European Community Positions for the 41 st Session of the Codex Committee on Pesticide Residues Beijing, China. 20-25 April 2009 Agenda Items 4a, 4b, 5, 6 and 10 Agenda Item 4a JMPR Report 2008, Point 2, General Consideration 2.1 Comments from JMPR on a pilot process for JMPR to recommend maximum residue levels prior to national government registration The EC agrees with the JMPR that procedure and timelines need to be discussed and drawn up. 2.2 Comments on the global assessment of chlorantraniliprole in terms of its usefulness as a work-sharing tool for JMPR The global assessment of chlorantraniliprole (particularly the accompanying reporting table according to the EC Peer Review Format) is considered to be helpful for the preparation of the JMPR monograph on this pesticide. The EC supports the suggestions by JMPR, to improve the global assessment and peer reviews, by having clear distinctions made between editorial and science based comments by peer reviewers. This project did demonstrate the benefit in working together with other regulatory bodies to an agreed format. However, unless there is a clear global peer review process involving EFSA to facilitate global authorisations, the benefit from this work sharing would be lost. 2.3 A process to ensure the scientific robustness and transparency of retrospective analyses of toxicity data on pesticide chemicals The EC supports the JMPR proposal. It can play an important role, in refining test methods and guiding changes in data requirements, in enhancing interpretation of data from current tests for toxicity, and in supporting predictions of toxicity with a reduced number of animals as it is recommended also by OECD Working Group on Pesticides. 2.6 Safety factors for acute Cmax-dependent effects: specific considerations with respect to carbamates such as carbofuran The EC takes note of the JMPR approach of possible decreases or increases of safety factors based on categorical factors. However, the EC considers it insufficiently proven that a lower AF should be applied based upon the assumption that the NMC (N-methyl carbamates) toxicity, dependent on a C max rather than on a AUC effect, would exhibit lower inter or intraspecies variability. Also other regulatory bodies like the EPA maintain the position that, in the absence of robust evidence of such equivalence, e.g. on the basis of proven effects in-vitro, the application of lower AF is not recommended. 1
2.7 Transparency in the maximum residue level estimation process of the JMPR New summaries of the derivation of MRL estimates are a welcome addition. They not only provide more openness of the calculation process, but also providing clear summaries of e.g. STMR and HR values. It should be noted that the OECD is working on a calculator that may overcome some of the deficiencies of the EU calculation models and the NAFTA calculator. JMPR should be opened to test the OECD calculator as soon as the model is available. The EC agrees that any calculator has to be used as a tool and not as the primary determinant of estimations which should be the debate by the entire FAO expert group. The EC welcomes the transparency by publishing the calculation summary table in annex to the JMPR report. 2.8 Nature of residue data populations and methods for combining residue trial data sets The EC welcomes the 10 principles for combining residue trial data sets recommended by the 2008 JMPR which makes the evaluation process more transparent. 2.9 Evaluation for follow-up crops The EC agrees that for an estimation of possible residues in follow up crops, the JMPR must rely on the information provided. The EC recommends that, if no data on follow up crops is submitted and therefore no long-term dietary intake calculation can be carried out, the MRLs estimated should not be advanced in the Codex step system (see Boscalid). 2.10 Selection of representative commodities when establishing commodity group MRLs The EC supports the opinion by the JMPR that all available data should be evaluated, whether on a representative commodity or not. In estimating a group MRL, all available data should be included, if valid and sufficient, from all commodities whether potentially representative or not. Residue behaviour cannot always be predicted, and therefore the residue data driving the group MRL will not necessarily arise from suggested representative commodities. 2.11 Proportionality of pesticide residue concentrations and application rates in supervised trials The EC supports the proposal by the JMPR, to invite researchers to publish their findings on the validity if proportionality the MRL equivalent to the GAP rate can be adjusted using residue trials other than the GAP rate. (e.g. cyfluthrin beta-cyfluthrin). 2
Agenda Item 4b JMPR Report 2008, Point 3, Response to specific concerns 3.1 Carbaryl (008) The EC has noted the response of the JMPR. However, there are important differences in toxicological endpoints set by JMPR an EFSA, especially for ARfD, that make both risk evaluations to be completely different. Background data on toxicology Carbaryl was evaluated by the JMPR for the first time for toxicology in 2001 where an ARfD of 0.2 mg/kg bw was established on the basis of neurotoxicity observed in dogs given this pesticide with NOAEL 0.5 mg/kg bw/day and using a safety factor of 25. The EC ARfD was established in 2006 as 0.01 mg/kg bw on the basis of neurotoxicity observed in dogs with a safety factor of 100. Following our risk evaluation Authority s criteria (EFSA) the EC considers the established EC ADI and ARfD to be still relevant for EC-consumers. A concern form will be submitted at the CCPR 41. 3.2 Lambda-Cyhalothrin (146) The EC has noted the response of the JMPR. However, there are important differences in the toxicological reference values set by JMPR and EC, the numerical values as well as the way these were established. Following our risk evaluation the EC considers the established EC ADI and ARfD to be still relevant to use in the risk assessment for EC-consumers. Background data on toxicology Lambda-cyhalothrin was evaluated by the JMPR for the first time for toxicology in 2007 where a group ADI of 0.02 mg/kg bw and group ARfD of 0.02 mg/kg bw was established for cyhalothrin / lambda-cyhalothrin. JMPR established the ADI and the ARfD on the basis of neurotoxicity observed in rats and dogs given lambda-cyhalothrin, NOAEL 0.5 mg/kg bw/day, safety factor 25. JMPR considered it appropriate to adjust the safety factor for the reduced variability in Cmax compared with AUC. The EC ADI (0.005 mg/kg bw) and ARfD (0.0075 mg/kg bw) for lambda-cyhalothrin was established in 2001 on the basis of neurotoxicity observed in dogs, NOAEL 0,5 and 0,75 mg/kg bw/day respectively and a safety factor of 100. Consequently, the EC submitted a concern form after CCPR 40 aiming at the toxicological reference values set by the JMPR. 3
3.3 Flusilazole (165) The EC notes the comments made by JMPR on the EC review report which sets the 2 mg/kg/bw/day as the start of a dose response relationship. JMPR did not consider the effects at that dose to be significant and reaffirmed the higher dose of 10 mg/kg/day to be such a start. The EC wishes to reconfirm the endpoint of 0.005 mg/kg/bw/day for the ARfD derived from the 2 mg/kg/bw/day dose level that was established at the EC peer review process with EFSA. 3.4 Oxamyl (126) The EC has established the ARfD in the basis of a study on rats and as a rule, do not use human data, when available to lower the safety factor. The EC reaffirms the ARfD set in 2005 of 0.001 mg/kg/bw/day and notes the comments made by JMPR that the difference in the endpoint set by the EC and JMPR is due to the use of human data. Agenda Item 5. Draft and Proposed Draft Maximum Residue Limits for Pesticides in Foods and Feeds at Steps 7 and 4 General: Regarding the evaluation of metabolites of triazoles the scientific conclusion in the EC is pending. Comments at Steps 3and 6 221 Boscalid Comments at Steps 3 Boscalid was first evaluated by the 2006 JMPR were an ADI of 0.04 mg/kg bw was established. The estimate of an ARfD was unnecessary. The EC confirmed the toxicological evaluation. The 2006 JMPR could not recommend STMR values for a large number of follow up crops in which residues may be present above the LOQ and decided that any estimation of the long term intake would be unrealistic. The 2008 JMPR recommended new MRLs for banana and kiwi fruit, but again no long term intake calculations including follow up crops could be carried out. Consequently, a long-term intake assessment including possible residues in follow up crops arising from the GAPs evaluated must be carried out at a future meeting before the MRL proposals made by JMPR can proceed. The EC has concern to advance the proposed MRLs before a calculation of a long term dietary intake was made. Therefore the EC proposes to use a conservative residue value of 0.5 mg/kg for all commodities from annual crops which are not treated directly but with possible residues by uptake from soil. Based on this worst-case approach a preliminary long-term intake assessment can be made to exclude any concerns for the consumers. In addition JMPR may use all data available on rotational crops to propose more realistic MRLs 4
for annual crops according the procedure described in the JMPR Report 2008. 096 Carbofuran The EC noted that the JMPR established an ADI and an ARfD of 0.001 mg/kg bw based on the overall NOAEL of 0.03 mg/kg bw/day identified on the basis of inhibition of brain acetylcholinesterase activity in rat pups aged 11 days and a AF of 25. However, the EC has established an ADI and an ARfD of 0.00015 mg/kg bw/d based on the acute rat neurotoxicity study and an assessment factor of 200 (2 AF to extrapolate the pup LOAEL (0.03 mg/kg bw/d) to a NOAEL (0.015 mg/kg bw/d) and an assessment factor of 100 to account for the interspecies and intraspecies extrapolation. These toxicological values were already peer reviewed and considered as acceptable in the frame of the EU review process of Benfuracarb (see EFSA Scientific Report on Benfuracarb issued on 18 February 2009). A concern form will be submitted at the CCPR 41. 230 Chlorantraniliprole The EC supports the advancement of the proposed MRLS The studies are currently being reviewed in several EC countries and there are MRLs based on import tolerances established in Annex III of the Regulation 396/2005. While rotational crops have been carried on root, leafy vegetables and cereal grains, the EC agrees with the comments in the JMPR report that more residue studies in other follow crops would be desirable. 201 Chlorpropham The EC supports the proposed MRL of 0.01* for milk. However, as agreed at the 2008 CCPR, the phrase should be added: for monitoring and regulatory purposes, whole milk is to be analyzed and the result compared to the MRL for whole milk". 146 Cyhalothrin/lambda-Cyhalothrin The EC opposes advancement of the proposed MRLs for apricots, peaches, tomatoes, peppers, sweet corn, broccoli, cauliflower, head cabbage and milk due to acute intake concerns. Using the EFSA model, the proposed MRLs with STMR and HR identified by JMPR, the EU ADI and ARfD, acute intake concern was identified for the following MRL proposals: apricots (DE child 109%), peaches and nectarines (DE child 192%), tomatoes (BE child 101%), peppers (DE child 108%), sweet corn (DE child 126%), broccoli (BE child 166%), cauliflower (NL child 264%, NL general population 127%), head cabbage (NL child 119%), milk and milk products from cattle (UK Infant 133%). As stated under agenda item 4b, the EC considers established EC reference values still relevant to use in the risk assessment for EC-consumers. 5
118 Cypermethrins In the 2008 JMPR report, new residue data were evaluated and presented. Since available analytical methods for the determination of cypermethrin residues in plants commodities are unable to distinguish between the different isomers, a global ADI value and a global ARfD value were considered as more appropriate (2006 JMPR report). -ADI proposal: 0-0.02 mg/kg bw/day, Dog, 3-month dietary study with alpha-cypermethrin, 100-fold safety factor. -ARfD proposal: 0.04 mg/kg bw/day, Rat, study of acute neurotoxicity with alphacypermethrin, 100-fold safety factor. The JMPR residue evaluation has been revised by the EC and based on the global toxicological end points for cypermethrins, the chronic and acute dietary intake calculation was performed according to EFSA PRIMo. There is no chronic intake concern (highest TMDI of 47% of the ADI, DE child). Using the HR values in the EFSA PRIMo, there is an acute intake concern for the children for the following crops: -Peaches (102,2% ARfD-VF=5) -Apples (101,1% ARfD-VF=5) -Cauliflower (107% ARfD-VF=5) -Scarole (broad-leaf) (113% ARfD-VF=5). No processing data on pome fruit and stone fruit were available in order to perform a refined dietary intake risk assessment. The EC opposes the advancement of the MRLs for peaches, apples, cauliflower and scarole (broad-leaf) because of acute intake concern. The EC has no objections to the advancement of the proposed MRLs in all other supported plant commodities. 027 Dimethoate The EC opposes the proposed MRL for peppers due to intake concerns. Using EC endpoints and risk assessment methodologies, peppers are 164% of the ARfD. Although dimethoate residues for lettuce do not indicate an intake concern, omethoate is not included in the Codex residue definition for dimethoate. Omethoate is one of the degradation products of dimethoate, and is 7 times more toxic than dimethoate. Hence, there may also be an intake concern for the proposed MRL for lettuce due to residues of omethoate. 030 Diphenylamine The EC supports the proposed MRL of 0.01* for milk. However as agreed at the 2008 6
CCPR, the phrase should be added: for monitoring and regulatory purposes, whole milk is to be analyzed and the result compared to the MRL for whole milk". 206 Imidacloprid Imidacloprid was evaluated by the JMPR in 2001 for toxicology where an ADI of 0.06 mg/kg bw/day and an ARfD of 0.4 mg/kg bw/day were established. In 2008, the EU confirmed the ADI of 0.06 mg/kg bw but an ARfD of 0.08 mg/kg bw was established, based on the 90 d dog study and rabbit developmental study using a safety factor of 100. The 2008 JMPR estimated an IESTI for the general population 0-10% and for children 0-50% of the ARfD (0.4 mg/kg bw). The Meeting concluded that the short-term intake of residues of imidacloprid from uses considered by the 2008 JMPR was unlikely to present a public health concern. Using the EFSA model and the proposed MRLs to calculate the long- and short-term intake for berries and small fruits, coffee, edible offal, eggs, milks, meat, peas, peanuts, pomegranate, root and tuber vegetables, strawberry, sunflower seed and tree nuts, neither a chronic nor an acute dietary risk exists for European consumers. 049 Malathion All uses of malathion have been withdrawn in the EU. All MRLs dropped to LOQ since early 2009. Existing CXLs based on the EU GAPs need to be withdrawn. 094 Methomyl The EC opposes the proposed MRL for apples and grapes due to intake concerns. Using EC endpoints and risk assessment methodologies, apples and grapes are 666% and 524% of the ARfD respectively. 126 Oxamyl The EC has established the residue definition for Oxamyl to be the parent compound only and is different to that of JMPR, which uses the sum of the parent compound oxamyl and oxamyl oxime. The notifier submitted alternative GAPS using drip irrigation for citrus, cucumbers, courgettes, melons, peppers and tomatoes with the analytical methods and residue data for the parent oxamyl only. The EC does not accept the JMPR conclusion that there is insufficient data and request that the residue definition be re-evaluated taking into account that the parent compound, oxamyl is the only residue of toxicological concern and can be analysed separately from the oxime. 189 Tebuconazole ADI = 0.03 mg/kg set by JMPR and EU ARfD = 0.03 mg/kg set by EU (NOAEL of 3 mg/kg bw/day from finding of hypertrophy in the adrenals in a 1-year dog study. Safety factor 100). No ARfD is allocated by JMPR. The EC opposes the advancement of MRLs for brassica, head lettuce and pome fruits 7
because of acute intake concern. Using the EFSA model with the new EU ARfD established by EFSA the ARfD of 0.03 mg/kg bw is exceeded for the proposed MRLs for cauliflower, apple and pears and lettuce as follows: lettuce 172%, cauliflower 123%, Apple 113 %, pears 103%. In addition the ARfD is exceeded for the CXLs for grapes, cherries and peaches as follows: table grapes 218 %, cherries 204 %, Peaches 145 %. A concern form will be submitted at the CCPR 41. 008 Carbaryl Comments at Steps 6 It is important to point out that the EC ARfD (0.01 mg/kg bw/day) is 20 times lower than JMPR ARfD (0.20 mg/kg bw/day Considering HRs established by JMPR (in stone fruits peaches and plums- 7.8, citrus fruit, edible portion 1.16 and in grcapes 33), and V=5, we can conclude that: Using ARfD JMPR= 0.2 mg/kg/bw/day there is an exceeding of ARfD: grapes 1080% (children), 524% (adults). Peaches: 170% (children). Plums 104% (children). Using ARfD EU = 0.01 mg/kg/bw/day there is an exceeding of ARfD: grapes 21608% (children), 10476% (adults). Peaches: 3395% (children) and 1057% (adults). Plums 2080% (children) and 600 (adults). Apricots 1931% (children) and 497% (adults). Cherries 953% (children) and 330% (adults). Oranges 1112% (children and 241% (adults). Mandarins 485% (children) and 121% (adults). Serious acute concerns are observed in risk assessment of CXL Carbaryl so the EC opposes to the proposed MRLs for stone fruits, citrus fruits and grapes. A concern form will be submitted at the CCPR 41. 096 Carbofuran Using the EFSA PRIMo with the following inputs for the dietary intake risk assessment: HR values for all crops except for oranges (sweet and sour) and mandarins (EC used the recovered residue levels in citrus pulp from a carbosulfan metabolism study on citrus (Metabolism of Carbosulfan in/on oranges (Weintraub, R.A., 1996)) submitted to the JMPR expert in January 2009-cfr. Carbosulfan DAR, July 2004) and the EU established ADI and ARfD (0.00015 mg/kg bw/d), a chronic intake concern was identified: highest TMDI calculated: 4113 % of the ADI (UK toddler). Acute intake concerns were identified for the following crops: melons/cantaloupe (13146%, BE child), cucumbers (11306%, NL child), potatoes (11275%, UK infant), courgettes/squash, summer (8058%, UK toddler), bananas (5573%, UK infant), cattle/goat milk and milk products (805-4140%, ES child-uk infant), sweet corn (corn-on-the-cob) (3916 %, DE child), sugar cane (322%, UK infant), bovine edible offal (242%, UK infant), maize (224%, UK infant), rice (210%, UK toddler), sunflower seed (205%, DE child) and 8
sugar beet root (8513%, UK 4-6 year old). The EC opposes to the advancement of the MRL proposals for cantaloupe (melons) (0.2 mg/kg), cucumbers (0.3 mg/kg), potatoes (0.2 mg/kg), squash, summer (courgettes) (0.3 mg/kg) and sweet corn (corn-on-the-cob) (0.1 mg/kg) beyond step 6 due to chronic and acute intake concerns. The EC is in favour of the advancement of the MRL proposal for mandarins (0.5 mg/kg) and oranges (sweet and sour) (0.5 mg/kg) beyond step 6 considering the residue level in citrus pulp from the carbosulfan metabolism study on citrus. The EC proposes revocation of the following CXLs: banana (0.1 mg/kg), edible offal (cattle, goats, horses, pigs and sheep) (0.05* mg/kg), maize (0.05* mg/kg), milks (0.05* mg/kg), potatoes (0.1* mg/kg), rice husked (0.1 mg/kg), sugar beet (0.2 mg/kg), sugar cane (0.1 mg/kg) and sunflower seed (0.1 mg/kg). A concern form will be submitted at the CCPR 41. 145 Carbosulfan The main metabolite of carbosulfan is carbofuran, which leads to unacceptable chronic and acute consumer exposure (see carbofuran). Consequently, the EC opposes to the advancement of the proposed carbosulfan MRLs for potatoes (0.05 mg/kg) beyond step 6 in line with the assessment for Carbofuran. The EC is in favour of the advancement of the MRL proposals for mandarins (0.1 mg/kg) and oranges (sweet and sour) (0.1 mg/kg) beyond step 6 in line with the assessment for Carbofuran. The EC propose revocation of the following CXLs: edible offal (mammalian) (0.05* mg/kg), maize (0.05* mg/kg), milks (0.03* mg/kg), sugar beet (0.3 mg/kg) in line with the assessment for Carbofuran. 157 Cyfluthrin / 228 Betacyfluthrin The EC objects the advancement beyond step 6 of the proposed MRLs for citrus fruits, broccoli, head cabbage and cauliflower because of acute intake concerns. The EC acute dietary risk assessment was carried out with an ARfD of 0.02 mg/kg, the use of variability factors of 7 or 5 and the consumption data of the EFSA model. The ARfD is exceeded for oranges (132%, UK infants), broccoli (437%, BE child), cauliflower (300%, NL child) and head cabbage (553%, NL child). The 2006 JMPR established for cyfluthrin and beta-cyfluthrin a group ADI of 0-0.04 mg/kg bw and an ARfD of 0.04 mg/kg bw based on a NOAEL of 1 mg/kg bw, for findings of acute neurotoxicity observed in a-4 week gavage study in rats with beta-cyfluthrin and a safety factor of 25. The active substances were included in Annex I of Directive 91/414/EEC in 2002. The ADI is 0.003 mg/kg bw. An ARfD of 0.02 mg/kg was derived from a NOAEL of 2 mg/kg bw in an acute neurotoxicity study on rats with beta-cyfluthrin and a safety factor of 100. 9
The 2007 JMPR proposed MRLs on a number of plant and animal commodities. The EC agrees that no long-term dietary intake concern exists (based on the STMR values and the EC ADI of 0.02 mg/kg bw). The EC acute dietary risk assessment was carried out with an ARfD of 0.02 mg/kg, the use of conservative variability factors of 7 or 5 and the consumption data of the EFSA model. The ARfD is exceeded for oranges (132%, UK infants), broccoli (437%, BE child), cauliflower (300%, NL child) and head cabbage (553%, NL child). 027 Dimethoate Alternative GAPs have been proposed. See EC comments for the substance at Step 3. 165 Flusilazole The EC does not support the advancement for apple, pear and edible offal (mammalian) due to exceedence of the ARfD established in the EC. 094 Methomyl Alternative GAPs have been proposed. See EC comments for the substance at Step 3. 126 Oxamyl The EC has established the residue definition for Oxamyl to be the parent compound only and is different to that of JMPR, which uses the sum of the parent compound oxamyl and oxamyl oxime. The notifier submitted alternative GAPS using drip irrigation for citrus, cucumbers, courgettes, melons, peppers and tomatoes with the analytical methods and residue data for the parent oxamyl only. The EC does not accept the JMPR conclusion that there is insufficient data and request that the residue definition be re-evaluated taking into account that the parent compound, oxamyl is the only residue of toxicological concern and can be analysed separately from the oxime. 133 Triadimefon The EC opposes the advancement of the MRL for grapes due to acute intake concerns. 168 Triadimenol The EC opposes the advancement of the MRL for grapes due to acute intake concerns 143 Triazophos Although supporting data are not sufficient to confirm consumer safety, the EC has no immediate concerns regarding the proposed MRL for soya bean (immature). However, the EC supports a re-assessment of consumer safety once data on edible portion residues are available. The EC has no concerns regarding chronic or acute intake from the proposed or retained MRLs for cotton seed; cotton seed oil, crude and cereal Grains. 10
Agenda Item 6. Proposed Draft Revision of the Codex Classification of Foods and Animal Feeds at Step 4 The EC welcomes the work done on the revision of the Classification of foods and animal feed done by The Netherlands and the USA and welcomes the effort to harmonize globally product Classifications for MRL setting purposes. Revision of the coding system The EC agrees with the proposed code system to add only new codes for new commodities and commodity groups and to delete the codes for synonyms. Comments on revised groups: Bulb vegetables The EC agrees with the revised group Bulb vegetables. Fruiting vegetables, other than Cucurbits The EC agrees with the revised group Fruiting vegetables, other than Cucurbits Edible fungi The EC agrees with the revised group Edible fungi to make a separate group of edible fungi and to draw edible fungi out of in the group of Fruiting vegetables, other than Cucurbits Citrus fruits The EC agrees with the revised group Citrus fruits. Pome fruits The EC has a reservation to classify azarole, Mayhaw and Tejocote (all Crataegus spp.) in the group of Pome fruits. The size of the fruit (up to 2,5 cm diameter) is more like a berry than a pome fruit. We propose to include these commodities in the group of Berries and other small fruits subgroup Large shrub/tree berries. Stone fruits The EC agrees with the revised group Stone fruits. 11
Agenda Item 10. Establishment of Codex Priority Lists of Pesticides The nomination of amitraz is supported by the EC. A re-evaluation should be conducted as soon as possible (2010 as proposed). - The evaluation is no longer up to date since residues were last evaluated in 1990 and toxicology in 1998 by JMPR. A short term risk assessment was not conducted in 1998. - The active substance is no longer authorised in the way described in the GAP used in the 1990 evaluation. - The CXLs exceed the ARfD.( for example over 2000% are observed in oranges according EFSA model). - The active substance is covered in the European Rapid Alert System as MRLs for pears are exceeded frequently. It should be noted that the nomination of fluopyram did not follow the CCPR rules. The nomination was not done in time for toxicological evaluation in 2009. Toxicological and residue evaluation should be done in the same year. 12