Reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate‐methyl
2021; Wiley; Volume: 19; Issue: 8 Linguagem: Inglês
10.2903/j.efsa.2021.6773
ISSN1831-4732
AutoresGiulia Bellisai, Giovanni Bernasconi, Alba Brancato, Luis Carrasco Cabrera, Lucien Ferreira, German Giner, Luna Greco, Samira Jarrah, Aija Kazocina, Renata Leuschner, José Oriol Magrans, Ileana Miron, Stéfanie Nave, Ragnor Pedersen, Hermine Reich, Silvia Ruocco, Miguel Santos, Alessia Pia Scarlato, Anne Theobald, Bénédicte Vagenende, Alessia Verani,
Tópico(s)Genetically Modified Organisms Research
ResumoEFSA JournalVolume 19, Issue 8 e06773 Reasoned OpinionOpen Access Reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate-methyl European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) pesticides.mrl@efsa.europa.eu Correspondence:pesticides.mrl@efsa.europa.euSearch for more papers by this authorGiulia Bellisai, Giulia BellisaiSearch for more papers by this authorGiovanni Bernasconi, Giovanni BernasconiSearch for more papers by this authorAlba Brancato, Alba BrancatoSearch for more papers by this authorLuis Carrasco Cabrera, Luis Carrasco CabreraSearch for more papers by this authorLucien Ferreira, Lucien FerreiraSearch for more papers by this authorGerman Giner, German GinerSearch for more papers by this authorLuna Greco, Luna GrecoSearch for more papers by this authorSamira Jarrah, Samira JarrahSearch for more papers by this authorAija Kazocina, Aija KazocinaSearch for more papers by this authorRenata Leuschner, Renata LeuschnerSearch for more papers by this authorJose Oriol Magrans, Jose Oriol MagransSearch for more papers by this authorIleana Miron, Ileana MironSearch for more papers by this authorStefanie Nave, Stefanie NaveSearch for more papers by this authorRagnor Pedersen, Ragnor PedersenSearch for more papers by this authorHermine Reich, Hermine ReichSearch for more papers by this authorSilvia Ruocco, Silvia RuoccoSearch for more papers by this authorMiguel Santos, Miguel SantosSearch for more papers by this authorAlessia Pia Scarlato, Alessia Pia ScarlatoSearch for more papers by this authorAnne Theobald, Anne TheobaldSearch for more papers by this authorBenedicte Vagenende, Benedicte VagenendeSearch for more papers by this authorAlessia Verani, Alessia VeraniSearch for more papers by this author European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) pesticides.mrl@efsa.europa.eu Correspondence:pesticides.mrl@efsa.europa.euSearch for more papers by this authorGiulia Bellisai, Giulia BellisaiSearch for more papers by this authorGiovanni Bernasconi, Giovanni BernasconiSearch for more papers by this authorAlba Brancato, Alba BrancatoSearch for more papers by this authorLuis Carrasco Cabrera, Luis Carrasco CabreraSearch for more papers by this authorLucien Ferreira, Lucien FerreiraSearch for more papers by this authorGerman Giner, German GinerSearch for more papers by this authorLuna Greco, Luna GrecoSearch for more papers by this authorSamira Jarrah, Samira JarrahSearch for more papers by this authorAija Kazocina, Aija KazocinaSearch for more papers by this authorRenata Leuschner, Renata LeuschnerSearch for more papers by this authorJose Oriol Magrans, Jose Oriol MagransSearch for more papers by this authorIleana Miron, Ileana MironSearch for more papers by this authorStefanie Nave, Stefanie NaveSearch for more papers by this authorRagnor Pedersen, Ragnor PedersenSearch for more papers by this authorHermine Reich, Hermine ReichSearch for more papers by this authorSilvia Ruocco, Silvia RuoccoSearch for more papers by this authorMiguel Santos, Miguel SantosSearch for more papers by this authorAlessia Pia Scarlato, Alessia Pia ScarlatoSearch for more papers by this authorAnne Theobald, Anne TheobaldSearch for more papers by this authorBenedicte Vagenende, Benedicte VagenendeSearch for more papers by this authorAlessia Verani, Alessia VeraniSearch for more papers by this author First published: 23 August 2021 https://doi.org/10.2903/j.efsa.2021.6773 Requestor: European Commission Question number: EFSA-Q-2020-00751 Declarations of interest: The declarations of interest of all scientific experts active in EFSA's work are available at https://ess.efsa.europa.eu/doi/doiweb/doisearch. Acknowledgement: EFSA wishes to thank Stathis Anagnos, Laszlo Bura, Andrea Mioč, Marta Szot, Aikaterini Vlachou for the support provided to this scientific output. Approved: 5 July 2021 AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract In compliance with Article 43 of Regulation (EC) No 396/2005, EFSA received from the European Commission a mandate to provide its reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate-methyl. Specifically, EFSA was asked to assess whether thiophanate-methyl or carbendazim have clastogenic potential and, in case clastogenic potential can be excluded, to derive toxicological reference values necessary for consumer risk assessment and assessment of maximum residue levels (MRLs). Although these active substances are no longer authorised within the European Union, MRLs were established by the Codex Alimentarius Commission (codex maximum residue limits; CXLs), and import tolerances are in place. Based on the assessment of the available data, toxicological reference values and MRL proposals were derived and a consumer risk assessment was carried out. Some information required by the regulatory framework was found to be missing and a possible acute risk to consumers was identified. Hence, the consumer risk assessment is considered indicative only, all MRL proposals derived by EFSA still require further consideration by risk managers and measures for reduction of the consumer exposure should also be considered. Summary Carbendazim was firstly included in Annex I to Directive 91/414/EEC in 2006 by Commission Directive 2006/135/EC. After the first approval, EFSA published in 2009 a reasoned opinion on the refined risk assessment regarding certain MRLs of concern for the active substance. Carbendazim was then evaluated by EFSA during the peer review for renewal of approval in 2010, in the framework of Commission Regulation (EC) No 1107/2009. On 10 May 2011, the approval of carbendazim was renewed by Commission Directive 2011/58/EU. Following the renewal of the approval, EFSA published two reasoned opinions, including the one on the review of the all existing MRLs in compliance with Article 12(2) of Regulation (EC) No 396/2005. On 11 March 2015, carbendazim was included in the list of candidates for substitution by Commission Implementing Regulation (EU) 2015/408, due to its classification as toxic for reproduction category 1B, in accordance with the provisions of Regulation (EC) No 1272/2008. Carbendazim is also classified as mutagenic category 1B. In 2019, the European Chemicals Agency (ECHA) published several opinions from the Biocidal Products Committee (BPC) for carbendazim as product types 7 (P7; film preservatives), 9 (P9; fibre, leather, rubber and polymerised materials preservatives) and 10 (P10; construction material preservatives). Carbendazim is currently not approved in the European Union for uses as pesticide. Thiophanate-methyl was firstly included in Annex I to Directive 91/414/EEC in 2005 by Commission Directive 2005/53/EC. After the first approval, EFSA published several reasoned opinions on the assessment and modification of the existing maximum residue levels (MRLs) for thiophanate-methyl, including the assessment of all the existing MRLs in compliance with Article 12(2) of Regulation (EC) No 396/2005. The active substance was then evaluated by EFSA during the peer review for renewal of approval in 2018, in the framework of Commission Regulation (EC) No 1107/2009 and according to Commission Implementing Regulation (EU) No 844/2012. On 15 October 2020, the approval of the active substance thiophanate-methyl was not renewed by Commission Implementing Regulation (EU) 2020/1498. Thiophanate methyl is classified as mutagenic category 2 in accordance with the provisions of Regulation (EC) No 1272/2008 and proposed for classification as carcinogen category 2, based on the latest evaluation by ECHA Committee for risk assessment (RAC) under the classification and labelling (CLH) process (ECHA, 2019b). Through the different assessments, the two active substances presented clear aneugenic properties, while their clastogenic potential remained outstanding. It is noted that during the re-assessment of thiophanate-methyl under the EFSA pesticide peer review, evidence of clastogenicity was found for thiophanate-methyl and carbendazim. On the other hand, during the assessment by ECHA RAC in 2019 under classification and labelling scheme, which also included the assessment of further data that were not available at the time of the EFSA pesticide peer review, it was confirmed the aneugenic potential of thiophanate-methyl but not the clastogenic potential. Based on the above, on 13 November 2020, EFSA received from the European Commission a mandate to deliver, in accordance with Article 43 of Regulation (EC) No 396/2005, a reasoned opinion on the toxicological properties and maximum residue levels (MRLs) for the benzimidazole substances carbendazim and thiophanate-methyl. EFSA was asked to first assess whether thiophanate-methyl or carbendazim have clastogenic potential. In case clastogenic potential can be excluded, EFSA shall derive toxicological reference values necessary to perform consumer risk assessment and assessment of MRLs. The European Commission also asked EFSA to involve ECHA and the respective Rapporteur Member States (Germany for carbendazim and Sweden for thiophanate-methyl) in the assessment, and to consult with the EU Reference Laboratories for Residues of Pesticides on the achievable limits of analytical determination for benomyl, carbendazim and thiophanate-methyl in different matrices. Subsequent to the request from the European Commission, EFSA compiled a master list on genotoxicity studies available, based on the data submitted to EFSA during the pesticides peer review; to ECHA in the context of the CLH process (for thiophanate-methyl) and for the application for approval of carbendazim as active substance in biocidal products under Reg. (EU) No 528/2012; also including the pertinent studies suggested in the mandate from European Commission and a screening of the published literature available (PubMed). This master list (Appendix F), was further screened for studies relevant to assess the aneugenic and in particular the clastogenic potential of carbendazim and thiophanate-methyl. The studies identified as relevant to assess these endpoints (Appendices G for carbendazim and H for thiophanate-methyl) were discussed at the related EFSA experts meeting which was held on 15 January 2021. In the meantime, EFSA initiated the collection of data in order to gather the most up to date information to review the MRLs of carbendazim and thiophanate methyl. Considering that the two active substances are no longer approved for use as pesticides in EU, Member States (including the two RMSs) and the UK11 The United Kingdom withdrew from EU on 1 February 2020. In accordance with the Agreement on the Withdrawal of the United Kingdom from the EU, and with the established transition period, the EU requirements on data reporting also apply to the United Kingdom data collected until 31 December 2020'. were invited to submit by 25 January 2021 Good Agricultural Practices (GAPs) in non-EU countries for which GAPs for import tolerance (IT) are authorised. On the basis of the feedback received by Member States and the information submitted by the EU Reference Laboratories for Pesticides Residues (EURLs) and the conclusions derived by EFSA in the framework of Regulation (EC) No 1107/2009, EFSA completed the Pesticide Residues Overview File (PROFile) and prepared in May 2021 a draft reasoned opinion, which was circulated to Member States, ECHA and EURLs for consultation via a written procedure. Comments received by 14 June 2021 were considered during the finalisation of this reasoned opinion. The following conclusions are derived. The experts of the peer review experts meeting on mammalian toxicology agreed that by considering the new data available to ECHA RAC, the weight of evidence suggests that there is direct evidence in vitro that thiophanate-methyl is not clastogenic but aneugenic whereas there is indirect evidence in vivo that thiophanate-methyl is not clastogenic but aneugenic. The majority of experts agreed that the most suitable basis for setting the acceptable daily intake (ADI) and acute reference dose (ARfD) for thiophanate-methyl is the no observed adverse effect level (NOAEL) of 2 mg/kg body weight (bw) per day for maternal and developmental toxicity in the rabbit and applying an uncertainty factor of 100. The resulting ADI and ARfD is 0.02 mg/kg bw (per day). Regarding carbendazim, the experts agreed that the weight of evidence suggests that there is direct evidence in vitro and in vivo that carbendazim is not clastogenic but aneugenic and agreed to maintain previous ADI and ARfD of carbendazim of 0.02 mg/kg bw (per day). The metabolism of thiophanate-methyl and carbendazim in plants was investigated in primary crops. According to the results of the metabolism studies and the available toxicological studies, the residue definitions for enforcement and risk assessment can be proposed as 'thiophanate-methyl' and 'carbendazim', separately. A specific residue definition for rotational crops is not deemed necessary considering that only import tolerances were considered in the present assessment. These residue definitions are also applicable to processed commodities. Fully validated analytical methods are available for the separate enforcement of the proposed residue definitions in the main four matrices at the limit of quantification (LOQ) of 0.01 mg/kg. According to the EURLs this LOQ is achievable by using the QuEChERS method in routine analyses. Nevertheless, the EURLs highlighted that during routine analyses, benomyl degrades rapidly to carbendazim and therefore using routine methods is not possible to analyse separately for benomyl and carbendazim. Available residue trials data were considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under evaluation. Considering that homogenisation of samples leads to a drastically reduced storage stability, pending additional data to ensure that no degradation of thiophanate-methyl and carbendazim occurred in samples during storage, all the derived MRLs should be considered tentative only. Thiophanate-methyl and carbendazim are authorised for use on citrus fruits that might be fed to livestock. Livestock dietary burden calculations were therefore performed for different groups of livestock according to OECD guidance. Based on the uses reported in the framework of this assessment, significant exposure to thiophanate-methyl and to carbendazim are expected for cattle and swine only; therefore, the nature and magnitude of residues in animals was investigated only in these groups of livestock. The metabolism of thiophanate-methyl and carbendazim residues in livestock was investigated in lactating goats and cow at dose rate covering the maximum dietary burdens calculated in this review. For thiophanate-methyl, the residue definition for enforcement and risk assessment was proposed as parent 'thiophanate-methyl' only. For carbendazim, the relevant residue definition for enforcement in all animal matrices was set as the 'sum of carbendazim and 5-hydroxy-carbendazim, expressed as carbendazim'. The same residue definition also applies for risk assessment in muscle, fat, liver and kidney while an additional metabolite (4-hydroxy-carbendazim) is also included for risk assessment in milk. Available feeding studies performed with thiophanate-methyl and carbendazim demonstrated that no residues above the LOQ are expected in cattle milk and in cattle and swine tissues following their exposure to thiophanate-methyl and carbendazim and MRLs for these commodities can be established at the enforcement LOQ. Fully validated analytical methods using LC-MS/MS (QuEChERS) are available for the separate enforcement of thiophanate-methyl, carbendazim and 5-hydroxy-carbendazim at the LOQ of 0.01 mg/kg for each compound in all animal matrices. According to the EURLs, it is expected that this LOQ would be achievable for the separate enforcement of thiophanate-methyl and carbendazim during routine analyses. Moreover, the same LOQ is also valid for benomyl (measured as carbendazim). Analytical methods for the enforcement of 5-hydroxy-carbendazim are currently not available to the EURLs but according to the information shared during the MSC on the draft reasoned opinion they will perform validation experiments in animal matrices to provide LOQs for routine analysis. According to the EURLs the analytical standards for carbendazim, benomyl, thiophanate-methyl and 5-hydroxy-carbendazim are commercially available. Chronic and acute consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 3.1 of the EFSA PRIMo. For thiophanate-methyl, the highest chronic exposure was calculated for German child, representing 8% of the acceptable daily intake (ADI). With regard to the acute exposure, however, an exceedance of the ARfD was identified for oranges, grapefruits, mandarins and papaya, representing 314%, 186%, 140% and 106% of the ARfD, respectively. For carbendazim, the highest chronic exposure was calculated for Dutch toddler, representing 7% of the acceptable daily intake (ADI) while the highest acute exposure was calculated for mandarins, representing 84% of the ARfD. Furthermore, before proposing a refinement of the risk assessment, a combined acute risk assessment was performed summing the results from the acute risk assessment of thiophanate-methyl and carbendazim. According to this calculation, an exceedance of the ARfD was identified for oranges, grapefruits, mandarins, mangoes, papaya and lemons, representing 342%, 203%, 224%, 143%, 133% and 129% of the ARfD. It is, however, noted by EFSA that the approach followed for the combined exposure assessment leads to an overestimation of the exposure in lemons, mandarins and limes, where residues resulting from the use of carbendazim and thiophanate-methyl have been combined while co-occurrence of these residues is not expected to occur in practice for these three crops. A second (scenario EU2, reflecting option 1 in Table 1) and a third (scenario EU3, reflecting option 2 in Table 1) exposure calculation were therefore performed, considering possible fall-back GAPs and assuming that residues from the uses of carbendazim and thiophanate-methyl are not co-occurring in lemons. According to the results of the second calculation (scenario EU2), the highest acute exposure for thiophanate-methyl is calculated for limes, representing 48% of the ARfD, the highest acute exposure for carbendazim is calculated for mandarins, representing 84% of the ARfD and the highest combined acute exposure is calculated for mandarins, representing 84% of the ARfD. According to the results of the third calculation (scenario EU3), the highest acute exposure for thiophanate-methyl is calculated for lemons, representing 81% of the ARfD, the highest acute exposure for carbendazim is calculated for mandarins, representing 84% of the ARfD and the highest combined acute exposure is calculated for lemons, representing 88% of the ARfD. These calculations show that no risk for consumers is identified for lemons in case residues from the uses of carbendazim and thiophanate-methyl are not co-occurring. In order to perform a combined chronic risk assessment, results from the chronic risk assessment of thiophanate-methyl and results from the chronic risk assessment of carbendazim from the refined calculations were summed (scenario EU2 and EU3). This calculation has been done for the Dutch diet (toddler), the British diet (infant) and the French diet (toddler) being the diets with the highest estimated exposure. The highest chronic exposure for scenario EU2 was calculated for the Dutch diet (toddler), representing 10% of the ADI. The highest chronic exposure for scenario EU3 was calculated for the Dutch diet (toddler), representing 9% of the ADI. Based on these calculations, an acute risk to consumers was identified for the most critical GAPs for thiophanate-methyl on oranges, grapefruits, mandarins, mangoes and papaya and for lemons, if the residues from the uses of carbendazim and thiophanate-methyl are co-occurring. However, fall-back GAPs were identified for mandarins and lemons, for which a second (scenario EU2) and a third (scenario EU3) risk assessments did not indicate risk to consumers. For the remaining commodities, although some major uncertainties remain due to the data gaps identified, the indicative exposure calculation did not indicate a risk to consumers. Background Carbendazim was firstly included in Annex I to Directive 91/414/EEC22 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, 19.8.1991, p. 1–32. Repealed by Regulation (EC) No 1107/2009. in 2006 by Commission Directive 2006/135/EC33 Commission Directive 2006/135/EC of 11 December 2006 amending Council Directive 91/414/EEC to include carbendazim as active substance.OJ L 349, 12.12.2006, p. 37–41. . After the first approval, EFSA published a reasoned opinion on the refined risk assessment regarding certain MRLs of concern for the active substance (EFSA, 2009). Carbendazim was then evaluated by EFSA during the peer review for renewal of approval in the framework of Commission Regulation (EC) No 1107/200944 Regulation (EC) No 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, 24.11.2009, p. 1–50. in 2010 (EFSA, 2010). On 10 May 2011, the approval of carbendazim was renewed by Commission Directive 2011/58/EU55 Commission Directive 2011/58/EU of 10 May 2011 amending Council Directive 91/414/EEC to renew the inclusion of carbendazim as active substance.OJ L 122, 11.5.2011, p. 71–75. . Following the renewal of the approval, EFSA published two reasoned opinions, including the one on the review of the all existing MRLs in compliance with Article 12(2) of Regulation (EC) No 396/200566 Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. OJ L 70, 16.3.2005, p. 1–16. (EFSA, 2012, 2014). On 11 March 2015, carbendazim was included in the list of candidates for substitution Commission Implementing Regulation (EU) 2015/40877 Commission Implementing Regulation (EU) 2015/408 of 11 March 2015 on implementing Article 80(7) of Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market and establishing a list of candidates for substitution.OJ L 67, 12.3.2015, p. 18–22., due to its classification as toxic for reproduction category 1B, in accordance with the provisions of Regulation (EC) No 1272/200888 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006.OJ L 353, 31.12.2008, p. 1–1355.. Carbendazim is also classified as mutagenic 1B. In 2019, the European Chemicals Agency (ECHA) published several opinions from the Biocidal Products Committee (BPC) for carbendazim as product types 7 (P7; film preservatives), 9 (P9; fibre, leather, rubber and polymerised materials preservatives) and 10 (P10; construction material preservatives) (ECHA, 2019a,c,d). Carbendazim is currently not approved in the European Union for uses as pesticide. Thiophanate-methyl was firstly included in Annex I to Directive 91/414/EEC in 2005 by Commission Directive 2005/53/EC99 Commission Implementing Regulation (EU) No 844/2012 of 18 September 2012 setting out the provisions necessary for the implementation of the renewal procedure for active substances, as provided for in Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market.OJ L 252, 19.9.2012, p. 26–32. . After the first approval, EFSA published several reasoned opinions on the assessment and modification of the existing maximum residue levels (MRLs) for thiophanate-methyl, including the assessment of all the existing MRLs in compliance with Article 12(2) of Regulation (EC) No 396/2005 (EFSA, 2009, 2012, 2014). The active substance was then evaluated by EFSA during the peer review for renewal of approval in the framework of Commission Regulation (EC) No 1107/2009 and according to Commission Implementing Regulation (EU) No 844/20121010 Commission Directive 2005/53/EC of 16 September 2005 amending Council Directive 91/414/EEC to include chlorothalonil, chlorotoluron, cypermethrin, daminozide and thiophanate-methyl as active substances. OJ L 241, 17.9.2005, p. 51–56. in 2018 (EFSA, 2018a). On 15 October 2020, the approval of the active substance thiophanate-methyl was not renewed by Commission Implementing Regulation (EU) 2020/14981111 Commission Implementing Regulation (EU) 2020/1498 of 15 October 2020 concerning the non-renewal of approval of the active substance thiophanate-methyl, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market, and amending the Annex to Commission Implementing Regulation (EU) No 540/2011. C/2020/7017. OJ L 342, 16.10.2020, p. 5–7..Thiophanate methyl is classified as mutagenic category 2 in accordance with the provisions of Regulation (EC) No 1272/2008, and proposed for classification as carcinogen category 2, based on the latest evaluation by ECHA RAC under the classification and labelling (CLH) process (ECHA, 2019b). Through the different assessments, the two active substances presented clear aneugenic properties, while their clastogenic potential remained outstanding. It is noted that during the re-assessment of thiophanate-methyl under the EFSA pesticide peer review, evidence of clastogenicity was found for thiophanate-methyl and carbendazim. On the other hand, during the assessment by ECHA RAC in 2019 under classification and labelling scheme, which also included the assessment of further data that were not available at the time of the EFSA pesticide peer review, the aneugenic potential of thiophanate-methyl was confirmed but not the clastogenic potential. Based on the above, on 13 November 2020, EFSA received from the European Commission a mandate to deliver, in accordance with Article 43 of Regulation (EC) No 396/2005, a reasoned opinion on the toxicological properties and maximum residue levels for the benzimidazole substances carbendazim and thiophanate-methyl. EFSA was asked to first assess whether thiophanate-methyl or carbendazim have clastogenic potential. In case clastogenic potential can be excluded, EFSA shall derive toxicological reference values necessary to perform consumer risk assessment and set MRLs. European Commission also asked EFSA to involve ECHA and the respective Rapporteur Member States (Germany for carbendazim and Sweden for thiophanate-methyl) in the assessment, and consult with the EU Reference Laboratories for Residues of Pesticides on the achievable limits of analytical determination for benomyl, carbendazim and thiophanate-methyl in different matrices. Subsequent to the request from the European Commission, EFSA compiled a master list on genotoxicity studies available, based on the data submitted to EFSA during the pesticides peer review; to ECHA in the context of the CLH process (for thiophanate-methyl) and for the application for approval of carbendazim as active substance in biocidal products under Reg. (EU) No 528/20121212 Regulation (EU) No 528/2012 of the European Parliament and of the Council of 22 May 2012 concerning the making available on the market and use of biocidal products. OJ L 167, 27.6.2012, p. 1–123. ; including the pertinent studies suggested in the mandate from European Commission and a screening of the published literature available (PubMed). This master list (Appendix F) was screened for studies relevant to assess the aneugenic and in particular the clastogenic potential of carbendazim and thiophanate-methyl (EFSA, 2021a,b). The studies identified as relevant to assess these endpoints (Appendices G for carbendazim and H for thiophanate-methyl) were discussed at the related experts meeting which was held on 15 January 2021 (EFSA, 2021c). In the meantime, EFSA initiated on 10 December 2020 the collection of data in order to gather the most up to date information to review the MRLs thiophanate methyl and carbendazim. Considering that the two active substances are no longer approved for use in EU, Member States (including the RMSs) and the UK were invited to submit
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