Conclusion regarding the peer review of the pesticide risk assessment of the active substance acequinocyl

Acequinocyl is a new active substance for which in accordance with Article 6 (2) of Council Directive 91/414/EEC1 the Netherlands received an application from Agro- Kanesho for inclusion in Annex I to Directive 91/414/EEC. Complying with Article 6 of Directive 91/414/EEC, the completeness of the dossier was evaluated and confirmed by Commission Decision 2003/636/EC2. Following the agreement between the EU- Commission and the EFSA for the EFSA to organise a peer review of those new active substances for which the decision on the completeness of the dossier had been published after June 2002, the designated rapporteur Member State the Netherlands made the report of its initial evaluation of the dossier on acequinocyl, hereafter referred to as the draft assessment report (DAR), available on 8 March 2005. This draft assessment report was distributed for consultation to the Member States and the notifier on 15 March 2005. The peer review was initiated on 15 March 2005 by dispatching the draft assessment report for consultation of the Member States and the notifier. Subsequently, the comments received on the DAR were examined by the rapporteur Member State and the need for additional data was agreed in an evaluation meeting in November 2005. Remaining issues as well as further data made available by the notifier upon request were evaluated in a series of scientific meetings with Member State experts in November 2006. A final discussion of the outcome of the consultation of experts took place with representatives from the Member States on 15 November 2007 leading to the conclusions as laid down in this report. The conclusion was reached on the basis of the evaluation of the representative uses as acaricide as proposed by the notifier which comprise foliar spraying to control spider mite in ornamentals, apples and pears. Full details of the GAP can be found in the attached end points. The representative formulated product for the evaluation was "Kanemite", a suspension concentrate (SC) containing 164 g/L acequinocyl, provisionally registered in Austria and Germany as Kanemite and in the Netherlands as Cantack. The technical specification is still open for formal reasons. A new specification was submitted and presented in an addendum to vol. 4 according to the requirements of the expert meeting PRAPeR6, however, this final specification was not peer reviewed. Adequate methods are available to monitor the compounds given in the respective residue definitions Sufficient analytical methods as well as methods and data relating to physical, chemical and technical properties are available to ensure that quality control measurements of the plant protection product are possible. Regarding the mammalian metabolism, there are distinct indications for sizeable biliary first pass elimination. However, based on the critical effect of acequinocyl, the extent of oral absorption was considered to represent 28% of the administered dose. Twenty-four hours after dosing, the highest concentrations of radioactivity were found in the gastro-intestinal tract and its contents; excretion occurs predominantly via faeces and no potential for accumulation was seen. Acequinocyl is extensively metabolized with 0-2.5% parent compound found in urine, bile or faeces. Acequinocyl has low acute toxicity and is not a skin or eye irritant; however classification is required for skin sensitization based on a Maximisation test. In repeated dose studies, acequinocyl caused haematological effects (increased platelet levels and blood clotting time) in rats, mice and dogs; in addition, ocular effects were observed in the rats and hepatotoxicity in mice. The relevant short term NOAEL was the dose level of 5 mg/kg bw/day derived from the 52-week dog study, and the long term relevant NOAEL was the dose level of 2.3 mg/kg bw/day derived from the 2-year rat study. No genotoxic or carcinogenic potential was observed. Acequinocyl showed no effect on fertility parameters and produced effects on the reproductive or developmental parameters in rats or rabbits only at parental toxic doses. No potential for neurotoxicity was evidenced. Four acute studies in rats and monkey were submitted to investigate the effects of acequinocyl on the blood clotting system resulting in an overall NOAEL of 8 mg/kg bw for prolongation of blood clotting time in rats. The acceptable daily intake (ADI) is set at 0.023 mg/kg bw/day and the acute reference dose (ARfD) at 0.08 mg/kg bw considering an assessment factor of 100; the acceptable operator exposure level (AOEL) is set at 0.014 mg/kg bw/day considering an assessment factor of 357 (correction of 28% for oral absorption). Dermal absorption is 3.6% when handling the concentrate formulation and 16.7% when handling the spray dilution. Considering the representative uses of Kanemite SC outdoor (apple/pear and ornamentals), the estimated operator exposure exceeds the AOEL according to the UK POEM model; according to the German model calculations, exposure is below the AOEL when the use of PPE as protective gloves during mixing/loading and gloves, protective garment and sturdy footwear during application is considered. According to the Dutch model for greenhouse applications (ornamentals), the exposure of operators was calculated to represent twice the AOEL when using a reduction factor of 10% for the use of PPE. Worker exposure after outdoor applications on apple and pear (mechanical upward spraying) is estimated to be below the AOEL even without the use of PPE, but for downward application on ornamentals, outdoor and in greenhouses, the use of gloves is required to obtain a level of exposure lower than the AOEL. Exposure of bystanders is estimated to be below the AOEL. The metabolism of acequinocyl in fruit crops is clearly elucidated. For PHIs up to 30 days, the parent compound is the major constituent of the residue and no metabolite was found in amounts suggesting a significant contribution to the toxicological burden. The residue definition for monitoring and risk assessment can therefore be restricted to acequinocyl. Supervised residue trials were performed in Northern and Southern Europe and form a sufficient basis for proposing an MRL to be set at 0.05 mg/kg in apples and pears. Considering this low residue level, no study on the effect of processing was estimated necessary. No information has been provided on the potential transfer of soil residues to rotational or succeeding crops considering that cultivation of edible agricultural or horticultural crops in rotation with the representative uses does not normally occurs in practice. In case this should be possible practice at national level, Member States should consider the opportunity of label restriction. A metabolism study in lactating goat was submitted although not required given that livestock exposure through consumption of apple pomace is extremely low. This study was considered but not used for proposing a residue definition. Consumer chronic and acute exposures are well below the toxicological reference values and no dietary risk is expected resulting from the use of acequinocyl following the supported representative uses. In soil under aerobic conditions acequinocyl exhibits very low to low persistence. The major metabolite was R13 (max 33.8% AR after 2 days) which exhibits low to moderate persistence. A second major metabolite was identified as AKM-184 (max 21.9% AR after 2 days), which showed low persistence in soil. Mineralisation to carbon dioxide accounted for 15.0-57.7 % AR after 120/180 days. The formation of unextractable residues was also a significant sink accounting for 46.3% AR after 120 days. Under anaerobic soil conditions no novel breakdown products were identified. Acequinocyl and its major metabolites can be classified as immobile in soil and have a very low potential for leaching in soil. There was no indication that adsorption of either acequinocyl or metabolites R1 and AKM-18 was pH dependant. Hydrolysis is pH dependant with more rapid hydrolysis under alkaline conditions. The water/sediment test showed that acequinocyl dissipated rapidly from the water phase by partitioning to sediment (max 26.4% AR after 1d). Unextracted sediment residues were a significant sink for radioactivity, representing 59.7-62.0% R after 30-60 days. Metabolites R1 and CBAA5 were detected as major metabolites in the water phase, metabolite AKM-18 is a major metabolite in the sediment phase. Predicted environmental concentrations in surface water to be used in the risk assessment for the representative uses form the spray drift route of exposure have been calculated for acequinocyl (actual and TWA PECsw) and metabolites R1 and CBAA (maximum PECsw). The runoff and drainage routes of exposure to surface water bodies should be taken into account by MS when these routes of exposure are relevant and the pertinent risk assessments to aquatic organisms should be completed by MS. For the representative uses proposed by the applicant, the potential for contamination of vulnerable groundwater by acequinocyl and its soil breakdown products above the drinking water limit of 0.1 mu g/L is considered minimal. The acute and short-term risk to birds and the acute risk to mammals was assessed as low in the firsttier risk assessment. A refined long-term risk assessment for birds and mammals was required. The suggested refinement steps were rejected in the experts meeting. The long-term TER of 4.3 for insectivorous birds in orchards was below the trigger of 5 but considered as sufficient to conclude on a low risk since the available information on residue decline in insects suggest a rapid decline with a DT50 of < 3 days. A data gap was identified to refine the long-term risk to herbivorous and insectivorous birds for the use in ornamentals. The PT values proposed to refine the long-term risk to mammals were rejected because no supporting data were made available. Acequinocyl is very toxic to aquatic invertebrates. In the meeting of experts it was agreed that the aquatic risk assessment should be based on the NOEC (population effects) of 3 mu g acequinocyl/L derived from a microcosm study together with an assessment factor of 3-5. No spray buffer zones of 30 m (orchards late application and ornamentals > 50 cm high) and 10 m (ornamentals < 50 cm high) are required to achieve TERs of > 5. In order to reach a TER of > 3 for the early use in orchards a no spray buffer zone of 30 m is required and the buffer zone needs to be extended to 50 m to achieve a TER of > 5. The risk to bees, other non-target arthropods, earthworms, other soil non-target macro-and microorganisms, non-target plants and biological methods of sewage treatment was assessed as low.