Peer review of the pesticide risk assessment of the active substance methiocarb.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the United Kingdom and co-rapporteur Member State Germany for the pesticide active substance methiocarb are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of methiocarb as an insecticide and a bird repellent on maize. 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 (hereinafter referred to as ‘the Regulation’) 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. Methiocarb is one of the active substances listed in Regulation (EU) No 686/2012.

In accordance with Article 1 of the Regulation, the rapporteur Member State (RMS), the United Kingdom, and co‐rapporteur Member State (co‐RMS), Germany, received an application from Bayer CropScience AG for the renewal of approval of the active substance methiocarb. Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the co‐RMS (Germany), the European Commission and the European Food Safety Authority (EFSA) about the admissibility.

The RMS provided its initial evaluation of the dossier on methiocarb in the renewal assessment report (RAR), which was received by EFSA on 13 July 2017. In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicant, Bayer CropScience AG, for comments on 29 November 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 30 January 2018.

Following consideration of the comments received on the RAR, 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.

In accordance with Article 13(1) of the Regulation, EFSA should adopt a conclusion on whether methiocarb can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009 of the European Parliament and of the Council.

The conclusions laid down in this report were reached on the basis of the evaluation of the representative uses of methiocarb as an insecticide and a bird repellent on maize, as proposed by the applicant. Full details of the representative uses can be found in Appendix A of this report.

According to the representative uses proposed at the European Union (EU) level the use of methiocarb results in a sufficient insecticidal and repellent efficacy against the target organisms.

A data gap was identified for a search of the scientific peer‐reviewed open literature on the active substance and its relevant metabolites for non‐target species.

In the area of identity, physical/chemical properties and analytical methods, data gaps were identified for spectra data for the relevant impurities, for the content of trichloroxylenolcarbamate before and after storage of the plant protection product, for information on the analytical method used in support of the toxicological studies, an analytical method for determination of the relevant impurities in the plant protection product, a monitoring method for analysis of the components of the residue definition in high water content, high acid content and dry plant matrix groups, and monitoring methods for all components of the residue definition in body fluids and tissues.

In the area of mammalian toxicology and non‐dietary exposure, a critical are of concern was identified since exposure for workers loading and sowing the treated seeds was above the acceptable operator exposure level (AOEL) and the acute AOEL (AAOEL). An in vivo comparative cholinesterase (ChE) inhibition study in adult and offspring rats on methiocarb is available and was submitted to US‐EPA in 2010. However, the study was neither submitted nor fully evaluated during the EU peer review and was identified as a data gap. Pending its analysis, the need to further address the developmental neurotoxic potential of methiocarb will have to be considered. A data gap was also identified to address the genotoxic potential of metabolite methiocarb sulfoxide (M01). Additional data gaps were identified for a new in vivo micronucleus (MN) test to confirm the lack of genotoxic potential in vivo of methiocarb and to address the phototoxic potential of methiocarb at ultraviolet B (UVB) ranges once an appropriate OECD test for UVB absorbers is available.

In the area of residues, a data gap was identified for storage stability data of methiocarb and the metabolite M01 in a representative commodity of the cereal crop group. The plant residue definitions for monitoring and risk assessment could not be finalised in the absence of toxicity data to rule out the genotoxicity potential of M01. As for the pending finalisation of the plant residue definition for risk assessment, a risk assessment for the consumer could not be conducted.

The data available on environmental fate and behaviour are sufficient to carry out the required environmental exposure assessments at EU level for the representative use. The potential for groundwater exposure by methiocarb and its metabolites (methiocarb sulfoxide (M01), methiocarb sulfoxide phenol (M04), methiocarb sulfone phenol (M05) and methiocarb methoxy sulfone (M10)) that triggered assessment above the parametric drinking water limit of 0.1 μg/L was assessed as low for this representative use. It should be noted that maize seeds are known to be dusty and have been shown to generate dust at drilling that contains active substances of seed treatment products. This dust can drift out of the field and can be deposited on adjacent surface water. This route of exposure (dust drift to surface water during drilling) has not been considered in the available aquatic exposure assessment, as this issue is not considered in the agreed EU guidance.

A number of data gaps were identified in the field of ecotoxicology in relation to the risk assessment of birds, mammals, bees and earthworms. A high risk to birds, mammals and earthworms was concluded leading to critical areas of concern. The risk assessment to bees could not be finalised.

Background

Commission Implementing Regulation (EU) No 844/20121 (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 1107/20092. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States, the applicant(s) 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(s) in accordance with Article 13(3).

In accordance with Article 1 of the Regulation, the RMS, the United Kingdom, and the co‐RMS, Germany, received an application from Bayer CropScience AG for the renewal of approval of the active substance methiocarb. Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the co‐RMS (Germany), the European Commission and EFSA about the admissibility.

The RMS provided its initial evaluation of the dossier on methiocarb in the RAR, which was received by EFSA on 13 July 2017 (United Kingdom, 2017).

In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicant, Bayer CropScience AG, for consultation and comments on 29 November 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 30 January 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 and the RMS on 9 March 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 took place with Member States via a written procedure in August 2018.

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 methiocarb as an insecticide and a bird repellent on maize, as proposed by the applicant. A list of the relevant end points for the active substance and the formulation is provided in Appendix A.

In addition, a key supporting document to this conclusion is the peer review report (EFSA, 2018), 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 (12 March 2018);

the evaluation table (18 September 2018);

the reports 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 (United Kingdom, 2018), 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 report 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

Methiocarb is the ISO common name for 4‐methylthio‐3,5‐xylyl methylcarbamate (IUPAC).

The representative formulated product for the evaluation was ‘Methiocarb FS 500’, a flowable concentrate for seed treatment (FS) containing 500 g/L methiocarb.

The representative uses evaluated were seed treatment applications on maize for the control of frit flies (Oscinella frit) and to repel birds, namely pheasants (Phasianus colchis), pigeons (Columba livia f. domestica), crows (Corvus corone) and rooks (Corvus frugilegus). Full details of the Good Agricultural Practice (GAP) can be found in the list of end points in Appendix A.

Data were submitted to conclude that the use of methiocarb according to the representative uses proposed at EU level results in a sufficient insecticidal and repellent efficacy against the target organisms, following the guidance document for the renewal of approval of active substances 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 non‐target species and published within the 10 years before the date of submission of the dossier. It should 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).

Identity, physical/chemical/technical properties and methods of analysis

The following guidance documents were followed in the production of this conclusion: SANCO/3029/99‐rev. 4 (European Commission, 2000a), SANCO/3030/99‐rev. 4 (European Commission, 2000b) and SANCO/825/00‐rev. 8.1 (European Commission, 2010).

The proposed specification for methiocarb is based on batch data from industrial plant and quality control data. The proposed minimum purity of the technical material is 980 g/kg. Methyl isocyanate, toluene and 2,4,6‐trichloro‐3,5‐dimethylphenyl methylcarbamate (trichloroxylenolcarbamate) are considered to be relevant impurities with a maximum content of 0.2, 1 and 3 g/kg, respectively (see Section 2). It should be noted that methyl isocyanate and toluene were not found above the limits of quantification (LOQs) of 0.2 and 0.5 g/kg in the batches. As a consequence of the consideration of these impurities as relevant an update of the reference specification is proposed by EFSA. The batches used in the (eco)toxicological assessment support the proposed specification (See Sections 2 and 5). The manufactured technical material meets the requirements of the existing FAO specification under the new procedure 165/TC (June, 2018) of min. 980 g/kg methiocarb content.

The assessment of the data package revealed no issues that need to be included as critical areas of concern with respect to the identity, physical, chemical and technical properties of methiocarb or the representative formulation. However, data gaps for spectra data for the relevant impurities and the content of trichloroxylenolcarbamate before and after storage of the plant protection product were identified. The main data regarding the identity of methiocarb and its physical and chemical properties are given in Appendix A.

Adequate methods are available for the generation of the majority of the data required for the risk assessment. However, a data gap for information on the analytical methods used in support of toxicological studies was identified (see Section 2). Methods of analysis are available for the determination of methiocarb in the technical material and in the representative formulation, and for the determination of the respective impurities in the technical material. A data gap for methods for determination of the relevant impurities in the plant protection product was identified.

Methiocarb and methiocarb‐sulfoxide residues in high oil content plant matrices could be monitored by the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method using high‐performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) with a LOQ of 0.01 mg/kg for both analytes. A data gap for a method for monitoring of the components of the residue definition in the other plant matrix groups (high water content, high acid content and dry) was identified. A monitoring method for food of animal origin is not required since no residue definition is set; however, a validated QuEChERS using HPLC–MS/MS exists for analysis of methiocarb, methiocarb sulfone, methiocarb sulfoxide, methiocarb phenol, methiocarb sulfone phenol, methiocarb sulfoxide phenol in food of animal origin with a LOQ of 0.01 mg/kg in all matrices.

Methiocarb and methiocarb‐sulfoxide residues in soil can be monitored by the DFG Method S 19 using HPLC‐MS/MS with a LOQ of 0.02 mg/kg for both analytes. Methiocarb and methiocarb sulfoxide residues in water can be analysed by HPLC–MS/MS with a LOQ of 0.05 μg/L for both analytes. Methiocarb residues in air can be determined by HPLC with a fluorescence detection with a LOQ of 0.4 μg/m3.

Gas chromatography–mass spectrometry (GC–MS) could be used for monitoring of methiocarb in body fluids (blood) and tissues (meat) with LOQs of 50 μg/L and 0.01 mg/kg, respectively. However, the residue definition in body fluids and tissues was concluded as methiocarb phenol (M03), methiocarb sulfone phenol (M05), methiocarb sulfoxide phenol (M04) and their conjugates (glucuronides and sulfates) and as a consequence a data gap for monitoring methods for all components of the residue definition in body fluids and tissues was identified.

Mammalian toxicity

The toxicological profile of the active substance methiocarb and its metabolites was discussed at the Pesticides Peer Review Experts’ Meeting 179 in June 2018 and assessed based on the following guidance documents: Guidance on relevant metabolites SANCO/221/2000 – rev. 10‐final (European Commission, 2003), Guidance on equivalence of technical materials SANCO/10597/2003 – rev. 10.1 (European Commission, 2012), Guidance on Dermal Absorption (EFSA PPR Panel, 2012) and Guidance on the Application of the CLP Criteria (ECHA, 2017).

To assess the toxicological profile of the active substance the applicant submitted a set of valid toxicity studies. These studies were representative of the proposed technical specification for the active substance and the associated impurities (see Section 1). For the impurities, the applicant and the RMS considered all impurities non‐relevant at the level proposed or found in the specification. Although EFSA agreed that the level proposed or found in the specification is of no toxicological concern, the current assessment of the impurities is based on a hazard assessment (European Commission, 2003) and therefore the impurities methyl isocyanate, toluene and trichloroxylenolcarbamate should be considered relevant based on their hazard but not of toxicological concern at the level proposed in the specification. Information on the analytical methods used in all dietary toxicity studies, including the assessment of their validity was not provided (see also Section 1) leading to an issue that could not be finalised.

In the toxicokinetic studies, methiocarb was rapidly absorbed. Oral absorption was estimated to be greater than 80% (84–90%). There was no evidence for accumulation. Excretion of methiocarb was predominantly through urine. No unique human metabolite is expected. Methiocarb is extensively metabolised, the major metabolic step is ester hydrolysis of the carbamate group. Inclusion of the methiocarb phenol (M03), methiocarb sulfone phenol (M05), methiocarb sulfoxide phenol (M04) metabolites and their conjugates (glucuronides and sulfates) in the residue definition for body fluids and tissues is proposed.

In the acute toxicity studies, methiocarb showed high acute toxicity when administered orally or by inhalation to rats and has low acute toxicity when administered dermally. It is not a skin or eye irritant. Methiocarb was not a skin sensitiser in the available studies (with some limitations3). Methiocarb was not phototoxic in the available OECD 3T3 NRU‐PT test. However, this test might not allow concluding properly on the phototoxicity potential of methiocarb since it is an ultraviolet B (UVB) absorber and the 3T3 NRU‐PT test might not be an appropriate test for UVB absorbers. It is noted however that there is no OECD test for an UVB absorber leading to a data gap.

After repeated (short‐ and long‐term) oral administration the critical effects were cholinesterase (AChE) inhibition and clinical signs indicative of cholinergic inhibition. Non‐specific adverse effects, such as reduced body weight gain, were also observed in rats and dogs. The dog was the most sensitive species. The relevant short‐term oral no observed adverse effect level (NOAEL) is 0.25 mg/kg body weight (bw) per day (90‐day dog study), whereas the relevant long‐term oral NOAEL is 9.3 mg/kg bw per day (2‐year rat study). The substance showed no carcinogenic potential in rats and mice.

The genotoxicity potential of methiocarb was extensively discussed during the Pesticides Peer Review Experts’ Meeting.4 Methiocarb showed a clear clastogenic potential in vitro and not in vivo in the micronucleus test. However, the in vivo MN test showed major deviations from current guideline. A slight majority of experts agreed with the RMS that there would be low concern for in vivo clastogenicity and aneugenicity and overall methiocarb should be considered unlikely to be genotoxic in vivo. To reduce the remaining uncertainties for the available in vivo MN test the experts identified a data gap for a new in vivo GLP‐ and OECD‐compliant MN test. The RMS did not agree with the data gap.

In reproductive toxicity studies, the agreed parental, reproductive and offspring NOAELs are 4.3 mg/kg bw per day. No developmental toxicity was observed in rats and rabbits, maternal NOAELs were 0.5 and 3 mg/kg bw per day in rats and rabbits, respectively, and were triggered by clinical signs indicative of cholinergic inhibition and reduction in body weight.

Methiocarb is a carbamate and as such an inhibitor of AChE, which acts on the nervous system of insects and vertebrates. AChE inhibition was measured in most of the toxicity studies but no specific acute and repeated dose neurotoxicity studies are available for methiocarb. The developmental neurotoxicity potential of methiocarb, including the need of a specific developmental neurotoxicity study was discussed during the experts’ meeting5: A literature publication (Moser, et al. 2010 in the RAR, United Kingdom, 2018) suggested that pups may be more sensitive to the AChE inhibition than the adults. In 2010, the US‐EPA required an in vivo comparative ChE inhibition study in adult and offspring rats for methiocarb. The summary of the study confirmed the higher sensitivity of pups compared to the adults. However, the study was neither submitted nor fully evaluated during the EU peer review (data gap). Pending its analysis, the need to further address the developmental neurotoxic potential of methiocarb will have to be considered.

No specific immunotoxicity studies are available; however no immunotoxicity potential has been observed in available toxicity studies.

Methiocarb is not classified or proposed to be classified as toxic for reproduction category 2 or carcinogenic category 2, in accordance with the provisions of Regulation (EC) No 1272/2008, and therefore, the conditions of the interim provisions of Annex II, Point 3.6.5 of Regulation (EC) No 1107/2009 concerning human health for the consideration of endocrine‐disrupting properties are not met. With regard to the scientific risk assessment, the experts agreed that methiocarb is unlikely to be an endocrine disruptor.

The re‐assessment of the toxicological profile of methiocarb lead to a revision of the existing toxicological reference values (European Commission, 2006). The agreed6 acceptable daily intake (ADI) and the acceptable operator exposure level (AOEL) are 0.00025 mg/kg bw per day, on the basis of the relevant short‐term NOAEL of 0.25 mg/kg bw in the 90‐day study in dogs based on reduced body weight gain in males and females at 1.3 mg/kg bw per day. The agreed acute reference dose (ARfD) and acute acceptable operator exposure level (AAOEL) are 0.00050 mg/kg bw based on the NOAEL of 0.5 mg/kg bw per day for clinical signs indicative of cholinergic inhibition observed at 1.5 mg/kg bw per day in the developmental toxicity study in rats. In addition to the standard uncertainty factor (UF) of 100, an additional UF of 10 was applied for the derivation of all reference values, in order to cover the lack of developmental neurotoxicity and the likely higher sensitivity to AChE inhibition of pups compared to adults. It is noted that in the Review Report for the first approval (European Commission, 2006), the ADI was 0.013 mg/kg bw per day, the ARfD was 0.013 mg/kg bw, and the AOEL was 0.013 mg/kg bw applying an UF of 100.

The RMS estimated non‐dietary exposure (both acute and longer term exposure) considering dermal absorption values of methiocarb in ‘Mesurol FS 500 g/L’ of 0.9% for the concentrate, 1% for the 1.18 dilution and 2% for the 1.8 dilution as input values. Considering the representative uses with ‘Mesurol FS 500 g/L’ as an insecticide in maize (seed treatment), the following two exposure groups were considered for operators: operators directly involved in the seed treatment process and operators within the seed‐treatment plant not directly involved in treatment. Exposure for these two operator groups was below the AOEL and AAOEL if specific control measures are applied and specific personal protective equipment are used (see Section 8). Exposure for workers loading and sowing the treated seed was above the AOEL (628% of the AOEL) and AAOEL (826% of the AAOEL) even with the use of workwear, gloves and FFP3 respiratory protective equipment (RPE) leading to a critical area of concern. It is considered that bystanders and residents will not be exposed to methiocarb during the seed treatment process in professional plants.

The toxicological studies provided for the metabolite M01 indicated that it is of higher toxicity than the parent (a relative potency factor of 3 might be derived). However, it is noted that before applying the relative potency factor it should be excluded that the metabolite is genotoxic (data gap).7 Regarding the metabolites M03, M04 and M05 (free and conjugated) although found in rat metabolism they do not contain the carbamate moiety of the parent. The carbamate moiety is responsible for the critical toxicity mode of action of methiocarb (i.e. AChE inhibition). This is confirmed by the acute toxicity studies on these metabolites showing a lower acute oral toxicity compared to the parent. These metabolites are not mutagenic in the Ames test. Overall, EFSA considered the metabolites M03, M04 and M05 of lower toxicity than the parent.8

Residues

The assessment in the residue section is based on the OECD guidance document on overview of residue chemistry studies (OECD, 2009), the OECD publication on maximum residue level (MRL) calculations (OECD, 2011), the European Commission guideline document on MRL setting (European Commission, 2011) and the Joint Meeting on Pesticide Residues (JMPR) recommendations on livestock burden calculations (JMPR, 2004, 2007).

Methiocarb was discussed at the Pesticides Peer Review Experts’ Meeting 180 in June 2018.

Metabolism of methiocarb in plants was investigated regarding foliar treatment in fruit crops (apples) and cereals (rice), regarding soil treatment in leafy crops (lettuces) and tomato plants and following seed treatment in rice foliage only and in pulses and oilseeds (oilseed rape) with methiocarb labelled in the [14C‐phenyl] ring. Although the metabolism data on apples, lettuces, tomato plants and rice are not suitable as guideline‐compliant metabolism studies, these data can be considered as supportive to the acceptable metabolism study on oilseed rape. Methiocarb was a major residue in apples (up to 65% total radioactive residues (TRR)), in lettuces and tomato plants at application (up to 19% TRR) whilst it was detected at a very low level (2% TRR) in the immature rice foliage after seed treatment. Following foliar treatment on rice a steady decline of the methiocarb residues from last application until harvest was observed in rice grain (94% to 18% TRR) and in rice stalks (90% to 20% TRR). Overall, methiocarb sulfoxide compound (M01) was the pertinent metabolite in apple pulp (64% TRR), lettuces (up to 34% TRR), tomato plants (up to 52% TRR), immature rice foliage (35‐46% TRR), rice grain and stalks (32% and 36% TRR, respectively). Significant proportions of methiocarb phenol (M03) and methiocarb sulfoxide phenol (M04) and their conjugates were also found at a total level of 48% TRR in lettuces, 29% TRR in rice foliage, 21% TRR in rice grain and M04 accounted for a level ≥ 10% TRR in apples and in rice stalks. In all oilseed rape plant parts, the parent compound was never detected and M01 was recovered at a low proportion in forage only (6% TRR; 0.05 mg eq/kg). In seeds the identification of metabolites was limited to M04 (6.6% TRR) and M05 (8.3% TRR) despite all analytical attempts to further characterise and identify metabolites; a significant fraction remains unknown (32% TRR; 0.05 mg eq/kg) and a major part of the radioactive residues were incorporated into fatty acids (38% TRR). M04, free and conjugated was predominant in forage and straw (60% and 29% TRR, respectively) whilst a significant proportion of M05 (mainly conjugated) was recovered in forage only (21% TRR).

A confined rotational crop study conducted at representative plant‐back intervals (PBIs) after soil application of methiocarb at a dose rate of 0.2 kg a.s./ha (1.3 N) in wheat, turnip and Swiss chard demonstrated a steady decline of the total residues in rotational crops over time in all crop parts. At 30 days PBI and in wheat straw, M03, M04 and M05 (free and conjugated) were the most abundant metabolites, accounting for 40% TRR (0.2 mg eq/kg), 31% TRR (0.15 mg eq/kg) and 15% TRR (0.07 mg eq/kg), respectively. The same pattern was observed in turnip tops and roots with M04 (free and conjugated) accounting, respectively, for 65% TRR (< 0.05 mg eq/kg) and 55% TRR (< 0.02 mg eq/kg) and M05 (free and conjugated) accounting for 18% TRR (< 0.02 mg eq/kg) and 31% TRR (< 0.01 mg eq/kg), respectively. Only residues of M04 (free and conjugated) were recovered at significant proportions in Swiss chard with up to 27% TRR (< 0.03 mg eq/kg) at 30 days PBI; the other identified components being recovered at or below the LOQ (0.01 mg/kg). Transfer of residues from soil into crops was shown to be limited at the PBI of 163 and 288 days as residues of methiocarb, M01, M02, M03, M04 and M05 were < 0.01 and < 0.05 mg/kg in food and feed commodities, respectively. In all crop parts at all tested intervals, methiocarb was never detected except in wheat grain at the 30 days PBI (22% TRR; < 0.01 mg eq/kg). Although the accumulation of methiocarb and its relevant soil metabolites (M01, M04, M05, M10) is not expected (DT90 < 1 year) when maize is treated in accordance with the GAP, significant residues of M03, M04 and M05 are expected mainly in wheat straw and of M04 in Swiss chard and in turnip roots at 30 days PBI. It is noted that overdosed field residue trials (2 × 120 g a.s./ha) conducted in northern and southern Europe on wheat grain and straw, leafy crops (cauliflower, cabbage, lettuce) and root crops (potatoes, sugar beet root) and following soil application were submitted to corroborate the residue situation in rotational crops at 30 days PBI. Residue levels of M04 and M05 and their conjugates were occasionally recovered above the LOQ in lettuces only (0.024 and 0.013 mg eq/kg, respectively) in a glasshouse trial and residues of methiocarb and all compounds were < 0.05 mg eq/kg in wheat straw, 90 days after treatment. Overall, the submitted data are sufficient to conclude that residue levels in rotational crops will unlikely exceed 0.01 mg/kg when maize is treated at GAP rate.

Based on the available metabolism data in primary crops upon soil/seed treatment and in rotational crops, the experts were of the opinion that the metabolic pathway of methiocarb was sufficiently investigated for all categories of crops and following soil/seed treatment and the metabolites M01 and M03, M04 and M05 under their conjugated form were quantitatively relevant.

With regard to the toxicological profile of the relevant metabolites, M01 was shown to have a higher toxicity compared to the parent compound and a relative potency factor of 3 might be applicable if the genotoxic potential of this metabolite can be ruled out (see data gap in Section 2). M03, M04 and M05 are concluded to be of lower toxicity than the parent compound (see Section 2). In the meantime, the residue definition for risk assessment in plants cannot be finalised (issue that could not be finalised) and is provisionally proposed as:

Methiocarb

M01 (a potency factor of 3 can be established to consider the sum of parent methiocarb and M01, if any genotoxicity potential can be ruled out for M01)

Sum of M03, M04 and M05, free and conjugated.

For monitoring, the plant residue definition is proposed as methiocarb and M01, the expression is pending upon the outcome of the requested data on the potential genotoxicity of M01.

The proposed residue definitions are extended to all crop categories upon soil and seed treatments.

The number of acceptable residue field trials to support the representative use on maize was sufficient. Analysis of residues of methiocarb, M01, M02, M03, M04 and M05 and their conjugates was conducted with a validated method and integrity of samples during storage prior to analysis was demonstrated for the sum of M03 and M04 for 24 months and for M04 and M05 for 23 months, respectively. Storage stability data were not submitted for methiocarb and M01 in maize grain and forage and are requested to cover the maximum storage time interval of the residue samples from the trials on maize (data gap).

Data on the nature and magnitude of methiocarb residues in processed commodities are not triggered as residues of all compounds included in the residue definitions for monitoring and risk assessment were below the LOQ of the method (< 0.01 mg/kg) in maize grain.

Currently, as the plant residue definition for risk assessment is not finalised, the calculation of the livestock dietary burden cannot be conducted. It is noted that metabolism studies in lactating goats and in laying hens with methiocarb are available but are not acceptable to derive residue definitions as these are not compliant with the current guidelines and showed several deficiencies. However, it can be concluded that the representative use on maize does not give rise to significant residues in livestock matrices considering that the residue levels of all compounds included in the risk assessment residue definition for plants are below the LOQ (< 0.01 mg/kg).

A fish metabolism study was not provided and is not requested for the representative use as residues of methiocarb and all metabolites included in the residue definition for risk assessment in maize grain are below the LOQ of the method (0.01 mg/kg).

It can confidently be concluded that the data requirement for the determination of the residues in pollen and bee products for human consumption resulting from residues taken up by honeybees from crops at blossom is addressed even though no data was provided considering the very limited translocation of methiocarb and metabolites residues throughout the different plant parts observed from the GAP compliant residue trials on maize. The consumer exposure to residues of methiocarb and metabolites in pollen and bee products is therefore expected to be negligible.

As for the pending finalisation of the plant residue definition for risk assessment in absence of toxicity data to rule out the genotoxicity potential of M01, a risk assessment for the consumer cannot be conducted.

Environmental fate and behaviour

Methiocarb was discussed at the Pesticides Peer Review Experts’ Teleconference 197 in June 2018.

The rates of dissipation and degradation in the environmental matrices investigated were estimated using FOCUS (2006) kinetics guidance. In soil laboratory incubations under aerobic conditions in the dark, methiocarb exhibited very low to moderate persistence, forming the major (> 10% applied radioactivity (AR)) metabolites: methiocarb sulfoxide (M01, max. 59% AR, exhibiting low to moderate persistence), methiocarb sulfoxide phenol (M04, max. 36% AR, exhibiting low to moderate persistence), methiocarb sulfone phenol (M05, max. 20% AR, exhibiting low to medium persistence) and methiocarb methoxy sulfone (M10, max. 13% AR, exhibiting moderate to medium persistence). Mineralisation of the phenyl ring 14C radiolabel to carbon dioxide accounted for 17–58% AR after 91–120 days. The formation of unextractable residues (not extracted by Soxhlet extraction with acidified chloroform/methanol or Soxhlet with methanol/water) for this radiolabel accounted for 31–50% AR after 91–120 days. Methiocarb exhibited medium to low mobility in soil. Methiocarb sulfoxide (M01) exhibited very high soil mobility, methiocarb sulfoxide phenol (M04) exhibited very high to high mobility, whilst methiocarb sulfone phenol (M05) and methiocarb methoxy sulfone (M10) both exhibited high to medium soil mobility. It was concluded that the adsorption of all these compounds was not pH dependent.

In laboratory incubations in dark aerobic natural sediment water systems, methiocarb exhibited low persistence, forming the major metabolites methiocarb phenol (M03, max. 15–16% AR, in both water and sediment exhibiting medium to high persistence) and methiocarb sulfoxide phenol (M04, max. 34% AR in water and 7% AR in sediment, exhibiting moderate persistence). The unextractable sediment fraction (not extracted by acidified acetonitrile/water with subsequent acetonitrile both under ambient temperature followed by microwave extraction with acidified acetonitrile/water) was the major sink for the phenyl ring 14C radiolabel, accounting for 45–59% AR at study end (90 days). Mineralisation of this radiolabel accounted for 12–25% AR at the end of the study. The rate of decline of methiocarb in laboratory sterile aqueous photolysis experiments was slow relative to that occurred in the aerobic sediment water incubations. Methiocarb sulfoxide (M01, max. 20% AR) was the only major metabolite formed. The necessary surface water and sediment exposure assessments (predicted environmental concentrations (PEC) calculations) were carried out for the metabolites methiocarb phenol (M03), methiocarb sulfoxide phenol (M04), methiocarb sulfone phenol (M05) and methiocarb methoxy sulfone (M10), using the FOCUS (2001) step 1 and step 2 approach (version 3.2 of the Steps 1–2 in FOCUS calculator). For the active substance methiocarb and the metabolite methiocarb sulfoxide (M01), appropriate step 3 (FOCUS, 2001) calculations that complied with EFSA (2004) were available.9 These calculations indicated that a minimum drilling depth of 3 cm for the maize seed should be specified as simulations for a 2 cm drilling depth gave predicted concentrations in surface water that would indicate a risk for aquatic organisms. It is noted that whilst these calculated PEC followed the agreed guidance approach, maize seeds are known to be dusty and have been shown to generate dust at drilling that contains active substances of seed treatment products. This dust can drift out of the field and be deposited on adjacent surface water. This route of exposure (dust drift to surface water during drilling) has not been considered in the available aquatic exposure assessment, as this issue is not considered in the agreed EU guidance.

The necessary groundwater exposure assessments were appropriately carried out using FOCUS (European Commission, 2014a) scenarios and the models PEARL 4.4.4, PELMO 5.5.3 and MACRO 5.5.4.9 The potential for groundwater exposure from the representative uses by methiocarb and its metabolites: methiocarb sulfoxide (M01), methiocarb sulfoxide phenol (M04), methiocarb sulfone phenol (M05) and methiocarb methoxy sulfone (M10) above the parametric drinking water limit of 0.1 μg/L was concluded to be low in geoclimatic situations that are represented by all eight FOCUS groundwater scenarios defined for the cultivation of maize.

The applicant provided appropriate information to address the effect of water treatments processes on the nature of the residues that might be present in surface water, when surface water is abstracted for drinking water. The conclusion of this consideration was that neither methiocarb nor any of its degradation products that trigger assessment (methiocarb sulfoxide (M01), methiocarb phenol (M03), methiocarb sulfoxide phenol (M04) and methiocarb methoxy sulfone (M10)) would be expected to be present at significant concentrations in water bodies (i.e. above 0.1 μg/L) where drinking water would be abstracted (i.e. the same situation that is predicted for groundwater), provided that a minimum drilling depth of 3 cm for the maize seed be specified. This conclusion was reached noting that, in the situation that there is at least a 3 cm seed drilling depth, FOCUS step 3 PECsw for methiocarb and metabolite methiocarb sulfoxide (M01) in small edge of field surface water bodies were < 0.001 μg/L and that the KFoc and maximum observed formation amounts in soil for the other metabolites were higher and lower respectively than those for metabolite M01.

The PEC in soil, surface water, sediment, and groundwater covering the representative uses assessed can be found in Appendix A of this conclusion.

Ecotoxicology

The risk assessment was based on the following documents: Guidance document on terrestrial ecotoxicology (European Commission, 2002a), Guidance document on aquatic ecotoxicology, (European Commission, 2002b), Guidance document on regulatory testing (SETAC, 2001), Guidance on risk assessment for birds and mammals (EFSA, 2009) and Guidance for tiered risk assessment for aquatic organisms (EFSA PPR Panel, 2013).

Methiocarb was discussed at the Pesticides Peer Review Experts’ Meeting 181 in June 2018.

The available information was sufficient to confirm that the batches used in the (eco)toxicity studies are compliant with the current reference specification (see Section 1).

Two acute toxicity studies on Japanese quail (one with the active substance and one with the representative formulation) and a reproductive toxicity study on mallard duck were available. During the Pesticides Peer Review Experts’ Meeting 181,10 the experts discussed the limitations of the Japanese quail study with the active substance and a data gap had been suggested for a more appropriate statistical re‐evaluation of the study. Nevertheless, it is considered that such re‐evaluation is unlikely to impact the current risk assessment for birds; therefore, no data gap has been set in this conclusion. In the chronic risk assessment to birds, a surrogate endpoint (LD50/10) on the Japanese quail study has been calculated. This endpoint is lower than the reproductive endpoint in mallard duck and it has been used for risk assessment following the recommendations of EFSA (2009). For mammals, the relevant ecotoxicological endpoint has been based on effects observed in the parental and 1st generation of a two‐generation rat study. It is noted that a data gap for further assessment of the developmental neurotoxicity potential has been set (see Section 2); therefore, pending on this data gap, the endpoint to be used in the wild mammals risk assessment may need to be re‐considered.

High risk (acute and chronic) from dietary exposure has been identified for birds (large granivorous birds) and for mammals (small omnivorous mammals) feeding on treated seeds and on contaminated seedlings for the representative use in maize. A refinement of the contaminated seedlings scenarios by using residue data from supervised residue trials in maize was discussed during the Pesticides Peer Review Experts’ Meeting 181. The experts agreed to not accept the proposed refinement since the residue calculation did not consider the whole seedling at the earliest stage of the crop that would represent the worst‐case residue situation for birds and mammals feeding on freshly emerging seedlings. Further refinements to conclude on the risk to birds and mammals were not provided (data gap; critical area of concern).

Regarding the risk from secondary poisoning due to methiocarb, a high risk was identified to earthworm‐eating birds (data gap; critical area of concern) whilst low risk was concluded for fish‐eating birds, earthworm‐eating mammals and fish‐eating mammals. An available field study aiming to refine the risk to earthworm‐eating birds has been discussed during the Pesticides Peer Review Experts’ Meeting 181.11 The study was not considered suitable for the refinement since key parameters on bioaccumulation in earthworms were not reported. Nevertheless, the study showed that earthworms dwelling in soil drilled with methiocarb‐treated seeds may contain residues potentially causing an acute risk to birds. Information to address the risk from secondary poisoning due to exposure to methiocarb phenol (M03) for fish‐eating birds and fish‐eating mammals was not available (data gap). The risk to birds and mammals from consumption of contaminated water was not assessed since the current risk assessment scheme does not require this scenario for seed treatment (EFSA, 2009).

The available information was not sufficient to address the risk to birds and mammals for the relevant plant metabolite (methiocarb sulfoxide) (data gap).

For aquatic organisms, toxicity data were available for fish (acute and chronic only for the active substance; only acute for pertinent aquatic metabolites), aquatic invertebrates (acute and chronic for the active substance and M01; only acute for M03, M04, M05) and for algae. Similar toxicity has been observed in methiocarb and M01. No chronic data have been provided for sediment dwelling organisms. However, considering the available acute data showing Daphnia magna as more sensitive and the very low exposure estimates in sediment, additional toxicity data are not deemed necessary.

High risk to aquatic invertebrates has been identified in two out of eight FOCUS Step 3 scenarios (R1/R4 stream scenarios) for the representative use in maize. To reduce the exposure concentrations in water bodies, a consideration was given to the possibility of a minimum drilling depth of 3 cm for maize seed. Under this condition of exposure, new PECs according to FOCUS Step 3 were derived. Thus, low acute and chronic risks were concluded for aquatic organisms for the use of methiocarb according to the representative use.

Based on the ecotoxicity data available for the metabolites, a low risk to aquatic organisms has been identified.

Acute ecotoxicity tests for honeybees (oral and contact) and for bumblebees (only contact) were available. Additionally, chronic ecotoxicity studies with honeybees (adult and larvae) were available. On the latest, the endpoint was derived from a single exposure study; a repeated‐dose test study for honeybee larvae is recommended.

The Guidance Document on terrestrial ecotoxicology (European Commission, 2002a) does not provide a risk assessment scheme which is able to use the chronic toxicity data for adult honeybees and the honeybee brood. Additionally, it must be noted that the hazard quotient (HQ) approach used in case of spray applications is not suitable to perform the acute risk assessment to bees in the seed treatment scenario. The applicant provided a risk assessment based on EPPO guidance (2010). A risk assessment according to the EFSA bee guidance (2013) was not provided (data gap). Field and semi‐field studies with bees were available, including a consideration for the guttation route of exposure that it is suitable to occur in maize. Based on the data available, the information was insufficient to draw a robust conclusion on the risk to honeybees; thus, further information to address the risk to bees was identified (data gap; issue that cannot be finalised). Insufficient information was available to perform a risk assessment for sub‐lethal effects on bees (e.g. hypopharyngeal glands (HPG), data gap), effects from occurring metabolites in pollen and nectar were not investigated (data gap) and accumulative effects. Information to perform a risk assessment for solitary bees was not available.

It is noted that for non‐target arthropods (NTAs), only extended laboratory studies were available. On the basis of these studies, a low risk to non‐target arthropods was concluded. It must be noted that, in absence of an agreed methodology to address the off‐field risk to NTAs due to dust exposure during seed drilling, the risk to NTAs remains uncertain.

For earthworms, high risk has been identified for methiocarb and for the metabolite methiocarb sulfoxide. The refinement for the earthworms’ scenario with laboratory‐modified exposure study has been discussed during the Pesticides Peer Review Experts’ Meeting 181.12 Experts agreed that the available information was insufficient to conclude on a low risk for earthworms due to the inappropriate test design (data gap; critical area of concern). For soil macroorganisms other than earthworms, low chronic risk has been identified in the first tier for the representative use and for all pertinent metabolites. Low risk has been identified to soil microorganisms for the representative use.

Low risk was identified to non‐target terrestrial plants. It must be noted that as for NTAs, the off‐field risk due to dust exposure when seed drilling remain uncertain.

Low risk was identified for organisms involved in biological methods for sewage treatment.

Regarding the potential for endocrine disruption, based on the information available in Section 2 it is unlikely that methiocarb is an endocrine disruptor for mammals. However, further data might be necessary to address the potential endocrine‐disrupting properties for non‐target organisms other than mammals.

Data gaps

This is a list of data gaps identified during the peer review process, including those areas in which a study may have been made available during the peer review process but not considered for procedural reasons (without prejudice to the provisions of Article 56 of Regulation (EC) No 1107/2009 concerning information on potentially harmful effects).

A search of the scientific peer‐reviewed open literature on the active substance and its relevant metabolites, dealing with side effects on 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) (relevant for the representative use evaluated; see Section 5).

Spectra data for the relevant impurities were not available (relevant for the representative use evaluated; see Section 1).

Data on the content of trichloroxylenolcarbamate before and after storage of the plant protection product was not available (relevant for the representative use evaluated; see Section 1).

Information on the analytical method used in support of the toxicological studies was not available (relevant for all representative use evaluated; see Sections 1 and 2).

An analytical method for determination of the relevant impurities in the plant protection product was not available (relevant for the representative use evaluated; unknown; see Section 1).

A monitoring method for analysis of the components of the residue definition in high water content, high acid content and dry plant matrix groups was not available (relevant for the representative use evaluated; see Section 1).

Monitoring methods for all components of the residue definition in body fluids and tissues were not available (relevant for the representative use evaluated; see Section 1).

The phototoxic potential of methiocarb at UVB ranges should be addressed once an appropriate OECD test for UVB absorbers is available (relevant for the representative use evaluated; see Section 2).

A new in vivo GLP‐ and OECD‐compliant MN test would need to be provided to reduce the remaining uncertainties for the available an in vivo MN test (relevant for the representative use evaluated; see Section 2).

A comparative ChE study in adults and offspring rats is available to US‐EPA and was not available in the EU dossier. In addition, a justification whether this comparative study could be sufficient to waive the conduction of a complete developmental neurotoxicity (DNT) study would be appropriate (relevant for the representative use evaluated; see Section 2).

In vitro genotoxicity test battery for metabolite M01 was not available (relevant for the representative use evaluated; see Section 2).

Storage stability data for methiocarb and M01 in cereal grain and forage and covering the maximum storage time interval of the residue samples from the residue trials on maize were not available (relevant for the representative use evaluated; see Section 3).

Further data for addressing the risk to birds including the risk to earthworm‐eating birds (relevant for the representative use in maize; see Section 5).

Further data for addressing the risk to mammals (relevant for the representative use evaluated; submission date proposed by the applicant: unknown; see Section 5).

Information to address the risk from secondary poisoning following exposure to methiocarb phenol for fish‐eating birds and fish‐eating mammals (relevant for the representative use evaluated; see Section 5).

Further information to address the risk to birds and mammals from relevant plant metabolites (i.e. methiocarb sulfoxide) (relevant for the representative use evaluated; see Section 5).

Further data for addressing the risk to bees (both acute and chronic) were considered necessary (relevant for the representative use evaluated; see Section 5).

Further data for addressing the risk to earthworms for methiocarb and M01 were concluded to be needed (relevant for the representative use evaluated; see Section 5).

Particular conditions proposed to be taken into account to manage the risk(s) identified

For operators, the following control measures should be applied: closed transfer systems during mixing/loading, automated/closed bagging line, automated/enclosed stacking, adequate dust aspiration system throughout the seed treatment process, enclosed transport of treated seed and ‘dry’ cleaning techniques. The following personal protective equipment is required to be worn by all personnel throughout the entire working shift, whilst in the operational area of the seed‐treatment plant: suitable protective coveralls (protective coverall – impermeable ‘Tyvek’ type of coverall) suitable protective gloves, and suitable respiratory protective equipment (Disposable filtering face piece respirator to at least EN149 FFP3 or equivalent) (see Section 2).

A minimum drilling depth for maize seed of 3 cm is needed to mitigate the level of exposure that may occur in aquatic water bodies, both to support the approach taken to address the issue of the nature of residues that might occur in drinking water when surface water is abstracted for drinking water and to conclude that the risk to aquatic organisms is low for all Step 3 FOCUS surface water scenarios (see Sections 4 and 5).

Concerns

Issues that could not be finalised

An issue is listed as ‘could not be finalised’ if there is not enough information available to perform an assessment, even at the lowest tier level, for the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/201113 and if the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses).

An issue is also listed as ‘could not be finalised’ if the available information is considered insufficient to conclude on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

Information on the analytical methods used in all dietary toxicity studies, including the assessment of their validity was not provided (see Sections 1 and 2).

The consumer risk assessment could not be conducted because the residue definition for risk assessment in plant commodities is not finalised due to outstanding toxicity data to rule out the genotoxic potential for M01 compound (see Section 3).

The risk to bees could not be finalised (see Section 5).

Critical areas of concern

An issue is listed as a critical area of concern if there is enough information available to perform an assessment for the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/2011, and if this assessment does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater, or any unacceptable influence on the environment.

An issue is also listed as a critical area of concern if the assessment at a higher tier level could not be finalised due to lack of information, and if the assessment performed at a lower tier level does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater, or any unacceptable influence on the environment.

An issue is also listed as a critical area of concern if, in the light of current scientific and technical knowledge using guidance documents available at the time of application, the active substance is not expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

Exposure for workers loading and sowing the treated seed was above the AOEL (628% of the AOEL) and AAOEL (826% of the AAOEL) even with the use of workwear, gloves and FFP3 RPE (see Section 2).

High risk to birds has been identified (see Section 5).

High risk to mammals has been identified (see Section 5).

High risk to earthworms has been identified (see Section 5).

Overview of the concerns identified for each representative use considered

(If a particular condition proposed to be taken into account to manage an identified risk, as listed in Section 8, has been evaluated as being effective, then ‘risk identified’ is not indicated in Table 5.)

Table 5

Overview of concerns

Representative use		Maize
Operator risk	Risk identified
	Assessment not finalised
Worker risk	Risk identified	X4
	Assessment not finalised
Resident/bystander risk	Risk identified
	Assessment not finalised
Consumer risk	Risk identified
	Assessment not finalised	X2
Risk to wild non‐target terrestrial vertebrates	Risk identified	X5,6
	Assessment not finalised
Risk to wild non‐target terrestrial organisms other than vertebrates	Risk identified	X7
	Assessment not finalised	X3
Risk to aquatic organisms	Risk identified
	Assessment not finalised
Groundwater exposure to active substance	Legal parametric value breached
	Assessment not finalised
Groundwater exposure to metabolites	Legal parametric value breacheda
	Parametric value of 10 µg/Lb breached
	Assessment not finalised

Columns are grey if no safe use can be identified. The superscript numbers relate to the numbered points indicated in Sections 9.1 and 9.2. Where there is no superscript number, see Sections 2, 3, 4, 5–6 for further information.

When the consideration for classification made in the context of this evaluation under Regulation (EC) No 1107/2009 is confirmed under Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.

Value for non‐relevant metabolites prescribed in SANCO/221/2000‐rev. 10 final, European Commission (2003).

Abbreviations

active substance

acute acceptable operator exposure level

acetylcholinesterase

acceptable daily intake

acceptable operator exposure level

applied radioactivity

acute reference dose

body weight

cholinesterase

draft assessment report

days after treatment

developmental neurotoxicity

period required for 50% dissipation (define method of estimation)

period required for 90% dissipation (define method of estimation)

European Chemicals Agency

European Economic Community

Food and Agriculture Organization of the United Nations

Forum for the Co‐ordination of Pesticide Fate Models and their Use

flowable concentrate for seed treatment

Good Agricultural Practice

gas chromatography

high‐pressure liquid chromatography with tandem mass spectrometry

hypopharyngeal glands

hazard quotient

International Chemical Identifier Keys

International Organization for Standardization

International Union of Pure and Applied Chemistry

Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues (Joint Meeting on Pesticide Residues)

organic carbon linear adsorption coefficient

Freundlich organic carbon adsorption coefficient

lethal dose, median; dosis letalis media

limit of quantification

micronucleus

maximum residue level

maximum water‐holding capacity

no observed adverse effect level

non‐target arthropod

Organisation for Economic Co‐operation and Development

predicted environmental concentration

predicted environmental concentration in air

predicted environmental concentration in groundwater

predicted environmental concentration in sediment

predicted environmental concentration in soil

predicted environmental concentration in surface water

Renewal Assessment Report

rapporteur Member State

respiratory protective equipment

simplified molecular‐input line‐entry system

total radioactive residue

uncertainty factor

ultraviolet B

World Health Organization

Appendix A can be found in the online version of this output (‘Supporting information’ section): https://doi.org/10.2903/j.efsa.2018.5429

List of end points for the active substance and the representative formulation

Click here for additional data file.

Table 1

Soil

Compound (name and/or code)	Persistence	Ecotoxicology
Methiocarb	Very low to moderate persistence Biphasic kinetics DT50 0.38–20.2 days (DT90 2.9–84 days, 20°C, 40% MWHC or 75% of pF 2.5)	High risk to earthworms Low risk to other soil organisms including microorganism
Methiocarb sulfoxide (M01)	Low to moderate persistence Single first‐order and biphasic kinetics DT50 1.7–14.6 days (DT90 5.48.3 days, 20 or 24°C, 40% MWHC or 75% of pF 2.5)	High risk to earthworms Low risk to other soil organisms including microorganisms
Methiocarb sulfoxide phenol (M04)	Low to moderate persistence Single first‐order DT50 2.8–41.9 days (DT90 9.2–139 days, 20 or 24°C, 40% MWHC or 75% of pF 2.5)	Low risk to soil organisms including microorganisms
Methiocarb sulfone phenol (M05)	Low to medium persistence Single first‐order DT50 4.7–61.8 days (DT90 15.6–205 days, 20 or 24°C, 40% MWHC or 75% of pF 2.5)	Low risk to soil organisms including microorganisms
Methiocarb methoxy sulfone (M10)	Moderate to medium persistence Single first‐order DT50 25.7–66.7 days (DT90 85.5–222 days, 20 or 24°C, 40% MWHC or 75% of pF 2.5)	Low risk to soil organisms including microorganisms

DT50: period required for 50% dissipation; DT90: period required for 90% dissipation; MWHC: maximum water‐holding capacity.

Table 2

Groundwater

Compound (name and/or code)	Mobility in soil	> 0.1 μg/L at 1 m depth for the representative usesa	Pesticidal activity	Toxicological relevance
Methiocarb	Medium to low mobility KFoc 408–1,000 mL/g	No	Yes	Yes
Methiocarb sulfoxide (M01)	Very high mobility Kdoc 31 mL/g	No	Assessment not triggered	data gap
Methiocarb sulfoxide phenol (M04)	Very high to high mobility KFoc 27–101 mL/g	No	Assessment not triggered	Assessment not triggered Not mutagenic in an Ames test. Likely to be less toxic than the parent
Methiocarb sulfone phenol (M05)	High to medium mobility KFoc 86–163 mL/g	No	Assessment not triggered	Assessment not triggered Not mutagenic in an Ames test. Likely to be less toxic than the parent
Methiocarb methoxy sulfone (M10)	High to medium mobility KFoc 123–252 mL/g	No	Assessment not triggered	No data

KFoc: Freundlich organic carbon adsorption coefficient; Kdoc: organic carbon linear adsorption coefficient.

FOCUS scenarios or a relevant lysimeter.

Table 3

Surface water and sediment

Compound (name and/or code)	Ecotoxicology
Methiocarb	Low risk to aquatic organisms (considering mitigation measures)
Methiocarb sulfoxide (M01)	Low risk to aquatic organisms
Methiocarb phenol (M03)	Low risk to aquatic organisms
Methiocarb sulfoxide phenol (M04)	Low risk to aquatic organisms
Methiocarb sulfone phenol (M05)	Low risk to aquatic organisms
Methiocarb methoxy sulfone (M10)	Low risk to aquatic organisms

Table 4

Air

Compound (name and/or code)	Toxicology
Methiocarb	Acute Tox. 2 (H330 – Fatal if inhaled)

Code/trivial name	IUPAC name/SMILES notation/InChiKeya	Structural formulab
methiocarb	4‐methylthio‐3,5‐xylyl methylcarbamate O=C(OC1=CC(C)=C(SC)C(C)=C1)NC YFBPRJGDJKVWAH‐UHFFFAOYSA‐N
methiocarb sulfoxide (M01)	3,5‐dimethyl‐4‐(methylsulfinyl)phenyl methylcarbamate O=C(OC1=CC(C)=C(S(C)=O)C(C)=C1)NC FNCMBMZOZQAWJA‐UHFFFAOYSA‐N
methiocarb sulfone (M02)	3,5‐dimethyl‐4‐(methylsulfonyl)phenyl methylcarbamate O=C(OC1=CC(C)=C(S(=O)(C)=O)C(C)=C1)NC RJBJMKAMQIOAML‐UHFFFAOYSA‐N
methiocarb phenol (M03)	3,5‐dimethyl‐4‐(methylthio)phenol OC1=CC(C)=C(SC)C(C)=C1 JGFZITGNFAVSKU‐UHFFFAOYSA‐N
methiocarb sulfoxide phenol (M04)	3,5‐dimethyl‐4‐(methylsulfinyl)phenol OC1=CC(C)=C(S(C)=O)C(C)=C1 ZHBBDQFXEDCQFI‐UHFFFAOYSA‐N
methiocarb sulfone phenol (M05)	3,5‐dimethyl‐4‐(methylsulfonyl)phenol OC1=CC(C)=C(S(=O)(C)=O)C(C)=C1 GRBGKIGVRUXTSK‐UHFFFAOYSA‐N
N‐hydroxymethyl methiocarb (M06)	3,5‐dimethyl‐4‐(methylthio)phenyl (hydroxymethyl)carbamate O=C(OC1=CC(C)=C(SC)C(C)=C1)NCO LUKCDDHGKFIAFC‐UHFFFAOYSA‐N
N‐hydroxymethyl sulfoxide	3,5‐dimethyl‐4‐(methylsulfinyl)phenyl (hydroxymethyl)carbamate O=C(OC1=CC(C)=C(S(C)=O)C(C)=C1)NCO NPCHCWBDFBJFDV‐UHFFFAOYSA‐N
N‐hydroxymethyl methiocarb sulfone	3,5‐dimethyl‐4‐(methylsulfonyl)phenyl (hydroxymethyl)carbamate O=C(OC1=CC(C)=C(S(=O)(C)=O)C(C)=C1)NCO RUEOHENLKMUASC‐UHFFFAOYSA‐N
methiocarb methoxy sulfone (M10)	5‐methoxy‐1,3‐dimethyl‐2‐(methylsulfonyl)benzene O=S(C)(C1=C(C)C=C(OC)C=C1C)=O IGTACSQQISZYGQ‐UHFFFAOYSA‐N
2,4,6‐trichloro‐3,5‐dimethylphenyl methylcarbamate (trichloroxylenolcarbamate)	2,4,6‐trichloro‐3,5‐dimethylphenyl methylcarbamate O=C(OC1=C(Cl)C(C)=C(Cl)C(C)=C1Cl)NC LNRKKTWXEANTDJ‐UHFFFAOYSA‐N

IUPAC: International Union of Pure and Applied Chemistry; SMILES: simplified molecular‐input line‐entry system: InChiKey: International Chemical Identifier Key.

ACD/Name 2015 ACD/Labs 2015 Release (File version N20E41, Build 75170, 19 December 2014).

ACD/ChemSketch 2015 ACD/Labs 2015 Release (File version C10H41, Build 75059, 17 December 2014).