Conclusion regarding the peer review of the pesticide risk assessment of the active substance metazachlor

Metazachlor is one of the 79 substances of the third stage Part A 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. The United Kingdom being the designated rapporteur Member State submitted the DAR on metazachlor in accordance with the provisions of Article 10(1) of the Regulation (EC) No 1490/2002, which was received by the EFSA on 30 September 2005. The peer review was initiated on 6 October 2006 by dispatching the DAR for consultation of the Member States and the two applicants BASF and Makhteshim Agan. Subsequently, the comments received on the DAR were examined by the rapporteur Member State and remaining issues were agreed on during a written procedure in July August 2007. The identified issues as well as further data made available by the applicant upon request were evaluated in a series of scientific meetings with Member State experts in November December 2007. A final discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in March 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 winter and spring oilseed rape and ornamentals for the control of annual grasses and broad-leaved weeds as proposed by the notifiers. Full details of the GAP can be found in the attached end points. The representative formulated products for the evaluation were Butisan S (BASF) and Fuego (MAK), both suspension concentrates (SC) containing 500 g/1 metazachlor. 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. Adequate methods are available to monitor all compounds given in the respective residue definitions for monitoring for food/feed of plant and animal origin and for environmental matrices, however subject to the final agreement on the hazard classification of metazachlor, additional analytical methods for groundwater monitoring would be required. As for mammalian toxicology, metazachlor acute toxicity is low via oral, dermal and inhalation routes (LD50>2000 mg/kg and LC50>34.5 mg/1). Metazachlor is neither a skin nor an eye irritant. Metazachlor was proposed to be classified as skin sensitiser R43 May cause sensitisation by skin contact. The relevant NOAELs for subacute and subchronic exposure in rats are 110 mg/kg bw/day and 21 mg/kg bw/day (BASF and FSG, LOAELs 330 and 137 mg/kg bw/day, respectively). Metazachlor did not show any genotoxic potential. Liver adenomas and thyroid tumours occurred in the rat, while the mouse showed slight increases in bladder transitional cell tumours at high dose levels. Since there was no genotoxicity and clear no effect levels for tumour development were seen in all tests, it was apparent that tumour development could be considered to involve a threshold mechanism. A classification as Care. Cat. 3 R40 (Limited evidence of a carcinogenic effect) was proposed. The parental NOAEL for the BASF study (limited validity) is 1000 ppm as well as the reproductive and the offspring NOAELs. The parental and the reproductive NOAELs of the FSG study are 151 and 192 mg/kg bw/day (2000 ppm), respectively. For the offspring the NOAEL is 20 mg/kg bw/day (200 ppm) based on reduced pup weight and survival in the F3 generation. No evidence of teratogenicity was seen in developmental toxicity studies in the rat and rabbit. The relevant maternal NOAELs are 50 mg/kg bw/day in rat and rabbit (BASF) and 30 and 250 mg/kg bw/day in rabbit and rat, respectively (FSG); the relevant developmental NOAELs are 250 and 450 mg/kg bw/day in rabbit and rat, respectively (BASF) and 120 and 250 mg/kg bw/day in rabbit and rat, respectively (FSG). Metazachlor did not show any potential for acute, repeated dose or delayed neurotoxicity. An ADI of 0.08 mg/kg bw/day was derived for metazachlor, based on the NOAEL of 8.5 mg/kg bw/day; an ARfD of 0.5 mg/kg bw was derived, based on the NOAEL of 50 mg/kg bw/day from the developmental study in rats, and the AOEL was set at 0.2 mg/kg bw/day, based on the relevant short term toxicity NOAEL 21 mg/kg bw/day in rat. The safety factor applied is 100. The operator exposure is below the AOEL for Butisan only with the use of gloves when handling the concentrate, coveralls and gloves during application (German model); for Fuego the exposure is below the AOEL even without PPE for field application estimated with the German model, with use of gloves during mixing/loading (tractor application, UK POEM) and with the use of gloves when handling the concentrate, coveralls and gloves during application (knapsack spraying, UK POEM). The re-entry exposure is estimated to be above the AOEL for both Butisan and below the AOEL for Fuego. Bystander exposure is below the AOEL for both plant protection products. The metabolism of metazachlor in plant and livestock is extensive and the parent compound does not participate to the toxicological burden the consumer is exposed to. The residue definition for monitoring is proposed to include all residual compounds containing the 2,6-dimethylaniline moiety. For monitoring of plant products, 3 metabolites have been identified as valid indicator compounds: metabolites 479M04, 479M08 and 479M16. A possible transfer of soil residues to rotational crops has been identified, but under usual rotation practices with rape seed no measurable residue level above the analytical limit of quantification is expected in food commodities from rotational crops. There is a low exposure of livestock to residues present in feeding stuff but their transfer to edible animal commodities is not expected to reach analytically measurable levels. No risk for the consumer has been identified resulting from short or long term dietary exposure to residues in food commodities and to metabolites contaminating groundwater resulting from the representative use of metazachlor in rape seed. The available data on the aerobic degradation in soil indicated that the metabolic pathway of metazachlor under aerobic conditions is complex. Two metabolites were found in soil at concentrations of greater than 10% applied radioactivity (AR), these were the metazachlor acid 479M04 (max. 16.2% AR at 91d) and the sulfonic acid derivative 479M08 (max. 21.6 at 181d). Two further metabolites, 479M09 and 479M11 were detected in smaller amounts, with 479M11 measured at levels > 5% AR on 3 consecutive time points. All metabolites identified contained both ring systems, (both the phenyl and the pyrazol rings). Cleavage of either of the ring systems is not a significant route of breakdown. Under anaerobic conditions, also 479M06 occurred in amounts greater than 10% AR. But it appeared in higher amounts only after longer incubation times under anaerobic conditions and therefore not considered to be of environmental relevance. Metazachlor degraded in soil under laboratory conditions fast with a mean first order DT50 value of 10.8 days (at 20 C and pF2) and under field conditions even faster, with a geometric mean value of 6.8 days (normalised to 20 degrees C). The degradation rates (first order DT5 degrees arc, pF2) of the major soil metabolites 479M04 and 479M08 in soil under laboratory conditions were 89.9 days and 123.2 day, respectively. Under field conditions the geometric mean value of the DT50 200c was 56.4 days for 479M04 and 71.1 days for 479M08. Metazachlor is adsorbing moderately to soil with Kfoc values between 53.8 and 220 mL/g. The adsorption of the metabolites 479M04, 479M06 and 479M08 is even weaker (Kfoc 1-94 mL/g, 44-62 mL/g and 4-78.5 mL/g, respectively). Therefore, lysimeter studies with metazachlor were performed on oilseed rape. There was no substantial leaching of metazachlor to groundwater. However, some metabolites were found in the lysimeter leachates, the most important were 479M04 (max annual average concentrations 6.33-21.39 g/L) and 479M08 (max concentrations in 2 leachate samples: 5.8-12 g/L). These results were confirmed by the results of FOCUS groundwater modelling. The potential for groundwater exposure from the applied for intended uses above the parametric drinking water limit of 0.1 mu g/L by parent metazachlor is concluded to be low. As for 479M04 and 479M08, FOCUS modelling results indicated that these metabolites are expected to exceed 0.75 mu g/L in all the FOCUS groundwater scenarios where it is defined that oilseed rape is grown. For soil metabolites 479M09, 479M11 and 479M12 the PECgw values could not be calculated using the FOCUS groundwater models. The PECgw, values were instead estimated for these metabolites on the basis of transfer factors derived from the comparison of simulated and measured concentrations of the metabolites BH479-4 and BH479-8, for which lysimeter and modelling results are available. Estimated PECgw values for FOCUS scenarios were in the range 0.31-1.72 mu g/L, 0.24-1.30 mu g/L and 0.34-1.88 mu g/L for BH479-9, BH479-11 and BH479-12 respectively. The classification as Carc. Cat. 3 R40 (Limited evidence of a carcinogenic effect) proposed by the expert meeting on mammalian toxicology has implications for the relevance of the metabolites with the potential to contaminate groundwater. Should the proposed classification of the parent, Carc. Cat.3 R40 be confirmed in the context of the European Chemicals Agency (ECHA) programme for classification and labelling under Directive 67/548/EEC this would, in line, with the guidance document on groundwater metabolites, require that, for those metabolites with the potential to contaminate groundwater, convincing evidence must be provided that the metabolites will not lead to the risk of carcinogenicity. Metazachlor is hydrolytically stable at pH 5, pH 7 and pH 9. It is also photolytically stable under the influence of light and it is not readily biodegradable. In water/sediment studies metazachlor disappeared from the water phase relatively rapidly and reached moderate (10.9-19.8% AR after 3-15 days) amounts in the sediment. The most significant metabolites identified were 479M04 (7.33-8.41% AR in water and 1.6-2.8% AR in sediment at 99 days) and 479M06 (ca. 8% AR in water and 5.1-8.0% AR in sediment extracts at 99d). The mineralisation rate was very low and the amount of bound residues high with values up to 67% AR at the end of the study (day 99). Metazachlor decreased in aerobic water sediment systems with first order DissT(5o) values from 13.4 to 27.8 days for the whole system. DT50 for the water phase was in the range 48.8-384 days, and DT50 for the sediment dissipation 3.0-6.8 days. The aquatic exposure assessments available are sufficient to complete the necessary EU level estimated of Predicted Environmental Concentrations (PEC) in surface water bodies for the representative uses applied for, for annex I listing. The volatility of metazachlor from aqueous system/soil water is likely to be low. Losses from plant surfaces are also low. The small proportion lost to the upper atmosphere is expected to degrade relatively rapidly (DT(50)air = 6.5 hours derived by the Atkinson method of calculation assuming a hydroxyl radical concentrations of 5x105 radicals/cm(3)). Metazachlor is therefore unlikely to be subject to long range transport. The acute and long-term TERs were above the Annex VI trigger for the acute and short-term risk to birds for all standard scenarios. However the long-term TERs were below the trigger. The suggested refinements were accepted by the experts for the uses of Butisan in oilseed rape. A data gap for further refinement of the risk to insectivorous birds was identified for the use of Fuego in ornamental trees and shrubs. The risk to mammals was assessed as low for the use of Butisan. The long-term TER for herbivorous mammals was below the trigger of 5 for the use of Fuego in ornamentals and a data requirement to refine the risk to herbivorous mammals was identified by the RMS and confirmed by the experts. Algae and higher aquatic plants were the most sensitive groups of organisms tested and a potential high risk to primary producers was indicated in the lower tier risk assessment. Refined risk assessments based on species sensitivity distribution (SSD) and mesocosm endpoints were presented by the applicants. A new risk assessment based on the geometric mean (113.6 jug a.s./L) was submitted by BASF. It was noted in the expert meeting that the tested emergent plants were less sensitive than the submerged plants and hence should not be combined in the SSD or geomean calculation. Based on the endpoints of the 4 submerged plants the geometric mean toxicity value is 40 mu g a.s./L. The number of endpoints (4 submerged species) was considered not sufficient to derive a robust HC5 estimation. Some Member States use a safety factor of 4 in combination with the lower limit HC5. The experts suggested to use the endpoint of 1.67 mu g a.s./L from the mesocosm study (NOAEC of 5 mu g a.s./L with a safety factor of 3) in the risk assessment. A FOCUS step 4 TER calculation was presented for the use of Fuego (0.75 kg a.s./ha). The full FOCUS step 4 scenarios D1, D3, D4, D5 and the part scenario R1 (pond) resulted in a TER above the trigger if a no spray buffer zone of 5 metres was applied. The trigger was not met in the full scenarios D2, R3 and the part scenario R1 (stream). No TER calculations were presented with FOCUSstep 4 PECsw for the use of Butisan (1 kg a.s./ha). However if the regulatory endpoint of 1.67 mu g a.s./L is compared to the FOCUS step 4 PECsw including a no-spray buffer zone of 10 metres than the trigger would be met in all scenarios except D2 and R3 (full scenarios). It is assumed that the use in ornamental trees and shrubs would not lead to higher concentrations of metazachlor in the aquatic environment and hence the risk assessment for oilseed rape covers also the risk from the use in ornamental trees and shrubs. The risk to aquatic organism from the metabolites 479M04, 479M06, 479M08, 479M09, 479M11, 479M12 was assessed as low. The acute and long-term TER values for earthworms were above the trigger for metazachlor and the metabolite 479M04. The long-term TER of 4.8 for metabolite 479M08 was below the trigger of 5. The NOEC used in the TER calculation was based on the highest concentration tested. Therefore the risk to earthworms was considered as addressed. Effects on reproduction of springtails (Folsomia candida) were tested with the two major soil metabolites 479M04, 479M08) and metazachlor formulated as Fuego. The TERs based on PECs from application of 1 kg metazachlor/ha in oilseed rape were markedly above the trigger of 5 indicating a low risk to other soil non-target macro-organisms. Since the DT9O( of 479M04 (BH479-4) and 479M08 (BH479-8) is >365 days a litter-bag study is triggered. No effects were observed in the litter bag study submitted by BASF. The concentrations were lower than the calculated accumulated peak PECsoil values. However the effect on soil micro organisms was <25%, the TERlt for earthworms was >5 (except for the endpoint for 479M08 from a study of MAK-FSG) and the studies with Folsomia candida gave an indication that the risk to soil dwelling arthropods is low. Therefore it was concluded that the risk to soil dwelling macro-organisms and organic matter breakdown is low for the representative uses of metazachlor. TERs for non-target plants based on the endpoints from glasshouse trials were below the trigger of 5. The TER is 6.05 if a no-spray buffer zone of 10 m is applied. Using the test results from the field trials then the TER is >5 for the pre-emergent exposure at 1 m distance from the treated field and the no -spray buffer zone can be reduced to 5m to achieve TERs above 5 for post-emergent exposure. In the studies with the formulation Fuego the lowest endpoints were observed for oat and sugar beet. The TERs were above the trigger of 5 for pre emergent exposure at the standard distance of lm but for the post -emergence exposure a no -spray buffer zone of 5m is required to achieve a TER > 5. The risk to non -target plants from the use in ornamental trees and shrubs is considered as covered by the risk assessment for oilseed rape. No higher drift rates are expected from the use in ornamental since the product is sprayed to reach weeds under the ornamental trees. The risk to bees, non-target arthropods, soil non-target micro-organisms and biological methods of sewage treatment was assessed as low.