Setting of an import tolerance for fenazaquin in hops

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Gowan Crop Protection Limited submitted a request to the competent national authority in Greece to set an import tolerance for the active substance fenazaquin in hops imported from the United States of America. The data submitted in support of the request were found to be sufficient to derive an maximum residue limit (MRL) proposal for hops. An adequate analytical method for enforcement is available to control the residues of fenazaquin in the plant matrix 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 of fenazaquin and its toxicologically relevant plant metabolite TBPE resulting from the use of fenazaquin on imported hops from United States according to the reported agricultural practice is unlikely to present a risk to consumer health.

SUMMARY

In accordance with Article 6 of Regulation (EC) No 396/2005, Gowan Crop Protection Limited submitted an application to the competent national authority in Greece (evaluating Member State, EMS) to set an import tolerance for the active substance fenazaquin in hops in support of the authorised use in the United States of America.

The application, alongside the dossier containing the supporting data in IUCLID format, was submitted through the EFSA Central Submission System on 20 December 2021. The appointed EMS Greece assessed the dossier and declared its admissibility on 13 July 2022. Subsequently, following the implementation of the EFSA's confidentiality decision, the non-confidential version of the dossier was published by EFSA and a public consultation launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, in order to identify whether other relevant scientific data or studies are available. The consultation run from 16 June 2023 to 7 July 2023. No additional data nor comments were submitted in the framework of the consultation.

At the end of the commenting period, the EMS proceeded drafting the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 31 July 2023. The EMS proposed to establish maximum residue levels (MRLs) for hops imported from the United States of America (USA) at the level of 30 mg/kg.

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation.

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

The metabolism of fenazaquin was investigated in the framework of the EU pesticides peer review in fruit crops following foliar treatment. On the basis of this study the enforcement residue definition in fruit crops was proposed as parent fenazaquin while for the risk assessment two separate residue definitions were derived as (1) fenazaquin and (2) 2-(4-tert-butylphenyl) ethanol (TBPE), considering that the metabolite was of higher toxicity than the parent compound. The review of the existing MRLs for fenazaquin according to Article 12 of Regulation (EC) No 396/2005 (MRL review) reconsidered the available metabolism study and on the basis of data in grape leaves concluded that residue definitions proposed by the EU pesticide peer review can tentatively be extended also to leafy crops to cover authorised import tolerance on teas. In the framework of the present assessment the applicant submitted a new metabolism study investigating the nature of fenazaquin in lettuce following foliar treatment. The results of the study confirm that the main component of total radioactive residues 7 days after the foliar application is parent fenazaquin with low amounts of TBPE present. On the basis of this study, EFSA concluded that residue definitions as derived by the EU pesticide peer review can be extended to the reported authorised use on hops. Further studies investigating nature of fenazaquin in this commodity are therefore not required. The residue definitions are also applicable to processed hop commodities.

Studies investigating the effect of processing on the nature of fenazaquin (hydrolysis studies) demonstrated that the active substance is readily degraded to quinazolin-4-ol (4-OHQ), especially when subject to pasteurisation. In the absence of a study with fenazaquin labelled on phenyl moiety, the MRL review concluded that further standard hydrolysis studies with fenazaquin phenyl label are only desirable since available processing study samples have been analysed for TBPE confirming the cleavage of the molecule. The processing studies representative for the beer production which were submitted for the present assessment also provide information on the magnitude of metabolites TBPE and 4-OHQ in beer and in its processing by-products (spent hops, yeast and flocs). Submitted data confirm the formation of TBPE and 4-OHQ during the processing of beer. In line with previous conclusions, for the present MRL application on hops the lack of standard hydrolysis studies with phenyl labelled fenazaquin is not considered a major deficiency.

Investigations of residues in rotational crops are not required for the import tolerance MRL application.

Fully validated analytical methods are available for the enforcement of fenazaquin in high-water, high-oil, high-acid and dry content commodities at the limit of quantification (LOQ) of 0.01 mg/kg. In the framework of the present MRL application, the applicant submitted validation data for the determination of fenazaquin residues in hops; an ILV was also provided. The method is considered sufficiently validated for the determination of fenazaquin residues in hops at the lowest validated LOQ of 0.01 mg/kg. Extraction efficiency of the enforcement method is not proven thus introducing additional uncertainty of the present assessment.

The available residue trials are sufficient to derive an import tolerance MRL proposal of 30 mg/kg for fenazaquin in hops. Risk assessment values for TBPE were derived as necessary according to the risk assessment residue definition.

In the framework of the present assessment, the applicant submitted two studies investigating the effect of processing on the magnitude of fenazaquin residues in beer. Samples of hops (dried cones), spent hops, yeast, flocs and beer were analysed for residues of fenazaquin, TBPE and 4-OHQ. In beer, the residues of fenazaquin and TBPE were not detected. The derived processing factors for beer are tentative as, according to the data requirements applicable for the present assessment, at least three studies are required to derive robust processing factors for enforcement purposes.

Residues of fenazaquin in commodities of animal origin were not assessed since hops are normally not fed to livestock.

The toxicological profile of fenazaquin was originally assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and confirmed under the framework of 1107/2009 (amendment of approval conditions). The data were sufficient to derive an acceptable daily intake (ADI) of 0.005 mg/kg bw per day and an acute reference dose (ARfD) of 0.1 mg/kg bw. The plant metabolite TBPE, relevant for the risk assessment, is more toxic than the parent compound. Therefore, separate toxicological reference values were derived for this compound: ADI of 0.002 mg/kg bw per day and ARfD of 0.002 mg/kg bw.

The consumer risk assessment was performed separately for parent fenazaquin and its metabolite TBPE with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). In the framework of the MRL review a comprehensive long-term exposure assessment for parent fenazaquin was performed, taking into account the existing uses of fenazaquin at EU level and existing import tolerances. EFSA now updated this calculation with the supervised trials median residue (STMR) values for the Codex MRLs for tree nuts and various animal commodities which were implemented in the MRL legislation after the MRL review and with the STMR value for hops as derived from the residue trials submitted in support of this MRL application. The estimated long-term dietary intake accounted for a maximum of 22% the ADI (NL toddler diet). The short-term exposure was calculated only for hops and did not exceed the ARfD, accounting for a maximum of 2.4% of the ARfD for adults.

For TBPE the long-term consumer exposure which was performed by the MRL review was updated with the risk assessment values as derived from the submitted residue trials on hops. Regarding commodities for which Codex MRLs have been implemented in the MRL legislation (e.g. subsequent to the MRL review), no information on TBPE concentrations is available and therefore potential residues in these commodities were not considered in the exposure calculation for TBPE. The highest chronic exposure accounted for 10% of the ADI (DE child diet) with the crop under consideration contributing for a maximum of 0.03% of ADI. The acute exposure for TBPE was calculated only for the residues in hops and accounted for 4.2% of the ARfD.

EFSA concluded that the authorised use of fenazaquin on hops in the United States and subsequent residues of fenazaquin and its plant metabolite TBPE in hops will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health. The long-term consumer risk assessment for fenazaquin shall be regarded as indicative pending the assessment of the data gaps identified in the MRL review. The consumer risk assessment for TBPE is affected by non-standard uncertainty related to limited information available on the residue concentrations in teas (unprocessed and processed) and no information on residue concentrations in crops for which the CXLs are implemented in the EU legislation.

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

Full details of all end points and the consumer risk assessment can be found in Appendices B–D.

Codea	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Fenazaquinb
0700000	Hops	0.05*	30	The submitted data are sufficient to derive an import tolerance (US GAP). Risk for consumers is unlikely The tolerance established in the USA and the Codex MRL is 30 mg/kg

ASSESSMENT

The European Food Safety Authority (EFSA) received an application to set an import tolerance for the active substance fenazaquin in hops. The detailed description of the authorised use of fenazaquin in the United States of America on hops, which is the basis for the current MRL application, is reported in Appendix A.

Fenazaquin is the ISO common name for 4-tert-butylphenethyl quinazolin-4-yl ether (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Fenazaquin was evaluated in the framework of Directive 91/414/EEC¹ with Greece designated as rapporteur Member State (RMS) for the representative uses as a foliar treatment on grapes, citrus and ornamentals. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2010b). Fenazaquin was approved² for the use as an acaricide on ornamentals in greenhouses only on 1 June 2011. In 2011, Greece received an application for amendment to the conditions of approval of the active substance fenazaquin in the framework of Regulation (EC) No 1107/2009³, in order to lift the restriction and allow uses on grapes and citrus (uses for which RMS previously applied for) as well as uses on pome fruit and stone fruit (additional uses) to be authorised. The addendum to the DAR prepared by the RMS under this framework has been peer reviewed by EFSA (EFSA, 2013). The conditions of approval of the active substance fenazaquin in the EU have been amended allowing the use in greenhouse only by Commission Implementing Regulation (EU) 2018/690⁴. Certain conditions and restrictions were kept (particular attention in protecting aquatic organism, operators, bees; risk to consumers, in particular, from the residues generated during processing and conditions of use to avoid exposure to residues of fenazaquin with respect to crops for human and animal consumption).

The EU MRLs for fenazaquin are established in Annex II of Regulation (EC) No 396/2005⁵. The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has been completed (EFSA, 2020). The proposals of the MRL review and certain Codex maximum residue limits (CXLs) for fenazaquin have been implemented in the EU legislation.^6,7 In the framework of the preparation of the EU position for 54th Session of the Codex Committee on Pesticide Residues (CCPR), EFSA recently issued a scientific report on Codex MRL proposals for fenazaquin in various plant and animal commodities (EFSA, 2023). In the 54th Session of the CCPR, a reservation of the EU on the advancement of the Codex MRL proposals for fenazaquin was noted, pending the outcome of the ongoing periodic re-evaluation of fenazaquin in the EU, and due to diverging residue definitions and acute risk for peaches (FAO, 2023). Therefore EFSA is not considering those CXLs in the present assessment. The existing Codex MRL for fenazaquin in hops is established at the level of 30 mg/kg (FAO, 2017).

In accordance with Article 6 of Regulation (EC) No 396/2005 and following the provisions set by the ‘Transparency Regulation’ (EU) 2019/1381⁸, the applicant Gowan Crop Protection Limited submitted on 20 December 2021 an application to the competent national authority in Greece, alongside the dossier containing the supporting data using the IUCLID format.

The appointed EMS Greece assessed the dossier and declared its admissibility on 13 July 2022. Subsequently, following the implementation of the EFSA's confidentiality decision, the non-confidential version of the dossier was published by EFSA and a public consultation launched on the dossier. The consultation aimed to consult stakeholders and the public on the scientific data, studies and other information part of, or supporting, the submitted application, in order to identify whether other relevant scientific data or studies are available. The consultation run from 16 June 2023 to 7 July 2023. No additional data nor comments were submitted in the framework of the consultation.

At the end of the commenting period, the EMS proceeded drafting the evaluation report, in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to EFSA on 31 July 2023. The EMS proposed to establish MRLs for hops imported from the USA at the level of 30 mg/kg.

EFSA based its assessment on the evaluation report submitted by the EMS (Greece, 2023), the DAR and its addenda (Greece, 2006, 2010, 2012, 2013) prepared under Council Directive 91/414/EEC and in the framework of Regulation (EC) No 1107/2009 for the approval and the amendment to the conditions of approval of fenazaquin, the Commission review report on fenazaquin and its addendum (European Commission, 2011, 2018), the conclusion on the peer review of the pesticide risk assessment of the active substance fenazaquin (EFSA, 2010b, 2013), as well as the conclusions from previous EFSA opinions on fenazaquin (EFSA, 2010a, 2018b), including the reasoned opinion on the MRL review according to Article 12 of Regulation No 396/2005 (EFSA, 2020) and the assessment of the CXLs implemented in the EU legislation (EFSA, 2021; FAO, 2019).

For this application, the data requirements established in Regulation (EU) No 544/2011⁹ and the guidance documents applicable at the date of submission of the IUCLID application are applicable (European Commission, 1997a, 1997b, 1997c, 1997d, 1997e, 1997f, 1997g, 2010, 2011, 2017, 2020, 2021; OECD, 2008). 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 546/2011¹⁰.

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 (Greece, 2023) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available as background documents to this reasoned opinion.¹¹

RESIDUES IN PLANTS

Nature of residues and methods of analysis in plants

Nature of residues in primary crops

The metabolism of fenazaquin in primary crops belonging to the group of fruit crops has been investigated in the framework of the EU pesticides peer review and MRL review (EFSA, 2013, 2020). In all studies fenazaquin was radiolabelled in the phenyl (P- study) and quinazoline (Q- study) ring of the molecule.

In grapes, a major proportion of the total residue was present as parent fenazaquin and the levels of individual metabolites or fractions did not exceed 5% of the total radioactive residue (TRR) at harvest of the mature crop (EFSA, 2013). The cleavage of the fenazaquin molecule at the ether bridge lead to the formation of quinazolin-4-ol (4-OHQ) and 2-(4-tert-butylphenyl) ethanol (TBPE). These two metabolites were present at relevant levels in grapefruits 78 days after the early application (0.0406 mg eq./kg in the Q-study and 0.0231 mg eq./kg in the P-study, respectively) and 28 days after the late application (0.1566 mg eq./kg in the Q-study and 0.0493 mg eq./kg in the P-study, respectively). Data on the toxicity of the metabolite 4-OHQ indicated that it is less toxic than the parent; however, TBPE is of higher toxicity than fenazaquin (EFSA, 2013).

In the framework of the present MRL application, a new metabolism study investigating the nature of [phenyl-U-¹⁴C]-fenazaquin and [quinazoline-¹⁴C]-fenazaquin in lettuce following one foliar treatment at an application rate of 0.54 kg/ha was submitted (Greece, 2023). Lettuce is the main leafy vegetable for human consumption which belongs to the leafy crop metabolism group as hops. Lettuce samples were harvested 7 days after the treatment at BBCH 49 and surface washed with acetonitrile. Residues were extracted from homogenised lettuce with acetonitrile (2×, acetonitrile extracts) and acetonitrile:water (2×, 80:20 and 50:50, v/v). Majority of radioactive residues was recovered from surface washes (83.5% TRR in phenyl study and 79.9% TRR in quinazoline study) while 16.5% TRR and 20.1% TRR remained in homogenised tissue for phenyl and quinazoline study, respectively. TRR in lettuce samples were higher in P-study (10.84 mg eq./kg) than in Q-study (7.68 mg eq./kg). In total 94.7% TRR and 93.8% TRR were extracted from the lettuce plants and surface washes in the quinazoline and phenyl study, respectively. Most of the radioactivity in lettuce (surface wash plus extracts) consisted of parent fenazaquin (89.9% TRR; 9.73 mg/kg) and metabolite TBPE (0.2% TRR; 0.026 mg/kg) in phenyl label study. In the quinazoline label study main component of the TRR was parent fenazaquin (88.4% TRR; 6.78 mg/kg). In studies with both labels some unknown compounds were detected but at low individual levels (< 1.1% TRR) and were therefore not further characterised. 4-OHQ was not detected in any of the samples. The samples were stored under frozen conditions and analysed within 6 months of sampling (Greece, 2023).

On the basis of available studies, it is concluded that the nature of fenazaquin in hops is sufficiently addressed. The treatment pattern used in the metabolism studies on lettuce reflects the treatment pattern as authorised on hops in the exporting country (USA). However, in case there are future intended uses on leafy crops involving treatment patterns with longer pre-harvest intervals (PHI), more consideration shall be given to the acceptability of lettuce metabolism study. Nevertheless, the submitted metabolism study will be subject to the EU pesticides peer review in the framework of the renewal of the approval process of fenazaquin.

EFSA concludes that further studies are not required for the present MRL application on hops.

Nature of residues in rotational crops

Investigations of residues in rotational crops are not required for imported crops.

Nature of residues in processed commodities

Studies investigating the nature of residues in processed commodities were assessed by the EU pesticides peer review and by the MRL review (EFSA, 2013, 2020). Studies were conducted with radiolabelled fenazaquin on the quinazoline ring only simulating representative hydrolytic conditions for pasteurisation (20 min at 90°C, pH 4), boiling/brewing/baking (60 min at 100°C, pH 5) and sterilisation (20 min at 120°C, pH 6). The studies demonstrated that fenazaquin is readily degraded especially when subject to pasteurisation. The main degradation product is metabolite 4-OHQ (60% of the applied radioactivity).

No studies with fenazaquin labelled on phenyl moiety are available. The MRL review concluded that since the cleavage of fenazaquin at the ether bridge results in the formation of 4-OHQ and TBPE, it can be assumed that TBPE is likely formed under standard hydrolytic conditions. However, as there were no studies with the phenyl label, MRL review could not conclude with certainty. For the crop uses assessed by the MRL review, the available processing studies were analysing for the presence of both the TBPE and 4-OHQ and therefore the MRL review concluded that further hydrolysis studies with fenazaquin phenyl label are only desirable (EFSA, 2020).

The processing studies representative for the beer production which were submitted for the present assessment (see Section 1.2.3) also provide information on the magnitude of metabolites TBPE and 4-OHQ in beer and its processing intermediate and by-products (spent hops, yeast and flocs). Submitted data confirm the formation of TBPE and 4-OHQ during the processing of beer. In line with previous conclusions (EFSA, 2020), for the present MRL application on hops the lack of standard hydrolysis studies with phenyl labelled fenazaquin is not considered a major deficiency.

Analytical methods for enforcement purposes in plant commodities

During the EU pesticides peer review, an analytical method based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) was validated in high-acid content commodities with an LOQ of 0.01 mg/kg (EFSA, 2013). In an addendum to the DAR, a multiresidue method QuEChERS, which allowed the determination of parent fenazaquin in dry commodities, high-water content, high-acid content and high-oil content commodities by LC–MS/MS with a LOQ of 0.01 mg/kg was reported and is supported by an independent laboratory validation (ILV) (EFSA, 2020). The MRL review concluded that residues of fenazaquin can be monitored in all four main plant matrices with an LOQ of 0.01 mg/kg.

In the framework of the present MRL application, the applicant submitted validation data for the determination of fenazaquin residues in hops; an ILV was also provided (Greece, 2023). Methods for commodities which are difficult to analyse, like hops, are required if an authorisation for use is requested (European Commission, 2021). Residues were extracted with acetonitrile and salt mixture (magnesium sulphate and sodium acetate buffering salts). The determination of residues was performed using high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In order to demonstrate the selectivity of the method, different analytical techniques were used: two different stationary and mobile phases with different selectivity. The method is considered sufficiently validated according to EU Guidance document SANTE/2020/12830 (European Commission, 2021) for the determination of fenazaquin residues in hops at the lowest validated LOQ of 0.01 mg/kg. The analytical method has been independently validated at the LOQ of 0.01 mg/kg the determination of fenazaquin in hops.

EFSA notes that the extraction efficiency of the proposed analytical enforcement method for hops could not be proven according to the requirements of the extraction efficiency guideline SANTE 2017/10632 (European Commission, 2017) due to the lack of metabolism study with a crop belonging to the same analytical matrix group as hops (matrix difficult to analyse). The lack of these data introduces additional uncertainty to the present assessment.

Storage stability of residues in plants

Fenazaquin and its metabolites (TBPE, 4-OHQ) were found to be stable for 12 months under frozen conditions in high-acid content matrices (orange, grapes) (EFSA, 2013). In high-oil content matrix group to which hops belong, storage stability data (almonds) have been submitted under a previous MRL application and demonstrated that residues of fenazaquin and its metabolites (TBPE and 4-OHQ) were stable for 17 and 20 months, respectively, when stored under frozen condition at least in a minimum of −10°C (EFSA, 2018b).

In the framework of the present MRL application the applicant submitted two studies investigating the freezer storage stability of fenazaquin and its metabolites TBPE and 4-OHQ specifically in hops (Greece, 2023). The investigated storage time points for parent fenazaquin were 0, 65 and 393 days. Samples were stored frozen at −25 C to −10 C. In the study investigating the freezer storage stability of metabolites TBPE and 4-OHQ the samples were stored at −20°C for maximum intervals of 262 (ca. 8.6 months) and 161 days (ca. 5.3 months), respectively.

It is concluded that the freezer storage stability of fenazaquin in hops is demonstrated for at least 13 months when stored at −25 to −10°C and of TBPE for at least 8.6 months when stored at approximately −20°C.

Proposed residue definitions

Based on the available metabolism data in fruit crops (grapes) and leafy crops (lettuce), the existing toxicological characterisation of the active substance and its metabolites, the residue definitions applicable for the crops assessed under the current MRL application and processed commodities are as follows:

• Residue definition for enforcement: fenazaquin.
• Residue definition for risk assessment: fenazaquin and TBPE, considered separately.

Fenazaquin parent compound has been considered a good marker and was concluded for the enforcement residue definition, whereas the need to set a separate residue definition for risk assessment covering TBPE (2-(4-tert-butylphenyl) ethanol) was based on toxicological considerations. Toxicological studies concluded that this metabolite is more toxic than the parent fenazaquin (EFSA, 2013).

The residue definition for enforcement set in Regulation (EC) No 396/2005 is identical with the one mentioned above.

EFSA concludes that for the use of fenazaquin on hops according to the authorised use pattern, the same residue definitions as derived by the EU pesticides peer review are applicable.

Magnitude of residues in plants

Magnitude of residues in primary crops

In support of the authorised use of fenazaquin on hops in the United States, the applicant submitted 15 GAP compliant residue trials on hops, which were performed in the main hop growing areas of United States (states of Washington, Oregon, Idaho) over growing seasons of 2008, 2012, 2014. The samples were analysed for the parent compound in all trials and for metabolites TBPE and 4-OHQ in four trials. Additionally, two residue trials which were performed in 2020 in the United States to produce data for processing studies were considered valid to estimate the magnitude of fenazaquin, TBPE and 4-OHQ in treated hops (Greece, 2023).

In all residue trails, according to the registered use pattern in the United States, an adjuvant was added.

In each of the submitted trials, two sampling replicates were taken and from these values an average residue value was selected. Trials from two sites (TCI-12-350-01/02) were not considered independent and therefore among these trial sites the highest residue value was selected. Moreover, one study (TCI-14-403) represented eight replicate trials and therefore among replicate trials the highest average value was selected. Overall, 12 residue trials are available to estimate the magnitude of residues of fenazaquin and 6 trials were available to investigate the magnitude of TBPE and 4-OHQ residues in treated hops. Since hops are classified as minor crop worldwide the number of valid trials is sufficient to derive an MRL proposal and risk assessment values (European Commission, 2021). Two of the submitted residue trials (representing four replicate plots) were designed as decline trials analysing samples at the day of the treatment and 7, 14 and 21 days later. Decline data demonstrate that an increase of fenazaquin residues beyond the PHI of 7 days is not expected; a slight increase of residues of TBPE was observed in one trial at the PHI of 14 days, followed by a decrease of residues 7 days later.

The average residues of fenazaquin in hops were within a range of 0.72–13.25 mg/kg. Metabolite TBPE ranged from 0.07 to 0.46 mg/kg and metabolite 4-OHQ from 0.11 to 0.94 mg/kg. The residue data are sufficient to support the authorised use of fenazaquin on hops in the United States and to derive an MRL proposal of 30 mg/kg. For metabolite TBPE, the risk assessment values were derived. An overview of the residue trials data, MRL proposal and risk assessment values is presented in Appendix B.1.2.1.

According to the assessment of the EMS, the analytical methods used were sufficiently validated and fit for purpose (Greece, 2023). The samples of hops from the residue trials were stored under conditions for which integrity of the samples has been demonstrated (Greece, 2023).

EFSA notes that the extraction efficiency of the analytical methods applied for residue trial analysis could not be proven according to the requirements of the extraction efficiency guideline SANTE 2017/10632 (European Commission, 2017) due to the lack of metabolism study with a crop belonging to the same analytical matrix group as hops (matrix difficult to analyse) and due to the lack of hop samples with incurred residues. The lack of these data introduces additional uncertainty to the present assessment.

Magnitude of residues in rotational crops

Not relevant for the present import tolerance MRL application.

Magnitude of residues in processed commodities

In the framework of the present assessment, the applicant submitted two studies investigating the effect of processing on the magnitude of fenazaquin residues in beer (Greece, 2023). Residue trials were performed according to the authorised use pattern of fenazaquin on hops in the United States. Samples of hops (dried cones), spent hops, yeast, flocs and beer were analysed for residues of fenazaquin, TBPE and 4-OHQ. In hop dried cones residues of fenazaquin ranged from 10.7 to 13.2 mg/kg, residues of TBPE from 0.33 to 0.46 mg/kg and residues of 4-OHQ from 0.106 to 0.36 mg/kg. The presence of TBPE and 4-OHQ in processed commodities confirms that the cleavage of fenazaquin molecule occurs under conditions representative of beer production (boiling, fermentation) and EFSA considers this information sufficient to address the uncertainty related to the lack of information on the possible formation of TBPE under processing conditions (see Section 1.1.3) for the present MRL application.

In beer, residues of fenazaquin and TBPE were not detected and residues of 4-OHQ were below the LOQ. Residues of TBPE were present at quantifiable levels in spent hops (0.359–0.63 mg/kg) and yeast (0.0145–0.021 mg/kg). Generally, residues of fenazaquin and metabolite 4-OHQ were found to decrease in all processed fractions. Residues of TBPE slightly concentrate in spent hops (PF of 1.23).

The processing factor (PF) derived for beer is reported in Appendix B.1.2.3. The processing factor is tentative since a limited number of studies is available to derive robust PFs for enforcement purposes according to Regulation (EU) No 544/2011.

Proposed MRLs

The available data are considered sufficient to derive an MRL proposal (import tolerance) as well as risk assessment values for hops (see Appendix B.1.2.1). In Section 3 EFSA assessed whether residues in hops resulting from the uses authorised in the United States are likely to pose a consumer health risk.

RESIDUES IN LIVESTOCK

Investigation of fenazaquin residues in livestock is not required as hops are not used for feed purposes.

CONSUMER RISK ASSESSMENT

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

The toxicological reference values for fenazaquin used in the risk assessment (i.e. ADI of 0.005 mg/kg bw per day and ARfD value of 0.1 mg/kg bw) were derived in the framework of the EU pesticides peer review (European Commission, 2018). The plant metabolite TBPE, relevant for the risk assessment, is more toxic than the parent compound and therefore separate toxicological reference values were derived for this compound: ADI of 0.002 mg/kg bw per day and ARfD of 0.002 mg/kg bw (European Commission, 2018). A separate risk assessment was performed for TBPE.

Fenazaquin

In the framework of the MRL review a comprehensive long-term exposure assessment for parent fenazaquin was performed, taking into account the existing uses of fenazaquin at EU level and existing import tolerances (EFSA, 2020). EFSA now updated this calculation with the STMR values for Codex MRLs which were implemented in the Regulation (EU) 2022/1342¹² after the MRL review for tree nuts and various commodities of animal origin plus the STMR value for hops as derived from the residue trials submitted in support of this MRL application. Available peeling factors were used to refine calculations in certain products with inedible peel. For bovine and equine products and milk, the STMR values were as reported by the MRL review (e.g. 0.01 mg/kg) since these values were higher than derived by the JMPR (FAO, 2019). Crops on which no uses have been reported in the MRL review and no safe CXL implemented in the EU legislation, were not considered in the exposure assessment. The estimated long-term dietary intake accounted for a maximum of 22% the ADI (NL toddler diet). The contribution of residues expected in hops to the overall long-term exposure was low (1.4% of the ADI for UK adult) and is presented in more detail in Appendix B.3.

The short-term exposure assessment was performed only for hops using the HR value as derived from the supervised field trials. The short-term exposure did not exceed the ARfD for hops and accounted for 2.4% of the ARfD for adults and 0.6% ARfD for children.

The complete list of input values used in the exposure calculations can be found in Appendix D.1.

EFSA concluded that the long-term and short-term intake of fenazaquin residues resulting from the existing uses and the authorised use on hops in the United States is unlikely to present a risk to consumer health. The long-term consumer risk assessment shall be regarded as indicative pending the assessment of the data gaps identified in the MRL review to confirm tentative MRLs for a number of commodities.

TBPE

In the framework of the MRL review the long-term and short-term consumer exposure to TBPE residues was performed considering the available residue data for citrus fruits, pome fruits, almonds, peaches, strawberries, sweet peppers/bell peppers, tomatoes, aubergines, okra/lady's fingers, cucumbers, melons, watermelons and tea (EFSA, 2020). Following the MRL review, the authorised uses of fenazaquin on peaches, sweet peppers/bell peppers, aubergines, okra/lady's fingers were not supported and therefore in these commodities the residues of TBPE are not expected and these crops were excluded from the exposure assessment. EFSA updated this calculation with the risk assessment values as derived from the submitted residue trials on hops. Regarding commodities for which Codex MRLs have been implemented in the EU MRL legislation, no information on TBPE concentrations is available¹³ and therefore the contribution of residues in these commodities was not considered in the exposure calculation for TBPE. For tea the input values are indicative, pending the confirmation of TBPE levels present in tea (EFSA, 2020). The acute exposure to TBPE was calculated only for the residues in hops. The calculated exposure was then compared with the toxicological reference values of TBPE as derived by the EU pesticides peer review. The complete list of input values used in the exposure calculations can be found in Appendix D.1.

The highest chronic exposure was calculated for DE child diet and accounted for 10% of the ADI. The contribution of residues in hops accounted for a maximum of 0.03% of the ADI for UK adult diet. The highest acute exposure for residues in hops accounted for 4.2% of the ARfD. The details of exposure calculations are presented in more detail in Appendix B.4.

EFSA concluded that the long-term and short-term intake of TBPE residues resulting from the existing uses of fenazaquin on various crops and the authorised use on hops in the United States is unlikely to present a risk to consumer health. The long-term consumer risk assessment is affected by non-standard uncertainty, because only limited information on the residue concentrations for TBPE is available for teas (EFSA, 2020) and no information is available for the CXLs implemented as EU MRLs in the EU legislation.

For further details on the exposure calculations, a screenshot of the Report sheets of the PRIMo for fenazaquin and TBPE are presented in Appendix C.

CONCLUSION AND RECOMMENDATIONS

The data submitted in this MRL application were found sufficient to derive an MRL proposal of 30 mg/kg for fenazaquin in hops in support of the authorised use in the United States.

EFSA concluded that the authorised use of fenazaquin on hops in the United States and subsequent residues of fenazaquin and its metabolite TBPE in hops will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health. The long-term consumer risk assessment for fenazaquin shall be regarded as indicative pending the assessment of the data gaps identified in the MRL review. The consumer risk assessment for TBPE is affected by non-standard uncertainty related to limited information available on the residue concentrations in teas (unprocessed and processed) and no information on residue concentrations in crops for which the CXLs are implemented in the EU legislation.

The MRL recommendations are summarised in Appendix B.4.

ABBREVIATIONS

• a.s.
• active substance
• ADI
• acceptable daily intake
• ARfD
• acute reference dose
• BBCH
• growth stages of mono- and dicotyledonous plants
• bw
• body weight
• CAC
• Codex Alimentarius Commission
• CAS
• Chemical Abstract Service
• CCPR
• Codex Committee on Pesticide Residues
• CF
• conversion factor for enforcement to risk assessment residue definition
• cGAP
• critical GAP
• CXL
• Codex maximum residue limit
• DALA
• days after last application
• DAR
• draft assessment report
• DAT
• days after treatment
• DT₉₀
• period required for 90% dissipation (define method of estimation)
• EMS
• evaluating Member State
• EURL
• EU Reference Laboratory (former Community Reference Laboratory (CRL))
• FAO
• Food and Agriculture Organization of the United Nations
• GAP
• Good Agricultural Practice
• HPLC
• high performance liquid chromatography
• 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
• IPCS
• International Programme of Chemical Safety
• ISO
• International Organisation for Standardisation
• IUPAC
• International Union of Pure and Applied Chemistry
• JMPR
• Joint FAO/WHO Meeting on Pesticide Residues
• LC
• liquid chromatography
• LOD
• limit of detection
• LOQ
• limit of quantification
• MRL
• maximum residue level
• MS
• Member States
• MS/MS
• tandem mass spectrometry detector
• MW
• molecular weight
• NEU
• northern Europe
• OECD
• Organisation for Economic Co-operation and Development
• PAFF
• Standing Committee on Plants, Animals, Food and Feed
• PBI
• plant back interval
• PF
• processing factor
• PHI
• pre-harvest interval
• PRIMo
• (EFSA) Pesticide Residues Intake Model
• QuEChERS
• Quick, Easy, Cheap, Effective, Rugged, and Safe (analytical method)
• RA
• risk assessment
• RAC
• raw agricultural commodity
• RD
• residue definition
• RMS
• rapporteur Member State
• SANCO
• Directorate-General for Health and Consumers
• SEU
• southern Europe
• STMR
• supervised trials median residue
• TMDI
• theoretical maximum daily intake
• TRR
• total radioactive residue
• WHO
• World Health Organization

ACKNOWLEDGEMENTS

EFSA wishes to thank: Stathis Anagnos, Mavriou Galini, Matteo Lazzari, Andrea Mioč, Marta Szot and Elena Taglianini for the support provided to this scientific output.

CONFLICT OF INTEREST

If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact [email protected].

REQUESTOR

European Commission

QUESTION NUMBER

EFSA-Q-2022-00458

COPYRIGHT FOR NON-EFSA CONTENT

EFSA may include images or other content for which it does not hold copyright. In such cases, EFSA indicates the copyright holder and users should seek permission to reproduce the content from the original source.

Appendix

APPENDIX A - SUMMARY OF AUTHORISED GAP TRIGGERING THE AMENDMENT OF EXISTING EU MRLs

Crop and/or situation	NEU, SEU, MS or country	F G or Ia	Pests or group of pests controlled	Preparation	Application	Application rate per treatment	PHI (days)d	Remarks
Typeb	Conc. a.s. (g/L)	Method kind	Range of growth stages and seasonc	Number min-max	Interval between application (days) min-max	g a.s./hL min–max	Water (L/ha) min-max	Rate min-max	Unit
Hops	USA	F	Tetranychidae (mites) Eriophyidae (mites) Tarsonemidae (mites) Diseases (powdery mildew) Insects	SC	200	Foliar spray	At infestation	1	n/a	38–58	Ground appl.: 935 Air appl.: 94	359–538	g/ha	7	Restrictions: Do not make more than one application per year. Do not exceed application rate of 36 fl oz of product (0.48 lb a.s.) per acre per year.e Product may be tank mixed with non-ionic surfactants

Appendix

APPENDIX B - LIST OF END POINTS

B.1

Residues in plants

B.1.1

Nature of residues and analytical methods for enforcement purposes in plant commodities

B.1.1.1

Metabolism studies, analytical methods and residue definitions in plants

Primary crops (available studies)	Crop groups	Crops	Application	Sampling (DAT)	Comment/Source
	Fruit crops	Grape	Foliar, 1 × 15 g/ha, 2–3 weeks after BBCH 68	Fruits: 0, 46, 76 Leaves: 0, 46, 76	Radiolabelled active substance: 14C-fenazaquin labelled in quinazoline (Q-fenazaquin) and in phenyl ring (P-fenazaquin) (EFSA, 2010a, 2013)
Foliar, 1 × 15 g/ha + 1 × 150 g/ha, 9–10 weeks after BBCH 68	Fruits: 0, 28 Leaves: 0, 28	Radiolabelled active substance: 14C-fenazaquin labelled in quinazoline (Q-fenazaquin) and in phenyl ring (P-fenazaquin) (EFSA, 2010a, 2013)
Leafy crops	Lettuce	Foliar, 1 × 540 g/ha, BBCH 49	7	Radiolabelled active substance: [phenyl-U-14C]- and [quinazoline-14C]-fenazaquin (Greece, 2023)
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Radish	Bare soil, 1 × 550 g/ha	30, 120, 365	Radiolabelled active substance: [phenyl-U-14C]- and [quinazoline-14C]-fenazaquin (EFSA, 2020)
Leafy crops	Lettuce
Cereal (small grain)	Wheat
Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	Inconclusive	Fenazaquin significantly degraded to 4-OHQ particularly during pasteurisation (EFSA, 2013). Fate of phenyl ring not investigated, it is uncertain if TBPE will be formed (EFSA, 2013, 2020).
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Inconclusive	Fate of phenyl ring not investigated, it is uncertain if TBPE will be performed (EFSA, 2013, 2020).
	Sterilisation (20 min, 120°C, pH 6)	Inconclusive	Fate of phenyl ring not investigated, it is uncertain if TBPE will be performed (EFSA, 2013, 2020).
	Other processing conditions	–	–

B.1.1.2

Stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)	Stability period	Compounds covered	Comment/Source
Value	Unit
	High-oil content	Almonds	−10 to −25	17	Months	Fenazaquin	EFSA (2018b)
−10 to −25	20	Months	TBPE/4-OHQ
Hops	−10 to −25	393	Days	Fenazaquin	Only one fortification level tested. Duration of study equal with the max. storage interval (Greece, 2023)
−20	262	Days	TBPE
−20	23a	Days	4-OHQ(a)
High-water content	Tomatoes Peaches Melons Cucumbers	−10	13	months	Fenazaquin	Only one fortification level tested (EFSA, 2020)
High-acid content	Oranges Grapes	−15	12	months	Fenazaquin	EFSA (2013)
	Orange pulp Grapes	–	12	months	TBPE/4-OHQ	Storage temperatures reported as ‘frozen conditions’ (EFSA, 2013)
Processed products	Raisins	–	12	Months	TBPE/4-OHQ	Storage temperatures reported as ‘frozen conditions’ (EFSA, 2013)
Tea (dried green tea and fermented black tea)	–	80	Days	Fenazaquin	Storage temperatures reported as ‘frozen conditions’ (EFSA, 2010a)

B.1.2

Magnitude of residues in plants

B.1.2.1

Summary of residues data from the supervised residue trials

Commodity	Region/a	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)	CFd
Enforcement residue definition (Mo): FenazaquinF Risk assessment residue definition (RA): (1) Fenazaquin; (2) TBPE
Hops	USA	Mo: 0.72; 1.01; 1.12; 9.34; 10.52; 10.58; 10.70; 11.05; 11.08; 12.15; 13.20; 13.25 Mo = RA (1): 0.72; 1.01; 1.12; 9.34; 10.52; 10.58; 10.70; 11.05; 11.08; 12.15; 13.20; 13.25 RA (2): 0.074; 0.087; 0.094; 0.114; 0.33; 0.46	Residue trials on hops compliant with the authorised GAP	30	RA (1): 13.25 RA (2): 0.46	RA (1): 10.64 RA (2): 0.10	n/a

B.1.2.2

Residues in rotational crops

B.1.2.3

Processing factors

Processed commodity	Number of valid studiesa	Processing Factor (PF)	Comment/Source
Individual values	Median PF
Enforcement residue definition: FenazaquinF Risk assessment (RA) residue definition: (1) Fenazaquin; (2) TBPE
Hops, beer	2	RA (1): < 0.00093; < 0.0008 RA (2): < 0.0299; < 0.0218	RA (1): < 1 (< 0.00085)b RA (2): < 1 (< 0.0259)b	Tentative (Greece, 2023). Residues of fenazaquin and TBPE in beer not detected. For calculation of the PF, residues assumed to occur below the LOQ of 0.01 mg/kg

B.2

Residues in livestock

Not relevant for the current assessment

B.3

Consumer risk assessment

B.3.1

Fenazaquin

B.3.2

TBPE

B.4

Recommended MRLs

Codea	Commodity	ExistingEU MRL (mg/kg)	ProposedEU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Fenazaquinb
0700000	Hops	0.05*	30	The submitted data are sufficient to derive an import tolerance (US GAP). Risk for consumers is unlikely The tolerance established in the USA and the Codex MRL is 30 mg/kg

Appendix

APPENDIX C - PESTICIDE RESIDUE INTAKE MODEL (PRIMo)

EFSA_Q_2022_00458_PRIMo_rev3_1_fenazaquin.xlsm

EFSA_Q_2022_00458_PRIMo_rev3_1_TBPE.xlsm

Appendix

APPENDIX D - INPUT VALUES FOR THE EXPOSURE CALCULATIONS

D.1

Consumer risk assessment

Commodity	Existing/Proposed MRL (mg/kg)	Source/type of MRL	Chronic risk assessment	Acute risk assessment
Input value (mg/kg)	Comment	Input value (mg/kg)	Commenta
Risk assessment residue definition 1: Fenazaquin
Grapefruits	0.3b	Existing MRL	0.00483	STMR-RAC × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Oranges	0.3b	Existing MRL	0.00483	STMR-RAC × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Lemons	0.3b	Existing MRL	0.00483	STMR-RA × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Limes	0.3b	Existing MRL	0.00483	STMR-RAC × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Mandarins	0.3b	Existing MRL	0.00483	STMR-RAC × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Other citrus fruits	0.3	Existing MRL	0.00483	STMR-RAC × PeF (EFSA, 2020)	0.0119	HR-RAC × PeF
Almonds	0.02	Existing MRL	0.01	STMR-RAC (EFSA, 2020)	0.0155	HR-RAC (FAO, 2019)
Brazil nuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Cashew nuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Chestnuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Hazelnuts/cobnuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Macadamia	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Pecans	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Pine nut kernels	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Pistachios	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Walnuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Other tree nuts	0.02	Codex MRL	0.01	STMR-RAC (FAO, 2019)	0.0155	HR-RAC (FAO, 2019)
Apples	0.15b	Existing MRL	0.026	STMR-RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Pears	0.15b	Existing MRL	0.026	STMR-RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Quinces	0.15b	Existing MRL	0.026	STMR-RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Medlar	0.15b	Existing MRL	0.026	STMR-RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Loquats/Japanese medlars	0.15b	Existing MRL	0.026	STMR-RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Other pome fruits	0.15	Existing MRL	0.026	STMR_RAC (EFSA, 2020)	0.09	HR-RAC (EFSA, 2020)
Strawberries	0.4b	Existing MRL	0.08	STMR-RAC (EFSA, 2020)	0.19	HR-RAC (EFSA, 2020)
Tomatoes	0.05b	Existing MRL	0.0155	STMR-RAC (EFSA, 2020)	0.029	HR-RAC (EFSA, 2020)
Cucumbers	0.15	Existing MRL	0.05	STMR-RAC (EFSA, 2020)	0.07	HR-RAC (EFSA, 2020)
Melons	0.07	Existing MRL	0.00285	STMR-RAC × PeF (EFSA, 2020)	0.0076	HR-RAC × PeF (EFSA, 2020)
Watermelons	0.07	Existing MRL	0.00285	STMR-RAC × PeF (EFSA, 2020)	0.0076	HR-RAC × PeF (EFSA, 2020)
Tea (dried leaves of Camellia sinensis)	9b	Existing MRL	2.8	STMR-RAC (EFSA, 2020)	5	HR-RAC (EFSA, 2020)
HOPS (dried)	30	Proposed MRL (IT)	10.64	STMR-RAC (Section B.1.2.1)	13.25	HR-RAC (Section B.1.2.1)
Swine: Muscle/meat	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.002	HR-RAC (FAO, 2019)
Swine: Fat tissue	0.02*	Codex MRL	0.00048	STMR-RAC (FAO, 2019)	0.0006	HR-RAC (FAO, 2019)
Swine: Liver	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Swine: Kidney	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.0002	HR-RAC (FAO, 2019)
Swine: Edible offal (other than liver and kidney)	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Swine: Other products	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Bovine: Muscle/meat	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Bovine: Fat tissue	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Bovine: Liver	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Bovine: Kidney	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Bovine: Edible offals (other than liver and kidney)	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Bovine: Other products	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Sheep: Muscle/meat	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.002	HR-RAC (FAO, 2019)
Sheep: Fat tissue	0.02*	Codex MRL	0.00048	STMR-RAC (FAO, 2019)	0.0006	HR-RAC (FAO, 2019)
Sheep: Liver	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Sheep: Kidney	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.0002	HR-RAC (FAO, 2019)
Sheep: Edible offal (other than liver and kidney)	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Goat: Muscle/meat	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.002	HR-RAC (FAO, 2019)
Goat: Fat tissue	0.02*	Codex MRL	0.00048	STMR-RAC (FAO, 2019)	0.0006	HR-RAC (FAO, 2019)
Goat: Liver	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Goat: Kidney	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.0002	HR-RAC (FAO, 2019)
Goat: Edible offal (other than liver and kidney)	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Equine: Muscle/meat	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Equine: Fat tissue	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Equine: Liver	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Equine: Kidney	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Equine: Edible offals (other than liver and kidney)	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Other farmed animals: Muscle/meat	0.02*	Codex MRL	0.0002	STMR -RAC (FAO, 2019)	0.002	HR-RAC (FAO, 2019)
Other farmed animals: Fat tissue	0.02*	Codex MRL	0.00048	STMR-RAC (FAO, 2019)	0.0006	HR-RAC (FAO, 2019)
Other farmed animals: Liver	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Other farmed animals: Kidney	0.02*	Codex MRL	0.0002	STMR-RAC (FAO, 2019)	0.0002	HR-RAC (FAO, 2019)
Other farmed animals: Edible offal (other than liver and kidney)	0.02*	Codex MRL	0.00041	STMR-RAC (FAO, 2019)	0.00048	HR-RAC (FAO, 2019)
Milk: Cattle	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	STMR-RAC (EFSA, 2020)
Milk: Sheep	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	STMR-RAC (EFSA, 2020)
Milk: Goat	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	STMR-RAC (EFSA, 2020)
Milk: Horse	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	STMR-RAC (EFSA, 2020)
Milk: Others	0.02*	Codex MRL	0.01	STMR-RAC (EFSA, 2020)	0.01	STMR-RAC (EFSA, 2020)
Risk assessment residue definition 2: TBPE
Grapefruits	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Oranges	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Lemons	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Limes	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Mandarins	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Other citrus fruit	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)		HR-RAC (EFSA, 2020)
Almonds	n/a	EFSA (2018b)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Apples	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Pears	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Quinces	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Medlar	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Loquats/Japanese medlars	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Other pome fruit	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)
Strawberries	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Tomatoes	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Cucumbers	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Melons	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Watermelons	n/a	EFSA (2020)	0.01	STMR-RAC (EFSA, 2020)	0.01	HR-RAC (EFSA, 2020)
Tea (dried leaves of Camellia sinensis)	n/a	EFSA (2020)	0.46	STMR-RAC (EFSA, 2020) (indicative value)	0.86	HR-RAC (EFSA, 2020)
HOPS (dried)	n/a	Import tolerance	0.1	STMR-RAC (Section B.1.2.1)	0.46	HR-RAC (Section B.1.2.1)

Appendix

APPENDIX E - USED COMPOUND CODES

Code/trivial name	IUPAC name/SMILES notation/InChiKeya	Structural formulab
Fenazaquin	4-tert-butylphenethyl quinazolin-4-yl ether CC(C)(C)c1ccc(cc1)CCOc1ncnc2ccccc21 DMYHGDXADUDKCQ-UHFFFAOYSA-N
TBPE	2-(4-tert-butylphenyl)ethanol CC(C)(C)c1ccc(CCO)cc1 NZGMMENPUKHODD-UHFFFAOYSA-N
4-OHQ	quinazolin-4-ol Oc1ncnc2ccccc21 QMNUDYFKZYBWQX-UHFFFAOYSA-N

References

EFSA (European Food Safety Authority). (2010a). Reasoned opinion on the modification of the existing MRL for fenazaquin in tea (dried or fermented leaves and stalks of Camellia sinensis). EFSA Journal, 8(5), 25. [DOI: https://dx.doi.org/10.2903/j.efsa.2010.1581]