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

Abstract

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 fenpyrazamine. To assess the occurrence of fenpyrazamine residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Directive 91/414/EEC as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent unacceptable risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and one MRL proposal derived by EFSA still requires further consideration by risk managers.

Summary

Fenpyrazamine was included in Annex I to Directive 91/414/EEC on 1 January 2013 by Commission Implementing Regulation (EC) No 595/2012, and has been deemed to be approved under Regulation (EC) No 1107/2009, in accordance with Commission Implementing Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011. As the active substance was approved after the entry into force of Regulation (EC) No 396/2005 on 2 September 2008, the European Food Safety Authority (EFSA) is required to provide a reasoned opinion on the review of the existing maximum residue levels (MRLs) for that active substance in compliance with Article 12(1) of the aforementioned regulation. To collect the relevant pesticide residues data, EFSA asked Austria, as the designated rapporteur Member State (RMS), to complete the Pesticide Residues Overview File (PROFile) and to prepare a supporting evaluation report. The PROFile and evaluation report provided by the RMS were made available to the Member States. A request for additional information was addressed to the Member States in the framework of a completeness check period, which was initiated by EFSA on 25 January 2017 and finalised on 24 March 2017. After having considered all the information provided, EFSA prepared a completeness check report which was made available to Member States on 22 May 2017.

EFSA prepared in August 2017 a draft reasoned opinion, which was circulated to Member States for consultation via a written procedure based on the conclusions derived by EFSA in the framework of Directive 91/414/EEC and the additional information provided by the RMS and Member States, Comments received by 25 September 2017 were considered during the finalisation of this reasoned opinion. The following conclusions are derived.

The metabolism of fenpyrazamine following foliar application was studied in grapevine (fruit crop), lettuce (leafy crop) and oilseed rape (pulses/oilseed) with the test substance labelled either on the phenyl‐ or pyrazolyl moiety. The metabolism of fenpyrazamine was comparable in all crops investigated. Standard processing studies evidenced that fenpyrazamine was stable under conditions simulating processing by pasteurisation, baking/brewing/boiling and sterilisation.

Following review of the available metabolism studies, the residue definition for enforcement was proposed as parent compound fenpyrazamine only and for risk assessment as the sum of parent and S‐1188‐DC, expressed as fenpyrazamine. The same definitions are applicable to rotational crops and processed commodities.

A validated liquid chromatography with tandem mass spectrometric (LC–MS/MS) method is available to enforce the proposed residue definition in plant with a limit of quantification (LOQ) of 0.01 mg/kg in high water and high oil content, acidic and dry commodities.

All residue trials were analysed for both the parent fenpyrazamine and the metabolite S‐2188‐DC. The available data are considered sufficient to derive MRL proposals as well as risk assessment values for apricots, cherries, peaches, plums, table and wine grapes, blackberries, dewberries, raspberries blueberries, tomatoes, peppers, aubergines and cucurbits with edible peel. For almonds, only a tentative MRL could be derived.

Residues of fenpyrazamine, S‐2188‐DC and S‐2188‐OH above LOQ are not expected in crops grown in rotation according to the supported use pattern and based on the submitted rotational crop field study. Robust processing factors could be derived for grape juice, white wine, red wine, wet pomace and raisins.

Fenpyrazamine is not authorised for use on crops that might be fed to livestock. Therefore, further investigation of the occurrence of residues in commodities of animal origin is not required and the setting of MRLs in these commodities is not considered necessary. However, available metabolism studies performed on goat and hen indicated that fenpyrazamine and S‐2188‐DC should be defined as the residue definition for monitoring while for risk assessment the inclusion of metabolites S‐2188‐CH₂OH‐DC and MZZP should be considered. A method for enforcement of fenpyrazamine and/or its metabolites in animal commodities is currently not available and at present not required. The EURLs provided a screening quantitative method for fenpyrazamine in honey, muscle (red meat, white meat, fish) and milk and milk products with a screening detection limit (SDL) of 0.005 mg/kg for monitoring purposes.

Chronic and acute consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). According to the results of this calculation, the highest chronic exposure represented 5.1% of the acceptable daily intake (ADI) (WHO, cluster diet B) and the highest acute exposure amounted to 78.2% of the acute reference dose (ARfD) (peaches).

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 fenpyrazamine was included in Annex I to Council Directive 91/414/EEC on 1 January 2013 by means of Commission Implementing Regulation (EU) No 595/20123, and has been deemed to be approved under Regulation (EC) No 1107/20094, in accordance with Commission Implementing Regulation (EU) No 540/20115, as amended by Commission Implementing Regulation (EU) No 541/20116, EFSA initiated the review of all existing MRLs for that active substance.

According to the legal provisions, EFSA shall base its reasoned opinion in particular on the relevant assessment report prepared under Directive 91/414/EEC. It should be noted, however, that, in the framework of Directive 91/414/EEC, 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 Directive 91/414/EEC 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.

Austria, the designated rapporteur Member State (RMS) in the framework of Directive 91/414/EEC, was asked to complete the PROFile for fenpyrazamine and to prepare a supporting evaluation report (Austria, 2013). The PROFile and the supporting evaluation report were submitted to EFSA on 11 March 2013 and made available to the Member States. A request for additional information was addressed to the Member States in the framework of a completeness check period which was initiated by EFSA on 25 January 2017 and finalised on 24 March 2017. Additional evaluation reports were submitted by Belgium, Germany, Italy and the European Union Reference Laboratories for Pesticide Residues (Belgium, 2017; EURLs, 2017; Germany, 2017; Italy, 2017) and, after having considered all the information provided by RMS and Member States, EFSA prepared a completeness check report which was made available to all Member States on 22 May 2017. Further clarifications were sought from Member States via a written procedure in May–June 2017.

Based on the conclusions derived by EFSA in the framework of Directive 91/414/EEC and the additional information provided by the Member States, EFSA prepared in August 2017 a draft reasoned opinion, which was submitted to Member States for commenting via a written procedure. All comments received by 25 September 2017 were considered by EFSA during the finalisation of the reasoned opinion.

The evaluation report submitted by the RMS (Austria, 2013) and the evaluation reports submitted by Member States Belgium, Germany, Italy and the European Union Reference Laboratories for Pesticide Residues (Belgium, 2017; EURL, 2017; Germany, 2017; Italy, 2017) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available.

In addition, key supporting documents to this reasoned opinion are the completeness check report (EFSA, 2017a) and the Member States consultation report (EFSA, 2017b). These reports are developed to address all issues raised in the course of the review, from the initial completeness check to the reasoned opinion. Also, the chronic and acute exposure calculations for all crops reported in the framework of this review performed using the EFSA Pesticide Residues Intake Model (PRIMo) (excel file) and the PROFile are key supporting documents and made publicly available as background documents to this reasoned opinion. Furthermore, 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

Fenpyrazamine is the ISO common name for S‐allyl 5‐amino‐2,3‐dihydro‐2‐isopropyl‐3‐oxo‐4‐(o‐tolyl) pyrazole‐1‐carbothioate (IUPAC).

Fenpyrazamine is a non‐systemic fungicide belonging to the pyrizole chemical family. It is used for the control of grey mould (Botrytis). Although it is classified as non‐systemic, limited translocation in plants was observed. Fenpyrazamine shows its fungicidal activity through inhibition on germ tube elongation and mycelium elongation. However, the biochemical mechanism of fungicidal activity is not clarified (EFSA, 2012a).

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

Fenpyrazamine was evaluated as a new active substance in the framework of Directive 91/414/EEC with Austria designated as the RMS. The representative uses supported for the peer review process were as a foliar application as a fungicide on tomato, aubergine, pepper, cucurbits with edible peel (glasshouse), and field use on grapes. Following the peer review, which was carried out by EFSA (2012a), it was approved in accordance with Regulation (EC) No 1107/2009 by Commission Implementing Regulation (EU) No 595/2012, which entered into force on 1 January 2013. According to Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011, fenpyrazamine is deemed to be approved under Regulation (EC) No 1107/2009. After the Annex I inclusion, confirmatory data in the area of physical chemical proprieties addressing the confirmatory data identified during the peer review were submitted in the framework of the Directive 91/414/EEC and assessed by EFSA (2014a).

The EU MRLs for fenpyrazamine are established in Annexes IIIA of Regulation (EC) No 396/2005 and CXL(s) for fenpyrazamine are not available. 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 under Article 10 of the Reg. 396/2005 (EFSA, 2016)	Regulation (EU) No 2016/1902	Modification of MRLs in blueberries and cane fruits
MRL application under Article 10 of the Reg. 396/2005 (EFSA, 2014a,b)	Regulation (EU) No 2015/401	Modification of MRLs in apricots, cherries, plums
MRL modification under Article 10 of the Reg. 396/2005 (EFSA, 2012a,b)	Regulation (EU) No 500/2013	Modification of MRLs in peaches and strawberries
MRL modification under Article 10 of the Reg. 396/2005 (EFSA, 2011)	Regulation (EU) No 322/2012	Modification of MRLs in table and wine grapes, tomatoes, peppers, aubergines, cucurbits with edible peel

For the purpose of this MRL review, the critical uses of fenpyrazamine currently authorised within the EU, as well as uses authorised in third countries that might have a significant impact on international trade, have been collected by the RMS and reported in the PROFile. The additional good agricultural practices (GAPs) reported by Member States during the completeness check were also considered. The details of the authorised GAPs for fenpyrazamine are given in Appendix A.

Assessment

EFSA has based its assessment on the PROFile submitted by the RMS, the evaluation report accompanying the PROFile (Austria, 2013), the draft assessment report (DAR) and its addendum prepared under Council Directive 91/414/EEC (Austria, 2011a,b), the conclusion on the peer review of the pesticide risk assessment of the active substance fenpyrazamine (EFSA, 2012a), the previous reasoned opinions on fenpyrazamine (EFSA, 2011, 2012b, 2014b, 2016) as well as the evaluation reports submitted during the completeness check (Belgium, 2017; EURL, 2017; Germany, 2017; Italy, 2017). 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 546/20117 and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (European Commission, 1997a, b, c, d, e, f, g, 2000, 2010a, b, 2016; 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.

1. Residues in plants

1.1. Nature of residues and methods of analysis in plants

1.1.1. Nature of residues in primary crops

The metabolism of fenpyrazamine following foliar application was studied in grapevine (fruit crop), lettuce (leafy crop) and oilseed rape (pulses/oilseed) with the test substance labelled on the phenyl‐ or pyrazolyl moiety in two independent studies for each crop. The metabolism of fenpyrazamine was comparable in all crops investigated.

The parent fenpyrazamine was the major component of radioactive residues with the majority found in surface rinses (88–95% total radioactive residue (TRR) (13.8–41.5 mg/kg) in grapes; 81–92% TRR (96–260 mg/kg) in grape foliage; 71–72% TRR (8.19–8.63 mg/kg) in lettuce; 61–67% TRR (0.88–1.22 mg/kg) in immature foliage of oil seed rape; 50–60% TRR (1.42–1.48 mg/kg) in oilseeds rape haulm and 16–22% TRR (0.005–0.007 mg/kg) in seeds) (Austria, 2011a).

In addition to the parent, the metabolite S‐2188‐DC was common to all crop metabolism studies and was found in lettuce leaves and in oilseed rape haulms at levels above 10% TRR and in grapes at levels of 1–5% TRR (0.22–1.17 mg/kg). The metabolite S‐2188‐OH was further common to all crop metabolism studies, however, below levels of 10% TRR in all crops (Austria, 2011a).

1.1.2. Nature of residues in rotational crops

Fenpyrazamine is authorised for use on strawberries, tomatoes, peppers, cucurbits with edible peel which may be grown in rotation. According to the soil degradation studies evaluated in the framework of the peer review, periods required for 90% dissipation (DT₉₀ values) of fenpyrazamine in field studies up to 134 days, which is higher than the trigger value of 100 days (EFSA, 2012a). Therefore, further investigation of residues in rotational crops was performed and evaluated.

During the peer review, the metabolism in rotational crops was studied in lettuce, carrots and wheat grown after soil application of pyrazolyl‐5‐¹⁴C‐labelled fenpyrazamine at 2.83 kg a.s./ha (corresponding to 4.7 N maximum rate). Since no cleavage of the bridge between the phenyl‐ and pyrazolyl ring was observed, labelling of one moiety was considered sufficient.

The metabolism of fenpyrazamine in three rotational crop studies covering cereals, root and tuber vegetables, and leafy crops was similar to the pathway in primary crops although the presence of the major metabolite S‐2188‐DC of the total residues in primary crops was found only in rotated wheat straw and grain and not in the edible parts of the other rotated crops because it was rapidly hydroxylated into S‐2188‐OH.

During the peer review, it was concluded that the metabolism of fenpyrazamine in rotational crops is similar to the pathway observed in primary crops (EFSA, 2012a). This conclusion is supported in this review.

1.1.3. Nature of residues in processed commodities

The effect of processing under standard hydrolyses conditions on the nature of residues was investigated in the framework of the peer review (Austria, 2011a). The residue behaviour of pyrazolyl‐labelled fenpyrazamine was studied under conditions simulating pasteurisation (20 min at 90°C, pH 4), baking/brewing/boiling (60 min at 100°C, pH 5) and sterilisation (20 min at 120°C, pH 6) in compliance with good laboratory practice (GLP). Since no cleavage of the bridge between the phenyl‐ and pyrazolyl ring was observed, labelling of one moiety was considered sufficient.

From these studies, it can be concluded that fenpyrazamine as major compound (99–101% before and 97–102% after incubation) is stable under conditions simulating processing by pasteurisation, baking/brewing/boiling and sterilisation while up to 8.6% of the applied radioactivity degraded into the metabolite S‐2188‐DC at sterilisation. No other degradation product was identified.

1.1.4. Methods of analysis in plants

A liquid chromatography with tandem mass spectrometric (LC–MS/MS) method is available for monitoring fenpyrazamine in all plant matrices with a limit of quantification (LOQ) of 0.01 mg/kg. The method is validated in high water, high acid, high oil and dry commodities (Austria, 2011a).

Furthermore, the EURLs provided a Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method for fenpyrazamine using LC–MS/MS supported by validation data in high water content and high acid content commodities, a LC–QqQ‐MS/MS method for dry commodities and a LC‐Q‐ToF method for high oil content commodities with a LOQ of 0.01 mg/kg (EURLs, 2017).

1.1.5. Stability of residues in plants

In the framework of the peer review, storage stability of fenpyrazamine and S‐2188‐DC together in one study was demonstrated in high acid, high water, high oil content and dry commodities at −18°C for 12 months. The metabolite S‐2188‐OH was investigate in an independent study and was stable in high acid, high oil and dry commodities for 12 months and in high water content commodities for 6 months at −18°C (EFSA, 2012a). A data gap was identified for almonds for storage stability study to confirm stability of fenpyrazamine and S‐2188‐DC in the samples for 818 days at −18°C (EFSA, 2012b).

1.1.6. Proposed residue definitions

As the parent was shown to be the major component of the residues, the peer review concluded that the definition for monitoring can be limited to parent fenpyrazamine. For risk assessment, considering that metabolite S‐2188‐DC was present at up to 11% TRR in lettuce (1.2 mg/kg) and detected in significant amounts in the supervised residue trials on grape, the definition was proposed as ‘sum of fenpyrazamine and S‐2188‐DC, expressed as fenpyrazamine’ (EFSA, 2012a).

Following review of the available metabolism studies, EFSA confirms that the residue definitions derived during the peer review are still considered valid. The same definitions are applicable to rotational crops and processed commodities.

A fully validated analytical method is available for the enforcement of the proposed residue definition in high water, high acid, high oil content and dry commodities with a LOQ of 0.01 mg/kg, respectively.

1.2. Magnitude of residues in plants

1.2.1. Magnitude of residues in primary crops

To assess the magnitude of fenpyrazamine residues resulting from the reported GAPs, EFSA considered all residue trials reported by the RMS in its evaluation report (Austria, 2013), including residue trials evaluated in the framework of the previous MRL applications (EFSA, 2011, 2012b, 2014b, 2016) and additional data submitted during the completeness check (Belgium, 2017; Germany, 2017; Italy, 2017).

Residue trial samples considered in this framework were stored in compliance with the demonstrated storage conditions with the exception of almonds supporting the import tolerance (US) which were stored for 818 days. Decline of residues during storage of the trial samples is not expected, except for the samples of almonds. Therefore, the validity of the residue trials supporting the import tolerance GAP on almonds is further to be demonstrated by providing adequate storage stability studies.

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, 2016).

All residue trials were analysed for both the parent fenpyrazamine and the metabolite S‐2188‐DC. For an expression of the magnitude of residue according to the residue definition for risk assessment for each pair of residues, the concentration of the metabolite was first converted into parent equivalent by using a molecular conversion factor of 1.43 based on the ratio between the molecular weights of the two compounds and was then added to the fenpyrazamine residue.

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

• Strawberries: only four trials on strawberries are available to support the northern and southern outdoor GAP, respectively. Although a MRL was derived from the fully supported EU indoor GAP and import tolerance (US), four additional trials on strawberries to support the northern EU outdoor GAP and four additional trials on strawberries to support the southern EU outdoor GAP are still required.

• Blueberries: one out of the seven available trials is overdosed at second application; however, since the residue level at harvest was within the range of the other GAP‐compliant trials it is considered acceptable. Therefore, no additional trials are required.

It is noted that for tomatoes, peppers, aubergines and cucurbits with edible peel, more critical indoor GAPs not supported by data are authorised in Belgium (see comment field of the GAP table in Appendix A for details).

1.2.2. Magnitude of residues in rotational crops

In the confined rotational crop studies evaluated during the peer review (see also Section 1.1.2), total TRRs recovered in all edible parts of rotational crops were very low with exception of mature carrot where fenpyrazamine was found at 0.57 mg eq./kg (30 days after treatment (DAT)) and 0.17 mg eq./kg (120 DAT). Considering that the application rate represented 4.7 N maximum rate, this is corresponding to 0.12 mg eq./kg and 0.08 mg eq./kg, respectively.

Considering the critical GAPs (cGAPs) reported in this review (three applications at BBCH 61–87 at a rate of 600 g a.s./ha), assuming a soil density of 1.5 g/L, soil depth of 5 cm, crop interception of 80% and considering a DT₅₀ in soil of 20.5 days, the plateau concentration derived in soil during the peer review, taking into account accumulation over the years, is 0.002 mg/kg soil over three years (EFSA, 2012a,b).

A rotational field crops study was performed in southern Europe (Spain and Italy). The tomato primary crop was treated at the application rate of 3 × 0.6 kg a.s./ha with a 6–8 days interval and was harvested 3 days after application. The application rate is covering the authorised GAP rate (Appendix A). The succeeding crops (carrot, lettuce, tomato and barley) were sown 1 month, 4 months (8 months in case of tomato) and 12 months after the last application on tomatoes and were grown to maturity.

At harvest, the edible parts of the rotational crops were analysed for the residues of fenpyrazamine and its metabolite S‐2188‐OH, none of which were found above the LOQ of the analytical method (0.01 mg/kg) in the succeeding crops sown 1, 4 (or 8) and 12 months after the final application on the primary tomato crop.

In this study, information on the soil used, soil cultivation practice (soil density, soil ploughing (mixing) depth is provided; however, the fenpyrazamine soil concentration in the root zone was not available. Therefore, it is not possible to conclude whether the plateau concentration expected after use of fenpyrazamine at the cGAP (0.002 mg/kg soil) is covered by these studies. Nevertheless, considering that the indicative plateau concentration is below the LOQ of 0.01 mg/kg, it can be concluded that a significant accumulation of fenpyrazamine in soil is not expected.

Therefore, based on the submitted confined and rotational crop field studies, it is concluded that residues of fenpyrazamine, S‐2188‐DC and S‐2188‐OH above the LOQ are not expected in crops grown in rotation according to the supported use pattern.

1.2.3. Magnitude of residues in processed commodities

Studies investigating the magnitude of residues using grapes for wine, juice, wet pomace and raisin production were evaluated during the peer review (Austria, 2011a,b). An overview of these studies is given in Appendix B.1.2.3.

Robust processing factors could be derived for grape juice, grape white wine, red wine, grape wet pomace and raisins analysed for fenpyrazamine and S‐2188‐DC. 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.

1.2.4. Proposed MRLs

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under assessment except for almonds, for which only tentative MRLs could be derived.

2. Residues in livestock

Fenpyrazamine is not authorised for use on crops that might be fed to livestock. Further investigation of the occurrence of residues in commodities of animal origin is not required and the setting of MRLs in these commodities is not considered necessary (European Commission, 2012). Nevertheless, goat and poultry metabolism studies are available and were assessed for completeness. The metabolism in rats, poultry and ruminants was similar. Contrary to plants, the metabolism in animals was more extensive and more complex, with numerous metabolites or fractions characterised, all accounting for very low levels (0.01–0.05 mg/kg).

Studies on hen and goats were performed with ¹⁴C‐fenpyrazamine labelled on the pyrazolyl moiety only, as no cleavage of the bridge between phenyl‐ and pyrazolyl rings occurred in the rat metabolism. Only 0.2% and 0.8% of the administered radioactivity was recovered in poultry (fed 0.7 mg/kg body weight (bw) per day for 7 days) and goat (fed 0.36 mg/kg bw per day for 5 days) matrices, respectively.

In hens, the TRR levels in egg, muscle, fat, liver and blood were very low. Fenpyrazamine was present at very low levels in egg yolk and egg white (0.001 mg/kg; 3.5% TRR), fat (0.008 mg/kg; 42.6% TRR) and liver (0.004 mg/kg; 2.1% TRR). The metabolite S‐2188‐DC was detected at very low levels in egg (0.004 mg/kg; 25.1% TRR), muscle (0.001 mg/kg; 4.5% TRR) and liver (0.005 mg/kg; 2.1% TRR). Dealkylation of S‐2188‐DC resulted in formation of MPPZ (chromatographic peaks not resolved) which was reported in eggs, muscle and liver above 10% TRR (15.9–34.1% TRR).

Fenpyrazamine was only found in goat liver (0.03 mg/kg; 13.7% TRR) and fat (0.002 mg/kg; 17.5% TRR). Metabolite S‐2188‐DC was found in milk (0.002 mg/kg; 8.6% TRR), muscle (0.003 mg/kg; 24.9% TRR), liver (0.04 mg/kg; 17.1% TRR), kidney (0.04 mg/kg; 21.5% TRR) and fat (0.002 mg/kg; 25.9% TRR). Metabolite S‐2188‐CH₂OH‐DC (free and conjugated) was reported above 10% TRR (12.7–29.2% TRR) in muscle, kidney and liver.

During the peer review, metabolism studies performed on domestic animals (goat and hen) indicated that fenpyrazamine and S‐2188‐DC should be defined as the residue definition for monitoring and for risk assessment the inclusion of metabolites S‐2188‐CH₂OH‐DC (relevant for ruminant matrices) and MZZP (relevant for poultry matrices) was proposed (EFSA, 2012a). During this review, these residue definitions for monitoring and risk assessment are still considered relevant. Nevertheless, it is underlined that the proposed residue definitions may need to be reconsidered in case uses on crops fed to livestock are authorised in the future.

A method for enforcement of fenpyrazamine and/or its metabolites was not provided during the peer review. During this review the EURLs provided a screening LC–MS‐Q‐ToF quantitative method for fenpyrazamine which is supported by validation data for honey, muscle (red meat, white meat, fish), and milk and milk products with a screening detection limit (SDL) of 0.005 mg/kg (EURLs, 2017).

Storage stability of fenpyrazamine and metabolites (including S‐2188‐DC, MPZZ, S‐2188‐OH, S‐2188‐CH₂OH‐DC) was demonstrated indicatively for 9 and 4 months in frozen stored samples of the goat and hen metabolism studies, respectively. It is reported that samples were stored frozen without specifying the storage temperature; however, it is assumed that it was at −18°C (Austria, 2011a).

3. Consumer risk assessment

Chronic and acute exposure calculations for all crops reported in the framework of this review were performed using revision 2 of the EFSA PRIMo (EFSA, 2007). 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.

The exposures calculated were compared with the toxicological reference values for fenpyrazamine, derived by EFSA (2012a) under Directive 91/414/EEC. The highest chronic exposure was calculated for WHO cluster diet B, representing 5.1% of the acceptable daily intake (ADI), and the highest acute exposure was calculated for peaches, representing 78.2% of the ARfD. Based on these calculations, EFSA concludes that although uncertainties remain due to the data gaps identified in the previous sections, this indicative exposure calculation did not indicate an unacceptable risk to consumers.

Conclusions

The metabolism of fenpyrazamine following foliar application was studied in grapevine (fruit crop), lettuce (leafy crop) and oilseed rape (pulses/oilseed) with the test substance labelled either on the phenyl‐ or pyrazolyl moiety. The metabolism of fenpyrazamine was comparable in all crops investigated. Standard processing studies evidenced that fenpyrazamine was stable under conditions simulating processing by pasteurisation, baking/brewing/boiling and sterilisation.

Following review of the available metabolism studies, the residue definition for enforcement was proposed as parent compound fenpyrazamine only and for risk assessment as the sum of parent and S‐1188‐DC, expressed as fenpyrazamine. The same definitions are applicable to rotational crops and processed commodities.

A validated LC–MS/MS method is available to enforce the proposed residue definition in plant with a LOQ of 0.01 mg/kg in high water and high oil content, acidic and dry commodities.

All residue trials were analysed for both the parent fenpyrazamine and the metabolite S‐2188‐DC. The available data are considered sufficient to derive MRL proposals as well as risk assessment values for apricots, cherries, peaches, plums, table and wine grapes, blackberries, dewberries, raspberries blueberries, tomatoes, peppers, aubergines and cucurbits with edible peel. For almonds, only a tentative MRL could be derived.

Residues of fenpyrazamine, S‐2188‐DC and S‐2188‐OH above LOQ are not expected in crops grown in rotation according to the supported use pattern and based on the submitted rotational crop field study. Robust processing factors could be derived for grape juice, white wine, red wine, wet pomace and raisins.

Fenpyrazamine is not authorised for use on crops that might be fed to livestock. Therefore, further investigation of the occurrence of residues in commodities of animal origin is not required and the setting of MRLs in these commodities is not considered necessary. However, available metabolism studies performed on goat and hen indicated that fenpyrazamine and S‐2188‐DC should be defined as the residue definition for monitoring while for risk assessment the inclusion of metabolites S‐2188‐CH₂OH‐DC and MZZP should be considered. A method for enforcement of fenpyrazamine and/or its metabolites in animal commodities is currently not available and at present not required. The EURLs provided a screening quantitative method for fenpyrazamine for honey, muscle (red meat, white meat, fish) and milk and milk products with a SDL of 0.005 mg/kg.

Chronic and acute consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 2 of the EFSA PRIMo. According to the results of this calculation, the highest chronic exposure represented 5.1% of the ADI (WHO, cluster diet B) and the highest acute exposure amounted to 78.2% of the ARfD (peaches).

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:

• a representative storage stability study covering fenpyrazamine and S‐2188‐DC for the storage period of samples of almond residue trials (818 days at −18°C) or four new residue trials on almonds supporting the import tolerance (US) with the residue samples stored according to the demonstrated storage stability conditions.

Table 2.

Proposed MRLs

Code numbera	Commodity	Existing EU MRL (mg/kg)	Outcome of the review
			MRL (mg/kg)	Comment
Enforcement residue definition: fenpyrazamine
0120010	Almonds	0.01*	0.01*	Further consideration neededb
0140010	Apricots	5	5	Recommendedc
0140020	Cherries (sweet)	4	4	Recommendedc
0140030	Peaches	4	5	Recommendedc
0140040	Plums	3	3	Recommendedc
0151010	Table grapes	3	3	Recommendedc
0151020	Wine grapes	3	3	Recommendedc
0152000	Strawberries	3	3	Recommendedc
0153010	Blackberries	5	5	Recommendedc
0153020	Dewberries	5	5	Recommendedc
0153030	Raspberries (red and yellow)	5	5	Recommendedc
0154010	Blueberries	4	4	Recommendedc
0231010	Tomatoes	3	3	Recommendedc
0231020	Sweet peppers/bell peppers	3	3	Recommendedc
0231030	Aubergines/eggplants	3	3	Recommendedc
0232010	Cucumbers	0.7	0.7	Recommendedc
0232020	Gherkins	0.7	0.7	Recommendedc
0232030	Courgettes	0.7	0.7	Recommendedc
–	Other commodities of plant and animal origin	See Regulation (EC) No 149/2008	–	Further consideration neededd

MRL: maximum residue level; CXL: codex maximum residue limit.

* Indicates that the MRL is set/proposed at the limit of quantification.

^aCommodity code number, as listed in Annex I of Regulation (EC) No 396/2005.

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

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

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

It is highlighted, however, that some of the MRLs derived result from a GAP in one climatic zone only, whereas other GAPs reported by the RMS were not fully supported by data. EFSA therefore identified the following data gaps which are not expected to impact on the validity of the MRLs derived but which might have an impact on national authorisations:

• Additional trials on strawberries;

It is also noted that for tomatoes, peppers, aubergines and cucurbits with edible peel, more critical indoor GAPs not supported by data are authorised in Belgium (see comment field of the GAP table in Appendix A for details).

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

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

CF

conversion factor for enforcement residue definition to risk assessment residue definition

cGAP

critical GAP

CXL

codex maximum residue limit

DAR

draft assessment report

DAT

days after treatment

DB

dietary burden

DM

dry matter

DT₉₀

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

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

GAP

Good Agricultural Practice

GLP

Good Laboratory Practice

HPLC–MS/MS

high performance liquid chromatography with tandem mass spectrometry

HR

highest residue

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ILV

independent laboratory validation

ISO

International Organisation for Standardization

IUPAC

International Union of Pure and Applied Chemistry

LC–MS/MS

liquid chromatography with tandem mass spectrometry

LOQ

limit of quantification

Mo

monitoring

MRL

maximum residue level

MS

Member States

MS/MS

tandem mass spectrometry detector

NEU

northern European Union

OECD

Organisation for Economic Co‐operation and Development

PBI

plant‐back interval

PF

processing factor

PHI

pre‐harvest interval

PRIMo

(EFSA) Pesticide Residues Intake Model

PROFile

(EFSA) Pesticide Residues Overview File

Q‐ToF

quadrupole time of flight

QqQ

triple quadrupole

QuEChERS

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

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

SDL

screening detection limit

SEU

southern European Union

SMILES

simplified molecular‐input line‐entry system

STMR

supervised trials median residue

ToF

time‐of‐flight

TRR

total radioactive residue

WG

water‐dispersible granule

WHO

World Health Organization

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

Crop		Region	Outdoor/indoora	Member state or country	Pest controlled	Formulation			Application										PHI or waiting period (days)d	Comments (max. 250 characters)
Common name	Scientific name					Typeb	Content		Method	Growth stagec		Number		Interval (days)		Rate
							Conc.	Unit		From BBCH	Until BBCH	Min.	Max.	Min.	Max.	Min.	Max.	Unit
Critical outdoor GAPs for northern Europe
Apricots	Armeniaca vulgaris, syn: Prunus armeniaca	NEU	Outdoor	AT, DE	Monilia laxa, Monilia fructigena	WG	500.0	g/kg	Foliar treatment – spraying	57	87		3	3	7	0.40	0.60	kg a.i./ha	1	–
Cherries	Cerasus avium, syn: Prunus avium	NEU	Outdoor	AT, DE	Monilia laxa, Monilia fructigena	WG	500.0	g/kg	Foliar treatment – spraying	57	87		3	3	7	0.40	0.60	kg a.i./ha	1	–
Peaches	Persica vulgaris, syn: Prunus persica	NEU	Outdoor	AT, CZ, HU, PL, RO, SK, SL	Monilia laxa, Monilia fructigena	WG	500.0	g/kg	Foliar treatment – spraying	57	87		3	7	7	0.40	0.60	kg a.i./ha	1	Including nectarines and similar hybrids (EFSA, 2012b)
Plums	Prunus domestica	NEU	Outdoor	AT, DE	Monilia laxa, Monilia fructigena	WG	500.0	g/kg	Foliar treatment – spraying	57	87		3	3	7	0.40	0.60	kg a.i./ha	1	–
Table grapes	Vitis vinifera	NEU	Outdoor	AT, BE, DE, CZ, HU, RO, SL, SK, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		1			0.30	0.60	kg a.i./ha	14	–
Wine grapes	Vitis vinifera	NEU	Outdoor	AT, BE, DE, CZ, HU, RO, SL, SK, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		1			0.30	0.60	kg a.i./ha	14	–
Strawberries	Fragaria x ananassa	NEU	Outdoor	AT, BE, CZ, HU, IE, NL, PL, RO, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	59	89		3	7	14	0.40	0.60	kg a.i./ha	1	–
Critical outdoor GAPs for southern Europe
Apricots	Armeniaca vulgaris, syn: Prunus armeniaca	SEU	Outdoor	BG, CY, EL, FR, ES, PT	Monilia sp.	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3		7	0.40	0.60	kg a.i./ha	1	–
Cherries	Cerasus avium, syn: Prunus avium	SEU	Outdoor	BG, CY, EL, FR, ES, PT	Monilia sp.	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3		7	0.40	0.60	kg a.i./ha	1	–
Peaches	Persica vulgaris, syn: Prunus persica	SEU	Outdoor	BG, CY, ES, FR, GR, PT	Monilia sp.	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	7	7	0.40	0.60	kg a.i./ha	1	Including nectarines and similar hybrids (EFSA, 2012b)
Plums	Prunus domestica	SEU	Outdoor	BG, CY, EL, FR, ES, PT	Monilia sp.	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3		7	0.40	0.60	kg a.i./ha	1	–
Table grapes	Vitis vinifera	SEU	Outdoor	BG, CY, ES, FR, GR, PT	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		1		7	0.40	0.60	kg a.i./ha	7	–
Wine grapes	Vitis vinifera	SEU	Outdoor	BG, CY, ES, FR, GR, PT	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		1		7	0.40	0.60	kg a.i./ha	14	–
Strawberries	Fragaria x ananassa	SEU	Outdoor	BG, CY, ES, FR, GR, IT, PT	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	7	14	0.40	0.60	kg a.i./ha	1	–
Critical indoor GAPs for northern and southern Europe (including post‐harvest treatments)
Strawberries	Fragaria x ananassa	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	59	89		3	7	14	0.40	0.60	kg a.i./ha	1	–
Tomatoes	Lycopersicon esculentum	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, IT, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Sweet peppers	Capsicum annuum	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Aubergines	Solanum melongena	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Cucumbers	Cucumis sativus	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Gherkins	Cucumis sativus	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, IT, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Courgettes	Cucurbita pepo Zucchini group	NEU/SEU	Indoor	AT, BG, CY, CZ, DE, DK, ES, FR, GR, HU, IE, LT, LV, NL, PL, PT, RO, SE, SK, SL, UK	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	61	87		3	10	14	0.40	0.60	kg a.i./ha	1	A more critical GAP is authorised in Belgium (BBCH 61‐87, 3 applications, interval 7–10 days, 1 kg a.s./ha); however, not supported by data
Critical GAPs for import tolerances (non‐European indoor, outdoor or post‐harvest treatments)
Almonds	Amygdalus communis, syn: Prunus dulcis	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/L	Foliar treatment – spraying	65	81		3				0.42	kg a.i./ha	21	Type of formulation also WG (500 g fenpyrazamine/kg)
Table grapes	Vitis vinifera	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/L	Foliar treatment – spraying	81	85		3				0.56	kg a.i./ha	3	See almonds
Wine grapes	Vitis vinifera	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/L	Foliar treatment – spraying	81	85		3				0.56	kg a.i./ha	3	See almonds
Strawberries	Fragaria x ananassa	non‐EU	Outdoor	US	Botrytis	WG	500.0	g/kg	Foliar treatment – spraying	81	87		4				0.56	kg a.i./ha	0	See almonds
Blackberries	Rubus sect. Rubus	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/kg	Foliar treatment – spraying				3	7	10		0.56	kg a.i./ha	0	Max. 3 applications per season. Max. 1,680 g/ha per season. First application at early bloom
Dewberries	Rubus caesius	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/kg	Foliar treatment – spraying				3	7	10		0.56	kg a.i./ha	0	See blackberries
Raspberries	Rubus idaeus	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/kg	Foliar treatment – spraying				3	7	10		0.56	kg a.i./ha	0	See blackberries
Blueberries	Vaccinium angustifolium; Vaccinium corymbosum; Vaccinium formosum; Vaccinium virgatum	Non‐EU	Outdoor	US	Botrytis	SC	436.0	g/kg	Foliar treatment – spraying				3	7	10		0.56	kg a.i./hL	0	Max. 3 applications per season. Max. 1,680  g/ha per season. Application when condition favour disease development and prior to infection

GAP: Good Agricultural Practice; BBCH: growth stages of mono‐ and dicotyledonous plants; PHI: preharvest interval; NEU: northern European Union; SEU: southern European Union; a.i.: active ingredient; SC: suspension concentrate; WG: water‐dispersible granule; MS: Member State.

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

^bCropLife International Technical Monograph no 2, 6th Edition. Revised May 2008. Catalogue of pesticide.

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

^dPHI: minimum preharvest interval.

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)
	Fruit crops	Grapes	Foliar, 2 × 0.75 kg a.s./ha	14, 21
	Leafy crops	Lettuce	Foliar, 3 × 0.85 kg a.s./ha	14, 28, 42
	Pulses/oilseeds	Oil seed rape	Foliar, 2 × 0.6 kg a.s./ha	46, 115
	Source: Austria (2011a)

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)
	Root/tuber crops	Carrots	Bare soil, 2.83 kg a.s./ha	30, 120, 365
	Leafy crops	Lettuce	Bare soil, 2.83 kg a.s./ha	30, 120, 365
	Cereal (small grain)	Wheat	Bare soil, 2.83 kg a.s./ha	30, 120, 365
	Source: Austria (2011a)

Processed commodities (hydrolysis study)	Conditions	Investigated?
	Pasteurisation (20 min, 90°C, pH 4)	Yes
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Yes
	Sterilisation (20 min, 120°C, pH 6)	Yes
	Source: Austria (2011a)

Can a general residue definition be proposed for primary crops?	Yes
Rotational crop and primary crop metabolism similar?	Yes
Residue pattern in processed commodities similar to residue pattern in raw commodities?	Yes
Plant residue definition for monitoring (RD‐Mo)	Fenpyrazamine
Plant residue definition for risk assessment (RD‐RA)	Sum of fenpyrazamine and S‐2188‐DC, expressed as fenpyrazamine
Conversion factor (monitoring to risk assessment)	See Appendix B.1.2.1
Methods of analysis for monitoring of residues (analytical technique, crop groups, LOQs)	High water, high acid, high oil and dry commodities: HPLC–MS/MS (DFG 19), LOQ: 0.01 mg/kg for fenpyrazamine in carrots, peppers, grapes, rape seed, and cereal (grain and straw), respectively; validation data and ILV available (Austria, 2011a) LC–MS/MS, LOQ: 0.01 mg/kg for fenpyrazamine, in high water and high acid commodities, validation data available (spinach, lemon) (EURLs, 2017) LC–QqQ‐MS/MS, LOQ: 0.01 mg/kg for fenpyrazamine in dry commodities, validation data available (oat, rye, wheat) (EURLs, 2017) LC‐Q‐ToF, LOQ: 0.01 mg/kg for fenpyrazamine in high oil commodities, validation data available (avocado) (EURLs, 2017)

a.s.: active substance; DAT: days after treatment; PBI: plant‐back interval; HPLC–MS/MS: high‐performance liquid chromatography with tandem mass spectrometry; LC–MS/MS: liquid chromatography with tandem mass spectrometry; LOQ: limit of quantification; ILV: independent laboratory validation; QqQ: triple quadrupole; ToF: time‐of‐flight.

B.1.1.2. Stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)	Stability (months)
	High water content	Lettuce	−18	12
	High oil content	Rape seed	−18	12
	Dry/high starch	Cereal grain	−18	12
	High acid content	Grapes	−18	12
	Two different storage stability studies are available: one investigating the stability of fenpyrazamine and S‐2188‐DC and a separate study investigating the metabolite S‐2188‐OH, alone for which in high water content commodities stability was demonstrated for 6 months only. Source: Austria (2011a)

B.1.2. Magnitude of residues in plants

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

Crop	Region/indoora	Residue levels observed in the supervised residue trials relevant to the supported GAPs (mg/kg)	Recommendations/comments (OECD calculations)	MRL proposals (mg/kg)	HRMo (mg/kg)b	STMRMo (mg/kg)c	CFd
Almonds	Import (US)	Mo: < 0.01; < 0.01; < 0.01; < 0.01;< 0.01 RA: < 0.02; < 0.02; < 0.02; < 0.02;< 0.02	GAP‐compliant trials on almonds (EFSA, 2012b; Austria, 2013)	0.01*, e (tentative)	0.01	0.01	1.0f
Apricots and peaches	NEU	Apricots: Mo: 0.43; 0.52 RA: 0.58; 0.67 Peaches: Mo: 0.36; 0.61; 0.76; 1.5 RA: 0.73; 0.77; 1.1; 1.59	Combined data set of trials on apricots (2) and peaches (4) compliant with GAP (Austria, 2013; EFSA, 2014b)	3	1.50	0.57	1.3
	SEU	Apricots: Mo: 0.89; 1.1; 1.6; 3.0 RA: 1.15; 1.57; 1.93; 3.79 Peaches: Mo: 0.44; 0.55; 0.7; 0.85; 0.94; 0.95; 1.1; 1.6; 2.5 RA: 0.61; 0.88; 0.94; 0.95; 1.12; 1.25; 1.26; 2.51	Combined data set of trials on apricots (4) and peaches (8) compliant with GAP (Austria, 2013; EFSA, 2014b)	5	3.00	0.95	1.3
Cherries (sweet)	NEU	Mo: 0.33; 0.36; 0.41; 0.54; 0.60; 0.82; 1.8; 1.9 RA: 0.47; 0.48; 0.59; 0.61; 0.70; 1.01; 1.94; 2.17	GAP‐compliant trials on cherries (EFSA, 2014b)	4	1.90	0.57	1.2
	SEU	Mo: 0.34; 0.61; 1.0; 1.0 RA: 0.45; 0.78; 1.23; 1.37	GAP‐compliant trials on cherries (EFSA, 2014b)	3	1.00	0.81	1.3
Plums	NEU	Mo: 0.12; 0.18; 0.19; 0.33; 0.40; 0.67; 0.84; 1.5 RA: 0.77; 0.93; 0.15; 0.21; 0.49; 1.69; 0.42; 0.22	GAP‐compliant trials on plums (EFSA, 2014b)	3	1.50	0.37	1.2
	SEU	Mo: 0.23; 0.23; 0.30; 0.36; 0.40; 0.56; 0.70; 0.87; 0.70 RA: 0.26; 0.83; 1.1; 0.67; 0.37; 0.43; 0.47; 0.44	GAP‐compliant trials on plums (EFSA, 2014b)	1.5	0.87	0.38	1.2
Table and wine grapes	Import (US)	Mo: 0.33; 0.53; 0.55; 0.71; 0.80; 0.88; 0.93; 0.91; 1.01; 1.06; 1.09; 1.10; 1.24; 2.08 RA: 0.37; 0.62; 0.66; 0.95; 1.03; 1.07; 1.39; 1.18; 1.28; 1.30; 1.26; 1.62; 1.43; 3.17	GAP‐compliant trials on grapes (EFSA, 2012b; Austria, 2013)	3	2.08	0.92	1.3
	NEU	Mo: 0.18; 0.23; 0.23; 0.29; 0.49; 0.52; 0.54; 0.74 RA: 0.22; 0.29; 0.26; 0.33; 0.60; 0.69; 0.63; 0.85	GAP‐compliant trials on grapes (Austria, 2011a,b, 2013; EFSA, 2011)	1.5	0.74	0.39	1.2
	SEU	Mo: 0.06; 0.08; 0.13; 0.15; 0.37; 0.62; 1.00; 1.20 RA: 0.07; 0.09; 0.16; 0.16; 0.44; 0.91; 1.11; 1.59	GAP‐compliant trials on grapes (Austria, 2011a,b, 2013; EFSA, 2011)	3	1.20	0.26	1.1
Strawberries	Import (US)	Mo: 0.39; 0.41; 0.54; 0.87; 0.88; 0.95; 1.3; 1.7 RA: 0.5; 0.58; 0.59; 0.94; 0.99; 1.22; 1.49; 1.8	GAP‐compliant trials on strawberries (EFSA, 2012b; Austria, 2013)	3	1.70	0.88	1.1
	NEU	Mo: 0.3; 0.64; 0.65; 1.3 RA: 0.39; 0.83; 0.84; 1.44	GAP‐compliant trials on strawberries (EFSA, 2012b; Austria, 2013)	3g (tentative)	1.30	0.65	1.3
	SEU	Mo: 0.28; 0.47; 0.54; 1.4 RA: 0.41; 0.7; 0.81; 1.66	GAP‐compliant trials on strawberries (EFSA, 2012b; Austria, 2013)	3g (tentative)	1.40	0.51	1.5
	EU	Mo: 0.24; 0.28; 0.35; 0.45; 0.76; 0.86; 0.92; 1.4 RA: 0.28; 0.36; 0.47; 0.54; 1.0; 1.07; 1.15; 2.03	GAP‐compliant trials on strawberries (EFSA, 2012b)	3	1.40	0.61	1.3
Blackberries, dewberries, raspberries	Import (US)	Blackberries: Mo: 0.53; 1.60; 2.81 RA: 0.62; 1.86; 3.22 Raspberries: Mo: 1.2; 1.55; 1,90 RA: 1.47; 2.04; 2.21	Combined data set on raspberries (3) and on blackberries (3) compliant with GAP (EFSA, 2016). Tentatively extrapolated to dewberries	5	2.81	1.58	1.2
Blueberries	Import (US)	Mo: 0.15; 0.35; 0.74; 0.92; 1.04; 1.80; 2.31; 0.38 RA: 0.22; 0.49; 0.85; 1.11; 1.27; 2.03; 2.80; 0.51	GAP‐compliant trials on blueberries (7) and one (underlined) with a second exaggerated application rate of 1,139 g/ha (EFSA, 2016). The last trial was included because last application was at requested dose rate (555 g/ha) and residue level at harvest within range of other residues (EFSA, 2016)	4	2.31	0.83	1.2
Tomatoes and aubergines	EU	Mo: 0.56; 0.65; 0.66; 0.71; 0.85; 1.40; 1.50; 1.80RA: 0.65; 0.67; 0.71; 0.74; 0.88; 1.43; 1.53; 1.83	GAP‐compliant trials on tomatoes (EFSA, 2011; Austria, 2013)	3	1.80	0.78	1.0
Sweet peppers/bell peppers	EU	Mo: 0.47; 0.58; 0.60; 0.69; 0.94; 1.20; 1.30; 1.40 RA: 0.53; 0.61; 0.75; 0.80; 1.00; 1.44; 1.46; 1.54	GAP‐compliant trials on peppers (EFSA, 2011; Austria, 2013)	3	1.40	0.82	1.1
Cucurbits with edible peel (Cucumbers, gherkins, courgettes)	EU	Mo: 0.12; 0.14; 0.15; 0.16; 0.22; 0.25; 0.33; 0.34 RA: 0.13; 0.16; 0.17; 0.17; 0.23; 0.26; 0.34; 0.38	GAP‐compliant residue trials on cucumber (EFSA, 2011; Austria, 2013)	0.7	0.34	0.19	1.1

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

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

^aNEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, Indoor: indoor EU trials or Country code: if non‐EU trials.

^bHighest residue according to the residue definition for monitoring.

^cSupervised trials median residue according to the residue definition for monitoring.

^dConversion factor for risk assessment; median of the individual conversion factors at the supported PHI for each residues trial.

^eTentative MRL is derived from trials with samples stored for a period not covered by the available storage stability studies.

^fSince both parent and the metabolite S‐2188‐DC were below LOQ, a conversion factor of 1 is proposed for risk assessment.

^gTentative MRL derived from reduced number of trials.

B.1.2.2. Residues in succeeding crops

Confined rotational crop study (quantitative aspect)

In the confined rotational crop studies evaluated during the peer review (see also Section 1.2.2), total radioactive residues (TRR) recovered in all edible parts of rotational crops were very low with exception of mature carrot where fenpyrazamine was found at 0.57 mg eq./kg (30 DAT) and 0.17 mg eq./kg (120 DAT). Considering that the application rate represented 4.7 N maximum rate, this is corresponding to 0.12 mg eq./kg and 0.08 mg eq./kg, respectively

Field rotational crop study

In succeeding crops (carrot, lettuce, tomato and barley) sown 1 month, 4 months (8 months in case of tomato) and 12 months after the last application (GAP rate) on tomatoes, were grown to maturity. Residues of fenpyrazamine and its metabolite S‐2188‐OH were below the LOQ of the analytical method (0.01 mg/kg). It is concluded that a significant accumulation of fenpyrazamine in soil and residues of fenpyrazamine above the LOQ are not expected in rotational crops

DAT: days after treatment; GAP: Good Agricultural Practice; LOQ: limit of quantification.

B.1.2.3. Processing factors

Processed commodity	Number of studiesa	Processing factor (PF)		CFP b
		Individual values	Median PF
Robust processing factors (sufficiently supported by data)
Grape, white wine	3	0.60; 0.78; 1.38	0.78	1.3
Grape, red wine (heated most)	3	0.19; 0.28; 0.48	0.28	3.4
Grape juice, pasteurised	4	0.06; 0.09; 0.16; 0.31	0.13	1.6
Grape, raisins	3	1.62; 1.67; 2.8	1.67	1.1
Grape, wet pomace	4	0.65; 1.4; 2.23; 6.29	1.82	1.04

^aStudies with residues in the RAC at or close to the LOQ were disregarded (unless concentration may occur).

^bConversion factor for risk assessment in the processed commodity; median of the individual conversion factors for each processing residues trial.

B.2. Residues in livestock

Relevant groups	Dietary burden expressed in				Most critical diet	Most critical commodity	Trigger exceeded (Y/N)
	mg/kg bw per day		mg/kg DM
	Med.	Max.	Med.	Max.
Commodities under assessment are not fed to livestock.

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)	N rate/comment
	Laying hen	0.70	7	Commodities under assessment are not fed to livestock
	Lactating goat	0.36	5	Commodities under assessment are not fed to livestock
	Source: Austria (2011a)

bw: body weight.

Time needed to reach a plateau concentration in milk and eggs (days)	Three to four days for milk and two to three days for egg white (six for egg yolk)
Metabolism in rat and ruminant similar (Yes/No)	Yes
Animal residue definition for monitoring (RD‐Mo)	Sum of fenpyrazamine and S‐2188‐DC, expressed as fenpyrazamine
Animal residue definition for risk assessment (RD‐RA)	Sum of fenpyrazamine, S‐2188‐DC, S‐2188‐CH2OH‐DC and MPPZ, expressed as fenpyrazamine (provisional)
Conversion factor (monitoring to risk assessment)	Not derived (commodities under assessments not fed to live stock)
Fat soluble residues (Yes/No)	No
Methods of analysis for monitoring of residues (analytical technique, crop groups, LOQs)	Not required and not provided during peer review Screening quantitative method: LC–MS‐Q‐ToF, SDL: 0.005 mg/kg for fenpyrazamine in animal commodities, validation data available (honey, muscle (red meat, white fish, fish), milk and milk products) (EURLs, 2017)

LC: liquid chromatography; MS: mass spectrometry; Q‐ToF: quadrupole time of flight; SDL: screening detection limit.

B.2.1.2. Stability of residues in livestock

Animal products (available studies)	Animal	Commodity	T (°C)	Stability (months)
	Laying hen lactating goat	Muscle	−18	4 9
	Laying hen lactating goat	Liver	−18	4 9
	Laying hen lactating goat	Kidney	−18	4 9
	Lactating goat	Milk	−18	9
	Laying hen	Egg	−18	4
	Storage stability studies are not available and not required. In the metabolism studies, fenpyrazamine and metabolites (including S‐2188‐DC, MPZZ, S‐2188‐OH, S‐2188‐CH2OH‐DC) were stable in animal tissues, milk and eggs for the whole duration of the studies (9 months for lactating goats and 4 months for laying hens). Source: Austria (2011a)

B.2.2. Magnitude of residues in livestock

B.2.2.1. Summary of the residue data from livestock feeding studies

Animal commodity	Residues at the closest feeding level (mg/kg)		Estimated value at 1N		MRL proposal (mg/kg)	CF
	Mean	Highest	STMR (mg/kg)	HR (mg/kg)
No studies available and not required since fenpyrazamine is not authorised for use on crops fed to livestock

B.3. Consumer risk assessment

B.3.1. Consumer risk assessment without consideration of the existing CXLs

ADI	0.13 mg/kg bw per day (EFSA, 2012a)
Highest IEDI, according to EFSA PRIMo	5.1% ADI (WHO, cluster diet B)
Assumptions made for the calculations	The calculation is based on the median residue levels in the raw agricultural commodities multiplied for the CF derived from the residue trials (Appendix B.1.2.1) The contributions of commodities where no GAP was reported in the framework of this review were not included in the calculation

ARfD	0.3 mg/kg bw (EFSA, 2012a)
Highest IESTI, according to EFSA PRIMo	78.2% ARfD (peaches)
Assumptions made for the calculations	The calculation is based on the highest residue levels in the raw agricultural commodities multiplied for the CF derived from residue trials (Appendix B.1.2.1)

ADI: acceptable daily intake; bw: body weight; IEDI: international estimated daily intake; PRIMo: (EFSA) Pesticide Residues Intake Model; WHO: World Health Organization; ARfD: acute reference dose; IESTI: international estimated short‐term intake; CF: conversion factor for enforcement residue definition to risk assessment residue definition; GAP: Good Agricultural Practice.

B.4. Proposed MRLs

Code numbera	Commodity	Existing EU MRL (mg/kg)	Outcome of the review
			MRL (mg/kg)	Comment
Enforcement residue definition: fenpyrazamine
0120010	Almonds	0.01*	0.01*	Further consideration neededb
0140010	Apricots	5	5	Recommendedc
0140020	Cherries (sweet)	4	4	Recommendedc
0140030	Peaches	4	5	Recommendedc
0140040	Plums	3	3	Recommendedc
0151010	Table grapes	3	3	Recommendedc
0151020	Wine grapes	3	3	Recommendedc
0152000	Strawberries	3	3	Recommendedc
0153010	Blackberries	5	5	Recommendedc
0153020	Dewberries	5	5	Recommendedc
0153030	Raspberries (red and yellow)	5	5	Recommendedc
0154010	Blueberries	4	4	Recommendedc
0231010	Tomatoes	3	3	Recommendedc
0231020	Sweet peppers/bell peppers	3	3	Recommendedc
0231030	Aubergines/eggplants	3	3	Recommendedc
0232010	Cucumbers	0.7	0.7	Recommendedc
0232020	Gherkins	0.7	0.7	Recommendedc
0232030	Courgettes	0.7	0.7	Recommendedc
–	Other commodities of plant and animal origin	See Regulation (EC) No 149/2008	–	Further consideration neededd

MRL: maximum residue level; CXL: codex maximum residue limit.

* Indicates that the MRL is set/proposed at the limit of quantification.

^aCommodity code number, as listed in Annex I of Regulation (EC) No 396/2005.

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

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

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

Appendix C – Pesticide Residue Intake Model (PRIMo)

• PRIMo(EU)

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
Commodities under assessment are not fed to livestock

D.2. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: fenpyrazamine and S‐2188‐DC, expressed as fenpyrazamine
Almonds	0.01*	STMRMo × CF (tentative)	0.01*	HRMo × CF (tentative)
Apricots	1.25	STMRMo × CF	3.96	HRMo × CF
Cherries (sweet)	1.05	STMRMo × CF	2.47	HRMo × CF
Peaches	1.25	STMRMo × CF	3.96	HRMo × CF
Plums	0.46	STMRMo × CF	1.81	HRMo × CF
Table grapes	1.15	STMRMo × CF	2.59	HRMo × CF
Wine grapes	1.15	STMRMo × CF	2.59	HRMo × CF
Strawberries	1.29	STMRMo × CF	2.51	HRMo × CF
Blackberries	1.84	STMRMo × CF	3.28	HRMo × CF
Dewberries	1.84	STMRMo × CF	3.28	HRMo × CF
Raspberries (red and yellow)	1.84	STMRMo × CF	3.28	HRMo × CF
Blueberries	1.01	STMRMo × CF	2.81	HRMo × CF
Tomatoes	0.81	STMRMo × CF	1.86	HRMo × CF
Sweet peppers/bell peppers	0.92	STMRMo × CF	1.58	HRMo × CF
Aubergines/eggplants	0.81	STMRMo × CF	1.86	HRMo × CF
Cucumbers	0.20	STMRMo × CF	0.36	HRMo × CF
Gherkins	0.20	STMRMo × CF	0.36	HRMo × CF
Courgettes	0.20	STMRMo × CF	0.36	HRMo × CF

STMR: supervised trials median residue; Mo: monitoring; CF: conversion factor for enforcement residue definition to risk assessment residue definition; HR: highest residue.

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

Appendix E – Decision tree for deriving MRL recommendations

Appendix F – Used compound codes

Code/trivial name	Chemical name	Structural formula
S‐2188‐DC	5‐amino‐4‐(2‐methylphenyl)‐2‐(propan‐2‐yl)‐1,2‐dihydro‐3H‐pyrazol‐3‐one O=C2C(c1ccccc1C)=C(N)NN2C(C)C
S‐2188‐OH	(4RS)‐5‐amino‐4‐hydroxy‐4‐(2‐methylphenyl)‐2‐(propan‐2‐yl)‐2,4‐dihydro‐3H‐pyrazol‐3‐one OC1(C(=O)N(N=C1N)C(C)C)c2ccccc2C
S‐2188‐CH2OH‐DC	5‐amino‐4‐[2‐(hydroxymethyl)phenyl]‐2‐(propan‐2‐yl)‐1,2‐dihydro‐3H‐pyrazol‐3‐one O=C2C(c1ccccc1CO)=C(N)NN2C(C)C
MPPZ	5‐amino‐4‐(2‐methylphenyl)‐1,2‐dihydro‐3H‐pyrazol‐3‐one NC=2NNC(=O)C=2c1ccccc1C
Fenpyrazamine (S‐2188)	S‐allyl 5‐amino‐2,3‐dihydro‐2‐isopropyl‐3‐oxo‐4‐(o‐tolyl)pyrazole‐1‐carbothioate CC(C)N1C(=O)C(=C(N)N1C(=O)SCC=C)c2ccccc2C

Suggested citation: EFSA (European Food Safety Authority) , Brancato A, Brocca D, De Lentdecker C, Erdos Z, Ferreira L, Greco L, Janossy J, Jarrah S, Kardassi D, Leuschner R, Lythgo C, Medina P, Miron I, Molnar T, Nougadere A, Pedersen R, Reich H, Sacchi A, Santos M, Stanek A, Sturma J, Tarazona J, Theobald A, Vagenende B, Verani A and Villamar‐Bouza L, 2017. Reasoned Opinion on the review of the existing maximum residue levels for fenpyrazamine according to Article 12 of Regulation (EC) No 396/2005. EFSA Journal 2017;15(12):5072, 34 pp. 10.2903/j.efsa.2017.5072