Conclusion on the peer review of the pesticide risk assessment of the active substance fluroxypyr (evaluated variant fluroxypyr-meptyl) 1

Transcription

1 CONCLUSION ON PESTICIDE PEER REVIEW Conclusion on the peer review of the pesticide risk assessment of the active substance fluroxypyr (evaluated variant fluroxypyr-meptyl) 1 SUMMARY European Food Safety Authority 2 European Food Safety Authority (EFSA), Parma, Italy Commission Regulation (EC) No 737/ (hereinafter referred to as the Regulation ) lays down the procedure for the renewal of the inclusion of a first group of active substances in Annex I to Council Directive 91/414/EEC and establishes the list of those substances. Fluroxypyr is one of the first group of active substances listed in the Regulation. In accordance with Article 6 of the Regulation, the notifier Dow AgroSciences submitted a dossier on fluroxypyr to Ireland and Poland, being the designated rapporteur Member State (RMS), and corapporteur Member State, respectively. In accordance with Article 10 of the Regulation, Ireland prepared an Assessment Report in consultation with Poland, which was submitted to the EFSA and the Commission of the European Communities (hereafter referred to as the Commission ). The Assessment Report was received by the EFSA on 26 November The updated Assessment Report was received on 2 March In accordance with Article 11 of the Regulation, the EFSA distributed the Assessment Report to Member States and the notifier for comments on 2 December 2009 and the updated Assessment Report was distributed on 1 July The EFSA collated and forwarded all comments received to the Commission on 18 August In accordance with Article 12, following consideration of the Assessment Report and the comments received, the Commission requested the EFSA to arrange an expert consultation on the Assessment Report as appropriate and deliver its conclusions on fluroxypyr. The conclusions presented in this report were reached on the basis of the evaluation of the representative uses of fluroxypyr as a herbicide in cereals, pasture/amenity and maize, as proposed by the notifier. Full details of the representative uses can be found in Appendix A to this report. No critical areas of concern were identified in the identity, physical/chemical/technical properties and methods of analysis section. Data gaps were identified for the specification, auto-flammability of the technical material and some of the methods of analysis. A conclusion on whether the batches used in the toxicological studies cover the current proposed technical specification cannot be drawn from the available information, leading to a critical area of concern and a data gap. A valid genotoxicity data package with the technical specification is needed to confirm the non-genotoxic potential of fluroxypyr. Further data gaps were identified concerning the relevance of the impurities present in the technical specification and the assessment of the 1 On request from the European Commission, Question No EFSA-Q , issued on 24 February Correspondence: praper@efsa.europa.eu 3 OJ L169, , p.10 Suggested citation: European Food Safety Authority; Conclusion on the peer review of the pesticide risk assessment of the active substance fluroxypyr.. [91 pp.]. doi: /j.efsa Available online: European Food Safety Authority, 2011

2 toxicological relevance of two groundwater metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine. Based on the metabolism studies conducted on cereals, the plant residue definition for monitoring and risk assessment is proposed as fluroxypyr, its esters, salts and its conjugates expressed as fluroxypyr. A data gap was identified for the notifier to confirm whether the various methods used to analyse the samples from the residue trials are able to consider the esters and the conjugates. MRLs were proposed for cereal and maize grains. The residue definition for animal products is provisionally limited to fluroxypyr and its salts expressed as fluroxypyr, pending the submission of further data in order to address the fate of the ester compounds in animals. Furthermore a data gap was identified for the notifier to provide further information on the stability of fluroxypyr residues in animal products. No chronic concern was identified for the consumers, the TMDI being 0.1% of the ADI. The acute risk was not regarded as the setting of an ARfD is considered not necessary for the active substance. Data necessary to assess the fate and behaviour of fluroxypyr in the environment were available in the dossier and no data gaps were identified. Potential for groundwater contamination above the limit of 0.1 µg /L by the metabolites fluroxypyr pyridinol (only when formed in alkaline soils) and fluroxypyr methoxypyridine was identified for some uses in vulnerable scenarios. Based on the available data in the dossier, a low ecotoxicological risk was indicated for the representative uses. The following data gaps were identified: to provide a study with a second aquatic plant and the active substance; to address the long-term risk for earthworms and for soil macroorganisms for the metabolite fluroxypyr methoxypyridine. Since the available tests were not valid for nitrogen turnover, a data gap was identified to provide studies assessing the effects of EF-1502 and fluroxypyr pyridinol respectively on soil micro-organisms. KEY WORDS Fluroxypyr, fluroxypyr-meptyl, peer review, risk assessment, pesticide, herbicide 2

3 TABLE OF CONTENTS Summary... 1 Table of contents... 3 Background... 4 The active substance and the formulated product... 6 Conclusions of the evaluation... 6 It should be noted that the active substance fluroxypyr has no isomers. However the meptyl ester has a pair of enantiomers. This issue is discussed in the relevant sections below 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 Groundwater 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 Issues that could not be finalised Critical areas of concern References Appendices Abbreviations

4 BACKGROUND Commission Regulation (EC) No 737/ (hereinafter referred to as the Regulation ) lays down the procedure for the renewal of the inclusion of a first group of active substances in Annex I to Council Directive 91/414/EEC and establishes the list of those substances. Fluroxypyr is one of the first group of active substances listed in the Regulation. In accordance with Article 6 of the Regulation, the notifier Dow AgroSciences submitted a dossier on fluroxypyr to Ireland and Poland, being the designated rapporteur Member State (RMS), and corapporteur Member State, respectively. In accordance with Article 10 of the Regulation, Ireland prepared an Assessment Report (Ireland, 2009) in consultation with Poland, which was submitted to the EFSA and the Commission of the European Communities (hereafter referred to as the Commission ). The Assessment Report was received by the EFSA on 26 November The updated Assessment Report was received on 2 March In accordance with Article 11 of the Regulation, the EFSA distributed the Assessment Report to Member States and the notifier for comments on 2 December 2009 and the updated Assessment Report was distributed on 1 July A 30 day period was provided for commenting. In addition, the EFSA conducted a public consultation on the Assessment Report. The EFSA collated and forwarded all comments received to the Commission on 18 August At the same time, the collated comments were forwarded to the RMS for compilation in the format of a Reporting Table. The notifier was invited to respond to the comments in column 3 of the Reporting Table. The RMS also provided a response to the comments in column 3. In accordance with Article 12, following consideration of the Assessment Report and the comments received, the Commission decided to further consult the EFSA. By written request, received by the EFSA on 25 October 2010, the Commission requested the EFSA to arrange a consultation with Member State experts as appropriate and deliver its conclusions on fluroxypyr. The need for expert consultation was considered in a telephone conference between the EFSA, the RMS and the Commission on 29 September On the basis of the comments received, the notifier s response to the comments, and the RMS subsequent evaluation thereof, it was concluded that the EFSA should organise a consultation with Member State experts in the area of environmental fate and behaviour. 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 consultation with Member State experts, were compiled by the EFSA in the format of an Evaluation Table. The conclusions arising from the consideration by the EFSA, and as appropriate by the RMS, of the points identified in the Evaluation Table, together with the outcome of the expert discussions where these 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 January - February 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 as a herbicide in cereals, pasture and maize as proposed by the notifier. A list of the relevant end points for the active substance as well as the formulation is provided in Appendix A. In addition, a key supporting document to this conclusion is the Peer Review Report (EFSA, 2011), 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 comprises the following documents: 4 OJ L169, , p.10 4

5 the comments received, Peer Review of the pesticide risk assessment of the active substance fluroxypyr the Reporting Table (revision 1.1; 29 September 2010), the Evaluation Table (18 February 2011), the report(s) of the scientific consultation with Member State experts (where relevant). Given the importance of the Assessment Report including its addendum (compiled version of January 2011 (Ireland, 2011) containing all individually submitted addenda) and the Peer Review Report, both documents are considered respectively as background documents A and B to this conclusion. 5

6 THE ACTIVE SUBSTANCE AND THE FORMULATED PRODUCT Fluroxypyr is the ISO common name for 4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetic acid (IUPAC). Due to the fact that the meptyl ester, a variant of fluroxypyr, is used in the formulated product, it should be noted that the evaluated data belong to the variant fluroxypyr-meptyl, unless otherwise specified. The representative formulated products for the evaluation were Starane 200 EC and Starane 180 EC, both are emulsifiable concentrate formulations (EC) containing respectively 200 and 180 g/l fluroxypyr as the meptyl ester. The representative uses evaluated comprise outdoor foliar spraying against broadleaved weeds in cereals, pasture/amenity and maize. Full details of the GAP can be found in the list of end points in Appendix A. CONCLUSIONS OF THE EVALUATION It should be noted that the active substance fluroxypyr has no isomers. However the meptyl ester has a pair of enantiomers. This issue is discussed in the relevant sections below. 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. 8.1 (European Commission, 2009), and SANCO/825/00 rev. 7 (European Commission, 2004a). The proposed minimum purity of the active substance and the specification of the impurities for the reference source were not supported by the available data and a data gap is identified for a new specification supported by the relevant data. Therefore the equivalence of the other sources cannot be concluded on. It was not possible to conclude on the relevance of the impurities (see section 2). A data gap was identified for auto-flammability of the technical material. The main data regarding the identity of fluroxypyr-meptyl and its physical and chemical properties are given in Appendix A. It should be noted that both formulations are classified as R65 Harmful: may cause lung damage if swallowed. The formulation Starane 180 EC showed poor emulsion stability characteristics and a labelling phrase such as once mixed the spray solution should be used immediately and should not be left in the sprayer overnight should be considered. A GC-MS method of analysis is available for products of plant origin however, it is not fully validated and a data gap has been identified. GC-MS and LC-MS/MS methods are available for the analysis of fluroxypyr and its salts in products of animal origin. Soil is analysed for fluroxypyr and its salts by GC-MS. Surface water is analysed by GC-MS for fluroxypyr-meptyl, fluroxypyr and its salts. A data gap has been identified for a method of analysis for groundwater/drinking water. An LC-MS/MS method is available to analyse fluroxypyr and its salts and fluroxypyr-meptyl in air. A method of analysis for body fluids and tissues is not required as the active substance is not classified as toxic or very toxic. 2. Mammalian toxicity The following guidance documents were followed in the production of this conclusion: SANCO/221/2000 rev. 10 (European Commission, 2003), SANCO/222/2000 rev. 7 (European Commission, 2004b), SANCO/10597/2003 rev. 8.1 (European Commission, 2009). Fluroxypyr is formulated as the fluroxypyr-meptyl (MHE) variant. A conclusion on whether the batches used in the toxicological studies cover the current proposed technical specification cannot be 6

7 drawn from the available information, leading to a critical area of concern and a data gap. The relevance of the impurities has not been addressed and a data gap was identified. Oral absorption of fluroxypyr and fluroxypyr-mhe was estimated to be higher than 90%. There was no evidence for accumulation. Fluroxypyr-MHE is almost completely and rapidly hydrolysed and excreted as fluroxypyr. Low acute toxicity is observed when fluroxypyr-mhe is administered by the oral, dermal and inhalation routes. No skin or eye irritation was observed, and there was no potential for skin sensitisation. Short-term oral studies with both fluroxypyr and fluroxypyr-mhe in rats, mice and dogs revealed the kidney as the target organ. Non-specific critical effects such as reduced body weight gain were also observed in mice and rats. Rats and mice were the most sensitive species. The relevant short-term oral NOAEL is 80 mg/kg bw/day (90-day rat and mice studies). No potential for genotoxicity is attributed to the active substance in studies performed in the early 1980s, however no information is available on the purity and impurity profile of the batches tested, which would not be acceptable according to current criteria. A valid genotoxicity data package with the technical specification is needed to confirm the non-genotoxic potential of fluroxypyr leading to a data gap. In long-term studies with fluroxypyr in rats and mice, the critical effects were also observed in the kidney. The relevant long-term NOAELs are 80 mg/kg bw/day for the rat and 100 mg/kg bw/day for the mouse. No evidence of carcinogenicity was observed. Reproductive toxicity studies were performed with fluroxypyr. Fertility and overall reproductive performance were not impaired. The parental, reproductive and offspring NOAELs are 500 mg/kg bw/day. In the developmental toxicity studies, there was no evidence of teratogenicity and the relevant maternal and developmental NOAELs are 250 mg/kg bw/day for the rat and 100 mg/kg bw/day for the rabbit. No potential for neurotoxicity was observed in the standard toxicity studies. No toxicological information is available on the metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine that were found in groundwater above 0.1 µg/l in a number of scenarios according to the fate modelling (see section 4), this is listed as a data gap for the assessment of the relevance of metabolites in groundwater according to the respective guidance document (European Commission, 2003). The acceptable daily intake (ADI) of fluroxypyr is 0.8 mg/kg bw/day, based on the NOAEL of 80 mg/kg bw/day found in the 2-year rat study and applying a safety factor of 100. The acceptable operator exposure level (AOEL) is 0.8 mg/kg bw/day, based on the NOAEL of 80 mg/kg bw/day found in the 90-day studies with rats and mice and applying a safety factor of 100. No correction for oral absorption is needed to derive the AOEL. The acute reference dose (ARfD) was not set and was considered not necessary. The relevant dermal absorption values for Starane 180 EC and Starane 200 EC are 4% for the concentrate and 22% for the dilution. Considering the representative use, the estimated operator exposure to Starane 180 EC (tractormounted and hand-held application, application rate 0.2 kg fluroxypyr/ha) is below the AOEL even without the use of personal protective equipment (PPE) according to the UK-POEM and German Model. Worker and bystander exposure are below the AOEL. It is noted that exposure assessments refer to the fluroxypyr-mhe while the AOEL is expressed as fluroxypyr; the resulting assessment is therefore an overestimate of the risk. No significative shift from one isomer to the other is expected to 7

8 occur on plants, there is a high margin of safety to the AOEL and no concern is raised for workers exposed to fluroxypyr-mhe applications. Estimates performed for Starane 180 EC are considered a worst-case scenario, and therefore cover the representative uses for Starane 200 EC. 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 recommendations on livestock burden calculations stated in the 2004 and 2007 JMPR reports (JMPR, 2004 and JMPR, 2007). In the DAR of August 1996 (Germany, 1996), the plant metabolism has been investigated in two wheat studies conducted with 14 C-fluroxypyr-meptyl (MHE) and, additional information was also provided on the fate of the active substance in broadleaved weed species. A new wheat metabolism study was evaluated in the Assessment Report, where plants were treated at stage BBCH 31 with either 14 C-fluroxypyr butoxypropyl ester (BPE) or 14 C-fluroxypyr-MHE at a dose rate of 200 g a.s./ha. Even if the breakdown of the parent ester was slightly faster for fluroxypyr-bpe than for fluroxypyr- MHE, the overall distribution of the radioactivity was seen to be similar for both esters. In immature plants, the proportion of the parent esters was gradually decreasing from c.a. 95% TRR just after the treatment, to 8-18% TRR 28 days after application. Inversely, the proportion of fluroxypyr slowly increased from 3% to 15% TRR two weeks after application, with significant amounts of polar unknowns that accounted for c.a. 50% TRR after 28 days. Following acid hydrolysis incubations (1M and 3M HCl), fluroxypyr was released from these polar fractions, suggesting that these are mainly composed of conjugated of fluroxypyr. In straw at harvest, the parent esters were almost not detected and TRRs were mostly composed of fluroxypyr (15% TRR), polar unknowns (17% TRR) and unextracted radioactivity (65% TRR) which was not further investigated. Given the low radioactive residues in grains at maturity ( mg/kg), no attempt was made to characterise the nature of the residues in grain. Based on these studies, the following residue definition was proposed in the DAR and the Assessment Report: fluroxypyr and its esters expressed as fluroxypyr. However, this residue definition does not take into account the fluroxypyr conjugates (polar unknown 1) that account for nearly 50% of the TRR in plant after 28 days, and are observed in similar amounts at harvest in straw (c.a. 16% TRR, 0.3 mg/kg). Therefore, EFSA is of the opinion that residues in cereals have to be defined as fluroxypyr, its esters, salts and its conjugates expressed as fluroxypyr. More than 80 supervised residue trials conducted on cereals were submitted. Most of them were disregarded, since they were performed with an exaggerated dose rate (300 to 600 g a.s./ha) and/or with an application performed at an inappropriate growth stage. Consequently, the MRL of 0.10 mg/kg proposed for cereals was derived from a total of 25 trials conducted on wheat, barley and rye, using a dose rate of 150 to 250 g a.s./ha and an application from stage BBCH 37 to 45. Only two trials are available in the Southern zone, but additional data are not required given that the residue levels were almost always below the LOQ in the trials conducted at exaggerated dose rates (up to 600 g a.s./ha). As for cereals, most of the trials conducted on pasture could not be considered since they were performed with an exaggerated dose rate of 400 g/ha. Therefore, only 5 trials in the Northern zone were considered acceptable. Additional Southern data are not required as the GAP defined for the Southern zone with a PHI of 14 days was seen to be less critical than the Northern GAP defined with a PHI of 7 days. For maize, all values were below the LOQ, even in the trials conducted at an exaggerated dose rate and the entire data set was taken into account to derive an MRL of 0.05* mg/kg in grain. No sufficient data are available to address the residue levels in maize silage, but this is of no consequence as far as the animal intakes are covered by the representative use on pasture. The samples from these residue trials were analysed using different analytical methods (ERC 83.7, ERC 89.5, ERC 90.3, ERC 92.1, ERC ) but it is unclear at this time, what these methods were capable to analyse for and a data gap was set to confirm whether they are effectively able to consider the esters and conjugates. The residue data are supported by the stability studies showing fluroxypyr residues to be stable up to 2 years in cereal matrices when stored frozen at -18 C. Processing studies were not provided and are not required. Confined studies conducted with 14 C-fluroxypyr-MHE at a dose rate of 594 to 676 g a.s./ha (c.a. 3N) indicate that significant residues are not expected to be present in 8

9 rotational crops as the highest TRRs are observed in cereal matrices, a group that is already covered as a primary crop. Metabolism studies in cow and hens conducted with 14 C-fluroxypyr were reported in the DAR of 1996 but they are not suitable to propose a residue definition as the nature of the residues has not been investigated in any matrices. A further goat study mentioned in the Assessment Report was evaluated by the RMS in the addendum of December This study confirms that, once administered to animals, fluroxypyr is rapidly and extensively excreted in urine and faeces (c.a. 99%) and the radioactivity in urine, faeces, milk, kidney and liver is almost entirely composed of fluroxypyr with limited amounts of fluroxypyr-pyridinol (2-7% TRR). These data suggest that fluroxypyr is an adequate marker for the residues in ruminant matrices. It is however questionable if such studies conducted with fluroxypyr are appropriate to address the fate of the fluroxypyr esters in animals, considering that: - based on the representative use on pasture, animals are mostly exposed to the esters rather than the acid, as the residues after 7 days are mainly composed of fluroxypyr esters (52-67%TRR). - in the wheat metabolism study, fluroxypyr-mhe was seen not to be totally hydrolysed under acid conditions (3M HCl, 60 C). It is therefore questionable if esters are totally hydrolysed in the animal digestive tract. - fluroxypyr-mhe is highly fat soluble (log P ow >5) contrary to fluroxypyr, and its behaviour in animals is therefore not comparable to that of the acid. Considering the points above and the significant levels of the esters animals are exposed to, it seems difficult without additional information to conclude that esters are not of concern in animal matrices. Further data are required to address the fate of the esters of fluroxypyr in ruminants and a data gap was identified. Provisionally, the animal residue definition is limited to fluroxypyr and its salts expressed as fluroxypyr, as proposed in the Assessment Report, and provisional MRLs are proposed for ruminant products from the cow feeding study conducted with fluroxypyr. In addition, further data on the stability of the fluroxypyr residues in animal matrices are required, as the available studies do not cover the length of time the samples were stored frozen before analysis. No chronic risk was identified as the TMDI calculated using the EFSA PRIMo model and the MRLs proposed for plant and animal products is only 0.1% of the ADI. The impact on the consumer risk assessment of a possible change in the isomeric ratio of the meptyl ester was not considered, as esters are no longer present in cereal grains and having regard to the very low calculated intake. This assessment is provisional as the residue definition for animals is not finalised. The acute risk was not regarded as the setting of an ARfD was considered not necessary. 4. Environmental fate and behaviour In the majority of the studies presented in the fate and behaviour in the environment section of the dossier the tested material is fluroxypyr-meptyl. This substance is present as a mixture of two enantiomers. However, in all environmental compartments it is rapidly transformed to fluroxypyr. In those situations where the PEC of fluroxypyr-meptyl has been used in the ecotoxicological risk assessment, these correspond to initial concentrations. Therefore, no further data are required to address the potential enantiomeric selective degradation or transformation of these isomers. Data on the fate and behaviour in the environment of fluroxypyr were discussed in the PRAPeR experts teleconference TC51. After the experts consultation, the RMS and Co-RMS reanalysed the kinetic data for Alconbury soil in Hawkins et al. (1983) (Ireland, 2009) because a factual error on the originally used data was identified. This resulted in a minor change of the input parameters agreed in the experts consultation. EFSA agrees that this change is appropriate to amend a previously undetected error. Fluroxypyr-MHE exhibits very low persistence in soil under laboratory dark aerobic conditions at 20 C and quickly transforms to the active substance fluroxypyr. Fluroxypyr is low to moderate persistent in soil under these conditions and degrades into two major metabolites: fluroxypyr pyridinol (max. 9

10 23.9 % after 28 d) and fluroxypyr methoxypyridine (max 38.2 % after 56 d). Both metabolites were also found as major metabolites in the field dissipation trials available. Kinetic analysis assuming a branched degradation scheme (fluroxypyr degrading into the two major metabolites in parallel) was agreed to derive the kinetic endpoints for environmental modelling. Under this analysis fluroxypyr pyridinol shows low to high persistence and fluroxypyr methoxypyridine shows moderate to very high persistence. Unextractable residues were formed up to a maximum of 41% AR and mineralization to CO 2 reached 65 % AR. Degradation was also investigated under anaerobic conditions where 2 additional metabolites 3-CP and 5-CP (the two mono dechlorinated fluroxypyr pyridinols) were identified at overall levels above 5%. The separation of these two metabolites was not possible in the available study. It is assumed that the level for each of these separated metabolites would be below 5 % AR and therefore would not need further assessment. Fluroxypyr MHE is stable to photolysis in soil. PECsoil have been calculated by the RMS after the experts consultation using worst case normalized half-lives and considering potential for accumulation in soil. Soil batch adsorption / desorption experiments indicate that fluroxypyr-mhe may be classified as immobile in soil, fluroxypyr (acid) as high to very high mobile, fluroxypyr methoxypyridine as medium mobile. For fluroxypyr pyridinol adsorption to soil was found to be ph dependent. Fluorpxypyr pyridinol was found to be medium to high mobile in neutral and acidic soils and high to very high mobile in alkaline soils. The results of two lysimeter studies are available. These studies are considered not relevant for the EU groundwater exposure assessment due to the short duration (only one application monitored for two years) and limited representativeness with respect to the whole set of FOCUS groundwater EU scenarios (only acidic and neutral ph, only sites in United Kingdom and Germany). Fluroxypyr-meptyl is stable to hydrolysis in neutral and acidic phs but readily hydrolyses at ph 9 (DT 50 = 3.2 d, 25 C). Fluroxypyr is stable at all environmentally relevant phs. No reliable study was available either in the original dossier or in the Annex I renewal dossier to investigate aqueous photolysis of fluroxypyr. However, no study is required since the molecular extinction coefficient (ε) < 10.0 L mol -1 cm -1 at 290 nm. Fluroxypyr is not readily biodegradable according to the available test. Aqueous dissipation was investigated in two dark aerobic water/sediment systems. Fluroxypyr-meptyl rapidly partitions to sediment and then hydrolyses to fluroxypyr (DT 50 whole system = d). No significant effect of ph on the degradation rate was observed. One study indicated that the presence of soil particles would catalyse the hydrolysis of fluroxypyr-meptyl at phs for which it is stable in purified water buffer solutions. Two major metabolites were identified in the water/sediment systems: fluroxypyr pyridinol / pyridinone (max 55.5 %) and 3-CP (max 25.2 %). In water, fluroxypyr pyridinone was the major tautomer of the pair pyridinol / pyridinone (5 % pyridinol vs. 46 % pyridinone). PEC SW/SED have been performed up to FOCUS SW Step 3 for fluroxypyr-meptyl and up to FOCUS SW Step 2 for fluroxypyr (acid), fluroxypyr pyridinol, fluroxypyr methoxypyridine (soil metabolite) and 3-CP (FOCUS, 2001). Potential for groundwater contamination was assessed by calculation of 80 th percentile concentration of fluroxypyr and its metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine with FOCUS GW models (PEARL and PELMO 3.3.2; FOCUS, 2000; EFSA, 2004) 5. There was no exceedance of the limit of 0.1 μg/l for fluroxypyr for any of the uses and scenarios simulated. The limit of 0.1 μg/l is exceeded for fluroxypyr pyridinol for the majority of uses and scenario combinations when alkaline soils are modelled (winter cereals-autumn application: 5 PELMO and 6 PEARL scenarios out of 9 scenarios; winter cereals-spring application: 2 PELMO and 4 PEARL scenarios out of 9 scenarios; spring cereals application: 1 PELMO and 4 PEARL scenarios out of 6 scenarios; maize application: 2 PELMO and 5 PEARL scenarios out of 8 scenarios). The limit of 0.1 μg/l is exceeded for fluroxypyr methoxypyridine in the Piazenza scenario for the use in winter cereals-autumn application. 5 Simulations correctly utilised the agreed Q10 of 2.58 (EFSA, 2007), Walker equation coefficient of 0.7 and were in accordance with the pertinent EFSA opinion. 10

11 5. Ecotoxicology Peer Review of the pesticide risk assessment of the active substance fluroxypyr The formulated product tested in the toxicity studies was EF-1502 (corresponding to Starane 180 EC ). The risk assessment was based on the following guidance documents: European Commission (2002a, 2002b, 2002c), SETAC (2001), EFSA (2009). For all the representative uses, the acute, short-term and long-term risk was indicated as low for large and medium herbivorous birds and insectivorous birds exposed to fluroxypyr-meptyl and fluroxypyr through the diet. The acute risk to birds was assessed as low also for the formulation EF A low risk was identified for small and medium herbivorous mammals and insectivorous mammals, except for the formulation EF The acute first tier TER was slightly below the trigger of Annex VI for small herbivorous mammals, indicating a potential high risk. However, a TER above the trigger was further calculated based on the guidance document (EFSA, 2009). Although the logpow of fluroxypyr-meptyl is greater than 3, the risk assessment for secondary poisoning of birds and mammals was not conducted because fluroxypyr-meptyl rapidly hydrolyses to fluroxypyr in the environment and it does not bioaccumulate in fish (measured BCF = 26). Due to the logpow=3.09 the risk assessment from secondary poisoning was provided for the metabolite fluroxypyr methoxypyridine. No chronic toxicity data were available for this metabolite therefore it was assumed to be ten times more toxic than the parent. Moreover, to cover the lack of an experimental measured BCF value on fish, a QSAR approach was used to attain an estimated BCF. On the basis of these assumptions the risk for earthworm- and fish-eating birds and mammals was assessed as low. A low risk was identified for birds and mammals which may be exposed to fluroxypyr-meptyl or fluroxypyr by the consumption of contaminated water, while it was noted that for the formulation EF-1502 the TER was below the trigger. Fluroxypyr-meptyl is very toxic to aquatic organisms while fluroxypyr is harmful. The most sensitive endpoint was observed in a chronic study with Daphnia magna with fluroxypyr-meptyl (NOEC = mg a.s./l). The acute risk to fish and the acute and chronic risk to aquatic invertebrates were assessed as high at FOCUS Step 1. The acute risk to aquatic invertebrates and fish was still high at FOCUS Step 2. However, the assessment based on FOCUS Step 3 indicated a low risk in all scenarios for the representative uses, except for aquatic invertebrates in the scenario D2-ditch for the use in winter cereals (i.e TER was slightly below the Annex VI trigger). Due to the mode of action of the active substance (i.e. auxin), a data gap was identified to provide a study with a second aquatic plant. The risk to aquatic organisms was assessed as low at FOCUS Step 1 for the water metabolites fluroxypyr pyridinol and monochloropyridinol (3-CP). Toxicity data for the metabolite fluroxypyr methoxypyridine were only available on algae and higher aquatic plant. Based on these data a low risk was indicated at FOCUS Step 1. The risk to bees, non-target arthropods, earthworms and other soil macro- and micro-organisms, nontarget plants and sewage treatment plants was assessed as low. The acute risk to earthworms was assessed as low for the soil metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine. Due to the persistence in soil of fluroxypyr methoxypyridine, a data gap was identified to provide a chronic study with earthworms and a data gap to address the risk to soil macro-organisms. Since the available tests were not valid for nitrogen turnover, a data gap was identified to provide studies assessing the effects of EF-1502 and fluroxypyr-pyridinol on soil microorganisms. 11

12 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) Persistence Ecotoxicology Fluroxypyr-meptyl (Fluroxypyr-MHE) Fluroxypyr Very low (DT C 0.5d 1.8 d) Low to moderate (DT C pf2 = 2.7 d 39.6 d) The risk was assessed as low for soil organisms. The risk was assessed as low for soil organisms. Fluroxypyr pyridinol Low to high (DT C pf2 = 4.1 d d) The risk was assessed as low for soil organisms. Data gap for soil micro-organisms (for nitrogen turnover). Fluroxypyr methoxypyridine Moderate to very high (DT C pf2 = 16.7 d d) The acute risk was assessed as low for soil organisms. A data gap was identified to address the long-term risk for soil organisms (earthworms and soil macroorganisms) Groundwater 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 12

13 Yes. Fluroxypyr-meptyl (Fluroxypyr-MHE) immobile (K doc = ml/g) No, modelling was not performed since risk of groundwater contamination was excluded on basis of short half-life and strong adsorption to soil. Yes Yes Very toxic to aquatic organisms. The lowest endpoint was observed in a chronic study with Daphnia magna (NOEC = mg a.s./l, regulatory concentration including a safety factor of 10 = mg a.s./l). A low risk to the aquatic organisms was demonstrated. Yes Fluroxypyr high to very high mobile (K Foc = ml/g) FOCUS GW: No Yes Yes Harmful to aquatic organisms. The lowest endpoint was observed in a study with Lemna gibba (LC50 = 12.3 mg a.s./l, regulatory concentration including a safety factor of 10 = 1.23 mg a.s./l). A low risk to the aquatic organisms was demonstrated. A data gap was identified for a second aquatic plant study. 13

14 Fluroxypyr pyridinol adsorption to soil was found to be ph dependent medium to high mobile in neutral and acidic soils (K doc = ml/g) high to very high mobile in alkaline soils (K doc = ml/g) FOCUS GW: Yes, 0.1 μg/l limit is exceeded for some uses and scenario combinations when alkaline soils are modelled (winter cereals-autumn appl.: 5-6/9 scenarios; winter cereals-spring appl.: 2-4/9 scenarios; spring cereals 1-4/6 scenarios; maize 2-5/8 scenarios) No data, data not required No data, data required The risk was assessed as low for aquatic organisms. Fluroxypyr methoxypyridine medium mobile (K Foc = ml/g) FOCUS GW: Yes, 0.1 μg/l limit is exceeded for autumn applications to winter cereals in Piacenza scenario (both with PELMO and PEARL models). No data, data not required No data, data required The risk was assessed as low for aquatic organisms Surface water and sediment Compound (name and/or code) Ecotoxicology 14

15 Fluroxypyr-meptyl (Fluroxypyr-MHE) Fluroxypyr Fluroxypyr pyridinol Fluroxypyr methoxypyridine (soil metabolite) 3-CP monochloropyridinol Very toxic to aquatic organisms. The lower endpoint was observed in a chronic study with Daphnia magna (NOEC = mg a.s./l, regulatory concentration including a safety factor of 10 = mg a.s./l). A low risk to the aquatic organisms was demonstrated. Harmful to aquatic organisms. The lower endpoint was observed in a study with Lemna gibba (LC50 = 12.3 mg a.s./l, regulatory concentration including a safety factor of 10 = 1.23 mg a.s./l). A low risk to the aquatic organisms was demonstrated. A data gap was identified for a second aquatic plant study. The risk was assessed as low for aquatic organisms. The risk was assessed as low for aquatic organisms. The risk was assessed as low for aquatic organisms Air Compound (name and/or code) Fluroxypyr-meptyl (Fluroxypyr-MHE) Fluroxypyr Toxicology Low acute toxicity (rat LC 50 inhalation: 1.0 mg/l air/4 hours, no classification proposed) No data available 15

16

17 LIST OF STUDIES TO BE GENERATED, STILL ONGOING OR AVAILABLE BUT NOT PEER REVIEWED Revised specification that is supported by 5 batch analysis and validated methods (relevant for all representative uses evaluated; new study has been submitted to the rapporteur Member State but has not been evaluated in accordance with Commission Regulation (EC) No. 737/2007; see section 1). Auto-flammability of the technical material (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Validation of the extraction, hydrolysis and derivitisation step for the plant method (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 1). Method of analysis for drinking/groundwater (relevant for all representative uses evaluated; new study has been submitted to the rapporteur Member State but has not been evaluated in accordance with Commission Regulation (EC) No. 737/2007; see section 1). The notifier to address whether the batches used in the toxicological studies cover the technical specification (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2). The toxicological relevance of the impurities to be addressed (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2). A new valid genotoxicity data package with the technical specification has to be submitted (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2). An assessment of the toxicological relevance of the groundwater metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine has to be performed according to the respective guidance document (European Commission, 2003) (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 2 and 4). Notifier to confirm if the various methods used to analyse the samples from the different residue trials performed on cereals, maize and pasture, take into account the esters and conjugates of fluroxypyr present in significant proportions and levels in plants (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 3). Notifier to provide information on the fate of the fluroxypyr esters in ruminants, considering that animals are mainly exposed to the esters and it was shown that esters may not be easily hydrolysed under acid conditions (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 3). Notifier to provide further information on the stability of fluroxypyr residues in animal products, that cover all relevant animals matrices and the length of time the samples were stored frozen prior to analysis (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 3). Notifier to provide study with a second aquatic plant (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5). 17

18 Notifier to provide a long-term study on earthworms with the metabolite fluroxypyr methoxypyridine (relevant for all representative uses evaluated; submission date proposed by the notifier: study finalised but not submitted in the AIR; see section 5). Notifier to provide a long-term risk assessment for soil macro-organisms for the metabolite fluroxypyr methoxypyridine (relevant for all representative uses evaluated; submission date proposed by the notifier: study finalised but not submitted in the AIR; see section 5). Notifier to provide studies assessing the effects of EF-1502 and fluroxypyr pyridinol on soil micro-organisms (relevant for all representative uses evaluated; submission date proposed by the notifier: unknown; see section 5). PARTICULAR CONDITIONS PROPOSED TO BE TAKEN INTO ACCOUNT TO MANAGE THE RISK(S) IDENTIFIED The formulation Starane 180 EC showed poor emulsion stability characteristics and a labelling phrase such as once mixed the spray solution should be used immediately and should not be left in the sprayer overnight should be considered (see section 1). Potential contamination of groundwater above the limit of 0.1 μg/l by the metabolite fluroxypyr pyridinol has been identified in a number of scenarios when soils are alkaline in cereal and maize uses. This may be mitigated limiting the use to acidic soils. The toxicological relevance of this metabolite is still pending. ISSUES THAT COULD NOT BE FINALISED Toxicological relevance of groundwater metabolites fluroxypyr pyridinol and fluroxypyr methoxypyridine needs to be assessed. The long-term risk assessment to earthworms and soil macro-organisms for the metabolite fluroxypyr methoxypyridine could not be finalised. The risk to soil micro-organisms (nitrogen turnover) for the formulation EF-1502 and the metabolite fluroxypyr pyridinol could not be finalised. CRITICAL AREAS OF CONCERN The proposed minimum purity of the active substance and the specification of the impurities for the reference source are not supported by available data and no conclusion could be reached whether the batches used in the toxicological studies are representative of the current proposed technical specification. In case of the genotoxicity studies, the purity of the tested active substance is unknown. 18

19 REFERENCES EFSA, Opinion of the Scientific Panel on Plant Health, Plant Protection Products and their Residues on a request of EFSA related to FOCUS groundwater models comparability and the consistency of this risk assessment of groundwater contamination. The EFSA Journal (2004) 93, EFSA, Scientific Opinion of the Panel on Plant Protection Products and their Residues on a request from EFSA related to the default Q10 value used to describe the temperature effect on transformation rates of pesticides in soil. The EFSA Journal (2007) 622, EFSA, Guidance Document on Risk Assessment for Birds and Mammals on request of EFSA. EFSA Journal 2009; 7(12):1438. EFSA, Peer Review Report to the conclusion regarding the peer review of the pesticide risk assessment of the active substance fluroxypyr. European Commission, Guidelines for the generation of data concerning residues as provided in Annex II part A, section 6 and Annex III, part A, section 8 of Directive 91/414/EEC concerning the placing of plant protection products on the market, 1607/VI/97 rev.2, 10/6/1999. European Commission, 2000, Technical Material and Preparations: Guidance for generating and reporting methods of analysis in support of pre- and post-registration data requirements for Annex II (part A, Section 4) and Annex III (part A, Section 5) of Directive 91/414. SANCO/3030/99 rev.4, July European Commission, 2002a. Guidance Document on Terrestrial Ecotoxicology Under Council Directive 91/414/EEC. SANCO/10329/2002 rev.2 final, 17 October European Commission, 2002b. Guidance Document on Aquatic Ecotoxicology Under Council Directive 91/414/EEC. SANCO/3268/2001 rev 4 (final), 17 October European Commission, 2002c. Guidance Document on Risk Assessment for Birds and Mammals Under Council Directive 91/414/EEC. SANCO/4145/2000. European Commission, Guidance Document on Assessment of the Relevance of Metabolites in Groundwater of Substances Regulated under Council Directive 91/414/EEC. SANCO/221/2000- rev. 10-final, 25 February European Commission, 2004a. Guidance document on residue analytical methods. SANCO/825/00 rev. 7, 17 March European Commission, 2004b. Guidance Document on Dermal Absorption. SANCO/222/2000 rev. 7, 19 March European Commission, Guidance document on the assessment of the equivalence of technical materials of substances regulated under Council Directive 91/414/EEC. SANCO/10597/2003 rev. 8.1, May FOCUS (2000). FOCUS Groundwater Scenarios in the EU review of active substances. Report of the FOCUS Groundwater Scenarios Workgroup, EC Document Reference SANCO/321/2000- rev pp, as updated by the Generic Guidance for FOCUS groundwater scenarios, version 1.1 dated April FOCUS (2001). FOCUS Surface Water Scenarios in the EU Evaluation Process under 91/414/EEC. Report of the FOCUS Working Group on Surface Water Scenarios, EC Document Reference SANCO/4802/2001-rev pp. Germany, Draft Assessment Report (DAR) on the active substance fluroxypyr prepared by the rapporteur Member State Germany in the framework of Directive 91/414/EEC, August

20 Ireland, Assessment Report on the active substance fluroxypyr prepared by the rapporteur Member State Ireland in consultation with Poland in the framework of Commission Regulation (EC) No 737/2007, October Ireland, Final Addendum to Assessment Report on fluroxypyr, compiled by EFSA, January JMPR, Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues, Rome, Italy, September 2004, Report 2004, 383 pp. JMPR, Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Core Assessment Group on Pesticide Residues, Geneva, Switzerland, September 2007, Report 2007, 164 pp. SETAC (Society of Environmental Toxicology and Chemistry), Guidance Document on Regulatory Testing and Risk Assessment procedures for Plant Protection Products with Non-Target Arthropods. ESCORT 2. 20

21 APPENDICES APPENDIX A LIST OF END POINTS FOR THE ACTIVE SUBSTANCE AND THE REPRESENTATIVE FORMULATION Identity, Physical and Chemical Properties, Details of Uses, Further Information Active substance (ISO Common Name) Fluroxypyr Fluroxypyr -meptyl Function (e.g. fungicide) Herbicide Herbicide Rapporteur Member State Ireland Ireland Co-rapporteur Member State Poland Poland Identity (Annex IIA, point 1) Chemical name (IUPAC) Chemical name (CA) 4-amino-3,5-dichloro-6- fluoro-2-pyridyloxyacetic acid 2-[(4-amino-3,5-dichloro-6- fluoro-2- pyridinyl)oxy]acetic acid CIPAC No (RS)-1-methylheptyl 4- amino-3,5-dichloro-6- fluoro-2-pyridyloxyacetate 1-methylheptyl 2-[(4- amino-3,5-dichloro-6- fluoro-2- pyridinyl)oxy]acetate CAS No EC No (EINECS or ELINCS) None FAO Specification (including year of publication) Minimum purity of the active substance as manufactured Identity of relevant impurities (of toxicological, ecotoxicological and/or environmental concern) in the active substance as manufactured None Not applicable None Open - Open Molecular formula C 7 H 5 Cl 2 FN 2 O 3 C 15 H 21 Cl 2 FN 2 O 3 Molecular mass Structural formula Cl NH 2 Cl Cl NH 2 Cl F N O O OH F N O O O CH 3 (C 5 H 10 ) 21