Scientific support for preparing an EU position in the 46 th Session of the Codex Committee on Pesticide Residues (CCPR) 1

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1 EFSA Journal 2014;12(7):3737 SCIENTIFIC REPORT OF EFSA Scientific support for preparing an EU position in the 46 th Session of the Codex Committee on Pesticide Residues (CCPR) 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT In accordance with Article 43 of Regulation (EC) No 396/2005, EFSA received a request from the European Commission to provide support for the preparation of the EU position for 46 th session of the Codex Committee on Pesticide Residues (CCPR). In 2013, JMPR evaluated 10 active substances regarding the setting of toxicological reference values to be used in consumer risk assessment (diquat, chlorfenapyr, picoxystrobin, benzovindiflupyr, bixafen, fenamidone, fluesulfone, isoxaflutole, tolfenpyrad, and trinexapac) and 31 active substances regarding the setting of Maximum Residue Limits (MRLs) (diquat, malathion, chlorpyrifos methyl, triazophos, glyphosate, propiconazole, bentazone, dithianon, fenpyroximate, fenbuconazole, flutriafol, cyprodinil, fludioxonil, indoxocarb, difenoconazole, pyrimethanil, azoxystrobin, chlorantraniliprole, mandipropamid, spirotetramate, cyproconazole, dicamba, sulfoxaflor, penthiopyrad, cyantraniliprole, imazapic, imazapyr, isoxaflutole, tolfenpyrad and trinexapac). European Food Safety Authority, 2014 KEY WORDS consumer risk assessment, toxicological evaluation, residue definitions, MRL setting, CCPR meeting On request from the European Commission, Question No from EFSA-Q to EFSA-Q , approved 2 on 10 June Correspondence: pesticides.mrl@efsa.europa.eu Suggested citation: EFSA (European Food Safety Authority), Scientific support for preparing an EU position in the 46 th Session of the Codex Committee on Pesticide Residues (CCPR). EFSA Journal 2014;12(7):3737, 182 pp. doi: /j.efsa Available online: European Food Safety Authority, 2014

2 SUMMARY In preparation of the 46 th session of the Codex Committee on Pesticide Residues (CCPR meeting) the European Commission requested EFSA to provide comments on the recommendations of the 2013 Joint FAO/WHO Meeting on Pesticide Residues (JMPR) and pesticide MRLs at step 3 and 6 of the Codex procedure. In 2013, JMPR evaluated 10 active substances regarding the setting of toxicological reference values to be used in consumer risk assessment (diquat, chlorfenapyr, picoxystrobin, benzovindiflupyr, bixafen, fenamidone, fluesulfone, isoxaflutole, tolfenpyrad, and trinexapac). EFSA compared the ADI and ARfD values derived by JMPR with the values derived at EU level and, in case differences were identified, EFSA provided further explanations for the reasons of the differences. JMPR assessed 31 substances regarding the setting of Maximum Residue Limits (MRLs) (diquat, malathion, chlorpyrifos methyl, triazophos, glyphosate, propiconazole, bentazone, dithianon, fenpyroximate, fenbuconazole, flutriafol, cyprodinil, fludioxonil, indoxocarb, difenoconazole, pyrimethanil, azoxystrobin, chlorantraniliprole, mandipropamid, spirotetramate, cyproconazole, dicamba, sulfoxaflor, penthiopyrad, cyantraniliprole, imazapic, imazapyr, isoxaflutole, tolfenpyrad and trinexapac). EFSA provided assessments on the scientific basis of the proposed MRLs and on possible consumer health concerns related to the MRL proposals. EFSA Journal 2014;12(7):3737 2

3 TABLE OF CONTENTS Abstract... 1 Summary... 2 Summary... 2 Table of contents... 3 Background... 7 Terms of reference... 8 Assessment Introduction Comments on the JMPR follow-up evaluation with regard to specific concerns Buprofezin (173) Background information Clothianidin (238)/Thiamethoxam (245) Background information Clothianidin (238) Background information Thiamethoxam (245) Glufosinate ammonium (175) Background information Propylene oxide (250) Background information Comments on the individual substances assessed Diquat (31) (T,R) Toxicological endpoints - Diquat Residue definitions - Diquat CXL proposals - Diquat Consumer risk assessment Diquat Malathion (049) (R) Toxicological endpoints -Malathion Residue definitions Malathion CXL proposals Malathion Consumer risk assessment - Malathion Chlorpyrifos-methyl (090) (R) Toxicological endpoints - Chlorpyrifos-methyl Residue definitions - Chlorpyrifos-methyl CXL proposals Chlorpyrifos-methyl Consumer risk assessment - Chlorpyrifos-methyl Triazophos (143) (R) Toxicological endpoints - Triazophos Residue definitions - Triazophos CXL proposals - Triazophos Consumer risk assessment - Triazophos Glyphosate (158) (R) Toxicological endpoints - Glyphosate Residue definitions - Glyphosate CXL proposals - Glyphosate Consumer risk assessment - Glyphosate Propiconazole (160) (R) Toxicological endpoints - Propiconazole Residue definitions - Propiconazole CXL proposals Propiconazole Consumer risk assessment - Propiconazole Bentazone (172) (R) EFSA Journal 2014;12(7):3737 3

4 Toxicological endpoints - Bentazone Residue definitions - Bentazone CXL proposals Bentazone Consumer risk assessment - Bentazone Dithianon (180) (R) Toxicological endpoints - Dithianon Residue definitions - Dithianon CXL proposals Dithianon Consumer risk assessment - Dithianon Fenpyroximate (193) (R) Toxicological endpoints - Fenpyroximate Residue definitions - Fenpyroximate CXL proposals Fenpyroximate Consumer risk assessment - Fenpyroximate Fenbuconazole (197) (R) Toxicological endpoints Fenbuconazole Residue definitions - Fenbuconazole CXL proposals - Fenbuconazole Consumer risk assessment - Fenbuconazole Flutolanil (205) (R) Toxicological endpoints - Flutolanil Residue definitions - Flutolanil CXL proposals Flutalonil Consumer risk assessment - Flutolanil Cyprodinil (207) (R) Toxicological endpoints - Cyprodinil Residue definitions - Cyprodinil CXL proposals Cyprodinil Consumer risk assessment - Cyprodinil Fludioxonil (211) (R) Toxicological endpoints - Fludioxonil Residue definitions - Fludioxonil CXL proposals Fludioxonil Consumer risk assessment - Fludioxonil Indoxacarb (216) (R) Toxicological endpoints - Indoxacarb Residue definitions - Indoxacarb CXL proposals Indoxacarb Consumer risk assessment - Indoxacarb Difenoconazole (224) (R) Toxicological endpoints - Difenoconazole Residue definitions - Difenoconazole CXL proposals Difenoconazole Consumer risk assessment - Difenoconazole Pyrimethanil (226) (R) Toxicological endpoints - Pyrimethanil Residue definitions - Pyrimethanil CXL proposals Pyrimethanil Consumer risk assessment - Pyrimethanil Azoxystrobin(229) (R) Toxicological endpoints - Azoxystrobin Residue definitions - Azoxystrobin CXL proposals Azoxystrobin EFSA Journal 2014;12(7):3737 4

5 Consumer risk assessment - Azoxystrobin Chlorantraniliprole (230) (R) Toxicological endpoints - Chlorantraniliprole Residue definitions - Chlorantraniliprole CXL proposals Chlorantraniliprole Consumer risk assessment - Chlorantraniliprole Mandipropamid (231) (R) Toxicological endpoints - Mandipropamid Residue definitions -Mandipropamid CXL proposals Mandipropamid Consumer risk assessment - Mandipropamid Spirotetramat (234) (R) Toxicological endpoints - Spirotetramat Residue definitions - Spirotetramat CXL proposals Spirotetramat Consumer risk assessment - Spirotetramat Cyproconazole (239) (R) Toxicological endpoints - Cyproconazole Residue definitions - Cyproconazole CXL proposals Cyproconazole Consumer risk assessment - Cyproconazole Dicamba (240) (T,R) Toxicological endpoints - Dicamba Residue definitions - Dicamba CXL proposals Dicamba Consumer risk assessment - Dicamba Sulfoxaflor (250) (T) Toxicological endpoints sulfoxaflor Residue definitions - Sulfoxaflor CXL proposals Sulfoxaflor Consumer risk assessment - sulfoxaflor Penthiopyrad (253) ( R) Toxicological endpoints - Penthiopyrad Residue definitions - Penthiopyrad CXL proposals Penthiopyrad Consumer risk assessment Penthiopyrad Chlorfenapyr (254) (T,R) Toxicological endpoints - Chlorfenapyr Residue definitions - Chlorfenapyr Picoxystrobin (258) (T) Toxicological endpoints - Picoxystrobin Residue definitions - Picoxystrobin Benzovindiflupyr (261) (T) Toxicological endpoints - Benzovindiflupyr Bixafen (262) (T) Toxicological endpoints - Bixafen Residue definitions - Bixafen Cyantraniliprole (263) (R) Toxicological endpoints - Cyantraniliprole Residue definitions - Cyantraniliprole CXL proposals Cyantraniliprole Consumer risk assessment - Cyantraniliprole Fenamidone (264) (T) EFSA Journal 2014;12(7):3737 5

6 Toxicological endpoints - Fenamidone Residue definitions - Fenamidone Fluensulfone (265) Toxicological endpoints - Fluesulfone Imazapic (266) ( T,R ) Toxicological endpoints - Imazapic Residue definitions - Imazapic CXL proposals Imazapic Consumer risk assessment - Imazapic Imazapyr (267) (T, R) Toxicological endpoints Imazapyr Residue definitions - Imazapyr CXL proposals Imazapyr Consumer risk assessment - Imazapyr Isoxaflutole (268) (T, R) Toxicological endpoints - Isoxaflutole Residue definitions - Isoxaflutole CXL proposals Isoxaflutole Consumer risk assessment - Isoxaflutole Tolfenpyrad (269) (T, R) Toxicological endpoints - Tolfenpyrad Residue definitions - Tolfenpyrad CXL proposals Tolfenpyrad Consumer risk assessment - Tolfenpyrad Triflumizole (270) (T, R) Toxicological endpoints - Triflumizole Residue definitions - Triflumizole CXL proposals Triflumizole Consumer risk assessment - Triflumizole Trinexapac-ethyl (271) (T, R) Toxicological endpoints Trinexapac-ethyl Residue definitions Trinexapac-ethyl CXL proposals Trinexapac-ethyl Consumer risk assessment Trinexapac-ethyl Conclusions and recommendations References Appendix A. Calculations of consumer exposure with Pesticide Residues Intake Model (PRIMo)136 Abbreviations EFSA Journal 2014;12(7):3737 6

7 BACKGROUND Manufacturers of pesticides submitted data to the JMPR (Joint Meeting on Pesticide Residues) for assessment with view of establishing new Codex maximum residue limits (CXLs). The recent JMPR evaluations of the toxicological data and the residue studies are summarised in the JMPR Report 2011 (WHO/FAO, 2012). It comprises 37 active substances, 3 of them (dichlorvos, dicofol, penthiopyrad) were assessed to derive toxicological reference values only, 15 active substances were assessed in view of setting new CXLs and 9 active substances were assessed for both, toxicology and residues. In preparation of the 46 th session of the Codex Committee on Pesticide Residues (CCPR meeting) the European Commission requested EFSA on 22 November 2013 to review the JMPR evaluations of the active substances which will be discussed in the upcoming CCPR meeting in May 2014 and which are reported in the JMPR Report EFSA should provide comments regarding the acceptability of the CXL proposals and the toxicological reference values. The comments of EFSA should be considered to derive a common EU position for the Codex Committee on Pesticide Residues (CCPR) and to obtain an agreement of the Council before presenting the EU position in the CCPR. For reasons of transparency and traceability, EFSA has created separate questions for each of the active substances covered by the mandate in the EFSA Register of Questions with the following reference numbers and subjects: Question number EFSA-Q Subject Diquat- EFSA comments on the toxicological reference values and the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q Malathion- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q Chlorpyrifos-methyl- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Triazophos- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Glyphosate- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Propiconazole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Bentazone- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q Dithianon- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA-Q Fenpyroximate- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Fenbuconazole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q Flutalonil- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q Cyprodinil- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Fludioxonil- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Indoxacarb- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Difenoconazole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Pyrimethanil - EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Azoxystrobin- EFSA comments on the proposed Codex MRLs evaluated by JMPR in EFSA Journal 2014;12(7):3737 7

8 Question number EFSA-Q EFSA-Q EFSA-Q EFSA-Q Subject 2013 Chlorantraniliprole - EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Mandipropamid- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Spirotetramat- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Cyproconazole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q Dicamba- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q EFSA-Q Sulfoxaflor- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Penthiopyrad - EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Chlorfenapyr - EFSA comments on the toxicological reference values evaluated by JMPR 2013 Benzovindiflupyr -EFSA comments on the toxicological reference values evaluated by JMPR 2013 Bixafen -EFSA comments on the toxicological reference values evaluated by JMPR 2013 Cyantraniliprole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Fenamidone- EFSA comments on the toxicological reference values evaluated by JMPR 2013 Fluensulfone- EFSA comments on the toxicological reference values evaluated by JMPR 2013 EFSA-Q Imazapic - EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q Imazapyr- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA-Q EFSA-Q EFSA-Q Isoxaflutole- EFSA comments on the toxicological reference values and the proposed Codex MRLs evaluated by JMPR in 2013 Tolfenpyrad- EFSA comments on the toxicological reference values and the proposed Codex MRLs evaluated by JMPR in 2013 Triflumizole- EFSA comments on the proposed Codex MRLs evaluated by JMPR in 2013 Trinexapac- EFSA comments on the toxicological reference values and the proposed Codex MRLs evaluated by JMPR in 2013 EFSA-Q EFSA comments on general considerations provided by JMPR in 2013 On 4 March 2014 the draft scientific report of EFSA was submitted for commenting to EU Member State experts and the European Commission for a Member State consultation. Comments were submitted by Belgium, Germany, Spain, Finland, Ireland and the Netherlands which have been taken into account in the final report. TERMS OF REFERENCE The European Commission requested EFSA to prepare a contribution for the 46 th session of the Codex Committee on Pesticide Residues (CCPR) held on May 2014 in China. The requested advice EFSA Journal 2014;12(7):3737 8

9 and comments on the recommendations of the 2013 Joint FAO/WHO meeting on pesticides residues (JMPR) and on the proposed Codex MRLs should contain the following information: Background information on all active substances under discussion regarding the status of the active substance at EU level (approval status of the active substance, availability of EFSA conclusions and availability of EFSA reasoned opinions on MRL applications or MRL review) were provided. In case new toxicological reference values were proposed by JMPR, a comparison of the proposed reference values with agreed EU reference values and an evaluation of the reasons for possible differences. As regard the proposed draft Codex MRLs for discussion in the CCPR 2014, EFSA should provide any relevant comments on the proposed MRLs and specifically address the following questions: o o o o o Whether the residue definitions derived by JMPR are comparable with the existing EU residue definitions, Whether the proposed Codex draft MRLs are comparable with the existing EU MRLs, Whether the proposed Codex draft MRLs are sufficiently supported by data, Whether the proposed Codex draft MRLs are appropriate in terms of the data that have been used to establish them and in terms of the method used for their calculation, Whether the proposed Codex draft MRLs are safe for European consumers with regard to chronic, and where relevant, to acute exposure. (Terms of reference as provided by the European Commision in the Mandate of 22 November 2013) EFSA agreed with the European Commission to respond to this request with a scientific report which will be adopted and published by end of July EFSA Journal 2014;12(7):3737 9

10 ASSESSMENT 1. Introduction EFSA provides the requested background information regarding the toxicological reference values (second bullet point of the Terms of Reference) by comparing the assessments performed by JMPR with the assessments performed at EU level in the framework of the peer review under Regulation (EC) No 1107/ The sources of information used are the EFSA conclusions available for the active substances under consideration, the Review Reports, Draft Assessment Reports prepared by the Rapporteur Member States and other sources of information if available. For deriving the comments on the third bullet point in the Terms of Reference (comments on the Codex MRL proposals), EFSA compared the levels of the Codex MRL proposals/mrls and the enforcement residue definition derived by JMPR with the residue definition established in the EU legislation (Regulation (EC) No 396/ ) or the legislation under preparation. The EU residue definitions for risk assessment were retrieved from the EFSA conclusions, EFSA reasoned opinions on MRL review under Art. 12 of Regulation 396/2005 or, where these documents are not available, the reports prepared by the European Commission in the framework of the peer review of active substances or Member State evaluations in Draft Assessment Reports (DARs). For assessing whether the draft Codex MRL proposals are sufficiently supported by data EFSA took into account the currently valid EU guidance documents for consumer risk assessment and the agreed EU policies (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2004, 2008, 2010, 2011 OECD 2011). It is noted that due to the different data requirements and policies in JMPR (FAO, 2009), the assessment of identical residue data sets submitted in support of a EU MRL and CXL request may result in different recommendations at EU level and by JMPR. In this report EFSA provides background information on the reasons for these differences. For calculating the numerical MRL value, EFSA used the same methodology as JMPR (OECD calculator). For the assessment of the safety of the CXL proposals, EFSA used the EFSA PRIMo rev. 2 (EFSA, 2007a). For assessing the acute consumer risk, EFSA applied the standard EU methodology, including the agreed EU variability s and the ARfD agreed at EU level. In those cases where a potential acute intake concern could not be excluded, EFSA calculated additional scenarios, aiming to provide risk managers with more information to decide on the acceptability of the CXL proposal. For the assessment of the long-term consumer risk, EFSA calculated the exposure resulting from the existing EU MRLs, including the risk assessment values (HR or STMR, where appropriate) for the proposed CXLs where the proposed CXLs are higher than the existing EU MRLs. It is noted that this approach overestimates the actual exposure, because it is not likely that each food item consumed contains residues at the maximum level allowed in the European legislation. The contribution of the individual crops under consideration in the CCPR meeting was calculated separately. In case the first conservative risk assessment indicated a potential consumer health risk EFSA performed more refined intake calculations, using appropriate data from other sources (e.g. STMR values instead of the EU MRL where available). The exposure assessments are usually based on the EU toxicological reference values, unless it was concluded that the toxicological reference values derived by JMPR are preferable. For some active substances, the exposure is calculated for both options. For CXL proposals for food of animal origin, EFSA focussed mainly on the consumer risk assessment and the validity of feeding studies and animal metabolism studies. For the CXLs for animal 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 Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC (1). OJ L 70, , p EFSA Journal 2014;12(7):

11 a full assessment of the expected dietary burden at EU level will not possible because relevant information may not be available to EFSA. It is noted that due to the short timelines available to prepare this report, the document can not replace a full, detailed assessment of the active substances under assessment. Thus, the comments and observations might be incomplete, or might need to be revised following an in-depth evaluation. 2. Comments on the JMPR follow-up evaluation with regard to specific concerns 2.1. Buprofezin (173) During 2013 Meeting the US delegation raised a concern on the study reports regarding the coffee cultivation practice and field trial conditions in Brazil and USA. Although the information provided shows that the cultivation practices are similar, a significant difference in the processing of coffee berries (cherries) to green coffee was noticed. Since this difference may have an impact on residue concentrations in green coffee, the Meeting concluded that is not appropriate to combine the residues from Hawaii and Brazil to estimate a maximum residue level for coffee. Thus, no MRL proposal was derived. The proposal of JMPR is acceptable Background information Buprofezin was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with Finland as Rapporteur Member State. A decision to approve the active substance (Commission Directive 2011/6/EC 5 ) was taken in For buprofezin an EFSA conclusion is available (EFSA, 2010d). The MRL review under the Article 12 of Regulation (EC) No 396/2005 has not yet started. The following toxicological reference values derived by EU level and by JMPR. Table 1: Comparison of toxicological reference values derived by JMPR and at EU level JMPR evaluation (1999 reviewed in 2009) EU evaluation (EFSA 2010) ADI mg/kg bw per day 2 years study on rats mg/ kg bw per day 2 years study in rats 100 ARfD 0.5 mg/kg bw mg/kg bw Rat developmental study 100 In the following table the residue definitions for risk assessment and enforcement purpose are compared. 5 Commission Directive 2011/6/EU of 20 January 2011 amending Council Directive 91/414/EEC to include buprofezin as active substance. OJ L 18, , p EFSA Journal 2014;12(7):

12 Table 2: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation RD enf Plant Animal Buprofezin Buprofezin This residue is fat soluble RD RA Plant Animal Buprofezin Sum of buprofezin and BF4 conjugates analysed as BF9+BF12 under acidic hydrolysis conditions and expressed as buprofezin This residue is fat soluble 2.2. Clothianidin (238)/Thiamethoxam (245) The EU delegation raised concern regarding the setting of MRL group for clothianidin for root and tuber vegetables. The 2013 Meeting agreed that a group maximum residue level for thiamethoxam (parent compound) in root and vegetables would not be appropriate since the thiamethoxam GAP for potatoes, radish, carrots and sugar beet are different. JMPR presented a detailed table summarising the GAPs for clothianidin, and thiamethoxam, split up for the different crops in the crop group under consideration, i.e. carrots, radish roots, chicory roots, potatoes and sugar beet roots. The table also contains a brief summary of the results of the residue trials for clothianidin (in case the trials were performed with thiamethoxam reflecting the thiamethoxam GAP, the results for metabolite CGA (=clothianidin) are reported). JMPR confirmed the group tolerance for root and tuber vegetables for clothianidin at the level of 0.2 mg/kg. EFSA notes that the detailed assessment of the GAPs and residue trials for the different crops confirmed that for potatoes a clothianidin MRL of 0.2 mg/kg is acceptable, reflecting the seed treatment with thiamethoxam (6.2 g thiamethoxam/100 kg seed). For sugar beet a clothianidin MRL of 0.03 mg/kg would be appropriate, resulting from the use of clothianidin seed treatment (0.6 mg ai/seed). However, for the remaining crops the situation is as follows: Crop Supporting residue trials Conclusion regarding MRL for clothianidin Carrots No GAP for clothianidin. MRL should be set at the LOQ of 0.01 mg/kg The foliar and the soil treatment GAP for thiamethoxam are sufficiently supported by data which demonstrate that no clothianidin residues will occur. Radish roots No clothianidin GAP MRL should be set at the LOQ of The thiamethoxam GAPs (foliar6 and soil treatment) are sufficiently supported by data that demonstrate 0.01 mg/kg 6 The application rate for the foliar treatment of radish roots is not correct. It should be 0.11 kg ai/ha. The error resulted from a typo in a document prepared by Belgium. However, this error does not have an impact on the assessment. EFSA Journal 2014;12(7):

13 Crop Supporting residue trials Conclusion regarding MRL for clothianidin Chicory roots that no clothianidin residues will occur. The GAP for clothianidin (0.3 mg ai/seed) is not sufficiently supported by trials (only one trial, <0.01 mg/kg). No GAP for thiamethoxam MRL should be set at the LOQ of 0.01 mg/kg It is noted that extrapolation from trials in sugar beet (seed treatment with 0.6 mg ai/seed) could be considered, using the proportionality principle. In this case a MRL of mg/kg might be appropriate. Thus, for potatoes the clothianidin MRL of 0.2 mg/kg is acceptable, for sugar beet a clothianidin MRL of 0.03 mg/kg is appropriate, for carrots and radish roots the clothianidin MRL should be set at the level of 0.01 mg/kg. For chicory roots, the residue trials on sugar beet could be used to derive a MRL proposal of mg/kg. (Considering the MRL classes of Codex, a CXL of 0.02 mg/kg would be appropriate.) The setting of a group tolerance for all root and tuber vegetables is not justified. EFSA does not agree with the rationale of JMPR that since a group MRL was set for thiamethoxam, also a group MRL for clothianidin needs to be set. There are sufficient residue data to derive MRL proposals. Also the argument that the setting of a group tolerance would be justified because it makes best use of the available data in a complex situation is not acceptable Background information Clothianidin (238) Clothianidin was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with Belgium as Rapporteur Member State. A decision to approve the active substance (Commission Directive 2006/41/EC7) was taken in For clothianidin no EFSA conclusion is available. The MRL review under Article 12 of Regulation (EC) No 396/2005 is not finalised. Table 3: The following toxicological reference values have been derived at EU level and by JMPR JMPR evaluation (1999 reviewed in 2009) EU evaluation (2006) ADI mg/kg bw/day 2 year study on rats mg/ kg bw per day 2 year study in rats 100 ARfD 0.6 mg/kg bw Rat acute neurotoxicity mg/kg bw Developmental toxicity rat and rabbit 100 In the following table the residue definitions for risk assessment and enforcement purpose are compared. 7 Commission Directive 2006/41/EC of 7 July 2006 amending Council Directive 91/414/EEC to include clothianidin and pethoxamid as active substances. OJ L 187, , p EFSA Journal 2014;12(7):

14 Table 4: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation RD enf Plant Clothianidin -Clothianidin and, thiamethoxam (sum of thiamethoxam and clothianidin, expressed as thiamethoxam). -Clothianidin (Peer review) Animal Clothianidin -Clothianidin and, thiamethoxam (sum of thiamethoxam and clothianidin, expressed as thiamethoxam) -.Not required (Peer review) RD RA Plant Clothianidin Clothianidin (Peer review) See also thiamethoxam Animal Clothianidin Clothianidin (Peer review) See also thiamethoxam Background information Thiamethoxam (245) Thiametoxam was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with Spain as Rapporteur Member State. A decision to approve the active substance (Commission Directive 2007/6/EC 8 ) was taken in For thiamethoxam an EFSA conclusion is available (EFSA, 2013a). The MRL review under Article 12 of Regulation (EC) No 396/2005 is not finalised. Table 5: The following toxicological reference values have been derived at EU level and by JMPR JMPR evaluation (2010) EU evaluation (2006) ADI mg/kg bw/day 90-day toxicity study in dogs mg/kg bw per day Long-term mouse study 100 ARfD 1 mg/kg bw Single-dose neurotoxicity study in rats mg/kg bw Rat developmental toxicity study 100 In the following table the residue definitions for risk assessment and enforcement purpose are compared. 8 Commission Directive 2007/6/EC of 14 February 2007 amending Council Directive 91/414/EEC to include metrafenone, Bacillus subtilis, spinosad and thiamethoxam as active substances. OJ L 43, , p EFSA Journal 2014;12(7):

15 Table 6: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation (EFSA, 2013) RD enf Plant Animal Thiamethoxam -Clothianidin and, -Thiamethoxam (sum of thiamethoxam and clothianidin, expressed as thiamethoxam) (Reg. 396/2005) -Thiamethoxam + N-(2-chloro-thiazol-5- ylmethyl)-n'-methyl-n''-nitro-guanidine (CGA ) expressed as thiamethoxam (Peer review LoEPs, 2006) RD RA Plant Thiamethoxam and clothianidin (considered separately) -Thiamethoxam + N-(2-chloro-thiazol-5- ylmethyl)-n'-methyl-n''-nitro-guanidine (CGA ) expressed as thiamethoxam (Peer review LoEPs, 2006) Animal (except poultry) Thiamethoxam and clothianidin (considered separately) -Thiamethoxam + N-(2-chloro-thiazol-5- ylmethyl)-n'-methyl-n''-nitro-guanidine (CGA ) expressed as thiamethoxam (Peer review LoEPs, 2006) Animal (for poultry) Sum of thiamethoxam, CGA and MU3, expressed as thiamthoxam; and clothanidin (clothianidin to be considered separately from thiamethoxam) Thiamethoxam + N-(2-chloro-thiazol-5- ylmethyl)-n'-methyl-n''-nitro-guanidine (CGA ) expressed as thiamethoxam (Peer review LoEPs, 2006) 2.3. Glufosinate ammonium (175) In 2012 JMPR established an ARfD for glufosinate ammonium (0.01 mg/kg bw) which was proposed to be applied also for the metabolites NAG, MPP and MPA, noting that the use of the ARfD is likely to be conservative, since there were indications that the metabolites are of lower toxicity. Since an acute intake concern could not be excluded for bananas (110% of ARfD), kiwifruit (110% of ARfD), lettuce (180% of ARfD), soy bean dry (120% of ARfD) and cattle liver (170% of ARfD) with this conservative approach, CCPR asked to derive toxicological potencies s which would allow refinement of the exposure calculations. In 2013 JMPR the Meeting concluded that NAG, MPP and MPA should be considered to be less toxic (potency of 0.1 for chronic and acute toxicity). In a revised risk assessment, JMPR concluded that for soya beans the exposure still exceeds the ARfD, taking into account the relatively lower toxicity of the metabolites (adjusted STMR mg/kg). Further data would be required to make more refined intake calculations for processed soya bean products. For the other crops where Codex MRLs were derived in 2012, a public health concern could be excluded. In the past, EFSA has assessed some studies available for the metabolites (31 studies for NAG, 19 studies for MPP, 6 studies for MPA) and concluded that these metabolites are likely to be less toxic than the parent compound glufosinate-ammonium. However, the EU ADI and ARfD are based on developmental toxicity study (in rabbits) with an UF of 300 (taking into account the severity of the effects), while JMPR used the dog study where a significant decrease in brain glutamine synthetase activity was observed. Thus, the relative potency s derived by JMPR are not directly applicable because they refer to the potency of the metabolites to decrease the brain glutamine synthetase which was not the demonstrated to be the mod of action for developmental toxicity. EFSA Journal 2014;12(7):

16 Considering that using the EU reference values no dietary health concerns were identified for the crops for which MRLs were proposed by JMPR in 2012, there is currently no need to implement these potency s in the EU risk assessment Background information Glufosinate was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with Sweden as Rapporteur Member State. A decision to approve the active substance (Commission Directive 2007/25/EC9) was taken in For glufosinate an EFSA conclusion is available (EFSA 2012c). The MRL review under the Article 12 of Regulation (EC) No 396/2005 is at stage 3 (drafting of reasoned opinion). Table 7: The following toxicological reference values have been derived at EU level and by JMPR JMPR evaluation (2012) EU evaluation (EFSA 2012c) ADI mg/kg bw/day Dog toxicity studies mg/kg bw per day Rabbit, developmental toxicity study 300 ARfD 0.01 mg/kg bw Dogs, 28-day capsule study mg/kg bw Rabbit developmental toxicity study 300 In the following table the residue definitions for risk assessment and enforcement purpose are compared. Table 8: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation RD enf Plant Animal Sum of glufosinate-ammonium, 3- [hydroxy(methyl)phosphinoyl]propioni c acid (MPP) and N-acetyl glufosinate (NAG), calculated as free acid Sum of glufosinate, its salts, 3-methylphosphinico-propionic acid (MPP), and N- acetyl-glufosinate (NAG) expressed as glufosinate equivalents RD RA Plant Sum of glufosinate-ammonium, 3- [hidroxy(methyl)phosphinoyl]propionic acid (MPP) and N-acetyl glufosinate (NAG), calculated as free acid Sum of glufosinate, its salts, 3-methylphosphinico-propionic acid (MPP), and N- acetyl-glufosinate (NAG) expressed as glufosinate equivalents Animal The residue is not fat soluble 9 Commission Directive 2007/25/EC of 23 April 2007 amending Council Directive 91/414/EEC to include dimethoate, dimethomorph, glufosinate, metribuzin, phosmet and propamocarb as active substances. OJ L 106, , p EFSA Journal 2014;12(7):

17 2.4. Propylene oxide (250) Scientific support for preparing EU position for the 2014 CCPR In 2011 JMPR derived toxicological reference values for propylene oxide (PPO) (ADI 0.04 mg/kg bw per day, ARfD 0.04 mg/kg bw, both based on a NOAEL for systemic effects from a chronic inhalation study in rats with a safety of 1000). Due to deficiencies in the database no toxicological reference values could be derived for the metabolites propylene chlorydrine and propylene bromohydrin. USA submitted a concern form requesting JMPR to provide explanations why an additional 10-fold uncertainty applied for the ARfD. In addition, USA asked JMPR to reassess the toxicological data for PCH and PBH. JMPR confirmed its conclusion on PPO that due to limitations in the available database (absence of non-rodent studies and of an adequate developmental toxicity study in rabbits), it was not possible to reliably assess the acute toxicity. Therefore the increased safety was found appropriate. EFSA agrees with the JMPR approach. For propylene chlorohydrin and propylene bromohydrin JMPR confirmed that the data are not sufficient to derive toxicological reference values. Also in this case EFSA supports the approach taken by JMPR Background information No dossier for approval has been submitted at EU level for the active substance propylene oxide. Thus, no evaluation and no EFSA conclusion are available Table 9: The following toxicological reference values have been derived at EU level and by JMPR JMPR evaluation (2011) EU evaluation ADI mg/kg bw/day Rat, chronic study by inhalation ARfD 0.04 mg/kg bw Rat, chronic study by inhalation In the following table the residue definitions for risk assessment and enforcement purpose are compared. EFSA Journal 2014;12(7):

18 Table 10: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation RD enf Plant Propylene oxide Not included in Annex II, III or IV of Regulation (EC) No 396/2005 Animal no data, no residues anticipated RD RA Plant Propylene oxide (PPO), and propylene chlorohydrin (PCH) plus propylene bromohydrin (PBH) to be considered separately from propylene oxide Not assessed at EU level. Animal no data, metabolism data in rats used for assessment, no RD proposed 3. Comments on the individual substances assessed 3.1. Diquat (31) (T,R) Diquat was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with United Kingdom as Rapporteur Member State and Sweden Co-Rapporteur Member State. A decision to approve the active substance (Commission Directive 2001/21/EC 10 ) was taken in For diquat no EFSA conclusion is available. The MRL review under Article 12 of Regulation 396/2005 is close to finalisation (status April 2014) Toxicological endpoints - Diquat The following toxicological reference values derived by EU level and by JMPR: Table 11: Comparison of toxicological reference values derived by JMPR and at EU level JMPR evaluation 1993 EU evaluation (2001) ADI ARfD mg/kg bw per day (diquat ion) 0.8 mg/kg bw (diquat ion) 2-years study of toxicity and carcinogenicity Acute neurotoxicity study in rats mg/kg bw per day (Diquat ion) 100 n.a 2 years rat study Commission Directive 2001/21/EC of 5 March 2001 amending Annex I to Council Directive 91/414/EEC concerning the placing of plant protection products on the market to include amitrole, diquat, pyridate and thiabendazole as active substances. OJ L 69, , p EFSA Journal 2014;12(7):

19 JMPR evaluation 1993 EU evaluation (2001) Conclusion JMPR concluded that 1,2,3,4-Tetrahydro-1-oxopyrido(1,2-a)-5-pyrazinium salt (TOPPS), a metabolite in livestock but not in rats, was less toxic than the parent compound. The acute oral LD50 of TOPPS in rats was 2449 mg/kg bw. There was no evidence of genotoxicity in the deoxyribonucleic acid (DNA) repair test. In the framework of the MRL review, EFSA will request that the toxicological relevance of the major photodegradation product TOPPS (1,2,3,4-tetrahydro-1-oxo-pyrido [1,2a]-5-pyrazinium chloride) recovered in the metabolism study on cereals should be addressed since there is no clear evidence whether this metabolite is present in the rat metabolism and whether its toxicological properties are covered by those of the parent compound Residue definitions - Diquat In the following table the residue definitions for risk assessment and enforcement purpose are compared. Table 12: Comparison of the residue definitions derived by JMPR and at EU level group JMPR evaluation EU evaluation RD enf RD RA Conclusion Plant Animal Plant Animal Diquat The residue is not fat soluble Diquat The residue is not fat soluble Diquat Diquat In the framework of the review of the existing EU MRLs under Article 12 of Regulation (EU) No 396/2005, EFSA derived a tentative residue definition for enforcement and risk assessment as diquat in plant, pending a decision on the toxicological relevance of TOPPS. Metabolism studies in lactating goat and poultry were reported in the JMPR report TOPPS is not considered as a potential metabolite to be included in the RD for RA for animal matrices. Diquat monopyridone and diquat dipyridone should be rediscussed as relevant metabolites to be potentially included in the RD for RA based on the calculated DB. In the framework of this assessment, the risk assessment will be based on parent diquat. If a revision of the RD for RA will be decided, the risk assessment needs to be reconsidered CXL proposals - Diquat In the table below the CXL proposals are compared with the EU MRL. EFSA Journal 2014;12(7):

20 Table 13: Comparison of CXL proposals derived by JMPR and EU MRLs CXL proposal derived by JMPR 2013 EU MRL Comment Alfalfa fodder (W) 100 No data are available. EFSA agrees on the withdrawal of the existing CXL. Banana 0.02* 0.05* Residue values: 6x<0.05 mg/kg complying with GAP (0.6 kg as/ha, PHI: not required) The Codex MRL proposal is acceptable. Barley 5 (W) 10 Since no data were provided the CXL is proposed for withdrawal. It is noted that at EU level a use was notified in the framework of the Art. 12 review. Beans (dry) The Codex MRL is based on the Canadian GAP (up to 0.41 kg as/ha for ground application and 0.55 kg as/ha for aerial application; PHI 4 days.) The MRL proposal replacing a previous recommendation of 0.2 mg/kg is acceptable. Cajou (pseudofruit) 0.02 * No available information on the GAP. Possible extrapolation from the complete residue dataset on citrus, apples, banana and coffee. The Codex MRL proposal is acceptable. Cashew apple 0.02 * No available information on the GAP. Possible extrapolation from the complete residue dataset on citrus, apples, banana and coffee. The Codex MRL proposal is acceptable. Cashew nut 0.02 * 0.05* No available information on the GAP. Possible extrapolation from the complete residue dataset on citrus, apples, banana and coffee. The Codex MRL proposal is acceptable. Citrus fruits 0.02 * 0.05* Residue values: 4x<0.01-<0.02 mg/kg complying with GAP (0.5 kg as/ha, PHI: 14 days). The Codex MRL proposal is acceptable. Coffee beans 0.02 * 0.1* Residue values: 6x<0.05 mg/kg complying with GAP ( kg as/ha, PHI: 0 day). The Codex MRL proposal is acceptable, however, the setting of the MRL at the level of the LOQ of the residue trials (i.e. 0.05* mg/kg) could be considered. Edible (Mammalian) offal 0.01* 0.05* The Codex MRL proposal is acceptable. Eggs 0.01* 0.05* The Codex MRL proposal is acceptable. Fruiting vegetables, other than cucurbits (except sweetcorn, fungi and mushrooms) 0.01* 0.05* Based on the reported information, the GAPs for all the fruiting vegetables, other than cucurbits (except sweet corn, fungi and mushrooms) are assumed to be similar. Sufficient residue trials were provided on tomatoes with a possible extrapolation to aubergines to support the CXL proposal of 0.01* mg/kg. The Codex MRL proposal is acceptable. Lentil (dry) 0.2 (W) 0.2 EFSA agrees on the CXL withdrawal based on insufficient residue trials. EFSA Journal 2014;12(7):

21 CXL proposal derived by JMPR 2013 EU MRL Comment Maize 0.05 (W) 1 No data are available. EFSA agrees on the withdrawal proposal. Meat (from mammals other than marine mammals) 0.01 * 0.05* The Codex MRL proposal is acceptable. Milks * 0.05* The Codex MRL proposal is acceptable. Oats 2 (W) 2 No data are available. EFSA agrees on the withdrawal proposal. Peas (dry) Underdosed residue trials (but within the 25% tolerance limit) were reported to support the Slovakian GAP (1 x 0.8 kg as/ha, PHI: 6 days) and to derive a MRL of 0.3 mg/kg The Codex MRL proposal is acceptable. Pome fruits 0.02* 0.05* Residue values of 10x<0.01-2x<0.05 mg/kg complying with GAP on apple (1 kg as/ha, PHI not specified). The Codex MRL proposal is acceptable. Potato * The Codex MRL proposal is acceptable. Poultry meat 0.01* 0.05* The Codex MRL proposal is acceptable. Poultry, offal of Edible 0.01* 0.05* The Codex MRL proposal is acceptable. Rape seed The Codex MRL proposal is acceptable. Rice (W) * No data are available. EFSA agrees on the withdrawal proposal. Rice, husked (W) 1 No data are available. EFSA agrees on the withdrawal proposal. Rice, polished (W) 0.2 No data are available. EFSA agrees on the withdrawal proposal. Sorghum (W) * No data are available. EFSA agrees on the withdrawal proposal. Soya bean (dry) residue trials were provided to support the GAP (CAN) (1*0.56 kg as/ha, PHI: 4 d) but were characterized by a PHI: 7-10 days. The Codex MRL proposal is acceptable. Stone fruits 0.02 * 0.05* The Codex MRL proposal is acceptable. Strawberry 0.05 * 0.05* The Codex MRL proposal is acceptable. Sunflower seed Slovakian GAP (1x0.6 kg as/ha, PHI: 6 d) is supported by sufficient residue trials. The Codex MRL proposal is acceptable. Vegetable Crude oils, Vegetables (except as otherwise listed) (W) 0.05 (W) 0.05 Not relevant None EFSA Journal 2014;12(7):

22 CXL proposal derived by JMPR 2013 EU MRL Comment Wheat (W) * No data are available. EFSA agrees on the withdrawal proposal. Wheat unprocessed bran, (W) 2 Not relevant Wheat flour (W) 0.05 Not relevant The CXL proposals are acceptable. *- limit of quantification Consumer risk assessment Diquat The result for the consumer risk assessment is presented in the Table below. Table 14: Summary of the consumer risk assessment for diquat (for detailed calculation see Appendix A) Chronic risk Acute risk Conclusion The chronic intake was calculated using the ADI agreed at EU level and the current EU MRLs; for the crops where the existing EU MRLs are lower than the proposed Codex MRLs the STMRs derived by JMPR were used (i.e. peas, dry, potatoes, soyabeans). TMDI: 233 % ADI (with maize being the major contributor to the intake with the EU MRL of 1 mg/kg). Further refinements would be possible, in particular as regards the existing EU MRLs The crops for which higher Codex MRLs have been proposed, contributed to max. 15% (potatoes), and less than 1 % for peas and soyabeans. Currently no ARfD is established at EU level. EFSA performed an indicative short term risk assessment using the ARfD derived by JMPR. No acute intake concern was identified considering only the Codex MRL proposals : 1.2% of ARfD for potatoes, 0.3% ARfD for oranges, 0.2% ARfD for apples, pears, grape fruit. There is a chronic intake concern when the current EU MRLs and the Codex MRL proposals are considered using the agreed ADI at EU level. No acute intake concern was identified considering only the codex MRL proposals and the ARfD proposed by the JMPR Malathion (049) (R) Malathion was evaluated under Directive 91/414/EEC, repealed by Regulation (EC) No 1107/2009 with Finland as Rapporteur Member State. A decision to approve the active substance (Commission Directive 2010/17/EU 11 ) was taken in For malathion an EFSA conclusion is available (EFSA, 2009d). The MRL review under Article 12 of Regulation (EC) No 396/2005 is at stage 0 (data pending). EFSA has issued a reasoned opinion on the modification of the existing MRLs for malathion in camomile (EFSA, 2011e). On February 2014, EFSA issued a reasoned opinion on the modification of the existing MRLs for malathion on various crops (citrus fruits, pome fruits, plums, strawberries and lettuce (EFSA, 2014). 11 Commission Directive 2010/17/EU of 9 March 2010 amending Council Directive 91/414/EEC to include malathion as active substance. OJ L 60, , p EFSA Journal 2014;12(7):