Evaluation of confirmatory data following the Article 12 MRL review for tebufenpyrad

Abstract

The applicant Belchim Crop Protection submitted a request to the competent national authority in Germany to evaluate the confirmatory data that were identified for tebufenpyrad in the framework of the maximum residue level (MRL) review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, new residue trials on peaches, apricots and raspberries (extrapolated to blackberries and dewberries) as well as a new analytical method for enforcement in animal commodities and its independent laboratory validation were submitted. The data gaps were considered satisfactorily addressed. The new information provided required a revision of the existing MRLs for peaches and apricots while the existing MRLs for blackberries and dewberries could be confirmed. An update of the consumer risk assessment for tebufenpyrad was performed in light of the new data submitted and it did not indicate any consumer intake concerns in relation to the chronic exposure and the acute exposure of the crops under consideration in the present assessment.

Summary

In 2016, when the European Food Safety Authority (EFSA) reviewed the existing maximum residue levels (MRLs) for tebufenpyrad according to Article 12 of Regulation (EC) No 396/2005, EFSA identified some information as unavailable (data gaps) and derived tentative MRLs for those uses which were not fully supported by data but for which no risk to consumers was identified. The following data gaps were noted:

1. A fully validated analytical method for enforcement in hops

2. A representative study investigating primary crop metabolism in leafy vegetables and pulses and oilseeds

3. A storage stability study in high oil content commodities

4. Additional residue trials supporting authorisations on peaches, apricots, blackberries, dewberries and beans with pods

5. A fully validated analytical method for enforcement in animal commodities

Tentative MRL proposals have been implemented in the MRL legislation by Commission Regulation (EU) No 2017/693, including footnotes related to data gaps 1, 4 and 5, indicating the type of confirmatory data that should be provided by a party having an interest in maintaining the proposed tentative MRLs by 13 April 2019. However, data gaps number 2 and 3 were not implemented in the MRL regulation.

In accordance with the agreed procedure set out in the working document SANTE/10235/2016, Belchim Crop Protection submitted an application to the competent national authority in Germany (rapporteur Member State, RMS) to evaluate the confirmatory data identified during the MRL review. The RMS assessed the new information in an evaluation report, which was submitted to the European Commission and forwarded to the European Food Safety Authority EFSA on 26 September 2022.

The summary table below provides an overview of the assessment of confirmatory data and the recommended MRL modifications to Regulation (EU) No 396/2005.

Code(a)	Commodity	Existing MRL(b)	Data gap(s) Art. 12 Review	Proposed MRL	Conclusion/recommendation
Enforcement residue definition: Tebufenpyrad(F)
0140010	Apricots	0.4 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.3	The data gap identified by EFSA concerning additional residue trials has been addressed. EFSA proposes to lower the existing MRL to 0.3 mg/kg based on a set of combined residue trials on peaches and apricots performed according to an adjusted GAP. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0140030	Peaches	0.4 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.3	The data gap identified by EFSA concerning additional residue trials has been addressed. EFSA proposes to lower the existing MRL to 0.3 mg/kg based on a set of combined residue trials on peaches and apricots performed according to an adjusted GAP. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0153010	Blackberries	0.05 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.05	The data gap identified by EFSA concerning additional residue trials has been addressed. The available residue trials on raspberries (extrapolated to blackberries and dewberries) confirmed the existing MRL. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0153020	Dewberries	0.05 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.05	The data gap identified by EFSA concerning additional residue trials has been addressed. The available residue trials on raspberries (extrapolated to blackberries and dewberries) confirmed the existing MRL. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0260010	Beans (with pods)	0.3 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.01*	The data gap identified by EFSA concerning additional residue trials has not been addressed. The applicant indicated that no additional residue trials in beans with pods were submitted since the authorisation in this crop is no longer sustained. Therefore, EFSA proposes to lower the existing MRL to the LOQ of 0.01 mg/kg.
0700000	HOPS	1.5 (ft 2)	Footnote related to data gap No 1. [analytical methods]	0.01*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in hops has not been addressed. The applicant indicated that no analytical method for enforcement in hops was submitted since the authorisation in this crop is no longer sustained. Therefore, EFSA proposes to lower the existing MRL to the LOQ of 0.01 mg/kg.
1010000 to 1070000 except 1040000	PRODUCTS OF ANIMAL ORIGIN (Except Honey and other apiculture products)	0.01* (ft 2)	Footnote related to data gap No 5. [analytical methods]	0.01*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in animal commodities has been addressed. Therefore, EFSA proposes to confirm the existing MRLs set at the LOQ of 0.01 mg/kg.
1040000	Honey and other apiculture products (7)	0.05* (ft 2)	Footnote related to data gap No 5. [analytical methods]	0.05*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in animal commodities has been addressed but since a specific analytical method for honey has not been provided, EFSA proposes to maintain the existing MRL at the LOQ of 0.05 mg/kg

MRL: maximum residue level; GAP: Good Agricultural Practice; LOQ: limit of quantification.

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

(a) Commodity code number according to Annex I of Regulation (EC) No 396/2005.

(b) Existing EU MRL and corresponding footnote on confirmatory data.

ft 1: The European Food Safety Authority identified some information on residue trials as unavailable. When re‐viewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 April 2019, or, if that information is not submitted by that date, the lack of it.

ft 2: The European Food Safety Authority identified some information on analytical methods as unavailable. When re‐viewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 April 2019, or, if that information is not submitted by that date, the lack of it.

(F) Fat‐soluble.

Assessment

The review of existing maximum residue levels (MRLs) for the active substance tebufenpyrad according to Article 12 of Regulation (EC) No 396/2005 ¹ (MRL review) has been performed in 2016 (EFSA, 2016). European Food Safety Authority (EFSA) identified some information as unavailable (data gaps) and derived tentative MRLs for those uses not fully supported by data but for which no risk to consumers was identified. The list of Good Agricultural Practices (GAPs) assessed in the framework of the MRL review that were not fully supported by data and for which confirmatory data were requested are listed in Appendix A.

Following the review of existing MRLs, the legal limits have been modified by Commission Regulation (EU) No 2017/693 ² , including footnotes for tentative MRLs that specified the type of information that was identified as missing. Any party having an interest in maintaining the proposed tentative MRL was requested to address the confirmatory data by 13 April 2019.

In accordance with the specific provisions set out in the working document of the European Commission SANTE/10235/2016 (European Commission, 2020a) the applicant, Belchim Crop Protection, on 4 June 2019 submitted an application to the competent national authority in Germany (designated rapporteur Member State, RMS) to evaluate the confirmatory data identified during the MRL review. To address the data gaps identified by EFSA, the applicant provided new residue trial studies on peaches, apricots and raspberries (extrapolated to blackberries and dewberries) as well as a new analytical method for enforcement in animal commodities and its independent laboratory validation.

The RMS assessed the new information in an evaluation report, which was submitted to the European Commission and forwarded to EFSA on 26 September 2022 (Germany, 2022). EFSA assessed the application as requested by the European Commission in accordance with Article 10 of Regulation (EC) No 396/2005.

EFSA based its assessment on the evaluation report submitted by the RMS (Germany, 2022) and the reasoned opinion on the MRL review according to Article 12 of Regulation (EC) No 396/2005 (EFSA, 2016).

For this application, the data requirements established in Regulation (EU) No 544/2011 ³ and the relevant guidance documents at the date of implementation of the confirmatory data requirements by Commission Regulation (EU) No 2017/693 are applicable. The assessment is performed in accordance with the legal provisions of the Uniform Principles for the Evaluation and the Authorisation of Plant Protection Products adopted by Commission Regulation (EU) No 546/2011 ⁴ .

An updated list of end points, including the end points of relevant studies assessed previously and the confirmatory data evaluated in this application, is presented in Appendix B.

The peer review of the renewal of approval of tebufenpyrad in accordance with Regulation (EC) No 1107/2009 is not yet started and therefore the conclusions reported in this reasoned opinion might need to be reconsidered in the light of the outcome of the future peer review.

The evaluation report submitted by the RMS (Germany, 2022) is considered a supporting document to this reasoned opinion and, thus, is made publicly available as a background document to this reasoned opinion.

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 tebufenpyrad has been investigated only in fruits.

In the framework of the peer review of the active substance under Directive 91/414/EEC, a metabolism study following foliar applications in apples has been assessed by the rapporteur member state and EFSA (Germany, 2007, 2008; EFSA, 2008). The metabolism studies were performed with the parent molecule labelled either in the phenyl‐ or the pyrazole ring. An additional study investigating the metabolism in grapes after foliar applications with phenyl‐ and pyrazole‐labelled tebufenpyrad was evaluated in the framework of the Art.12 MRL review (Germany, 2013; EFSA, 2016).

In both studies, tebufenpyrad represented the main compound, accounting for 63% of the total radioactive residue (TRR) and 78% TRR in apples and grapes, respectively. No other relevant compounds were found at significant levels in apples and in grapes. It was concluded that the only relevant component in apples and grapes treated with both types of radiolabelled tebufenpyrad is the parent compound. In view of the limited number of crop groups tested, the residue definitions were restricted to ‘fruits and fruiting vegetables’ only.

EFSA notes that the MRL review (EFSA, 2016) highlighted the absence of metabolism studies in other crop groups and set a data gap for a representative study investigating primary crop metabolism in leafy vegetables and pulses and oilseeds. Meanwhile, the proposed residue definition was tentatively applied also to hops, beans with pods and cotton seed in the framework of the MRL review. EFSA further notes that this data gap from the MRL review was not implemented in the MRL legislation by Commission Regulation (EU) No 2017/693.

1.1.2. Nature of residues in rotational crops

Not relevant for the current assessment.

1.1.3. Nature of residues in processed commodities

Not relevant for the current assessment.

1.1.4. Analytical methods for enforcement purposes in plant commodities

In the framework of the MRL review (EFSA, 2016), a data gap for a fully validated analytical method for enforcement in hops was established and a tentative MRL proposal with a footnote that specified the type of information that was identified as missing was implemented in the MRL legislation by Commission Regulation (EU) No 2017/693, related to data gap 1. ⁵

However, with the present application, the applicant informed that no fully validated analytical method for enforcement in hops was submitted as the applicant did not intend to sustain an authorisation in this crop. Therefore, EFSA proposes to lower the existing MRL for hops to the limit of quantification (LOQ) of 0.01 mg/kg and remove the related footnote.

1.1.5. Stability of residues in plants

Not relevant for the current assessment.

1.1.6. Proposed residue definitions

The previously derived residue definitions are still applicable.

1.2. Magnitude of residues in plants

During the MRL review (EFSA, 2016), a data gap was set for additional residue trials supporting authorisations on peaches, apricots, blackberries, dewberries and beans with pods, for which only tentative MRLs and risk assessment values could be derived. Tentative MRL proposals have been implemented in the MRL legislation by Commission Regulation (EU) No 2017/693, including footnotes related to data gaps 4, ⁶ indicating the type of confirmatory data that should be provided by a party having an interest in maintaining the proposed tentative MRLs by 13 April 2019.

In order to address the data gap number 4, the applicant provided new residue trial studies on peaches, apricots and raspberries (extrapolated to blackberries and dewberries). According to the assessment of the RMS, the analytical methods used were sufficiently validated and fit for purpose and the samples of these residue trial studies were stored under conditions for which integrity of the samples has been demonstrated.

EFSA assessed whether these new data were sufficient to address the data gaps and whether the existing MRLs, and risk assessment values might need to be recalculated (see sections below).

Moreover, the applicant indicated that no additional residue trials on beans with pods were submitted as the applicant did not intend to sustain the authorisation in this crop. Therefore, EFSA proposes to lower the existing MRL for beans with pods to the LOQ of 0.01 mg/kg and remove the related footnote.

Peaches and apricots

$$\mathit{MRL}\mathit{\text{review}}\left(\mathit{SEU}\right)\mathit{GAP}\mathit{:}\mathit{1}\mathit{\times }\mathit{100}\mathit{g}\mathit{a}.\mathit{s}./\mathit{ha},\mathit{PHI}=\mathit{14}\mathit{\text{days}}$$

$$\mathit{\text{Article}}\mathit{12}\mathit{\text{confirmatory data adjusted}}\left(\mathit{SEU}\right)\mathit{GAP}\mathit{:}\mathit{1}\mathit{\times }\mathit{100}–\mathit{130}\mathit{g}\mathit{a}.\mathit{s}./\mathit{ha},\mathit{PHI}=\mathit{14}\mathit{\text{days}}$$

In the framework of the MRL review (EFSA, 2016), it was concluded that for peaches and apricots the number of residue trials supporting the SEU GAP was not compliant with the data requirements for these crops (seven trials reported for peaches and no trials reported for apricots). Consequently, one additional trial on peaches and four trials on apricots compliant with the SEU GAP were required.

EFSA notes that, with the current application, the applicant provided additional residue trial studies on peaches and apricots performed in the SEU but according to an adjusted GAP with a higher application rate than the one considered in the MRL review. In fact, for both peaches and apricots, the GAP assessed as part of the MRL review was based on a single application with an application rate of 100 g a.s./ha and a PHI of 14 days. However, with the present application, the applicant provided an adjusted GAP with a single application but with an application rate ranging from 100 to 130 g a.s./ha, still with a PHI of 14 days. This adjusted GAP was derived from the existing registrations in Greece and in Italy with an application rate of 130 g a.s./ha, and this higher application rate was used to generate the missing trials in peaches and apricots. Therefore, the applicant provided two additional residue trials on peaches performed in Spain and in Greece in 2015 with an application rate of 130 g a.s./ha and four additional residue trials on apricots performed in Italy in 2015, also with an application rate of 130 g a.s./ha. The applicant also proposed to derive an MRL for peaches and apricots based on a data set combining seven residue trials on peaches and four residue trials on apricots, all performed with an application rate of 130 g a.s./ha. This approach was supported by the RMS. EFSA is also in agreement with the proposed approach and derived MRL accordingly.

Firstly, in relation to the use of an adjusted GAP, EFSA notes that, according to the Commission working document (SANTE/10235/2016 Rev. 4.1, European Commission, 2020a), ‘as a matter of principle, confirmatory data should support the cGAP identified in the MRL review. Alternatively, an adjusted GAP may be supported, if it confirms the tentative MRL or leads to a lower MRL proposal’. Considering that the combined data set consisting of peaches and apricots residue trials compliant with the adjusted GAP results in an MRL proposal of 0.3 mg/kg, which is lower than the existing MRL of 0.4 mg/kg, the requirements of SANTE/10235/2016 Rev. 4.1 regarding the submission of an adjusted GAP are fulfilled.

Secondly, in relation to the MRL proposal based on a combined dataset on peaches and apricots, EFSA agrees to consider only the residue trials compliant with the adjusted GAP and performed at the application rate of 130 g a.s./ha. Therefore, a sufficient number of GAP‐compliant and independent residue trials are now available on peaches (7) and apricots (4) with a minimum 50% of residue trials on apricots which allow to extrapolate the derived MRL from this combined dataset to both peaches and apricots in line with the applicable EU guidance document on setting MRLs, comparability of residue trials and extrapolation, SANTE/2019/12752 (European Commission, 2020b).

EFSA concluded that the data gap identified in the framework of the MRL review is addressed.

Blackberries and dewberries

$$\mathit{MRL}\mathit{\text{review}}\left(\mathit{NEU}\right)\mathit{GAP}\mathit{:}\mathit{1}\mathit{\times }\mathit{75}\mathit{g}\mathit{a}.\mathit{s}./\mathit{ha},\mathit{PHI}=\mathit{21}\mathit{\text{days}}$$

In the framework of the MRL review (EFSA, 2016), it was concluded that for blackberries and dewberries the number of residue trials performed in raspberries supporting the NEU GAP was not compliant with the data requirements for these crops (four residue trials instead of six). The request for 6 trials at time of the MRL review was justified in accordance with the extrapolation guidance in place at time of the MRL review assessment (European Commission, 2011. Appendix D. – rev.9 March 2011): ‘Trials on raspberries alone or on two representatives (6 trials) → whole group’. Therefore, two additional residue trials supporting the NEU uses were still required.

With the current application, the applicant provided two additional residue trial studies conducted in UK on raspberries to support the NEU uses on blackberries and dewberries. Still, out of these two residue trials only one is compliant with the NEU GAP of the MRL review. Considering only the GAP‐compliant residue trials in raspberries provided in the framework of the MRL review and with the current application (4 trials overall), the applicant proposed to derive by means of extrapolation an MRL of 0.05* mg/kg for blackberries and dewberries. The RMS also agreed with this approach.

EFSA agrees to consider this revised data package of GAP‐compliant residue trials sufficient for minor crops based on the new guidance document on setting MRLs, comparability of residue trials and extrapolation, SANTE/2019/12752 (European Commission, 2020b). Additionally, EFSA also agrees with the extrapolation from raspberries to blackberries and dewberries since according to the extrapolation guidance, four trials per zone are sufficient to extrapolate to the whole group containing minor crops.

EFSA concluded that the data gap identified in the framework of the MRL review is addressed. However, EFSA notes that a lower LOQ is achievable for these crops (0.01 mg/kg).

2. Residues in livestock

The confirmatory data for a fully validated analytical method for enforcement in animal commodities has been provided with the present application and it allows to confirm the existing MRLs of tebufenpyrad in products of animal origin at the enforceable LOQ of 0.01 mg/kg. The other new data submitted with this application, i.e. residue trial studies on peaches, apricots and raspberries (extrapolated to blackberries and dewberries) are not relevant for livestock and therefore do not impact the livestock dietary burden and previous assessment of the MRL review (EFSA, 2016) concluding that based on livestock metabolism and feeding studies residues are not expected in any tissue, milk and eggs at the calculated dietary burden.

Thus, the previous assessment of residues in livestock (EFSA, 2016) remains valid, the existing MRLs can be confirmed, and the related footnotes removed.

2.1. Methods of analysis in livestock

In the framework of the MRL review (EFSA, 2016), it was reported that an analytical method for the determination of tebufenpyrad in matrices of animal origin was evaluated during the peer‐review of tebufenpyrad (Germany, 2007, 2008). This method was based on high‐performance liquid chromatography with tandem mass spectrometry (HPLC–MS/MS) and allowed the determination of tebufenpyrad residues in milk, liver, kidney, muscle, fat and eggs at the LOQ of 0.01 mg/kg. The MRL review however pointed out that for this analytical method an independent laboratory validation (ILV) was not available. Therefore, in the framework of the MRL review, EFSA concluded that a sufficiently validated analytical method to monitor tebufenpyrad residues in matrices of animal origin was not available and it was required.

Therefore, in order to address data gap number 5, ⁷ with the present application, the applicant provided a new study on an analytical method for the determination of tebufenpyrad in matrices of animal origin, and an its ILV, based on HPLC–MS/MS and performed in samples of milk, eggs, meat, fat and liver (Germany, 2022). Details on the analytical method and its validation are presented below and summarised in Appendix B.1.2.1.

This new study and its ILV were conducted according to Good Laboratory Practice (GLP) criteria in 2018 and in 2019 respectively and they were performed in line with the requirements of the Guidance document on pesticide residue analytical methods, SANCO/825/00 rev 8.1 (European Commission, 2010). EFSA notes that all requirements of this analytical method Guidance are fulfilled, as further explained below.

The HPLC–MS/MS determination was conducted by monitoring two different mass transitions (m/z 335→148 and m/z 335→118). A blank sample and two control samples per matrix were analysed to investigate the presence of residue and/or background interference. For both mass transitions followed, the samples showed no significant interferences above 30% of the LOQ, showing that the method is highly selective. The linearity of the detection system was demonstrated by calibration at seven concentrations ranging from 0.003 to 0.3 mg/kg.

The accuracy of the method was determined by fortification of control samples at the LOQ and 10 times the LOQ with 5 samples per matrix, while precision was determined by repeatability in terms of relative standard deviation (RSD). All mean recovery values at fortification levels of 0.01 mg/kg (LOQ) or 0.1 mg/kg (10 × LOQ) for the two mass transitions followed were in the range 82%–102% and RSD always below 6%, so in compliance with the criteria of the SANCO GD and demonstrating accuracy and repeatability of the method. The LOQ was successfully established at the lowest validated fortification level (0.01 mg/kg) in milk, egg, fat, meat and liver. The LOD was set at 0.003 mg/kg for all matrices (at 30% of the LOQ).

EFSA notes that the extraction efficiency of the method was not reported and in the full study report the applicant indicated that testing of extraction efficiency as mentioned in the SANCO GD was not conducted as part of this study. EFSA further notes that the SANCO GD indeed indicates that extraction efficiency of the analytical method should be verified for all matrix groups for which residues above the LOQ are expected. In all matrices of animal origin analysed no residue above the LOQ are expected since the MRL review concluded that based on livestock metabolism and feeding studies residues are not expected in any tissue, milk and eggs at the calculated dietary burden.

EFSA therefore agrees that demonstration of the extraction efficiency of the method is not required, and the method is considered valid according to the criteria of the analytical method Guidance SANCO/825/00 for the determination of tebufenpyrad in milk, egg, fat, meat and liver at the LOQ of 0.01 mg/kg.

EFSA concluded that the data gap identified in the framework of the MRL review is addressed.

2.2. Magnitude of residues in livestock

Not relevant for the current assessment.

3. Consumer risk assessment

EFSA updated the consumer risk assessment conducted in the framework of the MRL review (latest consumer risk assessment of tebufenpyrad, EFSA, 2016), considering the new data submitted under this application. Since the supervised trials median residue (STMR) and highest residue (HR) input values derived for peaches and apricots in the present assessment are lower than the ones derived in the framework of the MRL review, MRLs for beans with pods and hops are proposed to be lowered to the LOQs and the other input values remain the same as the ones of the MRL review, it is expected that the confirmatory data submitted in the context of the present application should not trigger a modification of the previous consumer dietary exposure calculations.

However, the dietary exposure calculations derived in the MRL review were updated to consider the revision 3.1 of the EFSA PRIMo (EFSA, 2018, 2019). The revision 3.1 of the EFSA PRIMo 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 profile of tebufenpyrad was assessed in the framework of the EU pesticides peer review and the data were sufficient to derive an acceptable daily intake (ADI) of 0.01 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.02 mg/kg bw (EFSA, 2008). The derived toxicological reference values were confirmed after the finalisation of the confirmatory data of the EU pesticides peer review (European Commission, 2012).

The input values used to perform the revised exposure assessment are reported in Appendix D.1. The outcome of the calculations is reported in Appendix B.3. The highest calculated chronic intake accounted for 31% of the ADI (NL toddler). The short‐term exposure did not exceed the ARfD for the crops under consideration in the framework of this Art.12 confirmatory data application. However, when performing the revised short‐term exposure calculation with the PRIMo version 3.1, EFSA notes an exceedance of the ARfD for table grapes in children (109% of ARfD vs. the 98% previously calculated with PRIMo 2 in the framework of the MRL review).

It is concluded that the revised consumer exposure assessment to tebufenpyrad is unlikely to pose a concern for public health in relation to the chronic exposure and the acute exposure of the crops under consideration in the present assessment but an exceedance of the ARfD for table grapes is observed in children with the revised calculation with PRIMo version 3.1 instead of PRIMo version 2.

4. Conclusion and Recommendations

To address data gaps identified in the framework of the MRL review (EFSA, 2016), new residue trial studies on peaches, apricots and raspberries (extrapolated to blackberries and dewberries) as well as a new analytical method for enforcement in animal commodities and its independent laboratory validation were submitted by the applicant. These data gaps were sufficiently addressed. However, EFSA notes that metabolism studies to cover the MRLs on hops (leafy crops) and beans and cotton (pulses and oilseeds) and storage stability study for oilseeds were identified as data gaps by the MRL review and are still missing. Despite the fact that these data gaps were not implemented in the MRL Regulation (EU) No 2017/693, EFSA highlights the uncertainties with the lack of such data. As indicated above, for hops and beans with pods the applicant indicated that the authorisations are no longer sustained, hence EFSA proposed to lower the MRL to the LOQ. However, this is not the case for cotton seeds where an MRL has been implemented without any footnote, but metabolism studies on pulses and oilseeds are still missing.

The tentative MRLs for peaches and apricots are proposed to be lowered from 0.4 to 0.3 mg/kg based on the provided residue trials performed according to an adjusted GAP while the tentative MRLs for blackberries and dewberries are confirmed based on extrapolation from the provided residue trials on raspberries. Moreover, the applicant indicated that no additional residue trials on beans with pods and no fully validated analytical method for enforcement in hops were submitted as the applicant did not intend to sustain the authorisation in these crops. Therefore, EFSA proposes to lower the existing MRLs for beans with pods and hops to the LOQ of 0.01 mg/kg and remove the related footnotes.

EFSA updated the consumer risk assessment conducted in the framework of the MRL review (EFSA, 2016), considering the new data submitted under this application and using the revision 3.1 of the EFSA PRIMo. EFSA concluded that the revised consumer exposure assessment to tebufenpyrad is unlikely to pose a concern for public health in relation to the chronic exposure and the acute exposure of the crops under consideration in the present assessment but an exceedance of the ARfD for table grapes is observed in children with the revised calculation with PRIMo version 3.1 instead of PRIMo version 2.

The overview of the assessment of confirmatory data and the recommended MRL modifications 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

CF

conversion factor for enforcement to risk assessment residue definition

cGAP

critical GAP

CXL

Codex maximum residue limit

DAT

days after treatment

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 Standardisation

IUPAC

International Union of Pure and Applied Chemistry

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

NEU

northern Europe

OECD

Organisation for Economic Co‐operation and Development

PBI

plant‐back interval

PeF

peeling factor

PF

processing factor

PHI

preharvest interval

PRIMo

(EFSA) Pesticide Residues Intake Model

RA

risk assessment

RAC

raw agricultural commodity

RD

residue definition

RMS

rapporteur Member State

RSD

relative standard deviation

SANCO

Directorate‐General for Health and Consumers

SEU

southern Europe

STMR

supervised trials median residue

TRR

total radioactive residue

WHO

World Health Organization

WP

wettable powder

Appendix A – Summary of GAPs assessed in the evaluation of confirmatory data

Crop and/or situation	NEU, SEU, MS or country	F, G or I(a)	Pests or group of pests controlled	Preparation		Application				Application rate per treatment				PHI (days)(d)	Remarks
				Type(b)	Conc. a.s.	Method kind	Range of growth stages & season(c)	Number min–max	Interval between application (min)	g a.s./hL min–max	Water L/ha min–max	Rate	Unit
MRL review GAPs (authorised uses) (EFSA, 2016)
Apricots	SEU	F	Mites	WP	20%	Foliar treatment – spraying	n/a	1	n/a	–	1,000–1,500	100	g a.i./ha	14
Peaches	SEU	F	Mites	WP	20%	Foliar treatment – spraying	n/a	1	n/a	–	1,000–1,500	100	g a.i./ha	14
Blackberries	NEU	F	Mites	WP	20%	Foliar treatment – spraying	n/a	1	n/a	–	400–1,000	75	g a.i./ha	21
Dewberries	NEU	F	Mites	WP	20%	Foliar treatment – spraying	n/a	1	n/a	–	400–1,000	75	g a.i./ha	21
New adjusted GAPs (confirmatory data) (Germany,  2022 )
Apricots	SEU	F	Panonychus ulmi, Tetranychus urticae	WP	20%	Foliar treatment – broadcast spraying	Upon infestation	1	n/a	–	1,000–1,500	100–130	g a.i./ha	14	spraying‐mist blowing
Peaches	SEU	F	Panonychus ulmi, Tetranychus urticae	WP	20%	Foliar treatment – broadcast spraying	Upon infestation	1	n/a	–	1,000–1,500	100–130	g a.i./ha	14	spraying‐mist blowing

NEU: northern European Union; SEU: southern European Union; MS: Member State; WP: wettable powder.

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

(b) CropLife International Technical Monograph no 2, 6th Edition. Revised May 2008. Catalogue of pesticide formulation types and international coding system.

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

(d) PHI: minimum preharvest interval.

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	Crop(s)	Application(s)	Sampling (DAT)	Comment/source
	Fruit crops	Apples	Foliar, 3 × 740 g a.s./ha	14	Metabolism studies performed with phenyl and pyrazole labelled tebufenpyrad (Sources: EFSA, 2016). Metabolism study on leafy vegetables and pulses and oilseed not available.
		Grapes	Foliar, 2 × 140 g a.s./ha	14
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/source
	Not available and not required
Processed commodities (hydrolysis study)	Conditions		Stable?		Comment/source
	Pasteurisation (20 min, 90°C, pH 4)		Yes		EFSA (2008)
	Baking, brewing and boiling (60 min, 100°C, pH 5)		Yes		EFSA (2008)
	Sterilisation (20 min, 120°C, pH 6)		Yes		EFSA (2008)
	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 water content	Apples	−18	24	Months	Tebufenpyrad	Storage stability study in high oil content and in complex matrices not available. (EFSA, 2016)
	High acid content	Grapes, citrus fruits	−18	24	Months	Tebufenpyrad

B.1.2. Magnitude of residues in plants

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

Commodity	Region/indoor(a)	Residue levels observed in the supervised residue trials (mg/kg)	Comments/source	Calculated MRL (mg/kg)	HR(b) (mg/kg)	STMR(c) (mg/kg)	CF(d)
Residue definition for enforcement and for risk assessment: Tebufenpyrad
Peaches, apricots	SEU	0.042, 0.047, 0.068, 0.077, 0.078, 0.086, 0.11, 0.115, 0.146, 0.162, 0.18 Underlined: trials already provided with the MRL review Italics: trials on apricots	Combined data set of residue trials on peaches (7) and apricots (4) compliant with the adjusted GAP. Combination and extrapolation of trials to both peaches and apricots is possible	0.3	0.18	0.09	n/a
Blackberries and dewberries	NEU	3 × ≤ 0.05, < 0.05 Underlined: trials already provided with the MRL review	Number of trials on raspberries in NEU (4) compliant with the GAP and sufficient to extrapolate to blackberries and dewberries EFSA notes that a lower LOQ is now achievable for these crops (0.01 mg/kg), therefore proposes to maintain the tMRL of 0.05 mg/kg	0.05	0.05	0.05	n/a

MRL: maximum residue level; tMRL: tentative maximum residue level; GAP: Good Agricultural Practice; Mo: monitoring; RA: risk assessment.

(a) NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, Indoor: indoor EU trials or Country code: if non‐EU trials.

(b) Highest residue. The highest residue for risk assessment refers to the whole commodity and not to the edible portion.

(c) Supervised trials median residue. The median residue for risk assessment refers to the whole commodity and not to the edible portion.

(d) Conversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment.

B.1.2.2. Residues in rotational crops

B.1.2.3. Processing factors

No processing studies were submitted in the framework of the present MRL application.

B.2. Residues in livestock

Not relevant for the current assessment.

B.3. Consumer risk assessment

B.4. Recommended MRLs

Code(a)	Commodity	Existing MRL(b)	Data gap(s) Art. 12 Review	Proposed MRL	Conclusion/recommendation
Enforcement residue definition: Tebufenpyrad(F)
0140010	Apricots	0.4 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.3	The data gap identified by EFSA concerning additional residue trials has been addressed. EFSA proposes to lower the existing MRL to 0.3 mg/kg based on a set of combined residue trials on peaches and apricots performed according to an adjusted GAP. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0140030	Peaches	0.4 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.3	The data gap identified by EFSA concerning additional residue trials has been addressed. EFSA proposes to lower the existing MRL to 0.3 mg/kg based on a set of combined residue trials on peaches and apricots performed according to an adjusted GAP. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0153010	Blackberries	0.05 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.05	The data gap identified by EFSA concerning additional residue trials has been addressed. The available residue trials on raspberries (extrapolated to blackberries and dewberries) confirmed the existing MRL. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0153020	Dewberries	0.05 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.05	The data gap identified by EFSA concerning additional residue trials has been addressed. The available residue trials on raspberries (extrapolated to blackberries and dewberries) confirmed the existing MRL. The updated consumer risk assessment for tebufenpyrad did not indicate any consumer intake concerns.
0260010	Beans (with pods)	0.3 (ft 1)	Footnote related to data gap No 4. [additional residue trials]	0.01*	The data gap identified by EFSA concerning additional residue trials has not been addressed. The applicant indicated that no additional residue trials in beans with pods were submitted since the authorisation in this crop is no longer sustained. Therefore, EFSA proposes to lower the existing MRL to the LOQ of 0.01 mg/kg.
0700000	HOPS	1.5 (ft 2)	Footnote related to data gap No 1. [analytical methods]	0.01*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in hops has not been addressed. The applicant indicated that no analytical method for enforcement in hops was submitted since the authorisation in this crop is no longer sustained. Therefore, EFSA proposes to lower the existing MRL to the LOQ of 0.01 mg/kg.
1010000 to 1070000 except 1040000	PRODUCTS OF ANIMAL ORIGIN (Except Honey and other apiculture products)	0.01* (ft 2)	Footnote related to data gap No 5. [analytical methods]	0.01*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in animal commodities has been addressed. Therefore, EFSA proposes to confirm the existing MRLs set at the LOQ of 0.01 mg/kg.
1040000	Honey and other apiculture products (7)	0.05* (ft 2)	Footnote related to data gap No 5. [analytical methods]	0.05*	The data gap identified by EFSA concerning a fully validated analytical method for enforcement in animal commodities has been addressed but since a specific analytical method for honey has not been provided, EFSA proposes to maintain the existing MRL at the LOQ of 0.05 mg/kg

MRL: maximum residue level; GAP: Good Agricultural Practice; LOQ: limit of quantification.

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

(a) Commodity code number according to Annex I of Regulation (EC) No 396/2005.

(b) Existing EU MRL and corresponding footnote on confirmatory data.

ft 1: The European Food Safety Authority identified some information on residue trials as unavailable. When re‐viewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 April 2019, or, if that information is not submitted by that date, the lack of it.

ft 2: The European Food Safety Authority identified some information on analytical methods as unavailable. When re‐viewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 April 2019, or, if that information is not submitted by that date, the lack of it.

(F) Fat‐soluble.

Appendix C – Pesticide Residue Intake Model (PRIMo)

Appendix D – Input values for the exposure calculations

D.1. Consumer risk assessment

Commodity	Existing/proposed MRL (mg/kg)	Source	Chronic risk assessment		Acute risk assessment
			Input value (mg/kg)	Comment	Input value (mg/kg)	Comment(a)
Citrus fruit	0.6	EFSA (2016)	0.01	STMR‐RAC x PF	0.03	HR‐RAC x PF
Apples	0.3	EFSA (2016)	0.1	STMR‐RAC (fall back GAP)	0.16	HR‐RAC (fall‐back GAP)
Pears	0.3	EFSA (2016)	0.1	STMR‐RAC (fall back GAP)	0.13	HR‐RAC (fall‐back GAP)
Quinces	0.8	EFSA (2016)	0.25	STMR‐RAC	0.43	HR‐RAC
Medlar	0.8	EFSA (2016)	0.25	STMR‐RAC	0.43	HR‐RAC
Loquats/Japanese medlars	0.8	EFSA (2016)	0.25	STMR‐RAC	0.43	STMR‐RAC
Apricots	0.3	Present assessment	0.12	STMR‐RAC (input values from MRL review)(c)	0.19	HR‐RAC (input values from MRL review)(c)
Peaches	0.3	Present assessment	0.12	STMR‐RAC (input values from MRL review)(c)	0.19	HR‐RAC (input values from MRL review)(c)
Plums	0.2	EFSA (2016)	0.05	STMR‐RAC	0.15	HR‐RAC
Table grapes	0.6	EFSA (2016)	0.13	STMR‐RAC	0.30	HR‐RAC
Wine grapes	0.6	EFSA (2016)	0.14	STMR‐RAC	0.32	HR‐RAC
Strawberries	1.0	EFSA (2016)	0.29	STMR‐RAC	0.58	HR‐RAC
Blackberries	0.05	Present assessment	0.05	STMR‐RAC	0.05	HR‐RAC
Dewberries	0.05	Present assessment	0.05	STMR‐RAC	0.05	HR‐RAC
Raspberries	0.15	EFSA (2016)	0.05	STMR‐RAC	0.06	HR‐RAC
Other small fruits and berries	1.5	EFSA (2016)	0.50	STMR‐RAC	0.84	HR‐RAC
Tomatoes	0.8	EFSA (2016)	0.26	STMR‐RAC	0.33	HR‐RAC
Aubergines	0.8	EFSA (2016)	0.26	STMR‐RAC	0.33	HR‐RAC
Cucumbers	0.3	EFSA (2016)	0.08	STMR‐RAC	0.19	HR‐RAC
Gherkins	0.5	EFSA (2016)	0.16	STMR‐RAC	0.20	HR‐RAC
Courgettes	0.3	EFSA (2016)	0.08	STMR‐RAC	0.19	HR‐RAC
Melons	0.3	EFSA (2016)	0.01	STMR‐RAC × PF	0.04	HR‐RAC × PF
Watermelons	0.3	EFSA (2016)	0.01	STMR‐RAC × PF	0.04	HR‐RAC × PF
Beans (with pods)	0.01*	Present assessment
Cotton seeds	0.05*	EFSA (2016)	0.05	STMR‐RAC	0.05	HR‐RAC
Hops	0.01*	Present assessment
Ruminant meat	0.01*	EFSA (2016)	0.01	0.8 x STMR muscle + 0.2 × STMR fat(b)	0.01	0.8 × HR muscle + 0.2 × HR fat(b)
Ruminant fat	0.01*	EFSA (2016)	0.01	STMR	0.01	HR
Ruminant liver	0.01*	EFSA (2016)	0.01	STMR	0.01	HR
Ruminant kidney	0.01*	EFSA (2016)	0.01	STMR	0.01	HR
Ruminant milk	0.01*	EFSA (2016)	0.01	STMR	0.01	HR

STMR‐RAC: supervised trials median residue in raw agricultural commodity; HR‐RAC: highest residue in raw agricultural commodity; PeF: peeling factor.

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

(a) Input values for the commodities which are not under consideration for the acute risk assessment are reported in grey.

(b) Consumption figures in the EFSA PRIMo are expressed as meat. Since the a.s. is a fat‐soluble pesticides, STMR and HR residue values were calculated considering a 80%/90% muscle and 20%/10% fat content for mammal/poultry meat respectively (FAO, 2016).

(c) Since the risk assessment values derived in the framework of the MRL review are higher than the ones derived from the adjusted GAP, the highest/median values derived in the MRL review (HR, STMR) are still considered in the consumer risk assessment.

Appendix E – Used compound codes

Code/trivial name(a)	IUPAC name/SMILES notation/InChiKey(b)	Structural formula(c)
Tebufenpyrad	N‐(4‐tert‐butylbenzyl)‐4‐chloro‐3‐ethyl‐1‐methyl‐1H‐pyrazole‐5‐carboxamide Clc2c(C(=O)NCc1ccc(cc1)C(C)(C)C)n(C)nc2CC ZZYSLNWGKKDOML‐UHFFFAOYSA‐N

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

(a) The metabolite name in bold is the name used in the conclusion.

(b) ACD/Name 2021.1.3 ACD/Labs 2021.1.3 (File Version N15E41, Build 123232, 7 July 2021).

(c) ACD/ChemSketch 2021.1.3 ACD/Labs 2021.1.3 (File Version C25H41, Build 123835, 28 August 2021).

Suggested citation: EFSA (European Food Safety Authority) , Bellisai G, Bernasconi G, Brancato A, Carrasco Cabrera L, Castellan I, Del Aguila M, Ferreira L, Giner Santonja G, Greco L, Jarrah S, Leuschner R, Magrans JO, Miron I, Nave S, Pedersen R, Reich H, Robinson T, Ruocco S, Santos M, Scarlato AP, Theobald A and Verani A, 2023. Reasoned Opinion on the evaluation of confirmatory data following the Article 12 MRL review for tebufenpyrad. EFSA Journal 2023;21(2):7774, 28 pp. 10.2903/sp.efsa.2023.7774