Review of the existing maximum residue levels for isoxaben according to Article 12 of Regulation (EC) No 396/2005.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance isoxaben. To assess the occurrence of isoxaben residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008, as well as the European authorisations reported by Member States and the UK (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

Summary

Isoxaben was included in Annex I to Directive 91/414/EEC on 1 June 2011 by Commission Directive 2011/32/EU, and has been deemed to be approved under Regulation (EC) No 1107/2009, in accordance with Commission Implementing Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011.

As the active substance was approved after the entry into force of Regulation (EC) No 396/2005 on 2 September 2008, the European Food Safety Authority (EFSA) is required to provide a reasoned opinion on the review of the existing maximum residue levels (MRLs) for that active substance in compliance with Article 12(1) of the aforementioned regulation.

As the basis for the MRL review, on 16 October 2020, EFSA initiated the collection of data for this active substance. In a first step, Member States and the UK were invited to submit by 13 November 2020 their national Good Agricultural Practices (GAPs) in a standardised way, in the format of specific GAP forms, allowing the designated rapporteur Member State, Sweden, to identify the critical GAPs in the format of a specific GAP overview file. Subsequently, Member States and the UK were requested to provide residue data supporting the critical GAPs, within a period of 1 month, by 15 February 2021. On the basis of all the data submitted by Member States, the UK and the EU Reference Laboratories for Pesticides Residues (EURLs), EFSA asked the RMS to complete the Pesticide Residues Overview File (PROFile) and to prepare a supporting evaluation report. The PROFile and the evaluation report were provided by the RMS to EFSA on 17 June 2021. Subsequently, EFSA performed the completeness check of these documents with the RMS. The outcome of this exercise including the clarifications provided by the RMS, if any, was compiled in the completeness check report.

Based on the information provided by the RMS, Member States, the UK and the EURLs, and taking into account the conclusions derived by EFSA in the framework of Commission Regulation (EC) No 33/2008, EFSA prepared in October 2021 a draft reasoned opinion, which was circulated to Member States and the EURLs for consultation via a written procedure. Comments received by 18 November 2021 were considered during the finalisation of this reasoned opinion. The following conclusions are derived.

The metabolism of isoxaben in plants was investigated in primary and rotational crops. According to the results of the metabolism studies, the residue definition for enforcement and risk assessment can be proposed as parent isoxaben for all crops following soil treatment and early post‐emergence applications. The investigation of the nature of residues in processed commodities is not required since residues in all commodities are below 0.1 mg/kg and the total theoretical maximum daily intake is below 10% of the ADI. Fully validated analytical methods are available for the enforcement of the proposed residue definition in all four main plant matrices at the limit of quantification (LOQ) of 0.01 mg/kg. However, analytical methods for hops and herbal infusions are not available. According to the EURLs, the LOQ of 0.01 mg/kg is achievable in the four main matrix groups of plant origin by using the QuEChERS method in routine analyses.

Available residue trials data were considered sufficient to derive (tentative) MRL proposals as well as risk assessment values for all commodities under evaluation, except for clover forage and grass forage.

Isoxaben is authorised for use on crops that might be fed to livestock. Since the calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg dry matter (DM), further investigation of residues as well as the setting of MRLs in commodities of animal origin is unnecessary.

Chronic consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 3.1 of the EFSA PRIMo. The highest chronic exposure was calculated for the Dutch toddler, representing 0.7% of the acceptable daily intake (ADI). Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not deemed necessary for this active substance.

Background

Regulation (EC) No 396/2005 (hereinafter referred to as ‘the Regulation’) establishes the rules governing the setting and the review of pesticide maximum residue levels (MRLs) at European level. Article 12(1) of that Regulation stipulates that the European Food Safety Authority (EFSA) shall provide within 12 months from the date of the inclusion or non‐inclusion of an active substance in Annex I to Directive 91/414/EEC a reasoned opinion on the review of the existing MRLs for that active substance.

Isoxaben was included in Annex I to Council Directive 91/414/EEC by means of Commission Directive 2011/32/EU which has been deemed to be approved under Regulation (EC) No 1107/2009 , in accordance with Commission Implementing Regulation (EU) No 540/2011 , as amended by Commission Implementing Regulation (EU) No 541/2011 . Therefore, EFSA initiated the review of all existing MRLs for that active substance.

By way of background information, isoxaben was evaluated by Sweden, designated as rapporteur Member State (RMS) upon resubmission in the framework of Commission Regulation (EC) No 33/2008 . Subsequently, a peer review on the initial evaluation of the RMS was conducted by EFSA, leading to the conclusions as set out in the EFSA scientific output (EFSA, 2010). The approval of isoxaben is restricted to uses as herbicide. Furthermore, according to the provisions of the approval regulation, confirmatory information was requested, among others, as regards residues in rotational crops, to be submitted by 31 May 2013. Confirmatory data on residues in rotational crops were submitted by the applicant, evaluated by the RMS (Sweden, 2014) and considered by risk managers in a revised review report (European Commission, 2020).

According to the legal provisions, EFSA shall base its reasoned opinion in particular on the relevant assessment report prepared under Directive 91/414/EEC repealed by Regulation (EC) No 1107/2009. It should be noted, however, that, in the framework of Regulation (EC) No 1107/2009, only a few representative uses are evaluated, whereas MRLs set out in Regulation (EC) No 396/2005 should accommodate all uses authorised within the European Union (EU), and uses authorised in third countries that have a significant impact on international trade. The information included in the assessment report prepared under Regulation (EC) No 1107/2009 is therefore insufficient for the assessment of all existing MRLs for a given active substance.

To gain an overview of the pesticide residues data that have been considered for the setting of the existing MRLs, EFSA developed the Pesticide Residues Overview File (PROFile). The PROFile is an inventory of all pesticide residues data relevant to the risk assessment and MRL setting for a given active substance. This includes data on:

the nature and magnitude of residues in primary crops;

the nature and magnitude of residues in processed commodities;

the nature and magnitude of residues in rotational crops;

the nature and magnitude of residues in livestock commodities;

the analytical methods for enforcement of the proposed MRLs.

As the basis for the MRL review, on 16 October 2020, EFSA initiated the collection of data for this active substance. In a first step, Member States and UK were invited to submit by 13 November 2020 their Good Agricultural Practices (GAPs) that are authorised nationally, in a standardised way, in the format of specific GAP forms. In the framework of this consultation, 15 Member States and the UK provided feedback on their national authorisations of isoxaben. Based on the GAP data submitted, the designated RMS, Sweden, was asked to identify the critical GAPs to be further considered in the assessment, in the format of a specific GAP overview file. Subsequently, in a second step, Member States and the UK were requested to provide residue data supporting the critical GAPs by 15 February 2021.

On the basis of all the data submitted by Member States, the UK and the EU Reference Laboratories for Pesticides Residues (EURLs), EFSA asked Sweden to complete the PROFile and to prepare a supporting evaluation report. The PROFile and the supporting evaluation report were submitted to EFSA on 17 June 2021. Subsequently, EFSA performed the completeness check of these documents with the RMS. The outcome of this exercise including the clarifications provided by the RMS, if any, was compiled in the completeness check report.

Considering all the available information, EFSA prepared in October 2021 a draft reasoned opinion, which was circulated to Member States and the EURLs for commenting via a written procedure. All comments received by 18 November 2021 were considered by EFSA during the finalisation of the reasoned opinion.

The evaluation report submitted by the RMS (Sweden, 2021), taking into account also the information provided by Member States and the UK during the collection of data, and the EURLs report on analytical methods (EURLs, 2021) are considered as main supporting documents to this reasoned opinion and, thus, made publicly available.

In addition, further supporting documents to this reasoned opinion are the completeness check report (EFSA, 2021a) and the Member States consultation report (EFSA, 2021b). These reports are developed to address all issues raised in the course of the review, from the initial completeness check to the reasoned opinion. Furthermore, the exposure calculations for all crops reported in the framework of this review performed using the EFSA Pesticide Residues Intake Model (PRIMo) and the PROFile as well as the GAP overview file listing all authorised uses are key supporting documents and made publicly available as background documents to this reasoned opinion. A screenshot of the report sheet of the PRIMo is presented in Appendix C.

Terms of reference

According to Article 12 of Regulation (EC) No 396/2005, EFSA shall provide a reasoned opinion on:

the inclusion of the active substance in Annex IV to the Regulation, when appropriate;

the necessity of setting new MRLs for the active substance or deleting/modifying existing MRLs set out in Annex II or III of the Regulation;

the inclusion of the recommended MRLs in Annex II or III to the Regulation;

the setting of specific processing factors as referred to in Article 20(2) of the Regulation.

The active substance and its use pattern

Isoxaben is the ISO common name for N‐[3‐(1‐ethyl‐1‐methylpropyl)‐1,2‐oxazol‐5‐yl]‐2,6‐dimethoxybenzamide (IUPAC).

The chemical structure of the active substance and its main metabolites is reported in Appendix F.

The EU MRLs for isoxaben are established in Annexes IIIA of Regulation (EC) No 396/2005. Codex maximum residue limits (CXLs) for isoxaben are not available. No MRL changes occurred since the entry into force of the Regulation mentioned above.

For the purpose of this MRL review, all the uses of isoxaben currently authorised within the EU as submitted by the Member States and the UK during the GAP collection, have been reported by the RMS in the GAP overview file. The critical GAPs identified in the GAP overview file were then summarised in the PROFile and considered in the assessment. The details of the authorised critical GAPs for isoxaben are given in Appendix A. The RMS did not report any use authorised in third countries that might have a significant impact on international trade.

Assessment

EFSA has based its assessment on the following documents:

the PROFile submitted by the RMS;

the evaluation report accompanying the PROFile (Sweden, 2021);

the draft assessment report (DAR), its addendum prepared under Council Directive 91/414/EEC and its revised addendum following the evaluation of confirmatory data (Sweden, 2006, 2010, 2014);

the additional report (AR) prepared under Commission Regulation (EC) No 33/2008 (Sweden, 2009);

the conclusion on the peer review of the pesticide risk assessment of the active substance isoxaben (EFSA, 2010).

The assessment is performed in accordance with the legal provisions of the uniform principles for evaluation and authorisation of plant protection products as set out in Commission Regulation (EU) No 546/2011 and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (European Commission, 1996, 1997a–g, 2000, 2010a,b, 2017; OECD, 2011, 2013).

More detailed information on the available data and on the conclusions derived by EFSA can be retrieved from the list of end points reported in Appendix B.

Residues in plants

Nature of residues and methods of analysis in plants

Nature of residues in primary crops

The metabolism of isoxaben was investigated after soil/foliar treatment in cereals (wheat and barley) and assessed in the framework of the peer review (Sweden, 2006; EFSA, 2010). In addition, studies in fruits (grapes) and leafy vegetables (leeks), after soil and foliar/soil treatment, respectively, were evaluated by the RMS in the framework of this review (Sweden, 2021). In all studies, isoxaben was radiolabelled on the 14C‐isoxazole (IS) or on the 14C‐phenyl (PH) ring of the molecule. An overview of all available metabolism studies is reported in Appendix B.1.1.1.

The metabolism studies were conducted in wheat and barley with pre‐ and early post‐emergence applications of 1 × 200 or 500 g a.s./ha. In mature straw and grain, the residue consisted of multicomponent polar compounds, mainly conjugates. Isoxaben, hydroxy isoxaben (2‐hydroxy isoxaben), 3‐hydroxy isoxaben and 1‐hydroxy isoxaben were present. Isoxaben residues were not expected to exceed 0.01 mg/kg in grain and 0.10 mg/kg in straw (EFSA, 2010).

Isoxaben was applied to soil surrounding grape vines at the rate of 2008–2204 g a.s./ha (Sweden, 2021). Mature grapes and leaves were collected 165 days after the application. Residues in both the IS‐ and PH‐treated grapes were below the limit of quantification (0.008 mg/kg), indicating limited translocation into the edible portion. The IS‐ and PH‐treated leaf samples contained 0.304 and 0.288 mg/kg isoxaben equivalents, respectively. No quantifiable level of parent isoxaben was observed in the leaves. The extractable radioactive residue in leaves was multicomponent, tentatively identified as hydroxylated on the aliphatic side chain metabolites, limited benzamide bridge cleavage metabolites and multiple, low‐level, polar components. One unknown metabolite was observed in the leaf samples of both radiolabels, and was characterised as aqueous‐soluble, containing both sides of the benzamide bridge.

Isoxaben was applied with a single foliar application to leeks at BBCH 14 (preharvest interval (PHI) of 119 days) and to the surrounding soil at 250 g a.s./ha (Sweden, 2021). Whole leek plants were sampled at maturity and separated into leaf blade and stem (including root). The phenyl label leaf blade and stem contained 0.001 and 0.004 mg eq/kg, respectively, while the isoxazole label leaf blade and stem contained 0.003 and 0.004 mg eq/kg, respectively. As the total radioactive residues were less than 0.01 mg isoxaben equivalents per kg, no characterisation of the nature of these residues was carried out. The results indicate that following application to immature plants and surrounding soil, residues are not translocated into the leaves and the stems/roots.

It is noted that the metabolism study on leeks does not cover all the GAPs reported for leafy crops under this review in terms of PHI. This is the case of the GAPs on celery leaves that have shorter PHIs than the one assessed in the metabolism study. Therefore, a metabolism study on leafy crops performed with a shorter PHI would be in principle still needed to confirm the metabolism of isoxaben in this commodity. Nevertheless, considering the overall data available and the results of the risk assessment (see Section 3), this additional study is considered desirable only.

Furthermore, it is highlighted that for courgettes, pumpkins, beans without pods, herbal infusions from roots and chicory roots, the NEU GAPs are reported for foliar application up to BBCH 16, corresponding to early post‐emergence which are in principle not supported by a metabolism study. However, based on the metabolism studies on primary crops and the phenological stage of the plants at treatment (BBCH stage between 13 and 16), limited uptake and translocation to edible parts of crop is expected. In addition, in the confined rotational crop study and in the available residue trials, a limited uptake is observed in all crops tested (see Sections 1.1.2 and 1.2.1). Therefore, it can be concluded that no additional metabolism studies are required to support these uses. Studies on cereals and leafy vegetables following soil and early post‐emergence treatment and in fruits following soil treatment show that isoxaben is the only relevant compound in plants.

Nature of residues in rotational crops

Isoxaben is authorised on crops that may be grown in rotation. The field DT90 reported in soil degradation studies evaluated in the framework of the peer review ranged from 219 to 1028 days for isoxaben, while for metabolite 1‐hydroxy isoxaben ranged from 258 to 697 days, and for metabolite oxypropyl isoxaben ranged between 285 and 927 days (EFSA, 2010). Therefore, further investigation on the nature of residue in rotational crops was required.

Thus, one confined rotational crop study with isoxaben radiolabelled on the 14C‐isoxazole (IS) or on the 14C‐phenyl (PH) ring of the molecule was submitted as confirmatory data and included in the revised addendum (Sweden, 2014). Isoxaben was applied at a rate of 250 g a.s./ha onto bare soil (sandy loam), and lettuce, radish and wheat were planted at back intervals (PBI) of 30, 120, 189 and 365 days after treatment (DAT). An overview of the study is reported in Appendix B.1.1.1.

The maximum TRR in immature lettuce was observed at 0.028 mg eq./kg 180 DAT. In mature lettuce, the maximum TRR was 0.026 mg eq./kg at 180 DAT while at 365 DAT, the TRR was below 0.01 mg/kg. In radish roots, the maximum TRR was 0.074 mg eq./kg at 30 DAT. At 180 and 365 DAT, the TRR was below 0.01 mg/kg in radish roots. At 30 and 120 DAT, there was slow growth and abnormal development of lettuces and radish roots. In wheat grain, the maximum TRR was 0.027 mg eq./kg at 120 DAT. At 180 DAT, no samples were taken for wheat grain, and at 365 DAT, the TRR was below 0.01 mg/kg. The highest individual levels of isoxaben found in the confined rotational crop were 0.012 mg eq./kg at 30 DAT in radish tops, 0.014 mg eq./kg at 30 DAT in radish root and 0.011 mg eq./kg at 120 DAT in wheat straw (Sweden, 2014). At 180 DAT, isoxaben was found below 0.01 mg/kg in lettuce (mature and immature) and radish roots, while in wheat grain, the TRR was below 0.01 mg eq./kg at 365 DAT. Metabolites were below 0.01 mg eq./kg in all crop fractions, except for hydroxy isoxaben (2‐hydroxy isoxaben) found only in wheat straw at 30 and 120 DAT at 0.011 and 0.012 mg eq./kg, respectively.

The metabolism and distribution of isoxaben in rotational crops are similar to the metabolic pathway observed in primary crops.

Nature of residues in processed commodities

There were no studies investigating the nature of residues of isoxaben in processed commodities available for this review. Nevertheless, in all commodities, residues were below 0.1 mg/kg and the total theoretical maximum daily intake is below 10% of the ADI. Therefore, the investigation of the nature of residues in processed commodities is not required.

Methods of analysis in plants

During the peer review, it was concluded that adequate analytical methods are available for the determination of isoxaben residues in high water content commodities (endives, wheat and barley forage, chicory roots and chicory leaves), dry content commodities (wheat grain, barley grain and in wheat and barley straw) by LC–MS/MS with an LOQ of 0.01 mg/kg (EFSA, 2010).

Additional analytical methods using LC–MS/MS, with confirmatory method and independent laboratory validation (ILV), were provided in the framework of this review for the enforcement of isoxaben in high water content commodities (wheat forage, lettuce leaves), dry commodities (barley grain and straw, wheat straw), high oil content commodities (rape seed, sunflower seed) and high acid content commodities (orange whole fruit, lemon whole fruit) with an LOQ of 0.01 mg/kg (Sweden, 2021).

It can be concluded that isoxaben can be monitored in high water content, high acid content, dry and high oil content commodities with an LOQ of 0.01 mg/kg. However, analytical methods for hops and herbal infusions are missing (data gap). An overview of the available studies is reported in Appendix B.1.1.1.

Based on data available to the EURLs, isoxaben can be monitored in high water content, high acid content, dry and high fat content commodities with an LOQ of 0.01 mg/kg. In high water content, high acid content and dry commodities, lower levels, down to 0.002 mg/kg, were successfully validated (EURLs, 2021).

Stability of residues in plants

The storage stability of isoxaben was investigated in the framework of the peer review (EFSA, 2010) and in new studies submitted under this review (Sweden, 2021). An overview of the available studies is reported in Appendix B.1.1.2.

Residues of isoxaben are stable for at least 12 months in endive (high water content commodities) and for at least 24 months in grapes and cereal grain and straw (high acid and dry/high starch content commodities, respectively) when stored at −20°C (EFSA, 2010). In addition, residues of isoxaben are stable in rapeseed and dry bean seed (high oil and high protein content commodities, respectively), for at least 12 months when stored at −18°C (Sweden, 2021).

It is noted that no specific study is available for the storage stability in herbal infusions from flowers and hops. However, as storage stability was investigated and demonstrated in the four main plant matrices, the most limiting storage stability conditions demonstrated for general matrices are assumed to be applicable to these matrices as well.

Proposed residue definitions

The metabolism of isoxaben was similar following soil and early post‐emergence application to cereals and to leafy vegetables and soil application to fruits. The metabolism studies on rotational crops (leafy, cereals and roots) confirmed that parent is the only relevant compound in plants upon soil application. The investigation of the metabolism of isoxaben upon processing is not required.

In some studies, no characterisation of the residues was possible (e.g. leafy vegetables), while in other studies, different compounds were present. However, a significant translocation into the edible parts of the crops after soil and early post‐emergence application was not observed in all the studies. Based on the overall data, the residue definition for enforcement and risk assessment in all crops is proposed as isoxaben only, for soil application and early post‐emergence applications. It is noted that isoxaben will undergo the renewal process soon, so the residue definition proposed in this review may be re‐considered.

An analytical method for the enforcement of the proposed residue definition at the LOQ of 0.01 mg/kg in all four main plant matrices is available (EFSA, 2010; Sweden, 2021). Analytical methods for hops and herbal infusions are missing. According to the EURLs, the LOQ of 0.01 is achievable in the four main matrix groups of plant origin by using the QuEChERS method in routine analyses (EURL, 2021).

Magnitude of residues in plants

Magnitude of residues in primary crops

To assess the magnitude of isoxaben residues resulting from the reported GAPs, EFSA considered all residue trials reported by the RMS in its evaluation report (Sweden, 2021) as well as the residue trials evaluated in the framework of the peer review (EFSA, 2010). Most residue trial samples considered in this framework were stored in compliance with the conditions for which storage stability of residues was demonstrated. Information on the storage stability is missing for the trials performed on melons, leeks and celery leaves, whereas samples from residue trials on courgettes and pumpkins were stored longer than the storage stability period for high water content commodities. However, since overall, according to the metabolism studies and the results of the trials available, isoxaben is not expected to be present at significant levels in fruits crops/leafy crops, additional information on the storage conditions and storage stability studies are only desirable.

The number of residue trials and extrapolations was evaluated in accordance with the European guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs (European Commission, 2017). An overview of the available residue trials is reported in Appendix B.1.2.1.

Residue trials are not available to support the authorisations on clover forage and grass forage. Therefore, MRL and risk assessment values could not be derived for these crops and the following data gaps were identified:

Clover forage, grass forage: four trials on clover forage and grass forage compliant with the northern outdoor GAP are required.

For all other crops, available residue trials are sufficient to derive (tentative) MRL and risk assessment values, taking note of the following considerations:

Strawberries: The number of residue trials supporting the indoor GAP is not compliant with the data requirements for this crop. However, significant residues are not expected to occur based on the metabolism in fruits following soil application and since the GAP is for application during dormant stage. Therefore, further residue trials are not required.

Raspberries (red and yellow) and blackberries: The number of residue trials supporting the northern GAP is not compliant with the data requirements for these crops. However, significant residues are not expected to occur based on the metabolism in fruits following soil application and since the GAP is for application during dormant stage. Therefore, further residue trials are not required.

Blueberries, gooseberries (green, red and yellow), rose hips: Although MRL and risk assessment values can be derived from the northern data, four trials compliant with the southern GAP would in principle still be required. However, significant residues are not expected to occur based on overdosed trials supporting the NEU GAP and the metabolism study on fruits following soil application. Therefore, further residue trials are not required.

Currants (black, red and white): Although MRL and risk assessment values can be derived from the northern data, four trials compliant with the southern GAP would in principle still be required. However, significant residues are not expected to occur based on overdosed trials on currants and the metabolism study on fruits following soil application. Therefore, further residue trials are not required.

Bananas: The number of residue trials supporting the southern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and according to the metabolism study, residues in fruits are not expected to occur when isoxaben is applied following soil application (confirmed as well by the available trials on pome and stone fruits). Therefore, further residue trials are not required.

Carrots: The number of residue trials supporting the northern outdoor GAP is not compliant with the data requirements for this crop. It is also noted that, although all results were below the LOQ, samples from trials were analysed using a method validated at an LOQ of 0.05 mg/kg while the LOQ for enforcement in high water content commodities is 0.01 mg/kg. However, based on the rotational crop metabolism study (performed at 3.3 N rate of the GAP on carrots), residues in carrots are expected to remain below the LOQ of 0.01 mg/kg when isoxaben is applied according to the authorised use. Therefore, MRL and risk assessment values can be derived at the LOQ of 0.01 mg/kg and further residue trials are not required.

Onions: The number of residue trials supporting the northern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ, the GAP is for an application every 2 years and the metabolism of isoxaben in roots/tuber vegetables following soil application indicates that significant residues are not expected to occur. Therefore, further residue trials are not required.

Melons: The number of residue trials supporting the southern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ, according to the metabolism study residues in fruits are not expected to occur when isoxaben is applied following soil application and the GAP is for a soil application every 2 years. Therefore, further residue trials are not required.

Celery leaves: The number of residue trials supporting the northern/southern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and according to the metabolism study residues in leafy vegetables are not expected to occur when isoxaben is applied following soil treatment with an application rate up to 250 g a.s./ha. Therefore, further residue trials are not required.

Sage, rosemary, thyme, basil and edible flowers: There are no residue trials to support the northern GAP for these crops. Since according to the metabolism study residues are not expected to occur following early post‐emergence application with isoxaben at up to 250 g a.s./ha, MRL and risk assessment values are tentatively proposed at the LOQ. However, two residue trials are needed to confirm that no significant residues are expected.

Asparagus: The number of residue trials supporting the northern/southern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and residues in the edible part are not expected to occur when isoxaben is applied according to the authorised use on asparagus (application at pre‐emergence or after harvest of the shoots). Therefore, further residue trials are not required.

Leeks: The number of residue trials supporting the northern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and residues in leafy vegetables are not expected to occur when isoxaben is applied following soil treatment with an application rate up to 250 g a.s./ha. Therefore, further residue trials are not required.

Spring onions/green onions and Welsh onions: Although MRL and risk assessment values can be derived from the northern data, four trials compliant with the southern GAP would in principle still be required. However, the SEU GAP is for an application every 2 years and residues are not expected based on trials with roots/tuber vegetables and the metabolism of isoxaben in roots following soil application. Therefore, further residue trials are not required.

Chives: Although MRL and risk assessment values can be derived from the northern data, four trials compliant with the southern GAP would in principle still be required. However, residues were below the LOQ in trials supporting the NEU GAP (that has the same GAP parameters), and residues are not expected to occur when isoxaben is applied to leafy vegetables as soil treatment at early growth stages. Therefore, further residue trials are not required.

Rapeseeds/canola seed: Although MRL and risk assessment values can be derived from the northern data, eight trials compliant with the southern GAP would in principle still be required. However, residues were below the LOQ in trials supporting the NEU GAP (that has the same GAP parameters), and according to the metabolism studies, residues are not expected to occur when isoxaben is applied as soil treatment. Therefore, further residue trials are not required.

Cotton seed: There are no residue trials supporting the southern outdoor GAP. Since according to the available studies, residues are not expected to occur when isoxaben is applied as soil treatment, MRL and risk assessment values are tentatively proposed at the LOQ. However, two residue trials are needed to confirm that no significant residues are expected.

Herbal infusions from flowers: There are no residue trials to support the northern/southern GAP. Since according to the metabolism study, residues are not expected to occur following early post‐emergence application with isoxaben at up to 250 g a.s./ha, MRL and risk assessment values are tentatively proposed at the LOQ. However, two residue trials compliant with the northern or with the southern outdoor GAP are needed to confirm that no significant residues are expected.

Herbal infusions from roots: There are no residue trials to support the northern GAP. Since according to the available studies, residues are not expected to occur when isoxaben is applied as soil treatment or at early post‐emergence, MRL and risk assessment values are proposed at the LOQ, based on an extrapolation from trials on carrots. It is noted that a dehydration factor was not applied because isoxaben was always below the LOQ in carrots and concentration of residues is not expected.

Hops: The number of residue trials supporting the northern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because residues were all below the LOQ of 0.01 mg/kg and because application is during dormant stage. Therefore, further residue trials are not required.

Chicory roots: Considering that the trials were performed according to a more critical GAP and residues were below or at the LOQ the MRL is proposed at the LOQ of 0.01 mg/kg and further residue trials are not required.

Magnitude of residues in rotational crops

There were no field rotational crop studies available for this review. Four accumulation soil studies (2 in NEU and 2 in SEU), where isoxaben and metabolites hydroxy isoxaben (2‐hydroxy isoxaben) and oxypropyl isoxaben were analysed, were assessed in the framework of the peer review (EFSA, 2010). The soils in the NEU studies were silty clay loam and a sandy clay loam, whereas in the SEU, the soils were clay loam. The studies conducted in the NEU were made with one application of 500 g a.s./ha made every year for 5 years, whereas in the SEU studies were made with one application of 1000 g a.s./ha every year for 5 years. According to the peer review, there was no accumulation of parent or metabolites in the soils tested (EFSA, 2010). It is noted that the longest soil field DT90 reported for isoxaben and metabolites hydroxy isoxaben (2‐hydroxy isoxaben) and oxypropyl isoxaben were reported for clay loam soils (EFSA, 2010). Since according to these studies, accumulation in soil is not expected over the years, the confined rotational crop study performed with 250 g a.s./ha on bare soil at 1N rate of the most critical GAPs for a crop that can be rotated reported in this review (e.g. cucurbits), is sufficient to conclude that significant residues of isoxaben and metabolites hydroxy isoxaben (2‐hydroxy isoxaben) and oxypropyl isoxaben are not expected to occur in crops grown in rotation (see also Section 1.1.2).

It is noted that some phytotoxicity was observed at earlier sampling intervals in the submitted study, thus a plant back interval of at least 180 days is recommended for some rotational crops (e.g. leafy vegetable, root crops). This information should be considered by risk managers for the adoption of mitigation measures.

Magnitude of residues in processed commodities

Studies on the effect of industrial processing and/or household preparation are not available and are not required (see also Section 1.1.3).

Proposed MRLs

The available data are considered sufficient to derive (tentative) MRL proposals as well as risk assessment values for all commodities under evaluation, except for clover forage and grass forage.

Tentative MRLs were also derived for cereals straw in view of the future need to set MRLs in feed items.

Residues in livestock

Isoxaben is authorised for use on crops that might be fed to livestock. Livestock dietary burden calculations were therefore performed for different groups of livestock according to OECD guidance (OECD, 2013), which has now also been agreed upon at European level. The input values for all relevant commodities are summarised in Appendix D.

Since the calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg dry matter (DM), further investigation of residues as well as the setting of MRLs in commodities of animal origin is unnecessary.

It is however noted that for some feed items (grass and clover forage), no residue data is available, and therefore, the calculated dietary burden might be underestimated.

Consumer risk assessment

Chronic exposure calculations for all crops reported in the framework of this review were performed using revision 3.1 of the EFSA PRIMo (EFSA, 2018, 2019). Input values for the exposure calculations were derived in compliance with the decision tree reported in Appendix E. Hence, for those commodities where a (tentative) MRL could be derived by EFSA in the framework of this review, input values were derived according to the internationally agreed methodologies (FAO, 2009). All input values included in the exposure calculations are summarised in Appendix D. Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not deemed necessary for this active substance.

The exposure values calculated were compared with the toxicological reference values for isoxaben, derived by EFSA (2010). The highest chronic exposure was calculated for the Dutch toddler, representing 0.7% of the acceptable daily intake (ADI). An overview of the consumer risk assessment is reported in Appendix B.3. Although uncertainties remain due to the data gaps identified in the previous sections, this indicative exposure calculation did not indicate a risk to consumer’s health.

Conclusions

The metabolism of isoxaben in plants was investigated in primary and rotational crops. According to the results of the metabolism studies, the residue definition for enforcement and risk assessment can be proposed as parent isoxaben for all crops following soil treatment and early post‐emergence applications. The investigation of the nature of residues in processed commodities is not required since residues in all commodities are below 0.1 mg/kg and the total theoretical maximum daily intake is below 10% of the ADI. Fully validated analytical methods are available for the enforcement of the proposed residue definition in all four main plant matrices at the LOQ of 0.01 mg/kg. However, analytical methods for hops and herbal infusions are not available. According to the EURLs, the LOQ of 0.01 mg/kg is achievable in the four main matrix groups of plant origin by using the QuEChERS method in routine analyses.

Available residue trials data were considered sufficient to derive (tentative) MRL proposals as well as risk assessment values for all commodities under evaluation, except for clover forage and grass forage.

Isoxaben is authorised for use on crops that might be fed to livestock. Since the calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg DM, further investigation of residues as well as the setting of MRLs in commodities of animal origin is unnecessary.

Chronic consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 3.1 of the EFSA PRIMo. The highest chronic exposure was calculated for the Dutch toddler, representing 0.7% of the acceptable daily intake (ADI). Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance.

Recommendations

MRL recommendations reported in Table 1 were derived in compliance with the decision tree reported in Appendix E of the reasoned opinion. All MRL values listed as ‘Recommended’ in the table are sufficiently supported by data and are therefore proposed for inclusion in Annex II to the Regulation. The remaining MRL values listed in the table are not recommended for inclusion in Annex II because they require further consideration by risk managers (see Table 1 footnotes for details). In particular, some tentative MRLs need to be confirmed by the following data:

Table 1

Summary table

Code number	Commodity	Existing EU MRL (mg/kg)		Outcome of the review
				MRL (mg/kg)	Comment
Isoxaben
110010	Grapefruit	0.02*		0.01*	Recommendeda
110020	Oranges	0.02*		0.01*	Recommendeda
110030	Lemons	0.02*		0.01*	Recommendeda
110040	Limes	0.02*		0.01*	Recommendeda
110050	Mandarins	0.02*		0.01*	Recommendeda
120010	Almonds	0.05		0.01*	Recommendeda
120040	Chestnuts	0.05		0.01*	Recommendeda
120060	Hazelnuts	0.05		0.01*	Recommendeda
120110	Walnuts	0.05		0.01*	Recommendeda
130010	Apples	0.05		0.01*	Recommendeda
130020	Pears	0.05		0.01*	Recommendeda
130030	Quinces	0.05		0.01*	Recommendeda
130040	Medlar	0.05		0.01*	Recommendeda
130050	Loquat	0.05		0.01*	Recommendeda
140010	Apricots	0.02*		0.01*	Recommendeda
140020	Cherries	0.05		0.01*	Recommendeda
140030	Peaches	0.02*		0.01*	Recommendeda
140040	Plums	0.05		0.01*	Recommendeda
151010	Table grapes	0.05		0.01*	Recommendeda
151020	Wine grapes	0.05		0.01*	Recommendeda
152000	Strawberries	0.05		0.01	Recommendeda
153010	Blackberries	0.05		0.01*	Recommendeda
153020	Dewberries	0.05		0.01	Recommendeda
153030	Raspberries	0.05		0.01*	Recommendeda
154010	Blueberries	0.05		0.01*	Recommendeda
154020	Cranberries	0.05		0.01*	Recommendeda
154030	Currants (red, black and white)	0.05		0.01*	Recommendeda
154040	Gooseberries	0.05		0.01*	Recommendeda
154050	Rose hips	0.05		0.01*	Recommendeda
154060	Mulberries	0.05		0.01*	Recommendeda
154070	Azarole (mediterranean medlar)	0.05		0.01*	Recommendeda
154080	Elderberries	0.05		0.01*	Recommendeda
162010	Kiwi	0.02*		0.01*	Recommendeda
163020	Bananas	0.02*		0.01*	Recommendeda
213020	Carrots	0.05		0.01*	Recommendeda
213040	Horseradish	0.05		0.01*	Recommendeda
213060	Parsnips	0.05		0.01*	Recommendeda
220010	Garlic	0.02*		0.01*	Recommendeda
220020	Onions	0.02*		0.01*	Recommendeda
220030	Shallots	0.02*		0.01*	Recommendeda
220040	Spring onions	0.02*		0.01*	Recommendeda
232030	Courgettes	0.05		0.05	Recommendeda
233010	Melons	0.05		0.01*	Recommendeda
233020	Pumpkins	0.05		0.01*	Recommendeda
255000	Witloof	0.02*		0.01*	Recommendeda
256020	Chives	0.05		0.01*	Recommendeda
256030	Celery leaves	0.05		0.01*	Recommendeda
256050	Sage	0.05		0.01*	Further consideration neededb data gap #2
256060	Rosemary	0.05		0.01*	Further consideration neededb data gap #2
256070	Thyme	0.05		0.01*	Further consideration neededb data gap #2
256080	Basil	0.05		0.01*	Further consideration neededb data gap #2
260020	Beans (fresh, without pods)	0.02*		0.02	Recommendedc
270010	Asparagus	0.05		0.01*	Recommendedc
270060	Leek	0.02*		0.01*	Recommendedc
270070	Rhubarb	0.02*		0.01*	Recommendedc
401060	Rape seed	0.02*		0.01*	Recommendedc
401090	Cotton seed	0.02*		0.01*	Further consideration neededb data gap #2
500010	Barley grain	0.1		0.01*	Recommendedc
500050	Oats grain	0.1		0.01*	Recommendedc
500070	Rye grain	0.1		0.01*	Recommendedc
500090	Wheat grain	0.1		0.01*	Recommendedc
631000	Herbal infusions (dried, flowers)	0.02*		0.01*	Further consideration neededb data gaps #1 and #2
633000	Herbal infusions (dried, roots)	0.02*		0.01*	Further consideration neededb data gap #1
700000	Hops (dried), including hop pellets and unconcentrated powder	0.05		0.01*	Further consideration neededb data gap #1
900030	Chicory roots	0.02*		0.01*	Recommendeda
–	Other commodities of plant and/or animal origin	See Reg. 149/2008	–	–	Further consideration neededc

MRL: maximum residue level.

Indicates that the MRL is set at the limit of quantification.

MRL is derived from a GAP evaluated at EU level, which is fully supported by data and for which no risk to consumers is identified; no CXL is available (combination H‐I in Appendix E).

Tentative MRL is derived from a GAP evaluated at EU level, which is not fully supported by data but for which no risk to consumers was identified (assuming the existing residue definition); no CXL is available (combination F–I in Appendix E).

There are no relevant authorisations or import tolerances reported at EU level; no CXL is available. Either a specific LOQ or the default MRL of 0.01 mg/kg may be considered (combination A–I in Appendix E).

Analytical methods for the enforcement in hops and herbal infusions;

Additional residue trials supporting the GAPs on sage, rosemary, thyme, basil and edible flowers, cotton seeds and herbal infusions from flowers.

Regarding MRLs in animal commodities, it is highlighted, however, that since no residue data is available to support the authorised uses on some animal feed items (grass and clover forage), the calculated livestock exposure might be underestimated. EFSA therefore identified the following data gap which is not expected to impact on the validity of the MRLs derived but which might have an impact on national authorisations:

residue trials supporting the northern outdoor GAP on clover forage and grass forage.

If the above‐reported data gap is not addressed in the future, Member States are recommended to withdraw or modify the relevant authorisations at national level.

EFSA also underlines that, according to the information provided by the EURLs, the analytical standard for isoxaben is commercially available.

Minor deficiencies were identified in the assessment, but these deficiencies are not expected to impact either on the validity of the MRLs derived or on the national authorisations. The following data are therefore considered desirable but not essential:

a representative study investigating the storage stability of isoxaben covering the residue trials performed with courgettes, melons, pumpkins, leeks and celery leaves;

A representative study investigating the metabolism in leafy vegetables at PHI covering the GAP on celery leaves.

Abbreviations

active ingredient

active substance

acceptable daily intake

applied radioactivity

acute reference dose

growth stages of mono‐ and dicotyledonous plants

Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany

body weight

Codex Alimentarius Commission

Chemical Abstract Service

Codex Committee on Pesticide Residues

European Committee for Standardization (Comité Européen de Normalisation)

conversion factor for enforcement residue definition to risk assessment residue definition

codex maximum residue limit

draft assessment report

days after treatment

dry matter

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

emulsifiable concentrate

residue expressed as a.s. equivalent

European Union Reference Laboratories for Pesticide Residues (former CRLs)

Food and Agriculture Organization of the United Nations

Good Agricultural Practice

gas chromatography

international estimated daily intake

independent laboratory validation

International Organisation for Standardization

International Union of Pure and Applied Chemistry

organic carbon adsorption coefficient

liquid chromatography

liquid chromatography with tandem mass spectrometry

limit of quantification

Monitoring

maximum residue level

Member States

mass spectrometry detector

tandem mass spectrometry detector

molecular weight

national estimated daily intake

national theoretical maximum daily intake

Organisation for Economic Co‐operation and Development

plant back interval

preharvest interval

partition coefficient between n‐octanol and water

parts per million (10−6)

(EFSA) Pesticide Residues Intake Model

(EFSA) Pesticide Residues Overview File

Quick, Easy, Cheap, Effective, Rugged, and Safe (analytical method)

risk assessment

raw agricultural commodity

residue definition

residue definition

rapporteur Member State

relative standard deviation

Directorate‐General for Health and Consumers

sterol biosynthesis inhibitors

suspension concentrate

Standing Committee on Plants, Animals, Food and Feed (formerly: Standing Committee on the Food Chain and Animal Health; SCFCAH)

southern European Union

water soluble granule

soluble concentrate

simplified molecular‐input line‐entry system

water soluble powder

total applied radioactivity

theoretical maximum daily intake

total radioactive residue

ultraviolet (detector)

water dispersible granule

World Health Organization

Appendix A – Summary of authorised uses considered for the review of MRLs

A.1. Authorised outdoor uses in northern EU

A.2. Authorised outdoor uses in southern EU

A.3. Authorised indoor uses in EU

Appendix B – List of end points

B.1. Residues in plants

B.1.1. Nature of residues and methods of analysis in plants

B.1.1.1. Metabolism studies, methods of analysis and residue definitions in plants

B.1.1.2. Stability of residues in plants

B.1.2. Magnitude of residues in plants

B.1.2.1. Summary of residues data from the supervised residue trials – Primary crops

B.1.2.2. Residues in rotational crops

(a) Overall summary

B.1.2.3. Processing factors

Studies are not available and are not required.

B.2. Residues in livestock

B.2.1. Nature of residues and methods of analysis in livestock

Studies on livestock are not available and are not required since MRLs for livestock commodities are not needed.

B.3. Consumer risk assessment

B.3.1. Consumer risk assessment

Acute risk assessment not relevant since no ARfD has been considered necessary.

Consumer exposure assessment through drinking water resulting from groundwater metabolite(s) according to SANCO/221/2000 rev.10 Final (25/02/2003)

B.4. Proposed MRLs

PRIMo(EU)

Appendix D – Input values for the exposure calculations

D.1. Livestock dietary burden calculations

D.2. Consumer risk assessment

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application				Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Almonds	UK	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	00	1		–	–	250 g a.i./ha	n.a.	Dormant stage
Chestnuts	UK	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	00	1		–	–	250 g a.i./ha	n.a.	Dormant stage
Hazelnuts	UK	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	00	1		–	–	250 g a.i./ha	n.a.	Dormant stage
Walnuts	UK	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	00	1		–	–	250 g a.i./ha	n.a.	Dormant stage
Apples	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Pears	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Quinces	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Medlars	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Loquats	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Apricots	AT, BE, DE	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	500 g a.i./ha	n.a.
Cherries	AT, BE, DE	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	500 g a.i./ha	n.a.
Peaches	AT, BE, DE	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	500 g a.i./ha	n.a.
Plums	AT, BE, DE	F	Weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	500 g a.i./ha	n.a.
Table grapes	BE	F	Weeds	SC	500 g/L	Soil treatment – spraying	0–59	1		–	–	500 g a.i./ha	n.a.
Wine grapes	FR	F	Weeds	SC	125 g/L	Soil treatment – spraying	0–3	1		–	–	750 g a.i./ha	n.a.	Do not apply on more than 30% of the surface of the plot
Strawberries	DE, BE, NL	F	Birdseed, shepherd's purse, charlock, common chickweed	SC	500 g/L	Soil treatment – general (see also comment field)	41	1		–	–	200 g a.i./ha	n.a.	Application at beginning of vegetation, before emergence of weeds, not in planting year
Blackberries	BE, AT, DE	F	Annual dicots	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	250 g a.i./ha		Up to 30% of the crops field can be treated. From November to beginning of March (dormant stage before flowering)
Dewberries	AT, DE	F	Annual dicotyledonous weeds	SC	500 g/L	Soil treatment – spraying	59	1		–	–	250 g a.i./ha	n.a.	In spring, before flowering, pre‐emergence of the weeds/Application from planting year, up to first bloom, pre‐emergence of the weeds, row treatment
Raspberries	IE, UK	F		SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	250 g a.i./ha	n.a.	Dormant stage
Blueberries	BE; AT, DE	F	Birdseed, common chickweed	SC	500 g/L	Soil treatment – spraying	59	1		–	–	500 g a.i./ha	n.a.	Aronia berries, Before flowering, pre‐emergence of weeds
Cranberries	BE; AT, DE	F	Annual dicots	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	250 g a.i./ha		up to 30% of the crops field can be treated. From November to beginning of March (dormant stage before flowering).
Currants	FR	F	Weeds	SC	125 g/L	Soil treatment – spraying	0–3	1		–	–	600 g a.i./ha	n.a.	Only on Black currants Extrapolated from strawberries and grapes trials
Gooseberries	BE	F	Annual dicots	SC	500 g/L	Soil treatment – general (see also comment field)	0–59	1		–	–	250 g a.i./ha		Up to 30% of the crops field can be treated. From November to beginning of March (dormant stage before flowering)
Rose hips	AT, DE	F	Annual dicotyledonous weeds	SC	500 g/L	Soil treatment – spraying	59	1		–	–	250 g a.i./ha	n.a.	In spring, before flowering, pre‐emergence of the weeds
Mulberries	AT, DE	F	Annual dicotyledonous weeds	SC	500 g/L	Soil treatment – spraying	59	1		–	–	250 g a.i./ha	n.a.	in spring, before flowering, pre‐emergence of the weeds
Azaroles	AT	F	Annual dicotyledonous weeds	SC	500 g/L	Soil treatment – spraying	59	1		–	–	250 g a.i./ha	n.a.	In spring, before flowering, pre‐emergence of the weeds
Elderberries	AT, DE	F	Annual dicotyledonous weeds	SC	500 g/L	Soil treatment – spraying	59	1		–	–	250 g a.i./ha	n.a.	In spring, before flowering, pre‐emergence of the weeds
Carrots	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	0–9	1		–	–	75 g a.i./ha	n.a.	Pre‐emergence Since application is done at early growth stage (up to BBCH 09), it is assumed that this represents a soil treatment and that the foliar treatment refers to the weed and not the crop
Horseradishes	IE, UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	0–9	1		–	–	75 g a.i./ha	n.a.	Pre‐emergence Since application is done at early growth stage (up to BBCH 09), it is assumed that this represents a soil treatment and that the foliar treatment refers to the weed and not the crop
Parsnips	IE, UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	0–9	1		–	–	75 g a.i./ha	n.a.	Pre‐emergence Since application is done at early growth stage (up to BBCH 09), it is assumed that this represents a soil treatment and that the foliar treatment refers to the weed and not the crop
Garlic	BE, IE, NL	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	11–12	1		–	–	100 g a.i./ha	n.a.	> BBCH11 or after planting
Onions	FR	F	Weeds	SC	125 g/L	Foliar treatment – broadcast spraying	0–0	1		–	–	250 g a.i./ha	n.a.	One application every 2 years. Since application is done at BBCH 00, it is assumed that this represents a soil treatment and that the foliar treatment refers to the weed and not the crop
Shallots	BE, IE, NL, UK	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	11–13	1		–	–	100 g a.i./ha		> BBCH11 or after planting
Spring onions	NL	F	Weeds		500 g/L	Foliar treatment – broadcast spraying	9–12	1		–	–	100 g a.i./ha	n.a.	–
Courgettes	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	250 g a.i./ha	n.a.	3 true leaf stage
Pumpkins	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	250 g a.i./ha	n.a.	3 true leaf stage
Witloofs	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	10–16	1		–	–	100 g a.i./ha		Dose splitting authorised
Chives	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	12–14	1		–	–	250 g a.i./ha	90
Celery leaves	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)		1		–	–	125 g a.i./ha	30	Only on Sorrel (Rumex spp.)
Sage	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	187.5 g a.i./ha		After planting
Rosemary	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	187.5 g a.i./ha		After planting
Thyme	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	187.5 g a.i./ha		Including hyssop, oregano and lemon savoury. After planting
Basil	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	187.5 g a.i./ha		Including lemon balm and min. After planting
Beans (without pods)	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	12–14	1		–	–	50 g a.i./ha
Asparagus	FR	F	Weeds	SC	107 g/L	Foliar treatment – broadcast spraying	0	1		–	–	267.5 g a.i./ha	n.a.	Application at BBCH 00 stage (pre‐emergence) or after harvest of shoots. – Do not apply on more than 75% of the surface in pre‐emergence
Leeks	FR	F	Weeds	SC	125 g/L	Foliar treatment – broadcast spraying	12–14	1		–	–	250 g a.i./ha	90	One application every 2 years
Rhubarbs	BE, NL, IE, UK	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	0	1		–	–	200 g a.i./ha		During dormancy Since application is done at BBCH 00, it is assumed that this represents a soil treatment and that the foliar application refers to the weed and not the crop
Rapeseeds	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	14–20	1		–	–	50 g a.i./ha	n.a.
Barley	NL, BE	F	Weeds		500 g/L	Foliar treatment – broadcast spraying	11–13	1		–	–	100 g a.i./ha	n.a.	–
Oat	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	100 g a.i./ha	n.a.	BBCH 13 or Before 31st January in year of harvest whichever is soonest
Rye	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	100 g a.i./ha	n.a.	BBCH 13 or Before 31st January in year of harvest whichever is soonest
Wheat	UK	F		SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	100 g a.i./ha	n.a.	BBCH 13 or Before 31 January in year of harvest whichever is soonest
Herbal infusions from flowers	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)		1		–	–	125 g a.i./ha	90	Only on Roman chamomile
Herbal infusions from roots	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	13	1		–	–	100 g a.i./ha	n.a.	Valerian. after pricking
Hops	BE, IE, UK	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	0–8	1		–	–	250 g a.i./ha		During dormancy. Up to 30% of the crops field can be treated
Chicory roots	BE, IE, NL, FR	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	10–16	1		–	–	100 g a.i./ha		Including yacon roots. Dose splitting authorised
Clover (for forage)	BE	F	Annual dicots	SC	500 g/L	Foliar treatment – general (see also comment field)	from 10	1		–	–	50 g a.i./ha	n.a.
Grass (for forage)	NL, BE	F	Weeds		500 g/L	Foliar treatment – broadcast spraying	0–13	1		–	–	50 g a.i./ha	n.a.	–

MS: Member State.

Outdoor or field use (F), greenhouse application (G) or indoor application (I).

CropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system.

Growth stage range from first to last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3‐8263‐3152‐4), including, where relevant, information on season at time of application.

PHI – minimum preharvest interval.

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application				Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Grapefruits	ES	F	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	450 g a.i./ha	n.a.	Application rate refers to the rate of use in the treated band (30% of the total crop area). Volume: 100–400 L/ha
Oranges	ES	F	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	450 g a.i./ha	n.a.	Application rate refers to the rate of use in the treated band (30% of the total crop area). Volume: 100–400 L/ha
Lemons	ES	F	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	450 g a.i./ha	n.a.	Application rate refers to the rate of use in the treated band (30% of the total crop area). Volume: 100–400 L/ha
Limes	ES	F	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	450 g a.i./ha	n.a.	Application rate refers to the rate of use in the treated band (30% of the total crop area). Volume: 100–400 L/ha
Mandarins	ES	F	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	450 g a.i./ha	n.a.	Application rate refers to the rate of use in the treated band (30% of the total crop area). Volume: 100–400 L/ha
Almonds	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Chestnuts	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Hazelnuts	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Walnuts	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–60	1		–	–	600 g a.i./ha	n.a.
Apples	ES	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – spraying	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Pears	ES, PT	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Pyrus pyrifolia is also included. ES, volume: 100–400 L/ha, PT, volume: 400–800 L/ha
Quinces	ES	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Medlars	IT	F	Bidens bipinnata	SC	500 g/L	Soil treatment – spraying	0–69	1		–	–	600 g a.i./ha	n.a.	Application timing: from dormancy to flowering (winter–spring) Application rate refers to the rate of use in the treated band (30% pf the total crop area)
Loquats	ES	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Apricots	ES	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Cherries	ES, IT	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Prunus cerasus is also included. Volume: 100–400 L/ha
Peaches	ES, IT	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Plums	ES, IT	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–69	1		–	–	600 g a.i./ha	n.a.	Volume: 100–400 L/ha
Table grapes	IT	F	Weeds	SC	500 g/L	Soil treatment – spraying	0–14	1		–	–	750 g a.i./ha	n.a.	Application timing: from dormancy to leaf development Application rate refers to the rate of use in the treated band (30% pf the total crop area)
Wine grapes	IT	F	Weeds	SC	500 g/L	Soil treatment – spraying	0–14	1		–	–	750 g a.i./ha	n.a.	Application timing: from dormancy to leaf development Application rate refers to the rate of use in the treated band (30% pf the total crop area)
Blueberries	IT	F	Weeds	SC	107 g/L	Soil treatment – spraying	0–3	1		–	–	535 g a.i./ha	n.a.	mixture of isoxaben + oryzalin 429 g/L established crops. Strip application (no more than 30% of the plot area) tractor‐mounted or hand sprayer
Currants	IT	F	Weeds	SC	107 g/L	Soil treatment – spraying	0–3	1		–	–	535 g a.i./ha	n.a.	mixture of isoxaben + oryzalin 429 g/L established crops. Strip application (no more than 30% of the plot area) tractor‐mounted or hand sprayer
Gooseberries	IT	F	Weeds	SC	107 g/L	Soil treatment – spraying	0–3	1		–	–	535 g a.i./ha	n.a.	mixture of isoxaben + oryzalin 429 g/L established crops. Strip application (no more than 30% of the plot area) tractor‐mounted or hand sprayer
Rose hips	IT	F	Weeds	SC	107 g/L	Soil treatment – spraying	0–3	1		–	–	535 g a.i./ha	n.a.	mixture of isoxaben + oryzalin 429 g/L established crops. Strip application (no more than 30% of the plot area) tractor‐mounted or hand sprayer
Kiwi fruits	ES, FR	F	Dicotyledonous weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0–14	1		–	–	750 g a.i./ha	n.a.	ES: Volume: 100–200 L/ha, FR: Do not apply on more than 30% of the surface.
Bananas	FR	F	Weeds	SC	107 g/L	Soil treatment – general (see also comment field)	0–15	1		–	–	481.5 g a.i./ha	n.a.	Row application only with a boom sprayer Do not apply on more than 30% of the surface of the plot
Garlic	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	0	1		–	–	250 g a.i./ha	n.a.
Spring onions	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	12–14	1		–	–	250 g a.i./ha	90	One application every 2 years
Melons	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)		1		–	–	250 g a.i./ha	45	One application every 2 years. Do not apply on more than 50% of the surface. Stage of application: early post‐planting.
Chives	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	12–14	1		–	–	250 g a.i./ha	90
Celery leaves	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)		1		–	–	125 g a.i./ha	30	Only on Sorrel (Rumex spp.)
Asparagus	FR, IT	F	Weeds	SC	107 g/L	Foliar treatment – broadcast spraying	0	1		–	–	267.5 g a.i./ha	n.a.	Application at BBCH 00 stage (pre‐emergence) or after harvest of shoots. Do not apply on more than 75% of the surface in pre‐emergence. Since application is done at BBCH 00, it is assumed that this represents a soil treatment
Rapeseeds	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)	14–20	1		–	–	50 g a.i./ha	n.a.
Cotton seeds	ES	F	Dicotyledonous weeds	SC	500 g/L	Foliar treatment – broadcast spraying	0	1		–	–	150 g a.i./ha	n.a.	Broadcast spray with incorporation (Pre‐sowing). Volume: 200–400 L/ha Since application is done at BBCH 00, it is assumed that this represents a soil treatment
Barley	ES, IT, PT	F	Dicotyledonous weeds	SC	125 g/L	Foliar treatment – broadcast spraying	0–13	1		–	–	125 g a.i./ha	n.a.	Volume: 100–400 L/ha
Oat	ES, IT, PT	F	Dicotyledonous weeds	SC	125 g/L	Foliar treatment – broadcast spraying	0–13	1		–	–	125 g a.i./ha	n.a.	Volume: 100–400 L/ha
Rye	ES, IT, PT	F	Dicotyledonous weeds	SC	125 g/L	Foliar treatment – broadcast spraying	0–13	1		–	–	125 g a.i./ha	n.a.	Volume: 100–400 L/ha
Wheat	ES, IT, PT	F	Dicotyledonous weeds	SC	125 g/L	Foliar treatment – broadcast spraying	0–13	1		–	–	125 g a.i./ha	n.a.	Volume: 100–400 L/ha
Herbal infusions from flowers	FR	F	Weeds	SC	125 g/L	Soil treatment – general (see also comment field)		1		–	–	125 g a.i./ha	90	Only on Roman chamomile

MS: Member State.

Outdoor or field use (F), greenhouse application (G) or indoor application (I).

CropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system. Growth stage ranges from first to last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3‐8263‐3152‐4), including, where relevant, information on season at time of application.

PHI – minimum preharvest interval.

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application				Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Strawberries	IE	I	Dicotyledonous weeds	SC	500 g/L	Soil treatment – general (see also comment field)	0	1		–	–	200 g a.i./ha	n.a.	Dormant stage

MS: Member State.

Outdoor or field use (F), greenhouse application (G) or indoor application (I).

CropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system.

Growth stage range from first to last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3‐8263‐3152‐4), including, where relevant, information on season at time of application.

PHI – minimum preharvest interval.

Primary crops (available studies)	Crop groups	Crop(s)	Application(s)	Sampling (DAT)	Comment/Source
	Fruit crops	Grapes	Soil treatment, 1 × 2,008–2,204 g a.s./ha g a.s./ha	At maturity	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2021)
	Leafy crops	Leeks	Soil/Foliar treatment, 1 × 250 g a.s./ha	119 (BBCH 49)	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2021). Treatment was done as foliar spray to the immature leek plants (growth stage BBCH 14) and the surrounding soil
	Cereals/grass	Barley	Soil/Foliar treatment, 1 × 200 g a.s./ha	7, 14, 28 and 87 days	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2006). Treatments were done at pre‐emergence to early post‐emergence stage
		Barley, wheat	Soil/Foliar treatment, 1 × 250 g a.s./ha or 1 × 200 or 500 g a.s./ha	8–9 months
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Radish	Bare soil, 250 g a.s./ha	30, 120, 189, 365	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2014). Phytotoxicity observed at 120 DAT
	Leafy crops	Lettuce	Bare soil, 250 g a.s./ha	30, 120, 189, 365	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2014). Phytotoxicity observed at 30 DAT and 120 DAT.
	Cereal (small grain)	Wheat	Bare soil, 250 g a.s./ha	30, 120, 365	Radiolabelled isoxaben: U‐phenyl‐14C radiolabel and isoxazole‐5‐14C radiolabel (Sweden, 2014)
Processed commodities (hydrolysis study)	Conditions		Stable?		Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)		Not triggered		–
	Baking, brewing and boiling (60 min, 100°C, pH 5)		Not triggered		–
	Sterilisation (20 min, 120°C, pH 6)		Not triggered		–

Plant products (available studies)	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/Source
				Value	Unit
	High water content	Endives	−20	12	Months	Isoxaben	EFSA (2010)
	High oil content	Rapeseed	−18	12	Months	Isoxaben	Sweden (2021)
	High protein content	Dry bean	−18	12	Months	Isoxaben	Sweden (2021)
	High starch content	Cereal grain	−20	24	Months	Isoxaben	EFSA (2010)
	High acid content	Grapes	−20	24	Months	Isoxaben	EFSA (2010)
	Others	Straw	−20	24	Months	Isoxaben	EFSA (2010)

Commodity	Regiona	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)
Pome fruits Citrus fruits Almonds, Chestnuts, Hazelnuts/cobnuts, Walnuts Stone fruits Kiwi	NEU	11 × < 0.01	Combined data set of trials on pome fruits (6 apples, 1 pear) and 4 trials on plums compliant with GAP (Sweden, 2021). Extrapolation to pome fruits, stone fruits and tree nuts is applicable. Not authorised for use on citrus fruits and kiwi in NEU. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	8 × < 0.01	Combined data set of 4 trials on apples and 4 trials on peaches compliant with GAP (Sweden, 2021). Extrapolation to citrus fruits, pome fruits, stone fruits, tree nuts and kiwi is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
Table/Wine grapes	NEU	8 × < 0.01	Trials on wine and table grapes compliant with GAP (Sweden, 2021). MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	8 × < 0.01	Trials on wine and table grapes compliant with GAP (Sweden, 2021). MRLOECD = 0.01	0.01*	0.01	0.01
Strawberries	NEU	7 × < 0.01; 0.01	Trials on strawberries compliant with GAP (Sweden, 2021). MRLOECD = 0.01	0.01	0.01	0.01
	EU	3 × < 0.01	Trials on strawberries compliant with GAP (Sweden, 2021). Residues not expected to occur based on the metabolism in fruits following soil application and since the GAP is for application during dormant stage. MRLOECD = 0.01	0.01*	0.01	0.01
Dewberries	NEU	10 × < 0.01; 0.01	Extrapolation from combined data set of trials on strawberries and raspberries (Sweden, 2021) to dewberries is applicable. MRLOECD = 0.01	0.01	0.01	0.01
Raspberries (red and yellow), Blackberries	NEU	3 × < 0.01	Trials on raspberries compliant with GAP (Sweden, 2021). Extrapolation to blackberries is applicable. Residues not expected to occur based on the metabolism in fruits following soil application and since the GAP is for application during dormant stage. MRLOECD = 0.01	0.01*	0.01	0.01
Cranberries, Mulberries (black and white), Azaroles/Mediterranean medlars, Elderberries	NEU	11 × < 0.01	Extrapolation from combined data set of trials on grapes performed with 700 g a.s./ha (8) and currants (3) performed with 500–2,000 g a.s./ha to cranberries, mulberries, azaroles/Mediterranean medlars and elderberries is applicable. Overdosed trials acceptable since residues were always below the LOQ. MRLOECD = 0.01	0.01*	0.01	0.01
Blueberries, Gooseberries (green, red and yellow), Rose hips	NEU	11 × < 0.01	Extrapolation from combined data set of trials on grapes performed with 700 g a.s./ha (8) and currants (3) performed with 500–2,000 g a.s./ha to blueberries, gooseberries, rose hips, is applicable. Overdosed trials acceptable because results were always below the LOQ. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	–	No residue trials available	–	–	–
Currants (black, red and white)	NEU	3 × < 0.01	Trials on currants with application rates between 500 g a.s./ha to 2,000 g a.s./ha (Sweden, 2021), considered acceptable because results were always below the LOQ. Residues are not expected to occur based on overdosed trials and the metabolism study on fruits following soil application. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	–	No residue trials available	–	–	–
Bananas	SEU	< 0.01	Trial on bananas compliant with GAP (Sweden, 2021). Reduced number of trials sufficient considering that the application is done on the soil under the tree and the results from trials on pome and stone fruits	0.01*	0.01	0.01
Carrots, Horse radishes, Parsnips	NEU	4 × < 0.05	Trials on carrots compliant with GAP (Sweden, 2021). Extrapolation to horseradishes and parsnips is applicable. The reduced number of residue trials is considered acceptable since all trials were below the LOQ. Moreover, based on the rotational crop metabolism study, residues in these root crops are expected to remain below the LOQ of 0.01 mg/kg when isoxaben is applied according to the authorised use. Therefore, MRL and risk assessment values are proposed at 0.01 mg/kg	0.01*	0.01	0.01
Garlic, Onions, Shallots	NEU	4 × < 0.01	Residue trials performed on onions with 2 × 100 g a.s./ha (Sweden, 2021), but at a later growth stage with residues below the LOQ considered acceptable. The reduced number of residue trials is considered acceptable since all trials were below the LOQ the GAP is for an application every 2 years and the metabolism of isoxaben in roots/tuber vegetables following soil application indicates that significant residues are not expected to occur. Extrapolation to garlic and shallots is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	4 × < 0.01	Residue trials performed on onions with 2 × 100 g a.s./ha (Sweden, 2021) at a later growth stage, considered acceptable. Extrapolation to garlic is applicable. No authorised use on onions and shallots in the SEU. MRLOECD = 0.01	0.01*	0.01	0.01
Courgettes	NEU	4 × < 0.05	Trials on courgettes compliant with GAP (Sweden, 2021). Samples were stored up to 427 days, which is longer than the demonstrated storage stability period in high water content commodities (12 months). However, since, overall, according to the metabolism studies and the results of the trials available, isoxaben is not expected to be present at significant levels in fruits crops, an additional storage stability study is only desirable. MRLOECD = 0.05	0.05	0.05	0.05
Melons pumpkins	NEU	4 × < 0.01	Trials on pumpkins compliant with GAP (Sweden, 2021). Samples were stored for 383 days, which is slightly more than storage stability for high water commodities (12 months). However, since, overall, according to the metabolism studies and the results of the trials available, isoxaben is not expected to be present at significant levels in fruits crops, an additional storage stability study is only desirable. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	2 × < 0.01	Trials on melons compliant with GAP (Sweden, 2021). Information on storage stability was not reported. The reduced number of residue trials is considered acceptable in this case because results were always below the LOQ and residues in fruits are not expected to occur when isoxaben is applied following soil application. No authorised for use on pumpkins in SEU. MRLOECD = –	0.01*	0.01	0.01
Witloofs/Belgian endives	NEU	5 × < 0.01	Residue trials on witloofs leaves (after forcing), performed with 1.5N (1 × 150 g a.s./ha) and 2N (2 × 100 g a.s./ha), considered acceptable because results were always below the LOQ (Sweden, 2021). MRLOECD = 0.01	0.01*	0.01	0.01
Celery leaves	NEU	2 × < 0.01	The authorised use is on sorrel, and the residue trials were performed on sorrel (Sweden, 2021). The reduced number of residue trials is considered acceptable in this case because results were always below the LOQ and residues are not expected to occur in leafy crops when isoxaben is applied following soil application. The storage period was not reported (indicated as > 30 days). However, since, overall, according to the metabolism studies and the results of the trials available, isoxaben is not expected to be present at significant levels in leafy crops, additional information on the storage conditions are only desirable. MRLOECD = –	0.01*	0.01	0.01
	SEU	2 × < 0.01	The authorised use is on sorrel, and the residue trials were performed on sorrel (Sweden, 2021). The reduced number of residue trials is considered acceptable in this case because results were always below the LOQ and residues are not expected to occur when isoxaben is applied following soil application. The storage period was not reported. However, since, overall, according to the metabolism studies and the results of the trials available, isoxaben is not expected to be present at significant levels in leafy crops, additional information on the storage conditions are only desirable. MRLOECD = –	0.01*	0.01	0.01
Sage, Rosemary, Thyme, Basil and edible flowers	NEU	–	No residue trials available. Residues in leafy vegetables are not expected to occur when isoxaben is applied following foliar/soil treatment at early growth stages with an application up to 250 g a.s./ha. However, two residue trials are needed to confirm that no significant residues are expected.	0.01* (tentative)d	0.01	0.01
Beans (without pods)	NEU	4 × < 0.02	Trials on beans without pods, compliant with GAP (Sweden, 2021). MRLOECD = 0.02	0.02	0.02	0.02
Asparagus	NEU	2 × < 0.01	Trials on asparagus compliant with GAP (Sweden, 2021). The reduced number of residues trials is acceptable because all results were below the LOQ and residues in the edible part are not expected to occur when isoxaben is applied according to the authorised use on asparagus. MRLOECD = –	0.01*	0.01	0.01
	SEU	2 × < 0.01	Trials on asparagus compliant with GAP (Sweden, 2021). The reduced number of residues trials is acceptable because all results were below the LOQ and residues in the edible part are not expected to occur when isoxaben is applied according to the authorised use on asparagus. MRLOECD = –	0.01*	0.01	0.01
Leeks Spring onions/green onions and Welsh onions Chives	NEU	2 × < 0.01	Trials on leeks compliant with GAP (Sweden, 2021). The reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and residues in leafy vegetables and roots crops are not expected to occur when isoxaben is applied following soil treatment at early growth stages with an application rate up to 250 g a.s./ha. Extrapolation to spring onions and chives is applicable. MRLOECD = –	0.01*	0.01	0.01
	SEU	–	No residue trials available. No authorised for use on leeks in SEU.	–	–	–
Rhubarbs	NEU	5 × < 0.01	Trials on rhubarbs compliant with GAP (4) or overdosed (1) (500 g a.s./ha) acceptable because results were always below the LOQ (Sweden, 2021). MRLOECD = 0.01	0.01*	0.01	0.01
Rapeseeds/canola seeds	NEU	4 × < 0.01	Trials on oilseed rape compliant with GAP (Sweden, 2021). The reduced number of residue trials is considered acceptable in this case because all results were below the LOQ and residues are not expected to occur based on the metabolism of isoxaben following soil application. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	–	No residue trials available	–	–	–
Cotton seeds	SEU	–	No residue trials available. Residues are not expected to occur when isoxaben is applied following soil treatment. However, two residue trials are needed to confirm that no significant residues are expected	0.01* (tentative)d	0.01	0.01
Barley grains, Oat grains	NEU	8 × < 0.01	Trials on barley grain compliant with GAP (EFSA, 2010). Extrapolation to oat grains is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	8 × < 0.01	Trials on barley grain compliant with GAP (EFSA, 2010). Extrapolation to oat grains is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
Wheat grains, Rye grains	NEU	8 × < 0.01	Trials on wheat grain compliant with GAP (EFSA, 2010). Extrapolation to rye grain is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
	SEU	8 × < 0.01	Trials on wheat grain compliant with GAP (EFSA, 2010). Extrapolation to rye grain is applicable. MRLOECD = 0.01	0.01*	0.01	0.01
Herbal infusions from flowers	NEU	–	No residue trials available. Residues are not expected to occur when isoxaben is applied following soil treatment at early growth stages with an application rate up to 250 g a.s./ha. However, two residue trials are needed to confirm that no significant residues are expected	0.01* (tentative)d, e	0.01	0.01
	SEU	–	No residue trials available. Residues are not expected to occur when isoxaben is applied following soil treatment at early growth stages with an application rate up to 250 g a.s./ha. However, two residue trials are needed to confirm that no significant residues are expected	0.01* (tentative) d, e	0.01	0.01
Herbal infusions from roots	NEU	4 × < 0.05	Extrapolated from carrots. It is noted that a dehydration factor was not applied because isoxaben was always below the LOQ and concentration of residues is not expected	0.01* (tentative)e	0.01	0.01
Hops	NEU	3 × < 0.01	Trials on hops compliant with GAP (Sweden, 2021). Reduced number of residue trials is considered acceptable in this case because residues were all below the LOQ of 0.01 mg/kg and because the application is done during dormant stage. MRLOECD = 0.01	0.01* (tentative) e	0.01	0.01
Chicory roots	NEU	3 × < 0.01; 2 × 0.01	Trials on chicory roots performed with 1.5N (1 × 150 g a.s./ha) and 2N (2 × 100 g a.s./ha) (Sweden, 2021). Considering that the trials were performed according to a more critical GAP and residues were below or at the LOQ the MRL is proposed at the LOQ of 0.01 mg/kg	0.01*	0.01	0.01
Clover forage	NEU	–	No residue trials are available	–	–	–
Grass forage	NEU	–	No residue trials are available	–	–	–
Barley straw, Oat straw	NEU	6 × < 0.01; 0.02; 0.03	Trials on barley straw compliant with GAP (EFSA, 2010). Extrapolation to oat straw is applicable. MRLOECD = 0.04	0.04 (tentative)f	0.03	0.01
	SEU	3 × < 0.01; 0.01; 4 × 0.02	Trials on barley straw compliant with GAP (EFSA, 2010). Extrapolation to oat straw is applicable. MRLOECD = 0.04	0.04 (tentative)f	0.02	0.02
Wheat straw, Rye straw	NEU	6 × < 0.01	Trials on wheat straw compliant with GAP (EFSA, 2010). Extrapolation to rye straw is applicable. MRLOECD = 0.01	0.01* (tentative)f	0.01	0.01
	SEU	7 × < 0.01; 0.02	Trials on wheat straw compliant with GAP (EFSA, 2010). Extrapolation to rye straw is applicable. MRLOECD = 0.03	0.03 (tentative)f	0.02	0.01

GAP: Good Agricultural Practice; OECD: Organisation for Economic Co‐operation and Development; MRL: maximum residue level; Mo: residue levels expressed according to the monitoring residue definition; RA: residue levels expressed according to risk assessment residue definition.

Indicates that the MRL is proposed at the limit of quantification.

NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, EU: indoor EU trials, Country code: if non‐EU trials.

Highest residue.

Supervised trials median residue.

MRL is tentative because additional trials are needed to confirm that no significant residues are expected.

MRL is tentative because analytical methods are missing.

MRL for feed items are proposed on a tentative basis.

Relevant groups (subgroups)	Dietary burden expressed in				Most critical subgroup a	Most critical commodity b	Trigger exceeded (Y/N)	Comments
	mg/kg bw per day		mg/kg DM
	Median	Maximum	Median	Maximum
Cattle (all)	0.001	0.001	0.03	0.03	Dairy cattle	Carrot, culls	N	–
Cattle (dairy only)	0.001	0.001	0.03	0.03	Dairy cattle	Carrot, culls	N	–
Sheep (all)	0.001	0.002	0.03	0.04	Lamb	Carrot, culls	N	–
Sheep (ewe only)	0.001	0.001	0.03	0.04	Ram/Ewe	Carrot, culls	N	–
Swine (all)	0.001	0.001	0.03	0.03	Swine (finishing)	Carrot, culls	N	–
Poultry (all)	0.001	0.001	0.02	0.02	Poultry layer	Carrot, culls	N	–
Poultry (layer only)	0.001	0.001	0.02	0.02	Poultry layer	Carrot, culls	N	–

When one group of livestock includes several subgroups (e.g. poultry ‘all’ including broiler, layer and turkey), the result of the most critical subgroup is identified from the maximum dietary burdens expressed as ‘mg/kg bw per day’.

The most critical commodity is the major contributor identified from the maximum dietary burden expressed as ‘mg/kg bw per day’.

Code number	Commodity	Existing EU MRL (mg/kg)		Outcome of the review
				MRL (mg/kg)	Comment
Isoxaben
110010	Grapefruit	0.02*		0.01*	Recommendeda
110020	Oranges	0.02*		0.01*	Recommendeda
110030	Lemons	0.02*		0.01*	Recommendeda
110040	Limes	0.02*		0.01*	Recommendeda
110050	Mandarins	0.02*		0.01*	Recommendeda
120010	Almonds	0.05		0.01*	Recommendeda
120040	Chestnuts	0.05		0.01*	Recommendeda
120060	Hazelnuts	0.05		0.01*	Recommendeda
120110	Walnuts	0.05		0.01*	Recommendeda
130010	Apples	0.05		0.01*	Recommendeda
130020	Pears	0.05		0.01*	Recommendeda
130030	Quinces	0.05		0.01*	Recommendeda
130040	Medlar	0.05		0.01*	Recommendeda
130050	Loquat	0.05		0.01*	Recommendeda
140010	Apricots	0.02*		0.01*	Recommendeda
140020	Cherries	0.05		0.01*	Recommendeda
140030	Peaches	0.02*		0.01*	Recommendeda
140040	Plums	0.05		0.01*	Recommendeda
151010	Table grapes	0.05		0.01*	Recommendeda
151020	Wine grapes	0.05		0.01*	Recommendeda
152000	Strawberries	0.05		0.01	Recommendeda
153010	Blackberries	0.05		0.01*	Recommendeda
153020	Dewberries	0.05		0.01	Recommendeda
153030	Raspberries	0.05		0.01*	Recommendeda
154010	Blueberries	0.05		0.01*	Recommendeda
154020	Cranberries	0.05		0.01*	Recommendeda
154030	Currants (red, black and white)	0.05		0.01*	Recommendeda
154040	Gooseberries	0.05		0.01*	Recommendeda
154050	Rose hips	0.05		0.01*	Recommendeda
154060	Mulberries	0.05		0.01*	Recommendeda
154070	Azarole (mediterranean medlar)	0.05		0.01*	Recommendeda
154080	Elderberries	0.05		0.01*	Recommendeda
162010	Kiwi	0.02*		0.01*	Recommendeda
163020	Bananas	0.02*		0.01*	Recommendeda
213020	Carrots	0.05		0.01*	Recommendeda
213040	Horseradish	0.05		0.01*	Recommendeda
213060	Parsnips	0.05		0.01*	Recommendeda
220010	Garlic	0.02*		0.01*	Recommendeda
220020	Onions	0.02*		0.01*	Recommendeda
220030	Shallots	0.02*		0.01*	Recommendeda
220040	Spring onions	0.02*		0.01*	Recommendeda
232030	Courgettes	0.05		0.05	Recommendeda
233010	Melons	0.05		0.01*	Recommendeda
233020	Pumpkins	0.05		0.01*	Recommendeda
255000	Witloof	0.02*		0.01*	Recommendeda
256020	Chives	0.05		0.01*	Recommendeda
256030	Celery leaves	0.05		0.01*	Recommendeda
256050	Sage	0.05		0.01*	Further consideration neededb data gap #2
256060	Rosemary	0.05		0.01*	Further consideration neededb data gap #2
256070	Thyme	0.05		0.01*	Further consideration neededb data gap #2
256080	Basil	0.05		0.01*	Further consideration neededb data gap #2
260020	Beans (fresh, without pods)	0.02*		0.02	Recommendedc
270010	Asparagus	0.05		0.01*	Recommendedc
270060	Leek	0.02*		0.01*	Recommendedc
270070	Rhubarb	0.02*		0.01*	Recommendedc
401060	Rape seed	0.02*		0.01*	Recommendedc
401090	Cotton seed	0.02*		0.01*	Further consideration neededb data gap #2
500010	Barley grain	0.1		0.01*	Recommendedc
500050	Oats grain	0.1		0.01*	Recommendedc
500070	Rye grain	0.1		0.01*	Recommendedc
500090	Wheat grain	0.1		0.01*	Recommendedc
631000	Herbal infusions (dried, flowers)	0.02*		0.01*	Further consideration neededb data gaps #1 and #2
633000	Herbal infusions (dried, roots)	0.02*		0.01*	Further consideration neededb data gap #1
700000	Hops (dried), including hop pellets and unconcentrated powder	0.05		0.01*	Further consideration neededb data gap #1
900030	Chicory roots	0.02*		0.01*	Recommendeda
–	Other commodities of plant and/or animal origin	See Reg. 149/2008	–	–	Further consideration neededc

MRL: maximum residue level

Indicates that the MRL is set at the limit of quantification.

MRL is derived from a GAP evaluated at EU level, which is fully supported by data and for which no risk to consumers is identified; no CXL is available (combination H‐I in Appendix E).

Tentative MRL is derived from a GAP evaluated at EU level, which is not fully supported by data but for which no risk to consumers was identified (assuming the existing residue definition); no CXL is available (combination F‐I in Appendix E).

There are no relevant authorisations or import tolerances reported at EU level; no CXL is available. Either a specific LOQ or the default MRL of 0.01 mg/kg may be considered (combination A‐I in Appendix E).

Feed commodity	Median dietary burden		Maximum dietary burden
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: isoxaben
Barley straw	0.02	STMR	0.03	HR
Oat straw	0.02	STMR	0.03	HR
Rye straw	0.01	STMR	0.02	HR
Triticale straw	0.01	STMR	0.02	HR
Wheat straw	0.01	STMR	0.02	HR
Carrot culls	0.01*	STMR	0.01*	HR
Barley grain	0.01*	STMR	0.01*	STMR
Oat grain	0.01*	STMR	0.01*	STMR
Rye grain	0.01*	STMR	0.01*	STMR
Triticale grain	0.01*	STMR	0.01*	STMR
Wheat grain	0.01*	STMR	0.01*	STMR
Apple pomace, wet	0.01*	STMRa	0.01*	STMRa
Brewer's grain dried	0.01*	STMRa	0.01*	STMRa
Canola (Rape seed) meal	0.01*	STMRa	0.01*	STMRa
Citrus dried pulp	0.01*	STMRa	0.01*	STMRa
Distiller's grain dried	0.01*	STMRa	0.01*	STMRa
Rape meal	0.01*	STMRa	0.01*	STMRa
Wheat gluten meal	0.01*	STMRa	0.01*	STMRa
Wheat milled by‐products	0.01*	STMRa	0.01*	STMRa

STMR: supervised trials median residue; HR: highest residue.

Indicates that the input value is proposed at the limit of quantification.

For fruit pomace, cereal bran and/or oilseed meals, no default processing factor was applied because isoxaben is applied early in the growing season and residues are expected to be below the LOQ. Concentration of residues in these commodities is therefore not expected.

Commodity	Chronic risk assessment
	Input value (mg/kg)	Comment
Risk assessment residue definition: isoxaben
Grapefruits	0.01*	STMR
Oranges	0.01*	STMR
Lemons	0.01*	STMR
Limes	0.01*	STMR
Mandarins	0.01*	STMR
Almonds	0.01*	STMR
Chestnuts	0.01*	STMR
Hazelnuts/cobnuts	0.01*	STMR
Walnuts	0.01*	STMR
Apples	0.01*	STMR
Pears	0.01*	STMR
Quinces	0.01*	STMR
Medlars	0.01*	STMR
Loquats/Japanese medlars	0.01*	STMR
Apricots	0.01*	STMR
Cherries (sweet)	0.01*	STMR
Peaches	0.01*	STMR
Plums	0.01*	STMR
Table grapes	0.01*	STMR
Wine grapes	0.01*	STMR
Strawberries	0.01	STMR
Blackberries	0.01*	STMR
Dewberries	0.01	STMR
Raspberries (red and yellow)	0.01*	STMR
Blueberries	0.01*	STMR
Cranberries	0.01*	STMR
Currants (black, red and white)	0.01*	STMR
Gooseberries (green, red and yellow)	0.01*	STMR
Rose hips	0.01*	STMR
Mulberries (black and white)	0.01*	STMR
Azaroles/Mediterranean medlars	0.01*	STMR
Elderberries	0.01*	STMR
Kiwi fruits (green, red, yellow)	0.01*	STMR
Bananas	0.01*	STMR
Carrots	0.01*	STMR
Horseradishes	0.01*	STMR
Parsnips	0.01*	STMR
Garlic	0.01*	STMR
Onions	0.01*	STMR
Shallots	0.01*	STMR
Spring onions/green onions and Welsh onions	0.01*	STMR
Courgettes	0.05	STMR
Melons	0.01*	STMR
Pumpkins	0.01*	STMR
Witloofs/Belgian endives	0.01*	STMR
Chives	0.01*	STMR
Celery leaves	0.01*	STMR
Sage	0.01*	STMR (tentative)
Rosemary	0.01*	STMR (tentative)
Thyme	0.01*	STMR (tentative)
Basil and edible flowers	0.01*	STMR (tentative)
Beans (without pods)	0.02	STMR
Asparagus	0.01*	STMR
Leeks	0.01*	STMR
Rhubarbs	0.01*	STMR
Rapeseeds/canola seeds	0.01*	STMR
Cotton seeds	0.01*	STMR (tentative)
Barley grains	0.01*	STMR
Oat grains	0.01*	STMR
Rye grains	0.01*	STMR
Wheat grains	0.01*	STMR
Herbal infusions from flowers	0.01*	STMR (tentative)
Herbal infusions from roots	0.01*	STMR (tentative)
Hops	0.01*	STMR (tentative)
Chicory roots	0.01	STMR

Indicates that the input value is proposed at the limit of quantification.

Code/trivial namea	IUPAC name/SMILES notation/InChiKeyb	Structural formulac
isoxaben	N‐[3‐(1‐ethyl‐1‐methylpropyl)isoxazol‐5‐yl]‐2,6‐dimethoxybenzamide PMHURSZHKKJGBM‐UHFFFAOYSA‐N CCC(C)(CC)c1cc(NC(=O)c2c(OC)cccc2OC)on1
hydroxy isoxaben or 2‐hydroxy isoxaben	N‐{3‐[(2RS)‐2‐hydroxybutan‐2‐yl]‐1,2‐oxazol‐5‐yl}‐2,6‐dimethoxybenzamide
1‐hydroxy isoxaben	N‐{3‐[(2RS)‐1‐hydroxybutan‐2‐yl]‐1,2‐oxazol‐5‐yl}‐2,6‐dimethoxybenzamide
3‐hydroxy isoxaben	N‐{3‐[(2RS,3RS)‐3‐hydroxybutan‐2‐yl]‐1,2‐oxazol‐5‐yl}‐2,6‐dimethoxybenzamide
oxypropyl isoxaben	2,6‐dimethoxy‐N‐{3‐[(3RS)‐3‐methyl‐2‐oxopentan‐3‐yl]‐1,2‐oxazol‐5‐yl}benzamide

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

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

ACD/Name 2019.1.3 ACD/Labs 2019 Release (File version N05E41, Build 111418, 3 September 2019).

ACD/ChemSketch 2019.1.3 ACD/Labs 2019 Release (File version C05H41, Build 111302, 27 August 2019).