Modification of the existing maximum residue levels for cycloxydim in various crops

TL;DR

This paper discusses the modification of maximum residue levels for the herbicide cycloxydim in several crops and dairy products to ensure consumer safety.

Contribution

The paper provides updated MRL proposals for cycloxydim in specific crops and confirms no changes are needed for others.

Findings

MRLs for cycloxydim were proposed for pome fruits, peas, maize, and sugar beet roots.

No changes to MRLs were needed for apricots, peaches, and sheep milk.

Available analytical methods can enforce residue levels of cycloxydim.

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in the Netherlands to modify the existing maximum residue levels (MRLs) for the active substance cycloxydim in pome fruits, apricots/peaches, peas (with pods), maize/corn, sugar beet roots and milk (sheep). The data submitted in support of the request were found to be sufficient to derive MRL proposals for pome fruits, peas (with pods), maize/corn and sugar beet roots while for apricots, peaches and sheep milk no changes to the existing MRLs were considered necessary. Adequate analytical methods for enforcement are available to control the residues of cycloxydim according to the current enforcement residue definition in the commodities under consideration. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the uses of cycloxydim according to the reported agricultural practices is unlikely to present a risk to consumer health.

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Full text

SUMMARY

In accordance with Article 6 of Regulation (EC) No 396/2005, BASF SE submitted an application to the competent national authority in the Netherlands (evaluating Member State, EMS) to modify the existing maximum residue levels (MRLs) for the active substance cycloxydim in pome fruits, apricots/peaches, peas (with pods), maize/corn, sugar beet roots and milk (sheep).

The application, alongside the dossier containing the supporting data in IUCLID format, was submitted through the European Food Safety Authority (EFSA) Central Submission System on 19 December 2022. The appointed EMS, the Netherlands, assessed the dossier and declared its admissibility on 10 February 2023. Subsequently, following the implementation of the EFSA's confidentiality decision, the non‐confidential version of the dossier was published by EFSA and a public consultation was launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, in order to identify whether other relevant scientific data or studies are available. The consultation ran from 16 June 2023 to 7 July 2023. No additional data nor comments were submitted in the framework of the consultation. At the end of the commenting period, the EMS proceeded to draft the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and to the European Food Safety Authority (EFSA) on 22 May 2024. To accommodate for the intended European uses of cycloxydim, the EMS proposed to raise the existing MRL from the limit of quantification (LOQ) of 0.09 mg/kg to 0.4 mg/kg for pome fruits and to raise the existing MRLs from 2 to 9 mg/kg for peas (with pods), from 0.2 to 0.3 mg/kg for maize/corn, from 0.2 to 0.3 mg/kg for sugar beets roots while for apricots/peaches and milk (sheep) no changes to the existing MRLs were considered necessary.

On 18 June 2024, the European Commission sent a mandate to EFSA to assess the application and the evaluation report as required by Article 10 of the MRL regulation.

Based on the conclusions derived by EFSA in the framework of Regulation (EC) No 1107/2009, the data evaluated under previous MRL assessment, and the additional data provided by the EMS in the framework of this application, the following conclusions are derived.

The metabolism of cycloxydim by foliar application was investigated in crops belonging to the groups of root crops, cereals/grass and pulses/oilseeds. Cycloxydim is rapidly and intensively metabolised to a large variety of metabolites, with the parent only detected in trace amounts following application.

Studies investigating the effect of processing on the nature of cycloxydim (hydrolysis studies) demonstrated that the active substance is readily and fully degraded when subject to hydrolytic conditions to its oxazol metabolite BH 517‐T2S (new code: M517H017; 75%–94% TRR) and to a lesser extent to the sulfoxide of the latter (BH 517‐T2SO, new code M517H005), both covered by the common moiety analytical methods.

Rotational crop metabolism studies have shown that the metabolism of cycloxydim in rotational crops is similar to the metabolic pathway observed in primary crops.

Based on the metabolic pattern identified in the available studies and the toxicological relevance of metabolites and/or degradation products, the residue definitions for plant products were proposed as ‘Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or methyl esters thereof, calculated in total as cycloxydim’ for both enforcement and risk assessment. It should be noted that during the course of the evaluation of the present MRL application, the existing residue definition for enforcement was superseded by ‘Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or derivatives thereof, calculated in total as cycloxydim’ according to Commission Regulation (EC) 2023/173. Considering that the modification of the enforcement residue definition only involves a terminological change without altering the practical implementation, the EMS and EFSA are of the opinion that the residue definitions for risk assessment and monitoring are equivalent.

EFSA concluded that for the crops assessed in this application, the metabolism of cycloxydim in primary and rotational crops, as well as the possible degradation in processed products have been sufficiently addressed and that the above derived residue definitions are applicable.

Sufficiently validated common moiety analytical methods based on high performance liquid chromatography (HPLC) are available to quantify residues in the crops assessed in this application according to the enforcement residue definition. The methods enable quantification of residues at or above 0.12 mg/kg in the crops assessed (LOQ).

The available residue trials are sufficient to derive MRL proposals of 0.4 mg/kg for pome fruits, 9 mg/kg for peas (with pods), 0.3 mg/kg for maize/corn and 0.3 mg/kg for sugar beet roots while for apricots, peaches and milk (sheep) no changes to the existing EU MRLs are considered necessary.

Specific studies investigating the magnitude of cycloxydim residues in processed commodities are not required, as the total theoretical maximum daily intake (TMDI) is below the trigger value of 10% of the ADI for the crops under assessment in the present application.

The occurrence of cycloxydim residues in rotational crops was investigated in the framework of the EU pesticides peer review. Based on the available information on the nature of residues and considering the low soil persistence of cycloxydim and its major soil metabolite, it was concluded that significant residue levels are unlikely to occur in rotational crops, provided that the active substance is used according to the proposed Good Agricultural Practice (GAP).

As some of the crops under consideration and their by‐products are used as feed products, a potential carry‐over of cycloxydim residues into food of animal origin was assessed. EFSA updated the most recent livestock dietary burden calculated in the MRL review with the residue data submitted to support new intended uses on the feed crops under consideration. The calculated livestock dietary burden exceeded the trigger value of 0.1 mg/kg dry matter (DM) for all relevant animal species. However, the contribution of cycloxydim residues in the crops under consideration to the existing livestock exposure was insignificant and therefore a modification of the existing MRLs for commodities of animal products is not necessary.

The toxicological profile of cycloxydim was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and an acceptable daily intake (ADI) of 0.07 mg/kg bw per day and an acute reference dose (ARfD) of 2 mg/kg bw were derived. The metabolites included in the residue definition are not of higher toxicity than the parent active substance.

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The short‐term (acute) exposure assessment was performed only for the crops under consideration and did not exceed the ARfD for any of the crops assessed in this application.

For the calculation of the chronic exposure, EFSA updated the most recent consumer exposure calculation performed in the MRL review with the median residue values (STMR) as derived for the crops under consideration from the residue trials submitted. The crops on which no uses were reported in the MRL review were excluded from the exposure calculation. The highest estimated long‐term dietary intake accounted for 80% of ADI (GEMS/Food G11 diet). The contributions of residues expected in the commodities assessed in the present MRL application to the overall long‐term exposure accounted for a maximum of 1.96% of the ADI (Apples, NL toddler diet). No long‐term consumer intake concerns were identified for any of the European diets incorporated in EFSA PRIMo.

EFSA concluded that the proposed use of cycloxydim on pome fruits, apricots/peaches, peas (with pods), maize/corn and sugar beet roots will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

The peer review for the renewal of approval of cycloxydim in accordance with Regulation (EC) No 1107/2009 is ongoing and not yet finalised, therefore the conclusions reported in this reasoned opinion might need to be reconsidered in the light of the outcome of the peer review.

EFSA proposes to amend the existing MRLs as reported in the summary table below.

Full details of all end points and the consumer risk assessment can be found in Appendices B to D.Codea CommodityExisting EU MRL (mg/kg)Proposed EU MRL (mg/kg)Comment/justification Enforcement residue definition: cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or derivatives thereof, calculated in total as cycloxydim0130000Pome fruits0.09* 0.4The submitted data are sufficient to derive an MRL proposal for the intended NEU and SEU use. Risk for consumers is unlikely0140010Apricots0.09* No changeThe residue data submitted in support of the intended SEU use are sufficient to confirm the existing EU MRL. Risk for consumers is unlikely0140030Peaches0.09* No change0260040Peas with pods29The submitted data are sufficient to derive an MRL proposal for the intended NEU and SEU uses. The MRL proposal reflects the more critical residue situation of the SEU use. Risk for consumers is unlikely0500030Maize/corn0.2 (ft 2)0.3 The submitted data are sufficient to derive an MRL proposal for the intended NEU and SEU uses. Risk for consumers is unlikely The confirmatory data set by the MRL review (additional residue trials on maize/corn) is met with this submitted data 0900010Sugar beet roots0.20.3The submitted data are sufficient to derive an MRL proposal for the intended NEU and SEU uses. Risk for consumers is unlikely1020020Sheep milk0.06No changeOn the basis of calculated livestock dietary burdens, there is no need to modify the existing EU MRLAbbreviations: MRL, maximum residue level; NEU, northern Europe; SEU, southern Europe.*Indicates that the MRL is set at the limit of analytical quantification (LOQ). ^a^ Commodity code number according to Annex I of Regulation (EC) No 396/2005. ^ft 2^ The European Food Safety Authority identified some information on residue trials as unavailable. When re‐viewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by [Office of Publication: please insert date 2 years after publication], or, if that information is not submitted by that date, the lack of it.

ASSESSMENT

The European Food Safety Authority (EFSA) received an application to modify the existing maximum residue level (MRL) for cycloxydim in various crops. The detailed description of the intended EU uses of cycloxydim, which are the basis for the current MRL application, is reported in Appendix A.

Cycloxydim is the ISO common name for (5RS)‐2‐[(EZ)‐1‐(ethoxyimino)butyl]‐3‐hydroxy‐5‐[(3RS)‐thian‐3‐yl]cyclohex‐2‐en‐1‐one (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Cycloxydim was evaluated in the framework of Directive 91/414/EEC1 with Austria designated as rapporteur Member State (RMS) for the representative uses as outdoor foliar applications against perennial grasses in rapeseeds/canola seeds, sugar beet roots, potatoes, beans and tolerant maize/corn (derived by natural plant breeding). The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2010). Cycloxydim has been approved2 for the use as herbicide on 1 June 2011. The approval of cycloxydim expires on 31 August 2026. The process of renewal of the first approval has not yet been initiated.

The EU MRLs for cycloxydim are established in Annex II of Regulation (EC) No 396/2005.3 The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has been performed (EFSA, 2020) and the proposed modifications have been implemented in the MRL legislation.4 Certain Codex maximum residue limits (CXLs) have been taken over in the EU MRL legislation.5

In accordance with Article 6 of Regulation (EC) No 396/2005 and following the provisions set by the ‘Transparency Regulation’ (EU) 2019/1381,6 the applicant BASF SE submitted on 19 December 2022 an application to the competent national authority in the Netherlands, alongside the dossier containing the supporting data using the IUCLID format. The appointed EMS, the Netherlands, assessed the dossier and declared its admissibility on 10 February 2023. Subsequently, following the implementation of the EFSA's confidentiality decision, the non‐confidential version of the dossier was published by EFSA and a public consultation launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, in order to identify whether other relevant scientific data or studies are available. The consultation ran from 16 June 2023 to 7 July 2023. No additional data or comments were submitted in the framework of the consultation. At the end of the commenting period, the EMS proceeded to draft the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and to EFSA on 22 May 2024. On 18 June 2024, the European Commission sent a mandate to EFSA to assess the application and the evaluation report as required by Article 10 of the MRL regulation.

To accommodate for the intended outdoor uses of cycloxydim in Europe, the EMS proposed to raise the existing MRL from the limit of quantification (LOQ) of 0.09 mg/kg to 0.4 mg/kg for pome fruits and from 2 mg/kg to 9 mg/kg for peas (with pods), from 0.2 mg/kg to 0.3 mg/kg for maize/corn, from 0.2 mg/kg to 0.3 mg/kg for sugar beets roots while for apricots/peaches and milk (sheep) no changes from the established MRLs were considered necessary by the EMS.

EFSA based its assessment on the evaluation report submitted by the EMS (the Netherlands, 2024), the draft assessment report (DAR) and its addendums (Austria, 2006, 2009, 2010) prepared under Council Directive 91/414/EEC, the confirmatory data submitted under the peer review (Austria, 2013), the Commission review report on cycloxydim (European Commission, 2014), the conclusion on the peer review of the pesticide risk assessment of the active substance cycloxydim (EFSA, 2010), as well as the conclusions from a previous EFSA opinion on cycloxydim (EFSA, 2015, 2018b8), including the reasoned opinion on the MRL review according to Article 12 of Regulation No 396/2005 (EFSA, 2020).

For this application, the data requirements established in Regulation (EU) No 544/20117 and the guidance documents applicable at the date of submission of the IUCLID application are applicable (European Commission, 1996, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2010, 2021, 2023; OECD, 2011, 2013). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/2011.8

It is noted that pome fruits and apricots and peaches are melliferous crops and the use of cycloxydim described in the current application during the flowering period could not be excluded. However, further data were not submitted by the applicant to investigate the potential carry‐over of residues in honey from the intended uses as such data are not required, according to the data requirements applicable for the assessment of the submitted application.

A selected list of end points of the studies assessed by EFSA in the framework of this MRL application including the end points of relevant studies assessed previously, is presented in Appendix B.

The evaluation report submitted by the EMS (the Netherlands, 2024) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available as background documents to this reasoned opinion.9

RESIDUES IN PLANTS

1

Nature of residues and methods of analysis in plants

1.1

Nature of residues in primary crops

1.1.1

The metabolism of cycloxydim was investigated in primary crops belonging to the group of root crops (sugar beet roots), cereals/grass (cycloxydim tolerant maize/corn) and pulses/oilseeds (soybean) in the framework of the EU pesticides peer review (EFSA, 2010). No additional studies were submitted in support of the current MRL application.

In the crops tested, the metabolism of cycloxydim was investigated by foliar application with ^14^C‐labelling on the cyclohexanone ring. As reported in the conclusion of the peer review of the pesticide risk assessment of the active substance cycloxydim (EFSA, 2010) ‘Cycloxydim is rapidly and intensively metabolised, the parent being never detected in plants except in trace amounts when samples are collected just after application. The metabolism proceeds first by oxidation to the sulphoxide and sulphone metabolites M517H003 and M517H022. Further loss of the alkyl side chain at the oxime group gives the imine metabolites M517H015 and M517H014, and the oxazole metabolites M517H005 and M517H006 are formed by Beckman rearrangement. All these metabolites are also found in their hydroxylated forms at the cyclohexanone moiety (M517H010, M517H030, etc.). In addition, cleavage of the cyclohexenone ring results in substituted glutaric acid derivative metabolites (M517H021, M517H001)’.

The metabolic pathway of cycloxydim follows a similar pattern in all crop groups investigated. For the intended uses on the crops under consideration, the metabolic behaviour in primary crops is considered sufficiently addressed.

Nature of residues in rotational crops

1.1.2

Cycloxydim is authorised on several crops that can be grown in rotation with other crops. According to the soil degradation studies evaluated in the framework of the peer review, the DT_90_ values reported were 8.6 days for cycloxydim and up to 46 days for the major soil metabolite BH 517‐TSO (EFSA, 2010). As the soil persistence of cycloxydim and its major soil metabolite is low, the investigation of the nature of residues in rotational crops was not required.

Nonetheless, a rotational crop metabolism study has been performed in the framework of the peer review. In this confined rotational crop study, cycloxydim ^14^C‐labelled on the cyclohexanone ring was applied at 650 g/ha onto bare soil and residues in succeeding crops were investigated in radish (root crop), lettuce (leafy crop) and wheat (cereals). Crops were planted at plant‐back intervals (PBI) of 30, 120 and 365 days after treatment (DAT). It was concluded that the metabolism of cycloxydim in rotational crops is similar to the metabolic pathway observed in primary crops (EFSA, 2010).

For the proposed uses assessed in this application, no further information is required and residue uptake by rotational crops is not expected.

Nature of residues in processed commodities

1.1.3

The effect of processing on the nature of cycloxydim was investigated in the framework of the EU pesticides peer review (EFSA, 2010). These studies were conducted with cycloxydim ^14^C‐labelled on the cyclohexanone ring by simulating representative hydrolytic conditions for pasteurisation (20 min at 90°C, pH 4), boiling/brewing/baking (60 min at 100°C, pH 5) and sterilisation (20 min at 120°C, pH 6).

The studies demonstrated that cycloxydim is readily and fully degraded under all hydrolytic conditions to its oxazol metabolite BH 517‐T2S (new code: M517H017, 75–94% AR) and to a lesser extent to the sulfoxide of the latter (BH 517‐T2SO, new code M517H005). Both metabolites are covered by the enforcement residue definition and analysed by the common moiety methods, hence no additional data on the nature of residue in processed commodities is required.

Analytical methods for enforcement purposes in plant commodities

1.1.4

Analytical methods for the determination of cycloxydim residues were assessed during the EU pesticides peer review (EFSA, 2010) and MRL review (EFSA, 2020). Cycloxydim residues are quantified via common moiety methods after oxidation as M517H001 and M517H002 (method 407/1) or as their methyl esters (method 263). These methods are considered adequate to determine residues of cycloxydim in plant matrices according to the current enforcement residue definition ‘Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (M517H001) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (M517H002) or derivatives thereof, calculated in total as cycloxydim’.

The current analytical method for enforcement, based on a common moiety method, has been further developed to account for more non‐hydroxylated and hydroxylated metabolites of cycloxydim (method L0018/01, the Netherlands, 2024). This upgraded analytical method still involves the extraction of parent and metabolites using isopropanol/water, oxidation of parent compound and relevant metabolites with hydrogen peroxide under alkaline conditions to M517H001 and M517H002 with a final determination of these metabolites using high performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS). The method is sufficiently validated to control residues of cycloxydim according to the enforcement residue definition in high water, high protein, high starch and high‐oil commodities (covering all crops under consideration), at the LOQ of 0.05 mg/kg for each analyte which were recalculated as parent equivalents (LOQ: 0.062 mg/kg for M517H001 and 0.058 mg/kg for M517H002) and added to derive a combined LOQ of 0.12 mg/kg.

The combined LOQ was previously established at 0.09* mg/kg for total cycloxydim based on the analytical method 407/1 (EFSA, 2020). With the upgraded method, the LOQ of total cycloxydim increases from 0.09* mg/kg (method 407/1) to 0.12* mg/kg (method L0018/01). The increase is solely due to refinement of the calculation since previously, findings of M517H001 were related to parent equivalents for expression of the LOQ and findings of M517H002 were related to M517H011 equivalents for expression of the LOQ. The validated LOQ of parent is 0.05 mg/kg and the validated LOQ of M517H011 is also 0.05 mg/kg, equivalent to a finding of 0.0436 mg/kg expressed as parent equivalent, leading to a previously combined LOQ of 0.09 mg/kg.

EFSA notes that the extraction efficiency of the analytical method for enforcement is not proven as indicated according to the requirements of the Technical Guideline on Evaluation of the Extraction Efficiency SANTE 2017/10632 (European Commission, 2023) and the lack of these data introduces additional uncertainty of the present assessment. In fact, EFSA notes that metabolism studies conducted in sugar beet and soybean utilised aqueous methanol for extraction, with hexane additionally used for soybean seeds, hence different solvent systems than the one applied by the current analytical method for enforcement (isopropanol/water mixture). Additionally, accountability studies on potatoes, soybean seeds and canola referred to in the Evaluation Report are not providing sufficient information to consider the extraction efficiency for this enforcement analytical method as demonstrated. Therefore, to satisfy the current criteria of the guidance, further investigation on this matter would be required. EFSA would recommend re‐assessing the extraction efficiency in the framework of the peer review for the renewal of approval of the active substance.

Storage stability of residues in plants

1.1.5

The storage stability of cycloxydim in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review (EFSA, 2010). Cycloxydim (determined as M517H001) and M517H011 (determined as M517H002) were found stable for up to 2 years in high water (maize forage), high starch (maize seeds), high oil (rapeseeds), high protein (pea seeds) and high‐acid (strawberries) content matrices, using the common moiety method 407/1.

It was concluded that the storage stability of cycloxydim determined as cycloxydim parent and all non‐hydroxylated metabolites to be oxidised to M517H001 (BH 517 TGSO2) and all hydroxylated metabolites to be oxidised to M517H002 (BH 517 5 OH TGSO2) was proven for 24 months in at least one commodity from all five crop group categories. Therefore, storage stability was demonstrated for all plant matrices, including processed commodities thereof.

Proposed residue definitions

1.1.6

Based on the metabolic pattern identified in metabolism studies, the results of hydrolysis studies, the toxicological relevance of metabolites and/or degradation products and the capabilities of enforcement analytical methods, the following residue definitions were proposed by the EU pesticides peer review and confirmed by the MRL review (EFSA, 2010, 2020):

• residue definition for risk assessment: Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or methyl esters thereof, calculated in total as cycloxydim.10
• residue definition for enforcement: Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or methyl esters thereof, calculated in total as cycloxydim.

It should be noted that during the course of the evaluation of the present MRL application, the previous residue definition for monitoring ‘Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or methyl esters thereof, calculated in total as cycloxydim’ was superseded in the EU pesticides database by ‘Cycloxydim including degradation and reaction products which can be determined as 3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐TGSO2) and/or 3‐hydroxy‐3‐(3‐thianyl)glutaric acid S‐dioxide (BH 517‐5‐OH‐TGSO2) or derivatives thereof, calculated in total as cycloxydim’ on August 16th 2023 according to Commission Regulation (No) 2023/173.11 The residue definition for risk assessment was not changed. Consequently, the residue definitions for risk assessment and monitoring that used to be the same, now differ from one another. Considering that the modification only involves a terminological change without altering the practical implementation, the EMS and EFSA are of the opinion that the residue definitions for risk assessment and monitoring are equivalent.

The same residue definitions are applicable to rotational crops and processed products. The residue definition for enforcement set in Regulation (EC) No 396/2005 is identical with the above‐mentioned residue definition.

As highlighted in the MRL review (EFSA, 2020), the EURLs emphasised that the monitoring of the current and complex residue definition is very difficult, entailing a complex analytical procedure not routinely used in enforcement labs and appealed for a simplified residue definition. Moreover, the residue definition is not specific to cycloxydim and may conceal a non‐authorised use of the more toxic non‐approved active substance profoxydim. In addition, EFSA notes that the possible impact of plant metabolism on the isomer ratio of cycloxydim was not assessed and further investigation on this matter would in principle be required. However, as cycloxydim (1:1 racemic mixture) is instantaneously metabolised following treatment, the isomeric ratio is unlikely to have a significant impact on its metabolism.

Nevertheless, EFSA is of the opinion that further investigation of the enforcement residue definition and the isomerisation of cycloxydim in the upcoming renewal of the approval of cycloxydim would allow the refinement of such information.

Magnitude of residues in plants

1.2

Magnitude of residues in primary crops

1.2.1

In support of the MRL application, the applicant submitted residue trials performed in apples and pears, apricots and peaches, beans and peas with pods, maize/corn and sugar beet roots. The samples were analysed for the parent compound cycloxydim and the metabolites included in the residue definitions for enforcement and risk assessment. The samples of these residue trials were stored under conditions for which integrity of the samples is demonstrated. According to the assessment of the EMS, the methods used were sufficiently validated and fit for purpose (The Netherlands, 2024). However, EFSA notes that extraction efficiency was not demonstrated according to the requirements of the Technical Guideline on Evaluation of the Extraction Efficiency SANTE 2017/10632 (European Commission, 2023), adding a source of uncertainty to the MRL estimation.

Pome fruit

NEU and SEU GAP outdoor, foliar 1 × 500 g cycloxydim/ha; PHI 28 days

In support of the MRL application, the applicant provided GAP‐compliant residue trials conducted on apples and pears in northern Europe (four trials) and southern Europe (four trials) in the growing seasons of 2018. Since the number of independent trials may be reduced to at least four per zone for major crops in case of a < LOQ residues situation, the four trials conducted in Northern Europe are sufficient to support the NEU GAP. However, this is not the case for the SEU where one trial shows residue level above the LOQ. Therefore, four SEU residue trials previously assessed by EFSA and conducted according to the same GAP were added to the SEU dataset (EFSA, 2020). Consequently, a total of 12 independent residue trials performed on apples and pears are now available: four trials already evaluated in 2020 (SEU) plus eight new trials (four NEU and four SEU trials). The applicant has proposed to combine the apple and pear trials and to extrapolate the data to the whole group of pome fruit. The proposed extrapolation is in line with the guidance document SANTE/2019/12752 (European Commission, 2023) and the combined number of trials (12) is sufficient.

EFSA notes that the NEU and SEU GAPs are equivalent, and the data sets belong to the same statistical population, but the MRLs proposals derived for the individual data sets (NEU and SEU) did not fall into the same or a neighbouring class (MRL of 0.15* mg/kg for NEU use and 0.4 mg/kg for SEU use). However, as out of the 12 trials, only one shows residues above LOQ (0.28 mg/kg with LOQ at 0.12 mg/kg) and the calculated MRL based on the most critical SEU data set equals the result of the pooled data set (e.g. 0.4 mg/kg), the EMS and EFSA agree that merging NEU and SEU is an acceptable approach. An MRL of 0.4 mg/kg is therefore derived in support of the intended SEU and NEU uses of cycloxydim on pome fruit from pooling the NEU and SEU dataset.

Apricots and peaches

SEU GAP outdoor, foliar 1 × 500 g cycloxydim/ha; PHI 28 days

In support of the MRL application, the applicant submitted GAP‐compliant residue trials performed in southern Europe on apricots (two trials) and peaches (two trials) in the growing seasons of 2017. In addition, five SEU residue trials on apricots (two trials) and peaches (three trials) previously assessed by EFSA and conducted according to the same GAP were added to the dataset (EFSA, 2020) to account for a total of nine independent residue trials. The applicant proposed to derive one MRL for both fruit crops based on a combined residue data set on apricots and peaches. According to the Technical Guidelines SANTE/2019/12752 (European Commission, 2023), the residue data on apricots and peaches can be combined to derive MRL proposal and extrapolated to both crops provided that a minimum of 50% of the trials were done on apricots. The requirement was fulfilled by the available trials.

The number of trials is sufficient to derive an MRL proposal of 0.09* mg/kg in support of the intended SEU use of cycloxydim on peaches and apricots. It is noted that the existing EU MRL for peaches and apricots is already set at the LOQ (0.09* mg/kg) therefore no changes from the established MRLs are considered necessary.

Peas (with pods)

GAP 1 (NEU) outdoor, foliar 1 × 500 g cycloxydim/ha; PHI 28 days

GAP 2 (SEU) outdoor, foliar 1 × 500 g cycloxydim/ha; PHI 35 days

In support of the MRL application, the applicant submitted GAP‐compliant residue trials performed in northern Europe on peas with pods (four trials) and in southern Europe on peas with pods (four trials) and beans with pods (four trials). The trials were conducted in the growing seasons of 2017, 2018 and 2019. In addition, nine NEU and one SEU residue trials on beans with pods conducted at GAP 1 and previously assessed by EFSA were added to the dataset (EFSA, 2020).

The applicant has proposed to extrapolate the residue trials on beans with pods to peas with pods. The proposed extrapolation is in line with the guidance document SANTE/2019/12752 (European Commission, 2023) and the number of trials per zone is sufficient. Peas with pods are considered a minor crop both in the NEU and in the SEU zone.

The data sets on beans and peas with pods were combined to derive an MRLs of 4 mg/kg for peas with pods in NEU and an MRL of 9 mg/kg for peas with pods in SEU. NEU and SEU trials were not pooled as the GAPs were different. An MRL of 9 mg/kg for peas with pods was derived based on the most critical SEU use.

Maize

NEU and SEU GAP outdoor, foliar 1 × 400 g cycloxydim/ha; BBCH 19, PHI n.a.

In support of the MRL application, the applicant submitted GAP‐compliant residue trials performed on maize in northern Europe (eight trials) and in southern Europe (eight trials), accounting for a total of 16 independent residue trials. The trials were conducted in the growing seasons of 2018 and 2019. Maize is a major crop both in the NEU zone and SEU zone. Number of trials is sufficient to derive an MRL for both zones.

EFSA notes that the NEU and SEU GAPs are equivalent, the data sets belong to the same statistical population but the MRLs proposals derived for the individual data sets (NEU and SEU) did not fall into the same or a neighbouring class. However, as out of the 16 trials only one showed residues above LOQ (0.24 mg/kg with LOQ at 0.12 mg/kg) and there are no reasons to exclude this trial from the data set, the EMS and EFSA agreed that merging NEU and SEU data sets is an acceptable approach according to the as low as reasonably achievable (ALARA) principle.

Therefore, NEU and SEU trials were combined and an MRL of 0.3 mg/kg was derived in support of the intended SEU and NEU use of cycloxydim on maize/corn. The confirmatory data set by the MRL review (additional residue trials on maize/corn) is met with this submitted data, leading to an increased MRL of 0.3 mg/kg. In addition, risk assessment values for straw were calculated since this product can be fed to livestock.

Sugar beet

SEU and NEU GAP outdoor, foliar 1 × 500 g cycloxydim/ha; BBCH 12–39, PHI n.a.

In support of the MRL application, the applicant submitted GAP‐compliant residue trials performed on sugar beet in northern Europe (eight trials) and in southern Europe (eight trials), accounting for a total of 16 independent residue trials. The trials were conducted in the growing seasons of 2018 and 2019. Sugar beet is a major crop both in the NEU zone and SEU zone. Number of trials is sufficient to derive an MRL for both zones.

EFSA notes that the NEU and SEU GAPs are equivalent, and the data sets belong to the same statistical population, but the MRLs proposals derived for the individual data sets (NEU and SEU) did not fall into the same or a neighbouring class. However, as out of the 16 trials, only one shows residues above LOQ (0.25 mg/kg with LOQ at 0.12 mg/kg) and there are no reasons to exclude this trial from the data set, the EMS and EFSA agree that merging NEU and SEU data sets is an acceptable approach according to the as low as reasonably achievable (ALARA) principle.

Therefore, NEU and SEU trials were combined and an MRL of 0.3 mg/kg for sugar beet roots was derived. In addition, risk assessment values for sugar beet tops were calculated since this product can be fed to livestock.

Magnitude of residues in rotational crops

1.2.2

The possible transfer of cycloxydim residues to crops that are grown in crop rotation has been assessed in EU pesticides peer review (EFSA, 2010). The available rotational crop metabolism studies demonstrated that only low levels of TRRs in succeeding crops (white radish, lettuce and wheat) were observed, also confirmed that residues from primary uses are not expected (EFSA, 2010). Since the maximum annual application rate on the crops under consideration (i.e. 0.5 kg a.s./ha) is lower than the application rate tested in the rotational crop study and as cycloxydim and its relevant soil metabolite BH 517‐TSO showed low soil persistence, it is concluded that no residues are expected, provided that the active substance is applied according to the proposed GAP.

Magnitude of residues in processed commodities

1.2.3

For the plant commodities under assessment, although cycloxydim residues are expected to occur at levels above 0.1 mg/kg in most of the raw plant commodities included in this application (i.e. pome fruits, peas with pods, maize/corn and sugar beet roots), considering the low individual contribution of these commodities to the total consumers' chronic exposure to cycloxydim residues (see Section B.3), investigations on the effect of processing on the magnitude of residues in processed commodities are not deemed necessary (European Commission, 1997d).

Proposed MRLs

1.2.4

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for the commodities under evaluation.

In Section 3 EFSA assessed whether residues resulting from the critical intended uses of cycloxydim assessed in this application are likely to pose a consumer health risk.

RESIDUES IN LIVESTOCK

2

Apples, maize/corn, sugar beet roots and their by‐products may be used for feed purposes. Hence, it was necessary to update the previous dietary burden calculation for livestock to estimate whether the new intended use of cycloxydim would have an impact on the residues expected in food of animal origin.

In the framework of the review of MRLs for cycloxydim (EFSA, 2020), the dietary burden for livestock was calculated. EFSA updated that dietary burden calculations with the new risk assessment values derived from the intended uses submitted under the scope of the present application (see Section D.1 for detailed input values) according to the applicable OECD guidelines (OECD, 2013).

The results of the dietary burden calculation (Section B.2) indicate that the trigger value of 0.1 mg/kg DM is exceeded for all livestock species, but residues in feed crops under consideration from the new intended uses do not have an impact on the dietary burden levels calculated previously by the MRL review. Thus, an update of the MRLs for commodities of animal origin proposed during the MRL review (EFSA, 2020) is not needed in the framework of the present application.

Nevertheless, the applicant made a proposal to change the MRL for sheep milk from the currently established value of 0.06 to 0.07 mg/kg. Neither the Evaluating Member State nor EFSA agree with this proposal. EFSA noted that for the calculation of MRL proposal in milk, the Applicant considered the highest residue values (HRs) from each cow once a plateau is reached, while the mean residues should be considered according to EFSA and EMS as milk is a bulked product (OECD, 2013). Thus, the proposal of the applicant to raise existing EU MRL in sheep milk is not supported.

CONSUMER RISK ASSESSMENT

3

EFSA performed a dietary risk assessment using revision 3.1 of the EFSA PRIMo (EFSA, 2018a, 2019). This exposure assessment model contains food consumption data for different sub‐groups of the EU population and allows the acute and chronic exposure assessment to be performed in accordance with the internationally agreed methodology for pesticide residues (FAO, 2016).

The toxicological reference values for cycloxydim used in the risk assessment (i.e. ADI of 0.7 mg/kg bw day and ARfD values of 2 mg/kg bw) were derived in the framework of the EU pesticides peer review (European Commission, 2014). The metabolites included in the risk assessment residue definition were considered to be of similar toxicity than the parent compound (EFSA, 2010).

Short‐term (acute) dietary risk assessment

The calculations were based on the HR or STMR (only for maize/corn) derived from supervised field trials and the complete list of input values can be found in Appendix D.2.

The short‐term exposure did not exceed the ARfD for any of the crops assessed in this application and was as follows: 1.2% of ARfD for apples (NL toddler) and pears (NL toddler), 0.3% of ARfD for quinces (ES child), 0.2% of ARfD for medlars (ES child), 0.2% of ARfD for apricots (DE child) and peaches (NL toddler), 3.7% of ARfD for peas (with pods) (NL child) and 0.1% of ARfD for maize/corn (UK infant). Acute exposure could not be calculated for loquats/Japanese medlars and sugar beet roots due to no consumption data being available (see Appendix B.3). Considering that loquat/Japanese medlar is a minor crop and that sugar beet root undergoes extensive processing prior to consumption (in form of sugar), it is not expected that residues in these commodities would have an impact on the acute exposure.

Long‐term (chronic) dietary risk assessment

In the framework of the MRL review a comprehensive long‐term exposure assessment was performed, taking into account the existing uses at EU level and the acceptable CXLs (EFSA, 2020). EFSA updated this calculation with the relevant STMR values derived for pome fruit, apricots and peaches, peas (with pods), maize/corn and sugar beet from the residue trials submitted in support of this MRL application. Crops on which no uses have been reported in the MRL review were excluded from the exposure calculation.

The input values used in the exposure calculations are summarised in Appendix D.2.

The estimated long‐term dietary intake was up to 80% of the ADI (GEMS/Food G11). The contribution of residues expected in the commodities assessed in this application to the overall long‐term exposure is low (maximum exposure was calculated for apple at 1.96% of the ADI, NL toddler diet) and is presented in more detail in Appendix B.3.

EFSA concluded that the long‐term and short‐term intake of residues of cycloxydim resulting from the existing and the intended uses is unlikely to present a risk to consumer health.

For further details on the exposure calculations, a screenshot of the Report sheet of the PRIMo is presented in Appendix C.

CONCLUSION AND RECOMMENDATIONS

4

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal for pome fruit, apricots and peaches, peas (with pods), maize/corn and sugar beet roots. No modification of the existing EU MRL was concluded for apricots and peaches. The calculated dietary burdens did not trigger a modification of existing EU MRLs in commodities of animal origin.

EFSA concluded that the proposed use of cycloxydim on pome fruit, apricots and peaches, peas (with pods), maize/corn and sugar beet roots will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

The MRL recommendations are summarised in Appendix B.4.

ABBREVIATIONSa.s.active substanceADIacceptable daily intakeARapplied radioactivityARfDacute reference doseBBCHgrowth stages of mono‐ and dicotyledonous plantsbwbody weightCACCodex Alimentarius CommissionCASChemical Abstract ServiceCFconversion factor for enforcement to risk assessment residue definitionCVcoefficient of variation (relative standard deviation)CXLCodex maximum residue limitDALAdays after last applicationDARdraft assessment reportDATdays after treatmentDMdry matterDT_90_ period required for 90% dissipation (define method of estimation)dwdry weightECemulsifiable concentrateEDIestimated daily intakeEMSevaluating Member Stateeqresidue expressed as a.s. equivalentEURLEU Reference Laboratory (former Community Reference Laboratory (CRL))FAOFood and Agriculture Organization of the United NationsGAPGood Agricultural PracticeGLPGood Laboratory PracticeGRgranuleGSgrowth stageHPLChigh performance liquid chromatographyHPLC‐MS/MShigh performance liquid chromatography with tandem mass spectrometryHRhighest residueIEDIinternational estimated daily intakeIESTIinternational estimated short‐term intakeILVindependent laboratory validationIPCSInternational Programme of Chemical SafetyISOInternational Organisation for StandardisationIUPACInternational Union of Pure and Applied ChemistryJMPRJoint FAO/WHO Meeting on Pesticide Residues K oc organic carbon adsorption coefficientLODlimit of detectionLOQlimit of quantificationMRLmaximum residue levelMSMember StatesMWmolecular weightNEUnorthern EuropeNOAELno observed adverse effect levelOECDOrganisation for Economic Co‐operation and DevelopmentPAFFStanding Committee on Plants, Animals, Food and FeedPBIplant back intervalPFprocessing factorPHIpre‐harvest intervalPRIMo(EFSA) Pesticide Residues Intake ModelRArisk assessmentRACraw agricultural commodityRDresidue definitionRMSrapporteur Member StateRPFrelative potency factorSANCODirectorate‐General for Health and ConsumersSCsuspension concentrateSEUsouthern EuropeSGwater‐soluble granuleSLsoluble concentrateSPwater‐soluble powderSTMRsupervised trials median residueTMDItheoretical maximum daily intakeTRRtotal radioactive residueUVultraviolet (detector)WGwater‐dispersible granuleWHOWorld Health Organization

CONFLICT OF INTEREST

If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu.

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐00066

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