CNCLUSIN N PESTICIDES PEER REVIEW APPRVED: 25 August 2015 PUBLISHED: 11 September 2015 doi:10.2903/j.efsa.2015.4221 Peer review of the pesticide risk assessment of the active substance Reynoutria sachalinensis extract Abstract European Food Safety Authority (EFSA) The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, the United Kingdom, for the pesticide active substance Reynoutria sachalinensis extract, and the considerations as regards the application to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005, are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of Reynoutria sachalinensis extract as a plant elicitor on grapes, wheat, tomato and strawberry. The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified. European Food Safety Authority, 2015 Key words: Reynoutria sachalinensis extract, peer review, risk assessment, pesticide, plant elicitor Requestor: European Commission Question number: EFSA-Q-2014-00332 Correspondence: pesticides.peerreview@efsa.europa.eu www.efsa.europa.eu/efsajournal EFSA Journal 2015;13(9):4221
Suggested citation: EFSA (European Food Safety Authority), 2015. Conclusion on the peer review of the pesticide risk assessment of the active substance Reynoutria sachalinensis extract. EFSA Journal 2015;13(9):4221, 73 pp. doi:10.2903/j.efsa.2015.4221 ISSN: 1831-4732 European Food Safety Authority, 2015 Reproduction is authorised provided the source is acknowledged. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. www.efsa.europa.eu/efsajournal 2 EFSA Journal 2015;13(9):4221
Summary Reynoutria sachalinensis extract is a new active substance for which, in accordance with Article 7 of Regulation (EC) No 1107/2009 of the European Parliament and of the Council (hereinafter referred to as the Regulation ), the rapporteur Member State (RMS), the United Kingdom, received an application from Marrone Bio Innovations on 3 November 2011 for approval. In accordance with Article 8(1)(g) of the Regulation, Marrone Bio Innovations submitted an application to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. Complying with Article 9 of the Regulation, the completeness of the dossier was checked by the RMS and the date of admissibility of the application was recognised as being 20 March 2012. The RMS provided its initial evaluation of the dossier on Reynoutria sachalinensis extract in the draft assessment report (DAR), which was received by the European Food Safety Authority (EFSA) on 22 July 2014. The DAR included a proposal to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. The peer review was initiated on 24 July 2014 by dispatching the DAR for consultation to the Member States and the applicant, Marrone Bio Innovations. Following consideration of the comments received on the DAR, it was concluded that additional information should be requested from the applicant, and that EFSA should conduct an expert consultation in the areas of mammalian toxicology, environmental fate and behaviour, and ecotoxicology. In accordance with Article 12 of the Regulation, EFSA should adopt a conclusion on whether Reynoutria sachalinensis extract can be expected to meet the approval criteria provided for in Article 4 of the Regulation taking into consideration recital (10) of the Regulation. Furthermore, this conclusion also includes considerations concerning the application to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. This conclusion also addresses the assessment required from EFSA under Article 12 of Regulation (EC) No 396/2005, provided the active substance will be approved under Regulation (EC) No 1107/2009 without restrictions affecting the residue assessment. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of Reynoutria sachalinensis extract as a plant elicitor for the control of a range of fungal diseases on grapes, wheat, tomato and strawberry, as proposed by the applicant. Full details of the representative uses can be found in Appendix A of this report. The degree of effectiveness seen in the trials is considered sufficient in case of low disease pressure. A data gap was identified for an appropriate search of the scientific peer-reviewed open literature on the active substance, its identified components and its relevant metabolites. In the area of identity, physical/chemical/technical properties and methods of analysis data gaps were identified as regards the five marker compounds, for storage stability data for the formulation as well as for methods of analysis for emodin in the environmental matrices. With regard to mammalian toxicology, two critical areas of concern were identified. The first one is related to the lack of representativeness of the test material used in the toxicity studies with regard to the technical specification of Reynoutria sachalinensis extract. The second one is related to the fact that no reference values could be derived, leading to an inconclusive risk assessment for human health. The toxicity profile of Reynoutria sachalinensis extract could not be finalised; data gaps were identified for acute toxicity studies, a 90-day oral toxicity study with rats, additional genotoxicity data in order to exclude the in vivo DNA binding/crosslinking properties observed in an in vivo Comet assay in the kidney, and further investigations of the reproductive and developmental toxicity of the substance (including considerations/screening for neurotoxicity and endocrine-mediated effects). Medical data on plant manufacturing personnel are also missing. Regarding the conditions of the interim provisions of Annex II, Point 3.6.5 of Regulation (EC) No 1107/2009 concerning human health for the consideration of endocrine disrupting properties, no conclusion can be reached due to the data gaps identified that do not allow to assess either the need for classification or the endocrine disrupting properties of the extract. As no reference values were set, a risk assessment of operator, worker, bystander and resident exposure could not be performed. Furthermore, considering the consistency of the positive results obtained in the mouse lymphoma and Ames assays and the equivocal results in www.efsa.europa.eu/efsajournal 3 EFSA Journal 2015;13(9):4221
the in vivo Comet assay, a mutagenic effect of Reynoutria sachalinensis ethanolic extract cannot be ruled out. A consumer risk assessment cannot be conducted in the residue section, as long as the data gaps identified in the section on toxicology have not been addressed. A conclusion on the possible inclusion of Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005 could not be drawn, either, pending on the outcome of the assessment of the outstanding data requested in the section on toxicology. The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at EU level for the representative uses, with the notable exception that information is missing regarding the effect of water treatment processes on active substance components that may be present in surface water and groundwater at the point of abstraction for drinking water. A critical area of concern is identified as, on the basis of the available information, the active ingredient components emodin glucoside and resveratrol glucoside are indicated to be in groundwater above the parametric drinking water limit of 0.1 µg/l in geoclimatic situations represented by all nine FCUS groundwater scenarios. For the active ingredient component resveratrol the same was indicated for eight out of nine FCUS groundwater scenarios. It has not been demonstrated that the test material used in the ecotoxicity studies is representative of the technical specification. For this reason a critical area of concern was identified. A low acute risk to birds and wild mammals was concluded, however the long-term risk assessments, including from exposure via contaminated water and the risk assessments from secondary poisoning, could not be finalised with the available information. No suitable aquatic toxicity data were available and therefore a risk assessment for aquatic organisms could not be performed. A low risk to honeybees, non-target arthropods, soil microorganisms and non-target plants was indicated. A low acute risk to earthworms was indicated for all representative uses. A high long-term risk to earthworms was indicated for the representative use on field strawberries but a low long-term risk was concluded for all other representative uses. A data gap has been identified for information to address the risk to sewage treatment organisms for the representative glasshouse uses. www.efsa.europa.eu/efsajournal 4 EFSA Journal 2015;13(9):4221
Table of contents Abstract... 1 Summary... 3 Background... 6 The active substance and the formulated product... 8 Conclusions of the evaluation... 8 1. Identity, physical/chemical/technical properties and methods of analysis... 8 2. Mammalian toxicity... 9 3. Residues... 10 4. Environmental fate and behaviour... 10 5. Ecotoxicology... 12 6. verview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments... 13 7. Data gaps... 15 8. Particular conditions proposed to be taken into account to manage the risk(s) identified... 16 9. Concerns... 16 9.1. Issues that could not be finalised... 16 9.2. Critical areas of concern... 17 9.3. verview of the concerns identified for each representative use considered... 18 References... 19 Abbreviations... 21 Appendix A List of end points for the active substance and the representative formulation... 26 Appendix B Used compound code(s)... 73 www.efsa.europa.eu/efsajournal 5 EFSA Journal 2015;13(9):4221
Background Regulation (EC) No 1107/2009 of the European Parliament and of the Council 1 (hereinafter referred to as the Regulation ) lays down, inter alia, the detailed rules as regards the procedure and conditions for approval of active substances. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicant(s) for comments on the initial evaluation in the draft assessment report (DAR), provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate. In accordance with Article 12 of the Regulation, EFSA is required to adopt a conclusion on whether an active substance can be expected to meet the approval criteria provided for in Article 4 of the Regulation (also taking into consideration recital (10) of the Regulation) within 120 days from the end of the period provided for the submission of written comments, subject to an extension of 30 days where an expert consultation is necessary, and a further extension of up to 150 days where additional information is required to be submitted by the applicant(s) in accordance with Article 12(3). Reynoutria sachalinensis extract is a new active substance for which, in accordance with Article 7 of the Regulation, the RMS, the United Kingdom (hereinafter referred to as the RMS ), received an application from Marrone Bio Innovations on 3 November 2011 for approval. In accordance with Article 8(1)(g) of the Regulation, Marrone Bio Innovations submitted an application to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. 2 Complying with Article 9 of the Regulation, the completeness of the dossier was checked by the RMS and the date of admissibility of the application was recognised as being 20 March 2012. The RMS provided its initial evaluation of the dossier on Reynoutria sachalinensis extract in the DAR, which was received by EFSA on 22 July 2014 (United Kingdom, 2014). The DAR included a proposal to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. The peer review was initiated on 24 July 2014 by dispatching the DAR to the Member States and the applicant, Marrone Bio Innovations, for consultation and comments. EFSA also provided comments. In addition, EFSA conducted a public consultation on the DAR. The comments received were collated by EFSA and forwarded to the RMS for compilation and evaluation in the format of a reporting table. The applicant was invited to respond to the comments in column 3 of the reporting table. The comments and the applicant s response were evaluated by the RMS in column 3. The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 12(3) of the Regulation were considered in a telephone conference between EFSA, the RMS, and the European Commission on 20 November 2014. n the basis of the comments received, the applicant s response to the comments and the RMS s evaluation thereof, it was concluded that additional information should be requested from the applicant, and that EFSA should conduct an expert consultation in the areas of mammalian toxicology, environmental fate and behaviour, and ecotoxicology. The outcome of the telephone conference, together with EFSA s further consideration of the comments is reflected in the conclusions set out in column 4 of the reporting table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in an expert consultation, were compiled by EFSA in the format of an evaluation table. The conclusions arising from the consideration by EFSA, and as appropriate by the RMS, of the points identified in the evaluation table, together with the outcome of the expert consultation where this took place, were reported in the final column of the evaluation table. In accordance with Article 12 of the Regulation, EFSA should adopt a conclusion on whether Reynoutria sachalinensis extract can be expected to meet the approval criteria provided for in Article 4 of the Regulation, taking into consideration recital (10) of the Regulation. Furthermore, this conclusion 1 Regulation (EC) No 1107/2009 of 21 ctober 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. J L 309, 24.11.2009, p. 1 50. 2 Regulation (EC) No 396/2005 of the European Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. J L 70, 16.3.2005, p. 1 16. www.efsa.europa.eu/efsajournal 6 EFSA Journal 2015;13(9):4221
also includes considerations concerning the application to include Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005. A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in July August 2015. This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulation evaluated on the basis of the representative uses of Reynoutria sachalinensis extract as a plant elicitor for the control of a range of fungal diseases on grapes, wheat, tomato and strawberry, as proposed by the applicant. Furthermore, this conclusion also addresses the assessment required from EFSA under Article 12 of Regulation (EC) No 396/2005. A list of the relevant end points for the active substance and the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the peer review report, which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The peer review report (EFSA, 2015) comprises the following documents, in which all views expressed during the course of the peer review, including minority views where applicable, can be found: the comments received on the DAR; the reporting table (21 November 2014); the evaluation table (20 August 2015); the reports of the scientific consultation with Member State experts (where relevant); the comments received on the assessment of the additional information (where relevant); the comments received on the draft EFSA conclusion. Given the importance of the DAR including its revisions (United Kingdom, 2015) and the peer review report, both documents are considered as background documents to this conclusion. It is recommended that this conclusion report and its background documents would not be accepted to support any registration outside the EU for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based. www.efsa.europa.eu/efsajournal 7 EFSA Journal 2015;13(9):4221
The active substance and the formulated product The material being considered by this conclusion is Reynoutria sachalinensis extract; there is no IS common name for this extract. The representative formulated product for the evaluation was Sakalia, a suspension concentrate formulation (SC) containing 20% w/w of the extract. The representative uses evaluated comprise outdoor foliar spraying to grapes and wheat, and indoor and outdoor foliar spray to tomato and strawberry. The mode of action of this material is to elicit the plants own defence response to fungal attack. Full details of the GAP can be found in the list of end points in Appendix A. Efficacy trials on tomato, strawberry, grapes and wheat conducted according to the guidance document SANC/10054/2013-rev. 3 (European Commission, 2013) were provided. In most of the cases, efficacy has been assessed following fewer applications than proposed and a limited number of trials have been provided at the exact representative GAPs. The degree of effectiveness seen in the trials has to be considered sufficient in case of low disease pressure. A data gap has been identified for a search of the scientific peer-reviewed open literature on the active substance, its identified components and its relevant metabolites, dealing with side effects on health, the environment and non-target species and published within the 10 years before the date of submission of the dossier, to be conducted and reported in accordance with the EFSA guidance on the submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (EFSA, 2011) (relevant for Sections 2, 3, 4 and 5). Conclusions of the evaluation 1. Identity, physical/chemical/technical properties and methods of analysis The following guidance documents were followed in the production of this conclusion: SANC/3030/99-rev.4 (European Commission, 2000), SANC/10597/2003-rev.10.1 (European Commission, 2012) and SANC/825/00-rev.8.1 (European Commission, 2010). To identify this material five marker compounds have been chosen; their names and quantity range are as follows: resveratrol glucoside: 1.0-8.0% w/w, resveratrol: 0.3-3.0% w/w, emodin glucoside: 2.0-10.0% w/w, emodin: 2.0-8.0% w/w and physcion: 0.5-2.5% w/w. Resveratrol is usually present as the trans or E isomer but is easily converted to the Z isomer. The main data regarding the identity of Reynoutria sachalinensis extract and its physical and chemical properties are given in Appendix A. For the marker compounds a data gap was identified for Henry s law constant, IR, NMR and MS spectra, water solubility, partition co-efficient, hydrolysis, photolysis, quantum yield and dissociation constant. For the formulation a data gap was identified for both accelerated and shelf-life storage stability studies. It is noted that some storage data were supplied that were considered not to be adverse by the RMS. A HPLC-UV method was provided for the analysis of the technical material and the plant protection product for the five marker compounds. It was considered that the validation data for the technical material could be extrapolated to the plant protection product. Currently no residue definition has been set for plants and animals and this issue remains open. This is also the case for body fluids and tissues (see Section 2). For environmental matrices it was agreed that the marker compound for monitoring is emodin and therefore a data gap for methods of analysis has been identified. www.efsa.europa.eu/efsajournal 8 EFSA Journal 2015;13(9):4221
2. Mammalian toxicity The following guidance documents were followed in the production of this conclusion: SANC/221/2000-rev.10-final (European Commission, 2003), SANC/10597/2003 rev.10.1 (European Commission, 2012) and Guidance on dermal absorption (EFSA PPR Panel, 2012). Reynoutria sachalinensis extract has been discussed at the Pesticides Peer Review Experts Meeting 131 (May 2015). The literature review provided was considered insufficient. n one hand it should include more databases; and on the other hand, exclusion criteria should be reconsidered and evaluation of relevant papers previously excluded should be provided (data gap). The material used in the toxicological studies cannot be considered as representative of Reynoutria sachalinensis (ethanolic) extract, therefore a critical area of concern has been identified. Further assessment of the toxicological relevance of the individual components (including isomers) of the extract needs to be provided (data gap). With regard to the toxicokinetic data available for the marker components emodin, physcion and resveratrol, a potential of bioaccumulation could not be excluded for emodin and physcion. The agreed oral absorption values were 56% for emodin and physcion, and 20% for resveratrol. Acknowledging the limitations of the available data for these components (covering ca. 10% of the plant extract) and the complexity of the plant extract, the experts agreed that, currently, no further toxicokinetic studies are needed. For acute and short-term toxicity, the data available with the plant powder (not representative of the ethanolic extract) or with the marker components were considered insufficient, resulting in data gaps for acute toxicity studies (including by inhalation) and for a 90-day rat study (including investigation of neurotoxic endpoints if relevant) with a test material representative of Reynoutria sachalinensis (ethanolic) extract. Pending on these data, the potential need for other short-term toxicity data (with dogs and by inhalation or dermal administration) will have to be reconsidered. With regard to genotoxicity, based on the consistency of the positive results obtained in the mouse lymphoma and Ames assays and on the equivocal results in the in vivo Comet assay in the kidney, a mutagenic effect of Reynoutria sachalinensis (ethanolic) extract cannot be ruled out. Further data should be provided to exclude the in vivo DNA binding/crosslinking properties of Reynoutria sachalinensis extract. Pending on the clarification of the genotoxic potential and the submission of a valid subchronic study with the ethanolic extract, further consideration will have to be given to the need for long-term toxicity data. With regard to reproductive and developmental toxicity, no data were provided for Reynoutria sachalinensis extract. In addition, no screening of the potential endocrine-mediated effects has been provided (data gaps). In developmental toxicity studies with rats and mice, no teratogenic effect was demonstrated for emodin and resveratrol. Regarding the conditions of the interim provisions of Annex II, Point 3.6.5 of Regulation (EC) No 1107/2009 concerning human health for the consideration of endocrine disrupting properties, no conclusion can be reached due to the data gaps identified that do not allow to assess either the need for classification or the endocrine disrupting properties of the extract. A data gap for medical data, at least on plant manufacturing personnel, was also identified. Considering all the identified data gaps in the assessment of the toxicity profile of Reynoutria sachalinensis (ethanolic) extract, the derivation of reference values cannot be concluded, and the toxicological information provided for the marker components of the extract (representing ca. 10% of the active substance) cannot be used to justify the waiving of data requirements for the whole plant extract. The RMS proposed a risk assessment for operators, workers, bystanders and residents based on background exposure to the marker components. This was deemed unacceptable during the peer review meeting because it did not take account of exposure to the remaining 90% of the extract. As a consequence, the risk assessment cannot be performed, leading to a critical area of concern. www.efsa.europa.eu/efsajournal 9 EFSA Journal 2015;13(9):4221
3. Residues The assessment in the residue section is based on the guidance documents listed in the document 1607/VI/97-rev. 2 (European Commission, 1999), the European Commission guideline document on MRL setting (European Commission, 2011), the Joint Meeting on Pesticide Residues (JMPR) recommendations on livestock burden calculations (JMPR, 2004, 2007) and the rganisation for Economic Co-operation and Development (ECD) publication on MRL calculations (ECD, 2011). The available literature review was considered insufficient, as clear indications on the criteria used to judge on the relevance of literature were not adequately reported. Given the nature of the active substance Reynoutria sachalinensis extract, plant metabolism studies were not provided and the applicant tried to address the metabolism of the key marker components (physcion, emodin, resveratrol ), referring to literature search data. Since the proposed fingerprint approach limited to approximately 10% of the constituent components was not agreed by the Pesticides Peer Review Experts Meeting 131 on mammalian toxicology and since toxicological endpoints could not be set for the active substance, a consumer risk assessment cannot be conducted at this stage. This has been indicated as a critical area of concern. Consequently, a conclusion on the possible inclusion of Reynoutria sachalinensis extract in Annex IV of Regulation (EC) No 396/2005 is pending on the outcome of the assessment of the outstanding data requested in the section on toxicology. 4. Environmental fate and behaviour Reynoutria sachalinensis extract was discussed by Member State environmental fate and behaviour experts at the Pesticides Peer Review Experts Teleconference 112 (May 2015). The available literature review was considered insufficient, as clear indications on the criteria used to judge on the relevance of literature was not adequately reported. The RMS suggestion that resulted in an EFSA request for further information that a search for indicator components in grass crops would be appropriate was not followed up by the applicant (data gap). The case has been made that application of Reynoutria sachalinensis extract according to the representative GAP is not expected to significantly increase the amount of the marker components physcion, emodin and resveratrol in soil and it is expected that the composition of soil as a whole will not be affected by the use of Reynoutria sachalinensis extract. The substances present in Reynoutria sachalinensis extract, including the marker substances, are expected to degrade in the environment via the same processes that would degrade the original Reynoutria sachalinensis plant material or other plant sources of these marker components as part of its natural decomposition during the seasonal growth cycle. The applicant provided published literature that indicated that grapes, tomatoes, cranberries, hops, cabbage, lettuce, beans, couch grass and rhubarb contain the marker components of Reynoutria sachalinensis extract. They combined this with yield information for the relevant plant components to estimate potential environmental exposure of these marker components. The calculated amounts were considered reasonable estimates. This exposure relates to compounds that will be primarily encased within plant cells. The calculated amounts per hectare are higher than will result from the representative uses being assessed. From the representative uses the components will not be encased within plant cells. The applicant provided guideline ready biodegradability studies that utilise a sewage sludge inoculum for the plant extract and the individual components physcion, emodin and resveratrol. The whole plant extract and the component resveratrol were not readily biodegradable. Physcion and emodin were readily biodegradable. The Member State experts agreed that these results justified the estimated water, soil and sediment first-order DT 50 of 15 days (moderate persistence), 30 days (moderate persistence) and 300 days (high persistence) respectively for the components physcion, emodin and emodin glucoside. This approach follows ECHA (2012) guidance. For resveratrol and resveratrol glucoside, in the absence of other relevant reliable information, the experts agreed that default DT 50 of 1000 days needed to be taken forward and used in the exposure calculations. To assess soil mobility QSAR (Advanced Chemistry Development (ACD/Labs) Software V11.02 estimated K doc (soil adsorption) values were available that indicate that at ph 7 emodin glucoside and resveratrol glucoside may exhibit very high mobility, emodin may exhibit high mobility, physcion may exhibit low mobility and resveratrol may exhibit low mobility in soil. It www.efsa.europa.eu/efsajournal 10 EFSA Journal 2015;13(9):4221
should be noted that these compounds are ionisable and the EPA model KCWIN (Version 2.00, September 2008) QSARS in the DAR are estimated for the unionised forms. Therefore these KCWIN estimates were not relied upon in this conclusion. Appropriate peer reviewed scientific information is available indicating that under the conditions of aqueous photolysis, any resveratrol component present as the trans isomer will convert to the cis isomer, but that further transformation/degradation did not occur. The necessary surface water and sediment exposure assessments (Predicted environmental concentrations (PEC) calculations) were carried out for the components emodin, emodin glucoside, resveratrol, resveratrol glucoside and physcion using the FCUS step 1 and step 2 (version 2.1 of the steps 1-2 in FCUS calculator), step 3 (FCUS, 2001) and step 4 simulation approaches 3. The step 4 calculations appropriately followed the FCUS (FCUS, 2007) guidance, with no-spray drift buffer zones of up to 10 m being implemented for the drainage scenarios (representing a 74 86% spray drift reduction), and combined no-spray buffer zones with vegetative buffer strips of up to 10 m (reducing solute flux in run-off by 60% and eroded soil solids by 85%) being implemented for the run-off scenarios. The SWAN tool (version 3.0.0) was appropriately used to implement these mitigation measures in the simulations. However, risk managers and others may wish to note that whilst run-off mitigation is included in the step 4 calculations available, the FCUS (FCUS, 2007) report acknowledges that for substances with K Foc < 2000 ml/g (i.e. Reynoutria sachalinensis components), the general applicability and effectiveness of run-off mitigation measures had been less clearly demonstrated in the available scientific literature, than for more strongly adsorbed compounds. For the representative protected uses, the necessary surface water and sediment exposure assessments (PEC) were appropriately carried out using the FCUS (2001) step 1 and step 2 approach (version 1.1 of the steps 1-2 in FCUS calculator), which was then modified by postprocessing the spray drift input results (option no run-off or drainage was selected) to obtain a 0.2% emission of Reynoutria sachalinensis components from greenhouses being re-deposited on adjacent surface water bodies. This approach has been accepted by Member State experts as an assumption that can be used in EU level surface water exposure assessments for greenhouse uses and is referred to in FCUS (2008) guidance. The necessary groundwater exposure assessments were carried out using FCUS (FCUS, 2009) scenarios and the models PEARL 4.4.4 and PELM 4.4.3 4 for the components emodin, emodin glucoside, resveratrol, resveratrol glucoside and physcion, using the available soil degradation and soil adsorption substance parameters described in this conclusion. The potential for groundwater exposure from the representative uses by the active substance components emodin and physcion above the parametric drinking water limit of 0.1 µg/l was concluded to be low in geoclimatic situations that are represented by all 9 FCUS groundwater scenarios. For the components emodin glucoside, resveratrol and resveratrol glucoside the potential for groundwater exposure as estimated by 80th percentile annual average recharge concentrations leaving the top 1m soil layer being above 0.1 µg/l was indicated as high in situations represented by all 9 FCUS groundwater scenarios, with the exception of resveratrol for the use on wheat and strawberry in geoclimatic situations represented by the Jokioinen scenario, wheat represented by the Châteaudun scenario and strawberry and tomato represented by the Sevilla scenario. These estimates indicated concentrations up to 2.59 µg/l for emodin glucoside, 0.63 µg/l for resveratrol and 47.81 µg/l for resveratrol glucoside, leading to a critical area of concern. The provision of less uncertain soil degradation rate and soil adsorption information for emodin glucoside, resveratrol and resveratrol glucoside might enable less conservative groundwater exposure simulations to be completed (data gap). The applicant has not provided appropriate information to address the effect of water treatment processes on the nature of the residues of the components that might be present in surface water (resveratrol and resveratrol glucoside) and groundwater (emodin glucoside, resveratrol and resveratrol glucoside), when surface water or groundwater are abstracted for drinking water (data gap). The PEC in soil, surface water, sediment and groundwater covering the representative uses assessed can be found in Appendix A of this conclusion. 3 Simulations correctly utilised the agreed Q 10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of 0.7 4 Simulations correctly utilised the agreed Q 10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of 0.7 www.efsa.europa.eu/efsajournal 11 EFSA Journal 2015;13(9):4221
5. Ecotoxicology The risk assessment was based on the following documents: European Commission (2002a, b), SETAC (2001) and EFSA (2009). Parts of the ecotoxicological assessment of Reynoutria sachalinensis extract was discussed at the Pesticides Peer Review Experts Meeting 130 (May 2015). A number of concerns regarding the suitability of the available literature review were noted by the RMS. Consequently, a data gap was concluded for a comprehensive literature search. It was not demonstrated that the test material used in the ecotoxicity studies is representative of the technical specification of Reynoutria sachalinensis extract (data gap and critical area of concern). The RMS does not agree with the data gap and critical area of concern. Acute toxicity data were available for birds (tested as Reynoutria sachalinensis extract) and wild mammals (tested as the formulated product Sakalia ). n the basis of the available risk assessments a low acute risk to birds and wild mammals was concluded from exposure via the diet and consumption of contaminated water. Insufficient data, demonstrating the long-term toxicity of Reynoutria sachalinensis extract, or the marker compounds, to birds or mammals were available and therefore no risk assessment could be performed. A data gap was therefore identified for information to assess the long-term risk to birds and wild mammals (covering both exposure via the diet and consumption of contaminated water). A data gap was identified for studies demonstrating the partition co-efficient of the marker compounds (see Section 1) and therefore the assessment of secondary poisoning of earthworm- and fish-eating birds and mammals could not be finalised and relevant data gaps have been identified. Furthermore, QSAR estimations of fish BCF values were available and were considered to support the need for an assessment of secondary poisoning of fish for emodin and physcion. Due to all these outstanding issues, the long-term risk assessments for birds and mammals could not be finalised. The available acute and chronic aquatic toxicity studies were discussed at the experts meeting. The experts agreed that the studies could not be considered as reliable as the chemical analysis used in the studies did not demonstrate that the concentration of the test substance had been maintained. No further information was available to perform a risk assessment for aquatic organisms and therefore a data gap was identified. This was also indicated as an assessment not finalised. n the basis of the available data a low risk was concluded for honeybees and non-target arthropods. Suitable acute and chronic toxicity studies with earthworms were available. Taking account of the peak soil PEC, a low acute risk to earthworms was concluded for all representative uses. A low chronic risk was also indicated for the representative uses on grapes, wheat and tomatoes. However, a high chronic risk to earthworms was concluded for the representative use on strawberries. Consequently, a data gap was identified. n the basis of the available data a low risk to soil microorganisms was concluded for all representative uses. Screening level data were available for a number of species of crop plants. No phytotoxic effects were observed and therefore a low risk to non-target plants was concluded. Insufficient information was available to exclude a risk to sewage treatment organisms and therefore a data gap was concluded (relevant for the representative uses in glasshouse only). For the ecotoxicological assessments, no studies were available to address the potential endocrine activity of Reynoutria sachalinensis extract. Pending on the outcome of the data gaps in Section 2, further ecotoxicological tests might be necessary to address the potential endocrine disrupting properties of Reynoutria sachalinensis extract. www.efsa.europa.eu/efsajournal 12 EFSA Journal 2015;13(9):4221
6. verview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Table 1: Soil Compound (name and/or code) Ethanolic extract of Reynoutria sachalinensis which includes marker components: physcion emodin emodin glucoside resveratrol resveratrol glucoside Persistence Moderately persistent, DT 50 estimated at 30 days Moderately persistent, DT 50 estimated at 30 days Moderately persistent, DT 50 estimated at 30 days Assumed very highly persistent in the absence of information Assumed very highly persistent in the absence of information Ecotoxicology High chronic risk to earthworms for the representative use in strawberries. A low risk for all other representative uses. Table 2: Groundwater Compound (name and/or code) Ethanolic extract of Reynoutria sachalinensis which includes marker components: physcion emodin emodin glucoside Mobility in soil low mobility QSAR estimated K doc 720 ml/g high mobility QSAR estimated K doc 105 ml/g very high mobility QSAR estimated K doc 3.5 ml/g > 0.1 μg/l at 1 m depth for the representative uses (at least one FCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicology Yes No - No - All 9 FCUS scenarios (0.19 to 2.59 µg/l) - Yes, based on positive in vitro gene mutations in bacterial cells Yes, based on (weakly) positive in vivo micronucleus assay in mice treated for 14 weeks Yes, based on the emodin results; no data on emodin glucoside, data required Data gap for aquatic toxicity data and surface water risk assessment. www.efsa.europa.eu/efsajournal 13 EFSA Journal 2015;13(9):4221
Compound (name and/or code) resveratrol resveratrol glucoside Mobility in soil low mobility QSAR estimated K doc 1045 ml/g very high mobility QSAR estimated K doc 40 ml/g > 0.1 μg/l at 1 m depth for the representative uses (at least one FCUS scenario or relevant lysimeter) 8/9 FCUS scenarios (0.12 to 0.63 µg/l) All 9 FCUS scenarios (5.3 to 47.81 µg/l) Pesticidal activity Toxicological relevance Ecotoxicology - - Yes, based on positive in vitro gene mutations and chromosome aberrations in mammalian cells Yes based on resveratrol results; no data on resveratrol glucoside, data required Table 3: Surface water and sediment Compound (name and/or code) Ethanolic extract of Reynoutria sachalinensis which includes marker components: physcion emodin emodin glucoside resveratrol resveratrol glucoside Ecotoxicology Data gap for aquatic toxicity data and surface water risk assessment. Table 4: Air Compound (name and/or code) Ethanolic extract of Reynoutria sachalinensis Toxicology No data; data required www.efsa.europa.eu/efsajournal 14 EFSA Journal 2015;13(9):4221
7. Data gaps This is a list of data gaps identified during the peer review process, including those areas in which a study may have been made available during the peer review process but not considered for procedural reasons (without prejudice to the provisions of Article 56 of the Regulation concerning information on potentially harmful effects). A search of the scientific peer-reviewed open literature on the active substance, its identified components and its relevant metabolites, dealing with side effects on health, the environment and non-target species (that the applicant might choose to extend to investigate the presence of relevant components that may be present in grass) and published within the 10 years before the date of submission of the dossier, adequately conducted and reported in accordance with the EFSA guidance on the submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (EFSA, 2011) was not available (relevant for all representative uses evaluated; submission date proposed by the applicant unknown) (see Sections 2, 3, 4, 5 and the evaluation table in EFSA, 2015). For the marker compounds a data gap is identified for Henry s law constant, IR, NMR and MS spectra, water solubility, partition co-efficient, hydrolysis, photolysis, quantum yield and dissociation constant (relevant for all representative uses evaluated; submission date proposed by the applicant unknown; see Section 1). Accelerated and shelf-life storage stability studies (relevant for all representative uses evaluated; submission date proposed by the applicant unknown; see Section 1). Methods of analysis for emodin in soil, water and air (relevant for all representative uses evaluated; submission date proposed by the applicant unknown; see Section 1). Further assessment of the toxicological relevance of the individual components of the extract (including isomers) (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2). Acute toxicity studies (including by inhalation) with a test material representative of Reynoutria sachalinensis ethanolic extract (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2). A 90-day rat study (including investigation of neurotoxic endpoints if relevant) with a test material representative of Reynoutria sachalinensis ethanolic extract (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2). Further genotoxicity data with Reynoutria sachalinensis ethanolic extract in order to exclude the in vivo DNA binding/crosslinking properties (based on the equivocal results of the in vivo Comet assay in the kidney) (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2). Further investigations of the reproductive/developmental toxicity properties of Reynoutria sachalinensis extract, including a screening of the potential for endocrine-mediated effects (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Sections 2 and 5). Medical data, at least on plant manufacturing personnel (relevant for all representative uses evaluated; submission date proposed by the applicant: unknown; see Section 2). As the available FCUS groundwater modelling indicates that emodin glucoside, resveratrol and resveratrol glucoside may be present in groundwater, it cannot be excluded that information might be needed on the effect of water treatment processes on the nature of residues that might be formed from emodin glucoside, resveratrol and resveratrol glucoside by water treatment processes, such as ozonation or chlorination. Alternatively, should less uncertain soil degradation rate and soil adsorption information become available for emodin glucoside, resveratrol and www.efsa.europa.eu/efsajournal 15 EFSA Journal 2015;13(9):4221
resveratrol glucoside, refined groundwater exposure assessments (modelling) might demonstrate groundwater exposure below the parametric drinking water limit (relevant for all representative uses evaluated; submission date proposed by the applicant unknown; see Section 4). Information to confirm that under natural sunlight conditions aqueous photolysis of resveratrol will mean that it will not be present in surface water at the point of drinking water abstraction was not available. Consequently, it cannot be excluded that information might be needed on the effect of water treatment processes on the nature of residues that might be formed from resveratrol and resveratrol glucoside by water treatment processes such as ozonation or chlorination (relevant for all representative uses evaluated; submission date proposed by the applicant unknown; see Section 4). Information to address the long-term risk to birds and mammals from exposure via the diet and consumption of contaminated water (relevant for all representative field uses evaluated; submission date proposed by the applicant unknown; see Section 5). Information to address the long-term risk to birds and mammals from secondary poisoning from residues in earthworms (field uses only) and fish (all representative field and glasshouse uses) (pending the outcome of the data gap for partition co-efficient values in Section 1; submission date proposed by the applicant unknown; see Section 5). Information to address the risk to aquatic organisms (fish, aquatic invertebrates and algae) (relevant for all representative field and glasshouse uses evaluated; submission date proposed by the applicant unknown; see Section 5). Information to address the chronic risk to earthworms (relevant for the representative field use in strawberries; submission date proposed by the applicant unknown; see Section 5). Information to address the risk to sewage treatment organisms (relevant for the representative glasshouse uses evaluated; submission date proposed by the applicant unknown; see Section 5). Information to demonstrate that the batches used in the ecotoxicity studies are suitably representative compared with the representative technical specification. 8. Particular conditions proposed to be taken into account to manage the risk(s) identified No particular conditions are proposed for the representative uses evaluated. 9. Concerns 9.1. Issues that could not be finalised An issue is listed as could not be finalised if there is not enough information available to perform an assessment, even at the lowest tier level, for the representative uses in line with the uniform principles in accordance with Article 29(6) of the Regulation and as set out in Commission Regulation (EU) No 546/2011 5 and if the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses). An issue is also listed as could not be finalised if the available information is considered insufficient to conclude on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of the Regulation. 1. The toxicity profile of Reynoutria sachalinensis extract could not be concluded due to data gaps for acute toxicity, short-term toxicity, genotoxicity, reproductive and developmental 5 Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. J L 155, 11.6.2011, p. 127 175. www.efsa.europa.eu/efsajournal 16 EFSA Journal 2015;13(9):4221
9.2. toxicity (including considerations/screening for neurotoxicity and endocrine mediated effects). Regarding the conditions of the interim provisions of Annex II, Point 3.6.5 of Regulation (EC) No 1107/2009 concerning human health for the consideration of endocrine disrupting properties, no conclusion can be reached due to the data gaps identified that do not allow to assess either the need for classification or the endocrine disrupting properties of the extract. 2. In the absence of information to refine surface water and groundwater exposure assessments, with the current information and assessments, information on the effect of water treatment processes on the nature of residues that may be present in surface water and groundwater at the point of abstraction for drinking water would be needed to conclude an assessment regarding the approval criterion regarding human and animal health risk from the consumption of drinking water. 3. The long-term risk assessment for birds and wild mammals, including exposure from contaminated water and the assessment of secondary poisoning from residues in earthworms (field uses only) and fish (field and glasshouse uses) could not be finalised with the available data. 4. The acute and chronic risk to aquatic organisms remains open in the absence of reliable toxicity data. Critical areas of concern An issue is listed as a critical area of concern if there is enough information available to perform an assessment for the representative uses in line with the uniform principles in accordance with Article 29(6) of the Regulation and as set out in Commission Regulation (EU) No 546/2011, and if this assessment does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. An issue is also listed as a critical area of concern if the assessment at a higher tier level could not be finalised due to a lack of information, and if the assessment performed at the lower tier level does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater or any unacceptable influence on the environment. An issue is also listed as a critical area of concern if, in the light of current scientific and technical knowledge using guidance documents available at the time of application, the active substance is not expected to meet the approval criteria provided for in Article 4 of the Regulation. 5. The test material with Reynoutria sachalinensis extract used for the toxicity and ecotoxicity studies cannot be considered as representative of the technical specification. 6. No reference values can be derived for Reynoutria sachalinensis extract on the basis of the studies performed with the individual components (individually < 5% w/w of the plant extract, and ca. 10% when summed up). The contribution of the remaining ca. 90% has not been investigated sufficiently. As a consequence, the operators, workers, bystanders and residents exposure and consumer risk assessments could not be conducted. Furthermore, considering the consistency of the positive results obtained in the mouse lymphoma and Ames assays and the equivocal results in the in vivo Comet assay, a mutagenic effect of Reynoutria sachalinensis ethanolic extract cannot be ruled out. 7. The active ingredient components emodin glucoside and resveratrol glucoside are indicated on the basis of the available information and the representative uses assessed to be in groundwater above the parametric drinking water limit of 0.1 µg/l in geoclimatic situations represented by all 9 FCUS groundwater scenarios. For the active ingredient component resveratrol the same was indicated for 8/9 FCUS groundwater scenarios. www.efsa.europa.eu/efsajournal 17 EFSA Journal 2015;13(9):4221