REASONED OPINION. European Food Safety Authority 2. European Food Safety Authority (EFSA), Parma, Italy

EFSA Journal 2014;12(1):3543 REASONED OPINION Reasoned opinion on the modification of maximum residue levels (MRLs) for fipronil following the withdrawal of the authorised uses on kale and head cabbage 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT In accordance with Article 43 of Regulation (EC) No 396/2005, EFSA received a request of the European Commission for a scientific opinion on the modification of MRLs for the active substance fipronil. The European Commission requested EFSA to recalculate the MRLs for fipronil in animal commodities which were recommended by EFSA in its previous reasoned opinion on the review of the existing MRLs for fipronil according to Article 12 of Regulation (EC) No 396/2005, and to update EFSA s conclusion on the safety of all proposed MRLs. For this assessment EFSA was also requested to take into account the existing emergency authorisation of fipronil on potatoes as granted in Germany and the recent withdrawal of fipronil authorisations in Europe on head cabbage and kale. MRL proposals were derived by EFSA according to different scenarios, as requested by the European Commission, and a consumer risk assessment was carried out for each scenario. Regardless of the scenario presented, no information required by the regulatory framework was found to be missing and no risk to consumers was identified. European Food Safety Authority, 2014 KEY WORDS fipronil, potatoes, food of animal origin, consumer risk assessment, phenylpyrazole, insecticide 1 On request from the European Commission, Question No EFSA-Q-2013-00843, approved on 15 January 2014. 2 Correspondence: pesticides.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority, 2014. Reasoned opinion on the modification of maximum residue levels (MRLs) for fipronil following the withdrawal of the authorised uses on kale and head cabbage. EFSA Journal 2014;12(1):3543, 37 pp. doi:10.2903/j.efsa.2014.3543 Available online: www.efsa.europa.eu/efsajournal European Food Safety Authority, 2014

SUMMARY In accordance with Article 43 of Regulation (EC) No 396/2005, EFSA received on 14 October 2013 a request of the European Commission to recalculate the maximum residue levels (MRLs) for fipronil in animal commodities which were previously recommended by EFSA in the framework of Article 12 of Regulation (EC) No 396/2005 (hereafter referred to as the Article 12 MRL review) and to update EFSA`s conclusion on the safety of all proposed MRLs. For this purpose EFSA was requested to take into account the recent amendments of Annex I to Regulation (EC) No 396/2005 as regards food of animal origin (replacing meat by muscle) and the recent withdrawal of the authorisations on head cabbage and kale; all other uses evaluated under the Article 12 MRL review are to be considered in EFSA s assessment (scenario 1). EFSA was also requested to assess another scenario where, in addition to the uses evaluated under the Article 12 MRL review (except head cabbage and kale), the emergency authorisation of fipronil on potatoes would be granted in Germany according to Article 53 of Regulation (EC) No 1107/2009 (scenario 2). EFSA bases its assessment on the conclusion on the peer review of the risk assessment of fipronil, the Draft Assessment Report (DAR) and its addenda prepared under Council Directive 91/414/EEC, as well as the reasoned opinions of EFSA on the review of the existing MRLs for fipronil and on the modification of the existing MRLs for fipronil in poultry fat. The following conclusions were derived. The toxicological profile of fipronil was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.0002 mg/kg bw per day and an ARfD of 0.009 mg/kg bw. Nature and magnitude of fipronil residues in primary crops resulting from the authorised uses of fipronil were already assessed during the previous assessments of EFSA, where the residue definitions for enforcement and risk assessment were proposed as the sum of fipronil and its sulfone metabolite (MB43136) expressed as fipronil. Validated analytical methods for enforcement of the proposed residue definitions were available with an LOQ of mg/kg in high oil content, high water content and dry commodities. The number of residues trials was sufficient to estimate residue levels in all crops considered in this assessment, and adequate MRL and risk assessment values could be derived by EFSA. The studies on the nature and magnitude of fipronil in rotational crops demonstrate that significant residues are not expected in rotational crops if fipronil is used on primary crops according to the GAPs considered for the current opinion. Regarding livestock, nature of residues was also assessed during the previous assessments of EFSA and the same residue definitions were derived as for the plant commodities. The residues in livestock were considered fat soluble and validated analytical methods for enforcement of the proposed residue definitions were available with an LOQ of 0.002 mg/kg in milk and mg/kg in other livestock commodities. The magnitude of residues in livestock commodities was re-calculated in the present assessment according to two different scenarios, as requested by the European Commission. Regardless of the scenario selected, data were sufficient to derive adequate MRL proposals and risk assessment values. The consumer risk assessment was performed for both scenarios requested by the European Commission using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). According to the first scenario (disregarding the emergency authorisation on potatoes), the highest chronic exposure was calculated for French toddlers (53 % of the ADI), and the highest acute exposure was calculated for milk (10 % of the ARfD). According to the second scenario (including the emergency authorisation on potatoes), the highest chronic exposure was also calculated for French toddlers (86 % of the ADI), and the highest acute exposure was calculated for milk (12 % of the ARfD). EFSA therefore concludes that both scenarios requested by the European Commission are unlikely to pose a consumer health risk. It is noted that new restrictions on the authorisations of fipronil in Europe have been established by Commission Implementing Regulation (EU) No 781/2013. Member States EFSA Journal 2014;12(1):3543 2

should implement these restrictions by 31 December 2013 with a period of grace expiring on 28 February 2014 at the latest. According to those restrictions, the reported uses on maize, sunflower, oilseed rape and potatoes should have been withdrawn, resulting in a situation where no more uses are authorised on feed crops in Europe. Risk managers should therefore consider, regardless of the scenarios presented in this reasoned opinion, whether it would not be more appropriate to establish the MRLs for maize, sunflower, oilseed rape, potatoes and commodities of animal origin at the level of their respective LOQs. An overview of the overall assessment is provided in the summary table. SUMMARY TABLE Code Commodity Existing Proposed EU MRL Justification for the proposal number (a) EU MRL Scenario Scenario 1 (b) 2 (c) Enforcement residue definition: sum of fipronil and its sulfone metabolite (MB43136) expressed as fipronil (F) 0220020 Onions 0.02 0.02 0.02 These MRL proposals are adequately 0220030 Shallots 0.02 0.02 0.02 supported by data and no risk to consumers is identified, regardless of 0241010 Broccoli 0.02 0.01 0.01 the scenarios requested by the EC. 0241020 Cauliflower 0.02 0.01 0.01 Also considering the most recent 0242010 Brussels sprouts 0.02 0.01 0.01 restrictions for the approval of 0270060 Leek 0.01 0.01 0.01 fipronil, these MRL proposals are still valid. 0211000 Potatoes 0.01 * 0.01 These MRL proposals are adequately 0401050 Sunflower seed * * * supported by data and no risk to consumers is identified, regardless of 0401060 Rape seed * * * the scenarios requested by the EC. 0500030 Maize grain * * * However, considering the latest 1011010 Swine muscle 0.02 * * restrictions on the approval of 1011020 Swine fat 0.1 0.015 0.07 fipronil, residues are no longer expected in these commodities and 1011030 Swine liver 0.02 * 0.015 lowering of MRLs to the LOQ might 1011040 Swine kidney 0.02 * 0.015 be more appropriate in these 1012010 Bovine muscle 0.02 * 0.006 commodities. 1012020 Bovine fat 0.5 0.06 0.09 1012030 Bovine liver 0.1 0.015 0.02 1012040 Bovine kidney 0.02 0.009 0.015 1013010 Sheep muscle 0.02 * 0.006 1013020 Sheep fat 0.5 0.06 0.09 1013030 Sheep liver 0.1 0.015 0.02 1013040 Sheep kidney 0.02 0.009 0.015 1014010 Goat muscle 0.02 * 0.006 1014020 Goat fat 0.5 0.06 0.09 1014030 Goat liver 0.1 0.015 0.02 1014040 Goat kidney 0.02 0.009 0.015 1016010 Poultry muscle 0.01 * 0.015 1016020 Poultry fat 0.01 0.006 0.02 1016030 Poultry liver 0.02 * 0.015 1020010 Cattle milk * 0.008 0.01 1020020 Sheep milk * 0.008 0.01 1020030 Goat milk * 0.008 0.01 1030000 Birds' eggs 0.02 * 0.015 EFSA Journal 2014;12(1):3543 3

Code Commodity Existing Proposed EU MRL Justification for the proposal number (a) EU MRL Scenario Scenario 1 (b) 2 (c) - Other products of See - - There are no relevant authorisations plant and animal App. C or import tolerances reported at EU origin level. Existing MRLs should be lowered to the appropriate LOQ. (*): Indicates that the MRL is set at the limit of analytical quantification. (a): According to Annex I of Regulation (EC) No 396/2005. (b): Includes all uses evaluated under the Article 12 MRL review (except head cabbage and kale). (c): Includes all uses evaluated under the Article 12 MRL review (except head cabbage and kale) and the emergency authorisation on potatoes. (F): Fat-soluble. EFSA Journal 2014;12(1):3543 4

TABLE OF CONTENTS Abstract... 1 Summary... 2 Table of contents... 5 Background... 6 Terms of reference... 7 The active substance and its use pattern... 7 Assessment... 9 1. Method of analysis... 9 1.1. Methods for enforcement of residues in food of plant origin... 9 1.2. Methods for enforcement of residues in food of animal origin... 9 2. Mammalian toxicology... 9 3. Residues... 10 3.1. Nature and magnitude of residues in plant... 10 3.1.1. Primary crops... 10 3.1.2. Rotational crops... 13 3.2. Nature and magnitude of residues in livestock... 13 3.2.1. Dietary burden of livestock... 13 3.2.2. Nature of residues... 15 3.2.3. Magnitude of residues... 15 4. Consumer risk assessment... 19 Conclusions and recommendations... 22 References... 24 Appendix A Good Agricultural Practice (GAPs)... 26 Appendix B Pesticide Residue Intake Model (PRIMo)... 27 Appendix C - Existing EU maximum residue levels (MRLs)... 32 Appendix D List of metabolites and related structural formula... 36 Abbreviations... 37 EFSA Journal 2014;12(1):3543 5

BACKGROUND Fipronil is an active substance in plant protection products and was included in Annex I to Directive 91/414/EEC 3 in 2007. MRLs for fipronil are set in Annex III A to Regulation (EC) No 396/2005 4 and were last modified by Commission Regulation (EU) No 750/2010 5. On 26 April 2012, EFSA provided a Reasoned Opinion on the review of the existing MRLs for fipronil in compliance with Article 12(2) of Regulation (EC) No 396/2005 in conjunction with Article 12(1) thereof. In that Reasoned Opinion, EFSA recommended MRLs for various commodities including head cabbage and kale. An additional use on potato as a band application with incorporation (granular bait) was proposed during the Member States consultation. However, since the approval of the active substance restricts authorisations to uses as insecticide for use as seed treatment only, this GAP was not considered further in that opinion. Therefore, EFSA did not make a recommendation on the MRL on potatoes but suggested that risk managers consider either the specific limit of quantification or the default MRL of 0.01 mg/kg. Further to a special derogation granted by Germany in accordance with Article 53 of Regulation (EC) No 1107/2009 6 and Article 18(4) of Regulation (EC) No 396/2005 for the use of fipronil on potatoes (emergency authorisation), the Commission asked EFSA for a scientific opinion on the safety of the fipronil MRLs proposed by Germany. EFSA responded to that request with the publication of a Reasoned Opinion on the modification of the existing MRL for fipronil in poultry fat on 15 May 2012. Based on the results of the feeding studies carried out with fipronil, EFSA concluded that for the use of fipronil on potatoes not only the MRL for poultry fat needs to be modified, but also other existing EU MRLs for animal origin commodities have to be amended. However, a potential long-term consumer health risk cannot be excluded, resulting from the residues in animal commodities. EFSA suggested considering either feeding studies to allow for further refinements of the chronic consumer risk assessment, or risk management options such as the withdrawal of authorisations for crops which have a significant influence on the dietary burden for milk ruminants, e.g. the uses on cabbage and kale. Subsequently, the authorisation holder for the uses on head cabbage and kale withdrew the authorisations. The withdrawal was confirmed by the competent national authority of the Netherlands. Meanwhile, Annex I to Regulation (EC) No 396/2005 was also replaced by Commission Regulation (EU) No 212/2013 7 which entered into force on 01 April 2013. Among other changes, meat as an individual product to which MRLs apply was replaced with muscle. This may have an impact on the concerned MRLs for the fat-soluble substance fipronil. On 14 October 2013, in light of the changes made to Annex I to Regulation (EC) No 396/2005 and the withdrawal of the authorisations on head cabbage and kale, EFSA received in compliance with Article 43 of that regulation a request from the European Commission to recalculate the expected residue levels of fipronil in commodities of animal origin and the consumer exposure resulting from 3 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, 19.8.1991, p. 1-32. 4 Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. OJ L 70, 16.03.2005, p. 1-16. 5 Commission Regulation (EU) No 750/2010 of 7 July 2010 amending Annexes II and III to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards maximum residue levels for certain pesticides in or on certain products. OJ L 220, 21.8.2010, p. 1 56. 6 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, 24.11.2009, p. 1-50. 7 Commission Regulation (EU) No 212/2013 of 11 March 2013 replacing Annex I to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards additions and modifications with respect to the products covered by that Annex. OJ L 68, 12.3.2013, p. 30 52. EFSA Journal 2014;12(1):3543 6

those residue levels. The European Commission considers that the available data should be assessed for two different scenarios to allow risk managers to understand the impact of both options. The request was included in the EFSA Register of Questions with the reference number EFSA-Q-2013-00843. TERMS OF REFERENCE The European Commission requested EFSA to recalculate the MRLs for fipronil in animal commodities which were recommended in its reasoned opinion on the review of the existing MRLs for fipronil according to Article 12 (hereafter referred to as the Article 12 MRL review), and to update its conclusion on the safety of all proposed MRLs. For this assessment EFSA should take into account Annex I to Regulation (EC) No 396/2005 in its present form, as well as the withdrawal of authorisations on head cabbage and kale as reported by the competent national authority of the Netherlands in September 2012. All other uses evaluated under the Article 12 MRL review (EFSA, 2012a) should be taken into account. EFSA is also requested to carry out the assessment for two scenarios: 1) absence of any uses for fipronil on potato; 2) use of fipronil as a band application with incorporation (granular bait) on potatoes as assessed in the EFSA reasoned opinion on the modification of the existing MRLs for fipronil in poultry fat (EFSA, 2012b). EFSA was requested to provide this assessment by 15 January 2014. THE ACTIVE SUBSTANCE AND ITS USE PATTERN Fipronil is the ISO common name for (±)-5-amino-1-(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4- trifluoromethylsulfinylpyrazole-3-carbonitrile (IUPAC). Molecular weight: 437.2 Fipronil has activity against various soil insects during their larval growth stage by contact and ingestion. The biochemical mode of action is explained by interfering with the passage of chloride ions through the GABA chloride channel having an effect on the neurotransmission. It is not clear whether fipronil is considered as a systemic molecule; however, some uptake by the plants is likely (EFSA, 2013). Fipronil was evaluated in the framework of Directive 91/414/EEC with France being the designated rapporteur Member State (RMS). Following the peer review a decision on inclusion of the active substance in Annex I to Directive 91/414/EEC was taken in 2007 by means of Commission Directive 2007/52/EC 8. EFSA conclusion on the peer review of the risk assessment of fipronil is available 8 Directive 2007/52/EC of 16 August 2007 amending Council Directive 91/414/EEC to include ethoprophos, pirimiphosmethyl and fipronil as active substances, OJ L 214, 17.8.2007, p. 3-8. EFSA Journal 2014;12(1):3543 7

(EFSA, 2006). According to Regulation (EU) No 540/2011 9, fipronil was approved under Regulation (EC) No 1107/2009. The approval was restricted to use as an insecticide for seed treatment only and only where the seed coating is performed in professional seed treatment facilities. In August 2012, European Commission asked EFSA to perform a risk assessment for the active substance fipronil and to provide conclusions as regards the risk to bees. EFSA performed the risk assessment on the basis of the evaluation of the currently authorised uses of fipronil on a variety of crops in Europe and issued a conclusion on the peer review of the pesticide risk assessment for bees for the active substance fipronil (EFSA, 2013). As a consequence of this assessment, additional use restrictions of fipronil were introduced by means of Commission Implementing Regulation (EU) No 781/2013 10. Member states should implement these restrictions by 31 December 2013 with a period of grace expiring on 28 February 2014 at the latest. According to this Regulation, only uses of fipronil as insecticide for seed treatment may be authorized; uses shall only be authorized for seeds intended to be sown in greenhouses and seeds of leek, onions, shallots and the group of Brassica vegetables intended to be sown in fields and harvested before flowering. The existing EU MRLs for fipronil are established in Annex IIIA of Regulation (EC) No 396/2005 (Appendix C). In accordance with the provisions of Article 12(2) of Regulation (EC) No 396/2005, the EU MRLs for fipronil in April 2012 were reviewed by EFSA (EFSA, 2012a); these recommendations which reflect the GAPs authorised in Member States in 2012 (thus, before the restrictions of Regulation 781/2013 entered into force) are also reported in Appendix C. EFSA recommended raising the existing MRL for kale, lowering the existing MRLs for broccoli, cauliflower, Brussels sprouts and head cabbage and deleting the MRLs for potatoes and sugar beet since the GAPs were no longer authorised. EFSA confirmed the existing MRLs for onions, shallots, leek, sunflower seed, rapeseed and maize. For food of animal origin, EFSA calculated the expected residue concentrations for animal tissues, milk and eggs resulting from the residues in feed and derived recommendations for amending the existing MRLs. In May 2012 EFSA received a request from Germany to raise the MRL for fipronil in poultry fat as a consequence of an emergency authorisation of fipronil on potatoes granted in Germany according to Article 53 of Regulation (EC) No 1107/2009. An EFSA reasoned opinion was issued but MRL proposals were not derived due to a potential long-term consumer health risk from the intake of animal commodities (milk) (EFSA, 2012b). In order to avoid consumer intake concerns and maintain the emergency authorisation on potatoes, EFSA suggested withdrawing authorisations for crops which have a significant influence on the dietary burden for milk ruminants (i.e., cabbage and kale). As a consequence, the authorisation holder decided in September 2012 to withdraw the uses of fipronil on head cabbage and kale. The European Commission now requested EFSA to recalculate the MRLs for fipronil in animal commodities as proposed under Article 12 MRL review and to update the consumer exposure calculation, considering the withdrawal of authorisations of fipronil on kale and cabbage, but still considering the emergency use on potatoes and other uses reported under Article 12 MRL review. All GAPs that need to be considered in the present assessment, as requested by the European Commission, are summarised in Appendix A. EFSA notes that meanwhile the reported uses on maize, sunflower, oilseed rape and potatoes should have been withdrawn in compliance with Commission Implementing Regulation (EU) No 781/2013 (see above). Although these restrictions result from the risk assessment for bees, MRLs should in principle be established on the basis of the authorised uses, and uses on maize, sunflower, oilseed rape and potatoes should no longer be considered for the MRL setting. Nevertheless, those uses were taken into account for the present assessment, as this was specifically requested by the European Commission. 9 Regulation (EU) No 540/2011 of 25 May 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards the list of approved active substances, OJ L 153, 11.6.2011, p. 63-64. 10 Commission Implementing Regulation (EU) No 781/2013 of 14 August 2013 amending Implementing Regulation (EU) No 540/2011, as regards the conditions of approval of the active substance fipronil, and prohibiting the use and sale of seeds treated with plant protection products containing this active substance, OJ L 219, 15.8.2013, p.22-25. EFSA Journal 2014;12(1):3543 8

ASSESSMENT EFSA bases its assessment on the conclusion on the peer review of the pesticide risk assessment of the active substance fipronil (EFSA, 2006), the Draft Assessment Report (DAR) and its addenda prepared under Council Directive 91/414/EEC (France, 2004, 2006) as well as the previous reasoned opinions of EFSA on the review of the existing MRLs for fipronil (EFSA, 2012a) and the modification of the existing MRLs for fipronil in poultry fat (EFSA, 2012b). 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 546/2011 11 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, 2010a, 2010b, 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 fipronil residues in plant commodities were assessed in the framework of the peer review under Directive 91/414/EEC and in the Article 12 MRL review (EFSA, 2006, 2012a). EFSA concluded that residues of fipronil and its sulfone metabolite MB46136 12 - both are part of the residue definition- can be controlled in food of plant origin with a combined LOQ of mg/kg in high oil content, dry, and high water content commodities. Thus, sufficiently validated analytical methods are available to control fipronil residues in the crops for which uses are reported. 1.2. Methods for enforcement of residues in food of animal origin The analytical methods for the determination of residues of fipronil and the sulfone metabolite in commodities of animal origin were evaluated in the peer review under Directive 91/414/EEC and in the Article 12 MRL review (EFSA, 2006, 2012a). EFSA concluded that sufficiently validated analytical methods are available for enforcing fipronil MRLs according to the enforcement residue definition for food of animal origin (sum of fipronil and its sulfone metabolite MB46136 expressed as fipronil) with a combined LOQ of mg/kg in milk, meat, fat, liver, kidney and eggs. 2. Mammalian toxicology The toxicological profile of fipronil was assessed in the framework of the peer review under Directive 91/414/EEC (EFSA, 2006). The data were sufficient to derive toxicological reference values for fipronil which are compiled in Table 2-1. Table 2-1: Overview of the toxicological reference values Fipronil Source Year Value Study relied upon Safety factor ADI EFSA 2006 0.0002 mg/kg bw per day Rat, carcinogenicity study 100 ARfD EFSA 2006 0.009 mg/kg bw Rat, developmental neurotoxicity study 100 11 Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. OJ L 155, 11.06.2011, p. 127-175. 12 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfonyl]-1H-pyrazole-3-carbonitrile, see Appendix D EFSA Journal 2014;12(1):3543 9

3. Residues Modification of MRLs for fipronil following the withdrawal of uses on head cabbage and kale 3.1. Nature and magnitude of residues in plant 3.1.1. Primary crops The metabolism of fipronil in primary crops was evaluated in the framework of the peer review under Directive 91/414/EEC and the MRL review under Article 12 of Regulation (EC) No 396/2005 (EFSA, 2006, 2012a). Based on metabolism studies in five different crops using either soil application or seed treatment, it was concluded to set the residue definition for enforcement and risk assessment in all plant commodities as the sum of fipronil and its sulfone metabolite (MB46136), expressed as fipronil. For the reported uses of fipronil, the plant metabolism is sufficiently addressed and the residue definitions for risk assessment and enforcement agreed at EU level are applicable. 3.1.1.1. Magnitude of residues The supervised residue trials on the crops for which the uses of fipronil are reported in Appendix A have been assessed in the Article 12 MRL review (EFSA, 2012a) or in the EFSA reasoned opinion on the modification of the existing MRLs for fipronil in poultry fat (EFSA, 2012b). For reasons of transparency, the residue trials data are summarized in the Table 3-1. The residue trials data are considered valid with regard to storage stability and analytical methods (EFSA, 2012a, 2012b). EFSA Journal 2014;12(1):3543 10

Table 3-1: Overview of the available residues trials data Commodity Residue region (a) Outdoor /Indoor Individual trial results Enforcement (sum of fipronil and sulfone metabolite (MB 46136) expressed as fipronil) Potatoes NEU Outdoor 3 x 0.0016; 2 x <0.02; 0.0025; 0.0027; 2 x 0.003; 0.0034; 0.0036; 0.0037; ; 4; 0.006 Onion Shallot Broccoli, Cauliflower Brussels sprout NEU Outdoor 0.0024; 0.0025; 2 x 0.004; ; 0.006; 0.008; 0.011 Risk assessment (sum of fipronil and sulfone metabolite (MB 46136) expressed as fipronil) 3 x 0.0016; 2 x <0.02; 0.0025; 0.0027; 2 x 0.003; 0.0034; 0.0036; 0.0037; ; 4; 0.006 0.0024; 0.0025; 2 x 0.004; ; 0.006; 0.008; 0.011 Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments 0.003 0.006 0.01 1.0 Trials compliant with GAP (EFSA, 2012b). R ber = 0.007 R max = 0.007 MRL OECD = 0.0094/0.01 0.0045 0.011 0.02 1.0 Trials on onions compliant with the GAP (EFSA, 2012a). R ber = 0.01 R max = 0.02 MRL OECD = 0.017/0.02 NEU Outdoor 23 x <0.004; 0.0091 23 x <0.004; 0.0091 <0.004 0.0091 0.01 1.0 Combined dataset on cauliflower (8), head cabbage (8) and Brussels sprouts (8) supporting the GAPs for all brassica vegetables (EFSA, 2012a). R ber = 0.0066 R max = 0.0081 MRL OECD = 0.0091/0.01 Leek NEU Outdoor 8 x <0.004; 5 8 x <0.004; 5 <0.004 5 0.01 1.0 Trials compliant with the GAP (EFSA, 2012a). R ber = 0.008 R max = 7 MRL OECD = 0.013/0.015 (e) EFSA Journal 2014;12(1):3543 11

Commodity Sunflower seed Rapeseed Residue region (a) Outdoor /Indoor Individual trial results Enforcement (sum of fipronil and sulfone metabolite (MB 46136) expressed as fipronil) Risk assessment (sum of fipronil and sulfone metabolite (MB 46136) expressed as fipronil) Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments NEU Outdoor 3 x <0.004 3 x <0.004 <0.004 <0.004 * 1.0 Trials on sunflower compliant with GAP (EFSA, 2012a). SEU Outdoor 6 x <0.004 6 x <0.004 <0.004 <0.004 * 1.0 Trials on sunflower compliant with GAP. Not authorized for use on rapeseed in SEU (EFSA, 2012a). Maize grain NEU Outdoor <0.004 <0.004 <0.004 <0.004 * 1.0 Trials compliant with GAP (EFSA, 2012a). SEU Outdoor 10 x <0.004 10 x <0.004 <0.004 <0.004 * 1.0 Trials compliant with GAP (EFSA, 2012a). Maize forage NEU Outdoor <0.001; 0.0011; 0.0018 <0.001; 0.0011; 0.0018 0.0011 0.0018 * 1.0 Trials compliant with GAP (EFSA, 2012a). R ber = - R max = 0.0046 MRL OECD = 0.0045/ SEU Outdoor 3 x <0.001; 0.0044 3 x <0.001; 0.0044 <0.001 0.0044 * 1.0 Trials compliant with GAP (EFSA, 2012a). R ber = 0.0071 R max = 0.0106 MRL OECD = 0.011/0.015 (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). (*): Indicates that the MRL is set at the limit of analytical quantification. (e) EFSA Journal 2014;12(1):3543 12

3.1.1.2. Effect of industrial processing and/or household preparation The effect of processing on the nature of fipronil was investigated in studies performed at three test conditions representing pasteurization, baking/brewing/boiling and sterilization (20 minutes at 90 C, ph 4; 60 minutes at 100 C ph 5; 20 minutes at 120 C, ph 6). The studies were reported in the DAR, in the conclusion on the peer review and the Article 12 MRL review (France, 2004; EFSA, 2006, 2012a). EFSA concluded that processing by pasteurisation, baking/brewing/boiling and sterilization is not expected to have a highly significant impact on the composition of residues (EFSA, 2006, 2012a). Thus, for processed commodities the same residue definition as for raw agricultural commodities (RAC) is applicable. The effect of processing on the magnitude of fipronil residues has been investigated in studies with sunflower seed, maize (EFSA, 2012a) and potatoes (EFSA, 2012b). In raw oilseed residues were below the LOQ and thus robust processing factors were not derived. For potatoes various processing factors were derived and proposed for inclusion in Annex VI of Regulation (EC) No 396/2005 (EFSA, 2012b). 3.1.2. Rotational crops In the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005, EFSA concluded that the studies on the metabolism of fipronil in rotational crops and the rotational crop field study were appropriate to demonstrate the absence of residues in rotational crops, provided that the compound is applied in compliance with the GAPs reported (EFSA, 2012a). As the GAP on potatoes is not more critical than the GAPs assessed under Article 12 the conclusion that no residues of fipronil or its sulfone metabolite are expected in rotational crops is valid also for the potato GAP. 3.2. Nature and magnitude of residues in livestock 3.2.1. Dietary burden of livestock Since potatoes, maize, sunflower seed, rape seed and their by-products can be fed to livestock, the nature and magnitude of fipronil residues in livestock was further assessed. Uses of fipronil on kale and head cabbage are no longer supported in Europe and therefore these crops were not included in the livestock dietary burden calculation. As requested by the European Commission, these calculations were carried out according to two different scenarios. The dietary burden of livestock was calculated considering the authorized uses of fipronil on maize, sunflower and oilseed rape as reported under Article 12 MRL review. Potatoes were excluded from the dietary burden calculation. The dietary burden of livestock was calculated considering the authorized uses of fipronil on maize, sunflower and oilseed rape as reported under Article 12 MRL review and the emergency authorisation of fipronil on potatoes as reported in the framework of the previous EFSA reasoned opinion on the modification of the existing MRLs in poultry fat (EFSA, 2012b). The median and maximum dietary burden of livestock was calculated according to both scenarios requested by the European Commission, 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). The input values for the relevant feed items were reported in the previous EFSA reasoned opinions (EFSA, 2012a, 2012b) and are compiled in the Table 3-2. EFSA Journal 2014;12(1):3543 13

Table 3-2: Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value Comment Input value Comment Risk assessment residue definition: sum of fipronil and its sulfone metabolite (MB 46136) expressed as fipronil Potatoes (a) 0.003 Median residue (EFSA, 2012b) Maize grain 0.004* Median residue (EFSA, 2012a) Maize silage 0.0011 Median residue (EFSA, 2012a) Rapeseed meal 0.004* Median residue (EFSA, 2012a) Sunflower seed meal 0.004* Median residue (EFSA, 2012a) (a): only in scenario 2 (*): Indicates that the input value is proposed at the limit of analytical quantification. 0.006 Highest residue (EFSA, 2012b) 0.004* Median residue (EFSA, 2012a) 0.0044 Highest residue (EFSA, 2012a) 0.004* Median residue (EFSA, 2012a) 0.004* Median residue (EFSA, 2012a) The results of the dietary burden calculation are summarised in the Table 3-3 (scenario 1) and in the Table 3-4 (scenario 2). Even though calculated animal intakes were well below the trigger of 0.1 mg/kg dry matter (DM) for both scenarios, there is a need to consider residues in animal products since fipronil is classified fat soluble and the ADI is very low. As requested in the terms of reference provided by the European Commission, the MRLs for food of animal origin derived under the Article 12 MRL review need to be reconsidered in view of the two scenarios. Table 3-3: Results of the dietary burden calculation excluding potatoes (scenario 1) Median dietary burden (mg/kg bw per d) Maximum dietary burden (mg/kg bw per d) Highest contributing commodity (a) Max dietary burden (mg/kg DM) Trigger exceeded (Y/N) Risk assessment residue definition: sum of fipronil and its sulfone metabolite (MB 46136) expressed as fipronil Dairy ruminants 0.00020 0.00080 Maize silage 0.022 N Meat ruminants 0.00024 0.00094 Maize silage 0.022 N Poultry 0.00024 0.00024 Maize grain 0.004 N Pigs 0.00014 0.00024 Maize silage 0.006 N (a): Calculated for the maximum dietary burden EFSA Journal 2014;12(1):3543 14

Table 3-4: Results of the dietary burden calculation including potatoes (scenario 2) Median dietary burden (mg/kg bw per d) Maximum dietary burden (mg/kg bw per d) Highest contributing commodity (a) Max dietary burden (mg/kg DM) Trigger exceeded (Y/N) Risk assessment residue definition: sum of fipronil and its sulfone metabolite (MB 46136) expressed as fipronil Dairy ruminants 0.00036 0.00100 Maize silage 0.027 N Meat ruminants 0.00061 0.00141 Potatoes 0.033 N Poultry 0.00049 0.00074 Potatoes 0.012 N Pigs 0.00056 0.00114 Potatoes 0.028 N (a): Calculated for the maximum dietary burden 3.2.2. Nature of residues The metabolism of fipronil in livestock was assessed in the peer review and in the Article 12 MRL review (EFSA, 2006, 2012a). EFSA concluded that the metabolism of fipronil in livestock was adequately elucidated to propose a general residue definition for enforcement and risk assessment as the sum of fipronil and its sulfone metabolite expressed as fipronil. The elevated residues in fat found in metabolism studies are consistent with the lipophilic nature of the compounds. The residues in animal commodities are therefore classified as fat soluble. 3.2.3. Magnitude of residues Livestock feeding studies were carried out on lactating cows (dose levels of 0.0011, 0.0031 and 0.0101 mg/kg bw per day for 35 consecutive days) and laying hens (dose levels of 0.0007, 0.0017 and 0.0067 mg/kg bw per day for 42 consecutive days) and were assessed in the peer review and in the Article 12 MRL review (EFSA, 2006, 2012a). Samples of muscle, fat, liver, kidneys, milk and eggs were taken from dosed animals and analysed for fipronil, its sulfone metabolite MB 46136 and its sulphide metabolite MB45950 13. As metabolite MB45950 was not detected in any of these studies, this compound was not further considered by EFSA. Results of both livestock feeding studies are summarised in Table 3-5. The available livestock feeding studies are also considered valid with regard to storage stability and analytical methods (EFSA, 2012a, 2012b). Consequently, the available data are considered sufficient for deriving MRLs in all commodities of animal origin according to both scenarios requested by the European Commission. These MRLs were derived in compliance with the latest recommendations on this matter (FAO, 2009) and are summarised in Table 3-5. EFSA notes that new restrictions on the authorisations of fipronil in Europe have been established by Commission Implementing Regulation (EU) No 781/2013. Member states should implement these restrictions by 31 December 2013 with a period of grace expiring on 28 February 2014 at the latest. According to those restrictions, fipronil can only be used for the seed treatment of crops grown in greenhouses and for the seed treatment of leek, onions, shallots and the group of Brassica intended to be sown in fields and harvested before flowering. This means that the currently reported uses on maize, sunflower, oilseed rape and potatoes should have been withdrawn, thus resulting in a situation where no more uses are authorised on feed crops in Europe. Consequently, regardless of the scenarios requested by the European Commission, all MRLs for fipronil in animal commodities should in principle be proposed at the LOQ of 0.002 mg/kg in milk and mg/kg in animal tissues and eggs. 13 5-amino-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-trifluoromethylthio-1-pyrazole-3-carbonitrile, see Appendix D EFSA Journal 2014;12(1):3543 15

Table 3-5: Overview of the values derived from the livestock feeding studies Modification of MRLs for fipronil following the withdrawal of uses on head cabbage and kale Commodity Dietary burden Results of the livestock feeding study Median residue No Enforcement (a) Risk Assessment (a) Median (mg/kg bw per day) Max. (mg/kg bw per day) Dose Level (mg/kg bw per day) Mean Max. Mean Max. Highest residue (b) MRL proposal CF for RA Enforcement and risk assessment residue definition: sum of fipronil and its sulfone metabolite expressed as fipronil Pig muscle 0.00014 0.00056 0.00024 0.00114 0.0011 3 <0.004 <0.004 See results for 0.0031 3 0.014 0.017 enforcement residue definition. 0.0101 3 0.046 0.066 * * 1.0 Pig fat 0.0011 3 0.055 0.063 0.0031 3 0.176 0.228 0.007 0.0101 3 0.501 0.588 0.028 0.014 0.066 0.015 0.070 1.0 Pig liver 0.0011 3 0.012 0.012 (c) 0.0031 3 0.049 0.061 (c) 0.0101 3 0.135 0.162 0.006 0.013 * 0.015 1.0 Pig kidney 0.0011 3 <0.01 <0.01 (c) 0.0031 3 0.019 0.024 0.0101 3 0.039 0.044 0.010 * 0.015 1.0 EFSA Journal 2014;12(1):3543 16

Commodity Dietary burden Results of the livestock feeding study Median residue No Enforcement (a) Risk Assessment (a) Median (mg/kg bw per day) Max. (mg/kg bw per day) Dose Level (mg/kg bw per day) Mean Max. Mean Max. Highest residue (b) MRL proposal CF for RA Poultry muscle 0.00024 0.00049 0.00024 0.00074 0.0007 10 <0.01 (c) <0.01 (c) See results for 0.0017 10 <0.01 (c) <0.01 (c) enforcement residue definition 0.0067 10 0.014 0.016 0.007 0.010 * 0.015 1.0 Poultry fat 0.0007 10 0.015 0.016 0.0017 10 0.062 0.07 0.0067 10 0.201 0.218 0.011 0.018 0.006 0.02 1.0 Poultry liver 0.0007 10 <0.01 (c) <0.01 (c) 0.0017 10 0.024 0.029 0.0067 10 0.079 0.081 0.007 0.011 * 0.015 1.0 Eggs 0.0007 24 (e) 0.01 (c) 0.013 (c) 0.0017 24 (e) 0.02 0.038 0.0067 24 (e) 0.084 0.126 0.007 0.014 * 0.015 1.0 (*): Indicates that the MRL is set at the limit of analytical quantification. (a): Some results of the livestock feeding study reported in the current table are slightly different from the results reported in the previous reasoned opinions of EFSA (2012a and 2012b). This is due to the correction of minor inconsistencies identified in the previous reasoned opinions. However, it is highlighted that those inconsistencies did not have any impact on the outcome of the previous assessments. (b): Median residue value according to the enforcement residue definition, derived by interpolation/extrapolation from the feeding study for the median dietary burden (FAO, 2009). (c): Highest residue value (tissues, eggs) or mean residue value (milk) according to the enforcement residue definition, derived by interpolation/extrapolation of the maximum dietary burden between the relevant feeding groups of the study (FAO, 2009). (d): The parent compound fipronil was not detectable at the relevant dose level. Since it was also not detectable at the next dose level, the contribution of parent fipronil was not taken into account for calculation of the total residue concentration (sum of fipronil and its sulfone metabolite). (e): Results derived from samples taken from day 7 until day 35 (7 sampling days, milk of 3 cows pooled and analysed in 3 replicates). (f): Results derived from samples taken from day 7 until day 41 (8 sampling days, eggs of 10 hens pooled and analysed in 3 replicates). EFSA Journal 2014;12(1):3543 18

4. Consumer risk assessment Following the emergency authorisation of fipronil on potatoes and the withdrawal of the authorised uses of fipronil on kale and cabbage, the European Commission requested EFSA to recalculate the consumer exposure to fipronil residues without consideration of kale and cabbage. In addition, EFSA was requested to consider two different scenarios where the potential use on potatoes is only considered in the second scenario. Chronic and acute exposure calculations reflecting both scenarios were performed using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo) (EFSA, 2007). The median and highest residue values selected for chronic and acute intake calculations in plant commodities are taken from the previous reasoned opinions of EFSA (2012a and 2012b) while the median and highest residue values selected for commodities of animal origin were derived in section 3.2.3, depending on the scenarios requested by the European Commission. Input values for both scenarios are summarised in Table 4-1 and Table 4-2. The contributions of other commodities, for which no relevant GAP was considered in the framework of this assessment, were not included in the calculation. The calculated exposures were compared with the toxicological reference values derived for fipronil (see Table 2-1); detailed results for the first scenario where the use on potatoes was not considered, are presented in Appendix B.1. The highest chronic exposure was calculated for French toddlers, representing 53 % of the ADI, and the highest acute exposure was calculated for milk, representing 10 % of the ARfD. Detailed results for the second scenario where the use on potatoes was considered, are presented in Appendix B.2. In this case, the highest chronic exposure was also calculated for French toddlers, but representing 86 % of the ADI, and the highest acute exposure was calculated for milk, representing 12 % of the ARfD. In its previous reasoned opinions, EFSA calculated that, prior to the withdrawal of the authorised uses on kale and cabbage, chronic exposure of European consumers to fipronil residues would amount to 92 % of the ADI in case the use on potatoes would not be authorised (EFSA, 2012a), and that this chronic exposure would increase to 149 % of the ADI in case the use on potatoes would be authorised (EFSA, 2012b). Based on the present calculations EFSA concludes that the withdrawal of the authorised uses on kale and cabbage has resulted in a significant reduction of the chronic exposure to a level that is unlikely to pose a public health concern, regardless whether the use on potatoes is authorised or not. In addition, it is noted by EFSA that new restrictions on the authorisations of fipronil in Europe have been established by Commission Implementing Regulation (EU) No 781/2013. Member states should implement these restrictions by 31 December 2013 with a period of grace expiring on 28 February 2014 at the latest. According to those restrictions, fipronil can only be used for the seed treatment of crops grown in greenhouses and for the seed treatment of leek, onions, shallots and the group of Brassica intended to be sown in fields and harvested before flowering. This means that uses on maize, sunflower, oilseed rape and potatoes, which have been considered in the above calculations upon request of the European Commission, should have been withdrawn, resulting in a situation where no more uses are authorised on feed crops in Europe. Consequently, regardless of the scenarios requested by the European Commission, residues in commodities of animal origin should in principle no longer occur, hereby further reducing the exposure of European consumers to fipronil residues. EFSA Journal 2014;12(1):3543 19

Table 4-1: Input values for the consumer dietary exposure assessment excluding potatoes (scenario 1) Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Risk assessment residue definition: sum of fipronil and its sulfone metabolite expressed as fipronil Onions 0.0045 Median residue (EFSA, 2012a) 0.011 Highest residue (EFSA, 2012a) Shallots 0.0045 Median residue (EFSA, 2012a) 0.011 Highest residue (EFSA, 2012a) Broccoli 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Cauliflower 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Brussels sprouts 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Leek 0.004* Median residue (EFSA, 2012a) 5 Highest residue (EFSA, 2012a) Sunflower seed 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Rape seed 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Maize grain 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Swine meat Median residue (a) 0.007 Highest residue (a) Swine fat 0.007 Median residue 0.014 Highest residue Swine liver * Median residue * Highest residue Swine kidney * Median residue * Highest residue Ruminant meat 0.006 Median residue (a) 0.015 Highest residue (a) Ruminant fat 0.012 Median residue 0.054 Highest residue Ruminant liver * Median residue 0.010 Highest residue Ruminant kidney * Median residue 0.009 Highest residue Poultry meat * Median residue (b) * Highest residue (b) Poultry fat * Median residue Highest residue Poultry liver * Median residue * Highest residue Ruminant milk 0.002* Median residue 0.007 Highest residue Birds' eggs * Median residue * Highest residue (*): Indicates that the input value is proposed at the limit of analytical quantification. (a): Consumption figures in the EFSA PRIMo are expressed as meat, therefore the median and highest residue values were calculated considering 80 % of the residue is derived from muscle and 20 % of the residue is derived from fat (FAO, 2009). (b): Consumption figures in the EFSA PRIMo are expressed as meat, therefore the median and highest residue values were calculated considering 90 % of the residue is derived from muscle and 10 % of the residue is derived from fat (FAO, 2009). EFSA Journal 2014;12(1):3543 20

Table 4-2: Input values for the consumer dietary exposure assessment including potatoes (scenario 2) Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Risk assessment residue definition: sum of fipronil and its sulfone metabolite expressed as fipronil Potatoes 0.003 Median residue (EFSA, 2012b) 0.006 Highest residue (EFSA, 2012b) Onions 0.0045 Median residue (EFSA, 2012a) 0.011 Highest residue (EFSA, 2012a) Shallots 0.0045 Median residue (EFSA, 2012a) 0.011 Highest residue (EFSA, 2012a) Broccoli 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Cauliflower 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Brussels sprouts 0.004* Median residue (EFSA, 2012a) 0.0091 Highest residue (EFSA, 2012a) Leek 0.004* Median residue (EFSA, 2012a) 5 Highest residue (EFSA, 2012a) Sunflower seed 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Rape seed 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Maize grain 0.004* Median residue (EFSA, 2012a) 0.004* Highest residue (EFSA, 2012a) Swine meat 0.010 Median residue (a) 0.017 Highest residue (a) Swine fat 0.028 Median residue 0.066 Highest residue Swine liver 0.006 Median residue 0.013 Highest residue Swine kidney Median residue 0.010 Highest residue Ruminant meat 0.010 Median residue (a) 0.022 Highest residue (a) Ruminant fat 0.030 Median residue 0.088 Highest residue Ruminant liver 0.006 Median residue 0.019 Highest residue Ruminant kidney 0.006 Median residue 0.012 Highest residue Poultry meat 0.007 Median residue (b) 0.011 Highest residue (b) Poultry fat 0.011 Median residue 0.018 Highest residue Poultry liver 0.007 Median residue 0.011 Highest residue Ruminant milk 0.003 Median residue 0.009 Highest residue Birds' eggs 0.007 Median residue 0.014 Highest residue (*): Indicates that the input value is proposed at the limit of analytical quantification. (a): Consumption figures in the EFSA PRIMo are expressed as meat, therefore the median and highest residue values were calculated considering 80 % of the residue is derived from muscle and 20 % of the residue is derived from fat (FAO, 2009). (b): Consumption figures in the EFSA PRIMo are expressed as meat, therefore the median and highest residue values were calculated considering 90 % of the residue is derived from muscle and 10 % of the residue is derived from fat (FAO, 2009). EFSA Journal 2014;12(1):3543 21

CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS The toxicological profile of fipronil was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.0002 mg/kg bw per day and an ARfD of 0.009 mg/kg bw. Nature and magnitude of fipronil residues in primary crops resulting from the authorised uses of fipronil were already assessed during the previous assessments of EFSA, where the residue definitions for enforcement and risk assessment were proposed as the sum of fipronil and its sulfone metabolite (MB43136) expressed as fipronil. Validated analytical methods for enforcement of the proposed residue definitions were available with an LOQ of mg/kg in high oil content, high water content and dry commodities. The number of residues trials was sufficient to estimate residue levels in all crops considered in this assessment, and adequate MRL and risk assessment values could be derived by EFSA. The studies on the nature and magnitude of fipronil in rotational crops demonstrate that significant residues are not expected in rotational crops if fipronil is used on primary crops according to the GAPs considered for the current opinion. Regarding livestock, nature of residues was also assessed during the previous assessments of EFSA and the same residue definitions were derived as for the plant commodities. The residues in livestock were considered fat soluble and validated analytical methods for enforcement of the proposed residue definitions were available with an LOQ of 0.002 mg/kg in milk and mg/kg in other livestock commodities. The magnitude of residues in livestock commodities was re-calculated in the present assessment according to two different scenarios, as requested by the European Commission. Regardless of the scenario selected, data were sufficient to derive adequate MRL proposals and risk assessment values. The consumer risk assessment was performed for both scenarios requested by the European Commission using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). According to the first scenario (disregarding the emergency authorisation on potatoes), the highest chronic exposure was calculated for French toddlers (53 % of the ADI), and the highest acute exposure was calculated for milk (10 % of the ARfD). According to the second scenario (including the emergency authorisation on potatoes), the highest chronic exposure was also calculated for French toddlers (86 % of the ADI), and the highest acute exposure was calculated for milk (12 % of the ARfD). EFSA therefore concludes that both scenarios requested by the European Commission are unlikely to pose a consumer health risk. It is noted that new restrictions on the authorisations of fipronil in Europe have been established by Commission Implementing Regulation (EU) No 781/2013. Member States should implement these restrictions by 31 December 2013 with a period of grace expiring on 28 February 2014 at the latest. According to those restrictions, the reported uses on maize, sunflower, oilseed rape and potatoes should have been withdrawn, resulting in a situation where no more uses are authorised on feed crops in Europe. Risk managers should therefore consider, regardless of the scenarios presented in this reasoned opinion, whether it would not be more appropriate to establish the MRLs for maize, sunflower, oilseed rape, potatoes and commodities of animal origin at the level of their respective LOQs. An overview of the overall assessment is provided in the summary table. EFSA Journal 2014;12(1):3543 22

RECOMMENDATIONS Code Commodity Existing Proposed EU MRL Justification for the proposal number (a) EU MRL Scenario Scenario 1 (b) 2 (c) Enforcement residue definition: sum of fipronil and its sulfone metabolite (MB43136) expressed as fipronil (F) 0220020 Onions 0.02 0.02 0.02 These MRL proposals are adequately 0220030 Shallots 0.02 0.02 0.02 supported by data and no risk to consumers is identified, regardless of 0241010 Broccoli 0.02 0.01 0.01 the scenarios requested by the EC. 0241020 Cauliflower 0.02 0.01 0.01 Also considering the most recent 0242010 Brussels sprouts 0.02 0.01 0.01 restrictions for the approval of 0270060 Leek 0.01 0.01 0.01 fipronil, these MRL proposals are still valid. 0211000 Potatoes 0.01 * 0.01 These MRL proposals are adequately 0401050 Sunflower seed * * * supported by data and no risk to consumers is identified, regardless of 0401060 Rape seed * * * the scenarios requested by the EC. 0500030 Maize grain * * * However, considering the latest 1011010 Swine muscle 0.02 * * restrictions on the approval of 1011020 Swine fat 0.1 0.015 0.07 fipronil, residues are no longer expected in these commodities and 1011030 Swine liver 0.02 * 0.015 lowering of MRLs to the LOQ might 1011040 Swine kidney 0.02 * 0.015 be more appropriate in these 1012010 Bovine muscle 0.02 * 0.006 commodities. 1012020 Bovine fat 0.5 0.06 0.09 1012030 Bovine liver 0.1 0.015 0.02 1012040 Bovine kidney 0.02 0.009 0.015 1013010 Sheep muscle 0.02 * 0.006 1013020 Sheep fat 0.5 0.06 0.09 1013030 Sheep liver 0.1 0.015 0.02 1013040 Sheep kidney 0.02 0.009 0.015 1014010 Goat muscle 0.02 * 0.006 1014020 Goat fat 0.5 0.06 0.09 1014030 Goat liver 0.1 0.015 0.02 1014040 Goat kidney 0.02 0.009 0.015 1016010 Poultry muscle 0.01 * 0.015 1016020 Poultry fat 0.01 0.006 0.02 1016030 Poultry liver 0.02 * 0.015 1020010 Cattle milk * 0.008 0.01 1020020 Sheep milk * 0.008 0.01 1020030 Goat milk * 0.008 0.01 1030000 Birds' eggs 0.02 * 0.015 - Other products of plant and animal origin See App. C - - There are no relevant authorisations or import tolerances reported at EU level. Existing MRLs should be lowered to the appropriate LOQ. (*): Indicates that the MRL is set at the limit of analytical quantification. (a): According to Annex I of Regulation (EC) No 396/2005. (b): Includes all uses evaluated under the Article 12 MRL review (except head cabbage and kale). (c): Includes all uses evaluated under the Article 12 MRL review (except head cabbage and kale) and the emergency authorisation on potatoes. (F): Fat-soluble. EFSA Journal 2014;12(1):3543 23

REFERENCES EC (European Commission), 1996. Appendix G. Livestock Feeding Studies. 7031/VI/95-rev.4. EC (European Commission), 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95- rev.3. EC (European Commission), 1997b. Appendix B. General recommendations for the design, preparation and realisation of residue trials. Annex 2. Classification of (minor) crops not listed in the Appendix of Council Directive 90/642/EEC. 7029/VI/95-rev.6. EC (European Commission), 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95-rev.2. EC (European Commission), 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. EC (European Commission), 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev.3. EC (European Commission), 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95- rev.5. EC (European Commission), 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. EC (European Commission), 2000. Residue analytical methods. For pre-registration data requirement for Annex II (part A, section 4) and Annex III (part A, section 5 of Directive 91/414). SANCO/3029/99-rev.4. EC (European Commission), 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SANCO 10634/2010 Rev. 0, finalised in the Standing Committee on the Food Chain and Animal Health at its meeting of 23-24 March 2010. EC (European Commission), 2010b. Residue analytical methods. For post-registration control. SANCO/825/00-rev.8.1. EC (European Commission), 2011. Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.9. EFSA (European Food Safety Authority), 2006. Conclusion on the peer review of the pesticide risk assessment of the active substance fipronil. The EFSA Journal 2006, 65r, 1-110. EFSA (European Food Safety Authority), 2007. Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. Available online: www.efsa.europa.eu EFSA (European Food Safety Authority), 2012a. Reasoned opinion on the review of the existing maximum residue levels (MRLs) for fipronil according to Article 12 of Regulation (EC) No 396/2005. EFSA Journal 2012;10(4):2688, 44 pp. doi:10.2903/j.efsa.2012.2688 EFSA (European Food Safety Authority), 2012b. Reasoned opinion on the modification of the existing MRLs for fipronil in poultry fat. EFSA Journal 2012;10(5):2707, 32 pp. doi:10.2903/j.efsa.2012.2707 EFSA (European Food Safety Authority), 2013. Conclusion on the peer review of the pesticide risk assessment for bees for the active substance fipronil. EFSA Journal 2013;11(5):3158, 51 pp. doi:10.2903/j.efsa.2013.3158 FAO (Food and Agriculture Organization of the United Nations), 2009. Submission and evaluation of pesticide residues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2 nd Ed. FAO Plant Production and Protection Paper 197, 264 pp. France, 2004. Draft assessment report on the active substance fipronil prepared by the rapporteur Member State France in the framework of Council Directive 91/414/EEC, April 2004. EFSA Journal 2014;12(1):3543 24

France, 2006. Final addendum to the draft assessment report on the active substance fipronil prepared by the rapporteur Member State France in the framework of Council Directive 91/414/EEC, Part 2 compiled by EFSA, January 2006 OECD (Organisation for Economic Co-operation and Development), 2011. OECD MRL Calculator: spreadsheet for single data set and spreadsheet for multiple data set, 2 March 2011. In: Pesticide Publications/Publications on Pesticide Residues. EFSA Journal 2014;12(1):3543 25

APPENDIX A GOOD AGRICULTURAL PRACTICE (GAPS) Potatoes Tuber form Solanum Spp NEU Outdoor DE GB 5.0 g/kg Soil treatment - general (see also comment field) From BBCH Until BBCH 0 0 1 50.00 g a.i./ha n.a. Onions Allium cepa NEU Outdoor BE FS 500.0 g/l Seed treatment - drenching 0 0 1 25.00 g a.i./unit n.a. Shallots Broccoli Cauliflower Brussels sprouts Allium ascalonicum (Allium cepa var. aggregatum) Brassica oleracea var. italica Brassica oleracea var. botrytis Brassica oleracea var. gemmifera NEU Outdoor BE FS 500.0 g/l Seed treatment - drenching 0 0 1 25.00 g a.i./unit n.a. NEU Outdoor NL FS 500.0 g/l Seed treatment - drenching 0 0 1 12.50 g a.i./unit n.a. NEU Outdoor NL FS 500.0 g/l Seed treatment - drenching 0 0 1 12.50 g a.i./unit n.a. NEU Outdoor NL FS 500.0 g/l Seed treatment - drenching 0 0 1 12.50 g a.i./unit n.a. Leek Allium porrum NEU Outdoor BE FS 500.0 g/l Seed treatment - drenching 0 0 1 50.00 g a.i./unit n.a. Band application to the soild following incorporation at planting 1 unit = 250000 seeds and 4 units/ha 1 unit = 250000 seeds and 4 units/ha 1 unit = 100000 seeds and 0,4 unit/ha 1 unit = 100000 seeds and 0,4 unit/ha 1 unit = 100000 seeds and 0,4 unit/ha 1 unit = 250000 seeds and 1,6 units/ha - Indicative PHI of 175 days according to the notifier. Sunflower seed Helianthus annuus NEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 30.00 g a.i./unit n.a. 1 unit = 75000 seeds and 1unit/ha Rape seed Brassica napus NEU Outdoor SK FS 500.0 g/l Seed treatment - drenching 0 0 1 30.00 g a.i./unit n.a. 1 unit = 75000 seeds and 1unit/ha Maize Zea mays NEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 250.00 Maize (for forage) Zea mays NEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 250.00 n.a.: not applicable Crop Outdoor/ Member state or Region Pests controlled Common name Scientific name Indoor Country Type Critical Outdoor GAPs for Northern Europe Formulation Application Application rate PHI or Content Growth stage Number Interval (days) wiaiting Method Min. rate Max. rate Rate Unit period Conc. Unit Min. Max. Min. Max. (days) g a.i./100 kg g a.i./100 kg n.a. n.a. Comments (max. 250 charachters) 20 kg seeds/ha 20 kg seeds/ha - indicative PHI of 80 days according to the Review Report Conc. Unit From BBCH Until BBCH Min. Max. Min. Max. Sunflower seed Helianthus annuus SEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 30.00 g a.i./unit n.a. Maize Zea mays SEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 250.00 Maize (for forage) Zea mays SEU Outdoor EU FS 500.0 g/l Seed treatment - drenching 0 0 1 250.00 n.a.: not applicable Crop Outdoor/ Member state or Region Pests controlled Common name Scientific name Indoor Country Type Formulation Content Critical Outdoor GAPs for Southern Europe Method Application Growth stage Number Interval (days) Application rate Min. rate Max. rate Rate Unit g a.i./100 kg g a.i./100 kg PHI or wiaiting period (days) n.a. n.a. Comments (max. 250 charachters) 1 unit = 75000 seeds and 1unit/ha - for Spain the max, application rate is 90g a;i/ha but there are not enough residue trials available for this GAP. 20 kg seeds/ha 20 kg seeds/ha - indicative PHI of 80 days according to the Review Report EFSA Journal 2014;12(1):3543 26

APPENDIX B PESTICIDE RESIDUE INTAKE MODEL (PRIMO) Appendix B.1 Scenario 1 including all EU MRL proposals resulting from the Article 12 MRL review (except kale and cabbage) Appendix B.2 Scenario 2 including all EU MRL proposals resulting from the Article 12 MRL review (except kale and cabbage) and the use on potatoes EFSA Journal 2014;12(1):3543 27

APPENDIX B.1 SCENARIO 1 INCLUDING ALL EU MRL PROPOSALS RESULTING FROM THE ARTICLE 12 MRL REVIEW (EXCEPT KALE AND CABBAGE) EFSA Journal 2014;12(1):3543 28

EFSA Journal 2014;12(1):3543 29

APPENDIX B.2 SCENARIO 2 INCLUDING ALL EU MRL PROPOSALS RESULTING FROM THE ARTICLE 12 MRL REVIEW (EXCEPT KALE AND CABBAGE) AND THE USE ON POTATOES EFSA Journal 2014;12(1):3543 30

EFSA Journal 2014;12(1):3543 31