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

TL;DR

This paper discusses the modification of maximum residue levels for cyflufenamid in various crops to ensure consumer safety.

Contribution

The study provides new maximum residue level proposals for cyflufenamid in multiple small fruits and berries.

Findings

Adequate analytical methods are available to control cyflufenamid residues at 0.01 mg/kg.

EFSA concluded that cyflufenamid residues are unlikely to pose a risk to consumer health.

MRL proposals were derived for parsley, berries, and other small fruits.

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Certis Belchim B.V. submitted a request to the competent national authority in France to modify the existing maximum residue levels (MRLs) for the active substance cyflufenamid in parsley, raspberries (red and yellow), blackberries, blueberries, cranberries, currants, gooseberries, rose hips, mulberries, azaroles/Mediterranean medlars, elderberries and other small fruits and berries. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all the requested crops. Adequate analytical methods are available to control the residues of cyflufenamid according to the enforcement residue definition in plant matrices under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of cyflufenamid according to the reported agricultural practices is unlikely to present a risk to consumer health.

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Full text

SUMMARY

In accordance with Article 6 of Regulation (EC) No 396/2005, Certis Belchim B.V. submitted an application to the competent national authority in France (Evaluating Member State, EMS) to modify the existing maximum residue levels (MRLs) for the active substance cyflufenamid in parsley, raspberries (red and yellow), blackberries and crops belonging to the subgroup ‘other small fruits and berries’ (blueberries, cranberries, currants (black, red and white), gooseberries (green, red and yellow), rose hips, mulberries (black and white), azaroles/Mediterranean medlars, elderberries).

The EMS drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to the European Food Safety Authority (EFSA) on 28 February 2023. To accommodate for the intended uses of cyflufenamid, the EMS proposed to raise the existing MRLs from the limit of quantification (LOQ) of 0.02 to 0.4 mg/kg for parsley; from the LOQ of 0.01 to 0.09 mg/kg for other small fruits and berries; and from 0.07 to 0.08 mg/kg for blackberries and raspberries (red and yellow). On 9 March 2023 the European Commission sent a mandate to EFSA to assess the application and the evaluation report as required by Article 10 of the MRL regulation.

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified data gaps and points which needed further clarification, which were requested from the EMS. On 11 July 2025, the EMS submitted the requested information in a revised evaluation report, which replaced the previously submitted evaluation report.

Based on the conclusions derived by EFSA in the framework of Directive 91/414/EEC, the data evaluated under previous MRL assessments and the additional data provided by the EMS in the framework of this application, the following conclusions are derived.

The metabolism of cyflufenamid in primary crop was investigated in crops belonging to the groups of fruit crops (apples, cucumbers), cereals/grass (wheat) and pulses/oilseeds (rapeseeds).

Studies investigating the effect of processing on the nature of cyflufenamid (hydrolysis studies) demonstrated that the active substance is stable. Only studies with cyflufenamid radiolabel in the fluorinated phenyl ring were available while the cyclopropyl ring was not investigated. Considering stability in the available hydrolysis study with fluorinated phenyl ring, no further data is required under this application.

In rotational crops, the available metabolism studies confirmed that the metabolic pathway is similar to that in primary crops.

Based on the metabolic pattern identified in metabolism studies, hydrolysis studies, the toxicological profile of E‐isomer (which is of similar toxicity as cyflufenamid (Z‐isomer)), the capability of the analytical methods and the potential isomerisation observed in the storage stability studies, the residue definition for enforcement set in the MRL legislation is the ‘sum of cyflufenamid (Z‐isomer) and its E‐isomer, expressed as cyflufenamid’. EFSA proposed a slightly different residue definition for enforcement and risk assessment in plant products: ‘sum of cyflufenamid (Z‐isomer) and its E‐isomer’. However, there is no substantial difference between the two expressions. The risk assessment residue definition is applicable to primary and rotational crops.

EFSA concluded that, for the crops assessed in this application, the metabolism of cyflufenamid has been sufficiently addressed and the previously derived residue definitions apply.

Sufficiently validated analytical methods based on gas chromatography with mass spectrometry (GC–MS) and liquid chromatography with tandem mass spectrometry (LC–MS/MS) are available to quantify residues in the crops assessed in this application. The methods enable quantification of the total residues of Z and E isomers (without differentiation) at or above the LOQ of 0.01 mg/kg in the crops assessed.

The available residue trials are sufficient to derive MRL proposals of 0.4 mg/kg for parsley, 0.08 mg/kg for blackberries and raspberries (red and yellow) and 0.09 mg/kg for crops belonging to the ‘other small fruits and berries’ subgroup. It is to be noted that the derived MRL for raspberries (red and yellow) and blackberries is based on a French use marked as ‘N or S’ (residue data accepted from south (S) and/or north (N) zone) in Annex II of SANCO 7525/VI/95. Therefore, the six available trials (3NEU + 3 SEU) were deemed sufficient to derive the proposed MRL.

Specific studies investigating the magnitude of cyflufenamid residues in processed commodities are not required, as residues above the threshold value of 0.1 mg/kg are not expected in raw agricultural commodities (RAC) of raspberries (red and yellow), blackberries and commodities belonging to the ‘other small fruits and berries’ and, since the total theoretical maximum daily intake (TMDI) is below the trigger value of 10% of the acceptable daily intake (ADI) for all the assessed crops. Although residue levels in parsley occur slightly above 0.1 mg/kg, considering its contribution to the overall exposure is 0.04% of ADI and 0.4% ARfD, the large margin of safety and given that it is a minor crop, no further data on processing is required under this application.

The occurrence of cyflufenamid residues in rotational crops was investigated in the framework of the EU peer review and the MRL review. Based on the available information on the nature of residues and considering the dose rate employed in the available metabolism study, it is concluded that significant residue levels are unlikely to occur in rotational crops, provided that the active substance is used according to the proposed Good Agricultural Practices (GAPs).

Residues of cyflufenamid in commodities of animal origin were not assessed since the crops under consideration in this MRL application are normally not fed to livestock.

The toxicological profile of cyflufenamid was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC, and the data were sufficient to derive an ADI of 0.04 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.05 mg/kg bw. The E‐isomer of cyflufenamid and the metabolite 149‐F1, included in their respective residue definitions, were considered of similar toxicity as the parent active substance (making the derived ADI and ARfD applicable to them as well).

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The short‐term exposure assessment was performed only for the commodities assessed in the present MRL application, in accordance with the internationally agreed methodology. The acute consumer exposure accounted for a maximum of 1% of ARfD (blackberries). It is noted that no specific data for the short‐term consumption of mulberries, elderberries, rose hips and Azarole/ Mediterranean medlar are available. However, the exposure calculations performed with the whole commodity subgroup (‘other small fruits and berries’ (0154000)) of respective crops indicate low acute exposure, thus confirming that no acute intake concerns will be associated with the consumption of these commodities. The highest estimated long‐term dietary intake accounted for 6% of the ADI (NL toddler diet). The maximum contribution of cyflufenamid residues expected from commodities assessed in the present MRL application to the overall long‐term exposure was 0.03% of the ADI (currants (red, black and white)).

EFSA concluded that the proposed use of cyflufenamid on parsley, raspberries (red and yellow), blackberries and other small fruits and berries will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

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

Full details of all end points and the consumer risk assessment can be found in Appendices B, C, D.Codea CommodityExisting EU MRL (mg/kg)Proposed EU MRL (mg/kg)Comment/justification Enforcement residue definition: Cyflufenamid (sum of cyflufenamid (Z‐isomer) and its E‐isomer, expressed as cyflufenamid)F 0153010Blackberries0.070.08 The submitted data on raspberries is sufficient for extrapolation to blackberries and to derive an MRL proposal from the French use (N or S). Risk for consumers is unlikely. 0153030Raspberries (red and yellow)0.070.08 The submitted data are sufficient to derive an MRL proposal from the French use (N or S). Risk for consumers is unlikely. 0154000Other small fruits and berries0.01* 0.09 The submitted data on black currants is sufficient for extrapolation to the whole subgroup and to derive an MRL proposal for the NEU use. Risk for consumers is unlikely. 0256040Parsley0.02* 0.4 The submitted data are sufficient to derive an MRL proposal for the SEU use. Risk for consumers is unlikely. Abbreviations: MRL, maximum residue level; N, North zone; NEU, northern Europe; S, South zone; SEU, southern Europe.*Indicates that the MRL is set at the limit of analytical quantification (LOQ). ^a^ Commodity code number according to Annex I of Regulation (EC) No 396/2005. ^F^ Fat soluble.

ASSESSMENT

The European Food Safety Authority (EFSA) received an application to modify the existing MRLs for cyflufenamid in parsley, raspberries (red and yellow), blackberries and crops belonging to the subgroup ‘other small fruits and berries’ (blueberries, cranberries, currants (black, red and white), gooseberries (green, red and yellow), rose hips, mulberries (black and white), azaroles/Mediterranean medlars, elderberries and ‘others’). The detailed description of the intended uses of cyflufenamid, which are the basis for the current MRL application, is reported in Appendix A.

Cyflufenamid is the ISO common name for (Z)‐N‐[−(cyclopropylmethoxyimino)‐2,3‐difluoro‐6‐(trifluoromethyl)benzyl]‐2‐phenylacetamide (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Cyflufenamid was evaluated in the framework of Directive 91/414/EEC1 with United Kingdom designated as rapporteur Member State (RMS) for the representative uses as a foliar treatment on wheat, rye and barley. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2009). Cyflufenamid was approved2 for the use as fungicide only on 1 April 2010.

The process of peer review for the renewal of the first approval has been completed not yet been initiated.

The EU MRLs for cyflufenamid are established in Annexes II of Regulation (EC) No 396/2005.3 The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has been performed (EFSA, 2018b) and the proposed modifications have been implemented in the MRL legislation. After completion of the MRL review, EFSA has issued reasoned opinions on the setting of an import tolerance for cyflufenamid in hops and modification of MRLs for blackberries and raspberries (red and yellow). The proposals from these reasoned opinions have been considered in recent MRL regulations.4

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified data gaps and points which needed further clarification, which were requested from the EMS. On 11 July 2025 the EMS submitted the requested information in a revised evaluation report (France, 2023), which replaced the previously submitted evaluation report.

EFSA based its assessment on the evaluation report submitted by the EMS (France, 2023), the DAR and its addendum (United Kingdom, 2006, 2008) prepared under Council Directive 91/414/EEC, the Commission review report on cyflufenamid (European Commission, 2009), the conclusion on the peer review of the pesticide risk assessment of the active substance cyflufenamid (EFSA, 2009), as well as the conclusions from previous EFSA opinions, including the opinion on the review of the existing maximum residue levels for cyflufenamid according to Article 12 of Regulation (EC) No 396/2005 (EFSA, 2011, 2014, 2016, 2018b, 2021a, 2021b).

For this application, the data requirements established in Regulation (EU) No 544/20115 and the guidance documents applicable at the date of submission of the application to the EMS are applicable (European Commission, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2000, 2010, 2017, 2021, 2023; OECD, 2011). The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/2011.6

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

The evaluation report submitted by the EMS (France, 2023) and the exposure calculations using the EFSA PRIMo are considered as supporting documents to this reasoned opinion and, thus, are made publicly available as background documents to this reasoned opinion.7

RESIDUES IN PLANTS

1

Nature of residues and methods of analysis in plants

1.1

Nature of residues in primary crops

1.1.1

The metabolism of cyflufenamid following foliar applications in primary crops belonging to the groups of fruit crops (apples and cucumbers), cereals/grass (wheat), pulses/oilseeds (rapeseeds) was investigated in the framework of the EU pesticides peer review and previous MRL applications (EFSA, 2009, 2011, 2016). These studies were also considered in the MRL review under Article 12 of Regulation (EC) No 396/2005 (EFSA, 2018b). In the crops tested, the metabolic pathway of cyflufenamid was similar. The parent compound (Z‐isomer) was the main residue, representing between 99% (forage) and 7% (grain and seeds) of the total radioactive residues (TRR). The TRR in grain and seed was generally low, as well as extractability and certain fractions were only characterised (up to 40% in seed). For this reason, the parent compound was low, but still the main identified compound in these two commodities. Other metabolites were identified in the investigated crops in insignificant amounts (< 10% TRR).

Cyflufenamid E‐isomer was quantified in wheat samples at levels up to approximately 10% of the level of cyflufenamid (up to 4% TRR), which is significantly higher than the content of the E‐isomer in the technical material of cyflufenamid. This indicated a shift in the isomer ratio of the Z‐isomer to the E‐isomer. The E‐isomer was found in low concentrations (up to 2% TRR) in apple, cucumber and rapeseed with no significant isomeric conversion from the Z‐isomer to E‐isomer.

The metabolism of cyflufenamid was investigated with radiolabel in the phenyl ring only (except in one wheat study where the cyclopropyl ring was investigated). However, further studies were not deemed needed or required (EFSA, 2018b).

For the intended uses, the metabolic behaviour in primary crops is sufficiently addressed.

Nature of residues in rotational crops

1.1.2

Cyflufenamid is proposed to be used on parsley, which may be grown in rotation. According to the soil degradation studies assessed in the framework of the peer review, the DT90 values for cyflufenamid and its soil‐relevant metabolites 149‐F1 and 149‐F6 exceed 100 days. Thus, an investigation of residues in rotational crops is required.

A confined rotational crop study with cyflufenamid radiolabeled on the fluorinated phenyl ring was assessed during the peer review and MRL review (EFSA, 2009, 2018b). Cyflufenamid was applied at 50 g a.s./ha on bare soil. Spring wheat (cereals) was planted at nominal plant‐back intervals (PBI) of 30, 120 and 270 days after treatment (DAT), carrots (root and tuber vegetables) at 30 and 120 DAT, and lettuce (leafy vegetables) at 30 DAT. The translocation of radioactive residues was low. The maximum TRR in crop parts intended for human consumption was 0.006 mg eq/kg in lettuce, sampled at 30 PBI. The highest levels of TRR were found in wheat straw, with a maximum of 0.09 mg eq/kg at 30 PBI. Parent cyflufenamid was not found in the plants. Due to the low TRR, limited characterisation was performed and only a single compound found in carrot foliage was identified as 149‐F6 (33% TRR, corresponding to 0.041 mg eq/kg). Although metabolism studies performed in primary crops and soil were conducted with one label only, no further investigation of the second label was required (EFSA, 2018b). Further rotational crop metabolism studies with different labelling were considered unnecessary, and the metabolism of primary and rotational crops was concluded to be similar.

Nature of residues in processed commodities

1.1.3

The effect of processing on the nature of cyflufenamid residues was investigated in the framework of the previous MRL application on hops (EFSA, 2021a). Studies were conducted with cyflufenamid radiolabelled in the fluorinated phenyl ring. As a result, unchanged cyflufenamid represented 91%–92% of applied radioactivity (AR), which demonstrates that it is hydrolytically stable under standard processing conditions of pasteurisation, baking, brewing, boiling and sterilisation.

Up to 7% of AR was converted to the (E)‐isomer under pasteurisation, baking, brewing, boiling and sterilisation. In addition, under sterilisation conditions, metabolite 149‐F was found up to 1% AR, while 5% of AR remained unidentified (others/unknown fractions, see Appendix B.1.1.1).

Since the stability of cyflufenamid is demonstrated by the available study with phenyl label, no significant degradation products containing cyclopropyl ring only are expected under the standard hydrolysis conditions (maximum observed degradation is 5% of the applied radioactivity under sterilisation, reported as ‘others/unknown’). For this reason, no further studies investigating the fate of the cyclopropyl ring are required under this application.

Analytical methods for enforcement purposes in plant commodities

1.1.4

Analytical methods for the determination of residues of cyflufenamid in plants were assessed during the EU pesticides peer review, previous MRL applications and the MRL review (EFSA, 2009, 2011, 2018b, 2021a). The GC–MS method is sufficiently validated for the determination of total residues of cyflufenamid (Z‐isomer) and its E‐isomer, in accordance with the residue definition for enforcement (sum of E and Z isomers), in high‐water and high‐acid content commodities and in dry commodities.

The multiresidue QuEChERS (quick, easy, cheap, effective, rugged and safe) method using LC–MS/MS is sufficiently validated for the determination of residues of cyflufenamid (Z‐isomer) in high‐water, high‐acid content and dry commodities. A variation of the QuEChERS method for vegetable oil samples (QuOil method) was also reported for routine analysis, although a validated primary analytical method for enforcement in high‐oil content commodities is not available (EFSA, 2018b). According to the MRL review, the two available QuEChERS methods could cover both isomers measured as Z‐isomer, since rapid conversion of the E‐ to the Z‐isomer occurs during the analysis. Thus, the methods could cover both isomers measured as Z‐isomer (EFSA, 2018b).

All methods allow determination of residues at or above the limit of quantification (LOQ) of 0.01 mg/kg for both isomers together (see Section B.1.1.1).

In a previous MRL application, the high performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) method has been validated for monitoring of cyflufenamid (Z‐isomer) in hops, with the LOQ of 0.01 mg/kg (EFSA, 2021a). The method was validated for the Z‐isomer only.

Crops under assessment belong to the high‐acid and high‐water content commodity groups; therefore, sufficiently validated analytical methods are available for the determination of the total residues of cyflufenamid (Z‐isomer) and its E‐isomer in the plant commodities under consideration. It is noted that the methods cannot specifically discriminate between both isomers.

EFSA notes that the extraction efficiency for the analytical methods applied for enforcement is not proven as indicated in SANCO/825/00. EFSA would therefore recommend reconsidering this point in the framework of the peer review for the renewal of approval of the active substance.

Storage stability of residues in plants

1.1.5

The storage stability of cyflufenamid (Z‐isomer) and its E‐isomer in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review and a previous MRL application (EFSA, 2009, 2014). These studies were also considered in the framework of the MRL review (EFSA, 2018b).

The storage stability of the sum of isomers, Z and E, was examined in high‐water content (immature barley shoots) commodity (EFSA, 2009). Samples were fortified with cyflufenamid (Z‐isomer); however, since the technical material contained low concentrations of E‐isomer, and the analytical method could not separate the two isomers, the study covered the stability of the sum of the two isomers. The data showed that residues of cyflufenamid (sum of isomers) are stable in high‐water commodity for at least 25 months when stored at −18°C.

The storage stability of the two isomers separately was investigated in high‐oil (oilseed rape), high‐protein (dry beans), high‐starch (wheat grain) and high‐acid (grape) content commodities (EFSA, 2014). In samples (fresh or frozen) fortified with cyflufenamid (Z‐isomer), a slight isomerisation to E‐isomer was observed (4%). In frozen and freshly fortified samples with E‐isomer, the isomerisation to cyflufenamid (Z‐isomer) ranged from 4% to 23% and 2% to 24% respectively, indicating that isomerisation primarily occurred during sample preparation.

In the investigated high‐acid, high‐starch and high‐protein content commodities, the available studies demonstrated the storage stability of cyflufenamid (Z‐isomer) and its E‐isomer, separately, for 24 months when stored at −18°C. Cyflufenamid (Z‐isomer) was stable in high‐oil content commodity for at least 18 months when frozen at −18°C, while for the E‐isomer, recoveries below 70% were observed at the sampling points of 3 (63% recovery) and 18 months (67%). Although it was not clearly elucidated whether these low recoveries were related to isomerisation to the Z‐isomer, it is not expected that this has an impact on the assessment, as no degradation was observed for the sum of isomers.

The summary of the demonstrated storage stability periods in different crop commodities is presented in Appendix B.1.1.2.

For the crops assessed in the framework of this application, storage stability of cyflufenamid (Z‐isomer) and its E‐isomer is addressed. Previously assessed studies demonstrate stability for 24 months in high‐acid commodities and 25 months in high‐water commodities when stored at −18°C.

Proposed residue definitions

1.1.6

Based on the metabolic pattern identified in metabolism studies, the results of hydrolysis studies, the toxicological profile of E‐isomer (which is of similar toxicity as cyflufenamid (Z‐isomer)), the capabilities of enforcement analytical methods (which cannot specifically discriminate between both isomers) and the storage stability studies (showing that potential isomerisation might occur), EFSA proposed the residue definition in primary crops as follows:

• residue definition for enforcement: sum of cyflufenamid (Z‐isomer) and its E‐isomer
• residue definition for risk assessment: sum of cyflufenamid (Z‐isomer) and its E‐isomer

However, EFSA's proposal for the enforcement residue definition has not been implemented in the MRL legislation. Therefore, the residue definition for enforcement set in Regulation (EC) No 396/2005 is:

• residue definition for enforcement: sum of cyflufenamid (Z‐isomer) and its E‐isomer, expressed as cyflufenamid.

Based on the metabolism data and the capability of the analytical methods available, there is no substantial difference between the two expressions (EFSA, 2018b, 2021a). The residue definitions are also applicable to rotational crops. EFSA concluded that these residue definitions are appropriate for the crops under assessment.

Magnitude of residues in plants

1.2

Magnitude of residues in primary crops

1.2.1

In support of the MRL application, the applicant submitted residue trials conducted in parsley, black currants and raspberries (red and yellow). The samples were separately analysed for the parent compound (Z‐isomer) and its E‐isomer, both included in the residue definitions for enforcement and risk assessment. According to the assessment of the EMS, the methods used were sufficiently validated and fit for purpose.

EFSA notes that the extraction efficiency of the analytical methods used in the residue trials is not proven, as indicated by SANTE 2017/10632. For the analytical methods used to analyse raspberry and black currant samples, the solvent used is comparable to the one used in the apple metabolism study (acetonitrile and acetonitrile/water). However, apple is a high‐water matrix while raspberries and black currants are belong to the high‐acid matrix group. No further bridging data between the apple matrix, which could be considered slightly acidic and the acidic matrix has been provided. The lack of these data introduces additional uncertainty into the present assessment.

The samples of the provided residue trials were stored under conditions for which the integrity of the samples has been demonstrated.

Parsley, SEU: SC; 2 × 15 g a.s./ha; 10 days application interval; BBCH 20–89; PHI 3 days

In support of the intended uses in SEU, the applicant submitted a total of four GAP‐compliant and independent supervised residue trials on parsley, conducted in 2017 in southern France. As per Regulation (EU) No 544/2011, residue field trials are required to be performed over two seasons. Additional justification on different soil types and crop varieties has been provided, and, together with the fact that a distance of at least 20 km is present among all of them, is considered sufficient to address the variability in weather conditions and agricultural practices. It is noted that the last application was made at an earlier growth stage (BBCH 19) compared to the most critical stage allowed by the intended GAP (BBCH 89). However, in the case of parsley, this is not expected to have an impact on the final residue levels since the edible part of the crop had already developed by the time of application, and because harvest of parsley leaves can occur at various stages of maturity, while the samples were taken at the intended PHI. Two field trials were designed as decline, with the sampling points at 0, 3 and 7 PHIs. Decline of cyflufenamid (Z‐isomer) has been observed over the tested time intervals, with the highest residues at 0 day of PHI and the lowest at 7 days of PHI. Decline of E‐isomer was observed from 0 day PHI to 3 and 7 days PHI, at which it was found < LOQ. The other two field trials were sampled in line with the intended GAP (3 days PHI).

Cyflufenamid (Z‐isomer) residues ranged from 0.05 to 0.15 mg/kg. Residues of its E‐isomer were below the LOQ (0.01 mg/kg) at the intended PHI. The data are considered sufficient to derive an MRL proposal of 0.4 mg/kg for cyflufenamid in parsley.

Other small fruits and berries, NEU: SC; 2 × 15 g a.s./ha; 10–11 days application interval; BBCH 19–87; PHI 3 days

In support of the intended uses in NEU, the applicant submitted a total of four GAP‐compliant and independent supervised residue trials on black currants, conducted in 2016 in northern France. As per Regulation (EU) No 544/2011, residue field trials are required to be performed over two seasons. Additional justification has been provided, including the use of different crop varieties, planting across different years (ranging from 1992 to 2014), and variations in rainfall. Combined with the fact that all locations are at least 20 km apart, this is considered sufficient to account for variability in weather conditions and agricultural practices. Two trials were designed as decline, with the sampling points at 0, 3 and 7 PHIs. Decline of cyflufenamid (Z‐isomer) has been observed over the tested time intervals, with the highest residues at 0 day of PHI and the lowest at 7 days of PHI. No decline could be addressed for the E‐isomer as residues were always below the LOQ (0.01 mg/kg) at all tested PHI intervals. The other two field trials were sampled in line with the intended GAP (3 days PHI).

Cyflufenamid (Z‐isomer) residues ranged from < 0.01 mg/kg (LOQ) to 0.04 mg/kg. Residues of its E‐isomer were always below the LOQ (0.01 mg/kg). The data is considered sufficient to derive an MRL proposal of 0.09 mg/kg for cyflufenamid for all the crops belonging to the subgroup of ‘other small fruits and berries’ as extrapolation from black currant is foreseen by SANTE/2019/12752 (European Commission, 2023).

Raspberries, blackberries (use reported by FR – NEU/SEU): SC; 2 × 15 g a.s./ha; 7–11 days application interval; BBCH 19–87; PHI 3 days

In support of the uses intended in France, the applicant submitted in total six GAP‐compliant and independent supervised residue trials on raspberry, conducted in 2016 and 2017 in northern (three trials) and southern (three trials) France.

As per Regulation (EU) No 544/2011, four residue trials per zone would be required to support a GAP intended in both NEU and SEU. For this reason, EFSA initially requested additional field trials per each zone, to satisfy the applicable data requirement and to derive an MRL covering both NEU and SEU zones. No further data was provided; however, since the requested uses are in France, additional considerations were given to SANTE/2019/12752 guidance.

According to Annex II of the guidance raspberries and blackberries (cane fruit) are minor crops without data on area and production and/or not clearly reattached to one zone in France (European Commission, 2023). In the guidance, these crops are reported as ‘N or S’ in Annex II (distribution of crops in France), which is further explained by specifying that a dataset consisting of both NEU and/or SEU field trials is sufficient to support French uses on these minor crops. Therefore, a minimum number of four trials (any combination of NEU and/or SEU trials) is deemed sufficient to support this French use on minor crops. Consequently, such a dataset is also deemed sufficient to derive an MRL. It is also noted that, under the new data requirements, as per Regulation (EU) No 283/2013, six trials equally distributed over both zones would be sufficient as the GAPs for the two zones are the same and on minor crops. Given the sufficiency of the field trials due to the use on minor crops and on French territory, taking also into account the future (new) data requirements, the combined data set of six submitted trials is considered sufficient to propose an MRL for raspberries and blackberries.

Two (one in NEU and one in SEU) out of the six provided field trials were designed as decline, with the sampling points at 0, 3 and 6–7 PHIs. Given the minority of the crops and the intended uses in France, a minimum of two decline trials is sufficient, as four trials in total is needed to derive an MRL for a minor crop. Decline of cyflufenamid (Z‐isomer) has been observed over the tested time intervals, with the highest residues at 0 day of PHI and the lowest at 7 days of PHI. No decline could be addressed for the E‐isomer as residues were always below the LOQ (0.01 mg/kg) at all tested PHI intervals. The other two field trials were sampled in line with the intended GAP (3 days PHI).

Cyflufenamid (Z‐isomer) residues ranged from < 0.01 mg/kg (LOQ) to 0.04 mg/kg. Residues of its E‐isomer were always below the LOQ (0.01 mg/kg). The combined NEU and SEU data is considered sufficient to derive an MRL proposal of 0.08 mg/kg for cyflufenamid for raspberries and blackberries. It should be noted that this MRL is derived from the use intended in France, using the specific rules of the EU guidance document on extrapolations that are applicable to French uses.

Magnitude of residues in rotational crops

1.2.2

There are no available studies investigating the magnitude of residues in rotational crops.

Based on the results of the rotational confined crop study and considering that cyflufenamid was applied to a bare soil (interception of the active substance by the plants is expected in practice), the MRL review concluded that residue levels of cyflufenamid in rotational commodities are not expected to exceed 0.01 mg/kg, provided that cyflufenamid is applied in compliance with the assessed GAPs (EFSA, 2018b).

Since the maximum annual application rate for the crops under consideration (i.e. 30 g a.s./ha) is lower from the maximum annual application rate assessed in the MRL review and lower than the application rate tested in the confined rotational crop study (50 g a.s./ha), it is concluded that no residues in rotated crops are expected following the uses under the present assessment, provided that the active substance is applied according to the proposed GAPs.

Magnitude of residues in processed commodities

1.2.3

Specific studies investigating the magnitude of cyflufenamid residues in processed commodities of crops belonging to the subgroup of other small fruits and berries, together with raspberries and blackberries, were not submitted and are not required. Residues in raw commodities from the provided residue field trials resulted below the trigger value of 0.1 mg/kg, and the overall dietary contribution of these commodities is less than 10% of ADI, when TMDI is considered (calculation with the proposed MRL values carried out) (European Commission, 1997d).

For parsley, residues occurred up to 0.16 mg/kg in the available field trials. Its contribution to the acute exposure accounts for 0.4% of ARfD, and the chronic exposure, when TMDI taken into account is 0.04% of ADI. Since parsley is a minor crop and given the large margin of safety for the acute and chronic exposure, no further data on the magnitude of cyflufenamid residues is considered as needed under this application.

Proposed MRLs

1.2.4

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for the commodities under evaluation (see Appendix B.4.).

For raspberries (red and yellow) and blackberries, it is highlighted that the MRL is based on a use intended in France. Therefore, the required number of trials was assessed considering the rules laid down in Annex II of SANCO 7525/VI/95. Hence, the six available trials (3NEU + 3SEU) were deemed sufficient to derive the proposed MRL.

In Section 3, EFSA assessed whether residues on all the assessed crops resulting from the intended uses are likely to pose a consumer health risk.

RESIDUES IN LIVESTOCK

2

Not relevant as crops under assessment are not used for feed purposes.

CONSUMER RISK ASSESSMENT

3

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

The toxicological reference values for cyflufenamid used in the risk assessment (i.e. ADI and ARfD values) were derived in the framework of the EU pesticides peer review (European Commission, 2009). The E‐isomer, included in the risk assessment residue definition in plants and animals, and the metabolite 149‐F1, included in the risk assessment residue definition in animals, were considered to be of similar toxicity as the parent (Z‐isomer) and the derived ADI and ARfD are applicable to them as well (EFSA, 2009).

Short‐term (acute) dietary risk assessment

The short‐term exposure assessment was performed on the commodities assessed in this application. The calculations were based on the HR (highest residue) values derived from supervised field trials and the complete list of input values can be found in Appendix D.1.

The estimated short‐term exposure did not exceed the ARfD for any of the crops assessed in this application. The acute consumer exposure accounted for the maximum of 1% of ARfD (blackberries) (see Appendix B.3). No specific data for the short‐term consumption of mulberries and elderberries (for both children and adults), for rose hips (for children) and Azarole/ Mediterranean medlar (for adults) are available. However, the exposure calculations performed with the whole commodity subgroup of respective crops (‘other small fruits and berries’ (0154000)) indicate low acute exposure, thus confirming that no acute intake concerns will be associated with the consumption of these commodities.

Long‐term (chronic) dietary risk assessment

In the framework of the previous MRL application on blackberries and raspberries (red and yellow) a comprehensive long‐term exposure assessment was performed, taking into account the existing uses at EU level, including also previously assessed use in hops (EFSA, 2021b). EFSA now updated the calculation with the relevant STMR (supervised trial median residue) values derived from the residue trials submitted in support of this MRL application for parsley, blackberries, raspberries (red and yellow) and crops belonging to the subgroup of ‘other small fruits and berries’ (blueberries, cranberries, currants (black, red and white), gooseberries (green, red and yellow), rose hips, mulberries (black and white), Azaroles/Mediterranean medlars, elderberries and ‘others’). An adjustment factor, derived and used for hops in EFSA (2021b) to take into consideration possible contribution of the E‐isomer (not measured in field trials) was considered for hops in the present calculation.

The input values used in the exposure calculations are summarised in Appendix D.1.

The estimated long‐term dietary intake accounted for a maximum of 6% of the ADI (NL toddler diet). The contribution of residues expected in the commodities assessed in this application to the overall long‐term exposure is presented in detail in Appendix B.3.

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

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

CONCLUSION AND RECOMMENDATIONS

4

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal for parsley, raspberries (red and yellow), blackberries and commodities belonging to the subgroup of other small fruits and berries (0154000).

It is to be noted that the derived MRL for raspberries (red and yellow) and blackberries is based on French use marked as ‘N or S’ in Annex II of SANCO 7525/VI/95. Therefore, the six available trials (3NEU + 3 SEU) were deemed sufficient to derive the proposed MRL.

EFSA concluded that the proposed use of cyflufenamid on assessed crops will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

The MRL recommendations are summarised in Appendix B.4.ABBREVIATIONSADIacceptable daily intakeARapplied radioactivityARfDacute reference dosea.s.active substanceBBCHgrowth stages of mono‐ and dicotyledonous plantsbwbody weightCACCodex Alimentarius CommissionCFconversion factor for enforcement to risk assessment residue definitionCXLCodex maximum residue limitDARdraft assessment reportDATdays after treatmentDT_90_ period required for 90% dissipation (define method of estimation)EMSevaluating Member StateGAPGood Agricultural PracticeGC–MSgas chromatography with mass spectrometryGLPGood Laboratory PracticeHPLC–MS/MShigh performance liquid chromatography with tandem mass spectrometryHPLC‐UVDhigh performance liquid chromatography with ultra‐violet detectorHRhighest residueIEDIinternational estimated daily intakeIESTIinternational estimated short‐term intakeILVindependent laboratory validationISOInternational Organisation for StandardisationIUPACInternational Union of Pure and Applied Chemistry K oc organic carbon adsorption coefficientLCliquid chromatographyLODlimit of detectionLOQlimit of quantificationMRLmaximum residue levelMS/MStandem mass spectrometry detectorNEUnorthern EuropeOECDOrganisation for Economic Co‐operation and DevelopmentPBIplant‐back intervalPFASpolyfluoroalkyl substancesPHIpre‐harvest interval P ow partition coefficient between n‐octanol and waterPRIMo(EFSA) Pesticide Residues Intake ModelQuEChERSQuick, Easy, Cheap, Effective, Rugged, and Safe (analytical method)RArisk assessmentRACraw agricultural commodityRDresidue definitionRMSrapporteur Member StateSANCODirectorate‐General for Health and ConsumersSCsuspension concentrateSMILESsimplified molecular‐input line‐entry systemSEUsouthern EuropeSTMRsupervised trials median residueTMDItheoretical maximum daily intakeTRRtotal radioactive residueWHOWorld Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2023‐000193

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