Conclusion on the peer review of the pesticide risk assessment of the active substance flurprimidol European Food Safety Authority

Flurprimidol is one of the 84 substances of the third stage Part B of the review programme covered by Commission Regulation (EC) No 1490/2002(3), as amended by Commission Regulation (EC) No 1095/2007(4). This Regulation requires the European Food Safety Authority (EFSA) to organise upon request of the EU-Commission 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. Finland being the designated rapporteur Member State submitted the DAR on flurprimidol in accordance with the provisions of Article 10(1) of the Regulation (EC) No 1490/2002, which was received by the EFSA on 20 April 2007. The peer review was initiated on 17 September 2007 by dispatching the DAR for consultation of the Member States and the sole applicant SePRO Europe Limited. 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 March-April 2008. A final discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in July 2008 leading to the conclusions set out in the EFSA Conclusion finalised on 31 July 2008 (EFSA Scientific Report (2008) 151). Following the Commission Decision of 13 January 2009 (2009/28/EC)(5) concerning the non-inclusion of flurprimidol in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing that substance, the applicant SePRO Europe Limited made a resubmission application for the inclusion of flurprimidol in Annex I in accordance with the provisions laid down in Chapter III of Commission Regulation (EC) No. 33/2008(6). The resubmission dossier included further data in response to the issues and concerns identified in the conclusions leading to the Decision on non-inclusion, as set out in the Review Report (SANCO/173/08)as follows: The risk to operators and workers The exceedence of the AOEL (acceptable operator exposure level) for operators and workers in all evaluated scenarios and conditions of use; The lack of information on impurities present in the batches used in the toxicological studies. In accordance with Article 18 of Commission Regulation (EC) No. 33/2008, Finland, being the designated RMS, submitted an evaluation of the additional data in the format of an Additional Report. The Additional Report was received by the EFSA on 10 March 2010. In accordance with Article 19 of Commission Regulation ( EC) No. 33/2008, the EFSA distributed the Additional Report to Member States and the applicant for comments on 11 March 2010. The EFSA collated and forwarded all comments received to the Commission on 26 April 2010. In accordance with Article 20, following consideration of the Additional Report and the comments received, the Commission requested the EFSA to conduct a focussed peer review in the area of mammalian toxicology and deliver its conclusions on flurprimidol. The conclusion of the resubmission was reached on the basis of the evaluation of the representative uses as a plant growth regulator in ornamentals as proposed by the applicant. Full details of the GAP can be found in Appendix A. The representative formulated product for the evaluation was 'Topflor', a micro-emulsion ( ME) containing 3.8 g/l flurprimidol. 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 products are possible. There are no adequate methods available to monitor flurprimidol in the environmental matrices and in body fluids and tissues. In mammalian metabolism studies, flurprimidol was rapidly but not completely absorbed after oral administration. It was extensively metabolised and distributed through the body. Excretion was rapid, mainly via urine although some excretion was observed via bile and faeces. Moderate acute oral toxicity was found in rat and mouse, requiring classification with Xn, R22 "harmful if swallowed", but no classification was needed related to acute dermal or inhalation toxicity. Flurprimidol was not a skin or eye irritant and no sensitisation potential was found. Main effects observed in short-term and long-term toxicity studies were liver toxicity including enzyme induction and histopathological findings, and uterine and ovary weight changes down to the lowest dose tested, indicative of endocrine disruption effects at low doses. Genotoxicity studies covering all required endpoints (in vitro bacterial and mammalian gene mutation, chromosomal aberration and in vivo micronucleus test) were negative and no carcinogenic potential was observed in either rats or mice upon 2-year oral exposure. Flurprimidol was thought to inhibit aromatase activity because the observed effects were similar to those observed with structurally related active substance fenarimol. However, no mechanistic study was performed with flurprimidol and sensitive end points for aromatase inhibition were not measured in studies conducted with flurprimidol. Reproductive toxicity was indicated by increased precoital period, dystocia, progeny mortality, reduced mating performance and fertility which were not considered secondary to parental systemic toxicity. Accordingly, classification as toxic, reproduction toxicity category 2 for fertility, R60 "may impair fertility", was proposed. In the rat developmental toxicity study, the proportion of foetuses with developmental variations and abnormalities was increased and could not be explained by maternal toxicity alone. Accordingly classification as harmful, reproduction toxicity category 3 for development, R63 "possible risk of harm to the unborn child" was proposed. The Acceptable Daily Intake (ADI) was 0.003 mg/kg bw/day, the Acceptable Operator Exposure ( AOEL) was 0.003 mg/kg bw/day and the Acute Reference Dose (ARfD) was 0.09 mg/kg bw. Dermal absorption was 6 % for the concentrate formulation and 15 % for the in-use spray dilution based on an in vitro study performed on human skin. The estimated level of operator exposure calculated for glasshouses' uses on ornamentals with the representative formulation 'Topflor' according to the EUROPOEM II and the Dutch model is below the AOEL when the use of personal protective equipment (PPE, i.e. gloves and protective clothing) is considered. Estimated exposure of workers is below the AOEL after one application of 'Topflor' when the use of gloves and coverall is considered. After 2 applications (assuming that there is no decay in the residues during the 14-days interval between applications), estimated worker exposure exceeds the AOEL (103 %) even when PPE are worn and a critical area of concern was identified. Furthermore, flurprimidol is a racemate and there is no information on the relative toxicity of each isomer or whether there is a shift in the isomer ratio workers are exposed to. A data gap is identified to address this. Bystander's exposure is not relevant for the representative use. No data were submitted to study and assess the residue behaviour of flurprimidol in plants and livestock in order to define the relevant residues for dietary consumer risk assessment. The representative use of flurprimidol in containerised ornamentals, pot and bedding plants are normally not expected to result in any dietary exposure to consumers or livestock. Potted herbs or any other edible container plants are not meant to be included in the representative use. A potential transfer of residues from recycled soil and/or compost to crops intended for human or animal consumption should be avoided, by taking appropriate restriction measures. Under conditions excluding any potential consumer exposure to flurprimidol residues through food, there will be no dietary consumer risk related to the representative use. All available fate and behaviour into the environment studies have been performed with flurprimidol labelled exclusively at the phenyl ring and / or at the carbinol bridge. The meeting of experts identified a data gap for a full fate and behaviour data package of studies performed with flurprimidol labelled at the pyrimidine ring. The data available for fate and behaviour of flurprimidol into the environment are very limited. Information on the fate of the individual enantiomers is not available. Data on the route of degradation in soil are insufficient to assess any use for which exposure could not be completely excluded. The data available show that flurprimidol exhibits medium to high persistence in soil (DT50 = 98 - 183 d) under laboratory aerobic conditions ( no field study available) and that it is not hydrolysed in buffered water in the range of environmental pHs. Photolysis of flurprimidol in water was relatively rapid ( DT50 = 1.4 d) and results in the formation of two photolysis metabolites that would need to be further assessed for the aquatic environment in the situation that exposure could not be completely excluded from the representative use. No water sediment study is available in the dossier. Potential groundwater contamination was precluded from the representative use if it is restricted as proposed by the meeting of experts. In general a number of data gaps for fate and behaviour into the environment were identified during the peer review, however, they were considered not to be essential for the assessment of the representative use if this can be effectively restricted / managed in order to avoid exposure to the environment, including the potential exposure arising from disposal of used soil and residues of plants. Note the PPR panel of EFSA, has questioned the effectiveness of risk management measures such as those proposed here, to limit environmental exposure from uses in glasshouses. The environmental risk assessment covers only the use in glasshouses that are permanent structures. No risk assessment was conducted for birds and mammals. Direct exposure of birds and mammals is expected to be negligible for the representative use in glasshouses. The log P-ow of flurprimidol is >3 and therefore a risk assessment should be conducted for secondary poisoning of earthworm-and fish-eating birds and mammals if treated substrate and plants are disposed of in the environment. The risk to fish, aquatic invertebrates and algae was assessed as low. A study with higher aquatic plants is needed since flurprimidol is a plant growth regulator. However, the study is not required to finalise the EU risk assessment for the representative use if the use is restricted to high technology glasshouse production systems with irrigation/excess water management systems. Effects of >50% on mortality and reproduction were observed in sensitive groups of non-target arthropods at concentrations below the suggested application rate of 60 g a.s./ha. Arthropods used in glasshouses for biological plant protection purpose are likely to be severely impacted by the use of flurprimidol. The risk to non-target arthropods in the environment surrounding the glasshouse was considered to be low due to negligible exposure. The acute risk to earthworms was assessed as low. No study was submitted to investigate long-term (reproductive) effects on earthworms. Such a study was considered not necessary provided that treated soil and plants are not disposed of in the environment. No risk assessment was conducted for other soil non-target organisms and non-target micro-organisms. However, the risk to soil dwelling organisms is assumed to be low for the use in high technology glasshouse production systems with irrigation/excess water management systems and provided that treated substrate and plants are not disposed of in the environment. The risk to non-target plants in the vicinity of glasshouses was considered to be low. The risk to bees and biological methods of sewage treatment was assessed as low.