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Iie, eect 15¢-zacoe fieldfisher Arsenal Boulevard Louis Schmidtiaan, 29 box 15 Z 5 1040 Brussels uropean Commission pila DG SANTE = Attn of: Mr. Mark Wiliams Unit £4 Pesticides and Biocides ets sher com F101 04/00 B-1049 Brussels eee Belgium European Food Safety Authority Via Carlo Magno 1A 43426 Parma Italy eldishorcom By Email: Ce: By registered mall and e-mail Brussels, 23 August 2019 Dear Mr. Wiliams, Re: Comments on the EFSA Statement and on the draft Renewal Report for Chlorpyrifos- methyl In response to your emails of 12 and 14 August 2019 respectively, we write to you on behalf of our client Ascenza Agro S.A. (hereafter “Ascenza’ or “Applicant’), in ts capacty as applicant for the renewal of the approval of the active substance Chlorpyrifos-methy| (hereafter "the Substance’) within the framework of Regulation (EC) No. 1107/2009 conceming the placing of plant protection preducts on the market ("the PPPR") in order to submit comments on the EFSA Statement and the Commission's draft renewal report on the Substance. At the outset, we find the commenting deadlines given to our client confusing. In your 12 August e-mail, you indeed state that comments on both documents must be given by 9 September at the latest since "you are consulting on both documents concurrently", however your 14 August e-mail you change this and impose a 30 August deadiine "ifthe Applicant) would ike [ts] comments on the EFSA statement on [Brussels / Dusseldort/ Hamburg / London / Manchester / Munich / Paris / Shanghai / Sicon Valley Iso ‘orn an ogun btm Se Raga hana Acres rent oth son ucts at tng e ee 27001 Fewer haan ua re aT wavered eeenpcaron ‘chlorpyrifos-methy to be taken into account by the experts". Our client fails to understand the procedure followed and the logic behind it: f both documents will be discussed concurrently surely commenting can ‘and should be synchronised. More importantly, however, our client fails to understand the procedure followed at EFSA, ie. the lacking of an ESFA Conclusion Report, the unexpected issuing of the EFSA ‘Statement (without involvement of the Applicant) and the untimely publication of the latter on 2 August 2019 and, despite this, the announcement that the conclusions can stil be changed at an EFSA expert meeting to be held in early September 2019. This way of proceeding is highly unusual, not to say irregular (see also below) and the Applicant is not in the position to fully understand the procedure followed by EFSA and ultimately by the European Commission In any case, the 17-day deadline until 30 August (expiring on a Saturday) granted to our client to submit ‘comments to the EFSA Statement is extremely short, especially as it falls in the middle of the summer season with many people being on holiday thereby making it dificult to properly consult relevant experts ‘and prepare a full response. Moreover, since comments on the draft renewal report can still be made until 9 September (also by Member States), and the conclusions therein could stil be altered following the expert meeting, we do not believe that there is a reason to precipitate things. We therefore hereby submit ‘our client's comments on a preliminary basis, with the understanding that there will be a further opportunity to submit observations in September 2019. 4. Background In April 2017, Spain as Rapporteur Member Stale (hereafter "RMS") concluded its examination of the Substance and issued its renewal assessment report (hereafter *RAR") in which it concluded that the approval of the Substance can be renewed. The RAR was subsequently sent to the Commission and the European Food Safety Authority ("EFSA") on 3 July 2017. A public consultation was also organized, and different NGO's (notably PAN Europe) submitted comments, In accordance with Article 13 of Commission Implementing Regulation (EU) No 844/2012, EFSA initiated the peer review of the RAR on 18 October 2017 and dispatched the RAR to the Member States and ‘Applicants for consultation and commenting. On 4 July 2018, EFSA requested the Applicant to provide further information on, #.¢.. mammalian toxicology in accordance with Article 13(3) of Regulation (EU) No 1844/2012, which was submitted, evaluated and included in an updated 2019 RAR, which still proposed that the approval of the Substance can be renewed. The Applicant took notice of the existing updated RAR in the EFSA Statement, never being formally informed by RMS. The Applicant took the initiative to ‘contact the RMS asking for the updated RAR, which was received on 16 August 2019. Between 1 and 5 April 2019, EFSA organised discussions between EFSA experts and Member States (including experts from the PPR Panel) to discuss mammalian toxicology and conduct a hazard ‘assessment largely based on the structural similarity of the Substance with Chlorpyrifos. However, EFSA did not conclude on the risk assessment of the Substance (in the form of an EFSA Conclusion Report regarding the peer review of the pesticide risk assessment) (On 1 July 2019, the Commission issued a mandate to EFSA asking it to review the human health assessment and to issue a statement as to whether the Substance can be expected to meet the human health approval criteria laid down in Article 4 of the PPPR. On 31 July 2019, EFSA sent to the Commission its statement, concluding in relevant pat that the Substance cannot be expected to meet the ‘approval criteria. In relevant part, the EFSA Statement concluded that "no reference values could be sel, a fact that made it impossible to perform a risk assessment for consumers, operators, workers, bystanders ‘end residents", Underiying this conclusion, it was alleges that: ‘+ While the available genotoxicity dataset did not show any concem, it lacked the additional relevant information retrieved e.g. from the literature for Chlorpyritos and that therefore the genotoxic Potential of the Substance remains unclear, and ‘+ while @ DNT study showed no relevant effects as regards developmental neurotoxicity, this study had some significant limitations related to the controls making a reliable statistic analysis impossible, so that a specific DNT NOAEL could not be set. As a result, the EFSA statement concluded that it was not possible to perform a risk assessment for consumers, operators, workers, bystanders and residents. Because of the developmental toxicity ‘concerns, it was further stated that the Substance would also meet the criteria for classification as toxic for reproduction category 1B. Importantly, the Statement also added that the read-across to Chiorpyrifos for the hazard identification would be re-discussed at a later experts meeting and that the outcome of the discussions “might impact ‘on the assessment of the specific studies, on the possiblity to identify a classification as well on the setting of reference values for chlorpyrifos-methy?. Despite this admission that the conclusion in the ‘Statement could stil be changed, the latter was made public and published on the EFSA website on 2 August 2019. By e-mail of 12 August, the Commission informed the Applicant that it had prepared a draft renewal report fon the Substance which was forwarded to the latter as an attachment. In the draft renewal report, the ‘overall conclusion is thet: * "The genotoxic potential of chlorpyrifos-methyl, which cannot be ruled out when taking into ‘account the concems raised for chlomyrfos conceming chromosome aberration and DNA damage that may also apply to chlorpyrifos-methyl. Consequently, health based reference values cannot be established for chiorpyrifos-methyl and the dietary and non-dletary risk assessments cannot be conducted. ‘© Developmental neurotoxicity (ONT) - the available DNT study on chlorpynitos-methyl did not allow for a full assessment of effects on brain development, in particular since effects on cerebellum hheight could not be evaluated due to the lack of controls in females. Since DNT effects were observed in the available developmental neurotoxicity on chlorpyritos (adverse effects were seen at the lowest dose tested in rats and @ no observed adverse effects level ‘NOAEL’ could not be established) concems exist also for chlorpyrifos-methyl. Moreover, epidemiological evidence ‘exists showing an association between exposure to chlorpyrifos-methyl during development and adverse neurodevalopmental outcomes in in children, * Based on the evidence for DNT, experts during the peor review suggested that classification of Cchiorpyritos-methyl as toxic for the reproduction category 18, H360D ‘May damage the unborn child, in accordance with the criteria set aut in Commission Regulation (EC) No 1272/2008 would be appropriate.” This overall conclusion is almost a word for word copy of the overall conclusions in the draft renewal report for Chlorpyrifos. On that basis, the draft renewal report concluded that the approval of the ‘Substance cannot be renewed. By @ Commission e-mail of 12 August 2019, the Applicant was initially invited to provide comments on both the EFSA Statement and the draft renewal report for the Substance by 9 September 2019. By a Subsequent 14 August 2019 email of the Commission, the following was stated: "if you would like your ‘comments on the EFSA statement on chlorpyrifos-methy! to be taken into account by the experts, please submit your comments earlier, by 30 August, also sending directly to EFSA (pesticides peorreview@efsa europa.ou) as well as to the Commission. Please note this applies only to cchiorpyrifos-methyl. Comments on the renewal report (and on the statement if you do not wish to submit in advance for the expert discussion) can be provided by 9 September." 2. Procedural comments ‘As noted above, the Applicant has serious concems regarding the procedure that was followed by EFSA ‘and the Commission. The Applicant provided comments in January 2018 on the final Renewal ‘Assessment Report ("RAR") which were also included in the so-called “reporting table" and timely provided additional data on, @.g., mammalian toxicology following the request made by EFSA in July 2018. ‘The Applicant understands that this data was included in an updated final RAR which still proposed that the renewal of the Substance can be approved. ‘The Applicant was never informed of any issues which prevented the adoption of the EFSA Conclusion Report or renewal of the approval of the Substance. After the discussions during the PRaPER meeting on Toxicology in April 2019, the Applicant was not informed that EFSA would not peer review the other sections of the dossier and he was also not informed of the reasons for not doing so. This is despite the fact that under Article 13 of Regulation (EU) No 84/2012, EFSA has an obligation to adopt a conclusion, which it must communicate to the Applicant who should be given the possibility to request confidential treatment of certain submitted data. The latter point too was not respected. Such approach is also contrary to the principle of transparency, which applies to every public authority in the EU. The Applicant was therefore legitimately and truly surprised to find out that the Commission had asked EFSA to prepare a statement and that allegedly the approval criteria were ~ according to EFSA and the Commission ~ not satisfied. Such a finding is contrary to the principle of legitimate expectation as recognised by relevant case law’. The Applicant could indeed legitimately expect the Commission to be Informed and propose the renewal of the Substance, as was proposed in the RAR. Moreover, the PPR Expert conclusions and the adverse effects which allegedly support the non-renewal proposal are all, without any exception, based on read-across data from chlorpyrifos-ethyl, which is @ different active substance. The Applicant firmly opposes such read-across where Substance specific data has been submitted and is available in its dossier. However, in a spirit of cooperation with the EFSA ‘experts and the Commission, the Applicants will provide further information to EFSA which clearly demonstrates substantial differences in the toxicity of the two substances and shows that read across of specific adverse effects from chlorpyrifos-ethy/ to chlorpyrifos-methy is neither warranted nor justified. The Applicant will do its best to provide this information within the 30 August 2019 deadline set in your 14 ‘August 2019 letter, although this should not be interpreted as an agreement with or admission of validity of this deadiine. ‘The EFSA Statement also noted that the PPR Expert conclusions on chlorpyrifos-methy| are preliminary ‘and that the experts are also not sure about the read-across conclusions. Specifically, itis stated: + Cases ¥-420/19 and Y-451/12, Bayer and Syogata v. Commission. Pararash 278.“ has conitnty bean held ht any Incl wom a0 Institon of the European Union has td to ene legals expeciators by ghrg im pecien surrey Ph the pe af e ‘rector of eitmate expaciatore Qarn f17 Maren "a8? Von don Bergh on sgans ard Ven O@ Food Prd (ch © EEG, 26088, Ec 1007121 param 44 se os omer of @ September 2010 Dott v Commision 7 2408 ELT 2010285 paragraph 47 one xenon tod” “it is noted that, after the Pesticides Peer Review Experts’ meting held between 1 and 5 April 2019, EFSA reconsidered the read-across approach applied for the hazard identification after a full comparison of the available toxicological data: it was agreed to re-discuss this issue in an experts’ meeting. The ‘outcome of the discussions might impact on the assessment of the specific studies, on the possibilty to identity a classification as well as on the setting of reference values for chlorpyrifos-methyL.” ‘This mere statement raises several important procedural (and also substantial) questions: Firstly, it seems crystal clear that the EFSA Statement is a preliminary document and that the conclusions contained therein are not final and, indeed, could still be changed substantially. This raises the immediate question as to why this document, which by its nature and content is commercially damaging for the Applicant, was published on EFSA's website on 2 August 2019. Indeed, because of the alleged developmental toxicity concerns, the EFSA Statement specifies that the ‘Substance would meet the orteria for classification as toxic for reproduction category 1B. It therefore puts into question the properties ofthe Substance, as wel asthe products containing it The publication of such Statement is irteparably affecting the reputation of the Substance, thereby adversely affecting the Applicant's commercial interests. Furthermore, EFSA Statement contains unfinalised and/or partial statements. Even if EFSA were to ‘Subsequently correct its Statement, this would not cure the damage done by incomplete andior unfinalised statements related to the Substance Secondly, it follows from the first point that the Commission's draft renewal report is, 1o say the least, premature and lacks scientifc foundation. Therefore, our client strongly opposes that this draft renewal feport forms the basis for commenting by not only the Applicant, but more importantly also the Member States. The risk clearly exists that Member States will comment on a flawed renewal report, so that also their commenting risks to be vitated by the same scientific: flaws. On that basis, our client asks that the draft renewal report be withdrawn and that any further commenting be suspended until atleast EFSA has finished its peer review and prepared a comprehensive Conclusion Report. Thirdly, in view of the above deficiencies, the Applicant is uncertain if and to what extent the EFSA Statement has identified any areas of concem for the Substance. In particular, as regards genotoxicity, it is stated that "the available genotoxicity dataset submitted for chlorpyritos-methyl did not show any ‘concern and also as regards developmental neurotoxicity, it is stated that "e DNT study was available which did not show relevent effects, however it had some significant limitations related to the controls, ‘making @ reliable statistical analysis impossible". In both cases, the endpoints for chlorpyrifos are conservatively read-across to chlompyrifos-methyl, without sound justification or metivation. As regards epidemiological data, US data was used which cannot be linked to exposure to chlorpyrifos-methyl based products Fourthly, the same flawed approach is applied for classification, where "the experts conservatively applied the same approach as for chlorpyrifos, considering that chlorpyrifos-methyl would also meet the criteria for classification as toxic for reproduction category 1B (regarding developmental toxicity)". Here again, any ‘motivation or justification is lacking. More fundamentally, the Applicant is at @ loss to understand how EFSA (or its experts) can make a proposal regarding the classification of the Substance, as this is clearly not within its competence during the renewal approval process; instead, this involves the exclusive competence ofthe Risk Assessment Committe ("RAC") at the European Chemicals Agency (see below). Overall, the Applicant fails to understand how these conclusions can be reconciled with the EFSA Conclusion that after the experts meeting "it reconsidered the read-across approach applied for the hazard ‘dentiication after a full comparison of the available toxicological data: it was agreed to re-discuss this issue in an exports’ meeting. The outcome of the discussions might Impact on the assessment of the specific stuties, on the possibiliy to identify a classification as well as on the setting of reference values for chlorpynitos-methy.” The Applicant also submits that a concem should be distinguished from “an issue that could not be finalised with respect to any decision on renewal. In addition, the Applicant refers to well established ‘case-law of the European Courts that the precautionary principle cannot be applied in cases where the risk is based upon conjecture which has not been scientifically verified". The risk cannot therefore be hypothetical. It must be real and it must be scientifically confirmed, which is not the case here until at least the additional data on chlorpyrifos-methyl has been assessed. Finally, the Commission draft renewal report on the Substance refers to potential “classification of ‘chlorpyrifos-methy! as toxic for the reproduction category 18, H360D “May damage the unborn chitd, in ‘accordance with the criteria set out in Commission Regulation (EC) No 1272/2008 However, a8 indicated in the draft renewal report on the Substance, this classification proposal comes from a suggestion of experts made during the peer review. ‘Such statement is therefore procedurally and legally incorrect since itis not for EFSA — or its experts — to ‘make a proposal regarding the classification of a substance such as chlorpyrifos-methyl while it is subject to the renewal of approval process. 3. Substantial comments a Genotoxicity ‘As to the issue of genotoxicity, a full dataset has been submitted by the Applicant which demonstrates that ‘no such concerns should in fact be raised in the context of the Substance. It is strongly disputed that this issue is one which could not be finalised due to a lack of available data, but rather seems to be a concern based exclusively on an unjustified read across from Clorphyrifos and not on the assessment of methyl. If further information is deemed necessary to finalize its assessment, this should be requested by EFSA to ‘applicant for submission within the stop-the-ciock period. In a spirit of collaboration with EFSA and the Commission (as stated above), the Applicant is wiling to provide information to EFSA which clearly demonstrates substantial differences in the toxicity of the two substances and shows that chlorpyrifos- ‘methyl is about significantly less toxic than chlorpyrifos and that effects of treatment are not identical. The following examples illustrate this: > Antenna otc rot be tae tar ot enough nemaon svelte te prt an assessment over a th owe! tr lov or ‘Re represeriaive uses li wth be unorm piles accordance ih Ale 200) of Regan (EC) No 176712008 ard se oe th ‘Conmisan Repuason (EL) No S4620'17 anf he as such penance at b co, when Wrebed, Dace 8 inca (res wkd ‘Sebi ac metic ren of concm Hit wo eavanc ol oprenertasve wes (ep add) + See eg, Cove 110, Pzeranmal oak SA v Counc! of he Eoropean Unam ECLEUT 2002200, prnraphs 143-48 ‘+ Chlorpyrifos-oxon is a metabolite in rat of chlorpyrifos (which in itself is more toxic than chlorpyrifos); for chlorpyrfos-methyl, however, this corresponding oxon metabolite is not found in the rat metabolism study, ‘+ Acute oral toxicity to the rat with chlorpyrifos-methy! is 2'500 — 51000 mghkg, whereas for chlorpyrifos this is 65-223 mg/kg; + Chlorpyrifos-methyl is a skin sensitizer, whereas chlorpyrifos is not; ‘+ In repeated dose studies, Cholinesterase inhibition occurs at significantly lower doses of chlorpyrifos compared to chlorpyritos-methy; ‘+The proposed AD! of chlorpyrifos-methy! is based on vacuolar changes in the adrenal cortex of the 2-year rat study. The proposed ADI of chlorpyrifos is based on inhibition of red blood cell cholinesterase in the 2-year rat and dog studies. Consequently, read across of specific adverse effects from chlorpyrifos-ethy| to chlorpyrifos-methy! is neither warranted nor justified, and certainly cannot be the basis for a suspected genotoxicity potential. ‘Therefore, if the genotoxicity assessment of methyl is inconclusive, this should not be the basis for a non- renewal of the Substance, as further studies should consequently be requested to finalize the assessment land propose specific reference values. ‘As a minimum, the Applicant requests that the additional information on the differences between both substances he will submit will be reviewed and considered by the EFSA experts during the meeting in early September 2019. Moreover, to exclude any concerns that may be related to methyl exclusively, the ‘Applicant is wiling to perform additional studies in coordination with RMS and EFSA either inthe scope of the curent review process or as confirmatory data or during Member State product authorisation phase. If data cannot be considered within the current stage of the process, then the reference values proposed by RMS in its RAR should be used to derive end points forthe Substance i) Developmental neurotoxicity ‘As to the issue of developmental neurotoxicity, the Applicant does not understand why this is being used {as a cutoff criterion by the Commission justifying an immediate decision not to renew the approval of chlorpyrifos-methy, even to the point where the EFSA Conclusion Report is deemed not necessary anymore, The procedure and criteria for the approval of active substances are set forth in Annex Io the PPPR, with specific focus on "impact on human health” in point 3.6 Itis clear from reading points 3.6.1 to 3.6.5 that the cutoff erteria, preventing the approvalenewal of approval of a substance relate to ‘substances that are a mutagen, carcinogenic, or toxic for reproduction Cat 1A or 1B, or that are endocrine disrupters. However, developmental neurotoxicity is not listed and is not per se a cut-off criterion as it seems to be used here. Neurotoxicity seems not to fall nto the reproduction category class, as defined in Regulation (EC) No 1272/2008 (the Classification and Labelling or CLP Regulation’) and could or should be addressed in a complete risk assessment. This is also stated in point 3.6.1 of Annex II to the PPR: "When the critical effect is judged of particular significance, such as developmental neurotoxic or ‘mmunotoxic effects, an increased margin of safety shall be considered, and applied if necessary.” Furthermore, from the information provided to the Applicant, it would seem that the outcome of epidemiological studies are one of the reasons for the non-renewal proposal. However, the vast majority Of the cited publications report data from the United States where chlorpyrifos-ethyl is a major insecticide Used in agriculture. On the contrary the use of chlorpyrifos-methy! is negligible in the US, and therefore reported findings cannot be linked to exposure to this active substance. Moreover, ail cited publications on ‘adverse effects in humans from outside US are directly linked to chlorpyrifos-ethyl and not fo chlorpyrifos- methyl, As explained above, such read-across is not justified and does not represent realistic proposed Conditions of use. The Applicant is also not aware of any epidemiological data that can be linked to ‘exposure to chlorpyrifos-methyl. ii) Classification As stated above, the Applicant does not understand and strongly opposes any classification proposal that is being made by EFSA, while a legally valid harmonised classification from ECHA is already in place in Europe Firstly, Article 13 of Regulation (EU) No 84/2012 is the most relevant in terms of the assessment EFSA can undertake within the renewal process. It states, in relevant part, “the Authority shall adopt a conclusion in the light of current scientific and technical knowledge using guidance documents applicable ‘at the date of the submission of the supplementary dossiers on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009". The reference to Article 4 of Regulation 1107/2008 does not, however, lead to a request for a classification review to be undertaken by EFSA. ‘Secondly, the mandate that EFSA received from the European Commission to conduct its review is restricted; this mandate does not contain wording to the effect of permitting EFSA to make proposals on classification of the Substance. The mandate reflects Article 12 of Regulation (EU) No 844/2012 which states that EFSA is limited to preparing an "“EFSA Conclusion regarding the renewal of the approval of ‘active substances in application of Article 18 of Regulation 1107/2009 and respective work programmes established by the Commission (Regulations 1141/2010 and 844/2012)". EFSA, or its experts, are therefore not competent to make a proposal forthe classification of the Substance, Thirdly, the CLP Regulation also does not grant EFSA any powers in respect of substance classification. The formal legal procedure for the proposal of a classification of a substances based on a hazard assessment involving only the RAC at the European Chemicals Agency. While itis true that @ proposal ‘can be submitted by a Member State (see Atcle 37 of the CLP Regulation) to the European Chemicals Agency with regard to a classification of a substance, the legislator excluded EFSA from thet list of proposers. Moreover, RMS Spain did not consider necessary to submit a new classification dossier to ECHA related to the Substance within the remit of ts scientific evaluation as it did net found grounds for a repro-toxic category 18 reclassification for the Substance. If newly available information raises questions ‘about the need for a new harmonised classification for the Substance, a CLH dossier should be submited by RMS (or other Member State) to ECHA for a scientific assessment by the RAC. ‘Therefore, until any classification of the Substance as repro-toxic category 1B has been formally adopted, the existing classification of the substance is the only one which is legally applicable and relevant within the framework of the renewal process. The EFSA Statement therefore cannot and should nat be used for ‘concluding on a non-renewal of the Substance under the PPPR. 4. Conclusion ‘The Applicant disagrees with the conclusions reached in both the EFSA Statement and in the Commission