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Peer review of the pesticide risk assessment of the active substance phosmet

2021; Wiley; Volume: 19; Issue: 3 Linguagem: Inglês

10.2903/j.efsa.2021.6237

1831-4732

Maria Anastassiadou, Maria Arena, Domenica Auteri, Alba Brancato, László Bura, Luis Carrasco Cabrera, Eugenia Chaideftou, Arianna Chiusolo, Federica Crivellente, Chloé De Lentdecker, Mark Egsmose, Gabriella Fait, Luna Greco, Alessio Ippolito, Frédérique Istace, Samira Jarrah, Dimitra Kardassi, Renata Leuschner, Alfonso Lostia, Christopher Lythgo, Oriol Magrans, Iris Mangas, Ileana Miron, Tünde Molnar, Laura Padovani, Juan Manuel Parra Morte, Ragnor Pedersen, Hermine Reich, Miguel Santos, Rachel Sharp, Csaba Szentes, Andrea Terron, Manuela Tiramani, Bénédicte Vagenende, Laura Villamar‐Bouza,

Pesticide Exposure and Toxicity

EFSA JournalVolume 19, Issue 3 e06237 Conclusion on Pesticides Peer ReviewOpen Access Peer review of the pesticide risk assessment of the active substance phosmet European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) pesticides.peerrevieew@efsa.europa.eu Correspondence:pesticides.peerrevieew@efsa.europa.euSearch for more papers by this authorMaria Anastassiadou, Maria AnastassiadouSearch for more papers by this authorMaria Arena, Maria ArenaSearch for more papers by this authorDomenica Auteri, Domenica AuteriSearch for more papers by this authorAlba Brancato, Alba BrancatoSearch for more papers by this authorLaszlo Bura, Laszlo BuraSearch for more papers by this authorLuis Carrasco Cabrera, Luis Carrasco CabreraSearch for more papers by this authorEugenia Chaideftou, Eugenia ChaideftouSearch for more papers by this authorArianna Chiusolo, Arianna ChiusoloSearch for more papers by this authorFederica Crivellente, Federica CrivellenteSearch for more papers by this authorChloe De Lentdecker, Chloe De LentdeckerSearch for more papers by this authorMark Egsmose, Mark EgsmoseSearch for more papers by this authorGabriella Fait, Gabriella FaitSearch for more papers by this authorLuna Greco, Luna GrecoSearch for more papers by this authorAlessio Ippolito, Alessio IppolitoSearch for more papers by this authorFrederique Istace, Frederique IstaceSearch for more papers by this authorSamira Jarrah, Samira JarrahSearch for more papers by this authorDimitra Kardassi, Dimitra KardassiSearch for more papers by this authorRenata Leuschner, Renata LeuschnerSearch for more papers by this authorAlfonso Lostia, Alfonso LostiaSearch for more papers by this authorChristopher Lythgo, Christopher LythgoSearch for more papers by this authorOriol Magrans, Oriol MagransSearch for more papers by this authorIris Mangas, Iris MangasSearch for more papers by this authorIleana Miron, Ileana MironSearch for more papers by this authorTunde Molnar, Tunde MolnarSearch for more papers by this authorLaura Padovani, Laura PadovaniSearch for more papers by this authorJuan Manuel Parra Morte, Juan Manuel Parra MorteSearch for more papers by this authorRagnor Pedersen, Ragnor PedersenSearch for more papers by this authorHermine Reich, Hermine ReichSearch for more papers by this authorMiguel Santos, Miguel SantosSearch for more papers by this authorRachel Sharp, Rachel SharpSearch for more papers by this authorCsaba Szentes, Csaba SzentesSearch for more papers by this authorAndrea Terron, Andrea TerronSearch for more papers by this authorManuela Tiramani, Manuela TiramaniSearch for more papers by this authorBenedicte Vagenende, Benedicte VagenendeSearch for more papers by this authorLaura Villamar-Bouza, Laura Villamar-BouzaSearch for more papers by this author European Food Safety Authority (EFSA), Corresponding Author European Food Safety Authority (EFSA) pesticides.peerrevieew@efsa.europa.eu Correspondence:pesticides.peerrevieew@efsa.europa.euSearch for more papers by this authorMaria Anastassiadou, Maria AnastassiadouSearch for more papers by this authorMaria Arena, Maria ArenaSearch for more papers by this authorDomenica Auteri, Domenica AuteriSearch for more papers by this authorAlba Brancato, Alba BrancatoSearch for more papers by this authorLaszlo Bura, Laszlo BuraSearch for more papers by this authorLuis Carrasco Cabrera, Luis Carrasco CabreraSearch for more papers by this authorEugenia Chaideftou, Eugenia ChaideftouSearch for more papers by this authorArianna Chiusolo, Arianna ChiusoloSearch for more papers by this authorFederica Crivellente, Federica CrivellenteSearch for more papers by this authorChloe De Lentdecker, Chloe De LentdeckerSearch for more papers by this authorMark Egsmose, Mark EgsmoseSearch for more papers by this authorGabriella Fait, Gabriella FaitSearch for more papers by this authorLuna Greco, Luna GrecoSearch for more papers by this authorAlessio Ippolito, Alessio IppolitoSearch for more papers by this authorFrederique Istace, Frederique IstaceSearch for more papers by this authorSamira Jarrah, Samira JarrahSearch for more papers by this authorDimitra Kardassi, Dimitra KardassiSearch for more papers by this authorRenata Leuschner, Renata LeuschnerSearch for more papers by this authorAlfonso Lostia, Alfonso LostiaSearch for more papers by this authorChristopher Lythgo, Christopher LythgoSearch for more papers by this authorOriol Magrans, Oriol MagransSearch for more papers by this authorIris Mangas, Iris MangasSearch for more papers by this authorIleana Miron, Ileana MironSearch for more papers by this authorTunde Molnar, Tunde MolnarSearch for more papers by this authorLaura Padovani, Laura PadovaniSearch for more papers by this authorJuan Manuel Parra Morte, Juan Manuel Parra MorteSearch for more papers by this authorRagnor Pedersen, Ragnor PedersenSearch for more papers by this authorHermine Reich, Hermine ReichSearch for more papers by this authorMiguel Santos, Miguel SantosSearch for more papers by this authorRachel Sharp, Rachel SharpSearch for more papers by this authorCsaba Szentes, Csaba SzentesSearch for more papers by this authorAndrea Terron, Andrea TerronSearch for more papers by this authorManuela Tiramani, Manuela TiramaniSearch for more papers by this authorBenedicte Vagenende, Benedicte VagenendeSearch for more papers by this authorLaura Villamar-Bouza, Laura Villamar-BouzaSearch for more papers by this author First published: 17 March 2021 https://doi.org/10.2903/j.efsa.2021.6237Citations: 2 Requestor: European Commission Question number: EFSA-Q-2016-00293 Amendment: A point in the bird and mammals section (ecotoxicoly, p. 12) has been now amended. The conclusion is slightly changed for two focal species, but it does not have any impact on the identification of the critical area of concern. Acknowledgements: EFSA wishes to thank the rapporteur Member State, Spain, for the preparatory work on this scientific output. Approved: 18 August 2020 The scientific output published here may be subject to adaptations pending the finalisation of the confidentiality decision making process. AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Spain, and co-rapporteur Member State, Greece, for the pesticide active substance phosmet and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of phosmet as an insecticide on citrus fruits, pome fruits, peaches/nectarines and potatoes (field uses). The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified. Summary Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659, lays down the procedure for the renewal of the approval of active substances submitted under Article 14 of Regulation (EC) No 1107/2009. The list of those substances is established in Commission Implementing Regulation (EU) No 686/2012. Phosmet is one of the active substances listed in Regulation (EU) No 686/2012. In accordance with Article 1 of Regulation (EU) No 844/2012, the rapporteur Member State (RMS), Spain, and co-rapporteur Member State (co-RMS), Greece, received an application from Gowan Comércio Internacional e Serviços, Limitada for the renewal of approval of the active substance phosmet. In addition, Gowan Comércio Internacional e Serviços, Limitada submitted applications for maximum residue levels (MRLs), as referred to in Article 7 of Regulation (EC) No 396/2005. An initial evaluation of the dossier on phosmet was provided by the RMS in the renewal assessment report (RAR) and subsequently, a peer review of the pesticide risk assessment on the RMS evaluation was conducted by EFSA in accordance with Article 13 of Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The following conclusions are derived. The uses of phosmet according to the representative uses as an insecticide on citrus fruits, pome fruits, peaches/nectarines and potatoes, as proposed at EU level result in a sufficient insecticidal efficacy against the target pests. The assessment of the data package revealed no issues that could not be finalised or that need to be included as critical areas of concern with respect to identity, physical/chemical properties and analytical methods. In the area of mammalian toxicology, the lack of a developmental neurotoxicity study (data gap) led to an issue that could not be finalised. Critical areas of concern were identified since the non-dietary exposure estimates (i.e. for operator, worker, bystander and resident) for all representative uses according to the GAP table were above the (A)AOEL even with the use of personal protective equipment or application of available mitigation measures in the EFSA calculator. In the section of residues, the provisional dietary exposure estimates for consumers exceeded the acceptable daily intake (ADI) and the acute reference dose (ARfD) for all representative uses assessed, leading to a critical area of concern. MRLs were not proposed for the representative uses in citrus, pome fruit, peaches/nectarines and potato. It is noted that residues at the level of the MRL default value of 0.01 mg/kg would also exceed the ARfD for several of the crops assessed. The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at EU level for the representative uses. In the area of ecotoxicology critical areas of concern have been identified for birds (reproductive risk), wild mammals (reproductive risk), aquatic invertebrates (acute and chronic risk), honey bees (acute risk) and non-target arthropods (in-field and off-field). Phosmet does not meet the criteria for endocrine disruption for humans and non-target organisms. Background Commission Implementing Regulation (EU) No 844/20121, as amended by Commission Implementing Regulation (EU) No 2018/16592, (hereinafter referred to as ‘the Regulation’), lays down the provisions for the procedure of the renewal of the approval of active substances, submitted under Article 14 of Regulation (EC) No 1107/20093. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States, the applicant and the public on the initial evaluation provided by the rapporteur Member State (RMS) and/or co-rapporteur Member State (co-RMS) in the renewal assessment report (RAR), and the organisation of an expert consultation where appropriate. In accordance with Article 13 of the Regulation, unless formally informed by the European Commission that a conclusion is not necessary, EFSA is required to adopt a conclusion on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009 within 5 months from the end of the period provided for the submission of written comments, subject to an extension of an additional 3 months where additional information is required to be submitted by the applicant in accordance with Article 13(3). Furthermore, in accordance with Article 13(3a), where the information available in the dossier is not sufficient to conclude the assessment on whether the approval criteria for endocrine disruption are met, additional information can be requested to be submitted in a period of minimum 3 months, not exceeding 30 months, depending on the type of information requested. In accordance with Article 1 of the Regulation, the RMS, Spain, and co-RMS, Greece, received an application from Gowan Comércio Internacional e Serviços, Limitada for the renewal of approval of the active substance phosmet. In addition, Gowan Comércio Internacional e Serviços, Limitada submitted applications for maximum residue levels (MRLs) as referred to in Article 7 of Regulation (EC) No 396/20054. Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the co-RMS (Greece), the European Commission and EFSA about the admissibility. The RMS provided its initial evaluation of the dossier on phosmet in the RAR, which was received by EFSA on 29 September 2017 (Spain, 2017). The RAR included a proposal to set MRLs, submitted under Article 7 of Regulation (EC) No 396/2005. In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicant, Gowan Comércio Internacional e Serviços, Limitada, for consultation and comments on 7 December 2017. EFSA also provided comments. In addition, EFSA conducted a public consultation on the RAR. EFSA collated and forwarded all comments received to the European Commission on 6 February 2018. At the same time, the collated comments were forwarded to the RMS for compilation and evaluation in the format of a reporting table. The applicant was invited to respond to the comments in column 3 of the reporting table. The comments and the applicant's response were evaluated by the RMS in column 3. The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 13(3) of the Regulation were considered in a telephone conference between EFSA, the RMS and co-RMS on 14 November 2018. On the basis of the comments received, the applicant's response to the comments and the RMS's evaluation thereof, it was concluded that additional information should be requested from the applicant, and that EFSA should conduct an expert consultation in the areas of mammalian toxicology, residues, environmental fate and behaviour and ecotoxicology. The outcome of the telephone conference, together with EFSA's further consideration of the comments, is reflected in the conclusions set out in column 4 of the reporting table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in an expert consultation, were compiled by EFSA in the format of an evaluation table. The conclusions arising from the consideration by EFSA, and as appropriate by the RMS, of the points identified in the evaluation table, together with the outcome of the expert consultation and the written consultation on the assessment of additional information, where these took place, were reported in the final column of the evaluation table. A final consultation on the conclusions arising from the peer review of the risk assessment and the MRL application took place with Member States via a written procedure in June 2020. This conclusion report summarises the outcome of the peer review of the risk assessment of the active substance and the representative formulation, evaluated on the basis of the representative uses of phosmet as an insecticide on citrus fruits, pome fruits, peaches/nectarines and potatoes, as proposed by the applicant. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the RAR and considered during the peer review are presented in the conclusion. MRLs were assessed in peaches/nectarines. A list of the relevant end points for the active substance and the formulation is provided in Appendix A. A key supporting document to this conclusion is the peer review report (EFSA, 2020), which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The peer review report comprises the following documents, in which all views expressed during the course of the peer review, including minority views, where applicable, can be found: the comments received on the RAR; the reporting table (15 November 2018); the evaluation table (17 August 2020); the report(s) of the scientific consultation with Member State experts (where relevant); the comments received on the assessment of the additional information (where relevant); the comments received on the draft EFSA conclusion. Given the importance of the RAR, including its revisions (Spain, 2020), and the peer review report, both documents are considered as background documents to this conclusion and thus are made publicly available. It is recommended that this conclusion and its background documents would not be accepted to support any registration outside the EU for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based. The active substance and the formulated product Phosmet is the ISO common name for O,O-dimethyl S-phthalimidomethyl phosphorodithioate or N-{[(dimethoxyphosphinothioyl)thio]methyl}phthalimide (IUPAC). The representative formulated product for the evaluation was ‘Imidan 50 WP’, a wettable powder (WP) containing 500 g/kg phosmet. The representative uses evaluated were foliar spray applications for the control of a wide variety of pests, of which Lepidoptera, Coleoptera, Thysanoptera and Hemiptera, and among these mostly scales, and Diptera, mostly fruit flies on citrus, pome fruits, peaches/nectarines and potatoes. Full details of the GAPs can be found in the list of end points in Appendix A. Data were submitted to conclude that the use of phosmet according to the representative uses proposed at EU level results in a sufficient insecticidal efficacy against the target organisms, following the guidance document SANCO/2012/11251-rev. 4 (European Commission, 2014b). A data gap has been identified for a search of the scientific peer-reviewed open literature on the active substance and its relevant metabolites, dealing with side effects on health, the environment and non-target species and published within the 10 years before the date of submission of the dossier, to be conducted and reported in accordance with EFSA guidance on the submission of scientific peer-reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (EFSA, 2011). RMS did not agree and considered the literature search submitted by applicant acceptable. Conclusions of the evaluation 1 Identity, physical/chemical/technical properties and methods of analysis The following guidance documents were followed in the production of this conclusion: European Commission, 2000a,b, 2010). The proposed specification for phosmet is based on batch data from industrial plant production. The proposed minimum purity of the technical material is 950 g/kg. Toluene was considered relevant impurity with maximum content of 1 g/kg (see Section 2). The batches used in the (eco) toxicological assessment support the original reference specification but not the new proposal however the new technical specification can be considered acceptable from a toxicological point of view (See Sections 2 and 5). It should be noted that based on the data of the renewal procedure higher minimum purity of the active substance could be set while a new relevant impurity and some of the impurities should not be included in the specification and for others lower levels could be set. Overall, it is proposed to update the reference specification concerning the relevant impurities. It should be noted that the RMS disagreed with the proposal to update the reference specification, but agreed with toluene as the sole relevant impurity. There is no FAO specification available for phosmet; however, an evaluation report is published (FAO/WHO 318/2019) according to the new procedure, belonging to the material of Gowan Company. The technical concentrate (TC) is in compliance with the specification proposed in the FAO evaluation report. The main data regarding the identity of phosmet and its physical and chemical properties are given in Appendix A. A data gap for information on self-heating for the representative formulation was set. Adequate methods are available for the generation of data required for the risk assessment. Methods of analysis are available for the determination of the active substance in the technical material and in the representative formulation and published CIPAC methods exist that are applicable for the determination of toluene in the technical material and in the representative formulation. Phosmet in food and feed of plant origin can be monitored by high-performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) with a limit of quantification (LOQ) of 0.01 mg/kg in all commodity groups. Phosmet residues in food of animal origin can be determined HPLC–MS/MS with LOQ of 0.01 mg/kg in all animal matrices; however, the residue definition is still open. Phosmet residues in soil and water can be monitored by HPLC-MS/MS with LOQs of 0.01 mg/kg and 0.05 μg/L, respectively. Phosmet residues in air can be monitored by GC-NPD with an LOQ of 0.3 μg/m3. HPLC-MS/MS method can be used for monitoring phosmet residues in body fluids with LOQ 0.05 mg/L and phosmet–oxon residues in body fluids and tissues with LOQs of 0.01 mg/L and 0.1 mg/kg, respectively. Phosmet residues in tissues can be determined by using the monitoring method for residues in food of animal origin. 2 Mammalian toxicity The toxicological profile of the active substance phosmet was discussed at the Pesticides Peer Review Experts’ Meetings PREV 07 (June 2019) and PREV 22 (January 2020) and based on the following guidance documents: European Commission (2003, 2012), EFSA PPR Panel, 2012, EFSA (2014a) and ECHA (2017). The toxicological profile of phosmet relied upon batches which were not considered representative of the proposed renewal technical specification but support the original reference specification (see Section 1). The toxicological relevance of old and new impurities was evaluated by QSAR analysis and experimental data, enabling the new technical specification to be considered acceptable from a toxicological point of view. Toluene was identified as a relevant impurity in the technical specification; however, it is not considered of toxicological concern at the level found of 1 g/kg. The analytical methods used in the toxicity studies were overall, considered fit-for-purpose. In the toxicokinetics studies in rats, phosmet was rapidly absorbed after oral administration, being mostly eliminated in urine (84% at 24 h after single dose) and to a lesser extent via faeces (5–10% at 24 h). The maximum concentration in plasma was attained at 0.5 h, with high affinity to red blood cells. Phosmet was widely distributed with highest levels of radioactivity detected in whole blood with no evidence of accumulation. The metabolic pathway is thiophosphoryl hydrolysis, S-methylation, oxidation of the sulfur to sulfoxide and then to sulfone, and hydrolysis of the phthalimide ring to the respective phthalimide acid. Two major metabolites were identified in urine: N-(methylsulfinylmethyl)-phthalamic acid (PaAMS(O)M) and the corresponding sulfoxide N-(methylsulfonylmethyl)-phthalamic acid (PaAMS(O2)M). Unique human metabolites were not formed in an in vitro interspecies comparative metabolism study which showed a quite high level of consistency across species. The residue definition for body fluids should include phosmet and phosmet-oxon for the purpose of human biomonitoring. Based on the av ailable acute toxicity studies, the peer review considered that the criteria for classification as toxic if swallowed may be met for phosmet, while the harmonised classification is harmful if swallowed. Low acute toxicity was observed via the dermal route, while the harmonised classification is harmful in contact with skin. Phosmet was shown to be harmful if inhaled while there is no current harmonised classification regarding inhalation. There was no evidence neither of skin irritation nor of skin sensitisation; moderate irritation was observed in the unwashed eyes in rabbits. No phototoxic potential was observed. In short-term dietary studies, the most sensitive finding was the inhibition of cholinesterase (ChE) activity in plasma, red blood cells (RBC) and brain. The proposed overall short-term no observed adverse effect level (NOAEL) is 1.88 mg/kg body weight (bw) per day from the 90-day dog and 90-day rat studies. In long-term dietary studies, the most relevant effect observed in rats and mice was reductions of RBC and brain AChE activity. For the 2-year rat study, the agreed systemic NOAEL was 1.8 mg/kg bw per day based on RBC AChE inhibition; the carcinogenicity NOAEL was set at the highest dose, 9.4 mg/kg bw per day, based on the absence of carcinogenicity findings. For the 2-year mouse study, the agreed systemic NOAEL was 4 mg/kg bw per day, based on increased incidence of convulsions in males, brain AChE inhibition in females and histopathological findings in the liver of the high-dose males (cytoplasmic hepatocellular vacuolar degeneration); the carcinogenicity NOAEL was 4 mg/kg bw per day, based on the statistically significant increase in the incidence of liver cell adenomas5. Based on the available genotoxicity studies, phosmet is unlikely to be genotoxic in vivo. In a two-generation reproduction study in rats, the agreed NOAEL for parental and reproductive toxicity of phosmet was 1 mg/kg bw per day based on decreased body weight and decreased RBC AChE activity at the mid dose and lower fertility indexes (i.e. mating index, fertility index and gestation index were reduced) from 4.2 mg/kg bw per day onwards. Whereas the adverse effects on the offspring were only observed at the high dose (reduced mean number of live pups and pup weight per litter, reducing the pup survival index for the two generations) and the agreed NOAEL for offspring toxicity was 4.2 mg/kg bw per day. Based on these fertility adverse effects, and that the observed parental effects are not considered enough to explain fertility adverse effects solely, phosmet is suspected of damaging fertility with a harmonised classification for reproduction Repr. Cat.2 H361f6. In the rat and rabbit teratogenicity studies, phosmet did not show significant embryo/fetotoxicity in the absence of clear signs of maternal toxicity. A maternal NOAEL was set at 5 mg/kg bw per day based on decrease of body weight gain at the dose of ≥ 10 mg/kg bw per day in rats and rabbits and a developmental NOAEL at 10 mg/kg bw per day in rats based on decreased foetus weight at 15 mg/kg bw per day and at 5 mg/kg bw per day in rabbits based on incidence of variations at 15 mg/kg bw per day. In regard to neurotoxicity, phosmet did not induce delayed neurotoxicity in two studies with adult domestic hens. The NOAEL for acute neurotoxicity was 4.5 mg/kg bw based on decreased ChE activity (RBC, plasma and brain), while the NOAEL for chronic neurotoxicity was set at 1.5 mg/kg bw per day based on decreased RBC AChE activity. Based on these neurotoxicity results, the experts agreed that the developmental neurotoxicity of phosmet should have been further investigated (data gap) since epidemiological evidence was available from organophosphates in general and not specifically for phosmet7 (issue not finalised). Phosmet showed no immunotoxic potential. The acceptable daily intake (ADI) of phosmet is 0.001 mg/kg bw per day based on the NOAEL of 1 mg/kg bw per day based on RBC AChE inhibition from the two-generation reproduction study in the rat and supported by the short-term rat and dog and long-term rat studies by applying an uncertainty factor (UF) of 1,000; the additional UF of 10 was applied on the basis of the lack of a DNT study and information from guideline-compliant studies to dismiss DNT concerns, and on the basis of epidemiological evidence.5 The acute reference dose (ARfD), the systemic acceptable operator exposure level (AOEL) and acute acceptable operator exposure level (AAOEL) were also 0.001 mg/kg bw (per day), on the same basis as the ADI. The previous toxicological reference values were: ADI 0.01 mg/kg bw per day, ARfD 0.045 mg/kg bw and AOEL 0.02 mg/kg bw per day European Commission, 2014c. Based on the human skin in vitro dermal absorption study, dermal absorption values for the representative formulation Imidan 50 WP are 0.7% for the concentrate and 4% for the aqueous dilution (for use on pome, stone fruits and potatoes) with a pro rata correction for the application in citrus leading to a value of 8%. The non-dietary exposure estimates (i.e. for operator, worker, bystander and resident) for all representative uses according to the GAP table were above the (A)AOEL even with the use of personal protective equipment or application of the available mitigation measures in the EFSA calculator (EFSA, 2014a) (critical area of concern). The toxicological profile of metabolites, found as residues, was concluded during the experts’ meeting based on QSAR analysis. The majority of experts proposed that for phthalimide and phthalamic acid, the same refere