European Food Safety Authority (EFSA)

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1 TECHNICAL REPORT APPROVED: 19 July 2017 doi: /sp.efsa.2017.en-1271 Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for clofentezine in light of confirmatory data Abstract European Food Safety Authority (EFSA) The European Food Safety Authority (EFSA) was asked by the European Commission to provide scientific assistance with respect to the risk assessment for an active substance in light of confirmatory data requested following approval in accordance with Article 6(1) of Directive 91/414/EEC and Article 6(f) of Regulation (EC) No 1107/2009. In this context EFSA s scientific views on the specific points raised during the commenting phase conducted with Member States, the applicant and EFSA on the confirmatory data and their use in the risk assessment for clofentezine are presented. The current report summarises the outcome of the consultation process organised by the rapporteur Member State the United Kingdom and presents EFSA s scientific views and conclusions on the individual comments received. European Food Safety Authority, 2017 Keywords: clofentezine, peer review, confirmatory data, risk assessment, pesticide, acaricide Requestor: European Commission Question number: EFSA-Q Correspondence: pesticides.peerreview@efsa.europa.eu EFSA Supporting publication 2017:EN-1271

2 Suggested citation: EFSA (European Food Safety Authority), Technical report on the outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for clofentezine in light of confirmatory data. EFSA supporting publication 2017:EN pp. doi: /sp.efsa.2017.en-1271 ISSN: European Food Safety Authority, 2017 Reproduction is authorised provided the source is acknowledged. 2 EFSA Supporting publication 2017:EN-1271

3 Summary Clofentezine was included in Annex I to Directive 91/414/EEC on 1 January 2009 by Commission Directive 2008/69/EC. Annex I to Directive 91/414/EEC was amended via Commission Directive 2010/39/EU to include a specific provision that the applicant was required to submit to the European Commission further studies on clofentezine relating to their toxicology and environmental risk assessment by 30 June Clofentezine has subsequently been deemed to be approved under Regulation (EC) No 1107/2009, in accordance with Commission Implementing Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011. In accordance with the specific provision, the applicant, Adama Agriculture BV, submitted an updated dossier in June 2012, which was evaluated by the designated rapporteur Member State (RMS), the United Kingdom, in the form of an addendum to the draft assessment report. In compliance with guidance document SANCO 5634/2009-rev.6.1, the RMS distributed the addendum to Member States, the applicant and EFSA for comments on 31 March The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 23 June EFSA added its scientific views on the specific points raised during the commenting phase in column 4 of the reporting table. The current report summarises the outcome of the consultation process organised by the RMS, the United Kingdom, and presents EFSA s scientific views and conclusions on the individual comments received. Clofentezine is the ISO common name for 3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine (IUPAC). The representative formulated product for the evaluation was Apollo 50 SC, a suspension concentrate (SC) containing 500 g/l clofentezine. The representative uses evaluated comprise foliar spraying to control Panonychus ulmi, Tetranychus spp. on pome fruit and stone fruit, on grapes, on strawberries and on ornamentals. The applicant submitted additional information on 2-chlorobenzonitrile ( 2-CBN AE F023666), 2-chlorobenzoic acid ( 2-CBA AE C500233, NC233), 2-chlorobenzoic acid (2- chlorobenzylidene) hydrazide ( Hydrazide-hydrazone AC C593600, FBC 93600) and 2- chlorobenzamide ( 2-CBZ AE F092117). The RMS did not consider these toxicologically relevant. The majority of Member States that commented on the confirmatory data considered that insufficient information is available to conclude on their toxicological profile. EFSA considered that available information on these does not satisfy the confirmatory data request. The submitted confirmatory data were not sufficient to perform a comprehensive consumer dietary risk assessment. Sufficient residue trials analysing for clofentezine and 2-chlorobenzonitrile (AE F023666) residues in apples/pears (NEU/SEU), plums (NEU/SEU), grapes (NEU/SEU) and strawberries (SEU, indoor) were not provided. Furthermore, information on the toxicity of 2-chlorobenzonitrile relevant for primary crops and processed commodities and on the toxicity of hydrazide-hydrazone (AE C593600) and 2-chlorobenzamide (AE F092117) identified as significant degradation products under standard hydrolysis conditions at processing were not provided. The respective magnitude of 2- chlorobenzonitrile, hydrazide-hydrazone and 2-chlorobenzamide in processed commodities of pome fruits, plums, grapes and strawberries was also not determined. The potential for groundwater exposure from the soil 2-chlorobenzoic acid and 2- chlorobenzonitrile was appropriately assessed using the FOCUS groundwater models and scenarios. For the representative uses assessed by the RMS, groundwater exposure for these two compounds above the parametric drinking water limit of 0.1 µg/l would not be expected when agreed EU endpoints for 2-chlorobenzoic acid from the EFSA conclusion for triflumuron were utilised as input in the modelling. The submitted confirmatory data were not sufficient to address the risk assessment for the dietary exposure of birds and wild mammals to the metabolite 2-chlorobenzonitrile. Furthermore, the risk assessment for the secondary poisoning of wild terrestrial vertebrates eating fish contaminated with the hydrazide-hydrazone (applicable to birds) and 2-chlorobenzonitrile (applicable to birds and mammals) could not be finalised. The submitted confirmatory data were sufficient to demonstrate that clofentezine pose a low risk to aquatic organisms, soil macro-organisms and soil micro-organisms. 3 EFSA Supporting publication 2017:EN-1271

4 Table of contents Abstract... 1 Summary Introduction Background and Terms of Reference as provided by the requestor Interpretation of the Terms of Reference Assessment... 6 Documentation provided to EFSA... 6 References... 6 Abbreviations... 7 Appendix A Collation of comments from Member States, applicant and EFSA on the pesticide risk assessment for the active substance clofentezine in light of confirmatory data and the conclusions drawn by EFSA on the specific points raised... 8 Appendix B List of Endpoints updated parts following confirmatory data Appendix C Used compound codes EFSA Supporting publication 2017:EN-1271

5 1. Introduction 1.1. Background and Terms of Reference as provided by the requestor Clofentezine was included in Annex I to Directive 91/414/EEC 1 on 1 January 2009 by Commission Directive 2008/69/EC 2. Following the finalisation of the EFSA Conclusion on this active substance on 4 June 2009 (EFSA, 2009), Annex I to Directive 91/414/EEC was amended via Commission Directive 2010/39/EU 3 to include a specific provision that the applicant was required to submit to the European Commission further studies on clofentezine relating to their toxicology and environmental risk assessment by 30 June Clofentezine has subsequently been deemed to be approved under Regulation (EC) No 1107/2009, in accordance with Commission Implementing Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011. In accordance with the specific provision, the applicant, Adama Agriculture BV, submitted an updated dossier in June 2012, which was evaluated by the designated rapporteur Member State (RMS), the United Kingdom, in the form of an addendum to the draft assessment report (United Kingdom, 2017). In compliance with guidance document SANCO 5634/2009-rev.6.1 (European Commission, 2013), the RMS distributed the addendum to Member States, the applicant and EFSA for comments on 31 March The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 23 June EFSA added its scientific views on the specific points raised during the commenting phase in column 4 of the reporting table. The current report summarises the outcome of the consultation process organised by the RMS, the United Kingdom, and presents EFSA s scientific views and conclusions on the individual comments received Interpretation of the Terms of Reference On 22 December 2014 the European Commission requested EFSA to provide scientific assistance with respect to the risk assessment of confirmatory data following approval of an active substance in accordance with Article 6(1) of Directive 91/414/EEC and Article 6(f) of Regulation (EC) No 1107/2009. EFSA s scientific views on the specific points raised during the commenting phase conducted with Member States, the applicant and EFSA on the risk assessment of confirmatory data for clofentezine are presented. To this end, a technical report containing the finalised reporting table is being prepared by EFSA. The deadline for providing the finalised report is 21 July On the basis of the reporting table, the European Commission may decide to further consult EFSA to conduct a full or focused peer review and to provide its conclusions on certain specific points. 1 Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, , p Commission Directive 2008/69/EC of 1 July 2008 amending Council Directive 91/414/EEC to include clofentezine, dicamba, difenoconazole, diflubenzuron, imazaquin, lenacil, oxadiazon, picloram and pyriproxyfen as active substances. OJ L 172, , p Commission Directive 2010/39/EU of 22 June 2010 amending Annex I to Council Directive 91/414/EEC as regards the specific provisions relating to the active substances clofentezine, diflubenzuron, lenacil, oxadiazon, picloram and pyriproxyfen. OJ L 156, , p EFSA Supporting publication 2017:EN-1271

6 2. Assessment The comments received on the pesticide risk assessment for the active substance clofentezine in light of confirmatory data and the conclusions drawn by the EFSA are presented in the format of a reporting table. The comments received are summarised in column 2 of the reporting table. The RMS considerations of the comments are provided in column 3, while EFSA s scientific views and conclusions are outlined in column 4 of the table. The finalised reporting table is provided in Appendix A of this report. Documentation provided to EFSA 1. United Kingdom, 2017a. Addendum to the assessment report on clofentezine, confirmatory data, March 2017, updated June Available online: 2. United Kingdom, 2017b. Reporting table, comments on the pesticide risk assessment for clofentezine in light of confirmatory data, June References EFSA (European Food Safety Authority), Conclusion on pesticide peer review regarding the risk assessment of the active substance clofentezine. EFSA Journal 2009;7(7):r269, 113 pp. doi: /j.efsa r European Commission, Guidance document on the procedures for submission and assessment of confirmatory information following approval of an active substance in accordance with Regulation (EC) No 1107/2009. SANCO 5634/2009-rev EFSA Supporting publication 2017:EN-1271

7 Abbreviations a.s. DAR GAP DG SANCO EU LC 50 LD 50 MRL MS NESTI OSR PBI PEC PEC sed PEC soil PEC sw PRIMo RMS TMDI active substance draft assessment report good agricultural practice European Commission Directorate General Health and Consumers European Union lethal concentration, median lethal dose, median; dosis letalis media maximum residue level Member State national estimated short-term intake oilseed rape Plant-back interval predicted environmental concentration predicted environmental concentration in sediment predicted environmental concentration in soil predicted environmental concentration in surface water Pesticide Residue Intake Model rapporteur Member State theoretical maximum daily intake 7 EFSA Supporting publication 2017:EN-1271

8 Appendix A Collation of comments from Member States, applicant and EFSA on the pesticide risk assessment for the active substance clofentezine in light of confirmatory data and the conclusions drawn by EFSA on the specific points raised 0. General General No. Column 1 Reference to addendum to assessment report 0(1) Addendum Introduction and background, page 2 (3 rd paragraph) & page 4 (1 st, 2 nd and penultimate paragraphs) 0(2) Addendum 0(3) Addendum Column 2 Comments from Member States / applicant / EFSA Notifier (ADAMA): Clarification on the sole notifier/applicant name: The notifier was Makhteshim Agan International Coordination Center on behalf of Irvita Plant Protection NV (currently ADAMA Irvita NV). ADAMA Irvita NV is now represented in the EU by ADAMA Agriculture BV. Notifier (ADAMA): Clofentezine is an acaricide ovicide. The biological activity of 2-CBA was assessed compared to that of clofentezine (Juan, D., 2011 See overall reference list). This study shows that 2-CBA has no biological activity at 3 times the maximum clofentezine rate. For completeness we think that this study should be evaluated and summarised in the present addendum. Notifier (ADAMA): In the opinion of the UK RMS the confirmatory data Column 3 Evaluation by rapporteur Member State RMS: Noted. Addendum has been updated to represent this clarification RMS: Noted. The UK RMS has evaluated data necessary to conclude that the metabolite 2- CBA is not toxicologically, environmentally or ecotoxicologically relevant. RMS: Noted. The new data should be evaluated at renewal as part of the Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data : Clarification was added in the addendum. See 2(1) Noted. 8 EFSA Supporting publication 2017:EN-1271

9 Overall document requirements are fulfilled and no further information is required (see RMS proposal page 7). In addition, these confirmatory data were submitted in June 2012 and since that period, additional physicochemistry, toxicity, residue, ecotoxicity and environmental fate studies were conducted with all and the risk assessments completed. The new data were submitted as part of the AIR dossier in June 2016, currently under evaluation. Overall the AIR dossier supports the RMS conclusion on 2-CBN, 2-CBA, hydrazide-hydrazone and 2-CBZ which are concluded to be not toxicologically, environmentally or ecotoxicilogically relevant. AIR dossier. 1. Physical/Chemical Properties; Details of Uses and Further Information; Methods of Analysis Methods of analysis (B.5) No. Column 1 Reference to addendum to assessment report Column 2 Comments from Member States / applicant / EFSA Column 3 Evaluation by rapporteur Member State Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data 1(1) Addendum - Method of analysis used in the freezer storage stability studies and residue trials (p 46) FR: The address of the test facility where the validation of the method and the ILV have been performed should be reported RMS: The name and address of the test facility has been added.. : The name and address of the test facility has been added 9 EFSA Supporting publication 2017:EN-1271

10 1(2) Addendum - Method of analysis used in the freezer storage stability studies and residue trials (p 46) FR: For the validation of the method and the ILV, please replace LC-MS by GC-MS in the linearity part RMS: For clarity this has been corrected.. : The correction was made. 1(3) Addendum - Method of analysis used in the freezer storage stability studies and residue trials (p 46) FR: It should be mentioned that the method is fully validated for high water and high acid matrices. In the case of other uses (dry, fat matrices, another fully validated method should be necessary) RMS: A statement has been added to the conclusion to confirm that the method is not validated for high oil and dry commodities.. : A statement has been added to the addendum to confirm that the method is not validated for high oil and dry commodities. 2. Mammalian toxicology Toxicity of non-active substances (B.6.13) No. Column 1 Reference to addendum to assessment report 2(1) Addendum Overall conclusion, 2-CBN, page 5 Column 2 Comments from Member States / applicant / EFSA Notifier (ADAMA): It is stated that 2- CBN has a higher acute oral toxicity than clofentezine. The studies on both compounds were not conducted according to the same protocol which tend to increase the apparent toxicity of 2-CBN compared to the parent, by the use of vehicle DMSO known to increase (oral) absorption and by a decision making on dose levels on 2/6 animals instead of 2/3. (See details in next Notifier s comment in this section.) Column 3 Evaluation by rapporteur Member State RMS: Noted, but based on the available information 2-CBN appears to be of higher toxicity. The indications are that it is not of lower acute oral toxicity. The addendum has been edited to reflect this comment. Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data The RMS did not consider 2-chlorobenzonitrile, 2-chlorobenzoic acid, 2-chlorobenzoic acid, hydrazide and 2-chlorobenzamide toxicologically relevant. The majority of Member States that commented on the confirmatory data considered that not sufficient information is available to conclude on their toxicological profile. EFSA considered that available information on these does not satisfy the confirmatory data request. See also 2(3) to 2 (30) EFSA Supporting publication 2017:EN-1271

11 2(2) Addendum Evaluation. B.6.1, 2- CBN a) acute oral toxicity, page 8 Notifier (ADAMA): The vehicle used in this study was DMSO which is known to increase absorption throught the skin and may increase oral absorption resulting in a higher systemic exposure than if an aqueous carboxymethylcellulose suspension had been used as the vehicle. Furthermore, the group size was 6, thus the decision to administer a lower dose was based on mortality of 2/6 rather than 2/3 animals. In principle a dose of 2000 mg/kg bw could have been administered and if all animals had died this would result in an LD 50 range of <2000 mg/kg bw. The notifier does not propose to repeat this study but requests that these comments are taken into consideration when comparing these results with the results of acute oral toxicity studies with clofentezine. RMS: See response to 2(1) above See 2(1). 2(3) Addendum Evaluation. B.6.1, 2- CBN b) Bacterial gene mutation, pages 8-9 Notifier (ADAMA): For information, this Ames test was completed by a mammalian cell gene mutation test and a mammalian chromosome aberration test in the AIR dossier whose results are both negative as well. These tests confirm the RMS conclusion that the metabolite is not toxicologically relevant. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. See 2(1). Outcome: 11 EFSA Supporting publication 2017:EN-1271

12 2(4) Addendum Evaluation. B.6.1, 2- CBN c) SAR, page 9 Notifier (ADAMA): For information, an updated QSAR modelling was provided in the AIR dossier. No alert was identified and the profile is similar to the one of the parent. This modelling confirms the RMS conclusion that the metabolite is not toxicologically relevant. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. See 2(1). Outcome: 2(5) Addendum Evaluation. B.6.2, 2- CBA b) Bacterial gene mutation, page 10 Notifier (ADAMA): The 2 published papers on the mutagenicity of 2-CBA were completed in the AIR dossier by 3 GLP genotoxicity studies (bacterial gene mutation test, mammalian cell gene mutation test and mammalian chromosome aberration test) which all are negative. These studies confirm the RMS conclusion that the metabolite is not toxicologically relevant. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. See 2(1). Outcome: 2(6) Addendum Evaluation. B.6.2, 2- CBA b) SAR, pages Notifier (ADAMA): For information, an updated QSAR modelling was provided in the AIR dossier. No alert was identified and the profile is similar to the one of the parent. This modelling confirms the RMS conclusion that the metabolite is not toxicologically relevant. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the See 2(1) EFSA Supporting publication 2017:EN-1271

13 context of the renewal assessment undertaken by ES. Outcome: 2(7) Addendum Evaluation. B.6.2, 2- CBA c) TTC and d) GW assessment, page 11 Notifier (ADAMA): The RMS indicated that the applicant needs to provide additional information to address 2- CBA levels in ground water. This point was addressed in the AIR dossier submitted in June Based on new environmental data, and in line with the PECgw calculations made by the RMS (see Table , p 90), the predicted 80 th percentile average annual concentrations as modelled using FOCUS PEARL, PELMO and MACRO for clofentezine and its were <0.001 µg/l at 1 m depth for all scenarios and thus lower than the 0.1 µg/l regulatory threshold in groundwater. No relevance assessment was triggered and dietary exposure to 2-CBA by drinking water is not expected. This confirms the RMS conclusion that safes uses can be clearly demonstrated. Noted See section 4 See 2(1). 2(8) Addendum Evaluation. B.6.3, Hydrazide-hydrazone a) SAR, page 11 Notifier (ADAMA): For information, an updated QSAR modelling was provided in the AIR dossier. No alert was identified and the profile is similar to the one of the parent. The modelling results are consistent with the negative results of the 3 genotoxicity tests provided in the AIR RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1) EFSA Supporting publication 2017:EN-1271

14 dossier (bacterial gene mutation test, mammalian cell gene mutation test and mammalian chromosome aberration test). These data confirm the RMS conclusion that the metabolite is not toxicologically relevant. This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(9) Addendum Evaluation. B.6.4, 2-CBZ a) SAR, page 12 Notifier (ADAMA): For information, an updated QSAR modelling was provided in the AIR dossier. the profile is similar to the one of the parent. The modelling results are consistent with the negative results of the 3 genotoxicity tests provided in the AIR dossier (bacterial gene mutation test, mammalian cell gene mutation test and mammalian chromosome aberration test). These data confirm the RMS conclusion that the metabolite is not toxicologically relevant. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: See 2(1). 2(10) Addendum Evaluation. B.6.4, 2-CBZ b) TTC, page 12 Notifier (ADAMA): For information, the lack of dietary exposure to 2-CBZ stated by the RMS was confirmed by experimental data presented in the AIR dossier (submitted in June 2016). See Notifier s comments in the residue section. Noted See section 3 See 2(1). 2(11) Addendum B.6, Conclusion, b) 2-CBA, page 12 Notifier (ADAMA): The RMS indicated that the applicant needs to provide additional information to address 2- CBA levels in ground water. This point was addressed in the AIR dossier submitted in June Based on new environmental data, and in line with the PECgw Noted See section 4 See 2(1) EFSA Supporting publication 2017:EN-1271

15 calculations made by the RMS (see Table , p 90), the predicted 80 th percentile average annual concentrations as modelled using FOCUS PEARL, PELMO and MACRO for clofentezine and its were <0.001 µg/l at 1 m depth for all scenarios and thus lower than the 0.1 µg/l regulatory threshold in groundwater. No relevance assessment was triggered and dietary exposure to 2-CBA by drinking water is not expected. This confirms the RMS conclusion that safes uses can be clearly demonstrated. 2(12) Addendum confirmatory data (March 2017) B.6 ES: Spain is RMS to the renewal process of clofentezine and is performing a renewal assessment report (RAR). Spain agrees to the conclusion of the confirmatory information from UK regarding toxicology. This conclusion is that the clofentezine 2- chlorobenzonitrile ( 2-CBN AE F023666), 2 chlorobenzoic acid ( 2- CBA AE C500233, NC233), 2- chlorobenzoic acid (2- chlorobenzylidene) hydrazide ( Hydrazide-hydrazone AC C593600, FBC 93600) and 2-chlorobenzamide ( 2-CBZ AE F092117) are concluded to be not toxicologically relevant. Thank you for this comment. This should be considered in the context of the renewal assessment undertaken by ES. Outcome: See 2(1). 2(13) Addendum confirmatory data (March 2017) B.6 DE: For 2-CBN and 2-CBA mainly AMES studies, acute oral toxicity studies and SAR predictions were presented. For hydrazine- RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data See 2(1) EFSA Supporting publication 2017:EN-1271

16 hydrazone, only SAR predictions were presented. For 2-CBZ no tox data at all were presented. The present data only allows for a preliminary assessment. Further data requirements might become necessary in the context of a full new assessment. supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(14) Addendum confirmatory data (March 2017), B.6.1 (2- Chlorobenzonitrile) and B.6.4 (2- Chlorobenzamide) DE: It is noted that REACH registration dossiers are available on 2-CBN (CAS: ) and 2-CBZ (CAS: ), which list further toxicological data. [The other were not checked.] Generally, this data can also be used for a refinement of the evaluation of the. Noted. Thank you for this suggestion. We have accessed data in REACH dossiers in the past, but have come across problems such as only having access to summaries rather than full study reports and data protection issues. This is an option the company should consider before performing any further studies. See 2(1). 2(15) Addendum confirmatory data (March 2017), B.6.2.d (2- Chlorobenzoic acid/groundwater) DE: As mentioned by RMS, the available data are not sufficient to support the predicted PEC(GW) of 1.56 µg/l for 2-CBA. This conclusion is supported. RMS (ES) for the AIR review confirms the absence of toxicological relevance. See 2(12) This should be considered in the context of the renewal assessment undertaken by ES. See 2(1). Outcome: 2(16) Toxicological assessment of 2-CBN AT: RMS concluded that a negative AMES assay and no structural alerts, RMS: The RMS (ES) for the AIR review confirms the absence of See 2(1) EFSA Supporting publication 2017:EN-1271

17 2(17) Toxicological assessment of 2-CBA as well as values below TTC are sufficient to conclude that 2-CBN is toxicologically not relevant. AT is of the opinion that if QSAR data are available these have to be evaluated to estimate if the used prediction tools are appropriate (in or out of domain). No evaluation of QSAR data could be found in addendum. RMS is kindly asked to add more information on provided QSARs in order to conclude if at least genotoxicity can be excluded. If QSARs are not applicable, please consider that AMES test is not sufficient to exclude genotoxicity. AT: If 2-CBA exceeds 0.1 µg/l or is residue in commoditios of plant or animal origin the same comment applies as for 2-CBN 2(18) Hydrazide-hydrazone AT: If hydrazide-hydrazone exceeds 0.1 µg/l or is residue in commoditios of plant or animal origin the same comment applies as for 2-CBN. 2(19) Toxicological assessment of 2-CBZ 2(20) B Chlorobenzonitrile. AT: If 2-CBZ exceeds 0.1 µg/l or is residue in commoditios of plant or animal origin the same comment applies as for 2-CBN. FR (May2017): The genotoxic potential has only been investigated in an Ames test and SAR analysis performed with a unique model. It is therefore questionable to use the TTC threshold of 1.5 µg/kg bw/d (not mutagenic, Cramer Class III) since no in vitro micronucleus test is available nor other QSAR analysis. toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: RMS: See response to 2(16) See 2(1). RMS: See response to 2(16) See 2(1). RMS: See response to 2(16) See 2(1). RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the See 2(1) EFSA Supporting publication 2017:EN-1271

18 2(21) B Chlorobenzoic acid 2(22) B.6.3 Hydrazide-hydrazone. In the absence of further information to exclude genotoxic potential, the TTC threshold of µg/kg bw/day should be used. As regard groundwater assessment, for other uses where PEC GW might be higher, even if its genotoxic potential is clarified, 2-Chlorobenzonitrile should be considered as relevant according to Sanco/221/2000 rev.10 since it is Toxic if swallowed FR (May2017): The same remark as for 2-Chlorobenzonitrile applies. In the absence of further information to exclude genotoxic potential, the TTC threshold of µg/kg bw/day should be used. As regard groundwater assessment, further information is needed to exclude any genotoxic potential as first step to assess 2-Chlorobenzoic acid relevance according Sanco/221/2000 rev.10. FR (May2017): Only A Derek analysis has been performed. No genotoxicity test is available. AC C is a hydrazide compound. Therefore, in case of dietary exposure a TTC threshold of µg/kg bw/day. As regard groundwater assessment, for other uses where PEC GW might be higher, further information is needed to exclude any genotoxic potential as first step to assess AC C relevance according Sanco/221/2000 context of the renewal assessment undertaken by ES. Outcome: RMS: See response to 2(20) See 2(1). RMS: See response to 2(20) See 2(1) EFSA Supporting publication 2017:EN-1271

19 2(23) B Chlorobenzamide 2(24) Addendum Confirmatory Data B Chlorobenzonitrile Page 8 rev.10. FR (May2017): Only A Derek analysis has been performed. No genotoxicity test is available. Therefore, in case of dietary exposure (for other uses) a TTC threshold of µg/kg bw/day. As regard groundwater assessment, for other uses where PEC GW might be higher, further information is needed to exclude any genotoxic potential as first step to assess 2-Chlorobenzamide relevance according Sanco/221/2000 rev.10. EFSA: No sufficient information is available to conclude on the genotoxic profile of metabolite 2- Chlorobenzonitrile since the clastogenicity and aneugenicity endpoint was not addressed. RMS: See response to 2(20) See 2(1). RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(25) Addendum Confirmatory Data B Chlorobenzonitrile Page 82- EFSA: No information is avaiable to compare the toxicological profile of the metabolite to the parent. No information is availabe to establish specific reference values for the metabolite. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment See 2(1) EFSA Supporting publication 2017:EN-1271

20 undertaken by ES. Outcome: 2(26) Addendum Confirmatory Data B Chlorobenzoic acid. Page 9 EFSA: No sufficient information is available to conclude on the genotoxic profile of metabolite 2-Chlorobenzoic acid since the clastogenicity and aneugenicity endpoint was not addressed. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(27) Addendum Confirmatory Data B Chlorobenzoic acid. Page 9 EFSA: No information is avaiable to compare the toxicological profile of the metabolite to the parent. No information is availabe to establish specific reference values for the metabolite. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(28) Addendum Confirmatory Data B.6.2 EFSA: two publications were retrieved on 2-Chlorobenzoic acid. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data See 2(1) EFSA Supporting publication 2017:EN-1271

21 2-Chlorobenzoic acid. Page 9 Please provide an assesment on the literature search conducted by the applicant. supplied by the company. See 2(3) 2(5), 2(8) and 2(12). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(29) Addendum Confirmatory Data B.6.3 Hydrazide-hydrazone. Page 11 EFSA: no mammalian toxicity data were submitted No conclusion can be drawn on the toxicological profile of metabolite Hydrazide-hydrazone. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 2(30) Addendum Confirmatory Data B Chlorobenzamide. Page 12 EFSA: no mammalian toxicity data were submitted No conclusion can be drawn on the toxicological profile of metabolite 2-Chlorobenzamide. RMS: The RMS (ES) for the AIR review confirms the absence of toxicological relevance based on additional genotoxicity data supplied by the company. See 2(3) 2(5), 2(8) and 2(12). See 2(1). This should be considered in the context of the renewal assessment undertaken by ES. Outcome: 21 EFSA Supporting publication 2017:EN-1271

22 3. Residues Storage Stability (B.7.0) No. Column 1 Reference to addendum to assessment report Column 2 Comments from Member States / applicant / EFSA Column 3 Evaluation by rapporteur Member State Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data 3(1) Addendum - B.7.7. Stability of residues prior to analysis Report R (Study IRV-1009 (S )) FR: According to the foot note under each tables of results, mean recoveries of stored samples were corrected with the freshly fortified samples only if < 100 %, else uncorrected. This is not in accordance with the Guidance 7032/VI/95 rev.5. APPENDIX H STORAGE STABILITY OF RESIDUE SAMPLES. RMS: It is stated prior to the tables that the applicant presented both corrected and uncorrected recoveries and, in accordance with SANCO 7032/VI/95 rev. 5, only uncorrected recoveries should be taken into account. To improve clarity the corrected recoveries have been removed from the tables and the wording updated to reflect this amendment. The uncorrected recoveries were reported in the study Report R (2) Addendum- Confirmatory data B.7.7 Stability of residues prior to analysis EFSA: Based on the submitted storage stability data, 2-chlorobenzonitrile residues are stable for up to 9 months in high water content commodities and up to 6 months in high acid content matrices. Storage stability data for clofentezine in high acid content commodities were nor provided and should be submitted in order to conclude on the validity of the residue trials on the different crops under assessment. RMS: An additional study has been presented in the addendum showing that clofentezine was stable in high acid commodities for 6 months in orange (pulp). This is sufficient to support the storage period of high acid commodities in the supervised trials evaluated in the addendum EFSA Supporting publication 2017:EN-1271

23 Residue definition (B.7.3) No. Column 1 Reference to addendum to assessment report Column 2 Comments from Member States / applicant / EFSA Column 3 Evaluation by rapporteur Member State Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data 3(3) Addendum Overall conclusion, lats paragraph on residue definition, page 7 and Proposal, page 7 Notifier (ADAMA): We agree with RMS that the residue definition should be further considered at the renewal. Based on new data submitted as part of the AIR dossier (submitted in June 2016 and currently under evaluation), the provisional conversion factor of 1.3 appears to be not justified and too conservative for most of the crops. RMS: Thank you for you agreement regarding the residue definition. It is considered that, based on the available data submitted for the confirmatory data assessment, a provisional conversion factor of 1.3 is worse case and will be protective for consumers. Further consideration of the conversion factor should be made at renewal on the basis of the AIR dossier. See 3(4). 3(4) Addendum Overall Conclusion on Residue Trials Data, 4th paragraph, page 30 Notifier (ADAMA): RMS proposed a provisional conversion factor of 1.3 and suggested to further discuss it at renewal. The notifier agrees with this later proposal for the following reasons. With the AIR dossier (submitted in June 2016) all necessary toxicity and residue data for 2-CBN have been provided. They confirm that this metabolite is not of toxicological concern, is generally <0.01 mg/kg in crops at harvest and usually below 10% of the parent clofentezine residue. With such low levels of consumer RMS: Thank you for your agreement. The RMS considers that, based on the available data submitted for the confirmatory data assessment, a provisional conversion factor of 1.3 is worse case and will be protective for consumers. Further consideration of the conversion factor should be made at renewal.. The proposed conversion factor of 1.3 should be regarded as provisional and be reconsidered in the light of a full assessment of the toxicity profile of 2- chlorobenzonitrile and based on complete residue data sets analysing for this compound in treated crops according to the representative uses (apples/pears, plums, grapes, strawberries) EFSA Supporting publication 2017:EN-1271

24 3(5) Addendum Overall Conclusion on Residue Trials Data, 1st paragraph, page 60 exposure the Applicant does not propose to include 2-CBN in the residue definition for risk assessment and this is consistent with OECD guidance document ENV/JM/MONO(2009)30, 28 July 2009 [Series on testing and assessment No. 63 and Series on pesticides No. 31 Guidance document on the definition of residue (as revised in 2009)] Notifier (ADAMA): The notifier agrees that the conversion factor is still considered as provisional and should be further discussed at renewal. With the AIR dossier (submitted in June 2016) all necessary toxicity and residue data for 2-CBN have been provided. They confirm that this metabolite is not of toxicological concern, is generally <0.01 mg/kg in crops at harvest and usually below 10% of the parent clofentezine residue. With such low levels of consumer exposure the Applicant does not propose to include 2-CBN in the residue definition for risk assessment and this is consistent with OECD guidance document ENV/JM/MONO(2009)30, 28 July (6) B.7. Residues ES: According UK, Overall 2-CBZ is concluded to be not toxicologically, environmentally or ecotoxicologically relevant. But UK RMS: Thank you for your agreement. The RMS considers that, based on the available data submitted for the confirmatory data assessment, a provisional conversion factor of 1.3 is worse case and will be protective for consumers. Further consideration of the conversion factor should be made at renewal.. RMS: The residue definition does not currently include 2-CBZ. The RMS considers that, based on the available data submitted for the confirmatory See 3(4) The residue definition for risk assessment in fruit crops is provisionally set as parent clofentezine 24 EFSA Supporting publication 2017:EN-1271

25 proposes that the residue definition for risk assessment should provisionally remain as Parent clofentezine and 2- chlorobenzonitrile (2-CBN), expressed as clofentezine to be further considered at renewal. We would like to know whether the UK might consider it acceptable to remove 2- CBZ from the residue definition for risk assessment. 3(7) Confirmatory data, p. 6 DE: Conflicting conclusions are drawn regarding metabolite 2-CBN: Overall 2-CBN is concluded to be not toxicologically, environmentally or ecotoxicologically relevant contrasts the provisional inclusion into the residue definition (see EFSA Conclusion 2009). RMS, please clarify. data assessment, the residue definition for risk assessment should provisionally remain as Parent clofentezine and 2-chlorobenzonitrile (2-CBN), expressed as clofentezine. The residue definition should be reconsidered at renewal.. RMS: 2-CBN was considered not to be toxicologically relevant based on the predicted exposure being below the TTC, according to the representative GAP on strawberries. The residue definition remains provisional. This should be considered further at renewal.. and 2-chlorobenzonitrile expressed as clofentezine. This residue definition for risk assessment in fruit crops will be revised pending upon the requested toxicological data on 2- chlorobenzonitrile and the magnitude of 2-chlorobenzonitrile residues according to the representative uses. See 2(1) 3(8) Confirmatory data, p. 52 DE: The argument that exposure to 2- CBN is below TTC CramerIII is based on estimated exposure levels for this metabolite resulting from the (almost) representative GAP in strawberries. While this holds true, it is of limited value to judge on a residue definition applicable to a wider range of crops and GAPs (positive detects in highly consumed crops like pome fruits, grapes, cherries, raspberries, stone fruits). RMS: Agree. The residue definition remains provisional partly on this basis. This will need to be addressed either at MS level or at renewal.. See 3(6), 2(1) 25 EFSA Supporting publication 2017:EN-1271

26 Use pattern, critical GAP, residues trials (B.7.4 to B.7.6) No. Column 1 Reference to addendum to assessment report 3(9) Addendum B.7.6, Strawberry, Conclusion/endpoint, page 15 and Table 7.3-1, page 31 3(10) Addendum B.7.6, Apple/pear, pages and Table 7.3-2, pages (11) Addendum B.7.6, Raspberry, page 18 Column 2 Comments from Member States / applicant / EFSA Notifier (ADAMA): For information, the data package on strawberry was completed by 10 GLP trials (5 protected and 5 in South outdoor) in the AIR dossier (submitted in June 2016, currently under evaluation). The residues of 2-CBN in fruit at harvest on these additional trials were 3x<0.01, 0.01 and 0.03 on the protected crop and 3x<LOD, 0.01 and 0.02 outdoor. These data confirm the very low level of 2-CBN residues. Notifier (ADAMA): For information, the data package on apple/pear was completed by 8 GLP trials (4 North and 4 South) in the AIR dossier (submitted in June 2016, currently under evaluation). The residues of 2-CBN in fruit at harvest on these additional trials were <LOD and 3x<0.01 in the North, and 2x<LOD and 2x<0.01 in the South. These data confirm the very low level of 2- CBN residues. Notifier (ADAMA): Four additional indoor trials were evaluated at step 2 by UK acting as zrms (Report R A). The residues of 2-CBN in fruit at harvest on these additional Column 3 Evaluation by rapporteur Member State RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. The new trials data should be evaluated at renewal.. RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. The new trials data should be evaluated at renewal.. RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. Any additional trials should be Column 4 EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of confirmatory data EFSA notes EFSA notes EFSA notes Raspberry use is not relevant in the framework of the assessment of the confirmatory data EFSA Supporting publication 2017:EN-1271

27 and Table 7.3-3, page 34 trials were <0.01, 0.03, 0.04 and submitted for evaluation at renewal. 3(12) Addendum B.7.6, Cucumber and tomato, Tomato, page 19 Notifier (ADAMA): For information, the data package on tomato was completed by 1 indoor and 2 South trials in the AIR dossier (submitted in June 2016, currently under evaluation). The residues of 2-CBN in fruit at harvest on these additional trials were <LOD (indoor) and <LOD and <0.01 in the South. These data confirm the very low level of 2-CBN residues. RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. The new trials data should be evaluated at renewal as part of the AIR dossier.. EFSA notes Tomato use is not relevant in the framework of the assessment of the confirmatory data. 3(13) Addendum B.7.6, Cucumber and tomato, Cucurbits, page 19 Notifier (ADAMA): Five additional South trials on courgettes were evaluated at step 2 by ES acting as zrms (Report R-29830A). The residues of 2-CBN in fruit at harvest on these additional trials were 3x<LOD and 2x<0.01. These data confirm the very low level of 2-CBN residues. RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. Any additional trials should be submitted for evaluation at renewal as part of the AIR dossier.. EFSA notes Courgettes use is not relevant in the framework of the assessment of the confirmatory data. 3(14) Addendum B.7.6, Citrus, pages and Table 7.3-4, pages Notifier (ADAMA): For information, the data package on citrus was completed by 2 mandarine and 2 orange South trials in the AIR dossier (submitted in June 2016, currently under evaluation). The residues of 2-CBN in fruit at harvest on these additional trials were <0.01, 0.02, 0.04 and 0.05 in peel, 4x<LOD in pulp and 2x<0.01, 0.01 and 0.02 in the whole fruit. These RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. The new trials data should be evaluated at renewal as part of the AIR dossier.. EFSA notes Citrus use is not relevant in the framework of the assessment of the confirmatory data EFSA Supporting publication 2017:EN-1271

28 data confirm the very low level of 2- CBN residues. 3(15) Addendum B.7.6, Cherry, pages and Table 7.3-5, page 37 Notifier (ADAMA): For information, the data package on cherry was completed by 3 North trials in the AIR dossier (submitted in June 2016, currently under evaluation). The residues of 2-CBN in fruit at harvest on these additional trials were 2x<LOD and <0.01. These data confirm the very low level of 2- CBN residues. RMS: This information is noted; however the confirmatory data assessment has been made based on only the confirmatory data submission. The new trials data should be evaluated at renewal as part of the AIR dossier.. EFSA notes Cherry use is not relevant in the framework of the assessment of the confirmatory data. 3(16) Confirmatory data, p. 52 DE: To decide on the relevance of metabolite 2-CBN based on the occurrence in field studies, it should be noted under which GAP the uses are authorised, i.e. whether the trials represent a realistic view on critical GAPs. RMS: The trials were submitted as supporting data only and not to address a specific GAP. The representative use was on strawberry. As such only the strawberry trials have been compared to a specific GAP. Consideration of the supporting data in relation to specific GAPs should be made at MS level and/or Article 12 review. It is noted that residue trials on peaches/apricot, raspberry, citrus, cherries, melon, cucumber and tomato have been submitted as supporting data only.. 3(17) Confirmatory data, p. 19 DE: It would be helpful to include cucumber and tomato trials in the overview tables (B to B.7.3-9). RMS: Table and have been added to the addendum to include an overview of the cucumber and tomato trials in which 2-CBN were determined.. 3(18) Addendum - B.7.6. Residues arising from supervised trials FR: the storage conditions (temperature, duration) of all the sample extracts should be reported. In cases where sample extracts were The notifier provided a document confirming the storage conditions (temperature and duration) of all samples extracts used in the studies 28 EFSA Supporting publication 2017:EN-1271