Reasoned opinion on the review of the existing maximum residue levels (MRLs) for iodosulfuron according to Article 12 of Regulation (EC) No 396/2005 1

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1 EFSA Journal 2012;10(11):2974 REASOED OPIIO Reasoned opinion on the review of the existing maximum residue levels (MRLs) for iodosulfuron according to Article 12 of Regulation (EC) o 396/ European Food Safety Authority 2, 3 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT According to Article 12 of Regulation (EC) o 396/2005, the European Food Safety Authority (EFSA) has reviewed the Maximum Residue Levels (MRLs) currently established at European level for the pesticide active substance iodosulfuron. In order to assess the occurrence of iodosulfuron residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (incl. the supporting residues data). Based on the assessment of the available data, MRL proposals were derived 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 one MRL proposal derived by EFSA still requires further consideration by risk managers. European Food Safety Authority, 2012 KEY WORDS Iodosulfuron-methyl-sodium, MRL review, Regulation (EC) o 396/2005, consumer risk assessment, sulfonylurea, herbicide, metsulfuron-methyl. 1 On request from EFSA, Question o EFSA-Q , approved on 21 ovember Correspondence: pesticides.mrl@efsa.europa.eu 3 Acknowledgement: EFSA wishes to thank the rapporteur Member State Germany for the preparatory work on this scientific output. Suggested citation: European Food Safety Authority; Reasoned opinion on the review of the existing maximum residue levels (MRLs) for iodosulfuron according to Article 12 of Regulation (EC) o 396/2005. EFSA Journal 2012;10(11):2974. [28 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 SUMMARY Iodosulfuron was included in Annex I to Directive 91/414/EEC on 01 January 2004, which is before the entry into force of Regulation (EC) o 396/2005 on 02 September EFSA is therefore required to provide a reasoned opinion on the review of the existing MRLs for that active substance in compliance with Article 12(2) of afore mentioned regulation. In order to collect the relevant pesticide residues data, EFSA asked Germany, as the designated rapporteur Member State (RMS), to complete the Pesticide Residues Overview File (PROFile). The requested information was submitted to EFSA on 07 July 2009 and, after having considered several comments made by EFSA, the RMS provided on 16 March 2010 a revised PROFile. Based on the conclusions derived in the framework of Directive 91/414/EEC under the supervision of the European Commission and the additional information provided by the RMS, EFSA issued on 29 May 2012 a draft reasoned opinion that was circulated to Member State experts for consultation. Comments received by 03 August 2012 were considered for finalisation of this reasoned opinion. Although the approval under Directive 91/414/EEC referred to iodosulfuron, this substance is currently only available on the market under its variant called iodosulfuron-methyl-sodium, which decomposes to iodosulfuron-methyl, the actual active substance. The following conclusions therefore refer to iodosulfuron-methyl instead of iodosulfuron. The toxicological profile of iodosulfuron-methyl was evaluated in the framework of Directive 91/414/EEC, which resulted in an ADI being established at 0.03 mg/kg bw per d. An ARfD was not deemed necessary. Primary crop metabolism of iodosulfuron-methyl was investigated for foliar applications on wheat. Considering that iodosulfuron-methyl does not hydrolyse to iodosulfuron, the relevant residue for both enforcement and risk assessment in cereals is defined as the sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl. In order to extend the proposed residue definition to oilseeds, a representative metabolism study for this crop group is in principle required. In the absence of information, it is proposed on a provisional basis to also define the residue for enforcement and risk assessment in linseeds as iodosulfuron-methyl and its salts expressed as iodosulfuron-methyl. Validated analytical methods for enforcement of the residue definition in foods of plant origin are available with an LOQ of 0.01 mg/kg in straw and dry content commodities. A validated analytical method for enforcement of residues in oilseeds is still required. Regarding the magnitude of residues, all GAPs were supported by a sufficient number of supervised residue trials for maize, barley, rye and wheat, which allowed EFSA to estimate the expected residue concentrations in the relevant plant commodities and to derive appropriate MRLs. For linseed, no residues trials are available. EFSA was therefore not able to derive reliable MRL proposal and risk assessment values, and further residues trials are required. As quantifiable residues of iodosulfuron-methyl are not expected in edible part of crops and total chronic exposure represents less than 10 % of the ADI, there is no need to investigate the effect of industrial and/or household processing. Specific processing factors for enforcement of processed commodities are therefore not proposed. The potential incorporation of soil residues into succeeding and rotational crops was investigated in three different crop groups. It was concluded that significant residues in rotational crops are not expected provided that iodosulfuron-methyl is applied according to the GAP supported in the framework of this review. EFSA Journal 2012;10(11):2974 2

3 Based on the uses reported by the RMS and provided that residue levels in maize silage are below 0.01 mg/kg, no significant exposure of livestock to iodosulfuron-methyl residues is expected. Hence no residue definition and no MRLs are required for commodities of animal origin. This should be confirmed by 4 residue trials complying with GAP on maize forage with an achieved LOQ of 0.01 mg/kg. Chronic consumer exposure resulting from the uses supported in the framework of this review was calculated using revision 2 of the EFSA PRIMo. For linseed, where data were insufficient to derive an MRL, EFSA considered the existing EU MRL for an indicative calculation. The highest chronic exposure was calculated for WHO cluster diet B, representing 0.4 % of the ADI. Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance. Based on the above assessment, EFSA does not recommend inclusion of this active substance in Annex IV to Regulation (EC) o 396/2005. MRL recommendations were derived in compliance with the decision tree reported in Appendix D of the reasoned opinion (see summary table). 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 value for linseed is not recommended for inclusion in Annex II because it requires further consideration by risk managers (see summary table footnotes for details). In particular, the existing EU MRL still needs to be confirmed by the following data: a representative study investigating primary crop metabolism in the oilseeds group; 4 residue trials supporting the northern outdoor GAP on linseed; 4 residue trials supporting the southern outdoor GAP on linseed; a storage stability study for commodities with high oil content; a validated method for enforcement of residues in high oil content commodities (including ILV). It is highlighted that no MRLs were derived in commodities of animal origin. This conclusion results from the assumption that residue levels in maize silage are below 0.01 mg/kg. This should still be confirmed by: 4 residue trials supporting the northern outdoor GAP on maize forage with an achieved LOQ of 0.01 mg/kg. 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. EFSA Journal 2012;10(11):2974 3

4 SUMMARY TABLE Code number Commodity Existing EU MRL (mg/kg) MRL (mg/kg) Outcome of the review Comment Enforcement residue definition (existing): iodosulfuron-methyl including its salts, expressed as Enforcement residue definition (proposed): sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl Linseed 0.02* 0.02 Further consideration needed (a) Barley grain 0.02* 0.01* Recommended (b) Maize grain 0.02* 0.01* Recommended (b) Rye grain 0.02* 0.01* Recommended (b) Wheat grain 0.02* 0.01* Recommended (b) - Other products of plant and animal origin See App. C - Further consideration needed (c) (*): Indicates that the MRL is set at the limit of analytical quantification. (a): GAP evaluated at EU level is not supported by data but no risk to consumers was identified for the existing EU MRL (also assuming the existing residue definition); no CXL is available (combination C-I in Appendix D). (b): MRL is derived from a GAP evaluated at EU level, which is fully supported by data and for which no risk to consumers is identified; no CXL is available (combination G-I in Appendix D). (c): There are no relevant authorisations or import tolerances reported at EU level; no CXL is available. Either a specific LOQ or the default MRL of 0.01 mg/kg may be considered (combination A-I in Appendix D). EFSA Journal 2012;10(11):2974 4

5 TABLE OF COTETS Abstract... 1 Summary... 2 Table of contents... 5 Background... 6 Terms of reference... 7 The active substance and its use pattern... 7 Assessment Methods of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues ature and magnitude of residues in plant Primary crops Rotational crops ature and magnitude of residues in livestock Consumer risk assessment Conclusions and recommendations Documentation provided to EFSA References Appendix A Good Agricultural Practices (GAPs) Appendix B Pesticide Residues Intake Model (PRIMo) Appendix C Existing EU MRLs Appendix D Decision tree for deriving MRL recommendations Appendix E List of metabolites and related structural formula Abbreviations EFSA Journal 2012;10(11):2974 5

6 BACKGROUD Regulation (EC) o 396/ establishes the rules governing the setting as well as the review of pesticide MRLs at European level. Article 12(2) of that regulation lays down that EFSA shall provide by 01 September 2009 a reasoned opinion on the review of the existing MRLs for all active substances included in Annex I to Directive 91/414/EEC 5 before 02 September As iodosulfuron was included in Annex I to the above mentioned directive on 01 January 2004, EFSA initiated the review of all existing MRLs for that active substance and a task with the reference number EFSA-Q was included in the EFSA Register of Questions. According to the legal provisions, EFSA shall base its reasoned opinion in particular on the relevant assessment report prepared under Directive 91/414/EEC. It should be noted, however, that in the framework of Directive 91/414/EEC only a few representative uses are evaluated while MRLs set out in Regulation (EC) o 396/2005 should accommodate for all uses authorised within the EC as well as uses authorised in third countries having a significant impact on international trade. The information included in the assessment report prepared under Directive 91/414/EEC is therefore insufficient for the assessment of all existing MRLs for a given active substance. In order to have an overview on the pesticide residues data that have been considered for the setting of the existing MRLs, EFSA developed the Pesticide Residue Overview File (PROFile). The PROFile is an electronic inventory of all pesticide residues data relevant to the risk assessment as well as the MRL setting for a given active substance. This includes data on: the nature and magnitude of residues in primary crops; the nature and magnitude of residues in processed commodities; the nature and magnitude of residues in rotational crops; the nature and magnitude of residues in livestock commodities and; the analytical methods for enforcement of the proposed MRLs. Germany, the designated rapporteur Member State (RMS) in the framework of Directive 91/414/EEC, was asked to complete the PROFile for iodosulfuron. The requested information was submitted to EFSA on 07 July 2009 and subsequently checked for completeness. On 16 March 2010, after having clarified some issues with EFSA, the RMS provided a revised PROFile. A draft reasoned opinion was issued by EFSA on 29 May 2012 and submitted to Member States (MS) for commenting. All MS comments received by 03 August 2012 were considered by EFSA for finalisation of the reasoned opinion. 4 Commission Regulation (EC) o 396/2005 of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July 1991, OJ L 230, , p EFSA Journal 2012;10(11):2974 6

7 TERMS OF REFERECE According to Article 12 of Regulation (EC) o 396/2005, EFSA shall provide a reasoned opinion on: the inclusion of the active substance in Annex IV to the Regulation, when appropriate; the necessity of setting new MRLs for the active substance or deleting/modifying existing MRLs set out in Annex II or III of the Regulation; the inclusion of the recommended MRLs in Annex II or III to the Regulation; the setting of specific processing factors as referred to in Article 20(2) of the Regulation. THE ACTIVE SUBSTACE AD ITS USE PATTER O HO O Iodosulfuron is the ISO common Hname for 4-iodo-2-[(4-methoxy-6-methyl-1,3,5-triazin-2- OMe H yl)carbamoylsulfamoyl]benzoic acid (IUPAC). SO 2 The only variant of iodosulfuron currently available on the market is iodosulfuron-methyl-sodium, which is the ISO common name for methyl-4-iodo-2-[3- (4-methoxy-6-methyl-1,3,5-triazin-2-yl)-ureidosulfonyl]benzoate, sodium salt (IUPAC). It is the I sodium salt form of iodosulfuron-methyl, which Iodosulfuron is considered to be the actual active component. a + HO O H O H OMe CH 3 O O SO 2 O H OMe C H 3 O O S O 2 O H O M e SO 2 I I I Iodosulfuron Iodosulfuron-methyl-sodium Iodosulfuron-methyl Iodosulfuron-methyl belongs to a the + group of sulfonylurea herbicides. It is a systemic substance, absorbed both by foliage and by roots, but with a predominant foliar absorbtion. It inhibits the O development of new leaves at the shoot apex by inhibiting acetolactate synthase. Iodosulfuron is used CH 3 O O OMe as post-emergence H herbicide in cereals mainly. SO 2 Iodosulfuron-methyl was evaluated in the framework of Directive 91/414/EEC with Germany being the designated I rapporteur Member State (RMS). The representative use supported for the peer review process was outdoor foliar treatment on wheat, barley, triticale and rye at growth stage BBCH in northern Iodosulfuron-methyl-sodium and southern Europe, with application rates up to 10 g a.s./ha. 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 2003/84/EC 6, entering into force on 01 January According to Regulation (EU) o 540/2011 7, iodosulfuron-methyl is deemed to have been approved under Regulation (EC) o 1107/ This approval is restricted to uses as herbicide only and although the assessment of the RMS referred to iodosulfuron-methyl only, the approval applies to all variants of iodosulfuron. As EFSA was not yet involved in the peer review of iodosulfuron, a conclusion of EFSA on this active substance is not available. The EU MRLs for iodosulfuron-methyl are established in Annexes II and IIIB of Regulation (EC) o 396/2005. All existing EU MRLs, which are established for the iodosulfuron-methyl including salts, 6 Commission Directive 2003/84/EC of 25 September 2003, OJ L 247/ , p Regulation (EU) o 540/2011 of 25 May 2011, OJ L 153, , p Regulation (EC) o 1107/2009 of 21 October 2009, OJ 309, , p EFSA Journal 2012;10(11):2974 7

8 expressed as iodosulfuron-methyl, are summarised in Appendix C to this document. CXLs for iodosulfuron or iodosulfuron-methyl are not available. For the purpose of this MRL review, the critical uses of iodosulfuron-methyl, applied as -sodium, currently authorised within the EU have been collected by the RMS and reported in the PROFile. The additional GAPs reported during the Member States consultation were also considered (see Appendix A). Iodosulfuron-methyl is mainly applied outdoor as foliar post-emergence treatments on wheat, barley, rye, maize and linseed in northern Europe, and on wheat, barley, rye and linseed southern Europe. The RMS did not report any use authorised in third countries that might have a significant impact on international trade. ASSESSMET EFSA bases its assessment on the PROFile submitted by the RMS, the Draft Assessment Report (DAR) prepared under Council Directive 91/414/EEC (Germany, 2000), the Review Report on iodosulfuron (EC, 2003) as well as the evaluation report submitted during the consultation of Member States (The etherlands, 2012). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation of the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) o 546/ and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2010a, 2010b, 2011). EFSA notes that all data reported below refer to iodosulfuron-methyl and its sodium salt. 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin During the peer review under Directive 91/414/EEC, an analytical method using HPLC-UV and its ILV were evaluated and adequately validated for the determination of iodosulfuron-methyl and its salts in plant matrices with an LOQ of 0.01 mg/kg in dry (wheat) commodities and 0.05 mg/kg for wheat shoot and straw. This method is confirmed by using columns of different polarity (Germany, 2000). evertheless, an analytical method and an ILV for the determination of iodosulfuron-methyl and its salts in high oil commodities are not reported. The multi-residue method using diatomaceous earth clean up in combination with LC-MS/MS method (CE, 2008) is also reported to analyse the iodosulfuron-methyl in high water content, dry and high oil commodities. evertheless, the validation data reported are too limited to conclude on the validity of this analytical method (EURL, 2012). Hence it is concluded that the sum of iodosulfuron-methyl and its salts, expressed as, can be enforced in food of plant origin with an LOQ of 0.01 mg/kg in dry commodities and 0.05 mg/kg in cereal straws. However, an analytical method and an ILV for the determination of iodosulfuron-methyl and its salts in high oil commodities are not available and still required Methods for enforcement of residues in food of animal origin o method is available for food of animal origin. Considering however that there is no significant intake of residues by livestock, no residue definition and no MRL were proposed for commodities of 9 Regulation (EU) o 546/2011 of 10 June OJ L 155, , p EFSA Journal 2012;10(11):2974 8

9 animal origin (see also section 3.2.). Therefore, an analytical method for enforcement of residues in food of animal origin is not necessary. 2. Mammalian toxicology The toxicological assessment of iodosulfuron-methyl was peer reviewed under Directive 91/414/EEC and an ADI was established by the European Commission (2003). The toxicological reference values are summarised in Table 2-1. Table 2-1: Overview of the toxicological reference values iodosulfuron-methyl Source Year Value Study relied upon Safety factor ADI EC mg/kg bw per d 24 months carcinogenicity rat study 100 ARfD EC 2003 ot necessary 3. Residues 3.1. ature and magnitude of residues in plant Primary crops ature of residues Metabolism of iodosulfuron-methyl was investigated for foliar treatment on cereals (wheat) using either 2-14 C-triazinyl or U- 14 C-phenyl labelled iodosulfuron-methyl-sodium (Germany, 2000). The characteristics of these studies are summarised in Table 3-1. Table 3-1: Summary of available metabolism studies in plants Group Crop Label position Method, F or G (a) Application and sampling details Rate (kg a.s./ha) o Sampling (DAT) 1 Forage: 3, 7, 22 Cereals Wheat 2-14 C-triazinyl Foliar, F 20 g/ha + safener (b) Hay: 35 Mature : 49 Harvest: 77 1 Forage: 0, 20, 23, U- 14 C-phenyl Foliar, G 20 g/ha + safener (b) 28 Hay: 43 Harvest: 87 (a): Outdoor/field application (F) or glasshouse/protected/indoor application (G) (b): The safener used is mefenpyr diethyl at ratio 3/1 Remarks - - At the exaggerated application rate (2X when compared to the approved uses on wheat, rye and barley; 13X when compared to the approved use on maize), the studies demonstrated that in general low residues were detected in plant samples. In analysed forage samples (22-28 DAT), a maximum TRR of 0.25 mg eq/kg was found. At harvest, a maximum TRR of 0.01 mg eq/kg was found in grain EFSA Journal 2012;10(11):2974 9

10 and 0.37 mg eq/kg in straw with a maximum of 0.05 mg eq/kg for parent compound and individual metabolites in straw and mg eq/kg in grain. Iodosulfuron-methyl related residues in cereals are likely to be considerably lower considering the critical uses with lower application rates evaluated in the framework of this review. The principal extractable residues for forage and straw in both studies were iodosulfuron-methyl and its salts accounting for 13 and 58 % TRR (0.05 and 0.12 mg/kg) in straw and 55.8 and 68 % TRR (0.14 and 0.09 mg/kg) in forage, for 14 C-triazinyl and 14 C-phenyl labels respectively. o other compound was deemed significant in forage. The remainder in straw comprised metsulfuron-methyl (M4) 10 and demethyl-triazin-iodosulfuron (M7) 11 (12.8 and 7.4 % TRR (0.05 and 0.03 mg eq/kg) respectively in the 14 C-triazinyl label study). M4 is a registered sulfonylurea herbicide resulting from loss of iodine and M7 results from demethylation of the triazinyl methoxy group. In addition, two metabolites resulting from cleavage of the sulfonylurea bridge, namely iodosulfuron triazin (M1) 12 (0.05 mg eq/kg, 13.4 % TRR) and demethyl-hydroxy-iodosulfuron-triazin (M17) 13 (0.04 mg eq/kg, 11.7 % TRR), were found in the extractable residue of the straw from the 14 C-triazinyl study. All these metabolites are not toxicologically relevant. Consequently, considering that iodosulfuron-methyl does not hydrolyse to iodosulfuron, the residue of concern in plant for enforcement and risk assessment was defined as the sum of iodosulfuron-methyl and its salts expressed as iodosulfuron-methyl. It is noted that iodosulfuron-methyl is also authorised for use on linseed, for which no representative metabolism study is available. In order to extend the proposed residue definition to oilseeds, a representative metabolism study for this crop group should be available. In the absence of such information, it is proposed on a provisional basis to also define the residue for enforcement and risk assessment in linseeds as iodosulfuron-methyl and its salts expressed as iodosulfuron-methyl. A validated analytical method for enforcement of the proposed residue definition is available for cereal grains and straw, but not for high oil content commodities (see section 1.1) Magnitude of residues According to the RMS, the active substance iodosulfuron-methyl is authorised for foliar outdoor treatment in wheat, barley, rye and linseed both in northern and southern Europe, and in maize, for both grain and forage production, in northern Europe only (see Appendix A). To assess the magnitude of iodosulfuron-methyl residues resulting from these GAPs, EFSA considered all residue trials reported in the PROFile, including residue trials evaluated in the framework of the peer review (Germany, 2000), and the evaluation report submitted during the Member States consultation (The etherlands, 2012). All available residue trials that, according to the RMS, comply with the authorised GAPs, are summarised in Table 3-2. The number of residue trials and extrapolations were evaluated in view of the European guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs (EC, 2011). A sufficient number of trials complying with the GAP was reported by the RMS for all crops under assessment, except for linseed where no residue trial is available. As it is a minor crop in northern and southern Europe, 4 additional trials complying with the GAPs are required for each area. 10 methyl 2-(4-methoxy-6-methyl-1,3,5-triazin-2-ylcarbamoylsulfamoyl)benzoate. See Appendix E hydroxy-triazinyl-iodosulfuron-methyl. See Appendix E amino-4-methoxy-6-methyl-1,3,5-triazin. See Appendix E amino-4-hydroxymethyl-6-hydroxy-1,3,5-triazin. See Appendix E. EFSA Journal 2012;10(11):

11 Table 3-2: Overview of the available residues trials data Commodity Residue region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement Risk assessment Median residue (mg/kg) (b) Highest residue (mg/kg) (c) MRL proposal (mg/kg) Enforcement and risk assessment residue definition: sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl Median CF (d) Comments Linseed EU Outdoor o trial available. SEU Outdoor o trial available. Maize grain EU Outdoor 18 x < x < * 1.00 Trials on maize compliant with the GAP. Maize forage EU Outdoor 8 x < x < Trials on maize compliant with the GAP (The etherlands, 2012). Wheat grain Barley grain Rye grain Wheat straw Barley straw Rye straw EU Outdoor 25 x < x < * 1.00 Trials on wheat compliant with the GAP for all small grain cereals. SEU Outdoor 26 x < x < * 1.00 Trials on wheat compliant with the GAP for all small grain cereals. EU Outdoor 20 x < x < * 1.00 Trials on wheat compliant with the GAP for all small grain cereals. SEU Outdoor 21 x < x < * 1.00 Trials on wheat compliant with the GAP for all small grain cereals. (a): EU (orthern and Central Europe), SEU (Southern Europe and Mediterranean), EU (i.e outdoor use) or Import (country code) (EC, 2011). (b): Median value of the individual trial results according to the enforcement residue definition. (c): Highest value of the individual trial results according to the enforcement residue definition. (d): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors for each residues trial. (*): Indicates that the MRL is set at the limit of analytical quantification. EFSA Journal 2012;10(11):

12 The potential degradation of residues during storage of the residue trial samples was also assessed. In the framework of the peer review, storage stability of iodosulfuron-methyl-sodium was demonstrated for a period of 18 months at -18 C in high water content commodities (wheat shoot) and in straw, and for a period of 24 months in dry commodities (wheat grain) (Germany, 2000). According to the RMS, all residues trial samples reported in the PROFile were stored in compliance with the above reported storage conditions and decline of residues during storage of these samples is not expected. evertheless, if residue trials in linseed are made available in the future, they should be accompanied by the appropriate storage stability data in high oil content matrices. Consequently, the available residue data are considered sufficient to derive MRL proposals as well as risk assessment values in cereals. For linseed, the available data were insufficient to derive tentative MRLs (see also Table 3-2). Tentative MRLs were also derived for cereal straw and maize forage in view of the future need to set MRLs in feed items Effect of industrial processing and/or household preparation As quantifiable residues of iodosulfuron-methyl are not expected in the treated crops, there is no need to investigate the effect of industrial and/or household processing. In addition, the chronic exposure does not exceed 10 % of the ADI Rotational crops Preliminary considerations All crops under consideration may be grown in rotation but, according to the soil degradation studies evaluated in the framework of the peer review, DT 90 values of iodosulfuron-methyl is expected to be lower than 49 days which is far below the trigger value of 100 days (Germany, 2000). evertheless, metsulfuron-methyl was identified as a relevant soil metabolite and for this compound DT 90 values in the field ranged between 26 and 190 days. ature and magnitude of residues in succeeding crops was therefore further investigated by means of a confined rotational crop study ature of residues The metabolism of iodosulfuron-methyl in rotational crops spinach, carrot and wheat has been evaluated (Germany, 2000). One field rotational crop study investigating the nature of residues following different plant-back intervals is available. The characteristics of this study are summarised in Table 3-3. Table 3-3: Summary of available metabolism studies in rotational crops Crop group Crop Label position Method, F or G (a) Application and sampling details Rate (kg a.s./ha) Sowing intervals (DAT) Harvest Intervals (DAT) Remarks Leafy vegetables Spinach 2-14 C- Soil, F (b) triazinyl 120 Root and tuber Carrot 252, vegetables Cereals Wheat 99, 239, (a): Outdoor/field application (F) or glasshouse/protected/indoor application (G) (b): Or climatic chamber simulating outdoor conditions EFSA Journal 2012;10(11):

13 The carrots planted 30 DAT as well as the spinach planted at 30 and 120 DAT showed important signs of phytotoxicity and therefore were not further considered. Total radioactive residues in mature carrots and spinach planted one year after treatment were too low for further characterisation (<0.05 mg eq/kg). Significant residues in rotational crops other than cereals are therefore not expected. The TRR in cereal grains were found to be below 0.01 mg eq/kg at all plant-back intervals. In cereal straw, the TRR ranged between 0.1 and 0.5 mg eq/kg depending on the plant-back interval. However, the main metabolites identified were also identified in the primary crop metabolism (iodosulfuron triazin and iodosulfuron-demethyl-hydroxy-triazin) and the metabolic pattern for primary crops and rotational crops were concluded to be similar (Germany, 2000) Magnitude of residues Based on the rotational field crop study, the individual metabolite fractions are not expected to exceed 0.05 mg/kg (=LOQ for cereal straw). Considering that it was carried out on a bare soil with twice the normal application rate and that the primary use of this active substance is authorised on cereal crops, it can be concluded that iodosulfuron residue levels in rotational commodities are not expected to exceed 0.01 mg/kg, provided that iodosulfuron is applied in compliance with the GAPs reported in Appendix A ature and magnitude of residues in livestock Iodosulfuron-methyl is authorised for use on linseed, cereal grain, cereal straw and maize forage that might be fed to livestock. The median and maximum dietary burdens were therefore calculated for the different types of livestock using to the agreed European methodology (EC, 1996). The input values for all relevant commodities have been selected according to the recommendations of the 2004 JMPR (WHO/FAO, 2005) and are summarised in the Table 3-4. For wheat and rye bran, a default processing factor of 8 has been included in the calculation in order to consider potential concentration of residues in this commodity. It is highlighted that the current calculation does not consider the possible contribution of linseed and linseed meal. However, considering that the current MRL for linseed is established at 0.02 mg/kg, this is not expected to have a significant impact on the outcome of the assessment. Table 3-4: Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value (mg/kg) Comment Input value (mg/kg) Comment Risk assessment residue definition: sum of iodosulfuron-methyl and its salts, expressed as Maize silage 0.05 Median residue 0.05 Highest residue Cereal grain 0.01 Median residue 0.01 Median residue Cereal bran 0.08 Median residue x Median residue x 8 Cereal straw 0.05 Highest residue 0.05 Highest residue The results of the calculations are reported in Table 3-5. According to this first calculation, the dietary burdens for dairy and meat ruminants were found to exceed the trigger value of 0.1 mg/kg DM. EFSA Journal 2012;10(11):

14 Table 3-5: Results of the initial 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/) Risk assessment residue definition: sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl Dairy ruminants Maize silage 0.25 Yes Meat ruminants Maize silage 0.25 Yes Poultry Wheat bran 0.01 o Pigs Maize silage 0.06 o Considering however that input values all commodities used in the dietary burden calculationscorrespond to LOQ values (up to 0.05 mg/kg for the highest contributing commodity), the exposure of ruminants is overestimated. Furthermore, in the overdosed metabolism studies performed on cereals (13X), iodosulfuron-methyl and its salts accounted for a maximum of 0.14 mg/kg in wheat forage sampled at 28 DAT. Consequently, residues levels in maize silage are likely to be around 0.01 mg/kg when the active substance is applied in compliance with the GAPs reported in Appendix A. Based on this assumption, a second dietary burden calculation was performed. The results of this calculation are reported in Table 3-6. Table 3-6: Results of the refined dietary burden calculation 2 (including median and highest residue values of 0.01 mg/kg for maize silage) 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/) Risk assessment residue definition: sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl Dairy ruminants Maize silage 0.06 o Meat ruminants Wheat straw 0.06 o Poultry Wheat bran 0.01 o Pigs Wheat bran 0.03 o Based on this second calculation, calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg DM. Consequently, provided that residue levels in maize silage are below 0.01 mg/kg, further investigation of residues as well as the setting of MRLs in commodities of animal origin is not necessary. evertheless, this should be confirmed by 4 residue trials complying with GAP on maize forage with an achieved LOQ of 0.01 mg/kg. 4. Consumer risk assessment Chronic exposure calculations for all crops supported in the framework of this review were performed using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo) (EFSA, 2007). Input values for the intake calculations were derived in compliance with Appendix D and are summarised in Table 4-1. For linseed, where data were insufficient to derive an MRL in section 3, EFSA considered the existing EU MRL for an indicative calculation. The contributions of other commodities, for which no GAP was reported in the framework of this review, were not included in the calculation. Acute EFSA Journal 2012;10(11):

15 exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance. Table 4-1: Input values for the consumer risk assessment Commodity Input value (mg/kg) Chronic risk assessment Comment Risk assessment residue definition: sum of iodosulfuron-methyl and its salts, expressed as Linseed 0.02 EU MRL (a) Barley grain 0.01* Median residue (b) Maize grain 0.01* Median residue (b) Rye grain 0.01* Median residue (b) Wheat grain 0.01* Median residue (b) (*): Indicates that the the input value is proposed at the limit of analytical quantification. (a): Use reported by the RMS is not fully supported by data; the existing EU MRL is used for indicative exposure calculations (also assuming the existing residue definition). (b): At least one relevant GAP reported by the RMS is fully supported by data for this commodity; the risk assessment value derived in section 3 are used for the exposure calculations. The calculated exposures were compared with the toxicological reference value derived for iodosulfuron-methyl (see Table 2-1); detailed results of the calculations are presented in Appendix B. The highest chronic exposure was calculated for WHO cluster diet B, representing 0.4 % of the ADI. Based on the above calculations, EFSA concludes that the use of iodosulfuron-methyl on crops fully supported by data (footnote b in Table 4-1), is acceptable with regard to consumer exposure. For linseed, major uncertainties remain due to the data gaps identified in section 3, in particular with regard to the residue definition, but considering the existing EU MRL in the exposure calculation did not indicate a risk to consumers. COCLUSIOS AD RECOMMEDATIOS COCLUSIOS The toxicological profile of iodosulfuron-methyl was evaluated in the framework of Directive 91/414/EEC, which resulted in an ADI being established at 0.03 mg/kg bw per d. An ARfD was not deemed necessary. Primary crop metabolism of iodosulfuron-methyl was investigated for foliar applications on wheat. Considering that iodosulfuron-methyl does not hydrolyse to iodosulfuron, the relevant residue for both enforcement and risk assessment in cereals is defined as the sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl. In order to extend the proposed residue definition to oilseeds, a representative metabolism study for this crop group is in principle required. In the absence of information, it is proposed on a provisional basis to also define the residue for enforcement and risk assessment in linseeds as iodosulfuron-methyl and its salts expressed as iodosulfuron-methyl. Validated analytical methods for enforcement of the residue definition in foods of plant origin are available with an LOQ of 0.01 mg/kg in straw and dry content commodities. A validated analytical method for enforcement of residues in oilseeds is still required. EFSA Journal 2012;10(11):

16 Regarding the magnitude of residues, all GAPs were supported by a sufficient number of supervised residue trials for maize, barley, rye and wheat, which allowed EFSA to estimate the expected residue concentrations in the relevant plant commodities and to derive appropriate MRLs. For linseed, no residues trials are available. EFSA was therefore not able to derive reliable MRL proposal and risk assessment values, and further residues trials are required. As quantifiable residues of iodosulfuron-methyl are not expected in edible part of crops and total chronic exposure represents less than 10 % of the ADI, there is no need to investigate the effect of industrial and/or household processing. Specific processing factors for enforcement of processed commodities are therefore not proposed. The potential incorporation of soil residues into succeeding and rotational crops was investigated in three different crop groups. It was concluded that significant residues in rotational crops are not expected provided that iodosulfuron-methyl is applied according to the GAP supported in the framework of this review. Based on the uses reported by the RMS and provided that residue levels in maize silage are below 0.01 mg/kg, no significant exposure of livestock to iodosulfuron-methyl residues is expected. Hence no residue definition and no MRLs are required for commodities of animal origin. This should be confirmed by 4 residue trials complying with GAP on maize forage with an achieved LOQ of 0.01 mg/kg. Chronic consumer exposure resulting from the uses supported in the framework of this review was calculated using revision 2 of the EFSA PRIMo. For linseed, where data were insufficient to derive an MRL, EFSA considered the existing EU MRL for an indicative calculation. The highest chronic exposure was calculated for WHO cluster diet B, representing 0.4 % of the ADI. Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance. RECOMMEDATIOS Based on the above assessment, EFSA does not recommend inclusion of this active substance in Annex IV to Regulation (EC) o 396/2005. MRL recommendations were derived in compliance with the decision tree reported in Appendix D of the reasoned opinion (see summary table). 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 value for linseed is not recommended for inclusion in Annex II because it requires further consideration by risk managers (see summary table footnotes for details). In particular, the existing EU MRL still needs to be confirmed by the following data: a representative study investigating primary crop metabolism in the oilseeds group; 4 residue trials supporting the northern outdoor GAP on linseed; 4 residue trials supporting the southern outdoor GAP on linseed; a storage stability study for commodities with high oil content; a validated method for enforcement of residues in high oil content commodities (including ILV). It is highlighted that no MRLs were derived in commodities of animal origin. This conclusion results from the assumption that residue levels in maize silage are below 0.01 mg/kg. This should still be confirmed by: EFSA Journal 2012;10(11):

17 4 residue trials supporting the northern outdoor GAP on maize forage with an achieved LOQ of 0.01 mg/kg. 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. SUMMARY TABLE Code number Commodity Existing EU MRL (mg/kg) MRL (mg/kg) Outcome of the review Comment Enforcement residue definition (existing): iodosulfuron-methyl including its salts, expressed as Enforcement residue definition (proposed): sum of iodosulfuron-methyl and its salts, expressed as iodosulfuron-methyl Linseed 0.02* 0.02 Further consideration needed (a) Barley grain 0.02* 0.01* Recommended (b) Maize grain 0.02* 0.01* Recommended (b) Rye grain 0.02* 0.01* Recommended (b) Wheat grain 0.02* 0.01* Recommended (b) - Other products of plant and animal origin See App. C - Further consideration needed (c) (*): Indicates that the MRL is set at the limit of analytical quantification. (a): GAP evaluated at EU level is not supported by data but no risk to consumers was identified for the existing EU MRL (also assuming the existing residue definition); no CXL is available (combination C-I in Appendix D). (b): MRL is derived from a GAP evaluated at EU level, which is fully supported by data and for which no risk to consumers is identified; no CXL is available (combination G-I in Appendix D). (c): There are no relevant authorisations or import tolerances reported at EU level; no CXL is available. Either a specific LOQ or the default MRL of 0.01 mg/kg may be considered (combination A-I in Appendix D). DOCUMETATIO PROVIDED TO EFSA 1. Pesticide Residues Overview File (PROFile) on iodosulfuron-methyl prepared by the rapporteur Member State Germany in the framework of Article 12 of Regulation (EC) o 396/2005. Submitted to EFSA on 07 July Last updated on 16 March REFERECES CE (European Committee for Standardisation), Foods of plant origin - Determination of pesticide residues using LC-MS/MS following methanol extraction and clean-up using diatomaceous earth. E 15637, ovember EC (European Commission), Appendix G. Livestock Feeding Studies. 7031/VI/95 rev.4. EC (European Commission), 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95- rev.3. EC (European Commission), 1997b. Appendix B. General recommendations for the design, preparation and realisation of residue trials. Annex 2. Classification of (minor) crops not listed in the Appendix of Council Directive 90/642/EEC. 7029/VI/95-rev.6. EC (European Commission), 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95-rev.2. EFSA Journal 2012;10(11):

18 EC (European Commission), 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. EC (European Commission), 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev.3. EC (European Commission), 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95- rev.5. EC (European Commission), 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. As amended by the document: classes to be used for the setting of EU pesticide maximum residue levels (MRLs). SACO 10634/2010. EC (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. SACO/3029/99-rev.4. EC (European Commission), Review report for the active substance iodosulfuron. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 4 July 2003 in view of the inclusion of iodosulfuron in Annex I of Council Directive 91/414/EEC. SACO/10166/2003-Final, 3 July EC (European Commission), 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SACO 10634/2010 Rev. 0, finalised in the Standing Committee on the Food Chain and Animal Health at its meeting of March EC (European Commission), 2010b. Residue analytical methods. For post-registration control. SACO/825/00-rev.8-1. EC (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 according to Regulation (EC) o 396/2005 on Maximum Residue Levels of Pesticides in Food and Feed of Plant and Animal Origin. 15 March EURL (European Union Reference Laboratories for Pesticide Residues), Data pool on method validation for pesticide residues. Status on 25 May Available online: FAO (Food and Agriculture Organisation of the United ations), Submission and evaluation of pesticide residues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2 nd Ed. FAO Plant Production and Protection Paper 197, 264 pp. Germany, Draft assessment report on the active substance iodosulfuron-methyl-sodium prepared by the rapporteur Member State Germany in the framework of Council Directive 91/414/EEC, May The etherlands, Evaluation Report prepared under Article 12 of Regulation (EC) o 396/2005. Authorised uses to be considered for the review of the existing MRLs for iodosulfuron, August EFSA Journal 2012;10(11):

19 APPEDIX A GOOD AGRICULTURAL PRACTICES (GAPS) Crop Outdoor/ Member state or Region Pests controlled Common name Scientific name Indoor Country Type Linseed Linum usitatissimum EU Outdoor UK Barley Hordeum spp. EU Outdoor SI Maize Zea mays EU Outdoor L Rye Secale cereale EU Outdoor -EU/DK Wheat Triticum aestivum EU Outdoor -EU/L Maize (for forage) Zea mays EU Outdoor L Grass weed species, dicot weed species Grass weed species, dicot weed species Poa annua, Dicotyledoneae ssp., Panicum crusgalli, except: Polygonum convolvulus Cirsium arvense Grass weed species, dicot weed species Grass weed species, dicot weed species Poa annua, Dicotyledoneae ssp., Panicum crusgalli, except: Polygonum convolvulus Cirsium arvense Critical Outdoor GAPs for orthern Europe Formulation Application Application rate PHI or Content Growth stage umber Interval (days) wiaiting Method Min. rate Max. rate Rate Unit period Conc. Unit Min. Max. Min. Max. (days) From BBCH Until BBCH Foliar treatment - spraying n.a ,50 g a.i./ha 90 OD 100,0 g/l Foliar treatment - spraying ,00 g a.i./ha n.a. WG 10,0 g/kg Foliar treatment - spraying ,50 g a.i./ha n.a. WG 50,0 g/kg Foliar treatment - spraying ,50 10,00 g a.i./ha 90 OF 100,0 g/l Foliar treatment - spraying ,00 g a.i./ha n.a. WG 10,0 g/kg Foliar treatment - spraying ,50 g a.i./ha n.a. Comments (max. 250 charachters) In FR: PHI = 75 days for a.i. "iodosulfuron", but lower application rate (2,5 g a.i./ha) In DK: PHI = 90 days for a.i. "iodosulfuron-methyl" Crop Outdoor/ Member state or Region Pests controlled Common name Scientific name Indoor Country Type Linseed Linum usitatissimum SEU Outdoor FR Barley Hordeum spp. SEU Outdoor EL Rye Secale cereale SEU Outdoor SI Wheat Triticum aestivum SEU Outdoor SI Grass weed species, dicot weed species Grass weed species, dicot weed species Grass weed species, dicot weed species Grass weed species, dicot weed species Formulation Conc. Content Critical Outdoor GAPs for Southern Europe Unit Method From BBCH Application Growth stage Until BBCH Interval (days) Min. Max. Min. Max. Application rate Min. rate Max. rate Rate Unit Foliar treatment - spraying n.a ,50 g a.i./ha 90 OD 8,0 g/l Foliar treatment - spraying ,00 10,00 g a.i./ha n.a. OD 100,0 g/l Foliar treatment - spraying ,00 g a.i./ha n.a. OD 100,0 g/l Foliar treatment - spraying ,00 g a.i./ha n.a. umber PHI or wiaiting period (days) Comments (max. 250 charachters) In FR: PHI = 75 days for a.i. "iodosulfuron", but lower application rate (2,5 g a.i./ha) In FR: PHI = 75 days for a.i. "iodosulfuron" EFSA Journal 2012;10(11):