Review of the existing maximum residue levels for

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Summary

Cyflumetofen was approved on 01 June 2013 by means of Commission Implementing Regulation (EU) No 22/2013 in the framework of Regulation (EC) No 1107/2009, as amended by Commission Implementing Regulations (EU) No 540/2011 and 541/2011. On 30 April 2019 conditions of approval of the active substance cyflumetofen were amended by the Commission Implementing Regulation (EU) No 2019/716.

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 15 June 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 15 July 2020 their national Good Agricultural Practices (GAPs) that are authorised nationally and the GAPs in non-EU countries for which import tolerances are authorised in a standardised way in a standardised way, in the format of specific GAP forms, allowing the designated rapporteur Member State, Spain, to identify the critical GAPs in the format of a specific GAP overview file. Subsequently, Member States were requested to provide residue data supporting the critical GAPs, within a period of 1 month, by 30 September 2020. On the basis of all the data submitted by Member States and by the EU Reference Laboratories for Pesticides Residues (EURLs), EFSA asked the rapporteur Member State (RMS) to complete the Pesticide Residues Overview File (PROFile) and to prepare a supporting evaluation report. The PROFile and evaluation report, together with Pesticide Residues Intake Model (PRIMo) calculations and an updated GAP overview file were provided by the RMS to EFSA on 15 December 2020. 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 and the EURLs, and taking into account the conclusions derived by EFSA in the framework of Commission Regulation (EU) No 188/2011 and the MRLs established by the Codex Alimentarius Commission, EFSA prepared in May 2021 a draft reasoned opinion, which was circulated to Member States and EURLs for consultation via a written procedure. Comments received by 10 June 2021 were considered during the finalisation of this reasoned opinion. The following conclusions are derived.

The metabolism of cyflumetofen in plants was investigated in primary and rotational crops. According to the results of the metabolism studies, the residue definition for enforcement can be proposed as cyflumetofen (sum of isomers) and for risk assessment as sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen. These residue definitions are also applicable to processed commodities. Fully validated analytical methods are available for the enforcement of the proposed residue definition in all major matrices at the limit of quantification (LOQ) of 0.01 mg/kg. According to the EURLs, this LOQ is achievable in routine analyses.

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under evaluation, except for cherries, plums, cane fruits and other small fruits and berries for which additional trials are required.

Robust processing factors could be derived for processed commodities from oranges, apples, peaches, strawberries, tomatoes and hops.

Cyflumetofen 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. The dietary burdens calculated for beef cattle were found to marginally exceed the trigger value of 0.1 mg/kg DM. Behaviour of residues was therefore assessed in this group of livestock. Based on the metabolism study in lactating goats, the residue definition for enforcement is proposed as 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

An analytical method using LC-MS/MS was fully validated for the determination of 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen in all animal tissues, milk and eggs, with a LOQ of 0.02 mg/kg. However, the independent laboratory validation (ILV) of the method is still required.

According to the EURLs, an LOQ of 0.01 mg/kg 2-(trifluoromethyl)benzoic acid is deemed achievable for routine analysis in milk and liver.

For risk assessment, the residue definition for animals is proposed as the sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

MRLs and risk assessment values for the relevant ruminant commodities can be established at the LOQ level.

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 represented 1% of the acceptable daily intake (ADI) (German child). Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not deemed necessary for this active substance.

Apart from the MRLs evaluated in the framework of this review, internationally recommended code maximum residue limits (CXLs) have also been established for cyflumetofen. Additional calculations of the consumer exposure, considering these CXLs, were therefore carried out, the highest chronic exposure represented 2% of the ADI (Dutch toddler).

Background

Regulation (EC) No 396/20051 (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/EEC2 a reasoned opinion on the review of the existing MRLs for that active substance. As cyflumetofen was approved on 01 June 2013 by means of Commission Implementing Regulation (EU) No 22/20133 in the framework of Regulation (EC) No 1107/20094 as implemented by Commission Implementing Regulations (EU) No 540/20115 and 541/20116, EFSA initiated the review of all existing MRLs for that active substance.

By way of background information, cyflumetofen was evaluated by the Netherlands, designated as rapporteur Member State (RMS) in the framework of Regulation (EC) No 1107/2009 as amended by Commission Implementing Regulations (EU) No 540/2011 and 541/2011. 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, 2012).

The approval of cyflumetofen has been restricted in 20197 to uses where the level of metabolite B3 in groundwater is expected to be below 0.1 μg/L, following the assessment of the confirmatory data (EFSA, 2016).

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 15 June 2020 EFSA initiated the collection of data for this active substance. In a first step, Member States and the UK8 were invited to submit by 15 July 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 16 Member States and the UK provided feedback on their national authorisations of cyflumetofen. Based on the GAP data submitted, the designated RMS Spain 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 30 September 2020.

On the basis of all the data submitted by Member States, the UK and the EU Reference Laboratories for Pesticides Residues (EURLs), EFSA asked Spain to complete the PROFile and to prepare a supporting evaluation report. The PROFile and the supporting evaluation report, together with the Pesticide Residues Intake Model (PRIMo) calculations and an updated GAP overview file, were submitted to EFSA on 15 December 2020. 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 and taking into account the MRLs established by the Codex Alimentarius Commission (CAC) (i.e. codex maximum residue limit; CXLs), EFSA prepared in May 2021 a draft reasoned opinion, which was circulated to Member States and EURLs for commenting via a written procedure. All comments received by 10 June 2021 were considered by EFSA during the finalisation of the reasoned opinion.

The evaluation report submitted by the RMS (Spain, 2020), 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, 2020) 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, 2021b) and the Member States consultation report (EFSA, 2021c). 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

Cyflumetofen is the ISO common name for 2-methoxyethyl (RS)-2-(4-tert-butylphenyl)-2-cyano-3-oxo-3-(α,α,α -trifluoro-o-tolyl)propionate (IUPAC).

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

The EU MRLs for cyflumetofen are established in Annexes IIIA of Regulation (EC) No 396/2005. Codex maximum residue limits (CXLs) for cyflumetofen were also established by the Codex Alimentarius Commission (CAC). An overview of the MRL changes that occurred since the entry into force of the Regulation mentioned above is provided below (Table 1).

Table 1 Overview of the MRL changes since the entry into force of Regulation (EC) No 396/2005

Procedure	Legal implementation	Remarks
MRL application	Commission Regulation (EU) 2021/10981	Citrus fruits, apricots, peaches, tomatoes, aubergines/eggplants, cucumbers, hops (EFSA, 2021a)
Implementation of CAC 2015	Commission Regulation (EU) 2016/5672	Citrus fruit, pome fruits, grapes, strawberries, Azaroles/Mediterranean medlars, Kaki/Japanese persimmons, tomatoes, liver (swine, bovine, sheep, goat, equine and other farmed terrestrial animals), kidney (swine, bovine, sheep, goat, equine and other farmed terrestrial animals), edible offals (swine, bovine, sheep, goat, equine and other farmed terrestrial animals) (EFSA, 2015)

For the purpose of this MRL review, all the uses of cyflumetofen currently authorised within the EU as submitted by the Member States 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 GAP for cyflumetofen 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 (Spain, 2020);
the draft assessment report (DAR) and its addendum prepared under Council Directive 91/414/EEC (Netherlands, 2010, 2011);
the conclusion on the peer review of the pesticide risk assessment of the active substance cyflumetofen (EFSA, 2012);
the conclusion on the peer review of the pesticide risk assessment for the active substance cyflumetofen in light of confirmatory data (EFSA, 2016);
the final review report on cyflumetofen (European commission, 2019);
the Joint Meeting on Pesticide residues (JMPR) Evaluation report (FAO, 2014a,b);
the previous reasoned opinion on cyflumetofen (EFSA, 2021a).

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 546/20119 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 cyflumetofen was investigated after foliar treatment in fruits (mandarin, apple and eggplant) (Netherlands, 2011) and assessed in the framework of the peer-review (EFSA, 2012). The studies were conducted with a single foliar application of ¹⁴C-cyflumetofen, either labelled on the tert -butyl phenyl ring or the trifluoromethyl phenyl ring at a dose of 600 g a.s./ha.

The major part of the radioactive residues remained on the surface of the fruits and on the leaves and was easily removed by solvent rinses. Metabolism was limited, with cyflumetofen constituting the major component of the total radioactive residues (TRR) ranging from 67% to 84% TRR and 77–87% TRR 7 days after application, and 44–65% TRR and 44–81% TRR after 30 days on fruits and leaves, respectively. Although several metabolites were identified, only 2-(trifluoromethyl)benzoic acid (metabolite B-1), free and conjugated) was detected above 10% TRR (up to 15% and 16% TRR, free and conjugated, respectively, in eggplant fruits) and AB-6 at 10% TRR in eggplant leaves.

There are no metabolism studies available for leafy crops that would in principle be required for a use on hops. Nonetheless, a possible metabolic pattern comparable to that observed in fruit crops was proposed and considered sufficient to address the metabolism of cyflumetofen for an intended use on hops (EFSA, 2021a). Considerations were based on the metabolic pattern observed, in particular in eggplant leaves, at PHI 14 days relevant for the intended use, combined with the results of the residue trials on hops. EFSA emphasises that these considerations are valid only for the use on hops and are not considered sufficient to cover all leafy vegetables.

Nature of residues in rotational crops

Cyflumetofen is authorised on crops that may be grown in rotation. According to the soil degradation laboratory studies the DT₉₀ value for cyflumetofen and its main soil metabolites AB-1 and B-3 is below the trigger value of 100 days, whereas the DT₉₀ value of metabolite B-1 is up to 120 days (EFSA, 2012).

A confined rotational crop metabolism study is available for this review (Spain, 2020) that was assessed in the framework of an MRL application (EFSA, 2021a). ¹⁴C-cyflumetofen, either labelled on the tert-butyl phenyl ring or the trifluoromethyl phenyl ring, was applied once at 400 g/ha to bare soil covering the authorised uses assessed. Crops (lettuces, radishes, spring wheat) were planted at nominal plant back intervals (PBI) of 30, 120 and 365 days after treatment (DAT).

The total radioactive residues in the edible parts of the rotational crops at harvest and at all plant back intervals were up to 0.06 mg/kg in lettuce, up to 0.03 mg/kg and 0.14 mg/kg in radish roots and tops, and up to 0.17 mg/kg, 0.64 mg/kg and 0.48 mg/kg in wheat grain, hay and straw, respectively, at the PBI of 30 days. Residues in all crops declined over time, with higher TRRs present in case of the benzyl label.

The only major radioactive residue, identified in all crop matrices, was trifluoroacetic acid (TFA). Highest levels of TFA were detected in radish tops (0.16 mg eq/kg, PBI 30 days) and wheat hay (0.64 mg eq/kg, PBI 30 days). All other metabolites, including metabolite B-1, were below < 0.01 mg/kg.

TFA was not identified in the primary crop metabolism in fruit crops, nor was it identified as a significant soil metabolite during the peer review (EFSA, 2012). It can be formed from the parent compound cyflumetofen by degradation in the soil and uptake by the plants or from metabolite B-1 (Spain, 2020). Furthermore, TFA is very persistent in soil (DT₅₀ > 1,000 days (EFSA, 2017) and occurs ubiquitously in the environment from a variety of other sources.

Nature of residues in processed commodities

Studies investigating the nature of residues in processed commodities are available for this review (Spain, 2020) that were also assessed in the framework of an MRL application (EFSA, 2021a). Studies were conducted with cyflumetofen radiolabelled on the butylphenyl ring or the trifluoromethyl phenyl ring. These studies showed that cyflumetofen remained stable under pasteurisation, degraded partially under cooking/boiling/baking and almost completely under sterilisation conditions into metabolites B-1, AB-1 and A-2 (see Appendix B.1.1.1). In the study using the butylphenyl-label, under standard boiling/baking/brewing conditions (60 min. 100°C, pH 5) and under sterilisation conditions (20 min. 120°C, pH 6) 40% and 49% of cyflumetofen degraded to metabolite AB-1 and 53% and 44% to metabolite A-2, respectively. Metabolite B-1 was the major degradation product (up to 75.3% AR, sterilisation conditions) in the trifluoromethyl phenyl ring labelled study.

Methods of analysis in plants

Validated methods to quantify residues of cyflumetofen by liquid chromatography with tandem mass spectrometry (LC-MS/MS) monitoring two ion transitions are available with a limit of quantification (LOQ) of 0.01 mg/kg in high water- (tomato, lettuce, lentils), high acid- (orange), high oil content (soybean seed), dry (dry bean, wheat and rice grain) and specific (raisins, hops, orange oil, straw) matrices. The analytical methods were assessed in the framework of zonal registration of products (Spain, 2020) and in a previous MRL application (EFSA, 2021a). The primary methods are supported by independent laboratory validations (ILV) for high water, high acid content, dry matrices as well as for hops (Spain, 2020; EFSA, 2021a).

According to the EURLs, cyflumetofen can be monitored in high water content, high acid content, dry and high oil content commodities with an LOQ of 0.01 mg/kg (EURLs, 2020).

Stability of residues in plants

The storage stability of cyflumetofen and its metabolite B-1 was investigated in the framework of an MRL application (Netherlands, 2016; EFSA, 2021a). The storage stability of cyflumetofen was demonstrated for at least 25 months in wheat grains (high starch content), almond nutmeal (high oil content), in apple fruits (high water content) and apple juice (processed products), in orange fruits (high acid content) and orange juice and oil (processed products), 3 months in lettuces (high water content) and radish roots (high water/high starch content) when stored frozen (–20°C to –10°C).

Regarding the storage stability of metabolite B-1, several deficiencies were observed in the studies. Uncorrected recovery data showed a large variation among sampling time points and matrices, with low recoveries observed also at time point zero and in freshly spiked samples. Uncorrected recoveries dropped below 70% at certain sampling times during the storage period of the studies. However, despite the variability, the graphical presentation of the recoveries according to current guidance (European Commission, 1997f) showed no large fluctuation attributable of the residue decline. Based on the available data and the interpolation method, residues of metabolite B-1 were considered stable for 22 months in wheat grains (high starch content), apple fruit and juice (high water content), about 30 months in orange fruit and juice (high acid content) and 30 months in almond nutmeal (high oil content matrix). For lettuces and orange oils the data were inconclusive (EFSA, 2021a).

It is noted that no specific study is available for the storage stability of A-2 or AB-1. For these metabolites, this data will only be required pending the requirement of further processing studies in the future.

Proposed residue definitions

The metabolism of cyflumetofen was assessed following foliar treatment in fruit crops.

Considering the results of both the metabolism studies and the magnitude of residues in primary and rotational crops, the parent compound was found to be a sufficient marker and the residue definition for enforcement is proposed as cyflumetofen (sum of isomers). This residue definition is limited to fruit crops and to the use on hops.

An analytical method for the enforcement of the proposed residue definition at the LOQ of 0.01 mg/kg in all matrices is available (Spain, 2020; EFSA, 2021a). According to the EURLs the LOQ of 0.01 in all 4 major matrices is achievable in routine analyses (EURLs, 2020).

TFA is the only major metabolite relevant for rotational crops. It is formed by the extensive metabolism of cyflumetofen in soil and was not identified in the metabolism of primary crops. It is a common metabolite found ubiquitously in the environment from various sources. Overall, considering the results of the rotational crop confined studies and an updated indicative risk assessment of TFA (EFSA, 2021a) it can be concluded that for the authorised uses of cyflumetofen, consumers are not expected to be exposed to significant residues of this metabolite and therefore a separate residue definition for risk assessment for rotational crops is not deemed necessary. In case of further uses, the need to consider TFA may need to be reviewed.

Metabolite B-1 is a major metabolite formed in rats following oral ingestion and was considered covered by the toxicological profile of the parent compound (EFSA, 2012).

The toxicological relevance of processing degradation products AB-1 and A-2 has been assessed in the framework of an MRL application (EFSA, 2021a). The data indicated that the toxicity of AB-1 is covered by the parent compound, whereas A-2 was considered as unlikely to be genotoxic in vitro but with a chronic toxicity qualitatively different than the parent compound. Based on the results of an oral 28-day toxicity study and applying an uncertainty factor of 1,800, a specific acceptable daily intake (ADI) of 0.0036 mg/kg body weight (bw) per day was set for A-2. An acute reference dose (ARfD) was not set and not considered necessary.

As metabolite B-1 is a major metabolite in fruit crops, a minor metabolite in rotational crops and a main degradation product during processing, the residue definition for risk assessment is proposed to be the sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

Standard hydrolysis studies showed a progressive degradation of cyflumetofen to metabolite AB-1 that is further degraded to metabolite B-1, and A-2. However, in the various processing studies, major degradation of parent to metabolites B-1 and A-2 was not observed (Appendix B.1.2.3). There are no data on the occurrence of AB-1 in processing studies. A-2 was analysed for in peach and apple processed commodities. Metabolite B-1 was analysed in apple, peach, strawberry, tomato and citrus processing studies. An additional risk assessment residue definition for processed products is not deemed necessary for the current uses, as based on the available studies formation of A-2 is expected to be low, and lower than B-1; metabolite B-1 was present at significantly lower levels than cyflumetofen in processed products, if at all (except in dried citrus fruits); exposure to cyflumetofen residues is low (up to 2% of ADI) and in view of the toxicity profiles of A-2 and AB-1 (see above), the residue definition for plants is proposed to be applicable also for processed products considering the current uses. In case further uses are authorised in the future, the need to consider AB-1 and/or A-2 in the residue definition may need to be reviewed.

In addition, EFSA emphasises that the above studies do not investigate the possible impact of plant metabolism on the isomer ratio of cyflumetofen and further investigation on this matter would in principle be required. However, in view of the large margin of safety in the exposure calculation, the potential change in isomer ratios in the final residue is not expected to be of concern for the authorised use in the framework of this review. In case future uses of active substance would lead to a higher consumer exposure, further information regarding the impact of plant metabolism on the isomer ratio might be required.

Magnitude of residues in plants

Magnitude of residues in primary crops

To assess the magnitude of cyflumetofen residues resulting from the reported GAPs, EFSA considered all residue trials reported by the RMS in its evaluation report (Spain, 2020), as well as the residue trials evaluated in the framework of a previous MRL application (EFSA, 2021a). All residue trial samples considered in this framework were stored in compliance with the conditions for which storage stability of residues was demonstrated, except for a few trials on strawberries. Out of thirteen trials in strawberries, in four trials samples were stored for a longer period than the demonstrated storage stability period. However, as results were in the same range as in the other trials, and disregarding them would lead to a lower MRL, the trials were considered acceptable. Decline of residues during storage of the trial samples is therefore not expected.

The number of residue trials and extrapolations were evaluated in accordance with the European guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs (European Commission, 2017).

Available residue trials are sufficient to derive (tentative) MRLs and risk assessment values for all crops under assessment, taking note of the following considerations:

Cherries, plums, cane fruits and other small fruits and berries: Although no trials are available, as the application is done after harvest, and considering the properties of the a.s. and the results of the metabolism studies, residues are not expected in the edible part of the crop and the MRL can be proposed at the LOQ. Nonetheless, two trials compliant with the northern outdoor GAPs and two trials compliant with the indoor GAPs are required.
Apricots and peaches: Although no residue trial supporting the northern outdoor GAP and indoor GAP is available, as residues are not expected according to the condition of use, and the southern GAP is clearly more critical, further trials are not required.

Magnitude of residues in rotational crops

A field rotational crop study was available for this review (Spain, 2020) that was assessed in the framework of zonal registration of products and in a previous MRL application (EFSA, 2021a). Cyflumetofen was applied to bare soil at 400 g a.s./ha covering the authorised uses. Leafy vegetables (spinach, broccoli), root crops (carrots) and cereals (wheat) were planted at the nominal plant back intervals of 30, 120 and 365 days after treatment. Residues of cyflumetofen and its metabolites AB-6 and B-1 were analysed for. These were all below the LOQ of 0.01 mg/kg at all plant-back intervals, in all crop parts. It is noted that samples were not analysed for TFA, the common metabolite that may be taken up in rotational crops. Nevertheless, levels of TFA from the confined rotational crops can be relied upon and no additional trials analysing for this metabolite are required.

Based on the studies, it can be concluded that apart from TFA, cyflumetofen residue levels in rotational commodities are not expected to exceed 0.01 mg/kg, provided that cyflumetofen is applied in compliance with the GAPs reported in Appendix A.

Magnitude of residues in processed commodities

The effect of industrial processing and/or household preparation was assessed in studies conducted on oranges, apples, peaches, strawberries, tomatoes and hops and evaluated during a previous MRL assessment (Netherlands, 2016; Spain, 2020; EFSA, 2021a). An overview of the available processing studies is presented in Appendix B.1.2.3. Robust processing factors (fully supported by data) could be derived for processed orange commodities (pulp, juice, marmalade, dried pulp, wet pomace), processed apple commodities (juice, dried fruit, dry and wet pomace), processed peach commodities (juice, canned fruit, jam, dried fruit), processed strawberries (jam, canned fruits), processed tomatoes (peeled and canned, paste, ketchup, juice), processed hop commodities (dried cones, hop extract, beer, brewer's yeast).

AB-1 was not analysed in the processing studies, whereas the presence of metabolite A-2 was investigated only in processed apple and peach products. After processing, A-2 was not detected (< 0.01 mg/kg) in processed products from apple (juice, dried fruit, dry and wet pomace) or peaches (canned fruit, juice and jam), except at low levels in dried peaches (< 0.01–0.036 mg/kg) (see Appendix B.1.2.3).

Based on the results of the standard hydrolysis studies (see Appendix B.1.1.1), the levels of metabolite B-1 are expected to be at the same level or higher in processed products compared to A-2. This is also supported by the findings of the available processing studies (Appendix B.1.2.3). Therefore, although the storage stability of A-2 was not investigated leading to additional uncertainty, the levels of metabolite B-1 observed in the processed commodities indicate that the levels of A-2 are also expected to be low.

Further processing studies are not required as they are not expected to affect the outcome of the risk assessment. However, if more robust processing factors were to be required by risk managers, in particular for enforcement purposes, additional processing studies would be needed.

Proposed MRLs

Residues in livestock

Cyflumetofen is authorised for use on pome fruits, and registration of authorisation is ongoing for citrus fruits 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. The dietary burdens calculated for beef cattle were found to marginally exceed the trigger value of 0.1 mg/kg DM. Behaviour of residues was therefore assessed in this group of livestock.

A study investigating the metabolism of cyflumetofen residues in lactating goats is available for the current review (Spain, 2020). Cyflumetofen, radiolabelled in the benzoyl ring or in the tert-butylphenyl ring of the molecule was administered at a rate of 0.27–0.30 mg/kg for 12 days or at a rate of 0.43–0.48 mg/kg for 10 days, respectively.

The studies indicate that the majority of cyflumetofen, 78.5–89.6% of the total administered radioactivity, is rapidly excreted. Highest residue levels were found in liver (0.29–0.40 mg eq./kg) and kidney (0.17–0.19 mg eq./kg) whilst limited transfer was observed in fat and muscle (≤ 0.03 mg eq./kg). In milk low proportions, 0.03–0.14% or 0.008–0.19 mg/kg, of the administered dose were found.

In the study using the benzoyl label, parent cyflumetofen in edible tissues was only identified in fat (21.0% TRR) but at low concentration of < 0.003 mg/kg. The predominant metabolite was 2-(trifluoromethyl)benzoic acid (metabolite B-1) accounting in tissues for 21–53.9% of the TRR and in milk for 4.5% TRR (0.13 mg/kg in liver, 0.1 mg/kg in kidney, < 0.01 mg/kg in muscle, fat and milk). In the study using the butylphenyl-label, cyflumetofen and its metabolites were all < 0.01 mg/kg.

EFSA concludes that the metabolism of cyflumetofen in livestock is adequately elucidated, and metabolite B-1 is the most relevant component of the residues in livestock commodities.

As cyflumetofen is not present in most matrices, whereas metabolite B-1 was found to be a sufficient marker in livestock commodities, the residue definition for enforcement is proposed as 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

It is noted that the existing residue definition is the same as for plants, i.e. cyflumetofen (sum of isomers).

An analytical method using LC-MS/MS, assessed in the framework of a zonal registration of products (Spain, 2020), was fully validated for the determination of 2-(trifluoromethyl)benzoic acid (metabolite B-1) in all animal tissues, milk and eggs, with a LOQ of 0.01 mg/kg. As the residue definition is expressed as cyflumetofen, the LOQ has been recalculated and is equivalent to 0.02 mg/kg 2-(trifluoromethyl)benzoic acid, expressed as cyflumetofen. However, the ILV of the method is still required.

During the data collection, the EURLs reported that the LOQ of 0.01 mg/kg for cyflumetofen in milk is achievable (EURLs, 2020). Moreover, in line with the proposed new residue definition, during the Member States consultation the EURLs reported that an LOQ of 0.01 mg/kg 2-(trifluoromethyl)benzoic acid is deemed achievable for routine analysis in milk and liver (EFSA, 2021a).

Storage stability data for animal commodities is not available and is not required.

For risk assessment, the residue definition is proposed as the sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

Based on the metabolism study using the benzoyl label (performed at ˜ 150N rate compared to the maximum dietary burden) it can be concluded that residues of cyflumetofen are not expected in cattle tissues. MRLs and risk assessment values for the relevant commodities in ruminants can be established at the LOQ level. These MRLs are all tentative due to the data gap on the analytical methods (ILV). For all other animal products, the derivation of residue definitions, risk assessment values and MRLs are not required.

Consumer risk assessment

In the framework of this review, only the uses of cyflumetofen reported by the RMS in Appendix A were considered; however, the use of cyflumetofen was previously also assessed by the JMPR (FAO, 2014a,b). The CXLs, resulting from this assessment by JMPR and adopted by the CAC, are now international recommendations that need to be considered by European risk managers when establishing MRLs. To facilitate consideration of these CXLs by risk managers, the consumer exposure was calculated both with and without consideration of the existing CXLs.

It is noted that while the residue definitions for plants derived by JMPR and at EU level are the same, the enforcement residue definition for animal commodities derived by JMPR includes also cyflumetofen, besides metabolite B-1. Despite the wider definition compared to the one proposed by EFSA, the residue definition can be considered comparable as parent is not expected to be present at significant levels in animal commodities, and the residue definition is proposed to be expressed as cyflumetofen. The risk assessment residue definition for animal commodities is the same.

Consumer risk assessment without consideration of the existing CXLs

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.2.

The exposure values calculated were compared with the toxicological reference value for cyflumetofen, derived by EFSA (EFSA, 2012). The highest chronic exposure was calculated for the German child, representing 1% of the acceptable daily intake (ADI). Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance. 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.

In addition, it is highlighted that an updated indicative risk assessment of TFA that considered its potential uptake following the use of cyflumetofen and from other sources was carried out in a recent reasoned opinion concluding that no chronic intake concern is expected (EFSA, 2021a). This conclusion is still valid for the uses assessed in the current review.

Consumer risk assessment with consideration of the existing CXLs

To include the CXLs in the calculations of the consumer exposure, CXLs were compared with the EU MRL proposals in compliance with Appendix E and all data relevant to the consumer exposure assessment have been collected from JMPR evaluations. For livestock commodities, the CXL of 0.01* mg/kg was rounded up to the LOQ of 0.02* mg/kg which was derived at EU level for enforcement of this matrix. An overview of the input values used for this exposure calculation is also provided in Appendix D.3.

Chronic exposure calculations were also performed using revision 3.1 of the EFSA PRIMo and the exposure values calculated were compared with the toxicological reference value derived for cyflumetofen. The highest chronic exposure was calculated for the Dutch toddler, representing 2% of the ADI. Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance. Although minor uncertainties remain due to the data gap identified on the analytical methods for animal commodities applicable for these CXLs (ILV missing), the exposure calculation did not indicate a risk to consumers.

In addition, EFSA emphasises that the assessment does not investigate the possible impact of plant and animal metabolism on the isomer ratio of cyflumetofen and further investigation on this matter would in principle be required. However, in view of the large margin of safety in the exposure calculation, the potential change in isomer ratios in the final residue is not expected to be of concern for the authorised use in the framework of this review. In case future uses of active substance would lead to a higher consumer exposure, further information regarding the impact of metabolism on the isomer ratio might be required.

Conclusions

The metabolism of cyflumetofen in plant was investigated in primary and rotational crops. According to the results of the metabolism studies, the residue definition for enforcement can be proposed as cyflumetofen (sum of isomers) and for risk assessment as sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen. These residue definitions are also applicable to processed commodities. Fully validated analytical methods are available for the enforcement of the proposed residue definition in all major matrices at the LOQ of 0.01 mg/kg. According to the EURLs this LOQ is achievable in routine analyses.

Robust processing factors could be derived for processed commodities from oranges, apples, peaches, strawberries, tomatoes and hops.

According to the EURLs an LOQ of 0.01 mg/kg 2-(trifluoromethyl)benzoic acid is deemed achievable for routine analysis in milk and liver.

For risk assessment, the residue definition for animals is proposed as the sum of cyflumetofen (sum of isomers) and 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen.

MRLs and risk assessment values for the relevant ruminant commodities can be established at the LOQ of 0.02 mg/kg 2-(trifluoromethyl)benzoic acid, expressed as cyflumetofen.

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 represented 1 % of the ADI (German child). Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance.

Apart from the MRLs evaluated in the framework of this review, internationally recommended CXLs have also been established for cyflumetofen. Additional calculations of the consumer exposure, considering these CXLs, were therefore carried out, the highest chronic exposure represented 2 % of the ADI (Dutch toddler).

Recommendations

MRL recommendations were derived in compliance with the decision tree reported in Appendix E of the reasoned opinion (see Table 2). 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 2 footnotes for details). In particular, some tentative MRLs need to be confirmed by the following data:

2 additional residue trials on cherries, plums, cane fruits and other small fruits and berries (except azaroles).
ILV of the analytical method for enforcement in animal commodities.

In addition, EFSA highlights that the proposed residue definition for enforcement in commodities of animal products is overlapping with the residue definition for enforcement for flutolanil in commodities of animal origin, which has been established for flutolanil as: Flutolanil and metabolites containing the 2-(trifluoromethyl)benzoic acid moiety, expressed as flutolanil. However, as according to the metabolism study with flutolanil under evaluation in the framework of the renewal (Netherlands, 2018) free 2-(trifluoromethyl)benzoic acid is not formed at significant levels in livestock following flutolanil use, the use of flutolanil is not expected to impact the MRLs proposed for cyflumetofen. Residues resulting from the use of cyflumetofen are not expected to trigger the need to modify the existing MRLs for flutolanil.

Table 2 Summary table

Code number	Commodity	Existing EU MRL (mg/kg)	Existing CXL (mg/kg)	Outcome of the review
MRL (mg/kg)	Comment #data gap
Enforcement residue definition (existing): cyflumetofen (sum of isomers) Enforcement residue definition (proposed): cyflumetofen (sum of isomers)
110000	Citrus fruits	0.5	0.3	0.5	Recommendeda
120000	Tree nuts	0.01*	0.01*	0.01*	Recommendedb
130000	Pome fruits	0.4	0.4	0.4	Recommendedc
140010	Apricots	0.3	–	0.3	Recommendedd
140020	Cherries	–	–	0.01*	Further consideration needede #1
140030	Peaches	0.3	–	0.3	Recommendedd
140040	Plums	–	–	0.01*	Further consideration needede #1
151010	Table grapes	0.6	0.6	0.6	Recommendedb
151020	Wine grapes	0.6	0.6	0.6	Recommendedb
152000	Strawberries	0.6	0.6	0.6	Recommendeda
153010	Blackberries	–	–	0.01*	Further consideration needede #1
153020	Dewberries	–	–	0.01*	Further consideration needede #1
153030	Raspberries	–	–	0.01*	Further consideration needede #1
154010	Blueberries	–	–	0.01*	Further consideration needede #1
154020	Cranberries	–	–	0.01*	Further consideration needede #1
154030	Currants (red, black and white)	–	–	0.01*	Further consideration needede #1
154040	Gooseberries	–	–	0.01*	Further consideration needede #1
154050	Rose hips	–	–	0.01*	Further consideration needede #1
154060	Mulberries	–	–	0.01*	Further consideration needede #1
154070	Azarole (mediterranean medlar)	0.4	0.4	0.4	Recommendedf
154080	Elderberries	–	–	0.01*	Further consideration needede #1
161060	Persimmon	0.4	0.4	0.4	Recommendedb
231010	Tomatoes	0.4	0.3	0.4	Recommendeda
231030	Aubergines (egg plants)	0.4	–	0.4	Recommendedd
232010	Cucumbers	0.4	–	0.4	Recommendedd
700000	Hops	30	–	30	Recommendedd
Enforcement residue definition (existing): cyflumetofen (sum of isomers) Enforcement residue definition (proposed): 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen
1011010	Swine meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1011020	Swine fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1011030	Swine liver	0.02	0.02	0.02	Further consideration neededg #2
1011040	Swine kidney	0.02	0.02	0.02	Further consideration neededg #2
1012010	Bovine meat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1012020	Bovine fat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1012030	Bovine liver	0.02	0.02	0.02*	Further consideration neededh #2
1012040	Bovine kidney	0.02	0.02	0.02*	Further consideration neededh #2
1013010	Sheep meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1013020	Sheep fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1013030	Sheep liver	0.02	0.02	0.02	Further consideration neededg #2
1013040	Sheep kidney	0.02	0.02	0.02	Further consideration neededg #2
1014010	Goat meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1014020	Goat fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1014030	Goat liver	0.02	0.02	0.02	Further consideration neededg #2
1014040	Goat kidney	0.02	0.02	0.02	Further consideration neededg #2
1015010	Horse meat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1015020	Horse fat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1015030	Horse liver	0.02	0.02	0.02*	Further consideration neededh #2
1015040	Horse kidney	0.02	0.02	0.02*	Further consideration neededh #2
1020010	Cattle milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020020	Sheep milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020030	Goat milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020040	Horse milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
–	Other commodities of plant and/or animal origin	See Reg. 2021/1098	–	–	Further consideration neededi

Abbreviations

a.i.
active ingredient

a.s.
active substance

ADI
acceptable daily intake

AR
applied radioactivity

ARfD
acute reference dose

BBCH
growth stages of mono- and dicotyledonous plants

bw
body weight

CAC
Codex Alimentarius Commission

CAS
Chemical Abstract Service

CF
conversion factor for enforcement residue definition to risk assessment residue definition

CIRCA
(EU) Communication & Information Resource Centre Administrator

CS
capsule suspension

CV
coefficient of variation (relative standard deviation)

CXL
codex maximum residue limit

DAR
draft assessment report

DAT
days after treatment

DB
dietary burden

DM
dry matter

DS
powder for dry seed treatment

DT₉₀
period required for 90% dissipation (define method of estimation)

EC
emulsifiable concentrate

EDI
estimated daily intake

EMS
evaluating Member State

eq
residue expressed as a.s. equivalent

EURLs
European Union Reference Laboratories for Pesticide Residues (former CRLs)

FAO
Food and Agriculture Organization of the United Nations

FID
flame ionisation detector

GAP
Good Agricultural Practice

GC
gas chromatography

GC-FID
gas chromatography with flame ionisation detector

GC-MS
gas chromatography with mass spectrometry

GC-MS/MS
gas chromatography with tandem mass spectrometry

GS
growth stage

HPLC
high-performance liquid chromatography

HPLC-MS
high-performance liquid chromatography with mass spectrometry

HPLC-MS/MS
high-performance liquid chromatography with tandem mass spectrometry

HR
highest residue

IEDI
international estimated daily intake

ILV
independent laboratory validation

ISO
International Organisation for Standardization

IUPAC
International Union of Pure and Applied Chemistry

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

LC
liquid chromatography

LC–MS/MS
liquid chromatography with tandem mass spectrometry

LOQ
limit of quantification

Mo
monitoring

MRL
maximum residue level

MS
Member States

MS
mass spectrometry detector

MS/MS
tandem mass spectrometry detector

MW
molecular weight

NEDI
national estimated daily intake

NTMDI
national theoretical maximum daily intake

OECD
Organisation for Economic Co-operation and Development

PBI
plant back interval

PF
processing factor

PHI
preharvest interval

PRIMo
(EFSA) Pesticide Residues Intake Model

PROFile
(EFSA) Pesticide Residues Overview File

RA
risk assessment

RD
residue definition

RAC
raw agricultural commodity

RD
residue definition

RMS
rapporteur Member State

SANCO
Directorate-General for Health and Consumers

SC
suspension concentrate

SEU
southern European Union

SMILES
simplified molecular-input line-entry system

SL
soluble concentrate

SP
water soluble powder

STMR
supervised trials median residue

TFA
trifluoroacetic acid

TAR
total applied radioactivity

TMDI
theoretical maximum daily intake

TRR
total radioactive residue

UV
ultraviolet (detector)

WHO
World Health Organization

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

A.1

Authorised outdoor uses in northern EU

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 and seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Apples	NL	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	14
Apricots	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	200 g a.i./ha	n.r.
Cherries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Peaches	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Plums	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Blackberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Dewberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Raspberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Blueberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Cranberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Currants	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Gooseberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Rose hips	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Mulberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Azaroles	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Elderberries	NL	F	Mites	SC	200 g/L	Foliar treatment	90–93	2	7	–	–	240 g a.i./ha	n.r.
Hops	NLe	F		SC	200 g/L	Foliar treatment – spraying	15–79	2	10	–	–	200 g a.i./ha	14	Based on EFSA (2021a)

A.2

Authorised outdoor uses in southern EU

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 and seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Grapefruits	NLe	F	Panonychus citri, Tetranychus urticae, Tetranychus sp	SC	200 g/L	Foliar treatment – spraying	11–85	2	10	–	–	200 g a.i./ha	7	Based on EFSA (2021a)
Oranges	NLe	F	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Lemons	NLe	F	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Limes	NLe	F	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Mandarins	NLe	F	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Apples	BG, ES	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Pears	BG, ES	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Quinces	BG, ES	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Medlars	BG, ES	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Loquats	BG, ES	F	Mites	SC	200 g/L	Foliar treatment	11–85	2	10	–	–	200 g a.i./ha	7
Apricots	NLe	F		SC	200 g/L	Foliar treatment	11–85	2		–	–	200 g a.i./ha	7	Based on EFSA (2021a)
Peaches	NLe	F		SC	200 g/L	Foliar treatment	11–85	2		–	–	200 g a.i./ha	7	Based on EFSA (2021a)
Tomatoes	BG	F	Mites	SC	200 g/L	Foliar treatment	11–89	2	10	–	–	200 g a.i./ha	1
Aubergines	NLe	F		SC	200 g/L	Foliar treatment – spraying	13–89	2	10	–	–	200 g a.i./ha	1	Based on EFSA (2021a)

A.3

Authorised indoor uses in EU

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 and seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Apricots	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	200 g a.i./ha	n.r.
Cherries	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Peaches	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Plums	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Strawberries	BE, BG, CZ, DE, NL, PL	I	Mites	SC	201 g/L	Foliar treatment – spraying	13–89	2	10	–	–	200 g a.i./ha	1
Blackberries	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Dewberries	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Raspberries	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Blueberries	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Cranberries	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Currants	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Gooseberries	NL, BE	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Rose hips	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Mulberries	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Azaroles	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Elderberries	NL	I	Mites	SC	200 g/L	Foliar treatment – spraying	90–93	2	7	–	–	240 g a.i./ha	n.r.
Tomatoes	NLe	I	Mites	SC	200 g/L	Foliar treatment – spraying	13–89	2	10	–	–	200 g a.i./ha	1
Aubergines	NLe	I	Mites	SC	200 g/L	Foliar treatment – spraying	13–89	2		–	–	200 g a.i./ha	1	Based on EFSA (2021a)
Cucumbers	NLe	I	Mites	SC	200 g/L	Foliar treatment – spraying	11–89	2	7	–	–	300 g a.i./ha	1	Based on EFSA (2021a)

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

Primary crops (available studies)	Crop groups	Crop(s)	Application(s)	Sampling (DAT)	Comment/Source
	Fruit crops	Apple	Foliar, 1 × 600 g/ha	Fruit: 1, 7, 30 Leaf: 7, 30	Radiolabelled active substance: [¹⁴C- butylphenyl] or [¹⁴C-trifluoromethyl phenyl] cyflumetofen (EFSA, 2012)
	Mandarin	Foliar, 1 × 600 g/ha	Fruit: 1, 7, 30 Leaf: 1, 7, 14
	Eggplant	Foliar, 1 × 600 g/ha	Fruit: 1, 7, 14 Leaf: 14
Leafy crops	–	–	–	Data on leaves in fruit crop metabolism studies considered sufficient to cover the use on hops (EFSA, 2021a).
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Radish	Bare soil, 1 × 400 g/ha	30, 120, 365	Cyflumetofen and metabolites (AB-1, B-3) DT₉₀ < 100 days; B-1 DT₉₀ max 120 days. Radiolabelled active substance: [¹⁴C- butylphenyl] or [¹⁴C-trifluoromethyl phenyl] cyflumetofen (EFSA, 2012)
Leafy crops	Lettuce	Bare soil, 1 × 400 g/ha	30, 120, 365
Cereal (small grain)	Wheat	Bare soil, 1 × 400 g/ha	30, 120, 365
Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	Yes	[¹⁴C-trifluoromethyl phenyl]/[¹⁴C- butylphenyl] labelled: Cyflumetofen 70.9% TRR/69.3% TRR AB-1: 4.2% TRR/39.9% TRR B-1: 23.2% TRR/not relevant for label A-2: not relevant for label/14.3% TRR (Spain, 2020; EFSA, 2021a)
Baking, brewing and boiling (60 min, 100°C, pH 5)	No	[¹⁴C-trifluoromethyl phenyl]/[¹⁴C- butylphenyl] labelled: Cyflumetofen 17.9% TRR/5% TRR AB-1: 31.7% TRR/39.9% TRR B-1: 58.7% TRR/not relevant for label A-2: not relevant for label/52.9% TRR (Spain, 2020; EFSA, 2021a)
Sterilisation (20 min, 120°C, pH 6)	No	[¹⁴C-trifluoromethyl phenyl]/[¹⁴C- butylphenyl] labelled: Cyflumetofen: not found/not found AB-1: 38.8% TRR/49.1% TRR B-1: 75.3% TRR/not relevant for label A-2: not relevant for label/44.4% TRR (Spain, 2020; EFSA, 2021a)
Other processing conditions	–	–

B.1.1.2

Stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)a	Stability (months)	Comment/Source
Cyflumetofen	Metabolite B-1b
	High water content	Apple	FS	25	25	EFSA (2021a)
Lettuce	FS	3	Inconclusive	EFSA (2021a)
Radish root	FS	3	21	EFSA (2021a)
High starch content	Wheat grains	FS	25	22	Netherlands (2016), Spain (2020)
High oil content	Almond nutmeal	FS	25	30	EFSA (2021a)
High acid content	Orange	FS	25	30	EFSA (2021a)
Processed products	Apple juice	FS	25	25	EFSA (2021a)
Orange juice	FS	25	30	EFSA (2021a)
Orange oil	FS	25	Inconclusive	EFSA (2021a)

B.1.2

Magnitude of residues in plants

B.1.2.1

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

Commodity	Region/Indoora	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)	CFd
Citrus fruits	SEU	Oranges: Mo: 0.05; 0.07; 0.08; 0.10; 0.11; 0.14; 0.27; 0.27 RA: 0.08; 0.10; 0.10; 0.12; 0.13; 0.16; 0.29; 0.29 Lemons: Mo: 0.07; 0.12; 0.13; 0.21 RA: 0.09; 0.14; 0.15; 0.23 Mandarins: Mo: 0.08; 0.10; 0.16; 0.22 RA: 0.11; 0.12; 0.18; 0.24	Residue trials on oranges, lemons, mandarins compliant with GAP. Extrapolation to citrus fruits possible (EFSA, 2021a). MRL_OECD = 0.42	0.5	0.27	0.12	1.2
Apples	NEU	Apples: Mo: 0.03; 0.05; 0.11; 0.15 RA: 0.05; 0.08; 0.13; 0.17 Pears: Mo: 0.02; 0.03; 0.08; 0.09 RA: 0.04; 0.06; 0.1; 0.11	Residue trials on pears and on apples compliant with the GAP (Spain, 2020). MRL_OECD = 0.25	0.3	0.15	0.06	1.4
Pome fruits	SEU	Apples: Mo: 0.03; 0.04; 0.06; 0.08 RA: 0.06; 0.06; 0.08; 0.10 Pears: Mo: 0.02; 0.03; 0.05; 0.07 RA: 0.05; 0.06; 0.07; 0.09	Residue trials on pears and on apples compliant with the GAP. Extrapolation to pome fruits possible (Spain, 2020). MRL_OECD = 0.14	0.15	0.08	0.04	1.6
Apricots, peaches	NEU	–	No residue trials available. Since the application is done after harvest, and considering the properties of the a.s. and the results of the metabolism studies, residues are not expected in the edible part of the crop and the MRL can be proposed at the LOQ (Spain, 2020). Additional trials not required, as the SEU GAP is clearly more critical.	0.01*	0.01	0.01	1e
	SEU	Apricots: Mo: < 0.01; 0.08; 0.11; 0.12 RA: 0.03; 0.11; 0.13; 0.14 Peaches: Mo: 0.03; 0.07; 0.10; 0.13 RA: 0.06; 0.09; 0.12; 0.15	Residue trials on apricots and peaches compliant with GAP (EFSA, 2021a). Extrapolation to apricots and peaches possible. MRL_OECD = 0.25	0.3	0.13	0.09	1.2
	EU	–	No residue trials available. Since the application is done after harvest, and considering the properties of the a.s. and the results of the metabolism studies, residues are not expected in the edible part of the crop and the MRL can be proposed at the LOQ (Spain, 2020). Additional trials not required, as the SEU GAP is clearly more critical.	0.01*	0.01	0.01	1e
Cherries, plums, cane fruits and other small fruits and berries	NEU	–	No residue trials available. Since the application is done after harvest, and considering the properties of the a.s. and the results of the metabolism studies, residues are not expected in the edible part of the crop and the MRL can be proposed at the LOQ (Spain, 2020).	0.01* (tentative)f	0.01	0.01	1e
EU	–	No residue trials available. Since the application is done after harvest, and considering the properties of the a.s. and the results of the metabolism studies, residues are not expected in the edible part of the crop and the MRL can be proposed at the LOQ (Spain, 2020).	0.01* (tentative)f	0.01	0.01	1e
Strawberries	EU	Mo: 0.07; 0.08; 0.11; 0.11g; 0.12; 0.12; 0.12g; 0.13; 0.13; 0.14g; 0.15g; 0.2; 0.45 RA: 0.09; 010; 0.13; 0.14; 0.15; 0.15; 0.15; 0.15; 0.16; 0.17; 0.21; 0.22; 0.47	Residue trials on strawberries compliant with the GAP (Spain, 2020). MRL_OECD = 0.53	0.6	0.45	0.12	1.3
Tomatoes Aubergines/eggplants	SEU	Mo: 0.06; 0.06; 0.05; 0.05; 0.09; 0.09; 0.04; 0.01 RA: 0.09; 0.08; 0.08; 0.08; 0.12; 0.12; 0.07; 0.04	Residue trials on tomatoes compliant with GAP (EFSA, 2021a). Extrapolation to aubergines possible. MRL_OECD = 0.17	0.2	0.09	0.06	1.4
	EU	Mo: 0.02; 0.03; 0.05; 0.05; 0.08; 0.09; 4 × 0.13; 0.16; 0.27 RA: 0.04; 0.05; 0.07; 0.1; 0.11; 0.114; 4 × 0.15; 0.18; 0.29	Residue trials on tomatoes compliant with GAP (EFSA, 2021a). Highest values measured at a longer PHI of 2–4 days or 7–8 days. MRL_OECD = 0.38	0.4	0.27	0.11	1.3
Cucumbers	EU	Mo: 0.06; 0.07; 0.09; 0.10; 0.10; 0.15; 0.16; 0.24 RA: 0.08; 0.09; 0.11; 0.17; 0.12; 0.17; 0.18; 0.26	Residue trials on cucumbers compliant with the GAP (EFSA, 2021a). MRL_OECD = 0.36	0.4	0.24	0.10	1.2
Hops	NEU	Mo: 3.6; 7.6; 8.0; 14 RA: 4.2; 8.5; 8.7; 14.6	Residue trials on hops compliant with the GAP (EFSA, 2021a). MRL_OECD = 25.45	30	14.00	7.80	1.1

B.1.2.2

Residues in rotational crops

a) Overall summary

B.1.2.3

Processing factors

Processed commodity	Number of valid studiesa	Processing Factor (PF)	CF_Pb	Comment/Source
Individual values	Median PF
Citrus, pulp	16	< 0.04; < 0.08; < 0.08; < 0.09; 0.09; < 0.12; 0.14; < 0.15; 0.18; < 0.19; 0.22; 0.24; 0.25; 0.27; 0.39; 0.62	0.17	1	EFSA (2021a) B-1: < 0.01 mg/kg in processed commodity
Oranges, pulp	4	< 0.05; < 0.05; 0.05; 0.07	0.05	1	EFSA (2021a), Spain (2020) B-1: < 0.01 mg/kg in processed commodity
Oranges, juice	4	< 0.05; 0.07; 0.08; 0.1	0.08	1.1	EFSA (2021a), Spain (2020) B-1: < 0.01–0.01 mg/kg in processed commodity
Orange, dried pulp	4	1.09; 1.2; 1.21; 1.4	1.2	3	EFSA (2021a), Spain (2020) B-1: 0.17–0.36 mg/kg in processed commodity
Oranges, wet pomace	4	0.08; 0.11; 0.14; 0.14	0.13	1	EFSA (2021a); Spain (2020) B-1: < 0.01 mg/kg in processed commodity
Oranges, marmalade	4	0.4; 0.4; 0.65; 0.65	0.5	1	EFSA (2021a); Spain (2020) B-1: < 0.01 mg/kg in processed commodity
Apples, juice	4	< 0.04; < 0.07; 0.07; < 0.10	0.07	1.1	EFSA (2021a), Spain (2020), Netherlands (2016) Residues in the processed commodity: B-1: < 0.01 mg/kg A-2: < 0.01 mg/kg
Apples, dried	6	3.25, 4.14, 5.17, 5.20, 7.30, 7.33	5.2	1.1	EFSA (2021a), Spain (2020), Netherlands (2016) Residues in the processed commodity: B-1: 0.01–0.03 mg/kg A-2: < 0.01 mg/kg
Apples, dry pomace	4	13.5; 14; 16.8; 30	15	1	Spain (2020), Netherlands (2016) Residues in the processed commodity: B-1: 0.03–0.06 mg/kg A-2: < 0.01 mg/kg
Apples, wet pomace	6	2.68, 3.13, 3.17, 3.31, 3.33, 4.70	3.3	1	EFSA (2021a), Spain (2020), Netherlands (2016) B-1: < 0.01–0.01 mg/kg in processed commodity A-2: < 0.01 mg/kg
Peaches, juice	3	0.4; 1.4; 1.7	1.4	1.1	EFSA (2021a), Spain (2020) Residues in the processed commodity: B-1: 0.011–0.019 mg/kg A-2: < 0.01 mg/kg
Peaches, canned	3	< 0.04; < 0.06; < 0.08	< 0.06	1	EFSA (2021a), Spain (2020) Residues in the processed commodity: B-1: < 0.01 mg/kg A-2: < 0.01 mg/kg
Peaches, jam	3	0.1; 0.1; 0.2	0.1	1	EFSA (2021a), Spain (2020) Residues in the processed commodity: B-1: < 0.01–0.014 mg/kg A-2: < 0.01 mg/kg
Peaches, dried fruit	3	6.6; 7.85; 20.9	7.85	1.3	EFSA (2021a), Spain (2020) Residues in the processed commodity: B-1: 0.12–0.46 mg/kg A-2: < 0.01–0.036 mg/kg
Strawberries, jam	4	0.11; 0.16; 0.40; 0.46	0.28	1	EFSA (2021a), Spain (2020) B-1: < 0.01–0.01 mg/kg in processed commodity
Strawberries, canned	4	0.23; 0.35; 0.37; 0.71	0.36	1	EFSA (2021a), Spain (2020) B-1: < 0.01–0.02 mg/kg in processed commodity
Tomatoes, peeled and canned (sterilised)	4	< 0.02; < 0.03; < 0.05; 0.19	< 0.04	1	EFSA (2021a), Spain (2020) B-1: < 0.01 mg/kg in processed commodity
Tomatoes, paste	4	0.18; 0.25; 0.28; 0.93	0.27	1	EFSA (2021a), Spain (2020) B-1: 0.01–0.04 mg/kg in processed commodity
Tomatoes, ketchup (pasteurised)	4	0.09; 0.12; 0.15; 0.44	0.14	1	EFSA (2021a), Spain (2020) B-1: < 0.01–0.03 mg/kg in processed commodity
Tomatoes, juice	4	0.03; 0.14; 0.14; 0.86	0.14	1	EFSA (2021a), Spain (2020) B-1: < 0.01–0.02 mg/kg in processed commodity
Hop, dried cones	4	3.6, 3.8, 5.4, 5.4	4.6	1.1	Field trial data, EFSA (2021a) B-1: 0.26–1.8 mg/kg in dried cones
Hop, dried cones	2	0.96, 1.00	0.98	1.3	Processing study data, EFSA (2021a) B-1: 1.1; 1.7 mg/kg in dried cones
Hop, extract	2	2.67, 2.75,	2.7	2	EFSA (2021a) B-1: 7.8–11 mg/kg in processed commodity
Hop, beer	2	< 0.0005, < 0.002	< 0.001	1	EFSA (2021a) B-1: < 0.01–0.02 mg/kg in processed commodity
Hop, brewer's yeast	2	< 0.0005, < 0.002	< 0.001	1	EFSA (2021a) B-1: 0.03–0.05 mg/kg in processed commodity

B.2

Residues in livestock

Relevant groups (subgroups)	Dietary burden expressed in	Most critical subgroupa	Most critical commodityb	Trigger exceeded (Y/N)	Comments
mg/kg bw per day	mg/kg DM
Median	Maximum	Median	Maximum
Cattle (all)	0.003	0.003	0.11	0.11	Beef cattle	Apple pomace, wet	Yes	–
Cattle (dairy only)	0.002	0.002	0.05	0.05	Dairy cattle	Apple pomace, wet	No	–
Sheep (all)	0.002	0.002	0.05	0.05	Lamb	Apple pomace, wet	No	–
Sheep (ewe only)	0.002	0.002	0.05	0.05	Ram/Ewe	Apple pomace, wet	No	–
Swine (all)	0.001	0.001	0.02	0.02	Swine (breeding)	Citrus dried pulp	No	–
Poultry (all)	–	–	–	–	–	–	No	–
Poultry (layer only)	–	–	–	–	–	–	No	–

B.2.1

Nature of residues and methods of analysis in livestock

B.2.1.1

Metabolism studies, methods of analysis and residue definitions in livestock

Livestock (available studies)	Animal	Dose (mg/kg bw per day)	Duration (days)	Comment/Source
	Laying hen	–	–	Not triggered, not required.
Lactating ruminants	0.27–0.48	10–12	Goat; [¹⁴C- butylphenyl] or [¹⁴C-trifluoromethyl phenyl] cyflumetofen (Spain, 2020)

B.2.1.2

Stability of residues in livestock

Not available, not required.

B.2.2

Magnitude of residues in livestock

B.2.2.1

Summary of the residue data from livestock metabolism studies

Calculations performed with Animal model 201710

Animal commodity	Residues at the closest feeding level (mg/kg)	Estimated value at 1N	MRL proposal (mg/kg)	CFc
Mean	Highest	STMR_Moa (mg/kg)	HR_Mob (mg/kg)
Cattle (all) – Closest feeding level (0.43 mg/kg bw; × ˜ 150 rate)d
Muscle	0.005	0.005	0.02	0.02	0.02* (tentative)e	1f
Fat	0.006	0.006	0.02	0.02	0.02* (tentative)e	1f
Liver	0.125	0.125	0.02	0.02	0.02* (tentative)e	1f
Kidney	0.102	0.102	0.02	0.02	0.02* (tentative)e	1f
Cattle (dairy only), sheep, swine, poultry – residue definitions, MRLs and input values do not need to be derived as no significant exposure is expected according to the authorised uses

B.3

Consumer risk assessment

B.3.1

Consumer risk assessment without consideration of the existing CXLs

Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not considered necessary.

Consumer exposure assessment through drinking water resulting from groundwater metabolite(s) according to SANCO/221/2000 rev.10 Final (25/2/2003)

B.3.2

Consumer risk assessment with consideration of the existing CXLs

Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not considered necessary.

B.4

Proposed MRLs

Code number	Commodity	Existing EU MRL (mg/kg)	Existing CXL (mg/kg)	Outcome of the review
MRL (mg/kg)	Comment #data gap
Enforcement residue definition (existing): cyflumetofen (sum of isomers) Enforcement residue definition (proposed): cyflumetofen (sum of isomers)
110000	Citrus fruits	0.5	0.3	0.5	Recommendeda
120000	Tree nuts	0.01*	0.01*	0.01*	Recommendedb
130000	Pome fruits	0.4	0.4	0.4	Recommendedc
140010	Apricots	0.3	–	0.3	Recommendedd
140020	Cherries	–	–	0.01*	Further consideration needede #1
140030	Peaches	0.3	–	0.3	Recommendedd
140040	Plums	–	–	0.01*	Further consideration needede #1
151010	Table grapes	0.6	0.6	0.6	Recommendedb
151020	Wine grapes	0.6	0.6	0.6	Recommendedb
152000	Strawberries	0.6	0.6	0.6	Recommendeda
153010	Blackberries	–	–	0.01*	Further consideration needede #1
153020	Dewberries	–	–	0.01*	Further consideration needede #1
153030	Raspberries	–	–	0.01*	Further consideration needede #1
154010	Blueberries	–	–	0.01*	Further consideration needede #1
154020	Cranberries	–	–	0.01*	Further consideration needede #1
154030	Currants (red, black and white)	–	–	0.01*	Further consideration needede #1
154040	Gooseberries	–	–	0.01*	Further consideration needede #1
154050	Rose hips	–	–	0.01*	Further consideration needede #1
154060	Mulberries	–	–	0.01*	Further consideration needede #1
154070	Azarole (mediterranean medlar)	0.4	0.4	0.4	Recommendedf
154080	Elderberries	–	–	0.01*	Further consideration needede #1
161060	Persimmon	0.4	0.4	0.4	Recommendedb
231010	Tomatoes	0.4	0.3	0.4	Recommendeda
231030	Aubergines (egg plants)	0.4	–	0.4	Recommendedd
232010	Cucumbers	0.4	–	0.4	Recommendedd
700000	Hops	30	–	30	Recommendedd
Enforcement residue definition (existing): cyflumetofen (sum of isomers) Enforcement residue definition (proposed): 2-(trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen
1011010	Swine meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1011020	Swine fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1011030	Swine liver	0.02	0.02	0.02	Further consideration neededg #2
1011040	Swine kidney	0.02	0.02	0.02	Further consideration neededg #2
1012010	Bovine meat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1012020	Bovine fat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1012030	Bovine liver	0.02	0.02	0.02*	Further consideration neededh #2
1012040	Bovine kidney	0.02	0.02	0.02*	Further consideration neededh #2
1013010	Sheep meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1013020	Sheep fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1013030	Sheep liver	0.02	0.02	0.02	Further consideration neededg #2
1013040	Sheep kidney	0.02	0.02	0.02	Further consideration neededg #2
1014010	Goat meat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1014020	Goat fat	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1014030	Goat liver	0.02	0.02	0.02	Further consideration neededg #2
1014040	Goat kidney	0.02	0.02	0.02	Further consideration neededg #2
1015010	Horse meat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1015020	Horse fat	0.01*	0.02*^,1	0.02*	Further consideration neededh #2
1015030	Horse liver	0.02	0.02	0.02*	Further consideration neededh #2
1015040	Horse kidney	0.02	0.02	0.02*	Further consideration neededh #2
1020010	Cattle milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020020	Sheep milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020030	Goat milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
1020040	Horse milk	0.01*	0.02*^,1	0.02*	Further consideration neededg #2
–	Other commodities of plant and/or animal origin	See Reg. 2021/1098	–	–	Further consideration neededi

Appendix C – Pesticide Residue Intake Model (PRIMo)

• PRIMo(EU)

• PRIMo(CXL)

Appendix D – Input values for the exposure calculations

D.1

Livestock dietary burden calculations

Feed commodity	Median dietary burden	Maximum dietary burden
Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: sum of cyflumetofen (sum of isomers) and 2- (trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen
Citrus fruits, dried pulp	0.14	STMR_Mo × CF_p (3) × PF (1.2)	0.14	STMR_Mo × CF_p (3) × PF (1.2)
Apple, pomace, wet	0.21	STMR_Mo × CF_p(1) × PF (3.3)	0.21	STMR_Mo × CF_p(1) × PF (3.3)

D.2

Consumer risk assessment without consideration of the existing CXLs

Commodity	Chronic risk assessment
Input value (mg/kg)	Comment
Risk assessment residue definition: sum of cyflumetofen (sum of isomers) and 2- (trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen
Citrus fruits	0.14	STMR_Mo × CF (1.2)
Pome fruits, azaroles/Mediterranean medlars, kaki/Japanese persimmons	0.1	STMR_Mo × CF (1.6)
Apricots	0.09	STMR_Mo × CF (1)
Cherries (sweet)	0.01*	STMR _Mo × CF (1) (tentative)
Peaches	0.09	STMR_Mo × CF (1)
Plums	0.01*	STMR _Mo × CF (1) (tentative)
Strawberries	0.15	STMR_Mo × CF (1.3)
Cane fruits, and other small fruits and berries	0.01*	STMR _Mo × CF (1) (tentative)
Tomatoes	0.16	STMR_Mo × CF (1.4)
Aubergines/eggplants	0.16	STMR_Mo × CF (1.4)
Cucumbers	0.12	STMR_Mo × CF (1.2)
Hops	8.6	STMR_Mo × CF (1.1)
Bovine and equine meat	0.02*	STMR _Mo × CF (1) (tentative)
Bovine and equine fat	0.02*	STMR _Mo × CF (1) (tentative)
Bovine and equine liver	0.02*	STMR _Mo × CF (1) (tentative)
Bovine and equine kidney	0.02*	STMR _Mo × CF (1) (tentative)

D.3

Consumer risk assessment with consideration of the existing CXLs

Commodity	Chronic risk assessment
Input value (mg/kg)	Comment
Risk assessment residue definition: sum of cyflumetofen (sum of isomers) and 2- (trifluoromethyl)benzoic acid (metabolite B-1), expressed as cyflumetofen
Citrus fruits	0.14	STMR_Mo × CF (1.2)
Tree nuts	0.01*	STMR_Mo (CXL) × CF (1)
Pome fruits	0.11	STMR_Mo (CXL) × CF (1.2)
Apricots	0.09	STMR_Mo × CF (1)
Cherries (sweet)	0.01*	STMR_Mo × CF (1) (tentative)
Peaches	0.09	STMR_Mo × CF (1)
Plums	0.01*	STMR _Mo × CF (1) (tentative)
Table and wine grapes	0.19	STMR_Mo (CXL) × CF (1.2)
Strawberries	0.15	STMR_Mo × CF (1.3)
Cane fruits, and other small fruits and berries	0.01*	STMR_Mo × CF (1) (tentative)
Tomatoes	0.16	STMR_Mo × CF (1.4)
Aubergines/eggplants	0.16	STMR_Mo × CF (1.4)
Cucumbers	0.12	STMR_Mo × CF (1.2)
Hops	8.6	STMR_Mo × CF (1.1)
Bovine and equine meat	0.02*	STMR _Mo × × CF (1) (tentative)
Bovine and equine fat	0.02*	STMR _Mo × CF (1) (tentative)
Bovine and equine liver	0.02*	STMR _Mo × CF (1) (tentative)
Bovine and equine kidney	0.02*	STMR _Mo × CF (1) (tentative)
Swine, sheep and goat meat	0.02*	STMR_Mo (CXL) × CF (1) muscle (tentative)
Swine, sheep and goat fat	0.02*	STMR_Mo (CXL) × CF (1) (tentative)
Swine, sheep and goat kidney	0.02*	STMR_Mo (CXL) × CF (1) (tentative)
Swine, sheep and goat liver	0.02*	STMR_Mo (CXL) × CF (1) (tentative)
Cattle, horse, sheep and goat milk	0.02*	STMR_Mo (CXL) × CF (1) (tentative)

Appendix E – Decision tree for deriving MRL recommendations

Appendix F – Used compound codes

Code/trivial name	IUPAC name/SMILES notation/InChiKeya	Structural formulab
Cyflumetofen	2-methoxyethyl 2-(4-tert-butylphenyl)-2-cyano-3-oxo-3-[2-(trifluoromethyl)benzamido]propanoate FC(F)(F)c1ccccc1C(=O)NC(=O)C(C#N)(c1ccc(cc1)C(C)(C)C)C(=O)OCCOC RAZUBFCBBHISOG-UHFFFAOYSA-N
2-(trifluoromethyl)benzoic acid B1	2-(trifluoromethyl)benzoic acid a,a,a-trifluoro-o-toluic acid FC(F)(F)c1ccccc1C(=O)O FBRJYBGLCHWYOE-UHFFFAOYSA-N
B-3	2-(trifluoromethyl)benzamide FC(F)(F)c1ccccc1C(N)=O QBAYIBZITZBSFO-UHFFFAOYSA-N
AB-1	3-oxo-2-phenyl-3-[2-(trifluoromethyl)phenyl]propanenitrile FC(F)(F)c1ccccc1C(=O)C(C#N)c1ccccc1 WTSIEPMTPQJZRF-UHFFFAOYSA-N
AB-6	2-methoxyethyl 2-(4-tert-butylphenyl)-3-oxo-3-[2-(trifluoromethyl)benzamido]propanoate FC(F)(F)c1ccccc1C(=O)NC(=O)C(c1ccc(cc1)C(C)(C)C)C(=O)OCCOC RKBXBKGAVYGWOD-UHFFFAOYSA-N
A-2	4-tert-butylphenyl)acetonitrile CC(C)(C)c1ccc(CC#N)cc1 FGFFQKZKAJOZKS-UHFFFAOYSA-N
TFA	Trifluoroacetic acid FC(F)(F)C(=O)O DTQVDTLACAAQTR-UHFFFAOYSA-N	CF₃COOH

References

EFSA (European Food Safety Authority), 2012. Conclusion on the peer review of the pesticide risk assessment of the active substance cyflumetofen. EFSA Journal 2012;10(1):2504, 77 pp. [DOI: https://dx.doi.org/10.2903/j.efsa.2012.2504]

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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 cyflumetofen. To assess the occurrence of cyflumetofen residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EU) No 188/2011 and the MRLs established by the Codex Alimentarius Commission as well as European authorisations reported by Member States and the UK. 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.

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Title

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

Author

Bellisai, Giulia; Bernasconi, Giovanni; Brancato, Alba; Carrasco Cabrera, Luis; Ferreira, Lucien; Giner, German; Greco, Luna; Jarrah, Samira; Kazocina, Aija; Leuschner, Renata; Magrans, Jose Oriol; Miron, Ileana; Nave, Stefanie; Pedersen, Ragnor; Reich, Hermine; Ruocco, Silvia; Santos, Miguel; Scarlato, Alessia Pia; Theobald, Anne; Vagenende, Benedicte; Verani, Alessia

Section

Reasoned Opinion

Publication year

2021

Publication date

Aug 1, 2021

Publisher

John Wiley & Sons, Inc.

ISSN

18314732

Source type

Scholarly Journal

Language of publication

English

DOI

https://doi.org/10.2903/j.efsa.2021.6812

ProQuest document ID

2566510397

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

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