Modification of the existing MRLs for dimethoate in various crops 1

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1 EFSA Journal 2011;9(4):2146 REASONED OPINION 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY According to Article 6 of the Regulation (EC) No 396/2005, United Kingdom herewith referred to as the Evaluating Member State (EMS), received an application from the company Cheminova to modify the existing MRL for dimethoate in barley, oats, broccoli, cauliflower, Brussels sprouts and cherry. In order to accommodate for the intended use of dimethoate on these crops in Northern European countries, it is proposed to raise the existing MRLs. The EMS United Kingdom 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 27 October EFSA derives the following conclusions based on the above mentioned evaluation report, the EFSA conclusion on the peer review, the EFSA previous reasoned opinions on the modification of the existing MRLs for dimethoate, the Draft Assessment Report (DAR) prepared by the United Kingdom under Directive 91/414/EEC as well as additional information submitted by the RMS in the framework of Article 12 of Regulation (EC) No 396/2005. The toxicological profile of dimethoate was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of mg/kg bw/day and an ARfD of 0.01 mg/kg bw. The metabolism of dimethoate in primary plants was investigated in potatoes (tubers and foliage) and wheat in the framework of the peer review. An additional study on olives was submitted and assessed under the current application. In the crop groups investigated dimethoate is rapidly degraded to yield a wide range of metabolites from which omethoate is the primary metabolism product. Even though omethoate is the most toxic metabolite of dimethoate, also other metabolites (O-desmethyl omethoate carboxylic acid (XX), des-o-methyl isodimethoate (XII) and dimethoate carboxylic acid (III)) presenting a lower potential for cholinesterase inhibition may provide a significant contribution to the toxicological burden given their presence in significantly higher amounts. The peer review concluded that the residue definition for enforcement can be set separately as dimethoate and omethoate. Pending the data on the toxicity of metabolites XX, XII and III, a provisional residue definition for risk assessment was proposed as the sum of dimethoate and 6 times omethoate expressed as dimethoate (for acute risk assessment) and the sum of dimethoate and 3 times omethoate expressed as dimethoate (for chronic risk assessment) taking into account that both compounds share a common toxicological mode of action but with different potencies. EFSA agrees with the peer review that separate enforcement residue definitions have to be set for dimethoate and 1 On request from the European Commission, Question No EFSA-Q , issued on 18 April Correspondence: praper.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority;. EFSA Journal 2011;9(4):2146. [33 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2011

2 omethoate, but, since the change of the existing residue definition (sum of dimethoate and omethoate, expressed as dimethoate) now would have an impact on the existing MRLs for dimethoate as established in Regulation (EC) No 396/2005, it is recommended to change the residue definition in the framework of the comprehensive MRL review for dimethoate under Article 12 (2) of this Regulation. EFSA concludes that the available metabolism studies indicate a similar metabolic pathway in three crop groups and therefore the residue definitions proposed by the peer review can be applicable to all primary crops. For the crops under consideration no further metabolism studies are required. However, further studies are required to investigate the potential for cholinesterase inhibition of the plant metabolites XX, XII and III as concluded in the framework of the peer review under Directive 91/414/EEC. The submitted residue trials indicate that a MRL of 0.03 mg/kg in barley, oats, broccoli, cauliflower, 0.1 mg/kg for Brussels sprouts and 0.3 mg/kg for cherries would be appropriate for the intended uses of dimethoate on these crops in Northern Europe. Analytical methods validated at the LOQ of 0.01 mg/kg for dimethoate and omethoate separately are available. Effects of processing on the nature of dimethoate were investigated in the framework of the peer review through hydrolysis studies simulating sterilisation, baking, brewing, boiling and pasteurization. These studies demonstrated that dimethoate and omethoate at the end of the processing are the major constituents of the residue, except under the most severe processing conditions (sterilisation) where desmethyl dimethoate (X) and O-desmethyl omethoate (XI) were major components. The peer review concluded that, based on the way the nature of residues is affected during processing there is no need to set specific residue definitions for processed commodities. No specific studies investigating the magnitude of dimethoate and omethoate residues in processed crops have been submitted under the current application. The occurrence of dimethoate and omethoate residues in rotational crops was also investigated. Since both substances degrade rapidly in the soil and no other relevant soil metabolites were identified, EFSA concluded that in rotational crops significant dimethoate and omethoate residues are not likely provided that dimethoate is applied according to the intended GAP. Since barley and oat grain and straw are fed to livestock, a potential carry-over of dimethoate and omethoate residues into food of animal origin was assessed. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg (dry matter) for dairy and meat ruminants and pigs but was mainly driven by the existing MRLs of feed products. The impact of dimethoate and omethoate residues in barley and oats to the total livestock exposure was insignificant and therefore the modification of the MRLs for commodities of animal origin is not further investigated in the framework of the current application. There are currently no EU MRLs established for animal commodities. A provisional consumer risk assessment was performed with revision 2 of the EFSA PRIMo. It is based on the assumption that metabolites XX, XII and III do not contribute to an overall toxicological burden. For the calculation of the chronic exposure for the crops under consideration, EFSA used the median residue values as derived form the residue trials according to the risk assessment residue definition for the chronic exposure assessment. For the remaining commodities the input values were chosen according to the available information on the use patterns as reported by the RMS. For several commodities the processing factors were available to refine the intake calculations. The acute exposure assessment was performed only with regard to the commodities under consideration assuming the consumption of a large portion of the food item as reported in the national food surveys containing residues at the highest level as observed in supervised field trials. The input values were expressed according to the risk assessment residue definition for acute exposure assessment. The calculated exposure was then compared with the toxicological reference values as derived for dimethoate. EFSA Journal 2011;9(4):2146 2

3 Taking into account the data that were provided to EFSA, no long-term consumer intake concerns were identified for any of the European diets included in the EFSA PRIMo. The total calculated intake values accounted for a maximum of 87% of the ADI for DE child diet. The contribution of residues in crops under consideration to the total consumer exposure in % of the ADI accounted for a maximum of 5.75% for cherries (DE child diet), 1.87% for cauliflower (NL child diet), 1.58% for broccoli (FR toddler diet), 1.06 % for Brussels sprouts (IE adult diet), 0.3% for barley (WHO Cluster diet E) and 0.158% for oats (DK child diet). No acute consumer risk was identified in relation to the MRL proposals for the crops under consideration. The calculated maximum exposure in percentage of the ARfD was 84.4% for cherries, 46.3% for cauliflower, 40.8% for broccoli, 10.5% for Brussels sprouts 2.5% for barley and 1.4% for oats. EFSA concludes that, according to the provisional risk assessment, the intended uses of dimethoate on the crops under consideration will not result in the consumer intake concerns. It has still to be confirmed that the contribution of metabolites XX, XII and III is not resulting in an exceedance of toxicological reference values. The studies on the toxicological relevance of these metabolites have been performed by the manufacturer as requested according to Directive 2007/25/EC, but have not yet been assessed by the RMS. Recommendations of EFSA are compiled in the table below: Code Commodity Existing EC number a MRL (mg/kg) Proposed EC MRL (mg/kg) Justification for the proposal Enforcement residue definition: The sum of dimethoate and omethoate expressed as dimethoate Cherries The MRL proposals are sufficiently Brussels sprouts 0.02* 0.1 supported by data and no consumer intake concerns were identified. It has Cauliflower 0.02* 0.03 still to be confirmed that the Broccoli 0.02* 0.03 contribution of metabolites XX, XII and III is not resulting in an exceedance of Barley grain 0.02* 0.03 toxicological reference values Oat grain 0.02* 0.03 (*): Indicates that the MRL is set at the limit of analytical quantification. a according to Annex I of Regulation (EC) No 396/2005 KEY WORDS Dimethoate, Brussels sprouts, broccoli, cauliflower, barley grain, oat grain, cherries, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, organo-phosphorous insecticide and acaricide, omethoate EFSA Journal 2011;9(4):2146 3

4 TABLE OF CONTENTS Summary... 1 Table of contents... 4 Background... 5 Terms of reference... 5 The active substance and its use pattern... 6 Assessment Methods of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues Nature and magnitude of residues in plant Primary crops Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Consumer risk assessment Conclusions and recommendations References Appendix A. Good Agricultural Practices (GAPs) Appendix B. Pesticide Residues Intake Model (PRIMo) Appendix C. Existing EU maximum residue limits (MRLs) Abbreviations EFSA Journal 2011;9(4):2146 4

5 BACKGROUND Commission Regulation (EC) No 396/ establishes the rules governing the setting of pesticide MRLs at Community 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. The United Kingdom, hereafter referred to as the evaluating Member State (EMS), received an application from the company Cheminova 5 to modify the existing MRLs for the active substance dimethoate in barley, oats, broccoli, cauliflower, Brussels sprouts and cherry. 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 27 October The application was included in the EFSA Register of Questions with the reference number EFSA-Q and the following subject: Dimethoate - Application to modify the existing MRLs in various crops. The EMS proposed the following MRLs: 0.03 mg/kg for barley, oats, broccoli and cauliflower, 0.1 mg/kg for Brussels sprouts and 0.3 mg/kg for cherry. 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 27 January Regulation of the Council and Parliament (EC) No 396/2005 of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July 1991, OJ L 230, , p Cheminova, P.O. Box 9, 7620, Lemvig, Denmark EFSA Journal 2011;9(4):2146 5

6 THE ACTIVE SUBSTANCE AND ITS USE PATTERN Dimethoate is the ISO common name for O,O-dimethyl S-methylcarbamoylmethyl phosphorodithioate or 2-dimethoxyphosphinothioylthio-N-methylacetamide (IUPAC). The major toxicologically relevant metabolite of dimethoate is omethoate which was in the past used also as an active substance in the EU and which is the oxygen analogue of dimethoate. The chemical structures of both substances are as follows: Dimethoate Molecular weight: Omethoate Molecular weight: Dimethoate is an organo-phosphorous insecticide and acaricide for the control of a wide range of pests. It acts by contact and systemic action by inhibiting the enzyme acetylcholinesterase. Its main plant metabolite omethoate has a similar biochemical mode of action but has a higher toxicity. Dimethoate has been assessed in the framework of Directive 91/414/EEC with the United Kingdom being the designated rapporteur Member State (RMS). The active substance was included in Annex I to Directive 91/414/EEC by Commission Directive 2007/25/EC 6 which entered into force on 1 October The Annex I inclusion was restricted to the use as insecticide only. In addition, within 2 years from the entry into force of the Annex I inclusion of the active substance, further studies to confirm the toxicological assessment of metabolites potentially present in crops have to be provided to the Commission. The EMS confirms that such studies have been provided by the notifier within the requested timeframe but have not yet been assessed by the RMS (UK, 2010b). The representative uses submitted for the peer review were foliar application of dimethoate on wheat, olives, sugar beet, tomatoes and lettuce. For omethoate the manufacturer did not submit a dossier to support the Annex I inclusion. Thus, for omethoate, the non-inclusion in Annex I was decided in 2002 by Regulation (EC) No 2076/ and consequently by 31 December 2003 all authorisations had to be revoked at MS level (except the essential use of omethoate on ornamentals in Austria which had to be withdrawn latest by 31 December 2007). The existing EU MRLs for dimethoate are included in Annexes II and IIIB of Regulation (EC) No 396/2005 and are summarized in Appendix C. The existing EU MRL in barley, oats, broccoli, Brussels sprouts, cauliflowers are set at the LOQ of 0.02 mg/kg and at 0.2 mg/kg in cherry. The EU MRL for cherry is set on a provisional basis, pending the review of dimethoate MRLs according to the Article 12(2) of Regulation (EC) No 396/2005. Codex Alimentarius Commission has established the CXLs for a wide range of crops and also a CXL of 2 mg/kg in barley, 0.2 mg/kg in Brussels sprouts, 2 mg/kg in cauliflower, broccoli and cherries. The summary of the intended GAPs for the use of dimethoate in various Northern European countries is given in Appendix A. 6 Commission Directive 2007/25/EC of 23 April 2007, OJ L 106, , p Commission Regulation (EC) No 2076/2002 of 20 November 2002, OJ L 319, , p EFSA Journal 2011;9(4):2146 6

7 ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the EMS (UK, 2010b), the EFSA conclusion on the peer review of dimethoate (EFSA, 2006), the Draft Assessment Report (DAR) prepared under Directive 91/414/EEC (United Kingdom, 2004), final addendum to the DAR (United Kingdom, 2006) the JMPR Evaluation report (WHO/FAO, 2004a), WHO/FAO Report 2004 (WHO/FAO, 2004b) the information submitted by the RMS in the framework of Article 12 of Regulation (EC) No 396/2005 (UK, 2010a) as well as previously issued EFSA reasoned opinions (EFSA, 2010a, 2010b). 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). 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for enforcement have been evaluated in the peer review (UK, 2006). The samples of plant origin are extracted with dichloromethane. Dimethoate and omethoate are determined with LC-MS. The individual LOQ value which can be achieved in routine monitoring is 0.01 mg/kg for dimethoate and omethoate, respectively. The validation data were provided for dry matrices as well as for matrices with high water-, high oil and high acid content. Alternative methods based on gaschromatography and FPD were reported with similar LOQ values (sorghum, peas, wheat, corn, oranges, potatoes and tomatoes). In the evaluation report the EMS United Kingdom provided new validation data for the applicability of the GC-FPD method for the determination of dimethoate and omethoate residues in cabbage, cauliflower and Brussels sprouts (UK, 2010b). Validation data indicate that the method is suitable for the determination of dimethoate and omethoate residues in these crops at the individual LOQs of 0.01 mg/kg. The current enforcement residue definition in Regulation (EC) No 396/2005 is set as: dimethoate and omethoate, expressed as dimethoate. Thus, the omethoate residues have to be converted to dimethoate, by using a molecular weight conversion factor which is calculated to be Since this factor is close to 1, in practice, this conversion can be omitted. The multi-residue QuEChERS method described in the European Standard EN 15662:2008 is also validated for the determination of dimethoate and omethoate in matrices with high water-, high acid content and in dry matrices at the individual validated LOQs of 0.01 mg/kg (CEN, 2008). EFSA concludes that sufficiently validated analytical methods are available to monitor all compounds given in the enforcement residue definition in crop Methods for enforcement of residues in food of animal origin The analytical methods for the determination of dimethoate and omethoate residues in commodities of animal origin were evaluated in the DAR and peer reviewed by EFSA (EFSA, 2006). The GC-FPD method is applicable to determine dimethoate and omethoate residues in milk and egg white at the LOQ of mg/kg, in goat liver, kidney and fat at 0.01 mg/kg and in whole egg at 0.05 mg/kg. According to the JMPR evaluation, the method is also validated for the determination of dimethoate and omethoate in hen muscle at the LOQ of 0.01 mg/kg (WHO/FAO, 2004a). EFSA Journal 2011;9(4):2146 7

8 EFSA concludes that sufficiently validated analytical methods are available to monitor all compounds given in the enforcement residue definition in animal matrices. 2. Mammalian toxicology The toxicological reference values for dimethoate were derived in the framework of the peer review and are compiled in the Table 2-1. Table 2-1. Overview of the toxicological reference values Dimethoate Source Year Value (mg/kg bw/d) Study relied upon ADI EFSA Overall NOAEL from 2 yr rat, multigeneration rat, rat neurotoxicity and rat developmental neurotoxicity study Safety factor ARfD EFSA Acute neurotoxicity 100 Metabolite: omethoate ADI EFSA Rat multigeneration study and 2 yr rat ARfD EFSA Acute neurotoxicity According to the EFSA conclusion on dimethoate, in the toxicology section, an estimate of the threshold for the toxicologically relevant inhibition of erythrocyte and/or brain cholinesterase activity was made by comparison of NOAELs and LOAELs for cholinesterase inhibition as well as the cholinesterase activity recovery in repeat-dose studies. Omethoate has higher toxicological potency than dimethoate and therefore for omethoate the relative potency factor of 3 for the chronic risk assessment and 6 for the acute risk assessment was agreed by the peer review (EFSA, 2006). Even though omethoate was expected to be the most toxic metabolite of dimethoate, also other metabolites (metabolites O-desmethyl omethoate carboxylic acid (metabolite XX) and des-o-methyl isodimethoate (XII) and dimethoate carboxylic acid (III)) presenting a lower potential for cholinesterase inhibition may bring a significant contribution to the toxicological burden given their presence in significantly higher amounts. The peer review therefore concluded that their relative toxicity compared with the parent compound needs to be clarified on the basis of further appropriate studies (EFSA, 2006). The EMS informed that specific studies on the toxicological assessment of metabolites potentially present in crops have been performed by the notifier as requested when the inclusion of dimethoate in Annex I of Directive 91/414/EEC was granted (Directive 2007/25/EC). The studies, however, are not yet evaluated by the RMS and are not available to EFSA. Therefore the risk assessment under the current applications is only provisional since it is still based on the assumption that metabolites identified in the crop metabolism and processing studies have no contribution to the toxicological burden. EFSA Journal 2011;9(4):2146 8

9 3. Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of dimethoate in potatoes and cereals was evaluated by the RMS (UK, 2004) and reviewed by EFSA (EFSA, 2006) in the framework of the peer review under Directive 91/414/EEC. Under the current application, the applicant has submitted a new metabolism study on olives which have been evaluated by the EMS United Kingdom in the evaluation report (UK, 2010b). The overview of the metabolism study designs is presented in the table below. Table 3-1: Summary of available metabolism studies in plants Group Crop Label position Fruits and fruiting vegetable Root and tuber vegetables Cereals Olives Potatoes Wheat 14 C- methoxy 14 C- methoxy 14 C- methoxy Method, F, G or P (a) Rate (kg a.s./ha) Application details No/ Interva l Sampling (DAT) F After each application and at maturity (28 d after last appl.) Remarks Foliar spray F Foliar spray F 0.68 (BBCH 24) and 0.4 (BBCH 69) (a): Outdoor/field use (F) or glasshouse/ /indoor application (G) or protected (P) Potatoes 2 0, 14 after 1 st appl. (samples of whole plant); 21, 32 after 2 nd appl. (maturity) Foliar spray At the relevant PHI of 14 and 28 days, the radioactive residues were mainly found in foliage (1.32 mg eq./kg and 3.46 mg eq./kg) with approximately 10 fold lower values in tubers (0.19 mg eq./kg and 0.24 mg eq./kg). In potato tubers dimethoate and omethoate were not found in significant concentrations (>0.1% TRR). In all tuber samples taken 14, 21 and 28 DAT three metabolites exceeded 10% of the TRR: O-desmethyl omethoate carboxylic acid (XX) (18.4%, 11.1%, 12.1% TRR), O-desmethyl-N-desmethyl omethoate (XXIII) (45.5%, 40.3%, 43.6% TRR) and O-desmethyl omethoate (XI) (12.5%, 17.7% and 14.8% TRR). Potato foliage EFSA Journal 2011;9(4):2146 9

10 The characterisation of the TRR in foliage indicated that parent dimethoate was the main component accounting for a maximum of 40.7% TRR (1.89 mg/kg) in PHI of 7 days and 15% TRR (0.2 mg/kg) in the PHI of 14 days. In foliage samples taken 7 DAT and 14 DAT omethoate accounted for 15.6 % TRR (0.72 mg/kg) and 9.3% TRR (0.12 mg/kg), respectively. O-desmethyl-N-desmethyl omethoate (XXIII) accounted for 8.75% TRR (0.11 mg/kg) in foliage samples taken 14 DAT and 5.2% TRR (0.24 mg/kg) in foliage samples taken 7 DAT. Wheat In mature wheat grain, hull and straw, 32 DAT the TRR accounted for 4.28 mg/kg, mg/kg and 7.83 mg/kg, respectively. The characterisation of the TRR in mature wheat grain, hull and straw indicated that the main compound in all crop parts was O-desmethyl-N-desmethyl omethoate (XXIII), which accounted up to 45.2% TRR (15.23 mg/kg) in hull, 40.5% TRR (3.17 mg/kg) in straw and 35% TRR (1.5 mg kg) in grain. Parent dimethoate and omethoate were not identified in mature wheat grain. Omethoate accounted for 10.2% TRR (2.37 mg/kg) in wheat hull sample taken 21 DAT. In the wheat plant 41 DAT, parent dimethoate was the main component of the TRR (83.2%; 13.4 mg/kg) with all other compounds being below 4.4%. Olives In mature olives, the total radioactivity accounted for 3.93 mg eq./kg in green olives and 3.69 mg eq./kg in black olives. The increasing radioactivity in olive stones ( mg eq./kg) indicate a residue transfer from flesh to stone. Good extraction of residues was achieved for olive flesh. In olives at harvest the main component of the residues was O-desmethyl N-desmethyl omethoate (XXIII) accounting for 57% (2.23 mg/kg) and 59.9 % (2.22 mg/kg) in green and black olives, respectively. Metabolite des-o-methyl isodimethoate (XII) accounted for % of the TRR ( mg/kg). Levels of dimethoate ( % TRR) were lower than those of omethoate ( %). Table 3-2: Overview of identified metabolites EFSA Journal 2011;9(4):

11 Consequently, the metabolism of dimethoate was explained to proceed as follows: - oxidation to yield omethoate (metabolite II) - O- and N-demethylation of omethoate to yield O-desmethyl-N-desmethyl omethoate (metabolite XXIII) - hydrolysis of the amide bond to give dimethoate carboxylic acid (metabolite III) and subsequent degradation to give O,O-dimethyl dithiophosphoric acid (XV) - demethylation and rearrangement to yield O-desmethyl dimethoate (metabolite X) or des-omethyl isodimethoate (metabolite XII) - demethylation of omethoate to give O-desmethyl omethoate (metabolite XI) and subsequent hydrolysis of the amide bond to give O-desmethyl omethoate carboxylic acid (metabolite XX) (EFSA, 2006). The metabolic profile in the foliar parts of plants investigated consists of a complex mixture of the parent compound and the above mentioned metabolites and is varying in time (with longer PHIs, the metabolic pattern consists of a complex mixture of compounds, depending on the crop and plant part). Quantitatively metabolite XXIII was the major residue at harvest in potato tubers as well as in wheat grain and straw and olives, but, according to toxicity studies, it has no anticholinesterase activity in the rat. The peer review concluded that for the enforcement the residue definition can be set separately as dimethoate and omethoate. EFSA agrees with the peer review that separate enforcement residue definitions have to be set for dimethoate and omethoate, but since the change of the existing enforcement residue definition (the sum of dimethoate and omethoate, expressed as dimethoate) now would have an impact on the existing MRLs for dimethoate as established in Regulation (EC) No 396/2005, it is recommended to change the residue definition in the framework of the comprehensive MRL review for dimethoate under Article 12 (2) of this Regulation. Pending the studies on the toxicity of metabolites XX, XII and III, a provisional residue definition for risk assessment was proposed as sum of dimethoate and 6 times omethoate expressed as dimethoate (for acute risk assessment) and sum of dimethoate and 3 times omethoate expressed as dimethoate (for chronic risk assessment). EFSA concludes that the available metabolism studies indicate a qualitatively similar metabolic pathway in three crop groups and therefore the residue definitions proposed by the peer review can be applicable to all primary crops. For the crops under consideration no further metabolism studies are required. In addition, EFSA confirms the need to investigate the potential for cholinesterase inhibition of the plant metabolites XX, XII and III as concluded in the EFSA conclusion in the framework of the peer review under Directive 91/414/EEC. Pending this information the risk assessment based on the provisional residue definition is affected by uncertainties which may underestimate the actual consumer risk Magnitude of residues All submitted residue trials were analysed separately for dimethoate and omethoate and individual residue trial data are given in Table 3-3. In table 3-5 the risk assessment input values are presented, derived from the results of the residue trials and expressed according to the risk assessment residue definitions. The MRL proposals according to the currently valid residue definition (sum of dimethoate and omethoate, expressed as dimethoate) are summarized in Table 3-4. EFSA Journal 2011;9(4):

12 a. Barley In support of the intended use in the Northern Europe, in total 8 GAP compliant residue trials on barley were submitted. The residue trials were performed in Poland, Denmark and the United Kingdom. The extrapolation of residue data from barley to oats is proposed and is supported. The samples of straw were also analysed for residues. b. Broccoli In support of the intended use of dimethoate on broccoli in total 4 GAP compliant residue trials on broccoli were submitted. All trials have been performed in 2008/2009 in Germany, Northern France and the United Kingdom. Broccoli is considered as a minor crop in the NEU and therefore 4 trials are sufficient to derive the MRL proposal. c. Cauliflower In support of the intended use of dimethoate on cauliflower in total 7 GAP compliant residue trials on cauliflower were submitted. All trials have been performed in 2008/2009 in Germany, Northern France, the United Kingdom and Poland. According to EU Guidance documents, cauliflower is a major crop in the NEU and at least 8 residue trials are required. However, taking into account the homogeneity of the residue trial results, 7 trials are considered sufficient to derive the MRL proposal. d. Brussels sprouts In support of the intended use of dimethoate on Brussels sprouts in total 8 GAP compliant residue trials were submitted. All trials have been performed in 2008/2009 in Germany, the United Kingdom and Denmark. The data are sufficient to derive the MRL proposal. e. Cherries In support of the intended use of dimethoate on cherries in total 4 GAP compliant residue trials on cherries were submitted. All trials have been performed in 2008/2009 in Germany and Poland. Cherries are considered as minor crop in the NEU and therefore 4 trials are sufficient to derive the MRL proposal. The storage stability of dimethoate and omethoate in primary crops was investigated in the DAR under Directive 91/414/EEC and peer reviewed by EFSA (EFSA, 2006). Dimethoate and omethoate residues have been shown to be stable when frozen between -10ºC and -20ºC for up to 27 months in potato, orange fruit, sorghum grain/forage and cottonseed as well as cherries stored for 6 months (EFSA, 2006). As the supervised residue trial samples were stored under conditions for which integrity of the samples was demonstrated, it is concluded that the residue data are valid with regard to storage stability. According to the EMS, the analytical method used to analyse supervised residue trial samples has been sufficiently validated and was proven to be fit for purpose (UK, 2010b). EFSA concludes that the MRL of 0.03 mg/kg in barley, oats, broccoli, cauliflower, 0.1 mg/kg for Brussels sprouts and 0.3 mg/kg for cherries would be appropriate for the intended uses of dimethoate on these crops in Northern Europe. EFSA Journal 2011;9(4):

13 Table 3-3: Overview of the available residues trials data Commodity Region (a) Outdoor/ Indoor Individual trial results (mg/kg) Enforcement Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Comments Proposed enforcement residue definition: Dimethoate Barley NEU Outdoor 7 x <0.001; Rber=0.002; Rmax= oats Broccoli NEU Outdoor 4 x < Rber=0.02; Rmax=0.01 Cauliflower NEU Outdoor 4 x <0.01; 3 x Rber=0.022; Rmax= Brussels sprouts NEU Outdoor <0.01; 0.012; 0.017; 0.021; 0.024; 0.027; 0.045; Rber=0.081; Rmax=0.082 Cherries NEU Outdoor <0.01; 0.02; 0.029; Rber=0.06; Rmax=0.07 Barley straw Oats straw NEU Outdoor 7 x <0.01; Rber=0.02; Rmax=0.065 Proposed enforcement residue definition: Omethoate Barley NEU Outdoor 7 x <0.001; Rber=0.002; Rmax=0.035 oats Broccoli NEU Outdoor 4 x < Rber=0.02; Rmax=0.01 Cauliflower NEU Outdoor 7 x < Rber=0.02; Rmax=0.01 Brussels sprouts NEU Outdoor 8 x < Rber=0.02; Rmax=0.01 Cherries NEU Outdoor 0.03; 0.04; 0.05; Rber=0.19; Rmax=0.24 Barley straw NEU Outdoor 8 x < Rber=0.02; Rmax=0.01 EFSA Journal 2011;9(4):

14 Table 3-4: Overview of the derived MRL proposals according to the residue definition in Regulation (EC) No 396/2005 (sum of dimethoate and omethoate) Commodity Region (a) Outdoor/ Indoor Barley oats Individual trial results (mg/kg) Enforcement (sum of dimethoate and omethoate expressed as dimethoate) MRL proposal (mg/kg) Comments NEU Outdoor 7 x <0.002; Rber=0.004; Rmax=0.023 Broccoli NEU Outdoor 4 x < Rber=0.04; Rmax=0.02 Cauliflower NEU Outdoor 4 x <0.02; 3 x Rber=0.042; Rmax=0.022 Brussels sprouts NEU Outdoor 0.02; 0.022; 0.027; 0.031; 0.034; 0.037; 0.055; Rber=0.10; Rmax=0.092 Cherries NEU Outdoor 0.04; 0.06; 0.079; Rber=0.25; Rmax=0.30 Barley straw NEU Outdoor 7 x <0.02; Rber=0.04; Rmax=0.075 Oats straw Table 3-5: Overview of the derived combined risk assessment values, taking into account the different toxicological potency for dimethoate and omethoate Commodity Region (a) Outdoor/Indoor Chronic risk assessment Median residue of dimethoate + 3 x Median residue of omethoate (Table 3-3) Acute risk assessment Highest residue of dimethoate + 6 x Highest residue of omethoate (Table 3-3) Median residue (mg/kg) (b) Highest residue (mg/kg) (c) Comments Barley NEU Outdoor x x oats Broccoli NEU Outdoor x x Cauliflower NEU Outdoor x x EFSA Journal 2011;9(4):

15 Commodity Region (a) Outdoor/Indoor Chronic risk assessment Median residue of dimethoate + 3 x Median residue of omethoate (Table 3-3) Acute risk assessment Highest residue of dimethoate + 6 x Highest residue of omethoate (Table 3-3) Median residue (mg/kg) (b) Highest residue (mg/kg) (c) Comments Brussels sprouts NEU Outdoor x x Cherries NEU Outdoor x x Barley straw NEU Outdoor x x Oat straw (a): NEU, SEU, EU or Import (country code). In the case of indoor uses there is no necessity to differentiate between NEU and SEU. (b): Median value of the individual trial results according to the enforcement residue definition. (c): Highest value of the individual trial results according to the enforcement residue definition. EFSA Journal 2011;9(4):

16 Modification of the exi Effect of industrial processing and/or household preparation Effects of processing on the nature of dimethoate were investigated in the framework of the peer review through hydrolysis studies simulating sterilisation, baking, brewing, boiling and pasteurization (EFSA, 2006). These studies demonstrated that dimethoate and omethoate are degraded to an extent depending on the severity of the ph and temperature conditions. Dimethoate is degraded to des-o-methyl isodimethoate (XII) (max 5.3% in sterilisation) and to desmethyl dimethoate (X) (28.1% in pasteurisation and 59.5% in sterilisation). Omethoate is degraded to metabolite O-desmethyl omethoate (XI) (36.2% in pasteurisation and 62.6% in sterilisation) and to O-O-dimethyl phosphoric acid (19.2% in sterilisation). Dimethoate and omethoate were at the end of the processing the major constituents of the residue, except under the most severe processing conditions (sterilisation) where desmethyl dimethoate and O-desmethyl omethoate were the major components. The peer review concluded that, based on the way the nature of residues is affected during processing there is no need to set specific residue definitions for processed commodities and the definitions proposed for raw commodities are applicable. No specific studies investigating the magnitude of dimethoate and omethoate residues in processed crops have been submitted under the current application Rotational crops Preliminary considerations The rate of degradation of dimethoate in the soil was investigated under the peer review of Directive 91/414/EEC (UK, 2004). The DT 90f value for dimethoate accounts for a maximum of 75.4 days. No relevant soil metabolites have been identified. The DT 50f value of omethoate has been determined and accounts for 22.7 days, and consequently it can be assumed that DT 90 value of omethoate will not exceed 100 days. Therefore it is concluded that according to the EU Guidance document (European Commission, 1997) no studies investigating the magnitude of dimethoate residues in rotational crops are required Nature and magnitude of residues in livestock Since cereals under consideration and/or their by-products are normally fed to livestock, the nature and magnitude of dimethoate residues in livestock was assessed in the framework of this application (EC, 1996) Dietary burden of livestock The median and maximum dietary burden for livestock was calculated using the agreed European methodology (EC, 1996). The input values for the dietary burden calculation were selected according to the latest FAO recommendations (FAO, 2009) considering the livestock intake from feed products under consideration and from all other feed products on which the use of dimethoate is authorized by Regulation (EC) No 396/2005, e.g. for which the existing EU MRL is set above the LOQ (wheat, rye, sugar beets) and on which there are authorized uses according to the information submitted by the EMS in the evaluation report (citrus fruits, cabbage, turnips) (UK, 2010b). To account for residues in cereal bran and citrus pomace, a default processing factor of 8 and 2.5, respectively, were used. EFSA Journal 2011;9(4):

17 Normally, the livestock dietary burden has to be calculated according to the risk assessment residue definition in plants. However, in the case of dimethoate, the risk assessment residue definitions for assessing acute and chronic exposure to dimethoate and omethoate residues have been set separately, considering the differences in the toxicological potency of the two compounds. The EMS calculated the livestock dietary intake separately for dimethoate and omethoate. However, EFSA is of the opinion that since both substances are present in feed commodities, their overall impact on the livestock exposure has to be assessed. Therefore for calculating livestock dietary burden, as input values EFSA chose the sum of the actual dimethoate and omethoate residues in the relevant feed items. The input values for the dietary burden calculation are summarized in Table 3-6. Table 3-6: Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value (mg/kg) Sum of dimethoate and omethoate Comment Barley, oat grain Median residue dimethoate + median residue omethoate (Table 3-3) Barley, straw oat 0.02 Median residue dimethoate + median residue omethoate (Table 3-3) Wheat, rye grain STMR dimethoate +STMR omethoate (EFSA, 2006) Wheat, rye bran STMR dimethoate +STMR omethoate (EFSA, 2006) *PF (8) Wheat, straw rye 0.09 STMR dimethoate +STMR omethoate (EFSA, 2006) Sugar beet tops STMR dimethoate +STMR omethoate (EFSA, 2006) Sugar beet roots 0.02 STMR dimethoate +STMR omethoate (EFSA, 2006) Cabbage HR a dimethoate +HR a omethoate (UK, 2010b) Citrus pomace 0.01 STMR dimethoate +STMR omethoate *PF (2.5) (UK, 2010b) Turnips HR a dimethoate +HR a omethoate (UK, 2010b) a HR values were used as STMR values could not be retrieved Input value (mg/kg) Comment Median residue dimethoate + median residue omethoate (Table 3-3) Highest residue dimethoate + highest residue omethoate (Table 3-3) STMR dimethoate +STMR omethoate (EFSA, 2006) STMR dimethoate +STMR omethoate (EFSA, 2006) *PF (8) 0.53 HR dimethoate +HR omethoate (EFSA, 2006) 0.2 HR dimethoate +HR omethoate (EFSA, 2006) 0.02 HR dimethoate +HR omethoate (EFSA, 2006) HR dimethoate +HR omethoate (UK, 2010b) 0.01 STMR dimethoate +STMR omethoate *PF (2.5) (UK, 2010b) HR dimethoate +HR omethoate (UK, 2010b) In order to estimate the contribution of dimethoate and omethoate residues in the feed crops under consideration to the total livestock dietary exposure, EFSA performed two dietary burden calculations: in scenario 1 barley and oat grain and straw were included in the calculation, while in scenario 2 barley and oat grain and straw were excluded from the dietary burden calculation. EFSA Journal 2011;9(4):

18 The results of the dietary burden calculation are summarized in the following table. Table 3-7: Results of the dietary burden calculation Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity The sum of dimethoate and omethoate, expressed as omethoate (Including all crops) scenario 1 Max dietary burden (mg/kg DM) (a) Trigger exceeded (Y/N) Dairy ruminants Sugar beet leaves 0.56 Y Meat ruminants Sugar beet leaves 0.71 Y Poultry Wheat bran 0.05 N Pigs Sugar beets 0.39 Y The sum of dimethoate and omethoate, expressed as omethoate (Excluding barley and oat grain and straw) scenario 2 Dairy ruminants Sugar beet leaves 0.56 Y Meat ruminants Sugar beet leaves 0.71 Y Poultry Wheat bran 0.05 N Pigs Sugar beets 0.39 Y (a): Dry matter feed The calculated dietary burdens indicate that the trigger value of 0.1 mg/kg dry matter (DM) is exceeded for dairy and meat ruminants and pigs. From the comparison of the two scenarios it is evident that the dietary burden is mainly driven by the existing uses and the contribution of the barley and oat grain and straw to the total livestock exposure is insignificant. Therefore the modification of the MRLs for commodities of animal origin was not further investigated in the framework of the current application. However, as the dietary burdens are triggered the possible carry-over of dimethoate and omethoate residues to food commodities have to be assessed with regard to all uses on feed crops in the framework of Article 12 of the Regulation (EC) No 396/2005. There are currently no EU MRLs for dimethoate established in animal commodities. 4. Consumer risk assessment A provisional consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo) This exposure assessment model contains the relevant European food consumption data for different sub-groups of the EU population 8 (EFSA, 2007). The consumer risk assessment has been performed assuming that plant metabolites XX, XII and III do not contribute to the overall toxicological burden. For the calculation of the chronic exposure for the crops under consideration, EFSA used the median residue values as derived form the residue trials according to the risk assessment residue definition for chronic exposure assessment in Table The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22 national diets collected from MS surveys plus 1 regional and 4 cluster diets from the WHO GEMS Food database; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collected from MS surveys is used. The complete list of diets incorporated in EFSA PRIMo is given in its reference section (EFSA, 2007). EFSA Journal 2011;9(4):

19 For the remaining commodities, the following considerations were taken with regard to the choice of the input values: - For those crops for which the EU MRL is above the LOQ and the residue trials are available (celeriac, spring onions, table olives, olives for oil production, rye, wheat and sugar beets), the STMR values, reported either by the RMS or in the EFSA conclusion of the peer review, were used as input values. STMR value was derived by the mean residue concentration of dimethoate and omethoate, taking into account the relevant potency of the two compounds; - For spices (seeds, fruits and berries, roots and rhizome) the existing EU MRLs are based on the CXLs and therefore the STMR values as derived by the JMPR were used as input values (WHO/FAO, 2004b). There is no information available on the amounts of omethoate in the crop, thus, to account for the worst case situation, it was assumed that omethoate is present at the levels of dimethoate; - For those crops for which the EU MRL is above the LOQ, but for which no residue trials are available (herbal infusions, bark of spices), the MRL, multiplied by the factor of 3 was used as an input value, assuming that the total residue contains exclusively the more toxic omethoate; - For some crops the STMR values as reported by the RMS (UK, 2010a), supporting the existing EU MRL at the LOQ (citrus fruits, beetroot, onions, head cabbage, peas (without pods)) were used as input values; - For those crops where the EU MRL is set at the LOQ, but for which GAPs have been notified without providing residue trials (apples, pears, peaches, grapes, strawberries, radishes, witloof, sage, rosemary, basil, thyme, bay leaves, tarragon, cotton seed, chicory roots), it was assumed that residues of dimethoate and omethoate are present in food at the LOQ of 0.01 mg/kg or at the LOQ of 0.02 mg/kg (cotton seed). These residue levels were recalculated according to the residue definition for the risk assessment: LOQ dimethoate (0.01 mg/kg) +3 LOQ omethoate (0.01 mg/kg)=0.04 mg/kg; LOQ dimethoate (0.02 mg/kg) +3 LOQ omethoate (0.02 mg/kg)= 0.08 mg/kg; - Those crops on which no uses are authorised according to the RMS (UK, 2010a) and/or requested uses have been previously rejected by EFSA (EFSA, 2010a, 2010b), were excluded from the exposure calculation. The processing studies assessed by the JMPR in 2003 allow deriving a processing factor of 0.2 for flour type 550 (derived from processing studies with wheat), a peeling factor of for citrus fruits (from residue trials on oranges), a processing factor of 0.01 for olives intended for oil production as well as a processing factor of 0.18 for table olives (WHO/FAO, 2004a). These processing factors were applied to the relevant commodities to refine exposure calculations. The model assumptions for the long-term exposure assessment are affected by various uncertainties as it is assumed that all food items consumed have been treated with the active substance under consideration. In reality, it is not likely that all food consumed will contain residues at the MRL or at levels of the median residue values identified in supervised field trials. The acute exposure assessment was performed only with regard to the commodities under consideration assuming the consumption of a large portion of the food item as reported in the national food surveys containing residues at the highest level as observed in supervised field trials (Table 3-5). The input values used for the dietary exposure calculation are summarized in Table 4-1. EFSA Journal 2011;9(4):

20 Table 4-1: Input values for the consumer dietary exposure assessment Commodity Chronic exposure assessment (sum of dimethoate and 3 x omethoate expressed as dimethoate) Input value (mg/kg) Comment Acute exposure assessment (sum of dimethoate and 6 x omethoate expressed as dimethoate) Input value (mg/kg) Comment Barley, oat grain Median residue Highest residue Cauliflower 0.04 Median residue 0.07 Highest residue Broccoli 0.04 Median residue 0.07 Highest residue Brussels sprouts Median residue 0.12 Highest residue Cherries 0.16 Median residue 0.69 Highest residue Citrus fruits STMR (UK, 2010a) * peeling factor (0.065) (WHO/FAO, 2004a) Apples, pears, peaches, table and wine grapes, strawberries, radishes, witloof, sage, rosemary, thyme basil, bay leaves, tarragon, chicory roots Beetroot, peas (without pods) 0.04 LOQ dimethoate + 3*LOQ omethoate 0.04 STMR (UK, 2010a) Table olives 0.06 STMR (EFSA, 2006) *PF (0.18) (WHO/FAO, 2004a) Olives for oil production STMR (EFSA, 2006) *PF (0.01) (WHO/FAO, 2004a) Celeriac STMR (UK, 2010a) Onions, head cabbage 0.08 STMR (UK, 2010a) Spring onions 0.54 STMR (UK, 2010a) Rye, wheat STMR (EFSA, 2006)* PF (0.2) (WHO/FAO, 2004a) Sugar beets 0 a See footnote Cotton seed 0.08 LOQ dimethoate + 3*LOQ omethoate Camomile flowers 3 MRL*3 Herbal infusions (dried flowers, dried leaves, dried roots) 0.3 MRL*3 Spices (bark) 1.5 MRL*3 Acute exposure assessment was undertaken only with regard crops under consideration. EFSA Journal 2011;9(4):