Conclusion on the peer review of the pesticide risk assessment of the active substance topramezone 1

Transcription

1 EFSA Journal 2014;12(2):3540 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance topramezone 1 ABSTRACT European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State France, for the pesticide active substance topramezone are reported. The context of the peer review was that required by Commission Regulation (EU) No 188/2011. The conclusions were reached on the basis of the evaluation of the representative use of topramezone as a herbicide on maize. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified that the potential for groundwater exposure above the parametric drinking water limit of 0.1µg/L that applies to pesticide active substances and their relevant metabolites, was assessed as high in the vulnerable groundwater situations, that are represented by the geoclimatic conditions of all eight pertinent FOCUS groundwater scenarios and a high long-term risk to mammals is indicated with the available data. European Food Safety Authority, 2014 KEY WORDS topramezone, peer review, risk assessment, pesticide, herbicide 1 On request from the European Commission, Question No EFSA-Q , approved on 10 January Correspondence: pesticides.peerreview@efsa.europa.eu Suggested citation: European Food Safety Authority, Conclusion on the peer review of the pesticide risk assessment of the active substance topramezone. EFSA Journal 2014;12(2):3540, 82 pp. doi: /j.efsa Available online: European Food Safety Authority, 2014

2 SUMMARY Topramezone (formerly BAS 670H) is a new active substance for which in accordance with Article 6(2) of Council Directive 91/414/EEC France (hereinafter referred to as the RMS ) received an application from BASF Aktiengesellschaft for approval. Complying with Article 6(3) of Directive 91/414/EEC, the completeness of the dossier was checked by the RMS. The European Commission recognised in principle the completeness of the dossier by Commission Decision 2003/850/EC. The RMS provided its initial evaluation of the dossier on topramezone in the Draft Assessment Report (DAR), which was received by the EFSA on 21 July The peer review was initiated on 26 July 2007 by dispatching the DAR for consultation of the Member States and the applicant BASF Belgium. In accordance with Commission Regulation (EU) No 188/2011 Article 11(6), additional information was requested. The RMS s evaluation of the additional information was submitted to the EFSA in the format of a revised DAR and addenda. The revised DAR and addenda were dispatched for consultation of the Member States and the applicant BASF Nederland B.V. on 9 August Following consideration of the comments received on the DAR, it was concluded that EFSA should conduct an expert consultation in the areas of mammalian toxicology, environmental fate and behaviour and ecotoxicology and EFSA should adopt a conclusion on whether topramezone can be expected to meet the conditions provided for in Article 5 of Directive 91/414/EEC, in accordance with Article 8 of Commission Regulation (EU) No 188/2011. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of topramezone as a herbicide on maize, as proposed by the applicant. Full details of the representative uses can be found in Appendix A to this report. In the section on identity, physical/chemical/technical properties and methods of analysis a data gap has been identified for verification of the extraction efficiency of the proposed enforcement method for food of plant origin. Data gaps were identified in the mammalian toxicology area to assess the relevance of one impurity present in the technical specification and to provide medical data on plant manufacturing personnel. In the area of residues no data gaps, issues not finalised or critical areas of concern were identified. The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at EU level for the representative uses assessed. The potential for groundwater exposure consequent to these representative uses, above the parametric drinking water limit of 0.1µg/L that applies to pesticide active substances and their relevant metabolites, was assessed as high in the vulnerable groundwater situations, that are represented by the geoclimatic conditions of all 8 FOCUS groundwater scenarios. This was the case for both the active substance topramezone and its metabolite M670H05, that was concluded as relevant for groundwater based on the available mammalian toxicology information. A high long-term risk to mammals was concluded for all representative uses. A high risk to aquatic plants was also indicated in 1/8 FOCUS surface water scenarios for the representative use to maize at 75 g a.s./ha. All other areas of the ecotoxicological risk assessment were addressed. Risk mitigation measures to protect aquatic plants and non-target terrestrial plants were indicated. EFSA Journal 2014;12(2):3540 2

3 TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background... 4 The active substance and the formulated product... 7 Conclusions of the evaluation Identity, physical/chemical/technical properties and methods of analysis Mammalian toxicity Residues Environmental fate and behaviour Ecotoxicology Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Soil Ground water Surface water and sediment Air List of studies to be generated, still ongoing or available but not peer reviewed Particular conditions proposed to be taken into account to manage the risk(s) identified Concerns Issues that could not be finalised Critical areas of concern Overview of the concerns identified for each representative use considered References Appendices Abbreviations EFSA Journal 2014;12(2):3540 3

4 BACKGROUND In accordance with Article 80(1)(a) of Regulation (EC) No 1107/2009, 3 Council Directive 91/414/EEC 4 continues to apply with respect to the procedure and conditions for approval for active substances for which a decision recognising in principle the completeness of the dossier was adopted in accordance with Article 6(3) of that Directive before 14 June Commission Regulation (EU) No 188/ (hereinafter referred to as the Regulation ) lays down the detailed rules for the implementation of Council Directive 91/414/EEC as regards the procedure for the assessment of active substances which were not on the market on 26 July This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicant(s) for comments on the initial evaluation in the Draft Assessment Report (DAR) provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate. In accordance with Article 8 of the Regulation, EFSA is required to adopt a conclusion on whether the active substance is expected to meet the conditions provided for in Article 5 of Directive 91/414/EEC within 4 months from the end of the period provided for the submission of written comments, subject to an extension of 2 months where an expert consultation is necessary, and a further extension of up to 8 months where additional information is required to be submitted by the applicant(s) in accordance with Article 8(3). In accordance with Article 6(2) of Council Directive 91/414/EEC France (hereinafter referred to as the RMS ) received an application from BASF Aktiengesellschaft for approval of the active substance topramezone (formerly BAS 670H). Complying with Article 6(3) of Directive 91/414/EEC, the completeness of the dossier was checked by the RMS. The European Commission recognised in principle the completeness of the dossier by Commission Decision 2003/850/EC. 6 The RMS provided its initial evaluation of the dossier on topramezone in the DAR, which was received by the EFSA on 21 July 2006 (France, 2006). The peer review was initiated on 26 July 2007 by dispatching the DAR to Member States and the applicant BASF Belgium for consultation and comments. In addition, the EFSA conducted a public consultation on the DAR. The comments received were collated by the EFSA and forwarded to the RMS for compilation and evaluation in the format of a Reporting Table. The applicant was invited to respond to the comments in column 3 of the Reporting Table. The comments and the applicant s response were evaluated by the RMS in column 3 of the Reporting Table. EFSA s further consideration of the comments and the RMS response is reflected in the conclusions set out in column 4 of the Reporting Table (final version dated 16 February 2009). All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration were compiled by the EFSA in the format of an Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the Evaluation Table were reported in the final column of the Evaluation Table (final version dated 21 November 2012). 3 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, , p Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, , p. 1-32, as last amended. 5 Commission Regulation (EU) No 188/2011 of 25 February 2011 laying down detailed rules for the implementation of Council Directive 91/414/EEC as regards the procedure for the assessment of active substances which were not on the market 2 years after the date of notification of that Directive. OJ L 53, , p Commission Decision 2003/850/EC of 4 December 2003 recognising in principle the completeness of the dossiers submitted for detailed examination in view of the possible inclusion of BAS 670H and silver thiosulphate in Annex I to Council Directive 91/414/EEC concerning the placing of plant protection products on the market. OJ L 322, , p EFSA Journal 2014;12(2):3540 4

5 In accordance with Article 11(6) of Commission Regulation (EU) No 188/2011 additional information was requested. The RMS s evaluation of the additional information was submitted to the EFSA in the format of a revised DAR and addenda (France, 2013). The addenda were dispatched for consultation of the Member States and the applicant BASF Nederland B.V. on 9 August The comments received on the revised DAR and addenda were collated by the EFSA and forwarded to the RMS for compilation and evaluation in the format of a second Reporting Table. The applicant was invited to respond to the comments in column 3 of the second Reporting Table. The comments and the applicant s response were evaluated by the RMS in column 3 of the second Reporting Table (final version dated 21 November 2012). The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 8(3) of the Regulation were considered in a telephone conference between the EFSA, the RMS, and the European Commission on 21 November On the basis of the comments received, the applicant s response to the comments and the RMS s evaluation thereof it was concluded that additional information should be requested from the applicant and that the EFSA should organise an expert consultation in the areas of mammalian toxicology, environmental fate and behaviour and ecotoxicology. The outcome of the telephone conference, together with EFSA s further consideration of the comments is reflected in the conclusions set out in column 4 of the second Reporting Table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in an expert consultation and the additional information to be submitted by the applicant, were compiled by the EFSA in the format of a second Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the second Evaluation Table, together with the outcome of the expert consultation where this took place, were reported in the final column of the second Evaluation Table. A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in December This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulation evaluated on the basis of the representative uses as a herbicide on maize, as proposed by the applicant. A list of the relevant end points for the active substance as well as the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the Peer Review Report, which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The Peer Review Report (EFSA, 2014) comprises the following documents, in which all views expressed during the course of the peer review, including minority views, can be found: the comments received on the DAR, the comments received on the revised DAR and addenda, the Reporting Table 1 (16 February 2009), the Reporting Table 2 (21 November 2012), the Evaluation Table 1 (21 November 2012), the Evaluation Table 2 (5 December 2013), EFSA Journal 2014;12(2):3540 5

6 the reports of the scientific consultation with Member State experts (where relevant), the comments received on the assessment of the additional information (where relevant), the comments received on the draft EFSA conclusion. Given the importance of the DAR including its addendum (compiled version of October 2013 containing all individually submitted addenda (France, 2013)) and the Peer Review Report, both documents are considered respectively as background documents A and B to this conclusion. It is recommended that this conclusion report and its background documents would not be accepted to support any registration outside the EU for which the applicant has not demonstrated to have regulatory access to the information on which this conclusion report is based. EFSA Journal 2014;12(2):3540 6

7 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Topramezone is the ISO common name for [3-(4,5-dihydro-1,2-oxazol-3-yl)-4-mesyl-o-tolyl](5- hydroxy-1-methylpyrazol-4-yl)methanone (IUPAC). The active substance was formerly coded as BAS 670 H. The representative formulated product for the evaluation was BAS H, a suspension concentrate (SC) containing 336 g/l pure topramezone. The representative use evaluated comprises spray application on maize against dicotyledonous weeds and grasses. Full details of the GAP can be found in the list of end points in Appendix A. CONCLUSIONS OF THE EVALUATION 1. Identity, physical/chemical/technical properties and methods of analysis The following guidance documents were followed in the production of this conclusion: SANCO/3030/99 rev.4 (European Commission, 2000) and SANCO/825/00 rev. 8.1 (European Commission, 2010). The minimum purity of the active substance is 970 g/kg. The specification is based on industrial scale production. No FAO specification exists. The relevance of the impurities has not been fully addressed (see Section 2). Te assessment of the data package revealed no issues that need to be included as critical areas of concern with respect to the identity, physical, chemical and technical properties of topramezone or the representative formulation. It can be noted that pending on the outcome on the relevance of the impurities spectral data (UV/VIS, IR, NMR and MS) might be required. The main data regarding the identity of topramezone and its physical and chemical properties are given in appendix A. Adequate analytical methods are available for the determination of topramezone in technical material and in the representative formulation as well as for the determination of the respective impurities in the technical material. Residues of topramezone in food and feed of plant origin can be monitored by LC-MS/MS with LOQs of 0.01 mg/kg (dry commodities and commodities with high water, high acid and high oil content). A data gap was identified for the verification of the extraction efficiency of this method. A method to monitor residues in food of animal origin is not required considering the representative use evaluated. However a LC-MS/MS method validated at LOQ of 0.01 mg/kg in fat, muscle, liver, kidney, milk and eggs is available. It should be noted that extraction efficiency for this method has not been addressed. Appropriate LC-MS/MS methods exist for monitoring of residues in soil, water and air with LOQs of mg/kg, 0.05 µg/l and 0.1 µg/m 3 respectively. A properly validated LC-MS/MS method for determination of topramezone in urine and blood is also available (LOQ of 0.1 mg/kg for urine and 0.01 mg/kg for blood). 2. Mammalian toxicity The following guidance documents were followed in the production of this conclusion: SANCO/221/2000 rev final (European Commission, 2003), SANCO/222/2000 rev. 7 (European Commission, 2004) and SANCO/10597/2003 rev. 8.1 (European Commission, 2009). Topramezone was discussed at the Pesticides Peer Review Meeting 106 in September The batches used in the toxicological studies that were used to derive the toxicological reference values support the technical specification. The relevance of the individual impurities has been partially addressed, however the assessment of the relevance of one impurity for which a potential structural EFSA Journal 2014;12(2):3540 7

8 alert is observed in comparison with the active substance has not been clarified and a data gap has been identified on this issue (see section 7). Topramezone is incompletely absorbed after oral administration. In rats, oral absorption value would be at least 30 %, a more realistic value could not be obtained as bile and urine excretion determinations were conducted in different studies. In rabbits, oral absorption is set at 60 % based on urine excretion obtained after a low dose administration of 10 mg/kg bw topramezone. The active substance is widely distributed, poorly metabolised, and extensively excreted mainly via faeces in rats, but mainly via urine in rabbits. Low acute toxicity has been observed when topramezone is administered by the oral, dermal or inhalation routes. Topramezone is not irritating to eyes and skin, and no potential for skin sensitisation was seen in a Maximisation test of Magnusson and Kligman. The primary effect of topramezone is the inhibition of 4-hydroxyphenylpyruvate dioxygenase (HPPD) in mammalians as in plants, a key enzyme of the tyrosine catabolic pathway, leading to increased concentrations of serum tyrosine. Rats are particularly prone to hypertyrosinaemia resulting from HPPD inhibition as, unlike other species including humans, they present a low activity of the main alternative tyrosine metabolising enzyme, the tyrosine aminotransferase (TAT). A recognised toxic outcome of tyrosinaemia is ocular toxicity (corneal lesions), that is particularly high in the rat and less relevant for humans. Target organs of topramezone upon short term administration in rats are the liver, kidneys, eyes and pancreas; in mice the liver is the main affected organ, while in dogs, kidney toxicity was observed. The relevant short term NOAEL is 1.1 mg/kg bw per day from a 90-day study in rats, based on increased liver and kidney weights and diffuse degeneration of the exocrine pancreas at the LOAEL of 4.2 mg/kg bw per day. Upon long term exposure, the same target organs were identified in rats and mice; furthermore, the thyroid glands were affected in rats presenting hypertrophy, focal follicular cell hyperplasia and follicular cell adenomas. The hypothesised mode of action (MOA) mediated by UDP glucuronyltransferase (UGT), that would be recognised as not relevant to humans (ECHA, 2009) was only demonstrated to potentially occur at high dose levels. As the thyroid adenomas were reported in both sexes at low dose levels, at which level no conclusion could be drawn on the MOA, a direct effect of topramezone on the thyroid could not be ruled out suggesting that the carcinogenic effects observed in rats may be relevant to humans, which indicates that topramezone may need to be classified as a carcinogen category 2 (H351). 7 The relevant long term NOAEL (which corresponds to the NOAEL for carcinogenicity) is 0.4 mg/kg bw per day from the 2-year study in rats, based on decreased body weight and body weight gain, corneal opacity and chronic keratitis, diffuse degeneration of pancreas cells, increased liver and kidney weights and thyroid follicular cell hyperplasia, hypertrophy and follicular adenomas. Topramezone has no genotoxic potential in vivo. No indications of neurotoxicity were seen in dedicated satellite measurements included the 90-day rat toxicity study or other general toxicity studies. In the reproductive toxicity studies, topramezone elicited increased litter losses and insufficient maternal care at parental toxic doses in the 2-generation toxicity study in rats; no reproductive or offspring toxicity was observed in a 3-generation toxicity study in mice. Developmental toxicity was extensively investigated in rats, mice and rabbits; no developmental effect were seen in mice, increased skeletal variations were observed in rats when no apparent maternal toxicity was reported, and severe malformations were observed in rabbits (kidney and urethra unilateral agenesis) at low dose levels that did not elicit maternal toxicity. The latter effects indicate that topramezone may need to be classified as a developmental toxicant category 1B (H360D), which is regarded as toxic (signal word: danger ). The developmental NOAEL in rabbit is 0.5 mg/kg bw per day and the LOAEL for the teratogenic effects is 1.5 mg/kg bw per day. 7 It should be noted that classification is formally proposed and decided in accordance with Regulation (EC) No 1272/2008. Proposals for classification made in the context of the evaluation procedure under Regulation (EC) No 1107/2009 are not formal proposals. EFSA Journal 2014;12(2):3540 8

9 Medical data on plant manufacturing personnel were not provided and is therefore listed as a data gap (see section 7). Toxicity studies were provided on the metabolite M670H05 that may occur in groundwater according to environmental fate and behaviour models (see section 4) above the parametric drinking water limit of 0.1 µg/l. No genotoxic potential is attributed to the metabolite and no evidence of teratogenic effects (as reported with the parent topramezone) was observed in a rabbit developmental toxicity study. The metabolite produced non-adverse tyrosinaemia at the top dose tested of 1197 mg/kg bw per day and thyroid homeostasis changes at ca. 870 mg/kg bw per day dose level. Based on these findings, the metabolite might share the carcinogenic effects observed with the parent topramezone and therefore the metabolite is considered relevant according to the guidance document on the relevance of groundwater metabolites (European Commission, 2003) (see sections 6.2 and 9.2). The acceptable daily intake (ADI) of topramezone is mg/kg bw per day, based on the NOAEL of 0.5 mg/kg bw per day from the rabbit developmental studies, applying an increased uncertainty factor (UF) of 500; it is supported by the long term toxicity and carcinogenicity study in rats. The acceptable operator exposure level (AOEL) is mg/kg bw per day, based on the same NOAEL of 0.5 mg/kg bw per day, 500 UF applied, and correcting for the limited oral absorption by 60 %. The acute reference dose (ARfD) is mg/kg bw, based on the same NOAEL and UF as the ADI. The five times increased uncertainty factor was applied to account for the severe teratogenic effects observed at low dose levels in rabbits (1.5 mg/kg bw per day) giving a margin of safety (MOS) of 500 to the overall developmental NOAEL and of 1500 to the overall LOAEL for teratogenic effects in rabbits. Dermal absorption is 1 % when handling the concentrate formulation and 3 % when handling the inuse spray dilutions; when the adjuvant DASH HC is added to the spray dilution, the dermal absorption increases to 7 %. Operator, worker and bystander exposure were calculated with a dermal absorption value of 3.2 % when handling the spray dilution as proposed by the RMS in the revised DAR of February 2009, rounding of this value to 3 % as concluded during the experts meeting does not have an impact on the outcome of the assessment. Estimated operator exposure is below the AOEL when personal protective equipment (PPE) is used, as gloves during mixing and loading operations, and gloves and coveralls during applications according to the German model (see section 8). Estimated worker exposure is below the AOEL when PPE is considered as gloves, long sleeved shirt and long trousers (see section 8) and bystander exposure is calculated to represent at most 11 % of the AOEL. 3. Residues The assessment in the residue section below is based on the guidance documents listed in the document 1607/VI/97 rev.2 (European Commission, 1999), and the JMPR recommendations on livestock burden calculations stated in the 2004 and 2007 JMPR reports (JMPR, 2004, 2007). The metabolism of topramezone was investigated in maize with radiolabelled active substance labelled in the pyrazole and phenyl position. The application was at a 2 N rate and samples were taken during the plants development up to the final harvest. The residue level in grain was low, representing up to 0.11 mg/kg; non extractable residues represented > 75.7 % TRR. Topramezone ( 2.5 % TRR) and M670H05 ( 3.4 %) represented each mg/kg. In forage (PHI days) and straw, intended as feeding stuffs, topramezone was the main component, detected up to 40.9 % TRR (0.3 mg/kg); besides, the free acid metabolite M670H05 was at 7.2 % of the TRR (0.052 mg/kg) in maize straw. However when this metabolite was analysed for in the residue trials it was never detected at any time interval. The residue definition is therefore topramezone for the cereals group only. In the confined circa N rotational crop study, the residue level was > 0.01 mg/kg only in rotational crops from the 34 DAT planting interval. The higher residues were in mustard green and winter wheat and these samples were explored further. The parent was the major component (1.6 % EFSA Journal 2014;12(2):3540 9

10 64.4 %) in all edible raw agricultural commodities (mustard green, wheat forage, hay, grain and straw) but mg/kg in wheat grain, mg/kg in mustard green and mg/kg in wheat hay. In addition, the free acid metabolite M670H05 was observed at 10.3 % of the TRR in mustard green ( mg/kg) and 45 % of the TRR ( mg/kg) in maize grain. No significant residues were observed for longer DAT planting intervals. It can therefore be concluded that no significant residues will be found in rotational crops. Animal metabolism studies are not needed for the representative use however they were provided and it was agreed that the residue definition was topramezone only. Sufficient residue trials data were available on maize for both the North and South of Europe all residues were below the LOQ 0.01 mg/kg for grain and 0.05 mg/kg for forage and straw. Storage stability data for the residue samples demonstrate that residues are stable for 26 months at -20 C this covers the period of storage that the residue samples were stored for. For the consumer the maximum intakes were 0.2 % of the ADI and 0.7 % of the ARfD, the consumer risk assessment can be considered finalised. The proposed MRL for maize grain is 0.01 mg/kg*. 4. Environmental fate and behaviour Topramezone was discussed at the Pesticides Peer Review Meeting 104 on environmental fate and behaviour in September In soil laboratory incubations under aerobic conditions in the dark, topramezone exhibited medium to very high persistence, forming the major (>10 % applied radioactivity (AR)) metabolite M670H05 (max. 19 % AR), which exhibited moderate persistence (result from a single reliable soil incubation). Mineralisation of the phenyl and pyrazole ring 14 C radiolabels to carbon dioxide accounted for 0 11 % AR after 120 days. The formation of unextractable residues (not extracted by sodium dihydrogen phosphate/ methanol) for these radiolabels accounted for % AR after 122 days. In anaerobic soil incubations topramezone exhibited moderate persistence with unextracted residues being the largest sink for the applied radiolabels. The metabolite M670H01 was identified in these anaerobic incubations, but was considered to have not reached levels triggering further consideration, though aerobic soil incubations are available for this metabolite, indicating it exhibits medium to very high persistence. A laboratory soil photolysis study was considered to indicate that photodegradation at the soil surface does not represent a significant process contributing to transformation. Topramezone exhibited very high to medium mobility in soil, with mobility increasing as soil ph increased. M670H05 exhibited very high soil mobility and M670H01 exhibited very high to high soil mobility, again like topramezone with the highest mobility being exhibited in alkaline soils. In satisfactory field dissipation studies carried out at three sites in Germany, one in Sweden and two in Spain (spray application to the soil surface on bare soil plots in May) topramezone exhibited moderate to very high persistence. M670H05 exhibited moderate to medium persistence. Field study DT 50 values were accepted as being reasonable estimates of degradation and were normalised to FOCUS reference conditions (20 C and PF2 soil moisture) using the time step normalisation procedure 8 in accordance with FOCUS (2006) kinetics guidance, after removing sampling time points before 10 mm of rain had fallen, as described in an EFSA PPR Panel (2010) opinion. The utility of following the opinion is to minimise the potential impact of surface processes on the transformation rates estimated. This 10 mm criteria meant that the Spanish trial sites were not normalised to reference conditions. In two field leaching studies of up to 4 years duration at sites where topsoils were acidic (ph ca. 6) groundwater well samples (groundwater depth 1.2 m or shallower and 1.9 3m) had concentrations of topramezone and M670H01 at up to µg/l and µg/l respectively. Values for M670H05 were above the parametric groundwater trigger for drinking water of 0.1 µg/l at up to µg/l at one of these two experimental sites (that where topsoil was sand and organic carbon was ca. 0.6 % and 8 Using a Q 10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of 0.7 EFSA Journal 2014;12(2):

11 groundwater depth was m). It should be noted that these experiments do not cover the higher leaching potential that will be encountered under neutral or alkaline topsoil conditions. In laboratory incubations in dark aerobic natural sediment water systems, topramezone exhibited moderate to very high persistence, forming the major metabolite M670H01 (max % AR in sediment). The unextractable sediment fraction (not extracted by sodium dihydrogen phosphate/ methanol) was the major sink for the phenyl and pyrazole ring 14 C radiolabels in the loam / 5.3 % oc sediment system, accounting for up to 79 % AR at study end (120 days). Mineralisation of these radiolabels accounted for only % AR at the end of the study. As in one of the systems (loam / 5.3 % oc sediment) unextracted residues were > 70 % and mineralisation was < 5 % an unless clause in the uniform principles for decision making on product authorisations is triggered requiring it to be demonstrated that there are not unacceptable effects from these less readily extractable residues on non target species. This is discussed further in section 5. In a water/sediment study carried out under outdoor conditions the metabolite M670H05 was a major transformation product accounting for 51 % AR in the water of the system after 100 days. The necessary surface water and sediment exposure assessments (Predicted environmental concentrations (PEC) calculations) were carried out for the metabolites M670H05 and M670H01, using the FOCUS (FOCUS, 2001) step 1 and step 2 approach (version 1.1 of the Steps 1-2 in FOCUS calculator). For the active substance topramezone, appropriate step 3 (FOCUS, 2001) and step 4 calculations were available. 9 The step 4 calculations appropriately followed the FOCUS (FOCUS, 2007) guidance, with no-spray drift buffer zones of up to 20 m being implemented (representing a % spray drift reduction), and combined no-spray buffer zones with vegetative buffer strips of up to 20 m (reducing solute flux and volume in run-off by 80 % and these values for erosion and sediment mass by 95 %) being implemented for the run-off scenarios. The SWAN tool (version 1.1.4) was appropriately used to implement these mitigation measures in the simulations. However, risk managers and others may wish to note that whilst run-off mitigation is included in the step 4 calculations available, the FOCUS (FOCUS, 2007) report acknowledges that for substances with K Foc < 2000 ml/g (i.e. topramezone), the general applicability and effectiveness of run-off mitigation measures had been less clearly demonstrated in the available scientific literature, than for more strongly adsorbed compounds. The necessary groundwater exposure assessments were appropriately carried out using FOCUS (FOCUS, 2009) scenarios and the models PEARL and PELMO for the active substance topramezone and the metabolite M670H05, (which has been assessed as relevant for groundwater, see section 2). The potential for groundwater exposure from the representative uses by topramezone above the parametric drinking water limit of 0.1 µg/l was concluded to be high in geoclimatic situations that are represented by all eight pertinent FOCUS groundwater scenarios following the reasonable assumption that a good proportion of any confined vulnerable aquifer will be overlain by soil with ph In addition a second set of simulations was carried out. These simulations matched soil adsorption with the ph defined for the soil column for each FOCUS scenario. When this approach was followed only 4/8 FOCUS groundwater scenarios (those with topsoil ph < 6.6 excluding Piacenza (ph 6.3)) had modelled annual average 80 th percentile recharge concentrations leaving the top 1 m predicted to be below the parametric drinking water limit of 0.1 µg/l. Risk managers and others should note that FOCUS scenario selection was based on vulnerability defined by soil profile texture/hydraulic conductivity and climate, with no consideration of the spatial distribution of soil ph. Few confined aquifers might be expected to be overlain by exclusively acidic soils as have been described for the FOCUS scenarios: Hamburg, Okehampton, Porto and Sevilla, which are the only situations that the available FOCUS simulations have demonstrated would have potential for groundwater exposure by topramezone below the parametric drinking water limit of 0.1 µg/l. For the relevant metabolite M670H05, the potential for groundwater exposure from the representative uses 9 Simulations correctly utilised the agreed Q10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of Simulations correctly utilised the agreed Q10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of When ph is measured in CaCl 2(aq). EFSA Journal 2014;12(2):

12 above the parametric drinking water limit of 0.1 µg/l was also concluded to be high in geoclimatic situations that are represented by all eight pertinent FOCUS groundwater scenarios (soil adsorption of this metabolite was low at all the ph investigated). The PEC in soil, surface water, sediment, and groundwater covering the representative uses assessed can be found in Appendix A of this conclusion. 5. Ecotoxicology The risk assessment was based on the following documents: European Commission (2002a, 2002b, 2002c) and SETAC (2001). Topramezone was discussed at the Pesticides Peer Review Expert Meeting 105 (September, 2013). A low acute and long-term risk to birds from dietary exposure was concluded. A low acute risk to wild mammals was also concluded. The long-term risk to mammals was indicated to be high using first-tier risk assessment assumptions. A refined risk assessment was available for the wood mouse (Apodemus syvalticus) and the European hare (Lepus europaeus). These focal species were selected using field studies performed in Southern France and Austria and therefore there is uncertainty in extrapolation to other areas of Europe. The risk to wood mice was refined using the proportion of food items in the diet (PD) and the proportion of diet obtained in the treated area (PT). No suitable data were available to refine PT and PD for the European hare and therefore were not refined. A refined time-weighted average factor was also calculated for plant material. However, taking account of the available risk assessments, a high long-term risk to both the European hare and the wood mouse was concluded. Therefore, a data gap is identified to address the long-term risk to wild mammals was identified. A low risk to birds and mammals from consumption of contaminated water was concluded (relevant for both representative uses to maize). Data and risk assessments were available for both the active substance and the formulated product with the adjuvant. A low risk to fish, aquatic invertebrates and algae from topramezone was concluded using FOCUS step 1 exposure estimates. The available FOCUS step 3 risk assessment for higher aquatic plants indicated a low risk without the need for risk mitigation in three FOCUS surface water scenarios for the representative use at 75 g a.s./ha and in 5 scenarios for the representative use at 50 g a.s./ha. Risk mitigation measures (such as no-spray buffer zones and vegetative grass buffer strips) were included in a refined risk assessment and indicated a low risk with the exception of the D4 scenario for representative use at 75 g a.s./ha. Therefore, a data gap is concluded for further information to address the risk to aquatic plants in situations which are represented by the D4 scenario (relevant only for the representative use to maize at 75 g a.s./ha). A low risk to aquatic organisms from surface water metabolites M670H05 and M670H01 was concluded. As discussed in section 4, a high amount of unextracted residues and low mineralisation was found in the available sediment water studies. It is acknowledged that topramezone does not exhibit high chronic toxic to Daphnia magna and metabolite M670H01 is not highly chronically toxic to Chironomus riparius. Furthermore, a study with the rooted macrophyte, Myriophyllum aquaticum, was available and indicated lower sensitivity to topramezone than Lemna gibba. However, there is no agreed methodology to characterise the long-term risk to sediment dwelling organisms from unextracted residues in sediment. A data gap is therefore concluded for information to characterise the risk from the unextracted residues in sediment (relevant for both representative uses on maize). On the basis of the available risk assessment a low risk to honey bees, non-target arthropods, earthworms, soil macro-organisms and soil micro-organisms was concluded. A low risk to soil organisms from the soil metabolite M670H05 was also concluded. A low risk to non-target plants was indicated provided risk mitigation measures such as a no-spray buffer zone of 5 m are used (relevant for both representative uses to maize). A low risk to organisms involved in biological methods of sewage treatment was concluded for the representative use of topramezone. EFSA Journal 2014;12(2):

13 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments 6.1. Soil Compound (name and/or code) Topramezone Metabolite M670H05 Persistence Moderate to very high persistence. European field dissipation studies biphasic decline DT days (DT >1000 days). Moderate to medium persistence. European field dissipation studies single first-order DT days. Ecotoxicology Low risk to soil dwelling organisms. Low risk to soil dwelling organisms. EFSA Journal 2014;12(2):

14 6.2. Ground water Compound (name and/or code) Mobility in soil >0.1 μg/l 1m depth for the representative uses (at least one FOCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicological activity Topramezone Very high to medium mobility. K Foc ml/g, ph dependent (lower mobility as ph decreases). Yes at all 8 FOCUS scenarios µg/L using adsorption for topsoil ph > 6.7. Yes at 4/8 FOCUS scenarios when the topsoil ph defined for the scenario is used ( µg/l at Piacenza (ph 6.3), Thiva & Kremsmunster (ph 7) & Châteaudun (ph 7.3)). Yes Yes High risk to aquatic organisms indicated in the surface water risk assessment (FOCUS sw D4 scenario for the representative use to maize at 75 g a.s./ha only). M670H05 Very high mobility. K Foc ml/g Yes at all 8 FOCUS scenarios µg/l. Also at µg/l at a German field leaching experimental site. No data Yes, based on the carcinogenic properties of the parent compound topramezone. (a) Low risk to aquatic organisms indicated in the surface water risk assessment. (a): It should be noted that classification is formally proposed and decided in accordance with Regulation (EC) No 1272/2008. Proposals for classification made in the context of the evaluation procedure under Regulation (EC) No 1107/2009 are not formal proposals. EFSA Journal 2014;12(2):

15 6.3. Surface water and sediment Compound (name and/or code) Topramezone Ecotoxicology High risk to aquatic plants in situations represented by the FOCUS sw D4 scenario for the representative use to maize at 75 g a.s./ha. A low risk to aquatic organisms was indicated for all other scenarios when risk mitigation measures are considered. Data gap regarding the risk to sediment dwelling organisms from unextracted residues in sediment. Metabolite M670H05 Metabolite M670H01 Low risk to aquatic organisms. Low risk to aquatic organisms Air Compound (name and/or code) Topramezone Toxicology Rat LC 50 inhalation > 5.05 mg/l air/4h, head-nose exposure to dust aerosol, no classification required. EFSA Journal 2014;12(2):

16 7. List of studies to be generated, still ongoing or available but not peer reviewed This is a complete list of the data gaps identified during the peer review process, including those areas where a study may have been made available during the peer review process but not considered for procedural reasons (without prejudice to the provisions of Article 7 of Directive 91/414/EEC concerning information on potentially harmful effects). Verification of the extraction efficiency of the proposed enforcement method for food of plant origin (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see section 1). Assessment of the relevance of one impurity present in the technical specification (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see section 2). Medical data on plant manufacturing personnel (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see section 2). Further information is required to address the long-term risk to mammals (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see section 5). Further information is required to address the risk to aquatic plants in situations which are represented by the D4 FOCUS surface water scenario (relevant for the representative use to maize at 75 g a.s./ha; submission date proposed by the applicant: unknown; see section 5). Information to characterise the long-term risk to sediment dwelling organisms from the unextracted residues in sediment (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see section 5). 8. Particular conditions proposed to be taken into account to manage the risk(s) identified Estimated operator exposure is below the AOEL when PPE is used, as gloves during mixing and loading operations, and gloves and coveralls during applications according to the German model (see section 2). Estimated worker exposure is below the AOEL when PPE is considered as gloves, long sleeved shirt and long trousers (see section 2). Risk mitigation measures to protect aquatic plants are required in the following FOCUS surface water scenarios: R1, R2 (e.g. 10 m no-spray buffer zone and a 10 m vegetative grass strip) and R4 (e.g. 20 m no-spray buffer zone and a 20 m vegetative grass strip), (relevant for both representative uses to maize, see section 5). Risk mitigation measures to protect non-target terrestrial plants are required (e.g. 5 m no-spray buffer zone) (relevant for both representative uses to maize, see section 5). 9. Concerns 9.1. Issues that could not be finalised An issue is listed as an issue that could not be finalised where there is not enough information available to perform an assessment, even at the lowest tier level, for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC and where the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses). EFSA Journal 2014;12(2):

17 No issues were identified that could not be finalised Critical areas of concern Peer review of the pesticide risk assessment of the active substance topramezone An issue is listed as a critical area of concern where there is enough information available to perform an assessment for the representative uses in line with the Uniform Principles of Annex VI to Directive 91/414/EEC, and where this assessment does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. An issue is also listed as a critical area of concern where the assessment at a higher tier level could not be finalised due to a lack of information, and where the assessment performed at the lower tier level does not permit to conclude that for at least one of the representative uses it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. 1. A high potential for groundwater exposure above the legal parametric drinking water limit of 0.1µg/L by the active substance topramezone in vulnerable aquifers in geoclimatic situations represented by all eight relevant FOCUS groundwater scenarios is identified for all the representative uses assessed. 2. The metabolite M670H05 is concluded as a relevant groundwater metabolites based the carcinogenic properties of the parent compound. According to the current assessment, metabolite M670H05 has the potential to contaminate groundwater above the legal parametric drinking water limit of 0.1 μg/l set for relevant metabolites in all the FOCUS groundwater scenarios for all the representative uses assessed. 3. A high long-term risk to mammals was concluded for all representative uses assessed Overview of the concerns identified for each representative use considered (If a particular condition proposed to be taken into account to manage an identified risk, as listed in section 8, has been evaluated as being effective, then risk identified is not indicated in this table.) Representative use Maize 75g/ha Maize 50g/ha Operator risk Worker risk Bystander risk Consumer risk Risk to wild non target terrestrial vertebrates Risk to wild non target terrestrial organisms other than vertebrates Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified Assessment not finalised Risk identified X 3 X 3 Assessment not finalised Risk identified Assessment not finalised Risk to aquatic Risk identified 1/8 FOCUS SW scenarios EFSA Journal 2014;12(2):

18 organisms Groundwater exposure active substance Groundwater exposure metabolites Comments/Remarks Peer review of the pesticide risk assessment of the active substance topramezone Assessment not finalised Legal parametric value breached X 1 X 1 Assessment not finalised Legal parametric value breached (a) X2 X 2 Parametric value of 10µg/L (b) breached Assessment not finalised The superscript numbers in this table relate to the numbered points indicated in sections 9.1 and 9.2. Where there is no superscript number see sections 2 to 6 for further information. (a): When the consideration for classification made in the context of this evaluation under Regulation (EC) No 1107/2009 is confirmed under Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December. (b): Value for non relevant metabolites prescribed in SANCO/221/2000-rev 10-final, European Commission, EFSA Journal 2014;12(2):