Metamitron is one of the 84 substances of the third stage Part B of the review programme covered by Commission Regulation (EC) No 1490/20021. 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. United Kingdom being the designated rapporteur Member State submitted the DAR on metamitron in accordance with the provisions of Article 10(1) of the Regulation (EC) No 1490/2002, which was received by the EFSA on 22 August 2007. The peer review was initiated on 24 October 2007 by dispatching the DAR for consultation of the Member States and the sole applicant Makhteshim Agan. 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 June July 2008. A final discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in September 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 herbicide on sugar and fodder beet for the control of annual grasses and broad-leaved weeds as proposed by the notifier. Full details of the GAP can be found in the attached list of endpoints. The representative formulated product for the evaluation was "Goltix SC 700", a suspension concentrate (SC) containing 700 g/1 of metamitron. The specification for the technical material as a whole should be regarded as provisional for the moment. 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 for monitoring for food/feed of plant origin and for environmental matrices. Mammalian toxicology of metamitron was assessed in a series of investigations. Metamitron is absorbed rapidly and almost completely. It is evenly distributed and has no potential for accumulation. It is rapidly excreted and also quickly and extensively metabolized. Metabolism involves an initial desamination step followed by hydroxylation, oxidation and conjugation reactions. Metamitron is of moderate oral and inhalation, and of very low dermal toxicity. It is neither a skin nor an eye irritant nor a skin sensitizer. Based on the data on acute toxicity a classification as Xn; R20 "Harmful; Harmful by inhalation" and Xn; R22 "Harmful; Harmful if swallowed" is proposed. In short term tests with rodents, liver effects (clinical changes and pathology) were predominant In dogs in addition, also haematological effects were observed. The lowest relevant short-term NOAEL of 3.6 mg/kg bw/d was obtained in a 90-day dog study. Metamitron is not genotoxic. Metamitron was not tumorigenic in chronic studies with rats, mice and dogs. The lowest chronic NOAEL of 3.0 mg/kg bw/d was derived from increased cholesterol levels detected in a 2-year dog study. In one of two multigeneration studies conducted, reduced corpora lutea and implantations were observed at doses already toxic to the dams. Neither in rats nor in rabbits were specific developmental effects observed. In single dose pharmacological tests metamitron induced behavioural changes in rats. The acceptable daily intake (ADI) was set at 0.03 mg/kg bw/d based on a NOAEL of 3 mg/kg bw/d obtained in a 2-year dog study applying a safety factor of 100. The acceptable operator exposure level (AOEL) was set at 0.036 mg/kg bw/d based on a NOAEL of 3.6 mg/kg bw/d obtained in a 90-day dog study. The Acute Reference Dose (ARfD) was set at 0.1 mg/kg bw based on a maternal NOAEL of 10 mg/kg bw/d obtained in a rat developmental study that was supported by NOAELs obtained in single dose pharmacologic and functional studies in rats. Only when gloves were used when handling the concentrate and when gloves, coverall and sturdy footwear were worn during application of the formulation, operator exposure resulted in a value below the AOEL in the German model (34%). In the UK POEM the AOEL was exceeded in all scenarios. Exposure of an unprotected worker amounted to 73% of the systemic AOEL. Maximum exposure of bystanders accounted for 23% of the AOEL. The metabolism of metamitron was investigated in sugar beet. Sucrose was the only identified radioactive compound in roots. The experts meeting decided that metabolites found in forage and leaves should not be included in a provisional residue definition for monitoring and risk assessment for root/tuber crops, as their levels were considered not to be significant in the diets of livestock. Therefore the proposed residue definition for monitoring and risk assessment for root/tuber crops is metamitron only. The residue definition is pending the submission of a metabolism study on rotational crops, which was requested by the experts meeting on the basis of the stability of metamitron in soil. The expert meeting concluded that four residue trials carried out in Northern Europe with acceptable validation data of the analytical methods indicating residues below the LOQ, and in addition trials performed in Southern Europe with residues also below the LOQ, were sufficient to propose a MRL. However, a data gap was formulated for validation data for the method of analysis used in four further residue trials to confirm the validity and completeness of the residue trial data set. Metamitron residues have been shown to be stable under freezing conditions. As residues found in beet roots and leaves at maturity are below the LOQ, processing studies and metabolism studies in livestock are not required. However, the experts meeting proposed a re-entry period after application of metamitron and EFSA notes that tops should not be fed after thinning or crop failure. These suggestions could be reconsidered after submission of validation data for the method of analysis used in further residue trials. On the basis of the calculations carried out by the RMS, chronic and acute intake of residues of metamitron after application according to the notified cGAP are not expected to exceed the ADI and ARfD respectively. In soil under aerobic conditions metamitron exhibits low to moderate persistence forming the major soil metabolite desamino-metamitron2 (accounting for up to 17.1% of applied radioactivity (AR)), which exhibits moderate persistence. Mineralisation to carbon dioxide of the applied [C-14-phenyl]- labelled metamitron accounted for 23.3-57.4% AR after 100-120 days. The formations of unextractable residues were a sink, accounting for 29.5-41.2% AR after 100-120 days. Metamitron exhibits medium to very high mobility in soil. Desamino-metamitron exhibits medium to high mobility in soil. There was no indication that adsorption of either metamitron or desaminometamitron was pH dependent. There was an unidentified soil metabolite (M3) present in soil that triggers a groundwater exposure assessment. However such an assessment is not available. Hydrolysis was considered to play a minor role, but photodegradation may be a significant route of degradation of metamitron in aquatic systems particularly close to the surface of natural water bodies where indirect photolysis may be significant due to the presence of photosensitizers. In natural sediment water systems metamitron exhibited moderate persistence (total system DT50 10.8-11.4 days) degrading to the major metabolite desamino-metamitron (maximum 54% AR in the water phase and 27.5% in the sediment). The terminal metabolite, CO2, was a minimal sink in the material balance accounting for only 1% AR at the study end. Residues not extracted from sediment accounted for 23-26% AR at study end. The necessary surface water and sediment exposure assessments were appropriately carried out using the agreed FOCUS scenarios approach for metamitron at steps 1-3 for metamitron and up to step 2 for desamino-metamitron. These values are the basis for the risk assessment discussed in this conclusion. The potential for groundwater exposure from the applied for intended uses above the parametric drinking water limit of 0.1 mu g/L was concluded to be low in geoclimatic situations that are represented by the FOCUS groundwater scenarios, except for the FOCUS Piacenza scenario where the limit of 0.1 mu g/L was exceeded by metamitron (0.002-0.139 mu g/L) and desamino-metamitron (0.139-1.440 mu g/L). The first-tier risk assessment for birds resulted in acute and short-term TERs that were above the Annex VI trigger value, except for the acute risk for medium herbivorous birds. The first-tier longterm risk assessment resulted in TERs below the Annex VI trigger value for medium herbivorous and insectivorous birds, respectively, indicating a potential high long-term risk to birds. The refined risk assessment for herbivorous birds was based on reliable foliar residue decline studies and indicated a low risk from acute exposure. The long-term risk for herbivorous and insectivorous birds was further refined by assessing the risk to skylark, yellowhammer and the yellow wagtail (as "focal species"). The RMS approach included refinements of the dietary consumption (PD) and the proportion of the diet obtained in the treated areas (PT). However, the long-term TERs obtained using the "focal species" approach were below the Annex VI triggers for all three focal species indicating that further refinement of the risk to herbivorous and insectivorous species was required. A less conservative approach was suggested by the applicant to assess the risk to herbivorous birds to estimate a 21 day time weighted average (twa) exposure based on a mean daily exposure level for the time period covering the first (day 1), second (day 6) and third (day12) applications, up to 21days after the first application (= 9 days after last treatment) assuming a DT50 of 1.9 days for foliar residues. This approach resulted in a long-term TER for herbivorous birds above the Annex VI trigger value, suggesting a low risk was expected to herbivorous birds. It was also considered that although a low long-term risk to insectivorous birds had not been demonstrated (long term TER for yellow wagtail = 4.1), a further refinement of the exposure estimate (in a similar way to that undertaken for foliar residues) may enable to conclude on a low risk to insectivorous birds. This could be considered at Member State level for product re-registration following Annex I inclusion. The acute and long-term risk to mammals was considered to be low. No risk assessment for secondary poisoning was triggered for metamitron since the log P(ow)A potential high risk to birds and mammals from intake of contaminated water from in-field puddle water was identified. In case of Annex I inclusion, risk mitigation measures or further refinements of the risk assessment should be considered at Member State level. Metamitron is very toxic to aquatic invertebrates, algae and to higher aquatic plants. The TERs based on FOCUS PECsw step 3 were above the Annex VI trigger value for all the representative scenarios, except for the R-3 run-off scenario. From the microcosm study a NOAEC of 1120 mu g a.s./L was proposed by the applicant. The RMS suggests to apply an assessment factor of 3 for the microcosm NOAEC = 1.12 mg a.s./L. The estimated TER values based on the FOCUS Step 3 PECsw were above the Annex VI trigger values for all the representative scenarios. Based on this it could be concluded that the acute and chronic risk to aquatic organisms from exposure to metamitron and the metabolite desamino-metamitron was low. The lowest ER50 values for the non-target plants were observed for rape (ER50 = 54.9 g a.s./ha, pre emergence exposure) and for lettuce (ER50 = 171.6 g a.s./ha, post-emergence exposure). The refined TER values for pre and post-emergence were respectively 0.99 and 4.4 from spray drift at 1 m and 4.9 and 21.5 from spray drift at 5 m. A potential high risk was identified from metamitron exposure to the off-crop non-target plants, therefore risk mitigation measures, similar to a 5 m non-spray buffer zone, were required to identify a low risk. The risk to bees, non-target arthropods, earthworms, soil macro and micro-organisms and biological methods of sewage treatment was assessed as low.
