Etofenprox is one of the 79 substances of the third stage Part A of the review programme covered by Commission Regulation (EC) No 1490/2002(1). This Regulation requires the European Food Safety Authority (EFSA) to organise a peer review of the initial evaluation, i.e. the draft assessment report (DAR), provided by the designated rapporteur Member State and to provide within six months a conclusion on the risk assessment to the EU-Commission. Italy being the designated rapporteur Member State submitted the DAR on etofenprox in accordance with the provisions of Article 10(1) of the Regulation (EC) No 1490/2002, which was received by the EFSA on 15 July 2005 and following a quality check on the DAR, on 14 February 2007. The peer review was initiated on 18 July 2007 by dispatching the DAR for consultation of the Member States and the sole applicant Landis Kane Consulting. Subsequently, the comments received on the DAR were examined and responded by the rapporteur Member State in the reporting table. This table was evaluated by EFSA to identify the remaining issues. The identified issues as well as further information made available by the applicant upon request were evaluated in a series of scientific meetings with Member State experts in October 2008. A final discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in November-December 2008 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 insecticide as proposed by the notifier, which comprise foliar spraying in oilseed rape, head cabbage, grapes, peach and apple for the control of biting and sucking insects. Full details of the GAP can be found in the endpoints. The representative formulated product for the evaluation was 'TREBON 30EC', an emulsifiable concentrate (EC) containing 287.5 g/L etofenprox. 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. Adequate methods are available to monitor all compounds given in the respective residue definitions in food/feed of plant and animal origin and environmental matrices. In the mammalian metabolism studies, etofenprox was rapidly but partially absorbed after oral administration. It was uniformly distributed through the body, and transferred via placenta and via milk. There was no evidence of bioaccumulation; etofenprox was rapidly eliminated, mainly via faeces, a major part as metabolites. The acute toxicity was low, either by the oral, dermal or inhalation route; no eye or skin irritation was observed and no potential for skin sensitisation was found in a modified maximisation test. The main target organs of etofenprox were the liver and thyroid upon short-term or long-term exposure in the rat, which was the most sensitive species. The mouse presented also renal toxicity, but at much higher dose levels and the dog was less sensitive, showing effect only in the liver. The relevant NOAEL for short-term exposure was the dose level of 20 mg/kg bw/day from the 90-day rat feeding study; for long-term exposure, the NOAELs in rat and mouse were similar. 3 1 mg/kg bw/day in mouse and 3.7 mg/kg bw/day in rat. No potential for genotoxicity or neurotoxicity was observed. The aetiology of the formation of the thyroid adenomas observed in rats was elucidated in a mechanistic study and considered not relevant for human risk assessment. Marginally increased renal cortical tumours found only in male mice at high doses were also not considered relevant to humans. No effect on the reproduction, fertility or development was found, however, considering the increased mortality of offsprings during the lactation phase, classification with R64, "May cause harm to breastfed babies", was proposed. Further studies were provided on the plant metabolite alpha-CO2, which showed that its toxicity is covered by the parent's toxicity studies. The acceptable daily intake (ADI) of etofenprox was 0.03 mg/kg bw/day based on the long-term mouse study and applying a safety factor of 100, which is supported by the long-term rat study. The acceptable operator exposure level (AOEL) was 0.06 mg/kg bw/day based on the oral 90-day rat study, applying a safety factor of 100 and a correction factor of 30 % for low oral absorption. The acute reference dose (ARfD) was set at 1.0 mg/kg bw, based on the NOAEL of 100 mg/kg bw/day from the rabbit developmental toxicity study and a safety factor of 100. A default value of 30 % was agreed for dermal absorption. The level of operator exposure calculated for the representative formulation "TREBON 30EC", at a maximum dose rate of 0.21 kg etofenprox/ha in high crops (grapes, peaches and apples) was below the AOEL when the use of gloves was considered; in field crops (oilseed rape and head cabbage), no personal protective equipment (PPE) was needed to achieve an operator exposure estimate below the AOEL, according to the German model. According to the UK POEM model, estimated operator exposure was above the AOEL, even when the use of PPE was considered. Estimated exposure of workers entering crops treated with etofenprox was below the AOEL, if PPE were worn (protective gloves, long-sleeved shirt and long trousers). Bystander exposure was estimated to be below the AOEL. Concerning the plant and animal metabolism studies, the meeting of experts discussed the unusual way the experiments were conducted, using applications of a 1:1 mixture of both labelled forms in a single study, instead of two distinct radioactive labels from two separate studies. After discussion, the experts were of the opinion that such studies may only be accepted when no extensive cleavage of the parent molecule is observed. Thus, in the specific case of etofenprox, this practice could be accepted as no extensive metabolism was observed in plants and animals Otherwise, in the case of an extensive metabolism and/or early cleavage of the parent molecule, the recovered levels of the different metabolites may be underestimated, when compared to the initial radioactive level of parent molecule. In such situation, the meeting re-enforced its opinion that metabolism studies must be conducted separately according to the different labelling forms, in order to depict the fate of each labelling portion of the molecule as completely as possible and to provide reliable quantitative information. In plants, the metabolism of etofenprox has been investigated in rapeseed, grape and lettuce. The metabolism was limited and etofenprox was found to be the major compound of the residues, the other metabolites being detected in very low proportions, up to 7% of the TRR for the alpha-CO metabolite. However and considering that the alpha-CO metabolite was observed in proportions higher than 10 % of the etofenprox levels in the supervised residue trials, the meeting of experts decided to define the residue for risk assessment and monitoring as the "sum of etofenprox and alpha-CO expressed as etofenprox". Sufficient supervised residue trials were submitted to propose MRLs on rape seed (Northern GAP) and on head cabbage, grape, peach and apple (Southern GAP). The storage stability studies demonstrated that etofenprox and alpha-CO residues were stable under freeze storage conditions for at least two years in oil and water-containing matrices. A standard hydrolytic study was identified as a data gap and additionally, one balance study and three follow-up studies were requested for red wine and for raisin. Processing transfer factors could be calculated for some rape seed, apple and peach processed commodities. For animals, the experts discussed the validity of the metabolism studies performed with the parent etofenprox only. Considering that the alpha-CO metabolite was shown to be a significant constituent of the residues in plants, the experts were of the opinion that information on the fate of this compound in the ruminant metabolism has to be requested. The parent etofenprox was found to be the major residue in all goat and hen matrices, and the residue definition for monitoring and risk assessment was set provisionally as "etofenprox", awaiting the requested information on the alpha-CO metabolite. Based on the cow feeding study and the animal burden calculations, MRLs were proposed for milk and ruminant products. The chronic and acute consumer risk assessments were performed using the EFSA and the UK PSD models. Using the MRLs proposed for plant and animal products, the calculated theoretical maximum daily intakes (TMDI) and international estimated short term intakes (IESTI) were shown to be below the ADI and ARfD values. Degradation of etofenprox in soil under dark aerobic conditions at 20 degrees C occurred through oxidation at different parts of the molecule followed by breaking down in smaller moieties (DT50 = 7 - 57.7 days). In one study, one of the metabolites, alpha-CO, was observed to exceed 5 % AR in one of the soils (DT50 = 12 - 45 days). Unextracted radioactivity amounted to a maximum of 55.8 % AR after 55 days, and mineralization (CO2) up to a maximum of 45.6 % AR after 120 days. Under dark anaerobic conditions at 20 degrees C, etofenprox is highly persistent in soil (DT50 = 174 days). Under these conditions metabolite 4'-OH3 was identified as a major metabolite. Mineralization was negligible, and unextractable residue in soil amounted to 9.5 % AR after 121 days. Photolysis only slightly enhanced degradation of etofenprox in soil. PEC soil were calculated for etofenprox based on the soil half-life of 25 days for all representative uses. The meeting of experts agreed that these values could be used for the risk assessment. According to the results of available soil batch adsorption/desorption experiments, etofenprox may be classified as immobile in soil (Koc = 8548 - 14923 mL/g). The meeting of experts identified a data gap for an additional batch soil adsorption/desorption study, but considered it not essential to finalize the EU risk assessment. The metabolites alpha-CO and 4'-OH were estimated to be immobile with PCKOCWIN (EPA). Chemical hydrolysis is not expected to contribute to the environmental degradation of etofenprox. The photolysis of etofenprox is relatively rapid. The major aqueous photolysis metabolites were alpha-CO (max 63.6 %) and PENA(4) (max. 14.4 %). The metabolite alpha-CO was also found to reach up to 10% of the parent's applied amount in the outdoor mesocosm study. On the basis of the available studies, etofenprox should be considered not ready biodegradable. In water/sediment systems, partition of etofenprox to the sediment occurs during the first seven days. The meeting of experts agreed on the half-lives calculated for etofenprox in the whole system (DT50 whole system = 6.5 days - 20.1 days). The metabolite 4'-OH was identified as a major metabolite in the sediment phase of both systems. The meeting of experts discussed the need to consider aqueous photolysis and photolysis metabolites for the EU risk assessment, and agreed that the risk assessment presented for the metabolite alpha-CO by the applicant could be regarded as conservative. PECSW were calculated with FOCUS SW modelling for the relevant scenarios based on the soil halflife of 25 days. Degradation in the water phase was assumed to occur with a half-life of 1000 days, and the mean whole water/sediment system half-life was applied to the sediment phase. Step 3 and Step 4 (only oilseed rape; assuming 30m spray drift buffer zone) were calculated for the representative uses. PECSW of the aqueous photolysis metabolite alpha-CO was estimated to be 63.6 % of the PECsw of the parent compound. Worst case PECsw were also estimated for the sediment metabolite 4'-OH as 21.9 % of the PECsw calculated for the parent compound. The meeting of experts identified the need to recalculate PECSED for the parent compound for the uses different from oilseed rape, to take into account the accumulation of etofenprox after multiple applications and the PECSED of the metabolites alpha-CO and 4'-OH. The necessary PECSW / SED values were provided by the rapporteur Member State in the addendum Volume 3 v3 after the meeting of experts. Neither etofenprox nor its soil metabolite alpha-CO is expected to exceed the trigger of 0.1 mu g /L for any of the representative uses and scenarios simulated. The environmental concentrations in air and transport through air of etofenrprox are considered negligible. The risk assessment indicated low risk to birds and mammals for all intended uses. Refinements of the long-term risk assessment for mammals were, however, required for the uses in head cabbage, grape, peach and apple to meet the Annex VI trigger. The risk to fish-eating birds and mammals was considered to be low for all of the intended uses, as was the risk to earthworm-eating birds and mammals for the intended use in oilseed rape. Further refinements were still required to address the risk to earthworm-eating birds and mammals for the intended uses in head cabbage, grapevine, peach and apple. The acute risk to birds and mammals from consumption of contaminated drinking water from puddles was assessed as low for all intended uses of etofenprox. Etofenprox was not considered to biomagnify in the terrestrial food chain, and the risk from plant metabolites was assessed to be low. The risk to aquatic organisms was not addressed for any of the intended uses. The TER values for aquatic organisms, based on tier 1 effect data and FOCUS Step 3 and 4, failed to meet the Annex VI trigger value. The use of an endpoint from the available higher tier mesocosm study would require further supportive data. Member State experts suggested that single species tests on the most sensitive species from the mesocosm study should be provided to consolidate the confidence in the data from the mesocosm. The design of the single species tests should take into account the multi-application uses. Based on the additional studies, a relevant assessment factor should be reconsidered for a refined aquatic risk assessment. A fish full life cycle (FFLC) study was required by the Member State experts, which should be included in the aquatic risk assessment. The risk to sediment dwellers should be addressed for etofenprox and for the metabolites 4'-OH and alpha-CO. Also, the aquatic risk assessment for alpha-CO would have to be refined further for uses in head cabbage, grapevine, peach and apple. In addition, the risk from biomagnification and potential endocrine disrupting effects on aquatic organisms should be addressed. Hazard quotient (HQ) values indicated a high risk to bees from all intended uses. Member State experts concluded that the available field studies did not address the risk to bees, and they agreed that mitigation measures were needed for pre-flowering/flowering uses in oilseed rape, grapevine and apple to avoid exposure of bees. The Tier I risk assessment indicated a high in-field risk to Aphidius rhopalosiphi and Typhlodromus pyri for all intended uses. The off-field risk was considered to be low for A. pyri and A. rhopalosiphi for uses in oilseed rape and head cabbage, based on no-spray buffer zone of 1 and 5m, respectively. Higher tier risk assessment based on extended laboratory studies with A. rhopalosiphi, T pyri, Orius laevigatues and Chrysoperla carnea still indicated a high in-field risk to non-target arthropods. The potential for in-field recovery was not addressed in the draft assessment report. The higher tier off-field risk assessment indicated a low risk to non-target arthropods for uses in oilseed rape and head cabbage, with no-spray buffer zones of 1 and 5m, respectively. For uses in grapevine, the assessment indicated a need for a no-spray buffer zone of 10m to identify a low risk. Further refinements were required to address the off-field risk to non-target arthropods for uses in peach and apple. The risk to earthworms, non-target micro- and macro-soil organisms and non-target plants was assessed as low for all intended uses.
