Conclusion on the peer review of the pesticide risk assessment of the active substance pyraflufen-ethyl 1

Transcription

1 EFSA Journal 2015;13(2):4001 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance pyraflufen-ethyl 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT 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 the Netherlands, for the pesticide active substance pyraflufen-ethyl are reported. The context of the peer review was that required by Commission Regulation (EU) No 1141/2010 as amended by Commission Implementing Regulation (EU) No 380/2013. The conclusions were reached on the basis of the evaluation of the representative uses of pyraflufenethyl as a herbicide on potato and grape vines. 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. European Food Safety Authority, 2015 KEY WORDS pyraflufen-ethyl, peer review, risk assessment, pesticide, herbicide 1 On request from the European Commission, Question No EFSA-Q , approved on 22 January Correspondence: pesticides.peerreview@efsa.europa.eu Suggested citation: EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance pyraflufen-ethyl. EFSA Journal 2015;13(2):4001, 80 pp. doi: /j.efsa Available online: European Food Safety Authority, 2015

2 SUMMARY Commission Regulation (EU) No 1141/2010, as amended by Commission Implementing Regulation (EU) No 380/2013, (hereinafter referred to as the Regulation ) lays down the procedure for the renewal of the approval of a second group of active substances and establishes the list of those substances. Pyraflufen-ethyl is one of the active substances listed in the Regulation. The RMS provided its initial evaluation of the dossier on pyraflufen-ethyl in the Renewal Assessment Report (RAR), which was received by the EFSA on 10 January The peer review was initiated on 27 January 2014 by dispatching the RAR for consultation of the Member States and the applicant Nihon Nohyaku Co. Ltd. Following consideration of the comments received on the RAR, it was concluded that the EFSA should conduct an expert consultation in the areas of mammalian toxicology, environmental fate and behaviour and ecotoxicology and that the EFSA should adopt a conclusion on whether pyraflufenethyl can be expected to meet the conditions provided for in Article 4 of Regulation (EC) No 1107/2009 of the European Parliament and the Council. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of pyraflufen-ethyl as a herbicide on potato and grape vines, as proposed by the applicant. Full details of the representative uses can be found in Appendix A to this report. In the area of identity, physical/chemical/technical properties and methods of analysis a data gap regarding the method of analysis for E-2 in surface water was identified. In the section mammalian toxicology, one data gap and one critical area of concern have been identified. The data gap is related to the need for further assessment of the toxicological relevance of the impurities in the technical specification. The critical area of concern is due to the fact that the batches used in the toxicity studies cannot be considered as representative of the technical specification. The assessment of the residue data package revealed no issues that need to be included as a critical area of concern with respect to the consumer exposure assessment. 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. For these representative uses, the potential for groundwater exposure above the parametric drinking water limit of 0.1 μg/l was concluded to be low in the geoclimatic situations represented by all the pertinent FOCUS groundwater scenarios. In the section on ecotoxicology data gaps have been identified to further address the risk for aquatic organisms from pyraflufen-ethyl and its pertinent metabolites E-1 and E-3 for some of the FOCUSsw scenarios. In addition data gaps have been also identified to address the risk to aquatic plants from pyraflufen-ethyl and to aquatic organisms from the metabolite E-2. A data gap has also been identified for further data to address the risk to non target terrestrial plants. In addition, the data gap and critical area of concern as reported in the mammalian toxicology section also apply to the ecotoxicology section. EFSA Journal 2015;13(2):4001 2

3 TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 3 Background... 4 The active substance and the formulated product... 6 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 EFSA Journal 2015;13(2):4001 3

4 BACKGROUND Commission Regulation (EU) No 1141/ as amended by Commission Implementing Regulation (EU) No 380/ (hereinafter referred to as the Regulation ) lays down the detailed rules for the procedure of the renewal of the approval of a second group of active substances. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicant for comments on the initial evaluation in the Renewal Assessment Report (RAR) provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate. In accordance with Article 16 of the Regulation, if mandated, EFSA is required to adopt a conclusion on whether the active substance is expected to meet the conditions provided for in Article 4 of Regulation (EC) No 1107/2009 within 6 months from the receipt of the mandate, subject to an extension of up to 9 months where additional information is required to be submitted by the applicant(s) in accordance with Article 16(3). In accordance with Article 4 of the Regulation, the Netherlands (hereinafter referred to as the RMS ) received an application from Nihon Nohyaku Co. Ltd for the renewal of approval of the active substance pyraflufen-ethyl. Complying with Article 11 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the Commission and EFSA about the admissibility. The RMS provided its initial evaluation of the dossier on pyraflufen-ethyl in the RAR, which was received by the EFSA on 10 January 2014 (the Netherlands, 2014). The peer review was initiated on 27 January 2014 by dispatching the RAR to Member States and the applicant Nihon Nohyaku Co. Ltd for consultation and comments. In addition, the EFSA conducted a public consultation on the RAR. 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. The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 16(3) of the Regulation were considered in a telephone conference between the EFSA, the RMS, and the European Commission on 22 May 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. According to Art. 16(2) of the Regulation COM decided to consult the EFSA. The mandate was received on 27 May 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 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 an Evaluation Table. 3 Commission Regulation (EU) No 1141/2010 of 7 December 2010 laying down the procedure for the renewal of the inclusion of a second group of active substances in Annex I to Council Directive 91/414/EEC and establishing the list of those substances. OJ L 322, , p Commission Implementing Regulation (EU) No 380/2013 of 25 April 2013 amending Regulation (EU) No 1141/2010 as regards the submission of the supplementary complete dossier to the Authority, the other Member States and the Commission. OJ L 116, , p. 4. EFSA Journal 2015;13(2):4001 4

5 The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the Evaluation Table, together with the outcome of the expert consultation where this took place, were reported in the final column of the 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 November 2014 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 potato and grape vines, 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, 2015) 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 RAR, the Reporting Table (22 May 2014), the Evaluation Table (14 January 2015), the report(s) 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 RAR including its addendum (compiled version of October 2014 containing all individually submitted addenda (the Netherlands, 2014)) 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 2015;13(2):4001 5

6 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Pyraflufen is the ISO common name for [2-chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3- yl)-4-fluorophenoxy]acetic acid (IUPAC). The variant considered in this conclusion is the ethyl ester variant pyraflufen-ethyl ethyl [2-chloro-5-(4-chloro-5-difluoromethoxy-1-methylpyrazol-3-yl)-4- fluorophenoxy]acetate (IUPAC). The representative formulated product for the evaluation was OS-169 an emulsifiable concentrate (EC) containing 26.5 g/l pyraflufen-ethyl. The representative uses evaluated comprise outdoor foliar spraying for the purpose of haulm desiccation in potatoes and the control of side shoots in grape vines. Full details of the GAP can be found in the list of end points in Appendix A. The dossier included a literature review of available scientific literature on the mechanism of action of pyraflufen-ethyl (see Section 2). No details are available on how it has been performed. No literature review was provided for both pyraflufen-ethyl and its metabolites dealing with side-effects on health, the environment and non-target species. This is identified as a data gap (see Section 7). 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), SANCO/10597/2003 rev (European Commission, 2012), and SANCO/825/00 rev. 8.1 (European Commission, 2010). The minimum purity of the technical material as manufactured is 956 g/kg. It is not yet clear if there are any relevant impurities (see Section 2). The main data regarding the identity of pyraflufen-ethyl and its physical and chemical properties are given in Appendix A. Methods of analysis are available to analyse the active substance in the technical material and the formulation namely GC-FID and HPLC-UV. The multi-residue method DFG-S19 LC-MS/MS is available to analyse for pyraflufen-ethyl and pyraflufen in products of plant origin. A method of analysis for products of animal origin is not required as no MRLs are proposed. LC-MS/MS methods are available for soil, water and air with appropriate LOQs. However as metabolite E-2 has been included in the residue definition for surface water a data gap is identified for a method of analysis. The active substance is not classified for any health hazard according to Regulation (EC) No 1272/2008 (CLP Regulation) 5 therefore a method of analysis is not required for body fluids and tissues. 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 (European Commission, 2012). 5 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. OJ No L 322, , p EFSA Journal 2015;13(2):4001 6

7 Pyraflufen-ethyl has been discussed by the experts in mammalian toxicology during the Pesticides Peer Review Experts Meeting 118 (September 2014). Insufficient information has been provided on the toxicological relevance of the impurities in the technical specification (data gap). Furthermore, the batches used during the toxicological studies cannot be concluded as representative of the technical specification due to lower levels of one impurity for which further genotoxicity tests should be provided according to the guidance document (European Commission, 2012) (critical area of concern). A literature review has been done by the applicant, but no details are available on how it has been performed and what were the selection criteria for the screened articles. Data from open literature are reported, mainly in relationship with the mechanism of action, which is inhibition of protoporphyrinogen IX oxidase (PPO), one of the key enzyme in porphyrin biosynthesis (part of heme synthesis). They are also describing human diseases (porphyrias) related to disorders of porphyrin or porphyrin-precursor metabolism. With an oral absorption value of 56%, pyraflufen-ethyl showed a limited distribution in tissues and organs, with no evidence of bioaccumulation. In acute toxicity studies, there were no significant adverse findings meeting the criteria for classification. With regard to short term toxicity, the critical target organs were the blood system (mild hemolytic anemia with a compensatory response from the spleen), the liver (in rats and mice) and the kidney. These toxic effects were attributed to the mechanism of action (inhibition of the enzyme protoporphyrinogen IX oxidase located in the liver mitochondria) causing porphyrin accumulation. The relevant short term NOAEL was 20 mg/kg bw per day (90-day mice). No adverse effect were observed in the dog (up to 1000 mg/kg bw per day). On the basis of the available genotoxicity studies, it can be concluded that pyraflufen-ethyl is unlikely to be genotoxic for humans. In long term studies, adverse effects were also related to porphyrin accumulation with blood, liver and kidneys as target organs. The NOAEL in the 2-year rat study is 20 mg/kg bw per day based on effects in blood (slight anisocytosis), in kidneys (increased weight) and in liver (electron lucent vacuoles in hepatocytic mitochondria). In the 78-week mouse study, only liver toxicity was observed, with a NOAEL of 20 mg/kg bw per day. No pre-cancerous changes (cell division detected by use of an antibody against proliferative cell nuclear antigen) were detected at this NOAEL. No carcinogenic potential was demonstrated for pyraflufen-ethyl. In the reproductive toxicity studies, no specific adverse effect was observed on fertility parameters and foetal development. From the multigeneration study with rats, a parental and offspring NOAEL of 70.8 mg/kg bw per day was derived based on decreased body weight (parents and offspring), decreased kidney weight and liver toxicity (parents). In the rat developmental toxicity study, the maternal and developmental NOAELs were 1000 mg/kg bw per day (the highest dose tested) in the absence of maternal toxicity, embryotoxic or teratogenic potential. In the rabbit developmental toxicity study, the maternal NOAEL was 20 mg/kg bw per day based on high mortality rate. This was attributed to gastro-intestinal disturbance (rabbits are known to be highly sensitive to alterations in their intestinal flora), but the experts agreed that a treatment-related effect relevant to humans could not be excluded (at 60 and 150 mg/kg bw per day). Post-implantation loss was increased at 60 and 150 mg/kg bw per day, outside historical control values only at 150 mg/kg bw per day but showing a clear dose-response relationship. This finding triggered a developmental NOAEL of 20 mg/kg bw per day. A biokinetic study with pyraflufen-ethyl showed an accumulation of porphyrin in several rat and mouse tissues, except in the skin and Harderian glands. Specific studies on hepatotoxicity in mice showed an inhibition of liver enzymes (cyt P450, catalase) and an induction of peroxisome proliferation and lipid peroxidation. At high dose, single cell necrosis was observed, followed by increased mitotic activity and formation of liver adenoma. Additional histochemical investigations for the 78-week mouse study demonstrated that the increased brown pigment in Kupffer cells could be due to accumulation of porphyrin. These results support the derivation of the NOAELs in the long term studies. EFSA Journal 2015;13(2):4001 7

8 For the metabolite E-1, an acute toxicity study showed an oral LD 50 between 1000 and 3000 mg/kg for male rats. The acceptable daily intake (ADI) is 0.2 mg/kg bw per day, based on the 2-year rat study and applying an UF of 100. The acute reference dose (ARfD) is 0.2 mg/kg bw based on the rabbit developmental toxicity study and applying an UF of 100. The acceptable operator exposure level (AOEL) is 0.1 mg/kg bw per day based on the 90-day mouse study, applying an UF of 100 and a correction for an oral absorption value of 56%. Pyraflufen-ethyl is not classified or proposed to be classified as carcinogen or as toxic for reproduction category 2, in accordance with the provisions of Regulation (EC) No 1272/2008, and therefore the conditions of the interim provisions of Annex II, Point of Regulation (EC) No 1107/2009 concerning human health for the consideration of endocrine disrupting properties are not met. No recognised endocrine disrupting effects were observed in the available toxicological studies and it is considered unlikely that any of the in vitro tests reported in the level 2 of the OECD Conceptual Framework (OECD, 2012) would add any relevant information. Therefore, pyraflufen-ethyl is unlikely to be an endocrine disruptor according to the current scientific state-of-play (EFSA SC, 2013). This is consistent with the mode of action of pyraflufen-ethyl (inhibitor of protoporphyrinogen IX oxidase) and the related effects (e.g. inhibition of heme biosynthesis). For the exposure estimates, the dermal absorption values for pyraflufen-ethyl are 4% for the undiluted formulation and 56% for the dilution. Both for mechanical and manual downward spraying in potato and vines, the operator exposure is predicted to be below the AOEL without the use of PPE (personal protective equipment). Similarly, the exposure of bystanders/residents and workers is predicted to be below the AOEL for the representative uses. 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 pyraflufen-ethyl was investigated for foliar application as a pre-harvest desiccant in root and tuber vegetables (potatoes), in pulses and oilseeds (cotton), for foliar application as a herbicide in cereals (wheat) using 14C-phenyl and 14C-pyrazole labelled pyraflufen-ethyl, and for soil application on fruit and fruiting vegetables (mandarin) using 14C-pyrazole labelled pyraflufen-ethyl only. Following foliar and soil applications, very low levels of radioactive residues (<0.001 mg/kg) were recovered in all the edible parts of the crops and metabolites identification was not further investigated in cotton seed, wheat grain and mandarin fruit. In potato tuber, metabolite E-1 occurred at a significant level (up to 16 % TRR) whilst pyraflufenethyl and metabolite E-9 were identified at a negligible proportion (1.7 % and 3 % TRR, respectively). In contrast, the total radioactive residues in potato leaves and wheat straw accounted for up to 7 mg/kg and 0.02 mg/kg, respectively with pyraflufen-ethyl and metabolite E-1 being the major compounds of the total residues in potato leaves (48-68 % and % TRR, respectively). Metabolite E-1 was also the relevant compound of the total residues identified in mature wheat straw (up to 13 % TRR) for both labels whilst the parent compound was never detected. Potatoes may be grown in rotation and a confined rotational crop study demonstrated that very low levels of radioactive residues (<0.001 mg/kg) were recovered in all the edible parts of the rotational crops. Pyraflufen-ethyl was never detected in any crop part whilst E-1, E-2 and E-3 metabolites were either not detected or recovered at a negligible amount (<0.001 mg/kg). The major route of degradation of pyraflufen-ethyl in primary and rotational crops consisted of the ester-ethyl hydrolysis of the parent molecule to form metabolite E-1 followed by the formation of either E-9 after demethylation of the pyrazole ring or E-2 after hydrolysis of the ether bond. A further methylation step of E-2 generated the methoxy metabolite E-3. Considering the metabolism of pyraflufen-ethyl depicted in primary and EFSA Journal 2015;13(2):4001 8

9 rotational crops, metabolite E-1 is shown to be the predominant compound of the total residues in plants although the total residues in all edible parts of primary and rotational crops are expected to be negligible (<0.01 mg/kg) based on the representative uses. Furthermore, considering the review of the existing MRLs of pyraflufen-ethyl for the authorized European uses in the framework of article 12 of Reg. (EC) No. 396/2005 (EFSA, 2013), metabolite E-1 was also shown to be a valid marker of residues, particularly in cereal straw. The residue definition for monitoring and risk assessment is therefore proposed as the sum of pyraflufen-ethyl and metabolite E-1, expressed as pyraflufen-ethyl. Processing studies addressing the nature and the magnitude of the residues in processed commodities are not triggered. A complete residue data set was provided respectively on potato tuber and grape vines that indicated residue levels below the LOQ (<0.01 mg/kg) respectively for pyraflufen-ethyl and metabolite E-1. Rotational crop field trials on leafy crops, root and tuber vegetables and cereals showed residue levels of pyraflufen-ethyl and metabolite E-1 below the LOQ of 0.01 mg/kg in all crop parts. Although the very persistent E-3 metabolite was not analysed for, significant residue levels of this compound are not expected since the rotational crops field trials were conducted at a rate covering the calculated plateau concentration of E-3 in soil. Although livestock metabolism data are not triggered based on the calculated dietary burden, the metabolism of pyraflufen-ethyl was depicted in ruminants and poultry. The parent compound was never detected whilst rapidly hydrolysed into E-1 and E-9 in milk, eggs, liver and kidney. Metabolites identification was not investigated in fat and muscle in view of the very low recovered residue levels in these matrices. A residue definition and MRLs are not proposed for livestock matrices. A consumer dietary risk assessment considering the proposed MRLs on potatoes and grape vines and using the EFSA PRIMo rev.2a indicated a negligible chronic and acute intake for all consumer groups (TMDI<1% ADI and IESTI=1.5% ARfD). 4. Environmental fate and behaviour Pyraflufen-ethyl was discussed at the Pesticide Peer Review Meeting 117 (September 2014). In soil laboratory incubations under aerobic conditions in the dark, pyraflufen-ethyl exhibited very low persistence, forming the major (>10% applied radioactivity (AR)) metabolites E-1 (max % AR), E-2 (max. 19.0% AR) and E-3 (max. 69 % AR), which exhibited low to moderate, low to high and high to very high persistence, respectively. Metabolite E-11 was detected at a maximum of 7.0% AR at the end of the study (occurring at >5% on two consecutive occasions, triggering a groundwater assessment). As only a single soil DT 50 value was available, the peer review agreed to perform a conservative groundwater exposure assessment for metabolite E-11 based on a DT 50 value of 1000 days. A single unknown radioactivity fraction (Unknown 2) was detected at significant levels (10.3% AR at 178 days) in a sandy loam soil under some of the experimental conditions. Further information on the identity/characterisation of Unknown 2 was provided and discussed at the Pesticide Peer Review Meeting 117. The experts on balance considered that whilst it appeared reasonable that Unknown 2 is in fact metabolite E-2, this had not been fully demonstrated by the applicant in the information that was provided in the document Attachment 1 (included in the revised RAR of October 2014). Therefore, a data gap was identified for an environmental exposure assessment of the unidentified metabolite Unknown 2. However, the EFSA experts consider the full information provided sufficient to support the conclusion that detections of Unknown 2 in the low dose 14 C- pyrazole samples are considered to be E-2. Mineralisation of the 14 C-pyrazole and 14 C-phenyl radiolabels to carbon dioxide accounted for % AR after 100 days. The formation of unextractable residues (not extracted by acetonitrile/aqueous ammonium chloride and acetonitrile/hcl) for this radiolabels accounted for % AR after 100 days. In soil under anaerobic conditions pyraflufen-ethyl is rapidly degraded (DT50 < 1d) to its major degradation product E-1. Based on the results of the soil photolysis study considered valid by the peer review, it was concluded that photolysis on soil is not an important route of degradation for pyraflufen-ethyl. EFSA Journal 2015;13(2):4001 9

10 The soil adsorption/desorption coefficient (log Koc) for pyraflufen-ethyl was estimated by HPLC simulation, indicating a low mobility for the active substance. Metabolite E-1 exhibited high to medium soil mobility; E-2 exhibited low to slight soil mobility and E-3 exhibited slight soil mobility. A study on adsorption/desorption characteristics of metabolite E-11 was not available. Its structure is very similar to that of E-3, therefore the lowest K Foc value for E-3 of 3098 ml/g with a Freundlich coefficient of 1 was considered acceptable for FOCUS modelling. This approach is supported by comparable determinations for the two compounds using KocWin (US EPA 2010). It was concluded that the adsorption of pyraflufen-ethyl and its metabolites was not ph dependent. In satisfactory field dissipation studies carried out at 2 sites in France, 1 in Germany and 1 in the UK (spray application to the soil surface on bare soil plots in spring and in autumn) pyraflufen-ethyl exhibited very low to low persistence. Sample analyses were carried out also for metabolite E-1, which exhibited moderate to high persistence in soil under field conditions. In aqueous photolysis studies pyraflufen-ethyl degraded rapidly (DT50 ca. 30 hours) to the major metabolite PD-1 (max. 32.2% AR), which degrades with an estimated DT50 of 15 hours to minor polar products. In laboratory incubations in dark aerobic natural sediment water systems, pyraflufenethyl exhibited very low persistence, forming the major metabolites E-1 (max. 94 % AR in water and max. ca. 39% AR in sediment, exhibiting moderate to high persistence), and E-2 which was detected at maximum of 54% AR in sediment (54.6% AR total system). For E-2 no DT50 value could be derived in one system, and therefore a default value of 1000 days was considered as the appropriate endpoint to be used in FOCUS modelling from this system. The overall DT50 of 281 days used for FOCUS modelling was then obtained by calculating the geometric mean with the whole system DT50 value for the other system (79 days). Mineralisation was negligible and unextractable residues occurred at maxima of 4.6 to 15.9% AR. Surface water modelling of pyraflufen ethyl and its metabolites E-1, E-2, E-3, and PD-1 has been undertaken using the FOCUS (FOCUS, 2001) step 1 and step 2 approach (version 1.1 of the Steps 1-2 in FOCUS calculator). The modelling undertaken in this exercise was based on the use of a foliar spray at an application rate of 2 x 21.2 g a.s./ha on potatoes and on vegetation under grapevines (early and late applications) representative of the GAP in the EU. Further Step 3 and Step 4 modelling was undertaken for the active substance and metabolites E-1, E-2 (Step 3 only) and E-3. For grape vines it was considered that only 50% of the area is treated as the herbicide is applied inter-row. Therefore, for drainage and run-off the reduced rate reaching the soil was considered for modelling, but for spray drift the full rate was still considered. The step 4 calculations appropriately followed the FOCUS (FOCUS, 2007) guidance, with no-spray drift buffer zones of 10 m or 14 m (vines) and 15 m (potatoes) being implemented for pyraflufen-ethyl. In addition, simulations for E-1 and E-3 incorporated either a 10 m (potatoes and early application to vines) or 18 m (potatoes) vegetative buffer strip in which run-off water and aqueous phase pesticide was reduced by 60% or 80% respectively, and eroded sediment and pesticide transported in the sorbed phase was reduced by 85% or 95% respectively using the SWAN tool. This is consistent with vegetative strips of 10 and 18 m width as defined by FOCUS (2007). 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 KFoc < 2000 ml/g (i.e. metabolite E-1), 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 by the RMS (the Netherlands, October 2014) using FOCUS (FOCUS, 2000) scenarios and the model PEARL for the active substance pyraflufen-ethyl and metabolites E-1, E-2, E-3 and E-11. The potential for groundwater exposure from the representative uses by pyraflufen-ethyl and its metabolites above the parametric drinking water limit of 0.1 µg/l was concluded to be low in the geoclimatic situations represented by the relevant FOCUS groundwater scenarios. 6 Simulations correctly utilised the agreed Q10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of 0.7 EFSA Journal 2015;13(2):

11 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), SETAC (2001), and EFSA (2009). The batches used in the ecotoxicological studies are not considered representative of the technical specification and in addition the information provided on the toxicological relevance of the impurities in the technical specification is not considered sufficient, leading to a critical area of concern and a data gap, respectively (see also Section 2). Based on the available data and the screening risk assessment a low risk to birds and mammals from dietary exposure, exposure via consumption of contaminated water and secondary poisoning was concluded for pyraflufen- ethyl for all the representative uses. The risk via consumption of contaminated water for the metabolite E-1 and E-3 and the risk of secondary poisoning for fish and earthworms eating birds and mammals for the pertinent metabolites E-1, E-3 and PD-1 was carried out using the same endpoint as the parent. This could be considered a source of uncertainty in the final outcome of the risk assessment; however, considering the large margin of safety in the calculated TER a low risk was concluded. Acute toxicity data were available on fish and aquatic invertebrates with the active substance, the formulation and the pertinent metabolite E-1. Chronic toxicity data were also available on fish and invertebrates with the active substance and the metabolite E-1. Algae were tested with the active substance and the pertinent metabolites E-1, E-3 and PD-1, while reliable data with aquatic plants were only available with the metabolite E-1. Therefore a data gap has been identified for studies testing pyraflufen-ethyl on aquatic plants. EFSA concluded that no reliable toxicity studies on the most sensitive aquatic species were available with the pertinent metabolite E-2 (data gap). The RMS does not agree with this conclusion. A low risk to fish and invertebrates was concluded using PECsw Step 1-2 for all the representative uses. Based on the available data a high risk to algae was identified for all the representative uses for the R2 and R3 FOCUS scenarios by using STEP 4 PECsw with the application of a no spray buffer zone up to 15 m and in addition for the FOCUS D6 scenario for the representative use on vine with the application of 14 m no spray buffer zone. Therefore higher tier risk assessment was performed. In this assessment further laboratory studies on additional algae species were considered. The higher tier risk assessment with the refinement steps and the underlying data were discussed at the Pesticides Peer Review Experts Meeting 119 (September 2014). The experts agreed that the HC5 value derived from the species sensitivity distribution (SSD) analysis combined with an assessment factor of 1.5 was appropriate for the risk assessment. In contrast, EFSA does not consider that it is appropriate to use the SSD for the risk assessment for algae considering that the SSD included some undefined values (> than values) as well as endpoints expressed as initial measured concentration instead of mean measured concentration. In addition the data do not fit the curve very well (normal distribution was not accepted at the higher level) and the TERs (using the median HC5 and the assessment factor of 1.5) were above the trigger but very close to it. Therefore, a high risk to algae for the FOCUS scenario D6, R2 and R3 cannot be excluded (data gap). A low risk to algae was concluded for the metabolite PD-1 using PECsw Step 1. A low risk to aquatic organisms for the metabolite E1 was concluded by using PECsw Step 3&4 for all the relevant FOCUS scenarios with the exception of D6 for the representative use on potatoes (data gap). A low risk to aquatic organisms for the metabolite E-3 was concluded by using PECsw Step 3&4 for all the relevant FOCUS scenarios with the exception of the FOCUS scenario D4 for the representative use on potatoes and for the FOCUS scenario D6 for all the representative uses (data gap). EFSA Journal 2015;13(2):

12 No reliable data were available with the metabolite E-2 and therefore the risk assessment could not be finalised for that metabolite (data gap). Considering the low exposure estimates, a high risk to aquatic organisms is not expected for the groundwater metabolite E11. Acute toxicity data on bees were available both with the active substance and the formulation. It was noted that the active substance when formulated could be potentially more toxic. However, the study with the formulation was not considered fully reliable. Based on the available data and risk assessment with the active substance a low risk to bees was concluded by EFSA. The RMS disagrees with this conclusion and is of the opinion that the risk assessment for bees could not be finalised with the available information. A low risk was concluded for non target arthropods other than bees. Acute toxicity data on earthworms were available with the active substance, the formulation and the pertinent metabolites E-2 and E-3. Chronic toxicity data were available with the active substance and the metabolite E-3. No chronic toxicity data on earthworms were available with the formulation, however, from the acute toxicity data, the active substance resulted in a higher toxicity when formulated. Based on the available data a low risk to earthworms was concluded for the active substance and for the metabolite E-2 and E-3 for all the representative uses. No toxicity data with soil organisms were available with the metabolite E-1, however considering that in soil pyraflufen-ethyl degrades very rapidly to E-1, the toxicity data with the parent are considered to cover the metabolite E-1.Therefore, a low risk is also concluded for this metabolite. A low risk was concluded on soil microorganisms for the active substance and the pertinent metabolites E-2 and E-3 for all the representative uses. No reliable studies were available on non target terrestrial plants. Therefore a data gap has been identified and the risk assessment could not be finalised for this group of organisms. A low risk could be concluded to organisms involved in biological methods for sewage treatment on the basis of the available data and assessments. With regard to the endocrine disruption potential, as discussed in Section 2, it is unlikely that pyraflufen-ethyl is an endocrine disruptor in mammals; however, no firm conclusion can be drawn regarding fish and birds. EFSA Journal 2015;13(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) pyraflufen-ethyl E-1 E-2 E-3 Persistence Very low persistence. Single first order (SFO) or biphasic DT days (DT days; 20 C and pf2.3 soil moisture). European field dissipation studies SFO DT days (not normalised to reference conditions 20 C and pf2). Low to moderate persistence. Single first order DT days (20 C and pf2.3 soil moisture). European field dissipation studies SFO or biphasic decline DT days (not normalised to reference conditions 20 C and pf2; DT days). Low to high persistence. Single first order or biphasic DT days (DT days; 20 C and pf2.3 or 45% MWHC soil moisture). High to very high persistence. Single first order DT days (20 C and 45% MWHC soil moisture). Ecotoxicology Low risk to soil dwelling organisms Low risk to soil dwelling organisms Low risk to soil dwelling organisms Low risk to soil dwelling organisms EFSA Journal 2015;13(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 pyraflufen-ethyl Low mobility estimated by HPLC K oc = 1949 ml/g No Yes Yes Data gap to further assess the risk to algae for 2 out of 6 FOCUS scenarios for the representative use on potatoes and for 3 out of 5 FOCUS scenario for the representative use on vines. E-1 High to medium mobility K Foc = ml/g No No data 1000 < rat oral LD 50 < 3000 mg/kg bw See Section 6.3 E-2 E-3 Low to slight mobility. K Foc = ml/g Slight mobility. K Foc = ml/g No No data No data See Section 6.3 No No data No data See Section 6.3 E-11 Estimated value based on the lowest K Foc for E-3 (slight mobility) K Foc = 3098 ml/g No No data No data Considering the low exposure estimates a high risk is not expected from the metabolite E-11 EFSA Journal 2015;13(2):

15 6.3. Surface water and sediment Compound (name and/or code) pyraflufen-ethyl E-1 Ecotoxicology Data gap to further assess the risk to algae for 2 out of 6 FOCUS scenarios for the representative use on potatoes and for 3 of 5 FOCUS scenarios for the representative use on vines. The risk to aquatic organisms was assessed as high for 1 out of 6 FOCUSsw scenarios for the representative use on potatoes. E-2 No data, data required. E-3 PD-1 (aqueous photolysis) The risk was assessed as high for 2 out of 6 FOCUSsw scenarios for the representative use on potato and for 1 out of 5 FOCUSsw scenarios for the representative use vine. Low risk to aquatic organisms Air Compound (name and/or code) Pyraflufen-ethyl Toxicology Rat LC 50 = 5.03 mg/l (4 hours exposure, nose only). EFSA Journal 2015;13(2):

16 7. List of studies to be generated, still ongoing or available but not peer reviewed This is a list of 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 56 of Regulation (EC) No 1107/2009 concerning information on potentially harmful effects). A complete search of the scientific peer-reviewed open literature covering both pyraflufen-ethyl and its metabolites, dealing with side-effects on health, the environment and non-target species, published within the last 10 years before the date of submission of the dossier (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown). Method of analysis for E-2 in surface water (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 1) Further assessment of the (eco)toxicological relevance of the impurities in the technical specification (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2 and 5) Identification/characterization of the radioactivity Unknown 2 formed after days that is major > 10% AR at 178 days in a sandy loam soil under some of the experimental conditions of laboratory degradation study. An environmental exposure assessment for this metabolite is not available. This data gap was identified at the Peer Review Meeting 117 and not considered necessary for EFSA (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 4) Further information is required to address the risk to aquatic organisms from pyraflufen-ethyl in situations which are represented by the D6 (relevant for the representative use on vines), R2 and R3 (relevant for all representative uses) FOCUS surface water scenarios (submission date proposed by the applicant: unknown; see Section 5) Further information is required to address the risk to aquatic organisms from metabolite E-2 (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 5) Further information is requested to address the risk to aquatic plants from pyraflufen-ethyl (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 organisms from the metabolite E-1 in situations which are represented by the D6 (relevant for the representative use on potatoes) FOCUS surface water scenarios (submission date proposed by the applicant: unknown; see Section 5) Further information is required to address the risk to aquatic organisms from the metabolite E-3 in situations which are represented by the D6 (relevant for all representative uses) and D4 (relevant for the representative uses on potatoes) FOCUS surface water scenarios (submission date proposed by the applicant: unknown; see Section 5) Further information is required to address the risk to non-target terrestrial plants from pyraflufenethyl (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 5) EFSA Journal 2015;13(2):

17 8. Particular conditions proposed to be taken into account to manage the risk(s) identified Risk mitigation measures to protect aquatic organisms from the active substance pyraflufen-ethyl are required in all the relevant FOCUSsw scenarios (e.g. up to 15 m no spray buffer zone, relevant for all the representative uses, see Section 5) Risk mitigation measures to protect aquatic organisms from the metabolite E-1 are required in the following FOCUS surface water scenarios: R3 (e.g. 10 m vegetative buffer strip) (relevant for the representative use on grape vines) and R2 and R3 (e.g. up to 18 m vegetative buffer strip) (relevant for the representative use on potatoes, see Section 5). Risk mitigation measures to protect aquatic organisms from the metabolite E-3 are required in the following FOCUS surface water scenarios: R3 and R4 (e.g. up to 18 m vegetative buffer strip) (relevant for the representative use on vines) and R1 and R3 (e.g. 10 m vegetative buffer strip) (relevant for the representative use on potatoes, 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 in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/ 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). An issue is also listed as an issue that could not be finalised where the available information is considered insufficient to conclude on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of the Regulation. 1. The risk assessment for non target terrestrial plants could not be finalised with the available information 9.2. Critical areas of concern 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 in accordance with Article 29(6) of Regulation (EC) No. 1107/2009 and as set out in Commission Regulation (EU) No 546/2011, 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. An issue is also listed as a critical area of concern the active substance is not expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/ Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. OJ L 155, , p EFSA Journal 2015;13(2):