REASONED OPINION Review of the existing maximum residue levels (MRLs) for oxamyl according to Article 12 of Regulation (EC) No 396/2005 1 European Food Safety Authority 2, 3 European Food Safety Authority (EFSA), Parma, Italy SUMMARY Article 12(2) of Regulation (EC) No 396/2005 lays down that EFSA shall provide a reasoned opinion on the review of the existing MRLs for oxamyl because this active substance was included in Annex I to Directive 91/414/EEC before 02 September 2008. In order to collect the pesticide residues data supporting the existing MRLs for that active substance, EFSA asked Ireland, as the designated rapporteur Member State, to complete the Pesticide Residues Overview File (PROFile). The completed PROFile was submitted to EFSA on 11 February 2009. On 13 July 2010, after having considered comments made by EFSA, the RMS provided a revised version of the PROFile. Based on the conclusions derived by EFSA in the framework of Directive 91/414/EEC and the additional information provided in the PROFile, EFSA issued a first draft reasoned opinion that was circulated to Member State experts for consultation. On 24 September 2010, the RMS submitted an updated version of the PROFile, which took into consideration all Member States comments, serving as a basis for finalisation of this reasoned opinion. The following conclusions were derived. The toxicological profile of oxamyl was already evaluated in the framework of Directive 91/414/EEC. Both the ADI and the ARfD were established at 0.001 mg/kg bw/d. Primary crop metabolism of oxamyl was investigated in potatoes following a granular soil application at planting. Confined rotational crop studies investigating the uptake of residues in beetroot, cabbage, sorghum, barley and lettuce were also reported. Based on these studies EFSA concluded that parent oxamyl is expected to be the only relevant residue when oxamyl is applied at or before planting. However, the use of oxamyl by drip irrigation in fruits and fruiting vegetables was also reported; these applications are carried out up to 7-21 days before harvest. At least one additional metabolism study investigating the nature of residues in fruits and fruiting vegetables following drip irrigation is therefore required. Pending availability of this study, the relevant residue for enforcement and risk assessment in commodities of plant origin is defined on a provisional basis as the parent compound. Regarding the magnitude of residues in primary crops, a sufficient number of supervised residues trials is available for all the GAPs reported by the RMS, except for oranges and mandarins where 4 1 On request of EFSA, Question No EFSA-Q-2008-597, issued on 29 September 2010. 2 Correspondence: praper.mrl@efsa.europa.eu 3 Acknowledgement: EFSA wishes to thank the rapporteur Member State Ireland for the preparatory work on this scientific output. Suggested citation: European Food Safety Authority; Review of the existing maximum residue levels (MRLs) for oxamyl according to Article 12 of Regulation (EC) No 396/2005.. [34 pp.] doi:10.2903/j.efsa.2010.1830. Available online: www.efsa.europa.eu/efsajournal.htm European Food Safety Authority, 2010 1
additional residues trials on each crop are required. In addition, EFSA identified the need for a storage stability study demonstrating that oxamyl residues will not decline during the storage of residues trials samples with high acid content. Despite these data gaps, EFSA estimated the expected residue concentrations in the relevant plant commodities and MRL proposals were derived. A validated analytical method for enforcement of the proposed MRLs is also available. In processed commodities, oxamyl was found to be converted to oxamyl oxime with increasing temperatures but, according to the available data, oxamyl oxime was not considered to be of toxicological relevance. For peeled melons and watermelons, a reliable processing factor of 0.8 could be derived but further studies investigating the magnitude of residues in processed commodities were not considered relevant because residues were found to be below the LOQ for all commodities that are likely to be processed. The potential incorporation of soil residues into succeeding and rotational crops was investigated in beetroot, cabbage, sorghum, barley and lettuce. These studies showed a comparable metabolism as in directly treated plants, but they also indicated that if crops are planted within 120 days of oxamyl application then residues of oxamyl and oxamyl oxime may occur in the roots and aerial parts of these crops. In order to minimize the possibility of residues being detected in the rotational crops EFSA recommends the setting of a restriction to crop rotation. The occurrence of oxamyl residues in commodities of animal origin was not evaluated in the framework of this review because exposure of livestock to oxamyl residues was found to be below the trigger value of 0.1 mg/kg DM. Residue definitions and MRLs for oxamyl in commodities of animal origin are therefore not required. Both chronic and acute consumer exposure resulting from the MRLs proposed in the framework of this review were calculated and an exceedance of the ARfD was identified for melons, watermelons and peppers, representing 206%, 166% and 139% of the ARfD, respectively. Excluding these MRLs from the intake calculations, the highest chronic exposure represented 28% of the ADI (UK toddlers) and the highest acute exposure amounted to 84% of the ARfD (bananas). Consequently, all MRL proposals derived in the framework of this review can be recommended for MRL setting, except for melons, watermelons and peppers. Apart from the MRLs evaluated in the framework of this review, internationally recommended CXLs have also been established for the sum of oxamyl and oxamyl oxime, expressed. Considering that EU MRLs are established for parent oxamyl only, inclusion of these CXLs in a European risk assessment was not possible. Moreover, residues trials data supporting the existing CXLs was found to be limited for several crops. Inclusion of the existing CXLs for oxamyl in European legislation is therefore not recommended. Based on the above assessment, EFSA does not recommend inclusion of this active substance in Annex IV to Regulation (EC) No 396/2005; MRL recommendations are summarized in the table below. Only the MRLs for potatoes, carrots, parsnips, salsify, Brussels sprouts and sugar beet are fully supported by data and therefore recommended for inclusion in Annex II to the Regulation. The calculated MRLs for oranges, mandarins, bananas, tomatoes, aubergines, cucumbers, gherkins and courgettes are not recommended for inclusion in Annex II because validity of these MRLs still needs to be confirmed by submission of the following date: a metabolism study with radioactive marker representative for the use of oxamyl by dripirrigation in fruits and fruiting vegetables ; 4 additional residues trials on oranges and 4 additional residues trials on mandarins compliant with southern outdoor GAPs for these crops ; a study demonstrating storage stability of oxamyl residues in commodities with high acid content. 2
Considering the low ARfD that was established for oxamyl, risk managers might also consider the need to set MRLs that reflect the risk assessment values more accurately, in particular for oranges and potatoes. In this case, EFSA would recommend the elaboration of a new analytical method that allows for the enforcement of oxamyl residues in commodities of plant origin with a LOQ of 0.005 mg/kg. Commodity Existing EC MRL (mg/kg) Residue definition for enforcement: oxamyl Calcul. EU MRL (mg/kg) (a) Recom. EU MRL (mg/kg) (b) Justification Potatoes 0.01* 0.01* 0.01* European authorisations are fully Carrots 0.01* 0.01* 0.01* supported by data and no risk to consumers is identified. Parsnips 0.01* 0.01* 0.01* Salsify 0.01* 0.01* 0.01* Brussels sprouts 0.01* 0.01* 0.01* Sugar beet (root) 0.01* 0.01* 0.01* Oranges 0.01* 0.01* - European authorisations show minor data Mandarins 0.02 0.01* - gaps but no risk to consumers is expected. Risk managers to decide Bananas 0.01* 0.01* - whether the calculated MRLs can be Tomatoes 0.02 0.01* - established pending submission of the appropriate data. Aubergines (egg plants) 0.02 0.02 - Cucumbers 0.02 0.01* - Gherkins 0.02 0.01* - Courgettes 0.03 0.01* - Peppers 0.02 0.03 - European authorisations show minor data Melons 0.01* 0.02 - gaps and acute risk to consumers cannot be excluded. Risk managers to decide Watermelons 0.01* 0.02 - whether a specific LOQ needs to be established or whether the default MRL of 0.01 mg/kg can apply. Other products of plant and/or animal origin see App C - - No European authorizations. Risk managers to decide whether a specific LOQ needs to be established or whether the default MRL of 0.01 mg/kg can apply. (*): Indicates that the MRL is set at the limit of analytical quantification. (a): Calculated EU MRLs result from the assessment of residues data available at EU level without consideration of consumer exposure. (b): Recommended EU MRLs result from the EU MRL proposals after being subject to consumer exposure calculations. KEY WORDS pesticide, oxamyl, MRL review, Regulation (EC) No 396/2005, consumer risk assessment, carbamate, insecticide, nematicide 3
TABLE OF CONTENTS Summary... 1 Table of contents... 4 Background... 5 Terms of reference... 6 The active substance and its use pattern... 7 Assessment... 8 1. Methods of analysis... 8 1.1. Methods for enforcement of residues in food of plant origin... 8 1.2. Methods for enforcement of residues in food of animal origin... 8 2. Mammalian toxicology... 8 3. Residues... 9 3.1. Nature and magnitude of residues in plant... 9 3.1.1. Primary crops... 9 3.1.2. Rotational crops... 14 3.2. Nature and magnitude of residues in livestock... 14 4. Consumer risk assessment... 15 4.1. Consumer risk assessment without the CXLs... 15 4.2. Consumer risk assessment including the CXLs... 16 Conclusions and recommendations... 17 Documentation provided to EFSA... 19 References... 19 Appendix A Good Agricultural Practices (GAPs)... 21 Appendix B Pesticide Residues Intake Model (PRIMo)... 22 Appendix C Existing EU MRLs... 27 Appendix D Existing CXLs... 30 Abbreviations... 33 4
BACKGROUND Regulation (EC) No 396/2005 4 establishes the rules governing the setting as well as the review of pesticide MRLs at Community level. Article 12(2) of that regulation lays down that EFSA shall provide by 01 September 2009 a reasoned opinion on the review of the existing MRLs for all active substances included in Annex I to Directive 91/414/EEC 5 before 02 September 2008. According to Article 12(1) of the Regulation, EFSA shall base its reasoned opinion in particular on the relevant assessment report prepared under Directive 91/414/EEC. It should be noted, however, that in the framework of Directive 91/414/EEC only a few representative uses are evaluated while MRLs set out in Regulation (EC) No 396/2005 should accommodate for all uses authorised within the EC as well as uses authorised in third countries having a significant impact on international trade. The information included in the assessment report prepared under Directive 91/414/EEC is therefore insufficient for the assessment of all existing MRLs for a given active substance. In order to have an overview on the pesticide residues data that have been considered for the setting of the MRLs under the former MRL legislation, EFSA developed the Pesticide Residue Overview File (PROFile). The PROFile is an electronic inventory of all pesticide residues data relevant to the risk assessment as well as the MRL setting for a given active substance. This includes data on: the nature and magnitude of residues in primary crops; the nature and magnitude of residues in processed commodities; the nature and magnitude of residues in rotational crops; the nature and magnitude of residues in livestock commodities and; the analytical methods for enforcement of the proposed MRLs. As oxamyl was included in Annex I to Directive 91/414/EEC on 01 August 2006, EFSA initiated the review of all existing MRLs for that active substance and a task with the reference number EFSA-Q- 2008-597 was included in the EFSA Register of Question. Ireland, the designated rapporteur Member State (RMS) in the framework of Directive 91/414/EEC, was asked to complete the PROFile for oxamyl. The first version of the PROFile was submitted by the RMS on 11 February 2009 and subsequently checked for completeness by EFSA. On 13 July 2010, after having considered comments made by EFSA, the RMS provided a revised version of the PROFile. Based on the PROFile and other publically available documents, EFSA prepared a draft reasoned opinion which was circulated to Member States (MS) on 26 July 2010 for commenting. All comments received by 06 September 2010 were considered for finalisation of the reasoned opinion. In addition, The RMS submitted on 24 September 2010 an updated version of the PROFile, which took into consideration all Member States comments. This updated PROFile served as a basis for finalisation of the reasoned opinion. 4 Commission Regulation (EC) No 396/2005 of 23 February 2005. OJ L 70, 16.3.2005, p. 1-16. 5 Council Directive 91/414/EEC of 15 July 1991, OJ L 230, 19.8.1991, p. 1-32. 5
TERMS OF REFERENCE According to Article 12(1) of Regulation (EC) No 396/2005, EFSA shall provide a reasoned opinion on: the inclusion of the active substance in Annex IV to the Regulation, when appropriate; the necessity of setting new MRLs for the active substance or deleting/modifying existing MRLs set out in Annex II or III of the Regulation; the inclusion of the recommended MRLs in Annex II or III to the Regulation; the setting of specific processing factors as referred to in Article 20(2) of the Regulation. According to Article 12(2) of the Regulation, the reasoned opinion shall be provided within 12 months of the entry into force of this regulation. As the Regulation entered into force on 02 September 2008, the legal deadline for providing the reasoned opinion was 01 September 2009. Considering several delays encountered at European level, the revised deadline of 01 September 2010 was discussed and agreed upon with the European Commission and Member States. 6
THE ACTIVE SUBSTANCE AND ITS USE PATTERN Oxamyl is the ISO common name for N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio) acetamide (IUPAC). CH 3 NH C O O N SCH 3 C CON(CH 3 ) 2 Oxamyl belongs to the group of carbamate compounds which are used as an insectice, acaricide or nematicide. This systemic compound is taken up by the plants through the roots or by direct contact and is mainly used for the control of nematodes, spider mites, chewing and sucking insects where it will act as a choline esterase inhibitor. Oxamyl was evaluated in the framework of Directive 91/414/EEC with Ireland being the designated rapporteur Member State (RMS). The representative use supported for the peer review process was the outdoor application in potatoes by soil incorporation at planting, both in northern and southern Europe. Following the peer review, which was carried out by EFSA, a decision on inclusion of the active substance in Annex I to Directive 91/414/EEC was published by means of Commission Directive 2006/16/EC 6, entering into force on 01 August 2006. The Annex I inclusion of oxamyl is restricted to uses as an insecticide or nematicide only. EU MRLs for oxamyl in products of plant origin have been set for the first time in 2006 by means of Directive 2006/59/EC 7 and modified in 2007 by means of Directive 2007/56/EC 8. These MRLs have been transferred to Annex II of Regulation (EC) No 396/2005 without further amendments. Additional MRLs for commodities that were not covered by the former European MRL legislation are established in Annex III B of the Regulation. These temporary MRLs were derived from the MRLs that have been set at national level before the Regulation entered into force. All existing EU MRLs, which have been established for the parent oxamyl only, are summarized in Appendix C to this document. CXLs for oxamyl were also established by the Codex Alimentarius Commission and are reported in Appendix D to this reasoned opinion. These CXLs refer to the sum of oxamyl and oxamyloxime, expressed. For the purpose of this MRL review, the critical uses of oxamyl currently authorized within the EU as well as uses authorised in third countries that might have a significant impact on international trade, have been collected by the RMS and reported in the PROFile (see Appendix A). According to the reported GAPs, two types of application are currently authorised for this active substance. In potatoes, carrots, parsnips, Brussels sprouts and sugar beets, oxamyl is applied directly to the soil at sowing or planting. In citrus fruits, bananas and fruiting vegetables, oxamyl is applied by drip irrigation until maturity of the fruits is reached. PHIs for this type of applications may vary between 7 and 21 days. 6 Commission Directive 2006/16/EC of 7 February 2006, OJ L 36, 8.2.2006, p. 37-39. 7 Commission Directive 2006/59/EC of 28 June 2006, OJ L 175, 29.6.2006, p. 61-76. 8 Commission Directive 2007/56/EC of 17 September 2007, OJ L 243, 18.9.2007, p. 50-60. 7
ASSESSMENT EFSA mainly bases its assessment on the PROFile submitted by Ireland, on the evaluation report accompanying the PROFile (Ireland, 2009) and on the conclusion of EFSA regarding the peer review of the risk assessment of oxamyl (EFSA, 2005). 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, 2000, 2008). 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin During the peer review under Directive 91/414/EC, Ireland reported the availability of a suitable analytical method for enforcement of parent oxamyl in commodities with high water content (lettuce, melons, potatoes and sugar beets) or with a high acid content (citrus peel and pulp). Using HPLC with a fluorescence detector, a LOQ of 0.01 mg/kg can be achieved. A confirmatory method using LC-MS was validated with the same LOQ for the same commodity groups (Ireland, 2003). These analytical methods were considered to be satisfactory (EFSA, 2005). In addition, the CEN reported suitability of the QuEChERS method, in combination with LC-MS/MS, for the determination of parent oxamyl in acidic, dry and water containing commodities (CEN, 2008). Hence it is concluded that parent oxamyl may be enforced with a LOQ of 0.01 mg/kg in all crops supported in the framework of this review. 1.2. Methods for enforcement of residues in food of animal origin Analytical methods for enforcement of oxamyl residues in commodities of animal origin are not required considering the fact that there is no significant intake of residues by livestock and that no MRLs are proposed (see section 3.2). 2. Mammalian toxicology The toxicological assessment of oxamyl was peer reviewed under Directive 91/414/EEC and toxicological reference values were established by EFSA (2005). These toxicological reference values are summarized in Table 2-1. Table 2-1. Overview of the toxicological reference values Oxamyl Source Year Value (mg/kg bw/d) Study relied upon ADI EFSA 2005 0.001 Acute neurotoxicity study (rat) ARfD EFSA 2005 0.001 Acute neurotoxicity study (rat) Safety factor 100 100 8
3. Residues 3.1. Nature and magnitude of residues in plant 3.1.1. Primary crops 3.1.1.1. Nature of residues A number of plant metabolism studies for oxamyl were presented in the framework of the peer review These studies included either foliar or granular applications on tobacco, peanuts, apples, oranges, tomatoes, beans, cotton and potatoes (EFSA, 2005). Studies with foliar applications were not considered relevant for the application methods supported in the framework of this review (granular soil application and drip-irrigation). In addition, most of the studies dated from the early 1970 s and showed various deficiencies; they were therefore considered as supporting information only. In one recent study that was carried out according to current guidelines, the metabolism of oxamyl was investigated in potatoes by applying radiolabelled oxamyl as a granular to the soil at planting. This study demonstrated that the main and only identified component of the residue in potato tubers and peels would be the metabolite N,N -dimethyloxamic acid, corresponding to circa 70% of the TRR. Residues of oxamyl and oxamyl-oxime were not present in potato tubers even when the application was made at 1.5N the recommended GAP. In addition, the confined rotational crop studies discussed under section 3.1.2. show that oxamyl is rapidly degraded to metabolites that no longer contain the carbamate moiety, such -oxime and N,N -dimethyloxamic acid. A toxicological assessment of these two metabolites was also carried out during the peer review, indicating that none of them were of toxicological concern (EFSA, 2005). Based on the above findings, EFSA concludes that following granular soil applications at sowing or planting, the parent compound will be the only residue of concern for both enforcement and risk assessment purposes. According to the RMS, above findings are also applicable to drip-irrigation in fruits and vegetables and further metabolism studies are not required (Ireland, 2009). However, dripirrigation treatments are carried out up to 7-21 days before harvest and above reported studies are not considered representative for such short intervals. At least one additional metabolism study investigating the nature of residues in fruits and fruiting vegetables following drip irrigation is therefore required. Pending availability of this study, the relevant residue for enforcement and risk assessment in commodities of plant origin is defined on a provisional basis as the parent compound. EFSA notes that the enforcement residue definition established by JMPR includes oxamyl-oxime. Although it is not of toxicological relevance, JMPR included this metabolite in the residue definition because analytical methods available at that time were not able to differentiate between oxamyl and oxamyl-oxime (WHO/FAO, 2002). However, analytical methods reported in section 1.1. indicate that differentiation between both compounds is nowadays possible and inclusion of oxamyl-oxime in the residue definition is therefore no longer relevant. 3.1.1.2. Magnitude of residues According to the RMS, the active substance oxamyl is authorised for granular soil application in potatoes, carrots, turnips, Brussels sprouts and sugar beets and for drip irrigation in oranges, mandarins, bananas and a wide range of fruiting vegetables grown under indoor conditions (see Appendix A). To assess the magnitude of oxamyl resulting from these GAPs, EFSA considered all residues trials reported by the RMS in its evaluation report (Ireland, 2009). Trials on potatoes that were considered in the framework of the peer review (EFSA, 2005) were no longer considered in the framework of this review because more recent trials with lower LOQ were reported by the RMS. Table 3-1 summarizes all available residues trials supporting the authorised GAPs. 9
Table 3-1. Overview of the available residues trials data Commodity Oranges Mandarins Region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (parent compound) SEU Outdoor 6 x <0.005; 0.005; 0.0055 Risk assessment (parent compound) 6 x <0.005; 0.005; 0.0055 STMR (mg/kg) (b) HR (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments 0.005 0.006 0.01* 1.0 Combined dataset on oranges (4) and mandarins (4) compliant with the GAP. Additional trials are required. Bananas SEU Outdoor 4 x <0.01 4 x <0.01 0.01 0.01 0.01* 1.0 Trials on bananas with 2N rate and PHI compliant with GAP. Additional 4 trials with 3N rate and longer PHI (60d) had residues <0,01 mg/kg. Potatoes NEU Outdoor 4 x <0.005 4 x <0.005 0.005 0.005 0.01* 1.0 Trials on potatoes compliant with GAP. Additional 4 trials with 6 applications of 0.7 kg a.i./ha (drip irrigation) and a PHI of 80d had residues <0,01 mg/kg. SEU Outdoor 6 x <0.005 6 x <0.005 0.005 0.005 0.01* 1.0 Trials on potatoes compliant with GAP. Additional 2 trials with 1 application of 3 kg a.i./ha (in furrow) at planting had residues <0,01 mg/kg. Carrots NEU Outdoor 4 x <0.01 4 x <0.01 0.01 0.01 0.01* 1.0 Trials on carrots compliant with GAP. SEU Outdoor 5 x <0.01 5 x <0.01 0.01 0.01 0.01* 1.0 Trials on carrots with 1.5-2N rate and PHI compliant with GAP. 10
Commodity Parsnips Salsify Tomatoes Peppers Aubergines Cucurbits with edible peel Melons Watermelons Region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (parent compound) Risk assessment (parent compound) STMR (mg/kg) (b) HR (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments NEU Outdoor 4 x <0.01 4 x <0.01 0.01 0.01 0.01* 1.0 The northern outdoor trials on carrots are reported because GAPs are similar (parsnips) or even less critical (salsify); extrapolation possible. NEU/ SEU NEU/ SEU NEU/ SEU NEU/ SEU NEU/ SEU Indoor 12 x <0.01 12 x <0.01 0.01 0.01 0.01* 1.0 Trials on tomatoes (8) and cherry tomatoes (4) compliant with GAP. Indoor 6 x <0.01; 0.014; 0.022 6 x <0.01; 0.014; 0.022 0.01 0.022 0.03 1.0 Trials on peppers compliant with the GAP. R max = 0.03 R ber = 0.03 Indoor 3 x <0.01; 0.01 3 x <0.01; 0.01 0.01 0.01 0.02 1.0 Trials on aubergines (egg plant) compliant with GAP. Dataset cannot be combined with tomatoes because GAPs are different. Indoor 8 x <0.01 8 x <0.01 0.01 0.01 0.01* 1.0 Trials on cucumbers (4) and courgettes (4) compliant with the GAP for all cucurbits with edible peel. Indoor <0.005; <0.005; <0.005; 0.007; 0.008; <0.01; 0.012; 0.017 <0.005; <0.005; <0.005; 0.007; 0.008; <0.01; 0.012; 0.017 0.008 0.017 0.02 1.0 Trials on melons compliant with the GAP for melons and watermelons; only representative for melons planted during spring period because 2 trials carried out in autumn indicated higher residue levels (0.012 and 0.100 mg/kg). R max = 0.02 R ber = 0.02 11
Commodity Region (a) Outdoor /Indoor Individual trial results (mg/kg) Enforcement (parent compound) Risk assessment (parent compound) STMR (mg/kg) (b) HR (mg/kg) (c) MRL proposal (mg/kg) Median CF (d) Comments Brussels sprouts NEU Outdoor 3 x <0.01 3 x <0.01 0.01 0.01 0.01* 1.0 Trials on Brussels sprouts compliant with GAP. Sugar beet (roots) NEU Outdoor 8 x <0.01 8 x <0.01 0.01 0.01 0.01* 1.0 Trials on sugar beet with analysis of roots and tops compliant with GAP. SEU Outdoor 10 x <0.01 10 x <0.01 0.01 0.01 0.01* 1.0 Trials on sugar beet with analysis of roots and tops compliant with GAP. Sugar beet (tops) NEU Outdoor 8 x <0.01 8 x <0.01 0.01 0.01 0.01* 1.0 Trials on sugar beet with analysis of roots and tops compliant with GAP. SEU Outdoor 10 x <0.01 10 x <0.01 0.01 0.01 0.01* 1.0 Trials on sugar beet with analysis of roots and tops compliant with GAP. (*): Indicates that the MRL is set at the limit of analytical quantification. (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. The individual conversion factor for each trial is defined as the ratio of the trial result according to the risk assessment residue definition and the result according to the enforcement residue definition. 12
The number of residues trials and extrapolations were evaluated in view of the European guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs (European Commission, 2008). A sufficient number of residues trials compliant with the GAPs was reported by the RMS for all crops under consideration, except in the following cases: For melons, two additional residues trials were reported with residue levels of 0.012 and 0.100 mg/kg at harvest. These trials were disregarded by the RMS because they were carried out on melons planted in autumn, which is not considered to be a common agricultural practice by the RMS. EFSA agrees that most of the melons are planted in spring and harvested during summer period but growing of melons during autumn and early winter under greenhouse conditions cannot be excluded. A label restriction indicating that oxamyl should only be applied to melons during spring and summer period is therefore required. For potatoes, carrots, parsnips, salsify and Brussels sprouts, the number of trials reported is not compliant with the data requirements but the reduced number was considered sufficient by EFSA because all available trial results were below the LOQ and applications of oxamyl at planting are not expected to leave quantifiable residues in these crops. For oranges and mandarins, 4 trials on oranges and 4 trials on mandarins were reported while 8 trials are normally required for each crop. Considering that after application of oxamyl by drip irrigation quantifiable residues cannot be excluded, 4 additional trials on oranges and 4 additional trials on mandarins are required. The potential degradation of residues during storage of the residues trials samples was also assessed. In the framework of the peer review, storage stability of oxamyl was demonstrated in potato tubers, sugar beet roots, lettuce, tomatoes and orange peel for a period of 12 months at -18 C. According to the RMS, all residues trials samples reported in the framework of this MRL review were stored for less than 12 months between -18 and -20 C. Degradation of residues during storage of samples is therefore not expected (Ireland, 2005). EFSA is of the opinion, however, that the above conclusions can only apply to commodities with high water content; the orange peel is not considered to be sufficiently representative for commodities with high acid content. In order to exclude degradation of residues during storage of orange and mandarin samples, a storage stability study carried out with a representative crop for commodities with a high acid content is desirable. Although some data gaps have been identified for citrus fruits, the available residues data are considered acceptable to derive MRL proposals and risk assessment values on a provisional basis (see Table 3-1). For sugar beet tops, a tentative MRL is derived in view of the future need to set MRLs in feed items. 3.1.1.3. Effect of industrial processing and/or household preparation The effect of processing on the nature of oxamyl residues was investigated in the framework of the peer review. A study was conducted simulating representative hydrolytic conditions for pasteurisation, boiling/baking and sterilisation. With increasing temperatures oxamyl was found to be increasingly labile with a rapid degradation to oxamyl oxime. According to the available data, oxamyl oxime was also not considered to be of toxicological relevance (EFSA, 2005). Studies investigating the magnitude of residues in processed commodities are not considered necessary because residues were found to be below the LOQ for all commodities that are likely to be processed. Several residues trials investigating the distribution of oxamyl residues in peel and pulp of oranges, mandarins, bananas and melons were reported by the RMS but peeling factors could not be derived because residues were below the LOQ for most of these crops, except for melons. Out of the 8 residues trials compliant with the GAP for melons, 4 residues trials gave measurable residue levels in 13
peel and pulp (Ireland, 2009). These 4 trials were used to derive a median processing factor of 0.8 for peeled melons and watermelons. The processing factor is sufficiently supported by data to be used for both enforcement and risk assessment purposes. 3.1.2. Rotational crops Soil degredation studies were evaluated during the peer review and a DT 90 value of 36 days was derived for oxamyl under field conditions. The main metabolites of oxamyl in soil were identified as oxamyl oxime and N,N -dimethyloxamic acid but these metabolites were not considered relevant based on the toxicological assessment. In addition, two crop rotation studies with radiolabelled material were undertaken to address the potential incorporation of soil residues into succeeding and rotational crops, such as beetroot, cabbage, sorghum, barley and lettuce. These studies showed a comparable metabolism as in directly treated plants, but they also indicated that if crops are planted within 120 days of oxamyl application then residues of oxamyl and oxamyl oxime may be detected in the roots and aerial parts of these crops. In order to minimize the possibility of residues being detected in the rotational crops EFSA recommended the setting of a restriction to crop rotation, clearly indicating that this restriction could be revoked through the submission of rotational crop residue trials ( cold studies ) (EFSA, 2005). In the framework of this review, the RMS reported three new cold studies that were carried out in the United Kingdom during the growing seasons of 2005 and 2006. Oxamyl was applied to bare soil according to the critical GAP for potatoes and several succeeding crops (lettuce, carrots, winter barley and winter wheat) were each planted at two different plant-back intervals (80 and 120 days). At harvest, levels of parent oxamyl in all mature plant parts were below the LOQ of 0.01 mg/kg (Ireland, 2009). These studies are not considered sufficient by EFSA to demonstrate absence of residues in rotational crops because the trials did not cover the plant-back intervals of 30 days. EFSA therefore proposes to maintain the restriction on crop rotation that was already derived in the framework of the peer review. 3.2. Nature and magnitude of residues in livestock Oxamyl is authorised for use on several crops that might be fed to livestock. The median and maximum dietary burdens were therefore calculated for the different types of livestock using to the agreed European methodology (European Commission, 1996). The input values for all relevant commodities have been selected according to the recommendations of the 2004 JMPR (WHO/FAO, 2005) and are summarized in the Table 3-2. For citrus pomace, a default processing factor of 2.5 has been included in the calculation in order to consider potential concentration of residues in this commodity. As the calculated dietary burdens for all types of livestock were found to be below the trigger value of 0.1 mg/kg DM, further investigation of residues as well as the setting of MRLs in commodities of animal origin is not necessary. Although not required, studies on the metabolism of oxamyl in lactating goats and laying hens were submitted and evaluated during the peer review. These metabolism studies confirm that oxamyl is highly metabolized when fed to these animals and indicate that the only identifiable residue possible in the goat and hen is the non-specific analyte thiocyanate. No residues of oxamyl or oxamyl oxime will be detected in these animals (EFSA, 2005). 14
Table 3-2. Input values for the livestock dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value (mg/kg) Residue definition for risk assessment: oxamyl Comment Input value (mg/kg) Comment Orange pomace 0.013 STMR x 2.5 0.013 STMR x 2.5 Mandarin pomace 0.013 STMR x 2.5 0.013 STMR x 2.5 Sugar beet tops 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Potatoes 0.005 STMR 0.005 HR Sugar beet roots 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Table 3-3. Results of the livestock dietary burden calculation Maximum dietary burden (mg/kg bw/d) Residue definition for risk assessment: oxamyl Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Dairy ruminants 0.001 0.001 Sugar beet tops 0.03 No Meat ruminants 0.002 0.002 Sugar beet roots 0.05 No Poultry 0.001 0.001 Sugar beet roots 0.01 No Pigs 0.002 0.002 Sugar beet roots 0.05 No 4. Consumer risk assessment In this review, only the GAPs reported by the RMS were considered but, previously, the use of oxamyl has also been assessed by the 1980 JMPR (WHO/FAO, 1981) and by the 2002 JMPR (WHO/FAO, 2002). The CXLs, resulting from these JMPR assessments and adopted by the CAC, are now international recommendations that need to be considered by European risk managers when establishing MRLs. In order to facilitate the consideration of CXLs by risk managers, the consumer exposure assessment was carried out both with and without consideration of the existing CXLs (see Appendix D). 4.1. Consumer risk assessment without the CXLs Chronic and acute intake calculations considering the MRLs proposed in the framework of this review were performed using revision 2 of the EFSA PRIMo (EFSA, 2007). The STMR and HR values that were used as the input values for the proposed MRLs are summarized in Table 4-1. For melons and watermelons, the peeling factor of 0.8 derived under section 3.1.1.3 was also applied. The detailed results of the chronic and acute intake calculations are reported in Appendix B.1 to this document. The highest chronic exposure was calculated for UK toddlers, representing 28% of the ADI. With regard to the acute exposure, however, an exceedance of the ARfD was identified for melons, watermelons and peppers, representing 206%, 166% and 139% of the ARfD, respectively. A second intake calculation was therefore performed, excluding the calculated MRLs for these three crops. According to the results of this second intake calculation (see Appendix B.2), the highest 15
chronic exposure remained unchanged but the highest acute exposure is then calculated for bananas, representing 84% of the ARfD. Based on the above calculations, EFSA concludes that uses of oxamyl reported in the framework of this review (see Appendix A) are acceptable with regard to consumer exposure, except for the European indoor uses on melons, watermelons and peppers. The MRLs resulting from the uses on these three crops can therefore not be recommended for EU MRL setting. For oranges and potatoes, it should also be noted that the STMR and HR values used for risk assessment were derived from residues trials with a LOQ of 0.005 mg/kg while the proposed MRLs are based on the enforcement LOQ of 0.01 mg/kg. Considering the low ARfD that was established for oxamyl, risk managers might consider the need to set MRLs that reflect the risk assessment values more accurately. In this case, EFSA would recommend the elaboration of a new analytical method that allows for the enforcement of oxamyl residues in commodities of plant origin with a LOQ of 0.005 mg/kg. Table 4-1. Input values for the consumer risk assessment without CXLs Commodity Chronic risk assessment Acute risk assessment Input value (mg/kg) Residue definition for risk assessment: oxamyl Comment Input value (mg/kg) Comment Oranges 0.005 STMR 0.006 HR Mandarins 0.005 STMR 0.006 HR Bananas 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Potatoes 0.005 STMR 0.005 HR Carrots 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Parsnips 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Salsify 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Tomatoes 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Peppers 0.01 STMR 0.022 HR Aubergines (egg plants) 0.01 STMR 0.01 HR Cucumbers 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Gherkins 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Courgettes 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Melons 0.006 STMR x PF 0.014 HR x PF Watermelons 0.006 STMR x PF 0.014 HR x PF Brussels sprouts 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) Sugar beet (root) 0.01 MRL (=LOQ) 0.01 MRL (=LOQ) 4.2. Consumer risk assessment including the CXLs In order to include the CXLs in the consumer exposure calculations, all data relevant to the consumer risk assessment of the CXLs have been collected by EFSA, the outcome of this data collection being reported in Appendix D to this document. Although oxamyl oxime was demonstrated not be of toxicological concern, all CXLs of oxamyl have been established for the sum of oxamyl and oxamyl 16
oxime, expressed. This residue definition was recommended by the JMPR because, at the time of evaluation, these two compounds could not be differentiated from an analytical point of view (WHO/FAO, 2002). In the meantime, analytical methods distinguishing both compounds have been developed and the relevant residue for both enforcement and risk assessment at European level has been defined as the parent compound only (see also sections 1.2 and 3.1.1.1.). Inclusion of the CXLs for oxamyl in a European risk assessment is therefore not possible. Moreover, residues trials data supporting the existing CXLs was found to be very limited, in particular for those CXLs that were evaluated by the 1980 JMPR. Existing CXLs for oxamyl are therefore not recommended for inclusion in European legislation. CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS The toxicological profile of oxamyl was already evaluated in the framework of Directive 91/414/EEC. Both the ADI and the ARfD were established at 0.001 mg/kg bw/d. Primary crop metabolism of oxamyl was investigated in potatoes following a granular soil application at planting. Confined rotational crop studies investigating the uptake of residues in beetroot, cabbage, sorghum, barley and lettuce were also reported. Based on these studies EFSA concluded that parent oxamyl is expected to be the only relevant residue when oxamyl is applied at or before planting. However, the use of oxamyl by drip irrigation in fruits and fruiting vegetables was also reported; these applications are carried out up to 7-21 days before harvest. At least one additional metabolism study investigating the nature of residues in fruits and fruiting vegetables following drip irrigation is therefore required. Pending availability of this study, the relevant residue for enforcement and risk assessment in commodities of plant origin is defined on a provisional basis as the parent compound. Regarding the magnitude of residues in primary crops, a sufficient number of supervised residues trials is available for all the GAPs reported by the RMS, except for oranges and mandarins where 4 additional residues trials on each crop are required. In addition, EFSA identified the need for a storage stability study demonstrating that oxamyl residues will not decline during the storage of residues trials samples with high acid content. Despite these data gaps, EFSA estimated the expected residue concentrations in the relevant plant commodities and MRL proposals were derived. A validated analytical method for enforcement of the proposed MRLs is also available. In processed commodities, oxamyl was found to be converted to oxamyl oxime with increasing temperatures but, according to the available data, oxamyl oxime was not considered to be of toxicological relevance. For peeled melons and watermelons, a reliable processing factor of 0.8 could be derived but further studies investigating the magnitude of residues in processed commodities were not considered relevant because residues were found to be below the LOQ for all commodities that are likely to be processed. The potential incorporation of soil residues into succeeding and rotational crops was investigated in beetroot, cabbage, sorghum, barley and lettuce. These studies showed a comparable metabolism as in directly treated plants, but they also indicated that if crops are planted within 120 days of oxamyl application then residues of oxamyl and oxamyl oxime may occur in the roots and aerial parts of these crops. In order to minimize the possibility of residues being detected in the rotational crops EFSA recommends the setting of a restriction to crop rotation. The occurrence of oxamyl residues in commodities of animal origin was not evaluated in the framework of this review because exposure of livestock to oxamyl residues was found to be below the trigger value of 0.1 mg/kg DM. Residue definitions and MRLs for oxamyl in commodities of animal origin are therefore not required. 17
Both chronic and acute consumer exposure resulting from the MRLs proposed in the framework of this review were calculated and an exceedance of the ARfD was identified for melons, watermelons and peppers, representing 206%, 166% and 139% of the ARfD, respectively. Excluding these MRLs from the intake calculations, the highest chronic exposure represented 28% of the ADI (UK toddlers) and the highest acute exposure amounted to 84% of the ARfD (bananas). Consequently, all MRL proposals derived in the framework of this review can be recommended for MRL setting, except for melons, watermelons and peppers. Apart from the MRLs evaluated in the framework of this review, internationally recommended CXLs have also been established for the sum of oxamyl and oxamyl oxime, expressed. Considering that EU MRLs are established for parent oxamyl only, inclusion of these CXLs in a European risk assessment was not possible. Moreover, residues trials data supporting the existing CXLs was found to be limited for several crops. Inclusion of the existing CXLs for oxamyl in European legislation is therefore not recommended. RECOMMENDATIONS Based on the above assessment, EFSA does not recommend inclusion of this active substance in Annex IV to Regulation (EC) No 396/2005; MRL recommendations are summarized in the table below. Only the MRLs for potatoes, carrots, parsnips, salsify, Brussels sprouts and sugar beet are fully supported by data and therefore recommended for inclusion in Annex II to the Regulation. The calculated MRLs for oranges, mandarins, bananas, tomatoes, aubergines, cucumbers, gherkins and courgettes are not recommended for inclusion in Annex II because validity of these MRLs still needs to be confirmed by submission of the following date: a metabolism study with radioactive marker representative for the use of oxamyl by dripirrigation in fruits and fruiting vegetables ; 4 additional residues trials on oranges and 4 additional residues trials on mandarins compliant with southern outdoor GAPs for these crops ; a study demonstrating storage stability of oxamyl residues in commodities with high acid content. Considering the low ARfD that was established for oxamyl, risk managers might also consider the need to set MRLs that reflect the risk assessment values more accurately, in particular for oranges and potatoes. In this case, EFSA would recommend the elaboration of a new analytical method that allows for the enforcement of oxamyl residues in commodities of plant origin with a LOQ of 0.005 mg/kg. Commodity Existing EC MRL (mg/kg) Residue definition for enforcement: oxamyl Calcul. EU MRL (mg/kg) (a) Recom. EU MRL (mg/kg) (b) Justification Potatoes 0.01* 0.01* 0.01* European authorisations are fully Carrots 0.01* 0.01* 0.01* supported by data and no risk to consumers is identified. Parsnips 0.01* 0.01* 0.01* Salsify 0.01* 0.01* 0.01* Brussels sprouts 0.01* 0.01* 0.01* Sugar beet (root) 0.01* 0.01* 0.01* Oranges 0.01* 0.01* - European authorisations show minor data Mandarins 0.02 0.01* - gaps but no risk to consumers is expected. Risk managers to decide Bananas 0.01* 0.01* - whether the calculated MRLs can be 18
Commodity Existing EC MRL (mg/kg) Calcul. EU MRL (mg/kg) (a) Recom. EU MRL (mg/kg) (b) Justification Tomatoes 0.02 0.01* - established pending submission of the Aubergines (egg plants) 0.02 0.02 - appropriate data. Cucumbers 0.02 0.01* - Gherkins 0.02 0.01* - Courgettes 0.03 0.01* - Peppers 0.02 0.03 - European authorisations show minor data Melons 0.01* 0.02 - gaps and acute risk to consumers cannot be excluded. Risk managers to decide Watermelons 0.01* 0.02 - whether a specific LOQ needs to be established or whether the default MRL of 0.01 mg/kg can apply. Other products of plant and/or animal origin see App C - - No European authorizations. Risk managers to decide whether a specific LOQ needs to be established or whether the default MRL of 0.01 mg/kg can apply. (*): Indicates that the MRL is set at the limit of analytical quantification. (a): Calculated EU MRLs result from the assessment of residues data available at EU level without consideration of consumer exposure. (b): Recommended EU MRLs result from the EU MRL proposals after being subject to consumer exposure calculations. DOCUMENTATION PROVIDED TO EFSA 1. Pesticide Residues Overview File (PROFile) on oxamyl prepared by the rapporteur Member State Ireland in the framework of Article 12 of Regulation (EC) No 396/2002. Submitted to EFSA on 11 February 2009. Last updated on 24 September 2010. REFERENCES CEN (European Committee for Standardization), 2008. Foods of plant origin Determination of pesticide residues using GC-MS and/or LC-MS/MS following acetonitrile extraction/partitioning and clean-up by dispersive SPE QuEChERS-method. EN 15662, November 2008. EFSA (European Food Safety Authority), 2005. Conclusion regarding the peer review of the risk assessment of the active substance oxamyl. EFSA Scientific Report (2005) 26, 1-78. EFSA (European Food Safety Authority), 2007. Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs according to Regulation (EC) No 396/2005 on Maximum Residue Levels of Pesticides in Food and Feed of Plant and Animal Origin. 15 March 2007. European Commission, 1996. Appendix G Livestock Feeding Studies. 7031/VI/95 rev.4, 22 July 1996. European Commission, 1997a. Appendix A - Metabolism and distribution in plants. 7028/VI/95-rev.3, 22 July 1997. European Commission, 1997b. Appendix C - Testing of plant protection products in rotational crops. 7524/VI/95-rev.2, 22 July 1997. 19
European Commission, 1997c. Appendix E - Processing studies. 7035/VI/95-rev.5, 22 July 1997. European Commission, 1997d. Appendix F - Metabolism and distribution in domestic animals. 7030/VI/95-rev.3, 22 July 1997. European Commission, 1997e. Appendix H - Storage stability of residues samples. 7032/VI/95-rev.5, 22 July 1997 European Commission, 1997f. Appendix I - Calculation of maximum residue levels and safety intervals.7039/vi/95, 22 July 1997 European Commission, 2000. Appendix B - General recommendations for the design, preparation and realization of residue trials. 7029/VI/95-rev.6, 17 August 2000. European Commission, 2008. Appendix D - Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/96-rev.8, 1 February 2008. Ireland, 2003. Draft Assessment Report (DAR) on the active substance oxamyl prepared by the rapporteur Member State Ireland in the framework of Directive 91/414/EEC, August 2003. Ireland, 2009. Evaluation report on the review of the existing MRLs for oxamyl prepared by the evaluating Member State Ireland under Article 12 of Regulation (EC) No 396/2005, May 2009. WHO/FAO, 1981. Pesticide residues in food - 1980. 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 26, 1981. WHO/FAO, 2002. Pesticide residues in food - 2002. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group. FAO Plant Production and Protection Paper, 172, 2002. WHO/FAO, 2005. Pesticide residues in food 2004. Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 178, 2005. 20
APPENDIX A GOOD AGRICULTURAL PRACTICES (GAPS) 21
APPENDIX B PESTICIDE RESIDUES INTAKE MODEL (PRIMO) Appendix B.1 PRIMo including all EU MRL proposals resulting from the GAPs reported by the RMS Appendix B.2 PRIMo including safe EU MRL proposals resulting from the GAPs reported by the RMS 22
APPENDIX B.1 PRIMO INCLUDING ALL EU MRL PROPOSALS RESULTING FROM THE GAPS REPORTED BY THE RMS 23
24
APPENDIX B.2 PRIMO INCLUDING SAFE EU MRL PROPOSALS RESULTING FROM THE GAPS REPORTED BY THE RMS 25