Modification of the existing MRLs for chlorpyrifos-methyl in various crops 1

EFSA Journal 2011;9(6):2219 REASONED OPINION Modification of the existing MRLs for chlorpyrifos-methyl in various crops 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY In accordance with Article 6 of Regulation (EC) No 396/2005, Spain, herewith referred as the evaluating Member State (EMS), received an application from Dow AgroSciences to modify the existing MRLs for the active substance chlorpyrifos-methyl in a wide range of crops. Spain drafted an evaluation report according to Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 16 August 2010. EFSA bases its assessment on the evaluation report, the Commission review report, the Draft Assessment Report (DAR) and its addenda prepared under the Directive 91/414/EEC and the JMPR evaluation report on chlorpyrifos-methyl. The toxicological profile of chlorpyrifos-methyl was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.01 mg/kg bw/day and an ARfD of 0.1 mg/kg bw. The metabolism of chlorpyrifos-methyl in primary crops was investigated during the peer review in tomatoes, oranges and cabbage after foliar application and in cereals after post-harvest application. The structurally related compound chlorpyrifos was also used to reveal the metabolic profile of the active substance. These data have been completed by two additional studies on peas and radish with chlorpyrifos assessed by the EMS in the framework of this application. EFSA concludes that the metabolism of chlorpyrifos-methyl in primary crops is sufficiently elucidated. The residue definitions established by the peer review can be extended to the various commodities under consideration. The parent chlorpyrifos-methyl is the residue definition for monitoring, whereas for risk assessment the definition is chlorpyrifos-methyl plus 3,5,6-trichloropyridinol (TCP) and its conjugates, expressed as chlorpyrifos-methyl and chlorpyrifos-methyl and desmethyl chlorpyrifos-methyl, expressed as chlorpyrifos-methyl for post-harvest use in stored grains. It is noted that 3,5,6-trichloropyridinol (TCP) is a metabolite resulting also from the use of the pesticides chlorpyrifos and triclopyr. The submitted supervised residue trials are sufficient and adequate to derive MRL proposals for the intended uses of chlorpyrifos-methyl as follow: 0.8 mg/kg on oranges (an extrapolation to grapefruits may be considered), 0.2 mg/kg on pome fruits, except pears, 0.15 mg/kg on apricots, 0.04 mg/kg on pears, peaches and cotton seeds, 0.09 mg/kg on strawberries and table grapes, 1.0 mg/kg on 1 On request from the European Commission, Question No EFSA-Q-2010-01050, issued on 07 June 2011. 2 Correspondence: pesticides.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Modification of the existing MRLs for chlorpyrifos-methyl in various crops. EFSA Journal 2011;9(6):2219. [67 pp.] doi:10.2903/j.efsa.2011.2219. Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2011

aubergines, 0.01* mg/kg on potatoes, soya beans and maize (foliar application) and 0.02 mg/kg on rape seeds. The proposal to lower the MRLs on pome fruits, peaches, table grapes and strawberries (plus tomatoes and aubergines, in case it is decided to propose a lower MRL of 0.15 mg/kg for tomatoes) is based on the GAP information submitted by the EMS. Although sufficiently supported by residue trials no final proposal could be derived for the intended foliar use on tomatoes and postharvest use on barley, oats, rye and wheat due to consumer safety concerns. Validated analytical methods are available to enforce the proposed MRLs for chlorpyrifos-methyl, however for enforcing the MRLs on the oil-based commodities additional data to complete the validation of the method of analysis according to EU guidelines should be submitted. The effect of processing on the nature of chlorpyrifos-methyl has not been investigated. From the studies on the magnitude of the residues in processed products, a reliable processing factor could only be derived for peeled oranges and mandarins. Other processing factors were also derived for processed orange, apple, grape, tomato and cereal products, but they are not proposed for enforcement since the required minimum number of trials is not always available and the nature of residues in processed commodities is not fully investigated. Therefore, EFSA proposes to include the following processing factor in Annex VI of regulation (EC) 396/2005: Citrus, peeled: <0.06 The occurrence of chlorpyrifos-methyl residues in rotational crops was assessed in the peer review. Based on the available information on the nature and magnitude of residues of the compound chlorpyrifos in succeeding crops, it was concluded that significant residue levels of chlorpyrifosmethyl and its soil metabolites are unlikely to occur in rotational crops provided that the compound is used according to the proposed use patterns. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg (dry matter) for all relevant animal species and was driven by the livestock intake of wheat. Based on the metabolism of chlorpyrifos-methyl in livestock, the enforcement residue definition as parent compound and the risk assessment residue definition as chlorpyrifos-methyl plus 3,5,6-trichloropyridinol (TCP) and its conjugates, expressed as chlorpyrifos-methyl were established by the peer review. The results of livestock feeding studies showed that at the calculated maximum dietary burdens chlorpyrifos-methyl will not occur in concentrations exceeding the LOQ of 0.01 mg/kg except in ruminant and swine fat. Thus, the existing MRLs in fat and meat (the pesticide is fat-soluble) should be amended as follow: swine meat and fat from 0.05* mg/kg to 0.05 mg/kg; ruminant meat and fat from 0.05* to 0.02 mg/kg. However, if the intended post-harvest use on cereals assessed in this opinion is not accepted, the proposed MRLs can be lowered to 0.02 mg/kg (swine fat, meat) and 0.01 mg/kg (ruminant fat, meat). The lowering of all the MRLs at 0.05* to 0.01* in the remaining animal products is also proposed based on the sensitivity of the analytical assay. A validated analytical method is available to enforce the proposed MRLs for chlorpyrifos-methyl. The consumer risk assessment was performed with revision 2 of the EFSA PRIMo. Due to the identification of commodities for which a potential consumer risk could not be excluded, three scenarios to assess the chronic (long-term) dietary exposure were performed. In the first exposure assessment (Scenario 1) a consumer risk was identified for 20 out of the 27 European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 6.2 % to 385 % of the ADI (WHO Cluster diet B). The highest contributor was wheat. Therefore, a more realistic chronic risk assessment was performed focusing on those commodities for which a potential consumer risk was identified: cereals. For the refinement EFSA used the available processing factors derived from processing studies on wheat and barley and detailed consumption EFSA Journal 2011;9(6):2219 2

data for processed wheat and barley products collected by EFSA for 15 European diets. It should be stressed that the information on the nature and magnitude of residues in processed food is hampered by the limited data available and therefore the refined calculation is affected by uncertainties. After the refined exposure estimation for cereals (Scenario 2), chronic intake concerns were identified for four out of the 27 European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 6.2 % to 126 % of the ADI. The major contributors were maize, rye and wheat and their products. To proceed with further refinements more detailed information on food consumption of processed cereals, in particular on rye and maize, and on chlorpyrifos-methyl residues on processed products would be required. In absence of such data, it is not possible to exclude the occurrence of chlorpyrifos-methyl residues above the toxicological reference value. A further dietary exposure assessment was performed (Scenario 3). In this case, the proposed increase of the application rate for the post-harvest use in wheat, barley, rye and oat grains was rejected and the existing post-harvest use in maize was withdrawn. The chronic intake concerns were solved for all commodities. The total calculated intake values ranged from 6.2 % to 89 % of the ADI (UK infant diet). An acute consumer risk was identified in relation to the MRL proposal for tomatoes (108.7 % of the ARfD). The exceedance is caused by the highest residue result (0.9 mg/kg), a potential outlier, which was selected in the assessment as there was no information to justify its exclusion. When the intended use on tomatoes was rejected or if the first highest value below the above cited value (0.07 mg/kg) was chosen to perform the acute risk assessment, no acute intake concerns were indentified with regard to the MRL proposals. The calculated maximum exposure in percentage of the ARfD was 46.8 % of the ARfD for aubergines in children. Consequently, EFSA concludes that the intended uses of chlorpyrifos-methyl on the crops under consideration will result in a short-term and long-term consumer exposure exceeding the toxicological reference values for tomatoes and for wheat, rye and maize, respectively. Nevertheless, also the existing post-harvest application on stored maize is potentially posing a public health concern. Thus, EFSA proposes to amend the current MRLs as in the table below. It is important to highlight that the conclusions reached in this opinion and the risk assessment are valid only if Member States confirm that no more critical GAP than that proposed by the EMS is still authorised for pome fruits, peaches, table grapes and strawberries (plus tomatoes and aubergines, in case it is decided to propose a lower MRL of 0.15 mg/kg for tomatoes), which requires maintaining the existing MRLs. A new consumer risk assessment is needed if the assumption is not valid. Code number (a) Commodity Existing EU MRL Enforcement residue definition: chlorpyrifos-methyl (F) 110010 Grapefruit (Shaddocks, pomelos, sweeties, tangelo (except mineola), ugli and other hybrids) Proposed EU MRL 0.05* 0.05* or 0.8 Justification for the proposal Residue data are not sufficient to derive a MRL proposal for the whole group of citrus fruits. A risk management decision has to be taken if a MRL on grapefruits can be supported based on extrapolation from data on oranges. No risk for consumers was identified for the intended use if the extrapolation is accepted. EFSA Journal 2011;9(6):2219 3

Code number (a) Commodity Existing EU MRL Proposed EU MRL Justification for the proposal 110020 Oranges (Bergamot, 0.5 0.8 The MRL proposal is sufficiently bitter orange, chinotto and other hybrids) supported by data and no risk for consumers was identified for the intended use. 110030 110040 Lemons (Citron, lemon) Limes 0.3 0.05* - - Residue data are not sufficient to derive a MRL proposal for the whole group of citrus fruits. 110050 Mandarins 1 - (Clementine, tangerine, mineola and other hybrids) 110990 Others citrus fruits 0.05* - 130000 Apples 0.5 0.2 The proposed SEU use only is sufficiently supported by data and no risk for consumers was identified for the intended uses. Before lowering the MRLs, it has to 130020 Pears (Oriental pears) 0.5 0.04 be clarified if a more critical GAP than that reported by the EMS is still authorized, which requires maintaining the existing MRL. 130030 Quinces 0.5 0.2 The MRL proposals are sufficiently 130040 Medlar 0.5 0.2 supported by data and no risk for 130050 Loquat 0.5 0.2 consumers was identified for the intended 130990 Others 0.5 0.2 uses. The MRL proposal was extrapolated from data on apples. Before lowering the MRLs, it has to be clarified if a more critical GAP than that reported by the EMS is still authorized, which requires maintaining the existing MRL. 140010 Apricots 0.05* 0.15 The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended use. 140030 Peaches (Nectarines and similar hybrids) 140020 Cherries (sweet cherries, sour cherries) 0.5 0.04 The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended use. Before lowering the MRL, it has to be clarified if a more critical GAP than that reported by the EMS is still authorized, which requires maintaining the existing MRL. 0.05* - Residue data are not sufficient to derive a MRL proposal. 151010 Table grapes 0.2 0.09 The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended use. Before lowering the MRL, it has to be clarified if a more critical GAP than that reported by the EMS is still authorized, which requires maintaining the existing MRL. EFSA Journal 2011;9(6):2219 4

Code number (a) Commodity Existing EU MRL Proposed EU MRL Justification for the proposal 151020 Wine grapes 0.2 - Residue data are not sufficient to derive a MRL proposal for the intended GAP. No risk for consumers was identified for the existing MRL. 152000 Strawberries 0.5 0.09 The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended use. Before lowering the MRL, it has to be clarified if a more critical GAP than that reported by the EMS is still authorized, which requires maintaining the existing MRL. 211000 Potatoes 0.05* 0.01* The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended use. 231010 Tomatoes (Cherry tomatoes, tree tomato, Physalis, gojiberry, wolfberry (Lycium barbarum and L. chinense) 231030 Aubergines (egg plants) (Pepino) 231020 Peppers (Chilli peppers) 401060 Rape seed (Bird rapeseed, turnip rape) 401070 Soya bean 0.05* 0.01* 401090 Cotton seed 0.05* 0.04 500000 Cereals, except barley, wheat, oats 0.5 - The proposed SEU use only is sufficiently supported by data, but for the intended use a potential short-term consumer risk can not be excluded. A risk management decision has to be taken concerning a possible MRL proposal of 0.15 mg/kg for the proposed outdoor use in SEU, pending evidence that the highest value (potential outlier) from the submitted dataset of residue studies is really incorrect and provided that a more critical GAP is not still authorized, which requires maintaining the existing MRL. No risk for the consumers was identified with the MRL proposal of 0.15 mg/kg. 0.5 1.0 The MRL proposal is based on extrapolation from data from the outdoor SEU use on tomatoes and no risk for consumers was identified for the intended use. If a MRL is proposed for the intended use on tomatoes (see above comment), the MRL proposal for aubergines may be lowered accordingly, provided that a more critical GAP is not still authorized, which requires maintaining the existing MRL. 0.5 - Residue data are not sufficient to derive a MRL proposal. 0.05* 0.02 The MRL proposals are sufficiently supported by data and no risk for consumers was identified for the intended uses. 3 - The extrapolation of residue data from barley and wheat to the whole group of EFSA Journal 2011;9(6):2219 5

Code number (a) Commodity Existing EU MRL Proposed EU MRL Justification for the proposal cereals is not envisaged in the EU guidelines. 500010 Barley 3 5 The proposed GAP is sufficiently 500050 Oats 3 or 3 supported by data but for the intended use a 500070 Rye, 3 potential long-term consumer risk can not 500090 Wheat (Spelt, 3 be excluded. triticale) A risk manager decision has to be taken. MRL 5 mg/kg: a potential risk for the consumer can not be excluded for rye and wheat intakes. No change: no risk for consumers was identified for the existing MRL. 500030 Maize 3 0.01* The assessment demonstrated that for the existing MRL a potential long-term consumer risk can not be excluded and EFSA recommends it s withdrawn. 1011010 Swine, meat 0.05* 0.05 (F) or 0.02 (F) 1012010 1013010 1014010 1015010 1016010 1017010 Bovine, sheep, goat, meat Horse, poultry, other farm animals, meat 1011020 Swine, fat of lean meat 1012020 Bovine, sheep, goat, 1013020 fat 1014020 1015020 1016020 1017020 1011030 1012030 1013030 1014030 1015030 1016030 Horses, poultry, other farm animals, fat Swine, bovine, sheep, goat, horse, poultry, other farm animals, liver 0.05* 0.02 (F) or 0.01 (F) The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the intended foliar use. The MRL proposals are sufficiently supported by data and no risk for consumers was identified. If the MRL proposal of 5 mg/kg for chlorpyrifos-methyl on stored wheat, barley, rye and oats is not accepted due to potential safety concerns, the MRL proposals for meat can be lowered. 0.05* 0.01* The assessment demonstrated that the existing MRLs are sufficient and no risk for consumers was identified. 0.05* 0.05 or 0.02 0.05* 0.02 or 0.01 The lowering of all the MRLs is recommended based on the sensibility of the enforcement analytical method. The MRL proposals are sufficiently supported by data and no risk for consumers was identified If the MRL proposal of 5 mg/kg for chlorpyrifos-methyl on stored wheat, barley, rye and oats is not accepted due to potential safety concerns, the MRL proposals for fat can be lowered. 0.05* 0.01* The assessment demonstrated that the existing MRLs are sufficient and no risk for consumers was identified. 0.05* 0.01* The lowering of all the MRLs is recommended based on the sensibility of the enforcement analytical method. EFSA Journal 2011;9(6):2219 6

Code number (a) Commodity Existing EU MRL 1017030 1011040 1012040 1013040 1014040 1015040 1016040 1017040 1011050 1012050 1013050 1014050 1015050 1016050 1017050 1011990 1012990 1013990 1014990 1015990 1016990 1017990 Swine, bovine, sheep, goat, horse, poultry, other farm animals, kidney Swine, bovine, sheep, goat, horse, poultry, other farm animals, edible offal Swine, bovine, sheep, goat, horse poultry, other farm animals, others Proposed EU MRL 0.05* 0.01* 0.05* 0.01* 0.05* 0.01* (a): According to Annex I of Regulation (EC) No 396/2005. (*): Indicates that the MRL is set at the limit of analytical quantification. (F): Fat-soluble. Justification for the proposal At any rate, it should be noted that the conclusions presented in this opinion are affected by a degree of uncertainty. The toxicological profile of the metabolites TCP and DEM, the nature and magnitude of chlorpyrifos-methyl residues in processed commodities as well as actual consumption data, in particular on cereals, should be further investigated. KEY WORDS Chlorpyrifos-methyl, citrus, pome, stone fruits, grapes, strawberries, potatoes, Solanaceae, oilseeds, cereals, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, organophosphates, trichloropyridinol (TCP). EFSA Journal 2011;9(6):2219 7

TABLE OF CONTENTS Summary... 1 Background... 9 Terms of reference... 10 The active substance and its use pattern... 11 Assessment... 12 1. Methods of analysis... 12 1.1. Methods for enforcement of residues in food of plant origin... 12 1.2. Methods for enforcement of residues in food of animal origin... 12 2. Mammalian toxicology... 13 3. Residues... 13 3.1. Nature and magnitude of residues in plant... 13 3.1.1. Primary crops... 13 3.1.2. Rational crops... 31 3.2. Nature and magnitude of residues in livestock... 32 3.2.1. Dietary burden of livestock... 32 3.2.2. Nature of residues... 34 3.2.3. Magnitude of residues... 34 4. Consumer risk assessment... 42 Conclusions and recommendations... 46 References... 52 Appendix A. Good Agricultural Practices (GAPs)... 54 Appendix B. Pesticide Residues Intake Model (PRIMo)... 56 Appendix C. Existing EU maximum residue limits (MRLs)... 63 Abbreviations... 66 EFSA Journal 2011;9(6):2219 8

BACKGROUND Regulation (EC) No 396/2005 3 establishes the rules governing the setting of pesticide MRLs at European Union level. Article 6 of that Regulation lays down that a party requesting an authorisation for the use of a plant protection product in accordance with Council Directive 91/414/EEC 4, shall submit to a Member State, when appropriate, an application to set or modify an MRL in accordance with the provisions of Article 7 of that Regulation. Spain, hereafter referred to as the evaluating Member State (EMS), received an application from the company Dow AgroSciences 5 to modify the existing MRLs for the active substance chlorpyrifosmethyl in various crops. This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation report of the EMS was submitted to the European Commission who forwarded the application, the evaluation report and the supporting dossier to EFSA on 16 August 2010. The application was included in the EFSA Register of Questions with the reference number EFSA-Q-2010-01050 and the following subject: Chlorpyrifos-methyl - Application to modify the existing MRLs in various crops. Spain proposed to modify the existing MRLs of chlorpyrifos-methyl as reported in the table below: Commodity Existing EU MRL Proposed EU MRL Enforcement residue definition: chlorpyrifos-methyl (F) Grapefruits, limes, other 0.05* citrus fruits Oranges 0.5 1 Lemons 0.3 Mandarins 1 Pome fruits 0.5 0.2 Apricots 0.05* Peaches 0.5 0.1 Cherries 0.05* 0.01* Table and wine grapes 0.2 0.2 Strawberries 0.5 0.1 Potatoes 0.05* 0.01* Tomatoes, peppers 0.5 - Aubergines 0.5 0.2 Barley, wheat, oats, rye 3 2(a) Maize, millet, sorghum 3 0.01* Rice 3 0.01* Other plant products 0.05* 0.01* Swine fat 0.05* 0.1 (a): According to the EMS assessment, lowering the MRL to 2 mg/kg leads to an acceptable chronic risk for consumer. The level of 3 mg/kg (existing MRL) could be an acceptable level but further data for refinement calculation are required. Besides these changes, the EMS proposed to decrease all existing MRL values for plant commodities equal to the LOQ of 0.05* to 0.01*. 3 Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February 2005. OJ L 70, 16.03.2005, p. 1-16. 4 Council Directive 91/414/EEC of 15 July 1991. OJ L 230, 19.08.1991, p. 1-32. 5 Dow Agrosciences Ltd, 3, Milton Park, OX14 4RN, Abingdon (Oxfordshire), United Kingdom. EFSA Journal 2011;9(6):2219 9

EFSA then proceeded with the assessment of the application as required by Article 10 of the Regulation. TERMS OF REFERENCE In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the evaluating Member State, provide a reasoned opinion on the risks to the consumer associated with the application. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within three months (which may be extended to six months where more detailed evaluations need to be carried out) from the date of receipt of the application. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. In this particular case the calculated deadline for providing the reasoned opinion is 16 November 2010. EFSA Journal 2011;9(6):2219 10

THE ACTIVE SUBSTANCE AND ITS USE PATTERN Chlorpyrifos-methyl is the ISO common name for O,O-dimethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate (IUPAC). The chemical structure of the compound is herewith reported. C l C l S O CH 3 C l N O P O CH 3 Molecular weight: 322.6 g/mol Chlorpyrifos-methyl is a non-systemic organophosphate (OP) insecticide with contact and stomach action. Like other OP insecticides its action is due to the inhibition of acetyl-cholinesterase (AChE inhibitor) in the pest nerves and subsequent accumulation of acetylcholine in the nerve endings. Noteworthy is that chlorpyrifos-methyl shares a common structure with another OP, chlorpyrifos 6, from which it differs for the presence of a methyl group instead of the ethyl group. Chlorpyrifos has been accepted as surrogate compound for certain studies (EC, 2005). Chlorpyrifos-methyl is active against sucking and chewing pests, representatives of Coleoptera, Diptera, Homoptera and Lepidoptera in a wide range of crops. It is also used as a grain storage insecticide for the control of coleopteran, Lepidoptera and mite pests. Chlorpyrifos-methyl is an active substance which was evaluated according to Directive 91/414/EEC with Spain designated as rapporteur Member State (RMS). It was included in Annex I of the above cited Directive by Commission Directive 2005/72/EC 7, which entered into force on 1 July 2006, for use as insecticide only. The representative uses evaluated in the peer review were the foliar application on grape vines and the post-harvest treatment on stored grains. The Draft Assessment Report (DAR) of chlorpyrifos-methyl was not peer reviewed by EFSA, therefore no EFSA conclusion is available. The EU MRLs for chlorpyrifos-methyl are established in Annexes II and IIIB of Regulation (EC) No 396/2005 (Appendix C). The existing EU MRLs for chlorpyrifos-methyl on the crops under consideration are set at a range from the LOQ of 0.01-0.05 mg/kg to the value of 3 mg/kg (stored cereal grains). Codex Alimentarius has established CXLs for several commodities, including the crops under consideration, for which the CXLs are set at 1 mg/kg for pome fruits, grapes, tomatoes, peppers, eggplants, at 2 mg/kg for citrus fruits, at 0.5 mg/kg for stone fruits, at 0.06 mg/kg for strawberries, at 0.01* mg/kg for potatoes. For wheat, barley and sorghum the CXL is currently fixed at the level of 10 mg/kg. The intended GAPs for which a modification of the existing MRLs are requested in the EU refer to foliar and post-harvest use of a 225 g/l chlorpyrifos-methyl emulsifiable concentrate at different application rates. The details of the GAPs are given in Appendix A. 6 O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphorothioate. S Cl N O P (OCH 2 CH 3 ) 2 7 Commission Directive 2005/72/EC of 21 October 2005. OJ L 279, 22.10.2005, p. 63-69. Cl Cl EFSA Journal 2011;9(6):2219 11

ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the EMS (Spain, 2010), the Draft Assessment Report (DAR) and its addenda prepared under Council Directive 91/414/EEC (Spain, 1997, 2000, 2002, 2003, 2004), the Commission Review Report on chlorpyrifos-methyl (EC, 2005) and the JMPR Evaluation Report (FAO, 2009b). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation of the Authorization of Plant Protection Products set out in Annex VI to Council Directive 91/414/EEC and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2004, 2008, 2010, 2011). 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of chlorpyrifos-methyl residues in plant commodities were assessed in the DAR and its addendum prepared for the peer review under Directive 91/414/EEC (Spain, 1997, 2002). Methods using capillary gas chromatography (GC) are available to determine parent chlorpyrifos-methyl on high water, high acid content and on dry matrices at the LOQ of 0.01 mg/kg. On sugar beet roots the LOQ of 0.02 mg/kg is achieved. For the group of oil-based content commodities, which is not covered by the methods assessed in the DAR, the proposed methods of analysis submitted in the framework of this application were lacking data on the repeatability (Spain, 2010). The multi-residue QuEChERS method developed by the EU Reference Laboratories for Residues of Pesticides (www.eurl-pesticides.eu) is also applicable for monitoring purposes. The capillary gas chromatography equipped with mass spectrum detection (GC-MSD) analyses chlorpyrifos-methyl residues in matrices with high water and high acid content at the LOQ of 0.005 mg/kg and in matrices with sugar content and in dry commodities at the LOQ of 0.01 mg/kg. Since the commodities under consideration belong to the group of high water, high acid, high oil content and dry matrices, EFSA concludes that sufficiently validated analytical methods for enforcing the proposed MRLs for chlorpyrifos-methyl in plants are available with the exception of oilseeds. For this commodity group, it is necessary to submit additional validation data (repeatability) in order to ensure that the analytical method is appropriate for enforcement purposes. 1.2. Methods for enforcement of residues in food of animal origin An analytical method for the quantification of chlorpyrifos-methyl residues in commodities of animal origin was evaluated in the DAR addendum prepared for the peer review under Directive 91/414/EEC (Spain, 2002). The method is using gas chromatography (GC) to determine parent chlorpyrifos-methyl in kidney, liver, milk, muscle, fat and egg samples and was validated at the LOQ of 0.01 mg/kg for all tested animal matrices. Thus, a sufficiently validated analytical method is available for the enforcement of the proposed MRL according to the residue definition in animal origin commodities. EFSA Journal 2011;9(6):2219 12

2. Mammalian toxicology The toxicological profile of the active substance chlorpyrifos-methyl was assessed in the framework of the peer review under Directive 91/414/EEC. The data were sufficient to derive toxicological reference values for chlorpyrifos-methyl (EC, 2005). The toxicological reference values are compiled in Table 2-1. Table 2-1: Overview of the toxicological reference values Chlorpyrifos-methyl Source Year Value Study relied upon Safety factor ADI EC 2005 0.01 mg/kg bw/d Rat, 2-yr study 100 ARfD EC 2005 0.1 mg/kg bw Rat, acute and delayed neurotoxicity studies Metabolism studies in both mammalians and plants have shown that chlorpyrifos-methyl, chlorpyrifos and triclopyr form 3,5,6-trichloropyridinol 8 (TCP) to a certain extent. Studies assessing the toxicological profile of TCP were not available for the EU review of chlorpyrifos-methyl but were assessed by EFSA in the framework of the peer review under Directive 91/414/EEC of the active substance triclopyr (EFSA, 2005). Although the database was not sufficient to derive final toxicological reference values, the experts confirmed that the metabolite is less toxic than the parent compound triclopyr, and agreed to tentatively apply the ADI (0.03 mg/kg bw/d ) and ARfD (0.25 mg/kg bw) of triclopyr for the consumer risk assessment of TCP. Besides TCP, the metabolite desmethyl chlorpyrifos-methyl 9 (DEM) was identified in significant amounts (> 10 %) in cereals during storage and in absence of data was considered as toxicological relevant as well. 100 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 studies of chlorpyrifos-methyl and chlorpyrifos assessed by the RMS in the peer review under Directive 91/414/EEC (Spain, 1997, 2000, 2003) have been completed by two additional studies performed with chlorpyrifos on peas and radish, which were assessed by the EMS in the framework of this application (Spain, 2010). The overview of the metabolism study designs is presented in Table 3-1. 8 3,5,6-trichloro-2-pyridinol: 3,5,6-trichloro-2(1H)-pyridinone. Molecular Weight: 198.4. 9 O-methyl-O-(3,5,6-trichloro-2-pyridinyl) phosphorothioate acid. Molecular Weight 308.6. EFSA Journal 2011;9(6):2219 13

Table 3-1: Summary of available metabolism studies in plants Group Crop Active and label position Fruits and fruiting vegetable Leafy vegetables Tomatoes Apples Oranges Lettuce Head cabbage 2,6 14 C chlorpyrifosmethyl 2,6 14 C chlorpyrifosmethyl 2,6 14 C chlorpyrifos 2,6 14 C chlorpyrifos 2,6 14 C chlorpyrifosmethyl 2,6 14 C chlorpyrifos Cereals Maize 2,6 14 C chlorpyrifos Root and tuber vegetables Wheat and maize grains Radish 2,6 14 C chlorpyrifosmethyl 2,6 14 C chlorpyrifos Application details Method Rate No F or G (a) (Interval) Spray, G Spray, F Spray, F Spray, F Spray, G Spray, G (3 d) then F Granul ar + Foliar 0.0075 g a.s./hl 0.99 kg a.s./ha 0.1 kg a.s./hl 3.97 kg a.s./ha 0.75 g a.s./hl 1.43 kg a.s./ha 223 mg a.s./ m row 0.275 kg a.s./ha Soil, G 2.2 kg a.s./ha Direct Spray, F 32.4 mg a.s./kg grain 1.92 kg a.s./ha 2 (8 d) Sampling During applications, 5, 20 DALA 1 0, 5, 13, 26, 42 DAT 7 (unlabell ed a.s) 2 (labelled a.s.) Remarks Supportive. BCCH 64-85 14 DALA Supportive. 1 0, 6, 21 DAT 2 (8 d) During applications, 21 DALA 1 0, 7, 14, 21, 42 DAT 2 (47 d) 49 (forage), 92 (fodder, grain), DALA Samples of fruits (peel, pulp) and leaves. Supportive. BCCH 46-49 Samples of head, leaves, secondary heads. Supportive. 1 14 DAT Supportive. 1 30, 90, 180 DAT 1 0, 7, 14, 21, 35 DAT Samples stored at 25 C BBCH 45. Not assessed in the peer review. Pulses oilseeds and Soya bean 2,6 14 C chlorpyrifos Spray, G 1.11 kg a.s./ha 1 14 (forage), 52 (beans) DAT Supportive. EFSA Journal 2011;9(6):2219 14

Group Crop Active and label position Peas with pods 2,6 14 C chlorpyrifos Application details Method Rate No F or G (a) (Interval) Spray, F 1.9 kg a.s./ha (a): Outdoor/field use (F) or glasshouse/protected crops/indoor application (G). Sampling 1 0, 7, 14, 21, 28 DAT Remarks BBCH 81. Not assessed in the peer review. The results of studies with chlorpyrifos-methyl and the structurally related active substance chlorpyrifos were used to reveal the metabolic profile of the active substance. Part of the studies assessed in the peer review did not allow to identify all residue components and were considered as supportive data. Only the studies performed in tomatoes, oranges and cabbage after foliar application and the study in cereals after post-harvest application were considered fully valid. After foliar application, the total residues rapidly declined during the first week. Thereafter a slower decline was observed in plants. The parent compound, 3,5,6-trichloropyridinol (TCP) and polar metabolites represented the main part of the residues. No other metabolite was present at significant level. The formation of the polar metabolites increased with time between application and harvest; in particular on cabbage and tomatoes, where they represented the majority of radioactive residues at harvest (75 % TRR at 42 DAT and 55.8 % TRR at 42 DAT, respectively). These polar metabolites were characterised as TCP conjugated mainly with glucose and malonic acid. In oranges, 99 % of the TRR remained associated with the peel, mostly as parent compound. Residues in pulp were < 0.01 mg-equivalent/kg at all time points. In wheat and maize stored grain after post-harvest application, parent compound represented 45 % on wheat and 33 % on maize of the total residues, while 3,5,6-trichloropyridinol (TPC) accounted for 19 % on wheat and 39 % on maize and desmethyl chlorpyrifos-methyl (DEM) represented the 19 % and 24 % of the TRR in wheat and maize, respectively. The peer review established the residue definition for monitoring as chlorpyrifos-methyl for grapes (EC, 2005). As TCP (free and conjugated) contributed significantly to the total residues and because it was considered to be of toxicological significance, the definition of chlorpyrifos-methyl plus TCP and its conjugates, expressed as chlorpyrifos-methyl was established for risk assessment. This residue definition postulated that TCP and its conjugates have the same toxicity and the same toxicological mode of action as the parent compound. A separate residue definition for risk assessment on stored grain was set: chlorpyrifos-methyl plus desmethyl chlorpyrifos-methyl, expressed as chlorpyrifos-methyl. Both risk assessment residue definitions apply as long as no information on each metabolite toxicological profile is available to allow either their exclusion from the residue definition or the setting of separate toxicological reference values. The results of the two new studies on peas and radish assessed by Spain in this application are consistent with the results from previous chlorpyrifos-methyl plant metabolism studies. They demonstrated that the parent compound is a good marker for monitoring and confirmed that the polar metabolites represent a major component of the residues at harvest (pods 42.5 % at 28 DAT; radish roots: 44.7 % at 35 DAT). The metabolic pattern after foliar application in the four different crop groups was similar and included the hydroxylation of the phosphate ester to form TCP and polar residues, mainly TCP conjugates. EFSA Journal 2011;9(6):2219 15

EFSA concludes that the metabolism of chlorpyrifos-methyl in primary crops is sufficiently elucidated and that the residue definitions established by the peer review can be extended to the various commodities under consideration. 3.1.1.2. Magnitude of residues Supervised field trials on several of the crops under consideration were submitted in support of the MRL application. The major part of the trials was conducted with two applications even when only one application was envisaged in the GAP. The last application prior to harvest is more relevant in predicting the terminal residue concentration in the harvested plants, therefore the deviation was considered acceptable (EC, 2011). The samples were analysed for chlorpyrifos-methyl and its metabolite TCP (foliar application) or DEM (post-harvest application) residues. It is noted that, differently from the EMS approach, the residues below the LOQ (0.01 mg/kg) and the LOD (0.003 mg/kg) were both considered as at the LOQ value for the calculation of the MRLs and other input values (i.e. conversion factors). Moreover, in some trials the residue values were higher at a longer PHI and EFSA has selected these values for the calculation. a. Citrus fruits (GAP: 2 x 2.25 kg a.s./ha; interval 110 d; PHI 21 d; SEU) For the intended use the applicant submitted 36 supervised residue trials (20 on oranges and 16 on mandarins, including clementines) performed over two seasons in Southern Europe (SEU). The extrapolation to the whole group of citrus fruits was proposed (EC, 2011). Only eleven trials on oranges and four trials on mandarins were in compliance with the proposed GAP (i.e. within the 25 % deviation). In the remaining studies either the application rate or the PHI were not reflecting the intended use pattern. The number of valid studies is not sufficient to derive a MRL proposal for the whole group of citrus fruits and an individual MRL on mandarins, which are a major crop in Southern Europe (EC, 2011). The results from the studies on oranges indicate that a MRL of 0.8 mg/kg would be required for the intended use in SEU. The MRL for oranges may be extrapolated to grapefruits, as both are fruits with a large diameter. However, since this extrapolation is not explicitly mentioned in the EU guideline document, a risk management decision needs to be taken regarding the acceptability of this proposal. The CF for enforcement to risk assessment of 1.7 was calculated. b. Pome fruits (GAP: 1 x 0.9 kg a.s./ha; PHI 21 d; EU) For the intended use 68 supervised residue trials (36 on apples and 32 on pears) conducted during more than two seasons in Southern Europe (20 trials on apples and 16 trials on pears) and Northern Europe (16 trials on apples and 16 trials on pears) were provided. The extrapolation to the whole group of pome fruits was proposed (EC, 2011). Only 12 trials on apples and seven trials on pears for SEU and one trial on apples and three trials on pears for NEU were reflecting the proposed GAP (i.e. within the 25 % deviation for application rate and PHI). In all these trials two applications instead of one were made. The result from a slightly underdosed trial was used to complete the data package and derive a MRL for pears in SEU. Since the SEU data on apples and pears have not a similar distribution (Mann-Whitney U-Test, FAO, 2009a), they were not pooled. The results from apples were extrapolated to the whole group of pome fruits, but as the use in pears resulted in significantly lower residues, according to the ALARA principle (As Low As Reasonably Achievable), a separate MRL is proposed for pears by EFSA. EFSA Journal 2011;9(6):2219 16

The number of valid trials is sufficient to derive a MRL proposal of 0.2 mg/kg for apples and of 0.04 mg/kg for pears for SEU. The number of trials on apples and pears in NEU matching with the proposed GAP is not sufficient to derive a MRL for the whole group or for each individual commodity, which are major crops in NEU (EC, 2011). The CF for enforcement to risk assessment of 1.6 and 9 was calculated from the apple and pear residue data, respectively. c. Peaches, nectarines, apricots (GAP: 1 x 1.02 kg a.s./ha; PHI 15 d; SEU) For the intended use the applicant submitted 29 supervised residue trials (14 on peaches and 15 on apricots) performed over two seasons in the Southern Europe (SEU). Only ten trials on peaches and eight trials on apricots were reflecting the proposed GAP (i.e. within the 25 % deviation). In the major part of the trials two applications instead of one were made. The number of valid trials is sufficient to derive a MRL proposal of 0.15 mg/kg for apricots and of 0.04 mg/kg on peaches, including nectarines, respectively. A CF for enforcement to risk assessment of 9.5 was calculated from the combined peach and apricot residue data. d. Cherries (GAP: 1 x 1.0 kg a.s./ha; PHI 21 d; NEU) For the intended use the applicant submitted 14 supervised residue trials on cherries, however none of them was conducted according to the proposed GAP. All trials were underdosed. Thus, no MRL proposal can be derived for cherries. e. Table grapes (GAP: 1 x 0.608 kg a.s./ha; interval min. 14 d; PHI 14 d; SEU) For the intended use the applicant submitted 20 residue trials on table grape varieties. Only seven trials were reflecting the proposed GAP (i.e. within the 25 % deviation) for application rate and PHI. All trials were conducted with two applications instead of one. The results of two additional trials performed with a higher dose rate (ca. + 45%) than the proposed dose rate were included to complete the dataset. Despite the use of high dose rate, residues of chlorpyrifos-methyl were not detected in these grape samples. Thus, in line with the results observed after the application of the intended dose rate. The number of valid trials is considered sufficient to derive a MRL proposal of 0.09 mg/kg for the intended SEU use on table grapes. A CF for enforcement to risk assessment of 5.2 was calculated. f. Wine grapes (GAP: 2 x 0.338 kg a.s./ha; PHI 14 d; EU) For the intended use the applicant submitted 30 supervised residue trials (19 conducted in NEU and 11 in SEU) on wine grape varieties. Only two SEU trials and six NEU trials were reflecting the proposed GAP (i.e. within the 25 % deviation for application rate and PHI). EFSA is of the opinion that the extrapolation from the SEU residue data on table grapes to wine grapes proposed by the EMS can not be accepted, because the GAPs are not comparable. The number of trials is not sufficient to derive a MRL proposal. At least two additional NEU trials and six additional SEU trials complying with the proposed GAP are required to complete the dataset. EFSA Journal 2011;9(6):2219 17

g. Strawberries (GAP: 1 x 0.54 kg a.s./ha; PHI 5 d; EU) For the intended outdoor use the applicant submitted 23 supervised residue trials (12 in NEU and 11 in SEU) over two seasons. Only eight studies per geographical area were reflecting the proposed GAP and were used to derive the MRL. Since the residue levels measured in the NEU trials were generally higher than the levels obtained from the SEU trials, the MRL of 0.09 mg/kg is derived from the NEU trials. A combined CF for enforcement to risk assessment of 8.25 was calculated. h. Potatoes (GAP: 1 x 0.54 kg a.s./ha; PHI 21 d; EU) For the intended outdoor use the applicant submitted 16 supervised residue trials (eight in NEU and eight in SEU) over two seasons. All trials were reflecting the proposed GAP (i.e. within the 25 % deviation) for application rate and PHI. Part of them was conducted with two applications instead of one. Chlorpyrifos-methyl residues were below the LOQ of 0.01 mg/kg, therefore the MRL proposal of 0.01* mg/kg for potatoes is sufficiently supported by data. A CF for enforcement to risk assessment of 2 was calculated. i. Tomatoes, aubergines (GAP: 1 x 0.675 kg a.s./ha; PHI 5 d; EU) For the intended outdoor use the applicant submitted 47 supervised residue trials (11 in NEU and 36 in SEU) on tomatoes over more than two seasons. The extrapolation to aubergines was proposed (EC, 2011). Four SEU trials were fully reflecting the proposed GAP. The dataset was completed with the results from six SEU trials conducted with two instead of one application. One result was markedly above the other residue concentrations (0.9 mg/kg) and statistically detected as outlier (Dixon's Q-test, FAO, 2009a). If the potential outlier is disregarded from the calculation, the estimated median and highest residue values are 0.06 mg/kg and 0.07 mg/kg, respectively, while the calculated MRL is 0.15 mg/kg. Despite its impact on the proposed MRL and HR values, EFSA has included the result in the calculation as there was no information to justify its exclusion. The remaining SEU and all the NEU studies were disregarded because either the application conditions (29 were conducted under greenhouse conditions) or the PHI were not reflecting the intended use pattern. The results from the studies indicate that a MRL of 1.0 mg/kg would be required to support the proposed use in the SEU. No data reflecting the proposed GAP were available to derive a MRL proposal for the NEU. A CF for enforcement to risk assessment of 2.08 was calculated. j. Peppers (GAP: 1 x 0.675 kg a.s./ha; PHI 5 d; EU) For the intended outdoor use the applicant submitted 18 supervised residue trials all performed in greenhouse conditions. As the proposed GAP is for field use, these studies are not suitable to derive a MRL proposal on peppers (EC, 1997b). Residue trials reflecting the GAP should be submitted to support the intended use on pepper. k. Rape seeds (GAP: 1 x 0.45 kg a.s./ha; PHI n.a; EU) For the intended outdoor use the applicant submitted 16 supervised residue trials (eight in NEU and eight in SEU) over two seasons. Seeds and straw or the whole rape plant were harvested between 51 to 120 days after the application, with the exception of one sample which was harvested at PHI of 31 days and showed the highest TCP value (0.18 mg/kg). Residues of chlorpyrifos methyl were below the LOQ of 0.01 mg/kg in 15 samples; the 16 th value of 0.015 mg/kg was determined in one NEU sample. The MRL of 0.02 mg/kg for rape seeds is derived from these data. A combined CF for enforcement to risk assessment of 2 was calculated. EFSA Journal 2011;9(6):2219 18

l. Soya beans (GAP: 1 x 0.45 kg a.s./ha; PHI n.a; SEU) For the intended outdoor use in SEU, the extrapolation from rape seeds to soya beans is proposed. The extrapolation from rape seeds to the whole group of oilseeds (except peanuts) and to linseeds and mustard seeds is possible in case the application is done before the consumable part of the crop has formed and provided that the GAPs are comparable and the same harvest time applies (EC, 2011). Although not explicitly mentioned in the guidelines, EFSA consider that the data from rape seeds (eight SEU trials) can be used to derive a MRL of 0.01* mg/kg for soya beans, because the general requirements for extrapolation are fulfilled. A CF for enforcement to risk assessment of 3 was calculated from the SEU rapeseed trial results. m. Cotton (GAP: 1 x 0.68 kg a.s./ha; PHI 14 d; SEU) For the intended outdoor use the applicant submitted 12 supervised residue trials in SEU over two seasons. Only eight studies were reflecting the proposed GAP and have been used to derive the MRL of 0.04 mg/kg for cotton seeds. A CF for enforcement to risk assessment of 3.5 was calculated. n. Maize (GAP: 1 x 0.9 kg a.s./ha; PHI n.a.; SEU) For the intended use the applicant submitted 24 supervised residue trials performed in SEU over three seasons. Only eight studies belonging to a single season were reflecting the proposed GAP and have been used to derive the MRL. Grains and stover were harvested between 56 to 103 days after the application, with the exception of two samples which were collected at the PHI of 22 days. Chlorpyrifos-methyl was below the LOQ (<0.01 mg/kg) in all samples. The derived MRL is 0.01* mg/kg and the CF is 2. o. Cereals (GAP: 1 x 5 mg a.s./kg grain; PHI n.a; EU, post-harvest application) For the intended application to stored cereal grains 17 supervised decline residue trials (eight on wheat and nine on barley) were submitted. Only eight trials per crop were reflecting the proposed GAP and have been used to derive the MRL. The samples were analysed for chlorpyrifos-methyl residues at application and up to approximately 6 months after the application. Chlorpyrifos-methyl values from one barley sample were 6.23 mg/kg and 6.69 mg/kg at 0 and 6 months time, respectively. These values are well above the range of the observed values and must result from an inhomogeneous distribution of the compound during application. They were identified as potential outlier (statistically confirmed by the Dixon's Q-test, FAO, 2009a) and excluded from the calculation. However, if the application method used for post-harvest treatment of cereals does not guarantee a homogeneous distribution of the active substance on stored grains, these two high values may be expected under practical conditions. In this case, a MRL proposal of 7 mg/kg would be required. Desmethyl chlorpyrifos-methyl (DEM), which is part of the residue definition for risk assessment, was analysed in seven samples. The number of trials is sufficient to derive for the intended GAP a MRL proposal of 5 mg/kg for wheat and barley, which is equivalent to the proposed application rate (FAO, 2009a). The extrapolation to oats and rye is possible since the GAPs are comparable. Extrapolation to the whole group is not foreseen in the EU guidance document (EC, 2011). However, the possibility of this extrapolation could be further discussed. A CF for enforcement to risk assessment of 1 (exactly 1.03) was calculated. The results of the residue trials, the related risk assessment input values (highest residue, median residue, CF from monitoring to risk assessment) and the MRL proposals are summarized in Table 3-2 (foliar application) and Table 3-3 (post-harvest application). EFSA Journal 2011;9(6):2219 19