Peer review of the pesticide risk assessment of the active substance halosulfuron‐methyl

TL;DR

This paper summarizes the peer review of the risk assessment for the pesticide halosulfuron-methyl, focusing on its use in rice crops.

Contribution

The paper provides a detailed evaluation of the regulatory risk assessment and identifies missing information and concerns.

Findings

The peer review evaluated halosulfuron-methyl's use as a herbicide in rice crops.

Reliable endpoints for regulatory risk assessment were identified.

Missing information and concerns were highlighted for further action.

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 Italy and co‐rapporteur Member State Poland for the pesticide active substance halosulfuron‐methyl are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2020/103. The conclusions were reached on the basis of the evaluation of the representative use of halosulfuron‐methyl as a herbicide in rice crops. 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 identified.

Figures

Tables

TABLE 1. Summary of the toxicological profile of the metabolites requiring further toxicological data.

Metabolite	Source(s)	Genotoxicity		General toxicity	Reference values/Data gap(s)
		Gene mutation	Chromosome aberrations
Chlorosulfonamide acid (CSA)	GW and residues	Negative Negative Ames test; Negative in vitro mammalian cell gene mutation test	Open Negative in vitro chromosome aberration test (only supportive); Negative in vivo mouse micronucleus test (only supportive)	Metabolite does not share the developmental toxicology profile of the parent 90‐day rat study, prenatal developmental toxicity rat study; no major mammalian metabolite	No conclusion Data gap genotoxicity
Halosulfuron rearrangement (HSR)	GW	Open No experimental data; no in silico/read‐across analysis	Open No experimental data; no in silico/read‐across analysis	No conclusion No experimental data; no in silico/read‐across analysis; no major mammalian metabolite	No conclusion Data gap genotoxicity; data gap general toxicity
Aminopyrimidine (AP)	Residues	Open No experimental data; no in silico/read‐across analysis	Open No experimental data; no in silico/read‐across analysis	No conclusion No experimental data; no in silico/read‐across analysis; no major mammalian metabolite	No conclusion Data gap genotoxicity; data gap general toxicity

TABLE 2. Soil.

Compound (name and/or code)	Ecotoxicology
halosulfuron‐methyl	Low risk to soil‐dwelling organisms.
halosulfuron‐methyl rearrangement	Low risk to soil‐dwelling organisms.
halosulfuron rearrangement	Low risk to soil‐dwelling organisms.
chlorosulfonamide	Low risk to soil‐dwelling organisms.
chlorosulfonamide acid	Low risk to soil‐dwelling organisms.
aminopyrimidine	Low risk to soil‐dwelling organisms.

TABLE 3. Groundwater. a

Compound (name and/or code)	> 0.1 μg/L at 1 m depth for the representative uses b Step 2	Biological (pesticidal) activity/relevance Step 3a.	Hazard identified Steps 3b. and 3c.	Consumer RA triggered Steps 4 and 5	Human health relevance
Halosulfuron‐methyl	Yes 1/2 MED‐RICE scenarios (0.483 μg/L)	Yes	Yes Repr Cat 1B	Open (no TRVs)	Yes
Halosulfuron‐methyl rearrangement (HSMR)	No	Not triggered	Not triggered	No	Not triggered
Halosulfuron rearrangement (HSR)	Yes 1/2 MED‐RICE scenarios (0.157 μg/L)	No	Yes No data on genotoxicity and general toxicity. Developmental toxicity of the parent (Repr Cat 1B) cannot be excluded	Open Pending the tox assessment and the data gap on the new metabolism study in rice.	Yes
Chlorosulfonamide CSE)	No	No	Not triggered	No	Not triggered
Chlorosulfonamide acid (CSA)	Yes, 2/2 MED‐RICE Scenarios (0.142–0.206 μg/L)	No	Open Not mutagenic; insufficient assessment of clastogenicity and aneugenicity Developmental rat study: no teratogenic effects identified	Open Pending the tox assessment and data gap on the new metabolism study in rice.	Open
Aminopyrimidine (AP)	No	Not triggered	Not triggered	No	Not triggered

TABLE 4. Surface water and sediment.

Compound (name and/or code)	Ecotoxicology
halosulfuron‐methyl	Assessment not finalised.
halosulfuron‐methyl rearrangement	Low risk to aquatic organisms.
halosulfuron rearrangement	Assessment not finalised.
chlorosulfonamide	Assessment not finalised.
aminopyrimidine	Assessment not finalised.
chlorosulfonamide acid	Assessment not finalised.
halosulfuron	Assessment not finalised.
possible aqueous photolysis transformation products	Assessment not finalised.

TABLE 5. Air.

Compound (name and/or code)	Toxicology
halosulfuron‐methyl	Rat LC50 inhalation > 6.0 mg/L air for 4 h (whole body)

TABLE 6. Overview of concerns reflecting the issues not finalised, critical areas of concerns and the risks identified that may be applicable for some but not for all uses or risk assessment scenarios.

Representative use		Rice
		Foliar spray
Operator risk	Risk identified
	Assessment not finalised	X10
Worker risk	Risk identified
	Assessment not finalised	X10
Resident/bystander risk	Risk identified
	Assessment not finalised	X10
Consumer risk	Risk identified
	Assessment not finalised	X3,10
Risk to wild non‐target terrestrial vertebrates	Risk identified
	Assessment not finalised
Risk to wild non‐target terrestrial organisms other than vertebrates	Risk identified
	Assessment not finalised	X5
Risk to aquatic organisms	Risk identified
	Assessment not finalised	X4
Groundwater exposure to active substance	Legal parametric value breached
	Assessment not finalised	1/27 MED‐RICE scenarios
Groundwater exposure to metabolites	Legal parametric value breached
	Parametric value of 10 μg/L a breached
	Assessment not finalised	2/28,9 MED‐RICE scenarios

Full text

SUMMARY

Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2020/103, 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, as amended by Commission Implementing Regulation (EU) No 2018/155. Halosulfuron‐methyl is one of the active substances listed in that Regulation.

In accordance with Article 1 of Regulation (EU) No 844/2012, the rapporteur Member State (RMS), Italy and co‐rapporteur Member State (co‐RMS), Poland, received an application from Nissan Chemical Europe S.A.S. for the renewal of approval of the active substance halosulfuron‐methyl.

An initial evaluation of the dossier on halosulfuron‐methyl was provided by the RMS in the renewal assessment report (RAR) and subsequently, a peer review of the pesticide risk assessment on the RMS evaluation was conducted by EFSA in accordance with Article 13 of Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2020/103.

The following overall conclusions were derived by the peer review.

The uses of halosulfuron‐methyl according to the representative use, i.e. applied by spraying as a herbicide on rice in paddy fields, as proposed at EU level result, in a sufficient herbicidal efficacy against the target weeds.

The assessment of the data package revealed no issues that could not be finalised or that need to be included as critical areas of concern with respect to identity, physical–chemical and technical properties of the active substance and the representative formulation and analytical methods.

With regard to mammalian toxicology, the assessment of the toxicological relevance of the impurities was not available leading to an issue that could not be finalised. Critical areas of concern were identified in relation to the harmonised classification as toxic for reproduction 1B (H360D) and the lack of valid toxicological reference values (acceptable daily intake (ADI), acute reference dose (ARfD), acceptable operator exposure level (AOEL) and acute acceptable operator exposure level (AAOEL)) due to the inconclusive assessment of endocrine disruption (ED) potential for oestrogen, androgen and steroidogenesis modalities (EAS)‐modalities in humans.

In the residue section, in view of the data gaps identified resulting in provisional residue definitions and absence of valid toxicological reference values, the consumer dietary risk assessment and risk assessment for consumption of drinking water could not be finalised.

The information available on environmental fate and behaviour was only sufficient to carry out the environmental exposure assessments at EU level required for the representative use, when some default assumptions for certain property values were used. Surface water exposure to halosulfuron‐methyl and to any transformation products that might be formed by aqueous photolysis and to its metabolites found in surface water (halosulfuron rearrangement (HSR), chlorosulfonamide (CSE), chlorosulfonamide acid (CSA), aminopyrimidine (AP), halosulfuron) could not be finalised. Based on the available estimates for the representative use, there is the potential for groundwater exposure by halosulfuron‐methyl and its metabolite HSR above the parametric drinking water limit of 0.1 μg/L in geoclimatic situations represented by one out of two MED‐RICE scenarios and potential for groundwater exposure by the metabolite CSA above the parametric drinking water limit of 0.1 μg/L in geoclimatic situations represented by both the MED‐RICE scenarios. Due to missing experimental data, groundwater exposure to halosulfuron‐methyl and to its metabolites CSA and HSR could not be finalised to the usually expected level of certainty; and pending several data gaps for these groundwater metabolites also their relevance assessment could not be finalised. The impact of water treatment processes on the nature of residues of both halosulfuron‐methyl and its identified metabolites potentially present in surface water and groundwater when surface water or groundwater is abstracted for the production of drinking water was also identified as not having been finalised.

In the area of ecotoxicology, in view of the data gaps identified, the assessment for aquatic organisms and non‐target terrestrial plants could not be finalised with the available information.

Based on the available information, halosulfuron‐methyl does not meet the ED criteria for the T‐modality for humans and non‐target organisms according to points 3.6.5 and 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605. For the EAS‐modalities, a conclusion could not be reached for humans and wild mammals leading to an issue that could not be finalised, whereas for non‐target organisms other than mammals, halosulfuron‐methyl does not meet the ED criteria.

BACKGROUND

Commission Implementing Regulation (EU) No 844/2012,1 as amended by Commission Implementing Regulation (EU) No 2020/103,2 (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 1107/2009.3 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 Italy and co‐RMS Poland received an application from Nissan Chemical Europe S.A.S. for the renewal of approval of the active substance halosulfuron‐methyl. Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the co‐RMS (Poland), the European Commission and EFSA about the admissibility.

The RMS provided its initial evaluation of the dossier on halosulfuron‐methyl in the RAR, which was received by EFSA on 8 March 2023 (Italy, 2023).

In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicant, Nissan Chemical Europe S.A.S., for consultation and comments on 14 July 2023. 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 15 September 2023. At the same time, the collated comments were forwarded to the RMS for compilation and evaluation in the format of reporting table. In addition, the applicant was invited to respond to the comments received. The comments and the applicant's response were evaluated by the RMS in column 3 of the reporting table.

The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 13(3) of the Regulation were considered in a telephone conference between EFSA, the RMS on 9 November 2023. 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.

In addition, the applicant requested a derogation under Article 4(7) of Regulation (EC) 1107/2009, submitting evidence regarding the necessity of halosulfuron‐methyl to control a serious danger to plant health. The evaluation of the relevant data is presented in the Appendices E and F to this conclusion.

The outcome of the telephone conference, together with EFSA's further consideration of the comments, is reflected in the conclusions set out in column 4 of the reporting table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in an expert consultation, were compiled by EFSA in the format of an evaluation table.

The conclusions arising from the consideration by EFSA, and as appropriate by the RMS, of the points identified in the evaluation table, together with the outcome of the expert consultation and the written consultation on the assessment of additional information, where these took place, were reported in the final column of the evaluation table.

A final consultation on the conclusions arising from the peer review of the risk assessment and on the outcome of the Article 4(7) derogation assessment took place with Member States via a written procedure in the course of April 2025.

This conclusion report summarises the outcome of the peer review of the risk assessment of the active substance and the formulation for representative use, evaluated on the basis of the representative use of halosulfuron‐methyl as a herbicide in rice crops, as proposed by the applicant. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the RAR and considered during the peer review, if any, are presented in the conclusion.

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

A key supporting document to this conclusion is the peer review report (EFSA, 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 comments received on the applicant's report submitted for the evaluation of data concerning the necessity of halosulfuron‐methyl to control a serious danger to plant health;
• the reporting table (9 November 2023);
• the evaluation table (30 April 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 comments received on the draft EFSA conclusion.

Given the importance of the RAR, including its revisions (Italy, 2024), and the peer review report, both documents are considered as background documents to this conclusion and thus are made publicly available.

It is recommended that this conclusion and its background documents would not be accepted to support any registration outside the EU for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based.

THE ACTIVE SUBSTANCE AND THE FORMULATION FOR REPRESENTATIVE USE

Halosulfuron‐methyl is the ISO common name for methyl 3‐chloro‐5‐{[(4,6‐dimethoxypyrimidin‐2‐yl)carbamoyl]sulfamoyl}‐1‐methyl‐1H‐pyrazole‐4‐carboxylate (IUPAC).

The formulation for representative uses for the evaluation is ‘Halosulfuron‐methyl 75WG’, a water‐dispersible granule (WG) containing 750 g/kg pure halosulfuron‐methyl.

The representative uses evaluated were post‐emergence spray applications in rice to control sedges (Bolboschoemus maritimus, Schoenoplectus mucronatus, Cyperus spp. and Alisma spp.) and broad‐leaf weeds. Full details of the GAP can be found in the list of endpoints in Appendix B.

The information on the active substance and the formulation for representative uses, including the co‐formulants in this formulation, was considered in the overall assessment during the peer review. Information on some properties of a co‐formulant is missing (data gaps, see Section 10). Two components of co‐formulants are unacceptable co‐formulants listed in Annex III of Regulation (EC) No 1107/2009, one of them below the level set in Regulation (EU) 2021/383 paragraph (14) for acceptable unintentional impurity,4 while the exact content of the other is missing5 (data gap, see Section 10). One component of a co‐formulant and one co‐formulant are currently non‐approved active substances under Regulation (EC) 1107/2009.6 Details on the composition of the formulation cannot be reported in conclusions because of the provisions in Article 63(2)(d) of Regulation (EC) No 1107/2009, however this information was fully available and evaluated during the peer review. A proposal for classification of the formulation according to Regulation (EC) 1272/2008 was provided by the applicant and assessed by the RMS (please see Volumes 3 CP of the RAR).

Information was submitted to conclude that the use of halosulfuron‐methyl, according to the representative uses proposed at EU level, results in a sufficient herbicidal efficacy against the target weeds, following the guidance document SANCO/2012/11251‐rev. 4 (European Commission, 2014).

A data gap has been identified for a search of the scientific peer‐reviewed open literature on the active substance and/or its relevant metabolites, dealing with side effects on health and non‐target species, and published within the 10 years before the date of submission of the dossier, to be conducted and reported in accordance with EFSA guidance on the submission of scientific peer‐reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (EFSA, 2011) (data gap, see Section 10).

CONCLUSIONS OF THE EVALUATION

General aspects

With regard to the mammalian toxicity information available for the formulation for representative uses ‘Halosulfuron‐methyl 75WG’, studies were performed for acute toxicity. With regard to the co‐formulants contained in ‘Halosulfuron‐methyl 75WG’, toxicological data were not available for all the components and were not assessed. Therefore, genotoxicity and repeated‐dose toxicity information over the short‐ and long‐term might be considered for further assessment. The collected information, including information from the existing uses other than plant protection products, under regulated EU frameworks, did not highlight any concern (see Section 10).

The availability of ecotoxicity data with the formulation for representative uses was discussed at the experts' meeting7 and data gaps were identified (see Sections 5 and 10). Furthermore, the experts also discussed the data retrieval search and the available data for the individual co‐formulants. Considering the reasoning agreed by the experts, no additional concerns for the individual co‐formulants were identified. Pending the outcome of the identified data gap for information on the content of a hazardous component in one of the co‐formulants and the missing data for toxicology for all of the components in the formulation for representative uses, further consideration to non‐target organisms may be necessary.

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

1

The following guidance documents were followed in the production of this conclusion: European Commission (2000, 2010, 2019).

The proposed specification for halosulfuron‐methyl is based on batch data from industrial scale production. The proposed minimum purity of the technical material is 980 g/kg. It is noted that the evaluation of the toxicological relevance of the impurities is open (see Section 2) and consequently, new data such as spectral data, content of the impurities before and after the storage of the formulation and methods for analysis of the relevant impurities in the formulation might be required. Based on the data for the renewal, the applicant proposed a slight amendment to the reference specification (increasing the level of one significant impurity). The RMS and EFSA are of the opinion that the current reference specification could be maintained, pending finalisation of the evaluation of the toxicological relevance of the impurities (see Section 2). It is noted that in the chromatograms of the batches a few unidentified peaks were observed, and explanation/identification of these unidentified peaks and assessment of their relevance is needed (data gap, see Section 10). Insufficient information was available to conclude on the representativeness of the batches used in the (eco)toxicological assessment, neither for the original nor for the newly proposed reference specification (see Sections 2 and 5). There is no FAO specification available for halosulfuron‐methyl.

The main data regarding the identity of halosulfuron‐methyl and its physical and chemical properties are given in Appendix B. Data gaps were identified for vapour pressure and UV/Vis absorption spectrum above 290 nm (up to 700 nm) of the active substance and n‐octanol/water partition coefficient (log Pow) for the active substance and all components included in the residue definition for risk assessment (data gaps, see Section 10).

Adequate methods are available for the generation of data required for the risk assessment. Methods of analysis are available for the determination of the active substance and impurities in the technical material, however a hazardous substance is used in these methods, therefore new validated methods which do not use hazardous substances is required (data gap, see Section 10). A method for determination of the active substance in the representative formulation is available.

A validated monitoring method for determination of halosulfuron‐methyl in food/feed of plant origin is missing (data gap, see Section 10). An analytical method for monitoring of residues in food/feed of animal origin is currently not required, however the residue definition for monitoring in animal products is open (see Section 3), therefore a validated monitoring method might be required.

Halosulfuron‐methyl residues in surface, ground and drinking water can be monitored by liquid chromatography with tandem mass spectrometry (LC–MS/MS) with a limit of quantification (LOQ) of 0.1 μg/L, however an Independent Laboratory Validation (ILV) of the monitoring method for drinking water is missing (data gap, see Section 10). In addition, it is noted that the residue definition for monitoring in water is open (see Sections 4, 5 and 9.1), therefore new validated monitoring method(s) might be required if new components are to be included in the residue definition. LC–MS/MS exists for determination of halosulfuron‐methyl residues in soil with a LOQ of 0.005 mg/kg, however the method uses a hazardous chemical, therefore a validated monitoring method which does not use hazardous substances is required (data gap, see Section 10). Appropriate LC–MS/MS method exists for monitoring of halosulfuron‐methyl residues in air with a LOQ of 2 μg/m^3^.

LC–MS/MS method can be used for monitoring of halosulfuron‐methyl and O‐demethyl halosulfuron‐methyl in body fluids (blood and urine) and body tissues (kidney) with LOQs of 0.01 mg/L (each analyte) and 0.01 mg/kg (each analyte), respectively.

MAMMALIAN TOXICITY

2

The toxicological profile of the active substance halosulfuron‐methyl and its metabolites was discussed at the Pesticides Peer Review Experts' Teleconference 136 in May 2024. The assessment is based on the following guidance documents: European Commission (2012), EFSA (2014, 2021), EFSA PPR Panel (2017) and ECHA (2017a).

Regarding the proposed reference specification, insufficient data are provided to conclude on the toxicological relevance of the impurities (data gap, see Section 9.1). No information is available to determine whether the test material used in toxicity studies is representative of the original and newly proposed reference specification (issue not finalised, see Section 9.1).

The oral absorption of halosulfuron‐methyl is estimated to account for > 80% of the administered low dose. Excretion occurs predominantly via the urine, with appreciable amounts excreted in bile. In the rat, halosulfuron‐methyl is widely distributed throughout the body, with the highest levels being reached in liver, kidney and lung. There was no evidence of bioaccumulation. The main metabolic pathway identified is demethylation and hydroxylation of the pyrimidine moiety to produce demethyl halosulfuron‐methyl and 5‐hydroxy demethyl halosulfuron‐methyl. Major rat metabolites are demethyl halosulfuron‐methyl and 5‐hydroxy demethyl halosulfuron‐methyl based on urinary and biliary excretion. Based on comparative in vitro metabolism, no major metabolic inter‐species (rat, human) differences have been observed and no unique human metabolites have been identified.8 The residue definition for body fluids and tissues is halosulfuron‐methyl and O‐demethyl halosulfuron‐methyl.

Halosulfuron‐methyl has low acute toxicity by oral, dermal and inhalation exposure, and has no irritating or sensitising properties. It is neither a skin nor eye irritant, nor is it a skin sensitiser. Halosulfuron‐methyl tested negative in an in vitro 3T3 NRU phototoxicity assay.

Short‐term oral toxicity studies were provided for rats and dogs. The dog was the most sensitive species, with a no observed adverse effect level (NOAEL) of 10 mg/kg body weight (bw) per day in both the 90‐day and in the 1‐year study based on body weight gain decreases and haematological effects.9 A NOAEL of 78 mg/kg bw per day was set in a rat 28‐day study based on reduced body weight gain and histopathological findings in the pancreas (increased incidence pancreatic acinar cell degeneration/necrosis). A NOAEL of 116 mg/kg bw per day was obtained from a 90‐day rat study based on reduced body weight and body weight gain and histopathological findings in the kidney (increased incidence tubular pigmentation (haemosiderin)).

Based on the available genotoxicity studies, there is no indication of genotoxicity for halosulfuron‐methyl, in line with the ECHA RAC Opinion (ECHA, 2017b) concluding that classification for genotoxicity is not warranted. However, a firm conclusion on the clastogenicity and aneugenicity potential of halosulfuron‐methyl remains open as the available in vitro chromosome aberration test and the in vivo micronucleus test were considered supportive only10 (see Section 10).

Testing for photomutagenicity is not required for halosulfuron‐methyl because the available phototoxicity test was negative.

After long‐term exposure, no target organ toxicity was found in rats or mice.11 The relevant NOAEL for systemic toxicity in rats is 56.3 mg/kg bw per day (2‐year study), based on decreased body weight and body weight gain observed at 138.6 mg/kg bw per day in females. The NOAEL for carcinogenicity is the top dose, i.e. 138.6 mg/kg bw per day. The substance showed no treatment‐related tumours in rats and mice and was concluded unlikely to be carcinogenic for humans.

With regard to reproductive toxicity studies, fertility and overall reproductive performance were not affected. In the multigeneration rat study, the parental NOAEL is 50.4 mg/kg bw per day based on reduced body weight and body weight gain at 223.2 mg/kg bw per day. The offspring NOAEL is 6.3 mg/kg bw per day based on reduced pup body weight in the F1 generation at 50.4 mg/kg bw per day. Finally, the reproductive NOAEL is 223.2 mg/kg bw per day, the highest dose tested.

With regard to foetal development, adverse effects were observed in rats and rabbits.12 In the rat teratogenicity study, the maternal NOAEL is 250 mg/kg bw per day based on decreased body weight and body weight gain, alopecia and yellow stained fur, and the developmental NOAEL is 250 mg/kg bw per day based on reduced foetal body weight, increased early resorptions and post‐implantation losses, increased external, skeletal (forked/fused ribs included) and visceral malformations, and skeletal variations at 750 mg/kg bw per day. In the rabbit teratogenicity study, the maternal NOAEL is 50 mg/kg bw per day based on decreased body weight gain, and the developmental NOAEL is 50 mg/kg bw per day based on increase in early resorption, increased post‐implantation loss, decreased foetal viability and increased incidence in forked/fused ribs at 150 mg/kg bw per day. Developmental effects were considered not secondary to maternal toxicity. Accordingly, the harmonised classification Repr Cat 1B (H360D) was established under the CLP Regulation13 (critical area of concern, see Section 9.2).

With respect to neurotoxicity,14 changes in the aerial righting reflex were observed in the acute neurotoxicity study in rats, triggering a NOAEL of 600 mg/kg bw. The acute systemic NOAEL also amounts to 600 mg/kg bw based on mortality and decreased body weight gain in males. No neurotoxic effects were found in the subchronic neurotoxicity study, and the related NOAEL amounts to 315.9 mg/kg bw per day (top dose). The subchronic NOAEL for systemic toxicity is 62.8 mg/kg bw per day in males based on increased relative liver weight, liver histopathological findings and body weight effects; no systemic effects were observed in females.

There is no evidence of immunotoxicity of halosulfuron‐methyl.

As the ED assessment is inconclusive,15 the toxicological reference values agreed by the experts16 cannot be considered as valid (critical area of concern, see Section 9.2). Therefore, although it is noted that the RMS included the exposure estimates in the RAR, the non‐dietary risk assessment cannot be concluded.17

Dermal absorption of halosulfuron‐methyl in the representative product ‘Halosulfuron‐methyl 75WG’ has been assessed in an in vitro study with human skin. Based on the EFSA guidance (EFSA, 2017), the dermal absorption values to be used for risk assessment are 0.31% for the wettable granules, 0.34% for the 0.075 g a.s/L for the spray dilution and 50% for the layer of water overlaying the flooded rice paddies.18

Toxicological studies and information have been provided for metabolites CSA, HSMR, CSA‐guanidine and CSE‐guanidine, as reported in Appendix B.

Metabolites of halosulfuron‐methyl found in groundwater and/or in animals/plants were discussed at a Pesticides Peer Review Experts' Teleconference.19 The ones requiring further toxicological considerations are presented and discussed in Table 1.

For metabolites CSA, AP and HSR genotoxicity data are missing (data gap leading to an issue not finalised, see Sections 3, 4 and 9.1). Based on the rat prenatal developmental toxicity study available for CSA, it was concluded that CSA does not share the developmental toxicity profile of the parent halosulfuron‐methyl. Further assessment of the toxicological profile for metabolites HSR and AP is needed (data gap leading to an issue not finalised, see Sections 3, 4 and 9.1).

RESIDUES

3

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

Halosulfuron‐methyl was discussed at the Pesticides Peer Review Experts' Teleconference 138 in May 2024.

The metabolism of halosulfuron‐methyl was investigated in rice, maize and sugar cane. Since the rice metabolism study had major deficiencies such as lack of GLP certificate, non‐compliance with the representative GAP and different rice growing practices from the ones common in the EU, the study was not acceptable and cannot be relied on for the peer review. A new GAP‐compliant metabolism study is needed to address the metabolism in rice (data gap, see Section 9.1).

In post‐emergence treated maize and sugar cane, halosulfuron‐methyl was recovered in straw and foliage up to 95% total radioactive residue (TRR). In pre‐emergence treated maize and sugar cane, halosulfuron‐methyl was recovered in low amounts (max. 12% TRR in cane). Overall, the qualitative metabolic pattern across all three crops was similar with the degradation of halosulfuron‐methyl into the major metabolite CSA which reached up to 56% TRR in maize grain and 22% TRR in sugar cane. The study in rice indicated that the metabolite AP was found at 40% of TRR in rice grain; it likely forms on the pyrimidine ring in maize as well, though no thorough residues identification in the maize study was done. Two additional metabolites (halosulfuron‐methyl rearrangement (HSMR) and HSR), that are specific to flooded soil, were identified in rice only. Considering this finding and that the rice growing agricultural practices differ (flooded soil) from other cereal/grass crops (dry soil) such as maize and sugar cane addressed by data, the whole data package in cereals/grass crops was not found sufficient to support the representative use in rice.

For the time being, halosulfuron‐methyl is proposed for the residue definition for enforcement. The proposed risk assessment‐residue definition (RA‐RD) is halosulfuron‐methyl, CSA and AP. The residue definitions and their applicability to rice and all cereal/grass crops after pre‐and post‐emergence treatment is provisional and should be confirmed by the new metabolism study on rice and by the outstanding toxicological data on CSA and AP (data gap, see Section 9.1).

Eight valid GAP‐compliant field trials in rice analysed for halosulfuron‐methyl were available. No residues were found > LOQ (0.01 mg/kg). Pending the finalisation of the RA‐RD in plants, additional field trials analysed in accordance with the RA‐RD might be needed.

No data is available on halosulfuron‐methyl metabolism in rotational crops. However, halosulfuron‐methyl and several metabolites (HSMR, HSR, CSE, CSA, AP) were found to persist in flooded soil. Since rice can be grown in rotation, the fate of these compounds in rotated crops needs to be investigated (data gap, see Section 9.1).

No animal studies nor studies in fish were submitted and might be required pending the finalisation of the RA‐RD in plants.

Nature of halosulfuron‐methyl under the standard hydrolysis conditions was not investigated as halosulfuron‐methyl residues were < 0.01 mg/kg in rice grain. Pending the finalisation of the RA‐RD in plants this data might be required.

Rice is not a melliferous crop, therefore investigation of residues in honey and bee products was not required.

In view of the inconclusive ED assessment and the fact that the toxicological reference values agreed by the experts at the Pesticides Peer Review Experts' TC 136 cannot be considered as valid (see Section 2), EFSA considers it more appropriate not to conclude on the consumer risk assessment, although it is noted that the RMS included an assessment in the RAR (Italy, 2024).

The consumer risk assessment for the groundwater metabolites CSA and HSR is pending due to data gaps identified on their toxicological profile and a reliable estimate of their concentrations in food items from the requested metabolism study in rice.

The consumer risk assessment from the consumption of drinking water could also not be finalised considering the lack of appropriate information to address the effect of water treatment processes on the nature of residues of the active substance and its identified metabolites, that might be present in surface water or groundwater, when surface water and/or groundwater are abstracted for the production of drinking water (see Sections 4 and 9.1).

ENVIRONMENTAL FATE AND BEHAVIOUR

4

Halosulfuron‐methyl was discussed at the Pesticides Peer Review Experts' Teleconference 137 in May 2024.

The rate of dissipation and degradation in the environmental matrices investigated were estimated using FOCUS (2006) guidance. In soil laboratory incubations under aerobic flooded conditions in the dark, halosulfuron‐methyl exhibited moderate persistence, forming the major metabolites (> 10% AR) HSMR (max. 46% AR) exhibiting moderate to medium persistence, CSA (max. 24%, still increasing at study end (data gap for rate of degradation studies in paddy soil conditions, see Section 9.1)), HSR (max. 23% AR, still increasing at study end) exhibiting high persistence, and CSE (max. 20% AR) exhibiting moderate persistence. AP (max. 9.5% AR) also reached levels triggering assessment (data gap for rate of degradation studies under paddy soil conditions in at least two soils, see Section 10). Mineralisation of the pyrimidine ^14^C radiolabels was accounted for 0.3%–12% after 120 days. No mineralisation was observed for the pyrazole ^14^C radiolabels after 120 days. The formation of unextractable residues (not extracted by sodium hydroxide) accounted for 24%–45% AR and 23%–40% AR for pyrimidine and pyrazole ^14^C radiolabels, respectively, after 120 days. The route and rate of aerobic soil degradation (non‐flooded conditions) of halosulfuron‐methyl in the dark was also evaluated. The findings from this study are instrumental in informing rotational crop assessments, particularly for persistent metabolites (i.e. flooded aerobic soil DT90 > 100 days) when transitioning from paddy rice cultivation to other crops.

Reliable adsorption endpoints are missing for the active substance halosulfuron‐methyl (at least four soils; data gap, see Section 9.1) and its metabolites CSA and halosulfuron (at least three soils; data gap, see Section 9.1). Reliable adsorption parameters are also missing for CSE (at least three soils; data gap, see Section 9.1) and HSMR (at least one soil; data gap, see Section 10). HSR exhibited very high soil mobility and AP can be considered immobile in soil or exhibited very high soil mobility. It was concluded that the adsorption of these metabolites was not pH dependent.

In one satisfactory paddy field dissipation study conducted at one site in Spain (with spray application on bare ground flooded test plots), sample analyses were carried out for the parent halosulfuron‐methyl and its metabolites: HSMR, HSR, CSE and CSA. A missed analysis was identified for AP. The field DT50 study value for the parent was accepted as a reasonable estimate of degradation when the overlying water and soil are considered separately indicating low persistence at the trial site. Reliable paddy field dissipation study for HSMR (data gap, see section 10) and HSR (data gap, see Section 9.1) are missing.

In laboratory incubations in dark aerobic natural sediment water systems, halosulfuron‐methyl exhibited low persistence, forming the major metabolites HSMR (max. 29% AR in water and max. 17% AR in sediment, exhibiting moderate persistence), HSR (max. 30% AR in water and max. 9% AR in sediment), CSE (max. 6% AR in water, exhibiting from low to moderate persistence), CSA (max. 8% AR in water and max. 5% AR in sediment), AP (max. 8% AR in water, exhibiting very low persistence) and halosulfuron (max. 8% AR in water and max. 6% in sediment, exhibiting moderate persistence). The unextractable sediment fraction (not extracted by sodium hydroxide) was the major sink for the pyrimidine and pyrazole ^14^C radiolabels, accounting for 23%–60% AR at study end (100 days). Mineralisation of these radiolabels accounted for 5%–6% AR at the end of the study. A data gap was identified for reliable water/sediment degradation rates for HSR (at least two systems), CSA (at least two systems), AP (at least one additional system) (data gap, see Section 10). The aqueous photochemical degradation of halosulfuron‐methyl has not been addressed. It is unknown if photolysis is a major route of degradation of halosulfuron‐methyl in the aquatic compartment and if novel metabolites are formed as a result of the direct photochemical degradation (data gap, see Section 9.1). This led to the residue definition needed for the aquatic risk assessment and subsequently for monitoring being open.

The necessary surface water and sediment exposure assessments (Predicted environmental concentrations (PEC) calculations) were carried out for halosulfuron‐methyl and its metabolites HSMR, HSR, CSE, CSA, AP and halosulfuron using MED‐RICE guidance document (European Commission, 2003) to calculate lower tier PEC after one application. Based on these aquatic exposure assessments, a high risk could not be excluded for aquatic organisms except for HSMR (see Section 5). Therefore, a higher tier aquatic exposure assessment is needed (excluding HSMR) (data gap, Section 9.1). In the Pesticides Peer Review Expert's Teleconference 137, the experts agreed to use a KFoc of 10 mL/g to calculate PEC in surface water and 500 mL/g to calculate PEC in sediment for halosulfuron‐methyl, CSE and CSA.20

The necessary groundwater exposure assessments were appropriately carried out using the MED‐RICE Guidance document (2003) by calculating the concentration at 1 m depth after a single application for the active substance halosulfuron‐methyl and its soil metabolites HSMR, HSR, CSE, CSA and AP.

The potential for groundwater exposure from the representative use by the metabolites HSMR, CSE and AP above the parametric drinking water limit of 0.1 μg/L was concluded to be low in geoclimatic situations that are represented by the two MED‐RICE scenarios. Concentrations moving below 1 m depth were predicted to be above the parametric drinking water limit of 0.1 μg/L in one (sandy soil scenario) out of two MED‐RICE scenarios for the parent halosulfuron‐methyl and the metabolite HSR, and in two out of two MED‐RICE scenarios for the metabolite CSA. Due to lack of experimental data, the groundwater exposure assessment of the parent halosulfuron‐methyl and the metabolites HSR and CSA was based on worst‐case values for soil adsorption and/or rate of degradation (data gap, see Section 9.1). Pending several data gaps (including the finalisation of the toxicological assessment and the data gap on the new metabolism study in rice), the assessment of relevance for metabolites HSR and CSA in groundwater could not be finalised (see Sections 2, 3 and 9.1).

Information to address the effect of water treatments processes is missing on the nature of the residues that might be present in surface water and groundwater, when surface water or groundwater are abstracted for the production of drinking water. This has led to the identification of a data gap and results in the consumer risk assessment that could not be finalised (data gap, see Sections 3 and 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.

ECOTOXICOLOGY

5

The risk assessment was based on the following documents: European Commission (2002), SETAC (2001), EFSA (2009), EFSA PPR Panel (2013) and EFSA (2013).

Some aspects of the ecotoxicological assessment were discussed during the Pesticides Peer Review Experts' Teleconference 139 in June 2024.

Insufficient information was available to demonstrate that the batches used in the ecotoxicology studies are compliant with the original and newly proposed reference specification (data gap, see Section 10).

Suitable acute and long‐term toxicity studies were available for birds and mammals. The appropriate endpoint for the long‐term assessment of wild mammals was discussed and agreed at the experts' meeting.21 The risk assessments for birds and mammals were presented in accordance with EFSA (2009) using the scenario for cereals as a surrogate for rice. The RMS pointed out that the use of cereals as surrogate for rice paddies is uncertain. Nevertheless, based on the available screening level assessments, a low acute and long‐term dietary risk to birds and mammals was concluded for the representative use.

A comprehensive assessment of the risk to birds and mammals from plant metabolites was not available (data gap, see Section 10). Furthermore, data gaps were identified (see Section 10) to consider the need for a risk assessment via secondary poisoning and from the consumption of contaminated water from halosulfuron‐methyl and metabolites (with the exception of HSMR) once the data gaps for Koc (see Section 4) and n‐octanol/water partition coefficient (log Po/w) (see Sections 1 and 10) values are addressed.

Aquatic acute and chronic toxicity data (fish, aquatic invertebrates, algae and aquatic plants) were available with the active substance halosulfuron‐methyl. Furthermore, toxicity data with the formulation for representative use (halosulfuron‐methyl 75WG) was available for fish (acute), aquatic invertebrates (acute), algae and aquatic plants. Several aspects related to the available aquatic toxicity studies were discussed at the experts' meeting. Moreover, the experts discussed the completeness of the data package and agreed on several data gaps. Specifically, the experts agreed whether several studies could be considered reliable22 ^,^ 23 and data gaps (see Section 9.1) were identified for:

• –toxicity data for a second algae species for halosulfuron‐methyl24;
• –toxicity data for aquatic plants such as Lemna spp. for halosulfuron‐methyl and with the formulation for representative uses (Halosulfuron‐methyl 75WG)^23^;
• –toxicity data for a rooted dicot species, e.g. with Myriophyllum, for halosulfuron‐methyl.25

The aquatic exposure assessment identified six pertinent metabolites which need a risk assessment in surface water (HSMR, HSR, CSE, CSA, AP, halosulfuron). Toxicity data for the metabolite HSMR were available for fish (acute), aquatic invertebrates (acute), algae and aquatic plants. For the metabolites halosulfuron and AP, toxicity data were available with algae. For the metabolites CSA and HSR toxicity data were available for aquatic plants only. The need for specific toxicity data for the metabolites was discussed at the experts' meeting^23^. For five metabolites (all except for halosulfuron) it was agreed that, as they have lost the sulfonylurea toxophore, toxicity data for the parent substance could be used for risk assessment. For the metabolite halosulfuron, it was also agreed that no additional toxicity data are necessary given the lower toxicity to algae compared to the parent substance and that this metabolite was shown to have no herbicidal activity.

The available aquatic risk assessment demonstrated a low acute and chronic risk to fish and aquatic invertebrates from halosulfuron‐methyl and all pertinent surface‐water metabolites. A high risk to algae could not be excluded for halosulfuron‐methyl.26 As the available surface water exposure assessment relied on a default value for the Koc (see Section 4), the aquatic risk assessment is considered not finalised (see Section 9.1).

The available risk assessment for metabolite HSMR indicated a low risk to aquatic organisms. The risk assessment for metabolites HSR and CSA was not sufficient to exclude a high risk to algae. Furthermore, owing to the lack of suitable toxicity data with the parent substance for a second algae species, aquatic plants and rooted macrophyte, the available aquatic risk assessment is not finalised for the parent substance and metabolites, other than for HSMR.

The available toxicity studies and risk assessments for honey bees were discussed at an expert meeting.27 No suitable acute oral and contact toxicity studies for honey bees with halosulfuron‐methyl were available (data gap, identified by the experts at the meeting, see Section 10 ^27^). Acute oral and contact toxicity studies for honey bees with the formulation for representative uses were available, however the acute oral toxicity endpoint was considered uncertain because of the lack of information on the amount of consumed treated diet (data gap, see Section 10 ^27^). Furthermore, a chronic toxicity study with adult honeybees and honey bee larvae with halosulfuron‐methyl were available. Acute oral and contact toxicity studies for bumble bees with halosulfuron‐methyl were available. No data for sublethal effects (data gap, see Section 10) or accumulative toxicity to honey bees were available. The experts discussed and agreed that chronic toxicity data on adult honey bees and honey bee larvae were also needed for the formulation for representative uses^27^ (data gap, see Section 10).

Using the acute toxicity data with the formulation for representative uses, a low acute risk to honey bees was indicated in accordance with both the guidance from the European Commission (2002) and EFSA (2013). A low chronic risk to honey bees and a low risk to honey bee larvae were also concluded based on the active substance endpoints. A risk assessment for honey bees from the plant metabolites was not available (data gap, see Section 10).

Tier 1 toxicity studies, performed with the formulation for representative uses and the two indicator species (Aphidius rhopalosiphi and Typhlodromus pyri) for non‐target arthropods other than bees were available. Based on the available tier 1 risk assessments, a low risk to non‐target arthropods was indicated for the representative use assessed.

Suitable chronic toxicity data for halosulfuron‐methyl for earthworms 28 and other soil macroorganisms (Folsomia candida and Hypoaspis aculeifer) were available. Although no toxicity data were available for the formulation for representative uses, the experts at the meeting agreed that, considering the composition of the formulation and the high margin‐of‐safety obtained in the assessment for the active substance, such data is considered to not be necessary.29

The available risk assessment for earthworms and other soil macroorganisms indicated a low chronic risk for the representative uses assessed. The soil exposure assessment identified five pertinent metabolites which need a risk assessment for soil‐dwelling organisms (HSMR, HSR, CSE, CSA, AP). A screening level assessment, assuming that each metabolite is 10 times more toxic than the parent substance, was sufficient to conclude a low chronic risk to earthworms and other soil macroorganisms for all soil metabolites.

Suitable toxicity data for halosulfuron‐methyl were available for soil nitrogen transformation processes. The data indicated a low risk for the representative uses assessed. Although no toxicity data was available for the formulation for representative uses, in line with the assessment for soil macroorganisms such data were not considered necessary in this case. A screening level assessment was sufficient to conclude a low risk to soil microorganisms for all soil metabolites.

The assessment of non‐target terrestrial plants was discussed at an expert meeting.30 The experts agreed that the available studies were not reliable (data gap, see Section 9.1). Consequently, no risk assessment could be performed, and the assessment is not finalised (see Section 9.1).

A low risk to organisms involved in biological methods for sewage treatment was concluded.

ENDOCRINE DISRUPTION PROPERTIES

6

The assessment of the endocrine disruption (ED) potential of halosulfuron‐methyl was discussed at the Pesticides Peer Review Experts' Teleconference 136 in May 2024.

With regard to the assessment of the endocrine disruption potential of halosulfuron‐methyl for humans according to the ECHA/EFSA guidance (2018), in determining whether halosulfuron‐methyl interacts with oestrogen, androgen and steroidogenesis (EAS) and thyroid (T) mediated pathways, the number and type of effects induced, and the magnitude and pattern of responses observed across studies were considered. Additionally, the conditions under which effects occur were considered, in particular, whether or not endocrine‐related responses occurred at dose(s) that also resulted in overt toxicity. The assessment is therefore providing a weight‐of‐evidence (WoE) analysis of the potential interactions of halosulfuron‐methyl with the EAS‐ and T‐signalling pathways using the available evidence in the data set.

The dataset for the T‐modality was considered complete and a pattern of T‐mediated adversity was not identified. Therefore, based on the available and sufficient dataset, it was concluded that the ED criteria are not met for the T‐modality (Scenario 1a of the ECHA/EFSA ED Guidance (2018)).

For the EAS‐modalities, no EAS‐mediated adversity was observed in the available dataset. However, EAS‐mediated parameters were not sufficiently investigated (i.e. lack of OECD TG 416, version from 2001 or OECD TG 443), ruling out the possibility to evaluate all the EAS‐mediated adverse effects. The EAS‐related endocrine activity was not sufficiently investigated either. Therefore, the following additional information was requested during the commenting phase to be able to conclude whether the approval criteria for endocrine disruption are met:

• –a study in line with OECD TG 455 (Stably Transfected Human Oestrogen Receptor‐alpha Transcriptional Activation Assay (ER STTA assay));
• –a study in line with OECD TG 440 (Uterotrophic assay) in case OECD TG 455 is negative;
• –a study in line with OECD TG 456 (H295R Steroidogenesis Assay);
• –a study in line with OPPTS 890.1200 (Aromatase assay);
• –a study in line with OECD TG 458 (Stably Transfected Human Androgen Receptor Activation Assay (AR STTA assay));
• –a study in line with OECD TG 441 (Hershberger Assay) in case OECD TG 456 and 458 and OPPTS 890.1200 are negative.

In case of positive result/s for at least one modality, the following additional testing would have been needed:

• –OECD TG 443 (with the inclusion of cohort 1B) or OECD TG 416 (according to the latest version from 2001).

However, no further data was submitted by the applicant. Therefore, currently, based on the available information, the assessment of the endocrine disrupting potential of halosulfuron‐methyl according to point 3.6.5 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, cannot be concluded (data gap leading to an issue not finalised, see Section 9.1).

The outcome of the assessment reported above for humans also applies to wild mammals as non‐target organisms.

For non‐target organisms other than mammals a xenopus eleutheroembryonic thyroid assay (XETA, OECD TG 248) and a fish short‐term reproduction assay (FSTRA, OECD TG 229) were available to sufficiently investigate the endocrine activity through the T‐ and EAS‐modalities, respectively.

Several limitations of the available XETA were reported (i.e. validity criteria not completely fulfilled) and those were discussed at an expert teleconference.31 The study was not considered as formally valid. However, considering: (i) the nature and extent of the deviations from the validity criteria, (ii) the absence of any significant effect in all treatments up to the highest tested concentration (i.e. 90 mg/L), (iii) no effects observed in the mammalian dataset, the uncertainties identified were not considered too high to draw a conclusion and overall no concern was anticipated related to the ED potential of halosulfuron‐methyl for non‐target organisms (NTOs) through the T‐modality. For the EAS‐modalities, no endocrine activity was observed in the available FSTRA.

Based on the available assessment, for non‐target organisms (non‐mammalian species and wild mammals for the T‐modality), it could be concluded that halosulfuron‐methyl does not meet the ED criteria as laid down in the point 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, while in line with the conclusion for humans, the assessment could not be finalised for mammals as non‐target organisms for EAS‐modalities for EATS‐modalities.

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)

7

TABLE 3: Groundwater. a

PARTICULAR CONDITIONS PROPOSED TO BE TAKEN INTO ACCOUNT BY RISK MANAGERS

8

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).

Where the assessment could be finalised, no particular conditions are proposed for the representative uses evaluated.

CONCERNS AND RELATED DATA GAPS

9

Issues that could not be finalised

9.1

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 546/201132 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. Compliance of the batches used in toxicological studies with the (original and newly proposed) reference specification could not be finalised (see Section 2).

• Assessment of the toxicological relevance of the impurities was not available (relevant for the representative use evaluated; see Section 2).

2. The ED assessment for EAS‐modalities for humans and wild mammals as non‐target organisms is inconclusive (see Section 6).

• EAS‐mediated parameters and EAS‐related endocrine activity were not sufficiently investigated.

3. The consumer dietary risk assessment could not be finalised since the risk assessment residue definition in plants could not be finalised due to data gaps identified and absence of valid toxicological reference values (see Sections 3 and 9.2).

• A metabolism study in rice, compliant with the representative use and common EU practices for rice growing (relevant for the representative use evaluated; see Section 3).
• Having regard to the persistence of halosulfuron‐methyl and soil metabolites HSMR, HSR, CSE, CSA, AP, confined rotational crops metabolism data addressing the fate of these compounds in leafy, cereals small grains and root crops at the different plant back intervals were not available (relevant for the representative use evaluated; see Section 3).
• Further assessment of the toxicological profile of CSA and AP was not available (relevant for the representative use evaluated; see Sections 2 and 3).

4. The exposure and risk assessment for aquatic organisms to halosulfuron‐methyl and surface water metabolites (HSR, CSE, CSA, AP, halosulfuron, aqueous photolysis transformation products if any) could not be finalised (see Sections 4 and 5).

• Toxicity data with a second algae species for halosulfuron‐methyl were not available (relevant for the representative use evaluated; see Section 5).
• Toxicity data for aquatic plants such as Lemna spp. for halosulfuron‐methyl and with formulation for representative uses (Halosulfuron‐methyl 75WG) were not available (relevant for the representative use evaluated; see Section 5).
• Toxicity data for a rooted dicot species (e.g. Myriophyllum) study for halosulfuron‐methyl were not available (relevant for the representative use evaluated; see Section 5).
• Adsorption parameters were not available for the active substance halosulfuron‐methyl and its metabolites CSE and CSA and halosulfuron. Also rate of degradation in soil and surface water was not available for CSA. Whilst for AP the rate of degradation was not available in soil. For HSR rate of degradation in surface water was not available (relevant for the representative use evaluated; see Section 4).
• The aqueous photochemical degradation of halosulfuron‐methyl has not been addressed. It is unknown whether photolysis is a significant degradation pathway for halosulfuron‐methyl in the aquatic compartment and whether it leads to the formation of new metabolites at levels that would trigger an aquatic risk assessment (relevant for the representative use evaluated; see Sections 4 and 5).
• Aquatic risk assessment could not exclude a high risk based on lower tier PECsw calculations for halosulfuron‐methyl and its metabolites (excluding HSMR). Therefore, a higher tier aquatic exposure assessment is needed to refine the risk assessment of aquatic organisms for the parent and its metabolites (relevant for the representative use evaluated; see Sections 4 and 5).

5. The risk assessment for non‐target terrestrial plants could not be finalised (see Section 5).

• Reliable toxicity studies, for seedling emergence and vegetation and vigour, with the formulation for representative uses were not available (relevant for the representative use evaluated; see Section 5).

6. The consumer risk assessment could not be finalised with regard to the unknown nature of residues that might be present in drinking water, consequent to water treatment following abstraction of groundwater and surface water that might contain the active substance and its metabolites (see Sections 3 and 4).

• Satisfactory information to address the effect of water treatment processes on the nature of residues that might be present in surface water and groundwater, when surface water or groundwater are abstracted for the production of drinking water was not available. 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 would be needed (relevant to comply with the conditions of approval, not dependent of any specific use; see Section 4).

7. Groundwater exposure to the active substance halosulfuron‐methyl could not be finalised due to the following data gap (see Section 4):

• Batch‐equilibrium adsorption studies to derive reliable Freundlich adsorption parameters for the parent halosulfuron‐methyl (at least four soils) triggered according to data requirement in Commission Regulation (EU) No 283/2013 (relevant for representative use evaluated; see Section 4).

8. A relevance assessment of metabolite CSA in groundwater could not be finalised due to the following data gaps (see sections 2, 3 and 4):

• Rate of degradation studies for the metabolite CSA in paddy soil conditions for at least two typical representative rice soils, triggered according to the MED‐RICE guidance (2003), were not available (relevant for representative use evaluated; see Section 4).
• Batch‐equilibrium adsorption studies to derive reliable Freundlich adsorption parameters for metabolite CSA (at least three soils), triggered according to data requirement in Commission Regulation (EU) No 283/2013, were not available (relevant for representative use evaluated; see Section 4).
• The assessment of genotoxicity (clastogenicity and aneugenicity) of the metabolite remains open. No conclusion can be reached on the general toxicity of the metabolite given that the genotoxicity is not clarified (relevant for representative use evaluated; see Section 2).
• A reliable estimate of CSA concentrations in food items from the requested metabolism study in rice is pending (relevant for the representative use evaluated; see also point 3a).

9. A relevance assessment of metabolite HSR in groundwater could not be finalised due to the following data gaps (see Sections 2, 3 and 4):

• Reliable paddy field dissipation study for metabolite HSR according to the MED‐RICE guidance (2003) is not available (relevant for the representative use evaluated; see Section 4).
• In the absence of genotoxicity and general toxicity data, no conclusion on the toxicological properties can be derived for the metabolite. It cannot be concluded whether the metabolite shares the developmental toxicity profile of the parent (relevant for the representative use evaluated; see Section 2).
• A reliable estimate of HSR concentrations in food items from the requested metabolism study in rice is pending (relevant for the representative use evaluated; see also point 3a).

Critical areas of concern

9.2

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 regarding the hazard cut‐off criteria outlined in Appendix A.

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:

• 10The toxicological reference values (ADI, ARfD, AOEL and AAOEL) can only be postulated, and they are considered not valid, due to the inconclusive ED assessment for EAS‐modalities in humans. Accordingly, the non‐dietary and dietary risk assessment cannot be concluded.
• 11Halosulfuron‐methyl has a harmonised classification as reproductive toxicant category 1B (H360D ‘may damage the unborn child’).33

Overview of the concerns identified for each representative use considered (Table 6)

9.2.1

In addition to the issues indicated below, the assessment of the endocrine disrupting properties of halosulfuron‐methyl for humans and wild mammals according to the scientific criteria for the determination of endocrine disrupting properties as set out in points 3.6.5 and 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, could not be finalised (see Section 6).

LIST OF OTHER OUTSTANDING ISSUES

10

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:

• Information on the content of a component in one of the co‐formulants and additional information on some properties of another co‐formulant (relevant for the representative use evaluated; see Section on ‘The active substance and the formulation for representative use’).
• A search of the scientific peer‐reviewed open literature on the active substance and/or its relevant metabolites, dealing with side effects on health and non‐target species, and published within the 10 years before the date of submission of the dossier, to be conducted and reported in accordance with EFSA guidance on the submission of scientific peer‐reviewed open literature for the approval of pesticide active substances under Regulation (EC) No 1107/2009 (EFSA, 2011) (relevant for the representative use evaluated; see Section on ‘The active substance and the formulation for representative use’).
• For all the components of the formulation for representative uses ‘Halosulfuron‐methyl 75WG’, genotoxicity and repeated‐dose toxicity information over the short‐ and long‐term was not available; therefore, in order to allow a final conclusion on the safety assessment of ‘Halosulfuron‐methyl 75WG’, genotoxicity and repeated‐dose toxicity data for the components (short‐ and long‐term) might be considered for further assessment (to be confirmed by Member States when assessing applications for PPP authorisation) (relevant for the representative use evaluated; see Section on ‘General aspects’).
• Explanation/identification of the unidentified peaks in the chromatograms of the technical material batches and assessment of their relevance (relevant for the representative use evaluated; see Section 1).
• Vapour pressure and UV/Vis absorption spectrum above 290 nm (up to 700 nm) of the active substance and n‐octanol/water partition coefficient (log Pow) for the active substance and all components included in the residue definition for risk assessment (relevant for the representative use evaluated; see Section 1).
• New validated methods which do not use hazardous substances for determination of the active substance and impurities in the technical material (relevant for the representative use evaluated; see Section 1).
• A validated monitoring method for determination of halosulfuron‐methyl in food/feed of plant origin (relevant for the representative use evaluated; see Section 1).
• An ILV of the monitoring method for drinking water (relevant for the representative use evaluated; see Section 1).
• A validated monitoring method for components of the residue definition for monitoring in soil which does not use hazardous substances (relevant for the representative use evaluated; see Section 1).
• A firm conclusion on the clastogenicity and aneugenicity potential of halosulfuron‐methyl could not be made since the available in vitro chromosome aberration test and the in vivo micronucleus test were considered supportive only (relevant for the representative use evaluated; see Section 2). It is noted that the data package does not provide any indication of genotoxicity for halosulfuron‐methyl, being in line with the ECHA RAC opinion on halosulfuron‐methyl (ECHA, 2017b).34
• Reliable flooded aerobic soil degradation rates for AP for at least two typical representative rice soils (relevant for the representative use evaluated; see Section 4).
• Batch‐equilibrium adsorption studies to derive reliable Freundlich adsorption parameters for the metabolite HSMR (at least one soil) are not available (relevant for the representative use evaluated; see Section 4).
• A reliable paddy field dissipation study for HSMR according to the MED‐RICE guidance (2003) is not available (relevant for the representative use evaluated; see Section 4).
• Water/sediment degradation rates for metabolite HSR (at least two systems), CSA (at least two systems) and AP (at least one additional system) were not available. (relevant for the representative use evaluated; see Section 4).
• Information on monitoring data on the fate and behaviour of halosulfuron‐methyl in paddy field condition, along with its relevant metabolites, degradation products and reaction products in soil, groundwater, surface water, sediment and air, was not available. (relevant for the representative use evaluated; see Section 4).
• Insufficient information was available to demonstrate that the batches used in the ecotoxicology studies are compliant with the original and newly proposed reference specification (relevant for the representative use evaluated; see Section 5).
• A comprehensive assessment of the risk to birds and mammals from plant metabolites was not available (relevant for the representative use evaluated; see Section 5).
• A consideration of the need for a risk assessment for birds and mammals via secondary poisoning and from the consumption of contaminated water from halosulfuron‐methyl and metabolites (with the exception of HSMR) pending on the data gaps for Koc and Pow values (relevant for the representative use evaluated; see Section 5).
• Acute oral and contact toxicity studies with honey bees with halosulfuron‐methyl were not available (relevant for the representative use evaluated; see Section 5).
• Acute oral toxicity studies with honey bees with the formulation for representative uses was not available (relevant for the representative use evaluated; see Section 5).
• A chronic oral toxicity study with adult honey bees and a honey bee larvae toxicity study with the formulation for representative uses were not available (relevant for the representative use evaluated; see Section 5).
• Further data were not available to address the risk to honeybees from sublethal effects and via exposure to plant metabolites (relevant for the representative use evaluated; see Section 5).

ABBREVIATIONSAAOELacute acceptable operator exposure levelADIacceptable daily intakeAOELacceptable operator exposure levelAPaminopyrimidineARapplied radioactivityARfDacute reference dosebwbody weightco‐RMSco‐rapporteur Member StateCSAchlorosulfonamide acidCSEchlorosulfonamideDT_50_ period required for 50% dissipation (define method of estimation)dwdry weightEASoestrogen, androgen and steroidogenesis modalitiesECHAEuropean Chemicals AgencyEDendocrine disruptionEECEuropean Economic CommunityFAOFood and Agriculture Organization of the United NationsFSTRAFish Short‐Term Reproduction AssayGAPGood Agricultural PracticeGLPGood Laboratory PracticeHSRhalosulfuron rearrangementHSMRhalosulfuron‐methyl rearrangementISOInternational Organization forIUPACInternational Union of Pure and Applied Chemistry K doc organic carbon linear adsorption coefficient K Foc Freundlich organic carbon adsorption coefficientLC–MS/MSliquid chromatography with tandem mass spectrometryLOQlimit of quantificationMSMember StateNOAELno observed adverse effect levelNOECno observed effect concentrationNTOsnon‐target organismsOECDOrganisation for Economic Co‐operation and DevelopmentPEC_sw_ predicted environmental concentration in surface waterRA‐RDrisk assessment residue definitionRACregulatory acceptable concentrationRARRenewal Assessment ReportRMMsrisk mitigation measuresRMSrapporteur Member StateSFOsingle first‐orderSMILESsimplified molecular‐input line‐entry systemTRRtotal radioactive residueUVultravioletWGwater‐dispersible granuleWoEweight‐of‐evidenceWHOWorld Health OrganizationXETAxenopus eleutheroembryonic thyroid assay

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00183

COPYRIGHT FOR NON‐EFSA CONTENT

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NOTE/UPDATE

This scientific output, approved on 23 May 2025, supersedes the previous output published on 6 December 2012 (EFSA, 2012).

Supporting information

APPENDIX B List of end points for the active substance and the formulation(s) for representative use

APPENDIX E Evaluation of data concerning the necessity of halosulfuron‐methyl as a fungicide to control a serious danger to plant health which cannot be contained by other available means, including non‐chemical methods

APPENDIX F Data collection set