Modification of the existing MRLs for chlorothalonil in barley and several food commodities of animal origin 1

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1 REASONED OPINION Modification of the existing MRLs for chlorothalonil in barley and several food 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY According to Article 6 of the Regulation (EC) No 396/2005, the United Kingdom received an application from Syngenta to modify the existing MRLs for chlorothalonil in barley and in several food. In order to accommodate the intended use of chlorothalonil on barley in the United Kingdom, it is proposed to raise the existing MRL in barley from 0.1 mg/kg to 0.3 mg/kg. It is also proposed to raise the existing MRLs for chlorothalonil in bovine, sheep and goat milk, fat, meat, kidney and liver. The United Kingdom 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 30 January On 30 April some data requirements were identified which prevented EFSA to conclude on the consumer risk assessment. An updated evaluation report, addressing those data requirements, was submitted by the EMS on 10 December 2009 and taken into consideration by EFSA for finalization of this reasoned opinion. EFSA derived the following conclusions based on the above mentioned evaluation report and the Draft Assessment Report (DAR) prepared under Directive 91/414/EEC. The toxicological studies submitted on chlorothalonil under the peer review were sufficient to conclude on an ADI value of mg/kg bw/d and an ARfD value of mg/kg bw. For the metabolite 2,5,6-trichloro-4-hydroxyphtalonitrile (SDS-3701), which was identified in plants and in significant concentrations in animals, an ADI of 0.01 mg/kg bw/d and an ARfD of 0.01 mg/kg bw was derived. The metabolism of chlorothalonil in primary plants was investigated under the peer review of Directive 91/414 in four crop categories. Studies were sufficient to conclude on the risk assessment and enforcement residue definition in all plant commodities as parent chlorothalonil. It has to be noted that available metabolism studies do not provide sufficient information on the nature of chlorothalonil residues in crops with PHI intervals exceeding 21/28 days. It is assumed that chlorothalonil is metabolised to a greater extent after longer intervals. Adequate analytical methods are available to control the compliance of the proposed MRL in barley. It has to be noted that laboratories performing residue analysis have to pay particular attention to the storage of the analytical samples prior analyses since losses of chlorothalonil have been observed during the laboratory processing of various fruit and vegetable samples. 1 On request from the European Commission, Question No EFSA-Q , issued on 26 February Correspondence: praper.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Modification of the existing MRLs for chlorothalonil in barley and several food.. [42 pp.]. doi: /j.efsa Available online: European Food Safety Authority,

2 The submitted supervised residue field trials indicate that an MRL of 0.3 mg/kg would be required to accommodate the intended GAP of chlorothalonil on barley in the United Kingdom. Chlorothalonil was stable under conditions simulating pasteurisation, but showed increased degradation in baking/brewing/boiling and sterilisation. Relevant degradation products were SDS and 3-cyano-2,4,5,6-tetrachlorobenzamide (SDS-19221). A processing study investigating the magnitude of chlorothalonil and metabolite SDS-3701 in beer and pot barley is available. No concentration of residues was observed. It is concluded that for the intended GAP, no significant concentrations of chlorothalonil or SDS-3701 are expected in beer or in pot barley. EFSA, however, recommends investigating the need for the inclusion of metabolite SDS-3701 and possibly SDS in the residue definition for processed commodities. The occurrence of chlorothalonil residues in rotational crops was also investigated. Studies indicate that metabolite 3-carboxy-2,5,6-trichloro benzamide (SDS-46851) is the main residue in rotational crops. The peer review decided that, based on the data on metabolites in plant products and in view of the information from toxicological studies, the residue in plant products has to be defined as the parent compound chlorothalonil only, although parent compound was found in significantly lower concentrations than SDS Considering the available data, EFSA concludes that the intended use of chlorothalonil on barley will not result in significant residues of chlorothalonil and its metabolites in rotational crops provided that the active substance is applied according to the intended GAP. The occurrence of chlorothalonil residues in was also investigated. The dietary burden for different types of livestock was calculated considering the residues in barley grain and straw as well as in other feed crops. The livestock dietary burden significantly exceeds the trigger value of 0.1 mg/kg DM for all livestock species. Based on the metabolism studies with lactating goats and laying hens the peer review concluded that the residue for enforcement and risk assessment in livestock should be provisionally defined as metabolite SDS From the toxicological studies, differences between metabolic patterns in ruminants and non-ruminants were observed indicating that mono-, di-, triglutathione conjugates of chlorothalonil are the main metabolites in monogastric animals. The available data give some evidence that the main residues in non-ruminants would be chlorothalonil conjugates, but there is no information on the quantity and distribution of these compounds in non-ruminant tissues. EFSA is of the opinion that the need of a pig metabolism study should be discussed with experts in the framework of Article 12(2) of Regulation (EC) No 396/2005 to elucidate the metabolism in non-ruminants. EFSA concludes that the current residue definition for animal products as established in the Regulation (EC) No 396/2005 does not comprise the compounds that were identified as major residues in ruminants. EFSA agrees with the residue definition derived in the peer review (SDS-3701) and recommends to amend the current residue definition for ruminants in Regulation (EC) No 396/2005 accordingly. Also for non-ruminants the residue definition may need to be changed but further information would be required for poultry and pigs. The magnitude of chlorothalonil and its metabolite SDS-3701 in livestock was studied in a feeding study where both substances were administered orally to lactating cows as a blend. For estimating the MRLs in the food commodities of bovine, sheep and goat, EFSA took into account the calculated dietary burdens for ruminants following their exposure to chlorothalonil and the results from the livestock feeding study. The derived MRL proposals for food are higher as proposed by the EMS because EFSA considered the livestock exposure to chlorothalonil residues not only from the intake of treated cereals but also from other feed crops. The derived MRL proposals are compiled in the table below. Metabolism studies with poultry indicate that no chlorothalonil or SDS-3701 residues will occur in poultry products above the LOQ at the calculated dietary burden. The MRL proposals for swine products were not derived since there are no sufficient data available on the nature and magnitude of chlorothalonil in pigs. 2

3 The consumer risk assessment for chlorothalonil is hampered by the lack of information on the full data set of all authorized uses of chlorothalonil and therefore this consumer risk assessment has to be considered as provisional giving the best estimate which is possible at the moment. The consumer intake assessment was performed with revision 2 of the EFSA PRIMo. For the chronic exposure assessment EFSA used the existing MRLs as established in Annex II and Annex IIIB of Regulation (EC) No 396/2005 as well as the derived STMR values for barley and relevant commodities of food origin. EFSA was able to derive STMR values for several other crops. The acute exposure assessment was performed only with regard to commodities for which the MRL proposals are made using the HR values as derived from the supervised residue trials (for barley) and the livestock feeding studies (for ). The calculated exposure to residues from plant products was compared with the toxicological reference values of chlorothalonil. The calculated exposure to residues from the products of animal origin was compared with the toxicological reference values of SDS Regarding food commodities of plant origin, no long-term intake concerns were identified for any of the European diets. The total calculated exposure values ranged from % of the ADI. The highest individual contribution of barley to the total exposure was identified for the Irish adult diet (0.41% of the ADI). No short-term intake concerns were identified with regard to the intake of barley (2.7% of the ARfD). Regarding food, no long-term concerns were observed with regard to the consumer exposure to SDS-3701 residues. The total calculated intake values accounted for a maximum of 24 % of the ADI. The highest contributing commodity was milk and cream (15.8% of the ADI) for FR toddler diet. No acute intake concerns were identified. The contribution of food to the total acute exposure to SDS-3701 accounted for 87% of the ARfD for milk and milk products, 11.3% of the ARfD for bovine kidney, 4.8 % of the ARfD for bovine liver and 3.8% of the ARfD for bovine meat. Consequently EFSA concludes that the proposed MRL of 0.3 mg/kg in barley and the derived MRL proposals for food are acceptable with regard to long-term and shortterm consumer exposure. In addition, the following recommendations were derived during the risk assessment and are proposed to be addressed the framework of the Article 12 (2) of Regulation (EC) No 396/2005: - the need for studies investigating the nature of chlorothalonil in pigs has to be further discussed and, depending on the outcome, a need for a pig feeding study has to be considered; - the residue definition for processed commodities has to be reconsidered in accordance with the results from the study on the effects of processing on the nature of chlorothalonil; - a possible formation of SDS-3701 in crops for which the GAP envisages long PHI intervals; - if a decision is taken to consider SDS-3701 residues in plant commodities, a sufficiently validated analytical method and a storage stability studies have to be provided; The derived MRL proposals are as follows: Food Commodity Existing EC code a MRL Existing enforcement residue definition: chlorothalonil Proposed EC MRL Justification for the proposal 3

4 Food Commodity Existing EC code a MRL Proposed EC MRL Justification for the proposal Barley The intended use is sufficiently supported by data and no consumer intake concerns were identified for the proposed MRL. Existing enforcement residue definition: chlorothalonil Proposed enforcement residue definition for ruminants: SDS Bovine meat 0.01* 0.05 The derived MRL proposals are Bovine fat 0.01* 0.1 acceptable with regard to short-term and long-term consumer exposure Bovine liver 0.01* Bovine kidney 0.01* Sheep meat 0.01* Sheep fat 0.01* Sheep liver 0.01* Sheep kidney 0.01* Goat meat 0.01* Goat fat 0.01* Goat liver 0.01* Goat kidney 0.01* Milk 0.01* 0.1 (*): Indicates that the MRL is set at the limit of analytical quantification. a according to the classification in Regulation (EC) No 396/2005. KEY WORDS Chlorothalonil, barley,, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, chloronitrile fungicide 4

5 TABLE OF CONTENTS Summary... 1 Table of contents... 5 Background... 6 Terms of reference... 6 The active substance and its use pattern... 7 Assessment Methods of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues Nature and magnitude of residues in plant Primary crops Rotational crops Nature and magnitude of residues in livestock Dietary burden of livestock Nature of residues Magnitude of residues Consumer risk assessment Conclusions and recommendations References Appendix A Good Agricultural Practices (GAPs) Appendix B Pesticide Residues Intake Model (PRIMo) Appendix C Existing EC MRLs Abbreviations

6 BACKGROUND Regulation (EC) No 396/2005 establishes the rules governing the setting of pesticide MRLs at Community level. Article 6 of that regulation lays down that a party requesting an authorisation for the use of a plant protection product in accordance with Directive 91/414/EEC, shall submit to a Member State, when appropriate, an application to set or modify an MRL in accordance with the provisions of Article 7 of that regulation. The United Kingdom, hereafter referred to as the evaluating Member State (EMS), received an application from the company Syngenta 3 to modify the existing MRL for the active substance chlorothalonil in barley grain and several food. This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation report of the EMS was submitted to the European Commission who forwarded the application, the evaluation report and the supporting dossier to EFSA on 30 January The application was included in the EFSA Register of Question with the reference number EFSA-Q and the following subject: Chlorothalonil - Application to modify the existing MRL for chlorothalonil in barley grain and in several food. EFSA then proceeded with the assessment of the application as required by Article 10 of the Regulation. On 30 April some data requirements were identified, which prevented EFSA to conclude on the consumer risk assessment. An updated evaluation report, addressing those data requirements, was submitted by the EMS on 10 December 2009 and taken into consideration by EFSA for finalization of this reasoned opinion. TERMS OF REFERENCE According to Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the evaluating Member State, provide a reasoned opinion on the risks to the consumer associated with the application. According to Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within 3 months from the date of receipt of the application. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. In this particular case the calculated deadline for providing the reasoned opinion is 11 December Syngenta, CPC4 Capital Park, Fulbourn, Cambridge, CB21 5XE, Cambridge, The United Kingdom 6

7 THE ACTIVE SUBSTANCE AND ITS USE PATTERN Chlorothalonil is the ISO common name for tetrachloroisophthalonitrile (IUPAC) with the following molecular structure: Cl CN Cl Cl Cl CN Molecular weight: Chlorothalonil is a broad spectrum, protectant contact fungicide which binds to sulfhydryl groups of amino acids, proteins and peptides (e.g., SH group of glutathion). Chlorothalonil ties up free glutathion in fungal cells and blocks enzyme activity. Chlorothalonil is not fat-soluble (Log Po/w = 2.94 at 25 C). Chlorothalonil was peer reviewed according to Directive 91/414/EEC with the Netherlands being the designated rapporteur Member State. The EC review report for the inclusion of the active substance in Annex I of the above mentioned directive was issued on 15 February Chlorothalonil was included in Annex I of Directive 91/414/EEC by Commission Directive 2005/53/EEC for the uses as fungicide only. The active substance was not peer reviewed by EFSA. The MRLs for chlorothalonil at European level were first established by Commission Directives 1993/57/EC and 1993/58/EC. The current MRLs for the active substance are set in Annexes II and IIIB of Regulation (EC) No 396/2005. The existing MRL for barley is set at 0.1 mg/kg. The MRLs for animal commodities are set at the LOQ of 0.01 mg/kg. Codex Alimentarius has established the CXL for barley at 0.1 mg/kg; no CXLs are set for animal commodities. The CXL for barley straw is set at 20 mg/kg. The GAP for which the authorization is requested in the United Kingdom refers to two applications of the active substance on barley (growth stage at the last application BBCH 61- beginning of flowering) at a rate of 1 kg a.s./ha. It is noted that the relevant PHI is not mentioned but would be recommended. The summary of the GAP is provided in Appendix A. 7

8 ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the United Kingdom (2009), the EC review report for the active substance chlorothalonil (2005), the Draft Assessment Report (DAR) prepared under Directive 91/414/EEC (NL, 2004), the JMPR Evaluation report (WHO/FAO, 1997). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation of the Authorization of Plant Protection Products set out in Annex VI to Directive 91/414/EEC and the currently valid EU guidance documents for consumer risk assessment (European Commission, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2008). 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin The analytical methods for the determination of chlorothalonil in foodstuffs of plant origin were evaluated in the framework of the peer review of Directive 91/414/EEC (The Netherlands, 2004). A GC-MS method is sufficiently validated at the LOQ of 0.01 mg/kg for the determination of chlorothalonil in plant matrices with high water-, high acid content and in dry commodities. Consequently there is an adequate analytical method to control the compliance of the proposed MRLs in barley grain. Laboratories performing residue analysis have to pay particular attention to the storage of the analytical samples prior to analyses since losses of chlorothalonil have been observed during the laboratory processing of various fruit and vegetable samples in the room temperature (WHO/FAO, 1997). No analytical methods are available for the determination of SDS-3701, a metabolite which was observed in significant concentrations in straw Methods for enforcement of residues in food of animal origin The enforcement residue definition agreed in the peer review for the foodstuffs of animal origin was SDS The existing enforcement definition for the residues in foodstuffs of animal origin according to Regulation (EC) No 396/2005 is parent chlorothalonil. For the determination of parent chlorothalonil in milk, eggs and animal tissues, a GC-MS method is validated at the LOQ of 0.01 mg/kg. For the determination of metabolite SDS-3701 in animal matrices a HPLC-UV method is validated at the LOQ of 0.01 mg/kg for milk, eggs and animal tissues. 2. Mammalian toxicology The toxicological reference values for chlorothalonil were derived in the peer review under Directive 91/414/EEC and are compiled in Table 2-1 (European Commission, 2005). Toxicological reference values were also derived for two metabolites which were observed in the plant and animal metabolism studies. 4 SDS-3701: 2,5,6-trichloro-4-hydroxyphtalonitrile (MW=247.5) 8

9 Table 2-1. Overview of the toxicological reference values Chlorothalonil Source Year Value (mg/kg bw/d) Study relied upon Safety factor ADI EC day rat 100 ARfD EC day rat 100 Metabolite SDS-3701 (2,5,6-trichloro-4-hydroxyphtalonitrile ) ADI EC day dog 100 ARfD EC day dog 100 Metabolite SDS (3-carboxy-2,5,6-trichloro benzamide) ADI EC day dog 100 ARfD EC day dog 100 It is noted that SDS-3701 and chlorothalonil have different mechanisms of action in organism. According to short- and long term studies, the target organs for toxicity of chlorothalonil and SDS are kidney and haemopoietic system, respectively (WHO/FAO, 2008). 3. Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The nature of chlorothalonil in primary plants was investigated in the framework of the peer review with [ 14 C-U-phenyl]-chlorothalonil in the following crop categories (The Netherlands, 2004): - leafy vegetables: foliar application on lettuce (4 x 1.75 kg a.s./ha; max PHI 21d), celery (12 x 2.5 kg a.s./ha; max PHI 21d) - fruiting vegetables: foliar application on tomatoes (4 x 2.33 kg a.s./ha; max PHI 14 d) - root and tuber vegetables: foliar application on carrots (3 x 1.6 kg a.s./ha; max PHI 21 d) - pulses and oilseeds: foliar application on snap beans (4 x 2.46 kg a.s./ha; max PHI 28 d) In lettuce the total TRR varied from 118 to 170 mg eq./kg and was independent from the PHI interval. The major component of the TRR was parent chlorothalonil (87-90% TRR). Metabolite SD-3701 accounted for 2% of the TRR. Tomato fruit and foliage were subject for characterisation and quantification of the TRR. Results indicate that the main component of the TRR in tomato fruit and leaves was the parent chlorothalonil accounting for up to 76% and 73% of the TRR (of combined organic rinse and organosoluble extract), respectively. Metabolite SDS-3701 did not account for more than 5% of the TRR in tomato fruit. In 5 SDS-46851: 3-carboxy-2,5,6-trichloro benzamide 9

10 tomato foliage SDS-3701 concentrations increased with a longer PHI intervals, from 4% TRR (1 DAT) to 14% TRR (14 DAT). In carrot roots and foliage the total residues 1-21 DAT were within a range of and mg eq./kg, respectively. The main compounds of the TRR in carrot roots (21 DAT) were parent chlorothalonil (79% of rinse and organosoluble residues) and SDS-3701 (6.2% of rinse and organosoluble residues). In the rinsed carrot foliage 24-32% of residues were organosoluble, 29-31% were watersoluble and 39-46% were not extractable. Organosoluble fraction consisted of chlorothalonil (15 % TRR (7 DAT) % TRR (21 DAT)) and its hydroxy metabolite SDS-3701 (2.4 %TRR (7 DAT) 12 % TRR (21 DAT). Translocation of TRR from foliage to root was very low. Celery stalks and foliar parts were analysed separately for the quantification and characterisation of the TRR. In samples harvested 7 DAT, the TRR accounted for and mg eq./kg in celery stalks and foliar parts, respectively. Chlorothalonil was the only identifiable component from the celery stalk ( mg/kg) and foliage ( mg/kg) and accounted for 72-80% of the TRR. With regard to fresh beans, the samples of beans and foliage were used to characterise and quantify the TRR. Results indicate that total residue levels in beans and leaves 7 DAT were and mg eq./kg, respectively. The major component of the TRR was parent chlorothalonil amounting between mg/kg (7 d PHI) and mg/kg (28 d PHI) in unwashed beans. The residues in foliar parts were significantly higher and chlorothalonil accounted for mg/kg (77-80% TRR) and mg/kg (33-70% TRR) at 7 and 28 d PHI. It was noted that watersoluble and not extracted residue components in washed beans accounted for up to 50-54% and 14-19% TRR at 7 day PHI, respectively. These residues were not further identified. Based on primary crop metabolism studies conducted with lettuce, tomato, carrot, celery, and snap beans, the parent compound appears to represent the major residue component. In general, it accounted for at least 50% of the total residue and over 90% of the identified residue components in edible parts of the crops investigated. Other identified residue components generally accounted for less than 5% of the total residue in edible portions and frequently remained below the LOD. Only in snap beans chlorothalonil constituted a relatively smaller part of the total residue. In carrot foliage at longer post harvest intervals, SDS-3701 was the major identified residue. The peer review concluded to establish the risk assessment and enforcement residue definition as parent chlorothalonil only. It has to be noted that available metabolism studies do not provide sufficient information on the nature of chlorothalonil residues in crops with PHI intervals exceeding 21/28 days. It can be assumed that chlorothalonil will be metabolised to a greater extent after longer intervals. In addition, the need to set a separate residue definition in cereal straw including SDS-3701 may be considered if in the future feed items will be included in the Annex I of Regulation (EC) No 396/2005 and the MRLs set Magnitude of residues For the proposed GAP the applicant submitted 11 residue trials on barley conducted in Northern Europe. The residues of chlorothalonil in barley grain were in the range of < mg/kg. In four trials residues of SDS-3701 were also determined in grain ( 0.01 mg/kg in all samples) and straw ( mg/kg). Ratio of SDS-3701 and parent chlorothalonil in barley straw was calculated to be ~1:12 and in grain ~1:5. As supplementary information, the applicant reported 12 residue trials on wheat conducted in Northern Europe. Eight of these trials were evaluated in the DAR and four of the trials have been submitted for the evaluation under this application. In four of the wheat trials residues of SDS-3701 were also determined in grain (<0.01 mg/kg in all four trials) and straw ( mg/kg). 10

11 The residue trials are summarised in Table 3-1. Modification of the existing MRLs for chlorothalonil in barley and several food Samples of wheat and barley were stored frozen (at <-18 C) for a maximum of 9 and 13 months, respectively. The storage stability of chlorothalonil in dry matrices was investigated in the framework of the peer review. At 18 C chlorothalonil residues are stable in wheat straw for 2 years and in wheat grain for 1 year. According to the EMS the residue trials data are valid with regard to analytical performance and the storage stability. EFSA also derived the MRL proposal for chlorothalonil in cereal straw by combining the data from wheat and barley trials since residues were in the same range. A MRL of 15 mg/kg would be required for straw if in the future MRLs will be established for feed items. Moreover, EFSA considered the SDS-3701 residues in the straw and derived the MRL proposal of 2 mg/kg. From the submitted data a MRL proposal of 0.3 mg/kg for chlorothalonil in barley would be required to accommodate the intended use. 11

12 Table 3-1. Overview of the available residues trials data Commodity Region (a) Outdoor /Indoor Individual trial results Enforcement Risk assessment STMR (b) HR (c) MRL proposal Median CF (d) Comments Residue definition for the risk assessment and enforcement: chlorothalonil Barley grain NEU O 3 x <0.01; 0.02; 0.03; 0.05; 0.08; 0.09; 0.11; 0.17; 0.23 Barley straw NEU O 0.2; 0.22; 0.97; 1.5; 1.9; 2.4; 3.7; 4.1; 5.0; 6.1; 13 Wheat straw NEU O 0.28; 0.75; 1.6; 2.2; 2.5; 2.8; 2.9; 3.8; 5; 7.1; 11; 16 Wheat grain NEU O 7 x <0.01; 2 x 0.02; 0.04; 0.05; 0.07 Metabolite SDS x <0.01; 0.02; 0.03; 0.05; 0.08; 0.09; 0.11; 0.17; ; 0.2; 0.22; 1.5; 1.9; 2.4; 3.7; 4.1; 5.0; 6.1; ; 0.75; 1.6; 2.2; 2.5; 2.8; 2.9; 3.8; 5; 7.1; 11; 16 7 x <0.01; 2 x 0.02; 0.04; 0.05; R ber = 0.22 mg/kg R max = 0.28 mg/kg R ber combined =10 mg/kg R max combined =13.8 mg/kg Barley grain NEU O 3 x <0.01; x <0.01; Wheat grain NEU O 4 x < x <0.01 <0.01 < Indicative MRL proposal to be considered if MRLs have to be established for feed items. Barley straw NEU O 0.04; 0.12; 0.34; ; 0.12; 0.34; R ber combined =1.43 mg/kg R maxcombined =1.95 mg/kg Wheat straw NEU O 0.02; 2 x 0.1; ; 2 x 0.1; Indicative MRL proposal to be considered if MRLs have to be established for feed items. Currently no valid analytical methods and the storage stability studies of SDS-3701 are available. (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. 12

13 Effect of industrial processing and/or household preparation Nature of residues The RMS in the framework of Article 12 (2) of Regulation (EC) No 396/2005 reported a study investigating the nature of chlorothalonil under conditions simulating pasteurisation, baking/brewing/boiling and sterilisation (The Netherlands, 2009). No degradation was observed at ph 4 and 90 C, but at ph 5 and 100 C some degradation occurred (the only degradation product was SDS-3701accounting for 19% AR). During incubation at ph 6 and 120 C in acetate buffer, significant degradation occurred, and degradation products were SDS-3701 (59% AR) and SDS (15% AR). Under similar conditions, but incubating in citrate buffer, degradation of chlorothalonil was almost complete and in addition to SDS-3701 (38% AR) and SDS (23%AR) a third compound was identified as 4-amino-2,5,6-trichloroisophtalonitrile (28% AR), This was explained as an artefact not formed by direct hydrolysis but as a result of using the ammonium citrate salt in the buffer solution. Chlorothalonil was stable under conditions simulating pasteurisation, but showed increased degradation under conditions simulating baking/brewing/boiling and sterilisation. Degradation products under conditions simulating baking/brewing/boiling and sterilisation, respectively, were SDS-3701 (19% and 59% AR) and SDS (3.4% and 15% AR). EFSA recommends investigating the need for the inclusion of metabolites SDS-3701 and possibly SDS in the residue definition for processed commodities in the framework of the comprehensive MRL review of chlorothalonil according to Article 12 (2) of Regulation (EC) No 396/2005. Magnitude of residues A processing study with barley is available. Barley samples were taken from field trials having been treated with chlorothalonil (2 x 3 kg a.s./ha (3N), 35 d PHI). Barley was further processed into pot barley and beer. Barley and processed fractions were then analysed for chlorothalonil, SDS-3701 and SDS The field samples contained 0.9 mg/kg of chlorothalonil and 0.06 mg/kg of metabolite SDS Residues of SDS in all raw barley samples were <0.01 mg/kg. The barley grain prior processing were stored in an ambient temperature for 2 months and afterwards cleaning and threshing the amount of chlorothalonil in samples accounted for 0.46 mg/kg, indicating that chlorothalonil concentrations were significantly reduced, whereas the concentrations of SDS-3701 had increased (~0.22 mg/kg in the sample). Barley and processed fractions before analyses were stored -18 C for a period for up to 22 months for chlorothalonil and SDS-3701 and for 12 months for SDS The results of the processing study are presented in Table SDS-19221: 3-cyano-2,4,5,6-tetrachlorobenzamide 13

14 Table 3-2. Overview of the available processing studies Processed commodity Number of studies Median PF (a) Median CF (b) Comments Chlorothalonil Barley grain, beer 4 < The residues of chlorothalonil in all beer samples were below the LOQ of 0.01 mg/kg. Barley grain, pot barley SDS-3701 Barley grain, beer 4 < The residues of SDS-3701 in all beer samples were below the LOQ of 0.01 mg/kg. Barley grain, pot barley (a): The median processing factor is obtained by calculating the median of the individual processing factors of each processing study. (b): The median conversion factor for enforcement to risk assessment is obtained by calculating the median of the individual conversion factors of each processing study. Results indicate no concentration of residues in the relevant processing products of barley. It can be concluded that for the intended GAP, no significant concentrations of chlorothalonil or SDS-3701 are expected in beer or in pot barley. Derived processing factors for barley are not recommended for the inclusion in Annex VI of Regulation (EC) No 396/2005 since the storage stability of SDS-3701 and SDS should be further addressed Rotational crops Preliminary considerations The rate of degradation of chlorothalonil in soil was investigated under the peer review of Directive 91/414/EEC (The Netherlands, 2004). Laboratory studies (aerobic conditions) indicate that the DT 90lab value for chlorothalonil accounts for a maximum of 287 days. According to field studies the maximum DT 90f value for chlorothalonil is 300 days. In soil chlorothalonil yields two metabolites which are more persistent than parent: SDS-3701 with a maximum DT 90 value of 1132 days (derived as extrapolation form DT 50 value) and R with a maximum DT 90 value of 818 days (derived as extrapolation form DT 50 value). Considering the above mentioned a possible occurrence of chlorothalonil residues in rotational crops has to be investigated. 7 R417888: 2-amido-3,5,6-trichloro-4-cyanobenzenesulfonic acid Cl Cl CONH 2 Cl COOH 14

15 Nature of residues Modification of the existing MRLs for chlorothalonil in barley and several food The nature of chlorothalonil in rotational crops was investigated under the peer review of Directive 91/414/EEC in a confined study with wheat, carrots and lettuce as well as in various field studies conducted with snap beans, spinach, peanuts, cucumbers, tomatoes, potatoes, soybean and broccoli (The Netherlands, 2004). In this confined study a 14 C-labelled chlorothalonil was applied on a bare soil with an application rate of 9.6 mg a.s./kg. After aging the soil, subsamples of soil were transferred to fibre planting pots. Wheat and carrots were sown and lettuce was planted 30 and 88 DAT. The mature plants were then used to characterize and quantify the TRR. The major identified metabolite was 3-carboxy-2,5,6- trichloro benzamide (SDS-46851) (partly present in a conjugated form, almost 25% of total soil residues) which accounted for up to 2 mg chlorothalonil eq./kg in lettuce at 30 DAT and 0.4 mg eq./kg at 88 DAT, up to 0.63 and 1.1 mg eq./kg in carrot roots and tops respectively, as well as 16.5 mg eq./kg and 33.1 mg eq./kg in wheat grain and straw, respectively. The parent compound accounted for 11% and 5% of the TRR in the soil at the relevant treatment days (30 and 88 days). Other soil metabolites (including SDS-3701) were also identified, but accounted for less than 10% of the total soil residue. Also in crops small amounts of SDS-3701 were identified: <0.1 mg eq./kg lettuce, <0.05 mg eq./kg carrot root, 6.3 mg eq./kg wheat straw and <0.5 mg eq./kg in wheat grain. SDS-3701 was mainly present in conjugated form. The results of the field studies confirm the results form the confined study that the major residue in rotational crops is metabolite SDS with only small amounts of SDS 3701 detected. Parent chlorothalonil in most cases were below the LOQ. The detailed results of the field studies are reported in the section The peer review decided that, based on the data on metabolites in plant products and in view of the information from toxicological studies, the residue for plant products has to be defined as the parent compound chlorothalonil only, although parent compound was found in significantly lower concentrations than SDS It is also important to note that hexachlorobenzene (HCB), a highly persistent organic pollutant, occurs as a manufacturing impurity to chlorothalonil. The maximum level of permissible impurity according to Directive 91/414/EEC is 0.01 g/kg/a.s. When released into soil, HCB is strongly adsorbed to organic matter and is generally considered immobile with respect to leaching. Its half-life value in soils is estimated to be in the range of 3-6 years. HCB is significantly bioaccumulated in both terrestrial and aquatic food chains (EFSA, 2006). Thus, residues of HCB may occur in crops that have been treated with chlorothalonil in the past Magnitude of residues The field studies were carried out in the USA. The active substance was applied 8 times at an application rate of 2.5 kg a.s./ha on a bare soil (7 day interval between applications). Wheat, carrots, snap beans and spinach were planted 14, 30, 60 and 90 DAT and 1 year after the last application. Mature crops were analysed for the TRR. Results were as follows: 1)Study 1. No residues of parent compound were identified in the rotational crops. The major residue in rotational crops was metabolite SDS which in all crops at all rotation intervals accounted for >0.1 mg/kg (except at lower levels in samples at 1 year rotation interval). The highest SDS residues were detected in wheat straw mg/kg at 60 DAT. Metabolite SDS-3701 was the main soil metabolite and was also identified in rotational crop samples. In spinach SDS-3701 residues ranged from 0.02 mg/kg (14 DAT) to 0.19 mg/kg (90 DAT). No residues above the LOQ of 0.01 mg/kg were identified in snap beans and wheat grain at all rotation intervals. In carrot roots and tops and in wheat straw the residues of SDS-3701 did not account for more than 0.04 mg/kg. 15

16 2) Study 2. No parent compound was identified in the rotational crops. Metabolite SDS-3701 was the major residue identified in spinach and wheat straw samples, accounting for a maximum of 0.04 mg/kg (60 DAT) and 0.02 mg/kg (372 DAT), respectively. SDS was the major residue compound in snap beans (max 0.74 mg/kg (60 DAT)), carrot roots (max 0.02 mg/kg in all DAT intervals) and carrot tops (max 0.04 mg/kg (30 DAT)). No residues were detected in wheat grain in the only analyzed sample (372 DAT). 3) Study 3. The parent compound was not detected in the crop samples. SDS was the major residue identified in wheat grain (max 0.06 (372 DAT) and straw (0.37 (372 DAT)) and in snap beans (max 0.03 mg/kg). SDS-3701 was the major residue in spinach (max 0.05 mg/kg (60 DAT)). Another field study is available performed by applying the active substance on a wide range of primary crops (potatoes, peanuts, cucumbers, tomatoes, potatoes, broccoli, soybeans) at an application rates ranging from 1.3 to 2.6 kg a.s./ha with an number of applications ranging from 3 to 11. After the harvest of the primary crops, rotational crops were planted at various rotation intervals. Considering the wide range of the available data, EFSA focused only on those studies which were performed with a comparable GAP as intended on barley in the United Kingdom. The field study with the primary crop soybean (treated with chlorothalonil 3 x 1.7 kg a.s./ha) indicate that in the rotational crop rice the residues of parent and its metabolites SDS-3701 and SDS will be below the LOQ. A field study with peanuts as a primary crop (application of chlorothalonil 6 x 1.3 kg a.s./ha), indicate that residues on metabolites SDS-3701 and SDS will be below the LOQ of 0.01 mg/kg and the LOQ of 0.03 mg/kg in rotational crops cotton seed, corn, sorghum, wheat grain and collards. Results from this study indicate that parent chlorothalonil would account for a maximum of 0.03 mg/kg in sorghum (392 d PHI) and 0.01 mg/kg in collards (286 d PHI). Generally, the data from all other field studies available indicate that the major residue in rotational crops is metabolite SDS-46851; metabolite SDS-3701 was the highest in pea fodder (0.07 mg/kg, 351 d PHI), but in other crops it was at or below 0.04 mg/kg. Rotational crops did not contain residues of parent chlorothalonil of levels exceeding 0.03 mg/kg, except in peanut vines (0.22 mg/kg (PHI 376 d)), pea fodder (0.06 mg/kg (351 d PHI)) and bean hay (0.09 mg/kg, PHI 374 d)). Considering the available data, EFSA concludes, that significant residues of chlorothalonil and its metabolites (SDS and SDS-3701) are not expected in rotational crops grown in crop rotation after primary crops treated with chlorothalonil at the application rate of 1 kg a.s./ha. It has to be noted that, considering the wide range of authorized uses of chlorothalonil, it cannot be excluded that due to a crop failure or because of higher application rates, the residues of SDS may occur in rotational crops and enter the food chain either from plant or from animal commodities. There is no data available on the metabolism of SDS in livestock. However, because of low toxicological relevance of SDS-46851, the experts in the peer review decided not to include it in the residue definition Nature and magnitude of residues in livestock Dietary burden of livestock Barley and its by products are used as livestock feeding items for dairy and meat ruminants, pigs and poultry according to EU Guidance document on the livestock feeding studies (European Commission, 1996). The median and maximum dietary burdens were calculated for the different types of livestock using to the agreed European methodology (European Commission, 1996). A first indicative livestock exposure to chlorothalonil residues was assessed taking into account the expected residues in barley grain and straw according to the intended use. The input values were as derived from the supervised residue field trials (Table 3-1). The results of the dietary burden calculation are presented in Table 3-3. From this calculation it is evident that the trigger value of 0.1 mg/kg DM for the livestock dietary burden is exceeded for ruminants. 16

17 Table 3-3. Results of the livestock exposure to chlorothalonil residues form the intake of barley grain and straw Chlorothalonil Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Dairy ruminants Barley straw 3.26 Yes Meat ruminants Barley straw 8.13 Yes Poultry Barley grain 0.05 No Pigs Barley grain 0.06 No Since data are available on the SDS-3701 levels present in barley and wheat grain and straw, EFSA performed another dietary burden calculation estimating the livestock exposure to SDS-3701 residues from the intake of cereals. These data are summarized in Table 3-4. The input values for SDS-3701 were used as derived from the residue trials (Table 3-1). From this calculation it is evident that the trigger value of 0.1 mg/kg DM is slightly exceeded for ruminants. Table 3-4. Results of the livestock exposure to SDS-3701 residues from the intake of barley grain and straw SDS-3701 Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Dairy ruminants Barley straw 0.33 Yes Meat ruminants Barley straw 0.82 Yes Poultry Wheat grain 0.01 No Pigs Wheat grain 0.01 No EFSA is of the opinion that the livestock dietary burden calculation cannot be limited to the livestock intake of barley only, because there are more feed crops in which residues of chlorothalonil may occur (apples, head cabbage, wheat, rye, oats and sugar beet), therefore EFSA performed an overall livestock dietary burden calculation (Table 3-6) for which the following assumptions were made: - for the wheat and rye bran the processing factor of 5 was applied as derived from the wheat processing studies reported in the DAR. For apples pomace the default processing factor of 2.5 was applied to the residues in apple; - the residues of SDS-3701 in barley and wheat grain and straw were also considered in the dietary burden calculation being expressed as parent chlorothalonil by applying the molecular weight conversion factor of In other crops it was assumed that no residues of SDS-3701 are present; - EFSA has no information on the authorized uses of chlorothalonil on sugar beets in the Europe and therefore the MRL was used instead of the STMR and HR values. The input values for the overall dietary burden calculation are given in the Table

18 Table 3-5. Input values for the dietary burden calculation Commodity Median dietary burden Maximum dietary burden Input value Comment Chlorothalonil and SDS-3701, expressed as chlorothalonil Pome fruit pomace 0.5 STMR*PF (The Netherlands, 2006) Head cabbage 0.25 STMR (The Netherlands, 2006) Input value Comment 0.5 STMR*PF (The Netherlands, 2006) 2.53 HR (The Netherlands, 2006) Barley grain STMR STMR Barley straw 2.65 STMR HR Wheat, rye grain 0.02 STMR (The United Kingdom, 2009) Wheat, rye bran 0.1 STMR*PF (5) (The Netherlands,2004) Wheat, rye straw 2.96 STMR (The United Kingdom, 2009) 0.02 STMR (The United Kingdom, 2009) 0.1 STMR*PF (5) (The Netherlands,2004) HR (The United Kingdom, 2009) Sugar beet 0.5 MRL 0.5 MRL Table 3-6. Results of the overall dietary burden calculation (including all feed crops) Chlorothalonil Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Dairy ruminants Sugar beets Yes Meat ruminants Wheat straw Yes Poultry Sugar beets 1.45 Yes Pigs Sugar beets 4.23 Yes Results of the overall livestock dietary burden calculation indicate a significant livestock exposure to chlorothalonil residues for all livestock species. It is noted that for all livestock, except meat ruminants, the main contributing commodity are sugar beets. Since for sugar beets only the MRL values is available, which leads to an overestimation in the dietary burden calculation, EFSA performed an impact assessment, performing the calculation without sugar beets (Table 3-7). Table 3-7. Results of the dietary burden calculation (excluding sugar beets) Chlorothalonil Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Dairy ruminants Wheat straw Yes 18

19 Maximum dietary burden (mg/kg bw/d) Median dietary burden (mg/kg bw/d) Highest contributing commodity Max dietary burden (mg/kg DM) Trigger exceeded? Meat ruminants Wheat straw Yes Poultry Cabbage 0.95 Yes Pigs Cabbage 2.76 Yes When excluding sugar beets form the dietary burden calculation, results indicate that the trigger value of 0.1 mg /kg DM is still exceeded for all livestock species. This means that a consideration has to be given to possible residues in all food. Currently the EC MRLs for the food of animal origin are set at the LOQ of 0.01 mg/kg according to Regulation (EC) No 396/ Nature of residues The nature of chlorothalonil and its metabolite SDS-3701 in livestock was investigated in the peer review of Directive 91/414/EEC in lactating goats and laying hens (The Netherlands, 2004). Lactating goats Lactating goats were administered 8 daily doses of 6 or 60 mg 14 C-chlorothalonil in a capsule (0.115 and 1.15 mg/kg bw/d). The majority of the radioactivity was excreted via faeces (61-63% TRR) and urine (~7% TRR). At sacrifice not more that % of the dose was recovered from each edible organ. The residue levels in milk were mg eq./kg and mg eq./kg in the low and high dose study, respectively. The non-extractable fraction in milk accounted for up to mg/kg in the high dose study. Highest total residues were detected in kidneys (0.22 and 2.2 mg eq./kg in low and high dose study), followed by liver ( mg eq./kg in low and high dose study) and muscle and fat (<0.01 and 0.03 mg eq./kg respectively in both dose groups). Parent chlorothalonil was not detected in milk and edible tissue samples (<0.01 mg/kg). SDS-3701 was the only identified metabolite of chlorothalonil in goat milk and tissue samples. In the high dose group, SDS-3701 levels were < mg/kg in milk (25% of the TRR), mg/kg in liver (10% of the TRR), and mg/kg in kidneys (3% of the TRR). No other compounds were identified. Considerable levels of unidentified residues were detected in milk, liver and kidney. In liver, between 17-37% of the residue was organosoluble and 20-30% of this fraction consisted of multiple non-polar residue. Between 21 and 31% of the total liver residue was watersoluble, presumably representing mono-, di-, triglutathione conjugates. Between 30 and 45% of the liver residue remained not extracted. The levels of unidentified residues in liver from low and high dose were <0.01 and 0.1mg/kg in the organosoluble fraction, 0.02 and 0.2 mg//kg in the watersoluble fraction and 0.03 and 0.3 mg/kg in the not extracted fraction. The watersoluble residues mainly consisted of protein bound and smaller conjugated residue compounds. It was noted that some of them, also glutathione conjugates are expected to exceed 0.01 mg/kg at high dose administration. In the second study, lactating goats were administered 9 daily doses at 0.4 and 4 mg of 14 C-labelled SDS-3701 in a capsule ( and mg/kg bw/d). Radiolabel excreted via urine accounted for 6-10% of total label and the amount excreted via faeces for 17-19%. Between 13-23% of the TRR was excreted via milk. Total residue levels in milk reached plateau in 5 to 7 days and accounted up to 0.15 and 1.0 mg eq./kg for the low and high dose group, respectively. Highest total residues were detected in kidneys ( and mg eq./kg for the low and high dose group, respectively), followed by liver (0.07 and mg eq./kg, respectively) and muscle and fat ( and mg eq./kg in the low and high does groups, respectively). Over 90% of the total residue in milk 19