Bromuconazole is one of the 79 substances of the third stage Part A of the review programme covered by Commission Regulation (EC) No 1490/2002(3). 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 one year a conclusion on the risk assessment to the EU-Commission. Belgium being the designated rapporteur Member State submitted the DAR on bromuconazole in accordance with the provisions of Article 10(1) of the Regulation (EC) No 1490/2002, which was received by the EFSA on 14 November 2005. Following a quality check on the DAR, the peer review was initiated on 5 May 2006 by dispatching the DAR for consultation of the Member States and the sole applicant Bayer CropScience (later Sumitomo Chemical Agro Europe SAS). Subsequently, the comments received on the DAR were examined by the rapporteur Member State and remaining issues were agreed during a written procedure in February - March 2007. 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 July and October 2007. A discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in February-March 2008 leading to the conclusions as set out in the EFSA Conclusion finalised on 26 March 2008 (EFSA Scientific Report (2008) 136). Following the Commission Decision of 3 November 2008 (2008/832/EC)4 concerning the non-inclusion of bromuconazole in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing that substance, the applicant Sumitomo Chemical Agro Europe S.A. made a resubmission application for the inclusion of bromuconazole in Annex I in accordance with the provisions laid down in Chapter III of Commission Regulation (EC) No. 33/2008(5). The resubmission dossier included further data in response to the areas of concern identified in the review report (SANCO/120/08) as follows: the potential for contamination of surface water and groundwater; the high toxicity to aquatic organisms. In accordance with Article 18 of Commission Regulation (EC) No. 33/2008, Belgium, being the designated rapporteur Member State, submitted an evaluation of the additional data on bromuconazole in the format of an Additional Report. The Additional Report was received by the EFSA on 8 October 2009. In accordance with Article 19, the EFSA distributed the Additional Report to the Member States and the applicant for comments on 20 October 2009. The EFSA collated and forwarded all comments received to the Commission on 7 December 2009. In accordance with Article 20, following consideration of the Additional Report, the comments received, and where necessary the DAR, the Commission requested the EFSA to conduct a focused peer review in the area of ecotoxicology and to deliver its conclusions on bromuconazole. The conclusion from the original review was reached on the basis of the evaluation of the representative use as a fungicide on wheat. The conclusion of the peer review of the resubmission was reached on the basis of the same representative use. Full details of the representative use can be found in Appendix A to this report. The representative formulated product for the evaluation was, Granit 200 SC.", a suspension concentrate formulation (SC). Adequate methods are available to monitor all compounds given in the respective residue definition. Residues in food of plant origin can be determined with a multi-method (the German S19 method has been validated). For the other matrices only single methods are available to determine residues of bromuconazole. 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. In mammals, bromuconazole oral LD50 is 328 mg/kg bw (classification as, harmful if swallowed. (Xn; R22), proposed). The acute toxicity by the dermal and inhalation routes is low (LD50>2000 mg/kg bw and LC50 > 5 mg/L). Bromuconazole is neither a skin nor an eye irritant. It is not a skin sensitiser. In repeated dose toxicity studies, the liver is the target organ. In subchronic tests, the dog is the most sensitive species, with an overall relevant NOAEL of 2.5 mg/kg bw/day, whereas in rat the NOAEL is 13.8 mg/kg bw/day. In genotoxicity testing there was some indication of weak clastogenicity in vitro, however there was no indication of positive results in vivo, neither in the micronucleus assay nor in the UDS assay. Overall, bromuconazole was considered devoid of genotoxic potential. The relevant NOAEL for long-term toxicity and carcinogenicity in rat is 0.88 mg/kg bw/day: treatment-related neoplastic lesions in rodents occurred at high doses: hepatocellular and cholangiocellular carcinomas in rats and hepatocellular carcinoma in mice. In both rats and mice, the tumours were likely caused by liver toxicity and subsequent cell renewal. Overall, it was agreed that bromuconazole does not have carcinogenic potential relevant to humans. Bromuconazole did not show any reproductive toxicity potential: parental and foetal toxicity NOAELs were established at 1.3 mg/kg bw/day, while the reproductive NOAEL was established at 141 mg/kg bw/day. As for developmental toxicity, in the rat the relevant maternal NOAEL is 70 mg/kg bw/day, whereas the developmental NOAEL is 10 mg/kg bw/day, based on a dose-dependent increase of placental weight and ossification delays or supernumerary bones in a number of skeletal structures. It was agreed to propose classification Cat 3, Xn; R63,, May cause harm to unborn child.. The ADI of 0.01 mg/kg bw/day was set based on the relevant long-term toxicity/carcinogenicity NOAEL of 0.88 mg/kg bw/day from the 2-year rat study, applying a safety factor (SF) of 100. For the ARfD, the value is based on the developmental NOAEL of 10 mg/kg bw/day from the rat study, with a SF of 100, leading to an ARfD of 0.1 mg/kg bw. The AOEL of 0.025 mg/kg bw/day was set on basis of the NOAEL of 2.5 mg/kg bw/day from the 90-day dog study (applying a standard SF of 100). The operator exposure assessment showed exposure levels below the AOEL (15.6%) according to the German model with the use of gloves during mixing/loading and application, and coveralls and sturdy footwear during application. The estimated exposure for re-entry activities (scouting) is 4.5% of the AOEL. The bystander exposure is estimated to be 1.6% of the AOEL. The metabolism of bromuconazole was investigated in wheat. Additional metabolism data were submitted for the category of fruit crops. A metabolic pathway could be established in cereals. At harvest, bromuconazole was still a major part of the terminal residue in cereal matrices, and identified metabolites were individually below 10% of the total residue. However, there was an indication of preferential metabolism of one bromuconazole diastereomer (LS 850647), as a significant shift in the ratio of diastereomers was found in the residues determined in the mature cereal crop when compared to the ratio in the initially applied bromuconazole. Whether the ratio of enantiomers in each diastereomer was subject to any shift was not investigated. In rotational crops studies there was uptake of residues from soil into succeeding cereal, oilseed, root and leafy crops. Upon analysis of the residues the two bromuconazole diastereomers were identified as major residue, and similar to the primary cereal metabolism their ratio had been shifted compared to the one in the bromuconazole applied to the soil. No information is available on the ratio of enantiomers in each diastereomer. The submitted livestock metabolism data in ruminants and poultry allows to establish a metabolic pathway, and suggests that no residues in food of animal origin above the limit of quantification are expected when cereals treated according to the cGAP are used in livestock diet. The data imply that there might be preferential metabolism of one diastereomer also in livestock animals. The ratio of enantiomers in each diastereomer was not investigated. As plant and livestock residue data indicate that from the representative use no significant consumer exposure to bromuconazole residues is expected, the observed shift of the isomer ratio in the terminal residue is currently not a concern with regard to consumer safety. This may have to be reconsidered when authorisation of uses is sought that lead to consumer exposure to bromuconazole residues above the limit of quantification. The meeting of experts noted that all studies were performed using phenyl-labelled bromuconazole only, and thus the fate of the triazole moiety of the molecule was not investigated. The experts agreed that, based on the available data and information, cleavage of the molecule cannot be excluded and further investigation of the triazole moiety of the molecule is required to address consumer exposure to potential metabolites originating from molecule breakdown, as e.g. triazole derivative metabolites. Until then, the plant and animal residue definition is provisional. Triazole derivative metabolites are considered of concern due to their toxicological profile. In the absence of data investigating the fate of the triazole moiety of the bromuconzole molecule and the magnitude of potentially occurring metabolites originating from the triazole moiety, the consumer exposure cannot be assessed and consequently the consumer risk assessment is not finalised. As a breakdown of the bromuconazole molecule leading to the occurrence of metabolites relevant to consumer safety cannot be excluded, the issue is regarded as a critical area of concern. In soil under aerobic conditions bromuconazole exhibits moderate to very high persistence forming several minor (< 10% AR) metabolites. Mineralisation was limited accounting for only 1-4.4% AR after 100-120 days. The formation of unextractable residues was a sink, accounting for 5-17.6 % AR after 100-120 days. A laboratory soil photolysis study indicated that photolysis may contribute to the degradation of bromuconazole at the soil surface. As a consequence, the experts agreed that the available field dissipation rates did not represent biodegradation that can be used as input to FOCUS modelling. However, following the resubmission application, field degradation rates normalised to FOCUS reference conditions that excluded photolysis losses were estimated. These estimates are considered appropriate for use as input to FOCUS modelling. Bromuconazole exhibits medium to low mobility in soil. Bromuconazole is essentially stable to hydrolysis, and photolysis is not expected to be a significant process in the breakdown of bromuconazole in natural aquatic systems. In dark natural sediment water systems bromuconazole partitioned from the water column to sediment where it exhibited very high persistence. The terminal metabolite, CO2, accounted for a maximum of 0.9 % AR at 100 days (study end). Unextracted sediment residues were a sink but represented maximum 15% AR at study end. Satisfactory FOCUS surface water exposure estimates were available for use in the EU level aquatic risk assessment, with spray drift and run-off mitigation being accounted for in step 4 calculations. The potential for groundwater contamination resulting from the representative use assessed, was concluded to be low in geoclimatic conditions represented by all 9 pertinent FOCUS groundwater scenarios. Bromuconazole belongs to the group of triazole fungicides that are suspected to have potential endocrine disrupting properties. No information was provided to address this point with regard to the potential effects on birds and fish, and a data gap was identified. No new information on this point was provided in the Additional Report and the data gap remains. The TER values for herbivorous birds were all above the Annex VI triggers, indicating a low risk for herbivorous birds. Also for insectivorous birds the TER values for acute and short-term exposure were well above the trigger, however the long-term TER was below the trigger of 5, indicating a potential high long-term risk. In the Additional Report higher tier studies (mainly from open literature) were presented to select the focal species and to determine the proportion of different food types (PD) of the focal species. Two different approaches were used to refine the risk assessment. The first approach included the selection of representative focal species, and estimations of PD for these species. The second approach was to include the decline of residues in insects (f(twa) = 0.53) in the first-tier long-term risk assessment. The TERlt values based on the PD refinements, and those based on the use of ftwa of decline of residues in insects, were all above the Annex VI trigger values. Therefore the long-term risk to insectivorous birds was assessed as low. The risk to earthworm- and fish-eating birds was assessed as low. The acute TERs for herbivorous and insectivorous mammals were above the Annex VI trigger of 10 (including refinement of residues in plant material), however the long-term TERs were below the Annex VI trigger, indicating a high risk. The choice of the long-term end point was discussed again in the experts. meeting (PRAPeR 75), and it was agreed that the NOAEL for mammals of 13.8 mg as/kg bw/d is the relevant ecotoxicological end point. TER calculations for insectivorous mammals based on this NOAEL are provided in the DAR and in the Additional Report and were above the Annex VI trigger value, indicating a low long-term risk for insectivorous mammals. In the resubmission, a higher tier risk assessment for herbivorous mammals was based on the rabbit as focal species in late cereal growth stages. The higher tier risk assessment for herbivorous mammals was discussed in the experts. meeting (PRAPeR 75), and it was concluded that the available information is not sufficient to address the potential high long-term risk for herbivorous mammals. The risk to earthworm- and fish-eating mammals was assessed as low. Bromuconazole is very toxic to aquatic organisms. The applicant provided a bridging study with the new formulation SCAE0307 and Daphnia magna. The formulation SCAE0307 is less toxic than the previously assessed formulation EXP 10064-B, and has a toxicity comparable to that of the active substance. Member States experts at PRAPeR 75 agreed that the end points for the active substance should be used in the risk assessment. A low long-term risk was identified from the FOCUS step3 PECsw values in the D3 ditch, D4 pond, D4 stream, D5 pond, D5 stream, D6 pond, R1 pond and R1 stream scenarios. However, a potential high long-term risk was indicated for aquatic invertebrates from the FOCUS step3 PECsw values for the D1 ditch, D1 stream, D2 ditch, D2 stream, R3 stream and R4 stream scenarios, and further refinement was needed. The TERs were re-calculated with a 10m no-spray buffer zone for the drainage scenarios and a 10m no-spray buffer zone including a vegetated filter strip to mitigate the run-off. The long-term TER values were above 10 in 2 full FOCUS run-off scenarios (R3 stream and R4 stream). However, the TER values estimated with the drainage scenarios D1 ditch, D1 stream, D2 ditch, D2 stream were below the Annex VI trigger values even with a 10m no-spray buffer zone. Overall, taking into account the FOCUS step 3 and 4 scenarios, it can be concluded that the risk of bromuconazole to aquatic organisms was assessed as low for more than the half of the scenarios. The risk assessment for non-target arthropods was not in accordance with the ESCORT II scheme. The standard glass plate tests suggest that there will be some adverse effects on sensitive non-target arthropods. Extended laboratory studies gave an indication that the risk to non-target arthropods is low. Concerns were raised with regard to the comparability of the different formulations used in the studies with non-target arthropods. EFSA agrees to the assessment of the RMS that the formulations are sufficiently similar to conclude on the risk to non-target arthropods for the representative use. The applicant informed that a different formulation than Granit will be marketed. It is suggested that a risk assessment for this formulation is conducted at Member State level after the decision on Annex I inclusion. The formulation Granit had no significant effect on organic matter decomposition over a six months period in a litter bag test at an application rate of 180 g a.s./ha and 500 g a.s./ha. The soil concentration was calculated in the DAR as 0.67 mg a.s./ha. This concentration covers the plateau maximum PECsoil of 0.232 mg a.s./kg soil (2 x 0.200 kg a.s./ha). In conclusion, the risk of bromuconazole to non-target macro-organisms was assessed as low. Effects of > 25% on nitrogen transformation were observed at an application rate of 400 g a.s./ha (0.53 mg a.s./kg soil). This concentration covers the plateau maximum PECsoil of 0.232 mg a.s./kg soil (2 x 0.200 kg a.s./ha). The risk of bromuconazole to soil non-target micro-organisms was assessed as low. The risk to bees, earthworms, non-target plants, and biological methods of sewage treatment was assessed as low.
