Modification of the existing MRLs for captan in certain stone fruits 1

Transcription

1 EFSA Journal 2011;9(4):2151 REASONED OPINION Modification of the existing MRLs for captan in certain stone fruits 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy SUMMARY In accordance with Article 6 of Regulation (EC) No 396/2005, Austria, herewith referred as the evaluating Member State (EMS), received an application from Makhteshim Agan and Arysta LifeScience to modify the existing MRLs for the active substance captan in plums and pome fruits. In order to accommodate for the intended uses of captan the EMS proposed to raise the existing MRL from the value of 1 mg/kg to 7 mg/kg on plums and to maintain the existing MRL of 3 mg/kg on pome fruits. Austria 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 25 October In accordance with Article 6 of Regulation (EC) No 396/2005, France, herewith referred as the evaluating Member State (EMS), received an application from Makhteshim Agan and Arysta LifeScience to modify the existing MRLs for the active substance captan on peaches and apricots. In order to accommodate for the intended uses of captan, the EMS proposed to raise the existing MRLs from the limit of quantification value of 0.02 mg/kg (peaches) and the value of 3 mg/kg (apricots) to the value of 4 mg/kg for monitoring the residues expressed as captan. France 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 1 December Considering that both applications refer to the modification of existing MRLs for captan, to optimise the evaluation work, EFSA addressed the MRL applications in one reasoned opinion. EFSA derives the following conclusions based on the submitted evaluation reports prepared by Austria and France, the Commmission review report on captan, the EFSA conclusion prepared in the framework of the peer review, the Draft Assessment Report (DAR) and its addenda prepared by the rapporteur Member State (RMS) Italy under Directive 91/414/EEC as well as the JMPR report on captan. The toxicological profile of captan was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.1 mg/kg bw/day and an ARfD of 0.3 mg/kg bw. The metabolism of captan in primary crops was investigated in apples and the peer review concluded to establish the residue definition for risk assessment and enforcement as the sum of captan and tetrahydrophthalimide (THPI), expressed as captan for the group of fruits and fruiting vegetables. 1 On request from the European Commission, Question No EFSA-Q and EFSA-Q , issued on 27 2 April Correspondence: praper.mrl@efsa.europa.eu Suggested citation: European Food Safety Authority; Modification of the existing MRLs for captan in certain stone fruits. EFSA Journal 2011;9(4):2151. [31 pp.] doi: /j.efsa Available online: European Food Safety Authority, 2011

2 For the use on the crops under consideration, which belong to the tested crop group, EFSA concludes that the metabolism of captan is sufficiently elucidated and no further studies are necessary. The current residue definition for most plant products, including plums, peaches and apricots, reported in Regulation (EC) No 396/2005 is the parent compound captan. EFSA therefore, will derive MRL proposals according to the existing (captan) and peer review (sum of captan and THPI, expressed as captan) residue definition. The latter MRLs to be taken into account if the residue definition is amended in the framework of the comprehensive review under Article 12(2) of the above cited Regulation. The submitted supervised residue trial data indicate that a higher MRL of 7 mg/kg for plums and of 4 mg/kg for peaches, including nectarines and apricots according to the enforcement residue definition as captan would be required in order to accommodate for the intended uses of captan on these stone fruits. Should the enforcement residue definition be revised to take into account the contribution of the metabolite THPI to the total residues, the derived MRLs are 8 mg/kg for plums and of 5 mg/kg for peaches, incl. nectarines and apricots. Sufficiently validated analytical methods for enforcing all compounds given in the residue definition for food are available. The studies investigating the effect of processing on the nature of captan residues demonstrated that under core processing conditions the compound is almost completely converted into THPI. Therefore, EFSA proposes as residue definition for enforcement and risk assessment in processed commodities the sum of captan and tetrahydrophthalimide (THPI), expressed as captan. Among the submitted processing studies on plums, peaches and apricots, the following processing factors for processed peaches could be derived and are recommended for inclusion in Annex VI of Regulation (EC) No 396/2005. Peaches, nectar: 0.06 Peaches, puree: 0.14 Peaches, jam: 0.07 Peaches, canned: 0.09 Since the intended uses of captan assessed in this reasoned opinion are on permanent crops, investigations of residues in rotational crops are not required. Residues of captan in commodities of animal origin were not assessed, since the products under consideration are normally not fed to livestock. The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). For the calculation of the chronic exposure, EFSA used the median residue values as derived from the residue trials on plums, peaches and apricots according to the broader residue definition sum of captan and THPI, expressed as captan. For the remaining commodities of plant and animal origin, the existing MRLs as established in Annexes II and IIIB of Regulation (EC) No 396/2005 were used as input values. To take into account the contribution of THPI to the consumer dietary exposure, the existing MRLs for pome fruits, cherries, strawberries and tomatoes were multiplied by the conversion factor (CF) for enforcement residue definition to risk assessment residue definition derived from the supervised residue trials submitted by the RMS in the context of the post- Annex I inclusion procedure. In absence of specific CF, the remaining crops for which the MRL is above the LOQ were multiplied by 4, which represents the rounded value of the highest CF derived from the available residue data on plants. The acute exposure assessment was performed only with regard to the commodities under consideration using the broader residue definition. The estimated exposure was then compared with the toxicological reference values. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 7 to 75 % of the ADI. No acute consumer risk was identified in relation to the MRL proposals for the crops under consideration. The EFSA Journal 2011;9(4):2151 2

3 calculated maximum exposure in percentage of the ARfD was 73.5 % for plums, 66.3 % for peaches, including nectarines, and 34.6 % for apricots. Consequently, EFSA concludes that the intended uses of captan on the stone fruit apricots, peaches, including nectarines and plums will not result in a consumer exposure exceeding the toxicological reference values and therefore will not pose a public health concern. Thus EFSA proposes to amend the existing MRLs as per the table below: Code Commodity Existing EU number MRL Proposed EU MRL Enforcement residue definition: captan (Regulation (EC) No 396/2005) Justification for the proposal Apricots 3 4 The MRL proposals are sufficiently Peaches (Nectarines and similar hybrids) 0.02* 4 supported by data and no risk for consumers was identified for the intended uses Plums (Damson, 1 7 The risk assessment was performed using greengage, the residue definition established during mirabelle) the peer review (sum of captan and THPI, expressed as captan). : According to Annex I of Regulation (EC) No 396/2005. (*): Indicates that the MRL is set at the limit of analytical quantification. In addition, EFSA also derived MRL proposals according to the enforcement residue definition established by the peer review, which shall be taken into account if the residue definition is amended in the framework of Article 12(2) of Regulation (EC) No 396/2005. Code number Commodity Existing EU MRL Proposed EU MRL Justification for the proposal Enforcement residue definition: sum of captan and THPI, expressed as captan (EFSA, 2009) Apricots 3 5 The MRL proposals are sufficiently Peaches (Nectarines and similar 0.02* 5 supported by data and no risk for hybrids) Plums (Damson, greengage, mirabelle) 1 8 consumers was identified for the intended uses. : According to Annex I of Regulation (EC) No 396/2005. (*): Indicates that the MRL is set at the limit of analytical quantification. KEY WORDS Captan, plums, peaches, apricots, MRL application, Regulation (EC) No 396/2005, consumer risk assessment, phthalimide, tetrahydrophthalimide (THPI). EFSA Journal 2011;9(4):2151 3

4 TABLE OF CONTENTS Summary... 1 Table of contents... 4 Background... 5 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 Consumer risk assessment Conclusions and recommendations References Appendix A. Good Agricultural Practices (GAPs) Appendix B. Pesticide Residues Intake Model (PRIMo) Appendix C. Existing EU maximum residue limits (MRLs) Appendix D. Estimation of conversion factors for risk assessment Abbreviations EFSA Journal 2011;9(4):2151 4

5 BACKGROUND Regulation (EC) No 396/ 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 Council Directive 91/414/EEC 4, 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. Austria, hereafter referred to as the evaluating Member State (EMS), received an application from the companies Makhteshim Agan 5 and Arysta LifeScience SAS 6 to modify the existing MRLs for the active substance captan in pome fruits and plums. This application was notified to the European Commission and EFSA and subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. France, hereafter referred to as the evaluating Member State (EMS), received an application from the above cited applicants to modify the existing MRLs for the active substance captan in apricots and peaches, including nectarines. 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 reports of the EMSs were submitted to the European Commission who forwarded the applications, the evaluation reports and the supporting dossiers to EFSA on 25 October and 1 December The applications were included in the EFSA Register of Questions with the reference numbers EFSA-Q and EFSA-Q and the following subjects: Captan - Application to modify the existing MRLs in various crops. Captan - Application to modify the existing MRLs in apricots and peaches. Austria proposed to modify the existing MRL of captan for plums from 1 mg/kg to 7 mg/kg and to maintain unchanged the existing MRL of 3 mg/kg on pome fruits, while France is proposing to raise the existing MRLs for peaches (incl. nectarines) and apricots from the limit of quantification (LOQ) of 0.02 mg/kg (peaches) and the value of 3 mg/kg (apricots) to 4 mg/kg. Austria and France also derived MRL proposals for plums, peaches (nectarines) and apricots based on the residue definition established in the framework of the peer review under Directive 91/414/EEC, namely the sum of captan and THPI 7, expressed as captan. In this case, the MRL proposals are 8 mg/kg for plums and 5 mg/kg for peaches and apricots. EFSA then proceeded with the assessment of the application as required by Article 10 of the Regulation. 3 Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February OJ L 70, , p Council Directive 91/414/EEC of 15 July OJ L 230, , p Makhteshim Agan International Coordination Center, Edmund-Rumpler Straße, Box 7, D Köln, Germany. 6 Arysta LifeScience SAS, Rte. d'artix, BP 80, F Nogueres, France. 7 THPI: 1,2,3,6-tetrahydrophthalimide. Molecular weight: g/mol. O NH O EFSA Journal 2011;9(4):2151 5

6 TERMS OF REFERENCE In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the evaluating Member State, provide a reasoned opinion on the risks to the consumer associated with the application. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within three months (which may be extended to six months where more detailed evaluations need to be carried out) from the date of receipt of the application. Where EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. In this particular case the calculated deadlines for providing the reasoned opinion are 27 January 2011 and 1 March EFSA Journal 2011;9(4):2151 6

7 THE ACTIVE SUBSTANCE AND ITS USE PATTERN Captan is the ISO common name for N-(trichloromethylthio)cyclohex-4-ene-1,2-dicarboximide (IUPAC). The chemical structure of the compound is herewith reported. O NSCCl 3 O Molecular weight: g/mol Captan is a contact fungicide belonging to class of phthalimides, such as folpet and captafol. Captan acts as a multi-site inhibitor, however, the precise nature of action is still unclear. It exerts protective and curative action against a broad range of fungi in fruits, vegetables and ornamental crops. Captan is an active substance which was evaluated according to Directive 91/414/EEC with Italy designated as rapporteur Member State (RMS). It was included in Annex I of this Directive by Commission Directive 2007/5/EC 8 which entered into force on 1 October 2007 for use as fungicide only. The representative use evaluated in the peer review for the Annex I inclusion was the foliar application on tomatoes. The Draft Assessment Report (DAR) of captan was peer reviewed by EFSA. The conclusion finalised on April 2006 has been amended in the section of mammalian toxicology and residue according to the outcome of experts meetings and an updated EFSA conclusion, which is replacing the previous version, has been issued (EFSA, 2009). The EU MRLs for captan are established in Annexes II and IIIB of Regulation (EC) No 396/2005 (Appendix C). The residue definition for enforcement in plant products reported in Regulation 396/2005 is captan or for certain crops the sum of captan and folpet (pome fruits, strawberries, blackberries, raspberries, currants, gooseberries, tomatoes, beans with and without pods), reflecting the residue definition established in the past by Council Directive 76/895/EEC 9. The proposal to lower the MRLs for celery, chervil, spinach and parsley was recently voted at the February 2011 meeting of the Standing Committee on the Food Chain and Animal Health (SCFCAH) because captan use on these crops has been revoked. Codex Alimentarius has established CXLs for several commodities, including plums, peaches and nectarines for which the CXLs are set at 10 mg/kg, 20 mg/kg and 3 mg/kg, respectively. The peer review under Council Directive 91/414/EEC concluded to establish a residue definition for enforcement and risk assessment in fruits and fruiting vegetables as sum of captan and tetrahydrophthalimide (THPI), expressed as captan (EFSA, 2009). The residue definition amendment shall be addressed in the framework of the comprehensive review under Article 12(2) of Regulation (EC) No 396/2005. The intended GAPs for which a modification of the existing MRLs is requested in Hungary, Romania, United Kingdom (plums), in Italy, Portugal, Greece and Spain (peaches, nectarines, apricots) and France (peaches, nectarines) refer to foliar applications on the crops under consideration of a 800 g/kg captan water dispersible granule formulation. The PHI for the crops under concerns is 21 days. The details of the GAPs are given in Appendix A. 8 Commission Directive 2007/5/EC of 7 February OJ L L 35, , p Council Directive 76/895/EEC of 23 November OJ L 340, , p EFSA Journal 2011;9(4):2151 7

8 ASSESSMENT EFSA bases its assessment on the evaluation report submitted by the EMSs (Austria, 2010; France, 2010), the Draft Assessment Report (DAR) and its addenda prepared in the framework of Council Directive 91/414/EEC (Italy, 2003, 2005) and in the context of post-annex I inclusion procedure (Italy, 2010), the Commission Review Report on captan (EC, 2008), the conclusion on the peer review of the pesticide risk assessment of the active substance captan (EFSA, 2009) and the JMPR Evaluation report (FAO, 2001). 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 Council Directive 91/414/EEC and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (EC, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2004, 2010, 2011; OECD, 2007, 2011a). 1. Methods of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of captan residues in plant commodities were assessed in the DAR and in the conclusion on the peer review under Directive 91/414/EEC (Italy, 2003; EFSA, 2009). Validated methods using capillary gas chromatography with electron capture detection (GC- ECD) are available to determine captan on high water matrices at a LOQ of 0.01 mg/kg in apples, pears, peaches, nectarines and tomatoes or with electrolytic conductivity detection (GC-ELCD) or GC-ECD at LOQ from 0.02 to 0.05 mg/kg in apples, tomatoes and processed tomato fractions. The multi-residue QuEChERS method described in the European Standard EN 15662:2008 is also applicable. The capillary gas chromatography equipped with mass spectrum detection (GC-MSD) method analyses captan residues in matrices with high water content at the LOQ of 0.02 mg/kg (CEN, 2008). For the determination of THPI the peer reviewed GC-NPD method with a LOQ of 0.02 mg/kg was not considered adequate to monitor the residues according to the recommended enforcement residue definition for food (EFSA, 2009). The analytical method using GC-MSD evaluated in the framework of one of the MRL modification applications has been validated on apples and tomatoes and fits for the purpose of monitoring THPI residues on high water content commodities at a LOQ of 0.01 mg/kg (Austria, 2010). A multi-residue method to analyse THPI residues was not provided. Since the commodities under consideration belong to the group of high water content commodities, EFSA concludes that sufficiently validated analytical methods for enforcing all compounds given in the residue definition for food are available Methods for enforcement of residues in food of animal origin Analytical methods for the determination of residues in food of animal origin are not evaluated in the current assessment, since the crops under consideration are normally not fed to livestock. EFSA Journal 2011;9(4):2151 8

9 2. Mammalian toxicology The toxicological profile of the active substance captan was assessed in the framework of the peer review under Directive 91/414/EEC. The data were sufficient to derive toxicological reference values for captan (EC, 2008) which are compiled in Table 2-1. Table 2-1: Overview of the toxicological reference values Captan Source Year Value Study relied upon Safety factor ADI EC mg/kg bw/d teratogenicity study in rabbits 100 ARfD EC mg/kg bw teratogenicity study in rabbits 100 For the metabolite THPI, which was observed in primary crops and was extensively formed in processed commodities produced with a heating step, the available toxicological data were not sufficient to conclude on its toxicological non relevance. Therefore the peer review established, as a worst case scenario, that the toxicological reference values agreed for captan apply to the metabolite as well (EFSA, 2009). 3. Residues 3.1. Nature and magnitude of residues in plant Primary crops Nature of residues The metabolism of captan on lettuce, tomatoes and apples was evaluated in the framework of the peer review under Directive 91/414/EEC (Italy, 2003, 2005; EFSA, 2009). The overview of the metabolism study designs is presented in the table below. Table 3-1: Summary of available metabolism studies in plants Group Crop Label position Fruits and fruiting vegetable apples tomatoes [Carbonyl- 14 C] captan [Trichloro methyl- 14 C] captan [Cyclohexe ne-1,2-14 C] captan Application details Method, Rate No F or G (Interval) Foliar, F 0.12 kg a.s./ hl Foliar, G 4.48 kg a.s./ha 1 2 (30 d) 3 (30-31 d) 4 (7 d) Sampling 0.3 DAT 20 DALA 0.13 DALA Remarks Samples: fruit (peel, pulp), surface wash Supportive. Samples: leaves, stern, fruits EFSA Journal 2011;9(4):2151 9

10 Group Crop Label position Leafy vegetables lettuce [Trichloro methyl- 14 C] captan [Cyclohexe ne-1,2-14 C] captan Application details Method, Rate No F or G (Interval) Foliar, G 4.48 kg a.s./ha : Outdoor/field use (F) or glasshouse/protected crops/indoor application (G). 4 (7 d) Sampling 0.13 DALA Remarks Supportive. Samples: leaves The results of the metabolism studies and the pattern of degradation were similar in all tested crops with most of the residues remaining on the plant or fruit surface. The studies on lettuce and tomatoes provided only supportive information, because the samples were analysed at the very short harvest time of three hours after the last application of the substance. However in the study on apples the sampling was carried out at 20 days after the last application, so the results provided realistic information. After foliar applications to apple trees, fruits collected at harvest lost about 90 % of the pesticide residues with washing. Captan formed the major part of residues (50-70 % of the TRR). Several metabolites were identified, among them THPI showed the highest amounts, even if less than 10 % of the TRR (ca. 5 % in fruit wash and 1.5 % of TRR in peel and pulp). The other identified metabolites were present at lower levels. The proposed metabolic pathway involved a cleavage of the N-S bond to form THPI, which is further metabolised to form THPAM 10, epoxidation to form THPI epoxide 11 and ring opening. During the peer review, after extensive discussion, the experts concluded that THPI should be considered to have the same toxicological profile of captan, unless differently proven, and agreed to establish the residue definition for enforcement and risk assessment as sum of captan and THPI, expressed as captan (EFSA, 2009). However the RMS, Italy, was and is still of the opinion that THPI is not a toxicological relevant metabolite and has recently presented argumentations and data to support its exclusion from the residue definition (Italy, 2010). For the use on the crops under consideration, which belong to the group of fruits and fruiting vegetables, EFSA concludes that the metabolism of captan is sufficiently elucidated. It is noted that the residue definition for enforcement is currently established in plant commodities as captan, except for pome fruits, strawberries, blackberries, raspberries, currants, gooseberries, tomatoes, beans with and without pods, where it is the sum of captan and folpet. The residue definition established by the peer review shall be addressed for amendment in the framework of the comprehensive review under Article 12(2) of the above cited Regulation. By the time, EFSA will use for the consumer risk assessment the residue definition as sum of captan and THPI expressed as captan, based on the assumption that THPI has the same toxicological properties as the parent compound. 10 THPAM: cis/trans-6-carbamoyl-3-cyclohexene-1 carboxylic acid. CONH 2 11 THPI epoxide: 7-oxabicyclol(2.2.1)-heptane-2,3-dicarboximide. COOH O O NH O EFSA Journal 2011;9(4):

11 Magnitude of residues Modification of the existing MRLs for captan in certain stone fruits Supervised field trials on plums, peaches, nectarines and apricots were submitted in support to the MRL applications. The samples were analysed for both captan and its metabolite THPI. EFSA assessed these trials in view of proposing tmrls according to the residue definition reported in Regulation 396/2005 (parent compound). In addition, EFSA derived MRL proposals according to the residue definition established by the peer review (sum of captan and THPI, expressed as captan) which shall be taken into account if the enforcement residue definition is amended in the framework of Article 12(2) of Regulation (EC) No 396/2005. a. Plums A total of sixteen supervised residue trials on plums reflecting the proposed GAPs was performed in the northern (NEU) and southern (SEU) European regions over two seasons. Part of them was designed as decline studies. At harvest, the residue levels ranged from 0.02 to 5.8 mg/kg for captan and from <0.02 to 0.47 mg/kg for THPI. In two studies the residue value was higher at a longer PHI (28 d) and therefore EFSA has used the values from this data point for deriving the MRL proposal. The data are sufficient to derive a MRL proposal according to the existing and the residue definition recommended under the peer review. Since the residue levels measured in the NEU trials were higher than the levels obtained from the SEU trials, the MRL of 7 mg/kg is derived according to the residue definition as captan from the NEU trials and covers also the residues which may occur in plums following the proposed higher application rate in SEU. A slightly higher MRL of 8 mg/kg is derived using the residue definition as sum of captan and THPI, expressed as captan. b. Peaches, including nectarines, apricots The applicant proposed to modify the existing MRLs on peaches, including nectarines and to extrapolate the residue data to apricots by means of eight supervised residue trials performed on peaches and nectarines in SEU already submitted during the peer review (Italy, 2003) and three supervised residue trials on apricots (France, 2010). All trials were performed according to a use pattern which is comparable between the crops (4 x 3 kg a.s/ha ± 25 %, interval 14 d; PHI 21 d). At harvest, the residue levels ranged from 0.43 to 2.2 mg/kg for captan and from 0.02 to 0.7 mg/kg for THPI. The data are sufficient to derive a MRL proposal of 4 mg/kg for peaches, including nectarines and to extrapolate it to apricots. Noteworthy is that due to the recent revision of the EU guidance document on extrapolation, at least four supervised residue trials on apricots are nowadays required (EC, 2011). A slightly higher MRL of 5 mg/kg is derived for the residue definition as sum of captan and THPI, expressed as captan. No supervised residue trials were performed reflecting the GAP on peaches and nectarines envisaging four applications of the active substance pre-flowering (4 x 3.6 kg a.s./ha; interval 10 d) and four applications at a lower rate from flowering to development of fruits (4 x 1.8 kg a.s./ha; interval 10/7 d) with the PHI of 21 days. As the number of applications prior to flowering is generally of lesser importance for the residue behaviour in the harvested crops, the proposed alternative use should represent a less critical situation (EC, 2011), so the residue trials cover this use as well. The results of the residue trials, the related risk assessment input values (highest residue, median residue) and the MRL proposals expressed according to the existing enforcement residue definition as captan are summarized in Table 3-2. In the following table (Table 3-3) the values are derived according to the residue definition established by the peer review (sum of captan and THPI, expressed as captan). EFSA Journal 2011;9(4):

12 The storage stability of captan and its metabolite in primary crops was assessed during the peer review under Directive 91/414/EEC (Italy, 2003). Residues of captan and THPI were found to be stable at -20 C for up to 9 months in apple and tomato matrices, when stored entire or coarsely ground. As the supervised residue trial samples were stored under conditions for which integrity of the samples was demonstrated and within this period, it is concluded that the residue data are valid with regard to storage stability (Austria, 2010; France, 2010). According to the EMSs, the analytical methods used to analyse the supervised residue trial samples, which were basically the same as proposed for post-registration monitoring, have been sufficiently validated and provided reliable results (Austria, 2010; France, 2010). In conclusion, EFSA considers that the data are sufficient and adequate to derive the MRL proposal of 7 mg/kg for plums and of 4 mg/kg for peaches, including nectarines and apricots for the intended use of captan according to the enforcement residue definition as captan. Should the enforcement residue definition be revised to take into account the contribution of the metabolite THPI to the total residues, the derived MRLs are 8 mg/kg for plums and of 5 mg/kg for peaches, nectarines and apricots. EFSA Journal 2011;9(4):

13 Table 3-2: Overview of the available residues trials data and MRL proposals according to the existing enforcement RD (Regulation (EC) No 396/2005). Commodity Region Outdoor/I ndoor Individual trial results Enforcement RD (captan) Enforcement residue definition: captan (Regulation No 396/2005) Plums NEU Outdoor 0.2; 0.61; 0.63; 0.68; 0.79; 0.93; 1.6 (e) ; 5.8 Peaches, nectarines apricots SEU Outdoor 0.02; 0.13; 2 x 0.17; 0.4; 0.43; 0.57; 0.67 SEU Outdoor Peaches: 0.56; 0.66; 1.7; 2.2 Nectarines: 0.43; 0.62; 0.90; 1.5 Apricots: 0.78; 1.56; 1.97 Risk assessment RD (sum of captan and THPI, expressed as captan) 0.32; 0.93; 0.99; 1.07 (e) ; 1.3; 1.42; 2.08 (e) ; ; 2 x 0.21; 0.27; 0.48; 0.93; 0.97; ; 0.67; 0.84; 1.02; 1.06; 1.34; 1.66; 1.88; 2.21; 2.53; 3.59 Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments Results from SEU trials showed a less critical residue situation. NEU: R ber = 2.87 R max = 7.2 OECD MRL= 9 SEU: R ber = 1.07 R max = 1.06 OECD MRL= Results were pooled as belonging to similar population according to the Kruskal-Wallis H- test (FAO, 2009). R ber = 3.40 R max = 2.94 OECD MRL= 4 : 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 residue trial. The sum of captan and THPI was obtained after molecular weight adjustment (THPI x 1.99 or /151.16). (e): The highest value measured at a longer PHI (28 d) was used as data point. EFSA Journal 2011;9(4):

14 Table 3-3: Overview of the available residues trials data and MRL proposals according to the enforcement RD established during the peer review. Commodity Region Outdoor/I ndoor Individual trial results Enforcement RD ((sum of captan and THPI, expressed as captan) Risk assessment RD (sum of captan and THPI, expressed as captan) Enforcement residue definition: sum of captan and THPI, expressed as captan (EFSA, 2009) Plums NEU Outdoor 0.32; 0.93; 0.99; 1.07 (e) ; 1.3; 1.42; 2.08 (e) ; 6.7 Peaches, nectarines apricots [THPI: 0.06; 0.14 (e) ; 0.15; 0.19; 0.2; 0.24 (e) ; 0.37; 0.47] SEU Outdoor 0.16; 2 x 0.21; 0.27; 0.48; 0.93; 0.97; 1.05 [THPI: 2 x <0.02; 0.04; 2 x 0.07, 0.13; 0.2; 0.31] SEU Outdoor 0.65; 0.67; 0.84; 1.02; 1.06; 1.34; 1.66; 1.88; 2.21; 2.53; 3.59 [THPI: peaches: 0.02; 0.23; 0.41; 0.7; nectarines: 2 x 0.11; 0.19; 0.22; apricots: 0.05; 0.12; 0.14] 0.32; 0.93; 0.99; 1.07 (e) ; 1.3; 1.42; 2.08 (e) ; ; 2 x 0.21; 0.27; 0.48; 0.93; 0.97; ; 0.67; 0.84; 1.02; 1.06; 1.34; 1.66; 1.88; 2.21; 2.53; 3.59 Median residue (b) Highest residue (c) MRL proposal Median CF (d) Comments Results from SEU trials showed a less critical residue situation. NEU R ber = 3.83 R max = 8.30 OECD MRL= 10 SEU R ber = 1.92 R max = 1.76 OECD MRL= Results were pooled as belonging to similar population according to the Kruskal-Wallis H- test (FAO, 2009). R ber = 4.15 R max = 4.42 OECD MRL= 6 : 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 residue trial. The sum of captan and THPI was obtained after molecular weight adjustment (THPI x 1.99 or /151.16). (e): The highest value measured at a longer PHI (28 d) was used as data point. EFSA Journal 2011;9(4):

15 Effect of industrial processing and/or household preparation The effect of processing on the nature of captan residues was investigated in studies performed at three test conditions representing pasteurization, baking/brewing/boiling and sterilization (20 minutes at 90 C, ph 4; 60 minutes at 100 C ph 5; 20 minutes at 120 C, ph 6). The studies were submitted in the framework of these MRL modification applications (Austria, 2010; France, 2010). Under the representative processing conditions the compound was almost completely converted into tetrahydrophthalimide (THPI). THPI was hydrolytically stable under conditions representing pasteurization, backing, boiling/brewing, but showed to be slightly unstable under sterilization conditions, forming degradation products at individual amount up to 11.4 % AR. The studies demonstrated that for processed commodities the residue definition shall take into account the occurrence of the metabolite THPI. Therefore EFSA proposes to set the residue definition for enforcement and risk assessment in processed products as sum of captan and tetrahydrophthalimide (THPI), expressed as captan. Noteworthy is that JMPR that established a residue definition for raw agricultural Commodities (RAC) as captan, is also considering the relevant contribution of THPI in processed products (FAO, 2001). The magnitude of residues in processed plums, peaches and apricots was investigated in follow-up studies and assessed by the EMSs (Austria, 2010; France, 2010). The samples for the studies were obtained from the supervised residue trials. Captan and its metabolite were analysed in both RAC and processed commodities. In processed products captan was found only in one sample (dry apricot), while the metabolite THPI was determined in all tested samples. Among the submitted processing studies on plums, peaches and apricots, the number of trials was sufficient to derive processing factors only for processed peaches. Since the residue definition for enforcement is currently different, the median conversion factors for enforcement to risk assessment obtained from the results of the supervised residue trials (see Table 3-2) may be used in order to monitor the compliance with the RAC MRL. All studies were considered valid with regard to the applied analytical methods and the storage stability, with the exception of THPI specimen in one of the three studies on apricots (France, 2010). The median processing factors for commodities for human consumption are summarized in Table 3-4. Table 3-4: Overview of the available processing studies Processed commodity Number of studies Median PF Median CF (b) Individual trial results Enforcement residue definition: captan (Regulation (EC) No 396/2005) Peaches, nectar ; 0.07; 0.05; 0.07 Peaches, cooked puree ; 0.17; 0.13; 0.15 Peaches, jam ; 0.07; 0.07; 0.09 Peaches, canned ; 0.11; 0.07; 0.09 Apricots, puree ; 0.57; 1.24 (c) Insufficient No. of studies. Plums, puree ; 0.92; 1.06 Insufficient No. of studies. : 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 from the results of the supervised residue trials (see Table 3-2). (c): Storage stability for THPI is not covering the period during which the trial sample was stored. EFSA Journal 2011;9(4):

16 EFSA concludes that the following processing factors for processed peaches could be derived and are recommended for inclusion in Annex VI of Regulation (EC) No 396/2005. Peaches, nectar: 0.06 Peaches, puree: 0.14 Peaches, jam: 0.07 Peaches, canned: Rotational crops Since the proposed use of captan is on permanent crops, investigations of residues in rotational crops are not required (OECD, 2007) Nature and magnitude of residues in livestock Since the crops under consideration are not normally fed to livestock, the nature and magnitude of captan residues in livestock is not assessed (EC, 1996). EFSA Journal 2011;9(4):

17 4. Consumer risk assessment The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). This exposure assessment model contains the relevant European food consumption data for different sub-groups of the EU population 12 (EFSA, 2007). For the calculation of the chronic exposure, EFSA used the median residue values as derived from the residue trials on plums, peaches, nectarines and apricots according to the broader residue definition sum of captan and THPI, expressed as captan (see Table 3-3). For the remaining commodities of plant and animal origin, the existing MRLs as established in Annexes II and IIIB of Regulation (EC) No 396/2005 were used as input values. To take into account the contribution of THPI to the consumer dietary exposure, the existing MRLs for pome fruits, cherries, strawberries and tomatoes were multiplied by the conversion factor (CF) for enforcement residue definition (captan) to risk assessment residue definition (sum of captan and THPI, expressed as captan) derived from the supervised residue trials submitted by the RMS in the context of the post-annex I inclusion procedure (Italy, 2010). In absence of specific CF, the remaining crops for which the MRL is above the LOQ (almonds, blackberries, raspberries, gooseberries, currants, mangos, potatoes, carrots, celeriac, peppers, melons, scarole, beans with/without pods and leek) were multiplied by 4, which represents the rounded value of the highest CF derived from the available residue data on plants. Anyway, the model assumptions for the long-term exposure assessment are considered to be rather conservative, assuming that all food items consumed have been treated with the active substance under consideration. In reality, it is not likely that all food consumed will contain residues at the MRL or at levels of the median residue values identified in supervised field trials. However, if this first tier exposure assessment, does not exceed the toxicological reference value for long-term exposure (i.e. the ADI), a consumer health risk can be excluded with a high probability. The acute exposure assessment was performed considering the broader residue definition only with regard to the commodities under consideration assuming the consumption of a large portion of the food items as reported in the national food surveys containing residues at the highest level as observed in supervised field trials. In addition, when required, a variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation. The input values used for the dietary exposure calculation are summarized in Table 4-1. Table 4-1: Input values for the consumer dietary exposure assessment Commodity Chronic exposure assessment Acute exposure assessment Input value Comment Input value Comment Risk assessment residue definition: sum of captan and THPI, expressed as captan (EFSA, 2009) Plums 1.19 Median residue (NEU, see Table 3-3) 6.7 Highest residue (NEU, see Table 3-3) Peaches, nectarines 1.34 Median residue 3.59 Highest residue Apricots 1.34 (see Table 3-3) 3.59 (see Table 3-3) 12 The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22 national diets collected from MS surveys plus 1 regional and 4 cluster diets from the WHO GEMS Food database; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collected from MS surveys is used. The complete list of diets incorporated in EFSA PRIMo is given in its reference section (EFSA, 2007). EFSA Journal 2011;9(4):

18 Commodity Chronic exposure assessment Acute exposure assessment Input value Cherries 7.25 (5*1.45) Pome fruits 4.44 (3*1.48) Strawberries 6.27 (3*2.09) Tomatoes 6.04 (2*3.92) Almonds 1.2 (0.3*4) Blackberries, Raspberries, Gooseberries, Currants Mangoes, Scarole, Beans with/without pods, Leek 12 (3*4) 8 (2*4) Potatoes 0.2 (0.05*4) Carrots, Celeriac, Pepper, Melons Other commodities of food and animal origin 0.4 (0.1*4) MRL Comment MRL*CF (see Appendix D) MRL*CF (see Appendix D ) MRL*CF (see Appendix D ) MRL*CF (see Appendix D) MRL*CF (4) MRL*CF (4) MRL*CF (4) MRL*CF (4) MRL*CF (4) See Appendix C Input value Comment Acute risk assessment was undertaken only with regard to the products for which a MRL proposal is requested. The estimated exposure was then compared with the toxicological reference values derived for captan (see Table 2-1). The results of the intake calculation are presented in Appendix B to this reasoned opinion. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 7 to 75 % of the ADI. The contribution of the residues in the crops under consideration to the total consumer exposure accounted for a maximum of 0.5 % of the ADI (DE child diet) for apricots and of 0.76 % and 0.37 % (IE adult diet) for peaches and plums, respectively. No acute consumer risk was identified in relation to the MRL proposals for the crops under consideration. The calculated maximum exposure for children and adults in percentage of the ARfD was 73.5 % and 21 % for plums, 66.3 % and 19.5 % for peaches, including nectarines, and 34.6 % and 8.5 % for apricots. Consequently, EFSA concludes that the intended uses of captan on the stone fruit apricots, peaches, including nectarines and plums will not result in a consumer exposure exceeding the toxicological reference values. EFSA Journal 2011;9(4):

19 CONCLUSIONS AND RECOMMENDATIONS CONCLUSIONS The toxicological profile of captan was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.1 mg/kg bw/day and an ARfD of 0.3 mg/kg bw. The metabolism of captan in primary crops was investigated in apples and the peer review concluded to establish the residue definition for risk assessment and enforcement as the sum of captan and tetrahydrophthalimide (THPI), expressed as captan for the group of fruits and fruiting vegetables. For the use on the crops under consideration, which belong to the tested crop group, EFSA concludes that the metabolism of captan is sufficiently elucidated and no further studies are necessary. The current residue definition for most plant products, including plums, peaches and apricots, reported in Regulation (EC) No 396/2005 is the parent compound captan. EFSA therefore, will derive MRL proposals according to the existing (captan) and peer review (sum of captan and THPI, expressed as captan) residue definition. The latter MRLs to be taken into account if the residue definition is amended in the framework of the comprehensive review under Article 12(2) of the above cited Regulation. The submitted supervised residue trial data indicate that a higher MRL of 7 mg/kg for plums and of 4 mg/kg for peaches, including nectarines and apricots according to the enforcement residue definition as captan would be required in order to accommodate for the intended uses of captan on these stone fruits. Should the enforcement residue definition be revised to take into account the contribution of the metabolite THPI to the total residues, the derived MRLs are 8 mg/kg for plums and of 5 mg/kg for peaches, incl. nectarines and apricots. Sufficiently validated analytical methods for enforcing all compounds given in the residue definition for food are available. The studies investigating the effect of processing on the nature of captan residues demonstrated that under core processing conditions the compound is almost completely converted into THPI. Therefore, EFSA proposes as residue definition for enforcement and risk assessment in processed commodities the sum of captan and tetrahydrophthalimide (THPI), expressed as captan. Among the submitted processing studies on plums, peaches and apricots, the following processing factors for processed peaches could be derived and are recommended for inclusion in Annex VI of Regulation (EC) No 396/2005. Peaches, nectar: 0.06 Peaches, puree: 0.14 Peaches, jam: 0.07 Peaches, canned: 0.09 Since the intended uses of captan assessed in this reasoned opinion are on permanent crops, investigations of residues in rotational crops are not required. Residues of captan in commodities of animal origin were not assessed, since the products under consideration are normally not fed to livestock. The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). For the calculation of the chronic exposure, EFSA used the median residue values as derived from the residue trials on plums, peaches and apricots according to the broader residue definition sum of captan and THPI, expressed as captan. For the remaining commodities of plant and animal origin, the existing MRLs as established in Annexes II and IIIB of Regulation (EC) No 396/2005 were used as input values. To take into account the contribution of THPI to the consumer dietary exposure, the existing MRLs for pome fruits, cherries, strawberries and tomatoes were EFSA Journal 2011;9(4):

20 multiplied by the conversion factor (CF) for enforcement residue definition to risk assessment residue definition derived from the supervised residue trials submitted by the RMS in the context of the post- Annex I inclusion procedure. In absence of specific CF, the remaining crops for which the MRL is above the LOQ were multiplied by 4, which represents the rounded value of the highest CF derived from the available residue data on plants. The acute exposure assessment was performed only with regard to the commodities under consideration using the broader residue definition. The estimated exposure was then compared with the toxicological reference values. No long-term consumer intake concerns were identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated intake values ranged from 7 to 75 % of the ADI. No acute consumer risk was identified in relation to the MRL proposals for the crops under consideration. The calculated maximum exposure in percentage of the ARfD was 73.5 % for plums, 66.3 % for peaches, including nectarines, and 34.6 % for apricots. Consequently, EFSA concludes that the intended uses of captan on the stone fruit apricots, peaches, including nectarines and plums will not result in a consumer exposure exceeding the toxicological reference values and therefore will not pose a public health concern. RECOMMENDATIONS Code Commodity Existing EU number MRL Proposed EU MRL Enforcement residue definition: captan (Regulation (EC) No 396/2005) Justification for the proposal Apricots 3 4 The MRL proposals are sufficiently Peaches (Nectarines and similar hybrids) 0.02* 4 supported by data and no risk for consumers was identified for the intended uses Plums (Damson, 1 7 The risk assessment was performed using greengage, the residue definition established during mirabelle) the peer review (sum of captan and THPI, expressed as captan). : According to Annex I of Regulation (EC) No 396/2005. (*): Indicates that the MRL is set at the limit of analytical quantification. In addition, EFSA also derived MRL proposals according to the enforcement residue definition established by the peer review, which shall be taken into account if the residue definition is amended in the framework of Article 12(2) of Regulation (EC) No 396/2005. Code number Commodity Existing EU MRL Proposed EU MRL Justification for the proposal Enforcement residue definition: sum of captan and THPI, expressed as captan (EFSA, 2009) Apricots 3 5 The MRL proposals are sufficiently Peaches (Nectarines and similar 0.02* 5 supported by data and no risk for hybrids) Plums (Damson, greengage, mirabelle) 1 8 consumers was identified for the intended uses. : According to Annex I of Regulation (EC) No 396/2005. (*): Indicates that the MRL is set at the limit of analytical quantification. EFSA Journal 2011;9(4):