Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for fluroxypyr in light of confirmatory data

Transcription

1 TECHNICAL REPORT APPROVED: 22 July 2015 PUBLISHED: 31 July 2015 Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for fluroxypyr 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 States, the applicant and EFSA on the and their use in the risk assessment for fluroxypyr are presented. The current report summarises the outcome of the consultation process organised by the rapporteur Member State Ireland and presents EFSA s scientific views and conclusions on the individual comments received. European Food Safety Authority, 2015 Key words: fluroxypyr, peer review,, risk assessment, pesticide, herbicide Requestor: European Commission Question number: EFSA-Q Correspondence: pesticides.peerreview@efsa.europa.eu EFSA Supporting publication 2015:EN-857

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 fluroxypyr in light of. EFSA supporting publication 2015:EN pp. European Food Safety Authority, 2015 Reproduction is authorised provided the source is acknowledged. 2 EFSA Supporting publication 2015:EN-857

3 Summary Fluroxypyr was approved on 1 January 2012 under Regulation (EC) No 1107/2009 by Commission Implementing Regulation (EU) No 736/2011. It was a specific provision of the approval that the applicant was required to submit to the European Commission further studies on (a) the relevance of the impurities present in the technical specifications; (b) the relevance of the test material used in the toxicity dossiers in view of the specification of the technical material; (c) the toxicological relevance of the metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine; (d) the residue analytical methods for plants; (e) the fate of fluroxypyr esters in animal matrices; (f) the long-term risk for earthworms and soil organisms by 1 July 2012 (point (a) and (b)) and by 31 December 2013 (points (c), (d), (e) and (f)). In accordance with the specific provision, the applicant, Dow AgroSciences, submitted an updated dossier in September 2013, which was evaluated by the designated rapporteur Member State (RMS), Ireland, in the form of an the draft assessment report. In compliance with guidance document SANCO 5634/2009-rev. 6.1, the RMS distributed the Member States, the applicant and EFSA for comments on 22 December The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 24 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, Ireland, and presents EFSA s scientific views and conclusions on the individual comments received. Fluroxypyr is the ISO common name for 4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetic acid (IUPAC). Due to the fact that the meptyl ester, a variant of fluroxypyr, is used in the formulated product, it should be noted that the evaluated data belong to the variant fluroxypyr-meptyl, unless otherwise specified. EFSA considers that the with regard to the methods of analysis for plants (d) has not been addressed. It should be noted that the RMS does not agree with this opinion. In the area of mammalian toxicology, concerning the on point (a) the relevance of the impurities present in the technical specifications EFSA agreed with the RMS that impurities (as proposed in the technical specification) other than N-methyl-2-pyrrolidone (NMP) are unlikely to alter the toxicological profile of fluroxypyr active ingredient and they should not be considered relevant. NMP should be considered a relevant impurity based on its hazards and its maximum content in the technical specification from the toxicological point of view should be 0.3%. EFSA considered that based on the proposed content (i.e. 0.3%) in the proposed technical specification and the lowest ED10 (225 mg/kg bw per day) derived by ECHA RAC (2014), it is highly unlikely that there would be acute consumer risk for developmental toxicity based on the presence of NMP as an impurity in the technical specification. The current proposed content of NMP in the technical specification (i.e. 0.5%) will however trigger classification of the technical fluroxypyr-meptyl with Repr. 1B with H360D. Concerning on point (b) the relevance of the test material used in the toxicity dossiers in view of the specification of the technical material ; EFSA noted that the proposed minimum purity of the active substance and the specification of the impurities for the reference source were not supported by the available data and a data gap was identified for a new specification supported by the relevant data (EFSA, 2011). No new data are available to support the proposed specification (i.e. the data as reported under are the same that were not accepted previously). Despite the limited information on the composition of the batches used in the toxicological studies EFSA would agree that the proposed specification for impurities other than NMP is acceptable from the toxicological point of view. However, since the proposed specification was not accepted during the peer review a further assessment on the compliance of the batches used in the toxicological studies will be needed once the specification is finally accepted. Concerning on point (c) the toxicological relevance of the metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine ; no toxicological assessment was done. A refinement of the groundwater exposure assessment on the basis of the results of new studies on soil degradation of methoxypyridine and soil sorption of pyridinol was provided. For the confirmatory data on relevance of metabolites to be concluded upon, it is essential for acceptable FOCUS 3 EFSA Supporting publication 2015:EN-857

4 groundwater exposure assessments to be available, where all aspects of input parameter selection have been completed appropriately. Such assessments are not available. This conclusion is contrary to that of the RMS. Regarding the fate of fluroxypyr esters in animal matrices (e), additional studies on animals conducted with the ester forms were not provided in the framework of these. A theoretical approach, based on the ph values observed in the ruminant gastro-intestinal (GI) tract and the time required for digestion, was proposed to conclude that esters will be hydrolysed to the acid form during digestion and therefore, that the metabolism of fluroxypyr esters in ruminants would be identical to the metabolism of fluroxypyr acid. Having regard to the significant estimated dietary residue intakes by livestock (1.8 mg/kg bw, beef cattle), EFSA is of the opinion that the theoretical approach proposed by the applicant is not sufficient to conclude that the fate of fluroxypyr esters in animal matrices is covered by the fate of the acid form of fluroxypyr. It is noted that the RMS is not in agreement with this. The submitted studies were considered sufficient to address the risk for fluroxypyr pyridinol and fluroxypyr methoxypyridine to earthworms and soil organisms. Two new studies on the aquatic macrophyte Myriophyllum spicatum, not covered by the list of, were also submitted. An assessment of these studies and the related risk assessment were carried out. 4 EFSA Supporting publication 2015:EN-857

5 Table of contents Abstract... 1 Summary Introduction Background and Terms of Reference as provided by the requestor Interpretation of the Terms of Reference Assessment... 7 Documentation provided to EFSA... 7 References... 7 Abbreviations... 8 Appendix A Collation of comments from Member States, applicant and EFSA on the pesticide risk assessment for the active substance fluroxypyr in light of and the conclusions drawn by EFSA on the specific points raised... 9 Appendix B Used compound code(s) EFSA Supporting publication 2015:EN-857

6 1. Introduction 1.1. Background and Terms of Reference as provided by the requestor Fluroxypyr was approved on 1 January 2012 under Regulation (EC) No 1107/ by Commission Implementing Regulation (EU) No 736/ It was a specific provision of the approval that the applicant was required to submit to the European Commission further studies on (a) the relevance of the impurities present in the technical specifications; (b) the relevance of the test material used in the toxicity dossiers in view of the specification of the technical material; (c) the toxicological relevance of the metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine; (d) the residue analytical methods for plants; (e) the fate of fluroxypyr esters in animal matrices; (f) the long-term risk for earthworms and soil organisms by 1 July 2012 (point a and b) and by 31 December 2013 (points (c), (d), (e) and (f)). EFSA previously finalised a Conclusion on this active substance on 8 March 2011 (EFSA, 2011). In accordance with the specific provision, the applicant, Dow AgroSciences, submitted an updated dossier in September 2013, which was evaluated by the designated rapporteur Member State (RMS), Ireland, in the form of an the draft assessment report (Ireland, 2014). In compliance with guidance document SANCO 5634/2009-rev.6.1 (European Commission, 2013), the RMS distributed the Member States, the applicant and the EFSA for comments on 22 December The RMS collated all comments in the format of a reporting table, which was submitted to EFSA on 24 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, Ireland, 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 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 States, the applicant and EFSA on the risk assessment of for fluroxypyr 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 23 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 Regulation (EC) No 1107/2009 of 21 October 2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, , p Commission Implementing Regulation (EU) No 736/2011 of 26 July 2011 approving the active substance fluroxypyr, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market, and amending the Annex to Commission Implementing Regulation (EU) No 540/2011. OJ L 195, , p EFSA Supporting publication 2015:EN-857

7 2. Assessment The comments received on the pesticide risk assessment for the active substance fluroxypyr 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. Ireland, Addendum to the assessment report on fluroxypyr,,. Available online: 2. Ireland, Reporting table, comments on the pesticide risk assessment for fluroxypyr in light of, June References EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance fluroxypyr. EFSA Journal 2011;9(3):2091, 91pp. doi: /j.efsa Available online: 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. 6.1 ECHA RAC (European Chemical Agency; Committee for Risk Assessment), Opinion proposing harmonised classification and labelling at EU level of 1-methyl-2-pyrrolidone (NMP). Adopted on 6 June Available online: EFSA Supporting publication 2015:EN-857

8 Abbreviations a.s. DAR ECHA RAC EC ED EFSA EU GAP LC 50 LD 50 MRL MS NESTI OSR PBI PEC PEC sed PEC soil PHI RMS TMDI TRR TSCF active substance draft assessment report European Chemicals Agency Committee for Risk Assessment emulsifiable concentrate effective dose European Food Safety Authority European Union good agricultural practice 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 pre-harvest interval rapporteur Member State theoretical maximum daily intake total radioactive residue transpiration stream concentration factor 8 EFSA Supporting publication 2015:EN-857

9 Appendix A Collation of comments from Member States, applicant and EFSA on the pesticide risk assessment for the active substance fluroxypyr in light of and the conclusions drawn by EFSA on the specific points raised 1. Physical/Chemical Properties; Details of Uses and Further Information; Methods of Analysis Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(1) Vol. 4, C.1 DE: The assessment of the RMS concerning the relevance of the impurities present in the technical specifications as well as the relevance of the test material used in the toxicity dossiers in view of the specification of the technical material is supported. RMS: Thank you for your support. 1(2) Vol. 4, C.1.2.2, p 14, Identity of isomers and impurities a) DK: line1-3 at the bottom. technical fluroxypyr methyl should be fluroxypyr-meptyl? RMS: Thank you. Typo noted. See 1(6) Addressed. 9 EFSA Supporting publication 2015:EN-857

10 Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(3) Vol. 4, C.1.2.2, p 14, Identity of isomers and impurities a) and Table C p4 DK: In the Table C p4 the max content RMS: of NMP in the technical specification is 5 g/kg Thank you for your comment. but in the bottom of page 14 it is stated to be 3 g/kg in technical fluroxypyr methyl (perhaps meptyl see comment 1). Could you specify in the text that the 5 g/kg is for the source of current Annex 1 and the 3 g/kg is for the source Drusinheim 2009, if that is the case? Furthermore it would be relevant to show that another source Midland 2009 is 6.3 g/kg. Addressed. The current content of NMP in the proposed specification will trigger classification of the technical The current Annex I specification for Fluroxypyr has a fluroxypyr-meptyl with Repr. 1B with max. specification level of 5 g/kg for NMP. The Annex I H360D. manufacturing facility is the Drusenheim plant. However NMP has recently been assigned a GCL 0f 0.3%, therefore the original specification level of 5 g/kg will need to be reconsidered. The quality of material manufactured in the Drusenheim and Midland sources will need to comply with the new Annex I specification proposal for NMP: max. 3 g/kg. 1(4) Vol. 4, C.1.2.2, general, Identity of isomers and impurities a) DK: we agree that NMP classification will trigger classification of the technical fluroxypyrmeptyl with Repr. 1B with H360D. Please note that the application will provide new batch data in June 2015 and the RMS will evaluate this and make it available. RMS: Thank you for your support. Addressed. The current content of NMP in the proposed specification will trigger classification of the technical fluroxypyr-meptyl with Repr. 1B with H360D EFSA Supporting publication 2015:EN-857

11 Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(5) Vol. 4, C.1.2.2, general, Identity of isomers and impurities a) DK: It should be considered to allocate an ARfD to fluroxypyr due to the content of NMP. RMS: Thank you for your comment. NMP is not acutely toxic/harmful. Doses at which developmental toxicity is noted are relatively high..it has been assigned a GCL of 0.3% (Cat 1B medium potency) on the basis of application of the new guidance on concentration limits for reproductive toxicants (see CLP Guidance nov 2013 Annex VI). NMP has been classified as Repro Cat 1B on the basis of developmental toxicity in the rat (retardationrelated affects from 250 mg/kg and malformations from 400 mg/kg bw.). The RMS does not consider this profile relevant for setting a ARfD for NMP in fluroxypyr.. Addressed. ECHA RAC derived the lowest ED10 of 225 mg/kg bw per day from the rabbit oral developmental toxicity study (ECHA RAC, 2014): 62/fa8e78f c7-b73ee3cc84349e3f EFSA agreed that based on the proposed content (0.3%) in the technical specification and the lowest ED10 (225 mg/kg bw per day) derived by ECHA RAC it is highly unlikely that there would be acute consumer risk for developmental toxicity based on the presence of NMP as an impurity in the technical specification EFSA Supporting publication 2015:EN-857

12 Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(6) Vol. 4, specification EFSA: The given specification in the addendum was not accepted during the peer review and a data gap was set. RMS: Thank you for your comment. It is our understanding that after the peer-review, it was decided by risk managers that Fluroxypyr would be re-included in Annex I with the same specification which was agreed under the original EU evaluation. However, two confirmatory issues remain outstanding in relation to this specification as outlined in the inclusion regulation. The outstanding issues that remain open in relation to the specification are tox. issues. The two outstanding tox. issues in relation to the specification are also discussed under 1(1), 1(7), 1(8) of this table. Other issues outlined as data gaps in the EFSA conclusion do not form part of the as outlined in the Inclusion Regulation. EFSA noted that the proposed minimum purity of the active substance and the specification of the impurities for the reference source were not supported by the available data and a data gap was identified for a new specification supported by the relevant data (EFSA, 2011). No new data are available to support the proposed specification (i.e. the data as reported under are the same that were not accepted previously). Despite the limited information on the composition of the batches used in the toxicological studies EFSA would agree that the proposed specification for impurities other than NMP is acceptable from the toxicological point of view. However, since the proposed specification was not accepted during the peer review a further assessment on the compliance of the batches used in the toxicological studies will be needed once the specification is finally accepted EFSA Supporting publication 2015:EN-857

13 Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(7) Vol. 4, Relevance of impurities Pages (8) Vol. 4, Compliance of the batches used in the toxicological studies compared to the technical specification. Pages EFSA: EFSA agreed with the assessment of the toxicological relevance of impurities and agreed that N-methyl-2-pyrrolidone (NMP) should be considered a relevant impurity based on its hazards ant its maximum content from the toxicological point of view should be 0.3%. EFSA: Since the given specification in the addendum was not accepted during the peer review a further assessment on the compliance of the batches used in the toxicological studies will be needed once the specification is finally accepted. 1(9) Vol 4, P14 NL: Minor remark: on P14 at the bottom below the table, technical fluroxypyr-methyl should probably be fluroxypyr-meptyl. RMS: Thank you for your support. RMS: Thank you for your comment. See RMS response under 1(6) above. Fluroxypyr was re-included in Annex I using the original Annex I specification, therefore the specification is already in place. However, the specification cannot be fully accepted until the two tox. confirmatory issues are finalised as outlined in the Inclusion Regulation: quality of test material used in the supporting tiox. studies, and also the relevance of the impurities in the specification. Two issues are identified in the Inclusion Regulation both tox. issues which need to be addressed in order to finalise the specification. Other issues outlined as data gaps in the EFSA conclusion do not form part of the as outlined in the Inclusion Regulation. RMS: Thank you. Typo noted. N-methyl-2-pyrrolidone (NMP) should be considered a relevant impurity based on its hazards and its maximum content from the toxicological point of view should be 0.3%. See 1(6) Addressed EFSA Supporting publication 2015:EN-857

14 Volume 4 assessment report commenting phase conducted on the RMS s assessment of 1(10) Vol 4, P15 NL: The issue with the NMP concentration should RMS: be resolved. If the upper limit remains at 0.5%, Thank you for your comment. whereas the classification limit for NMP is 0.3% and the technical material actually contains up to This should be dealt with at product authorisation. 0.63% NMP (source II), this would lead to Applicants will to need to reduce the level of NMP. complicated situation with regard to the risk assessment and C&L. Please note that the application will provide new batch data in June 2015 and the RMS will evaluate this and make it available. 1(11) Vol 4, P15 NL: The RMS mentions an AMES test was done with the TC. What was the NMP concentration in the batch tested? RMS: Thank you for your comment. The report did not mention an exact concentration level for NMP, other than the fact it was a batch that was produced under normal manufacturing practice at the Annex I plant (Drusenheim). Based on the concentration level of NMP from 2006 batch data (presented in the RAR), it can be assumed that NMP was present at somewhere between a range of 2 3 g/kg (mean + 3sd = 4.24 g/kg) in the tested batch. Addressed. N-methyl-2-pyrrolidone (NMP) should be considered a relevant impurity based on its hazards ant its maximum content from the toxicological point of view should be 0.3%. The current proposed content of NMP in the specification will trigger classification of the technical fluroxypyr-meptyl. Addressed. The content of NMP in the Ames test was not measured EFSA Supporting publication 2015:EN-857

15 Methods of analysis (B.5) assessment report commenting phase conducted on the RMS s assessment of 1(1) Vol. 3, B.5 DE: The assessment of the RMS concerning the analytical method for food of plant origin is supported. 1(2) Vol. 5 EFSA: Two data requirements were set in the EFSA conclusion for methods (details in column 3). Unfortunately the detail provided is not sufficient. What is needed is a full comparison of all the methods e.g. concentration of the alkali used, length of hydrolysis etc., this also applies for extraction and derivitisation. RMS: Thank you for your support. RMS: Thank you for your comment. IE considers that sufficient detail has been provided. Addressed The data provided did not address the outstanding issues on residue analytical methods for plants. It is noted that the RMS is not in agreement with this. 3. Residues Storage Stability (B.7.0) assessment report commenting phase conducted on the RMS s assessment of 3(1) Vol.3, Confirmatory information, B.7 DE: It is noted that no documented evidence is provided to address the fate of the ester in livestock matrices and satisfy data requirements. We suggest that at least an artificial system is set-up to address this case. The argumentation is not considered RMS: Thank you for your comment. IE considers that strong argumentation has been provided by the applicant with respect to the conditions that esters would encounter in the cow Since ruminants are mostly exposed to fluroxypyr esters (see point 3(2)), as Germany, EFSA remains of the opinion that sufficient information has not been provided to address the fate of the esters in ruminant matrices EFSA Supporting publication 2015:EN-857

16 Storage Stability (B.7.0) assessment report commenting phase conducted on the RMS s assessment of sufficient. (intestine and duration of food passing), to suggest that esters will be converted to the acid. Please see NL comment 3(3) below. It is noted that the RMS is not in agreement with this. 3(2) Addendum Vol. 3, December 2014, Vol. B.7 EFSA: It is erroneous to report that studies have also shown that fluroxypyr esters will be present, but to a lesser extent than their acid counter parts in forage, straw and grain. AR should be amended stating that, based on the representative use on pastures, livestock animals will be mostly exposed to fluroxypyr esters and in a significant lesser extent, to fluroxypyr (acid). For clarification, what exactly would an artificial system involve? RMS: Thank you for your comment. IE considers that strong argumentation has been provided by the applicant with respect to the conditions that esters would encounter in the cow (intestine and duration of food passing), to suggest that esters will be converted to the acid. Please see NL comment 3(3) below. Contrary to what is mentioned by the RMS in the Addendum of December 2014, and considering that fluroxypyresters account for 41% to 67% TRR in wheat forage 7 to 14 days after applications (supported PHI on pasture 7 days NEU, 14 days SEU), It should be concluded that ruminants are mainly exposed to fluroxypyr esters. 3(3) Vol 3, B.7 Residues, point (e) NL: agrees with the argumentation in the addendum on the conditions in the cow intestine and the duration of food passing, that luroxypyr esters will be converted to fluroxyoyr acid. The fate of fluroxypyr esters in ruminant matrices is sufficiently addressed. RMS: Thank you for your support. See point 3(1) 16 EFSA Supporting publication 2015:EN-857

17 4. Environmental fate and behaviour Route and rate of degradation in soil (B.8.1) addendum to assessment report commenting phase conducted on the RMS s assessment of 4(1) Vol. 3, B.8.1, Annex IIA 7.1.1; Annex IIIA 9.1.1, Route and rate of degradation in soil 4(2) Vol. 3, B Rate of degradation DK: We agree that the degradation scheme needs to be amended to reflect that DMP degraded to CO 2 and NER ultimate degradation products, via formation of DCP. Furthermore, we agree that the unknown degradation product of DMP can be classified as a minor metabolites fraction and does not require further identification. DK: We support the kinetically evaluation made by the RMS. RMS/CoRMS: comment noted, no action taken. RMS/CoRMS: comment noted, no action taken. Addressed The kinetic evaluation of the new DMP dosed study is clear and transparent. However the selection of modelling endpoints (DT50 and kinetic formation fractions) carried out by the RMS does not follow the agreed FOCUS kinetics guidance. DFOP fits should not be selected for modelling when <10% of the initial measured amount of test substance is achieved at study end which is the case here for 3 of the 4 soils. In this situation FOMC-SFO (FOMC DT90/3.32) or SFO-SFO approaches are the only options that the guidance recommends. Use of K2 from DFOP as has been done is not in accordance with any guidance. The correct selection of 17 EFSA Supporting publication 2015:EN-857

18 Route and rate of degradation in soil (B.8.1) addendum to assessment report commenting phase conducted on the RMS s assessment of 4(3) Addendum Vol. 3, December 2014 B , rate of degradation laboratory studies, pages EFSA: The RMS has made a transparent evaluation of their kinetic fitting. In all cases they selected DFOP fit for the dosed methoxypyridine and SFO for its transformation product pyridinol, then the slow phase methoxypyridine value was selected as the modelling endpoint. This will be conservative in terms of modelling for methoxypyridine but will underestimate the mass of pyridinol formed in any modelling as the slow phase occurs when most of the mass of methoxypyridine is already depleted. For simulations for pyridinol, the fast phase rate constant from the DFOP fit for methoxypyridine as precursor would need to be used to generate more reasonable amounts of pyridinol. EFSA would therefore propose that in line with previous discussions on other substances as the fits of SFO-SFO RMS/CoRMS: The selection of the kinetic model was based on the thorough analysis of the results of fitting and took into account the way this was done. First of all, it shall be pointed out that because DMP was volatile, the concentrations at the given time points had to be corrected adequately to compensate that effect. This was done for both DMP and DCP. From the fact that DMP was volatile it may be deduced that for this compound the degradation follows bi-phasic pattern rather than that in line with SFO model. Secondly, it was noted that SFO/SFO option resulted in worst kinetic fitting results for both DMP and DCP, while the option DFOP/SFO gave acceptable, both visually and statistically, fits for both compound. DT values and kinetic formation fractions is key here as the groundwater exposure assessment is sensitive to these parameters. For the on relevance of metabolites to be concluded upon, it is essential for acceptable groundwater exposure assessments to be available, where all aspects of input parameter selection have been completed appropriately. The RMS selection of kinetic endpoints for DMP and DCP use in modelling is not in accordance with FOCUS kinetics guidance. To have a robust assessment, experts would need to agree for each soil incubation in the experiment of Gesell and Balcer (2011) whether SFO-SFO or FOMC-SFO fits should be selected, with the exception of the Farditch soil where DFOP-SFO, FOMC-SFO or SFO-SFO fits would be possibilities in line with FOCUS kinetics guidance. The selection should consider the mass of DCP that would be generated in simulations and how reasonable this would be and not just the goodness of fit observed and 18 EFSA Supporting publication 2015:EN-857

19 Route and rate of degradation in soil (B.8.1) addendum to assessment report commenting phase conducted on the RMS s assessment of are not too bad, these should have been selected as the modelling endpoints. We consider that it would be necessary to repeat groundwater modelling for pyridinol where a median (in total 16 incubations available) of the SFO-SFO half lives of 105 days for methoxypyridine is used with formation fractions of from parent and from methoxypyridine to pyridinol in combination with a median (in total 16 incubations available) pyridinol DT50 of 13 days. The list of endpoints probably needs to be updated accounting for this comment (DT endpoints and further groundwater modelling). Methoxypyridine SFO DT50: 65.4, 185.5, 542.5, 16.7, 146.4, 118, , 271.7, 1000, 44.5, 92.7, 243.3, 6.1, 9.78, 20.83, 28.5 days All that taken into account RMS/CoRMS is of the opinion that due to the some uncertainty related to the fitting, and resulting from the high volatility of DMP, it is better to use the fits that are both visually and statistically acceptable. Finally, it shall be also pointed out that, according to the refined transformation pathway DCP is formed twice, once from furoxypyr acid and for the second time from DMP. These events would be separated in time, with main formation peak for DCP coming from Fluroxypyr (and hence higher risk to GW comnpartment) so there is no risk of underestimation of the leaching potential of that compound, moreover because of the would-be overlap (this can be excluded because DCP is not persistent in soil). indicated by the statistics. SFO-SFO pyridinol kinetic formation fractions from methoxypyridine: , 1, 1, 1 Pyridinol SFO DT50: 16.3, 14, 12.6, 4.1, 58, 11.5, 24.6, 8.4, 58.7, 11.2, 13.5, 105.4, 10.52, 7.85, 18.92, 7.87 days 4(4) Addendum to Vol. 3, NL: excellent kinetic re-analysis from RMS. B , ; The new DFOP DT 50 degradation parameters for Table P.A. Ad. B RMS/CoRMS: Yes, this can be done. As the soil moisture was reported by the Applicant at pf 2.5 (⅓ Bar), to do the normalisation it was The maximum water holding capacity for each soil (MHC) that was used for the soil incubations 19 EFSA Supporting publication 2015:EN-857

20 Route and rate of degradation in soil (B.8.1) addendum to assessment report commenting phase conducted on the RMS s assessment of 4(5) Addendum to Vol. 3, B , ; Table P.A. Ad. B metabolite DMP are added to the already available parameters in the LoEP. However, the new values are not normalised for moisture content, whereas the already available values are normalised to pf2/10kpa. Is het possible to normalise the new values for moisture as well and adjust Table accordingly? NL: as n > 6, median values of resp days and 13.8 days for metabolites methoxypyridine and pyridinol are preferred necessary to use the data presented in the Table 5.2 of the FOCUS GW Guidance document (SANCO/321/2000). The resulting fully normalised DT 50 values are following: For DMP: in soil M807 DT 50 = days, in soil M808 DT 50 = days, in soil M809 DT 50 = days, and in soil M810 DT 50 = days. For DCP : in soil M807 DT 50 = days, in soil M808 DT 50 = days, in soil M809 DT 50 = days, and in soil M810 DT 50 = 8.85 days. When averaged the values recommended for modelling are then following: For DMP: geomean DT 50 = days; median DT 50 = days For DCP: geomean DT 50 = days; median DT 50 = days RMS/CoRMS: Until recently the common practice in selection of averaged input parameters for GW/SW modelling was, in case when in Gesell and Balcer (2011) is not available in the study report. This must have been known for the incubations to have been carried out at 50% MHC as is stated in the study report. These data would be needed to calculate meaningful correction factors for normalising soil half lives to reference conditions as required by FOCUS modelling guidance. This information should be available in the raw data of this GLP study. Appropriate reliable normalisation is needed in this case as the correct selection of DT values is key here, as the groundwater exposure assessment is sensitive to the DT parameter. For the on relevance of metabolites to be concluded upon, it is essential for acceptable groundwater exposure assessments to be available, where all aspects of input parameter selection have been completed appropriately. Addressed. When there are no indications that 20 EFSA Supporting publication 2015:EN-857

21 Route and rate of degradation in soil (B.8.1) addendum to assessment report commenting phase conducted on the RMS s assessment of for PECgw and PECsw calculations. (The same comment counts for input parameters PECgw calculations, as summarized in Table P.A. Ad. B ) geomean and median values were available, to use the worse-case, i. e. longer value. Such was also recommendation given for DMP and DCP for the renewal of Annex-I inclusion. For DMP with recalculated average values (after full normalisation of the four newly derived DT 50 value) the matter of choice of median or geaomean is irrelevant, as both values are almost the same (the difference is of 0.02 day in favour of median). In case of DCP the new geomean DT 50 is still 3.67 days longer than the median, so using the principle evoked above, geomean may be still considered as more appropriate. DT50 can be correlated to a soil property such as ph (which is the case here) the geomean value has be selected for modelling with this quantity of data. The original comment of the NL (and the RMS reply) do not reflect the FOCUS guidance and EU evaluation practice (including that in place at the time of submission). Use of a median (as opposed to a geomean) DT50 was only accepted by the peer review when 9 or more reliable values were available. In more recent guidance only the geomean should be selected for DT50 when use of any kind of average value is appropriate EFSA Supporting publication 2015:EN-857

22 Adsorption, desorption and mobility in soil (B.8.2) addendum to assessment report commenting phase conducted on the RMS s assessment of 4(6) Add. Vol. 3, B Summary of adsorption/ desorption studies DE: It is stated that a ph-dependence of the adsorption of DCP onto soil was determined. However, plotting the available K foc or K f values as a function of ph does not support this conclusion: Moreover, there is no statistical indication of a phdependence (as an analysis with InputDecision shows). More information would be required in order to justify the use of separate mean K foc RMS/CoRMS: For the degradation product pyridinol (DCP) it was stated that on the basis of the available extended data base on soil sorption it can be stated that no ph-dependence of adsorption is observed. This claim is supported by the results of the statistical analysis of the data. It shall be pointed out however, that when these data are thoroughly analysed, this conclusion is not that evident. Two K foc measured at ph > 7 are very close, in range ml/g. In case of the K foc values determined in soils having ph < 7 all values are higher that 100 ml/g, clearly indicating that something is happening. What is more, the data reported in LoEP from the study by Hale and Gardinal when combined with these from the study by Ostrander and Cleveland (these are K d and, in particular, K doc values) clearly indicate that such relationship exists. The study by Simmonds and Burgess only confirmed that observation. It was indicated elsewhere that there was a mistake in LoEP with regard to the study by Ostrander and Cleveland the soils and the sorption parameters determined See comment 4(7). Clarity has to be provided for all soils, which ph is associated with which adsorption value. Note when EFSA checked the data of Ostrander and Cleveland all the attributions in the list of agreed endpoints of the published EFSA conclusion regarding soil ph, Kd, Kdoc, KF, and KFoc would appear correct. The mistake in the coupling that EFSA could identify was just the reported oc values. This does not appear to impact on the consideration of ph dependence. However the checking of EFSA indicates that the statements in column 3 appear erroneous. As far as EFSA can tell the text in column 3 should say: in clay soil, having ph = 5.7 K foc = ml/g, while in sand soil, having ph = 6.4 K foc = ml/g; for the two other soils, both having ph = 6.8, in silt loam K foc = ml/g and in sandy loam K foc = ml/g. Below EFSA has plotted all the available data including that of Hale and Gardinal (1995) 22 EFSA Supporting publication 2015:EN-857

23 Adsorption, desorption and mobility in soil (B.8.2) addendum to assessment report values for acidic/neutral and alkaline soils as proposed by the RMS. for them were wrongly coupled. This is in principle true, However, the correct coupling would lead to the interesting conclusion even for acidic soils the ph dependence becomes now clearly visible: in clay soil, having ph = 5.7 K foc = 1791 ml/g, while in sand soil, having ph = 6.4 K foc = 708 ml/g; for the two other soils, both having ph = 6.8, in silt loam K foc = 1741 ml/g and in sandy loam K foc = 913 ml/g. All this taken into account, RMS/Co-RMS is of the opinion that the conclusion non the ph-dependence of the soil sorption for DCP should be maintained as there is enough experimental evidence supporting it. commenting phase conducted on the RMS s assessment of 4(7) Addendum Vol. 3, December 2014 B , Summary of adsorption studies, page 55 EFSA: There is no explanation why the agreed adsorption endpoints for pyridinol that were discussed and agreed as reliable in the expert teleconference 51 for fate and behaviour from the study Hale and Gardinal (1995) have been excluded from the data set and not used in the newly supplied RMS/CoRMS: The results of the study by Hale and Gardinal (1995) are K d /K doc values, which are simple distribution coefficients measured at one concentration. All other values are Freundlich isotherm constants, the values representing thermodynamic constants. The RMS exclusion of reliable Kdoc values agreed as reliable in the expert teleconference 51 for fate and behaviour from the study Hale and Gardinal (1995) is not in accordance with previous peer review decisions or FOCUS modelling input guidance. EFSA 23 EFSA Supporting publication 2015:EN-857

24 Adsorption, desorption and mobility in soil (B.8.2) addendum to assessment report commenting phase conducted on the RMS s assessment of groundwater modelling. Combining the previously agreed reliable endpoints with the new study supplied as results in 8 Koc values in soils below ph 7 giving an arithmetic mean KFoc of 786mL/g (arithmetic mean 1/n=0.83) and 5 Koc values in soils above ph 7 giving an arithmetic mean KFoc of 54mL/g (arithmetic mean 1/n=0.89). We consider that it would be necessary to repeat groundwater modelling for pyridinol using these adsorption values. The list of endpoints probably needs to be updated accounting for this comment. KFoc for soils < ph 7: 345, 913, 337, 99.8, 1741, 352, 179, 708 ml/g 1/n for soils < ph 7: 0.79, 0.81, 0.754, 1, 0.81, 0.744, 0.85, 0.87 KFoc for soils > ph 7: 41.4, 61, 76, 36.5, 55.1 ml/g 1/n for soils > ph 7: 1, 0.717, 0.731, 1, 1 4(8) Addendum to Vol. 3, NL: arith. mean for Freundlich isotherm adsorption B , ; parameters for alkaline soils only is based on 2 Table P.A Ad. B soils. Does RMS this consider an adequate and sufficient basis for deriving these parameters? Furthermore, according to NL, 1/n value for acidic and neutral soil could be based on arith. mean The meaning of the two is different. Until recently the practice was not to merge the two types of values, because while in general they describe the same phenomenon, they do this in a different way. It shall be also pointed out that attributing the 1/n =1.0 value to the K d /K doc value is somehow artificial, because by definition this cannot be done. For that reason it was decided not to include the values from Hale and Gardinal s [1995] study into the data-set for adsorption used in modelling. What does not mean, on the other hand, that it was decided to exclude them totally they are kept as valuable supporting the statement on the ph dependence of soil sorption of DCP. RMS/CoRMS: Agree with the comment. Indeed in light of the current Guidelines for alkaline soils, as only two values are available, the lowest K foc with corresponding 1/n should be used, so the information on the input parameters should be updated in line with the considers that all reliable values should be used. Note the RMS statement that Until recently the practice was not to merge the two types of values is simply not true. Experts also need to conclude on the ph dependence of DCP adsorption and how this should be used to parameterise the model inputs. For a useful discussion complete clarity has to be provided for all soils, which ph is associated with which adsorption value. See comment 4(7). Note use of a median 1/n value for DCP as was done, was not in accordance with FOCUS groundwater and surface water guidance EFSA Supporting publication 2015:EN-857

25 Adsorption, desorption and mobility in soil (B.8.2) addendum to assessment report commenting phase conducted on the RMS s assessment of instead median value. The same counts for input parameters PECgw calculations, as summarized in Table P.A. Ad. B comment. This may result in updating the calculations as well, at least for alkaline soils, if requested. As for the selection of 1/n obtained in acidic neutral soils to be used in modelling, RMS/CoRMS is of the opinion that the same averages of K foc and 1/n should be used as these values are coupled by definition. Although this is only modelling, the selection of median K foc and arithmetic mean 1/n value may result by challenging such modelling on the basis that such practice is not scientifically justified and sound. PEC in soil (B.8.3) addendum to assessment report commenting phase conducted on the RMS s assessment of No comments submitted 25 EFSA Supporting publication 2015:EN-857

26 Fate and behaviour in water and impact on water treatment procedures (B.8.4-B.8.5) addendum to assessment report commenting phase conducted on the RMS s assessment of No comments submitted PEC in surface water and in ground water (B.8.6) addendum to assessment report commenting phase conducted on the RMS s assessment of 4(9) Add. Vol. 3, B Predicted environmental concentrations in ground water (PECgw) DE: An assessment of the toxicological relevance of the groundwater metabolites fluroxpyrpyridinol and fluroxypyr-metoxypyridine was required by the EU as confirmatory information. A (apparently new) calculation of groundwater contamination seems to suggest that such an assessment was not needed anymore, as the PEC GW -values for the above mentioned metabolites are now lower than 0.1 µg/l. Due to the ongoing discussions on the plant uptake factor on EU Level (York Workshop 9/2013, ring tests) a default value of 0.5, as has been used for active substance RMS/CoRMS: In principle agree. It shall however be pointed out that although the Addendum bears the date December 2014, its B.8 Environmental Fate and Behaviour section was prepared in December 2012, when the recommendation on PUF brought forth by DE was not in force. However, if required, the modelling may be repeated with that new requirement concerning PUF taken into account. See comment 4(10) EFSA Supporting publication 2015:EN-857

27 PEC in surface water and in ground water (B.8.6) addendum to assessment report commenting phase conducted on the RMS s assessment of fluroxypyr, should not be applied for groundwater modelling, unless there is experimental evidence that an uptake of the substance into the plant occurs. Otherwise a plant uptake of 0 should be used as worst case. 4(10) Add. Vol. 3, B Predicted environmental concentrations in ground water (PECgw) The reference originally given to the comment was following: Overall conclusion of commenter If the plant uptake factor of 0 is used and the metabolites will be modelled above 0.1 µg/l then the confirmatory information concerning the toxicological relevance will still be needed. EFSA: The available groundwater modelling is insufficient to demonstrate that where aquifers are overlaid by predominantly alkaline soils, groundwater concentrations would not be above the parametric drinking water limit for the transformation product pyridinol. Further FOCUS groundwater simulations with input parameters as discussed in EFSA comments 1 and 2 above would be needed to clarify this situation. RMS/Co-RMS: Comment noted but RMS believes that no further action is needed for confirmation information. Appropriate groundwater exposure modelling using metabolite input values that are in line with FOCUS kinetics and FOCUS groundwater guidance is not available. For the on relevance of metabolites to be concluded upon, it is essential for acceptable groundwater exposure assessments to be available, where all aspects of input parameter selection have been completed appropriately. This includes the TSCF selection for the fluroxypyr metabolite of parent fluroxypyr-meptyl which should be 0 in the absence of any evidence / data indicating a value > 0 can be 27 EFSA Supporting publication 2015:EN-857

28 PEC in surface water and in ground water (B.8.6) addendum to assessment report commenting phase conducted on the RMS s assessment of justified. 5. Ecotoxicology assessment report Comments from Member States / applicant EFSA s scientific views on the specific points raised in the commenting phase conducted on the RMS s assessment of 5(1) 1. Summaries of studies 5(2) 2. Revised risk assessment AT: AT agrees with the RMS on the assessment of the two Myriophyllum studies. AT: It seems that the risk assessment for aquatic organisms was not conducted according to the new EFSA GD RMS: Noted RMS: As pointed out in the document: In cases where endpoints have not been previously defined at EU level, EC 50 values based on growth rates have been considered in the risk assessment. This approach is in line with the recommendations of the AMRAP workshop (Maltby et al., 2010) 3, the report on the statistical evaluation Addressed Addressed Please note that two new studies on the aquatic macrophyte Myriophyllum 3 Maltby L., Arnold D., Arts G., Davies J., Heimbach F., Pickl C., Poulsen V. (Eds) (2010). Aquatic Macrophyte Risk Assessment for Pesticides. SETAC Press & CRC Press, Taylor & Francis Group, Boca Raton, FL, 140 pp EFSA Supporting publication 2015:EN-857