REASONED OPINION. European Food Safety Authority 2, ABSTRACT. European Food Safety Authority (EFSA), Parma, Italy KEY WORDS

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1 EFSA Journal 2012;10(10):2920 REASONED OPINION Reasoned opinion on the modification of the existing MRL(s) for in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons1 ABSTRACT European Food Safety Authority 2, European Food Safety Authority (EFSA), Parma, Italy In accordance with Article 6 of Regulation (EC) No 396/2005, The Netherlands received an application from Chemtura to modify the existing MRL(s) for the active substance in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons. In order to accommodate for the intended use of, the evaluating Member State (EMS) proposed to raise the existing MRLs for all of the crops except for pepper where a lowering of the MRL was proposed, and for tomatoes and aubergines, where it was concluded that no modification of the MRL would be required. The EMS drafted an evaluation report according to Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 6 January According to EFSA the data are sufficient to derive MRL proposals of 0.9 mg/kg for citrus fruit, 0.5 mg/kg for pome fruit, 0.5 mg/kg peaches/nectarines and plums, 0.7 mg/kg for grapes, 3 mg/kg for strawberries, 0.5 mg/kg for tomatoes and aubergines, 0.4 mg/kg for sweet pepper, 3 mg/kg for chilli pepper, 0.6 mg/kg for cucurbits with inedible peel and 20 mg/kg for hops. Adequate analytical enforcement methods are available to control the residues of on the commodities under consideration at the validated LOQ of 0.01 mg/kg. Since for some of these crops higher MRLs were proposed in a previously issued reasoned opinion of EFSA, they need to be considered to avoid trade disruption. Based on the risk assessment results, EFSA concludes that the proposed use of on citrus fruit, pome fruit, stone fruit, table- and wine grapes, strawberries, tomatoes, peppers, aubergines, melons, watermelons and hops will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a consumer health risk. European Food Safety Authority, 2012 KEY WORDS Bifenazate, citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons, watermelons, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, carbazide acaricide, -diazene. 1 On request from European Commission, Question No EFSA-Q , approved on 15 October Correspondence: pesticides.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Reasoned opinion on the modification of the existing MRL(s) for in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons. EFSA Journal 2012;10(10):2920. [45 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 SUMMARY In accordance with Article 6 of Regulation (EC) No 396/2005 3, The Netherlands, herewith referred to as the evaluating Member State (EMS), received an application from Chemtura to modify the existing MRL(s) for the active substance in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons. In order to accommodate for the intended use of, the EMS proposed to raise the existing MRLs from the limit of quantification to proposed MRL 0.9 mg/kg for citrus fruit, 0.4 mg/kg for pome fruit, 0.5 mg/kg for apricot, nectarine, peach and plum, 0.7 mg/kg for grape, 0.4 mg/kg for cucurbits with inedible peel (melon and watermelon) and 20 mg/kg for hop. The EMS proposed to decrease the value of existing MRL 2 mg/kg to proposed MRL 0.4 mg/kg for pepper. The EMS proposed to maintain the value of existing MRLs of 0.5 mg/kg for tomato and aubergine. The EMS drafted an evaluation report according to Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 6 January EFSA bases its assessment on the evaluation report submitted by the EMS (The Netherlands, 2006, 2011, 2012), the Draft Assessment Report (DAR) prepared by the rapporteur Member State (RMS) the Netherlands under Directive 91/414/EEC (The Netherlands, 2003), the JMPR Evaluation report (FAO, 2006, 2008, 2010) as well as the conclusions from a previous EFSA opinion on (EFSA 2012) and the reasoned opinion on the review of the existing MRLs for according to Article 12 of Regulation (EC) No 396/2005 (Article 12 MRL review, EFSA 2011). The toxicological profile of was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI value of 0.01 mg/kg bw per day. Due to the low acute toxicity of the active substance the setting of an ARfD was considered not necessary. The metabolism of in primary crops was investigated in oranges, apples and grapes (fruits and fruiting vegetables), radishes (root and tuber vegetables), cotton (pulses and oilseeds) and maize (cereals). From these studies residue definitions for enforcement and risk assessment were derived which comprise the sum of and -diazene, expressed as. For the use on citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons, EFSA concludes that the metabolism of in primary crops is sufficiently addressed and that the derived residue definitions are applicable. EFSA considers that the submitted supervised residue trials are sufficient to derive MRL proposals of 0.9 mg/kg for citrus fruit, 0.5 mg/kg for pome fruit, 0.5 mg/kg peaches/nectarines and plums, 0.7 mg/kg for grapes, 3 mg/kg for strawberries, 0.5 mg/kg for tomatoes and aubergines, 0.4 mg/kg for sweet pepper, 3 mg/kg for chilli pepper, 0.6 mg/kg for cucurbits with inedible peel and 20 mg/kg for hops. Adequate analytical enforcement methods are available to control the residues of on the commodities under consideration at the validated LOQ of 0.01 mg/kg for all commodities except for hops with a LOQ of mg/kg. Since for some of the crops MRL recommendations have been derived in a previously issued reasoned opinion (Article 12 MRL review) which are higher than the MRLs required for the intended uses assessed in the application, the higher MRLs had to be considered in the risk assessment of EFSA. Studies investigating the nature of residues in processed commodities were assessed in the framework of this application for MRL modification and showed that the compound is hydrolytically stable under the processing conditions representative for pasteurisation, boiling/cooking and sterilisation. Therefore for processed commodities the same residue definition as for raw agricultural commodities (RAC) has been proposed. 3 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October OJ L 309, , p EFSA Journal 2012;10(10):2920 2

3 The occurrence of residues in rotational crops was investigated in the framework of the Article 12 MRL review. Based on the available information on the nature and magnitude of residues in succeeding crops, it was concluded that significant residue levels are unlikely to occur in rotational crops provided that the compound is used on strawberries, aubergines, tomatoes, peppers and hops according to the proposed pattern. Since the pomace or pulp of orange and apple are used as feed items, a potential carry-over into food of animal origin was assessed. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg (dry matter) for all relevant species but was much lower than the dietary burden estimated in 2006 and 2010 by JMPR. As the MRL proposals for food of animal origin derived in the framework of the Article 12 MRL review are based on the higher JMPR dietary burden calculations, EFSA concludes that for the intended uses assessed in the framework of this application no modification of these MRL recommendations is required. In the framework of the Article 12 MRL review a comprehensive long-term consumer exposure assessment was performed, taking into account the existing uses of at EU level which are supported by data, and the existing acceptable CXLs (EFSA, 2011). Those food commodities, for which no uses of were reported in the framework of Article 12 of Regulation (EC) No 396/2005 and for which no safe CXLs were identified, were excluded from the exposure calculation, assuming that there is no use on these crops. This risk assessment was updated including the median residue concentrations observed in citrus fruit, tomatoes and cucurbits with inedible peel derived from the residue trials submitted in support of this MRL application. For pome fruit, stone fruit, grapes, hops, strawberries, peppers and aubergines the more conservative median residue value reflecting the MRLs recommended in the Article 12 MRL review are used as an input value. This consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). No acute exposure calculation was performed since no ARfD was established for due to its low acute toxicity. The estimated long-term exposure was then compared with the ADI value derived for. Under the assumption that the MRLs will be amended as proposed in this and in the previously issued reasoned opinion, no long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 7.4 to 65% of the ADI (maximum intake for DE child diet). The contribution of residues in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons under consideration to the total consumer exposure accounted for a maximum of 21.1% for apples (DE child diet), 10.3% for citrus fruit (DE child diet), 5.5% for peppers (WHO Cluster diet B), 4.3% for tomatoes (WHO Cluster diet B) and 4.6% for wine grapes (PT General population). EFSA concludes that the proposed use of on citrus fruit, pome fruit, stone fruit, table- and wine grapes, strawberries, tomatoes, peppers, aubergines, melons, watermelons and hops will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a consumer health risk. EFSA recommends that the MRLs proposed for in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 and in the framework of the current application are implemented simultaneously. Thus EFSA proposes to amend the existing MRLs as reported in the summary table. EFSA Journal 2012;10(10):2920 3

4 Summary table Code number (a) Commodity Existing EU MRL (mg/kg) Proposed EU MRL (b) (mg/kg) Justification for the proposal Enforcement residue definition: sum of and -diazene, expressed as Citrus fruit 0.01* 0.9 The MRL proposal reflects the intended SEU GAP. It is sufficiently supported by data and no consumer intake concerns were identified Pome fruit 0.01* 0.5/0.7 The MRL proposal of 0.5 mg/kg reflects the intended NEU GAP which is sufficiently supported by data. The MRL proposal of 0.7 mg/kg is derived from the existing CXL which was according to the previously issued reasoned opinion of EFSA found to be not adequately supported by data (EFSA, 2011). Both MRL proposals are acceptable from a consumer safety point of view Stone fruit 0.01* 2 The MRL proposal is derived from the existing CXL which was according to the previously issued reasoned opinion of EFSA found to be supported by data, and for which no consumer risk was identified (EFSA, 2011). Apricot See stone fruit For the intended use submitted in this application data were not sufficient to derive a MRL. The group tolerance proposed in the previous reasoned opinion covers also apricots. Peaches/ nectarines Table and wine grapes See stone fruit For the intended SEU use submitted in the framework of this application a MRL of 0.5 mg/kg was derived. Since the MRL proposal for stonefruit is higher, priority is given to the MRL of 2 mg/kg. Plums See stone fruit For the intended NEU use submitted in the framework of this application a MRL of 0.5 mg/kg was derived. Since the MRL proposal for stonefruit is higher, priority is given to the MRL of 2 mg/kg. 0.01* 0.7 The MRL proposal reflects the intended NEU use. It is sufficiently supported by data and no consumer intake concerns were identified. The same MRL was proposed in the previous EFSA opinion (EFSA, 2011) Strawberries 2 3 The MRL reflects the SEU outdoor use and the indoor use EFSA Journal 2012;10(10):2920 4

5 Code number (a) Commodity Existing EU MRL (mg/kg) Proposed EU MRL (b) (mg/kg) Justification for the proposal in the EU. It is sufficiently supported by data and no consumer intake concerns were identified. Since this MRL proposal is higher than the MRL derived in the previous EFSA opinion, priority is given to the value of 3 mg/kg Tomatoes The MRL reflects the indoor use in the EU. It is sufficiently supported by data and no consumer intake concerns were identified. The same MRL was proposed in the previous EFSA opinion (EFSA, 2011) Peppers 2 2/3 The MRL proposal of 2 mg/kg is derived from the existing CXL which was according to the previously issued reasoned opinion of EFSA found to be supported by data, and for which no consumer risk was identified (EFSA, 2011). For the intended indoor use on sweet peppers in the EU submitted in the framework of this application a MRL proposal of 0.4 mg/kg was derived. For the intended indoor use on chilli pepper a MRL proposal of 3 mg/kg was derived. Both MRLs are safe for consumers. A risk management decision should be taken whether the EU MRL should be based on the CXL or the value derived for chilli peppers Aubergines (egg plants) Cucurbits inedible peel The MRL reflects the indoor use in the EU. It is sufficiently supported by data and no consumer intake concerns were identified. The same MRL was proposed in the previous EFSA opinion (EFSA, 2011). 0.01* 0.6 The MRL reflects the SEU outdoor use. It is sufficiently supported by data and no consumer intake concerns were identified. Since this MRL proposal is higher than the MRL derived in the previous EFSA opinion, priority is given to the value of 0.6 mg/kg Hops (dried) 0.02* 20 The MRL proposal reflects the intended NEU GAP. It is sufficiently supported by data and no consumer intake concerns were identified. EFSA Journal 2012;10(10):2920 5

6 Code number (a) Commodity Existing EU MRL (mg/kg) Proposed EU MRL (b) (mg/kg) Justification for the proposal The same MRL was proposed in the previous EFSA opinion (EFSA, 2011). (a): According to Annex I of Regulation (EC) No 396/2005. (b): MRL proposals have been derived according to the proposed enforcement residue definition: the sum of and -diazene, expressed as. (*): Indicates that the MRL is set at the limit of analytical quantification. EFSA Journal 2012;10(10):2920 6

7 TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 7 Background... 8 Terms of reference... 8 The active substance and its use pattern... 9 Assessment Method of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues Nature and magnitude of residues in plant Primary crops Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Consumer risk assessment Conclusions and recommendations References Appendices Abbreviations EFSA Journal 2012;10(10):2920 7

8 BACKGROUND Regulation (EC) No 396/ establishes the rules governing the setting of pesticide MRLs at European Union level. Article 6 of that Regulation lays down that any party having a legitimate interest or requesting an authorisation for the use of a plant protection product in accordance with Council Directive 91/414/EEC 5, repealed by Regulation (EC) No 1107/2009 6, shall submit to a Member State, when appropriate, an application to modify an MRL in accordance with the provisions of Article 7 of that Regulation. The Netherlands, hereafter referred to as the evaluating Member State (EMS), received an application from the company Chemtura 7 to modify the existing MRL(s) for the active substance in citrus fruit, pome fruit, stone fruit, grapes, hops, strawberries, tomatoes, peppers, aubergines, melons and watermelons. This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation report was submitted to the European Commission who forwarded the application, the evaluation report and the supporting dossier to EFSA on 6 January The application was included in the EFSA Register of Questions with the reference number EFSA-Q and the following subject: Bifenazate- Application to modify the existing MRLs in various crops The Netherlands proposed the following MRLs: 0.9 mg/kg for citrus fruit, 0.4 mg/kg for pome fruit, 0.5 mg/kg for apricots, peaches/nectarines and plums, 0.7 mg/kg for grapes, 3 mg/kg for strawberries, 0.5 mg/kg for tomatoes and aubergines, 0.4 mg/kg for sweet peppers, 0.4 mg/kg for cucurbits (inedible peel) and 20 mg/kg for hops. During the assessment of the application, EFSA identified some data gaps which were essential to conclude on the consumer risk assessment. Thus, EFSA asked for further data which were provided by the applicant and evaluated by the EMS. An addendum to the evaluation report was provided on 25 July Upon reception of this data, EFSA proceeded with the assessment of the application and the evaluation report as required by Article 10 of the Regulation. TERMS OF REFERENCE In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the evaluating Member State, provide a reasoned opinion on the risks to the consumer associated with the application. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within three months (which may be extended to six months where more detailed evaluations need to be carried out) from the date of receipt of the application. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. In this particular case the calculated deadline for providing the reasoned opinion is 21 April Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July OJ L 230, , p Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October OJ L 309, , p Chemtura Europa Ltd. Kennet House, 4 Langley Quay, Slough. SL3 6EH. Berkshire. The United Kingdom EFSA Journal 2012;10(10):2920 8

9 THE ACTIVE SUBSTANCE AND ITS USE PATTERN Bifenezate is the ISO common name for isopropyl 2-(4-methoxybiphenyl-3-yl)hydrazinoformate (IUPAC). The chemical structure of the compound is herewith reported. O CH 3 H 3 C H 3 C HN O NH O Molecular weight: g/mol Bifenazate belongs to the group of carbazate compounds which are used as acaricides. Bifenazate is a non-systemic active substance. Bifenazate was evaluated in the framework of Directive 91/414/EEC with the Netherlands being the designated rapporteur Member State (RMS). The representative use supported for the peer review process was foliar treatment of protected and field grown ornamentals. Following the peer review, a decision on inclusion of the active substance in Annex I to Directive 91/414/EEC was published by means of Commission Directive 2005/58/EC 8, entering into force on 01 December The Annex I inclusion of is restricted to uses as acaricide only. As EFSA was not yet involved in the peer review of, a conclusion of EFSA on this active substance is not available. The EU MRLs for are established in Annexes II and IIIB of Regulation (EC) No 396/2005 (Appendix C). The existing EU MRLs for citrus fruit, pome fruit, stone fruit, melon and hops are set at the LOQ (i.e mg/kg for citrus fruit, pome fruit, stone fruit, melon and watermelon and 0.02 mg/kg for hops). The existing EU MRLs for strawberry, tomatoes, aubergines and peppers are set at 2, 0.5, 0.5 and 2 mg/kg respectively. EFSA finalized the review of the existing MRLs for according to Article 12 of Regulation (EC) No 396/2005 (Article 12 MRL review) (EFSA, 2011). In the framework of this MRL review modifications were proposed for several crops including pome fruit, stone fruit, grapes, strawberries, tomatoes, aubergines, peppers, melons and hops, taking into account the acceptable Codex Limits (CXLs) and the authorised uses at EU level. The MRLs recommended by EFSA are also reported in Appendix C in a separate column. The MRL proposals derived in the framework of the Article 12 MRL review have not been enforced yet but are taken into consideration for assessment of the current MRL application. The intended GAPs refers to outdoor uses of on citrus fruit, pome fruit, stone fruit, grapes and hops and indoor and outdoor uses of on strawberries, tomatoes, peppers, aubergines, melons and watermelons. The details of the intended GAPs for bifenezate are given in Appendix A. ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the EMS (The Netherlands, 2006, 2011, 2012), the Draft Assessment Report (DAR) prepared by the rapporteur Member State (RMS) the Netherlands under Directive 91/414/EEC (The Netherlands, 2003), the JMPR Evaluation report (FAO, 2006, 2008, 2010) as well as the conclusions from a previous EFSA opinion on (EFSA 8 Commission Directive 2005/58/EC of 21 September 2005, OJ L 246, , p EFSA Journal 2012;10(10):2920 9

10 2012) and the reasoned opinion on the review of the existing MRLs for according to Article 12 of Regulation (EC) No 396/2005 (Article 12 MRL review, EFSA 2011). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/ and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2010a, 2010b, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin The availability of the analytical enforcement methods for the determination of residues of and -diazene 10 in commodities of plant origin was investigated in the framework of the review of the existing MRLs for under Article 12 of Regulation (EC) No 396/2005 (EFSA, 2011). There it was concluded that, according to the methods submitted to JMPR, the sum of and -diazene can be enforced in food of plant origin with an LOQ of 0.01 mg/kg in high water content, high fat content, acidic and dry commodities. Most of the methods are based on HPLC with electrochemical (coulometric) detection. Another method using HPLC-MS/MS is suitable as confirmatory method for analysing residues of and -diazene at the LOQ of 0.01 mg/kg in commodities with high water content and high oil content commodities (almonds) and in raisins (FAO, 2006). An ILV was performed for the method. Additional validation data were provided for hops. The applicability of the method was demonstrated with a LOQ of mg/kg (The Netherlands, 2011). EFSA concludes that adequate analytical methods are available to monitor residues in the crops under consideration Methods for enforcement of residues in food of animal origin The availability of the analytical enforcement methods for the determination of residues of and -diazene in food of animal origin was investigated in the framework of the review of the existing MRLs for under Article 12 of Regulation (EC) No 396/2005 (EFSA, 2011). It was concluded that, according to the methods submitted to JMPR, the sum of and diazene can be enforced in food of animal origin with an LOQ of 0.01 mg/kg in muscle, liver, kidney, milk and fat. EFSA concludes that sufficiently validated analytical methods for enforcing the proposed MRL(s) for in food of animal origin are available. 2. Mammalian toxicology The toxicological assessment of was peer reviewed under Directive 91/414/EEC and toxicological reference values were established by the European Commission (EC, 2005). The data were sufficient to derive toxicological reference values for which are compiled in Table Commission Regulation (EU) No 546/2011 of 10 June OJ L 155, , p diazenecarboxylic acid, 2-(4-methoxy-[1,1'-biphenyl]-, 1-methylethyl ester EFSA Journal 2012;10(10):

11 Table 2-1: Overview of the toxicological reference values Modification of the existing MRLs for in various crops Source Year Value Study relied upon Safety factor Bifenazate ADI EC mg/kg bw per day ARfD EC 2005 Not necessary 90 d +1yr oral dog, 104 wk oral rat 100 Bifenazate diazene, the main metabolite identified in metabolism studies which was included in the residue definition for risk assessment, is expected to be of comparable toxicity. The toxicological reference value derived for the parent compound can be also applied for the risk assessment of this metabolite. 3. Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues In the framework of the Article 12 MRL review EFSA assessed the available metabolism studies of in fruits and fruiting vegetables (oranges, apples and grapes) following foliar treatment (EFSA, 2011). Most of the TRR in fruits was recovered as surface residue. Bifenazate was the main component of the TRR with -diazene present at significant levels (4.6% to 40% of the TRR). Additional metabolism studies in root and tuber vegetables (radishes), pulses and oilseed (cotton) and cereals (maize) were evaluated by the EMS (The Netherlands, 2006, 2011). These studies were never peer reviewed at EU level but metabolism studies in radish and cotton were evaluated by 2006 JMPR (FAO, 2006). In radish plant, after single application of 14 C- (1.12 and 2.24 kg a.s./ha) most of the TRR in radish remained on the foliage with low transfer to the roots. The majority of the residue remained on the surface. Parent was the main residue in radishes tops (60%-70%) with diazene as major metabolite (4.8-15%TRR). In cotton plants treated with a single application 14 C- (0.56 and 2.2 kg a.s./ha), and identifiable metabolites were present at very low levels in the cotton seed harvested 112 days after treatment. A high proportion (77-82%) of the cotton gin trash residue was extractable, with approximately 50% of the extractable residue and -diazene, -diazene oxide and 4- methoxybiphenyl identified as minor residue components. In maize, recovery in maize grain was low showing poor translocation to the grain. The major residue in grain was characterized as bound residues (78% TRR). The major residues in forage and stover included parent (2.4%-15% TRR) and its oxidation product diazene (6.5%-12% TRR), biphenyl-4-yl-sulfate (3.7%-12% TRR) and carbamate (7.6%-14%). Various other metabolites (<10% TRR) were identified in forage and stover. The additional metabolism data in radish, cotton and maize showed low translocation to radish roots, cotton seed and maize grain. Metabolism data in radish tops and cotton gin trash confirmed that parent was the major residue. Metabolism in maize forage/stover resulted in a range of metabolites and the parent compound could be identified as one of the major residues. EFSA Journal 2012;10(10):

12 The overview of the metabolism study designs is presented in the table below. Table 3-1: Summary of available metabolism studies in plants Group Crop Label position Fruits and fruiting vegetable Root and tuber vegetables Pulses and oilseeds Oranges Apples Grapes Radishes Cotton Substituted phenyl ring Substituted phenyl ring Substituted phenyl ring Substituted phenyl ring Substituted phenyl ring Cereals Maize Substituted phenyl ring Method, F or G (a) Foliar, F Foliar, F Foliar, F Foliar, G Foliar, F Foliar, F Rate (kg a.s./ha) 0.42 or or or or 2.24 (a): Outdoor/field use (F) or glasshouse/protected crops/indoor application (G) Application details No Sampling (DAT) 1 43, 184, 274, (leaf), , or Remarks Evaluated by the RMS after Annex I inclusion and by the 2006 JMPR 1 7 Evaluated by the EMS and by 2006 JMPR 0.85 or (forage), 103 (stover and grains) Evaluated by the EMS. In the framework of the Article 12 MRL review EFSA proposed to define the residue for both enforcement and risk assessment in fruits and fruiting vegetables as the sum of and -diazene, expressed as (EFSA, 2011). It is noted that the current enforcement residue definition according to Regulation (EC) No 396/2005 is set as parent only. For the uses on citrus fruit, pome fruit, stone fruit, grapes, strawberries, tomatoes, peppers, aubergines, melons, watermelons and hops, EFSA concludes that the metabolism of is sufficiently addressed and the residue definitions proposed under Article 12 review are applicable. The conclusions reached by EFSA reflect the views of the RMS and are also in line with those of the JMPR (FAO, 2006). Anticipating the amendment of the enforcement residue definition proposed in the framework of the MRL review, EFSA derives the MRL proposals for the crops under consideration which reflect the extended residue definition (i.e. sum of and diazene, expressed as ) Magnitude of residues a. Citrus fruit In support of the intended GAP the applicant submitted 16 GAP compliant outdoor residue trials (eight trials on mandarins and eight trials on oranges). The trials were performed during 2002, 2003 and 2009 in Italy, Spain and Greece (SEU region). The applicant submitted additional residue trials which were considered not acceptable because the samples were stored longer than the period for which the integrity of the samples was demonstrated in storage stability studies. A sufficient number of trials is available for mandarin and orange. The extrapolation of residue data from mandarin and orange to the whole group of citrus fruit is acceptable (EC, 2011). EFSA Journal 2012;10(10):

13 b. Pome fruit Modification of the existing MRLs for in various crops In support of the intended GAP in the NEU region the applicant submitted nine GAP compliant outdoor residue trials (five trials on pears and four trials on apples). The trials were performed during 2003, 2004 and 2009 in France, Poland and Germany. The applicant submitted additional residue trials that were considered not acceptable because the samples were stored longer than the period for which the integrity of the samples was demonstrated in storage stability studies. In support of the intended GAP in the SEU region the applicant submitted 14 GAP compliant outdoor residue trials (ten trials on pears 11 and four trials on apples). The trials were performed during 2003, 2004 and 2009 in Spain, Italy and France. The applicant submitted additional residue trials that were considered not acceptable because the samples were stored longer than the period for which the integrity of the samples was demonstrated in storage stability studies. A sufficient number of trials is available for pome fruits in NEU and SEU. The extrapolation of residue data from pear and apple to the whole group of pome fruit is acceptable (EC, 2011). It is noted that the MRL proposal of 0.5 mg/kg in pome fruit is lower than the MRL proposal derived in the framework of the MRL review (0.7 mg/kg), which is the current CXL based on a US GAP ( kg a.s./ha, 7 d PHI). In the Article 12 review EFSA commented that further consideration was needed before the EU MRL is set at the level of the CXL since the existing CXL was found to be not adequately supported by data; however, no risk to consumers was identified. The MRL proposal of 0.5 mg/kg derived from the studies evaluated in the framework of this application would be an alternative MRL to be considered by risk managers which is fully supported by data. c. Apricot In support of the intended GAP in the NEU and SEU regions the applicant submitted one trial from USA; no EU trials are available. The data are not sufficient to derive a MRL proposal for apricots. d. Peach and nectarine In support of the intended GAP in the SEU region the applicant submitted eight GAP compliant outdoor residue trials (four trials on peaches and four trials on nectarines). The trials were combined. The trials were performed during 2008 and 2009 in France, Spain and Greece. It is noted that no residues trials on peach and nectarine have been submitted in support of the intended outdoor GAPs in NEU region. A sufficient number of trials is available for nectarine and peach in SEU region. Four trials complying with the northern GAPs are still required. The MRL proposal of 0.5 mg/kg in peach/nectarine is lower than the MRL recommended in the framework fo the MRL review (2 mg/kg in stone fruit), which is the current CXL based on a US GAP ( kg a.s./ha, 3 d PHI). e. Plum In support of the intended GAP in the SEU region the applicant submitted one GAP compliant outdoor residue trials from Spain. In support of the intended GAP in the NEU region the applicant submitted eight GAP compliant outdoor residue trials on plum. The trials were performed during 2009 and 2010 in France, Germany and Poland. 11 In one trial on pears the application rate of 0.61 kg a.s./ha was just above the limit of 0.48 kg a.s./ha ± 25%. Despite this deviation this trial was considered acceptable and included since the result was in the same range as the other trials. EFSA Journal 2012;10(10):

14 A sufficient number of trials is available for plum in the northern region. Plums, according to the EU guidance document, until 1 April 2013 are considered as minor crop in the SEU (EC, 2011) and therefore 3 additional trials complying with the southern GAPs would be required to derive a MRL for this GAP. The MRL proposal of 0.5 mg/kg in plums is lower than the MRL recommended in the framework of the MRL review (2 mg/kg in stone fruit), which is the current CXL based on a US GAP ( kg a.s./ha, 3 d PHI). f. Grape In support of the intended GAP in the SEU region the applicant submitted eight GAP compliant outdoor residue trials (four trials on wine grapes and four trials on table grapes). The trials were performed during 2008 and 2009 in France, Spain and Italy. In support of the intended GAP in the NEU region the applicant submitted 8 GAP compliant outdoor residue trials on grapes. The trials were performed during 2008 and 2009 in France and Germany. A sufficient number of trials is available for grapes in SEU and NEU. g. Strawberry In support of the intended GAP in the SEU region the applicant submitted seven GAP compliant outdoor residue trials. One trial was excluded since it was underdosed. The trials were performed during 2002 and 2003 in France, Spain and Italy. In support of the intended GAP in the NEU region the applicant submitted two GAP compliant outdoor residue trials. The trials were performed during 2005 in the United Kingdom. In support of the intended indoor GAP the applicant submitted sixteen GAP compliant residue trials on strawberry. The trials were performed during 2002 and EFSA concludes that a sufficient number of trials is available for the indoor GAP; although according to the EU data requirements one additional trial would be required for the SEU outdoor GAP EFSA considers the database robust enough to derive a MRL for this situation. For the northern GAP no MRL proposal was derived because the dataset is not sufficient. It is noted that the MRL proposal of 3 mg/kg for strawberry derived in this application is higher than the CXL of 2 mg/kg, which was recommended by EFSA in the Article 12 review (EFSA, 2011). h. Tomato and aubergine In support of the intended GAP for tomatoes and aubergines in the SEU region the applicant submitted four GAP compliant residue trials performed on tomatoes 12. The trials were performed during 2000 and 2002 in Spain and Italy. No data were provided for the NEU GAP. In support of the intended indoor GAP the applicant submitted 16 GAP compliant indoor residue trials on tomato. The trials were performed during 2001, 2002 and A sufficient number of trials is available for tomatoes grown under indoor conditions. The data sets representing the SEU and the NEU outdoor GAP are not sufficient. However, the available SEU residues give an indication that the residue situation under indoor conditions might be more critical than under outdoor conditions. 12 One outdoor trial was performed at 100 g a.s./ha instead of 200 g a.s./ha. Therefore, three days after the first application an additional application was made at 100 g a.s./ha in order to compensate for the reduced first application rate. Since the last (and third) application was at 0.20 kg a.s./ha, this is considered to have no effect on the residue levels and the trial was accepted and included. EFSA Journal 2012;10(10):

15 Results from the indoor trials on tomatoes can be extrapolated to aubergines since the same GAP has been reported (EC, 2011). Therefore, EFSA derived MRL proposals for tomatoes and aubergines. It is noted that in the framework of the Article 12 review EFSA proposed a tentative MRL of 0.5 mg/kg in aubergine. This tentative MRL was derived from a more critical GAP (0.24 kg a.s./ha, 1 d PHI), which was not fully supported by data. i. Pepper In support of the intended NEU GAP the applicant submitted two GAP compliant residue trials in sweet pepper. The trials were performed during 2008 in Hungary. It is noted that no residues trials on sweet pepper have been submitted in support of the intended outdoor southern GAPs. In support of the intended indoor GAP the applicant submitted seventeen GAP compliant residue trials (13 trials on sweet pepper and four trials on chilli pepper). The trials were performed during 2001 and The trials were not combined because the residue levels in chilli peppers were significantly higher than the levels in sweet peppers. A risk management decision needs to be taken whether the MRL for peppers should be based on the more critical results for chilli peppers. A sufficient number of trials is available for sweet pepper and chilli pepper reflecting the indoor GAP. According to the EU guidance document, two additional trials complying with the NEU GAP and eight trials complying with the SEU GAP are required. The MRL proposal of 0.4 mg/kg for sweet pepper is lower than the MRL recommended in the Article 12 review (2 mg/kg) which is the CXL derived for a US GAP ( kg a.s./ha, 3 d PHI) However, the MRL of 3 mg/kg derived for chilli peppers should be considered by risk managers, too. j. Melon and watermelon In support of the intended northern GAPs the applicant submitted two GAP compliant outdoor residue trials on watermelons. The trials were performed during 2009 in France and Germany. In support of the intended southern GAPs the applicant submitted twelve GAP compliant outdoor residue trials (ten on melons and two on watermelons). The trials were performed during 2002, 2003, 2009 in France, Italy and Spain. In support of the intended indoor GAP the applicant submitted twelve GAP compliant residue trials. The trials were performed during 2002 and A sufficient number of trials is available for melon reflecting the indoor GAP and the SEU outdoor GAPs. The trials are sufficient to be extrapolated to the whole group of cucurbits with inedible peel (including watermelons) grown under indoor conditions and SEU outdoor conditions (EC 2001). For the NEU GAP two additional trials would be required. It is noted that the MRL proposal of 0.6 mg/kg in cucurbit with inedible peel derived in this application is higher than the CXL of 0.5 mg/kg, which was recommended by EFSA in the Article 12 review (EFSA, 2011). k. Hops In support of the intended northern GAPs the applicant submitted 11 GAP compliant outdoor residue trials. The trials were performed during 2002, 2003 and 2009 in Germany and Poland. A sufficient number of trials is available for northern GAPs. EFSA Journal 2012;10(10):

16 The results of the residue trials, the related risk assessment input values (highest residue, median residue, conversion factor) and the MRL proposals are summarised in Table 3-2. The potential degradation of residues during storage of the residue trials samples was assessed (FAO, 2006; EFSA 2011, The Netherlands 2011). The stability of residues (assessed as the sum of and -diazene expressed as ) was demonstrated for at least 6 months in a large range of commodities with high water and high acid content and in special crops (dried hops). The selected residue trial samples described in the paragraphs a) to k) were stored under conditions for which integrity of the samples was demonstrated. According to the EMS, the analytical method used to analyse the supervised residue trial samples has been sufficiently validated and was proven to be fit for purpose (The Netherlands, 2011). EFSA Journal 2012;10(10):

17 Table 3-2: Overview of the available residues trials data Commodity Residue region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (sum of and -diazene, expressed as ) Risk assessment (sum of and -diazene, expressed as ) Enforcement residue definition: sum of and -diazene, expressed as. Oranges and mandarins citrus fruit Apples and pears pome fruit Apricot SEU Outdoor (f) ; 0.12; 0.15; 0.16 (f) ; 0.17 (f) ; 0.17 (f) ; 0.19; 0.22; 0.23 (f) ; 0.25; 0.28; 0.34 (f) ; 0.42 (f) ; 0.42; 0.48; 0.55 (f) NEU Outdoor (g) ; 0.038; 0.06 (g) ; (g) ; 0.12; 0.12; 0.18 (g) ; 0.23 (g) ; 0.24 SEU Outdoor 0.06 (g) ; 0.07 (g) ; 0.07 (g) ; (g) ; 0.10; 0.10; 0.11 (g) ; 0.11 (g) ; 0.11; 0.11 (g) ; 0.11 (g) ; 0.16 (g) ; 0.16 (g) ; 0.19 NEU SEU Outdoor No EU trials US trial: (f) ; 0.12; 0.15; 0.16 (f) ; 0.17 (f) ; 0.17 (f) ; 0.19; 0.22; 0.23 (f) ; 0.25; 0.28; 0.34 (f) ; 0.42 (f) ; 0.42; 0.48; 0.55 (f) (g) ; 0.038; 0.06; (g) ; 0.12; 0.12; 0.18 (g) ; 0.23 (g) ; (g) ; 0.07 (g) ; 0.07; (g) ; 0.10; 0.10; 0.11 (g) ; 0.11 (g) ; 0.11; 0.11; 0.11; 0.16 (g) ; 0.16 (g) ; 0.19 Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments R ber =0.80 R max =0.62 MRL OECD = 0.82/0.9 mg/kg R ber =0.41 R max =0.36 MRL OECD = 0.44/0.5 mg/kg R ber =0.25 R max =0.21 MRL OECD = 0.33/0.4 mg/kg Data not sufficient to derive MRL proposal (e) Nectarine and peach NEU Outdoor No residue trials available SEU Outdoor 0.05; 0.09; 0.11; 0.11; 0.12; 0.20; 0.20; ; 0.09; 0.11; 0.11; 0.12; 0.20; 0.20; R ber =0.40 R max =0.38 MRL OECD = 0.43/0.5 EFSA Journal 2012;10(10):

18 Commodity Residue region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (sum of and -diazene, expressed as ) Plum NEU Outdoor 0.015; 0.026; 0.031; 0.053; 0.12; 0.13; 0.23; 0.24 Risk assessment (sum of and -diazene, expressed as ) 0.015; 0.026; 0.031; 0.053; 0.12; 0.13; 0.23; 0.24 Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments R ber =0.41 R max =0.39 MRL OECD = 0.47/0.5 mg /kg SEU Outdoor <0.01 < No sufficient trials available. Grape SEU Outdoor 0.041; 0.045; 0.049; 0.05; 0.05; 0.09; 0.09; 0.10 NEU Outdoor 0.04; 0.09; 0.12; 0.12; 0.18; 0.18; 0.23; 0.47 Strawberry EU Indoor 0.12; 0.12; 0.15; 0.19; 0.20; 0.25; 0.27; 0.33; 0.39; 0.58; 0.66; 0.78; 0.82; 0.83; 0.85; 1.95 Tomato aubergine SEU Outdoor 0.09; 0.15; 0.18; 0.18; 0.35; 0.75; ; 0.045; 0.049; 0.05; 0.05; 0.09; 0.09; ; 0.09; 0.12; 0.12; 0.18; 0.18; 0.23; ; 0.12; 0.15; 0.19; 0.20; 0.25; 0.27; 0.33; 0.39; 0.58; 0.66; 0.78; 0.82; 0.83; 0.85; ; 0.15; 0.18; 0.18; 0.35; 0.75; R ber =0.18 R max =0.14 MRL OECD = 0.19/0.2 mg/kg R ber =0.44 R max =0.60 MRL OECD = 0.71/0.7 mg/kg R ber =1.62 R max =1.71 MRL OECD = 2.4/3 mg/kg Rber=1.5 Rmax=2.5 MRLOECD = 2.8/3 mg/kg NEU Outdoor 0.04; ; No sufficient trials available. EU Indoor 0.01; 0.02; 0.07; 0.07; 0.09; 0.13; 0.13; 0.13; 0.15; 0.15; 0.17; 0.20; 0.21; 0.21; 0.24; ; 0.02; 0.07; 0.07; 0.09; 0.13; 0.13; 0.13; 0.15; 0.15; 0.17; 0.20; 0.21; 0.21; 0.24; R ber =0.42 R max =0.34 MRL OECD = 0.5/0.5 mg/kg (e) EFSA Journal 2012;10(10):

19 Commodity Residue region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (sum of and -diazene, expressed as ) Risk assessment (sum of and -diazene, expressed as ) Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments SEU Outdoor 0.02; 0.04; 0.05; ; 0.04; 0.05; trials give an indication that the outdoor GAP is not more critical than the indoor GAP. NEU Outdoor No trials available (e) Pepper (sweet) EU Indoor 0.04; 0.05; 0.06; 0.08; 0.08; 0.11; 0.12; 0.14; 0.15; 0.18; 0.20; 0.20; ; 0.05; 0.06; 0.08; 0.08; 0.11; 0.12; 0.14; 0.15; 0.18; 0.20; 0.20; R ber =0.38 R max =0.31 MRL OECD = 0.41/0.4mg/kg NEU Outdoor 0.08; ; No sufficient trials available. SEU Outdoor No trials available Pepper (chilli) EU Indoor 0.50; 0.82; 1.1; ; 0.82; 1.1; R ber =2.20 R max =2.35 MRL OECD = 2.64/3 mg/kg NEU Outdoor No trials available SEU Outdoor No trials available Melon and watermelon cucurbits with inedible peel EU Indoor 0.01; 0.01; 0.03; 0.037; 0.04; 0.04; 0.05; 0.093; 0.11; 0.11; 0.21; ; 0.01; 0.03; 0.037; 0.04; 0.04; 0.05; 0.093; 0.11; 0.11; 0.21; R ber =0.22 R max =0.28 MRL OECD = 0.37/0.4 mg/kg EFSA Journal 2012;10(10):

20 Commodity Residue region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (sum of and -diazene, expressed as ) SEU Outdoor 0.01 (h) ; 0.012; 0.015; 0.017; <0.02; 0.02, 0.02 (h) ; <0.03; <0.03; 0.03; 0.03; 0.03 Risk assessment (sum of and -diazene, expressed as ) 0.01 (h) ; 0.012; 0.015; 0.017; <0.02; 0.02, 0.02 (h) ; <0.03; <0.03; 0.03; 0.03; 0.03 Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments R ber =0.06 R max =0.04 MRL OECD = 0.055/0.06 mg/kg NEU Outdoor 0.020; ; No sufficient trials available. Hop (dried) NEU Outdoor 2.5; 3.3; 4.2; 4.3; 4.7; 4.9; 4.9; 5.9; 6.9; 8.1; ; 3.3; 4.2; 4.3; 4.7; 4.9; 4.9; 5.9; 6.9; 8.1; R ber =13.80 R max =12.49 MRL OECD = 16.6/20 mg/kg (a): NEU (Northern and Central Europe), SEU (Southern Europe and Mediterranean), EU (i.e. outdoor use) or Import (country code) (EC, 2011). (b): Median value of the individual trial results according to the enforcement residue definition. (c): Highest value of the individual trial results according to the enforcement residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residue trial. (e): Statistical estimation of MRLs according to the EU methodology (R ber, R max ; EC, 1997g) and unrounded/rounded values according to the OECD methodology (OECD, 2011). (f): Residues trials performed in mandarins. (g): Residues trials performed in pears. (h): Residues trials performed in watermelons. (*): Indicates that the MRL is set at the limit of analytical quantification. (e) EFSA Journal 2012;10(10):

21 Effect of industrial processing and/or household preparation Modification of the existing MRLs for in various crops The effect of processing on the nature of was investigated in studies performed at three test conditions representing pasteurisation, baking/brewing/boiling and sterilisation. The studies were reported in the framework of this application (The Netherlands, 2012). Test conditions representing baking/brewing/boiling were performed at 20 minutes (100 C; ph 5) instead of 60 minutes as recommended by EU guidance document (EC, 1997d). However, since no degradation was observed within 20 minutes it is unlikely that degradation occurs after 60 minutes. EFSA concludes that the compound is hydrolytically stable under the representative processing conditions. Thus, for processed commodities the same residue definition as for raw agricultural commodities (RAC) is applicable. Studies investigating the effect of processing on the magnitude of residues (assessed as the sum of and -diazene expressed as ) in processed products were evaluated by JMPR (FAO, 2006) and in the evaluation report (The Netherlands, 2011). Processing data were available for oranges, mandarins, apple, nectarine, peach, plum, grapes, tomato, and melon 13. Processing factors are summarized in Table 3-3. a. Citrus fruit Distribution of residues between peel and pulp was assessed in the trials selected for MRL derivation (i.e. 8 trials in oranges and 8 trials in mandarins). A peeling factor of indicates that the majority of residue is present in the peel. Oranges from field trials treated with an exaggerated application rate of 2.9 kg a.s./ha were collected and processed into juice, canned orange, marmalade, dried oranges and essential oil (five trials) and processed into dried peels, wet pomace and dry pomace (two trials). Residues in raw oranges accounted for mg/kg. A reduction of residues is observed in juice (PF of 0.13), canned orange (PF of 0.074), marmalade (PF of 0.10) whereas an increase is observed in dried oranges (PF of 5.3), essential oil (PF of 163), dried peels (30), wet pomace (1.7) and dry pomace (9.6). b. Apple Apples from field trials at an exaggerated application rate of 2.8 kg a.s./ha were harvested 7 days after a treatment and processed into juice 14 and wet pomace in four trials. Residues in raw apple accounted for mg/kg. An increase of residues is observed in wet pomace (PF of 1.8). JMPR derived a PF of 1.8 and 0.17 for wet pomace and apple juice respectively (FAO, 2006) c. Peach and nectarine Distribution of residues between flesh and whole fruit was assessed in the trials selected for MRL derivation (i.e. four trials in peach and four trials in nectarine). A PF of 1.1 is derived. d. Plum Plums were harvested 3 days after treatment and processed into dried plums in 4 trials. Residues in raw plum accounted for 0.02 mg/kg. In dried plums a reduction of the residues was observed (PF of 0.42). e. Grapes Grapes from field trials according to the intended GAP were used to produce pasteurized juice and wine processing. Processing factors of 0.16 for juice (two trials), 0.94 for wet pomace (four 13 Additional studies investigating the effect of processing in the magnitude of residues on processed product from mint and cotton have been assessed by the EMS (2011) but not evaluated by EFSA in the framework of this MRL opinion. 14 According to the EMS (2011) reported apple juice results could not be used for derivation of processing factors for apple juice because untreated samples had residues of mg/kg. EFSA Journal 2012;10(10):