Modification of the existing MRLs for spirotetramat in onions and the setting of new MRLs in kidney 1

Transcription

1 REASONED OPINION Modification of the existing MRLs for in onions and the setting of new 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY According to Article 6(2) of Regulation (EC) No 396/2005, Germany received an application from the company Bayer CropScience to modify the existing MRL for in onions and to set new MRLs for in bovine, sheep, goat and swine kidney. Germany as the Evaluating Member State (EMS) drafted an evaluation report according to Article 8 of Regulation (EC) No 396/2005 which was submitted to the European Commission and forwarded to EFSA on 27 October EFSA derives the following conclusions based on the submitted evaluation report prepared by Germany as well as the Draft Assessment Report (DAR) prepared by Austria under Directive 91/414/EEC. As the DAR has not yet been peer reviewed by EFSA, conclusions reached in this reasoned opinion are temporary and might be reconsidered after finalization of the peer review. Metabolism of was investigated by foliar applications in cotton, lettuce, potatoes and apples. Three different crop groups are covered by the available studies and the relevant residue for enforcement and risk assessment in all plant commodities was defined by the RMS as the sum of BYI BYI BYI monohydroxy and BYI An analytical method for enforcement of this residue definition in onions is also available. A sufficient of supervised residues field trials supporting the intended GAP for on onions is available indicating that an MRL of 0.3 mg/kg for in onions would be required to accommodate the intended use. The effect of industrial and household processing on the nature of residues was investigated. Total residue can be considered as stable when subject to conditions of pasteurization and baking/brewing/boiling, but during the process of sterilisation is completely hydrolyzed. Onions under normal processing practices are not subject to sterilisation practices therefore the same residue definition as for the raw commodities is applicable. No studies on the effects of processing on the magnitude of residues in onions were submitted and are also not necessary considering the low contribution of onions to the total dietary intake. Onions can be grown in a crop rotation and therefore a possible occurrence of residues in rotational crops was investigated. The RMS concluded that for rotational crops the same residue 1 On request from the European Commission, Question No EFSA-Q issued 11 February Correspondence: praper.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Modification of the existing MRLs for in onions and the setting of new.. [31 pp.]. doi: /j.efsa Available online: European Food Safety Authority,

2 definition as in primary crops is applicable even though a wider range of were identified. In the DAR the RMS concluded that at the plant back interval of 30 days, no residues in rotational crops are expected. Taking into account that the rotational crop study was performed with a lower application rate, residues in succeeding crops cannot be fully excluded. Therefore EFSA recommends that the Member States, before granting national authorisations, should assess the need of defining restrictions (e.g. minimum plant-back intervals) in order to avoid residues in succeeding crops. The livestock dietary burden was calculated considering the existing MRLs for. The calculated dietary burden exceeds the trigger value of 0.1 mg/kg DM for all livestock species and is mainly driven by the residues in kale. The nature of in livestock has been sufficiently investigated to propose an enforcement residue definition as and BYI and the risk assessment residue definition as, BYI enol and BYI enolglucuronide,. The calculated dietary burdens and the results of livestock feeding studies were used to derive the MRL proposal for kidney at the level of 0.02 mg/kg. For other commodities of animal origin no residues above the LOQ are expected. The proposed analytical enforcement method is capable to determine the residues of BYI enol in kidney, but the applicant still has to provide the relevant validation data. The proposed analytical enforcement method for the determination of parent in kidney is not confirmed. A similar method, which was used in analyzing the livestock feeding study samples, is available and is considered as validated for the determination of all compounds included in the residue definition for the risk assessment. The applicant has to confirm if this method is suitable for the enforcement purposes. The consumer exposure assessment was performed with the revision 2 of the EFSA PRIMo. For the chronic exposure assessment EFSA used the existing MRLs as established in Annex IIIA of Regulation (EC) No 396/2005 as well as the STMR values for onions and kidney. The acute exposure assessment was performed only with regard to onions and kidney. No long-term consumer intake concerns were identified for the proposed MRLs for in onions and kidney. The total calculated intake values ranged from 5.2 to 30.5% of the ADI. The contribution of residues in onions to the total consumer exposure accounted for a maximum of % of the ADI (WHO Cluster diet B). The consumer exposure to residues from the intake of kidneys is insignificant. No short-term intake concerns were identified regarding the MRL proposals in onions and in kidney. EFSA concludes that the proposed MRL of 0.3 mg/kg in onions and 0.02 mg/kg in bovine, sheep, goat and swine kidney are acceptable as they will not raise any consumer intake concerns. These recommendations should be considered for the inclusion in Annex III of the Regulation as the peer review of the active substance under Directive 91/414/EEC is not yet finalized. Food Commodity Existing EC code a MRL Proposed EC MRL Justification for the proposal Enforcement residue definition: the sum of and BYI BYI BYI monohydroxy and BYI Onions The MRL proposal is sufficiently supported by data and no consumer intake concerns were identified. Proposed provisional enforcement residue definition: and BYI Swine kidney The MRL proposals are sufficiently Bovine kidney supported by data and no consumer intake concerns were identified Sheep kidney

3 Food Commodity Existing EC code a MRL Proposed EC MRL Justification for the proposal Goat kidney a according to Regulation (EC) No 396/2005. KEY WORDS, onions, kidney, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, tetramic acid insecticide 3

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

5 BACKGROUND Regulation (EC) No 396/2005 establishes the rules governing the setting of pesticide MRLs at Community level. Article 6 of that regulation lays down that a party requesting an authorisation for the use of a plant protection product in accordance with Directive 91/414/EEC, shall submit to a Member State, when appropriate, an application to set or modify an MRL in accordance with the provisions of Article 7 of that regulation. Germany, hereafter referred to as the evaluating Member State (EMS), received an application from the company Bayer CropScience 3 to modify the existing MRL for the active substance in onions and to set the new MRLs for in kidney. This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation report of the EMS was submitted to the European Commission who forwarded the application, the evaluation report and the supporting dossier to EFSA on 27 October The application was included in the EFSA Register of Question with the reference EFSA-Q and the following subject: - Application to modify the existing MRLs in onions and kidney. EFSA then proceeded with the assessment of the application as required by Article 10 of the Regulation. TERMS OF REFERENCE According to Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the evaluating Member State, provide a reasoned opinion on the risks to the consumer associated with the application. According to Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within 3 months from the date of receipt of the application. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. In this particular case the calculated deadline for providing the reasoned opinion is 27 January Bayer CropScience, Elisabeth-Selbert-Strasse 4a, 40764, Langefeld, Germany 5

6 THE ACTIVE SUBSTANCE AND ITS USE PATTERN is the ISO common name for cis-4-(ethoxycarbonyloxy)-8-methoxy-3-(2,5-xylyl)-1- azaspiro[4.5]dec-3-en-2-one (IUPAC). CH 3 O CH 2 CH 3 O O C O N H O CH 3 CH 3 MW: g/mol belongs to the class of tetramic acid insecticides. The active substance is systemic and requires oral ingestion or feeding from the plants by the insect. It then acts on acetyl CoA carboxylase inhibiting the lipid biosynthesis. is evaluated in the framework of Directive 91/414/EEC as a new active substance with Austria being the designated Rapporteur Member State (RMS) and a Draft Assessment Report (DAR) resulting from the OECD Joint Review Project between Canada, USA and Austria was submitted. The representative uses evaluated in the DAR are foliar applications on citrus and lettuce, but the peer review of this DAR by EFSA is not yet finalised. A decision on the inclusion of the active substance in Annex I to the Directive has therefore not yet been taken. Although representative uses in the framework of Directive 91/414/EEC are only for citrus fruits and lettuce, the use of is intended for a broad range of crops. Provisional authorisations for in several vegetable crops have already been issued by Member States and temporary EC MRLs accommodating for these provisional authorisations have been set by Regulation (EC) No 839/2008, which entered into force on 01 September 2008 (Appendix C). Since then EFSA has issued two reasoned opinions on the modification of the existing MRLs for. The MRL recommendations for in various fruit crops (EFSA, 2009a) were included in Regulation (EC) No 822/2009. The MRL proposals for in plums and cherries (EFSA, 2009b) on which the SCoFCAH gave a favourable opinion on 8-9 December 2009, will be incorporated in a new MRL regulation. The setting of CXLs for is currently under discussion, but not yet finalised (FAO/WHO, 2009). The GAP for which an authorization is requested in Germany refers to an outdoor application of on onions four times at an application rate of kg a.s./ha. The minimum PHI and the interval between applications is 7 days. The details of the GAP are given in Appendix A. 6

7 ASSESSMENT EFSA bases its assessment on the evaluation report submitted by Germany (2009) and the Draft Assessment Report (DAR) prepared under Directive 91/414/EEC (Austria, 2008). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation of the Authorization of Plant Protection Products set out in Annex VI to Directive 91/414/EEC and the currently valid EU guidance documents for consumer risk assessment (European Commission, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2008). Awaiting the peer review of this DAR to be finalized, conclusions reached in this reasoned opinion are temporary and might be reconsidered in the light of the outcome of the peer review. 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin An analytical method was evaluated in the DAR prepared by Austria in the framework of Directive 91/414/EEC (Austria, 2008). The analytical method reported is based on the LC-ESI-MS/MS principle and is able to analyse for and its BYI enol 4, BYI ketohydroxy 5, BYI monohydroxy 6 and BYI enol-glucoside 7. The method has been validated for commodities with a high water content (tomatoes, potatoes), high acid content (citrus) and high oil content (avocados) with a LOQ of 0.01 mg/kg for each analyte. It is noted that an independent laboratory validation was not provided for the analytical method reported. It is concluded that an analytical method to control the compliance of the proposed MRL in onions is available but necessary validation data has yet to be submitted by the applicant Methods for enforcement of residues in food of animal origin The availability of analytical methods for the determination of residues in matrices of animal origin was evaluated in the DAR by Austria in the framework of Directive 91/414/EEC (Austria, 2008). The analytical method proposed for the enforcement is based on HPLC-MS/MS principle and is able to analyse for BYI enol in kidney, muscle, milk and eggs. The method, however, was validated at the LOQ of 0.01 mg/kg for muscle, eggs and at the LOQ of mg/kg for milk. No validation data for kidney are available. No enforcement method is available for the determination of residues in kidney. In the livestock feeding studies a similar analytical method, based on HPLC-MS/MS principle, was used. The method was validated for the determination of, enol and BYI enol-GA (BYI enol-glucuronide) 8 in all livestock matrices at the LOQ of 0.01 mg/kg and in milk at the LOQ of mg/kg for each analyte. 4 BYI enol: cis-3-(2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-one 5 BYI ketohydroxy: cis-3-(2,5-dimethylphenyl)-3-hydroxy-8-methoxy-1-azaspiro[4.5]decane-2,4-dione 6 BYI monohydroxy: cis-3-(2,5-dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl beta-d glucopyranoside 7 BYI enol-glucoside: cis-3-(2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]decan-2-one 8 BYI enol-GA: glucuronic acid conjugate of cis-3-(2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1-azaspirol [4.5]dec-3-en-2-one 7

8 Since both methods are identical, it can be assumed that an appropriate analytical method is available to control the compliance of the proposed. Nevertheless, the applicant has to provide the validation data for the determination of BYI enol in kidney. Moreover, the applicant has to confirm that the method proposed for the enforcement is also applicable for the determination of parent in animal matrices. 2. Mammalian toxicology The toxicological properties of have been evaluated in the DAR prepared under Directive 91/414/EEC (Austria, 2008) and reference values have been derived. These reference values are summarized in Table 2-1. It is noted that a lower ARfD of 0.1 mg/kg bw has been used by EFSA for the assessment of the temporary EC MRL (EFSA, 2008). The ARfD of 1 mg/kg, however, results from a more recent assessment and it was also confirmed by the 2008 JMPR. Table 2-1. Overview of the toxicological reference values Source Year Value Study relied upon Safety factor ADI DAR mg/kg bw/d 1 year dog 100 ARfD DAR mg/kg bw Acute rat neurotoxicity Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues Plant metabolism for was investigated in apples, potatoes, lettuce and cotton and a detailed evaluation of the studies is provided in the DAR (Austria, 2008). According to the RMS, metabolism in the different crop groups was found to be similar and nature of residues in plant commodities is adequately understood. Overall, a high level of identification was obtained with the major part of the residue being composed of, BYI BYI BYI monohydroxy and BYI enol-glucoside. Other were identified but not further considered because they were present in insignificant concentrations. The RMS proposed to establish the risk assessment and enforcement residue definition in all plant commodities as the sum of and BYI BYI BYI monohydroxy and BYI The same enforcement residue definition is currently established for in Regulation (EC) No 839/2008. Awaiting the finalisation of the peer review of the DAR, it is therefore proposed to maintain the proposed residue definition for enforcement and risk assessment in all plant commodities as the sum of BYI BYI BYI monohydroxy and BYI

9 Table 3-1. Overview of the identified in the primary crops Metabolite CAS Name Chemical structure BYI enol cis-3-(2,5-dimethylphenyl)-4-hydroxy- 8-methoxy-1-azaspiro[4.5]dec-3-en-2- one BYI ketohydroxy cis-3-(2,5-dimethylphenyl)-3-hydroxy- 8-methoxy-1-azaspiro[4.5]decane-2,4- dione BYI monohydroxy cis-3-(2,5-dimethylphenyl)-8-methoxy- 2-oxo-1-azaspiro[4.5]dec-3-en-4-yl beta-d-glucopyranoside BYI enol-glucoside cis-3-(2,5-dimethylphenyl)-4-hydroxy- 8-methoxy-1-azaspiro[4.5]decan-2-one It is concluded that metabolism of in onions is sufficiently addressed and no further studies are required Magnitude of residues For the intended GAP the applicant submitted eight residue trials on onions conducted in northern Europe. All trials were designed as residue decline studies. In two trials the residue levels within a trial were higher in a longer PHI of 8 and 14 day and therefore these higher values were used in the database for deriving the MRL proposal and risk assessment values. The residues from all trials were in the range of to 0.2 mg/kg. Summary of residue trials data is given in the Table 3-2. The storage stability of was investigated and is reported in the DAR (Austria, 2008). is considered as stable in all crop matrices for 24 months. According to the EMS, residue data are valid regarding storage stability and analytical performance. Data indicate that a MRL of 0.3 mg/kg would be necessary to accommodate the intended use of on onions. 9

10 Table 3-2. Overview of the available residues trials data Commodity Region (a) Outdoor /Indoor Individual trial results Enforcement (the sum of and BYI BYI BYI monohydroxy and BYI enolglucoside, ) Risk assessment (the sum of and BYI BYI BYI monohydroxy and BYI enolglucoside, ) STMR (b) HR (c) MRL proposal Median CF (d) Comments Onions NEU O 0.054; 0.084; 0.092; 0.097; 2 x 0.11 e ; 0.16 f ; ; 0.084; 0.092; 0.097; 2 x 0.11 e ; 0.16 f ; R ber =0.295 mg/kg R max =0.26 mg/kg (a): NEU, SEU, EU or Import (country code). In the case of indoor uses there is no necessity to differentiate between NEU and SEU. (b): Median value of the trial results according to the enforcement residue definition. (c): Highest value of the 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 conversion factors for each residues trial. (e): residue value at a longer PHI of 14 days (f); residue value at a longer PHI of 8 days 10

11 Effect of industrial processing and/or household preparation Studies investigating the effect of processing on the nature of residues under conditions simulating pasteurization, baking/brewing and sterilization are reported in the DAR (Austria, 2008). Although hydrolysis of both and BYI enol-glucoside to BYI enol was observed, the total residue can be considered as stable when subject to conditions for pasteurization (20 min at 90 C, ph 4) or baking/brewing (60 min at 100 C, ph 5). Under these conditions only minor amounts of a new metabolite, BYI MA-amide 9, were identified. Under sterilization conditions (20 min at 120 C, ph 6) BYI ketohydroxy was completely hydrolyzed to BYI MA-amide. Onions under normal processing practices are not subject to sterilisation practices therefore the same residue definition as for the raw commodities is applicable. The applicant did not provide studies on the effects of processing on the magnitude of residues in onions. Such studies, however, are not necessary since the contribution of onions to the total consumer exposure to residues is below 10% of the ADI Rotational crops Preliminary considerations In soil, the parent and the - -ketohydroxy and 4-methoxy-cyclohexanone are considered major compounds. has a low volatility and undergoes rapid photochemical degradation (DT 90 value days). According to laboratory studies are more persistent in the soil. The DT 90 value for -enol ranges from days, for -ketohydroxy from days and for - MA-amide from days. The available field studies indicate that under aerobic conditions the maximum DT 90 value for is 3.5 days. For the sum of -enol and -ketoxydroxy this value is in the range of days. For the sum of all residues (, - -ketohydroxy and -MA-amide) the DT 90 value accounts for a maximum for 77.8 days. The trigger value of 100 days is slightly exceeded for the sum of -enol and ketoxydroxy and therefore the occurrence residues in rotational crops have to be further investigated. The rotational crop studies are available and are reported in the sections below Nature of residues Metabolism of in rotational crops was investigated in spring wheat, Swiss chard and turnips following spray application of [azaspirodecenyl-3-14 C]- on a bare soil at an application rate of kg a.s./ha (Austria, 2008). Crops were sown 30, 135 and 260 DAT. Immature and mature plant samples were analysed. 9 BYI MA-amide: 1-{[(2,5-dimethylphenyl)(hydroxy)acetyl]amino}-4-methoxycyclohexanecarboxylicacid 11

12 The major part of the TRR was present in a conjugated form and BYI desmethyl-di-hydroxy, BYI ketohydroxy-alcohol, and BYI desmethyl-ketohydroxy were identified as the major constituents of the residues after hydrolysis. The TRR was highest in wheat straw 30 DAT (0.998 mg/eq./kg), wheat hay (0.38 mg eq./kg) turnip leaves (0.123 mg eq./kg), Swiss chard (0.078 mg eq./kg), wheat grain (0.026 mg eq./kg), wheat forage (0.024 mg eq./kg) and turnip roots (0.021 mg eq./kg). A significant decline of TRR from the 30 DAT to 260 DAT rotation was observed. Only in wheat hay and wheat straw residues above 0.01 mg eq./kg were observed 260 DAT. The parent compound was not found in any of rotational crop matrices following the soil application of. Major (above 10% TRR) in the 30 and 135 day rotation were BYI ketohydroxy (wheat forage, Swiss chard, turnip roots), BYI desmethyl-keothydroxy glucoside (two isomers) (wheat forage and hay, Swiss chard), BYI desmethyl-ketohydroxy- Glc-MA (two isomers) (wheat hay), BYI desmethyl-di-hydroxy-Glc (wheat straw and wheat forage), BYI desmethyl-di-hydroxy-Glc-MA 10 (wheat hay), and BYI di-hydroxy 11. A major primary plant metabolite enol was only detected in the wheat grain (2.9% TRR, mg/kg) from the wheat study. desmethyl-di-hydroxy and its conjugates were found in rotational crops but were not detected in primary crops. All other rotational crop were also found in the primary crops. As assumed, the metabolism of in rotational crops proceeds via two major routes, starting with the soil BYI ketohydroxy and BYI enol. Another route starts with the addition of water to the tetramic acid ring of BYI enol resulting in the formation of BYI di-hydroxy, followed by the demethylation of the metabolite. Most of were rapidly conjugated. The following potential components of the residue definition were identified in the confined rotational crop study, and free and conjugated desmethyl desmethyl-di-hydroxy and BYI ketohydroxy-alcohol. It was concluded by the RMS that metabolism of in rotational crops proceeds in a qualitatively similar pathway as in primary plants Magnitude of residues The magnitude of in rotational crops was investigated in a field study in the USA by applying the active substance 2 times with 5 to 7 day interval to a primary crop at a total application rate of kg a.s./ha (0.6 N of the intended seasonal application rate on onions). After primary crops (leafy brassica or fruiting vegetables) were harvested, rotational crops - mustard greens, turnips and wheat - were planted at a 30 day plant-back interval. At maturity, samples of mustard greens, turnip (tops and roots), wheat (forage, hay, straw and grain) were analyzed for residues of, BYI BYI desmethyl- 10 BYI desmethyl-dihydroxy-Glc-MA: glucosyl-malonic acid conjugate of (5s,8s)-3-(2,5-dimethylphenyl)-3,4,8- trihydroxy-1-azaspiro[4.5]decan-2-one 11 BYI di-hydroxy: cis-3-(2,5-dimethylphenyl)-3,4-dihydroxy-8-methoxy-1-azaspiro[4.5]decan-2-one 12

13 ketoxyhydroxy, BYI desmethyl-di-hydroxy and BYI ketohyhydroxy-alcohol. No residues above the LOQ were detected in any of the rotational crop matrices. In the DAR the RMS concluded that at the plant back interval of 30 days, no residues in rotational crops are expected. Taking into account that the rotational crop study was performed with a lower application rate, residues in succeeding crops cannot be fully excluded. Therefore EFSA recommends that the Member States before granting national authorisations consider the need of defining restrictions (e.g. minimum plant-back intervals) in order to avoid residues in succeeding crops Nature and magnitude of residues in livestock Dietary burden of livestock The MRL application for in onions would not require the investigation of the nature and magnitude of residues in livestock as onions are not common livestock feeding items according to the EU Guidance document on the livestock feeding studies (European Commission, 1996). The EMS, however, has identified the need to consider residues in the food of animal origin following the livestock exposure to residues from the intake of treated brassica vegetables (kale and/or cabbage). EFSA calculated the livestock dietary burden following the livestock intake of the feed crops on which there are currently authorized uses of : pome fruit, citrus fruit head cabbage and kale. The livestock dietary burden was calculated using the EFSA dietary burden calculator. As fruit pomaces are processed commodities, the STMR values multiplied by the processing factors as derived in the EFSA reasoned opinion on the modification of the existing MRLs for in various fruit crops were used as input values (EFSA, 2009a). For kale and cabbage the STMR and HR values were as reported in the DAR (Austria, 2008) and by the EMS. The input values were summarized in the Table 3-3. Table 3-3. Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value Comment Input value Comment Sum of and BYI BYI BYI monohydroxy and BYI Cabbage 0.10 STMR (Austria, 2008) 0.26 HR (Austria, 2008) Kale 0.46 STMR (Austria, 2008) 0.77 HR (Austria, 2008) Citrus pomace 0.42 STMR*PF (EFSA, 2009b) 0.42 STMR*PF (EFSA, 2009b) Apples pomace 0.34 STMR*PF (EFSA, 2009b) 0.34 STMR*PF (EFSA, 2009b) Results of the dietary burden calculation are compiled in the table below. 13

14 Table 3-4. Results of the dietary burden calculation Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Sum of and BYI BYI BYI monohydroxy and BYI Dairy ruminants Kale Yes Meat ruminants Kale Yes Poultry Kale Yes Pigs Kale Yes The calculated dietary burdens exceed the trigger value of 0.1 mg/kg DM for all relevant livestock species and are mainly driven by the existing MRL for kale. Therefore the need to set MRLs in food commodities of animal origin has to be considered (European Commission, 1996) Nature of residues The nature of in livestock was investigated in lactating goats and laying hens and the relevant studies are reported in the DAR (Austria, 2008). Lactating goat received 4 daily administrations of at a mean dose rate of 2.22 mg a.s./kg bw/d (73.03 mg/kg feed). Approximately 90% of the administered dose was eliminated via urine (78.4%), faeces (11.6%), milk (0.014%) and edible organs/tissues (0.061%). The highest TRR was observed in kidney (0.184 mg eq./kg) and liver (0.05 mg eq./kg). Significantly lower residues were detected in the muscle (up to mg eq./kg) and fat (up to mg eq./kg). The TRR in milk samples was in the range of mg eq./kg within the observed period of 96 hours. The parent compound was not detected in samples of milk, muscle, fat, liver and kidney. The major detected were BYI enol ( % TRR, in all matrices) and BYI enolglucuronide (BYI enol-GA) ( % TRR in all matrices, except muscle). Laying hens were administered 14 oral doses of at a daily dose rate of 1.01 mg a.s./kg bw/d (12.86 mg/kg feed). The majority of the radioactivity was detected in excreta (90% of the administered dose). Only 0.045% and 0.023% of the total administered dose was detected in eggs and edible tissues/organs, respectively. The highest TRR was detected in kidneys (0.039 mg eq./kg) and liver (0.017 mg eq./kg), followed by fat (0.004 mg eq./kg) and muscle (0.003 mg eq./kg). The average TRR in eggs was mg eq./kg. The parent was not detected in any of the samples. BYI enol was the major metabolite in eggs (84% TRR), liver (50% TRR), fat (18.4% TRR) and muscle (64.4% TRR). The BYI enol-GA was also detected above 10% of the TRR in liver (15.1% TRR). Metabolism of in livestock proceeds via cleavage of the ester group to the primary metabolite BYI enol followed by conjugation of the enol hydroxy group with glucuronic acid to BYI enol-GA. The metabolic pathway is consistent with the metabolism found in rat. It was concluded in the DAR that the enforcement residue definition in livestock can be proposed as and BYI and the risk assessment residue definition can be proposed as, BYI enol and BYI enol-GA,. EFSA agrees with the proposed enforcement and risk assessment residue definitions for the commodities of animal origin and considers them as provisional since the peer review is not yet finalized. 14

15 Magnitude of residues Modification of the existing MRLs for in onions and the setting of new The studies investigating the magnitude of in livestock are reported in the DAR (Austria, 2008). was administered via capsule to ten lactating dairy cows for 29 consecutive days. The dose rates were 3.0 mg/kg feed/days, 9.0 mg/kg feed /days, or 30 mg/kg feed/day. The samples were analyzed for and the BYI enol and BYI enol-glucuronide (BYI enol-GA) and the results were summed up to give a total residue. No conversion factors for the risk assessment were derived considering both the low residue situation in livestock tissues and the fact that the molecular weight conversion factor would be of a low practical significance. The analytical LOQ was mg/kg for each analyte in milk matrices and 0.01 mg/kg for each analyte in the tissue matrices. The samples were analyzed within 19 days following the collection. At a dose level of 3 mg/kg feed/day, all analytes were below the LOQ except in kidney where BYI enol ( ) was quantified at mg/kg. At a dose level of 9 mg/kg feed/d all analytes except BYI enol were below the LOQ in all tissues. The metabolite was measured in fat, kidney and liver, but was not present in muscle. At a dose level of 30 mg/kg feed/d metabolite BYI enol was identified in fat, muscle, kidney and liver and BYI enol- GA was identified in liver and kidney. Total residue in the milk samples from the 30 mg/kg feeding level were at or below the LOQ (0.005 mg/kg) in all cows throughout the study with the exception of a maximum residue of mg/kg in one cow on study day 10. Residues of parent equivalents did not concentrate in samples of skim milk or milk fat separated from whole milk. Results of the feeding studies are summarized in Table 3-5. The calculated maximum dietary burden of 1.92 mg/kg DM for ruminants is below the lowest dosing level of 3 mg/kg DM. To estimate the residue levels in animal tissues the mean transfer factor between two lowest feeding levels were derived and the calculated concentrations of residues in kidney for the median and maximum calculated dietary burdens were derived. Derived MRL proposals are compiled in the Table 3-5. EFSA concludes that the MRL of 0.02 mg/kg would be required for bovine, sheep, goat and swine kidney. For muscle, fat, liver and milk no residues above the LOQ are expected. 15

16 Table 3-5. Overview of the values derived from the livestock feeding studies Commodity Dietary burden Results of the livestock feeding study STMR Med. Max. n Result for enf. Result for RA (mg/kg (mg/kg DM) DM) Dose Level (mg/kg DM) Mean Max. Mean Max. Enforcement residue definition: and BYI BYI enol Risk assessment residue definition:, BYI enol and BYI enolglucuronide, HR MRL proposal Ruminant meat <0.01 <0.01 <0.01 < * 9 <0.01 <0.01 <0.01 < Ruminant fat 3 <0.01 <0.01 <0.01 < * Ruminant liver 3 <0.01 <0.01 <0.01 < * Ruminant kidney CF for RA Milk < < * (*): indicates the limit of analytical quantification 16

17 4. Consumer risk assessment The consumer risk assessment was performed with revision 2 of the EFSA PRIMo (Pesticide Residue Intake Model) (EFSA, 2007). For the calculation of the chronic exposure EFSA used the existing MRLs as established in Annex IIIA of Regulation (EC) No 396/2005 as well as the STMR values for onions (derived from the supervised field trials) and kidney (derived from livestock feeding studies). In addition, for several crops the STMR values were available to refine the intake calculations (EFSA, 2009a, 2009b). The acute exposure assessment was performed only with regard to onions and kidney. The relevant HR values as derived from the residue trials (for onions) and livestock feeding studies (for kidney) were used as input values in the acute exposure assessment. Input values are summarized in Table 4-1. Table 4-1. Input values for the consumer exposure assessment Commodity Chronic risk assessment Acute risk assessment Input value Comment Input value Comment Residue definition for the risk assessment: the sum of BYI BYI BYI monohydroxy and BYI Onions STMR 0.2 HR Citrus fruit 0.33 STMR (EFSA, 2009a) Acute intake assessment was Apples, pears 0.18 STMR (EFSA, 2009a) undertaken only with regard to onions. Apricots, peaches 0.74 STMR (EFSA, 2009a) Plums 0.38 STMR (EFSA, 2009b) Cherries 0.48 STMR (EFSA, 2009b) Table and wine grapes 0.45 STMR (EFSA, 2009a) Other commodities of plant origin MRL See Appendix B Residue definition for the risk assessment:, BYI enol and BYI enolglucuronide, Bovine, sheep, goat, swine kidney STMR HR The calculated chronic and acute exposure was compared with the ADI and ARfD for. The summary of intake calculations is given in Appendix B. No long-term consumer intake concerns were identified for the proposed MRLs for in onions and kidney. The total calculated exposure values accounted for a maximum of 30.5% of the ADI. The contribution of residues in onions to the total consumer exposure accounted for a maximum of % of the ADI (WHO Cluster diet B). The consumer exposure to residues from the intake of kidneys is insignificant. 17

18 No short-term intake concerns were identified neither regarding the MRL proposal in onions nor regarding the MRL proposals in kidney. EFSA concludes that the proposed MRL of 0.3 mg/kg in onions and the proposed MRLs of 0.02 mg/kg in bovine, sheep, goat and swine kidney are acceptable as they will not raise any consumer intake concerns. 18

19 CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS Metabolism of was investigated by foliar applications in cotton, lettuce, potatoes and apples. Three different crop groups are covered by the available studies and the relevant residue for enforcement and risk assessment in all plant commodities was defined by the RMS as the sum of BYI BYI BYI monohydroxy and BYI An analytical method for enforcement of this residue definition in onions is also available. A sufficient of supervised residues field trials supporting the intended GAP for on onions is available indicating that an MRL of 0.3 mg/kg for in onions would be required to accommodate the intended use. The effect of industrial and household processing on the nature of residues was investigated. Total residue can be considered as stable when subject to conditions of pasteurization and baking/brewing/boiling, but during the process of sterilisation is completely hydrolyzed. Onions under normal processing practices are not subject to sterilisation practices therefore the same residue definition as for the raw commodities is applicable. No studies on the effects of processing on the magnitude of residues in onions were submitted and are also not necessary considering the low contribution of onions to the total dietary intake. Onions can be grown in a crop rotation and therefore a possible occurrence of residues in rotational crops was investigated. The RMS concluded that for rotational crops the same residue definition as in primary crops is applicable even though a wider range of were identified. In the DAR the RMS concluded that at the plant back interval of 30 days, no residues in rotational crops are expected. Taking into account that the rotational crop study was performed with a lower application rate, residues in succeeding crops cannot be fully excluded. Therefore EFSA recommends that the Member States, before granting national authorisations, should assess the need of defining restrictions (e.g. minimum plant-back intervals) in order to avoid residues in succeeding crops. The livestock dietary burden was calculated considering the existing MRLs for. The calculated dietary burden exceeds the trigger value of 0.1 mg/kg DM for all livestock species and is mainly driven by the residues in kale. The nature of in livestock has been sufficiently investigated to propose an enforcement residue definition as and BYI and the risk assessment residue definition as, BYI enol and BYI enolglucuronide,. The calculated dietary burdens and the results of livestock feeding studies were used to derive the MRL proposal for kidney at the level of 0.02 mg/kg. For other commodities of animal origin no residues above the LOQ are expected. The proposed analytical enforcement method is capable to determine the residues of BYI enol in kidney, but the applicant still has to provide the relevant validation data. The proposed analytical enforcement method for the determination of parent in kidney is not confirmed. A similar method, which was used in analyzing the livestock feeding study samples, is available and is considered as validated for the determination of all compounds included in the residue definition for the risk assessment. The applicant has to confirm if this method is suitable for the enforcement purposes. The consumer exposure assessment was performed with the revision 2 of the EFSA PRIMo. For the chronic exposure assessment EFSA used the existing MRLs as established in Annex IIIA of Regulation (EC) No 396/2005 as well as the STMR values for onions and kidney. The acute exposure assessment was performed only with regard to onions and kidney. 19

20 No long-term consumer intake concerns were identified for the proposed MRLs for in onions and kidney. The total calculated intake values ranged from 5.2 to 30.5% of the ADI. The contribution of residues in onions to the total consumer exposure accounted for a maximum of % of the ADI (WHO Cluster diet B). The consumer exposure to residues from the intake of kidneys is insignificant. No short-term intake concerns were identified regarding the MRL proposals in onions and in kidney. EFSA concludes that the proposed MRL of 0.3 mg/kg in onions and 0.02 mg/kg in bovine, sheep, goat and swine kidney are acceptable as they will not raise any consumer intake concerns. These recommendations should be considered for the inclusion in Annex III of the Regulation as the peer review of the active substance under Directive 91/414/EEC is not yet finalized. RECOMMENDATIONS Food Commodity Existing EC code a MRL Proposed EC MRL Justification for the proposal Enforcement residue definition: the sum of and BYI BYI BYI monohydroxy and BYI Onions The MRL proposal is sufficiently supported by data and no consumer intake concerns were identified. Proposed provisional enforcement residue definition: and BYI Swine kidney The MRL proposals are sufficiently Bovine kidney supported by data and no consumer intake concerns were identified Sheep kidney Goat kidney a according to Regulation (EC) No 396/2005. REFERENCES Germany, Evaluation report on the modification of the MRLs for in onions and kidney prepared by the evaluating Member State Germany under Article 8 of Regulation (EC) No 396/2005, 29 September Austria, Draft Assessment Report on prepared by the Rapporteur Member State Austria under Directive 91/414/EEC. April EFSA, Addendum to the reasoned opinion of EFSA prepared by PRAPeR on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs according to Regulation (EC) 396/2005 on maximum residue levels of pesticides in food and feed of plant and animal origin. EFSA Scientific Report (2008) 132, EFSA (European Food Safety Authority), 2009a. Reasoned opinion of EFSA prepared by the Pesticides Unit (PRAPeR) on the modification of the existing MRLs for in various fruit crops. EFSA Scientific Report (2009) 242. EFSA (European Food Safety Authority), 2009b. Reasoned opinion of EFSA prepared by the Pesticides Unit (PRAPeR) on the modification of the existing MRLs for in plums and cherries. EFSA Scientific Report (2009) 306, European Commission, 1997a. Appendix A - Metabolism and distribution in plants. 7028/VI/95-rev. 3, 22 July

21 European Commission, 1997b. Appendix B - General recommendations for the design, preparation and realization 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, 17 August European Commission, 1997c. Appendix C - Testing of plant protection products in rotational crops. 7524/VI/95-rev. 2, 22 July European Commission, Appendix D - Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/96-rev.8, 1 February European Commission, 1997d. Appendix E - Processing studies. 7035/VI/95 Rev 5, 22 July European Commission, 1997e. Appendix F - Metabolism and distribution in domestic animals. 7030/VI/95-rev 3, 22 July European Commission, Appendix G - Livestock feeding studies. 7031/VI/95 rev.4, 22 July European Commission, 1997f. Appendix H - Storage stability of residues samples. 7032/VI/95-rev.5, 22 July European Commission, 1997g. Appendix I - Calculation of maximum residue levels and safety intervals.7039/vi/95, 22 July FAO/WHO, 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

22 APPENDIX A GOOD AGRICULTURAL PRACTICES (GAPS) Crop and/or situation (a) Member State or Country F G or I (b) Pests or Group of pests controlle d (c) Onions Germany F Thrips spp. Formulation Application Application rate per treatment PHI Type kg as/hl kg as/ha (d-f) min max min max Conc. of a.s (i) method kind (f-h) growth stage & season (j) OD 150 spray With beginning of infestation min max (k) interval between appl. (min) (a) In case of group of crops the x classification should be used (b) Outdoor or field use (F), glasshouse application (G) or indoor application (I) ( c) e.g. biting and sucking insects, soil born insects, foliar fungi (d) Type of formulation (e) Use CIPAC/FAO s where appropriate (f) All abbreviations used must be explained (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (h) Kind, e.g. overall, broadcast, aerial spraying, row, plant, between the plants (i) g/kg or g/l (j) Growth stage at last treatment (k) PHI = Pre-harvest interval (l) Remarks may include: Extent of use/economic importance/restrictions (e.g. feeding,grazing)/minimal intervals between applications water L/ha min max (days) (l) 22

23 APPENDIX B PESTICIDE RESIDUES INTAKE MODEL (PRIMO) Status of the active substance: Pending no. #N/A LOQ (mg/kg bw): 0.1 proposed LOQ: Toxicological end points ADI (mg/kg bw/day): 0.05 ARfD (mg/kg bw): 1 Source of ADI: DAR Source of ARfD: DAR Year of evaluation: 2008 Year of evaluation: 2008 TMDI (range) in % of ADI minimum - maximum 5 31 No of diets exceeding ADI: --- Highest calculated TMDI values in % of ADI MS Diet Highest contributor to MS diet (in % of ADI) Commodity / group of commodities 2nd contributor to MS diet (in % of ADI) Commodity / group of commodities 3rd contributor to MS diet (in % of ADI) Commodity / group of commodities ptmrls at LOQ (in % of ADI) 30.5 WHO Cluster diet B 12.3 Tomatoes 3.6 Lettuce 2.0 Peppers DE child 4.3 Apples 3.9 Tomatoes 2.5 Oranges NL child 2.5 Tomatoes 2.3 Apples 2.1 Oranges IE adult 1.6 Tomatoes 1.1 Wine grapes 1.1 Aubergines (egg plants) WHO regional European diet 4.4 Tomatoes 3.8 Lettuce 0.8 Potatoes ES child 4.2 Lettuce 3.9 Tomatoes 1.4 Oranges IT kids/toddler 5.7 Tomatoes 2.9 Lettuce 1.3 Wheat ES adult 5.4 Lettuce 3.1 Tomatoes 0.9 Oranges UK Toddler 4.6 Sugar beet (root) 2.4 Tomatoes 1.3 Oranges IT adult 4.7 Tomatoes 3.8 Lettuce 0.8 Wheat WHO cluster diet D 4.0 Tomatoes 1.3 Wheat 0.8 Potatoes WHO Cluster diet F 3.0 Lettuce 2.7 Tomatoes 0.7 Wheat WHO cluster diet E 2.1 Tomatoes 1.4 Wine grapes 0.9 Lettuce PT General population 3.6 Tomatoes 2.2 Wine grapes 1.1 Potatoes FR toddler 3.1 Tomatoes 1.3 Oranges 1.0 Potatoes SE general population 90th percentile 3.1 Tomatoes 0.8 Potatoes 0.8 Chinese cabbage DK child 2.1 Tomatoes 1.4 Lettuce 1.1 Wheat FR all population 3.6 Wine grapes 1.7 Tomatoes 0.9 Lettuce NL general 1.7 Tomatoes 1.2 Lettuce 1.0 Oranges UK vegetarian 2.5 Tomatoes 1.4 Lettuce 0.8 Sugar beet (root) UK Infant 2.0 Sugar beet (root) 1.5 Tomatoes 0.9 Oranges PL general population 3.5 Tomatoes 0.7 Apples 0.7 Potatoes UK Adult 1.7 Tomatoes 1.2 Lettuce 1.0 Wine grapes FR infant 0.9 Apples 0.8 Potatoes 0.6 Oranges LT adult 2.5 Tomatoes 0.7 Apples 0.6 Potatoes DK adult 1.7 Tomatoes 1.3 Wine grapes 0.4 Peppers FI adult 1.7 Tomatoes 0.8 Lettuce 0.6 Oranges 0.9 Conclusion: The estimated Theoretical Maximum Daily Intakes (TMDI), based on ptmrls were below the ADI. A long-term intake of residues of is unlikely to present a public health concern. Chronic risk assessment - refined calculations 23

24 Acute risk assessment /children - refined calculations Acute risk assessment / adults / general population - refined calculations Processed commodities Unprocessed commodities The acute risk assessment is based on the ARfD. For each commodity the calculation is based on the highest reported MS consumption per kg bw and the corresponding unit weight from the MS with the critical consumption. If no data on the unit weight was available from that MS an average European unit weight was used for the IESTI calculation. In the IESTI 1 calculation, the variability factors were 10, 7 or 5 (according to JMPR manual 2002), for lettuce a variability factor of 5 was used. In the IESTI 2 calculations, the variability factors of 10 and 7 were replaced by 5. For lettuce the calculation was performed with a variabilty factor of 3. Threshold MRL is the calculated residue level which would leads to an exposure equivalent to 100 % of the ARfD. No of commodities for which ARfD/ADI is exceeded (IESTI 1): No of commodities for which No of commodities for which ARfD/ADI No of commodities for which ARfD/ADI is exceeded --- ARfD/ADI is exceeded (IESTI 2): --- is exceeded (IESTI 1): --- (IESTI 2): --- IESTI 1 *) **) IESTI 2 *) **) IESTI 1 *) **) IESTI 2 *) **) Highest % of ARfD/ADI Commodities ptmrl/ threshold MRL Highest % of ARfD/ADI Commodities ptmrl/ threshold MRL Highest % of ARfD/ADI Commodities ptmrl/ threshold MRL Highest % of ARfD/ADI Commodities ptmrl/ threshold MRL 0.80 Onions 0.2 / Onions 0.2 / Onions 0.2 / Onions 0.2 / Bovine: Kidney / Bovine: Kidney / Bovine: Kidney / Bovine: Kidney / Swine: Kidney / Swine: Kidney / Swine: Kidney / Swine: Kidney / - No of critical MRLs (IESTI 1) --- No of critical MRLs (IESTI 2) --- No of commodities for which ARfD/ADI is exceeded: Highest % of ARfD/ADI Processed commodities No of commodities for which ARfD/ADI --- is exceeded: --- ***) ***) ptmrl/ threshold MRL Highest % of Processed ARfD/ADI commodities ptmrl/ threshold MRL *) The results of the IESTI calculations are reported for at least 5 commodities. If the ARfD is exceeded for more than 5 commodities, all IESTI values > 90% of ARfD are reported. **) ptmrl: provisional temporary MRL ***) ptmrl: provisional temporary MRL for unprocessed commodity Conclusion: For IESTI 1 and IESTI 2 were calculated for food commodities for which ptmrls were submitted and for which consumption data are available. No exceedance of the ARfD/ADI was identified for any unprocessed commodity. For processed commodities, no exceedance of the ARfD/ADI was identified. 24