REASONED OPINION. Reasoned opinion on the modification of the existing MRLs for propamocarb in radishes and kale 1. European Food Safety Authority 2

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1 EFSA Journal 2012;10(4):2684 REASONED OPINION Reasoned opinion on the modification of the existing MRLs for propamocarb in radishes and kale 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy This reasoned opinion, published on 06 July 2012, replaces the earlier version published on 30 April SUMMARY According to Article 6 of the Regulation (EC) No 396/2005, Greece, herewith referred to as the Evaluating Member State (EMS), received an application from the company Bayer CropScience to modify the existing MRL for propamocarb in radishes and kale. In order to accommodate for the intended use of propamocarb on radishes in Germany and Switzerland and on kale in the Netherlands and France, it is proposed to lower the existing MRL from 10 mg/kg to 3 mg/kg on radishes and to increase the existing MRL from 10 mg/kg to 20 mg/kg on kale. The EMS Greece 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 13 September EFSA derives the following conclusions based on the submitted evaluation report prepared by the EMS, the EFSA conclusion on the peer review of propamocarb, the Draft Assessment Report (DAR) prepared by the rapporteur Member State (RMS) Ireland under Directive 91/414/EEC, the previously issued EFSA reasoned opinion on the modification of the existing MRLs for propamocarb in leek, spinach, witloof and lamb s lettuce as well as the JMPR Evaluation Report. The toxicological profile of propamocarb hydrochloride was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.29 mg/kg bw/day and an ARfD of 1 mg/kg bw. In order to perform the risk assessment compliant with the risk assessment residue definition, the ADI and ARfD for propamocarb hydrochloride were recalculated to propamocarb equivalents by applying the molecular weight conversion factor. The recalculated ADI and ARfD values for propamocarb are mg/kg bw/d and 0.84 mg/kg bw, respectively. 1 On request from European Commission, Question No EFSA-Q , approved on 26 April Correspondence: pesticides.mrl@efsa.europa.eu 3 The corrigendum was prepared to take into account the following information: processing studies for cooked vegetable (chapter , page 14) and more recent data on the unit weight for kale (chapter 4, page 15). These changes have an impact on the consumer risk assessment and the overall conclusions (chapter 4, page 16). To avoid confusion, the original version of the reasoned opinion has been removed from the website, but is available on request showing all the changes made. Suggested citation: European Food Safety Authority; Reasoned opinion on the modification of the existing MRLs for propamocarb in radishes and kale. EFSA Journal 2012;10(4):2684. [30 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2012

2 The metabolism of propamocarb hydrochloride in primary crops was investigated in fruiting vegetables, leafy vegetables and root and tuber vegetables. The residue definition in plant commodities for monitoring and risk assessment was proposed by the peer review to be restricted to propamocarb and its salts, the sum being expressed as propamocarb. The same residue definition is established in Regulation (EC) No 396/2005. EFSA concludes that the metabolism of propamocarb hydrochloride in the crops under consideration is sufficiently addressed and no further metabolism studies are required. The same residue definitions as derived by the peer review are applicable for the crops under consideration. The supervised residue trials are sufficient and adequate to derive MRL proposals for the intended uses on radishes and kale. The studies demonstrated that a MRL of 3 mg/kg on radishes and 20 mg/kg on kale are appropriate for the intended uses of propamocarb on the crops under consideration. Before it is decided to lower the existing MRL for radishes it needs to be confirmed that no more critical GAP is authorised which would require the maintain of the current MRL of 10 mg/kg. An analytical method is available to enforce the proposed MRLs on the commodities under consideration. The effect of processing on the nature of propamocarb residues was not investigated in the framework of the peer review under Directive 91/414/EEC. Studies investigating the effect of processing on the magnitude of propamocarb residues on spinach demonstrated that washing has a low impact on the residue concentration in spinach (median washing factor: 0.86); also in cooked spinach leaves only a slight reduction was observed accounting for 86% to 93% of the initial residue level measured in the unprocessed spinach (median processing factor 0.88). The possible occurrence of propamocarb residues in rotational and or/succeeding crops was investigated. It was concluded that the nature of residues in rotational crops and in primary crops is expected to be similar; significant residue levels in rotational crops (exceeding 0.01 mg/kg) will not occur provided that the active substance is applied according to the proposed GAP. Since kale can be used as a feed item, a potential carry-over into food of animal origin was assessed. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg (dry matter) for all animal species but was mainly driven by the existing MRLs on crops which can be used as feed items. The impact of propamocarb residues in kale to the total livestock exposure was insignificant and therefore the modification of the current MRLs for commodities of animal origin is not further investigated in the framework of this MRL application. The consumer risk assessment was performed with a revised version of the EFSA PRIMo, taking into account the recent data provided by the Netherlands on the unit weight for kale. For the calculation of the chronic exposure EFSA used the median residue value for radishes and kale as derived from the supervised field trials as well as the median residue values reported in the previously issued EFSA reasoned opinion on the modification of the existing MRLs for propamocarb in spinach, witloof and lamb s lettuce. Since kale and spinach are mainly consumed in processed form the median processing factor derived for cooking was used to refine the intake calculation. For other food commodities of animal and plant origin, the existing MRLs as established in Annexes IIIA of Regulation (EC) No 396/2005 were used as input values. The acute exposure assessment was performed only with regard to the crops under consideration. The HR values as derived from the supervised residue field trials were used as input values. A second calculation was performed with the existing MRL on radishes to provide risk managers the relevant facts needed to decide whether the lowering of the existing MRL is indicated for reasons of consumer safety. EFSA Journal 2012;10(4):2684 2

3 No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 10.1% to 77.4% of the ADI (DE child). The contribution of residues in radishes and kale to the total consumer exposure accounted for less than 1% of the ADI. Using the internationally agreed standard methodology, based on the highest residue observed in residue trials and the processing factor for cooking, no acute consumer risk was identified. The calculated maximum exposure in percentage of the ARfD was 60% for kale (NL child) and 3.1% for radishes (UK toddler). Using the existing MRL for radishes, the acute exposure accounted for 26% of the ARfD. EFSA concludes that the intended uses of propamocarb on radishes and kale do not lead to a chronic consumer intake concern. The acute exposure resulting from propamocarb residues in radishes and kale does not pose a consumer health risk. The recommendations of EFSA are compiled in the table below: Code number a Commodity Existing EU MRL Proposed EU MRL Justification for the proposal Enforcement residue definition: Propamocarb (Sum of propamocarb and its salts expressed as propamocarb) Radishes 10 3 The MRL proposal is sufficiently supported by data and no risk for the consumers was identified. It is noted that before lowering the existing MRL it needs to be confirmed that no more critical GAP is authorised at EU level which would require to maintain the MRL of 10 mg/kg Kale The data are sufficient to derive a MRL proposal of 20 mg/kg. For this MRL neither a chronic nor an acute consumer intake concern was identified. a according to Annex I of Regulation (EC) No 396/2005 KEY WORDS Propamocarb, propamocarb hydrochloride, radishes, kale, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, carbamate fungicide. EFSA Journal 2012;10(4):2684 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 Method of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues Nature and magnitude of residues in plant Primary crops Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Consumer risk assessment Conclusions and recommendations Appendix A. Good Agricultural Practices (GAPs) Appendix B. Pesticide Residues Intake Model (PRIMo) Appendix C. Existing EU maximum residue limits (MRLs) Abbreviations EFSA Journal 2012;10(4):2684 4

5 BACKGROUND Commission Regulation (EC) No 396/ establishes the rules governing the setting of pesticide MRLs at Community level. Article 6 lays down that a party requesting an authorisation for the use of a plant protection product in accordance with Council Directive 91/414/EEC 5, repealed by Regulation (EC) No 1107/2009 6, 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. Greece, hereafter referred to as the evaluating Member State (EMS), received an application from the company Bayer CropScience 7 to modify the existing MRLs for the active substance propamocarb in radishes and kale. This application was notified to the European Commission and to 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 13 September The application was included in the EFSA Register of Questions with the reference number EFSA-Q and the following subject: Propamocarb - Application to modify the existing MRLs in radishes and kale The applicant proposed the following MRLs for propamocarb: 2 mg/kg in radishes and 20 mg/kg in kale. The EMS after the assessment of the application proposed the same MRLs. EFSA then proceeded with the assessment of the application as required by Article 10 of the Regulation. TERMS OF REFERENCE In accordance with 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. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within three months (which may be extended to six months where more detailed evaluations need to be carried out) from the date of receipt of the 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 13 December Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July 1991, OJ L 230, , p Regulation (EC) No 1107/2009 of the European Parliament of the Council of 21 October 2009, OJ L 309, , p Bayer CropScience Europe, Rue Jean Marie Leclair 16, 69009, Lyon, France EFSA Journal 2012;10(4):2684 5

6 THE ACTIVE SUBSTANCE AND ITS USE PATTERN Propamocarb is the ISO common name for propyl 3-(dimethylamino) propylcarbamate (IUPAC) while the variant propamocarb hydrochloride is the ISO common name of propyl 3-(dimethylamino) propylcarbamate hydrochloride (IUPAC). The chemical structures of both compounds are herewith reported: MW=188.3 g/mol Propamocarb MW=224.7 g/mol Propamocarb hydrochloride Propamocarb and propamocarb hydrochloride belong to the chemical group of carbamate fungicides. The active substances are systemic and are taken up via leaves and roots and act as multi-site inhibitors with protective action which specifically controls phycomycetous diseases. Propamocarb was evaluated according to Directive 91/414/EEC with Ireland designated as a rapporteur Member State (RMS). The peer review of propamocarb was finalized and an EFSA conclusion was issued on 12 May 2006 (EFSA, 2006). It has to be noted that the peer review was performed with respect to propamocarb hydrochloride. Propamocarb was included in Annex I of this Directive by Directive 2007/25/EC 8 for use as a fungicide only. The representative uses evaluated in the peer review were foliar spraying, drenching or dip irrigation to control a broad spectrum of plant diseases in lettuce, potatoes, tomato (grown in soil and rock wool). The active substance in the formulation was propamocarb hydrochloride. The EU MRLs are established for propamocarb and its salts, the sum being expressed as propamocarb (enforcement residue definition) regardless whether propamocarb or propamocarb hydrochloride is applied as an active substance. The EU MRLs for propamocarb are set in Annex IIIA of Regulation (EC) No 396/2005 (Appendix C). The existing EU MRL for propamocarb in radishes and kale is set at 10 mg/kg. Codex Alimentarius Commission has set CXLs for a wide range of crops, including a CXL of 1 mg/kg for radishes while no CXL is set for kale. The intended GAPs for which a modification of the existing MRL is requested refer to outdoor foliar spray applications of the active substance propamocarb hydrochloride on radishes and kale. The details of the GAPs are given in Appendix A. 8 Commission Directive (EC) 2007/25 of 23 April OJ L 106, p EFSA Journal 2012;10(4):2684 6

7 ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the EMS (Greece, 2011), the Draft Assessment Report (DAR) prepared under Council Directive 91/414/EEC (Ireland, 2004), the conclusion on the peer review of the pesticide risk assessment of the active substance propamocarb (EFSA, 2006), the previously issued EFSA reasoned opinion on the modification of the existing MRLs for propamocarb in leek, spinach, witloof and lamb s lettuce and the JMPR Evaluation Report (FAO, 2006). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/ and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2010a, 2010b, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of propamocarb residues in plant commodities were assessed in the DAR and in the conclusion on the peer review under Directive 91/414/EEC (Ireland, 2004; EFSA, 2006). An analytical method is available for the analysis of residues of propamocarb and its salts in food of plant origin using HPLC analysis with MS/MS detection at the LOQ of 0.01 mg/kg. The method was independently validated for high water content matrices (tomatoes, lettuce). The common multi-residue methods are not applicable for the determination of propamocarb residues in plant matrices. Since radishes and kale belong to the group of high water content commodities, EFSA concludes that a sufficiently validated analytical method is available to monitor all the compounds given in the respective residue definition, i.e. propamocarb and its salts Methods for enforcement of residues in food of animal origin Considering the intended uses assessed in the framework of the peer review, an analytical method for food of animal origin was not required since there was no need to establish any residue definition nor MRLs for animal commodities. 9 Commission Regulation (EU) No 546/2011 of 10 June OJ L 155, , p EFSA Journal 2012;10(4):2684 7

8 2. Mammalian toxicology The toxicological profile of propamocarb hydrochloride was assessed in the framework of the peer review under Directive 91/414/EEC (Ireland, 2004, EFSA, 2006). As the residue definition for risk assessment is expressed as propamocarb, whilst the toxicological reference values have been derived for propamocarb hydrochloride, the toxicological reference values for propamocarb were recalculated by applying the molecular weight conversion factor of The derived toxicological end points are compiled in Table 2-1. Table 2-1: Overview of the toxicological reference values Propamocarb hydrochloride Source Year Value Study relied upon Safety factor ADI EFSA mg/kg bw/d 52 week rat study 100 ARfD EFSA mg/kg bw 28 d gavage study in rats 100 Propamocarb ADI EFSA mg/kg bw/d - - ARfD EFSA mg/kg bw Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of propamocarb hydrochloride in primary crops was evaluated by the RMS (Ireland, 2004) and reviewed by EFSA (EFSA, 2006) in the framework of the peer review under Directive 91/414/EEC. The overview of the metabolism study designs is presented in the table below. Table 3-1: Summary of available metabolism studies in plants Group Crop Label position Method, F, G or P (a ) Rate (kg a.s./ha) Application details No/ Interval (d) Sampling (DAT) Remarks Fruit and fruiting vegetables Tomatoes 14 C- carbon G 7.22 g 4 14, 21, 28, a.s./m g a.s./ 4 m 2 Soil treatment , 14, 21, 28 Foliar treatment spray 10 MW propamocarb/mw propamocarb hydrochloride 188.3/224.7=0.84 EFSA Journal 2012;10(4):2684 8

9 Group Crop Label position Method, F, G or P (a ) Rate (kg a.s./ha) Application details No/ Interval (d) Sampling (DAT) Remarks Cucumbers 14 C- carbon n.r Foliar spray n.r mg/plant (aqueous) 1 21 Hydroponically grown cucumbers (soil treatment) Leafy vegetables Spinach 14 C- carbon F / 20 d 0 d after the 1 st appl.; prior to the 2 nd appl.; 3 d after the 2 nd appl. Foliar spray treatment Lettuce 14 C- carbon G drench: 7.22 g a.s./m 2 3 / 14, 28 d 38 Soil treatment Root and tuber vegetables Potatoes 14 C- carbon G foliar spray: / Foliar spray treatment F / 20 PHI of 6 weeks (a): Outdoor/field use (F) or glasshouse/ /indoor application (G) or protected (P) n.r. not report in the DAR Foliar spray treatment F Foliar spray; After the 6 th application the foliage had died and the spray was sprayed on soil The metabolic pattern of propamocarb depicted in plants is strongly influenced by the mode of application of the product. In lettuce, no information was provided on the amount of the total residues that could remain on the surface of the leaves at harvest. After foliar applications, residues are highly extractable (90% of the TRR) and consist essentially of propamocarb. Two minor metabolites, accounting for less than 5% of the TRR were also identified, hydroxypropyl-propamocarb and propamocarb-n-oxide, indicating that the degradation of propamocarb hydrochloride proceeds through hydroxylation and oxidation. A similar pattern was observed in spinach after foliar treatment, with two further metabolites identified, resulting from N-demethylation and cyclization of the hydroxy metabolite identified in lettuce. Foliar treatment of tomato plants also resulted in propamocarb being the major constituent in tomato fruits (75% of the TRR). Propamocarb hydrochloride applied hydroponically or as soil treatment in tomatoes or lettuce results in a quite different metabolic pattern in harvested lettuce and tomatoes. The amounts of unchanged parent and of its structurally related metabolites are low, demonstrating a high rate of degradation in plants and in the soil. The total residues are essentially constituted of polar material rather similar for EFSA Journal 2012;10(4):2684 9

10 both crops, indicating the incorporation of labelled carbon in the endogenous material. In contrast to the observations made in lettuce and tomatoes, cucumbers grown hydroponically and treated with propamocarb hydrochloride applied in the nutrient solution showed significantly higher levels of parent propamocarb (50% of the TRR). In potato tubers unchanged propamocarb was present at 2-15% of the TRR. The vast majority of the radioactivity could be allocated to natural plant constituents (mainly starch), demonstrating the incorporation in plant material of CO 2 produced by the degradation of propamocarb hydrochloride. The residue definition in plant commodities for monitoring and risk assessment was proposed by the peer review to be restricted to propamocarb and its salts, the sum being expressed as propamocarb since no metabolite structurally related to propamocarb would contribute significantly to the toxicological burden. This residue definition is in line with the residue definition established in Regulation (EC) No 396/2005. Codex Alimentarius Commission has established the residue definition for risk assessment and enforcement purposes in all plants as propamocarb (free base). EFSA concludes that the metabolism of propamocarb hydrochloride in the crops under consideration is sufficiently addressed and no further metabolism studies are required. The same residue definitions as derived by the peer review are applicable Magnitude of residues The intended uses on radish and kale refer to the application of propamocarb hydrochloride. It has to be noted that the residue data on radish and kale were expressed as propamocarb equivalents. a. Radishes NEU critical GAP: 2 foliar spray applications at 1 kg a.s./ha up to BBCH 47; PHI 14 d-outdoor conditions 5 GAP compliant residue trials were conducted in Germany under outdoor conditions. This dataset was considered sufficient to derive MRL proposal and risk assessment values. b. Kale NEU critical GAP: 3 foliar spray applications at 1 kg a.s./ha up to BBCH 49; PHI 14 d Outdoor conditions SEU critical GAP: 2 foliar spray applications at 1 kg a.s./ha up to BBCH 49; PHI 14 d Outdoor conditions 6 residue trials compliant with the Dutch GAP were submitted. In accordance with the current guidance document (EC, 2011) the dataset was considered sufficient to derive MRL proposal and risk assessment values. The results of the residue trials, the related risk assessment input values (highest residue, median residue) and the MRL proposals are summarized in Table 3-2. The storage stability of propamocarb in primary crops was investigated in the DAR under Directive 91/414/EEC (Ireland, 2004, EFSA, 2006). Residues of propamocarb were found to be stable at - 18 C for up to 24 months in matrices with high water-content matrices. The storage time interval of the samples from the residue trials is covered by the available storage stability data. It is concluded that the residue data are valid with regard to storage stability. EFSA Journal 2012;10(4):

11 According to the EMS, the analytical method used to analyse supervised residue trial samples has been sufficiently validated and was proven to be fit for purpose (Greece, 2011). EFSA concludes that the data are sufficient to derive MRL proposals. MRLs of 3 mg/kg on radishes and 20 mg/kg on kale would be appropriate for the intended uses of propamocarb on the crops under consideration in the Member States for which these authorizations are intended. Before it is decided to lower the existing MRL for radishes it needs to be confirmed that no more critical GAP is authorised which would require the maintain of the current MRL of 10 mg/kg. It is also noted that the MRL proposal of 30 mg/kg for kale derived from the OECD calculator was not favoured by EFSA considering that the highest residue level observed in supervised field trials was well below the MRL calculated by the OECD calculator. EFSA Journal 2012;10(4):

12 Table 3-2: Overview of the available residue trials data Commodity Region (a) Outdoor/Indoor Individual trial results Median residue (b) Enforcement (sum of propamocarb and its salts, expressed as propamocarb) Radishes NEU Outdoor 0.14; 0.47; 0.61; 0.92; 1.2 Kale NEU Outdoor 0.46; 3.9; 4.0; 4.0; 10.7; 11.8 Risk assessment (sum of propamocarb and its salts, expressed as propamocarb) Highest residue (c) MRL proposal Median CF (d) Comments 0.14; 0.47; 0.61; 0.92; R ber = 2.12 R max = 2.39 MRL OECD = 2.30/3 0.46; 3.9; 4.0; 4.0; 10.7; R ber = R max = MRL OECD = 23.57/30 (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 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. (e): Statistical estimation of MRLs according to the EU methodology (R ber, R max ; EC, 1997g) and unrounded/rounded values according to the OECD methodology (OECD, 2011). (*): Indicates that the MRL is set at the limit of analytical quantification. (e) EFSA Journal 2012;10(4):

13 Effect of industrial processing and/or household preparation The effect of processing on the nature of propamocarb residues was not investigated in the framework of the peer review under Directive 91/414/EEC (Ireland, 2004). Studies investigating the effect of processing on the magnitude of propamocarb residues on spinach have been submitted in the framework of another MRL application (Ireland, 2012). Washing was found to have a low impact on the residue concentration in spinach (average transfer factor for washing: 0.97); in cooked of spinach leaves a slight reduction was observed, resulting in 86% to 93% of the initial residue level measured in the unprocessed spinach (median processing factor 0.88). Since kale is mainly consumed cooked, the median processing factor derived for spinach could be considered in a refined intake calculation. EFSA would like to highlight that studies investigating the effect of processing on the nature of propamocarb residues would be desirable to ensure that no degradation products are formed which might be of relevance Rotational crops Preliminary considerations Radishes and kale can be grown in rotation with other plants and therefore the possible occurrence of residues in rotational/succeeding crops resulting from the use on primary crops has to be assessed. The degradation of propamocarb hydrochloride in soil under field conditions proceeds faster (maximum DT 90f =78.6 d) than under laboratory conditions (maximum DT 90lab = mean d) (EFSA, 2006) and confined rotational crops studies can be waived. Nevertheless, these studies were submitted in the framework of the peer review (Ireland, 2004, EFSA, 2006) and showed that the metabolic pattern in succeeding crops was similar to that observed in primary crops and the same residue definitions for monitoring and risk assessment in primary crops can also apply to the rotational crops. Field trials on rotational crops were considered as not necessary Nature and magnitude of residues in livestock The use of propamocarb resulted in significant residue levels in kale which might be fed to livestock Dietary burden of livestock The median and maximum dietary burden for livestock was calculated using the agreed European methodology (EC, 1996) considering the crops for which MRLs are set above the LOQ. EFSA calculated two scenarios for estimating the dietary burden on livestock, estimating the impact of the intended use on kale. In scenario 1 the dietary burden was calculated for citrus/apple pomace, potatoes and turnips using the respective established MRLs values, whereas in scenario 2, also kale was included. EFSA used the default processing factor of 2.5 for citrus and apple pomace (EFSA, 2009). The input values for the dietary burden calculation are summarized in Table 3-3. EFSA Journal 2012;10(4):

14 Table 3-3: Input values for the dietary burden calculation Modification of MRLs for propamocarb in radishes and kale Commodity Median dietary burden Maximum dietary burden Input value Comment Input value Risk assessment residue definition: Sum of propamocarb and its salts expressed as propamocarb Comment Citrus fruit (except oranges) - Not available 25 MRL*PF (2.5) Apples - Not available 25 MRL*PF (2.5) Potatoes 0.01 Median residue (PROFile) 0.02 HR (PROFile) Turnip - Not available 10 MRL Head cabbage - Not available 10 MRL Kale (included only in scenario 2) 4.0 Median residue HR (a): Table footnote The results of the dietary burden calculations are summarized in the tables 3-4 and 3-5. Table 3-4: Results of the dietary burden calculation Scenario 1 Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Risk assessment residue definition: Sum of propamocarb and its salts expressed as propamocarb Trigger exceeded? Dairy ruminants Turnips 55.0 Yes Meat ruminants Turnips Yes Poultry Turnips Yes Pigs Turnips 70.7 Yes Table 3-5: Results of the dietary burden calculation - Scenario 2 Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Risk assessment residue definition: Sum of propamocarb and its salts expressed as propamocarb Trigger exceeded? Dairy ruminants Turnips Yes Meat ruminants Turnips Yes Poultry Turnips Yes Pigs Turnips Yes From the comparison of the two scenarios it is evident that the dietary burden exceeds the trigger of 0.1 mg/kg DM for ruminants, poultry and pigs and that it is mainly driven by the existing uses on feed EFSA Journal 2012;10(4):

15 items, the contribution of kale to the total livestock exposure having a negligible impact. EFSA concluded that there is no need to revise the current MRLs for commodities of animal origin in the frame of this MRL application. 4. Consumer risk assessment The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). This exposure assessment model contains the relevant European food consumption data for different sub-groups of the EU population 11 (EFSA, 2007). For the calculation of the acute exposure EFSA updated the standard settings of the EFSA PRIMo with more recent data submitted by the Netherlands on the unit weight for kale (672 g/unit instead of 165 g/unit) (The Netherlands, 2010). It is noted that this update also has an impact on the variability factor to be used in the IESTI calculation (5 instead of 7). For the calculation of the chronic exposure, EFSA used the median residue values as derived from the residue trials on the crops under consideration (see Table 3-2) as well as the median residue values reported in the previously issued EFSA reasoned opinion on the modification of the existing MRLs for propamocarb in spinach, witloof and lamb s lettuce (EFSA, 2011). For the remaining commodities of plant and animal origin, the existing MRLs as established in Annexe IIIA of Regulation (EC) No 396/2005 were used as input values. Since kale and spinach are mainly consumed in processed form the median processing factor derived for cooked spinach was used to refine the intake calculation. The model assumptions for the long-term exposure assessment are considered to be sufficiently conservative for a first tier exposure assessment, assuming that all food items consumed have been treated with the active substance under consideration. In reality, it is not likely that all food consumed will contain residues at the MRL or at levels of the median residue values identified in supervised field trials. However, if this first tier exposure assessment does not exceed the toxicological reference value for long-term exposure (i.e. the ADI), a consumer health risk can be excluded with a high probability. The acute exposure assessment was performed only with regard to the commodities under consideration assuming the consumption of a large portion of the food items as reported in the national food surveys containing residues at the highest level as observed in supervised field trials. A variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation (EFSA, 2007). EFSA also estimated the acute consumer exposure resulting from the existing MRL for radishes to provide risk managers the relevant facts needed to decide whether the lowering of the existing MRL is indicated for reasons of consumer safety. The input values used for the dietary exposure calculation are summarized in Table 4-1. Table 4-1: Input values for the consumer dietary exposure assessment Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Risk assessment residue definition: sum of propamocarb and its salts, expressed as propamocarb Comment 11 The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22 national diets collected from MS surveys plus 1 regional and 4 cluster diets from the WHO GEMS Food database; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collected from MS surveys is used. The complete list of diets incorporated in EFSA PRIMo is given in its reference section (EFSA, 2007). EFSA Journal 2012;10(4):

16 Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Radishes 0.61 Median residue 1.20 Highest residue Kale 3.66 Median residue * PF (0.88) Spinach 5.68 Median residue (NEU database) *PF (0.88) (EFSA, 2011) Witloof Median residue (EFSA, 2011) Other commodities of food and animal origin MRL See Appendix C 10 Existing MRL Highest residue * PF (0.88) Acute risk assessment was undertaken only with regard to the crops under consideration. The estimated exposure was then compared with the toxicological reference values derived for propamocarb (see Table 2-1). The results of the intake calculation are presented in Appendix B to this reasoned opinion. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 10.1% to 77.4% of the ADI (DE child). The contribution of residues in radishes and kale to the total consumer exposure accounted for less than 1% of the ADI. Using the internationally agreed standard methodology for acute risk assessment, based on the highest residue observed in residue trials, no acute consumer risk was identified. The calculated maximum exposure in percentage of the ARfD was 60% for kale (NL child) and 3.1% for radishes (UK toddler). The exposure resulting from the existing MRL for radishes accounted for 26.1% of the ARfD. EFSA concludes that the intended uses of propamocarb on radishes and kale do not lead to a chronic consumer intake risk. Regarding the acute exposure to propamocarb residues in radishes neither the existing MRL of 10 mg/kg nor the residues resulting from the intended use are posing a consumer health risk. For kale the acute exposure calculated according to the internationally agreed methodology does not pose a consumer health concern. EFSA Journal 2012;10(4):

17 CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS The toxicological profile of propamocarb hydrochloride was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.29 mg/kg bw/day and an ARfD of 1 mg/kg bw. In order to perform the risk assessment compliant with the risk assessment residue definition, the ADI and ARfD for propamocarb hydrochloride were recalculated to propamocarb equivalents by applying the molecular weight conversion factor. The recalculated ADI and ARfD values for propamocarb are mg/kg bw/d and 0.84 mg/kg bw, respectively. The metabolism of propamocarb hydrochloride in primary crops was investigated in fruiting vegetables, leafy vegetables and root and tuber vegetables. The residue definition in plant commodities for monitoring and risk assessment was proposed by the peer review to be restricted to propamocarb and its salts, the sum being expressed as propamocarb. The same residue definition is established in Regulation (EC) No 396/2005. EFSA concludes that the metabolism of propamocarb hydrochloride in the crops under consideration is sufficiently addressed and no further metabolism studies are required. The same residue definitions as derived by the peer review are applicable for the crops under consideration. The supervised residue trials are sufficient and adequate to derive MRL proposals for the intended uses on radishes and kale. The studies demonstrated that a MRL of 3 mg/kg on radishes and 20 mg/kg on kale are appropriate for the intended uses of propamocarb on the crops under consideration. Before it is decided to lower the existing MRL for radishes it needs to be confirmed that no more critical GAP is authorised which would require the maintain of the current MRL of 10 mg/kg. An analytical method is available to enforce the proposed MRLs on the commodities under consideration. The effect of processing on the nature of propamocarb residues was not investigated in the framework of the peer review under Directive 91/414/EEC. Studies investigating the effect of processing on the magnitude of propamocarb residues on spinach demonstrated that washing has a low impact on the residue concentration in spinach (median washing factor: 0.86); also in cooked spinach leaves only a slight reduction was observed accounting for 86% to 93% of the initial residue level measured in the unprocessed spinach (median processing factor 0.88). The possible occurrence of propamocarb residues in rotational and or/succeeding crops was investigated. It was concluded that the nature of residues in rotational crops and in primary crops is expected to be similar; significant residue levels in rotational crops (exceeding 0.01 mg/kg) will not occur provided that the active substance is applied according to the proposed GAP. Since kale can be used as a feed item, a potential carry-over into food of animal origin was assessed. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg (dry matter) for all animal species but was mainly driven by the existing MRLs on crops which can be used as feed items. The impact of propamocarb residues in kale to the total livestock exposure was insignificant and therefore the modification of the current MRLs for commodities of animal origin is not further investigated in the framework of this MRL application. The consumer risk assessment was performed with a revised version of the EFSA PRIMo, taking into account the recent data provided by the Netherlands on the unit weight for kale. For the calculation of the chronic exposure EFSA used the median residue value for radishes and kale as derived from the supervised field trials as well as the median residue values reported in the previously issued EFSA reasoned opinion on the modification of the existing MRLs for propamocarb in spinach, witloof and EFSA Journal 2012;10(4):

18 lamb s lettuce. Since kale and spinach are mainly consumed in processed form the median processing factor derived for cooking was used to refine the intake calculation. For other food commodities of animal and plant origin, the existing MRLs as established in Annexes IIIA of Regulation (EC) No 396/2005 were used as input values. The acute exposure assessment was performed only with regard to the crops under consideration. The HR values as derived from the supervised residue field trials were used as input values. A second calculation was performed with the existing MRL on radishes to provide risk managers the relevant facts needed to decide whether the lowering of the existing MRL is indicated for reasons of consumer safety. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 10.1% to 77.4% of the ADI (DE child). The contribution of residues in radishes and kale to the total consumer exposure accounted for less than 1% of the ADI. Using the internationally agreed standard methodology, based on the highest residue observed in residue trials and the processing factor for cooking, no acute consumer risk was identified. The calculated maximum exposure in percentage of the ARfD was 60% for kale (NL child) and 3.1% for radishes (UK toddler). Using the existing MRL for radishes, the acute exposure accounted for 26% of the ARfD. EFSA concludes that the intended uses of propamocarb on radishes and kale do not lead to a chronic consumer intake concern. The acute exposure resulting from propamocarb residues in radishes and kale does not pose a consumer health risk. RECOMMENDATIONS The recommendations of EFSA are compiled in the table below: Code number a Commodity Existing EU MRL Proposed EU MRL Justification for the proposal Enforcement residue definition: Propamocarb (Sum of propamocarb and its salts expressed as propamocarb) Radishes 10 3 The MRL proposal is sufficiently supported by data and no risk for the consumers was identified. It is noted that before lowering the existing MRL it needs to be confirmed that no more critical GAP is authorised at EU level which would require to maintain the MRL of 10 mg/kg Kale The data are sufficient to derive a MRL proposal of 20 mg/kg. For this MRL neither a chronic nor an acute consumer intake concern was identified. a according to Annex I of Regulation (EC) No 396/2005 EFSA Journal 2012;10(4):

19 REFERENCES Anastassiades M, Lehotay SJ, Stajnbaher D, Schenck FJ, Fast and Easy Mutliresidue Method Employing Acetonitrile Extraction/Partitioning and Dispersive Solid-Phase Extraction for the Determination of Pesticide Residues in Produce. Journal of AOAC International, 86, 22, EC (European Commission), Appendix G. Livestock Feeding Studies. 7031/VI/95 rev.4. Available from: EC (European Commission), 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95- rev.3. Available from: EC (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. Available from: EC (European Commission), 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95-rev.2. Available from: EC (European Commission), 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. Available from: EC (European Commission), 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev. 3. Available from: EC (European Commission), 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95- rev.5. Available from: EC (European Commission), 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. Available from: 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. SANCO/3029/99-rev.4. Available from: EC (European Commission), 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SANCO 10634/2010 Rev. 0, finalized 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. SANCO/825/00-rev Available from: EC (European Commission), Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.9. Available from: EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance Propamocarb. EFSA Scientific Report (2006) 78, pp.1-80 EFSA (European Food Safety Authority), Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. Available online: EFSA (European Food Safety Authority), Reasoned opinion on the modification of the existing MRLs for propamocarb in leek, spinach, witloof and lamb s lettuce prepared by EFSA Pesticide Risk Assessment Peer Review (PRAPeR) Unit. EFSA Journal 2011; volume 9(3):2094, 28 pp. FAO (Food and Agriculture Organization of the United Nations), Propamocarb. In: Pesticide residues in food Report of the Joint Meeting of the FAO Panel of Experts on Pesticide EFSA Journal 2012;10(4):

20 Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 187, 84 pp. FAO (Food and Agriculture Organization of the United Nations), Submission and evaluation of pesticide residues data for the estimation of Maximum Residue Levels in food and feed. Pesticide Residues. 2 nd Ed. FAO Plant Production and Protection Paper 197, 264 pp. Germany, 2011 New dietary intake model for the German population aged 14 to 80 years in order to calculate the intake of pesticide residues in food developed by BfR Opinion No.046/2011 of BfR of 19 October Greece, Evaluation report on the modification of MRLs for propamocarb in radishes and kale prepared by the evaluating Member State Greece under Article 8 of Regulation (EC) No 396/2005, 25 August 2011, 34 pp. Ireland, Draft assessment report on the active substance propamocarb prepared by the rapporteur Member State Ireland in the framework of Council Directive 91/414/EEC, September Ireland, Evaluation report on the modification of MRLs for propamocarb in leek prepared by the Rapporteur Member State Ireland under Article 10 of Regulation (EC) No 396/2005, March 2012, 115 pp. Meier U, Growth Stages of mono- and dicotyledonous plants. BBCH Monograph, 2 nd Ed., Federal Biological Research Centre of Agriculture and Forest. Braunschweig, Germany. Available from: Netherlands, 2010 Revision of Dutch dietary risk assessment models for pesticide authorisation purposes (RIVM report /2010) (Koopman N., Ossendorp B., Van Donkersgoed, G., Van der Velde-Koerts, T., 2010) OECD (Organization for Economic Co-operation and Development), OECD MRL Calculator: spreadsheet for single data set and spreadsheet for multiple data set, 2 March In: Pesticide Publications/Publications on Pesticide Residues. EFSA Journal 2012;10(4):

21 Appendix A. GOOD AGRICULTURAL PRACTICES (GAPS) Crop and/or situation (a) Radishes Kale Member State or Country Germany, Switzerland The Netherlands F G or I (b) F Pest or group of pests controlled (c) Phytophthora DE BARY spp. Formulation Application Application rate per treatment PHI type conc. method number interval kg as/hl kg a.s./ha (days) of a.s. kind min max min max min max min max (d - f) (i) (f - h) growth stage & season (j) (k) water L/ha min max SC 625g/L Foliar BBCH F P. brassicae SC 625g/L Foliar BBCH France F P. brassicae SC 625g/L Foliar BBCH (l) Remarks (m) The intended uses refer to propamocarb hydrochloride application. Remarks: (a) (b) (c) (d) (e) (f) (g) For crops, EU or other classifications, e.g.codex, should be used; where relevant, the use situation should be described (e.g. fumigation of a structure) Outdoor or field use (F), glasshouse application (G) or indoor application (I) e.g. biting and suckling insects, soil born insects, foliar fungi, weeds e.g. wettable powder (WP), emulsifiable concentrate (EC), granule (GR) GCPF Technical Monograph No 2, 4 th Ed., 1999 or other codes, e.g. OECD/CIPAC, should be used All abbreviations used must be explained Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (h) (i) (j) (k) (l) (m) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants - type of equipment used must be indicated g/kg or g/l Growth stage at last treatment (Growth stages of mono-and dicotyledonous plants. BBCH Monograph, 2 nd Ed., 2001), including where relevant, information on season at time of application The minimum and maximum number of application possible under practical conditions of use must be provided PHI - minimum pre-harvest interval Remarks may include: Extent of use/economic importance/restrictions (i.e. feeding, grazing) EFSA Journal 2012;10(4):