Formetanate is one of the 52 substances of the second stage of the review programme covered by Commission Regulation (EC) No 451/20001, as amended by Commission Regulation (EC) No 1490/20022. This Regulation requires the European Food Safety Authority (EFSA) to organise 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. Italy being the designated rapporteur Member State submitted the DAR on formetanate in accordance with the provisions of Article 8(1) of the amended Regulation (EC) No 451/2000, which was received by the EFSA on 13 July 2004. Following a quality check on the DAR, the peer review was initiated on 23 July 2004 by dispatching the DAR for consultation of the Member States and the sole applicant Margarita Internacional. Subsequently, the comments received on the DAR were examined by the rapporteur Member State and the need for additional data was agreed in an evaluation meeting on 9 February 2005. Remaining issues as well as further data made available by the notifier upon request were evaluated in a series of scientific meetings with Member State experts in June and July 2005. A final discussion of the outcome of the consultation of experts took place with representatives from the Member States on 6 April 2006 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 acaricide and insecticide comprise broadcast spraying to control the thrips and mites in tomatoes and ornamental shrubs at an application rate of 500 g formetanate per hectare. Formetanate can be as acaricide and insecticide. The representative formulated product for the evaluation was " Dicarzol 500 SG" ("AEB036056 00 SG58 A200"), a water soluble granule (SG), registered in France, Portugal and Spain. Adequate methods are available to monitor all compounds given in the respective residue definition, i. e. formetanate and its salts in food of plant origin, soil and water. In the case of air it should be noted that the analytical method is not specific as required in, because it is not possible to differentiate between residue of formetanate and its salts. Also an analytical method for blood (plasma) is available to cover Annex point 4.2.5 of Directive 96/46/EC. Only single methods for the determination of residues are available since a multi-residue-method like the German S19 or the Dutch MM1 is not applicable due to the nature of the residues. 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. Formetanate hydrochloride is rapidly and extensively absorbed after oral administration. It is mainly excreted in urine. No tendency for bioaccumulation was observed. It is highly toxic after oral administration and by inhalation, not toxic after dermal exposure, not irritant, but a skin sensitizer. The proposed classification is: T+, R26/28 " Highly toxic by inhalation and if swallowed"; Xi, R43 " May cause sensitisation by skin contact". Short term toxicity is manifested by cholinesterase inhibition in all species, the dog being the most sensitive. Formetanate hydrochloride has a mutagenic potential in vitro, but not in vivo, and there is no evidence of carcinogenicity in rats and mice. No reproductive or teratogenic effects have been observed in rats and rabbits. All the tested metabolites are less toxic than formetanate hydrochloride. The kinetics of cholinesterase inhibition was studied in female rats and in dogs. The Acceptable Daily Intake (ADI) is 0.004 mg/kg bw/day, the Acceptable Operator Exposure Level (AOEL) is 0.004 mg/kg bw/day, and the Acute Reference Dose (ARfD) is 0.005 mg/kg bw. All the reference values were derived with a safety factor of 100. According to the German model, the estimated operator exposure during field use is 55% of the AOEL with PPE for the tractor mounted scenario, and 99% of the AOEL with PPE and RPE for the hand held scenario. According to calculations with the German and UK models, application with automated gantry sprayers in glasshouse gives an operator exposure of 31 and 8.3% of the systemic AOEL with PPE. The worker exposure (during tomatoes harvest) and the bystander exposure estimates are below the AOEL. The metabolism of formetanate in plants has been fully elucidated and proceeds through hydrolysis steps. The parent compound has been identified as the major constituent of the residue on various crops and for various PHIs. The identified metabolites are less toxic than the parent compound. Therefore the residue definition can be restricted to parent compound only, for both risk assessment and monitoring. Under processing, formetanate is degraded at temperature of 100 degrees C or higher to a less toxic compound, 3-hydroxyformanilide. The processed commodities obtained after boiling or sterilisation have a significantly lower concentration of formetanate than raw tomatoes. There is no exposure of livestock to formetanate residues. The soil uptake by rotational crops is minimal and there is no need for setting plant back restriction. The chronic exposure of the consumer is well below the ADI of formetanate. Acute intake calculations have indicated a potential acute risk for infants and toddlers resulting from the consumption of treated tomatoes grown under glass house conditions. The level of the proposed MRL in tomatoes, which is significantly higher than the level considered in exposure assessments, causes still higher concern in terms of consumer safety. In acidic soils the main sink for the dissipation of formetanate was the formation of unextracted residues with mineralisation to CO2 accounting for 2.7-13.7% of the applied radioactivity (AR) at 41 to 91 days. However in an alkaline soil (pH 7.2), after 59 days mineralisation to CO2 accounted for 80% AR with unextracted residue accounting for only 9.2% AR. No major (> 10% AR) breakdown products were identified in methanol or water extracts. The use of a more harsh methanol Soxhlet extraction released more radioactivity from soil samples, but was also shown to hydrolyse formetanate to the major breakdown products 3-FAPMC(3)53-58% AR after 28 days. No major metabolites were present in sediment extracts. In water the major metabolites were 3-HF (max. 39% AR), 3-FAPMC (max. 34% AR), 3-AP (max. 23% AR), 3-APMC (max. 13% AR) and 3-HPDMF (max. 12% AR). These maximum concentrations all occurred between 0.5 and 7 days. These metabolites exhibited very low to low persistence in the water. The first tier risk assessment for birds indicates acute and long term risk to birds. Short-term TERs were above the trigger but were based on a LC50 value that was questioned by the experts' meeting due to strong food avoidance observed in the study. A refined acute and long-term assessment is available based on measured residues in food items and selected focal species. Due to the late submission date this assessment has not been peer reviewed or discussed by Member States. It should be noted that the refined acute assessment is based on the questioned LC50 value from a short-term dietary study. Also for mammals the first tier assessment indicated an acute risk, while the long-term risk was considered low. A refined assessment of the acute risk for different focal species taking recommendations given in the PPR Panel opinions for pirimicarb and metamidophos into account is available but has not been peer reviewed. Therefore, no final conclusion on the risk to birds and mammals can be reached at this stage. Formetanate is very toxic to aquatic invertebrates, particularly cladocerans. Based on the results from an available microcosm study the risk is however considered to be low for the evaluated representative uses. Toxicity towards bees and other non-target arthropods is high. Formetanate should not be applied later than two weeks before flowering to protect bees. Even though a potential for in-field recolonisation has been demonstrated, the risk to sensitive nontarget arthropods off-field is high even at a distance of 50 m from the field border. Further data is required to fully address the impact off-field and the potential for recolonisation. Furthermore a higher tier study with T. pyri is required. The risk to earthworms, other soil macro-and microorganisms, flora and biological methods of sewage treatment is considered as low., 3-APMC4 and 3-HF5. As it is not possible to know if the radioactive residue in soil released by methanol Soxhlet extraction was present as parent formetanate or breakdown products, the available environmental exposure assessments have been carried out assuming all the Soxhlet extractable radioactivity was parent formetanate and also, as a worst case assuming 100% conversion of applied formetanate to the breakdown products identified in extracts, which were 3-FAPMC (max 20.2% AR), 3-APMC (max 50.6% AR), 3-HF (max 17.6% AR), 3-HPDMF6 (max 23% AR in a photolysis study, utilising oven dried soil), and 3-AP7 (max 5.7% AR). Formetanate exhibits low to moderate persistence in soil. 3-FAPMC exhibits very low persistence, 3-AMPC and 3-HF very low to low persistence with 3-HPDMF exhibiting low persistence in soil. Formetanate exhibits high to low soil mobility and as it is a basic substance with a pKa of 8.1 would be expected to be more mobile under high soil pH conditions. However the higher mobility under alkali conditions is unlikely to lead to an increased risk of formetanate leaching due to the more rapid hydrolytic degradation of formetanate under alkali soil conditions. There was no evidence that the adsorption of any of the soil metabolites was pH dependant. 3-AMPC exhibits very high to high mobility, 3-FAPMC exhibits high mobility, 3-HF exhibits medium mobility and 3-HPDMF exhibits medium to low mobility in soil. Based on the evidence from FOCUS groundwater scenario modelling for the notified intended uses, the potential for groundwater exposure by formetanate or its potential soil metabolites 3-FAPMC, 3-HPDMF, 3-HF and 3-APMC above the parametric drinking water limit of 0.1 mu g/L, is considered low. In natural sediment water systems (laboratory) 20 degrees C formetanate dissipated rapidly from water from a combination of adsorption to sediment and rapid degradation, with formetanate exhibiting very low persistence in both water and sediment. Mineralisation to CO2 accounted for 14-30% AR after 28-70 days, with unextracted sediment residues being the major sink in the material balance accounting for 53-58% AR after 28 days. No major metabolites were present in sediment extracts. In water the major metabolites were 3-HF (max. 39% AR), 3-FAPMC (max. 34% AR), 3-AP (max. 23% AR), 3-APMC (max. 13% AR) and 3-HPDMF (max. 12% AR). These maximum concentrations all occurred between 0.5 and 7 days. These metabolites exhibited very low to low persistence in the water. The first tier risk assessment for birds indicates acute and long term risk to birds. Short-term TERs were above the trigger but were based on a LC50 value that was questioned by the experts' meeting due to strong food avoidance observed in the study. A refined acute and long-term assessment is available based on measured residues in food items and selected focal species. Due to the late submission date this assessment has not been peer reviewed or discussed by Member States. It should be noted that the refined acute assessment is based on the questioned LC50 value from a short-term dietary study. Also for mammals the first tier assessment indicated an acute risk, while the long-term risk was considered low. A refined assessment of the acute risk for different focal species taking recommendations given in the PPR Panel opinions for pirimicarb and metamidophos into account is available but has not been peer reviewed. Therefore, no final conclusion on the risk to birds and mammals can be reached at this stage. Formetanate is very toxic to aquatic invertebrates, particularly cladocerans. Based on the results from an available microcosm study the risk is however considered to be low for the evaluated representative uses. Toxicity towards bees and other non-target arthropods is high. Formetanate should not be applied later than two weeks before flowering to protect bees. Even though a potential for in-field recolonisation has been demonstrated, the risk to sensitive nontarget arthropods off-field is high even at a distance of 50 m from the field border. Further data is required to fully address the impact off-field and the potential for recolonisation. Furthermore a higher tier study with T. pyri is required. The risk to earthworms, other soil macro-and microorganisms, flora and biological methods of sewage treatment is considered as low.
