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(1). 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 as laid down in this report. The conclusion 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 the attached end points. The representative formulated product for the evaluation was "Topflor", a micro-emulsion (ME) containing 3.8 g/1 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. There is no agreed specification. A critical area of concern was raised by the experts in mammalian toxicology on the lack of information on impurities present in the batches used in the toxicological studies. 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 endpoints 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 10 % for the concentrate formulation (default value, taking into account that measurements were available in an in vivo monkey study with the active substance) and 100 % for the in-use spray dilution (default value for no data). The level of operator exposure calculated for glasshouses' uses on ornamentals with the representative formulation Topflor exceeded the AOEL, even when the use of protective clothing was considered, according to the EUROPOEM II and the Dutch model. Estimated exposure of workers entering crops treated with flurprimidol exceeded also the AOEL, even after only one application and when the use of gloves was considered. Bystander's exposure was not relevant for this type of use. No data was submitted to study and assess the residue behaviour of flurprimidol in plants and livestock animals in order to define the relevant residues for dietary consumer risk assessment. The representative uses of flurprimidol in containerized ornamentals, pot and bedding plants are normally not expected to result in any dietary exposure to consumers or livestock animals Potted herbs or any other edible container plants are not meant to be included in these notified uses. A potential transfer of residues from recycled soil and/or compost to crops intended for human or animal consumption should be avoided, possibly by 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 notified representative uses. All fate and behaviour into the environment studies available 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 is very limited. Data on the route of degradation in soil is insufficient to assess any use for which exposure could not be completely excluded. The data available shows that flurprimidol is medium to high persistent 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 aquatic environment in case exposure could not be completely excluded from the use proposed. No water sediment study is available in the dossier. Potential ground water contamination was precluded from the representative use proposed 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 is restricted / managed in order to avoid exposure to the environment, including the potential exposure arising from disposal of soil used and residues of plants. The environmental risk assessment covers only the use in greenhouses 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 greenhouse. 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 proposed use if the use is restricted to high technology greenhouse 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 greenhouse 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 greenhouse 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 greenhouses was considered to be low. The risk to bees and biological methods of sewage treatment was assessed as low.
