TECHNICAL REPORT APPROVED: 12 January 2016 PUBLISHED: 02 February 2016 Outcome of the consultation with Member s, the applicant and EFSA on the pesticide risk assessment for tri-allate in light of 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 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 s, the applicant and EFSA on the and their use in the risk assessment for tri-allate are presented. The current report summarises the outcome of the consultation process organised by the rapporteur Member the United Kingdom and presents EFSA s scientific views and conclusions on the individual comments received. European Food Safety Authority, 2016 Key words: tri-allate, peer review,, risk assessment, pesticide, herbicide Requestor: European Commission Question number: EFSA-Q-2015-00842 Correspondence: pesticides.peerreview@efsa.europa.eu www.efsa.europa.eu/publications EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Suggested citation: EFSA (European Food Safety Authority), 2016. Technical report on the outcome of the consultation with Member s, the applicant and EFSA on the pesticide risk assessment for tri-allate in light of. EFSA supporting publication 2016:EN-953. 48 pp. European Food Safety Authority, 2016 Reproduction is authorised provided the source is acknowledged. www.efsa.europa.eu/publications 2 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Summary Tri-allate was included in Annex I to Directive 91/414/EEC on 1 January 2010 by Commission Directive 2009/77/EC, and has 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. It was a specific provision of the approval that the applicant was required to submit to the European Commission further information to assess the primary plant metabolism, further information on the fate and behaviour of the soil metabolite diisopropylamine, further information on the potential for biomagnification in aquatic food chains, information to further address the risk to fish-eating mammals and the long-term risk to earthworms by 31 December 2011. In accordance with the specific provision, the applicant, Gowan Comércio Internacional e Servicos Ltda, submitted an updated dossier in December 2011, which was evaluated by the designated rapporteur Member (RMS), the United Kingdom, in the form of an the draft. In compliance with guidance document SANCO 5634/2009-rev.6.1, the RMS distributed the Member s, the applicant and EFSA for comments on 23 September 2015. The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 16 December 2015. 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. Toxicological studies were not submitted on the soil metabolite diisopropylamine (DIPA). The RMS based its toxicological assessment on IUCLID summaries of short term oral toxicity studies submitted under Regulation (EC) No 1907/2006 (REACH Regulation), concluding that DIPA is not toxicologically relevant as a groundwater metabolite and that the reference values of tri-allate apply to the metabolite. This is not considered sufficient by EFSA; complete studies including raw data are needed to perform an independent assessment of the data. At least, in vitro genotoxicity test battery and acute and repeated-dose oral toxicity studies are needed. Conclusion can not be reached on the toxicological profile of the metabolite without the submission of the referred studies. It is therefore considered that the do not address the toxicological relevance of DIPA as a groundwater metabolite or regarding its health-based reference values relevant to consumer risk assessment. A peer review is proposed to further address the plant residue definition for risk assessment, the plant residue definition for monitoring (identification of suitable marker(s)) and to define whether some of the plant metabolites could be relevant in food and feed commodities. EFSA suggests that the relevance of metabolite peak 14 in terms of relative and absolute occurrence is further addressed whilst the RMS considers that this point has been Pending a conclusion regarding the plant residue definition for risk assessment, the relevance of livestock exposure to tri-allate residues, the need for livestock metabolism studies, the relevance of rotational crop residues and a need for rotational crops studies in line with the risk assessment need to be A revised risk assessment would be needed once the residue definition has been concluded on. Regarding the route and rate of degradation in soil, a peer review is proposed to further address the issue of how to calculate the formation fractions when a substantial part of tri-allate is volatilised. The RMS considers that this point has been The available assessment is considered to sufficiently address the requests related to the ecotoxicology assessment; the potential for biomagnification in aquatic food chains was addressed, a low risk to fish-eating mammals was concluded provided that risk mitigation measures equivalent to a 5 m no-spray buffer zone are used and a low long-term risk to earthworms was also concluded. www.efsa.europa.eu/publications 3 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Table of contents Abstract... 1 Summary... 3 1. Introduction... 5 1.1. Background and Terms of Reference as provided by the requestor... 5 1.2. Interpretation of the Terms of Reference... 5 2. Assessment... 6 Documentation provided to EFSA... 6 References... 6 Abbreviations... 7 Appendix A Collation of comments from Member s, applicant and EFSA on the pesticide risk assessment for the active substance tri-allate in light of and the conclusions drawn by EFSA on the specific points raised... 8 Appendix B Used compound code(s)... 48 www.efsa.europa.eu/publications 4 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate 1. Introduction 1.1. Background and Terms of Reference as provided by the requestor Tri-allate was included in Annex I to Directive 91/414/EEC 1 on 1 January 2010 by Commission Directive 2009/77/EC 2, and has been deemed to be approved under Regulation (EC) No 1107/2009 3, in accordance with Commission Implementing Regulation (EU) No 540/2011 4, as amended by Commission Implementing Regulation (EU) No 541/2011 5. EFSA previously finalised a Conclusion on this active substance on 26 September 2008 in the EFSA Scientific Report (2008). It was a specific provision of the approval that the applicant was required to submit to the European Commission further information to assess the primary plant metabolism, further information on the fate and behaviour of the soil metabolite diisopropylamine, further information on the potential for biomagnification in aquatic food chains, information to further address the risk to fish-eating mammals and the long-term risk to earthworms by 31 December 2011. In accordance with the specific provision, the applicant, Gowan Comércio Internacional e Servicos Ltda, submitted an updated dossier in December 2011, which was evaluated by the designated rapporteur Member (RMS), the United Kingdom, in the form of an the draft (United Kingdom, 2015). In compliance with guidance document SANCO 5634/2009-rev.6.1 (European Commission, 2013), the RMS distributed the Member s, the applicant and the EFSA for comments on 23 September 2015. The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 16 December 2015. 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. 1.2. 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 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. specific points raised during the commenting phase conducted with Member s, the applicant and EFSA on the risk assessment of for tri-allate 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 14 January 2016. 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, 19.08.1991, p.1-32. 2 Commission Directive 2009/77/EC of 1 July 2009 amending Council Directive 91/414/EEC to include chlorsulfuron, cyromazine, dimethachlor, etofenprox, lufenuron, penconazole, tri-allate and triflusulfuron as active substances. OJ L 172, 2.7.2009 3 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. 4 Commission Implementing Regulation (EU) No 540/2011 of 25 May 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards the list of approved active substances. OJ L 153, 11.6.2011, p.1-186. 5 Commission Implementing Regulation (EU) No 541/2011 of 1 June 2011 amending Implementing Regulation (EU) No 540/2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards the list of approved active substances. OJ L 153, 11.6.2011, p.187-188. www.efsa.europa.eu/publications 5 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate 2. Assessment The comments received on the pesticide risk assessment for the active substance tri-allate in light of 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, 2015. Addendum to the on tri-allate,, December 2015. Available online: www.efsa.europa.eu. 2. United Kingdom, 2015. Reporting table, comments on the pesticide risk assessment for tri-allate in light of, December 2015. References EFSA (European Food Safety Authority) 2008. EFSA Scientific Report (2008) 181, 1-100, Conclusion on the peer review of tri-allate. Available at http://www.efsa.europa.eu/en/efsajournal/pub/181r EFSA PPR Panel (EFSA Panel on Plant Protection Products and their Residues), 2013. Guidance on tiered risk assessment for plant protection products for aquatic organisms in edge-of-field surface waters. EFSA Journal 2013;11(7):3290, 268 pp. doi:10.2903/j.efsa.2013.3290 European Commission, 2003. Guidance Document on Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated under Council Directive 91/414/EEC. SANCO/221/2000-rev. 10 - final, 25 February 2003. European Commission, 2013. 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. 6.1 www.efsa.europa.eu/publications 6 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Abbreviations a.s. active substance DAR draft GAP good agricultural practice EU European Union IUCLID International Uniform ChemicaL Information Database LC 50 LD 50 MRL NESTI PBI PEC PEC sed PEC soil PEC sw PRIMo RMS SANCO TMDI lethal concentration, median lethal dose, median; dosis letalis media maximum residue level national estimated short-term intake 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 Directorate-General for Health and Consumers theoretical maximum daily intake www.efsa.europa.eu/publications 7 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Appendix A Collation of comments from Member s, applicant and EFSA on the pesticide risk assessment for the active substance tri-allate in light of and the conclusions drawn by EFSA on the specific points raised 0. General General 0(1) General comment environmental fate and behaviour FR: The report is easy to read. The information was well presented by the RMS. UK RMS: Noted - thank you. Addressed. Noted www.efsa.europa.eu/publications 8 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate 2. Mammalian toxicology Acute toxicity (B.6.2) No comments received. Short-term toxicity (B.6.3) No comments received. Genotoxicity (B.6.4) No comments received. www.efsa.europa.eu/publications 9 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Long-term toxicity and carcinogenicity (B.6.5) No comments received. Reproductive toxicity (B.6.6) No comments received. Neurotoxicity (B.6.7) No comments received. www.efsa.europa.eu/publications 10 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Other toxicological studies & Medical data (B.6.8-B.6.9) No comments received. Summary of mammalian toxicology and setting of ADI, AOEL and ARfD (B.6.10) 2(1) B.6 Toxicology FR: Considering the limited data on DIPA, FR disagrees with proposed specific ADI and ARfD derived for DIPA. In short-term repeat dose studies, DIPA seems to be of no greater toxicity than tri-allate. Therefore, FR proposes that ADI and ARfD of tri-allate can be used for risk assessment of DIPA. UK RMS: Noted and agreed. DIPA specific endpoints were proposed by the applicant as the level of DIPA in groundwater exceeded 10% of the ADI for tri-allate. Given the number of comments received, the RMS has revised the addendum so that risk assessment is carried out against the ADI for triallate. See comment 2(6) DIPA is not considered to be a relevant metabolite in groundwater. Intakes from tri-allate and all metabolites using the ADI for tri-allate are less than 100% of the ADI. www.efsa.europa.eu/publications 11 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Summary of mammalian toxicology and setting of ADI, AOEL and ARfD (B.6.10) 2(2) 0Confirmatory Data, Addendum 8, 3.B.6 Toxicology pp.9-10 2(3) B.6, derivation of an ARfD for DIPA, p. 10 2(4) Section 2. Overall conclusions and Section 3, B6 Toxicology AT: DIPA specific reference values (ADI, ARfD) were derived based on data reported in IUCLID (link to ECB website). AT prefers to use the reference values proposed by the applicant, that is to use the ADI and ARfD for tri-allate. These are also used for the metabolite TCPSA and are based on a more sound and valid database than the values derived by IUCLID data. EFSA: Provided that the short term studies are submitted, an acute effect should be identified on which to derive an ARfD; some endpoints relevant for the derivation of an ARfD are not available such as a developmental toxicity study in rats and rabbits, and acute neurotoxicity. If not available an increased uncertainty factor could be considered. NL: The ARfD value contains the unit per day, however this is not correct. The ARfD should be 1 mg/kg bw instead of 1 mg/kg bw/d. UK RMS: See response to 2(1) See comment 2(6) UK RMS: See response to 2(1). As the RMS is no longer proposing to derive DIPA specific endpoints these studies are no longer relied. Assessment is therefore no longer required. UK RMS: Noted and agreed. However the RMS is no longer proposing to derive DIPA specific reference values, and these have been deleted from the See comment 2(6) Addressed. www.efsa.europa.eu/publications 12 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Summary of mammalian toxicology and setting of ADI, AOEL and ARfD (B.6.10) addendum. 2(5) B.6, derivation of an ADI for DIPA, p. 10 EFSA: The proposed additional uncertainty factor of 6 to extrapolate from subacute to chronic should be further explained. Furthermore reproductive, developmental and neurotoxicity potential of DIPA were not A comparison of the toxicity profiles of tri-allate and DIPA may help identifying whether it would be suitable to apply the reference values of the parent triallate to DIPA. UK RMS: See response to 2(1) See comment 2(6) Toxicity of the product(s) (B.6.11) Not relevant to the assessment. www.efsa.europa.eu/publications 13 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Dermal absorption (B.6.12) Not relevant to the assessment. Toxicity of non-active substances (B.6.13) 2(6) B.6 Toxicology FR: Were the final reports on genotoxicity, acute and repeated oral dose toxicity studies available to the RMS or only summaries reported in ECHA website have been consulted? UK RMS: Only the summaries reported on iuclid were consulted. However, as the RMS is no longer proposing to use DIPA specific endpoints these studies are no longer relied upon. The peer review cannot base its assessment on summaries reported in IUCLID. The complete studies including raw data are needed to perform an independent assessment of the toxicological data. In order to assess whether the reference values of the parent tri-allate may apply to the metabolite, toxicological studies are required, including, at least, in vitro genotoxicity test battery, and acute and repeated-dose oral toxicity. Therefore conclusion can not be reached on the toxicological profile of the metabolite DIPA (either regarding reference values or toxicological relevance as groundwater metabolite) without the www.efsa.europa.eu/publications 14 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Toxicity of non-active substances (B.6.13) submission of the referred studies. See also 2(7, 8, 9, 10, 11) 2(7) Confirmatory Data Assessment Addendum 8 B.6. Toxicology 2(8) Confirmatory Data Assessment Addendum 8 B.6. Toxicology 2(9) Confirmatory Data Assessment Addendum 8 Appendix 2 DE: There is some confusion whether the mentioned study reports with DIPA were submitted and evaluated by the RMS. It seems the results were just cited from the disseminated REACH registration dossier. RMS, please clarify. DE: Detailed study summaries are missing for the studies with DIPA. Hence no peer-review of the studies assessments is possible. Due to the short timelines and for transparency reasons it is not sufficient just to insert cross references to studies from other EU proceedings. In summary, currently, it cannot be agreed with the proposed reference doses (ADI, ARfD). RMS, please add the detailed study summaries for the studies with DIPA. DE: Apparently, no toxicological study reports with the groundwater metabolite DIPA were submitted. Hence, it cannot be agreed with the toxicological conclusions of the UK RMS: See response to 2(6) See 2(6) UK RMS: See response to 2(1) See 2(6) UK RMS: See response to 2(1). The relevance assessment has been amended to consider all possible sources of exposure to tri-allate and the metabolites that rely on the ADI for See 2(6) www.efsa.europa.eu/publications 15 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Toxicity of non-active substances (B.6.13) 2(10) B.6, toxicity studies conducted with DIPA metabolite, p. 9 relevance assessment. Based on the lack of toxicological data on DIPA, neither the non-relevance can be concluded nor can reference doses be established. RMS, please add at least the study reports for the studies that where considered for stage 2 of step 3: screening for genotoxicity. Furthermore, for step 5, only exposure via drinking water was taken into account, but not further possible sources of DIPA exposure. RMS, please amend accordingly. According to the addendum, DIPA s PECgw exceed 10 µg/l in all scenarios with PEARL. For Germany a PECgw >10 µg/l is in general not acceptable. EFSA: Toxicity (including genotoxicity) studies conducted with diisopropylamine (DIPA) have to be submitted to enable an independent assessment. tri-allate. Germany s position regarding acceptable levels of metabolites is noted, however there is nothing in the guidance document to automatically preclude levels of metabolites from exceeding 10 µg/l. UK RMS: As the RMS is no longer proposing to use DIPA specific endpoints these studies are no longer relied upon. An assessment is therefore no longer required. According to publically available MSDSs DIPA is not toxic or very toxic and is not genotoxic. These were prepared in accordance with Regulation (EC) 1907/2006 and therefore the classification reported is legally binding. See 2(6) www.efsa.europa.eu/publications 16 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Toxicity of non-active substances (B.6.13) 2(11) Section 3, B6 Toxicology NL: Please indicate in the addendum that the data from the REACH dossier for DIPA can be used to assess the set for tri-allate. UK RMS: As the RMS is no longer proposing to use DIPA specific endpoints this is not relevant as these studies are no longer relied upon. See 2(6) Exposure data (B.6.14) Not relevant to the assessment. www.efsa.europa.eu/publications 17 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Other comments No comments received. www.efsa.europa.eu/publications 18 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate 3. Residues Storage Stability (B.7.0) Not relevant to the assessment. Metabolism in plants (B.7.1) 3(1) B.7.3 Cereal metabolism EFSA: From the diisopropylamine labelled study it is concluded that no other metabolites are observed at levels that would trigger identification, however it has been disregarded that the study was not conducted at N rate but at a lower rate (0.76N). The OECD guidance requests metabolism studies to be conducted at the critical GAP rate, or even at exaggerated rates to aid full elucidation (90%TRR) of the identity of residues. In wheat grain, a peak at 14 min was 0.008 mg/kg, and could have been above 0.01 mg/kg if the study would have been conducted at N rate. Further UK RMS: RMS agrees that the peak at 14 minutes in wheat grain may have required characterisation and/or identification if adjustment is made for the N rate. However in view of the low %TRR and high level of DIPA in the sample, it would seem unwarranted to set a further data requirement. Text to this effect has been added under Table B.7.15. The level of this metabolite, when adjusted for the N rate, would trigger further characterisation and/or identification. It is not ideal that this has not been undertaken. However in Refer to 3(5) Peer review proposed: It has been proposed in the following points to discuss the pertinent residues in plants in order to agree on the residue definition. It is therefore suggested that this issue (i.e. the relevance of metabolite peak 14 in terms of relative and absolute occurrence) is considered during the discussion of the residue definition as well. www.efsa.europa.eu/publications 19 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Metabolism in plants (B.7.1) discussion is necessary. view of the low %TRR and high level of DIPA in the sample, it would seem unwarranted to set a further data requirement. Metabolism in livestock (B.7.2) 3(2) B.7.4 Livestock metabolism EFSA: Livestock exposure seems significant and livestock studies in line with the risk assessment definition are triggered but are not available. This should be a data gap. UK RMS: Livestock exposure to tri-allate residues is artificially high due to worst case assumptions made with respect to rotational crops. The RMS therefore considers that this should not be considered a data gap until more accurate estimates of livestock exposure are available. Peer review proposed: Pending a conclusion regarding the plant residue definition for risk assessment, the relevance of livestock exposure to these residues and a need for livestock metabolism studies to be discussed. Open point; RMS recommends expert discussion to confirm the residue definition for risk assessment. www.efsa.europa.eu/publications 20 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate 3(3) B.7.3, Metabolism study, label at the allyl portion NL: Minor remark: it is not fully clear whether it has been tried to specifically identify M14 and M15; or was there no attempt to identify these conjugates. However, in later paragraphs (B.7.16), this has been explained in more detail. It would be helpful if this information could be added to paragraph B.7.3 as well. UK RMS: Agree, additional wording explaining that identification of metabolite was not attempted until after hydrolysis, which would de-conjugate M14 and M15, has been added. Addressed. Identification of metabolite was not attempted until after hydrolysis, which would de-conjugate M14 and M15. Residue definition (B.7.3) 3(4) B.7 Notifier: There is a great margin of safety applying the RMS s approach by using a conversion factor for the M14 and M15 glycosides and conducting a dietary risk assessment with the estimated levels of DIPA. Further data would not be needed. The Notifier is of the opinion that the TCPSA glycosides do not need to be included into the residue definition neither for enforcement nor for dietary risk assessment. Even if considering the significantly overestimated levels of glycosides (i.e. TRR used in case of rotational crops other than cereals) and the unrealistically high conversion factor UK RMS: The RMS considers that the issue of the residue definition for monitoring and risk assessment should be subject to expert discussion. Open point, RMS recommends expert discussion to confirm the residue definition for risk assessment and monitoring. Refer to 3(5) www.efsa.europa.eu/publications 21 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Residue definition (B.7.3) for cereals, there is no indication of a chronic or acute dietary risk. In addition, in Addendum 7 (July 2008) to the DAR, the RMS already made the following points which are still considered to be valid: - In plants, TCPSA is the main residue component in supported plant commodities and this occurs only in animal feed (wheat forage, straw and hay). - Conjugated Tri-allate metabolites M15 and M14 are expected to metabolise to TCPSA. - No TCPSA (or Tri-allate or any unidentified metabolite) occurs in cereal grain at levels above 0.01 mg/kg. - No TCPSA or any TCPSA related metabolite (or Tri-allate) occurs in animal tissues and milk at levels above 0.01 mg/kg even at exaggerated dose rates (10N)." Thus, further data on the TCPSA glycosides are generally not needed. For DIPA, the Notifier also refers to the very high margin of safety in the RMS s dietary risk assessment (<1% ADI/ARfD) www.efsa.europa.eu/publications 22 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Residue definition (B.7.3) and emphasizes that further data are not needed. 3(5) B.7 FR: France is of the opinion that the metabolite DIPA should be included in the residue definition for risk assessment together with TCPSA. Indeed consumers will be exposed to both TCPSA and DIPA at the same time, since tri-allate is almost completely metabolized in DIPA and TCPSA. France wonders whether a separate risk assessment for DIPA and TCPSA is relevant in this case and if a separate evaluation wouldn t underestimate exposure. In any case, inclusion of DIPA in the residue definition involves that it has to be taken into account in all parts of the residues section: residue trials, animal feeding, rotational crops, processing studies. Today, in the light of the new metabolism study, available data do UK RMS: In light of changes in the Toxicology section the RMS has conducted a new risk assessment for DIPA. This has been combined with the current risk assessment for triallate as both risk assessments now use the same end points. If DIPA is confirmed as being required in the residue definition for risk assessment a new risk assessment can be performed once additional data are available. RMS agrees that there are a number of uncertainties in the risk assessment. These cannot be fully addressed until a residue definition is confirmed. The RMS shares the concerns regarding the lack of data for DIPA exposure, but considers that the worst case assumptions made, particularly with respect to rotational crops, means the current risk assessment is as robust as is possible with the available data. Open point; RMS recommends expert Peer review proposed: The plant residue definition for risk assessment to be discussed. Considerations should be made on whether or not the following plant metabolites could be relevant in food and feed commodities: - Cereal Met. Peak 14 - Conjugated tri-allate Met. (M14 and M15) - DIPA - TCPSA See also 3(1), 3(4) and 3(9) www.efsa.europa.eu/publications 23 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Residue definition (B.7.3) not allow to achieve consumer risk assessment. 3(6) B.7.5 Residue definition EFSA: EFSA agree with the RMS that given the presence of a significant new plant metabolite DIPA and the presence, for which there is indication that it might be also of toxicological relevance, the residue definition for risk assessment needs to be amended. This is also the case in view of the TCPSA conjugates. Since in the light of the new data consumer and livestock dietary toxicological burden will be increased, this situation has to be considered an adverse outcome compared to the previous review and a reassessment of the consumer risk is triggered. 3(7) B.7.5, Definition of the residue NL: Indeed it is complicated to decide on the plant residue definition for monitoring. However, TCPSA seems to be more appropriate, since this metabolite is present in straw and grain in the metabolism study, while tri-allate was not detected at all. Furthermore, TCPSA was also detected in the residues trials. In addition, in the rotational crop metabolism study, TCPSA was more abundant than tri- discussion to confirm the residue definition for risk assessment. UK RMS: A revised risk assessment will be performed once the residue definition is confirmed and/or additional data are available if required. Open point, RMS recommends expert discussion to confirm the residue definition for risk assessment. UK RMS: The RMS agrees that there is a case to be made for TCPSA to be, or be included in, the residue definition for monitoring (this was highlighted in the discussion of the residue definition). However there is also a case for DIPA or tri-allate. For this reason the RMS considers that expert discussion to confirm the residue definition for monitoring is necessary, ideally once residues trials data for Peer review proposed: A revised risk assessment to be performed once the residue definition has been concluded on. See also 3(9) and 3(10) Peer review proposed: The plant residue definition for monitoring to be discussed in order to identify the most suitable marker(s). www.efsa.europa.eu/publications 24 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Residue definition (B.7.3) allate in almost all crop samples. DIPA are available (although this may not be possible/practical). Open point, RMS recommends expert discussion to confirm the residue definition for monitoring. Use pattern, critical GAP, residues trials (B.7.4 to B.7.6) No comments received. Processing (B.7.7) No comments received. www.efsa.europa.eu/publications 25 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Livestock feeding (B.7.8) No comments received. Succeeding/Rotational crops (B.7.9) 3(8) B.7.10 Rotational crops EFSA: Rotational crops studies in line with the risk assessment definition are triggered but are not available. This should be a data gap. UK RMS: RMS agrees further rotational crop studies may be required. However this will be dependent on the conclusion of the residue definition for risk assessment and monitoring. Open point, RMS recommends expert discussion of the residue definition for risk assessment to confirm if further rotational crop studies are required. Peer review proposed: Pending a conclusion regarding the plant residue definition for risk assessment, the relevance of rotational crop residues and a need for rotational crops studies in line with the risk assessment definition to be discussed. See also 3(9) www.efsa.europa.eu/publications 26 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate MRLs related issues and Consumer Risk Assessment (B.7.10 to B.7.15) 3(9) Confirmatory Data Assessment Addendum 8 B.7. Residues DE: Agreed to entire assessment of triallate, DIPA and TCPSA. It is stated that additional residues/rc trials data would be required before the risk assessment can be considered reliable. This data requirement is supported in general. However, in view of the likely low to moderate toxicity of DIPA it is proposed that the RMS adds a basic statement on the actual level of uncertainty for DIPA exposure and the resulting consumer risk. In other words, is there a realistic case conceivable where DIPA exposure may exceed the ARfD? (It is noted, that the ARfD for DIPA has still to be agreed.) A statement by the RMS could possibly waive the data requirements for plant studies. Furthermore it should be addressed by the RMS (i) at what level do DIPA residues in grain need to be in order to significantly contribute to reference values, and are these levels within the range of reliability and (ii) can TRR values from an existing RC metabolism study be used as surrogate for DIPA levels in rotational crops? UK RMS: Due to changes in the Toxicology section the risk assessment has been revised to include DIPA in the risk assessment for tri-allate rather than separately. As a result it is not appropriate to consider DIPA separately. The RMS considers that it is unlikely that DIPA exposure would lead to an exceedance of the ARfD, given the worst case assumptions taken for triallate and TCPSA conjugates would compensate for the uncertainties to some extent, however little data are available for DIPA to conclude with certainty. Open point, RMS recommends expert discussion to confirm the residue definition for risk assessment. Refer to 3(5), 3(6) and 3(8) www.efsa.europa.eu/publications 27 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate MRLs related issues and Consumer Risk Assessment (B.7.10 to B.7.15) 3(10) B.7.16 Consumer risk assessment Finally a further assessment by the RMS may give additional information for decision on requirements for animal studies. EFSA: Many assumptions were used to conduct the risk assessment which is therefore highly uncertain. The core studies that are necessary according to current data requirements (residues and toxicology) should be required and in order to conduct a reliable consumer risk assessment. UK RMS: A revised risk assessment will be performed once the residue definition is confirmed and/or additional data are available if required. Open point, RMS recommends expert discussion to confirm the residue definition for risk assessment. Refer to 3(6) Other comments No comments received. 4. Environmental fate and behaviour www.efsa.europa.eu/publications 28 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) 4(1) Page 5; Route of degradation of DIPA 4(2) Page 5; Rate of degradation of DIPA FR: The maximum occurrence observed in soil of the metabolite DIPA could be mentioned here (maximum 16.9% AR, mean of both replicates; maximum of 18.2%, individual value). Please update. FR: Data on the soil adsorption of metabolite DIPA was presented in the paragraph on the rate of degradation of DIPA in soil. These data should be reported in different section. UK RMS: Agreed. The addendum has been updated with the maximum occurrence of tri-allate (amine label) soil metabolite DIPA (16.9% AR). UK RMS: The title above the paragraph is written as rate of degradation in error and should be Adsorption and desorption. This has been amended in the addendum. Addressed Addressed 4(3) B.8.1 Route and rate of degradation in soil DE: In the study Herzog (2011), a significant portion of the parent compound volatised and was trapped in the PU plugs at 20 C. As far as we understand, these amounts were added to the soil amount of not degraded parent in the modelling of the degradation. We propose to discuss the implications for modelling of this circumstance. We propose to set the formation fraction of DIPA to 1 as a result. UK RMS: We note that a significant proportion of tri-allate volatilised and was trapped in the PU plugs in the Herzog (2011) study. Characterisation of the volatile material confirmed it to be mostly tri-allate. It should be noted that volatilised parent ranged between 29 to 50% AR in the three soils tested. The volatilised tri-allate does not contribute to the metabolite DIPA formed in soil. Considering the high proportion of tri-allate that is volatilised, it is unlikely that the Peer review proposed: Further discussion on how to calculate the formation fractions when a substantial part of the substance is volatilised is needed. In general it has been agreed that the amounts volatilised should be added to the soil amount to calculate the half-life. However, this results in a lower formation fraction of subsequent metabolites because the www.efsa.europa.eu/publications 29 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) 4(4) Table B8.1 and Table B.8.11, pages 72 and 78 FR: In table B8.1, the soil texture determined according to the USDA soil taxonomy should be mentioned since this information is needed to normalise the soil DT50 values. formation fraction would be 1. The RMS considers that the value of 0.66 calculated by the applicant to be reasonable. It may be argued that the volatilised triallate may reach soil due to deposition but this seems unlikely since the calculated half-life in air is 3.85 hours. In addition, any metabolites formed due to reaction with hydroxyl radicals are unlikely to be the same ones as formed in soil. In terms of adding the amounts of volatilised tri-allate to the amounts of tri-allate extracted from soil in the calculation of the tri-allate soil DT50 in the Herzog (2011) study, and a comparison with the soil DT50 calculation in the DAR, this is further discussed in point 4(10) below. UK RMS: For soils Speyer 2.2 (loamy sand) and 5M (sandy loam) normalising these soils with USDA classification would make no difference. In the case of soil 6S (clayey loam DIN or clay USDA) the amount volatilised had not contributed to the formation of subsequent metabolite but is considered in the degradationformation equations. The issue is that if only the amount remaining in the soil and actually contributing to the formation of the metabolites should be accounted for the estimation the formation fraction would be high (probably 1 in this case). The principle behind this is that actual volatilisation occurring in field cannot be estimated from the volatilisation occurring in the experimental laboratory test setting. Therefore, worst case degradation/formation parameters need to be derived from the laboratory experiments so contribution of volatilization can be independently considered by the modelling (without double counting it) Addressed www.efsa.europa.eu/publications 30 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) In addition, the DT50 normalisation was performed using the soil texture according to DIN classification. Therefore, the DT50 values are inadequately normalised to pf2. Without the soil texture (USDA classification), a correction factor of 1 should be used in the DT50 normalisation (table B8.11). default FOCUS moisture content at pf2 for a clay soil (48%) is greater than the maximum water holding capacity in the soil analysis (45.9%). Normalising according a clay soil would be nonsensical and less conservative than normalising to a clay loam. We consider the normalisation as presented in the report should remain unchanged. 4(5) Table B8.1 and Table B.8.11, pages 72 and 78 Normalised DT50 should be updated. FR agrees not to include the DT50 derived at 10 C from the speyer 2.2 in the geomean calculation (this information is missing in the table B8.11) in order to not introduce uncertainties (since for this soil the DT50 was normalised at 20 C using a Q10 default value of 2.58). This should be explained in the table 4(6) Table B8.12, page 79 FR: see comment 4 on the normalisation of DT50 to pf2. FR agrees with the UK RMS to calculate an overall geomean from the whole dataset. UK RMS: A footnote has been added below the Table (B.8.11). UK RMS: Thank you Addressed Addressed 4(7) Page 85 FR: The soil degradation of metabolite DIPA UK RMS: In the soil metabolism study of Addressed www.efsa.europa.eu/publications 31 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) seemed to be bi-phasic. Bi-phasic models should be also tested. Conservative DT50 calculated from slow phase may then be used to derive modelling endpoints. Please note that conservative derived DT50 may also be needed since in the lab study performed with the parent as item test no soil decline was observed for this metabolite. metabolite DIPA (Moser 2011), while the best fit for the Speyer 2.2 soil was DFOP which would be appropriate for persistence endpoint, the SFO fit was visually and statistically acceptable (Chi 2 5.5) and suitable for modelling. The SFO fits were also acceptable for 5M and 6S soils (Chi 2 6.3 and 4.3% respectively). Where possible, if SFO fit is good enough, which in this case it is, it should always be considered for selecting modelling endpoints. 4(8) Formation fraction of DIPA, page 86 FR: The kinetic modellings presented page 87 were visually acceptable. However, the DT50 of metabolite should be fixed to the default value of 1000 days as no soil decline of metabolite DIPA was observed for all soil. A ffm value may be then back calculated. UK RMS: The RMS does not agree with using a default DT50 of 1000 days for metabolite DIPA when experimental data are available. The use of experimental data is more appropriate. See also the response to point 4(3) in relation to the formation fraction. Addressed Note: The RMS approach is acceptable in this case since the metabolite dose studies were performed in the same soils than the parent studies. 4(9) B.8.1 Route and rate of degradation in soil - formation fraction of DE: We doubt that the procedure of using the degradation rate of Moser (2011) for calculation of the ff in the study of UK RMS: Setting the formation fraction of DIPA to 1 is a conservative estimate. However, in the groundwater See 4(3). Note: A general discussion on the www.efsa.europa.eu/publications 32 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) DIPA Herzog (2011) is correct. As in the previous comment (at 4(3)), we propose to set the formation fraction to 1 as a conservative estimate. modelling, in which the formation fraction of 0.66 was used it should be noted that DIPA exceeds 0.75 µg/l in 8 out of 9 scenarios simulated with PELMO and exceeds 10 µg/lin all 9 scenarios when simulated with PEARL (max 83 µg/l). Setting the formation fraction to 1 is unlikely to change the regulatory outcome. harmonisation of the approach may be needed. However, it is acknowledged that for the particular case of DIPA, the groundwater exposure assessment probably would not change. 4(10) B.8.1.1 Aerobic and anaerobic studies 4(11) B.8.1.1 Aerobic and anaerobic studies. Table 8.20 and following figures NL: What is the reason for not including the Speyer 2.2 soil 10 degrees test in the normalized overall value in Table B.8.12? NL has the opinion to include this value since it is normalized to 20 degrees and pf2. The value may be averaged with the Speyer 2.2 soil 20 degrees test be for the geometric mean over all soils is calculated. NL: The presented DFOP fit for Speyer2.2 soil showed visually perfect fit. Please explain the reason for not using the DFOP as modelling endpoint. NL has the opinion that according to FOCUS kinetics DFOP slow phase should be UK RMS: The Speyer 2.2 soil conducted at 10 C was not included as it was not conducted at reference temperature. We appreciate that the soil may be normalised to reference conditions but it is not appropriate to included this in the geomean DT50 calculation. UK RMS: We agree that DFOP provides a better visual and statistical fit for the Speyer 2.2 soil. In addition you are correct that where 10% of the initial concentration is not reached FOMC would not be appropriate and DFOP is Addressed Addressed www.efsa.europa.eu/publications 33 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate Route and rate of degradation in soil (B.8.1) used in this case. Also for soil Speyer 5M DFOP will give a better fit! FOCUS kinetics states that FOMC should not be used if 10% of the initial is not reached however. HS and DFOP can still be used to fit the obtained values! more appropriate and could be used for persistence endpoints. In this case, the SFO fit was visually and statistically acceptable (Chi2 5.5) and suitable for modelling. The SFO fits were also acceptable for 5M and 6S soils (Chi2 6.3 and 4.3% respectively). Where possible, if SFO fit is good enough, which in this case it is, it should always be considered for selecting modelling endpoints. Please also see response to 4(7). Adsorption,desorption and mobility in soil (B.8.2) No comments received. www.efsa.europa.eu/publications 34 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate PEC in soil (B.8.3) 4(12) PECsoil calculations, page 93 FR: The highest uncorrected DT50 value of 285.3 days should be used in PECsoil calculations. An updated PECsoil accumulation should be proposed. UK RMS: We note that the highest unnormalised laboratory soil DT50 is 285.3 days. However the PECsoil and accumulation calculations have been calculated based on the longest unnormalised field DT50 which was used in the DAR and is the agreed endpoint for Annex I listing. In the opinion of the RMS, the longest field DT50 is more realistic and more representative of the effects of environmental conditions which cannot be reproduced in a laboratory study. It should also be noted that the soil DT50 method of calculation in the original DAR was different to the method used in the by the applicant. In the original DAR (p 498) the following multi-compartment model was used to determine degradation rates using ModelMaker based on SFO kinetics in which separate rate constants were determined for volatilisation of parent and degradation of parent in soil (data from Mackie and Saunders, 1998): Addressed www.efsa.europa.eu/publications 35 EFSA Supporting publication 2016:EN-953
Outcome of the consultation on used in risk assessment for tri-allate PEC in soil (B.8.3) The rate of degradation of tri-allate in soil was determined from the rate constant k2. In calculating the volatilisation rate constant, k1.it should be noted that in the Mackie 1998 study, it was assumed that all the volatilised material in the PU plug was tri-allate although it was not characterised. In the Herzog (2011) study the volatilised material was characterised and known to be tri-allate. In the confirmatory data, a different approach was taken whereby the amount of triallate volatilised at each timepoint was added to the amount of tri-allate extracted from soil (as % extractables) resulting in a more conservative soil DT50. It should be noted that the soil DT50s from the Herzog (2011) study are significantly longer (232.2 to 285.3 days) than those from the original DAR (38.4 to 75.2 days). To illustrate the difference, the RMS has recalculated the soil DT50 from the Herzog (2011) www.efsa.europa.eu/publications 36 EFSA Supporting publication 2016:EN-953