Reasoned opinion on the modification of the existing MRLs for fluopicolide in various vegetable crops 1

Transcription

1 EFSA Journal 2012;10(9):2895 REASONED OPINION Reasoned opinion on the modification of the existing MRLs for fluopicolide in various vegetable crops 1 ABSTRACT European Food Safety Authority 2, European Food Safety Authority (EFSA), Parma, Italy In accordance with Article 6 of Regulation (EC) No 396/2005, the United Kingdom, herewith referred to as the evaluating Member State (EMS-UK), received an application from Bayer CropScience to set import tolerances for the active substance fluopicolide on carrots, radishes and sugar beet. In accordance with Article 6 of Regulation (EC) No 396/2005, Italy, hereafter referred to as the evaluating Member State (EMS-IT), received an application from Bayer CropScience to modify the existing MRLs for the active substance fluopicolide on certain leaf vegetables and herbs. Both the United Kingdom and Italy drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA. EFSA combined both applications in one reasoned opinion. According to EFSA the data are sufficient to derive the following MRL proposals: 0.2 mg/kg for radishes and carrots; 0.15 mg/kg for sugar beet; 9 mg/kg for the crop group of lettuce and other salad plants, including Brassicaceae and for the crop group of herbs; 4 mg/kg for the crop group of spinach and similar (leaves). Adequate analytical enforcement methods are available to control the residues of fluopicolide in the crops under consideration. Based on the risk assessment results, EFSA concludes that the intended uses of fluopicolide on the crops under consideration, except the more critical indoor use and outdoor use in Southern Europe on scarole, will not result in a consumer exposure exceeding the toxicological reference values of fluopicolide and the metabolite M-01 and therefore is unlikely to pose a public health risk. For scarole, EFSA proposes a MRL derived from a less critical use, which is not leading to a consumer concern. European Food Safety Authority, 2012 KEY WORDS Fluopicolide, carrots and radishes, sugar beet, leaf vegetables and herbs, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, benzamido-pyridine fungicides, M-01 (2,6-dichlorobenzamide). 1 On request from European Commission, Question No EFSA-Q and EFSA-Q , approved on 24 September Correspondence: pesticides.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Reasoned opinion on the modification of the existing MRLs for fluopicolide in various vegetable crops. EFSA Journal 2012;10(9):2895. [43 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 SUMMARY In accordance with Article 6 of Regulation (EC) No 396/2005, the United Kingdom, herewith referred to as the evaluating Member State (EMS-UK), received an application from Bayer CropScience to set import tolerances for the active substance fluopicolide on carrots, radishes and sugar beet reflecting the authorised uses in the United States of America. The United Kingdom proposed to set the MRLs at the level of 0.2 mg/kg for radishes and carrots and 0.1 mg/kg for sugar beet and drafted an evaluation report according to Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 6 January In accordance with Article 6 of Regulation (EC) No 396/2005, Italy, hereafter referred to as the evaluating Member State (EMS-IT), received an application from Bayer CropScience to modify the existing MRLs for the active substance fluopicolide on certain leaf vegetables and herbs. In order to accommodate the intended uses of fluopicolide, Italy proposed to raise the existing MRLs from 8 mg/kg on lettuce and the limit of quantification (LOQ) of 0.01 mg/kg on the other salad plants and on fresh herbs to 10 mg/kg (except scarole). For spinach and similar (leaves), the EMS-IT proposed to raise the exiting MRL from the LOQ of 0.01 mg/kg to 3 mg/kg. Italy drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 21 March For reasons of efficiency EFSA combined both applications in one reasoned opinion. EFSA bases its assessment on the evaluation reports, the Draft Assessment Report (DAR) prepared under Council Directive 91/414/EC, the Commission Review Report on fluopicolide, the conclusion on the peer review of the pesticide risk assessment of the active substance fluopicolide, the JMPR evaluation report as well as the conclusions from previous EFSA opinions on fluopicolide. The toxicological profile of fluopicolide was investigated in the peer review under Council Directive 91/414/EC and data were sufficient to conclude on an ADI of 0.08 mg/kg bw per day and an ARfD of 0.18 mg/kg bw. For the metabolite 2,6-dichlorobenzamide (M-01) separate toxicological reference values were set (ADI: 0.05 mg/kg bw per day; ARfD: 0.3 mg/kg bw). The metabolism of fluopicolide in primary crops was investigated in three plant groups: leafy crops (lettuce), fruit crops (grapes) and root/tuber crops (potatoes). From these studies the peer review concluded to establish the residue definition for enforcement as the parent compound fluopicolide. For risk assessment two separate residue definitions were proposed: parent fluopicolide and the M-01 (2,6- dichlorobenzamide). For the use on the crops under consideration, EFSA concludes that the metabolism of fluopicolide in primary crops is sufficiently addressed and that the derived residue definitions are applicable. EFSA concludes that the submitted supervised residue trials are sufficient to derive the following MRL proposals: 0.2 mg/kg for radishes and carrots; 0.15 mg/kg for sugar beet; 9 mg/kg for the crop group of lettuce and other salad plants, including Brassicaceae and for the crop group of herbs; 4 mg/kg for the crop group of spinach and similar (leaves). In accordance with the guidance document applicable at the time when the MRL application was submitted to the EMS-IT, the MRL proposals for the lettuce and herb groups were derived by extrapolation from residue trials on lettuce (open leaf and head forming varieties). Since in the meantime more strict rules are applicable for the extrapolation (a full data set on only open leaf varieties is needed), EFSA recommends conducting additional trials on open-leaf lettuce to complete the dataset as required in the current guidance document. Adequate analytical enforcement methods are available to control the residues of fluopicolide in the crops under consideration at or above the validated LOQ of 0.01 mg/kg. Fluopicolide showed to be stable under hydrolytic processing conditions representing boiling, pasteurisation and sterilisation. Thus, for processed commodities the same residue definition as for raw agricultural commodities is applicable. For the crops under consideration no processing studies have been submitted and, according to the European requirements, are not necessary. EFSA Journal 2012;10(9):2895 2

3 Based on the available information on the nature and magnitude of residues in succeeding crops assessed during the peer review, EFSA concludes that significant residue levels of fluopicolide and its metabolite are unlikely to occur in rotational crops provided that the compound is used in lettuce and other salad plants, fresh herbs and spinach and similar (leaves) according to the intended GAPs. Since sugar beet, if imported from the USA, may be used as feed item, the potential carry-over of residues into food of animal origin was assessed. EFSA concludes that a modification of the existing MRLs for the commodities of animal origin is not required in the framework of the import tolerance application. The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). Separate consumer exposure assessments were performed for fluopicolide and the metabolite M-01. The calculated exposures were compared with the toxicological reference values as derived for fluopicolide and M-01. The short-term risk assessment resulted in a potential consumer health risk associated with the exposure to residues of fluopicolide in scarole. For the most critical indoor use and outdoor use in SEU the exposure accounted for 238 % and 165 % of the ARfD, respectively. A third exposure calculation was therefore performed considering the less critical outdoor use in NEU for scarole; in this scenario the maximum exposure for scarole did not lead to a consumer intake concern (39.8 % of the ARfD). With regard to the other crops under consideration no short-term consumer intake concerns were identified. No acute consumer risk was identified in relation to the exposure to the metabolite M-01 from the intake of the crops for which a MRL is proposed. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. Regarding fluopicolide, the total calculated intake values accounted for less than 3 % of the ADI (WHO Cluster diet B). Among the crops under consideration, the major contribution of residues to the total consumer exposure was identified for sugar beet which accounted for a maximum of 1.1 % of the ADI. Regarding the metabolite M-01, the total calculated intake values accounted for up to 0.6 % of the ADI (UK toddler diet). The contribution of residues in the crops under consideration to the total consumer exposure accounted for a maximum of 0.5 % of the ADI in sugar beet roots. EFSA concludes that the intended uses of fluopicolide on the crops under consideration, except the more critical indoor use and outdoor use in Southern Europe on scarole, will not result in a consumer exposure exceeding the toxicological reference values of fluopicolide and the metabolite M-01 and therefore is unlikely to pose a public health risk. For scarole, EFSA proposes a MRL derived from a less critical use, which is not leading to a consumer concern. Thus EFSA proposes to amend the existing MRLs as reported in the summary table. Summary table Code Commodity Existing number (a) EU MRL Enforcement residue definition: fluopicolide Proposed EU MRL Justification for the proposal Carrots 0.01* 0.2 The MRL proposals are sufficiently Radishes supported by data and no risk for consumers was identified for the import tolerance requests Lamb s lettuce 0.01* 9 The MRL proposal is sufficiently Cress Land cress Rocket, Rucola supported by data (extrapolation form residue trials on head-forming and openleaf lettuce) (b) and no risk for consumers EFSA Journal 2012;10(9):2895 3

4 Code Commodity Existing number (a) EU MRL Red mustard Leaves and sprouts of Brassica spp Others Lettuce Scarole (broad-leaf endive) Spinach Purslane Beet leaves (chard) Others Chervil Chives Celery leaves (fennel leaves, coriander leaves, dill leaves, caraway leaves, lovage, angelica, sweet cisely and other Apiacea leaves) Parley Sage Rosemary Thyme Basil Bay leaves Tarragon Others Modification of the existing MRLs for fluopicolide in various crops Proposed EU MRL Justification for the proposal was identified for the intended uses. 0.01* 1.5 EFSA derived a MRL proposal (by extrapolation from on head-forming and open-leaf lettuce) (b) for the NEU outdoor GAP; for this MRL no consumers risk was identified. For the more critical SEU outdoor GAP and the indoor use a potential acute consumer intake concern could not be excluded. 0.01* 4 The MRL proposal is sufficiently supported by data (extrapolation from residue trials on spinach) and no risk for consumers was identified for the intended uses. 0.01* 9 The MRL proposal is sufficiently supported by data (extrapolation form residue trials on head-forming and openleaf lettuce) (b) and no risk for consumers was identified for the intended uses Sugar beet (root) 0.01* 0.15 The MRL proposal is sufficiently supported by data and no risk for consumers was identified for the import tolerance request. (a): According to Annex I of Regulation (EC) No 396/2005. (b): Based on the extrapolation rules in place up to 31 March 2011 (revision 8 of the EU guidance document SANCO 7525/VI/95). (*): Indicates that the MRL is set at the limit of analytical quantification. EFSA Journal 2012;10(9):2895 4

5 TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 5 Background... 6 Terms of reference... 6 The active substance and its use pattern... 7 Assessment Method of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues Nature and magnitude of residues in plant Primary crops Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Consumer risk assessment Conclusions and recommendations References Appendices A. Good Agricultural Practice (GAPs) B. Pesticide Residues Intake Model (PRIMo ) C. Existing EU maximum residue levels (MRLs) D. List of metabolites and related structural formula Abbreviations EFSA Journal 2012;10(9):2895 5

6 BACKGROUND Regulation (EC) No 396/ establishes the rules governing the setting of pesticide MRLs at European Union level. Article 6 of that Regulation lays down that any party having a legitimate interest or requesting an authorisation for the use of a plant protection product in accordance with Council Directive 91/414/EEC 4, repealed by Regulation (EC) No 1107/2009 5, shall submit to a Member State, when appropriate, an application to modify an MRL in accordance with the provisions of Article 7 of that Regulation. The United Kingdom, hereafter referred to as the evaluating Member State (EMS-UK), received from the company Bayer CropScience 6 an application to set import tolerances for the active substance fluopicolide in carrots, radishes and sugar beet reflecting the authorised uses in the United States of America (USA). This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS-UK in accordance with Article 8 of the Regulation. Italy, hereafter referred to as the evaluating Member State (EMS-IT), received an application from the above mentioned company to modify the existing MRLs for the active substance fluopicolide in lettuce and other salad plants, including Brassicaceae, fresh herbs, spinach and similar (leaves). This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS-IT in accordance with Article 8 of the Regulation. After completion, the evaluation reports were submitted to the European Commission who forwarded the applications, the evaluation reports and the supporting dossiers to EFSA on 6 January 2012 and 21 March 2012, respectively. The applications were included in the EFSA Register of Questions with the reference numbers EFSA- Q and EFSA-Q and the following subjects: Fluopicolide - Application to modify the existing MRLs in carrots, radishes and sugar beet Fluopicolide - Application to modify the existing MRLs in various leafy crops The EMS-UK and EMS-IT proposed the following MRLs for fluopicolide: 0.2 mg/kg for carrots and radishes; 0.1 mg/kg for sugar beet; 10 mg/kg for lettuce and the other salad plants including Brassicaceae, except scarole; 10 mg/kg for herbs; 3 mg/kg for spinach and similar (leaves). EFSA proceeded with the assessment of the applications and the evaluation reports as required by Article 10 of the Regulation. For reasons of efficiency EFSA combined both applications in one reasoned opinion. TERMS OF REFERENCE In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation reports provided by the evaluating Member States, provide a reasoned opinion on the risks to the consumer associated with the applications. In accordance with Article 11 of that Regulation, the reasoned opinions 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 applications. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. 3 Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July OJ L 230, , p Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October OJ L 309, , p Bayer CropScience, 16 rue Jean-Marie Leclair, CS 90106, 69266, Lyon Cedex 09, France. EFSA Journal 2012;10(9):2895 6

7 In this particular case the calculated deadlines for providing the reasoned opinions are 6 April 2012 and 21 June 2012, respectively. THE ACTIVE SUBSTANCE AND ITS USE PATTERN Fluopicolide is the ISO common name for 2,6-dichloro-N-[3-chloro-5-(trifluoromethyl)-2- pyridylmethyl]benzamide (IUPAC). The chemical structure is as follows: F 3 C Cl Cl N NH O Cl Molecular weight: g/mol Fluopicolide belongs to the class of benzamido-pyridine fungicides. Its biochemical mode of action is currently not fully known, however it was shown that fluopicolide modifies the distribution of fungal spectrin-like proteins. Fluopicolide has protectant, antisporulant activity and potential for curative activity against a range of phytopathogens of the oomycete class. Fluopicolide was evaluated in the framework of Council Directive 91/414/EEC with the United Kingdom designated as rapporteur Member State (RMS). It was included in Annex I of this Directive by Commission Directive 2010/15/EU 7 which entered into force on 1 June 2010 for use as fungicide. In accordance with Commission Implementing Regulation (EU) No 540/ fluopicolide is approved under Regulation (EC) No 1107/2009, repealing Council Directive 91/414/EEC. The representative uses evaluated in the peer review were foliar applications on potatoes and grape. The Draft Assessment Report (DAR) of fluopicolide has been peer reviewed by EFSA (EFSA, 2009b). The EU MRLs for fluopicolide are established in Annex IIIA of Regulation (EC) No 396/2005 (Appendix C). EFSA recommendations to modify the existing MRLs on various crops (EFSA, 2009a, 2011, 2012) have been implemented in four Regulations between 2009 and The existing EU MRLs for fluopicolide are set at the LOQ of 0.01 mg/kg on carrots, sugar beet and the groups of other salad plants (except lettuce), fresh herbs and spinach and similar leaves, whereas the MRLs are at 8 mg/kg on lettuce and 0.06 mg/kg on radishes. Codex Alimentarius has established CXLs for a range of commodities, including leafy vegetables for which the CXL is set at 30 mg/kg. The details of the GAPs authorised in the USA and the intended European GAPs for fluopicolide are given in Appendix A. 7 Commission Directive 2010/15/EU of 8 March 2010, OJ L 58, , p Commission Implementing Regulation (EU) No 540/2011 of 23 May OJ L 153, , p EFSA Journal 2012;10(9):2895 7

8 ASSESSMENT EFSA bases its assessment on the submitted evaluation reports (the United Kingdom, 2011; Italy, 2011), the Draft Assessment Report (DAR) prepared under Council Directive 91/414/EC (the United Kingdom, 2005), the Commission Review Report on fluopicolide (EC, 2010a), the conclusion on the peer review of the pesticide risk assessment of the active substance fluopicolide (EFSA, 2009b), the JMPR Evaluation report (FAO, 2010) as well as the conclusions from previous EFSA opinions on fluopicolide (EFSA, 2009a, 2011, 2012). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/ and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2008, 2010b, 2010c, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of fluopicolide residues in plant commodities were assessed during the peer review under Directive 91/414/EEC (the United Kingdom, 2005; EFSA, 2009b). Fluopicolide residues can be determined in high water, high acid content commodities and in dry commodities using a modified version of the German multi-residue method DFG S19 with validated LOQs of 0.1 mg/kg (grapes) and 0.02 mg/kg (potatoes and wheat grain). An independent laboratory validation (ILV) was performed. It should be noted that the method is able also to analyse separately residues of the metabolites M (EFSA, 2009b). A high performance liquid chromatography coupled with tandem mass spectrum detection (HPLC- MS/MS) method for the determination of fluopicolide residues in matrices with high water content proposed in the framework of a previous MRL application was sufficiently validated at or above the LOQ of 0.01 mg/kg. An ILV was provided for the method (EFSA, 2011). The multi-residue QuEChERS method described in the European Standard EN 15662:2008 is also applicable. The LC-MS/MS method analyses fluopicolide residues in matrices with high water, high acid, fat and dry content at or above the LOQ of 0.01 mg/kg (CEN, 2008). Since the commodities under consideration belong to the group of high water content commodities, EFSA concludes that sufficiently validated analytical methods for enforcing the proposed MRLs for fluopicolide on the crops under consideration are available Methods for enforcement of residues in food of animal origin Analytical methods for the determination of fluopicolide residues in commodities of animal origin were assessed during the peer review under Directive 91/414/EEC (the United Kingdom, 2005; EFSA, 2009b). Fluopicolide residues can be determined using HPLC-MS/MS with LOQs ranging from of mg/kg. The analytical method detects parent and metabolite M-01 separately (EFSA, 2009b). The multi-residue DFG method S19 (modified version) for the determination of residues of fluopicolide in meat, liver, eggs, milk and cream was validated at the LOQ of 0.01 mg/kg. An ILV was performed (FAO, 2010). EFSA concludes that sufficiently validated analytical methods for enforcing MRLs for fluopicolide in food of animal origin are available. 9 Commission Regulation (EU) No 546/2011 of 10 June OJ L 155, , p M-01: 2,6-dichlorobenzamide. See Appendix D. EFSA Journal 2012;10(9):2895 8

9 2. Mammalian toxicology Modification of the existing MRLs for fluopicolide in various crops The toxicological profile of the active substance fluopicolide was assessed in the framework of the peer review under Directive 91/414/EEC (EFSA, 2009b; EC, 2010a). The data were sufficient to derive toxicological reference values for fluopicolide which are compiled in Table 2-1. For the metabolite M-01, which is not unique to fluopicolide, but was also observed from the use of the active substance dichlobenil (EFSA, 2010), specific toxicological reference values were derived (EFSA, 2009b). They are also reported in Table 2-1. Table 2-1: Overview of the toxicological reference values Fluopicolide Source Year Value Study relied upon Safety factor ADI EC 2010a 0.08 mg/kg bw per day Mice, 78-week dietary 100 ARfD EC 2010a 0.18 mg/kg bw Rat, 28-day dietary study 100 Metabolite M-01 ADI EFSA 2009b 0.05 mg/kg bw per day Rat and dog, 2-year study 100 ARfD EFSA 2009b 0.3 mg/kg bw Rabbit, developmental study Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of fluopicolide in primary crops was evaluated in the framework of the peer review under Directive 91/414/EEC (the United Kingdom, 2005; EFSA, 2009b). 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 Leafy vegetables Grapes [ 14 C] Phenyl [ 14 C] Pyridinyl Lettuce [ 14 C] Phenyl [ 14 C] Pyridinyl Application details Method, Rate No/ F or G (a) Interval Foliar, I 0.17 (1 st appl.), 0.12 kg a.s./ha 1.7 (1 st appl.), 1.2 kg a.s./ha 0.17 (1 st appl.), 0.12 kg a.s./ha 1.7 (1 st appl.), 1.2 kg a.s./ha Foliar, I 0.2 kg a.s./ha 3 (n.r.) 2 (21 d) Sampling 0, 27-28, d after the 1 st application 0, 21, 35 d after the 1 st application Remarks EFSA Journal 2012;10(9):2895 9

10 Group Crop Label position Root and tuber vegetables [ 14 C] Phenyl Potato [ 14 C] Phenyl [ 14 C] Pyridinyl [ 14 C] Phenyl [ 14 C] Pyridinyl Application details Method, Rate No/ F or G (a) Interval Soil drench 0.2 kg a.s./ha Foliar, F 0.02 kg a.s./ha 2.0 kg a.s./ha (a): Outdoor/field use (F) or glasshouse/protected crops/indoor application (G). n.r. not reported in the DAR (the United Kingdom, 2005). Sampling 1 21, 35 DAT 2 (50) 0, 41, d after the 1 st application Remarks Following foliar or soil applications of fluopicolide, plant metabolism was found to be limited with fluopicolide being the major component of the total radioactive residues (TRR) at harvest (lettuce/foliar: 96.4 % of TRR; lettuce/soil: 74.5 % of TRR; grapes: 91.2 % of TRR; potato tubers: 70.2 % of TRR). Besides fluopicolide, the metabolites M-01, M and M were identified in significant amounts only in potato tubers (M-01 up to 25.4 % of TRR; M-02 up 12 % of TRR and M- 06 up to 2.4 % of TRR) and in lettuce grown after soil drench application (M-01 up to 19.8 % of TRR). The metabolic pathway of fluopicolide showed to be similar in the three crop groups, involving hydrolysis of the urea bond to form metabolites M-01 and M-02 and hydroxylation of the phenyl ring to form metabolite M-06. With the exception of M-01 for which an ADI and an ARfD were set, the other metabolites were regarded as less toxic than the parent compound. The residue definition for monitoring was defined as fluopicolide parent compound. The current residue definition set in Regulation (EC) No 396/2005 is identical to the residue definition for enforcement derived in the peer review. For risk assessment two separate plant residue definitions were established: 1) fluopicolide and 2) M-10 (2,6-dichlorobenzamide) (EFSA, 2009b). For the uses on the crops under consideration, EFSA concludes that the metabolism of fluopicolide is sufficiently addressed and the residue definitions agreed in the peer review are applicable Magnitude of residues All the samples from the submitted supervised residue trials were analysed for both the parent compound and the metabolite M-01, which is included in the residue definition for risk assessment. a. Radishes In support of the import tolerance request six supervised residue trials (one designed as residue decline study) on radish were submitted. The trials were conducted during a single season but in different geographical locations in the USA and were compliant with the GAP in terms of number of applications (3), application rate and the PHI. EFSA concludes that the data are sufficient to support the MRL proposal of 0.2 mg/kg. 11 M-02: 3-chloro-5-(trifluoromethyl)pyridine-2-carboxylic acid. See Appendix D. 12 M-06: 2,6-dichloro-N-[(3-chloro-5-trifluoromethylpyridin-2-yl) methyl]-3-hydroxybenzamide. See Appendix D. EFSA Journal 2012;10(9):

11 b. Carrots Modification of the existing MRLs for fluopicolide in various crops In support of the import tolerance request seven supervised residue trials (one designed as residue decline study) on carrots were submitted. The trials were conducted during a single season but in different geographical locations in the USA and were compliant with the GAP in terms of number of applications (3), application rate and the PHI. As carrot is a major crop worldwide, at least eight trials would be required to support the import tolerance request (EC, 2008, 2011). Although only seven residue trials are available, EFSA is of the opinion that despite the deficiency of the dataset a MRL proposal can be derived taking into account the distribution of the results (six trials between <0.01 to 0.04 mg/kg, one sample: 0.13 mg/kg). The MRL proposal derived from the seven trails is 0.2 mg/kg. c. Sugar beet In support of the import tolerance request ten supervised residue trials (one designed as residue decline study) on sugar beet were submitted. The trials were conducted during a single season but in different geographical locations in the USA and were compliant with the GAP in terms of number of applications (3), application rate and the PHI. EFSA concludes that the data are sufficient to support the MRL proposal of 0.15 mg/kg. d. Lettuce and other salad plants, including Brassicaceae and herbs. In support of the intended uses the applicant proposed to extrapolate the residue data from lettuce to: the whole crop group of lettuce and other salad plants, including Brassicaceae (251000) the whole group of herbs (256000) Considering that the application was submitted when the previous version of the guidance document was in place, the previous extrapolation rules 13 apply and both extrapolations are acceptable (EC, 2008). Since the residue levels measured in the trials conducted on head-forming and open-leaf lettuce (indoor and SEU use) showed to belong to a similar population (Mann-Whitney U-Test), the extrapolation can be extended to lamb s lettuce and cress. Nevertheless, the MRL proposal based on the combined dataset is affected by uncertainties as it might underestimate the actual residue levels expected on certain crops. Therefore, EFSA recommends conducting additional trials on open-leaf lettuce varieties to complete the dataset as required in the current guidance document on extrapolation (EC, 2011). Outdoor-NEU: eight decline residue trials on lettuce (two on open-leaf varieties) are compliant with the intended critical GAP (cgap) and the data are sufficient to derive by extrapolation a MRL proposal for the crop group of lettuce and other salad plants, including Brassicaceae (251000). Outdoor-SEU: eight decline residue trials on lettuce (four on open-leaf varieties) are compliant with the intended cgap and the data are sufficient to derive by extrapolation a MRL proposal for the crop group of lettuce and other salad plants, including Brassicaceae (251000) and the crop group of herbs (256000). Indoor-EU: eight decline residue trials on lettuce (three on open leaf varieties) are compliant with the intended cgap and the data are sufficient to derive by extrapolation a MRL proposal for the crop group of lettuce and other salad plants, including Brassicaceae (251000) and the crop group of herbs (256000). EFSA concludes that the data are sufficient to propose a MRL of 9 mg/kg for the intended indoor use on the crop group of lettuce and other salad plants, including Brassicaceae (251000) and the crop 13 A general extrapolation is possible from lettuce, regardless to the variety, to the whole group of fresh herbs and to the whole group of lettuce and other salad plants, but possible residues in lamb s lettuce and cress should be considered, in case the active substance is used up to or close to harvest and the GAP is comparable. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. SANCO 7525/VI/95 - rev.8, 1 February 2008 (EC, 2008). EFSA Journal 2012;10(9):

12 group of herbs (256000). For the less critical GAPs (SEU and NEU outdoor use) alternative MRL proposals of 6 mg/kg and 1.5 mg/kg are calculated. e. Spinach Outdoor-NEU: four residue trials on spinach (two designed as residue decline studies) are compliant with the intended GAP for spinach. Spinach is classified as a minor crop in NEU. The data are sufficient to derive a MRL proposal of 0.8 mg/kg. Outdoor-SEU: four residue trials on spinach (two designed as residue decline studies) are compliant with the intended GAP for spinach. Spinach is classified as a minor crop in SEU. The data are sufficient to derive the MRL proposal of 4 mg/kg. EFSA concludes that the data are sufficient to propose a MRL of 4 mg/kg for the intended uses on spinach derived from the dataset representing the more critical use in SEU. f. Purslane, beet leaves (chard) and others similar spinach leaves In support to the intended outdoor use in SEU the applicant proposed to extrapolate the residue data from spinach to the whole group of spinach and similar leaves (252000). Since the GAPs are identical, the extrapolation is acceptable according to both the current and the previous version of the EU guidance document (EC, 2008, 2011). EFSA concludes that the data on spinach are sufficient to support the MRL proposal of 4 mg/kg for the group of spinach and similar (leaves). The results of the residue trials, the related input values (highest residue, median residue) for the risk assessments residue definition fluopicolide and the MRL proposals are summarised in Table 3-2, while the input values to perform the risk assessment according to the second residue definition (M- 01) are reported in Table 3-3. The storage stability of fluopicolide in primary crops was investigated in the DAR under Directive 91/414/EEC (the United Kingdom, 2005). Residues of fluopicolide and M-01 were found to be stable at -18 C for up to 30 months in matrices with high water and high acid content and in dry commodities (grapes, potatoes, cabbages and wheat grain). As the supervised residue trial samples on lettuce and spinach were stored for up to 256 and 391 days, respectively (Italy, 2011) under conditions for which integrity of the samples was demonstrated, it is concluded that the residue data are valid with regard to storage stability. The samples from the supervised residue trials on carrots, radishes and sugar beet were stored deep frozen for up to 44, 46 and 40 months, respectively, thus exceeding the period assessed in the stability studies (the United Kingdom, 2011). Considering that no significant degradation (<13 %) was observed for fluopicolide and M-01 during 30-month storage in the four tested crops, it is likely that no degradation occurred also in the samples from the residue trials stored for a longer period. However, the validity of residue trial data is further to be demonstrated by providing adequate storage stability studies in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005. According to the EMSs, the analytical methods used to analyse the supervised residue trial samples have been sufficiently validated and were proven to be fit for purpose (the United Kingdom, 2011; Italy, 2011). EFSA concludes that the data are sufficient to derive the following MRL proposals: 0.2 mg/kg for radishes and carrots; 0.15 mg/kg for sugar beet; 9 mg/kg for the crop group of lettuce and other salad plants, including Brassicaceae; 9 mg/kg for the crop group of herbs; 4 mg/kg for the crop group of spinach and similar (leaves). EFSA Journal 2012;10(9):

13 Table 3-2: Overview of the available residues trials data on fluopicolide Commodity Residue region (a) Outdoor /Indoor Individual trial results Enforcement (fluopicolide) Risk assessment (fluopicolide) Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments (e) Enforcement residue definition: fluopicolide Risk assessment residue definition: fluopicolide Radishes Import Outdoor 3 x 0.02; 0.03; 0.05; x 0.02; 0.03; 0.05; R ber = 0.13 R max = 0.16 MRL OECD = 0.17/0.2. Carrots Import Outdoor <0.01; 2 x 0.01; 2 x 0.03; 0.04; 0.13 Sugar beet Import Outdoor <0.01; 2 x 0.01; 0.03; 2 x 0.04; 0.04 (f) ; 2 x 0.05; 0.06 Lettuce Other salad plants, including Brassicaceae (251000) Lettuce Other salad plants, including Brassicaceae (251000) Lettuce Herbs (256000) NEU Outdoor Open-leaf lettuce: 0.36; 0.41 Head-forming lettuce: 0.07; 0.12; 0.31; 0.6; 0.74; 0.82 SEU Outdoor Open-leaf lettuce: 0.14; 0.91; 1.8; 3.4 Head-forming lettuce: 0.07; 0.41; 0.46; 1.0 EU Indoor Head-forming lettuce: 0.63; 0.68; 1.5; 2.7; 4.9 Open-leaf lettuce: 2 x 0.4; 4.0 <0.01; 2 x 0.01; 2 x 0.03; 0.04; 0.13 <0.01; 2 x 0.01; 0.03; 2 x 0.04; 0.04 (f) ; 2 x 0.05; ; 0.12; 0.31; 0.36; 0.41; 0.6; 0.74; ; 0.14; 0.41; 0.46; 0.91; 1.0; 1.8; x 0.4; 0.63; 0.68; 1.5; 2.7; 4.0; R ber = 0.08 R max = 0.18 MRL OECD = 0.21/ R ber = 0.1 R max = 0.09 MRL OECD = 0.11/ The combined dataset supports the extrapolation (EC, 2008). NEU outdoor R ber = 1.41 R max = 1.30 MRL OECD = 1.52/1.5 SEU outdoor R ber = 3.20 R max = 4.57 MRL OECD = 5.47/6 EU indoor R ber = 7.35 R max = 7.53 MRL OECD = 8.96/9 EFSA Journal 2012;10(9):

14 Commodity Residue region (a) Outdoor /Indoor Individual trial results Enforcement (fluopicolide) Risk assessment (fluopicolide) Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments (e) Spinach NEU Outdoor 0.05; 0.15; 0.30; ; 0.15; 0.30; R ber = 0.65 R max = 0.88 MRL OECD = 0.73/0.8 Spinach Spinach and similar (leaves) (252000) SEU 0.14; 0.17; 0.38; ; 0.17; 0.38; R ber = 2.74 R max = 4.42 MRL OECD = 3.57/4 (a): NEU (Northern and Central Europe), SEU (Southern Europe and Mediterranean), EU (i.e. indoor use) or Import (country code) (EC, 2011). (b): Median value of the individual trial results according to the enforcement residue definition. (c): Highest value of the individual trial results according to the enforcement residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residue trial. (e): Statistical estimation of MRLs according to the EU methodology (R ber, R max ; EC, 1997g) and unrounded/rounded values according to the OECD methodology (OECD, 2011). (f): Highest value measured in the decline study at a longer PHI (10 days) than the PHI of the intended GAP. EFSA Journal 2012;10(9):

15 Table 3-3: Overview of the available residues trials data on M-01 (2,6-dichlorobenzamide) Commodity Residue region (a) Outdoor/ Indoor Individual trial results Enforcement (fluopicolide) Risk assessment (M-01) Median residue RA (b) Highest residue RA (c) MRL proposal Median CF (d) Comments (e) Risk assessment residue definition: M-01 (2,6-dichlorobenzamide) Radishes Import Outdoor See Table x < 0.01 <0.01 < Carrots Import Outdoor 7 x <0.01 <0.01 < Sugar beet Import Outdoor 8 x <0.01; 2 x Lettuce Other salad plants, including Brassicaceae (251000) Lettuce Other salad plants, including Brassicaceae (251000) Lettuce Herbs (256000) NEU Outdoor 2 x <0.01; 0.01; 3 x 0.01 (d) ; 0.02 (d) ; 0.03 SEU Outdoor 3 x <0.01; 0.01; 0.016; 0.02 (d) ; 0.03 (d) ; 0.04 EU Indoor <0.01; 0.01 (d) ; (d) ; 2 x 0.017; 0.018; 0.022; (d) Spinach NEU Outdoor 0.02; 0.04; 0.04 (e) ; Spinach Spinach and similar (leaves) (252000) SEU 0.03 (e) ; 2 x 0.05; (a): NEU (Northern and Central Europe), SEU (Southern Europe and Mediterranean), EU (i.e. indoor use) or Import (country code) (EC, 2011). (b): Median value of the individual trial results according to the risk assessment residue definition. (c): Highest value of the individual trial results according to the risk assessment residue definition. (d): Highest values measured in the decline studies at a longer PHI (lettuce outdoor: days; lettuce indoor: days) than the PHI of the intended GAPs. (e): Highest values measured in the decline studies at a longer PHI (spinach: 21 days) than the PHI of the intended GAP. EFSA Journal 2012;10(9):

16 Effect of industrial processing and/or household preparation Modification of the existing MRLs for fluopicolide in various crops The effect of processing on the nature of fluopicolide was investigated during the peer review and fluopicolide was shown to be hydrolytically stable under conditions representing pasteurisation, baking/brewing/boiling and sterilisation (20 minutes at 90 C, ph 4; 60 minutes at 100 C ph 5; 20 minutes at 120 C, ph 6). Thus, for processed commodities the same residue definition as for raw agricultural commodities (RAC) is applicable (EFSA, 2009b). The effect of processing under hydrolytic conditions of the metabolite M-01 was not investigated. EFSA considers that the data gap has a negligible impact on the overall dietary risk assessment because of the low residue levels of M- 01 observed in crops under consideration. Specific studies to assess the magnitude of fluopicolide residues during the processing of the crops under consideration were not provided. However they are not necessary as either the crop is mostly eaten raw (i.e. lettuce) or the residue levels in raw agricultural commodities (RAC) did not exceed the trigger value of 0.1 mg/kg and the total theoretical maximum daily intake (TMDI) amounts to less than 10 % of the ADI (EC, 1997d) Rotational crops Preliminary considerations The residues of fluopicolide in rotational crops are of no relevance for the import tolerance application submitted by the EMS-UK, but lettuce and other salad plants, herbs and spinach can be grown in rotation with other plants and therefore the possible occurrence of residues in succeeding crops resulting from the use on primary crops has to be assessed. The soil degradation studies demonstrated that the degradation rate of fluopicolide is slow; the maximum DT 90f was of 1184 days. Furthermore, the metabolite M-01 was also persistent in soil, with a maximum DT 90f of 1046 days. The rate of degradation in soil was investigated for other fluopicolide metabolites out of which metabolites M and M were found to be moderately to highly persistent in the soil, with a maximum DT 90f of 432 days and 840 days, respectively (EFSA, 2009b). Since the trigger value of 100 days is exceeded, further studies investigating the nature and magnitude of the compound and its metabolites uptake in rotational crops are required (EC, 1997c) Nature of residues The metabolism of fluopicolide in rotational crops was investigated in wheat, lettuce and radishes during the peer review. The crops were grown in soil treated with fluopicolide labelled in either the phenyl or the pyridinyl ring at a rate of 0.4 kg a.s./ha (the United Kingdom, 2005). The overview of the study designs and the details of the results are reported in the conclusion of the peer review and in a previous EFSA reasoned opinion (EFSA, 2009b, 2012). The metabolism in rotational crops showed to be similar to the pathway observed in primary crops, thus the same residue definitions apply (EFSA, 2009b) Magnitude of residues Rotational field crop studies were assessed in the DAR and in the conclusion of the peer review (the United Kingdom, 2005; EFSA, 2009b). Nine field trials were conducted growing winter wheat, spring wheat, field beans and cabbage in soil previously used to grow potatoes, which had been treated with foliar applications of fluopicolide (4 x 0.1 kg a.s./ha). In the rotational crops the residues of fluopicolide were below the LOQ (0.01 mg/kg) at maturity with the exception of wheat straw (0.12 mg/kg). With regard to the occurrence of the metabolites, individual residues were low (<0.1 mg/kg), with M-01 found in quantifiable concentrations in cabbage (maximum 0.04 mg/kg) and wheat straw (maximum 0.03 mg/kg). 14 M-05: 3-methylsulfinyl-5-trifluoro-methylpyridine-2-carboxylic acid. See Appendix D. 15 M-10: 3-sulfo-5-trifluoromethyl pyridine-2-carboxylic acid. See Appendix D. EFSA Journal 2012;10(9):

17 As the seasonal application rates of fluopicolide on the crops under consideration are lower (0.75N) than the investigated ones, EFSA concludes that relevant residue levels of fluopicolide and its metabolites are unlikely to occur in rotational crops provided that the compound is used on lettuce and other salad plants, fresh herbs and spinach and similar (leaves) according to the proposed GAPs Nature and magnitude of residues in livestock Among the crops under consideration sugar beet root, for which an import tolerance request was made, may potentially enter the European feed market 16. Since sugar beet root may be fed to livestock, the nature and magnitude of fluopicolide 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 sugar beet roots and from all other feed products on which the existing EU MRL is set above the LOQ (head cabbage, kale, potatoes). To refine the calculations, EFSA used the risk assessment values reported for fluopicolide and M-01 in previously issued EFSA reasoned opinions (EFSA, 2011, 2012). The input values for the dietary burden calculation are summarised in Table 3-4. Table 3-4: Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value Risk assessment residue definition: fluopicolide Comment Input value Comment Sugar beet 0.04 Median residue 0.06 Highest residue Head cabbage 0.02 Median residue (EFSA, 2011) Kale 0.75 Median residue (EFSA, 2012) Potato 0.01 Median residue (EFSA, 2012) Risk assessment residue definition: M-01 (2,6-dichlorobenzamide) 0.18 Highest residue (EFSA, 2011) 0.84 Highest residue (EFSA, 2012) 0.02 Highest residue (EFSA, 2012) Sugar beet 0.01 Median residue 0.01 Highest residue Head cabbage 0.01 Median residue (EFSA, 2011) Kale 0.02 Median residue (EFSA, 2012) Potato 0.01 Median residue (EFSA, 2012) 0.01 Highest residue (EFSA, 2011) 0.02 Highest residue (EFSA, 2012) 0.01 Highest residue (EFSA, 2012) In order to estimate the contribution of fluopicolide and M-01 residues from sugar beet to the total livestock dietary exposure compared with the existing uses on products used as feed items (EFSA, 16 EFSA did not consider the livestock exposure to fluopicolide and M-01 residues originating from the non-european use on sugar beet leaves, because this part of the plant is unlikely to be imported to Europe for livestock feeding. EFSA Journal 2012;10(9):

18 2012), EFSA performed two dietary burden calculations: in Scenario 1 sugar beet was included in the calculation, while in Scenario 2 sugar beet was excluded from the dietary burden calculation. The results of the dietary burden calculation are summarised in the following tables. Table 3-5: Results of the dietary burden calculation Scenario 1 (including sugar beet) Maximum dietary burden (mg/kg bw per d) Risk assessment residue definition: fluopicolide Median dietary burden (mg/kg bw per d) Highest contributing commodity (a) Max dietary burden (mg/kg DM) Trigger exceeded (Y/N) Dairy ruminants Kale 2.19 Y Meat ruminants Kale 2.28 Y Poultry Kale 0.36 Y Pigs Kale 1.08 Y Risk assessment residue definition: M-01 (2,6-dichlorobenzamide) Dairy ruminants Kale 0.07 N Meat ruminants Kale 0.09 N Poultry Potatoes 0.02 N Pigs Potatoes 0.06 N (a): Calculated for the maximum dietary burden Table 3-6: Results of the dietary burden calculation Scenario 2 (excluding sugar beet) Maximum dietary burden (mg/kg bw per d) Risk assessment residue definition: fluopicolide Median dietary burden (mg/kg bw per d) Highest contributing commodity (a) Max dietary burden (mg/kg DM) Trigger exceeded (Y/N) Dairy ruminants Kale 2.14 Y Meat ruminants Kale 2.18 Y Poultry Kale 0.33 Y Pigs Kale 0.98 Y Risk assessment residue definition: M-01 (2,6-dichlorobenzamide) Dairy ruminants Kale 0.07 N Meat ruminants Kale 0.09 N Poultry Potatoes 0.02 N Pigs Potatoes 0.06 N (a): Calculated for the maximum dietary burden The calculated dietary burdens for fluopicolide indicated that in both scenarios (with and without sugar beet) the trigger value of 0.1 mg/kg dry matter (DM) was exceeded for all relevant livestock species. However it was driven by the existing uses (mainly kale) and the contribution of fluopicolide residues in sugar beet to the total livestock exposure is insignificant. EFSA Journal 2012;10(9):

19 The calculated dietary burden for M-01 indicated that in both scenarios (with and without sugar beet) the trigger value of 0.1 mg/kg dry matter (DM) was not exceeded for any relevant livestock species. EFSA is of the opinion that the presence of residues of fluopicolide and its metabolite M-01 on sugar beet treated according to the authorised GAP in USA is not requiring revising the existing MRLs for animal commodities established in Regulation (EC) No 396/2005. EFSA Journal 2012;10(9):

20 4. Consumer risk assessment The 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 17 (EFSA, 2007). Separate consumer exposure assessments were performed with regard to the exposure to fluopicolide and metabolite M-01 residues. For the calculation of the chronic exposure, EFSA used the median residue values as derived for fluopicolide and M-01 from the residue trials on the crops under consideration (see Table 3-2 and Table 3-3, respectively), the median residue values reported in previously issued EFSA reasoned opinions (EFSA, 2011, 2012), in the peer review conclusion (EFSA, 2009b) and by the JMPR (FAO, 2010). For the remaining commodities of plant and animal origin, the existing MRLs as established in Annexes IIIA of Regulation (EC) No 396/2005 were used as input values for fluopicolide. It is noted that the chronic risk assessment for the metabolite M-01 is not finalised as no information is available on its concentration in the commodities for which the existing MRLs are used as input values. A full chronic risk assessment for M-01 will be performed in the framework of Article 12 of the Regulation (EC) No 396/2005. However, it is unlikely that the metabolite would pose a public health concerns due to the very low residues levels observed in crops for human consumption. The model assumptions for the long-term exposure assessment are considered to be sufficiently conservative for a first tier exposure assessment, assuming 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. However, if this first tier exposure assessment does not exceed the toxicological reference value for long-term exposure (i.e. the ADI), a consumer health risk can be excluded with a high probability. The acute exposure assessment was performed only with regard to the commodities under consideration assuming the consumption of a large portion of the food items as reported in the national food surveys containing residues at the highest level as observed in supervised field trials. A variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation, when required (EFSA, 2007). The input values used for the dietary exposure calculation are summarised in Table 4-1. Table 4-1: Input values for the consumer dietary exposure assessment Commodity Chronic exposure assessment Acute exposure assessment Input value Risk assessment residue definition: fluopicolide Comment Radishes 0.03 Median residue (import, USA) Carrots 0.03 Median residue (import, USA) Sugar beet 0.04 Median residue (import, USA) Lettuce and other salad plant, except scarole 1.09 Median residue (lettuce, indoor) Input value Comment 0.1 Highest residue (import, USA) 0.13 Highest residue (import, USA) 0.06 Highest residue (import, USA) 4.9 Highest residue (lettuce, indoor) 17 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 2012;10(9):