Review of the existing maximum residue levels for 6‐benzyladenine according to Article 12 of Regulation (EC) No 396/2005

Abstract

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance 6‐benzyladenine. To assess the occurrence of 6‐benzyladenine residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008, as well as the European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. All information required by the regulatory framework was present and a risk to consumers was not identified.

Summary

6‐Benzyladenine was included in Annex I to Directive 91/414/EEC on 1 June 2011 by Commission Directive 2011/1/EU, and has been deemed to be approved under Regulation (EC) No 1107/2009, in accordance with Commission Implementing Regulation (EU) No 540/2011, as amended by Commission Implementing Regulation (EU) No 541/2011.

As the active substance was approved after the entry into force of Regulation (EC) No 396/2005 on 2 September 2008, the European Food Safety Authority (EFSA) is required to provide a reasoned opinion on the review of the existing maximum residue levels (MRLs) for that active substance in compliance with Article 12(1) of the aforementioned regulation.

As the basis for the MRL review, on 12 April 2019, EFSA initiated the collection of data for this active substance. In a first step, Member States were invited to submit by 10 May 2019 their national Good Agricultural Practices (GAPs) in a standardised way, in the format of specific GAP forms, allowing the designated rapporteur Member State, Sweden, to identify the critical GAPs in the format of a specific GAP overview file. Subsequently, Member States were requested to provide residue data supporting the critical GAPs, within a period of 1 month, by 21 October 2019. On the basis of all the data submitted by Member States and by the EU Reference Laboratories for Pesticides Residues (EURL), EFSA asked the rapporteur Member State (RMS) to complete the Pesticide Residues Overview File (PROFile) and to prepare a supporting evaluation report. The PROFile and evaluation report, together with Pesticide Residues Intake Model (PRIMo) calculations and an updated GAP overview file were provided by the RMS to EFSA on 20 December 2019. Subsequently, EFSA performed the completeness check of these documents with the RMS. The outcome of this exercise including the clarifications provided by the RMS, if any, was compiled in the completeness check report.

Based on the information provided by the RMS, Member States and the EURL, and taking into account the conclusions derived by EFSA in the framework of Commission Regulation (EC) No 33/2008, EFSA prepared in March 2020 a draft reasoned opinion, which was circulated to Member States and EURL for consultation via a written procedure. Comments received by 29 April 2020 were considered during the finalisation of this reasoned opinion. The following conclusions are derived.

The metabolism of 6‐benzyladenine in plant was investigated in primary crops. According to the results of the metabolism studies, the residue definition for enforcement and risk assessment can be proposed as 6‐benzyladenine. No hydrolysis study is available and is not required as no residues are expected in the raw commodities.

An analytical method for the enforcement of the proposed residue definition at the LOQ of 0.01 mg/kg in high acid and dry matrices is available. Validation of the analytical method in high water matrices is desirable.

According to the EURL, 6‐benzyladenine can be monitored in dry commodities with an LOQ of 0.01 mg/kg, and based on validation data, it can also be monitored in high water content and high acid content, as well as high oil content commodities with an LOQ of 0.01 mg/kg.

Available residue trials data were considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under evaluation. A no residue situation is expected for all commodities.

6‐Benzyladenine is authorised for use on crops that might be fed to livestock. Livestock dietary burden calculations were therefore performed for different groups of livestock according to OECD guidance. Since the calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg dry matter (DM), further investigation of residues as well as the setting of MRLs in commodities of animal origin is unnecessary.

Chronic consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 3.1 of the EFSA PRIMo. The highest chronic exposure represented 2% of the ADI (Dutch toddler). Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not deemed necessary for this active substance.

Background

Regulation (EC) No 396/20051 (hereinafter referred to as ‘the Regulation’) establishes the rules governing the setting and the review of pesticide maximum residue levels (MRLs) at European level. Article 12(1) of that Regulation stipulates that the European Food Safety Authority (EFSA) shall provide within 12 months from the date of the inclusion or non‐inclusion of an active substance in Annex I to Directive 91/414/EEC2 a reasoned opinion on the review of the existing MRLs for that active substance.

6‐Benzyladenine was included in Annex I to Council Directive 91/414/EEC on 1 June 2011 by means of Commission Directive 2011/1/EU3 which has been deemed to be approved under Regulation (EC) No 1107/20094, in accordance with Commission Implementing Regulation (EU) No 540/20115, as amended by Commission Implementing Regulation (EU) No 541/20116. Therefore, EFSA initiated the review of all existing MRLs for that active substance.

By way of background information, in the framework of Commission Regulation (EC) No 33/2008, 6‐benzyladenine was evaluated by the United Kingdom, designated as rapporteur Member State (RMS). Subsequently, a peer review on the initial evaluation of the RMS was conducted by EFSA, leading to the conclusions as set out in the EFSA scientific output (EFSA, 2010). The approval of 6‐benzyladenine is restricted to uses as plant growth regulator.

According to the legal provisions, EFSA shall base its reasoned opinion in particular on the relevant assessment report prepared under Directive 91/414/EEC repealed by Regulation (EC) No 1107/2009. It should be noted, however, that, in the framework of Regulation (EC) No 1107/2009, only a few representative uses are evaluated, whereas MRLs set out in Regulation (EC) No 396/2005 should accommodate all uses authorised within the European Union (EU), and uses authorised in third countries that have a significant impact on international trade. The information included in the assessment report prepared under Regulation (EC) No 1107/2009 is therefore insufficient for the assessment of all existing MRLs for a given active substance.

To gain an overview of the pesticide residues data that have been considered for the setting of the existing MRLs, EFSA developed the Pesticide Residues Overview File (PROFile). The PROFile is an inventory of all pesticide residues data relevant to the risk assessment and MRL setting for a given active substance. This includes data on:

• the nature and magnitude of residues in primary crops;

• the nature and magnitude of residues in processed commodities;

• the nature and magnitude of residues in rotational crops;

• the nature and magnitude of residues in livestock commodities;

• the analytical methods for enforcement of the proposed MRLs.

As the basis for the MRL review, on 12 April 2019, EFSA initiated the collection of data for this active substance. In a first step, Member States were invited to submit by 10 May 2019 their Good Agricultural Practices (GAPs) that are authorised nationally, in a standardised way, in the format of specific GAP forms. In the framework of this consultation, 18 Member States provided feedback on their national authorisations of 6‐benzyladenine. Based on the GAP data submitted, the designated RMS, Sweden, was asked to identify the critical GAPs to be further considered in the assessment, in the format of a specific GAP overview file. Subsequently, in a second step, Member States were requested to provide residue data supporting the critical GAPs by 21 October 2019.

On the basis of all the data submitted by Member States and the EU Reference Laboratories for Pesticides Residues (EURL), EFSA asked Sweden to complete the PROFile and to prepare a supporting evaluation report. The PROFile and the supporting evaluation report, together with the Pesticide Residues Intake Model (PRIMo) calculations and an updated GAP overview file, were submitted to EFSA on 20 December 2019. Subsequently, EFSA performed the completeness check of these documents with the RMS. The outcome of this exercise including the clarifications provided by the RMS, if any, was compiled in the completeness check report.

Considering all the available information, EFSA prepared in March 2020 a draft reasoned opinion, which was circulated to Member States and EURL for commenting via a written procedure. All comments received by 29 April 2020 were considered by EFSA during the finalisation of the reasoned opinion.

The evaluation report submitted by the RMS (Sweden, 2019), taking into account also the information provided by Member States during the collection of data (Germany, 2019), and the EURL report on analytical methods (EURL, 2019) are considered as main supporting documents to this reasoned opinion and, thus, made publicly available.

In addition, further supporting documents to this reasoned opinion are the completeness check report (EFSA, 2020a) and the Member States consultation report (EFSA, 2020b). These reports are developed to address all issues raised in the course of the review, from the initial completeness check to the reasoned opinion. Furthermore, the exposure calculations for all crops reported in the framework of this review performed using the EFSA Pesticide Residues Intake Model (PRIMo) and the PROFile as well as the GAP overview file listing all authorised uses are key supporting documents and made publicly available as background documents to this reasoned opinion. A screenshot of the report sheet of the PRIMo is presented in Appendix Appendix C – Pesticide Residue Intake Model (PRIMo).

Terms of Reference

According to Article 12 of Regulation (EC) No 396/2005, EFSA shall provide a reasoned opinion on:

• the inclusion of the active substance in Annex IV to the Regulation, when appropriate;

• the necessity of setting new MRLs for the active substance or deleting/modifying existing MRLs set out in Annex II or III of the Regulation;

• the inclusion of the recommended MRLs in Annex II or III to the Regulation;

• the setting of specific processing factors as referred to in Article 20(2) of the Regulation.

The active substance and its use pattern

6‐Benzyladenine is the ISO common name for N ⁶‐benzyladenine (IUPAC).

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

For 6‐benzyladenine default MRL of 0.01 mg/kg is established according to Art 18(1)(b) of Regulation (EC) No 396/2005. Codex maximum residue limits (CXLs) for 6‐benzyladenine are not available. There are no MRL changes occurred since the entry into force of the Regulation mentioned above.

For the purpose of this MRL review, all the uses of 6‐benzyladenine currently authorised within the EU as submitted by the Member States during the GAP collection have been reported by the RMS in the GAP overview file. The critical GAPs identified in the GAP overview file were then summarised in the PROFile and considered in the assessment. The details of the authorised critical GAPs for 6‐benzyladenine are given in Appendix Appendix A – Summary of authorised uses considered for the review of MRLs. The RMS did not report any use authorised in third countries that might have a significant impact on international trade.

In the framework of the peer review, 6‐benzyladenine was initially assumed to be a naturally occurring plant hormone. As information was found only on similar compounds, but not on 6‐benzyladenine itself, a data gap was set to provide quantitative evidence that 6‐benzyladenine is naturally occurring in edible crops (EFSA, 2010). In the absence of this information, the toxicological reference values were reconsidered and an ADI was established (European Commission, 2011). No further information to support this assumption was received to date.

Assessment

EFSA has based its assessment on the following documents:

• the PROFile submitted by the RMS;

• the evaluation report accompanying the PROFile (Sweden, 2019);

• the draft assessment report (DAR) prepared under Council Directive 91/414/EEC (France, 2007);

• the additional report (AR) and its addenda prepared under Commission Regulation (EC) No 33/2008 (United Kingdom, 2009);

• final addendum to the additional report (AR) (United Kingdom, 2010);

• the conclusion on the peer review of the pesticide risk assessment of the active substance 6‐benzyladenine (EFSA, 2010);

• the review report on 6‐benzyladenine (European Commission, 2011).

The assessment is performed in accordance with the legal provisions of the uniform principles for evaluation and authorisation of plant protection products as set out in Commission Regulation (EU) No 546/20117 and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (European Commission, 1997a, 1997b, 1997c, 1997d, e, f, g, 2000, 2010a, 2010b, 2017; OECD, 2011, 2013).

More detailed information on the available data and on the conclusions derived by EFSA can be retrieved from the list of end points reported in Appendix B.

1. Residues in plants

1.1. Nature of residues and methods of analysis in plants

1.1.1. Nature of residues in primary crops

In the framework of the peer review, the metabolism of 6‐benzyladenine was investigated following foliar treatment in fruits (apples) (United Kingdom, 2009; EFSA, 2010). The study was conducted at an application rate of 0.7N covering the uses reported in this review. The metabolites identified in this study were either conjugates of 6‐benzyladenine or benzoic acid. In addition, scientific review reports on root vegetables, cereals and pulses/oilseeds were also considered to establish the metabolic pathway in crops (France, 2007; EFSA, 2010).

1.1.2. Nature of residues in rotational crops

6‐Benzyladenine is authorised only on perennial and/or semi‐permanent crops. In addition, the field DT₅₀ reported in the soil degradation studies evaluated in the framework of the peer review was 1–1.2 days (EFSA, 2010). Therefore, studies investigating the nature of 6‐benzyladenine on rotational crops were not reported and are not required.

1.1.3. Nature of residues in processed commodities

There were no studies investigating the nature of residues of 6‐benzyladenine in processed commodities available for this review. In all commodities, residues were below 0.01 mg/kg and the total theoretical maximum daily intake is 2% of the ADI. Therefore, the investigation of the nature of residues in processed commodities is not required.

1.1.4. Methods of analysis in plants

During the peer review, a hyphenated analytical method based on HPLC detection coupled to MS/MS was validated in dry commodities (maize) with an LOQ of 0.01 mg/kg (EFSA, 2010). An independent laboratory validation (ILV) is not available, nor is it considered needed for this matrix as there are no uses currently authorised on dry commodities.

For high water content commodities, the peer review identified a data gap considering the submitted method of analysis not acceptable due to unexplained low recoveries and communications between the primary and ILV laboratories (EFSA, 2010). During the data collection phase of the current review, a fully validated method, including ILV for high acid content commodities was submitted (Sweden, 2019). This method, validated in strawberries, is the same analytical method assessed in the peer review for apples. In addition, an analytical method used in residue trials to determine 6‐benzyladenine residues in apples has been validated and found capable of determining 6‐benzyladenine residues at an LOQ of 0.01 mg/kg using HPLC detection coupled to UV (Germany, 2019). Therefore, the submission of a fully validated analytical method according to SANCO/825/00 rev. 8.1 guidance in high water content commodities is only desirable.

According to the EURL, 6‐benzyladenine can be monitored in dry commodities with an LOQ of 0.01 mg/kg. The EURL reported that validation data show 6‐benzyladenine can also be monitored in high water content and high acid content, as well as high oil content commodities with an LOQ of 0.01 mg/kg (EURL, 2019).

1.1.5. Stability of residues in plants

The storage stability of 6‐benzyladenine was investigated in the framework of the peer review (France, 2007; EFSA, 2010). Accordingly, in high water content matrices, the storage stability for 6‐benzyladenine was demonstrated for a period of 18 months when stored at –18°C. A storage stability study in acidic commodities is not available. Nevertheless, this study is not required in the framework of this review, as samples from trials on strawberries were analysed within one month.

1.1.6. Proposed residue definitions

During the peer review, based on the metabolism study and other supporting information, and that at harvest no significant residues were present, it was concluded that the residue definition for risk assessment and monitoring is 6‐benzyladenine (EFSA, 2010). This conclusion is considered still applicable for the present review.

An analytical method for the enforcement of the proposed residue definition at the LOQ of 0.01 mg/kg in high acid (Sweden, 2019) and dry matrices is available (EFSA, 2010); no further analytical method for the enforcement in other matrices was provided. Validation of the analytical method in high water matrices is desirable.

According to the EURL, 6‐benzyladenine can be monitored in all major matrices with an LOQ of 0.01 mg/kg (EURL, 2019). The analytical standard for 6‐benzyladenine is commercially available (EURL, 2019).

1.2. Magnitude of residues in plants

1.2.1. Magnitude of residues in primary crops

To assess the magnitude of 6‐benzyladenine residues resulting from the reported GAPs, EFSA considered all residue trials reported by the RMS in its evaluation report (Sweden, 2019), additional residue trials submitted during data collection (Germany, 2019), as well as the residue trials evaluated in the framework of the peer review (EFSA, 2010). All residue trial samples considered in this framework were either stored in compliance with the conditions for which storage stability of residues was demonstrated or was analysed within 30 days. Decline of residues during storage of the trial samples is therefore not expected.

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

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

Pome fruits: The number of residue trials supporting the southern outdoor GAP is not compliant with the data requirements for this crop. However, the reduced number of overdosed residue trials is considered acceptable in this case because all results were below the LOQ of 0.01 mg/kg and a no residues situation is expected. This is also supported by the eight residue trials supporting the northern outdoor GAP. Further residue trials are therefore not required.

Stone fruits (apricots, cherries, peach): Although no residue trials are available, as for these crops, 6‐benzyladenine is authorised for the use in nurseries, and considering the results of the metabolism studies and the properties of the active substance, a no residue situation is expected. Therefore, the MRLs can be set at the LOQ and no further residue trials are required.

Strawberries: The number of residue trials supporting the indoor GAP is not compliant with the data requirements for this crop. However, the reduced number of residue trials is considered acceptable in this case because all results were below the LOQ of 0.01 mg/kg even on the day of application. Further residue trials are therefore not required.

1.2.2. Magnitude of residues in rotational crops

There are no studies investigating the magnitude of residues in rotational crops available. Based on the uses and the persistence of 6‐benzyladenin no further studies are required (see also Section 1.1.2).

1.2.3. Magnitude of residues in processed commodities

The effect of industrial processing and/or household preparation was assessed in studies conducted on apples (France, 2007, EFSA, 2010). An overview of all available processing studies is available in Appendix B.1.2.3. Concentration of 6‐benzyladenine was not observed, in processed commodities, residues were below the LOQ of 0.005 mg/kg. Tentative processing factors based on one study were derived for apple juice and apple wet pomace. Further processing studies are not required as residues in the raw commodities under assessment are below the LOQ of 0.01 mg/kg.

1.2.4. Proposed MRLs

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under evaluation.

2. Residues in livestock

6‐Benzyladenine is authorised for use on pome fruits that might be fed to livestock. However, the dietary burdens of livestock are not expected to be significant, as residues in the raw commodities are below the LOQ and the processing studies show that only further reduction of residues is expected in processed commodities. Therefore, further investigation of the occurrence of residues in commodities of animal origin is not required and the setting of MRLs in these commodities is not considered necessary.

3. Consumer risk assessment

Chronic exposure calculations for all crops reported in the framework of this review were performed using revision 3.1 of the EFSA PRIMo (EFSA, 2018, 2019). Input values for the exposure calculations were derived in compliance with the decision tree reported in Appendix E. Hence, for those commodities where an MRL could be derived by EFSA in the framework of this review, input values were derived according to the internationally agreed methodologies (FAO, 2009). All input values included in the exposure calculations are summarised in Appendix D. Acute exposure calculations were not carried out because an acute reference dose (ARfD) was not deemed necessary for this active substance.

The exposure values calculated were compared with the toxicological reference value for 6‐benzyladenine, included in the Review Report (European Commission, 2011). The highest chronic exposure was calculated for the Dutch toddler, representing 2% of the acceptable daily intake (ADI).

These calculations indicate that the uses assessed under this review result in a consumer exposure lower than the toxicological reference value. Therefore, these uses are unlikely to pose a risk to consumer's health.

4. Conclusions

The metabolism of 6‐benzyladenine in plant was investigated in primary crops. According to the results of the metabolism studies, the residue definition for enforcement and risk assessment can be proposed as 6‐benzyladenine. No hydrolysis study is available and is not required as no residues are expected in the raw commodities.

An analytical method for the enforcement of the proposed residue definition at the LOQ of 0.01 mg/kg in high acid and dry matrices is available. Validation of the analytical method in high water matrices is desirable.

According to the EURL, 6‐benzyladenine can be monitored in dry commodities with an LOQ of 0.01 mg/kg, and based on validation data, it can also be monitored in high water content and high acid content, as well as high oil content commodities with an LOQ of 0.01 mg/kg.

Available residue trials data were considered sufficient to derive MRL proposals as well as risk assessment values for all commodities under evaluation. A no residue situation is expected for all commodities.

6‐Benzyladenine is authorised for use on crops that might be fed to livestock. Livestock dietary burden calculations were therefore performed for different groups of livestock according to OECD guidance. Since the calculated dietary burdens for all groups of livestock were found to be below the trigger value of 0.1 mg/kg dry matter (DM), further investigation of residues as well as the setting of MRLs in commodities of animal origin is unnecessary.

Chronic consumer exposure resulting from the authorised uses reported in the framework of this review was calculated using revision 3.1 of the EFSA PRIMo. The highest chronic exposure represented 2% of the ADI (Dutch toddler). Acute exposure calculations were not carried out because an ARfD was not deemed necessary for this active substance.

5. Recommendations

MRL recommendations were derived in compliance with the decision tree reported in Appendix E of the reasoned opinion (see Table 11). All MRL values listed as ‘Recommended’ in the table are sufficiently supported by data and are therefore proposed for inclusion in Annex II to the Regulation.

Table 1.

Summary table

Code number	Commodity	Existing EU MRL (mg/kg)	Existing CXL (mg/kg)	Outcome of the review
				MRL (mg/kg)	Comment
Enforcement residue definition: 6‐benzyladenine
130010	Apples	0.01*	–	0.01*	Recommendeda
130020	Pears	0.01*	–	0.01*	Recommendeda
130030	Quinces	0.01*	–	0.01*	Recommendeda
130040	Medlar	0.01*	–	0.01*	Recommendeda
130050	Loquat	0.01*	–	0.01*	Recommendeda
140010	Apricots	0.01*	–	0.01*	Recommendeda
140020	Cherries (sweet)	0.01*	–	0.01*	Recommendeda
140030	Peaches	0.01*	–	0.01*	Recommendeda
140040	Plums	0.01*	–	0.01*	Recommendeda
152000	Strawberries	0.01*	–	0.01*	Recommendeda
–	Other commodities of plant and/or animal origin	Art. 18(1)b Reg 396/2005	–	–	Further consideration neededb

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

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

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

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

Minor deficiencies were identified in the assessment, but these deficiencies are not expected to impact either the validity of the MRLs derived or the national authorisations. The following data are therefore considered desirable but not essential:

• Full validation of the analytical method for high water commodities according to European Commission Guidance (European Commission, 2010b).

Abbreviations

a.i.

active ingredient

a.s.

active substance

ADI

acceptable daily intake

AL

any other liquid

AR

applied radioactivity

ARfD

acute reference dose

BBCH

growth stages of mono‐ and dicotyledonous plants

BVL

Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany

bw

body weight

CAC

Codex Alimentarius Commission

CAS

Chemical Abstract Service

CCPR

Codex Committee on Pesticide Residues

CEN

European Committee for Standardization (Comité Européen de Normalisation)

CF

conversion factor for enforcement residue definition to risk assessment residue definition

CIRCA

(EU) Communication & Information Resource Centre Administrator

CS

capsule suspension

CV

coefficient of variation (relative standard deviation)

CXL

codex maximum residue limit

DALA

days after last application

DAR

draft assessment report

DAT

days after treatment

DB

dietary burden

DM

dry matter

DS

powder for dry seed treatment

DT₉₀

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

DTU

Danish Technical University

EC

emulsifiable concentrate

EMS

evaluating Member State

EURL

European Union Reference Laboratories for Pesticide Residues (former CRLs)

FAO

Food and Agriculture Organization of the United Nations

FID

flame ionisation detector

FLD

fluorescence detector

FPD

flame photometric detector

GAP

Good Agricultural Practice

GC

gas chromatography

GC‐ECD

gas chromatography with electron capture detector

GC‐FID

gas chromatography with flame ionisation detector

GC‐FPD

gas chromatography with flame photometric detector

GC‐MS

gas chromatography with mass spectrometry

GC‐MS/MS

gas chromatography with tandem mass spectrometry

GC‐NPD

gas chromatography with nitrogen/phosphorous detector

GCPF

Global Crop Protection Federation (formerly International Group of National Associations of Manufacturers of Agrochemical Products; GIFAP)

GLP

Good Laboratory Practice

GR

Granule

GS

growth stage

HPLC

high‐performance liquid chromatography

HPLC‐MS

high‐performance liquid chromatography with mass spectrometry

HPLC‐MS/MS

high‐performance liquid chromatography with tandem mass spectrometry

HPLC‐UVD

high‐performance liquid chromatography with ultra‐violet detector

HR

highest residue

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ILV

independent laboratory validation

IPCS

International Programme of Chemical Science

ISO

International Organisation for Standardization

IUPAC

International Union of Pure and Applied Chemistry

JMPR

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

LC

liquid chromatography

LC-MS/MS

liquid chromatography with tandem mass spectrometry

LOAEL

lowest observed adverse effect level

LOD

limit of detection

LOQ

limit of quantification

Mo

Monitoring

MRL

maximum residue level

MS

Member States

MS

mass spectrometry detector

MS/MS

tandem mass spectrometry detector

MW

molecular weight

NEU

northern European Union

NOAEL

no observed adverse effect level

NPD

nitrogen/phosphorous detector

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

P_ow

partition coefficient between n‐octanol and water

Ppm

parts per million (10⁻⁶)

PRIMo

(EFSA) Pesticide Residues Intake Model

PROFile

(EFSA) Pesticide Residues Overview File

RA

risk assessment

RAC

raw agricultural commodity

RD

residue definition

RMS

rapporteur Member State

RPF

relative potency factor

RSD

relative standard deviation

SANCO

Directorate‐General for Health and Consumers

SBI

sterol biosynthesis inhibitors

SC

suspension concentrate

SCPAFF

Standing Committee on Plants, Animals, Food and Feed (formerly: Standing Committee on the Food Chain and Animal Health; SCFCAH)

SEU

southern European Union

SMILES

simplified molecular‐input line‐entry system

SG

water soluble granule

SL

soluble concentrate

SP

water soluble powder

STMR

supervised trials median residue

TAR

total applied radioactivity

TMDI

theoretical maximum daily intake

UV

ultraviolet (detector)

WG

water dispersible granule

WHO

World Health Organization

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

A.1. Authorised outdoor uses in northern EU

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application			Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	Number min–max	a.s./hL min–max	Water L/ha min–max	Rate and unit
Apples	NL	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	225 g a.i./ha	90	–
Pears	BE	F	Excessiv fruit production	SL	20 g/L	Foliar treatment – general (see also comment field)	71–71	1	–	–	227.8 g a.i./ha	90	–
Quinces	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–
Medlars	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–
Loquats	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–

MS: Member State; SL: soluble concentrate.

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

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

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

^dPHI – minimum preharvest interval.

A.2. Authorised outdoor uses in southern EU

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application			Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	Number min–max	a.s./hL min–max	Water L/ha min–max	Rate and unit
Apples	IT	F	PGR; Fruit thinning and fruit size improvement	AL	21 g/L	Foliar treatment – spraying	See remarks	1	–	–	210 g a.i./ha	90	Applications occurs when fruit is between 12 and 14 mm on old woods (2 years and more)
Pears	EL	F	Fruit thinning	AL	100 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	200 g a.i./ha	n.a.	‘When the fruits have a diameter 10–13 mm’
Quinces	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–
Medlars	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–
Loquats	FR	F	Fruit thinning	SL	20 g/L	Foliar treatment – general (see also comment field)	71–74	1	–	–	150 g a.i./ha	90	–
Apricots	PT	F	Stimulation of lateral branching	SL	19 g/L	Foliar treatment – general (see also comment field)	55	1	–	–	570 g a.i./ha	n.a.	Stone fruit nurseries
Cherries	PT	F	Stimulation of lateral branching	SL	19 g/L	Foliar treatment – general (see also comment field)	55	1	–	–	570 g a.i./ha	n.a.	Stone fruit nurseries
Peaches	PT	F	Stimulation of lateral branching	SL	19 g/L	Foliar treatment – general (see also comment field)	55	1	–	–	570 g a.i./ha	n.a.	Stone fruit nurseries
Plums	PT	F	Stimulation of lateral branching	SL	19 g/L	Foliar treatment – general (see also comment field)	55	1	–	–	570 g a.i./ha	n.a.	Stone fruit nurseries

MS: Member State; AL: any other liquid; SL: soluble concentrate.

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

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

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

^dPHI – minimum preharvest interval.

A.3. Authorised indoor uses in EU

Crop and/or situation	MS or country	F G or Ia	Pests or group of pests controlled	Preparation		Application				Application rate per treatment			PHI (days)d	Remarks
				Typeb	Conc. a.s.	Method kind	Range of growth stages & seasonc	Number min–max	Interval between application (min)	a.s./hL min–max	Water L/ha min–max	Rate and unit
Strawberries	ES	I	Increased flowering and peduncle enlargement	SL	19 g/L	Foliar treatment – spraying	60–87	4	14	–	–	1.9 g a.i./ha	n.a.	600–1000 L/ha of water

MS: Member State; SL: soluble concentrate.

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

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

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

^dPHI – minimum preharvest interval.

Appendix B – List of end points

B.1. Residues in plants

B.1.1. Nature of residues and methods of analysis in plants

B.1.1.1. Metabolism studies, methods of analysis and residue definitions in plants

Primary crops (available studies)	Crop groups	Crop(s)	Application(s)	Sampling (DAT)	Comment/Source
	Fruit crops	Apples	Foliar, ~ 15 g as/hl	0, 7, 50, 90	United Kingdom (2009), EFSA (2010)
	Root crops	Radish seedlings	–	–	Supporting publications were considered to establish the metabolic pathway (France, 2007; EFSA, 2010)
	Leafy crops	Celery cell culture	–	–
	Cereals/grass	Wheat shoots	–	–
	Pulses/oilseeds	Soybean tissue	–	–

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	–	–	–	Not triggered, rapid degradation DT50 between 1 day to 1.2 days (EFSA, 2010) and uses only on (semi) permanent crops
	Leafy crops	–	–	–
	Cereal (small grain)	–	–	–

Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	Not triggered	Studies on the nature and levels of residues following processing are not required as there are no residues in the raw commodities
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Not triggered
	Sterilisation (20 min, 120°C, pH 6)	Not triggered

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	Apple	−18	18	Months	6‐Benzyladenine	France (2007), EFSA (2010)
	High acid content	–	–	–	–	–	Not available and not required in this review as samples were analysed within 1 month. (Sweden, 2019)

B.1.2. Magnitude of residues in plants

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

Commodity	Region/Indoora	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)
Apples Pears Quinces Medlars Loquats/Japanese medlars	NEU	6 × < 0.005 2 × < 0.01	Overdosed and GAP compliant trials on apples (France, 2007; Germany, 2019)	0.01*	0.01	0.01
	SEU	4 × < 0.005	Overdosed trials on apples (France, 2007)	0.01*	0.01	0.01
Strawberries	EU	4 × < 0.01	Trials on strawberries compliant with the GAP (Sweden, 2019)	0.01*	0.01	0.01
Apricots Cherries (sweet) Peaches Plums	SEU	–	As authorised uses are for nurseries and based on the metabolism study, no residues are expected	0.01*	0.01	0.01

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

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

^aNEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, EU: indoor EU trials.

^bHighest residue. The highest residue for risk assessment (RA) refers to the whole commodity and not to the edible portion.

^cSupervised trials median residue. The median residue for risk assessment (RA) refers to the whole commodity and not to the edible portion.

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
Apples, juice	1	0.04	0.04	Tentativeb
Apples, wet pomace	1	0.04	0.04	Tentativeb

PF: Processing factor (=Residue level in processed commodity expressed according to RD‐Mo/residue level in raw commodity expressed according to RD‐Mo).

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

^bA tentative PF is derived based on a limited data set.

B.2. Residues in livestock

Following normal practice of the authorised uses, significant residues are not expected to occur in livestock feed.

B.3. Consumer risk assessment

B.3.1. Consumer risk assessment

Acute exposure calculations were not carried out since no ARfD has been considered necessary.

B.4. Proposed MRLs

Code number	Commodity	Existing EU MRL (mg/kg)	Existing CXL (mg/kg)	Outcome of the review
				MRL (mg/kg)	Comment
Enforcement residue definition: 6‐benzyladenine
130010	Apples	0.01*	–	0.01*	Recommendeda
130020	Pears	0.01*	–	0.01*	Recommendeda
130030	Quinces	0.01*	–	0.01*	Recommendeda
130040	Medlar	0.01*	–	0.01*	Recommendeda
130050	Loquat	0.01*	–	0.01*	Recommendeda
140010	Apricots	0.01*	–	0.01*	Recommendeda
140020	Cherries (sweet)	0.01*	–	0.01*	Recommendeda
140030	Peaches	0.01*	–	0.01*	Recommendeda
140040	Plums	0.01*	–	0.01*	Recommendeda
152000	Strawberries	0.01*	–	0.01*	Recommendeda
–	Other commodities of plant and/or animal origin	Art. 18(1)b Reg 396/2005	–	–	Further consideration needed b

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

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

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

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

Appendix C – Pesticide Residue Intake Model (PRIMo)

1.

• PRIMo(EU)

Appendix D – Input values for the exposure calculations

D.1. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: 6‐benzyladenine
Pome fruits	0.01*	STMR	0.01*	HR
Stone fruits	0.01*	STMR	0.01*	HR
Strawberry	0.01*	STMR	0.01*	HR

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

Appendix E – Decision tree for deriving MRL recommendations

1.

Appendix F – Used compound codes

1.

Code/trivial namea	IUPAC name/SMILES notation/InChiKeyb	Structural formulac
6‐Benzyladenine	N 6‐benzyladenine or N‐benzyl‐9H‐purin‐6‐amine n1cnc(NCc2ccccc2)c2nc[NH]c12 NWBJYWHLCVSVIJ‐UHFFFAOYSA‐N
Benzoic acid	benzoic acid O=C(O)c1ccccc1 WPYMKLBDIGXBTP‐UHFFFAOYSA‐N

^aThe metabolite name in bold is the name used in the conclusion.

^bACD/Name 2019.1.1 ACD/Labs 2019 Release (File version N05E41, Build 110555, 18 July 2019).

^cACD/ChemSketch 2019.1.1 ACD/Labs 2019 Release (File version C05H41, Build 110712, 24 July 2019).

Suggested citation: EFSA (European Food Safety Authority) , Anastassiadou M, Bernasconi G, Brancato A, Carrasco Cabrera L, Greco L, Jarrah S, Kazocina A, Leuschner R, Magrans JO, Miron I, Nave S, Pedersen R, Reich H, Rojas A, Sacchi A, Santos M, Stanek A, Theobald A, Vagenende B and Verani A, 2020. Reasoned Opinion on the review of the existing maximum residue levels for 6‐benzyladenine according to Article 12 of Regulation (EC) No 396/2005. EFSA Journal 2020;18(7):6220, 27 pp. 10.2903/j.efsa.2020.6220