Modification of the existing maximum residue levels for penthiopyrad in stone fruits and cereals. European Food Safety Authority (EFSA)

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1 REASONED OPINION APPROVED: 15 November 2016 doi: /j.efsa Modification of the existing maximum residue levels for penthiopyrad in stone fruits and cereals European Food Safety Authority (EFSA) Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, the evaluating Member States (EMS), France and Bulgaria, sent an application to modify the existing maximum residue levels (MRL) for the active substance penthiopyrad in apricots, peaches, barley and oat. To accommodate for the intended uses of penthiopyrad, France and Bulgaria proposed to raise the existing MRLs from 0.2 to 0.3 mg/kg for barley and oat, and from 2 to 4 mg/kg for apricots and peaches. France and Bulgaria drafted the evaluation reports in accordance with Article 8 of Regulation (EC) No 396/2005, which were submitted to the European Commission and forwarded to EFSA. According to EFSA, the data are sufficient to derive the MRL proposals of 0.3 mg/kg for barley and oat, and 4 mg/kg for apricots and peaches. Adequate analytical enforcement methods are available. Based on the risk assessment results, EFSA concludes that the proposed use of penthiopyrad on apricots, peaches, barley and oat will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a consumer health risk European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. Keywords: penthiopyrad, PAM, various crops, MRL application, consumer risk assessment Requestor: European Commission Question numbers: EFSA-Q ; EFSA-Q Correspondence: pesticides.mrl@efsa.europa.eu EFSA Journal 2016;14(12):4648

2 Suggested citation: EFSA (European Food Safety Authority), Reasoned opinion on the modification of the MRLs for penthiopyrad in stone fruits and cereals. EFSA Journal 2016;14(12):4648, 19 pp. doi: /j.efsa ISSN: European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. 2 EFSA Journal 2016;14(12):4648

3 Summary In accordance with Article 6 of Regulation (EC) No 396/2005, the evaluating Member State (EMS), Bulgaria, received an application from DuPont EOOD to modify the existing maximum residue levels (MRL) for the active substance penthiopyrad in apricots and peaches. In addition, the EMS France also received an application from DuPont Solutions S.A.S to modify the existing MRLs for penthiopyrad in barley and oat. To accommodate for the intended uses of penthiopyrad, France and Bulgaria proposed to raise the existing MRLs from 0.2 to 0.3 mg/kg for barley and oat, and from 2 to 4 mg/kg for apricots and peaches. The EMSs (Bulgaria and France) drafted the evaluation reports in accordance with Article 8 of Regulation (EC) No 396/2005, which were submitted to the European Commission and forwarded to the European Food Safety Authority (EFSA) on 2 September EFSA bases its assessment on the evaluation reports submitted by the EMSs, the draft assessment report (DAR) prepared under Council Directive 91/414/EEC and its addendum, the conclusion on the peer review of the pesticide risk assessment of the active substance penthiopyrad, the outcome on the confirmatory data on PAM metabolite, the Commission review report on penthiopyrad, the Joint Meeting on Pesticide Residues (JMPR) Evaluation report as well as the conclusions from a previous EFSA opinion on penthiopyrad. The toxicological profile of penthiopyrad was assessed during the peer review under Directive 91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.1 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.75 mg/kg bw. For 753-A-OH metabolite, peer review experts concluded that it is of a similar toxicity as the parent. For PAM metabolite, no sufficient information was provided to conclude on its toxicity during the peer review. Thus, confirmatory data were requested and recently assessed by EFSA where the ADI of mg/kg bw per day and an ARfD of mg/kg bw were derived. The metabolism of penthiopyrad in primary crops was investigated under peer review in the fruits, leafy, cereal and oilseeds crop groups following foliar application. Based on these metabolism studies, the residue definition for enforcement was proposed as penthiopyrad while for risk assessment two separate residue definitions were proposed: penthiopyrad and 753-A-OH expressed as penthiopyrad; and PAM metabolite. For the uses on crops under consideration, EFSA concludes that the metabolism of penthiopyrad in primary crops has been sufficiently addressed and the residue definitions derived are applicable. EFSA concludes that the submitted supervised residue trials are sufficient to derive the MRL proposals of 0.3 mg/kg for barley and oat, and 4 mg/kg for apricots and peaches. Adequate analytical enforcement methods are available to monitor the residues of penthiopyrad in the crops under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Studies investigating the nature of penthiopyrad residues under standard hydrolysis conditions were assessed during the peer review showing that the active substance is hydrolytically stable; thus, the same residue definitions as for raw agricultural commodities (RAC) are applicable. In addition, several processing factors (PF) were derived for penthiopyrad in apple, tomato, barley and wheat. It is noted that the behaviour of PAM under conditions simulating processing required during the peer review was not provided. However, considering that the theoretical maximum daily intake (TMDI) for the crops under consideration is below 10% of the ADI, these studies are not deemed to be necessary for the current applications. The occurrence of penthiopyrad residues in rotational crops was investigated in leafy, roots and cereals during the peer review. Since the metabolic pattern was similar to the primary crops, the same residue definitions were proposed as for primary crops. Regarding the magnitude of penthiopyrad residues in the succeeding crops, the data provided during the peer review were not sufficient to conclude on the residue levels taken up from the soil. Considering that no additional studies were submitted under current applications, EFSA keeps the recommendation from peer review that the Member States granting authorisations for penthiopyrad uses to consider the possible occurrence in the succeeding crops. Cereals are used as feed items; therefore, the potential carry-over into food of animal origin was assessed. The nature of penthiopyrad residues in livestock has been investigated during the peer review and the residue definition for enforcement was proposed as penthiopyrad and PAM expressed as penthiopyrad; for risk assessment, two separate residue definitions were derived, penthiopyrad and PAM, respectively. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg dry matter (DM) for all relevant species for penthiopyrad. For PAM metabolite, the calculated livestock dietary burden exceeded the level of 0.1 mg/kg only for ruminants. During the peer review, feeding 3 EFSA Journal 2016;14(12):4648

4 studies for penthiopyrad and PAM (intake from penthiopyrad) in dairy cows and laying hens were submitted and no residues above LOQ were found at the closest feeding level. Therefore, EFSA does not recommended the change in the existing MRLs in animal commodities. The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). EFSA conducted separate risk assessment calculation for penthiopyrad and PAM metabolite. No long-term consumer intake concerns or acute risks were identified for penthiopyrad and PAM; the highest chronic intake accounted 7% of the ADI for penthiopyrad and 16% for PAM, while the highest acute exposure was calculated for penthiopyrad up to 16% of the ARfD for peaches and 1.3% for PAM for apricots. EFSA concludes that the proposed use of penthiopyrad on the crops under consideration will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a health risk to consumers. EFSA proposes to amend the existing MRLs as reported in the summary table below. Code (a) Commodity Existing EU MRL (mg/kg) Proposed EU MRL (mg/kg) Comment/justification Enforcement residue definition: Penthiopyrad Apricots 2 4 The MRL proposal is sufficiently supported Peaches 2 4 by data reflecting the SEU intended use on stone fruit. The results of the trials were scaled down using a factor of No consumer health risk was identified Barley The MRL proposal is sufficiently supported by data reflecting the NEU and SEU intended uses. No consumer health risk was identified. No change in the MRL in animal commodities is necessary Oat Extrapolation from barley MRL: maximum residue level; SEU: southern Europe; NEU: northern Europe. (a): Commodity code number according to Annex I of Regulation (EC) 396/ EFSA Journal 2016;14(12):4648

5 Table of contents Abstract... 1 Summary... 3 Background... 6 The active substance and its use pattern... 6 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 Nature of residues Magnitude of residues Effect of industrial processing and/or household preparation Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Nature of residues Magnitude of residues Consumer risk assessment Sum of penthiopyrad and 753-A-OH, expressed as penthiopyrad PAM metabolite Conclusions and recommendations References Abbreviations Appendix A Good Agricultural Practice Appendix B Used compound codes EFSA Journal 2016;14(12):4648

6 Background Regulation (EC) No 396/ (hereinafter referred to as the Regulation ) establishes the rules governing the setting of pesticide maximum residue levels (MRLs) at the European Union (EU) 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, 2 repealed by Regulation (EC) No 1107/2009 3, shall submit to a Member State, when appropriate, an application to modify a MRL in accordance with the provisions of Article 7 of that Regulation. France, hereafter referred to as the evaluating Member State (EMS-FR), received an application from the company DuPont Solutions (France) S.A.S 4 to modify the existing MRLs for the active substance penthiopyrad in barley and oat. In addition, DuPont Bulgaria EOOD, 5 submitted an application to the evaluating Member State Bulgaria (EMS-BG) to modify the existing MRLs for the penthiopyrad in apricots and peaches. These applications were notified to the European Commission and the European Food Safety Authority (EFSA), and were subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation reports were submitted to the European Commission and to EFSA on 2 September The applications were included in the EFSA Register of Questions with the reference numbers and the following subject: EFSA-Q : Penthiopyrad Modification of the existing MRLs in barley and oats EFSA-Q : Penthiopyrad Modification of the existing MRLs in apricots and peaches For the reasons of efficiency, EFSA combined both applications in a single reasoned opinion. France proposed to raise the existing MRLs of penthiopyrad in barley and oats from the value of mg/kg, while Bulgaria proposed to raise the MRLs from 2 to 4 mg/kg for apricots and peaches. On 2 December 2015, EFSA asked both EMS (BG and FR) to consider the toxicological endpoints on PAM metabolite and to reassess the application considering this information. Moreover, EMS-BG was asked for additional information (i.e. details on the residue trials). Since in the meantime, the EFSA assessed the toxicological data on a metabolite of penthiopyrad in the framework of the peer review (assessment of confirmatory data), the EMS (BG and FR) updated the ER in September 2016 (Bulgaria, 2016, France, 2016). EFSA proceeded with the assessment of the application and the evaluation report as required by Article 10 of the Regulation. In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the EMS, provide a reasoned opinion on the risks to the consumer associated with the application. The updated evaluation reports submitted by the EMSs (Bulgaria, 2016 and France, 2016) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within 3 months (which may be extended to 6 months if more detailed evaluations need to be carried out) from the date of receipt of the application. If EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. The active substance and its use pattern Penthiopyrad is the ISO common name for (RS)-N-[2-(1,3-dimethylbutyl)-3-thienyl]-1-methyl-3- (trifluoromethyl)pyrazole-4-carboxamide (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix B. 1 Regulation (EC) No 396/2005 of the 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. OJ L 70, , p Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, , p 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 Dupont Solutions S.A.S, Defense Plaza; rue Delariviere, 92800, Puteaux, France. 5 Dupont EOOD, Mlasdost 4, Business Park Sofia, 1766 Sofia, Bulgaria. 6 EFSA Journal 2016;14(12):4648

7 The details of the intended good agricultural practice (GAPs) for penthiopyrad which are the basis of these MRL applications are given in Appendix A. Penthiopyrad was evaluated in the framework of Directive 91/414/EEC with the United Kingdom designated as the rapporteur Member State (RMS) in conjunction with Regulation (EU) No 188/2011 6, laying down detailed rules for the assessment of new active substances and the transitional provisions foreseen in Article 80(1)(a) of Regulation (EC) No 1107/2009, repealing Directive 91/414/EEC. It has been approved under Regulation (EC) No 1107/2009 on 1 May 2014 by Commission Implementing Regulation (EU) No 1187/2013 7, with specific provisions requesting confirmatory data including data on toxicological profile of metabolite PAM, to be submitted by 30 April The representative uses evaluated in the peer review were foliar applications on pome fruit, tomato, aubergines, cucurbits, cucumbers, courgettes and cereals. The draft assessment report (DAR) has been peer reviewed by EFSA, and the conclusions have been published in 2013 (EFSA, 2013a). The EU MRLs for penthiopyrad are established in Annexes IIIA of Regulation (EC) No 396/2005. Since the entry into force of this regulation, EFSA issued one reasoned opinion under Article 10 on the modification of MRLs for penthiopyrad (EFSA, 2012); the proposals from these reasoned opinions have been considered in the EU legislation. Codex Alimentarius has established Codex maximum residue limits (CXLs) for a wide range of commodities, including the crops under consideration for which the CXLs are set at 0.2 mg/kg for oat and barley, and 4 mg/kg for stone fruits (apricots, peaches and nectarines). Assessment EFSA has based its assessment on the evaluation reports submitted by the EMSs (Bulgaria, 2016 and France, 2016), the DAR (and its addendum) prepared under Directive 91/414/EEC (United Kingdom, 2012, 2013), the conclusion on the peer review of the pesticide risk assessment of the active substance penthiopyrad (EFSA, 2013a), the outcome of the confirmatory data on PAM metabolite (EFSA, 2016), the Commission review report on penthiopyrad (European Commission, 2013), the Joint Meeting on Pesticide Residues (JMPR) Evaluation report (FAO, 2012) as well as the conclusions from previous EFSA opinion on penthiopyrad (EFSA, 2012). 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 (European Commission, 1996, 1997a g, 2000, 2010a,b, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of penthiopyrad residues in plant commodities were assessed during the peer review (EFSA, 2013a). The multiresidue method DFG-S19 based on liquid chromatography with tandem mass spectrometry detector (LC MS/MS) was validated for parent penthiopyrad in acidic, high water, high oil content commodities at the level of 0.01 mg/kg. A validated independent laboratory validation (ILV) for acidic and high water commodities was also submitted. An additional single residue method based on high-performance liquid chromatography with tandem mass spectrometry detector (HPLC MS/MS) to be used the determination of penthiopyrad and its PAM metabolite involving a hydrolysis step was validated at a level of 0.01 mg/kg for matrices with high water, high acid and high oil content and for dry commodities (high starch/protein content). The method was also evaluated under the peer review (EFSA, 2013a). 6 Commission Regulation (EU) No 188/2011 of 25 February 2011 laying down detailed rules for the implementation of Council Directive 91/414/EEC as regards the procedure for the assessment of active substances which were not on the market 2 years after the date of notification of that Directive. OJ L 53, , p Commission Implementing Regulation (EU) No 1187/2013 of 21 November 2013 approving the active substance penthiopyrad, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market, and amending the Annex to Commission Implementing Regulation (EU) No 540/2011. OJ L 313, , p Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. OJ L 155, , p EFSA Journal 2016;14(12):4648

8 As the commodities under consideration belong to the group of matrices with high water and high starch content, EFSA concludes that sufficiently validated analytical methods to monitor the proposed MRLs are available Methods for enforcement of residues in food of animal origin The analytical methods for the determination of penthiopyrad residues in animal commodities were evaluated during the peer review (EFSA, 2013a). An analytical method based on LC MS/MS was validated at 0.01 mg/kg level for penthiopyrad and for metabolite PAM in milk, eggs, bovine meat and liver but not for fat. However, a validated HPLC MS/MS single residue method is available for the determination of penthiopyrad and PAM at the limit of quantification (LOQ) of 0.01 mg/kg in all animal matrices. EFSA concludes that sufficiently validated analytical methods able to monitor residues of penthiopyrad and PAM in food of animal origin are available. 2. Mammalian toxicology The toxicological profile of penthiopyrad was assessed under the peer review where sufficient data were available to derive toxicological reference values (EFSA, 2013a). For metabolite PAM, additional data on the toxicological profile were required which were recently assessed by EFSA (EFSA, 2016); consequently, the toxicological reference values applicable for penthiopyrad and metabolite PAM are reported in Table 1. Table 1: It is noted that JMPR established an acceptable daily intake (ADI) of 0.1 mg/kg body weight (bw) per day and the acute reference dose (ARfD) of 1 mg/kg bw for penthiopyrad (FAO, 2012); no toxicological reference values were derived for PAM. 3. Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of penthiopyrad in primary crops was assessed during the peer review in fruits, leafy crops, cereals and oilseeds (EFSA, 2013a). An overview of the available metabolism studies is presented in Table 2. Table 2: Overview of the toxicological reference values Source Year Value Study Safety factor Penthiopyrad ADI EFSA mg/kg bw per day Two-generation rat 100 ARfD EFSA mg/kg bw Developmental rabbits 100 PAM metabolite ADI EFSA mg/kg bw per day 28-day study on rat 3,000 ARfD EFSA mg/kg bw 14- and 28-day study on rat 300 ADI: acceptable daily intake; ARfD: acute reference dose; bw: body weight. Summary of available metabolism studies in plants Crop group Crops Application Sampling (day, DAT) Comments Fruit Grapes Foliar ( g/ha) 20 and 60 DAT 1 [14C]-pyrazole and thienyl Tomatoes Foliar (19 1,500 g/ha) 14 and 21 DAT 1 penthiopyrad ring Leafy Cabbage Foliar ( g/ha) 21 DAT 1 Foliar (19 1,000 g/ha) 21 DAT 1 Cereals Wheat Foliar ( g/ha) 32 DAT 2 Oilseeds Canola Foliar ( g/ha) 14 DAT 1 DAT: days after treatment; DAT 1 : days after first treatment; DAT 2 : days after second treatment. 8 EFSA Journal 2016;14(12):4648

9 Based on these metabolism studies assessed in the peer review, the following residue definitions were proposed (EFSA, 2013a, 2016): Residue definition for monitoring: penthiopyrad Residue definition for risk assessment: sum of penthiopyrad and metabolite 753-A-OH expressed as penthiopyrad PAM The current residue definition set in Regulation (EC) No 396/2005 is identical to the residue definition for monitoring reported above. For the use on crops under consideration, EFSA concludes that the metabolism of penthiopyrad is sufficiently addressed and the residue definitions derived under the peer review are applicable Magnitude of residues Stone fruits (apricots and peaches) The EMS-BG submitted 10 residue trials conducted in southern Europe (SEU) on stone fruits (five on apricots, four on peaches and one on nectarine) during 2011 and The application rate was higher ( g/ha) compared to the proposed GAP ( g/ha), thus, slightly beyond the tolerated deviation of 25%. Four of the submitted trials were declined studies. The samples (fruit pulp) were analysed for penthiopyrad and its metabolites 753-A-OH and PAM, the results were reported for the whole fruit. Penthiopyrad residues ranged from 0.26 to 2.59 mg/kg while metabolite 753-A-OH ranged from 0.01 to mg/kg. Metabolite PAM, was detected only in one sample (0.011 mg/kg) while in the remaining samples PAM was either not detected or below the LOQ. Since the residue trials were performed with higher application rate compared to the proposed GAP, the proportionality approach was used and the results were scaled down using the factor It is noted that for two residue trials the level of residues was higher at longer preharvest interval (PHI) (7 days) than the proposed one (3 days). Since no justification was provided, which would qualify these results as outliers, the residue concentration measured at 7 days PHI were included in the calculation, resulting in the MRL proposal of 4 mg/kg for apricots and peaches. Barley grains and straw The EMS-FR reported a total of 18 residue trials (northern Europe (NEU) and SEU) conducted on barley during 2007/2008 and 2012/2013 according to the intended GAP. Samples of barley grain and straw were analysed for penthiopyrad, PAM and 753-A-OH; the residue levels of penthiopyrad in grain ranged from 0.01 up to 0.2 mg/kg, and 753-A-OH and PAM were found in concentrations up to and mg/kg, respectively. In straw, penthiopyrad residues ranged from 0.05 up to 4.7 mg/kg, the two metabolites 753-A-OH and PAM accounted for up to 0.42 and 0.94 mg/kg, respectively. The data sets from SEU and NEU were found to be similar based on the Mann Whitney test (U < 5%); thus, the data were pooled to derive the MRL proposal of 0.3 mg/kg. The applicant proposed the MRL extrapolation to oat which is possible according to the EU guidance document (European Commission, 2011). The results of the residue trials, the related risk assessment input values (highest residue and median residue) and the MRL proposals are summarised in Table 3. The stability of penthiopyrad and its metabolites in plant under storage conditions was assessed during the peer review and it was demonstrated that the residues are stable for 18 months when are stored at 20 C in all crop matrices (EFSA, 2013a). According to the EMSs, the samples were stored up to 10 months in frozen conditions; therefore, it is concluded that the residues are covered by storage stability. According to the EMS, the analytical methods used to analyse the samples have been sufficiently validated and were proven to be fit for the purpose (Bulgaria, 2016; France, 2016). EFSA concludes that the data are sufficient to derive the following MRL proposals: 4 mg/kg apricots and peaches outdoor use in SEU; 0.3 mg/kg barley and oat in outdoor use in the EU. 9 EFSA Journal 2016;14(12):4648

10 Table 3: Overview of the available residues trials data Crop (GAPs) Stone fruits: apricot and peaches ( g/ha, PHI 3 days) Barley grains ( g/ha) Barley straw ( g/ha) Region/ Residue levels observed in the supervised indoor (a) residue trials (b) (mg/kg) SEU RD Mo: 0.26; 0.59; 0.62; 0.63; 0.67; 1.23; 1.31; 1.4; 2.31; 2.59 Scaled results RD Mo: 0.2; 0.45; 0.47; 0.48; 0.51; 0.83; 0.93; 0.99; 1.06; 1.76; 1.97 RD RA 1: 0.27; 0. 61; 0.64; 0.65; 0.69; 1.11; 1.27; 1.35, 1.44, 2.38, 2.67 Scaled results RD RA: 0.20; 0.46; 0.49; 0.49; 0.52; 0.85; 0.96; 1.03; 1.10; 1.81; 2.03 RD RA 2 (PAM): 99 < 0.01; NEU RD Mo: < 0.010; 0.010; 0.022; 0.034; 0.069; 0.071; 0.072; 0.074; 0.086; RD RA 1: < 0.020; 0.020; 0.032; 0.047; 0.080; 0.081; 0.082; 0.087; RD RA 2 (PAM): 79 < 0.010; SEU RD Mo: 59 < 0.010; 0.044; 0.058; 0.120; RD RA 1: 59 < 0.02; 0.066; 0.07; 0.15; 0.23 RD RA 2 (PAM): 69 < 0.01; 0.017; 0.018; NEU RD Mo: 0.051; 0.15; 0.18; 0.20; 0.26; 0.28; 0.3; 0.6; 0.68 RD RA 1: 0.10; 0.20; 0.23; 0.25; 0.31; 0.33; 0.39; 0.71; 0.73 RD RA 2 (PAM): ; 0.08 SEU RD Mo: < 0.05; 0.075;0.076; 0.085; 0.17; 0.26; 0.32; 0.38; 4.7 RD RA 1: 0.10; 0.13; 0.14; 0.155; 0.22; 0.37; 0.54; 0.6; 5.12 RD RA 2 (PAM): ; 0.12; 0.14; 0.94 MRL Recommendations/comments (c) proposal (mg/kg) The overdosed field trials were multiplied with the proportionality factor of 0.76 to match the intended GAP MRLOECD: 3.21/4 MRL, STMR and HR derived from pooled (NEU and SEU) data, the population are similar (U < 5%) and extrapolated to oat MRLOECD: 0.21/0.3 HR (d) (mg/kg) 4 HRMO: 1.97 HRRA: 2.03 HR PAM: HRMO: 0.2 HRRA: 0.23 HR PAM: HR: HRMO: 4.7 HR RA : 5.12 HR PAM: STMR (e) (mg/kg) STMRMO: 0.83 STMRRA: 0.85 STMR PAM: 0.01 STMRMO: 0.04 STMRRA: 0.06 STMR PAM: STMR: 0.01 STMRMO: 0.23 STMR RA : 0.28 STMR PAM: 0.05 GAP: good agricultural practice; MRL: maximum residue level; OECD: Organisation for Economic Co-operation and Development. (a): NEU: Outdoor trials conducted in northern Europe; SEU: Outdoor trials conducted in southern Europe; Indoor: indoor EU trials or Country code: if non-eu trials. (b): Individual residue levels considered for MRL calculation are reported in ascending order. RD Mo: residue level according to the monitoring residue definition. RD RA: residue level according to the residue definition for risk assessment. (c): Any information/comment supporting the decision and the OECD MRL calculation (unrounded/rounded values). (d): HRRA: Highest residue level according to the residue definition for risk assessment. HRMo: Highest residue level according to residue definition for monitoring. (e): STMR RA : Median residue level according to residue definition for risk assessment. STMR Mo : Median residue level according to residue definition for monitoring EFSA Journal 2016;14(12):4648

11 All samples of stone fruits and barley were analysed for penthiopyrad and for metabolite 753-A-OH which is included in the residue definition for risk assessment. Conversion factors for risk assessments (CF) were derived from the supervised residue trials and they are reported below. Samples with residues at or close to the LOQ were disregarded from the calculation. Based on the available information submitted by the EMSs (Bulgaria and France), the following overall CFs are proposed for risk assessment: Stone fruits (apricots and peaches): 1.02 Cereals grains (barley and oat): 1.3 Cereal straw (barley and oat): Effect of industrial processing and/or household preparation The effect on the nature of penthiopyrad residues under standard processing conditions, such as pasteurisation, boiling and sterilisation, were assessed during the peer review and it was concluded that the parent compound is hydrolytically stable. For metabolite 753-A-OH, no experimental data were submitted; however, based on the similarity of the structure with the parent compound, it was concluded to have the same behaviour under processing conditions. Thus, for processed commodities, the same residue definition as for raw agricultural commodities is applicable (EFSA, 2013a). Studies investigating the magnitude of penthiopyrad residues in processed product were assessed in the conclusion on the peer review prepared under Directive 91/414/EEC and processing factors (PF) were proposed for certain processed products of the following crops: apple, tomato, barley and wheat. No processing studies are available for PAM metabolite and they were requested during the peer review (EFSA, 2013a). Since the theoretical maximum daily intake (TMDI) of PAM for the crops under consideration is below the trigger value (10% of the ADI), specific processing studies are not deemed to be necessary for the current application. Nevertheless, the nature of PAM metabolite under processing should be further investigated with appropriate studies for future applications Rotational crops Cereals can be grown in rotation with other plants; thus, the possible occurrence of residues in succeeding crops resulting from the use on primary crops has to be assessed. According to the laboratory studies, the persistence of penthiopyrad in soil was moderate to high persistence, with a maximum period required for 90% dissipation (DT 90 ) of over 1,000 days; for metabolite DM-PCA, the maximum was 558 days. The DT 90 for two additional metabolites (753-A-OH and 753-T-DO) also exceeded the trigger value of 100 days (172 and 158 days, respectively) (EFSA, 2013a). In the field studies, the parent penthiopyrad degraded faster with a maximum DT 90 value of 169 days. For metabolite PAM, PCA and DM-PCA, only the period required for 50% dissipation (DT 50 ) values were calculated (maximum of 45 days for metabolite PAM, 78 days for metabolite PCA and 476 days for DM-PCA) and indicated that the trigger value for the DT 90 value would be exceeded for all these compounds (EFSA, 2013a). Therefore, further studies on rotational crops are required (European Commission, 1997c). Studies on the nature and magnitude of penthiopyrad residues in rotational crops were assessed during the peer review where it was concluded that the metabolic pathway is the same as for primary crops thus, the same residue definitions are applicable. Field rotational crop studies with a total seasonal application rate of 800 g/ha were available (1.3N compared to the intended GAP in barley and oat) showed that the major residues in rotational crops are metabolites DM-PCA, PCA and the parent penthiopyrad. However, during the peer review it could not be concluded whether the rotational crops studies are representative for the plateau level that will be reached after multiple year application of penthiopyrad. An accumulation of DM-PCA cannot be excluded following multiple years of consecutive applications (EFSA, 2013a). Since no additional studies were provided under current application, EFSA reiterates the previous recommendation that the Member States should take appropriate risk mitigation measures when granting authorisations to avoid or reduce residues of penthiopyrad and relevant metabolites in rotational crops Nature and magnitude of residues in livestock Since cereals are fed to livestock, the nature and magnitude of penthiopyrad and PAM residues in livestock are assessed in the framework of this application (European Commission, 1996) EFSA Journal 2016;14(12):4648

12 Dietary burden of livestock The median and maximum dietary burden for livestock was calculated using the agreed European methodology (European Commission, 1996). The input values for the dietary burden calculation were selected according to the current FAO recommendations (FAO, 2009) considering the livestock intake from barley and oats and all other feed items assessed in the previously issued reasoned opinion of EFSA (EFSA, 2012). The input values for the dietary burden calculation are summarised in Table 4. Table 4: Input values for the dietary burden calculation Median dietary burden Maximum dietary burden Feed commodity Input (mg/kg) Comment Input (mg/kg) Comment Risk assessment residue definition (1): Sum of penthiopyrad and its metabolite 753-A-OH, expressed as penthiopyrad Barley, oat grains 0.06 STMR (Table 3) 0.23 HR (Table 3) Barley, oat straw 0.28 STMR (Table 3) 5.12 HR (Table 3) Risk assessment residue definition (2): PAM metabolite Barley, oat grains 0.01 STMR (Table 3) HR (Table 3) Barley, oat straw 0.05 STMR (Table 3) HR (Table 3) Other feed items See the tables 3 7 from the reasoned opinion on the setting of the MRLs for penthiopyrad in various crops (EFSA, 2012) STMR: supervised trials median residue; HR: highest residue. The estimated animal dietary intakes are summarised in Table 5. In the last column of the table, the results of the previously calculated dietary burden are presented (EFSA, 2012). Table 5: Results of the dietary burden calculation Animal Maximum Median burden burden (mg/kg bw) (mg/kg bw) Comparing the results of the previous dietary burden calculation with the current one, it becomes evident that the intended use on barley grain has a significant impact on the result. Therefore, the need to amend the MRLs for penthiopyrad in animal origin has to be investigated Nature of residues Highest contributing commodity (a) Maximum burden (mg/kg DM) > 0.1 mg/kg DM (Y/N) Max burden mg/kg DM Previous assessment (EFSA, 2012) Risk assessment residue definition (1): Penthiopyrad and 753-A-OH, expressed as penthiopyrad Dairy cattle Barley straw 1.55 Y 0.86 (apple pomace) Beef cattle Barley straw 3.57 Y 2.0 (apple pomace) Poultry Barley grain Y 0.1 (barley grain) Pigs Barley grain 0.27 Y 0.13 (barley grain) Risk assessment residue definition (2): PAM metabolite Dairy cattle Barley straw 0.26 Y 0.08 (cotton seed meal) Beef cattle Barley straw 0.57 Y 0.18 (wheat straw) Poultry Barley grain N (cotton seed meal) Pigs Barley grain 0.05 N (cotton seed meal) bw: body weight; DM: dry matter. (a): Considering the maximum dietary animal burden. The metabolism of penthiopyrad in livestock was investigated in lactating goat and laying hens during the peer review (EFSA, 2013a). The enforcement residue definition was derived as the sum of penthiopyrad and PAM, expressed as penthiopyrad. For the risk assessment, two separate residue definition were proposed, i.e. penthiopyrad and PAM metabolite EFSA Journal 2016;14(12):4648

13 It was noted that the metabolism of PAM in livestock was not investigated separately during the peer review. Since this metabolite was formed during the metabolism of penthiopyrad, it was concluded that the metabolism is covered by the studies performed with the parent compound (EFSA, 2013a). Penthiopyrad is a fat-soluble compound (log P o/w > 3); however, in metabolism studies, penthiopyrad was found not to accumulate in fat (EFSA 2013a). The log P o/w of PAM is lower than 0.5. For current application, EFSA concluded the metabolism of penthiopyrad in livestock was sufficiently elucidated Magnitude of residues Livestock feeding studies were submitted and assessed in the framework of the peer review (EFSA, 2013a). On dairy cows, the study was carried out at the dose levels of 0.15, 0.48 and 1.65 mg/kg bw per day for 28 consecutive days (equivalent to 8.4, 24.1 and 74.6 mg/kg dry matter (DM)), representing 2N, 7N and 21N of the maximum dietary burden estimated for dairy/beef cattle (see Table 5). In a feeding study with laying hens, animals were dosed at the levels of 0.4, 1.2 and 4 mg/kg/bw for 28 days, (equivalent to 5.85, and mg/kg DM), representing 27N, 81N and 269N of the maximum dietary burden reported in Table 5. In all investigated animal matrices, penthiopyrad and its metabolites were below 0.01 mg/kg at the feeding level closest to the expected maximum dietary burden (2N for ruminants and 27N for laying hens). EFSA concludes that penthiopyrad-related residues above the LOQ are unlikely to occur in animal products. Consequently, no change in the existing MRLs of animal commodities is necessary. 4. Consumer risk assessment The consumer risk assessment was performed for the two residue definitions derived for penthiopyrad using revision 2 of the PRIMo. This exposure assessment model contains the relevant European food consumption data for different subgroups of the EU population 9 (EFSA, 2007) Sum of penthiopyrad and 753-A-OH, expressed as penthiopyrad For the chronic exposure calculation, EFSA used the STMR from the residue trials on apricots, peaches and barley (see Table 4), the accepted CXLs (FAO, 2012; EFSA, 2013b) and the median values for the crops evaluated on the previous reasoned opinion (EFSA, 2012) implemented in the EU legislation. The acute exposure assessment was performed only with regard to the commodities under consideration assuming the consumption of a large portion of the food items as reported in the national food surveys and that these items contained residues at the highest residue (HR) level as observed in supervised field trials (see Table 3). A variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation for peaches and apricots (EFSA, 2007). The input values used for the dietary exposure calculation are summarised in Table 6. Table 6: Input values for the consumer dietary exposure assessment Chronic exposure assessment Acute exposure assessment Commodity Input (mg/kg) Comment Input (mg/kg) Comment Risk assessment residue definition (1): Sum of penthiopyrad and its metabolite 753-A-OH, expressed as penthiopyrad Apricots 0.76 STMR 1.87 HR Peaches 0.76 STMR 1.87 HR Barley grains 0.06 STMR 0.06 STMR Oat grains 0.06 STMR 0.06 STMR 9 The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22 national diets collected from the Member State surveys plus one regional and four cluster diets from the WHO GEMS Food database; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collected from the Member State surveys is used. The complete list of diets incorporated in the EFSA PRIMo is given in its reference section (EFSA, 2007) EFSA Journal 2016;14(12):4648

14 Commodity Chronic exposure assessment Acute exposure assessment Input (mg/kg) Comment Input (mg/kg) Comment Other plant and animal commodities Crops assessed under Article 10 the input values used are listed in tables 4-1 (EFSA, 2012). For the remaining crops, the EU MRLs reported in the Regulation (EU) 2015/845 (covering the acceptable CXL) were used as the input values Acute risk assessment was calculated only for the crops assessed in this application STMR: supervised trials median residue; HR: highest residue; MRL: maximum residue level; CXL: Codex maximum residue limit. The estimated exposure was then compared with the toxicological reference values derived for penthiopyrad and PAM metabolite (see Table 1). The results of the intake calculation using the EFSA PRIMo is a key supporting document and is made publicly available as a background document to this reasoned opinion. A long-term consumer intake concern was not identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated chronic intake accounted for up to 7% of the ADI (FR, toddler). The contribution of residues to the total consumer exposure accounted less than 0.5% of the ADI for the crops under consideration. An acute consumer risk was not identified in relation to the MRL proposals for apricots, peaches, barley and oat; the highest acute consumer exposure was calculated for peaches accounting 16% of the ARfD (DE, diet) PAM metabolite For the calculation of the chronic exposure, EFSA used STMRs for residue values as derived from the residue trials for barley and oat and the median values for the crops assessed during the MRL setting under previous Article 10 Application (EFSA, 2012). The acute exposure assessment was performed only for crops evaluated under current application (apricots, peaches, barley and oat) assuming the consumption of a large portion of the food items as reported in the national food surveys containing residues at the highest/median level as observed in supervised field trials. A variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation, when required (EFSA, 2007). Commodity Chronic exposure assessment Acute exposure assessment Input (mg/kg) Comment Input (mg/kg) Comment Risk assessment residue definition (2): PAM Apricots and peaches 0.01 STMR HR Barley grains 0.01 STMR 0.01 STMR Oat grains 0.01 STMR 0.01 STMR Other plant and animal commodities See table 4-1 of the reasoned opinion issued under Art. 10 of Regulation (EC) 396/2005 (EFSA, 2012) Acute risk assessment was calculated only for the crops assessed in this application STMR: supervised trials median residue; HR: highest residue. The estimated exposure was then compared with the toxicological reference values derived for penthiopyrad and PAM metabolite (see Table 1). The results of the intake calculation using the EFSA PRIMo is a key supporting document and is made publicly available as a background document to this reasoned opinion. A long-term consumer intake concern was not identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated chronic intake accounted for up to 16% of the ADI (FR, toddler). The contribution of PAM residues to the total consumer exposure accounted up to 0.5% of the ADI for the crops under consideration. An acute consumer risk was not identified in relation to the MRL proposals for apricots, peaches, barley and oat; the highest acute consumer exposure was calculated for apricots accounting 1.2% of the ARfD (DE, diet) EFSA Journal 2016;14(12):4648

15 EFSA concludes that the intended use of penthiopyrad on apricots, peaches, barley and oat will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a concern for public health. Conclusions and recommendations EFSA proposes to amend the existing MRLs as reported in the summary table below. Code (a) Commodity Existing EU MRL (mg/kg) Proposed EU MRL (mg/kg) Comment/Justification Enforcement residue definition: Penthiopyrad Apricots 2 4 The MRL proposal is sufficiently supported by data Peaches 2 4 reflecting the SEU intended use on stone fruit. The results of the trials were scaled down using factor of No consumer health risk was identified Barley The MRL proposal is sufficiently supported by data reflecting the NEU and SEU intended uses. No consumer health risk was identified. No change in the MRL in animal commodities is necessary Oat Extrapolation from barley MRL: maximum residue level; SEU: southern Europe; NEU: northern Europe. (a): Commodity code number according to Annex I of Regulation (EC) 396/2005. References Bulgaria, Evaluation report on the modification of MRLs for penthiopyrad in stone fruit (apricots, nectarines and peaches) prepared by the evaluating Member State Bulgaria under Article 8 of Regulation (EC) No 396/2005. April 2015 revised in September 2016, 84 pp. EFSA (European Food Safety Authority), Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. Available online: EFSA (European Food Safety Authority), Reasoned opinion on the setting of new MRLs for penthiopyrad in various crops. EFSA Journal 2012;10(10):2948, 96 pp. doi: /j.efsa EFSA (European Food Safety Authority), 2013a. Conclusion on the peer review of the pesticide risk assessment of the active substance penthiopyrad. EFSA Journal 2013;11(2):3111, 144 pp. doi: /j.efsa EFSA (European Food Safety Authority), 2013b. Scientific support for preparing an EU position for the 45th Session of the Codex Committee on Pesticide Residues (CCPR), including the active substance penthiopyrad, EFSA Journal 2013;11(7):3312, 210 pp. doi: /j.efsa EFSA (European Food Safety Authority), Technical report on the outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for penthiopyrad in light of confirmatory data. EFSA supporting publication 2016:EN pp. European Commission, Appendix G. Livestock Feeding Studies. 7031/VI/95-rev.4. European Commission, 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95-rev.3. European Commission, 1997b. Appendix B. General recommendations for the design, preparation and realisation of residue trials. Annex 2. Classification of (minor) crops not listed in the Appendix of Council Directive 90/642/EEC. 7029/VI/95-rev.6. European Commission, 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95- rev.2. European Commission, 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. European Commission, 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev.3. European Commission, 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95-rev.5. European Commission, 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. European Commission, Residue analytical methods. For pre-registration data requirement for Annex II (part A, section 4) and Annex III (part A, section 5 of Directive 91/414). SANCO/3029/99-rev.4. European Commission, 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SANCO 10634/2010 Rev. 0, finalised in the Standing Committee on the Food Chain and Animal Health at its meeting of March European Commission, 2010b. Residue analytical methods. For post-registration control. SANCO/825/00-rev.8.1. European Commission, Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev EFSA Journal 2016;14(12):4648

16 European Commission, Review report for the active substance Penthiopyrad. Finalised in the Standing Committee on the Food Chain and Animal Health as its meeting on 3 October 2013 in view of the approval of Penthiopyrad as active substance in accordance with Regulation (EC) No 1107/2009. SANCO/12078/2013 rev 2, 3 October 2013, 9 pp. FAO (Food and Agriculture Organization of the United Nations), Submission and evaluation of pesticide residues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2nd Ed. FAO Plant Production and Protection Paper 197, 264 pp. FAO (Food and Agriculture Organization of the United Nations), Penthiopyrad In: Pesticide residues in food Evaluations. Part I. Residues. FAO Plant Production and Protection Paper 216. France, Evaluation report on the modification of MRLs for penthiopyrad in barley and oats prepared by the evaluating Member State France under Article 8 of Regulation (EC) No 396/2005, July 2015 revised in September pp. OECD (Organisation for Economic Co-operation and Development), OECD MRL calculator: spreadsheet for single data set and spreadsheet for multiple data set, 2 March In: Pesticide Publications/Publications on Pesticide Residues. Available online: United Kingdom, Draft assessment report on the active substance penthiopyrad prepared by the rapporteur Member State the United Kingdom in the framework of Directive 91/414/EEC, January Available online: United Kingdom, Final addendum to the draft assessment report on the active substance penthiopyrad, prepared by the rapporteur Member State the United Kingdom in the framework of Directive 91/414/EEC. January Available online: Abbreviations a.s. ADI ARfD BBCH bw CF CXL DAR DAT DM DT 50 DT 90 EC EMS FAO GAP GCPF HPLC HR ILV ISO IUPAC JMPR LC LOQ MRL MS/MS MW NEU OECD P o/w PF PHI PRIMo RA active substance acceptable daily intake acute reference dose growth stages of mono- and dicotyledonous plants body weight conversion factor for enforcement to risk assessment residue definition Codex maximum residue limit (Codex MRL) draft assessment report days after treatment dry matter period required for 50% dissipation (define method of estimation) period required for 90% dissipation (define method of estimation) emulsifiable concentrate evaluating Member State Food and Agriculture Organization of the United Nations good agricultural practice Global Crop Protection Federation (formerly International Group of National Associations of Manufacturers of Agrochemical Products (GIFAP)) high-performance liquid chromatography highest residue independent laboratory validation International Organisation for Standardisation International Union of Pure and Applied Chemistry Joint FAO/WHO Meeting on Pesticide Residues liquid chromatography limit of quantification maximum residue level tandem mass spectrometry detector molecular weight northern Europe Organisation for Economic Co-operation and Development partition coefficient between n-octanol and water processing factor preharvest interval (EFSA) Pesticide Residues Intake Model risk assessment 16 EFSA Journal 2016;14(12):4648