Combined review of the existing maximum residue levels (MRLs) for the active substances metalaxyl and metalaxyl-m

Transcription

1 REASONED OPINION ADOPTED: 1 April 2015 PUBLISHED: 2 April 2015 doi: /j.efsa Combined review of the existing maximum residue levels (MRLs) for the active substances metalaxyl and metalaxyl-m European Food Safety Authority (EFSA) Abstract In compliance with Article 43 of Regulation (EC) No 396/2005, the European Food Safety Authority (EFSA) received from the European Commission (EC) a mandate to update its previous review of the maximum residue levels (MRL) for metalaxyl, taking into account new information provided in the Renewal Assessment Report for metalaxyl-m and taking into account previous MRL assessments for metalaxyl-m. EFSA is providing a reasoned opinion combining the MRL reviews of metalaxyl and metalaxyl-m and taking into consideration the additional data. Based on the assessment of the available data, one set of MRL proposals was derived for metalaxyl and metalaxyl-m (using the OECD calculator) and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was found to be missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA require further consideration by risk managers. European Food Safety Authority, 2015 Keywords: metalaxyl, metalaxyl-m, MRL review, Regulation (EC) No 396/2005, consumer risk assessment, fungicide, phenylamide Requestor: European Commission Question number: EFSA-Q Correspondence: pesticides.mrl@efsa.europa.eu EFSA Journal 2015;13(4):4076

2 Suggested citation: EFSA (European Food Safety Authority), Reasoned opinion on combined review of the existing maximum residue levels (MRLs) for the active substances metalaxyl and metalaxyl-m. EFSA Journal 2015;13(4):4076, 56 pp. doi: /j.efsa ISSN: European Food Safety Authority, 2015 Reproduction is authorised provided the source is acknowledged. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. 2 EFSA Journal 2015;13(4):4076

3 Summary Both metalaxyl and metalaxyl-m are authorised as pesticide active substances, with metalaxyl being a racemic mixture of metalaxyl-m and its S-enantiomer. Although both compounds share the same residue definition for the setting of maximum residue levels (MRLs), the existing EU MRLs for metalaxyl and metalaxyl-m were reviewed separately by the European Food Safety Authority (EFSA), as foreseen by the legal framework. In December 2011, EFSA published a reasoned opinion on the review of existing MRLs for metalaxyl-m, which was before the implementation of the OECD MRL calculator at EU level, while the reasoned opinion on the review of existing MRLs for metalaxyl was published in February 2014, taking into consideration the OECD MRL calculator. In order to fully address the needs of risk managers, it would have been more appropriate to derive one set of MRLs for all relevant crops derived with the OECD MRL calculator. Furthermore, metalaxyl-m was evaluated for renewal of approval in the framework of Commission Regulation (EC) No 1107/2009 where new data relevant for the assessment of residues in livestock were identified. EFSA therefore received on 4 February 2015, in accordance with Article 43 of Regulation (EC) No 396/2005, a mandate from the European Commission to update the assessment of metalaxyl taking into account the above. For this assessment, EFSA mainly relied on its previous reasoned opinions for metalaxyl and metalaxyl-m, its recent conclusion on the peer review of metalaxyl-m and on the Renewal Assessment Report (RAR) for metalaxyl-m prepared by Belgium in the framework of Commission Regulation (EU) No 1141/2010. The following conclusions were derived. The toxicological profile of metalaxyl and metalaxyl-m was evaluated in the framework of Directive 91/414/EEC, which resulted in an acceptable daily intake (ADI) and an acute reference dose (ARfD) being established at 0.08 mg/kg bw per d and 0.5 mg/kg bw, respectively. Primary crop metabolism of metalaxyl and metalaxyl-m was investigated in four different crop groups (fruit crops, root and tuber crops, leafy crops and cereals) and according to three different types application (foliar, seed and soil treatments), hereby covering all uses of metalaxyl and metalaxyl-m evaluated in this framework. The residue definition for enforcement and risk and risk assessment in all plant commodities is defined as metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers). Validated analytical methods for enforcement of this residue definition are available with a limit of quatification (LOQ) of 0.01 mg/kg for all plant commodities, except for complex matrices such as cocoa and hops. Regarding the magnitude of residues in primary crops, available trials are considered sufficient to derive MRL proposals as well as risk assessment values for all crops under assessment, except for apples, pears and soya beans where data were insufficient to derive an MRL. Considering that an analytical method for enforcement of residues in complex matrices is not available and that residue trials are still required for some crops, MRL proposals for flowering brassica, herbs, cocoa and hops should be considered tentative. Furthermore, it is highlighted that all MRL proposals were derived from the use of metalaxyl-m but it cannot be excluded that the use of metalaxyl leads to higher residue levels than those observed for metalaxyl-m. The effect of processing on the nature of metalaxyl was investigated under standard hydrolysis conditions. The compound was found to be hydrolytically stable under these conditions and the residue definition derived for primary crops is also applicable to processed commodities. Studies investigating the effect of processing on the magnitude of metalaxyl and metalaxyl-m residues were also reported, allowing EFSA to derive robust processing factors for processed products of tomatoes (juice, paste and canned tomatoes) and grapes (raisins, juice, must, white wine, red wine, dry pomace and wet pomace). Further processing studies are not required for the time being as they are not expected to affect the outcome of the risk assessment but if there would be the intention to derive more robust processing factor, in particular for enforcement purposes, additional processing studies would still be required. Confined rotational crop studies investigating the uptake of metalaxyl and metalaxyl-m from soil were reported in four different crop groups (root and tuber crops, leafy crops, cereals, and pulses and oilseeds), and the residue definition for primary crops can also be applied to the rotational crops. 3 EFSA Journal 2015;13(4):4076

4 Based on further rotational crop field trials, it was also concluded that significant residues in rotational crops are not expected, provided that metalaxyl and metalaxyl-m are applied according to the GAPs reported for these substances. Based on the uses reported, significant livestock dietary burden were calculated for dairy ruminants, meat ruminants, pigs and poultry. The metabolism of metalaxyl in livestock was evaluated and the relevant residue for enforcement and risk assessment in all commodities of animal origin is defined as the sum of metalaxyl (sum of isomers) and its metabolites containing the 2,6-dimethylaniline moiety, expressed as metalaxyl. For enforcement purposes, the residue might be simplified to metabolie CGA in animal tissues and metabolite CGA in milk, but analytical methods and livestock feeding studies supporting such a simplified residue definition are currently not available. Meanwhile, based on the available feeding studies and the proposed residue definition, MRLs can be derived at the LOQ of 0.01 mg/kg in muscle, fat, milk and eggs and at the LOQ of 0.05 mg/kg in liver. In swine kidney and ruminant kidney, MRL proposals of respectively 0.3 and 0.15 mg/kg were derived. Considering that the analytical method for enforcement purposes is not fully validated, these MRL proposals are to be considered as tentative. Chronic and acute consumer exposure resulting from the authorised uses of metalaxyl and metalaxyl M was calculated using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). For each commodity, risk assessment values obtained for metalaxyl and metalaxyl-m were compared and the most critical values were selected for the exposure calculations. For those commodities where available residue trials were only sufficient to derive risk assessment values for the use of metalaxyl-m while the use of metalaxyl was not supported by residue trials, EFSA followed the most conservative approach by considering the existing EU MRL for indicative exposure calculation, unless the existing EU MRL was not higher than the MRL proposal derived for the use of metalaxyl-m. Also for those commodities where data were not sufficient to derive an MRL, neither for metalaxyl, nor for metalaxyl-m, EFSA considered the existing EU MRL. Following this approach, the highest chronic exposure represented 23 % of the ADI (German children) and the highest acute exposure amounted to 32 % of the ARfD (scarole). Inclusion of the existing Codex maximum residue limits (CXLs) for metalaxyl in the EU risk assessment was not considered appropriate at this stage because information supporting those CXLs is very limited and a review of those CXLs is scheduled for the JMPR in MRL recommendations were derived in compliance with the assessment summarised above although some information required by the regulatory framework was found to be missing. Some MRL proposals derived by EFSA will therefore require further consideration by risk managers. 4 EFSA Journal 2015;13(4):4076

5 Table of contents Abstract... 1 Summary... 3 Background... 6 The active substances and their use pattern... 6 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 Nature of residues Magnitude of residues Consumer risk assessment Conclusions Recommendations References Abbreviations Appendix A Good Agricultural Practices (GAPs) for metalaxyl Appendix B Good Agricultural Practices (GAPs) for metalaxyl-m Appendix C Pesticide Residue Intake Model (PRIMo) Appendix D Used compound codes EFSA Journal 2015;13(4):4076

6 Background Both metalaxyl and metalaxyl-m are authorised as pesticide active substances, with metalaxyl being a racemic mixture of metalaxyl-m and its S-enantiomer and with metalaxyl-m being the most effective enantiomer. In December 2011, the European Food Safety Authority (EFSA) published a reasoned opinion on the review of existing maximum residue levels (MRL) for metalaxyl-m, which was before the implementation of the OECD MRL calculator at EU level (EFSA, 2011). In February 2014, EFSA also published a reasoned opinion on the review of existing MRLs for metalaxyl, which took into consideration the OECD MRL calculator (EFSA, 2014). Although both compounds share the same residue definition for MRL setting, each compound was assessed separately as foreseen by the legal framework. In view of satisfying the needs of risk managers, MRL proposals for metalaxyl-m derived in the 2011 reasoned opinion were incorporated in the 2014 reasoned opinion. The European Commission (EC) commented that it would have been more appropriate to reconsider the previous assessment of metalaxyl-m and to derive one set of MRLs for all relevant crops derived with the OECD MRL calculator. Furthermore, metalaxyl-m was evaluated for renewal of approval in the framework of Commission Regulation (EU) No 1141/ with Belgium being the designated rapporteur Member State (RMS). In its Renewal Assessment Report (Belgium, 2013), the RMS presented a new cow feeding study that was not peer reviewed under the renewal procedure as considered not relevant for the representative uses assessed. The RMS indicated during the written commenting procedure on the draft EFSA conclusion that this new study might trigger a change in the MRL for kidney. On 4 February 2015, EFSA received from the EC a mandate according to Article 43 of Regulation (EC) No 396/ to update the assessment of metalaxyl taking into account the new information provided in the Renewal Assessment Report for metalaxyl-m. This update should take fully into account the 2011 metalaxyl-m reasoned opinion and propose one set of MRLs for both substances for all relevant crops derived with the same methodology (the OECD calculator). The active substances and their use pattern Metalaxyl is the ISO common name for methyl N-(methoxyacetyl)-N-(2,6-xylyl)-DL-alaninate (IUPAC). Metalaxyl-M, formerly named mefenoxam, is the ISO common name for methyl N-(methoxyacetyl)-N- (2,6-xylyl)-D-alaninate (IUPAC). Metalaxyl is the racemic mixture of metalaxyl-m and its S-enantiomer and both compounds are recognised as pesticide active substances. O CH 3 O CH 3 CH 3 O C CH 2 N CH CO 2 CH 3 CH 3 O C CH 2 N CH CO 2 CH 3 CH 3 CH 3 CH 3 CH 3 Figure 1: Chemical structure of metalaxyl Figure 2: Chemical structure of metalaxyl-m Metalaxyl and metalaxyl-m belong to the group of phenylamide compounds which are used as fungicide for the control oomycete pathogens. They are systemic compounds which inhibit mycelial growth and spore formation by selectively interfering with the synthesis of ribosomal RNA in fungi. Metalaxyl-M is considered as the most effective enantiomer. 1 Commission Regulation (EU) No 1141/2010 of 7 December 2010 laying down the procedure for the renewal of the inclusion of a second group of active substances in Annex I to Council Directive 91/414/EEC and establishing the list of those substances. OJ L 322, , p Regulation (EC) No 396/2005 of the European 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, , p EFSA Journal 2015;13(4):4076

7 Metalaxyl was evaluated in the framework of Directive 91/414/EEC 3 with Portugal being the designated RMS. The representative uses supported for the peer review process were foliar treatments on potatoes (outdoor only) and tomatoes (outdoor and indoor), with PHIs of days. Following the peer review, a decision on inclusion of the active substance in Annex I to Directive 91/414/EEC was published by means of Commission Directive 2010/28/EU, 4 which entered into force on 1 July According to Regulation (EU) No 540/2011, 5 metalaxyl is deemed to have been approved under Regulation (EC) No 1107/ This approval is restricted to use as fungicide only. As EFSA was not involved in the peer review of metalaxyl, an EFSA Conclusion on this active substance is not available. Metalaxyl-M was included in Annex I to Directive 91/414/EEC by means of Commission Directive 2002/64/EC, 7 entering into force on 1 October 2002, and is deemed to have been approved under Regulation (EC) No 1107/2009 by means of Regulation (EU) No 540/2011. This approval is restricted to uses as fungicide only. Meanwhile, Metalaxyl-M was also evaluated for renewal of approval in the framework of Commission Regulation (EU) No 1141/2010 with Belgium being the designated RMS. The representative uses supported at EU level were as a seed treatment to field grown spinach and sunflower and an outdoor spray application to tomato and grapes. EFSA published its conclusion on the peer review of the pesticide risk assessment of the active substance metalaxyl-m on 3 March 2015 (EFSA, 2015). A final decision concerning the renewal of approval under Regulation (EC) No 1107/2009 has not been taken. The EU MRLs for metalaxyl (including other mixtures of constituent isomers including metalaxyl-m, sum of isomers) are established in Annexes II and IIIB of Regulation (EC) No 396/2005. Codex maximum residue limits (CXLs) for metalaxyl were also established by the Codex Alimentarius Commission (CAC) but they were not implemented in European legislation so far. An overview of the MRL changes that occurred since the entry into force of the abovementioned regulation is provided below. Table 1: Overview of the MRL changes since the entry into force of Regulation (EC) No 396/2005 Procedure Legal implementation Remarks MRL review metalaxyl-m (EFSA, 2011) Not yet legally implemented pending a combined assessment for metalaxyl and metalaxyl-m. MRL application metalaxyl-m (EFSA, 2012) MRL application metalaxyl-m (EFSA, 2013) Reg. (EU) No 441/ Reg. (EU) No 36/ Modification of the existing MRL in lettuce and other salad plants. Modification of the existing MRL in currants. MRL review metalaxyl Not yet legally implemented pending a combined 3 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, , p Commission Directive 2010/28/EU of 23 April 2010 amending Council Directive 91/414/EEC to include metalaxyl as active substance. OJ L 104, , p Commission Implementing 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, , p 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, , p Commission Directive 2002/64/EC of 15 July 2002 amending Council Directive 91/414/EEC to include cinidon-ethyl, cyhalofop butyl, famoxadone, florasulam, metalaxyl-m and picolinafen as active substances. OJ L 189, , p Commission Regulation (EU) No 441/2012 of 24 May 2012 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 bifenazate, bifenthrin, boscalid, cadusafos, chlorantraniliprole, chlorothalonil, clothianidin, cyproconazole, deltamethrin, dicamba, difenoconazole, dinocap, etoxazole, fenpyroximate, flubendiamide, fludioxonil, glyphosate, metalaxyl-m, meptyldinocap, novaluron, thiamethoxam, and triazophos in or on certain products. OJ L 135, , p Commission Regulation (EU) No 36/2014 of 16 January 2014 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 aminopyralid, chlorantraniliprole, cyflufenamid, mepiquat, metalaxyl-m, propamocarb, pyriofenone and quinoxyfen in or on certain products. OJ L 17, , p EFSA Journal 2015;13(4):4076

8 (EFSA, 2014) Procedure Legal implementation Remarks assessment for metalaxyl and metalaxyl-m. For the purpose of this assessment, the critical uses of metalaxyl and metalaxyl-m, as previously reported to EFSA (2011, 2014), were considered. Additional uses reported to EFSA in the framework of previous MRL applications (EFSA, 2012, 2013) were also included in the assessment. An overview of all the Good Agricultural Practices (GAPs) considered for this assessment is provided in Appendices A and B. According to GAPs reported, both metalaxyl and metalaxyl-m are authorised in northern and southern Europe for foliar applications in a wide variety of crops, both under outdoor and indoor conditions. In addition to the foliar treatments, metalaxyl-m is also authorised for a wide range of soil treatments and seed treatments in the EU. Outside the EU, only the use of metalaxyl-m on cocoa beans was reported. Assessment EFSA bases its assessment mainly on the Review Report on metalaxyl-m (EC, 2002), the Review Report on metalaxyl (EC, 2010a), the previous EFSA reasoned opinions on metalaxyl-m (EFSA, 2011, 2012, 2013), the previous EFSA reasoned opinion on metalaxyl (EFSA, 2014) and the EFSA conclusion on metalaxyl-m prepared in the framework of Regulation (EC) No 1107/2009 (EFSA, 2015). For the assessment in commodities of animal origin, EFSA also relied on the Renewal Assessment Report (RAR) and its addendum on metalaxyl-m prepared in the framework of Regulation (EC) No 1141/2010 (Belgium, 2013, 2014). Although some of the studies included in this report were not relied upon by EFSA during the recent peer review due to an insignificant exposure of livestock to residues (EFSA, 2015), many of these studies were considered relevant in the framework of this assessment. Furthermore, the RAR for metalaxyl-m and its addendum provide a comprehensive overview of all available studies for metalaxyl and metalaxyl-m. Therefore, readers are generally referred to the RAR for further details on the studies relied upon by EFSA, unless specified otherwise in the text. The assessment was performed in accordance with the legal provisions of the Uniform Principles for the Evaluation of the Authorization 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-g, 2000, 2010b,c, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin When the MRLs of metalaxyl were reviewed by EFSA, the QuEChERS method in combination with HPLC-MS/MS, as described by CEN (2008), was considered appropriate for enforcement of metalaxyl in plant commodities with a limit of quantification (LOQ) of 0.01 mg/kg, except for complex matrices (EFSA, 2014). These findings were also confirmed during the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009, where validation (including confirmatory mass transitions) of both the QuEChERS method and the DFG-S19 method was provided in plant matrices, except complex ones (EFSA, 2015). During the previous reviews of MRLs for metalaxyl and metalaxyl-m, other analytical methods were considered by EFSA, supporting higher LOQ values in commodities of plant origin (EFSA, 2011). However, considering the latest analytical developments described above, these data are no longer considered relevant. Hence it is concluded that metalaxyl (sum of isomers) can be enforced in food of plant origin with an LOQ of 0.01 mg/kg in high water content, high oil content, acidic and dry commodities. Applicability of this method to complex matrices such as cocoa and hops was however not demonstrated. 10 Regulation (EU) No 546/2011 of 10 June 2011, OJ L 155, , p EFSA Journal 2015;13(4):4076

9 1.2. Methods for enforcement of residues in food of animal origin During the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009, the RMS reported an analytical method for enforcement of metalaxyl and its metabolites containing the 2,6-dimethylaniline moiety. The primary method uses HPLC-MS/MS and was validated with an LOQ of 0.01 mg/kg in muscle, fat, milk and eggs, and with an LOQ of 0.05 mg/kg in liver and kidneys (including a confirmatory mass transition). An independent laboratory validation (ILV) was only provided for eggs, liver and milk and is still missing for fat. Furthermore, the efficiency of the extraction, hydrolysis and derivatisation steps could not be demonstrated (Belgium, 2013). During the previous review of MRLs for metalaxyl-m, another analytical method was tentatively considered by EFSA, supporting higher LOQ values in commodities of animal origin (EFSA, 2011). Considering the poor validation of this method (only 2 replicates at LOQ, no ILV), the above method is now considered more appropriate. Hence there is evidence that metalaxyl and its metabolites containing the 2,6-dimethylaniline moiety can be enforced in food of animal origin with an LOQ of 0.01 mg/kg in muscle, fat, milk and eggs, and with an LOQ of 0.05 mg/kg in liver and kidneys, but further validation data demonstrating the efficiency of the extraction, hydrolysis and derivatisation steps are still required. An ILV for fat is also required. 2. Mammalian toxicology The toxicological assessments of metalaxyl and metalaxyl-m were peer reviewed under Directive 91/414/EEC and the same toxicological reference values were established by the European Commission (2002, 2010a) for both compounds. These toxicological reference values were confirmed by the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009 (EFSA, 2015) and are now summarised in Table 2. Table 2: Overview of the toxicological reference values Source Year Value Study relied upon Safety factor Metalaxyl and metalaxyl-m ADI EC 2002, 2010a ARfD EC 2002, 2010a 0.08 mg/kg bw per day Dog studies with metalaxyl (90 days, 6 months, 1 year and 2 years) 0.5 mg/kg bw Developmental rat study with metalaxyl-m Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of metalaxyl and metalaxyl-m in primary crops was initially assessed when the MRLs for both active substances were reviewed (EFSA, 2011, 2014). Further metabolism studies for metalaxyl-m were peer reviewed by EFSA in the framework of Regulation (EC) No 1107/2009 (EFSA, 2015). An overview of the most relevant metabolism studies is presented in Table 3. The above reported studies were previously relied upon by EFSA to conclude that parent isomers of metalaxyl constituted the most relevant part of the residue, that metabolic patterns in the different studies were shown to be similar and that no preferential metabolism of the isomers is expected (EFSA, 2011, 2014, 2015). Considering that the above reported studies cover four different crop groups and three different modes of application, conclusions previously derived by EFSA are also applicable to the uses of metalaxyl and metalaxyl-m evaluated in this framework. 9 EFSA Journal 2015;13(4):4076

10 Hence the residue definition for enforcement and risk and risk assessment in all plant commodities is defined as metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers). Validated analytical methods for enforcement of this residue definition are available for all plant commodities, except for complex matrices such as cocoa and hops. Table 3: Summary of available metabolism studies in plants Crop group Crops Application Sampling (DAT) References Metalaxyl Fruit crops Grapes Foliar (7 x 50 g/hl) 52 EFSA, 2011, 2014 Root/tuber Potato Foliar (5 x 200 g/ha) 37 EFSA, 2011, 2014 Foliar (6 x 426 g/ha) 7 EFSA, 2011, 2014 Foliar (6 x 1280 g/ha) 7 EFSA, 2011, 2014 Leafy crops Lettuce Foliar (2 x 250 g/ha) 14 EFSA, 2011, 2014 Metalaxyl and metalaxyl-m Tobacco Soil (a) EFSA, 2011, 2014 Leafy crops Lettuce Foliar (3 x 200 g/ha) 21 EFSA, 2011, 2014 Metalaxyl-M Fruit crops Tomato Foliar (3 x 160 g/ha) 3, 14 EFSA, 2015 Cereals Wheat Seed (19.3 g/100 kg seeds) 83, 127 EFSA, 2015 Seed (157 g/100 kg seeds) 83, 127 EFSA, 2015 (a): Three different application rates were tested (280 g/ha at transplanting, 560 g/ha at transplanting and 3530 g/ha a preplant soil incorporation treatment Magnitude of residues According to the GAPs reported in Appendices A and B, both metalaxyl and metalaxyl-m are authorised in northern and southern Europe for foliar applications in a wide variety of crops, both under outdoor and indoor conditions. In addition to the foliar treatments, metalaxyl-m is also authorised for a wide range of soil treatments and seed treatments in the EU. Outside the EU, only the use of metalaxyl-m on cocoa beans was reported. To assess the magnitude of residues resulting from these GAPs, EFSA considered all residue trials previously reported in the framework of the MRL reviews under Article 12 of Regulation (EC) No 396/2005 (EFSA, 2011, 2014) and in the framework of MRL applications for metalaxyl-m (EFSA, 2012, 2013). Regarding the residues trials recently reported by EFSA for the peer review of metalaxyl-m under Regulation (EC) No 1107/2009 (EFSA, 2015), only the residue trials on spinach were considered as they were the only trials to support the critical GAPs evaluated in the current framework. Regarding rape forage, it is noted that some trials reported during the review of MRLs for metalaxyl-m (Finland, 2011) were omitted. They are now also included in this assessment. All residue trials supporting authorisations for metalaxyl and metalaxyl-m are summarised in Tables 4 and 5, respectively. The number of residue trials and extrapolations were evaluated in accordance with the European guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs (EC, 2011). Regarding the use of metalaxyl, available residue trials were sufficient to derive MRL and risk assessment values in potatoes, tomatoes and lettuce, taking note of the following considerations: Potatoes: the number of residue trials supporting the southern GAP is not compliant with the data requirements for this crop (4 trials instead of 8) and no residue trials are available to 10 EFSA Journal 2015;13(4):4076

11 support the northern GAP and the indoor GAP. Considering the overall availability of residue trials on potatoes (also considering the trials for metalaxyl-m reported further), no further trials are required for potatoes and the MRL can be proposed at the LOQ of 0.02 mg/kg. However, 8 trials compliant with the northern GAP and 8 trials compliant with the indoor GAP are still required; Tomatoes: the number of residue trials supporting the indoor GAP is not compliant with the data requirements for this crop (5 trials instead of 8) and no residue trials are available to support the northern and southern GAPs. The available indoor trials are considered sufficient to demonstrate that the indoor GAP for metalaxyl is not more critical than the indoor GAP for metalaxyl-m (see also further). However, 8 trials compliant with the northern GAP and 8 trials compliant with the southern GAP are still required; Lettuce: although MRL and risk assessment values can be derived from the southern GAP, which is sufficiently supported by data, 8 trials compliant with the indoor GAP are still required. For all other crops, residue trials are not available to support the authorisations or the number of available residue trials was insufficient. Therefore, MRL or risk assessment values could not be derived by EFSA and the following data gaps were identified: Citrus fruits: 8 trials on oranges and 8 trials on either mandarins or lemons, all compliant with the southern GAP for citrus fruits, are required; Apples: 8 trials compliant with the southern GAP are required; Table grapes: 8 trials compliant with the northern GAP and 5 additional trials compliant with the southern GAP are required; Wine grapes: 8 trials compliant with the northern GAP and 8 trials compliant with the southern GAP are required; Strawberries: 8 trials compliant with the indoor GAP are required; Carrots: 8 trials compliant with the southern GAP are required; Onions: 8 trials compliant with the northern GAP, 8 trials compliant with the southern GAP and 8 trials compliant with the indoor GAP are required; Peppers: 8 trials compliant with the indoor GAP are required; Cucumbers: 8 trials compliant with the northern GAP, 4 trials compliant with the southern GAP and 8 trials compliant with the indoor GAP are required; Melons: 8 trials compliant with the southern GAP and 8 trials compliant with the indoor GAP are required; Watermelons: 8 trials compliant with the southern GAP and 8 trials compliant with the indoor GAP are required; Flowering brassica: 4 trials on broccoli and 4 trials on cauliflower compliant with the southern GAP, and 4 trials on broccoli and 4 trials on cauliflower compliant with the indoor GAP are required; Globe artichoke: 4 trials compliant with the southern GAP are required; Soya beans: 8 trials compliant with the southern GAP are required. Regarding the use of metalaxyl-m, residue trials are not available to support the authorisations on apples and pears. Therefore, MRL or risk assessment values could not be derived by EFSA and the following data gaps were identified: Apples and pears: 8 trials on apples compliant with the southern GAP are required. For some crops, the number of residue trials reported is not compliant with the data requirements, only tentative MRL and risk assessment values could be derived by EFSA and the following data gaps were identified: 11 EFSA Journal 2015;13(4):4076

12 Flowering brassica: 4 trials on broccoli compliant with the northern GAP and 3 additional trials on cauliflower compliant with the southern GAP are required; Herbs: 4 trials on parsley or open leaf lettuce compliant with the indoor GAP are required (because extrapolation from a more critical GAP on lettuce is in principle not allowed); Cocoa: 2 additional trials supporting the import tolerance are required. For all other crops, available residue trials are sufficient to derive MRL and risk assessment values, taking note of the following considerations: Citrus fruits: according to the guidance documents 1 additional trial on mandarins and 1 additional trial on oranges, both compliant with the southern GAP on citrus fruits, would still be required. These additional trials are however not expected to significantly impact on the outcome of the assessment and are therefore only considered desirable by EFSA; Strawberries: although MRL and risk assessment values are derived from the indoor GAP, which is sufficiently supported by data, 7 additional trials compliant with the northern GAP and 6 additional trials compliant with the southern GAP are still required; Tomatoes: although MRL and risk assessment values are derived from the indoor GAP, which is sufficiently supported by data, 6 additional trials compliant with the southern GAP are still required; Peppers: although MRL and risk assessment values are derived from the indoor GAP, which is sufficiently supported by data, 5 additional trials compliant with the southern GAP are still required; Cucumbers: according to the guidance documents 1 additional trial on cucumbers compliant with the indoor GAP would still be required. This additional trial is however not expected to significantly impact on the outcome of the assessment and is therefore only considered desirable by EFSA; Salad plants: although MRL and risk assessment values are derived from the indoor GAP, which is sufficiently supported by data for open leaf lettuce, 8 trials on open leaf lettuce compliant with the northern GAP and 8 trials on open leaf lettuce compliant with the southern GAP are still required; Spinach: although MRL and risk assessment values are derived from the southern GAP, which is sufficiently supported by data, further trials under indoor conditions are still required for confirmation; Cane fruit, kiwi, potatoes (SEU only), beetroot, onions, Chinese cabbage, beet leaves, dry beans, dry peas and oilseeds (SEU only): the number of trials reported for these authorisations is not compliant with the data requirements. However, considering the overall availability of residue trials in these crops, residues exceeding the LOQ of 0.02 mg/kg are not expected and no further residue trials are required. The potential degradation of residues during storage of the residue trial samples was also assessed. During the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009, storage stability of metalaxyl was also demonstrated for a period of 24 months at -18 C in commodities with high water content (tomato and potato) high oil content (oilseed rape), acidic (orange) and dry commodities (wheat grain) (EFSA, 2015). Other storage stability studies were previously considered by EFSA when the MRLs for metalaxyl and metalaxyl-m were reviewed (EFSA, 2011, 2014). These older studies are no longer considered relevant because analytical methods used were not specific enough. Residue trial samples for cane fruit, cranberries, lettuce and spinach (used to derive MRLs in beet leaves and Chinese cabbage) were stored in compliance with the above conditions. For the remaining residue trials, storage conditions of the samples remain unknown. However, considering that storage stability was demonstrated for a long period, decline of residues in the residue trial samples is not expected EFSA Journal 2015;13(4):4076

13 Consequently, combining the assessments for metalaxyl and metalaxyl-m, available residues data are considered sufficient to derive MRL proposals as well as risk assessment values for all crops under assessment, except for apples, pears and soya beans where data were insufficient to derive an MRL. Considering that an analytical method for enforcement of residues in complex matrices is not available and that residue trials are still required for some crops, MRL proposals for flowering brassica, herbs, cocoa and hops should be considered tentative. Furthermore, it is highlighted that all MRL proposals were derived from the use of metalaxyl-m but it cannot be excluded that the use of metalaxyl leads to higher residue levels than those observed for metalaxyl-m EFSA Journal 2015;13(4):4076

14 Table 4: Overview of the available residues trials data supporting authorisations of metalaxyl Grapefruit Oranges Lemons Limes Mandarins Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments MRL proposals HR (b) SEU No residue trials available. Apples SEU No residue trials available. Table grapes NEU No residue trials available. SEU <0.04; 0.14; 0.26 Trials compliant with GAP but insufficient to derive an MRL. Sample storage conditions unknown (EFSA, 2014). STMR (c) Wine grapes NEU No residue trials available. SEU No residue trials available. Strawberries Indoor No residue trials available. Potatoes NEU No residue trials available. SEU 4 <0.05 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2014). 0.02* Indoor No residue trials available. Carrots SEU No residue trials available. Onions NEU No residue trials available. SEU No residue trials available. Indoor No residue trials available. Tomatoes NEU No residue trials available. SEU No residue trials available. Indoor 5 <0.05 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2014). 0.05* EFSA Journal 2015;13(4):4076

15 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments MRL proposals HR (b) Peppers Indoor No residue trials available. Cucumbers NEU No residue trials available. SEU No residue trials available. Indoor No residue trials available. Melons SEU No residue trials available. Indoor No residue trials available. Watermelons SEU No residue trials available. Indoor No residue trials available. Flowering brassica SEU No residue trials available. Indoor No residue trials available. Lettuce SEU 2 <0.01; 0.02; 0.025; 0.026; 0.03; 0.087; 0.10 Trials compliant with GAP (deviations on application rate within 25 %). Sample storage conditions compliant with stability studies (EFSA, 2014). R ber = 0.15 R max = 0.15 MRL OECD = 0.18 STMR (c) Indoor No residue trials available. Globe artichokes SEU No residue trials available. Soya bean SEU No residue trials available. (*): Indicates that the MRL is derived from trial results at the limit of quantification (LOQ). (a): NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, Indoor: indoor EU trials or Country code: if non-eu trials (EC, 2011). (b): Median value of the individual trial results according to residue definition for risk assessment. (c): Highest value of the individual trial results according to the residue definition for risk assessment EFSA Journal 2015;13(4):4076

16 Table 5: Overview of the available residues trials data supporting authorisations of metalaxyl-m Grapefruit Oranges Limes Mandarins Apples Pears Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs SEU Oranges: 0.02; 0.03; ; 0.07; Lemons: Mandarins: 0.08; 0.12; 0.14; 0.145; 0.17; 0.2 Recommendations/comments Combined data set on oranges, lemons and mandarins compliant with the southern GAP on citrus fruits. Sample storage conditions unknown (EFSA, 2011). R ber = 0.28 R max = 0.24 MRL OECD = MRL proposals HR (b) STMR (c) SEU No residue trials available. Table and wine grapes NEU <0.02; ; 0.07;0.1; 0.11; 0.12; ; ; 0.3; 0.34; 0.52 SEU 0.04; 0.06; 0.15; 0.16; ; 0.21; 0.55 Trials on grapes compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.48 R max = 0.53 MRL OECD = 0.72 Trials on grapes compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.41 R max = 0.69 MRL OECD = 0.82 Strawberries NEU 0.08 Trial compliant with GAP; insufficient to derive MRL for this GAP. Sample storage conditions unknown (EFSA, 2011). SEU 0.11; 0.02 Trials compliant with GAP; insufficient to derive MRL for this GAP. Sample storage conditions unknown (EFSA, 2011). Indoor 0.04; 0.06; 0.084; 0.1; 0.11; ; Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.26 R max = 0.2 MRL OECD = EFSA Journal 2015;13(4):4076

17 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Cane fruit NEU 4 <0.02 Trials on raspberries compliant with GAP; extrapolation to other cane fruit possible because a no residue situation is expected. Sample storage conditions compliant with stability studies (EFSA, 2011). Currants (red, black and white) NEU 2 <0.02; 0.024; 0.17 Trials compliant with GAP. Sample storage conditions compliant with stability studies (EFSA, 2013). R ber = 0.27 R max = 0.44 MRL OECD = 0.36 Kiwi SEU 4 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Potatoes NEU 13 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). SEU 7 <0.02 Trials compliant with GAP (deviations within 25 %). Sample storage conditions compliant with stability studies (EFSA, 2011). Beetroot NEU 2 <0.02 Trials compliant with GAP. Sample storage conditions compliant with stability studies (EFSA, 2011). Carrots Horseradish Parsnips NEU 7 <0.02; 0.02; 0.07 Trials on carrots compliant with GAP; extrapolation to horseradish and parsnips possible. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.08 MRL OECD = 0.09 SEU 8 <0.02 Trials compliant with GAP; not authorised for use on horseradish and parsnips in SEU. Sample storage conditions unknown (EFSA, 2011). MRL proposals HR (b) STMR (c) 0.02* * * * * * EFSA Journal 2015;13(4):4076

18 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Radishes NEU 3 <0.02; 0.04 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.07 R max = 0.08 MRL OECD = 0.06 Salsify NEU 6 <0.02 Trials performed on carrots at exaggerated dose rates ( g a.s./ha instead of 2 100g a.s./ha). Sample storage conditions unknown (EFSA, 2011). Garlic Onions Shallots NEU 9 <0.02 Trials on onions compliant with GAP (deviations on applications rate within 25 %); extrapolation to garlic and shallots possible. Sample storage conditions unknown (EFSA, 2011). SEU 7 <0.02 Trials on onions compliant with GAP; extrapolation to garlic and shallots possible. Sample storage conditions unknown (EFSA, 2011). Spring onions NEU 4 <0.02; 0.023; 0.024; 0.17 Trials compliant with GAP (PHI deviations within 25 %). Sample storage conditions unknown (EFSA, 2011). R ber = 0.23 R max = 0.05 MRL OECD = 0.27 MRL proposals HR (b) STMR (c) * * * EFSA Journal 2015;13(4):4076

19 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Tomatoes NEU 4 <0.02; Trials compliant with GAP (deviations on application rate within 25 %). Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.02 MRL OECD = 0.03 SEU 2 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Indoor 2 <0.02; 0.02; 0.04; 0.05; 0.08; 0.09; 0.115; 0.18 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.2 R max = 0.23 MRL OECD = 0.28 Peppers SEU 2 <0.02; 0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Indoor 2 <0.02; 0.02; 0.03; 0.08; 0.105; 0.135; 0.24 Cucumbers SEU 0.1; 0.12; 0.14; ; 0.17; 0.18; 0.19 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.26 R max = 0.33 MRL OECD = 0.39 Trials compliant with GAP (deviations on application rate within 25 %). Sample storage conditions unknown (EFSA, 2011). R ber = 0.36 R max = 0.25 MRL OECD = 0.45 Indoor 0.05; ; 0.15; 0.19; 0.21; Trials compliant with GAP (deviations on application rate within 25 %). Sample storage conditions unknown (EFSA, 2011). R ber = 0.42 R max = 0.38 MRL OECD = 0.49 MRL proposals HR (b) STMR (c) EFSA Journal 2015;13(4):4076

20 Melons Watermelons Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments SEU 5 <0.02; 0.02; Trials on melons compliant with GAP; extrapolation to watermelons possible. Sample storage conditions unknown (EFSA, 2011). R ber = 0.06 R max = 0.04 MRL OECD = 0.04 Indoor 6 <0.02; 0.02; 0.1 Trials on melons compliant with GAP (deviations on application rate within 25 %); extrapolation to watermelons possible. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.12 MRL OECD = 0.14 Sweet corn NEU 4 <0.02; <0.04; 2 <0.05 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). SEU 3 <0.02; 3 <0.04; 2 <0.05 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Flowering brassica NEU 6 <0.02; ; 0.06; 0.11 Dataset on cauliflower compliant with GAP; tentative extrapolation to broccoli possible. Sample storage conditions unknown (EFSA, 2011). R ber = 0.06 R max = 0.12 MRL OECD = 0.15 SEU 5 <0.02 Combined dataset on broccoli (4) and cauliflower (1) compliant with GAP. Sample storage conditions unknown (EFSA, 2011). MRL proposals HR (b) STMR (c) * * (d) (tentative) 0.02* (d) (tentative) EFSA Journal 2015;13(4):4076

21 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Brussels sprouts NEU 4 <0.02; ; 0.03 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.03 MRL OECD = 0.05 Head cabbage NEU 4 <0.02; ; Trials compliant with GAP (deviations on application rate within 25 %). Sample storage conditions unknown (EFSA, 2011). R ber = 0.07 R max = 0.05 MRL OECD = 0.06 Chinese cabbage NEU 3 <0.02 Overdosed trials on spinach (72 g a.s./100 kg seeds instead of 17 g a.s./100 kg seeds; EFSA, 2015); these trials are sufficient to demonstrate absence of residues in Chinese cabbage. Sample storage conditions compliant with stability studies. Kale NEU 5 <0.05; 0.05; 0.11; 0.21 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.19 R max = 0.26 MRL OECD = 0.31 Kohlrabi NEU 4 <0.02 Trials compliant with GAP (PHI deviations within 25 %). Sample storage conditions unknown (EFSA, 2011). MRL proposals HR (b) STMR (c) * * EFSA Journal 2015;13(4):4076

22 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments MRL proposals HR (b) STMR (c) Lettuce and other salad plants Herbs NEU 2 <0.02; ; Trials on lettuce (closed variety or variety unknown) compliant with GAP (EFSA, 2012); tentative extrapolation to other salad plants and herbs possible. Sample storage conditions compliant with stability studies. R ber = 0.06 R max = 0.04 MRL OECD = (tentative) SEU 2 <0.02; ; ; 0.09 Trials on lettuce (closed variety or variety unknown) compliant with GAP (EFSA, 2012); tentative extrapolation to other salad plants and herbs possible. Sample storage conditions compliant with stability studies. R ber = 0.16 R max = 0.16 MRL OECD = (tentative) Indoor 0.19; 0.20; 0.72; 1.00; ; 1.80 Trials on open leaf lettuce varieties compliant with GAP (EFSA, 2012); extrapolation to other salad plants possible but extrapolation to herbs is tentative because indoor GAP on fresh herbs is less critical. Sample storage conditions compliant with stability studies. R ber = 2.2 R max = 2.59 MRL OECD = (tentative for herbs only) EFSA Journal 2015;13(4):4076

23 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Spinach NEU 5 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). SEU 6 <0.02; trials compliant with GAP. 4 trials with shorter PHI were also considered as residues were close to the LOQ. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.03 MRL OECD = 0.04 MRL proposals HR (b) STMR (c) 0.02* Indoor No residue trials available. Beet leaves (chard) NEU 3 <0.02 Trials on spinach compliant with GAP on beet leaves. Sample storage conditions compliant with stability studies (EFSA, 2015). Witloof Indoor Spray on roots: 0.12; 0.05; Nutrient solution: 0.08; 0.21; 0.15 Beans (fresh, with pods) Beans (fresh, without pods) Peas (fresh, with pods) Peas (fresh, without pods) 3 trials according to method 1 (spray on roots) and 3 trials according to method 2 (via nutrient solution). Sample storage conditions unknown (EFSA, 2011). R ber = 0.33 R max = 0.33 MRL OECD = 0.36 NEU 10 <0.02 Trials on beans with pods compliant with GAP; extrapolation to all fresh legumes is acceptable because residues are below LOQ with pods. Sample storage conditions unknown (EFSA, 2011). Asparagus NEU 4 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Globe artichokes SEU 4 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). 0.02* * * * EFSA Journal 2015;13(4):4076

24 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Leek NEU 7 <0.02; 0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.02 MRL OECD = 0.03 Beans (dry) Peas (dry) NEU 7 <0.02 Trials on dry beans compliant with GAP; extrapolation to dry peas possible. Sample storage conditions unknown (EFSA, 2011). Lupins (dry) NEU 12 <0.02 Trials on peas compliant with GAP on lupins (only the seed treatment is authorised). Sample storage conditions unknown (EFSA, 2011). Linseed Poppy seed Sunflower seed Rape seed Mustard seed Gold of pleasure NEU 10 <0.02 Trials on rape seed compliant with GAP; extrapolation to other oilseeds possible. Sample storage conditions unknown (EFSA, 2011). SEU 5 <0.02 Trials on rape seed compliant with GAP; extrapolation to other oilseeds possible. Sample storage conditions unknown (EFSA, 2011). Not authorised for use on linseed in SEU. Maize grain NEU 8 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Cocoa SEU 10 <0.02 Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). Import (CI) 3 <0.02; Trials compliant with GAP. Sample storage conditions unknown (EFSA, 2011). R ber = 0.04 R max = 0.02 MRL OECD = 0.04 MRL proposals HR (b) STMR (c) * * * * * * (d)(e) (tentative) EFSA Journal 2015;13(4):4076

25 Crop Region/ Indoor (a) Residue levels observed in the supervised residue trials relevant to the supported GAPs Recommendations/comments Hops (dried) NEU 0.61; 0.66; 2.1; 3.1; 4.4; 6 Trials compliant with GAP (dried cones analysed). Sample storage conditions unknown (EFSA, 2011). R ber = 9.6 R max = MRL OECD = Rape forage NEU 10 <0.04 Trials on rape seed compliant with GAP and with samplings at forage stage. Sample storage conditions unknown (Finland, 2011). MRL proposals 15 (e) (tentative) HR (b) STMR (c) * (*): Indicates that the MRL is derived from trial results at the limit of quantification (LOQ). (a): NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, Indoor: indoor EU trials or Country code: if non-eu trials (EC, 2011). (b): Median value of the individual trial results according to residue definition for risk assessment. (c): Highest value of the individual trial results according to the residue definition for risk assessment. (d): MRL proposal is indicated as tentative because further residue trials are still required (e): MRL proposal is indicated as tentative because further validation of the analytical method for enforcement purposes is still required EFSA Journal 2015;13(4):4076

26 Effect of industrial processing and/or household preparation The effect of processing on the nature of metalaxyl was investigated under standard hydrolysis conditions. This study was previously considered by EFSA when the MRLs for metalaxyl-m and metalaxyl were reviewed (EFSA, 2011, 2014) and validity of this study was recently confirmed in the framework of Regulation (EC) No 1107/2009 (EFSA, 2015). EFSA already concluded that the compound is hydrolytically stable under the representative processing conditions and that the residue definition derived for primary crops is also applicable to processed commodities. Studies investigating the effect of processing on the magnitude of metalaxyl and metalaxyl-m residues were reported in different frameworks (EFSA, 2011, 2015). An overview of all available processing studies and the median processing factors derived from these studies is provided in Table 6. Only the processing factors derived for tomatoes and grapes are adequately supported by data and therefore recommended. The remaining processing factors should be considered as indicative only since they are not sufficiently supported by data; a minimum of 3 trials is normally required. Further processing studies are not required for the time being as they are not expected to affect the outcome of the risk assessment but if there would be the intention to derive more robust processing factor, in particular for enforcement purposes, additional processing studies would still be required. Table 6: Overview of the available processing studies Processed commodity Number of studies Median PF (a) Median CF (b) Comments Processing factors recommended (sufficiently supported by data) Tomatoes, juice Trials reported for metalaxyl-m Tomatoes, paste (EFSA, 2015). Tomatoes, peeled and canned Table grapes, dried (raisins) Trials reported for metalaxyl-m Wine grapes, juice (EFSA, 2015). Wine grapes, must Wine grapes, red wine (unheated) Wine grapes, white wine Trials with metalaxyl (8 trials with measurable levels in RAC and PC; Portugal, 2000) and with metalaxyl-m (4 trials; EFSA, 2015) were merged. Wine grapes, dry pomace Trials for metalaxyl-m in juice pomace Wine grapes, wet pomace (4), red wine pomace (4) and white wine pomace (4) were merged (EFSA, 2015). Indicative processing factors (limited dataset) Oranges, juice Trials reported for metalaxyl-m Oranges, marmelade (EFSA, 2011). Strawberries, canned Trials reported for metalaxyl-m Strawberries, jam (EFSA, 2011). Strawberries, sauce (a): The median processing factor (PF) is obtained by calculating the median of the individual processing factors of each processing study. (b): The median conversion factor (CF) for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors of each processing study EFSA Journal 2015;13(4):4076

27 Rotational crops Preliminary considerations Both metalaxyl and metalaxyl-m are authorised for use on several crops that may be grown in rotation with other plants, and soil degradation studies for metalaxyl (in the framework of Directive 91/414/EEC; EC, 2010a) and metalaxyl-m (in the framework of Regulation (EC) No 1107/2009; EFSA, 2015) resulted in maximum DT 90f values of 289 and 103 days respectively, which is above the trigger value of 100 days for both compounds. Therefore, a more detailed assessment on the possible occurrence of residues in succeeding crops was performed by EFSA Nature of residues The metabolism of metalaxyl in rotational crops was initially assessed by when the MRLs for both active substances were reviewed (EFSA, 2011, 2014). Further metabolism studies for metalaxyl-m were peer reviewed by EFSA in the framework of Regulation (EC) No 1107/2009 (EFSA, 2015). An overview of the most relevant metabolism studies is presented in Table 7. Table 7: Overview of the available confined rotational crop studies Crop group Metalaxyl Rotational crop Method Leafy crops Lettuce Primary crop (foliar, potato) Primary crop (soil, tobacco) Root/tuber Sugar beet Primary crop (foliar, potato) Primary crop (soil, tobacco) Cereals Wheat Primary crop (foliar, potato) Oat Maize Primary crop (soil, tobacco) Primary crop (foliar, potato) Primary crop (foliar, potato) Pulse/oilseed Soya bean Primary crop (foliar, potato) Metalaxyl-M Primary crop (soil, tobacco) Application Rate (g/ha) PBI (days) Harvest (DAT) 6 x , 308, 322 References EFSA, 2011, EFSA, 2011, x , 308, 350, 385 EFSA, 2011, EFSA, 2011, x , 259, 287, 315 EFSA, 2011, EFSA, 2011, x , 294, 322, x , 322, 357, x , 336, 357, 406 Leafy crops Lettuce Bare soil , 120, 270 Root/tuber Carrot Bare soil , 120, 270 Cereals Wheat Bare soil , 120, 270 EFSA, 2011, 2014 EFSA, 2011, 2014 EFSA, 2011, EFSA, 2011, 2014 BBCH and at harvest EFSA, 2015 At harvest EFSA, 2015 BBCH 22-30, BBCH and at harvest EFSA, EFSA Journal 2015;13(4):4076

28 These studies were previously relied upon by EFSA to conclude that the metabolic pathway of metalaxyl and metalaxyl-m in rotational crops is similar to that in primary crops but with a greater proportion of sugar conjugates (EFSA, 2011, 2014, 2015). Conclusions previously derived by EFSA are also applicable to the uses of metalaxyl and metalaxyl-m evaluated in this framework and the residue definition for primary crops can be applied to the rotational crops Magnitude of residues When the MRLs for metalaxyl and metalxyl-m were reviewed, EFSA previously considered three rotational crop field trials, where metalaxyl-m was applied to potatoes at g a.s./ha and rotational crops (carrot, lettuce, cauliflower/broccoli and wheat/barley) were planted with a plant-back interval of days after treatment. All residues were <0.02 mg/kg, except in one trial where residues in immature lettuce and immature broccoli ranged between mg/kg (EFSA, 2011, 2014). In the framework of Regulation (EC) No 1107/2009, EFSA recently considered 4 additional field trials where metalaxyl-m was applied on a bare soil at 600 g a.s./ha and rotational crops (carrot, spinach and wheat/barley) were planted with plant-back intervals of 30, 60, 180, 365 and 465 days after treatment, depending on the crops. Residues were generally found to be below <0.01, except for the two shortest plant-back intervals in spinach (up to 0.03 mg/kg), carrot tops (up to 0.02 mg/kg), cereal forage (up to 0.12 mg/kg) and cereal straw (up to 0.06 mg/kg) (EFSA, 2015). The highest seasonal application rates reported for metalaxyl and metalaxyl-m in annual crops are 1200 and 600 g a.s./ha, respectively. Considering that the most recent trials include applications to a bare soil (overestimation of residues is expected and confirmed by the older trials), EFSA concludes that significant residues are not expected in rotational crops provided that metalaxyl and metalaxyl-m are applied in compliance with the GAPs reported in appendices A and B. If seasonal application rates are however further increased in the future (for metalaxyl in particular), more adequate field trials would be required Nature and magnitude of residues in livestock Dietary burden of livestock Both metalaxyl and metalaxyl-m are authorised for use on several crops that might be fed to livestock. The median and maximum dietary burdens were therefore calculated for the different groups of livestock using the agreed European methodology (EC, 1996). The input values for all relevant commodities were selected according to the recommendations of JMPR (FAO, 2009) and are summarised in Table 8. For citrus pomace and oilseed press cakes, default processing factors of respectively 2.5 and 2 were included in the calculation in order to consider the potential concentration of residues in these commodities. Table 8: Input values for the dietary burden calculation Commodity Median dietary burden Input value Comment Maximum dietary burden Input value Comment Risk assessment residue definition: metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers) Cabbage 0.02 STMR 0.04 HR Kale 0.05 STMR 0.21 HR Rape forage 0.04 STMR 0.04 HR Citrus pomace 0.24 STMR STMR 2.5 Maize grain 0.02 STMR 0.02 STMR 28 EFSA Journal 2015;13(4):4076

29 Commodity Median dietary burden Input value Comment Maximum dietary burden Input value Comment Pulses 0.02 STMR 0.02 STMR Potatoes 0.02 STMR 0.02 HR Rape seed meal 0.04 STMR STMR 2 Linseed meal 0.04 STMR STMR 2 Sunflower seed meal 0.04 STMR STMR 2 The results of the calculations are reported in Table 9. The calculated dietary burdens were found to exceed the trigger value of 0.1 mg/kg DM for all groups of livestock. Further assessment of residues in all commodities of animal origin is therefore relevant. It is highlighted that residue data were not available for the use of metalaxyl-m on apples and for the use of metalaxyl on citrus fruits, apples and soya beans. Although these authorisations may in principle lead to an increase of the livestock dietary burden, they are also expected to generate residue levels in a range similar to the residue levels observed for the uses of metalaxyl-m in citrus fruits and oilseeds, which were already included in the livestock dietary burden calculation. Hence the impact of the above mentioned data gaps on the outcome of the assessment for livestock is expected to be limited. Table 9: Results of the dietary burden calculation Maximum dietary burden (mg/kg bw per d) Median dietary burden (mg/kg bw per d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded (Y/N) Risk assessment residue definition: metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers) Dairy cattle Kale Y Beef cattle Kale Y Poultry Kale Y Pigs Kale Y Nature of residues The metabolism of metalaxyl in livestock was previously assessed by EFSA when the MRLs for metalaxyl-m were reviewed (EFSA, 2011). The reported studies included one study with lactating goats (dosed with 3.9 mg a.s./kg bw per day, approximately 150 N rate) and one study with laying hens (dosed with 6 mg a.s./kg bw per day, approximately 800 N rate). The presence of many metabolites and the low levels of parent compound indicate extensive metabolism with metabolite CGA (see Appendix D) being the major metabolite in animal tissues and metabolite CGA (see Appendix D) being the major metabolite in milk. Metabolic patterns identified for ruminants and hens were consistent with the rat metabolism and findings can be extrapolated to pigs. During the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009, an additional metabolism study in ruminants was reported (Belgium, 2013). This study is consistent with the metabolism study previously considered by EFSA. Hence, based on the above findings and the analytical method reported for enforcement (see also section 1.2), the relevant residue for enforcement and risk assessment in all commodities of animal origin is defined as the sum of metalaxyl (sum of isomers) and its metabolites containing the 2, EFSA Journal 2015;13(4):4076

30 dimethylaniline moiety, expressed as metalaxyl. It is noted that for enforcement purposes the residue might be simplified to metabolie CGA in animal tissues and metabolite CGA in milk, but analytical methods and livestock feeding studies supporting such a simplified residue definition are currently not available and would be desirable Magnitude of residues When the MRLs for metalaxyl-m were reviewed, a first livestock feeding study on lactating cows (dose level of 4.28 mg/kg bw per day for 14, 21 and 28 consecutive days) was initially considered (EFSA, 2011). Meanwhile, an additional livestock feeding study on lactating cows (dose level of 0.07, 0.36 and 0.68 mg/kg bw per day for 14, 21 and 28 consecutive days) was recently reported in the framework of the peer review of metalaxyl-m under Regulation (EC) No 1107/2009 (Belgium, 2013). In both studies, samples of muscle, fat, liver, kidneys and milk were analysed for total residues of metalaxyl as 2,6-dimethylaniline. In terms of study design and dose levels tested, the feeding study recently reported under Regulation (EC) No 1107/2009 is more adequate than the feeding study previously considered by EFSA, although some minor deficiencies were identified such as the high variability of residues observed in liver and kidney. Since the study only investigated one animal for each dose level and for each duration of treatment, it cannot be ascertained that the variations observed are resulting from an intra-species variability, and a livestock feeding study compliant with current guidelines and investigating residues according to two residue definitions (including a simplified residue definition, see section 3.2.2) would still be desirable. Meanwhile, it was assumed that the variation of residues was mainly due to intraspecies variability and data were merged per dose level. Results of this feeding study are reported in Table 10. The potential degradation of residues during storage of the study samples was also assessed. During the recent peer review of metalaxyl-m under Regulation (EC) No 1107/2009, storage stability of metalaxyl and metabolite CGA (both determined as 2,6-dimethylaniline) was demonstrated for a period of 21 months at -18 C in muscle, liver, milk and eggs (Belgium, 2013). Since the samples of the most relevant livestock feeding study were stored for 11 months under frozen conditions, decline of residues in the study samples is not expected. Consequently, the available data are considered sufficient for deriving MRLs in ruminants and pigs. These MRLs were derived in compliance with the latest recommendations on this matter (FAO, 2009) and are summarised in Table 10. Considering that the analytical method for enforcement purposes is not fully validated, these MRL proposals are to be considered as tentative. Regarding poultry, the metabolism study reported under section (maximum TRR of approximately 1.5 mg eq/kg at a 800 N rate) is sufficient to tentatively propose MRL and risk assessment values for poultry at the LOQ level. Poultry feeding studies were also reported in the framework of Regulation (EC) No 1107/2009 (Belgium, 2013); they were not reported in detail because they confirmed findings observed in the metabolism study EFSA Journal 2015;13(4):4076

31 Table 10: Overview of the values derived from the livestock feeding studies Commodity Dietary burden Results of the livestock feeding study Median No Enforcement Risk assessment residue (a) Median (mg/kg bw per d) Max. (mg/kg bw per d) Dose level (mg/kg bw per day) Mean Max. Mean Max. Highest residue (b) MRL proposal Pig muscle (d) (e) <0.05 <0.05 <0.05 < * (i) (e) <0.05 <0.05 <0.05 < (e) <0.05 <0.05 <0.05 <0.05 (tentative) Pig fat (d) (f) <0.05 <0.05 <0.05 < * (i) (f) <0.05 <0.05 <0.05 < (f) <0.05 <0.05 <0.05 <0.05 (tentative) Pig liver (d) (g) < < * (i) (g) (g) (tentative) Pig kidney (d) (g) (i) (g) (g) (tentative) Ruminant muscle (e) <0.05 <0.05 <0.05 < * (i) (e) <0.05 <0.05 <0.05 < (e) <0.05 <0.05 <0.05 <0.05 (tentative) Ruminant fat (f) <0.05 <0.05 <0.05 < * (i) (f) <0.05 <0.05 <0.05 < (f) <0.05 <0.05 <0.05 <0.05 (tentative) Ruminant liver (g) < < * (i) (g) (g) (tentative) CF for RA (c) EFSA Journal 2015;13(4):4076

32 Commodity Dietary burden Results of the livestock feeding study Median No Enforcement Risk assessment residue (a) Median (mg/kg bw per d) Max. (mg/kg bw per d) Dose level (mg/kg bw per day) Mean Max. Mean Max. Highest residue (b) Ruminant kidney (g) (i) (g) (g) MRL proposal (tentative) Milk (h) <0.01 n.a. <0.01 n.a * (i) (h) <0.01 n.a. <0.01 n.a (h) <0.01 n.a. <0.01 n.a. (tentative) n.a.: not applicable only the mean values are considered for calculating MRLs in milk (*): Indicates that the MRL is proposed at the limit of quantification (LOQ). (a): Median residue value according to the enforcement residue definition, derived by interpolation/extrapolation from the feeding study for the median dietary burden (FAO, 2009) (b): 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). (c): Median conversion factor for enforcement to risk assessment. (d): Although the feeding study results originate from the ruminant study, the MRL and risk assessment values are based on the calculated dietary burden for pigs. (e): 2 samples per animal (tenderloin muscle and round muscle), animals with different durations of treatment (14, 21, 28 and 40 days, the latter only for the middle dose) were merged. (f): 2 samples per animal (perirenal fat and omental fat), animals with different durations of treatment (14, 21, 28 and 40 days, the latter only for the middle dose) were merged. (g): Animals with different durations of treatment (14, 21, 28 and 40 days, the latter only for the middle dose) were merged. (h): Milk samples were collected at 7, 14, 21 and 28 days for all dose levels with an additional sampling at 40 days for the middle dose level. (i): MRL proposal is indicated as tentative because further validation of the analytical method for enforcement purposes is still required. CF for RA (c) EFSA Journal 2015;13(4):4076

33 4. Consumer risk assessment Chronic and acute exposure calculations for all crops reported in the framework of this review were performed using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo) (EFSA, 2007). Considering that metalaxyl and metalaxyl-m share the same residue definition and toxicological reference values, the use of both compounds was combined in one exposure assessment. For each commodity, risk assessment values obtained for metalaxyl and metalaxyl-m were compared and the most critical values were selected for the exposure calculations. For certain commodities however the available residue trials were only sufficient to derive risk assessment values for the use of metalaxyl-m while the use of metalaxyl was not supported by residue trials, and it cannot be excluded that the use of metalaxyl will result in higher residue levels than the use of metalaxyl-m, in particular when the existing EU MRL is higher than the MRL proposal derived for the use of metalaxyl-m. In this case EFSA decided, as a conservative approach, to use the existing EU MRL for indicative exposure calculation. Also for those commodities where data were not sufficient to derive an MRL, neither for metalaxyl, nor for metalaxyl-m, EFSA considered the existing EU MRL. The contributions of other commodities, for which no GAP was reported in the framework of this review, were not included in the calculation. All input values refer to the residues observed in the raw agricultural commodities; an overview of the input values is provided in Table 11. Table 11: Input values for the consumer dietary exposure assessment Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Risk assessment residue definition: metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers) Grapefruit 0.50 EU MRL (a) 0.50 EU MRL (a) Oranges 0.50 EU MRL (a) 0.50 EU MRL (a) Lemons 0.50 EU MRL (b) 0.50 EU MRL (b) Limes 0.50 EU MRL (a) 0.50 EU MRL (a) Mandarins 0.50 EU MRL (a) 0.50 EU MRL (a) Apples 1.00 EU MRL (b) 1.00 EU MRL (b) Pears 1.00 EU MRL (b) 1.00 EU MRL (b) Table grapes 2.00 EU MRL (a) 2.00 EU MRL (a) Wine grapes 1.00 EU MRL (a) 1.00 EU MRL (a) Strawberries 0.50 EU MRL (a) 0.50 EU MRL (a) Cane fruit 0.02* STMR (c) 0.02* HR (c) Currants (red, black and white) 0.02 STMR (c) 0.17 HR (c) Kiwi 0.02* STMR (c) 0.02* HR (c) Potatoes 0.02* STMR (d) 0.02* HR (d) Beetroot 0.02* STMR (c) 0.02* HR (c) Carrots 0.02* STMR (e) 0.07 HR (e) Horseradish 0.02* STMR (c) 0.07 HR (c) Parsnips 0.02* STMR (c) 0.07 HR (c) 33 EFSA Journal 2015;13(4):4076

34 Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Radishes 0.02* STMR (c) 0.04 HR (c) Salsify 0.02* STMR (c) 0.02* HR (c) Garlic 0.02* STMR (c) 0.02* HR (c) Onions 0.50 EUMRL (a) 0.50 EU MRL (a) Shallots 0.02* STMR (c) 0.02* HR (c) Spring onions 0.02* STMR (c) 0.17 HR (c) Tomatoes 0.05 STMR (d) 0.18 HR (d) Peppers 0.50 EUMRL (a) 0.50 EU MRL (a) Cucumbers 0.15 STMR (e) 0.26 HR (e) Melons 0.20 EUMRL (a) 0.20 EU MRL (a) Watermelons 0.20 EUMRL (a) 0.20 EU MRL (a) Sweet corn 0.04* STMR (c) 0.05* HR (c) Flowering brassica 0.20 EUMRL (f) 0.20 EU MRL (f) Brussels sprouts 0.02* STMR (c) 0.03 HR (c) Head cabbage 0.02* STMR (c) 0.04 HR (c) Chinese cabbage 0.02* STMR (c) 0.02* HR (c) Kale 0.05 STMR (c) 0.21 HR (c) Kohlrabi 0.02* STMR (c) 0.02* HR (c) Lamb's lettuce 1.05 STMR (c) 1.80 HR (c) Lettuce 1.05 STMR (d) 1.80 HR (d) Scarole (broad-leaf endive) 1.05 STMR (c) 1.80 HR (c) Cress 1.05 STMR (c) 1.80 HR (c) Land cress 1.05 STMR (c) 1.80 HR (c) Rocket, Rucola 1.05 STMR (c) 1.80 HR (c) Red mustard 1.05 STMR (c) 1.80 HR (c) Leaves and sprouts of Brassica spp 1.05 STMR (c) 1.80 HR (c) Spinach 0.02* STMR (c) 0.03 HR (c) Beet leaves (chard) 0.02* STMR (c) 0.02* HR (c) Witloof 0.11 STMR (c) 0.21 HR (c) Herbs 1.05 STMR (tentative) (g) 1.80 HR (tentative) (g) Beans (fresh, with pods) 0.02* STMR (c) 0.02* HR (c) Beans (fresh, without pods) 0.02* STMR (c) 0.02* HR (c) Peas (fresh, with pods) 0.02* STMR (c) 0.02* HR (c) Peas (fresh, without pods) 0.02* STMR (c) 0.02* HR (c) Asparagus 0.02* STMR (c) 0.02* HR (c) Globe artichokes 0.05 EU MRL (a) 0.05 EU MRL (a) 34 EFSA Journal 2015;13(4):4076

35 Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Leek 0.02* STMR (c) 0.02 HR (c) Beans (dry) 0.02* STMR (c) 0.02* HR (c) Peas (dry) 0.02* STMR (c) 0.02* HR (c) Lupins (dry) 0.02* STMR (c) 0.02* HR (c) Linseed 0.02* STMR (c) 0.02* HR (c) Poppy seed 0.02* STMR (c) 0.02* HR (c) Sunflower seed 0.02* STMR (c) 0.02* HR (c) Rape seed 0.02* STMR (c) 0.02* HR (c) Soya beans 0.1 EU MRL (b) 0.1 EU MRL (b) Mustard seed 0.02* STMR (c) 0.02* HR (c) Gold of pleasure 0.02* STMR (c) 0.02* HR (c) Maize grain 0.02* STMR (c) 0.02* HR (c) Cocoa (fermented beans) 0.02* STMR (tentative) (g) 0.02 HR (tentative) (g) Hops (dried) 2.60 STMR (tentative) (g) 6.00 HR (tentative) (g) Risk assessment residue definition: sum of metalaxyl (sum of isomers) and its metabolites containing the 2,6-dimethylaniline moiety, expressed as metalaxyl Swine meat 0.01* STMR muscle (tentative) (h) 0.01* HR muscle (tentative) (h) Swine fat (free of lean meat) 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Swine liver 0.05* STMR (tentative) (h) 0.05* HR (tentative) (h) Swine kidney 0.05* STMR (tentative) (h) 0.11 HR (tentative) (h) Ruminant meat 0.01* STMR muscle (tentative) (h) 0.01* HR muscle (tentative) (h) Ruminant fat 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Ruminant liver 0.05* STMR (tentative) (h) 0.05* HR (tentative) (h) Ruminant kidney 0.08 STMR (tentative) (h) 0.23 HR (tentative) (h) Poultry meat 0.01* STMR muscle (tentative) (h) 0.01* HR muscle (tentative) (h) Poultry fat 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Poultry liver 0.05* STMR (tentative) (h) 0.05* HR (tentative) (h) Cattle milk 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Sheep milk 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Goat milk 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) Birds eggs 0.01* STMR (tentative) (h) 0.01* HR (tentative) (h) (*): Indicates that the input value is derived from trial results at the limit of quantification (LOQ). (a): At least one GAP for metalaxyl-m is fully supported by data and, although the existing EU MRL for this commodity is higher than the MRL proposal derived for metalaxyl-m, the use of metalaxyl is not supported by data; the existing EU MRL is used for indicative exposure calculations. (b): The use of metalaxyl and/or metalaxyl-m is not supported by data for this commodity; the existing EU MRL is used for indicative exposure calculations 35 EFSA Journal 2015;13(4):4076

36 (c): At least one GAP for metalaxyl-m is fully supported by data and the use of metalaxyl is not authorised for this commodity; the risk assessment values derived for metalaxyl-m are used for the exposure calculations. (d): At least one GAP for metalaxyl and at least one GAP for metalaxyl-m are fully supported by data for this commodity; the risk assessment values derived for the most critical GAP are used for the exposure calculations. (e): At least one GAP for metalaxyl-m is fully supported by data and, although the use of metalaxyl is not supported by data for this commodity, the existing EU MRL is equal to the MRL proposal derived for metalaxyl-m; the risk assessment values derived for metalaxyl-m are used for the exposure calculations. (f): GAP for metalaxyl-m is not fully supported by data and the GAP for metalaxyl is not supported by data at all; the existing EU MRL is used for indicative exposure calculations. (g): GAP for metalaxyl-m is not fully supported by data and the use of metalaxyl is not authorised for this commodity; the tentative risk assessment values derived for metalaxyl-m are used for indicative exposure calculations. (h): Dietary burden relevant to this commodity of animal origin, resulting from the GAPs reported, is not fully supported by data; the tentative risk assessment values derived in section 3 are used for indicative exposure calculations. The calculated exposures were compared with the toxicological reference values derived for metalaxyl and metalaxyl-m (see Table 1); detailed results of the calculations are presented in Appendix C. The highest chronic exposure was calculated for German children, representing 23% of the ADI, and the highest acute exposure was calculated for scarole, representing 32% of the ARfD. Based on the above calculations, EFSA concludes that the use of metalaxyl and/or metalaxyl-m on crops sufficiently supported by data (footnotes (c), (d) and (e) in Table 10), is acceptable with regard to consumer exposure. For the other crops, major uncertainties remain due to the data gaps identified in section 3 but considering tentative MRLs or existing EU MRLs in the exposure calculation did not indicate a risk to consumers. It is noted that CXLs for metalaxyl were also adopted by the CAC; these international recommendations should in principle be considered by European risk managers when establishing MRLs. However, most of these CXLs were assessed by the JMPR between 1982 and 1992, when information provided in the JMPR reports was very limited. EFSA was therefore not able to retrieve all information supporting the CXLs that are currently in place. The use of metalaxyl-m was assessed more recently by JMPR (FAO, 2004), but recommendations resulting from this assessment were not yet adopted by the CAC pending the periodic review of metalaxyl, which is scheduled for the JMPR meeting in Also considering that CXLs for metalaxyl are currently not implemented in European legislation, inclusion of the CXLs in the EU risk assessment for metalaxyl and metalaxyl-m was not considered appropriate at this stage. Conclusions The toxicological profile of metalaxyl and metalaxyl-m was evaluated in the framework of Directive 91/414/EEC, which resulted in an ADI and an ARfD being established at 0.08 mg/kg bw per d and 0.5 mg/kg bw, respectively. Primary crop metabolism of metalaxyl and metalaxyl-m was investigated in four different crop groups (fruit crops, root and tuber crops, leafy crops and cereals) and according to three different types application (foliar, seed and soil treatments), hereby covering all uses of metalaxyl and metalaxyl-m evaluated in this framework. The residue definition for enforcement and risk and risk assessment in all plant commodities is defined as metalaxyl including other mixtures of constituent isomers including metalaxyl-m (sum of isomers). Validated analytical methods for enforcement of this residue definition are available with an LOQ of 0.01 mg/kg for all plant commodities, except for complex matrices such as cocoa and hops. Regarding the magnitude of residues in primary crops, available trials are considered sufficient to derive MRL proposals as well as risk assessment values for all crops under assessment, except for apples, pears and soya beans where data were insufficient to derive an MRL. Considering that an analytical method for enforcement of residues in complex matrices is not available and that residue trials are still required for some crops, MRL proposals for flowering brassica, herbs, cocoa and hops should be considered tentative. Furthermore, it is highlighted that all MRL proposals were derived from the use of metalaxyl-m but it cannot be excluded that the use of metalaxyl leads to higher residue levels than those observed for metalaxyl-m EFSA Journal 2015;13(4):4076

37 The effect of processing on the nature of metalaxyl was investigated under standard hydrolysis conditions. The compound was found to be hydrolytically stable under these conditions and the residue definition derived for primary crops is also applicable to processed commodities. Studies investigating the effect of processing on the magnitude of metalaxyl and metalaxyl-m residues were also reported, allowing EFSA to derive robust processing factors for processed products of tomatoes (juice, paste and canned tomatoes) and grapes (raisins, juice, must, white wine, red wine, dry pomace and wet pomace). Further processing studies are not required for the time being as they are not expected to affect the outcome of the risk assessment but if there would be the intention to derive more robust processing factor, in particular for enforcement purposes, additional processing studies would still be required. Confined rotational crop studies investigating the uptake of metalaxyl and metalaxyl-m from soil were reported in four different crop groups (root and tuber crops, leafy crops, cereals, and pulses and oilseeds), and the residue definition for primary crops can also be applied to the rotational crops. Based on further rotational crop field trials, it was also concluded that significant residues in rotational crops are not expected, provided that metalaxyl and metalaxyl-m are applied according to the GAPs reported for these substances. Based on the uses reported, significant livestock dietary burden were calculated for dairy ruminants, meat ruminants, pigs and poultry. The metabolism of metalaxyl in livestock was evaluated and the relevant residue for enforcement and risk assessment in all commodities of animal origin is defined as the sum of metalaxyl (sum of isomers) and its metabolites containing the 2,6-dimethylaniline moiety, expressed as metalaxyl. For enforcement purposes, the residue might be simplified to metabolie CGA in animal tissues and metabolite CGA in milk, but analytical methods and livestock feeding studies supporting such a simplified residue definition are currently not available. Meanwhile, based on the available feeding studies and the proposed residue definition, MRLs can be derived at the LOQ of 0.01 mg/kg in muscle, fat, milk and eggs and at the LOQ of 0.05 mg/kg in liver. In swine kidney and ruminant kidney, MRL proposals of respectively 0.3 and 0.15 mg/kg were derived. Considering that the analytical method for enforcement purposes is not fully validated, these MRL proposals are to be considered as tentative. Chronic and acute consumer exposure resulting from the authorised uses of metalaxyl and metalaxyl-m was calculated using revision 2 of the EFSA PRIMo. For each commodity, risk assessment values obtained for metalaxyl and metalaxyl-m were compared and the most critical values were selected for the exposure calculations. For those commodities where available residue trials were only sufficient to derive risk assessment values for the use of metalaxyl-m while the use of metalaxyl was not supported by residue trials, EFSA followed the most conservative approach by considering the existing EU MRL for indicative exposure calculation, unless the existing EU MRL was not higher than the MRL proposal derived for the use of metalaxyl-m. Also for those commodities where data were not sufficient to derive an MRL, neither for metalaxyl, nor for metalaxyl-m, EFSA considered the existing EU MRL. Following this approach, the highest chronic exposure represented 23 % of the ADI (German children) and the highest acute exposure amounted to 32 % of the ARfD (scarole). Inclusion of the existing CXLs for metalaxyl in the EU risk assessment was not considered appropriate at this stage because information supporting those CXLs is very limited and a review of those CXLs is scheduled for the JMPR in Recommendations MRL recommendations were derived in compliance with the assessment described above; they are summarised in Table 12. All MRL values listed as Recommended in the table are sufficiently supported by data and are therefore proposed for inclusion in Annex II to the Regulation. The remaining MRL values listed in the table are not recommended for inclusion in Annex II because they require further consideration by risk managers (see footnotes of Table 12 for details). In particular, some tentative MRLs or existing EU MRLs need to be confirmed by the following data: validation of the analytical method for enforcement in complex matrices such as cocoa and hops; 37 EFSA Journal 2015;13(4):4076

38 further validation data demonstrating the efficiency of the extraction, hydrolysis and derivatisation steps included in the proposed analytical method for enforcement of residues in livestock; independent laboratory validation (ILV) of the proposed analytical method for enforcement of residues in fat; residue trials supporting authorisations of metalaxyl in citrus fruits, apples, table grapes, wine grapes, strawberries, carrots, onions, peppers, melons, watermelons, flowering brassica, globe artichoke and soya beans; residue trials supporting authorisations of metalaxyl-m in apples, pears, flowering brassica, herbs and cocoa. Furthermore, it is highlighted that some of the MRLs derived may result from a fully supported GAP, while other GAPs reported were not fully supported by data. EFSA therefore identified the following data gaps which are not expected to impact on the validity of the MRLs derived but which might have an impact on national authorisations: residue trials supporting further authorisations of metalaxyl on potatoes, tomatoes, cucumbers and lettuce; residue trials supporting further authorisations of metalaxyl-m on strawberries, tomatoes, peppers, salad plants and spinach. If the above reported data gaps are not addressed in the future, Member States are recommended to withdraw or modify the relevant authorisations at national level. Minor deficiencies were also identified in the assessment but these deficiencies are not expected to impact either on the validity of the MRLs derived or on the national authorisations. The following data are therefore considered desirable but not essential: 1 additional residue trial on mandarins and 1 additional residue trial on oranges, both compliant with the southern GAP of metalaxyl-m on citrus fruits; 1 additional residue trial on cucumbers compliant with the indoor GAP of metalaxyl-m; an analytical method for enforcement of a simplified residue definition in livestock; a livestock feeding study compliant with current guidelines and investigating residues according to two residue definitions (including a simplified residue definition) EFSA Journal 2015;13(4):4076

39 Table 12: Summary table of the MRL review Code (a) Commoditiy Current EU MRL Current CXL (b) MRL Outcome of the review Comment Residue definition for enforcement: metalaxyl including other mixtures of constituent isomers including metalaxyl m (sum of isomers) Grapefruit Further consideration needed (c) Oranges Further consideration needed (c) Lemons Further consideration needed (d) Limes Further consideration needed (c) Mandarins Further consideration needed (c) Apples Further consideration needed (d) Pears Further consideration needed (d) Quinces 1 1 Further consideration needed (j) Medlar 1 1 Further consideration needed (j) Loquat 1 1 Further consideration needed (j) Table grapes Further consideration needed (c) Wine grapes Further consideration needed (c) Strawberries Further consideration needed (c) Blackberries 0.05* 0.02* Recommended (e) Dewberries 0.05* 0.02* Recommended (e) Raspberries 0.05* * Recommended (e) Currants (red, black and white) Recommended (e) Kiwi 0.05* 0.02* Recommended (e) Avocados 0.05* 0.2 Further consideration needed (j) Potatoes 0.05* 0.05* 0.02* Recommended (f) Beetroot 0.05* 0.02* Recommended (e) Carrots * 0.1 Recommended (g) Horseradish Recommended (e) Parsnips Recommended (e) Radishes Recommended (e) Salsify 0.05* 0.02* Recommended (e) Garlic * Recommended (e) Onions Further consideration needed (c) Shallots * Recommended (e) Spring onions Recommended (e) Tomatoes Recommended (f) Peppers Further consideration needed (c) Cucumbers Recommended (g) Gherkins 0.05* 0.5 Further consideration needed (j) 39 EFSA Journal 2015;13(4):4076

40 Code (a) Commoditiy Current EU MRL Current CXL (b) MRL Outcome of the review Comment Courgettes 0.05* 0.2 Further consideration needed (j) Melons Further consideration needed (c) Pumpkins 0.05* 0.2 Further consideration needed (j) Watermelons Further consideration needed (c) Sweet corn 0.05* 0.05* Recommended (e) Flowering brassica Further consideration needed (h) Brussels sprouts 0.05* Recommended (e) Head cabbage Recommended (e) Chinese cabbage 0.05* 0.02* Recommended (e) Kale Recommended (e) Kohlrabi 0.05* 0.02* Recommended (e) Lamb's lettuce 3 3 Recommended (e) Lettuce Recommended (f) Scarole (broad leaf endive) 3 3 Recommended (e) Cress 3 3 Recommended (e) Land cress 3 3 Recommended (e) Rocket, Rucola 3 3 Recommended (e) Red mustard 3 3 Recommended (e) Leaves and sprouts of Brassica spp 3 3 Recommended (e) Spinach 0.05* Recommended (e) Beet leaves (chard) 0.05* 0.02* Recommended (e) Witloof Recommended (e) Herbs 2 3 Further consideration needed (i) Beans (fresh, with pods) Beans (fresh, without pods) 0.05* 0.02* Recommended (e) 0.05* 0.02* Recommended (e) Peas (fresh, with pods) 0.05* 0.02* Recommended (e) Peas (fresh, without pods) 0.05* 0.05* 0.02* Recommended (e) Asparagus 0.05* 0.05* 0.02* Recommended (e) Globe artichokes 0.05* 0.05 Further consideration needed (c) Leek Recommended (e) Beans (dry) 0.05* 0.02* Recommended (e) Peas (dry) 0.05* 0.02* Recommended (e) Lupins (dry) 0.05* 0.02* Recommended (e) Linseed 0.1* 0.02* Recommended (e) Peanuts 0.1* 0.1 Further consideration needed (j) 40 EFSA Journal 2015;13(4):4076

41 Code (a) Commoditiy Current EU MRL Current CXL (b) MRL Outcome of the review Comment Poppy seed 0.1* 0.02* Recommended (e) Sunflower seed 0.1* 0.05* 0.02* Recommended (e) Rape seed 0.1* 0.02* Recommended (e) Soya bean 0.1* 0.05* 0.1 Further consideration needed (d) Mustard seed 0.1* 0.02* Recommended (e) Cotton seed 0.1* 0.05* Further consideration needed (j) Gold of pleasure 0.1* 0.02* Recommended (e) Barley grain 0.05* 0.05* Further consideration needed (j) Buckwheat grain 0.05* 0.05* Further consideration needed (j) Maize grain 0.05* 0.05* 0.02* Recommended (e) Millet grain 0.05* 0.05* Further consideration needed (j) Oats grain 0.05* 0.05* Further consideration needed (j) Rice grain 0.05* 0.05* Further consideration needed (j) Rye grain 0.05* 0.05* Further consideration needed (j) Sorghum grain 0.05* 0.05* Further consideration needed (j) Wheat grain 0.05* 0.05* Further consideration needed (j) Cocoa (fermented beans) 0.1* Further consideration needed (i) Hops (dried) Further consideration needed (i) Spices (seeds) 0.1* 5 Further consideration needed (j) Sugar beet (root) * Further consideration needed (j) Other commodities of plant origin See Regulation 36/2014 Further consideration needed (j) Residue definition for enforcement (existing): metalaxyl including other mixtures of constituent isomers including metalaxyl m (sum of isomers) Residue definition for enforcement (proposed): sum of metalaxyl (sum of isomers) and its metabolites containing the 2,6 dimethylaniline moiety, expressed as metalaxyl Swine meat 0.05* 0.01* Further consideration needed (k) Swine fat (free of lean meat) 0.05* 0.01* Further consideration needed (k) Swine liver 0.05* 0.05* Further consideration needed (k) Swine kidney 0.05* 0.15 Further consideration needed (k) Bovine meat 0.05* 0.01* Further consideration needed (k) Bovine fat 0.05* 0.01* Further consideration needed (k) Bovine liver 0.05* 0.05* Further consideration needed (k) Bovine kidney 0.05* 0.3 Further consideration needed (k) Sheep meat 0.05* 0.01* Further consideration needed (k) Sheep fat 0.05* 0.01* Further consideration needed (k) Sheep liver 0.05* 0.05* Further consideration needed (k) 41 EFSA Journal 2015;13(4):4076

42 Code (a) Commoditiy Current EU MRL Current CXL (b) MRL Outcome of the review Comment Sheep kidney 0.05* 0.3 Further consideration needed (k) Goat meat 0.05* 0.01* Further consideration needed (k) Goat fat 0.05* 0.01* Further consideration needed (k) Goat liver 0.05* 0.05* Further consideration needed (k) Goat kidney 0.05* 0.3 Further consideration needed (k) Poultry meat 0.05* 0.01* Further consideration needed (k) Poultry fat 0.05* 0.01* Further consideration needed (k) Poultry liver 0.05* 0.05* Further consideration needed (k) Cattle milk 0.05* 0.01* Further consideration needed (k) Sheep milk 0.05* 0.01* Further consideration needed (k) Goat milk 0.05* 0.01* Further consideration needed (k) Birds eggs 0.05* 0.01* Further consideration needed (k) Other commodities of plant origin See Regulation 36/2014 Further consideration needed (j) (*): Indicates that the MRL is derived from trial results at the limit of quantification (LOQ). (a): According to Annex I of Regulation (EC) 396/2005 (b): Although it was not considered appropriate at this stage to include the current CXLs in the EU assessment, the list of current CXLs is provided in this table for transparency. (c): GAP evaluated at EU level for metalaxyl is not supported by data but no risk to consumers was identified for the existing EU MRL; the GAP evaluated at EU level for metalaxyl-m is fully supported by data and may serve as a basis for deriving a fall-back MRL. (d): GAP evaluated at EU level for metalaxyl or metalaxyl-m is not supported by data but no risk to consumers was identified for the existing EU MRL. (e): MRL is derived from a GAP evaluated at EU level for metalaxyl-m, which is fully supported by data and for which no risk to consumers is identified; there are no relevant authorisations or import tolerances reported at EU level for metalaxyl. (f): MRL is derived from a GAP evaluated at EU level for metalaxyl-m, which is fully supported by data and for which no risk to consumers is identified; GAP evaluated at EU level for metalaxyl is also supported by data and covered by the proposed MRL. (g): MRL is derived from a GAP evaluated at EU level for metalaxyl-m, which is fully supported by data and for which no risk to consumers is identified; GAP evaluated at EU level for metalaxyl is not supported by data but the existing EU MRL is covered by the MRL proposal. (h): GAP evaluated at EU level for metalaxyl is not supported by data but no risk to consumers was identified for the existing EU MRL; the GAP evaluated at EU level for metalaxyl-m is not fully supported by data but may serve as a basis for deriving a tentative fall-back MRL. (i): Tentative MRL is derived from a GAP evaluated at EU level for metalaxyl-m, which is not fully supported by data but for which no risk to consumers was identified; there are no relevant authorisations or import tolerances reported at EU level for metalaxyl. (j): There are no relevant authorisations or import tolerances reported at EU level, neither for metalaxyl, nor for metalaxyl-m; either a specific LOQ or the default MRL of 0.01 mg/kg may be considered. (k): Tentative MRL is derived from the livestock dietary burden calculated for metalaxyl and metalaxyl-m, which is not fully supported by data but for which no risk to consumers was identified EFSA Journal 2015;13(4):4076

43 References Belgium, Renewal Assessment Report (RAR) on the active substance metalaxyl-m prepared by the rapporteur Member State Belgium in the framework of Regulation (EC) No 1141/2010, November Available at Belgium, Final Addendum to the Renewal Assessment Report on metalaxyl-m, compiled by EFSA, November Available at CEN (European Committee for Standardisation), Foods of plant origin Determination of pesticide residues using GC-MS and/or LC-MS/MS following acetonitrile extraction/partitioning and clean-up by dispersive SPE. QuEChERS-method. EN November European Commission, Appendix G. Livestock Feeding Studies. 7031/VI/95-rev.4. European Commission, 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95-rev.3. European Commission, 1997b. Appendix B. General recommendations for the design, preparation and realisation of residue trials. Annex 2. Classification of (minor) crops not listed in the Appendix of Council Directive 90/642/EEC. 7029/VI/95-rev.6. European Commission, 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95-rev.2. European Commission, 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. European Commission, 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev.3. European Commission, 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95-rev.5. European Commission, 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. European Commission, Residue analytical methods. For pre-registration data requirement for Annex II (part A, section 4) and Annex III (part A, section 5 of Directive 91/414). SANCO/3029/99- rev.4. European Commission, Review report for the active substance metalaxyl-m. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 19 April 2002 in view of the inclusion of metalaxyl-m in Annex I of Council Directive 91/414/EEC. SANCO/3037/99-Final, 18 September 2002, 27 pp. European Commission, 2010a. Review report for the active substance metalaxyl. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 12 March 2010 in view of the inclusion of metalaxyl in Annex I of Council Directive 91/414/EEC. SANCO/10476/2010-rev.1, 12 March 2010, 36 pp. European Commission, 2010b. 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 March European Commission, 2010c. Residue analytical methods. For post-registration control. SANCO/825/00-rev.8.1. European Commission, Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.9. EFSA (European Food Safety Authority), Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. Available online: EFSA (European Food Safety Authority), Reasoned opinion on the review of the existing maximum residue levels (MRLs) for metalaxyl-m according to Article 12 of Regulation (EC) No 396/2005. EFSA Journal 2011;9(12):2494, 74 pp. doi: /j.efsa EFSA Journal 2015;13(4):4076

44 EFSA (European Food Safety Authority), Reasoned opinion on the modification of the existing MRL(s) for metalaxyl-m in lettuce and other salad plants. EFSA Journal 2012;10(1):2549, 25 pp. doi: /j.efsa EFSA (European Food Safety Authority), Reasoned opinion on the modification of the existing MRL(s) for metalaxyl-m in currant (ref, black and white). EFSA Journal 2013;11(7):3297, 25 pp. doi: /j.efsa EFSA (European Food Safety Authority), Reasoned opinion on the review of the existing maximum residue levels (MRLs) for metalaxyl according to Article 12 of Regulation (EC) No 396/2005. EFSA Journal 2014;12(2):3570, 58 pp. doi: /j.efsa EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance metalaxyl-m. EFSA Journal 2015;13(3):3999, 105 pp. doi: /j.efsa FAO (Food and Agriculture Organization of the United Nations), Metalaxyl-M. In: Pesticide residues in food Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 178, FAO (Food and Agriculture Organization of the United Nations), Submission and evaluation of pesticide residues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2nd Ed. FAO Plant Production and Protection Paper 197, 264 pp. Finland, Evaluation Report prepared under Article 12 of Regulation (EC) No 396/2005 Authorised uses to be considered for the review of the existing MRLs for metalaxyl-m, August OECD (Organisation for Economic Co-operation and Development), OECD MRL Calculator: User Guide. In: Series on Pesticides No 56. ENV/JM/MONO(2011)2, 01 March Portugal, Draft assessment report on the active substance metalaxyl prepared by the rapporteur Member State Portugal in the framework of Council Directive 91/414/EEC, December EFSA Journal 2015;13(4):4076

45 Abbreviations a.s. ADI ARfD BBCH bw CAC CEN CF CXL d DAT DM DT 90f EC EFSA eq EU FAO GAP hl ha HPLC-MS/MS HR ILV ISO IUPAC JMPR LOQ MRL NEU OECD PF PBI PRIMo QuEChERS RA active substance acceptable daily intake acute reference dose growth stages of mono- and dicotyledonous plants body weight Codex Alimentarius Commission European Committee for Standardisation (Comité Européen de Normalisation) conversion factor for enforcement to risk assessment residue definition Codex maximum residue limit (Codex MRL) day days after treatment dry matter period required for 90 % dissipation (under field conditions) European Commission European Food Safety Authority residue expressed as a.s. equivalent European Union Food and Agriculture Organization of the United Nations good agricultural practice hectolitre hectare high performance liquid chromatography with tandem mass spectrometry highest residue independent laboratory validation International Organisation for Standardisation International Union of Pure and Applied Chemistry Joint FAO/WHO Meeting on Pesticide Residues limit of quantification maximum residue level northern Europe Organisation for Economic Co-operation and Development processing factor plant back interval (EFSA) Pesticide Residues Intake Model Quick, Easy, Cheap, Effective, Rugged, and Safe (method) risk assessment 45 EFSA Journal 2015;13(4):4076

46 RAR R ber R max RMS SEU STMR TRR WHO Renewal Assessment Report statistical calculation of the MRL by using a non-parametric method statistical calculation of the MRL by using a parametric method rapporteur Member State southern Europe supervised trials median residue total radioactive residue World Health Organization 46 EFSA Journal 2015;13(4):4076

47 Appendix A Good Agricultural Practices (GAPs) for metalaxyl 47 EFSA Journal 2015;13(4):4076

48 48 EFSA Journal 2015;13(4):4076

49 Appendix B Good Agricultural Practices (GAPs) for metalaxyl-m 49 EFSA Journal 2015;13(4):4076

50 50 EFSA Journal 2015;13(4):4076

51 51 EFSA Journal 2015;13(4):4076

52 52 EFSA Journal 2015;13(4):4076

53 53 EFSA Journal 2015;13(4):4076

54 Appendix C Pesticide Residue Intake Model (PRIMo) 54 EFSA Journal 2015;13(4):4076