Cadusafos is one of the 52 substances of the second stage of the review programme covered by Commission Regulation (EC) No 451/20002, as amended by Commission Regulation (EC) No 1490/20023. 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. Greece being the designated rapporteur Member State submitted the DAR on cadusafos in accordance with the provisions of Article 8(1) of the amended Regulation (EC) No 451/2000, which was received by the EFSA on 1 June 2004. Following a quality check on the DAR, the peer review was initiated on 4 August 2004 by dispatching the DAR for consultation of the Member States and the sole applicant FMC Chemical. 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 discussion of the outcome of the consultation of experts following the procedure set out in Commission Regulation (EC) 451/2000 took place with representatives from the Member States on 9 February 2006 leading to the conclusions set out in the EFSA Conclusion issued on 24 April 2006 (EFSA Scientific Report (2006) 68) Following the Commission Decision of 18 June 2007 (2007/428/EC) 4 concerning the noninclusion of cadusafos in Annex I to Council Directive 91/414/EEC and the withdrawal of authorisations for plant protection products containing that substance, the notifier FMC Chemical made a resubmission application for the inclusion of cadusafos in Annex I in accordance with the provisions laid down in Chapter III of Commission Regulation (EC) No. 33/2008. The resubmission dossier included further data in response to the areas of concern identified in the review report as follows: the potential contamination of groundwater. the operators exposure. the risk to birds and mammals. its possible impact on non-target organisms Greece, being the designated rapporteur Member State, submitted the additional report on cadusafos to the EFSA on 15 October 2008. In accordance with Article 19 of Commission Regulation (EC) No. 33/2008, the EFSA dispatched the additional report to Member States and the notifier for consultation. The comments received were subsequently submitted to the Commission for evaluation. In accordance with Article 20 of Commission Regulation (EC) No. 33/2008, the Commission subsequently requested the EFSA, by letter received on 8 January 2009, to arrange a peer review of the evaluation, i. e. the additional report provided by the rapporteur Member State, and to deliver its conclusion on the risk assessment within 90 days. The peer review was initiated on 14 January 2009 by dispatching the comments received on the additional report to the rapporteur Member State for examination. The rapporteur provided a response to the comments in the reporting table, which was subsequently evaluated by EFSA to identify the remaining issues to be further considered in a series of scientific meetings via teleconferences with Member State experts in March 2009. A final discussion of the outcome of the consultation of experts took place during a written procedure with the Member States in March-April 2009. The EFSA conclusion has therefore been re-issued to update the risk assessment in the areas of identity, physical, chemical and technical properties and methods of analysis, mammalian toxicology, residues, environmental fate and behaviour, and ecotoxicology. The original conclusion from the review was reached on the basis of the evaluation of the representative uses as insecticide and nematicide as presented in the DAR, which comprise application by spraying or via the drip irrigation system to control a range of soil insects and nematodes in potatoes and bananas at application rates of up to 6 kg cadusafos per hectare. In case of potatoes incorporation into soil takes place after the application. It should be noted that during the peer review process the applicant stated that only the use in bananas will be supported in the EU review process. The conclusion of the peer review of the resubmission was reached on the basis of the evaluation of the representative use as insecticide and nematicide, which comprise application via the drip irrigation system to control a range of soil insects and nematodes in bananas at application rates of up to 4 kg cadusafos per hectare. It should be noted that the use on potatoes was not supported in the resubmission application either, and therefore the conclusion has only been updated in relation to the risk assessment of the representative uses presented in the additional report, i.e. only the use on bananas at application rates of up to 4 kg cadusafos per hectare. The risk assessment presented for potatoes has not been updated. The representative formulated product for the evaluation was, Rugby 200 CS., a capsule suspension (CS). Preparations containing cadusafos were registered in Cyprus, France, Greece and Spain. 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 analytical methods are available to monitor cadusafos in food of plant origin, environmental matrices and body fluids and tissues. The absorption of cadusafos is extensive and rapid; the excretion is mainly via urine, without evidence of body accumulation. The acute oral toxicity is high, and the acute inhalation and dermal toxicity are very high. The proposed classification is T+, R26/27 "Very toxic by inhalation and in contact with skin"; T, R25 "Toxic if swallowed". The main effect after short-term oral administration is the decrease of cholinesterase activities in all species. Cadusafos has no genotoxic potential and is not considered to be carcinogenic. In the two-generation rat study, there was no effect on reproductive performance or fertility, and in the rat-and rabbit teratology studies, there was no evidence of teratogenic effects in the absence of maternal toxicity. Supplementary studies were performed due to the introduction of a new impurity in the technical material. The acute and subchronic oral tests revealed no difference in toxicity. The Ames test was negative but not valid. A further assessment of the genotoxic potential of the impurity was required. The Acceptable Daily Intake (ADI) is 0.0004 mg/kg bw/day, the Acceptable Operator Exposure Level (AOEL) is 0.0007 mg/kg bw/day, and the Acute Reference Dose (ARfD) is 0.003 mg/kg bw. The comparison of the oral and dermal LD50 values results in a dermal absorption value of 100%. The operator exposure estimates are based solely on one specific and restricted representative use in bananas, with automatic drip irrigation, work rate of 1 ha/day, application rate of 4 kg a. s./ha, and assuming that the microcapsules in the formulation do not release cadusafos until they are diluted for application. The results are below the AOEL, with the use of gloves, according to the currently used models, which do not apply properly to this particular scenario. Worker and bystander exposures are expected to be very low due to the mode of application by drip irrigation. The metabolism of cadusafos has been investigated on several crops after soil application. The use on potatoes can be considered as adequately covered by these data and the residue definition for this use can be cadusafos only, for both monitoring and risk assessment. The available residue trials in potatoes for Southern Europe are however not sufficient to draw a robust conclusion on the residue levels consumers may be exposed to. The available data suggest that residues are below 0.01 mg/kg, but results from trials in Northern Europe indicate that the currently available data may underestimate the actual situation. Further supervised residue trials should be carried out. For the representative use on bananas, two metabolism studies for this crop were originally submitted, and the data were not sufficient to propose a residue definition. This was due to major deficiencies in the studies, making it impossible to evaluate the possible presence of degradation products still exhibiting the anticholinesterase activity of the parent compound. Therefore, a new metabolism study in bananas was needed, as well as residue trials carried out according to the representative use pattern. The situation for rotational crops has not been addressed by the notifier, although the soil persistence of the compound exceeds the trigger value for conducting uptake and metabolism studies in succeeding crops. Therefore these studies should be requested. Based on the current knowledge of the residue situation in potatoes, the exposure of livestock is very low and metabolism studies in domestic animals do not need to be carried out. Only preliminary acute and chronic exposure assessments could be conducted for the use on potatoes, but these assessments need to be re-examined on the basis of complete and robust data. No MRLs can be proposed at this stage. In the resubmission, only the use on banana is supported with a lower application rate of 4 kg as/ha instead of 6 kg as/ha, and a harvest interval of 90 days instead of 14 days. A new plant metabolism study showed that no significant metabolites are formed. None of the minor metabolites formed will have the anticholinesterase activity of cadusafos. The study confirms that the residue definition is cadusafos only. Overdosed residue trials showed that no significant residues will be present at harvest even with shorter harvest intervals. A TMDI calculation using the EFSA model showed that the highest intakes were < 5% of the ADI. The acute risk assessment gave intakes at < 30 % of the ARfD. The proposed MRL for banana is 0.01* mg/kg. It should be noted however, that cadusafos has two chiral carbons and it is not known if the ratio of the isomers remains the same as the material tested in the mammalian toxicity studies. The available data demonstrate that in soil cadusafos degrades to the minor (< 10% applied radioactivity (AR)) metabolite methyl-2-butyl sulfone5. Mineralisation of the butyl-2-[C-14] radiolabel accounted for 43-71% AR after 90-120 days incubation at 25 degrees C. The values for residues not extracted by acetonitrile/water were 25-32% AR after 90-120 days. In soil cadusafos exhibited moderate persistence and methyl-2-butyl sulfone exhibited low persistence, though this categorisation for methyl-2-butyl sulfone is based only a single experimental DT50 value. In guideline batch soil adsorption studies cadusafos exhibited medium mobility. There was no evidence of pH dependant adsorption. Data on the adsorption of methyl-2-butyl sulfone were not available. As this metabolite accounted for > 5% AR at two consecutive sampling points in a soil route of degradation study, data on its mobility in soil are required to enable a groundwater exposure assessment for this metabolite to be carried out. In sediment water systems cadusafos exhibited moderate persistence and produced no major metabolites. It dissipated by partitioning to sediment, volatilising and mineralising to CO2 (butyl-2-[C-14] radiolabel accounted for 12-18% AR after 100 days incubation at 20 degrees C). Residues not extracted from sediment by acetonitrile/water accounted for only 6-8% AR at 100 days. The available aquatic exposure assessment from the use on bananas (application via drip irrigation) just in Tenerife indicated that surface water exposure and consequently sediment exposure would be negligible. This conclusion is specific to this use in Tenerife and should not be applied to bananas grown elsewhere. The available aquatic exposure assessment from the use on potatoes is appropriate for addressing just the spray drift route of entry to surface water for initial PEC in aquatic systems. Surface water exposure and consequent aquatic risk assessments from the run-off and drainage routes of entry are not available for the potato use. The available FOCUS groundwater modelling for bananas in Tenerife for the parent cadusafos and for the metabolite methyl-2-butyl sulfone are not satisfactory, and the potential for groundwater contamination is therefore currently unclear. New groundwater modelling is therefore required for cadusafos and for the soil metabolite methyl-2-butyl sulfone. Cadusafos is moderately volatile and volatilisation will contribute to dissipation from soil and water. However, cadusafos is not expected to be subject to long-range transport via the upper atmosphere due to a relatively rapid calculated photochemical oxidative degradation rate with hydroxyl radicals. In the first-tier assessment an acute and long-term risk was identified for insectivorous birds. A risk was also identified for earthworm-eating birds and mammals, as well as for fish-eating birds and mammals for the use in potatoes. Since the use in potatoes was withdrawn by the applicant, the refinements of the risk to birds and mammals from this use were not further considered. For the use in banana plantations a high risk was identified for insectivorous and earthwormeating birds and mammals in a first-tier risk assessment. The proposed refinement was not accepted by the experts due to the lack of supporting data. However, due to the mode of application (drip-irrigation), only 16% of the in-field area is treated, leaving the majority of food items uncontaminated (the exposure of epigaec insects was considered negligible). This information could be used in a weight of evidence approach for a qualitative risk assessment. Cadusafos is very toxic to fish and aquatic invertebrates. The assessment indicates a high risk. However, for the specific use in banana plantations in Tenerife, the risk to aquatic organisms is considered low based on negligible contamination of surface water. The toxicity to bees is high, but since for the proposed uses application will be to bare soil, the risk is considered low. No in-field exposure of leaf-dwelling non-target arthropods is expected from the evaluated uses. For the application of cadusafos by drip irrigation to banana plants no off-field exposure is expected. No new data was provided with the resubmission dossier. No further data was considered necessary for the use in banana plantations, since only 16% of the in-field area is treated leaving enough uncontaminated refuges, which would allow the recolonisation of the treated area. A high acute and long-term risk was identified for earthworms. The field study conducted in the United Kingdom was considered not appropriate for the risk assessment for banana plantations. A data gap was identified to provide information on the potential for recolonisation of earthworms in the treated area of banana plantations, or alternatively, a study on effects on earthworm populations in banana plantations. A study with Collembola and mites was required to address the risk to other soil macroorganisms. No study with Collembola was provided with the resubmission dossier. However, the experts considered further data not necessary for banana plantations, since only 16% of the in-field area is treated leaving enough uncontaminated refuges, which would allow the recolonisation of the treated area. The risk to soil micro-organisms and biological methods of sewage treatment plants is low. For the drip irrigation use in banana no off-crop exposure is expected, and hence the risk to non-target plants is considered low.
