Updated peer review of the pesticide risk assessment of the active substance metalaxyl‐M (amendment of approval conditions)

Abstract

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co‐rapporteur Member State, Greece, for the pesticide active substance metalaxyl‐M are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses for the amendment to the conditions of approval of metalaxyl‐M as a fungicide seed treatment for sunflower and spinach seeds intended to be sown in field and on the basis of data submitted to update the specified level of an impurity in the technical active substance. This assessment was updated following a request from the Commission to integrate the risk assessment for birds and mammals with the application of refined good agricultural practices (GAPs). The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

SUMMARY

Regulation (EC) No 1107/2009 of the European Parliament and of the Council lays down, inter alia, the detailed rules as regards the procedure for the assessment of applications for amendment to the conditions of approval of active substances.

Metalaxyl‐M was renewed on 01 June 2020 by Commission Implementing Regulation (EU) 2020/617, following a peer review of the risk assessment as set out in the EFSA Conclusion on metalaxyl‐M, approved on 19 January 2015. It was a specific provision of the approval that, when used for seed treatment, only the treatment of seeds intended to be sown in greenhouses may be authorised. In accordance with Article 7 of the Regulation, the rapporteur Member State (RMS), Belgium, received an application from Syngenta Crop Protection AG on 17 June 2020 for an amendment to the conditions of approval of the active substance metalaxyl‐M to lift the restriction and to allow uses to be authorised as a seed treatment where treated seed may also be sown outside in fields, and to update the specified level of an impurity in the technical active substance.

An initial evaluation of the dossier on metalaxyl‐M was provided by the RMS in a revised 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 12 of Regulation (EC) No 1107/2009 of the European Parliament and of the Council.

EFSA published its conclusion on the peer review of the pesticide risk assessment of metalaxyl‐M on 31 October 2023. On 12 February 2024, the European Commission sent a mandate to EFSA with a request to integrate the risk assessment for birds and mammals with the application of refined GAPs. The following conclusions are derived.

The uses of metalaxyl‐M according to the representative uses as a fungicide on sunflower and spinach (seed treatment), as proposed at EU level result in a sufficient fungicidal efficacy against the targets Plasmopara halstedii, Peronospora spp. and Pythium spp.

The data provided with the current assessment do not change the conclusions reached during the previous peer review with respect to the identity, physical and chemical properties of the active substance and the formulation for representative uses, and analytical methods. However, based on the current toxicological assessment, an updated specified level was proposed for an impurity in the technical active substance.

In the mammalian toxicology section, the newly submitted data for one metabolite and one impurity did not impact on the conclusions of the renewal assessment, including toxicological reference values and risk assessment for operators, workers, residents and bystanders.

In the residue section, no new studies were submitted under the current procedure; thus, the conclusions reached during the previous peer review for the consumer risk assessment are still valid. However, following the submission of new data in the environmental fate section, an update on the consumer risk assessment via the consumption of drinking water was triggered resulting in the consumer risk assessment being not finalised.

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, except that information to address the effect of water treatment processes on the nature of the residues that might be present in surface water and groundwater, when surface water or groundwater are abstracted for drinking water purposes, was not available.

In the area of ecotoxicology, a high acute and long‐term risk was identified for birds and wild mammals with standard drilling equipment. However, low risk for birds and wild mammals was concluded when treated spinach is sown using precision drilling equipment at sowing densities below 2,000,000 seeds/ha.

Endocrine disrupting properties were not discussed in this conclusion, being dealt as part of the legally binding requirement established in the renewal of the approval of metalaxyl‐M (confirmatory information under Commission Implementing Regulation (EU) 2020/617).

BACKGROUND

Regulation (EC) No 1107/2009 of the European Parliament and of the Council ¹ (hereinafter referred to as ‘the Regulation’) lays down, inter alia, the detailed rules as regards the procedure for the assessment for an amendment to the conditions of an approval of active substances. This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States and the applicant(s) for comments on the initial evaluation in the draft assessment report (DAR), provided by the rapporteur Member State (RMS), and the organisation of an expert consultation, where appropriate.

In accordance with Article 12 of the Regulation, EFSA is required to adopt a conclusion on whether an active substance can be expected to meet the approval criteria provided for in Article 4 of the Regulation (also taking into consideration recital (10) of the Regulation) within 120 days from the end of the period provided for the submission of written comments, subject to an extension of 30 days where an expert consultation is necessary, and a further extension of up to 150 days where additional information is required to be submitted by the applicant(s) in accordance with Article 12(3).

Metalaxyl‐M is a substance covered by the second stage of the renewal programme (AIR II) in accordance with Regulation (EU) No 1141/2010 ² and was renewed on 01 June 2020 by Commission Implementing Regulation (EU) 2020/617, ³ following a peer review of the risk assessment as set out in the EFSA Conclusion on metalaxyl‐M, approved on 19 January 2015 (EFSA, 2015). It was a specific provision of the approval that, when used for seed treatment, only the treatment of seeds intended to be sown in greenhouses may be authorised. In accordance with Article 7 of Regulation (EC) No 1107/2009, Belgium (hereinafter referred to as the rapporteur Member State, ‘RMS’) subsequently received an application from Syngenta Crop Protection AG on 17 June 2020 for amendment to the conditions of approval of the active substance metalaxyl‐M to lift the restriction and allow uses to be authorised as a fungicide for seed treatment where seeds are sown outside in fields. The representative uses applied for were for sunflower and spinach seeds and included an extended use pattern covering lower application rates for spinach seed treatment than those had been assessed previously (EFSA, 2015).

The RMS provided its initial evaluation of the dossier on metalaxyl‐M in the form of a revised renewal assessment report (RAR), which was received by EFSA on 09 March 2021 (Belgium, 2021). The peer review was initiated on 08 April 2021 by dispatching the revised RAR to Member States and the applicant, Syngenta Crop Protection AG, for consultation and comments. EFSA also provided comments. In addition, EFSA conducted a public consultation on the revised RAR. The comments received were collated by EFSA and 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 12(3) of the Regulation were considered in a telephone conference between EFSA and the RMS on 09 November 2021. 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 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.

In accordance with Article 12 of the Regulation, EFSA should adopt a conclusion on whether metalaxyl‐M can be expected to meet the approval criteria provided for in Article 4 of the Regulation, taking into consideration recital (10) of the Regulation and in particular to amend the conditions of approval as a fungicide for seed treatment and allow uses to be authorised in fields. The representative uses applied for were for sunflower and spinach seeds treatment and included an extended use pattern covering lower application rates for spinach seed treatment than those that had been assessed previously (EFSA, 2015).

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 July–August 2023.

EFSA published its conclusion on the peer review of the pesticide risk assessment of the active substance metalaxyl‐M on 31 October 2023 (EFSA, 2023a), in which, inter alia, EFSA identified a critical area of concern for the risk to birds and mammals from the representative uses as a seed treatment. However, the conclusion and the background documents indicate that a safe use for treatment and sowing of treated spinach seeds may be possible, at least in the Member States in the Southern Zone of the EU (based on the relevant representative focal species there) when considering precision drilling of seeds. In the Standing Committee on Plants, Animals, Food and Feed (PAFF Committee), discussions on a possible decision on amending the existing approval of metalaxyl‐M took place in December 2023. Therefore, taking into account the views of Member States expressed in the PAFF Committee and pursuant to Article 31 of Regulation (EC) No 178/2002 ⁴ in conjunction with Regulation (EC) No 1107/2009, EFSA was requested to provide risk assessment conclusions for birds and mammals to take into account the following aspects. Given the current outcome, as reported in the EFSA Conclusion (2023b), the assessment should be limited to the lowest application rate on spinach seeds.

1. A consideration of lower, realistic seed sowing densities than the maximum value specified in the GAP should be undertaken – based on feedback from the applicant and from Member States, sowing densities for spinach range between 1 and 12 million seeds per hectare.

2. A consideration of precision sowing techniques – Member States have confirmed that the use of precision drilling equipment for sowing of treated seeds is already being used and is a realistic method of application; therefore, the use of such equipment should be taken into account in the risk assessment.

3. The risk to birds and mammals in each zone of the EU should be reported, taking into account the relevant higher tier refinements (e.g. focal species).

In addition, EFSA was requested to evaluate any additional information supporting the implementation of risk mitigation measures, if proposed by the RMS or Member States during the peer review.

The RMS has been requested by EFSA to provide a revised assessment taking into consideration the specific aspects indicated above. EFSA was requested to consult experts on these points and, where necessary, request the RMS to provide revisions of the assessment following any expert meetings. The existing Conclusion from 2023 would be updated to reflect the outcomes of the assessment and peer review. EFSA was requested to update its conclusion as the results of this mandate ⁵ within 8 months of receiving the revised assessment from the RMS, which was delivered on 31 July 2024 (Belgium, 2024).

This conclusion report summarises the outcome of the peer review of the risk assessment on the active substance and the formulation for representative uses evaluated on the basis of the representative uses of metalaxyl‐M as a fungicide on sunflower and spinach (seed treatment) as proposed by the applicant. The assessment was updated following the request from the Commission to review the risk assessment as regards birds and mammals on metalaxyl‐M. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the revised RAR and considered during the peer review, if any, are presented in the conclusion.

A list of the relevant end points for the active substance and the formulation is provided in Appendix B. In addition, the considerations as regards the cut‐off criteria for metalaxyl‐M according to Annex II of Regulation (EC) No 1107/2009 are summarised in Appendix A.

In addition, a key supporting document to this conclusion is the peer review report (EFSA, 2023b, updated in 2025), 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 (09 November 2021);

• the evaluation table (15 September 2023, updated in 2025);

• 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 consolidated commenting table with comments received on the revised RAR containing the RMS evaluations in the context of the mandate to review of the risk assessment as regards birds and mammals;

• the comments received on the draft EFSA conclusion and the updated EFSA conclusion.

Given the importance of the RAR, including its revisions (Belgium, 2023, 2024, 2025), and the peer review report, both documents are considered 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 formulation(s) for representative uses

Metalaxyl‐M is the ISO common name for methyl N‐(2,6‐dimethylphenyl)‐N‐(methoxyacetyl)‐D‐alaninate (IUPAC). Metalaxyl‐M is a single enantiomer (R enantiomer) of the racemic mixture metalaxyl.

The formulated product for the representative uses for this evaluation was ‘Apron XL’ an emulsion for seed treatment (ES) containing 339 g/L metalaxyl‐M.

The representative uses for this evaluation are fungicide seed treatments of spinach and sunflower seeds to be sown outside in fields as requested for the amendment to the approval conditions. Full details of the GAP (good agricultural practice) can be found in the list of end points in Appendix B.

The formulation ‘Ridomil Gold MZ 68WG/Fubol Gold’ water dispersible granules (WG) containing 38.8 g/kg metalaxyl‐M and 640 g/kg mancozeb ⁶ included for the renewal of approval of the active substance (EFSA, 2015) which had representative uses of foliar spray applications to tomatoes and grapes was not part of the current evaluation.

Data were submitted to conclude that the uses of metalaxyl‐M according to the representative uses proposed at EU level as seed treatments result in a sufficient fungicidal efficacy against the target diseases following the relevant guidance document (European Commission, 2014).

1. IDENTITY, PHYSICAL/CHEMICAL/TECHNICAL PROPERTIES AND METHODS OF ANALYSIS

The following guidance documents were followed in the production of this conclusion: European Commission, 2000, 2012.

Data submitted for the amendment of approval conditions do not change the minimum purity of 920 g/kg; the specification levels of the relevant impurities CGA72649 (2,6‐dimethyl‐phenylamine, 0.5 g/kg) and CGA363736 (4‐methoxy‐5‐methyl‐5H‐[1,2]oxathiole 2,2‐dioxide, 1 g/kg); and the specification levels of the significant impurities as proposed in the assessment previously conducted (EFSA, 2015). The toxicological relevance of an impurity, considered as relevant previously (EFSA, 2015), was not concluded in the current assessment (see Section 2); however, an updated specified level of < 10 g/kg was proposed for this impurity based on the current toxicological assessment (see Section 2). As a consequence, it is recommended to update the reference specification of the renewal of approval. The batches used in the toxicological and ecotoxicological assessments support the proposed updated specification.

The data submitted for amendment of approval conditions do not change the previous conclusions (EFSA, 2015) relevant to the physical and chemical properties; the analytical methods used for the generation of renewal pre‐approval data; and the methods for post‐approval control and monitoring purposes. Adequate methods were available for the generation of pre‐approval data required for the amendment of approval conditions.

2. MAMMALIAN TOXICITY

The following guidance documents were followed in the production of this conclusion: European Commission (2012).

In the occasion of the amendment to the conditions of approval, an updated search of the scientific peer‐reviewed open literature was conducted and included in the RAR (Belgium, 2021, 2023); however, the results did not indicate new information that could have an impact on the toxicological assessment previously conducted (EFSA, 2015).

During the renewal assessment, three impurities (including CGA72649 and CGA363736) were considered toxicologically relevant. As previously agreed, the maximum acceptable levels in the reference specification for CGA72649 and CGA363736 are 0.5 and 1 g/kg respectively. Based on the new data provided, the third impurity can finally be concluded as unlikely to be genotoxic; however, the limited assessment provided for the other toxicological endpoints (e.g. developmental toxicity and neurotoxicity) does not allow a full conclusion on its toxicological relevance. On this basis, a maximum level below 10 g/kg in the reference specification can be considered of no toxicological concern.

The groundwater metabolite NOA409045 is also concluded to be unlikely to be genotoxic based on the available data including a new in vivo micronucleus assay. Since NOA409045 (formed from metalaxyl‐M) is the R‐isomer of CGA62826 (racemate), it is assumed that, as the parent molecules (metalaxyl and metalaxyl‐M), the metabolites are toxicologically equivalent. Based on the 28‐day rat study with CGA62826, the derived acceptable daily intake (ADI) also applicable to NOA409045 is 0.5 mg/kg bw per day, applying to the NOAEL of 1000 mg/kg bw per day an increased uncertainty factor (UF) of 2000 (using a standard UF of 100, an additional UF of 10 due to the limited data package, and an additional UF of 2 to cover the possibility that the R‐isomer would be of higher toxicity than the racemate).

For the representative uses of the product APRON XL EC (A9642C) supported with the application for amendment to the conditions of approval, the decreased application rates on spinach seed (i.e. 50 and 100 mL product/100 kg seed) are covered by the one supported for the renewal (200 mL product/100 kg spinach seed). Consequently, the conclusions of the peer review for the renewal process can be retained (EFSA, 2015).

3. RESIDUES

The assessment in the residue section is based on the following guidance documents: OECD (2009, 2011), European Commission (2011) and JMPR (2004, 2007).

In the occasion of the amendment of approval conditions, only an update from the open literature was conducted and included in the RAR (Belgium, 2021, 2023); however, the new information has no impact on the consumer risk assessment via dietary intake conducted previously.

Since no new studies were submitted for metalaxyl‐M under current procedure in the residue section, the assessment of representative uses in sunflower and spinach conducted under the peer review process for which no data gaps were identified and the consumer dietary risk assessment was finalised is still valid (see EFSA, 2015).

Following the submission of new data in environmental fate (see Section 4), an update of the consumer risk assessment via consuming drinking water was conducted for the groundwater metabolite NOA409045 (see Table 3, Section 7) resulting in an exposure below 0.1% of the ADI. However, the consumer risk assessment from the consumption of drinking water is not finalised, considering the lack of appropriate information to address the effect of water treatment processes on the nature of residues potentially present in surface water and groundwater when surface water or groundwater is abstracted for drinking water (see Sections 4 and 9.1).

TABLE 3.

Groundwater. ^a

Compound (name and/or code)	> 0.1 μg/L at 1 m depth for the representative uses b	Biological (pesticidal) activity/relevance	Hazard identified	Consumer RA triggered	Human health relevance
	Step 2	Step 3a	Steps 3b and 3c	Steps 4 and 5
Metalaxyl‐M	No	Yes	–	–	Yes
NOA409045	No for sunflower Yes for spinach all 7 scenarios for loading rate of 200 mL/100 kg seed at up to 3.28 μg/L Yes 6/7 scenarios for loading rate of 100 mL and 50 mL/100 kg seed at up to 1.55 and 0.732 μg/L respectively	No	No Rat oral LD50 > 2000 mg/kg bw 28‐day rat oral NOAEL 1000 mg/kg bw per day Negative Ames test, gene mutation in vitro and micronucleus in vivo; positive clastogenicity in vitro; unlikely to be genotoxic ADI 0.5 mg/kg bw per day	Yes Consumer intake < 0.1% of the ADI	No for the representative use(s) assessed
CGA67868	No for sunflower Yes for spinach at 1/7 scenarios for loading rate of 200 mL/100 kg seed at 0.119 μg/L No for loading rate of 100 mL and 50 mL /100 kg seed	No	No (up to stage 3 of step 3) Negative Ames test, gene mutation and chromosome aberration in vitro assays	No	No for the representative uses assessed
SYN546520	No for sunflower Yes for spinach at 6/7 scenarios for loading rate of 200 mL/100 kg seed at up to 0.304 μg/L Yes for 2/7 scenarios for loading rate of 100 mL/100 kg seed at up to 0.155 μg/L No for loading rate of 50 mL/100 kg seed	No	No Rat oral and dermal LD50 > 2000 mg/kg bw 28‐day oral rat NOAEL 200 mg/kg bw per day Negative Ames test, gene mutation and chromosome aberration in vitro assays Reference values of the parent may apply to this metabolite	No	No for the representative uses assessed

^a Assessment according to European Commission guidance of the relevance of groundwater metabolites (2003).

^b FOCUS scenarios or relevant lysimeter.

4. ENVIRONMENTAL FATE AND BEHAVIOUR

Metalaxyl‐M was discussed at the Pesticides Peer Review Experts' Meeting Teleconference (TC) 90 on 20 September 2022. ⁷

In soil laboratory incubations under aerobic conditions in the dark, metalaxyl‐M exhibited low to medium persistence, forming the major (> 10% applied radioactivity (AR)) metabolite NOA409045 (max. 72% AR) which exhibited low to high persistence. The metabolites CGA67868 (max. 6% AR) and SYN546520 (max. 4% AR, still increasing at study end) were assessed as needing consideration for groundwater exposure; they exhibited low persistence and moderate to high persistence, respectively. Mineralisation of the phenyl ring ¹⁴C radiolabel to carbon dioxide accounted for 2%–33% AR after 84–86 days. The formation of unextractable residues (not extracted by acetone/water, methanol/water or acetonitrile/water) for this radiolabel accounted for 14%–73% AR after 84–86 days. In anaerobic soil incubations, metalaxyl‐M degraded more slowly than under aerobic conditions, with the route of degradation being the same as in the aerobic investigations. Data indicated that in soil, epimerisation of metalaxyl‐M, NOA409045 or SYN546520 to their racemates was not observed. Metalaxyl‐M exhibited very high to low mobility in soil. NOA409045 exhibited very high to high soil mobility, with CGA67868 and SYN546520 exhibiting very high soil mobility. It was concluded that the adsorption of these compounds was not pH dependent. In satisfactory European field dissipation studies carried out at 10 sites (spray application to the soil surface on bare soil plots in late spring) metalaxyl‐M and NOA409045 both exhibited low to moderate persistence.

Lysimeter studies where racemic metalaxyl was dosed have been evaluated in the DAR and included in the list of reliable endpoints. It should be noted that the experimental designs did not reflect the representative uses being assessed in this conclusion, so the annual average leachate concentrations indicated in the list of endpoints are not directly relevant for the representative uses.

In laboratory incubations in dark aerobic natural sediment water systems, the racemic metalaxyl dosed exhibited moderate persistence, forming the major metabolite CGA62826 (code given to the racemate of NOA409045, max. 69% AR in water at 112 days, exhibiting very high persistence). This metabolite also accounted for up to 23% AR of the extractable residue in sediment. The unextractable sediment fraction (not extracted by acetone/water followed by methanol water) was a limited sink for the phenyl ring ¹⁴C radiolabel, accounting for 10%–14% AR at study end (240 days). Mineralisation of this radiolabel accounted for 4%–8% AR at the end of the study. The peer review accepted the applicant's case that, based on the behaviour in soil where metalaxyl‐M was dosed and it was confirmed by chiral analyses that epimerisation had not occurred, it would be expected that only NOA409045 would be formed in natural sediment water systems when exposed to metalaxyl‐M. The peer review also accepted that, based on the soil evidence, the transformation rate of metalaxyl‐M in natural sediment water systems might be expected to be faster than that which had been estimated in the available experiments in these systems dosed with racemic metalaxyl. The necessary surface water and sediment exposure assessments (predicted environmental concentrations (PEC) calculations) were carried out for metalaxyl‐M and the metabolite NOA409045, using the FOCUS (FOCUS, 2001) step 1 and step 2 approach (version 3.2 of the Steps 1–2 in FOCUS calculator).

The necessary groundwater exposure assessments were appropriately carried out using FOCUS (European Commission, 2014) scenarios and the models PEARL 5.5.5, PELMO 6.6.4 (and MACRO 5.5.4 for spinach uses) ⁸ for the active substance metalaxyl‐M and its metabolites NOA409045, CGA67868 and SYN546520. The FOCUS crop cabbage was used for the simulations for the spinach uses. Which of the available kinetic formation fractions for SYN546520 from NOA409045 to use in the groundwater modelling was discussed in the teleconference 90. The value the experts agreed for use with the data that were available to them was 0.013, being the arithmetic mean kinetic formation fraction from reliable incubations in three different soils. The potential for groundwater exposure from the representative uses by metalaxyl‐M 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 pertinent FOCUS groundwater scenarios. This was also the case for both pertinent FOCUS groundwater scenarios (Piacenza and Sevilla) for the representative use on sunflower for the three metabolites NOA409045, CGA67868 and SYN546520. For the uses on spinach NOA409045, SYN546520 and CGA67868, 80th percentile annual average concentrations moving below 1‐m depth were predicted to be above the parametric drinking water limit of 0.1 μg/L in all 7, 6/7 and 1/7 of the pertinent FOCUS groundwater scenarios, respectively, for the seed loading rate of 200 mL/100 kg seed. This was reduced to 6/7, 2/7 and none of the pertinent FOCUS groundwater scenarios, respectively, for the seed loading rate of 100 mL/100 kg seed and 6/7, none and none, respectively, for the loading rate of 50 mL/100 kg seed. These three metabolites were assessed as being non relevant (see Sections 2 and 7).

The applicant did not provide appropriate information to address the effect of water treatment processes on the nature of the residues that might be present in surface water and groundwater, when surface water or groundwater are abstracted for drinking water. This has led to the identification of a data gap and results in the consumer risk assessment not being finalised (see Section 9.1).

The PEC in soil, surface water, sediment and groundwater covering the representative uses assessed can be found in Appendix B of this conclusion. A key to the wording used to describe the persistence and mobility of the compounds assessed can be found in Appendix C of this conclusion.

5. ECOTOXICOLOGY

In the remit of the amendment of approval conditions and the subsequent mandate by the European Commission, an updated risk assessment for birds and mammals was submitted following EFSA (2009).

The risk assessment conclusion for birds and mammals (EFSA, 2023a) is reported hereafter for completeness.

Metalaxyl‐M was discussed at the Pesticides Peer Review Experts' Meeting Teleconference 91 in September 2022 (EFSA, 2023b, updated in 2025).

Sufficient data were available to perform a risk assessment for birds and wild mammals.

The risk assessment for birds was conducted using the reproductive endpoint agreed at the meeting. ⁹

For the representative seed treatment use in sunflower and for the use in spinach at 81.4 g a.s./ha (67.8 g a.s./100 kg seeds; hereafter ‘high rate’), a high acute and reproductive risk to small granivorous birds consuming seeds and a high reproductive, but not acute, risk to small omnivorous birds consuming seedlings were identified at Tier I.

For the representative seed treatment use in spinach at 40.7 g a.s./ha (33.92 g a.s./100 kg seeds; hereafter ‘medium rate’), a low acute risk to birds consuming seeds and seedlings and a high reproductive risk to small granivorous and omnivorous birds consuming seeds and seedlings were identified at Tier I.

For the representative seed treatment use in spinach at 20.4 g a.s./ha (16.96 g a.s./100 kg seeds; hereafter ‘low rate’), a low acute risk to birds consuming seeds and seedlings and a high reproductive risk to small birds consuming seeds (but not seedlings) were identified at Tier I.

At the meeting, ¹⁰ the (i) higher tier acute and reproductive risk assessment for birds consuming sunflower seeds and seedlings; (ii) the higher tier acute (high rate) and reproductive risk assessment for birds consuming spinach seeds (low, medium and high rate) and (iii) the reproductive risk assessment for birds consuming seedlings (medium and high rate) were discussed in relation to the acceptability of the following refinements in risk assessment:

• – Ecological data, such as specific focal species studies, studies quantifying the proportion of food items in their diet (PD) or the refined proportion of food obtained in the treated area (i.e. PT). ¹¹
• – The energy and moisture content of crop seeds.
• – Residue and metabolism data in seeds and seed shoots.
• – The Weight of Evidence (WoE), including (i) the number of treated seeds required to reach toxicity; (ii) the foraging area required to reach toxicity; (iii) the de‐husking and avoidance of seeds.

Overall, the higher tier risk assessment was deemed insufficient to address (i) the acute and long‐term risk for birds consuming sunflower seeds and (ii) the long‐term risk assessment for birds consuming sunflower seedlings (data gap, see Section 9). ¹² Additionally, the higher tier risk assessment was deemed insufficient to address the acute (high rate) and long‐term (all rates) risk identified at Tier I for birds consuming spinach seeds ¹³ and the long‐term risk assessment for birds consuming spinach seedlings (medium and high rate).¹²

The risk assessment for wild mammals is summarised hereafter:

For the representative seed treatment use in sunflower, a high acute and long‐term risk was identified for small mammals consuming seeds and seedlings at Tier I. Additionally, for the representative seed treatment uses in spinach (all rates) a high acute and long‐term risk was identified for small mammals consuming seeds, but not seedlings at Tier I.

At the meeting, ¹⁴ the higher tier acute and reproductive risk assessment for mammals consuming sunflower seeds and seedlings and the higher tier acute and reproductive risk assessment for mammals consuming spinach seeds were discussed in relation to the acceptability of the following refinements in risk assessment:

• – Ecological data, such as specific focal species studies, PD and PT studies;
• – The energy and moisture content of crop seeds;
• – Residue and metabolism data in seeds and seed shoots;
• – The Weight of Evidence (WoE), including (i) the number of treated seeds required to reach toxicity; (ii) the foraging area required to reach toxicity; (iii) the de‐husking and avoidance of seeds.

Overall, the higher tier risk assessment was deemed insufficient to address the acute and long‐term risk for mammals consuming sunflower seeds and seedlings and the acute ¹⁵ and long‐term risk for mammals consuming spinach seeds for sowing techniques other than precision drilling. ¹⁶

The risk for birds and mammals from exposure to plant metabolites was not quantified, under the assumption that it would be covered by the risk assessment conducted for the parent compound.

An updated literature search was submitted, including relevant ecotoxicity studies in fish, which were discussed at the meeting. ¹⁷ However, such information was not considered to impact the hazard assessment previously conducted by EFSA (2015).

Following the publication of the conclusion (EFSA, 2023a), the risk assessment was updated considering additional clarifications on the representative seed treatment uses of Metalaxyl‐M provided by the European Commission. Specifically, it was clarified that spinach can be sown with precision machinery at lower densities than those reported in the GAP, with no expected impact on efficacy, ¹⁸ and that the influence of these use patterns on the risk assessment should be considered. Accordingly, the following risk assessment clarifies whether, under the new assumptions outlined in Table 1, the representative use in spinach resulting in the lowest application rate (i.e. 16.96 g a.s./100 kg seeds) would lead to high risk in any of the EU zones. Additionally, all risk mitigation measures proposed in the revised assessment report by the RMS were considered.

TABLE 1.

The representative uses considered in EFSA (2023a) and in this assessment.

Uses considered in EFSA (2023a)		Use considered in the current assessment
Sunflower 300 mL Apron XL (101.7 g a.s.)/100 kg seed		Spinach 50 mL Apron XL (16.95 g a.s.)/100 kg seed**
Spinach	200 mL Apron XL (67.8 g a.s.)/100 kg seed*
	100 mL Apron XL (33.9 g a.s.)/100 kg seed*
	50 mL Apron XL (16.95 g a.s.)/100 kg seed*

^*With standard drilling machinery and a sowing density of 12,000,000 seeds/ha.

^**With standard or precision drilling and sowing densities from 1,000,000 to 12,000,000 seeds/ha.

Following the European Commission mandate, Metalaxyl‐M was discussed at the Pesticides Peer Review Experts' Teleconference 155 in December 2024.

Low acute and reproductive risk for birds consuming seedlings and low acute risk for birds consuming seeds was concluded based on Tier‐1 calculations. However, a high reproductive risk for seed‐eating birds was identified at Tier‐1. Consequently, the risk assessment was refined for the three EU regulatory zones:

• – For the Southern EU zone ¹⁹ : Low risk was quantitatively concluded at all sowing densities considering focal species (Linnet, Greenfinch and Crested lark), residue dissipation, food intake rate divided by the body weight (FIR/bw) and the proportion of food obtained in the treated area (PT) for the focal species listed above;
• – For the Central EU zone ²⁰ : A refined risk assessment considering focal species (i.e. rook, wood pigeon, red‐legged partridge, skylark), residue dissipation, FIR/bw and a refined proportion of dietary items obtained in the treated area (PD) for skylark was available, which did not allow excluding high risk for the focal species skylark and rook. Furthermore, uncertainties were identified as to whether smaller species than the skylark, which could be present in the Central EU zone, were covered by the available focal species selection. Therefore, a refined weight‐of‐evidence (WoE) approach was discussed at the meeting based on which low reproductive risk for seed‐eating birds was concluded for uses with precision drilling machinery below 2,400,000 seeds/ha. For densities higher than 2,400,000 seeds/ha a reproductive risk could not be excluded.
• – For the Northern EU zone ²¹ : A refined risk assessment considering focal species (i.e. skylark), residue dissipation, FIR/bw and PD was available, which did not allow quantitatively excluding high risk. However, a refined WoE approach was available, based on which low reproductive risk for seed‐eating birds was concluded for uses with precision drilling machinery below 4,700,000 seeds/ha. For densities higher than 4,700,000 seeds/ha, a reproductive risk could not be excluded.

High acute and reproductive risk was identified at Tier‐1 for wild mammals consuming seeds but not seedlings. A refined acute assessment was available considering focal species, FIR/bw and (for Southern EU only) qualitative use of PD. Based on these refined TERs, a low acute risk for seed‐eating mammals was concluded for all zones and sowing densities when precision drilling equipment is used. Refined reproductive TERs were also available, considering residue dissipation, focal species, FIR bw and PT. Based on these refined TERs, a low reproductive risk for seed‐eating mammals was concluded for all zones and sowing densities when precision drilling equipment is used.

A high risk for birds and mammals was identified when treated spinach seeds are sown with standard drilling techniques in any of the EU zones and at any of the sowing densities in the GAP.

A conclusion for the whole EU (i.e. protective of all regulatory zones) was also drawn based on a risk envelope approach and taking into account the WoE and the uncertainty analysis discussed at the meeting. ²² Low risk for birds and wild mammals was concluded across all EU zones when treated spinach is sown using precision drilling equipment at sowing densities below 2,000,000 seeds/ha, but not above this value (see Tables 6 and 7). ²³ Key uncertainties acknowledged at the meeting are reported below in relation to:

• – The likelihood of birds digging up buried seeds, potentially leading to underestimating risks.
• – How equipment and scattered data availability may affect the quantification of seed availability upon drilling, which might lead to over‐ or underestimating risks.
• – How seed burying affects residue decline, which could lead to underestimating risks.
• – Ecological data derivation, with unclear directionality.
• – Limited evidence on seed (un)palatability, avoidance or de‐husking, which was considered qualitatively and with low weight.

TABLE 6.

Risk mitigation measures proposed for the representative uses assessed.

Representative use	Spinach (100 mL/ha)	Spinach (50 mL/ha)	Sunflower
	Seed treatment + sowing	Seed treatment + sowing	Seed treatment + sowing
Operator risk	Use of PPE is required a	Use of PPE is required a
Risk for birds and mammals		Use of precision drilling equipment and sowing densities below 2,000,000 seeds/ha

^a Based on surrogate exposure study: gloves and respiratory protective equipment for operators during mixing/loading, treatment and cleaning.

TABLE 7.

Overview of concerns reflecting the issues not finalised, critical areas of concern, and the risks identified that may be applicable for some but not for all uses or risk assessment scenarios.

Representative use		Sunflower field	Spinach field 200 mL/100 kg seed	Spinach field 100 mL/100 kg seed	Spinach field 50 mL/100 kg seed
		Seed treatment	Seed treatment	Seed treatment	Seed treatment
Operator risk	Risk identified	X b
	Assessment not finalised
Worker risk	Risk identified
	Assessment not finalised
Resident/bystander risk	Risk identified
	Assessment not finalised
Consumer risk	Risk identified
	Assessment not finalised	X1	X1	X1	X1
Risk to wild non‐target terrestrial vertebrates	Risk identified	X c	X c	X c	X d
	Assessment not finalised
Risk to wild non‐target terrestrial organisms other than vertebrates	Risk identified
	Assessment not finalised
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 breached
	Parametric value of 10 μg/L a breached
	Assessment not finalised

Note: 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, 7 for further information.

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

^b Based on Seed Tropex model (EFSA, 2015).

^c High risk for birds and wild mammals.

^d High risk for birds and wild mammals, when standard drilling equipment is used or when precision drilling equipment is used with sowing densities above 2,000,000 seeds/ha.

6. ENDOCRINE DISRUPTION PROPERTIES

Endocrine disrupting (ED) properties according to the ECHA/EFSA Guidance (2018) were not assessed in this application to amend the approval conditions. It was agreed by risk managers that this was out of the scope of the evaluation since according to Commission Regulation (EU) 2020/617 the ED assessment should be dealt as part of the confirmatory information process.

7. OVERVIEW OF THE RISK ASSESSMENT OF COMPOUNDS LISTED IN RESIDUE DEFINITIONS TRIGGERING ASSESSMENT OF EFFECTS DATA FOR THE ENVIRONMENTAL COMPARTMENTS (TABLES 2, 3, 4, 5)

TABLE 2.

Soil.

Compound (name and/or code)	Ecotoxicology
Metalaxyl‐M	Low risk to soil‐dwelling organisms (EFSA, 2015)
NOA409045	Low risk to soil‐dwelling organisms (EFSA, 2015)

TABLE 4.

Surface water and sediment.

Compound (name and/or code)	Ecotoxicology
Metalaxyl‐M	Low risk to aquatic organisms (EFSA, 2015)
NOA409045	Low risk to aquatic organisms (EFSA, 2015)

TABLE 5.

Air.

Compound (name and/or code)	Toxicology
Metalaxyl‐M	Rat LC50 by inhalation > 2.29 mg/L air/4 h (nose‐only), no classification required

8. PARTICULAR CONDITIONS PROPOSED TO BE TAKEN INTO ACCOUNT BY RISK MANAGERS

Risk mitigation measures (RMMs) identified following consideration of Member State (MS) and/or applicant's proposal(s) during the peer review, if any, are presented in this section. These measures applicable for human health and/or the environment leading to a reduction of exposure levels of operators, workers, bystanders/residents, environmental compartments and/or non‐target organisms for the representative uses are listed below. The list may also cover any RMMs as appropriate, leading to an acceptable level of risks for the respective non‐target organisms.

It is noted that final decisions on the need of RMMs to ensure the safe use of the plant protection product containing the concerned active substance will be taken by risk managers during the decision‐making phase. Consideration of the validity and appropriateness of the RMMs remains the responsibility of MSs at product authorisation, taking into account their specific agricultural, plant health and environmental conditions at national level.

Particular conditions are proposed considering the scope of this evaluation. Furthermore, the RMM already identified in the approval conclusion (EFSA, 2015) are still applicable.

9. CONCERNS AND RELATED DATA GAPS

9.1. 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 one or more of 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 ²⁴ 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.

The following issues or assessments that could not be finalised have been identified, together with the reasons including the associated data gaps where relevant, which are reported directly under the specific issue to which they are related:

1. The consumer risk assessment is not finalised with regard to the unknown nature of residues that might be present in drinking water, consequent to water treatment following abstraction of groundwater or surface water when it might contain the active substance (predicted to be for surface water only) and its metabolites (both surface and groundwater) (see Sections 3 and 4).

   1. Satisfactory information regarding the effect of water treatment processes on the nature of residues present in surface water and groundwater, when surface water or groundwater are abstracted for drinking water, was not available. Probably in the first instance, a consideration of the processes of ozonation and chlorination would appear appropriate. If an argumentation is made that concentrations at the point of abstraction for drinking water purposes will be low, this argumentation should cover metabolites predicted to be in groundwater and surface water, as well as the active substance. Should this consideration indicate that novel compounds might be expected to be formed from water treatment, the risk to human or animal health through the consumption of drinking water containing them should be addressed (relevant to comply with the conditions of approval, not dependent of any specific use, see Section 4).

9.2. 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 the 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.

The following critical areas of concern are identified, together with any associated data gaps, where relevant, which are reported directly under the specific critical area of concern to which they are related:

No critical areas of concern were identified.

9.3. Overview of the concerns identified for each representative use considered (Table 7)

(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 7).

10. LIST OF OTHER OUTSTANDING ISSUES

Remaining data gaps not leading to critical areas of concern or issues not finalised but considered necessary to comply with the data requirements, and which are relevant for some or all of the representative uses assessed at EU level. Although not critical, these data gaps may lead to uncertainties in the assessment and are considered relevant.

These data gaps refer only to the representative uses assessed and are listed in the order of the sections. Data gaps from EFSA ( 2015 ) that were not addressed in this conclusion have been also listed for completeness:

• Spectra for the relevant impurity CGA363736 (relevant for all representative uses evaluated; see Section 1).

• Methods of analysis for the relevant impurities CGA72649 and CGA363736 in both formulations (relevant for all representative uses evaluated; see Section 1).

• A final study report was not available for the study used to calculate the proportion of food obtained in the treated area (i.e. PT) for greenfinch, linnet and crested lark in SEU in the higher tier long‐term risk assessment for birds consuming spinach seeds (relevant for all representative use on spinach; see Section 5).

ABBREVIATIONS

a.s.

active substance

ADE

actual dermal exposure

ADI

acceptable daily intake

AF

assessment factor

AMA

Amphibian Metamorphosis Assay

AP

alkaline phosphatase

AR

androgen receptor

AR

applied radioactivity

AST

aspartate aminotransferase (SGOT)

AUC

area under the blood concentration/time curve

AV

avoidance factor

bw

body weight

CAS

Chemical Abstracts Service

CHO

Chinese hamster ovary cells

CI

confidence interval

CL

confidence limits

DAR

draft assessment report

DAT

days after treatment

EEC

European Economic Community

FAO

Food and Agriculture Organization of the United Nations

FID

flame ionisation detector

FIR

food intake rate

FOB

functional observation battery

FOCUS

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

GAP

Good Agricultural Practice

GC

gas chromatography

GGT

gamma glutamyl transferase

GM

geometric mean

HQ

hazard quotient

HR

hazard rate

ISO

International Organization for Standardization

IUPAC

International Union of Pure and Applied Chemistry

iv

intravenous

LC

liquid chromatography

LC–MS

liquid chromatography–mass spectrometry

LC–MS‐MS

liquid chromatography with tandem mass spectrometry

LDH

lactate dehydrogenase

LOD

limit of detection

M/L

mixing and loading

MCV

mean corpuscular volume

MOA

mode of action

MS

mass spectrometry

MSDS

material safety data sheet

NOEL

no observed effect level

NPD

nitrogen–phosphorus detector

OECD

Organisation for Economic Co‐operation and Development

OM

organic matter content

Pa

pascal

PD

proportion of different food types

PEC

predicted environmental concentration

PHI

preharvest interval

PIE

potential inhalation exposure

PPE

personal protective equipment

ppm

parts per million (10⁻⁶)

PT

proportion of diet obtained in the treated area

PTT

partial thromboplastin time

RAR

Renewal Assessment Report

RBC

red blood cells

REACH

Registration, Evaluation, Authorisation of Chemicals Regulation

SC

suspension concentrate

SD

standard deviation

SMILES

simplified molecular‐input line‐entry system

TK

technical concentrate

TWA

time‐weighted average

UV

ultraviolet

W/S

water/sediment

WBC

white blood cell

WHO

World Health Organization

REQUESTOR

European Commission

QUESTION NUMBERS

EFSA‐Q‐2020‐00666, EFSA‐Q‐2024‐00098

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NOTE/UPDATE

This scientific output, approved on 30 June 2025, supersedes the previous output published on 31 October 2023 (EFSA, 2023a).

Supporting information

APPENDIX B List of end points for the active substance and the formulation for representative uses relevant for the amendment of approval conditions

APPENDIX A. Consideration of cut‐off criteria for metalaxyl‐M according to Annex II of Regulation (EC) No 1107/2009 of the European Parliament and of the Council

Properties		Conclusion a
CMR	Carcinogenicity (C)	Metalaxyl‐M is not considered to be a carcinogen according to point 3.6.3 of Annex II of Regulation (EC) No 1107/2009
	Mutagenicity (M)	Metalaxyl‐M is not considered to be a mutagen according to point 3.6.2 of Annex II of Regulation (EC) No 1107/2009
	Toxic for Reproduction (R)	Metalaxyl‐M is not considered to be a reproductive toxicant according to point 3.6.4 of Annex II of Regulation (EC) No 1107/2009
Endocrine disrupting properties		The endocrine disruption properties of metalaxyl‐M according to points 3.6.5 and 3.8.2 of Annex II of Regulation No 1107/2009, as amended by Commission Regulation (EU) 2018/605 were not discussed in this conclusion
POP	Persistence	Metalaxyl‐M is not considered to be a persistent organic pollutant (POP) according to point 3.7.1 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation
	Long‐range transport
PBT	Persistence	Metalaxyl‐M not considered to be a persistent, bioaccumulative and toxic (PBT) substance according to point 3.7.2 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation
	Toxicity
vPvB	Persistence	Metalaxyl‐M not considered to be a very persistent, very bioaccumulative substance according to point 3.7.3 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation

^a Origin of data to be included where applicable (e.g. EFSA, ECHA RAC, Regulation).

APPENDIX B. List of end points for the active substance and the formulation for representative uses relevant for the amendment of approval conditions

Appendix B can be found in the online version of this output (‘Supporting Information’ section): https://doi.org/10.2903/j.efsa.2025.9573

APPENDIX C. Wording EFSA used in Section 4 of this conclusion, in relation to DT and Koc ‘classes’ exhibited by each compound assessed

Wording	DT50 normalised to 20°C for laboratory incubations 25 or not normalised DT50 for field studies (SFO equivalent, when biphasic, the DT90 was divided by 3.32 to estimate the DT50 when deciding on the wording to use)
Very low persistence	< 1 day
Low persistence	1 to < 10 days
Moderate persistence	10 to < 60 days
Medium persistence	60 to < 100 days
High persistence	100 days to < 1 year
Very high persistence	A year or more

Note: These classes and descriptions are unrelated to any persistence class associated with the active substance cut‐off criteria in Annex II of Regulation (EC) No 1107/2009. For consideration made in relation to Annex II, see Appendix A.

Wording	K oc (either K Foc or K doc) mL/g
Very high mobility	0–50
High mobility	51–150
Medium mobility	151–500
Low mobility	501–2000
Slight mobility	2001–5000
Immobile	> 5000

Note: Based on McCall et al. (1980).

APPENDIX D. Used compound codes

Code/trivial name a	IUPAC name/SMILES notation/InChiKey b	Structural formula c
Metalaxyl CGA48988	Methyl N‐(2,6‐dimethylphenyl)‐N‐(methoxyacetyl)‐DL‐alaninate CC(N(C(=O)COC)c1c(C)cccc1C)C(=O)OC ZQEIXNIJLIKNTD‐UHFFFAOYSA‐N
Metalaxyl‐M CGA329351	Methyl N‐(2,6‐dimethylphenyl)‐N‐(methoxyacetyl)‐D‐alaninate C[C@@H](N(C(=O)COC)c1c(C)cccc1C)C(=O)OC ZQEIXNIJLIKNTD‐GFCCVEGCSA‐N
CGA62826	(RS)‐2‐[(2,6‐Dimethyl‐phenyl)‐(2‐methoxy‐acetyl)‐amino]‐propionic acid CC(N(C(=O)COC)c1c(C)cccc1C)C(=O)O ZRIKZVLHMGYCIR‐UHFFFAOYSA‐N
NOA409045	(R)‐2‐[(2,6‐Dimethyl‐phenyl)‐(2‐methoxy‐acetyl)‐amino]‐propionic acid C[C@@H](N(C(=O)COC)c1c(C)cccc1C)C(=O)O ZRIKZVLHMGYCIR‐LLVKDONJSA‐N
CGA108906	2‐[((RS)‐1‐Carboxy‐ethyl)‐(2‐methoxy‐acetyl)‐amino]‐3‐methyl‐benzoic acid CC(N(C(=O)COC)c1c(C)cccc1C(=O)O)C(=O)O WFTHOCDLKYPFJX‐UHFFFAOYSA‐N
SYN546520	2‐[((R)‐1‐Carboxy‐ethyl)‐(2‐methoxy‐acetyl)‐amino]‐3‐methyl‐benzoic acid C[C@@H](N(C(=O)COC)c1c(C)cccc1C(=O)O)C(=O)O WFTHOCDLKYPFJX‐SECBINFHSA‐N
CGA67868	N‐(2,6‐Dimethyl‐phenyl)‐2‐methoxy‐acetamide O=C(Nc1c(C)cccc1C)COC OXXYGGDIKKXTFB‐UHFFFAOYSA‐N
CGA72649	2,6‐dimethyl‐phenylamine Cc1cccc(C)c1N UFFBMTHBGFGIHF‐UHFFFAOYSA‐N
CGA363736	4‐methoxy‐5‐methyl‐5H‐[1,2]oxathiole 2,2‐dioxide CC1OS(=O)(=O)C=C1OC IJLLPHSCBOYYAG‐UHFFFAOYSA‐N

^a The metabolite name in bold is the name used in the conclusion.

^b ACD/Name 2021.1.3 ACD/Labs 2021.1.3 (File Version N15E41, Build 123232, 07 Jul 2021).

^c ACD/ChemSketch 2021.1.3 ACD/Labs 2021.1.3 (File Version C25H41, Build 123835, 29 Aug 2021).

EFSA (European Food Safety Authority) , Álvarez, F. , Arena, M. , Auteri, D. , Leite, S. B. , Binaglia, M. , Castoldi, A. F. , Chiusolo, A. , Colagiorgi, A. , Colas, M. , Crivellente, F. , De Lentdecker, C. , De Magistris, I. , Egsmose, M. , Fait, G. , Ferilli, F. , Broussard, M. F. , Santonja, G. G. , Gouliarmou, V. , … Villamar‐Bouza, L. (2025). Updated peer review of the pesticide risk assessment of the active substance metalaxyl‐M (amendment of approval conditions). EFSA Journal, 23(7), e9573. 10.2903/j.efsa.2025.9573