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

Penoxsulam is a new active substance for which in accordance with Article 6 (2) of Council Directive 91/414/EEC2 Italy received an application from Dow AgroScience for inclusion in Annex I to Directive 91/414/EEC. Complying with Article 6 of Directive 91/414/EEC, the completeness of the dossier was evaluated and confirmed by Commission Decision 2004/131/EC . Following the agreement between the EU-Commission and the EFSA for the EFSA to organise a peer review of those new active substances for which the decision on the completeness of the dossier had been published after June 2002, the designated rapporteur Member State Italy made the report of its initial evaluation of the dossier on penoxsulam, hereafter referred to as the draft assessment report (DAR), available on 10 February 2005. The peer review was initiated on 16 February 2005 by dispatching the DAR for consultation of the Member States and the applicant. Subsequently, the comments received on the DAR were examined by the rapporteur Member State and the need for additional data was agreed by EFSA. Remaining 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 September 2006 and January 2007. A final discussion of the outcome of the consultation of experts took place during a written procedure with Member States in April 2009 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 herbicide on rice for the control of Echinochloa crus-galli, sedges and broad leaf weeds 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 ` penoxsulam DE-638' (GF-657), an oil dispersion (OD) containing 20.4 g/l of penoxsulam. 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. In the mammalian metabolism studies, penoxsulam was rapidly and almost completely absorbed upon oral administration. There was no evidence of bioaccumulation. Excretion was rapid, but dose and sex dependent as excretion was primarily observed via faeces in males and primarily excreted in urine in females. Penoxsulam was bio-transformed to a large number of metabolites; however the majority of the radioactivity was eliminated as unchanged parent compound. Plant and environmental metabolites BST4 and BSTCA5 were not identified in the rat metabolism studies. Toxicological information was lacking on the metabolite BSTCA to conclude on its relevance as a plant metabolite, moreover, it cannot be ruled out that BSTCA is also relevant according to the guidance document on the relevance of metabolites in groundwater. The acute toxicity of penoxsulam was low by the oral, dermal and inhalation route; slight skin and eye irritation were observed, but no potential for skin sensitisation. The dog was found to be the most sensitive species with the kidneys as the main target organ; the overall short-term NOAEL in dogs was 18 mg/kg bw/day. Long-term toxicity reflected the same target organ observed in the short-term studies: the liver in mice and the kidneys in rats. The relevant long-term NOAEL was the dose level of 5 mg/kg bw/day from the 2-year rat study. No potential for genotoxicity, carcinogenicity or neurotoxicity was observed. No effect was seen on the reproductive performance and parameters; no developmental effect was observed either in rats. In rabbits, a slight increase in resorption rate parameters was associated with maternal toxicity, evidenced by gastro-intestinal upset and decreased body weight gain during the middle gestation. The Acceptable Daily Intake (ADI) of penoxsulam was 0.05 mg/kg bw/day based on the NOAEL from the 2-year rat study and applying a safety factor of 100; the Acceptable Operator Exposure Level (AOEL) was 0.18 mg/kg bw/day based on the short-term dog studies and a safety factor of 100, no correction factor was needed to account for enteral resorption; no Acute Reference Dose (ARfD) was allocated. Dermal absorption was 10% for both the concentrate and in-use spray dilution of the representative formulation. The level of operator exposure for a maximum application rate of 0.04 kg penoxsulam/ha in rice was below the AOEL even without the use of personal protective equipment (PPE) according to both the German7 and the UK POEM8 models. Worker and bystander exposure were considered negligible. A metabolism study in rice demonstrated that following foliar application of penoxsulam the total residues decreased rapidly to insignificant levels present at harvest of the crop. Therefore, the residue definition in rice grain was proposed as penoxsulam by default. In supervised residue trials penoxsulam was found to be always below the Limit of Quantification of 0.01 mg/kg in rice grain, while in rice straw residues ranged up to 0.08 mg/kg. Consequently, an MRL for grain was proposed at 0.01 mg/kg, which is the lowest validated level of the analytical method. For straw an MRL is not required. Rice may be grown in monoculture but also in rotation with other crops. A submitted confined crop rotation study showed that after a plant back interval of 90 days low residues could still be found in some crops. Other plant back intervals were not investigated. Moreover, a metabolite BSTCA, identified at significant levels in rotated crops, was neither found in primary crop metabolism nor in rat metabolism. The toxicological relevance of this metabolite for consumer risk assessment could not be addressed. As rotation practices in Member States seem to differ and the submitted data on rotational crops were limited, a final conclusion on the relevance of residues in rotated crops other than cereals could not be reached. Hence the experts agreed that further elaboration on the issue is required. A data requirement for further rotational crop data is proposed. If only the scenarios of rice grown in monoculture and of rice rotated with other cereals are considered it can be concluded that exposure to livestock is not expected to be significant. Under these conditions, on the basis of the submitted animal metabolism studies, residues in food of animal origin are expected to occur at extremely low levels that would not be appropriate for monitoring. The experts therefore agreed that, for the time being, it would not be necessary to propose a residue definition and MRLs for food of animal origin. However, it should be noted that the assessment is not finalised with regard to potential livestock exposure to residues in rotational crops other than cereals. Consumer exposure to residues of penoxsulam in rice grain is insignificant and thus in a chronic risk assessment intakes were well below to ADI. No acute assessment was conducted as an ARfD was not allocated. However, the consumer risk assessment cannot be finalised with regard to residues of metabolite BSTCA since a lack of sufficient occurrence data and toxicological data was identified. As BSTCA may also occur in drinking water derived from ground water at a level > 0.1 mu g/L, total consumer exposure to BSTCA has to be assessed in order to conclude on the consumer risk assessment. Based on the available environmental fate and behaviour studies in soil and 2 field studies in rice paddies, penoxsulam and the breakdown products 5-OH-penoxsulam (max 40.5% applied radioactivity (AR) in soil) and BSTCA (max 53% AR in soil), were concluded as requiring environmental exposure assessments. In a sterilised laboratory aqueous photolysis study TPSA, 2amino-TP and 5-OH-2-amino-TP12 were major metabolites but it was concluded that these did not need to be assessed, as though sought, they were not detected in relevant field studies in rice paddies. Penoxsulam and 5-OH-penoxsulam were characterised as exhibiting moderate persistence in soil with BSTCA exhibiting medium to high persistence. Additionally in aerobic natural sediment water systems the metabolites PCA-5-OH and OH-BSTCA were formed at up to 16% AR (sum of both compounds) in sediment, so exposure assessments were necessary for these metabolites and are available. In the aerobic laboratory incubations mineralisation of both the phenyl and the 2-triazolopyrimidine rings to carbon dioxide was low accounting for only 0.3-2.4 % AR after 99 to 120 days. The formation of unextractable residues was a sink, accounting for 10-16 % AR in aerobic soil (same radiolabels) after 120 days and 21-58 % AR in aerobic natural sediment water studies after 99 days. Penoxsulam was characterised as exhibiting high to medium mobility, 5-OH-penoxsulam high mobility and BSTCA very high to medium mobility. Further details are necessary regarding a refined higher tier surface water exposure assessment that included definitions of novel scenarios, not prescribed by EU MED-Rice (2003) guidance15. It can be concluded that the potential for penoxsulam or its metabolite 5-OH-penoxsulam to contaminate vulnerable groundwater above the parametric drinking water limit of 0.1 mu g/L from the applied for intended uses is low. For the metabolite BSTCA the potential to contaminate vulnerable groundwater above the parametric drinking water limit of 0.1 mu g/L is low in situations represented by the MED-Rice clay scenario. However in situations represented by the MED-Rice sand scenario, BSTCA may be present in vulnerable groundwater at > 0. 1 mu g/L (calculations indicate concentrations up to 0.23 mu g/L). Therefore a non-relevance assessment for BSTCA was triggered. In the risk assessment for birds, species representing insectivorous birds (wren), omnivorous birds eating large aquatic insects (mallard), omnivorous birds eating aquatic plants (mallard), large herbivorous birds (geese) and piscivorous birds (heron) were considered. All TER values were well above the relevant Annex VI trigger indicating a low risk to birds from the use of penoxsulam in rice paddies. Water vole (small herbivorous mammal), water shrew (eating aquatic invertebrates) and otter (eating fish and amphibians) were selected as focal species for the " in-field" risk assessment for mammals. The lowest TER obtained was 25 for the long-term risk to water vole. Since this was above the relevant Annex VI trigger a low risk was concluded. For both birds and mammals the exposure from intake of contaminated paddy water was included in the estimation of the daily dose by simply adding the drinking water dose to the dietary dose. The log P-ow for penoxsulam is <3 and also the surface water metabolites were considered to have a log P-ow<3, hence the potential for bioaccumulation and secondary poisoning was considered as low. Penoxsulam was classified as very toxic to aquatic organisms. The first tier risk assessment for algae and aquatic plants, based on PECsw in the "off-field" area, gave TERs of 46 and 2.9, respectively. An assessment was provided for fish and aquatic invertebrates in paddy water. No assessment was provided for algae or higher plants in paddy water, considering the herbicidal activity of penoxsulam. The lowest acute TER value was 202, which was obtained for Daphnia using the EC50 for the formulation. The lowest long-term TER was 83. It was concluded that the first tier risk to aquatic plants in the "off-field" area was high. Refinements based on a higher tier study with Lemna were not accepted in the peer review, and the risk to aquatic plants remains to be addressed. The risk to aquatic organisms from metabolites was addressed, as was the risk from bioaccumulation (log P-ow<3). The risk to bees, non-target arthropods, earthworms, soil micro-organisms and non-target plants was assessed as low.