg florasulam. KIIIA /01 Brockmann, A., Korfmacher, R., Teresiak, H. (2011a) Report: Title: Brockmann, A., Korfmacher, R., Teresiak, H. (2011a) Evaluation of the phytotoxicity of (clopyralid 300 g as/l + florasulam 25 g as/l, SC) GLP vegetative vigour test terrestrial non target plants (based on OECD Guideline 227) Europe 2010 Document No: Dow AgroSciences Study Number: Guidelines: OECD 227 GLP Yes Test material Test item: Purity: Description: Lot No./Batch No.: 305 g/l clopyralid and 24 g/lflorasulam liquid TSN , Lot No. 199/199-A Evaluator: Germany Date: April 2013

325 Part B Section 6 Core Assessment Germany Central Zone Page 90 of 102 Test system Monocotyledon species: Oat (Avena sativa); Ryegrass (Lolium perenne); Onion (Allium cepa) Dicotyledon species: Oilseed rape (Brassica napus); Radish (Raphanus sativus) Soybean (Glycine max); Carrot (Daucus carota); Cucumber (Cucumis sativa); Sugar Beet (Beta vulgaris); Lettuce (Lactuca sativa) Tomato (Lycopersicon esculentum) Study Type: Glasshouse study assessing vegetative vigour Guideline deviations reported by Study Director: Duration of study: Observation intervals: Parameters measured: Growth conditions: Growth medium: By mistake, no picture of the control carrots was taken at the end of the study. This deviation had no impact on the study as the growth stage and phytotoxicity results demonstrated that control carrots were healthy at harvest date. 21 days after treatment application Every 7 days Number of dead plants; foliar fresh weight; visual injury Temperature (range): C Photoperiod: 16 hour per day with supplementary lighting when outdoor illumination was below lux. Relative humidity: % Water regime and schedules: watered by hand into saucers Water source/type: mains water Pest control method/fertilization, if used: none. Soil type: silty loamy sand; Details of nutrient medium, if used: nitrogen fertiliser applied to all test plants as needed; ph: 7.29 Test concentrations: Nominal: 0, 0.82, 2.47, 7.41, 22.2, 66.7, 200 and 600 ml/ha Analytical verification: A sample from the stock solution equivalent to the highest treatment rate was analysed. Measured concentrations of clopyralid were 97 and 98% of nominal for the main and the cucumber application, respectively. Method of test item application: Method: Track sprayer Application interval: N/A Evaluator: Germany Date: April 2013

326 Part B Section 6 Core Assessment Germany Central Zone Page 91 of 102 Seed/plant: Source: commercial seed batches. Method of seeding: By hand in plastic pots. Prior seed treatment/sterilization: None Number of plants per replicate pot: 5, except 3 for cucumber Growth stage at application: BBCH Number of control replicates: 5 Number of test concentration replicates: 5 Methodology Seeds were sown on a range of dates to produce plants at the required growth stage at spray application. Treatments were applied using a track sprayer calibrated to deliver 200 L/ha water. After treatment the pots were removed to a glasshouse and laid out in a randomised fashion. Plants were assessed for visual injury and plant death. Fresh weight was recorded at harvest, 21 days after treatment application. The ER 50 values for susceptible species were calculated based on foliar fresh weight and survival data. Where a 50% reduction in foliar fresh weight did not occur, or regression analysis could not be run because of the high tolerance of species to the test item, the ER 50 values were considered to be greater than the highest rate tested. Table : Effects of on mean shoot fresh weight (g) of non-target plants in a vegetative vigour study (21 days post application) Treatment (ml Primus Perfect/ha) Control Oat * Ryegrass * * Onion Oilseed rape * * * - Radish * * 9.750* 5.520* 2.494* - Soybean * * - Carrot * * - Cucumber * * - Sugarbeet * * - Lettuce * 5.545* 2.092* 1.941* - Tomato * * * 5.040* - *: Statistically different from the control. Table : Effects of on mean shoot fresh weight (g) of non-target plants in a vegetative vigour study as a percentage of control (21 days post application) Treatment Control Evaluator: Germany Date: April 2013

327 Part B Section 6 Core Assessment Germany Central Zone Page 92 of 102 (ml Primus Perfect/ha) Oat Ryegrass Onion Oilseed rape Radish Soybean Carrot Cucumber Sugarbeet Lettuce Tomato *: Statistically different from the control. Table : Reported ER 50 values for based on foliar fresh weight reduction (vegetative vigour) Species ER 50 (ml product/ha) Regression R 2 Avena sativa >600 N/A Lolium perenne >600 N/A Allium cepa >200 N/A Brassica napus Raphanus sativus Glycine max Daucus carota >200 N/A Cucumis sativa >200 N/A Beta vulgaris >200 N/A Lactuca sativa Lycopersicon esculentum N/A: Not applicable Conclusions The most sensitive species in the vegetative vigour test was Lactuca sativa with an ER 50 value of ml product/ha based on foliar fresh weight reduction. The ER 50 values of all the other species tested (Avena sativa, Lolium perenne, Allium cepa, Glycine max, Brassica napus, Beta vulgaris, Daucus carota, Cucumis sativa, Raphanus sativus and Lycopersicon esculentum) ranged from to >600 ml product/ha. Comments of zrms [Commenting box] Study Comments: The study is acceptable. Evaluator: Germany Date: April 2013

328 Part B Section 6 Core Assessment Germany Central Zone Page 93 of 102 IIIA /01 Agreed Endpoints: IIIA /01 Lowest ER 50 = ml /ha (Lactuca sativa) KIIIA /01 Brockmann, A., Teresiak, H. (2011b) Report: Title: Brockmann, A., Teresiak, H. (2011b) Evaluation of the phytotoxicity of (clopyralid, 300 g as/l + florasulam, 25 g as/l, SC) GLP seedling emergence and seedling growth test terrestrial non target plants (based on OECD Guideline 208) Europe 2010 Document No: Dow AgroSciences Study Number: Guidelines: OECD 208 GLP Yes Test material Test item: Purity: Description: Lot No./Batch No.: 305 g/l clopyralid and 24 g/lflorasulam Liquid TSN , Lot No. 199/199-A Test system Monocotyledon species: Oat (Avena sativa); Ryegrass (Lolium perenne); Onion (Allium cepa) Dicotyledon species: Oilseed rape (Brassica napus); Radish (Raphanus sativus) Soybean (Glycine max); Carrot (Daucus carota); Cucumber (Cucumis sativa); Sugar Beet (Beta vulgaris); Lettuce (Lactuca sativa) Tomato (Lycopersicon esculentum) Study Type: Glasshouse study assessing seedling emergence and seedling growth Guideline deviations reported by Study Director: None. Duration of study: 21 or 28 (carrot and onion only) days after application Observation intervals: At 7, 14 and 21 days after application, except for carrot and onion for which assessments were made at 14, 21 and 28 days after application. Parameters measured: Emergence counts, number of dead plants, foliar fresh weight, visual injury Evaluator: Germany Date: April 2013

329 Part B Section 6 Core Assessment Germany Central Zone Page 94 of 102 Growth conditions: Growth medium: Test concentrations: Analytical verification: Method of test item application: Seed/plant: Number of control replicates: Number of test concentration replicates: Temperature (range): C. Photoperiod: 16 hour per day with supplementary lighting when outdoor illumination was below lux. Relative humidity: %. Water regime and schedules: watered by hand into saucers Water source/type: mains water Pest control method /fertilization, if used: None. Soil type: silty loamy sand; Details of nutrient medium, if used: nitrogen fertiliser applied to all plants as needed; ph: Nominal: 0, 0.82, 2.47, 7.41, 22.22, 66.67, and ml/ha A sample from the stock solution equivalent to the highest treatment rate was analysed. Measured concentrations of clopyralid were 97% of nominal. Method: Track sprayer Application interval: N/A Source: commercial seed batches. Method of seeding: By hand Prior seed treatment/sterilization: None Number of plants per replicate pot: 4 for cucumber; 7 for soybean, sugar beet, lettuce and tomato; 8 for oilseed rape and radish; 10 for oat; 12 for ryegrass, onion and carrot Growth stage at application: pre-emergence 4 for oat, ryegrass, onion and carrot; 8 for cucumber and 5 for all other species 4 for oat, ryegrass, onion and carrot; 8 for cucumber and 5 for all other species Methodology Seeds were sown prior to treatment application. Treatments were applied using a track sprayer calibrated to deliver 200 L/ha water. After treatment the pots were removed to a glasshouse and laid out in a randomised fashion. All pots were placed in saucers with watering applied into saucers. Seedlings were assessed for emergence, visual injury and plant death. Fresh weight was recorded at harvest, 21 or 28 days after treatment. The ER 50 values for susceptible species were calculated using foliar fresh weight data, expressed as the percent of the untreated. Where a 50% reduction in foliar fresh weight did not occur, or Evaluator: Germany Date: April 2013

330 Part B Section 6 Core Assessment Germany Central Zone Page 95 of 102 regression analysis could not be run because of the high tolerance of species to the test item, the ER 50 values were considered to be greater than the highest rate tested. Table : Effects of on mean shoot fresh weight (g) of non-target plants in a seedling emergence study (21 or 28 days after treatment) Treatment (ml Primus Perfect/ha) Control Oat Ryegrass * 0.621* Onion * 1.571* - Oilseed rape * 4.654* - Radish * 5.376* - Soybean Carrot * - Cucumber * * - Sugarbeet Lettuce * 0.713* 0.117* - Tomato * 2.346* - *: Statistically different from the control. Table : Effects of on mean shoot fresh weight (g) of non-target plants in a seedling emergence study as a percentage of control (21 or 28 days after treatment) Treatment (ml Primus Perfect/ha) Control Oat Ryegrass Onion Oilseed rape Radish Soybean Carrot Cucumber Sugarbeet Lettuce Tomato *: Statistically different from the control. Evaluator: Germany Date: April 2013

331 Part B Section 6 Core Assessment Germany Central Zone Page 96 of 102 Table : Reported ER 50 values for based on foliar fresh weight reduction (seedling emergence and growth) Species ER 50 (ml product/ha) Regression R 2 Avena sativa >600 N/A Lolium perenne Allium cepa Brassica napus Raphanus sativus Glycine max >200 N/A Daucus carota >200 N/A Cucumis sativa >200 N/A Beta vulgaris >200 N/A Lactuca sativa Lycopersicon esculentum N/A: Not applicable Conclusions The most sensitive species in the seedling emergence and seedling vigour test was Lactuca sativa with an ER 50 value of ml product/ha based on foliar fresh weight reduction. The ER 50 values of all the other species tested (Avena sativa, Lolium perenne, Allium cepa, Glycine max, Brassica napus, Beta vulgaris, Daucus carota, Cucumis sativa, Raphanus sativus and Lycopersicon esculentum) ranged from to >600 ml product/ha. Comments of zrms [Commenting box] Study Comments: IIIA /01 Agreed Endpoints: IIIA /01 The study is acceptable. Lowest ER 50 = ml /ha (Lactuca sativa) KIIIA /01 Porch, J.R., Kendall, T.Z., Krueger, H.O. (2011b) Report: Porch, J.R., Kendall, T.Z., Krueger, H.O. (2011b) Title: : A 7-day static-renewal toxicity test with duckweed (Lemna gibba G3). Document No: Dow AgroSciences Study Number: Guidelines: OECD Guideline 221; ASTM Standard Guide E GLP Yes Test material Test item: Purity: 26.2% w/w clopyralid and 2.05%w/w florasulam Evaluator: Germany Date: April 2013

332 Part B Section 6 Core Assessment Germany Central Zone Page 97 of 102 Description: Lot No./Batch No.: liquid TSN , Lot No. 199/199-A Test system Organism (Species): Study Type: Guideline deviations reported by Study Director: Freshwater aquatic plant, Lemna gibba Static renewal The nominal 0.15 mg/l test solution was inadvertently prepared (on Day 0 only) at a nominal concentration of mg/l. Since mean measured concentrations were used to derive the study endpoints, this deviation had no impact on the study. 7 days Duration of study: Test conditions: Static-renewal, renewals on Days 3 and 5 Parameters measured: Observation intervals: Age of inoculum: Initial number of fronds: Growth medium: Test concentrations: Method of test item added to the test In culture medium medium: No. of control replicates: 3 No. of test concentration replicates: 3 Analytical confirmation of test concentrations: Number of fronds and biomass, yield, and growth rate 0, 3, 5 and 7 days 14 days 12 per vessel Name: 20X freshwater algal medium ph of fresh solutions: ph at spent solutions: Nominal: 0, , 0.015, 0.048, 0.15 and 0.50 mg /L Geometric mean measured: <LOQ (control), , 0.018, 0.055, 0.17, and 0.58 mg /L Method: measuring concentrations of florasulam using LC-MS/MS Samples taken: days 0, 3, 5 and 7 both in fresh and spent solutions Limit of Quantitation: µg florasulam/l Recoveries from QC fortifications: 95.5 to 112% Test substance renewal days: 3 and 5 Environmental conditions: Test solution ph (range): Temperature (range): C Photoperiod: continuous light Evaluator: Germany Date: April 2013

333 Part B Section 6 Core Assessment Germany Central Zone Page 98 of 102 Light intensity (range): lux Methodology Fronds of duckweed, Lemna gibba G3, were exposed to a geometric series of five test concentrations and a negative (culture medium) control, under static-renewal test conditions for seven days. The nominal test concentrations were , 0.015, 0.048, 0.15 and 0.50 mg /L, geometric mean measured test concentrations were , 0.018, 0.055, 0.17, and 0.58 mg/l. Three replicate test chambers were maintained in each treatment and control group. Measured test concentrations of florasulam were determined from samples of test medium collected at test initiation and on Days 3, 5 and 7. Samples were collected from new solutions of each treatment and control group on Days 0, 3 and 5. Samples were collected from pooled old solutions on Days 3, 5 and 7. Effects upon the duckweed were assessed through direct counts of duckweed frond numbers conducted on Days 0, 3, 5 and 7 of the test. Observations of chlorosis, necrosis, break-up of duckweed colonies, death and any other abnormalities in plant or frond appearance were also performed at those times. EC 50 values based on replicate frond counts, frond count yield, replicate biomass (dry weight), biomass yield and on growth rates derived from both frond number and biomass on Day 7 of the test were calculated using non-linear interpolation. The no-observedeffect concentration (NOEC) representing the highest concentration that induced no adverse effects on plant and frond production or appearance, was determined through evaluation of the statistical analyses, the concentration-response pattern and other observed effects. The lowestobserved effect concentration (LOEC), which represents the lowest concentration that induced a statistically adverse effect on plant and frond production or appearance, was determined based upon evaluation of the statistical results, the concentration-response pattern, and other observed effects. Table : Effects of on frond number, growth rate and frond dry weight of Lemna gibba Treatment mg Primus Perfect/L Geometric mean measured concentrations Frond number Biomass (dry weight) Yield Growth rate (day -1 ) Yield (mg) Growth rate (day -1 ) Mean at 7 days % change Mean (0-7 days) % change Mean at 7 days % change Mean (day 7) Control * * * * * * * * * * * * * * * -51 * Significant reduction compared to control. Table : Statistical endpoints from the study (based on mean measured concentrations) Endpoint (mg/l) Frond Number Frond Number Yield Frond Number Growth Rate Biomass Biomass Yield EC % change Biomass Growth Rate Evaluator: Germany Date: April 2013

334 Part B Section 6 Core Assessment Germany Central Zone Page 99 of 102 NOEC Conclusions The doubling time of frond numbers in the control was less than 2.5 days (60h), corresponding to at least an eight-fold increase in seven days, and was 1.9 days. Duckweed, Lemna gibba G3, were exposed to five geometric mean measured concentrations of ranging from to 0.58 mg/l. Test organisms were evaluated for effects on frond number, frond number yield, biomass, biomass yield, and growth rates based on frond number and biomass. Calculated 7-day EC 50 estimates ranged from mg/l (frond number yield) to 0.36 mg/l (biomass growth rate). The NOEC based on frond number, frond number growth rate, biomass, biomass yield, and biomass growth rate was mg/l. The NOEC based on frond number yield was mg/l. Comments of zrms [Commenting box] Study Comments: KIIIA /01 Agreed Endpoints: KIIIA /01 The study is acceptable. 7-d E y C 50 = mg /L (mean measured concentrations) Evaluator: Germany Date: April 2013

335 Part B Section 6 Core Assessment Germany Central Zone Page 100 of 102 Appendix 3: Table of intended uses, GAP and justification for the risk envelope Introduction This document summarises the information related to country GAPs supported and cgaps derived from the GAPs, followed by the rationale for the risk envelope used in the Ecotoxicological and Environemental Fate & behaviour risk assessment. The formulation covered in this document is: Formulation Code Type Active Substance(s) SC Clopyralid; Florasulam Detailed GAP for uses: Crop and/ or situation Member State or Country Product Name F G or I Pests or Group of pests controlle d Formulation Application Application rate per treatment PHI (days) Remarks: (a) (b) (c) Winter wheat, Winter barley Winter triticale, Winter rye Spelt wheat Spring wheat, Spring barley, Spring oats Durum wheat Germany florasulam + clopyralid Primus Perfect Germany florasulam + clopyralid Primus Perfect Type (d-f) Conc of as (i) method kind (f-h) F BLWs SC 325 Tractor mounted spray F BLWs SC 325 Tractor mounted spray Growth stage & season (j) BBCH Spring (March- May) BBCH Spring (March- June) number min max (k) interval between application s (min) g as/hl min max 1 NA to NA to water L/ha min max g as/ha min max (l) (m) NA 200 ml/ha use rate NA 200 ml/ha use rate Evaluator: Germany Date: April 2013

336 Part B Section 6 Core Assessment Germany Central Zone Page 101 of 102 Risk envelope rationale for Environmental fate and behaviour 1) Soil: The GAPs for, as relevant to Germany, were considered for a risk envelope approach for the calculation of the PECsoil. The risk envelope was determined by grouping all cereal crops together according to the FOCUS groundwater crop category and then selecting the maximum use rate associated with cereals and then applying a crop interception factor applicable to the earliest growth-stage at application to give an effective soil loading. The risk envelope GAP is shown below. Risk Envelope for Clopyralid, Florasulam and - Soil Crop Group Winter and spring cereals * Based upon a formulation density of 1.16 g/ml Max. Rate 0.2 L /ha (232 * g Primus Perfect/ha) 60 g as/ha (clopyralid) 5 g as/ha (florasulam) Application Interval (d) NA Typical Application Dates 1 Mar 31 May Intercept at Application (Min. GS) 25% (BBCH 13) Effective Rate 174 g /ha 45 g as/ha (clopyralid) 3.75 g as/ha (florasulam) 2) Groundwater The same procedure as described under point 3.1 was used to select the risk envelope GAP for the calculation of the PECgw values, with the earliest calendar timing (1 March) selected as a worst case. The risk envelope GAP is shown below. Risk Envelope for Clopyralid and Florasulam - Groundwater Crop Group Winter and spring cereals Max. Rate 60 g as/ha (clopyralid) 5 g as/ha (florasulam) Application Interval (d) NA Typical Application Dates 1 Mar 31 May Intercept at Application (Min. GS) 25% (BBCH 13) Effective Rate 45 g as/ha (clopyralid) 3.75 g as/ha (florasulam) Evaluator: Germany Date: April 2013

337 Part B Section 6 Core Assessment Germany Central Zone Page 102 of 102 3) Surface water A similar approach was also adopted for the calculation of the PECsw (and PECsed), and the risk envelope GAP is shown below. Risk Envelope for Clopyralid, Florasulam and Surface Water Crop Group Winter and spring cereals Max. Rate for Drift Loading 0.2 L Primus Perfect/ha ( 232 * g Primus Perfect/ha) 60 g/ha (clopyralid) 5 g/ha (florasulam) * Based upon a formulation density of 1.16 g/ml NA = not applicable Application Interval (d) NA Typical Application Dates 1 Mar 31 May Intercept at Application (Min. GS) 25% (BBCH 13) Effective Rate for Soil Loading NA 45 g/ha (clopyralid) 3.75 g/ha (florasulam) Risk envelope rationale for Ecotoxicological risk assessment: is proposed for applications in Germany to winter cereals at BBCH growth stages 13 to 32 between March and May and to spring cereals at BBCH growth stages 13 to 30 between March and June. The worst-case critical GAP for uses considered in the ecotoxicological risk assessment is summarised in the following table. Table Appendix 3-1: Critical GAP for uses Crop Zone Time of application No. of applications per year Maximum rate per application 0.2 L /ha Cereals Central BBCH equivalent to 1 March to June florasulam: 5 g/ha clopyralid: 60 g/ha Evaluator: Germany Date: April 2013

338 Part B Section 6 National addendum DE Germany - Central Zone Page 1 of 21 REGISTRATION REPORT Part B Section 6 Ecotoxicological Studies Detailed summary of the risk assessment Product code: Active Substance: Florasulam 25 g/l Clopyralid 300 g/l Central Zone Zonal Rapporteur Member State: Germany (DE) NATIONAL ADDENDUM Applicant: Dow AgroSciences Date: April 2013 Evaluator: zrms DE Date April 2013

339 Part B Section 6 National addendum DE Germany - Central Zone Page 2 of 21 Table of content SEC 6 ECOTOXICOLOGICAL STUDIES PROPOSED USE PATTERN AND CONSIDERED METABOLITES Proposed use pattern Consideration of metabolites EFFECTS ON BIRDS Effects on Terrestrial Vertebrates Other Than Birds Effects on Terrestrial Vertebrates Other Than Birds EFFECTS ON AQUATIC ORGANISMS Overview and summary Toxicity to Exposure ratio Acute toxicity and chronic toxicity of the formulation Metabolites of florasulam and clopyralid Accumulation in aquatic non-target organisms EFFECTS ON BEES Effects on Arthropods Other Than Bees Overview and summary Risk assessment for Arthropods other than Bees EFFECTS ON EARTHWORMS, OTHER NON-TARGET SOIL ORGANISMS AND ORGANIC MATTER BREAKDOWN Overview and summary Toxicity to Exposure Ratio Residue content of earthworms EFFECTS ON SOIL MICROBIAL ACTIVITY Overview and summary EFFECTS ON NON-TARGET PLANTS Overview and summary OTHER NON-TARGET SPECIES (FLORA AND FAUNA) OTHER/SPECIAL STUDIES PRECAUTIONS NECESSARY TO AVOID/MINIMISE ENVIRONMENTAL CONTAMINATION AND TO PROTECT NON-TARGET SPECIES (IIIA )...18 APPENDIX 1 LIST OF DATA SUBMITTED IN SUPPORT OF THE EVALUATION...19 APPENDIX 2 DETAILED EVALUATION OF STUDIES RELIED UPON...20 APPENDIX 3 TABLE OF INTENDED USES JUSTIFICATION AND GAP TABLES...21 Evaluator: zrms DE Date April 2013

340 Part B Section 6 National addendum DE Germany - Central Zone Page 3 of 21 Sec 6 ECOTOXICOLOGICAL STUDIES Please refer to the core dossier for the central zone. This document presents the national addendum for Germany and should be read in conjunction with the core assessment for section 6. The national addendum addresses national requirements differing from the standard EU modelling and risk assessment procedures. It refers moreover to specific management and risk mitigation practices that can be implemented in Germany. 6.1 Proposed use pattern and considered metabolites Please refer to the core dossier for the central zone Proposed use pattern The critical GAP used for exposure assessment are presented in Table that reports also a classification of intended uses for (see also Section 5). A list of all intended uses within the zone/eu is given in Appendix 3. Table 6.1-1: Critical use pattern of Group/ use No Crop/growth stage Application method Drift scenario Number of applications, Minimum application interval, application time, interception Application rate, cumulative (g as/ha) Soil effective application rate (g as/ha) Winter wheat, Winter barley, Winter triticale, Winter rye, Spelt wheat, Spring wheat, Spring barley, Spring oats, Durum wheat (BBCH 13) spraying agriculture 1 x 0.2 L/ha Primus Perfect (eq. 232 g/ha Primus Perfect) containing 60 g as/ha clopyralid & 5 g as/ha florasulam 25% crop interception 0.2 L/ha Primus Perfect (eq. 232 g/ha ) containing 60 g as/ha clopyralid & 5 g as/ha florasulam 25% crop interception 174 g Primus Perfect/ha with 45 g as/ha clopyralid and 3.75 g as/ha florasulam Consideration of metabolites Please refer to the core dossier for the central zone. 6.2 Effects on Birds Please refer to the core dossier for the central zone. Evaluator: zrms DE Date April 2013

341 Part B Section 6 National addendum DE Germany - Central Zone Page 4 of Effects on Terrestrial Vertebrates Other Than Birds Please refer to the core dossier for the central zone Effects on Terrestrial Vertebrates Other Than Birds Please refer to the core dossier for the central zone. 6.3 Effects on Aquatic Organisms Overview and summary Please refer to the core dossier for the central zone Toxicity Please refer to the core dossier for the central zone Exposure is an herbicidal formulation containing florasulam and clopyralid as active substances and is intended to be used against will be used against weeds in cereals. The product is formulated as SC. According to the GAP table of intended uses (Appendix 3) a single application is considered to take place in spring after appearance of the weeds. Aquatic organisms may be exposed to plant protection products as a result of emission from treated fields. When is applied according to good agricultural practice, the active ingredients can reach surface waters unintentionally by spray-drift during application, by run-off and drainage. In agreement with the German modelling scheme TER values are calculated for all relevant exposure routes. The predicted environmental concentrations in surface water (PEC SW ) have been calculated based on the worst case application rates. In addition to the FOCUS based evaluation presented in the core dossier, an aquatic risk assessment is presented based on the two German evaluation models: EXPOSIT 3.0 and EVA 2.1. The risk evaluations are based on the most sensitive aquatic endpoints EC 50 = mg/l (Lemna gibba) for florasulam, NOEC = 10.8 mg/l (Oncorhynchus mykiss) for clopyralid and EC 50 = 0.02 mg/l (Lemna gibba) for. The calculation of concentrations in surface water is based on spray drift data by Rautmann and Ganzelmeier. The vapour pressure of the active substances florasulam is < 10-5 Pa. Hence the active substance florasulam is regarded as non-volatile. The vapour pressure of the active substances clopyralid is 1.36 x 10-3 Pa at 20 C. Thus the active substance clopyralid is regarded as semi-volatile and a calculation of inputs resulting from volatilization is necessary. The model EVA 2.1 is used for the calculation of PECsw after exposure via spraydrift for the active ingredients clopyralid and florasulam as well as for considering also deposition following volatilization for clopyralid. Evaluator: zrms DE Date April 2013

342 Part B Section 6 National addendum DE Germany - Central Zone Page 5 of 21 For details on the EXPOSIT and EVA 2.1modelling, see RR NA Part B, Section Risk assessment overall conclusions The risk to aquatic organisms following exposure to via spray-drift is not acceptable without drift reducing measures or without buffer zones. Due to the toxicity of the active ingredients as well as the formulation, the following labels must be indicated: NW262: The product is toxic for algae. [NOEC Florasulam = mg/l, S.capricornutum] NW265: The product is toxic for aquatic plants. [NOEC = mg/l, Lemna gibba] Conditions for use NW468 Formulation must not get into water bodies. NW609-1 Non-sprayed buffer strip 5 m or drift reducing nozzles (with at least 50% reduction), [EC50 = 20 µg/l, Lemna gibba] Toxicity to Exposure ratio The risk for aquatic organisms exposed to clopyralid, florasulam and its metabolites was assessed according to the intended uses. As first step, the initial maximum PEC SW values were compared to the relevant acute and long-term toxicity endpoints available for clopyralid, florasulam, and. Based on all studies on aquatic toxicity as well as the corresponding safety factors, the relevant endpoint for clopyralid is NOEC = 10.8 mg clopyralid/l (Oncorhynchus mykiss). For florasulam, the relevant endpoint is EC 50 = mg florasulam/l (Lemna gibba). For, the relevant endpoint is EC 50 = mg Primus Perfect/L (Lemna gibba). Risk assessment is driven by these endpoints; the ratio endpoint/corresponding safety factor is higher for all other organisms. Table 6.3-1: Fish long-term TER values for clopyralid after applications of caused by spraydrift and deposition Substance Clopyralid use no: application rate (g/ha) 60 relevant PEC PECact scenario/percentile: 90th percentile, agriculture cereals distance (m) PECsw via drift PECsw via volatilisation PECsw (via drift and volatilisation) (µg/l) depending on application technique (drift reduction) (%) (µg/l) (%) (µg/l) common 90% red. 75% red. 50% red Relevant toxicity: NOEC = µg/l, Oncorhynchus mykiss relevant TER: 10 distance TER-values (calculated) (m) Evaluator: zrms DE Date April 2013

343 Part B Section 6 National addendum DE Germany - Central Zone Page 6 of 21 Risk mitigation measure: None Table 6.3-2: Fish long-term TER values for clopyralid after applications of caused by run-off and drainage substance: Clopyralid Use no: / Application rate (g/ha): 60 Interception 25 % Relevant toxicity: NOEC = µg/l, Oncorhynchus mykiss relevant TER: 10 Exposure by surface runoff vegetated buffer strip (m) PECsw in adjacent ditch (µg/l) TER (calculated) Exposure by drainage time of application PECsw in adjacent ditch (µg/l) TER (calculated) autumn/winter/early spring Spring/summer Risk mitigation measure: None TERs shown in bold fall below the relevant trigger. Table 6.3-3: Aquatic higher plant TER values for florasualm after applications of caused by spraydrift and volatisation Substance Florasulam use no: application rate (g/ha) 5 relevant PEC PECact scenario/percentile: 90th percentile, agriculture cereals distance (m) PECsw via drift PECsw via volatilisation PECsw (via drift and volatilisation) (µg/l) depending on application technique (drift reduction) (%) (µg/l) (%) (µg/l) common 90% red. 75% red. 50% red Relevant toxicity: EC 50 = 1.18 µg/l, Lemna gibba relevant TER: 10 distance TER-values (calculated) (m) Risk mitigation measure: None TERs shown in bold fall below the relevant trigger. Table 6.3-4: Aquatic higher plant long-term TER values for florasulam after applications of Primus Perfect caused by run-off and drainage substance: Florasulam Indikation: / Application rate (g/ha): 5 Evaluator: zrms DE Date April 2013

344 Part B Section 6 National addendum DE Germany - Central Zone Page 7 of 21 Interception 25 % Relevant toxicity: EC 50 = 1.8 µg/l, Lemna gibba relevant TER: 10 Exposure by surface runoff vegetated buffer strip (m) PECsw in adjacent ditch (µg/l) TER (calculated) Exposure by drainage time of application PECsw in adjacent ditch (µg/l) TER (calculated)) autumn/winter/early spring Spring/summer Risk mitigation measure: None TERs shown in bold fall below the relevant trigger. Table 6.3-5: Aquatic higher plant TER values for after applications GF Substance use no: application rate (g/ha) 5 relevant PEC PECact scenario/percentile: 90th percentile, agriculture cereals distance (m) PECsw via drift PECsw via volatilisation PECsw (via drift and volatilisation) (µg/l) depending on application technique (drift reduction) (%) (µg/l) (%) (µg/l) common 90% red. 75% red. 50% red Relevant toxicity: EC 50 = 20 µg/l, Lemna gibba relevant TER: 10 distance TER-values (calculated) (m) Risk mitigation measure: NW609-1 (5 m buffer or 50 % drift reduction) TERs shown in bold fall below the relevant trigger. Based on the calculated concentrations clopyralid and florasulam in surface water (PEC SW ), the calculated TER values for the risk resulting from an exposure of aquatic organisms to containing the active ingredients clopyralid and florasulam according to the GAP of the formulation achieve the acceptability criteria TER 10, according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point for long-term effects. The results of the assessment indicate an acceptable risk for aquatic organisms due to the intended use of in cereals according to the label if an unsprayed drift-buffer of 5 m or drift reduction technique is used (NW609-1 (5 m buffer or 50 % drift reduction). Evaluator: zrms DE Date April 2013

345 Part B Section 6 National addendum DE Germany - Central Zone Page 8 of 21 According to the results of the TER-values calculations based on PEC values for the intended use in cereals, the implementation of management practices will be necessary to reduce the exposure of aquatic organisms to. Management practices relevant for Germany are given in chapter Acute toxicity and chronic toxicity of the formulation Please refer to section for a summary of the provided studies on the effects of on aquatic organisms. Section 6.3.2, page 5, gives the details of the risk assessment for aquatic organisms on the basis of all available data Metabolites of florasulam and clopyralid Please refer to the core assessment for the assessment of the metabolites of florasulam. Please refer to the core assessment Annex 2 for a summary of the provided studies on the effects of florasulam metabolites on aquatic organisms. Section 6.3.2, page 5, gives the details of the risk assessment for aquatic organisms on the basis of all available data. The comparison of the study results for the florasulam metabolites 5-OH-XDE-570, DFP-ASTCA, and ASTCA with the results of studies performed with florasulam shows that florasulam is more toxic for aquatic organisms than the metabolites. It is predicted that the risk for aquatic organisms exposed to florasulam metabolites according to the intended use of will be low. There are no relevant metabolites of clopyralid occurring in surface water or sediment (please refer to the core assessment) Accumulation in aquatic non-target organisms Bioaccumulation of any of the active substances under natural conditions is not expected to occur (K ow values of clopyralid and florasulam are < 3 (-2.63 and -1.22, respectively; refer to RR CA Part B, Section and 5.3.2) and a study is not necessary to determine bioaccumulation in aquatic non-target organisms. 6.4 Effects on Bees Please refer to Part B Section 6 of the Core Dossier Effects on Arthropods Other Than Bees Overview and summary With TERs based on laboratory data with the standard species above the trigger, no unacceptable risk of treatment with for non-target arthropods is indicated without any risk mitigation. Evaluator: zrms DE Date April 2013

346 Part B Section 6 National addendum DE Germany - Central Zone Page 9 of 21 Table 6.4-1: Tier 1 off-field TER values for non-target arthropod species other than bees after uses of in cereals Test substance Primus Perfect Use pattern / max. use rate [ml prod./ha] 200 Typhlodromus pyri 200 Aphidius rhopalosiphi Species Test type Endpoint ER 50 [ml prod./ha] TERs shown in bold are above the relevant trigger Toxicity Laboratory 2-dimentional Laboratory 2-dimentional Please refer to the core dossier for the central zone. Worstcase PER off-field (1 m) [ml prod./ha] TER Off-field > > > > TER trigger value Exposure The risk assessment for areas immediately surrounding the crop is considered important since these areas represent a natural reservoir for immigration, emigration and reproduction of arthropod populations and provide increased species diversity. Exposure of non-target arthropods living in off-field areas to Primus Perfect will mainly be due to spray drift from field applications. Off-field PER values were calculated from in-field PERs in conjunction with drift values published by the BBA (2000) 1 as shown in the following equation: Off - field foliar PER Maximum in - field PER x (% drift/100) vegetation distribution factor Vegetation distribution factor: The model used to estimate spray drift was developed for drift onto a twodimensional water surface and, as such, does not account for interception and dilution by threedimensional vegetation in off-crop areas. Therefore, a vegetation distribution or dilution factor is incorporated into the equation when calculating PERs to be used in conjunction with toxicity endpoints derived from two-dimensional (glass plate or leaf disc) studies. A dilution factor of 10 is recommended by ESCORT 2. In line with German national requirements, a vegetation distribution factor of 5 has to be applied, based on experimental data. However, for 3-dimensional studies, i.e. where spray treatment is applied onto whole plants, the dilution factor is not used, as any dilution over the 3-dimensional vegetation surface is accounted for in the study design. 1 90th percentile drift according to BBA (2000): Bundesanzeiger Jg. 52 (Official Gazette), Nr 100, S ( ) Bekanntmachung über die Abtrifteckwerte, die bei der Prüfung und Zulassung von Pflanzenschutzmitteln herangezogen werden Evaluator: zrms DE Date April 2013

347 Part B Section 6 National addendum DE Germany - Central Zone Page 10 of 21 2-dimensional structures were used for application in the laboratory studies on Aphidius rhopalosiphi and Typhlodromus pyri. Therefore, a vegetation distribution factor of 10 was used for the off-field assessment for these species. The drift value at 1 m distance is 2.77% of the application rate (90th percentile drift). The drift factor (% drift/100) is therefore 2.77/100 = As for a herbicide ground-directed application is assumed, the field crop drift values are used for all crops. The resulting PERoff-field value is shown in the following Table: 6.4-2: Off-field PER values for application of Substance Maximum in-field PER (ml /ha) Drift factor (% drift/100) Vdf Off-field PER (ml /ha) 200 ml/ha ml/ha Risk assessment for Arthropods other than Bees The risk assessment for non-target arthropods is done on basis of the calculation of toxicity-exposure ratio (TER) values as in line with German national requirements according the following formula: LR 50 / ER 50 [L product/ha]. max. exposure level x MAF x (% drift / 100 x correction factor 5 ) [L product/ha] The risk is considered acceptable if the off-field TER obtained is > 10 (tier 1) or > 5 (higher tier assessment). The resulting TERoff-field values are given in the following Table: 6.4-3: Tier 1 off-field TER values for non-target arthropods Species Test type Endpoint ER 50 [ml prod./ha] Typhlodromus Laboratory pyri Aphidius rhopalosiphi 2-dimen-tional Laboratory 2-dimen-tional TERs shown in bold fall below the relevant trigger. PER off-field (1 m) [ml prod./ha] TER Off-field > > > > TER trigger value The off-field TER values for Typhlodromus pyri and Aphidius rhopalosiphi are above the trigger value, indicating that at rates up to 0.2 L/ha does not pose an unacceptable risk to terrestrial non-target arthropods in the off-field areas. The results of the assessment indicate an acceptable risk for non-target arthropods due to the intended use of in cereals according to the label without risk mitigation measures. Evaluator: zrms DE Date April 2013

348 Part B Section 6 National addendum DE Germany - Central Zone Page 11 of Effects on Earthworms, other Non-target Soil Organisms and Organic Matter Breakdown Overview and summary Please refer to the core dossier of the central zone Toxicity Please refer to the core dossier for the central zone Exposure According to the GAP, GF 2643 is intended to be applied once in spring with a maximum application rate of 0.2 L formulation/ha (equivalent to 5 g florasulam/ha and 60 g clopyralid/ha). It will be used against weeds (annual dicotyledonous plants) on cereals (winter and summer; BBCH 13 32, March to June). For PEC calculations reference is made to the environmental fate section (Part B, Section 5, chapter 5.6) of this submission. The resulting maximum PECsoil values for the active substances clopyralid and florasulam and the major soil degradation products are presented in Table Calculations considered the maximum application rate of (i.e. a single application at 0.2 L/ha) and a minimum of 25% foliar interception for applications to cereals at BBCH of at least 13. PEC values for the soil metabolites were calculated considering the maximum percentage of their formation observed in either the aerobic or anaerobic soil degradation studies and correcting for molecular weight. Calculations assumed an even distribution of the substances in the top 2.5 cm horizon (1.0 cm for substances with a K f,oc > 500) with a soil bulk density of 1.5 g/ml. Table 6.5-1: Maximum PEC S for, clopyralid, florasulam and their major soil degradation products after applications of (expressed as a.s.) Substance Maximum PECS (mg/kg), 25% foliar interception Clopyralid Florasulam OH-florasulam DFP-ASTCA ASTCA The florasulam metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA were formed in concentrations >10 % TAR at the end of the study in the soil (see although section 5, Table 6.5-2) Risk assessment TER values and overall conclusions All acute and chronic TERs for the active substances and the major soil degradation products are above the respective trigger values indicating that the acute and chronic risk to earthworms and other soil non- Evaluator: zrms DE Date April 2013

349 Part B Section 6 National addendum DE Germany - Central Zone Page 12 of 21 target macro-organisms following treatment with is low and acceptable at the intended worst-case uses. The risk assessment results are summarized in the following Table: Table 6.5-3: Toxicity/exposure ratios for earthworms (Eisenia foetida) after applications of Primus Perfect in cereals Test substance Worst-case use pattern Timescale Endpoint (mg/kg dw soil) PEC (mg/kg dw soil TERs shown in bold fall below the relevant trigger. TER TER risk assessment trigger Table 6.5-4: Toxicity/exposure ratios for non-target macro-organisms (Folsomia candida and Hypoaspis aculeifer) after applications of in cereals Test substance Primus 0.2 L Primus Acute >2000 > Perfect Perfect/ha Long-term Clopyralid equivalent to Acute > > florasulam: 5 g/ha Long-term Florasulam clopyralid: 60 g/ha Acute > > OHflorasulam Acute > > DFP- Acute > > ASTCA ASTCA Acute > > Long-term OHflorasulam DFP- ASTCA ASTCA Worst-case use pattern 0.2 L Primus Perfect/ha equivalent to florasulam: 5 g/ha clopyralid: 60 g/ha Organism Hypoaspis aculeifer Folsomia candida Folsomia candida TERs shown in bold fall below the relevant trigger. Endpoint (mg/kg dw soil) PEC (mg/kg dw soil TER TER risk assessment trigger Toxicity to Exposure Ratio Acute risk The potential acute risk of, the active substances clopyralid and florasulam as well as their major soil degradation products was assessed by comparing the maximum instantaneous PECsoil with the 14-day LC 50 value to generate acute TER values. The log KOW value for clopyralid, florasulam is below 2. Therefore, no correction of the endpoints is required in order to account for the relatively high organic matter content of the artificial test soil compared to agricultural soils. The TER A was calculated as follows: TER A LC = PEC 50 soil (mg/kg) (mg/kg) Evaluator: zrms DE Date April 2013

350 Part B Section 6 National addendum DE Germany - Central Zone Page 13 of 21 The resulting TER A values are shown in the following Table, considering the highest initial PEC in soil (i.e. 25% interception during applications): Table 6.5-5: Acute TER values for earthworms following applications of Test substance Maximum initial Timescale LC 50 or NOEC TER PEC (mg/kg) (mg/kg) Acute >2000 >4310 Long-term Clopyralid Acute >1000 >8333 Long-term Florasulam Acute >1320 > OH-florasulam Acute >1120 > DFP-ASTCA Acute >0.1 >100 ASTCA Acute >100 >50000 Long-term TERs shown in bold fall below the relevant trigger. Based on the worst case scenario, the acceptability criteria TER 10 for acute effects, according to Annex VI to directive 1107/2009 (EG), uniform principles, point is reached Chronic risk For a study on the reproduction of earthworms was submitted and the long term risk of is assessed. There is no need to address the long term risk of the active substances clopyralid and florasulam and its metabolites 5-OH and DFP-ASTCA for earthworms, because their degradation in soil (DT 90 < 365 d, Kinetic, laboratory/field data) is fast. The major soil metabolite ASTCA of florasulam degrades slowly with normalized DT 90 values > 365 d. Therefore, a long term risk assessment is necessary for this metabolite (see Section 5, chapter and 9.4.). TER LT NOEC (m g/kg) = PEC (mg/kg) soil The resulting TER lt values are shown in the following Table, considering the highest initial PEC in soil (i.e. 25% interception during applications): Table 6.5-6: Long-term TER values for earthworms following applications of Test substance Maximum initial Timescale LC50 or NOEC TER PEC (mg/kg) (mg/kg) Acute >2000 >4310 Long-term Clopyralid Acute >1000 >8333 Long-term Florasulam Acute >1320 > OH-florasulam Acute >1120 > DFP-ASTCA Acute >0.1 >100 ASTCA Acute >100 >50000 Long-term Evaluator: zrms DE Date April 2013

351 Part B Section 6 National addendum DE Germany - Central Zone Page 14 of 21 TERs shown in bold fall below the relevant trigger. Based on the worst case scenario, the acceptability criteria TER 5 for long term effects, according to directive 1107/2009 (EG), Annex VI, uniform principles, point is reached for the formulation as well as the relevant metabolites 5-OH-florasulam, DFP-ASTCA, and ASTCA. The results of the assessment indicate an acceptable risk for soil organisms due to the intended use of Primus Perfect in cereals according to the label Residue content of earthworms Please refer to the core dossier for the central zone. 6.6 Effects on Soil Microbial Activity Overview and summary The risk assessment results are summarised in the following table: 6.6-1: Risk assessment for soil microflora functions Substance (< 25% effect at 28 d) PEC (mg/kg), 25% foliar interception Clopyralid 2.0 a Florasulam ASTCA as clopyralid b as florasulam b a Converted to mg/kg soil from the endpoint of 1500 g/ha listed in the EFSA Scientific Report (2005) 50, 1-65 assuming a soil bulk density of 1.5 g/ml and distribution in 5 cm of soil. b Based on data for GF-1374, a formulation containing clopyralid (80 g/l), florasulam (2.5 g/l) and an additional active substance: fluroxypyr at g a.i./l. MoS applied at the proposed worst-case use patterns does not pose an unacceptable risk to soil microorganisms. For the active ingredients in, clopyralid, florasulam, and their metabolite ASTCA, the soil concentrations which caused no deviations greater than 25% in the activity of the soil microorganisms are at least 3-times higher than the corresponding maximum PEC in soil. Considering concurrent exposure to both the active ingredients in at the time of application, a low risk to soil microflora is also concluded. Based on the predicted concentrations of, clopyralid, florasulam, and their metabolite ASTCA in soils, the risk to soil microbial processes following exposure to clopyralid, florasulam, and their metabolite ASTCA according to the GAP of the formulation is considered to be Evaluator: zrms DE Date April 2013

352 Part B Section 6 National addendum DE Germany - Central Zone Page 15 of 21 acceptable according to commission implementing regulation (EU) No 546/2011, Annex, Part I C, 2. Specific principles, point Toxicity Please refer to the core dossier for the central zone Exposure See section 1 of this document for the PECsoil values Risk assessment overall conclusions SANCO/10329/2002 rev 2-final states that testing soil micro-organisms is always required when contamination of the soil is possible. The Predicted Environmental Concentrations of the formulation, the two active substances and the major soil degradation product ASTCA are below the concentrations at which no unacceptable effects (< 25%) were observed after 28 days of exposure. The results of the comparison expressed as Margin of Safety (MoS) considering the highest initial PEC in soil (i.e. 25% interception during applications) is presented in the following Table: Table 6.6-2: Risk assessment to soil micro-organisms following applications of Substance Test type Maximum initial Effects <25% MoS PEC (mg/kg) (mg/kg) a N transformation 1.15 as clopyralid 9.6 C transformation as clopyralid as florasulam as florasulam 1.15 as clopyralid as florasulam Clopyralid N transformation C transformation Florasulam N transformation C transformation ASTCA N transformation C transformation a: Based on data for GF-1374, a formulation containing clopyralid (80 g/l), florasulam (2.5 g/l) and an additional active substance: fluroxypyr at g a.e./l. TERs shown in bold fall below the relevant trigger. For the active ingredients in, clopyralid and florasulam, and their metabolites the soil concentrations which caused no deviations greater than 25% in the micro-organism studies are at least 5- times higher than the corresponding maximum PEC in soil. Considering concurrent exposure to both the active ingredients in at the time of application, a low risk to soil microflora is also concluded being concentrations causing no deviations greater than ±25% at least 3.3-times higher than the maximum PEC in soil. Consequently, it may be concluded that there will be no unacceptable risk to soil micro-organisms following the use of. Evaluator: zrms DE Date April 2013

353 Part B Section 6 National addendum DE Germany - Central Zone Page 16 of 21 Based on the worst case scenario, the acceptability criteria according to directive 1107/2009 (EG), Annex VI, uniform principles, point is reached. 6.7 Effects on Non-Target Plants Overview and summary The risk assessment results are summarized in the following Table: Table 6.7-1: Minimum TER values for terrestrial non-target plants after uses of in cereals Study type Vegetative vigour Critical Distance (m) endpoint (ml/ha) TERs shown in bold are below the relevant trigger. Drift reducing nozzles PER (ml/ha) TER 0% % % % Thus, an acceptable risk to terrestrial non-target plants of treatments with in accordance with the proposed worst-case use pattern is indicated by TERs above the trigger of 5 if as risk mitigation drift reduction technique of at least 90 % in combination with a buffer of 1 m is kept Toxicity Please refer to the core dossier for the central zone Exposure Effects on non-target plants are of concern in the off-field environment, where they may be exposed to spray drift. The amount of spray drift reaching off-crop habitats is calculated using the 90th percentile estimates derived by the BBA (2000) 2 from the spray-drift predictions of Ganzelmeier & Rautmann (2000) 3. Any dilution over the 3-dimensional vegetation surface is accounted for in the study design. Therefore, in contrast to the assessment of risks to arthropods from standard laboratory tests, no vegetation distribution factor is considered here. PECoff-field= Maximum in-field PER x (%DRIFT/100) The exposure assessment for the intended uses, due to the ground-directed application of, which is a herbicide is most appropriately addressed by the drift values for field crops. The highest single 2 BBA (2000) Bundesanzeiger Jg. 52 (Official Gazette), Nr 100, S ( ) Bekanntmachung über die Abtrifteckwerte, die bei der Prüfung und Zulassung von Pflanzenschutzmitteln herangezogen werden. Public domain. 3 Ganzelmeier H., Rautmann D. (2000) Drift, drift-reducing sprayers and sprayer testing. Aspects of Applied Biology 57, 2000, Pesticide Application. Public domain. Evaluator: zrms DE Date April 2013

354 Part B Section 6 National addendum DE Germany - Central Zone Page 17 of 21 application rate of is 0.2 L product/ha corresponding to 5 g florasulam /ha and 60 g clopyralid/ha. The resulting maximum off-field predicted environmental rates (PERoff-field) are summarized in the following Table: Table 6.7-2: Maximum off-field predicted environmental rates of GF-1463 Maximum intended in-field rate Maximum PERoff-field Maximum PERoff-field (PECin-field) at 1m (2.77% drift) at 5 m (0.57% drift) 200 ml product/ha 5.54 ml product/ha 1.14 ml product/ha Risk assessment TER values For plant protection products exerting effects of more than 50% at the maximum application rate (common for herbicides as ) a quantitative second tier risk assessment based on doseresponse endpoints represented by ER50 values is required according to the terrestrial guidance document. Based on an evaluation of tests (vegetative vigour) on plants with mono-formulations containing those substances (e.g. the representative formulation for the EU) Daucus carota, Brassica napus as well as Allium cepa turned out to be sensitive species if they are faced with clopyralid or florasulam. These three species were included in the studies with the actual formulation. The most sensitive species of this test turned out to be Lactuca sativa, Brassica napus, Raphanus sativus and Lycopersicon esculentum. Other tested species as Avena sativa and Glycine max did not show special sensitivity if clopyralid or florasulam were applied. Since 11 plant species, including sensitive ones, were tested with the actual formulation, the relevant TER for the risk assessment of the formulation can be reduced to 5. Predicted exposure rates (PER) by spray drift in off-field areas were calculated considering the spray drift deposition rates as determined by Rautmann et al. ( ) for field crops. As risk mitigation a specific buffer strip of 1 or 5 m can be used. Additionally, a reduction of the spray drift in areas surrounding the treated field may also be considered with the use of drift reducing nozzles. PER values, in areas immediately adjacent to the treated areas, were calculated assuming the use of 0%, 50% or 75% or 90% drift reducing nozzles. In the table below, TER values are calculated, comparing the lowest ER 50 value determined for Primus Perfect (5.22 ml prod./ha; Lactuca sativa, vegetative vigour) to the predicted exposure rate (PER) in offfield areas after treatment with in accordance to the maximum proposed use rate of 0.2 L product/ha. Table 6.7-3: Risk assessment for non-target plants after applications of Study type Vegetative vigour Critical endpoint (ml/ha) Distance from treated area (m) % drift Drift reducing nozzles PER (ml/ha) TER 0% % % Rautmann et al. (2001) Evaluator: zrms DE Date April 2013

355 Part B Section 6 National addendum DE Germany - Central Zone Page 18 of 21 Relevant TER: 5 Risk mitigation: NT TERs shown in bold are below the relevant trigger. 90% % % % % Thus, an acceptable risk to terrestrial non-target plants of treatments with in accordance with the proposed worst-case use pattern is indicated by TERs above the trigger of 5 if as risk mitigation drift reduction technique of at least 50 % in combination with a buffer of 5 m is kept. Alternatively it must be used drift reduction technique of at least 90 % at 1 m buffer zone. According to the results of the TER-values calculations based on PEC values for the intended use in cereals, the implementation of management practices will be necessary to reduce the exposure of terrestrial non-target plants to. Management practices relevant for Germany are given in chapter Conditions for use All uses NT Other Non-Target Species (Flora and Fauna) Please refer to the core dossier for the central zone. 6.9 Other/Special Studies Please refer to the core dossier for the central zone Precautions necessary to avoid/minimise environmental contamination and to protect non-target species (IIIA ) NW262: NW265: NW468: NW609-1 NT103: The product is toxic for algae. [NOEC Florasulam = mg/l, S.capricornutum] The product is toxic for aquatic plants. [NOEC = mg/l, Lemna gibba] Fluids left over from application and their remains, products and their remains, empty containers a nd packaging, and cleansing and rinsing fluids must not be dumped in water. This also applies to indirect entry via the urban or agrarian drainage system and to rain-water and sewage canals. non prayed buffer strip 5 m or drift reducing nozzles (with at least 50% reduction), Formulation must not get into water bodies. [EC50 = 20 µg/l, Lemna gibba] Non-sprayed buffer strip 1 m with at least 90% drift reducing techniques or non-sprayed buffer strip 5 m with at least 50% drift reduction. [ER50 = 5.22 ml prod./ha; Lactuca sativa, vegetative vigour] Evaluator: zrms DE Date April 2013

356 Part B Section 6 National addendum DE Germany - Central Zone Page 19 of 21 Appendix 1 List of data submitted in support of the evaluation Please refer to the core dossier for the central zone. Evaluator: zrms DE Date April 2013

357 Part B Section 6 National Addendum DE Germany-Central Zone Page 20 of 21 Appendix 2 Detailed evaluation of studies relied upon Please refer to the core dossier for the central zone. Evaluator: zrms DE Date April 2013

358 Part B Section 6 National Addendum DE Germany-Central Zone Page 21 of 21 Appendix 3 Table of Intended Uses justification and GAP tables Please refer to the core dossier for the central zone. Evaluator: zrms DE Date April 2013

359 Part B Section 7 Core Assessment GF /00 Central Zone Page 1 of 47 REGISTRATION REPORT Part B Section 7: Efficacy Data and Information Detailed Summary Product Code: GF-2463 Reg. No.: /00 Active Substance: 25 g/l florasulam, 300 g/l clopyralid Central Zone Zonal Rapporteur Member State: Germany CORE ASSESSMENT Date: September 2011 Evaluator: Julius Kühn-Institut Date: Julius Kühn-Institut

360 Part B Section 7 Core Assessment GF /00 Central Zone Page 2 of 47 Table of Contents IIIA1 6 Efficacy Data and Information on the Plant Protection Product...3 General information...3 Recent registration situation/history of the PPP...3 Information on the active substances (Uptake and mode of action)...3 Information on crops and pests...4 Information on the intended uses ( )...4 IIIA1 6.1 Efficacy data...5 IIIA Preliminary range-finding tests...5 IIIA Minimum effective dose tests...5 IIIA Efficacy tests...6 IIIA Effects on yield and quality...9 IIIA Impact on the quality of plants and plant products...9 IIIA Effects on the processing procedure...9 IIIA Effects on the yield of treated plants and plant products...9 IIIA1 6.2 Adverse effects...10 IIIA Phytotoxicity to host crop...10 IIIA Adverse effects on health of host animals...13 IIIA Adverse effects on site of application...13 IIIA Adverse effects on beneficial organisms (other than bees)...13 IIIA Adverse effects on parts of plant used for propagating purposes...21 IIIA Impact on succeeding crops...21 IIIA Impact on other plants including adjacent crops...22 IIIA Possible development of resistance or cross-resistance...23 IIIA1 6.3 Economics...25 IIIA1 6.4 Benefits...25 IIIA Survey of alternative pest control measures...25 IIIA Compatibility with current management practices including IPM...25 IIIA Contribution to risk reduction...25 IIIA1 6.5 Other/special studies...25 IIIA1 6.6 Summary and assessment of data according to points 6.1 to IIIA1 6.7 List of test facilities including the corresponding certificates...26 Appendix 1: List of data submitted in support of the evaluation...27 Appendix 2: GAP table(s)...46 Julius Kühn-Institut

361 Part B Section 7 Core Assessment GF /00 Central Zone Page 3 of 47 IIIA1 6 Efficacy Data and Information on the Plant Protection Product General information This application is submitted under Regulation (EC) 1107/2009 by Dow AgroSciences to the zonal RMS Germany. The applicant is asking for approval of this cereal herbicide, code name GF-2463 containing the active substances clopyralid (300 g/l) and florasulam (25 g/l). Tab : Zonal rapporteur member state (zrms) and concerned member states (cms). zrms Germany DE cms none Recent registration situation/history of the PPP There are no existing registrations for GF-2463 at current. The individual active substances of GF-2463 hold however approvals in cereals in Europe. Information on the active substances (Uptake and mode of action) Clopyralid (3,6-Dichlorpyridin-2-carbonsäure) belongs to the chemical group of pyridine carboxylic acids and works as such as a synthetic auxin. When applied in post-emergence, clopyralid will mainly be absorbed through green leaves. Uptake through roots is of much less importance. Acropetal translocation of clopyralid in xylem into young meristems and youngest leaves as well as basipetal transport in phloem into roots is possible. It has been shown that clopyralid is being accumulated in meristematic tissue and influencing cell division, cell elongation and cell extension as well as RNA synthesis. Consequently, meristematic tissue dies off. Typical symptoms of susceptible plants are deformation and curling of young leaves and stem followed by growth stop and necrosis. The tissues of dicotyledonous plants are destroyed, while monocotyledonous plants are not affected. Favourable growth conditions linked to good plant metabolism enhance the herbicidal activity of clopyralid, poor growth conditions can lead to delay of activity. Plants which have reached their growth already in the generative phase, react only little on clopyralid. Clopyralid was only slowly metabolised in plants. In Cirsium arvense-plants no metabolites of clopyralid were recovered from foliage, root or nutrient solution up to 9 days after application. On the other hand, it was reported that clopyralid was partially converted to water soluble metabolites and may be converted to a carboxylic acid amide derivative in oilseed rape. Site of action (HRAC-group): O Florasulam belongs to the chemical group of triazolpyrimidine sulfonanilides. Florasulam is taken up by roots or by foliage and redistributes throughout the plant. Due to a rapid degradation in soils, only a small soil effect is expected. Translocation pattern are consistent with mobility in both the xylem and the phloem. Accumulation of florasulam occurs at primary and axillary meristems, which are primary locations for the action of sulfonanilide herbicides. Florasulam is known to inhibit the plant enzyme acetolactate synthase enzyme (ALS) which is essential for the creation of amino acids with branched chain such as valine, leucine or isoleucine. Therefore florasulam affect the formation of protein and the plants die. This is done in a time frame of 2 to 3 weeks but may take up to 6-8 weeks under less ideal conditions. The inhibition of ALS results in a number of distinctive whole plant symptoms. Growth of sensitive species is retarded within a matter of hours of application although visible effects may not be observed for several days. Symptoms appear first in the upper meristematic region of the plants as chlorosis and necrosis. The upper new leaves often take on a wilted appearance. The effects then spread to the remaining parts of the plant. In comparison to sensitive weeds the tolerance in cereals turns on a Julius Kühn-Institut

362 Part B Section 7 Core Assessment GF /00 Central Zone Page 4 of 47 faster metabolisation. In cereals a rapid degradation of the active substance is verifiable. In winter wheat the half-life period is up to 4 hours; in Galium aparine 48 hours. Degradation in plants take place via the main metabolite 5-Hydroxy-DE 570 to TSA (1H-1,2,4-triazol-3-sulphonamid). Site of action (HRAC-group): B Information on crops and pests GF-2463 is intended as herbicide for post-emergence applications in spring over a wide application window in spring and winter cereals to control annual dicotyledonous weeds. The intended use rate is 0.2 L/ha corresponding to 5 g/ha florasulam plus 60 g/ha clopyralid. It can be applied to winter wheat, winter barley, winter triticale, winter rye and spelt from BBCH 13 growth stage (three leaves) to BBCH 32 stage (second node), and to spring wheat, spring barley, spring oats and durum wheat from BBCH 13 growth stage (three leaves) to BBCH 30 stage (end of tillering). The proposed used pattern is presented in Appendix 2. Harmful organisms against which protection is afforded: GF-2463 is intended as herbicide for post-emergence use in spring in cereals to control annual dicotyledonous weeds. Primary target weeds in Central Zone are: Galium aparine (GALAP) Matricaria species (MATCH, MATIN, ) Cruciferous weeds (BRSNW, CAPBP, SINAR,THLAR,...) Stellaria media (STEME) Centaurea cyanus (CENCY) Polygonum species (POLCO, POLPE, POLAV,...) Table Importance of intended target/crop in Germany target/crop EPPO Country Classification target Galium aparine GALAP Germany major Matricaria species MATSS Germany major Stellaria media STEME Germany major Polygonum species POLSS Germany major crop Winter and spring cereals Germany major Information on the intended uses ( ) Use No / Area of application Agriculture (field crops) Crop(s)/object(s) winter soft wheat (TRZAW), winter barley (HORVW), winter rye (SECCW), spelt (TRZSP), winter triticale (TTLWI) Crop stage(s) (BBCH) 13 to 32 Pest(s)/target(s)/aim(s) annual dicotyledonous weeds (TTTDS) Area of use Outdoors Time of treatment After emergence, spring, after emergence of weeds Max. number of treatments 1 for the use Max. number of treatments 1 per crop or sea- Julius Kühn-Institut

363 Part B Section 7 Core Assessment GF /00 Central Zone Page 5 of 47 son Application technique/type spraying of treatment Dose rate(s) in amount 0.2 L/ha in 200 to 400 L water/ha of water to be used Use No / Area of application Agriculture (field crops) Crop(s)/object(s) spring soft wheat (TRZAS), spring durum wheat (TRZDS), spring barley (HORVS), oats (AVESS) Crop stage(s) (BBCH) 13 to 30 Pest(s)/target(s)/aim(s) annual dicotyledonous weeds (TTTDS) Area of use Outdoors Time of treatment After emergence, spring, after emergence of weeds Max. number of treatments 1 for the use Max. number of treatments 1 per crop or sea- son Application technique/type spraying of treatment Dose rate(s) in amount 0.2 L/ha in 200 to 400 L water/ha of water to be used IIIA1 6.1 Efficacy data IIIA Preliminary range-finding tests Both florasulam and clopyralid are acknowledged as herbicides and have not exhibited any insecticidal or fungicidal activities since their introduction in Europe. Preliminary range-finding tests were carried out for florasulam and clopyralid in early stage herbicide, fungicide and insecticide screens by Dow AgroSciences, and are reported in literature (Brown et al. 1976, Thompson et al. 1999). No preliminary data were presented. IIIA Minimum effective dose tests To determine the minimum effective dose of GF-2463 in winter cereals, 20 efficacy trials have been conducted (2 UK, 18 Germany) targeting a broad range of dicotyledonous weeds and treated at various application timings in spring (Tab ). The trial results demonstrate that a use rate of 0.2 L/ha GF-2463 is needed to reach sufficient control of Centaurea cyanus (CENCY), Galium aparine (GALAP), Matricaria sp. (MATCH, MATIN, MATSS) and volunteer oilseed rape (BRSSS). Polygonum convolvulus (POLCO) and Stellaria media (STEME) can be controlled at lower rates (Tab ). To determine the minimum effective dose of GF-2463 in spring cereals, 12 efficacy trials have been conducted in Germany on a broad range of target weeds and treated at various application timings in spring (Tab ). The trial results demonstrate that a use rate of 0.2 L/ha GF is needed to reach sufficient control of Capsella bursa-pastoris (CAPBP), Galium aparine (GALAP), Matricaria recutita (MATCH), Stellaria media (STEME) and volunteer oilseed rape (BRSSS), whilst Centaurea cyanus (CENCY), Matricaria inodora (MATIN), Raphanus raphanistrum (RAPRA), Polygonum convolvulus (POLCO), Sinapis arvense (SINAR) and Solanum nigrum (SOLNI) can be controlled at lower rates (Tab ). Tab : Number of minimum effective dose trials ( ). Julius Kühn-Institut

364 Part B Section 7 Core Assessment GF /00 Central Zone Page 6 of 47 Germany United Kingdom total Winter cereals (use 001) Spring cereals (use 002) total 32 Tab : Efficacy (%) in minimum effective dose trials in winter cereals in the maritime EPPO zone. Tab : Efficacy (%) in minimum effective dose trials in spring cereals in the maritime EPPO zone. IIIA Material and methods Efficacy tests Tab : Number of efficacy trials ( ). Germany United Kingdom total Winter cereals (001) Spring cereals (002) total 43 Tab : Guidelines and trial design. GEP yes (all) EPPO standards Yes (all) plot design, plot size RCBD (all) trials per crop winter wheat (12), winter barley (4), winter rye (7), triticale (3), spring wheat (5), spring barley (8), spring oat (4) application date winter cereals: spring cereals: reference products Hoestar Super (0.2 kg/ha), Primus ( kg/ha) Julius Kühn-Institut

365 Part B Section 7 Core Assessment GF /00 Central Zone Page 7 of 47 Results Winter cereals (use 001): Efficacy data to support the label claims in winter cereals were generated in a total of 26 efficacy trials carried out during the period in Germany (24 trials) and UK (2 trials) (Tab ; ). One spring application of GF-2463 at a use rate of 0.2 L/ha controls Galium aparine, Centaurea cyanus, Matricaria sp., Stellaria media, Polygonum convolvulus, volunteer oil seed rape and smaller stages of Capsella bursa-pastoris. Cirsium arvense is being controlled (suppressed) sufficiently in the year of treatment. Other weeds such as Geranium sp., Veronica sp., Viola arvensis and volunteer potatoes will not be controlled at a commercially acceptable level (Tab ): Highly Susceptible (HS) % BRSSS, CENCY, DESSO, ERPVE, GALAP, MATCH, MATIN, CAPBP (BBCH 30 of the crop) Susceptible (S) % CIRAR (year of treatment), POLCO, POLLA, STEME Moderately Susceptible (MS) % MYOAR, PAPRH, SENVU, SPRAR, SSYOF, THLAR Moderately Tolerant (MT) % CAPBP (BBCH >30 of the crop) Tolerant (T) % APHAR, GERRT, LAMAM, LAMPU, SOLTU, VERSS, VIOAR Tab : Efficacy (%) of GF-2463 in winter cereals in the maritime EPPO zone, 26 trials, Germany and United Kingdom, Julius Kühn-Institut

366 Part B Section 7 Core Assessment GF /00 Central Zone Page 8 of 47 Spring cereals (use 002): Efficacy data to support the label claims in spring cereals were generated in a total of 17 efficacy trials carried out during the period in Germany (Tab ; ). One spring application of GF-2463 at a use rate of 0.2 L/ha controls volunteer oilseed rape, Capsella bursa-pastoris, Galium aparine, Centaurea cyanus, Matricaria sp., Stellaria media, Polygonum convolvulus, P. persicaria, Raphanus raphanistrum, Sinapis arvense, and Solanum nigrum. Cirsium arvense is being controlled (suppressed) sufficiently in the year of treatment. Other weeds such as Veronica species, Lamium amplexicaule, Chenopodium species, Thlaspi arvense and Viola arvensis will not be controlled at a commercially acceptable level (Tab ):. Highly Susceptible (HS) % CENCY, GALAP, MATCH, MATIN, PHCSS, POLCO, POLPE RAPRA, SINAR, SOLNI, STEME Susceptible (S) % BRSSS, CAPBP, CIRAR (in year of application), MATMA, POLAV, SSYOF Moderately Susceptible (MS) % AMARE, DESSO, PAPRH, THLAR Moderately Tolerant (MT) % CHEAL, CHEFI, LAMPU Tolerant (T) % MENAR, VIOAR Tab : Efficacy (%) of GF-2463 in spring cereals in the maritime EPPO zone, 17 trials, Germany, Julius Kühn-Institut

367 Part B Section 7 Core Assessment GF /00 Central Zone Page 9 of 47 IIIA Effects on yield and quality IIIA Impact on the quality of plants and plant products No data have been provided. The applicant described effects on thousand grain weight by mistake. In contrast to typical quality parameters like protein content, hectolitre weight, the thousand grain weight is a yield defining parameter. So far, negative effects on the quality of other herbicides containing florasulam or clopyralid have not been reported yet. IIIA Effects on the processing procedure No data have been provided. The residue pattern of the active substances as described in Annex IIIA, Section 4, Point 8.3, together with the lack of evidence from similar commercial herbicides suggests that GF-2463 would have no effect on brewing or baking processes. IIIA Effects on the yield of treated plants and plant products Yield data of the efficacy trials have not been reported. According to the relevant EPPO standards yield data are available from the selectivity tests (Trial design and methods are described in the following chapter 6.2.1). Julius Kühn-Institut

368 Part B Section 7 Core Assessment GF /00 Central Zone Page 10 of 47 Winter cereals (use 001): The effects on yield was studied following the EPPO guideline 1/93 (3) Weeds in cereals. Selectivity trials were conducted to establish whether treatments with GF-2463 would have any effect on the yield of treated cereals. GF-2463 was applied at the proposed label rate of 0.2 L/ha and at double the proposed label rate. Yield data were presented from 7 trials in winter wheat, 6 in winter barley, 5 in rye, 5 in triticale, 2 trials in spelt and further from 4 trials in spring wheat, 6 in spring barley, 5 in oats and 3 in durum wheat. All trials were conducted in Germany and comprised two application timings, covering the window of application for winter cereals (BBCH 13 to 32) and spring cereals (BBCH 13 to 30). For none of these crops, significant reductions in yield could be observed (Tab ; ). Therefore, it is submitted that the application of GF-2463 at the proposed label rate of 0.2 L/ha is safe to winter wheat, winter barley, winter triticale, winter rye and spelt from BBCH 13 growth stage (three leaves) to BBCH 32 stage (second node), and to spring wheat, spring barley, spring oats and durum wheat from BBCH 13 growth stage (three leaves) to BBCH 30 stage (end of tillering). Tab : Yield effect in selectivity trials in winter cereals in the maritime EPPO zone, 25 trials, Germany, Tab : Yield effect in selectivity trials in spring cereals in the maritime EPPO zone, 18 trials, Germany, IIIA1 6.2 Adverse effects IIIA Phytotoxicity to host crop Material and methods Julius Kühn-Institut

369 Part B Section 7 Core Assessment GF /00 Central Zone Page 11 of 47 Data on phytotoxicity in efficacy trials have not been reported. The phytotoxicity to the host crops was studied following the EPPO standard 1/135 (3) Phytotoxicity assessment. Data are presented from phytotoxicity assessments carried out in selectivity (Tab ; ) and efficacy trials. The trials did comprise a total of 11 varieties of winter wheat, 7 varieties of winter barley, 6 varieties of rye and 4 varieties of triticale, 1 variety of spelt, 7 varieties of spring wheat, 5 varieties of spring barley, 8 varieties of oats and 2 varieties of durum wheat. The trials were sprayed in spring at growth stages ranging from BBCH 13 to BBCH 32 for winter cereals and from BBCH 13 to BBCH 30 for spring cereals, covering the anticipated period of application. Tab : Number of selectivity trials, Germany Winter cereals (use 001) 25 Spring cereals (use 002) 18 total 43 Tab : Guidelines and trial design. GEP Yes (all) EPPO-standards Yes (all) plot design, plot size RCB (all) trials per crop winter wheat (7), winter barley (6), winter rye (5), triticale (5), spelt (2) spring wheat (4), spring barley (6), spring oat (5), durum (3) application date winter cereals : spring cereals: reference product Hoestar Super (0.2 and 0.4 kg/ha) Results Winter cereals (use 001): Phytotoxicity symptoms were rare (Tab ). If symptoms of injury were noticed, mostly it concerned chlorosis (lighter green leaves) that appeared around 7 days after application. The presence of phytotoxic symptoms was related to unfavourable growth conditions known to influence selectivity of ALS products. Symptoms were of temporary nature and disappeared in general seven days later. Whenever phytotoxicity symptoms were noticed after GF-2463 treatments, it did not affect the crop yield. The total absence of injury in the majority of the trials, and the temporary nature of the injury if present, demonstrate that GF-2463 is safe to winter wheat, winter barley, winter triticale, winter rye and spelt from BBCH 13 growth stage (three leaves) to BBCH 32 stage (second node), and to spring wheat, spring barley, spring oats and durum wheat from BBCH 13 growth stage (three leaves) to BBCH 30 stage (end of tillering), even in case of spray overlap. Julius Kühn-Institut

370 Part B Section 7 Core Assessment GF /00 Central Zone Page 12 of 47 Tab : Phytotoxicity (%) at single (N) / double (2 N) dose rate in selectivity trials in winter cereals the maritime EPPO zone, 25 trials, Germany, Spring cereals (use 002): Similar to the results in winter cereals, spring cereals did not show any significant damage after treatment with GF A maximum damage of 10% was observed in 2 of 18 trials but only in a short term (Tab ). Tab : Phytotoxicity (%) at single (N) / double (2 N) dose rate in selectivity trials in spring cereals the maritime EPPO zone, 18 trials, Germany, Julius Kühn-Institut