Modification of the existing maximum residue levels forpenthiopyrad 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 theactive substance penthiopyrad in apricots, peaches, barley and oat. To accommodate for the intendeduses of penthiopyrad, France and Bulgaria proposed to raise the existing MRLs from 0.2 to 0.3 mg/kgfor barley and oat, and from 2 to 4 mg/kg for apricots and peaches. France and Bulgaria drafted theevaluation reports in accordance with Article 8 of Regulation (EC) No 396/2005, which were submittedto the European Commission and forwarded to EFSA. According to EFSA, the data are sufficient toderive 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, EFSAconcludes that the proposed use of penthiopyrad on apricots, peaches, barley and oat will not result ina consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose aconsumer health risk.
Suggested citation: EFSA (European Food Safety Authority), 2016. Reasoned opinion on themodification of the MRLs for penthiopyrad in stone fruits and cereals. EFSA Journal 2016;14(12):4648,19 pp. doi:10.2903/j.efsa.2016.4648
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 nomodifications or adaptations are made.
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Modification of existing MRLs for penthiopyrad in stone fruits and cereals
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 alsoreceived an application from DuPont Solutions S.A.S to modify the existing MRLs for penthiopyrad inbarley and oat. To accommodate for the intended uses of penthiopyrad, France and Bulgaria proposedto raise the existing MRLs from 0.2 to 0.3 mg/kg for barley and oat, and from 2 to 4 mg/kg forapricots and peaches. The EMSs (Bulgaria and France) drafted the evaluation reports in accordancewith Article 8 of Regulation (EC) No 396/2005, which were submitted to the European Commission andforwarded to the European Food Safety Authority (EFSA) on 2 September 2015.
EFSA bases its assessment on the evaluation reports submitted by the EMSs, the draft assessmentreport (DAR) prepared under Council Directive 91/414/EEC and its addendum, the conclusion on thepeer review of the pesticide risk assessment of the active substance penthiopyrad, the outcome on theconfirmatory data on PAM metabolite, the Commission review report on penthiopyrad, the JointMeeting on Pesticide Residues (JMPR) Evaluation report as well as the conclusions from a previousEFSA opinion on penthiopyrad.
The toxicological profile of penthiopyrad was assessed during the peer review under Directive91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.1 mg/kg bodyweight (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, nosufficient 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 0.0024 mg/kg bwper day and an ARfD of 0.024 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 twoseparate 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 metabolismof penthiopyrad in primary crops has been sufficiently addressed and the residue definitions derivedare applicable.
EFSA concludes that the submitted supervised residue trials are sufficient to derive the MRLproposals of 0.3 mg/kg for barley and oat, and 4 mg/kg for apricots and peaches. Adequate analyticalenforcement methods are available to monitor the residues of penthiopyrad in the crops underconsideration at the validated limit of quantification (LOQ) of 0.01 mg/kg.
Studies investigating the nature of penthiopyrad residues under standard hydrolysis conditions wereassessed during the peer review showing that the active substance is hydrolytically stable; thus, thesame residue definitions as for raw agricultural commodities (RAC) are applicable. In addition, severalprocessing factors (PF) were derived for penthiopyrad in apple, tomato, barley and wheat. It is notedthat the behaviour of PAM under conditions simulating processing required during the peer review wasnot provided. However, considering that the theoretical maximum daily intake (TMDI) for the cropsunder consideration is below 10% of the ADI, these studies are not deemed to be necessary for thecurrent applications.
The occurrence of penthiopyrad residues in rotational crops was investigated in leafy, roots andcereals during the peer review. Since the metabolic pattern was similar to the primary crops, the sameresidue definitions were proposed as for primary crops. Regarding the magnitude of penthiopyradresidues in the succeeding crops, the data provided during the peer review were not sufficient toconclude on the residue levels taken up from the soil. Considering that no additional studies weresubmitted under current applications, EFSA keeps the recommendation from peer review that theMember States granting authorisations for penthiopyrad uses to consider the possible occurrence inthe succeeding crops.
Cereals are used as feed items; therefore, the potential carry-over into food of animal origin wasassessed. The nature of penthiopyrad residues in livestock has been investigated during the peerreview and the residue definition for enforcement was proposed as penthiopyrad and PAM expressedas penthiopyrad; for risk assessment, two separate residue definitions were derived, penthiopyrad andPAM, respectively. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg drymatter (DM) for all relevant species for penthiopyrad. For PAM metabolite, the calculated livestockdietary burden exceeded the level of 0.1 mg/kg only for ruminants. During the peer review, feeding
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
studies for penthiopyrad and PAM (intake from penthiopyrad) in dairy cows and laying hens weresubmitted and no residues above LOQ were found at the closest feeding level. Therefore, EFSA doesnot recommended the change in the existing MRLs in animal commodities.
The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues IntakeModel (PRIMo). EFSA conducted separate risk assessment calculation for penthiopyrad and PAMmetabolite. No long-term consumer intake concerns or acute risks were identified for penthiopyrad andPAM; the highest chronic intake accounted 7% of the ADI for penthiopyrad and 16% for PAM, whilethe highest acute exposure was calculated for penthiopyrad up to 16% of the ARfD for peaches and1.3% for PAM for apricots.
EFSA concludes that the proposed use of penthiopyrad on the crops under consideration will notresult in a consumer exposure exceeding the toxicological reference values and therefore is unlikely topose a health risk to consumers.
EFSA proposes to amend the existing MRLs as reported in the summary table below.
Code(a) CommodityExisting EU
MRL (mg/kg)Proposed EU MRL
(mg/kg)Comment/justification
Enforcement residue definition: Penthiopyrad
0140010 Apricots 2 4 The MRL proposal is sufficiently supportedby data reflecting the SEU intended use onstone fruit. The results of the trials werescaled down using a factor of 0.76. Noconsumer health risk was identified
0140030 Peaches 2 4
0500010 Barley 0.2 0.3 The MRL proposal is sufficiently supportedby data reflecting the NEU and SEUintended uses. No consumer health risk wasidentified. No change in the MRL in animalcommodities is necessary
0500050 Oat 0.2 0.3 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.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
Abstract................................................................................................................................................... 1Summary................................................................................................................................................. 3Background ............................................................................................................................................. 6The active substance and its use pattern ................................................................................................... 6Assessment.............................................................................................................................................. 71. Method of analysis ...................................................................................................................... 71.1. Methods for enforcement of residues in food of plant origin ........................................................... 71.2. Methods for enforcement of residues in food of animal origin ......................................................... 82. Mammalian toxicology ................................................................................................................. 83. Residues..................................................................................................................................... 83.1. Nature and magnitude of residues in plant .................................................................................... 83.1.1. Primary crops.............................................................................................................................. 83.1.1.1. Nature of residues....................................................................................................................... 83.1.1.2. Magnitude of residues ................................................................................................................. 93.1.1.3. Effect of industrial processing and/or household preparation .......................................................... 113.1.2. Rotational crops .......................................................................................................................... 113.2. Nature and magnitude of residues in livestock............................................................................... 113.2.1. Dietary burden of livestock........................................................................................................... 123.2.2. Nature of residues....................................................................................................................... 123.2.3. Magnitude of residues ................................................................................................................. 134. Consumer risk assessment ........................................................................................................... 134.1. Sum of penthiopyrad and 753-A-OH, expressed as penthiopyrad .................................................... 134.2. PAM metabolite ........................................................................................................................... 14Conclusions and recommendations ............................................................................................................ 15References............................................................................................................................................... 15Abbreviations ........................................................................................................................................... 16Appendix A – Good Agricultural Practice..................................................................................................... 18Appendix B – Used compound codes ......................................................................................................... 19
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
Regulation (EC) No 396/20051 (hereinafter referred to as ‘the Regulation’) establishes the rulesgoverning 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 requestingan authorisation for the use of a plant protection product in accordance with Council Directive91/414/EEC,2 repealed by Regulation (EC) No 1107/20093, shall submit to a Member State, whenappropriate, an application tomodify 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 applicationfrom the company DuPont Solutions (France) S.A.S4 to modify the existing MRLs for the activesubstance penthiopyrad in barley and oat. In addition, DuPont Bulgaria EOOD,5 submitted anapplication to the evaluating Member State Bulgaria (EMS-BG) to modify the existing MRLs for thepenthiopyrad 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 EFSAon 2 September 2015.
The applications were included in the EFSA Register of Questions with the reference numbers andthe following subject:
EFSA-Q-2015-00498: Penthiopyrad – Modification of the existing MRLs in barley and oatsEFSA-Q-2015-00499: 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
0.2–0.3 mg/kg, while Bulgaria proposed to raise the MRLs from 2 to 4 mg/kg for apricots andpeaches.
On 2 December 2015, EFSA asked both EMS (BG and FR) to consider the toxicological endpoints onPAM metabolite and to reassess the application considering this information. Moreover, EMS-BG wasasked for additional information (i.e. details on the residue trials). Since in the meantime, the EFSAassessed 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 byArticle 10 of the Regulation.
In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluationreport provided by the EMS, provide a reasoned opinion on the risks to the consumer associated withthe application.
The updated evaluation reports submitted by the EMSs (Bulgaria, 2016 and France, 2016) and theexposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered assupporting 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 aspossible and at the latest within 3 months (whichmay be extended to 6 months if more detailed evaluationsneed to be carried out) from the date of receipt of the application. If EFSA requests supplementaryinformation, 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 andits 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 ofpesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. OJ L 70, 16.3.2005,p. 1–16.
2 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230,19.8.1991, p. 1–32.
3 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing ofplant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, 24.11.2009,p. 1–50.
4 Dupont Solutions S.A.S, D�efense Plaza; rue Delarivi�ere, 92800, Puteaux, France.5 Dupont EOOD, Mlasdost 4, Business Park Sofia, 1766 Sofia, Bulgaria.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
The details of the intended good agricultural practice (GAPs) for penthiopyrad which are the basisof these MRL applications are given in Appendix A.
Penthiopyrad was evaluated in the framework of Directive 91/414/EEC with the United Kingdomdesignated as the rapporteur Member State (RMS) in conjunction with Regulation (EU) No 188/20116,laying down detailed rules for the assessment of new active substances and the transitional provisionsforeseen in Article 80(1)(a) of Regulation (EC) No 1107/2009, repealing Directive 91/414/EEC. It hasbeen approved under Regulation (EC) No 1107/2009 on 1 May 2014 by Commission ImplementingRegulation (EU) No 1187/20137, with specific provisions requesting confirmatory data including data ontoxicological profile of metabolite PAM, to be submitted by 30 April 2016. The representative usesevaluated 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 byEFSA, 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 themodification of MRLs for penthiopyrad (EFSA, 2012); the proposals from these reasoned opinions havebeen considered in the EU legislation.
Codex Alimentarius has established Codex maximum residue limits (CXLs) for a wide range ofcommodities, including the crops under consideration for which the CXLs are set at 0.2 mg/kg for oatand 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, 2016and France, 2016), the DAR (and its addendum) prepared under Directive 91/414/EEC (UnitedKingdom, 2012, 2013), the conclusion on the peer review of the pesticide risk assessment of the activesubstance penthiopyrad (EFSA, 2013a), the outcome of the confirmatory data on PAM metabolite(EFSA, 2016), the Commission review report on penthiopyrad (European Commission, 2013), the JointMeeting on Pesticide Residues (JMPR) Evaluation report (FAO, 2012) as well as the conclusions fromprevious EFSA opinion on penthiopyrad (EFSA, 2012). The assessment is performed in accordance withthe legal provisions of the Uniform Principles for the Evaluation and the Authorisation of PlantProtection Products adopted by Commission Regulation (EU) No 546/20118 and the currentlyapplicable 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 wereassessed during the peer review (EFSA, 2013a). The multiresidue method DFG-S19 based on liquidchromatography with tandem mass spectrometry detector (LC–MS/MS) was validated for parentpenthiopyrad in acidic, high water, high oil content commodities at the level of 0.01 mg/kg. A validatedindependent laboratory validation (ILV) for acidic and high water commodities was also submitted.
An additional single residue method based on high-performance liquid chromatography withtandem mass spectrometry detector (HPLC–MS/MS) to be used the determination of penthiopyrad andits PAM metabolite involving a hydrolysis step was validated at a level of 0.01 mg/kg for matrices withhigh water, high acid and high oil content and for dry commodities (high starch/protein content). Themethod 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 CouncilDirective 91/414/EEC as regards the procedure for the assessment of active substances which were not on the market 2 yearsafter the date of notification of that Directive. OJ L 53, 26.2.2011, p. 51–55.
7 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 ofplant protection products on the market, and amending the Annex to Commission Implementing Regulation (EU) No 540/2011.OJ L 313, 22.11.2013, p. 42–46.
8 Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the EuropeanParliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. OJ L155, 11.6.2011, p. 127–175.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
As the commodities under consideration belong to the group of matrices with high water and highstarch content, EFSA concludes that sufficiently validated analytical methods to monitor the proposedMRLs are available.
1.2. Methods for enforcement of residues in food of animal origin
The analytical methods for the determination of penthiopyrad residues in animal commodities wereevaluated during the peer review (EFSA, 2013a). An analytical method based on LC–MS/MS was validatedat 0.01 mg/kg level for penthiopyrad and for metabolite PAM in milk, eggs, bovine meat and liver but notfor fat. However, a validated HPLC–MS/MS single residue method is available for the determination ofpenthiopyrad 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 ofpenthiopyrad 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 datawere available to derive toxicological reference values (EFSA, 2013a). For metabolite PAM, additionaldata 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 arereported in 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); notoxicological reference values were derived for PAM.
3. Residues
3.1. Nature and magnitude of residues in plant
3.1.1. Primary crops
3.1.1.1. 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 ispresented in Table 2.
Table 2: Summary of available metabolism studies in plants
Crop group Crops Application Sampling (day, DAT) CommentsFruit Grapes Foliar (19 400 g/ha) 20 and 60 DAT1 [14C]-pyrazole and thienyl
Based on these metabolism studies assessed in the peer review, the following residue definitionswere 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 residuedefinition for monitoring reported above.
For the use on crops under consideration, EFSA concludes that the metabolism of penthiopyrad issufficiently addressed and the residue definitions derived under the peer review are applicable.
3.1.1.2. Magnitude of residues
Stone fruits (apricots and peaches)
The EMS-BG submitted 10 residue trials conducted in southern Europe (SEU) on stone fruits (fiveon apricots, four on peaches and one on nectarine) during 2011 and 2012. The application rate washigher (2 9 450 g/ha) compared to the proposed GAP (2 9 345 g/ha), thus, slightly beyond thetolerated deviation of � 25%. Four of the submitted trials were declined studies. The samples (fruitpulp) were analysed for penthiopyrad and its metabolites 753-A-OH and PAM, the results werereported for the whole fruit. Penthiopyrad residues ranged from 0.26 to 2.59 mg/kg while metabolite753-A-OH ranged from 0.01 to 0.067 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. Sincethe residue trials were performed with higher application rate compared to the proposed GAP, theproportionality approach was used and the results were scaled down using the factor 0.76. It is notedthat 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 resultsas 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 onbarley during 2007/2008 and 2012/2013 according to the intended GAP. Samples of barley grain andstraw were analysed for penthiopyrad, PAM and 753-A-OH; the residue levels of penthiopyrad in grainranged from 0.01 up to 0.2 mg/kg, and 753-A-OH and PAM were found in concentrations up to 0.029and 0.048 mg/kg, respectively.
In straw, penthiopyrad residues ranged from 0.05 up to 4.7 mg/kg, the two metabolites 753-A-OHand 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 applicantproposed 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 andmedian residue) and the MRL proposals are summarised in Table 3.
The stability of penthiopyrad and its metabolites in plant under storage conditions was assessedduring the peer review and it was demonstrated that the residues are stable for 18 months when arestored at �20°C in all crop matrices (EFSA, 2013a). According to the EMSs, the samples were storedup to 10 months in frozen conditions; therefore, it is concluded that the residues are covered bystorage stability.
According to the EMS, the analytical methods used to analyse the samples have been sufficientlyvalidated 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.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
All samples of stone fruits and barley were analysed for penthiopyrad and for metabolite 753-A-OHwhich 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 withresidues at or close to the LOQ were disregarded from the calculation.
Based on the available information submitted by the EMSs (Bulgaria and France), the followingoverall 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): 1.2
3.1.1.3. Effect of industrial processing and/or household preparation
The effect on the nature of penthiopyrad residues under standard processing conditions, such aspasteurisation, boiling and sterilisation, were assessed during the peer review and it was concludedthat the parent compound is hydrolytically stable. For metabolite 753-A-OH, no experimental data weresubmitted; however, based on the similarity of the structure with the parent compound, it wasconcluded 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 assessedin 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 peerreview (EFSA, 2013a). Since the theoretical maximum daily intake (TMDI) of PAM for the crops underconsideration is below the trigger value (10% of the ADI), specific processing studies are not deemedto be necessary for the current application. Nevertheless, the nature of PAM metabolite underprocessing should be further investigated with appropriate studies for future applications.
3.1.2. Rotational crops
Cereals can be grown in rotation with other plants; thus, the possible occurrence of residues insucceeding crops resulting from the use on primary crops has to be assessed. According to thelaboratory studies, the persistence of penthiopyrad in soil was moderate to high persistence, with amaximum period required for 90% dissipation (DT90) of over 1,000 days; for metabolite DM-PCA, themaximum was 558 days. The DT90 for two additional metabolites (753-A-OH and 753-T-DO) alsoexceeded 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 DT90 value of169 days. For metabolite PAM, PCA and DM-PCA, only the period required for 50% dissipation (DT50)values were calculated (maximum of 45 days for metabolite PAM, 78 days for metabolite PCA and476 days for DM-PCA) and indicated that the trigger value for the DT90 value would be exceeded forall 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 assessedduring the peer review where it was concluded that the metabolic pathway is the same as for primarycrops thus, the same residue definitions are applicable. Field rotational crop studies with a totalseasonal application rate of 800 g/ha were available (1.3N compared to the intended GAP in barleyand oat) showed that the major residues in rotational crops are metabolites DM-PCA, PCA and theparent penthiopyrad. However, during the peer review it could not be concluded whether the rotationalcrops studies are representative for the plateau level that will be reached after multiple yearapplication of penthiopyrad. An accumulation of DM-PCA cannot be excluded following multiple yearsof consecutive applications (EFSA, 2013a).
Since no additional studies were provided under current application, EFSA reiterates the previousrecommendation that the Member States should take appropriate risk mitigation measures whengranting authorisations to avoid or reduce residues of penthiopyrad and relevant metabolites inrotational crops.
3.2. Nature and magnitude of residues in livestock
Since cereals are fed to livestock, the nature and magnitude of penthiopyrad and PAM residues inlivestock are assessed in the framework of this application (European Commission, 1996).
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
The median and maximum dietary burden for livestock was calculated using the agreed Europeanmethodology (European Commission, 1996). The input values for the dietary burden calculation wereselected according to the current FAO recommendations (FAO, 2009) considering the livestock intakefrom barley and oats and all other feed items assessed in the previously issued reasoned opinion ofEFSA (EFSA, 2012). The input values for the dietary burden calculation are summarised in Table 4.
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).
Comparing the results of the previous dietary burden calculation with the current one, it becomesevident that the intended use on barley grain has a significant impact on the result. Therefore, theneed to amend the MRLs for penthiopyrad in animal origin has to be investigated.
3.2.2. Nature of residues
The metabolism of penthiopyrad in livestock was investigated in lactating goat and laying hensduring the peer review (EFSA, 2013a). The enforcement residue definition was derived as the sum ofpenthiopyrad and PAM, expressed as penthiopyrad. For the risk assessment, two separate residuedefinition were proposed, i.e. penthiopyrad and PAM metabolite.
Table 4: Input values for the dietary burden calculation
Feed commodityMedian dietary burden Maximum dietary burden
Input (mg/kg) Comment Input (mg/kg) Comment
Risk assessment residue definition (1): Sum of penthiopyrad and its metabolite 753-A-OH, expressed aspenthiopyrad
It was noted that the metabolism of PAM in livestock was not investigated separately during the peerreview. Since this metabolite was formed during the metabolism of penthiopyrad, it was concluded thatthe metabolism is covered by the studies performed with the parent compound (EFSA, 2013a).
Penthiopyrad is a fat-soluble compound (log Po/w > 3); however, in metabolism studies, penthiopyradwas found not to accumulate in fat (EFSA 2013a). The log Po/w of PAM is lower than 0.5.
For current application, EFSA concluded the metabolism of penthiopyrad in livestock was sufficientlyelucidated.
3.2.3. 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 perday 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/bwfor 28 days, (equivalent to 5.85, 17.54 and 58.46 mg/kg DM), representing 27N, 81N and 269N of themaximum dietary burden reported in Table 5.
In all investigated animal matrices, penthiopyrad and its metabolites were below 0.01 mg/kg at thefeeding level closest to the expected maximum dietary burden (2N for ruminants and 27N for layinghens). EFSA concludes that penthiopyrad-related residues above the LOQ are unlikely to occur inanimal 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 forpenthiopyrad using revision 2 of the PRIMo. This exposure assessment model contains the relevantEuropean food consumption data for different subgroups of the EU population9 (EFSA, 2007).
4.1. 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 medianvalues for the crops evaluated on the previous reasoned opinion (EFSA, 2012) implemented in the EUlegislation.
The acute exposure assessment was performed only with regard to the commodities underconsideration assuming the consumption of a large portion of the food items as reported in thenational food surveys and that these items contained residues at the highest residue (HR) level asobserved in supervised field trials (see Table 3). A variability factor accounting for the inhomogeneousdistribution 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
9 The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22national diets collected from the Member State surveys plus one regional and four cluster diets from the WHO GEMS Fooddatabase; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collectedfrom the Member State surveys is used. The complete list of diets incorporated in the EFSA PRIMo is given in its referencesection (EFSA, 2007).
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
The estimated exposure was then compared with the toxicological reference values derived forpenthiopyrad and PAM metabolite (see Table 1). The results of the intake calculation using the EFSAPRIMo is a key supporting document and is made publicly available as a background document to thisreasoned opinion.
A long-term consumer intake concern was not identified for any of the European diets incorporatedin 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 theADI 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% ofthe ARfD (DE, diet).
4.2. PAM metabolite
For the calculation of the chronic exposure, EFSA used STMRs for residue values as derived fromthe residue trials for barley and oat and the median values for the crops assessed during the MRLsetting 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 asreported in the national food surveys containing residues at the highest/median level as observed insupervised field trials. A variability factor accounting for the inhomogeneous distribution on theindividual items consumed was included in the calculation, when required (EFSA, 2007).
Other plant and animal commodities See table 4-1 of the reasonedopinion issued under Art. 10 ofRegulation (EC) 396/2005(EFSA, 2012)
Acute risk assessment wascalculated only for the cropsassessed in this application
STMR: supervised trials median residue; HR: highest residue.
The estimated exposure was then compared with the toxicological reference values derived forpenthiopyrad and PAM metabolite (see Table 1). The results of the intake calculation using the EFSAPRIMo is a key supporting document and is made publicly available as a background document to thisreasoned opinion.
A long-term consumer intake concern was not identified for any of the European diets incorporatedin 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% ofthe 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% ofthe ARfD (DE, diet).
Crops assessed under Article 10 the inputvalues 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 acceptableCXL) were used as the input values
Acute risk assessment was calculatedonly for the crops assessed in thisapplication
STMR: supervised trials median residue; HR: highest residue; MRL: maximum residue level; CXL: Codex maximum residue limit.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
EFSA concludes that the intended use of penthiopyrad on apricots, peaches, barley and oat will notresult in a consumer exposure exceeding the toxicological reference value and therefore is unlikely topose a concern for public health.
Conclusions and recommendations
EFSA proposes to amend the existing MRLs as reported in the summary table below.
Code(a) CommodityExistingEU MRL(mg/kg)
ProposedEU MRL(mg/kg)
Comment/Justification
Enforcement residue definition: Penthiopyrad
0140010 Apricots 2 4 The MRL proposal is sufficiently supported by datareflecting the SEU intended use on stone fruit. The resultsof the trials were scaled down using factor of 0.76. Noconsumer health risk was identified
0140030 Peaches 2 4
0500010 Barley 0.2 0.3 The MRL proposal is sufficiently supported by datareflecting the NEU and SEU intended uses. No consumerhealth risk was identified. No change in the MRL in animalcommodities is necessary
0500050 Oat 0.2 0.3 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.
ReferencesBulgaria, 2016. 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), 2007. Reasoned opinion on the potential chronic and acute risk toconsumers health arising from proposed temporary EU MRLs. Available online: www.efsa.europa.eu
EFSA (European Food Safety Authority), 2012. Reasoned opinion on the setting of new MRLs for penthiopyrad invarious crops. EFSA Journal 2012;10(10):2948, 96 pp. doi:10.2903/j.efsa.2012.2948
EFSA (European Food Safety Authority), 2013a. Conclusion on the peer review of the pesticide risk assessment ofthe active substance penthiopyrad. EFSA Journal 2013;11(2):3111, 144 pp. doi:10.2903/j.efsa.2013.3111
EFSA (European Food Safety Authority), 2013b. Scientific support for preparing an EU position for the 45thSession of the Codex Committee on Pesticide Residues (CCPR), including the active substance penthiopyrad,EFSA Journal 2013;11(7):3312, 210 pp. doi:10.2903/j.efsa.2013.3312
EFSA (European Food Safety Authority), 2016. Technical report on the outcome of the consultation with MemberStates, the applicant and EFSA on the pesticide risk assessment for penthiopyrad in light of confirmatory data.EFSA supporting publication 2016:EN-1072. 21 pp.
European Commission, 1996. 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, 2000. 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 itsmeeting of 23–24 March 2010.
European Commission, 2010b. Residue analytical methods. For post-registration control. SANCO/825/00-rev.8.1.European Commission, 2011. Appendix D. Guidelines on comparability, extrapolation, group tolerances and data
requirements for setting MRLs. 7525/VI/95-rev.9.
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
European Commission, 2013. Review report for the active substance Penthiopyrad. Finalised in the StandingCommittee on the Food Chain and Animal Health as its meeting on 3 October 2013 in view of the approval ofPenthiopyrad as active substance in accordance with Regulation (EC) No 1107/2009. SANCO/12078/2013 rev2, 3 October 2013, 9 pp.
FAO (Food and Agriculture Organization of the United Nations), 2009. Submission and evaluation of pesticideresidues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2nd Ed. FAOPlant Production and Protection Paper 197, 264 pp.
FAO (Food and Agriculture Organization of the United Nations), 2012. Penthiopyrad In: Pesticide residues in food –2012. Evaluations. Part I. Residues. FAO Plant Production and Protection Paper 216.
France, 2016. Evaluation report on the modification of MRLs for penthiopyrad in barley and oats prepared by theevaluating Member State France under Article 8 of Regulation (EC) No 396/2005, July 2015 revised inSeptember 2016. 26 pp.
OECD (Organisation for Economic Co-operation and Development), 2011. OECD MRL calculator: spreadsheet forsingle data set and spreadsheet for multiple data set, 2 March 2011. In: Pesticide Publications/Publications onPesticide Residues. Available online: http://www.oecd.org
United Kingdom, 2012. Draft assessment report on the active substance penthiopyrad prepared by the rapporteurMember State the United Kingdom in the framework of Directive 91/414/EEC, January 2012. Available online:www.efsa.europa.eu
United Kingdom, 2013. 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 2013. Available online: www.efsa.europa.eu
Abbreviations
a.s. active substanceADI acceptable daily intakeARfD acute reference doseBBCH growth stages of mono- and dicotyledonous plantsbw body weightCF conversion factor for enforcement to risk assessment residue definitionCXL Codex maximum residue limit (Codex MRL)DAR draft assessment reportDAT days after treatmentDM dry matterDT50 period required for 50% dissipation (define method of estimation)DT90 period required for 90% dissipation (define method of estimation)EC emulsifiable concentrateEMS evaluating Member StateFAO Food and Agriculture Organization of the United NationsGAP good agricultural practiceGCPF Global Crop Protection Federation (formerly International Group of National Associations of
Manufacturers of Agrochemical Products (GIFAP))HPLC high-performance liquid chromatographyHR highest residueILV independent laboratory validationISO International Organisation for StandardisationIUPAC International Union of Pure and Applied ChemistryJMPR Joint FAO/WHO Meeting on Pesticide ResiduesLC liquid chromatographyLOQ limit of quantificationMRL maximum residue levelMS/MS tandem mass spectrometry detectorMW molecular weightNEU northern EuropeOECD Organisation for Economic Co-operation and DevelopmentPo/w partition coefficient between n-octanol and waterPF processing factorPHI preharvest intervalPRIMo (EFSA) Pesticide Residues Intake ModelRA risk assessment
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
RAC raw agricultural commodityRD residue definitionRMS rapporteur Member StateSC suspension concentrateSEU southern EuropeSTMR supervised trials median residueTMDI theoretical maximum daily intakeWHO World Health Organization
Modification of existing MRLs for penthiopyrad in stone fruits and cereals
