Conclusion on the peer review of the pesticide risk assessment of the active substance bentazone 1

Transcription

1 EFSA Journal 2015;13(4):4077 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance bentazone 1 European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy ABSTRACT 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 Netherlands, for the pesticide active substance bentazone are reported. The context of the peer review was that required by Commission Regulation (EU) No 1141/2010 as amended by Commission Implementing Regulation (EU) No 380/2013. The conclusions were reached on the basis of the evaluation of the representative uses of bentazone as a herbicide on a variety of crops in the EU. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified. European Food Safety Authority, 2015 KEY WORDS bentazone, peer review, risk assessment, pesticide, herbicide 1 On request from the European Commission, Question No EFSA-Q , approved on 8 April Correspondence: pesticides.peerreview@efsa.europa.eu Suggested citation: EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance bentazone. EFSA Journal 2015;13(4):4077, 153 pp. doi: /j.efsa Available online: European Food Safety Authority, 2015

2 SUMMARY Commission Regulation (EU) No 1141/2010 (hereinafter referred to as the Regulation ), as amended by Commission Implementing Regulation (EU) No 380/2013, lays down the procedure for the renewal of the approval of a second group of active substances and establishes the list of those substances. Bentazone is one of the active substances listed in the Regulation. The RMS provided its initial evaluation of the dossier on bentazone in the Renewal Assessment Report (RAR), which was received by EFSA on 8 January The peer review was initiated on 27 January 2014 by dispatching the RAR for consultation of the Member States and the applicants BASF SE and AgriChem BV. Following consideration of the comments received on the RAR, it was concluded that additional information should be requested from the applicants and EFSA should conduct an expert consultation in the areas of mammalian toxicology, residues, environmental fate and behaviour, and ecotoxicology, and that EFSA should adopt a conclusion on whether bentazone can be expected to meet the conditions provided for in Article 4 of Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of bentazone as a herbicide on a variety of crops in the EU, as proposed by the applicants. Full details of the representative uses can be found in Appendix A to this report. In the area of identity, physical/chemical/technical properties and methods of analysis a data gap was identified for an analytical method for monitoring all the components of the residue definition in surface water. Data gaps were identified in the mammalian toxicology area to address the relevance of the individual impurities present in the technical specifications of both applicants. Bentazone is proposed by the EFSA peer review to be classified as toxic for reproduction category 2 in accordance with the provisions of Regulation (EC) No 1272/2008 (no classification regarding this endpoint is included in the current harmonised classification according to the same CLP Regulation). As an endocrinemediated mode of action could not be ruled out regarding the critical effects observed in the developmental toxicity study in rats (increased post implantation loss, reduced number of live foetuses and retarded foetal development), a data gap for the Level 2/3 tests currently indicated in the OECD Conceptual Framework and analysed in the EFSA Scientific Opinion on the hazard assessment of endocrine disruptors (EFSA Journal 2013;11(3):3132) is identified, and the assessment could not be finalised. This data gap is relevant for the interpretation of the interim provisions of Annex II, Point of Regulation (EC) No 1107/2009 for the deteration of potential endocrine disrupting properties. A data gap was also identified for further toxicological data allowing to establish reference values for the metabolite 6-hydroxy-bentazone as it is included in the residue definition for risk assessment. Furthermore, a critical area of concern was identified as the technical material specifications proposed for both applicants were not comparable to the material used in the testing that was used to derive the toxicological reference values. The consumer risk assessment is not finalised since the proposed residue definitions for risk assessment in plants and for enforcement in livestock are considered as provisional due to the identified data gaps. 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 potential for groundwater exposure when annual application rates are above 960 g a.s./ha. (Note that representative uses of up to 1440 g a.s./ha were applied for). For the representative uses on winter cereals at 960 g a.s./ha a potential for groundwater exposure by the parent bentazone above the parametric drinking water limit of 0.1 µg/l was indicated EFSA Journal 2015;13(4):4077 2

3 with 80 th percentile annual average concentrations moving below 1m being predicted to be up to 0.11 and 0.16 µg/l at the FOCUS Hamburg and Okehampton scenarios, respectively. A high long-term risk to mammals was concluded for the representative uses of bentazone applied as BAS H to grass seed, grazing land and turf. A high acute and/or long-term risk to birds and mammals was also concluded for several of the representative uses of bentazone applied as Bentazone 480 SL. A low risk to all other groups of non-target organisms was concluded. A data gap has been identified to address the ecotoxicological relevance of the individual impurities present in the technical specifications for both applicants. In addition, a critical area of concern is indicated as it has not been demonstrated that the technical material used in the ecotoxicity studies is suitably representative of the technical specifications. EFSA Journal 2015;13(4):4077 3

4 TABLE OF CONTENTS Abstract... 1 Summary... 2 Background... 5 The active substance and the formulated product... 7 Conclusions of the evaluation Identity, physical/chemical/technical properties and methods of analysis Mammalian toxicity Residues Environmental fate and behaviour Ecotoxicology Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments Soil Ground water Surface water and sediment Air List of studies to be generated, still ongoing or available but not peer reviewed Particular conditions proposed to be taken into account to manage the risk(s) identified Concerns Issues that could not be finalised Critical areas of concern Overview of the concerns identified for each representative use considered References Appendices Abbreviations EFSA Journal 2015;13(4):4077 4

5 BACKGROUND Commission Regulation (EU) No 1141/ (hereinafter referred to as the Regulation ), as amended by Commission Implementing Regulation (EU) No 380/2013, 4 lays down the detailed rules for the procedure of the renewal of the approval of a second group of active substances. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicants for comments on the initial evaluation in the Renewal Assessment Report (RAR) provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate. In accordance with Article 16 of the Regulation, if mandated, EFSA is required to adopt a conclusion on whether the active substance is expected to meet the conditions provided for in Article 4 of Regulation (EC) No 1107/ within 6 months from the receipt of the mandate, subject to an extension of up to 9 months where additional information is required to be submitted by the applicant(s) in accordance with Article 16(3). In accordance with Article 4 of the Regulation, the Netherlands (hereinafter referred to as the RMS ) received an application from BASF SE and AgriChem BV for the renewal of approval of the active substance bentazone. Complying with Article 11 of the Regulation, the RMS checked the completeness of the dossier and informed the applicants, the European Commission and EFSA about the admissibility. The RMS provided its initial evaluation of the dossier on bentazone in the RAR, which was received by EFSA on 8 January 2014 (Netherlands, 2013). The peer review was initiated on 27 January 2014 by dispatching the RAR to the Member States and the applicants BASF SE and AgriChem BV for consultation and comments. In addition, EFSA conducted a public consultation on the RAR. The comments received were collated by EFSA and forwarded to the RMS for compilation and evaluation in the format of a Reporting Table. The applicants were invited to respond to the comments in column 3 of the Reporting Table. The comments and the applicants 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 applicants in accordance with Article 16(3) of the Regulation were considered in a telephone conference between EFSA, the RMS, and the European Commission on 26 June On the basis of the comments received, the applicants response to the comments and the RMS s evaluation thereof it was concluded that additional information should be requested from the applicants and EFSA should organise an expert consultation in the areas of mammalian toxicology, residues, environmental fate and behaviour, and ecotoxicology. According to Article 16(2) of the Regulation, the European Commission decided to consult EFSA. The mandate was received on 4 July 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, and the additional information to be submitted by the applicants, were compiled by EFSA in the format of an Evaluation Table. 3 Commission Regulation (EU) No 1141/2010 of 7 December 2010 laying down the procedure for the renewal of the inclusion of a second group of active substances in Annex I to Council Directive 91/414/EEC and establishing the list of those substances. OJ L 322, , p Commission Implementing Regulation (EU) No 380/2013 of 25 April 2013 amending Regulation (EU) No 1141/2010 as regards the submission of the supplementary complete dossier to the Authority, the other Member States and the Commission. OJ L 116, , p.4 5 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 EFSA Journal 2015;13(4):4077 5

6 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. 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 March This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the representative formulations evaluated on the basis of the representative uses as a herbicide on a wide range of crops in the EU, as proposed by the applicants. A list of the relevant end points for the active substance as well as the formulations 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 ority views, where applicable, can be found: the comments received on the RAR, the Reporting Table (27 June 2014), the Evaluation Table (30 March 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 RAR including its final addendum (compiled version of January 2015 containing all revisions to the RAR (Netherlands, 2015)) and the Peer Review Report, both documents are considered respectively as background documents A and B 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 to have regulatory access to the information on which this conclusion report is based. EFSA Journal 2015;13(4):4077 6

7 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Bentazone is the ISO common name for 3-isopropyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide (IUPAC). Bentazone-sodium, sodium 3,4-dihydro-3-isopropyl-4-oxo-2,1,3-benzothiadiazin-1-ide 2,2-dioxide (IUPAC), is a derivative of bentazone. The representative formulated products for the evaluation were BAS H and Bentazone 480 g/l SL ; both are soluble concentrates (SL) containing 480 g/l bentazone as the sodium salt. The representative uses evaluated are outdoor foliar spraying against annual dicotyledonous in various crops. Full details of the GAPs can be found in the list of end points in Appendix A. 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: SANCO/3030/99 rev.4 (European Commission, 2000), SANCO/10597/2003 rev (European Commission, 2012) and SANCO/825/00 rev. 8.1 (European Commission, 2010). Bentazone is manufactured either as a technical concentrate (TK), meeting the requirements of the FAO specification 366/TK (1999), (BASF), with the imum purity of the active substance on a dry weight basis of 960 g/kg bentazone, or as a technical material (TC) (AgriChem) with a imum purity of 980 g/kg. The imum purity of bentazone in the FAO specification for the technical material, 366/TC (1999), is 960 g/kg (BASF). 1,2-dichloroethane is considered a relevant impurity at a imum content of 3 mg/kg, but only for the BASF source (see Section 2). The proposed specifications are based on batch data from industrial scale production. The assessment of the data package revealed no issues that need to be included as critical areas of concern with respect to the identity, physical, chemical and technical properties of bentazone or the representative formulations. The main data regarding the identity of bentazone and its physical and chemical properties are given in Appendix A. Methods of analysis are available for the active substance in the technical material and the formulations, and also for the relevant impurity. Bentazone residues can be monitored in food and feed of plant origin by LC-MS/MS methods with a LOQ of 0.01 mg/kg in each commodity group. 6-hydroxy-bentazone, expressed as bentazone was proposed as provisional residue definition for monitoring in food and feed of animal origin (see Section 3). LC-MS/MS methods exist for monitoring 6-hydroxy-bentazone in eggs, meat, liver, milk, with a LOQ of 0.01 mg/kg in each commodity. It should be noted however that for milk 6-hydroxybentazone (sulphate) conjugates were proposed as provisional residue definition for monitoring (see Section 3). Appropriate LC-MS/MS method exists for monitoring residues in milk according to this residue definition, too. Residues of bentazone and its metabolite N-methyl-bentazone in soil can be detered by LC- MS/MS with a LOQ of 0.01 mg/kg for each compound. Appropriate LC-MS/MS method exists for monitoring residues of bentazone in groundwater and surface water with a LOQ of 0.03 µg/l. It should be noted however that the residue definition for surface water was proposed as bentazone and its metabolite N-methyl-bentazone (see Section 5 and the ecotoxicologically relevant compounds in Appendix A), and as a consequence additional validation data are required to demonstrate the applicability of the existing method to the new residue definition. Residues of bentazone in air can be monitored by LC-MS/MS with a LOQ of 0.37 µg/m 3. EFSA Journal 2015;13(4):4077 7

8 The active substance is not classified as toxic according to Regulation (EC) No 1272/2008 (CLP Regulation) 6, therefore a method of analysis is not required for body fluids and tissues. 2. Mammalian toxicity The following guidance documents were followed in the production of this conclusion: SANCO/221/2000 rev final (European Commission, 2003), SANCO/10597/2003 rev (European Commission, 2012) and the Guidance on Dermal Absorption (EFSA PPR Panel, 2012). Bentazone was discussed at the Pesticides Peer Review Experts Meeting 122 in November The technical specifications of both applicants are not supported by the toxicological studies and the relevance of the individual impurities has not been addressed in comparison with the toxicological profile of the parent compound, therefore a data gap was identified to address the relevance of the impurities present in the technical specification for each applicant and a critical area of concern is identified regarding both technical specifications. A relevant impurity has been identified in the BASF source, 1,2-dichloroethane, which is classified as carcinogen category 1B in accordance with the provisions of Regulation (EC) No 1272/2008 (harmonised classification); its imum concentration limit (3 mg/kg) is based on the analytical limit of quantification, no concern is raised at this concentration limit. Bentazone is almost completely absorbed after oral adistration, poorly metabolised and rapidly excreted mainly via urine; showing no potential for accumulation. Moderate acute toxicity was observed in a number of species tested by oral adistration, while low toxicity was seen via the dermal and inhalation routes. The active substance may cause serious eye irritation and skin sensitisation. The target organs of bentazone are the blood (with prolonged coagulation time in rats, mice and dogs, reduced haematocrit and haemoglobin), liver and kidneys. The relevant short-term NOAEL is 13 mg/kg bw per day for blood effects, increased liver and kidney weight, and clinicochemical changes observed in the 1-year toxicity study in dogs. The relevant long-term NOAEL is 9 mg/kg bw per day for blood, liver and kidney effects observed in the 2-year toxicity and carcinogenicity study in rats. Bentazone did not present genotoxic, carcinogenic or neurotoxic potential. The reproduction and fertility parameters were not affected by bentazone adistration, however it is noted that sensitive endpoints were not investigated, such as sperm parameters or sex ratio in a twogeneration reproductive toxicity study in rats. Developmental effects, such as increased post implantation loss, reduced number of live foetuses and retarded foetal development were observed in a rat developmental study in the absence of clear maternal toxicity, supported by evidence in other developmental studies in rats. Based on these developmental effects the experts suggested that classification regarding reproductive toxicity, Repr. Cat 2 H361d suspected of damaging the unborn child may be appropriate 7 (no classification regarding this endpoint is included in the current harmonised classification according to Regulation (EC) No 1272/2008). The developmental NOAEL is 100 mg/kg bw per day and the maternal NOAEL is 250 mg/kg bw per day in rats. Published literature did not identify receptor-mediated (anti)oestrogenic or (anti)androgenic activity in vitro. However, the available data are not sufficient to clarify the potential endocrine activity of bentazone. As an endocrine-mediated mode of action could not be ruled out regarding the critical effects observed in the developmental toxicity study in rats (increased post implantation loss, reduced number of live foetuses and retarded foetal development), a data gap for the Level 2/3 tests currently indicated in the OECD Conceptual Framework (OECD, 2012) and analysed in the EFSA Scientific 6 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. OJ L 353, , It should be noted that classification is formally proposed and decided in accordance with Regulation (EC) No 1272/2008. Proposals for classification made in the context of the evaluation procedure under Regulation (EC) No 1107/2009 are not formal proposals. EFSA Journal 2015;13(4):4077 8

9 Opinion on the hazard assessment of endocrine disruptors (EFSA Scientific Committee, 2013) is identified, and the assessment could not be finalised. This data gap is relevant for the interpretation of the interim provisions of Annex II, Point of Regulation (EC) No 1107/2009 for the deteration of potential endocrine disrupting properties. The RMS disagrees with the data gap, considering unlikely that the increased post implantation loss, reduced number of foetuses and retarded foetal development are caused by an endocrine mediated effect. Toxicological studies have been provided on two bentazone metabolites: 8-hydroxy-bentazone and 6- hydroxy-bentazone. 8-hydroxy-bentazone was found to be less toxic than the parent bentazone from the acute, short-term and developmental toxicity point of view; as a worst case, the reference values of the parent would apply to this metabolite. Regarding 6-hydroxy-bentazone, insufficient toxicological information is available and a data gap has been identified for further data allowing to establish reference values for this metabolite as it has been included in the residue definition for risk assessment (see Section 3). The acceptable daily intake (ADI) of bentazone is 0.09 mg/kg bw per day, based on the NOAEL of 9 mg/kg bw per day for blood, liver and kidney toxicity observed in the 2-year study in rats and applying the standard uncertainty factor (UF) of 100. The acute reference dose (ARfD) is 1 mg/kg bw, based on the NOAEL of 100 mg/kg bw per day for increased post implantation loss, reduced number of live foetuses and retarded foetal development observed in a developmental toxicity study in rats, 100 UF applied. The acceptable operator exposure level (AOEL) is 0.13 mg/kg bw per day based on the NOAEL of 13 mg/kg bw per day for blood, liver and kidney effects observed in the 1-year toxicity study in dogs, 100 UF applied but no correction being necessary regarding oral absorption. Based on a human skin in vitro dermal absorption study, dermal absorption values for one of the representative SL formulation containing 480 g bentazone/l, BAS H, is 0.2 % for the concentrate and 0.9 % for the in-use spray dilution. The estimated operator, worker, bystander and residential exposure levels were below the AOEL even when the use of personal protective equipment (PPE) is not considered for operators and workers. Regarding the representative formulation Bentazone 480 g/l SL, default dermal absorption values of 25 % for the concentrate and 75 % for the in-use field dilutions were applied and the use of PPE has to be considered for operators (such as gloves during mixing and loading, and gloves, coveralls and sturdy footwear during application) and workers (gloves, long-sleeved shirt and trousers) to ensure that the AOEL is not exceeded. Hand-held operator exposure has not been assessed for this formulation. Bystander and residential exposure estimates are below the AOEL. 3. Residues The assessment in the residue section below is based on the guidance documents listed in the document 1607/VI/97 rev.2 (European Commission, 1999) and the JMPR recommendations on livestock dietary burden calculations stated in the 2004 and 2007 JMPR reports (JMPR, 2004, 2007). The metabolism of bentazone was investigated for foliar application on pulses and oilseeds (soya bean), root and tuber crops (potato) and cereals (rice, maize, wheat) using 14 C-phenyl labelled bentazone. The parent bentazone was hardly ever detected in any crop parts (up to 8 % of the total radioactive residues (TRR)), except in wheat forage and straw (up to 56 % TRR). Besides, the metabolite 6-hydroxy-bentazone in its conjugated form was also identified in significant proportions mainly in the feedingstuff commodities (24 % TRR in maize forage up to 41 % TRR in wheat hay), whilst the glucoside conjugate of 8-hydroxy-bentazone was detected but at a or level in soya bean forage (28 % TRR) and in wheat straw (3 % TRR) only. The major part of the radioactivity in the seeds, potato tuber and cereal grain was found to be incorporated into natural plant constituents (up to 70 % TRR). Additional metabolism data on foliar treated potato and wheat grown as a rotational crop following the harvest of potatoes showed that in potato tubers numerous fractions were recovered at a level > 10 % of TRR, but were not further identified as their actual levels were mostly below EFSA Journal 2015;13(4):4077 9

10 0.01 mg/kg and consist mainly of a mixture of polar compounds. However, in wheat straw, a significant unidentified fraction M3 (57 % TRR mg eq/kg) was found and a data gap has been identified for any further attempt of characterisation and identification of this fraction based on all analytical evidence available from the wheat metabolism study and considering also the potential uptake by the plants of soil metabolites. Confined rotational crop metabolism studies on leafy crops, root and tuber crops, and cereals after a bare soil application of 14 C-phenyl labelled bentazone showed that the radioactive residues were characterised as polar fractions further incorporated into the natural compounds of the plant tissues (30 % of TRR in wheat straw, up to 75 % of TRR in wheat grain). A specific residue definition for rotational crops is not deemed necessary. The metabolic pathway of bentazone in plants consisted mainly of hydroxylation of the parent molecule to form the metabolites 6-hydroxy and 8-hydroxy-bentazone, followed by an O-glycosilation conjugation step. The residue definition for enforcement is set as bentazone only. For risk assessment and considering the magnitude of the conjugates of 6-hydroxy-bentazone residues observed in the residue trials on grass, which is a major feed item, the residue definition is proposed as the sum of bentazone, 6-hydroxybentazone and its conjugates, expressed as bentazone. This residue definition should however be considered as provisional and needs to be revised pending on the clarification with regard to the identity of fraction M3 in wheat straw. Sufficient residue trials were available for potatoes (NEU Northern Europe GAP), onions (shallots, garlic) (NEU GAP), sweet corn, beans (green) without pods, beans (dry), soya bean (poppy seed) (SEU Southern Europe GAP), linseed, maize, sorghum, cereals (barley, oats, wheat, rye and triticale) (NEU GAP) and herbal infusions (dried). All the residue trials were supported by acceptable storage stability data. Additional residue trials are required to complete the residue data set for all the other representative uses on potatoes (SEU GAP), onions (shallots, garlic) (SEU GAP), herbs (t, chives), peas (green) without pods (NEU/SEU GAPs), beans and peas (green) with pods (NEU/SEU GAPs), peas (dry) (NEU/SEU GAPs), soya bean (NEU GAP), cereals (SEU GAP) and fodder crops (alfalfa (NEU/SEU GAPs), grass (NEU/SEU GAPs), clover (NEU/SEU GAPs), pasture). The nature of the residues under processing representative of pasteurisation, baking/brewing/boiling and sterilisation was not investigated, but further studies are not triggered. Processing studies on soya bean, maize and rice revealed negligible transfer of residues of bentazone and its related metabolite in the processed commodities. Ruants and poultry metabolism studies were conducted with respectively bentazone, 6-hydroxy-bentazone and 8-hydroxy-bentazone, each compound labelled on the phenyl ring. Based on these data and considering that 6-hydroxy-bentazone and its conjugate residues were shown to contribute predoantly to the dietary burden when grass (fresh) is fed to livestock, the residue definition for risk assessment is set as the sum of bentazone, 6-hydroxybentazone and their conjugates, expressed as bentazone. For enforcement purposes, 6-hydroxybentazone was considered as a sufficient marker of the residues in all animal matrices, whilst this compound was recovered only in its sulphate conjugated form in milk. The residue definition is therefore set as 6-hydroxy-bentazone, expressed as bentazone for all animal commodities, except in milk where the residue is defined as 6-hydroxy-bentazone (sulphate) conjugates, expressed as bentazone. Furthermore, since residues above 0.01 mg/kg are expected in milk, fat, kidney and liver at the calculated dietary burden, a data gap was identified for the submission of a ruant feeding study dosing a representative mixture of bentazone and 6-hydroxy-bentazone, with the deteration of the residues of bentazone, 6-hydroxy-bentazone and their conjugates separately in all animal commodities. The proposed residue definition for enforcement in livestock matrices is provisional and should be revisited accordingly. The consumer risk assessment was performed with the EFSA Pesticides Residues Intake Model (PRIMo rev 2A). No chronic or acute intake concerns were identified as the TMDI and the IESTI accounted for respectively < 1 % of the ADI (WHO Cluster diet B) and 1.7 % of the ARfD (sweet corn). EFSA highlights that the consumer dietary intake calculation should be reconsidered pending on the agreed residue definitions for risk assessment in plants and for enforcement in livestock, on the outcome of the requested residue trials, the revised livestock dietary burden and the feeding study in ruants. EFSA Journal 2015;13(4):

11 4. Environmental fate and behaviour Peer review of the pesticide risk assessment of the active substance bentazone Bentazone was discussed at the Pesticides Peer Review Experts Meeting 121 in November In soil laboratory incubations under aerobic conditions in the dark, bentazone exhibited low to moderate persistence, forg the metabolite N-methyl-bentazone (. 5.7 % applied radioactivity (AR)), which triggered further consideration for groundwater exposure and exhibited moderate to high persistence (first-order DT days, 20 ºC pf 2 soil moisture). Mineralisation of the phenyl ring 14 C radiolabel to carbon dioxide accounted for 8-11 % AR after days. The formation of unextractable residues (not extracted by methanol followed by methanol/water) for this radiolabel accounted for % AR after days. In anaerobic soil incubations bentazone was essentially stable. Bentazone degraded faster under the conditions of a laboratory soil photolysis study than in the dark control. The only transformation product accounting for > 1 % AR was carbon dioxide. Bentazone exhibited high to medium mobility in soil. In the scientific peer reviewed literature data indicated that bentazone can be more strongly adsorbed under acidic soil conditions when metal oxides, such as iron oxides, are present in soils. Because the iron oxide content of the soils used in the batch adsorption experiments was not known, the Member State experts attending the Pesticides Peer Review Experts Meeting 121 agreed that it would be appropriate to exclude soils with a ph water < 6.6 from the soil adsorption database subsequently used to model the leaching potential of bentazone, as many soils overlaying vulnerable aquifers will not contain metal oxides, therefore this mechanism for higher soil adsorption will not always be available to reduce leaching risks. Therefore this ph criterion was selected as an unbiased way to exclude soil adsorption measurements that may have included such metal oxide interactions causing higher adsorption being included in the database used to derive the adsorption input for leaching modelling. This is relevant as the FOCUS groundwater scenarios were not selected considering vulnerability regarding soil content of metal oxides. N-methyl-bentazone exhibited medium soil mobility. In satisfactory field dissipation studies carried out at 8 sites across Europe (spray application to the soil surface on bare soil plots in late spring) bentazone exhibited low to moderate persistence. Sample analyses were only carried out for the parent bentazone. Field study DT 50 values were accepted as being reasonable estimates of degradation and were normalised to FOCUS reference conditions (20 ºC and pf2 soil moisture), using the time step normalisation procedure in accordance with FOCUS (2006) kinetics guidance at 6 of these sites. The procedures as outlined in the EFSA PPR Panel (2010) opinion were used to exclude the impact of soil surface processes, including photolysis, when deriving these field degradation endpoints. In laboratory incubations in dark aerobic natural sediment water systems, bentazone exhibited high persistence, remaining in the water column and forg the major metabolite N-methyl-bentazone ( % AR in water 30 days after dosing). The unextractable sediment fraction (not extracted by methanol/water) was a sink for the phenyl ring 14 C radiolabel, accounting for 16 % AR at study end (100 days). Mineralisation of this radiolabel accounted for only 2.6 % AR at the end of the study. The rate of decline of bentazone in a laboratory sterile aqueous photolysis experiment was fast relative to that occurred in the aerobic sediment water incubations. The major phototransformation products were M 1 ( 30 % AR), M 2 ( 25 % AR) and 8-hydroxy-bentazone ( 11 % AR). The necessary surface water and sediment exposure assessments (Predicted environmental concentrations (PEC) calculations) were carried out for bentazone, N-methyl-bentazone and the three aqueous photolysis metabolites, using the FOCUS (FOCUS, 2001) step 1 and step 2 approach (version 2.1 of the steps 1-2 in FOCUS calculator). The groundwater exposure assessments were appropriately carried out using FOCUS (FOCUS, 2009) scenarios and the models PEARL and PELMO for the active substance bentazone and the soil metabolite N-methyl-bentazone in relation to the applied for representative uses with annual application rates up to 960 g a.s./ha, simulated as a single application. The potential for groundwater exposure from these representative uses by bentazone and N-methyl-bentazone above the parametric drinking water limit of 0.1 µg/l was concluded to be low in geoclimatic situations that are represented 8 Simulations used the agreed Q10 of 2.58 (following EFSA, 2007) and Walker equation coefficient of 0.7 EFSA Journal 2015;13(4):

12 by all 9 FOCUS groundwater scenarios, with the exception of the use on winter cereals where concentrations of the parent bentazone were predicted to be up to 0.11 and 0.16 µg/l at the FOCUS Hamburg and Okehampton scenarios, respectively (80 th percentile annual average recharge concentrations moving below 1m as defined by FOCUS). Groundwater exposure assessments using agreed substance input parameters for the applied for representative uses, with annual application rates higher than 960 g a.s./ha, were not available. This is identified as a data gap (see Section 7) and as assessments not finalised (see Section 9). The Member State experts attending the Pesticides Peer Review Experts Meeting 121 discussed the RMS evaluation of the available EU groundwater monitoring data for the parent bentazone. Whilst the quantity of monitoring data available was concluded as sufficient to comply with the guidance on the use of monitoring information in the FOCUS (2009) guidance, it was less clear if enough of the available information really complied with the quality criteria that are specified as being necessary in this guidance. The view of the experts on these monitoring data was, that whilst this provided indications that it might be expected that bentazone can be used without contaating groundwater for a number of representative uses in the EU, for some uses and vulnerable situations groundwater contaation cannot be excluded. (I.e. groundwater monitoring appears to show a problem of groundwater exposure above the parametric drinking water limit for uses on soya bean in Austria and further data may be needed to clarify findings in Germany, for example in karstic areas.) The PEC in soil, surface water, sediment, covering the representative uses assessed, can be found in Appendix A of this conclusion. The PEC for groundwater in Appendix A only cover the representative uses assessed for annual application rates up to 960 g a.s./ha. 5. Ecotoxicology The risk assessment was based on the following documents: European Commission (2002a, b), SETAC (2001) and EFSA (2009). Bentazone was discussed at the Pesticides Peer Review Experts Meeting 124 in December It has not been demonstrated that the technical material used in the ecotoxicity studies is suitably representative of the technical specifications for both applicants. A data gap was identified to address the relevance of the impurities present in the technical specification for each applicant and a critical area of concern is identified regarding both technical specifications. The available risk assessments for birds and wild mammals from the representative uses of bentazone applied as BAS H considered the worst case generic focal species, as defined in EFSA (2009), in a risk envelope approach. A low acute risk to birds and mammals was concluded for all generic focal species for the representative uses of BAS H. The first-tier long-term risk assessment for birds indicated a low risk to birds with the exception of the medium herbivorous/granivorous birds. However, on the basis of a weight-of-evidence approach, considering the available residue data, a low risk to medium herbivorous/granivorous birds was concluded. The experts at the peer review meeting agreed that a refined endpoint could be used in the assessment of the long-term risk to mammals. However, even using the refined endpoint, a high long-term risk was indicated for the small herbivorous mammal generic focal species (relevant for the representative uses summarised in Table 1 below). A low long-term risk was indicated to all other generic focal species for mammals. As the representative uses of Bentazone 480 g/l SL were more complex encompassing a variety of application rates, number of applications and growth stages, the risk envelope approach was not suitable. On the basis of the available assessments a high acute risk to birds and mammals was concluded for a number of the representative uses of Bentazone 480 g/l SL (summarised in Table 1). The first-tier long-term risk assessment indicated a high long-term risk to the generic focal species medium herbivorous/granivorous birds and large herbivorous birds. However, on the basis of a weight-of-evidence approach, considering the available residue data, a low risk to medium EFSA Journal 2015;13(4):

13 herbivorous/granivorous birds was concluded. No information was available to address the risk to large herbivorous birds and therefore a high risk was concluded for a number of the representative uses of Bentazone 480 g/l SL (summarised in Table 1). Using the refined endpoint to assess the long-term risk to mammals, a high risk was indicated to both small and large herbivorous mammals. However, on the basis of a weight-of-evidence approach, considering the available residue data, a low risk to large herbivorous mammals was concluded. No suitable refinements were available to further refine the risk to small herbivorous mammals and therefore a high risk was concluded for a number of the representative uses of Bentazone 480 g/l SL (summarised in Table 1). Data gaps are identified to address the acute and/or long-term risk to birds and mammals for several of the representative uses of bentazone. Table 1: Summary of the representative uses of bentazone for which a high risk to birds and/or mammals was concluded Representative Use Terrestrial vertebrate risk assessment for which a high risk was indicated Crop kg a.s./ha No. of applications Acute risk to birds Acute risk to mammals Long-term risk to birds Long-term risk to mammals Grass seed High risk Grazing land High risk Turf High risk Soya beans Vining peas High risk High risk Vining peas High risk French beans High risk Field beans and broad beans High risk - - High risk Combining peas High risk Combining peas High risk Alfalfa High risk Cereals High risk Linseed (oil) High risk - High risk - Flax (fibre) High risk - High risk - Grassland High risk High risk High risk All crops 2 (mentioned) against Cyperus esculentus L High risk High risk High risk High risk 1 Relevant for BAS H. 2 Relevant for Bentazone 480 SL. For the ecotoxicological assessments, no specific studies were available to address the potential endocrine activity of bentazone. Pending on the outcome of the data gap in Section 2, further ecotoxicological tests might be necessary to address the potential endocrine disrupting properties of bentazone. The surface water metabolite, N-methyl-bentazone, was found to be more toxic to fish and aquatic invertebrates than the parent substance. Nevertheless, on the basis of the available assessment a low EFSA Journal 2015;13(4):

14 risk to aquatic organisms was concluded for metabolite N-methyl-bentazone, the parent substance (bentazone) and the additional three surface water metabolites (M 1, M 2 and 8-hydroxy-bentazone). On the basis of the available data and risk assessments a low risk was concluded for honeybees, nontarget arthropods, earthworms, soil microorganisms and sewage treatment organisms. The first-tier risk assessment for non-target plants indicated a high risk. For the representative uses of bentazone applied as BAS H, a weight-of-evidence assessment was provided and a low risk was concluded. For the representative uses of bentazone applied as Bentazone 480 g/l SL, a refined risk assessment using a probabilistic approach was available. On the basis of the available assessment, considering an assessment factor of 1 (as defined in European Commission, 2002a), a low risk was concluded. EFSA Journal 2015;13(4):

15 6. Overview of the risk assessment of compounds listed in residue definitions triggering assessment of effects data for the environmental compartments 6.1. Soil Compound (name and/or code) bentazone Persistence low to moderate persistence Single first-order DT days (20 ºC pf 2 soil moisture) European field dissipation studies single first-order DT days Ecotoxicology Low risk to soil organisms. EFSA Journal 2015;13(4):

16 6.2. Ground water Compound (name and/or code) Mobility in soil >0.1 μg/l 1m depth for the representative uses (at least one FOCUS scenario or relevant lysimeter) Pesticidal activity Toxicological relevance Ecotoxicological activity 1 x 0.96 kg a.s./ha/yr 2/9 FOCUS scenarios for the winter cereal use with concentrations predicted at 0.11 and 0.16 µg/l. bentazone high to medium mobility K Foc ml/g No for other uses. > 0.96 kg a.s./ha/yr Yes Yes Yes Data gap 1 x 0.96 kg a.s./ha/yr N-methyl-bentazone medium mobility K Foc ml/g No > 0.96 kg a.s./ha/yr No data available. No data available, data may be required Yes Data gap EFSA Journal 2015;13(4):

17 6.3. Surface water and sediment Compound (name and/or code) bentazone N-methyl-bentazone M 1 M 2 8-hydroxy-bentazone Ecotoxicology Low risk to aquatic organisms. Greater toxicity to fish and aquatic invertebrates than bentazone. A low risk to aquatic organisms was indicated for the representative uses. Low risk to aquatic organisms. Low risk to aquatic organisms. Low risk to aquatic organisms Air Compound (name and/or code) bentazone Toxicology Rat LC 50 inhalation > 5.1 mg/l air/4h (head-nose only), no classification required EFSA Journal 2015;13(4):

18 7. List of studies to be generated, still ongoing or available but not peer reviewed This is a list of data gaps identified during the peer review process, including those areas where 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 Regulation (EC) No 1107/2009 concerning information on potentially harmful effects). Analytical method for monitoring all the components of the residue definition in surface water (relevant for all representative uses evaluated; submission date proposed by the applicants: unknown; see Section 1). Assessment of the relevance of the individual impurities present in the technical specification in comparison with the toxicological and ecotoxicological profile of the parent compound of both applicants (relevant for all representative uses evaluated; submission date proposed by the applicants: unknown; see Sections 2 and 5). Level 2/3 tests currently indicated in the OECD Conceptual Framework to address the potential for endocrine-mediated mode of action regarding the developmental effects observed in a developmental toxicity study in rats (increased post implantation loss, reduced number of live foetuses and retarded foetal development in the absence of clear maternal toxicity suggesting that classification as reprotoxic category 2 may be appropriate) (relevant for all representative uses evaluated; submission date proposed by the applicants: unknown; see Sections 2 and 5). Further toxicological information on 6-hydroxy-bentazone allowing to establish reference values for the metabolite as it has been included in the residue definition for risk assessment (relevant for all representative uses evaluated; submission date proposed by the applicants: unknown; see Sections 2 and 3). Characterisation and identification of the fraction M3 in wheat straw based on all analytical evidence available in the raw data from the wheat metabolism study and considering also the potential uptake by the plants of soil metabolites (relevant for AgriChem; submission date proposed by the applicant: unknown; see Section 3). Additional residue trials are required to complete the residue data set for the representative uses on potatoes (SEU GAP), onions (shallots, garlic) (SEU GAP), herbs (t, chives), peas (green) without pods (NEU/SEU GAPs), beans and peas (green) with pods (NEU/SEU GAPs), peas (dry) (NEU/SEU GAPs), soya bean (NEU GAP), cereals (SEU GAP) and fodder crops (alfalfa (NEU/SEU GAPs), grass (NEU/SEU GAPs), clover (NEU/SEU GAPs), pasture) (relevant for BASF and AgriChem; submission date proposed by the applicants: unknown; see Section 3). A ruant feeding study dosing a representative mixture of bentazone and 6-hydroxy-bentazone with the deteration of the residues of bentazone, 6-hydroxy-bentazone and their conjugates separately in all animal commodities (relevant for BASF and AgriChem; submission date proposed by the applicants: unknown; see Section 3). The published reference Clausen, L., Fabricius, I. (2001): Atrazine, Isoproturon, Mecoprop, 2,4- D, and Bentazone adsorption onto iron oxides J. Environ. Qual. 30: was not included in the dossier that has been provided by the applicants. This reference was identified by the co-rms Germany as relevant information to be considered during the peer review. It has been evaluated by the RMS and taken into account in the EFSA conclusion (relevant for all representative uses evaluated; submission date proposed by the applicants: unknown; see Evaluation Table section 4 in EFSA, 2015). Satisfactory groundwater exposure simulation modelling to cover the representative uses for the representative formulation Bentazone 480 g/l SL, where annual application rates were higher EFSA Journal 2015;13(4):

19 than 960 g/ha, was not available (relevant for representative uses of the formulation Bentazone 480 g/l SL on grassland, potatoes, cereals, linseed, flax, combining peas, vining peas, French beans, field beans, broad beans, soya beans and all the other crops requested for Bentazone 480 g/l SL when Cyperus esculentus L. control is needed; submission date proposed by the applicant: unknown; see Section 4). Information to address the long-term risk to mammals (relevant for the representative uses of bentazone applied as BAS H to grass seed (0.96 kg a.s./ha) grazing land (0.96 kg a.s./ha) and turf (0.96 kg a.s./ha); submission date proposed by the applicant: unknown; see Section 5). Information to address the acute risk to mammals (relevant for the representative uses of bentazone applied as Bentazone 480 g/l SL to grassland (1.44 kg a.s./ha) and all the other crops requested for Bentazone 480 g/l SL when Cyperus esculentus L. control is needed (1.44 kg a.s./ha); submission date proposed by the applicant: unknown; see Section 5). Information to address the long-term risk to mammals (relevant for the representative uses of bentazone applied as Bentazone 480 g/l SL to field/broad beans (1.44 kg a.s./ha), alfalfa (0.96 kg a.s./ha), grassland (1.44 kg a.s./ha) and all the other crops requested for Bentazone 480 g/l SL when Cyperus esculentus L. control is needed (1.44 kg a.s./ha); submission date proposed by the applicant: unknown; see Section 5). Information to address the acute risk to birds (relevant for the representative uses of Bentazone 480 g/l SL to soya beans ( kg a.s./ha), vining peas (3 applications of or 1 application of kg a.s./ha), French beans (1.44 kg a.s./ha), field beans/broad beans (1.44 kg a.s./ha), combing peas (3 applications of or 1 application of kg a.s./ha), linseed (1.44 kg a.s./ha), flax (1.44 kg a.s./ha) and all crops requested for Bentazone 480 g/l SL when Cyperus esculentus L. control is needed (1.44 kg a.s./ha); submission date proposed by the applicant: unknown; see Section 5). Information to address the long-term risk to birds (relevant for the representative uses of bentazone applied as Bentazone 480 g/l SL to cereals (1.44 kg a.s./ha), flax (1.44 kg a.s./ha), grassland (1.44 kg a.s./ha), linseed (1.44 kg a.s./ha) and all the other crops requested for Bentazone 480 g/l SL when Cyperus esculentus L. control is needed (1.44 kg a.s./ha); submission date proposed by the applicant: unknown; see Section 5). 8. Particular conditions proposed to be taken into account to manage the risk(s) identified Personal protective equipment (PPE), such as gloves during mixing and loading operations, and gloves, coveralls and sturdy footwear during application have to be considered to ensure that operator exposure does not exceed the AOEL according to the German model for mechanical downward spraying of the Bentazone 480 g/l SL formulation (see Section 2). PPE, such as gloves, long-sleeved shirt and trousers have to be considered to ensure that worker exposure does not exceed the AOEL in case of the Bentazone 480 g/l SL formulation (see Section 2). 9. Concerns 9.1. Issues that could not be finalised An issue is listed as an issue that could not be finalised where 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 Regulation (EC) No 1107/2009 and as EFSA Journal 2015;13(4):