Modification of the existing maximum residue level for acrinathrin in lettuce

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Cheminova A/S submitted a request to the competent national authority in Spain to modify the existing maximum residue level (MRL) for the active substance acrinathrin in lettuce. The data submitted in support of the request were found to be sufficient to derive an MRL proposal for lettuce. Adequate analytical methods for enforcement are available to control the residues of acrinathrin on the commodity under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of acrinathrin according to the reported agricultural practice and the current approval restrictions of acrinathrin is unlikely to present a risk to consumer health. However, uncertainties remain, particularly on the toxicological profile of the different isomers. Hence, the consumer risk assessment is considered tentative.

Summary

In accordance with Article 6 of Regulation (EC) No 396/2005, Cheminova A/S submitted an application to the competent national authority in Spain (Evaluating Member State, EMS) to modify the existing maximum residue level (MRL) for the active substance acrinathrin in lettuce. The EMS drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to the European Food Safety Authority (EFSA) on 18 March 2020. To accommodate for the intended SEU use of acrinathrin, the EMS proposed to raise the existing MRL from the limit of quantification (LOQ) to 0.1 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 conclusions on the review of the existing EU MRLs of acrinathrin according to Article 12 of Regulation (EU) No 396/2005 (MRL review) and the additional data provided by the EMS in the framework of this application, the following conclusions are derived.

The metabolism of acrinathrin following foliar application was investigated during the EU pesticides review in crops belonging to the groups of fruits and leafy vegetables. In the framework of the current assessment, the applicant submitted a new metabolism study on lettuce. Among all available metabolism studies, only the metabolism study in grapes (which detects the enantiomeric pair of isomers but not acrinathrin enantiomer) and the newly provided metabolism study in lettuce (which detects the enantiomeric pair of isomers as well as acrinathrin enantiomer) could be considered valid to address the metabolism in primary crops.

Standard hydrolysis studies investigating the stability of acrinathrin under conditions representative for pasteurisation, boiling/cooking and sterilisation are not available and are not required, considering low contribution of residues in lettuce to the total theoretical maximum daily intake (TMDI).

In rotational crops, a significant translocation of residues is not expected (total residue less than 0.01 mg/kg) if crops are grown in rotation with lettuce, which were treated according to the intended good agricultural practice (GAP).

Based on the metabolic pattern identified in grape metabolism study, the toxicological significance of metabolites and the capabilities of analytical enforcement methods, the residue definitions for fruit crops were proposed by the EU pesticides peer review as acrinathrin and its enantiomer for enforcement and acrinathrin and all isomers for the risk assessment. The risk assessment residue definition has been proposed on a provisional basis, pending the investigation of the toxicological profile of the 15 acrinathrin isomers. Now with a new lettuce metabolism study available, the residue definitions can be extended also for leafy crop group. However, since the toxicological profile of all 15 acrinathrin isomers is not fully addressed yet, the revision of the existing provisional residue definition for risk assessment is not proposed in the framework of the current assessment.

According to the EU pesticides peer review, for rotational crops, there is no need to set a specific residue definition due to low residues expected.

EFSA concluded that for lettuce, metabolism of acrinathrin has been sufficiently addressed and that the previously derived residue definitions are still applicable. A conversion factor of 1.1 was derived on the basis of the grape metabolism study and in the absence of adequate metabolism studies covering crop groups other than fruits and leafy vegetables, the proposed residue definition and conversion factor has been tentatively applied to all crops as a worst‐case assumption to conduct the consumer risk assessment.

Sufficiently validated analytical methods based on GC/MS are available to quantify residues in lettuce according to the enforcement residue definition. The methods enable quantification of residues at or above 0.01 mg/kg in the crop assessed (LOQ).

The available residue trials are sufficient to derive an MRL proposal of 0.1 mg/kg for lettuce in support of the intended SEU use of acrinathrin.

Specific studies investigating the magnitude of acrinathrin residues in processed commodities have not been provided and are not necessary since lettuce is normally consumed raw.

Residues of acrinathrin in commodities of animal origin were not assessed since lettuce is normally not fed to livestock.

The toxicological profile of acrinathrin was assessed in the framework of the EU pesticides peer review under Regulation (EC) No 1107/2009 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 0.01 mg/kg bw. However, a data gap was set by the EU pesticides peer review for the investigation of the toxicological profile of all 15 acrinathrin isomers and translated into confirmatory data to be submitted by the applicant 2 years after adoption of the specific guidance. In the framework of the current assessment, the applicant has provided additional toxicity studies and information, which allow to conclude that acrinathrin isomers are not genotoxic, three of them are expected to be less acutely neurotoxic than the parent, but for the other 12 isomers, no conclusion can be made regarding their general toxicity. In lettuce, according to metabolism studies, none of these isomers, including enantiomer of acrinathrin, were present at relevant concentrations. Therefore, the data gap set by the EU pesticides review regarding the toxicological profile of acrinathrin isomers is not relevant for lettuce.

It is also noted that only few of the existing uses – on grapes and some lettuces – were maintained after the MRL review. It can therefore be concluded that for the existing uses of acrinathrin and the proposed use on lettuce, isomers other than acrinathrin and its enantiomer will be of no concern. Nevertheless, pending the assessment of the toxicological profile of acrinathrin isomers, the consumer exposure assessment is considered tentative.

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The exposure assessment was performed taking into account the supervised trials median residue (STMR) and HR values derived for lettuce from the residue trials submitted in the framework of the current assessment, multiplied by the conversion factor of 1.1 for the risk assessment, as derived by the MRL review. In the chronic assessment, for the remaining commodities covered by the MRL regulation, the median residue levels derived in the MRL review were used as input values, multiplied by the conversion factor of 1.1 for the risk assessment. Those crops on which authorised uses were not reported for the MRL review or were not supported after the MRL review (i.e. the commodities where the GAPs were not compliant with the restriction of use of acrinathrin) were not included in the exposure calculation. No long‐term and short‐term consumer intake concerns were identified for the crop under assessment; the calculated long‐term exposure accounted for a maximum of 2% of the ADI (PT general diet) and the short‐term exposure for lettuce accounted for a maximum of 21% of the ARfD in children and 7% of the ARfD in adults.

EFSA concludes that, although uncertainties remain, particularly on the toxicological profile of the different isomers, this tentative exposure calculation did not indicate a risk to consumer health from the existing uses of acrinathrin and the intended use on lettuce. Nevertheless, as soon as the toxicity of acrinathrin isomers is addressed, the risk assessment residue definition shall be confirmed and the consumer exposure updated.

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

Full details of all endpoints 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: AcrinathrinF
251020	Lettuce	0.02*	0.1	The submitted data are sufficient to derive an MRL proposal for the intended SEU use. Risk for consumers unlikely

^*Indicates that the MRL is set at the limit of analytical quantification (LOQ).

MRL: maximum residue level; SEU: southern Europe.

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

^FFat soluble.

Assessment

The European Food Safety Authority (EFSA) received an application to modify the existing maximum residue level (MRL) for acrinathrin in lettuce. The detailed description of the intended SEU use of acrinathrin in lettuce, which is the basis for the current MRL application, is reported in Appendix A.

Acrinathrin is the ISO common name for (S)‐α‐cyano‐3‐phenoxybenzyl (Z)‐(1R,3S)‐2,2‐dimethyl‐3‐[2‐(2,2,2‐trifluoro‐1‐trifluoromethylethoxycarbonyl)vinyl]cyclopropanecarboxylate or (S)‐α‐cyano‐3‐phenoxybenzyl(Z)‐(1R)‐cis‐2,2‐dimethyl‐3‐[2‐(2,2,2‐trifluoro‐1trifluoromethylethoxycarbonyl)vinyl] cyclopropanecarboxylate (IUPAC name).

The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Acrinathrin was evaluated in the framework of Regulation (EC) No 1107/20091 with France designated as rapporteur Member State (RMS) for the representative uses as an insecticide and acaricide on wine grapes, table grapes and ornamentals. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2010, 2013). Acrinathrin was approved2 for the use as insecticide and acaricide on 1 January 2012.

The EU MRLs for acrinathrin are established in Annex II of Regulation (EC) No 396/20053. The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has been performed (EFSA, 2015) and the proposed modifications have been implemented in the MRL legislation only for the commodities where the GAPs are compliant with the current approval restrictions of acrinathrin (authorised at rates not exceeding 22.5 g/ha per application).

In accordance with Article 6 of Regulation (EC) No 396/2005, Cheminova A/S submitted an application to the competent national authority in Spain (evaluating Member State, EMS) to modify the existing maximum residue level (MRL) for the active substance acrinathrin in lettuce. The EMS drafted an evaluation report in accordance with Article 8 of Regulation (EC) No 396/2005, which was submitted to the European Commission and forwarded to the European Food Safety Authority (EFSA) on 18 March 2020. To accommodate for the intended use of acrinathrin, the EMS proposed to raise the existing MRL from the limit of quantification (LOQ) to 0.1 mg/kg.

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

EFSA based its assessment on the evaluation report submitted by the EMS (Spain, 2020), the draft assessment report (DAR) and its addenda (France, 2007, 2010, 2012, 2013) prepared under Regulation (EC) 1107/2009, the Commission review report on acrinathrin (European Commission, 2017a), the conclusions on the peer review of the pesticide risk assessment of the active substance acrinathrin (EFSA, 2013) and the MRL review (EFSA, 2015).

For this application, the data requirements established in Regulation (EU) No 544/20114 and the guidance documents applicable at the date of submission of the application to the EMS are applicable (European Commission, 1997a, b, c, d, e, f, g, 2000, 2010a, b, 2017b; OECD, 2011, 2013). 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 546/20115.

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, are presented in Appendix B.

The evaluation report submitted by the EMS (Spain, 2020) 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.

1. Residues in plants

1.1. Nature of residues and methods of analysis in plants

Acrinathrin is an enantiomerically pure synthetic pyrethroid having three stereogenic centres and a double bond in a defined configuration. Having three stereogenic centres and a double bond, a total of 16 possible isomers – which comprise eight pairs of enantiomers – exist. It is important to note that except for acrinathrin and its own enantiomer, reference standards of only one compound of each enantiomeric pair were synthetised. The chemical structure of acrinathrin is provided in Appendix E. The complete list of acrinathrin isomers is reported in the Evaluation Report (Spain, 2020). It should be further noted that under natural sunlight, and in common with other pyrethroids, acrinathrin has the potential to isomerise, which could lead to formation of isomers on crops.

1.1.1. Nature of residues in primary crops

The metabolism of acrinathrin on fruit crops (grapes, apples, cucumbers and oranges) and on leafy crops (cabbage) has been investigated in the framework of the EU pesticides peer review (EFSA, 2013) and the MRL review (EFSA, 2015). During the peer review and MRL review, it was concluded that, since the levels of each of the isomers or enantiomeric pairs of isomers present had not been quantified in apples, cabbage, cucumbers and oranges, these studies were considered insufficient to determine the nature of acrinathrin residues in primary crops.

Therefore, based on the metabolism study in grapes, which was the only study analysing all pairs of isomers, it was concluded that isomerisation could occur as part of the normal metabolic process and the isomer profile is dependent on the PHI. It should be, however, noted that this study did not use chiral high‐performance liquid chromatography (HPLC) method and it was therefore not able to distinguish between acrinathrin and its own enantiomer. Based on the grape metabolism study, EFSA concluded that following foliar application, the residue definition proposed for risk assessment is acrinathrin and all 15 isomers (as long as the toxicity of the individual isomers including enantiomers has not been addressed by eligible data), and for monitoring is acrinathrin and its enantiomer (EFSA, 2013).

New metabolism studies representing fruit crops (tomato) and leafy crops (lettuce) were submitted in support of the current MRL application (Spain, 2020) and results are reported in Appendix B. The study on tomato was not assessed as not relevant for the current application.

The new metabolism study in lettuce is considered valid to address the nature of acrinathrin in this commodity. Moreover, this study was performed with the specific intention to further evaluate isomerisation and the presence of the different isomers of acrinathrin. Reverse‐phase HPLC analysis was used to separate acrinathrin from its metabolic transformation products, normal‐phase HPLC analysis was used to separate enantiomeric pairs of acrinathrin from each other and, where appropriate, chiral HPLC analysis was also used to separate enantiomers from each other.

In lettuce, acrinathrin was the most prominent component detected from both radiolabelled samples (cyclopropyl‐1‐¹⁴C and phenoxy‐U‐¹⁴C) and accounted for 37.2–64.5% of total radioactive residue (TRR) (0.103–1.197 mg/kg). The results of normal‐phase and chiral HPLC analysis showed no significant photo‐isomerisation of acrinathrin and no detection of the acrinathrin enantiomer. Only a low level of the R‐acrinathrin and/or its enantiomer was detected in phenoxy 3 and 7 days after last application (DALA) rinses (equivalent to 1% of TRR, 0.019 mg/kg in 3 DALA lettuce and 0.8% of TRR, 0.009 mg/kg in 7 DALA lettuce). No other isomers of acrinathrin were present in lettuce at relevant levels. Other identified metabolites were detected at individual levels ranging from 0.4% to 8.0% of TRR (0.003–0.064 mg/kg). Moreover, other unassigned components were also detected, the few above 10% TRR (after 3 and 7 DALA) were shown to consist of multiple compounds by TLC with all individual compounds below 10% TRR and no unassigned components in the raw agricultural commodity 14 DALA above 10% of TRR and 0.05 mg/kg.

The low levels of isomers found in the new metabolism study in lettuce suggested that in lettuce, the main component of the residues is parent acrinathrin only. Other isomers, for which the data gap regarding their toxicological profile was set in the peer review and the MRL review, are not present at significant amounts. Although metabolism studies in lettuce and grapes indicate low extent of isomerisation, it was also noted in the peer review, that isomerisation varies between crops and depends on the PHI. Thus, on the basis of two studies in grapes and lettuce and, pending the assessment of the toxicological profile for all acrinathrin isomers, a final conclusion on the need for revision of existing risk assessment residue definition cannot be taken. Thus, as a worst scenario, the consumer risk assessment is still performed using the existing residue definition for risk assessment in force.

For the intended use on lettuce, the metabolic behaviour in primary crops is sufficiently addressed.

1.1.2. Nature of residues in rotational crops

Acrinathrin is authorised or is proposed to be used on several crops that can be grown in rotation with other crops. According to the soil degradation studies evaluated in the framework of the peer review (EFSA, 2013), the DT₉₀ value of acrinathrin and its enantiomer and their relevant soil metabolites ranged from 0.5 to 887 days. The trigger value of 100 days was exceeded, and therefore, further studies investigating the nature and magnitude of residues in rotational crops were required.

The metabolism of acrinathrin in rotational crops (wheat, spinach, carrots and kohlrabi) has been evaluated during the peer review (EFSA, 2013) with ¹⁴C‐labelled acrinathrin (cyclopropyl‐1‐¹⁴C and ¹⁴C‐benzyl). The residues were partitioned into organo‐soluble and water‐soluble fractions but could not be further identified due to the very low amount detected. Therefore, a specific residue definition for rotational crops was not deemed necessary due to the very low residue levels expected.

For the proposed use assessed in this application, no further information was provided.

1.1.3. Nature of residues in processed commodities

Standard hydrolysis studies regarding the stability of acrinathrin under conditions representative for pasteurisation, boiling/cooking and sterilisation are not available. Such studies are not required, considering low contribution of residues in lettuce to the total theoretical maximum daily intake (TMDI).

1.1.4. Methods of analysis in plants

Analytical methods for the determination of acrinathrin residues were assessed during the MRL review (EFSA, 2015). Sufficiently validated methods are available for the determination of residues of acrinathrin in lettuce. However, these methods are not stereoselective and allow quantifying residues of acrinathrin together with its enantiomer at an LOQ of 0.02 mg/kg in crops belonging to the group of high‐water content commodity.

In addition, a new analytical method has been validated with an associated independent laboratory validation (ILV) in crop matrices with high acid content (strawberry), high water content (sweet pepper, tomato), high oil content (soybean) and high starch content (wheat grain) with a lower LOQ of 0.01 mg/kg. Since chiral analysis was not employed, also for this analytical method the acrinathrin peak could include its enantiomer. This new analytical method has been validated in lettuce and used to analyse residues of acrinathrin in the supervised crop residue trials provided in this application.

1.1.5. Storage stability of residues in plants

The storage stability of acrinathrin in plants stored under frozen conditions was investigated in the framework of the pesticides peer review demonstrating storage stability for acrinathrin in high water content commodities up to 24 months (EFSA, 2013). During the EU pesticides peer review and the MRL review, a data gap regarding the freezer storage stability in high acid content crop matrices was noted (EFSA, 2013, 2015).

1.1.6. Proposed residue definitions

Based on the metabolic pattern identified in metabolism studies, the toxicological significance of metabolites, the capabilities of enforcement analytical methods, the following residue definitions were tentatively proposed in the context of the pesticide peer review and MRL review (EFSA, 2013, 2015):

• residue for risk assessment: acrinathrin and all isomers (as long as the toxicity of the individual isomers including enantiomers has not been addressed by eligible data)

• residue definition for enforcement: acrinathrin and its enantiomer

This residue definition is limited to the use on fruit crops. The MRL review concluded, that in order to extend the residue definition to other crop groups, representative metabolism studies are required. As long as studies representative for relevant crop groups are not available, the MRL review proposed to tentatively extend proposed enforcement and risk assessment residue definitions to other crop groups (EFSA, 2015).

Now with a new and reliable lettuce metabolism study available, the residue definitions can be confirmed also for leafy crop group. It is noted, however, that the inclusion of the isomers in the residue definition for risk assessment could eventually be reviewed due to the very low amount of isomers found in the new metabolism study in lettuce. However, considering the uncertainty in the previous metabolism studies in grapes, where no chiral analysis was performed, and the absence of metabolism studies on other crop categories (root, cereals and pulses/oilseed), the revision of the existing risk assessment residue definition is not proposed in the framework of the current assessment. Moreover, the data gap identified by the pesticides peer review regarding the toxicological profile of acrinathrin isomers still remains.

On the basis of grape metabolism study, the peer review derived a tentative conversion factor of 1.1 from enforcement to risk assessment, which, in order to account for a worst‐case scenario, is applied to all crops in the consumer risk assessment. A specific residue definition for rotational crops was not deemed necessary due to the very low residue levels expected.

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

1.2. Magnitude of residues in plants

1.2.1. Magnitude of residues in primary crops

In support of the intended SEU use, the applicant submitted residue trials on lettuce. The samples were analysed for the parent compound including its enantiomer as in the residue definition for enforcement.

In total, eight supervised crop residue trials compliant with the intended SEU GAP and the current approval restrictions of acrinathrin (authorised at rates not exceeding 22.5 g/ha per application) were submitted. The eight trials in the SEU included four harvest and four decline trials and were conducted on open leaf lettuce from April to September 2016 by using five different varieties in eight different geographical locations, thus demonstrating the independency of these trials.

The applicant submitted also four residue trials on lettuce representing NEU, but these were not considered under the current assessment, since no GAP has been reported for acrinathrin on lettuce in the NEU.

EFSA agrees with the approach proposed by the EMS, concluding that the eight residue trials conducted in the SEU region are considered acceptable according to the proposed SEU GAP and the current approval restrictions of acrinathrin and therefore could be considered to derive a new MRL of 0.1 mg/kg.

According to the assessment of the EMS, the methods used were sufficiently validated using an LOQ of 0.01 mg/kg and the samples of all these residue trials were stored under conditions for which integrity of the samples has been demonstrated.

1.2.2. Magnitude of residues in rotational crops

The possible transfer of acrinathrin residues to crops that are grown in crop rotation has been assessed in the EU pesticides peer review (EFSA, 2013). The available studies demonstrated that significant residues (above 0.01 mg/kg) are not expected in succeeding crops when planted in soil treated at 0.113–0.158 kg a.s./ha.

Since the application rate for the crop under consideration (i.e. 0.0225 kg a.s./ha) is lower than the application rate tested in the rotational crop studies, it is concluded that no residues are expected in following crops grown in rotation with lettuce, provided that the active substance is applied according to the proposed GAP.

1.2.3. Magnitude of residues in processed commodities

Specific processing studies for the crop under assessment are not available and not deemed necessary as lettuce is not a crop expected to undergo further processing.

1.2.4. Proposed MRLs

The available data are considered sufficient to derive an MRL proposal as well as risk assessment values for lettuce in support of the intended SEU use of acrinathrin. In Section 3, EFSA assessed whether residues on crops resulting from the intended uses are likely to pose a consumer health risk.

2. Residues in livestock

Not relevant as lettuce is not used for feed purposes.

3. Consumer risk assessment

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

The toxicological reference values for acrinathrin used in the risk assessment were derived in the framework of the EU pesticides peer review where an ADI of 0.01 mg/kg body weight (bw) per day and an ARfD of 0.01 mg/kg bw were set (EFSA, 2013). During the EU pesticides peer review, the data gap regarding the further assessment of the toxicological profile of the 15 isomers of acrinathrin was established (EFSA, 2013). For the MRL review, the assessment of the toxicological profile of all isomers was still missing, and therefore, the MRL review proposed to consider the toxicological reference values set for acrinathrin tentatively valid also for the other isomers and to use a conversion factor for risk assessment of 1.1 based on the grape metabolism study. The applicant in the framework of the current assessment has provided additional information, which allows to conclude that isomers included in the residue definition are not genotoxic and three of these acrinathrin isomers are expected to be less acutely neurotoxic than the parent, but for the other 12 isomers, no conclusion can be made regarding their general toxicity (high, equal, less acutely neurotoxic than the parent). The acute toxicity of acrinathrin enantiomer has not been addressed, but it is not of concern in lettuce as this enantiomer was not detected in the metabolism study.

As reported in the nature of residues in primary crops section, the very low levels of isomers found in the new metabolism study in lettuce suggests that the exposure to the acrinathrin isomers in lettuce is very low. However, since this evidence is only based on metabolism study in lettuce and only partially confirmed by the metabolism study in grapes (with the uncertainty regarding the presence of the enantiomer), the residue definition for risk assessment currently in force and conversion factor of 1.1 as proposed by the MRL review is still applied for consumer exposure assessment. It is also noted that only few of the existing uses – on grapes and some lettuces – were maintained after the MRL review. It can therefore be concluded that for the existing uses of acrinathrin and the proposed use on lettuce, isomers other than acrinathrin and its enantiomer will be of no concern. Nevertheless, pending the assessment of toxicity of acrinathrin isomers the consumer exposure assessment is considered tentative.

Short‐term (acute) dietary risk assessment

The short‐term exposure assessment was performed for lettuce only in accordance with the internationally agreed methodology (EFSA, 2019).

The calculations were based on the highest residue level in lettuce as derived from the submitted residue trials, multiplied by the conversion factor for the risk assessment. The complete list of input values can be found in Appendix D.1.

The short‐term exposure did not exceed the ARfD for the crop assessed in this application, accounting for a maximum of 21% of the ARfD in children and 7% of the ARfD in adults; therefore, EFSA concludes that the use of acrinathrin according to the reported agricultural practice is unlikely to present a short‐term (acute) risk to consumer health.

Long‐term (chronic) dietary risk assessment

The long‐term exposure assessment was performed, taking into account the median residue levels expected in lettuce as derived from the submitted residue trials, multiplied by the conversion factor for the risk assessment as derived by the MRL review. For the remaining commodities covered by the MRL regulation, the median residue levels derived in the MRL review were selected, multiplied by the conversion factor for the risk assessment. Those crops on which authorised uses were not reported for the MRL review or were not supported after the MRL review (i.e. the commodities where the GAPs were not compliant with the restriction of use of acrinathrin) were not included in the exposure calculation. The complete list of input values can be found in Appendix D.1.

The estimated long‐term dietary intake accounted for a maximum of 2% of the ADI (PT general diet). The contribution of residues expected in lettuce to the overall long‐term exposure accounted for a maximum of 0.6% of the ADI.

EFSA concludes, that although uncertainties remain, particularly on the toxicological profile of the different isomers, this tentative exposure calculation did not indicate a risk to consumer health from the existing uses of acrinathrin and the intended use on lettuce. Nevertheless, as soon as the toxicological profile of acrinathrin isomers is addressed, the risk assessment residue definition shall be confirmed and the consumer exposure updated.

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

4. Conclusion and Recommendations

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal for lettuce in support of the intended SEU use of acrinathrin.

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

However, it should be noted that uncertainties remain particularly on the toxicological profile of the different isomers and on the metabolism in different crop groups. Hence, the consumer risk assessment is considered tentative only.

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

CF

conversion factor for enforcement to risk assessment residue definition

cGAP

critical GAP

CIRCA

(EU) Communication & Information Resource Centre Administrator

CS

capsule suspension

CV

coefficient of variation (relative standard deviation)

DALA

days after last application

DAR

draft assessment report

DAT

days after treatment

DM

dry matter

DP

dustable powder

DS

powder for dry seed treatment

DT₉₀

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

EC

emulsifiable concentrate

EDI

estimated daily intake

EMS

evaluating Member State

eq

residue expressed as a.s. equivalent

EW

emulsion, oil in water

FID

flame ionisation detector

GAP

Good Agricultural Practice

GC

gas chromatography

GC‐FID

gas chromatography with flame ionisation detector

GC‐MS

gas chromatography with mass spectrometry

GC‐MS/MS

gas chromatography with tandem mass spectrometry

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

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

MS

mass spectrometry detector

MS/MS

tandem mass spectrometry detector

MW

molecular weight

NEU

northern Europe

OECD

Organisation for Economic Co‐operation and Development

PBI

plant back interval

PF

processing factor

PHI

preharvest interval

PRIMo

(EFSA) Pesticide Residues Intake Model

RA

risk assessment

RD

residue definition

RMS

rapporteur Member State

SANCO

Directorate‐General for Health and Consumers

SC

suspension concentrate

SEU

southern Europe

SL

soluble concentrate

SP

water‐soluble powder

STMR

supervised trials median residue

TAR

total applied radioactivity

TLC

Thin layer chromatography

TMDI

theoretical maximum daily intake

TRR

total radioactive residue

UV

ultraviolet (detector)

WHO

World Health Organization

Appendix A – Summary of intended GAP triggering the amendment of existing EU MRLs

1.

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 & seasonc	Number min–max	Interval between application (min)	G a.s./hL min–max	Water L/ha min–max	Rate	Unit
Lettuces	SEU	F	Red mites and thrips	EW	75.0	Foliar treatment – broadcast spraying	From BBCH 10	1–2	10		500–700	22.50	g a.s./ha	14	Against mobile forms. At first signs of pest 40–60 mL fp/hL (max. 0.3 L fp/ha)

MRL: maximum residue level; GAP: Good Agricultural Practice; NEU: northern European Union; SEU: southern European Union; MS: Member State; a.s.: active substance; EW: emulsion, oil in water.

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

^bCropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system.

^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	Grape vines	Foliar, Fa 2 × 0.0225 kg a.s./ha (both radiolabelled samples) 2 × 0.225 kg a.s./ha (14C‐gem‐dimethyl sample only)	0, 13, 27, 41	13 day sample just prior to second application Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl (EFSA, 2015)
		Apples	Foliar, Fa 1 × 45‐91 μg per fruit, 52‐145 μg per leafb (both radiolabelled samples)	0, 7, 14, 21, 28, 42, 56c 0, 28d	Supportive, not fully valid (EFSA, 2015) Application by brush to individual fruits and leaves Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl
		Oranges	Foliar, Fa 2 × 0.09 kg a.s./ha (all radiolabelled samples)	21	Identification of individual isomers not undertaken (EFSA, 2015) Radiolabelled active substance: cyclopropyl‐1‐14C, 14C‐benzyl and 14C‐hexafluoroisopropyl
		Cucumbers	Foliar, Fa 2 × 0.078 kg a.s./ha (all radiolabelled samples)	0, 14, 42	Study invalid due to photo‐isomerisation (EFSA, 2015) Radiolabelled active substance: cyclopropyl‐1‐14C, 14C‐benzyl and 14C‐hexafluoroisopropyl
		Tomato	Foliar, Fa 3 × 0.060 kg a.s./ha (both radiolabelled samples)	3, 7, 14	Radiolabelled active substance: Cyclopropyl‐1‐14C and phenoxy‐U‐14C (Spain, 2020)
	Leafy crops	Cabbage	Foliar, Fa 2 × 587‐679 μg per plantb (both radiolabelled samples)	0, 28, 56c 0, 14, 28d	Supportive, not fully valid (EFSA, 2015) Application by brush to heart and four innermost leaves Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl
		Let tuce	Foliar, Fa 2 × 0.060 kg a.s./ha (both radiolabelled samples)	3, 7, 14	Radiolabelled active substance: Cyclopropyl‐1‐14C and phenoxy‐U‐14C (Spain, 2020)

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Carrots, kohlrabi	0.113–0.158 kg a.s./ha	29, 70	Treatment to bare soil Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl (EFSA, 2013)
	Leafy crops	Spinach	0.113–0.158 kg a.s./ha	29, 70	Treatment to bare soil Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl (EFSA, 2013)
	Cereal (small grain)	Wheat	0.113–0.158 kg a.s./ha	29, 70	Treatment to bare soil Radiolabelled active substance: cyclopropyl‐1‐14C and 14C‐benzyl (EFSA, 2013)

Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	n/a	Hydrolysis study not available.
	Baking, brewing and boiling (60 min, 100°C, pH 5)	n/a
	Sterilisation (20 min, 120°C, pH 6)	n/a
	Other processing conditions	–

^aOutdoor/field application (F) or glasshouse/protected/indoor application (G).

^bTotal applied radioactivity (TAR) for each sample.

^cApplication 8 weeks before normal harvest.

^dApplication 4 weeks before normal harvest.

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	Cucumber, whole green beans	−18°C	24	months	Acrinathrin	EFSA (2013) From available study is not clear if the enantiomer was tested

B.1.2. Magnitude of residues in plants

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

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)	CF d
Lettuce	SEU	Mo: 6 × < 0.01, 2 × 0.05 RA: –	Residue trials on lettuce compliant with GAP. Sufficient number of trials to derive an MRL for the SEU Residue trial samples were analysed for acrinathrin and its enantiomer. Samples were not analysed for other isomers since these were not present or were present at insignificant levels, according to lettuce metabolism study	0.1	Mo: 0.05 RA: –	Mo: 0.01 RA: –	n/a

MRL: maximum residue level; GAP: Good Agricultural Practice; Mo: monitoring; RA: risk assessment; n/a: not applicable.

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

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

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

^dConversion 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.

B.3. Consumer risk assessment

B.4. Recommended MRLs

Codea	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: AcrinathrinF
251020	Lettuce	0.02*	0.1	The submitted data are sufficient to derive an MRL proposal for the intended SEU use. Risk for consumers unlikely

^*Indicates that the MRL is set at the limit of analytical quantification (LOQ).

MRL: maximum residue level; SEU: southern Europe.

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

^FFat soluble.

Appendix C – Pesticide Residue Intake Model (PRIMo)

1.

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
Lettuce	0.011	STMR proposed MRL × CF	0.055	HR proposed MRL × CF
Table grapes	0.055	STMR MRL review × CF	Acute exposure was performed only for the crop under consideration
Wine grapes	0.055	STMR MRL review × CF
Lamb's lettuce/corn salads	0.022	STMR MRL review × CF
Escaroles/broadleaved endives	0.022	STMR MRL review × CF
Cress and other sprouts and shoots	0.022	STMR MRL review × CF
Roman rocket/rucola	0.022	STMR MRL review × CF
Red mustards	0.022	STMR MRL review × CF

MRL: maximum residue level; STMR: supervised trials median residue; HR: highest residue; CF: conversion factor.

Appendix E – Used compound codes

1.

Code/trivial namea	IUPAC name/SMILES notation/InChiKeyb	Structural formulac
Acrinathrin	(S)‐cyano(3‐phenoxyphenyl)methyl (1R,3S)‐3‐{(1Z)‐3‐[(1,1,1,3,3,3‐hexafluoropropan‐2‐yl)oxy]‐3‐oxoprop‐1‐en‐1‐yl}‐2,2‐dimethylcyclopropane‐1‐carboxylate CC1(C)[C@@H]([C@@H]1\C=C/C(=O)OC(C(F)(F)F)C(F)(F)F)C(=O)O[C@H](C#N)c1cccc(Oc2ccccc2)c1 YLFSVIMMRPNPFK‐WEQBUNFVSA‐N
R‐Acrinathrin	(R)‐cyano(3‐phenoxyphenyl)methyl (1R,3S)‐3‐{(1Z)‐3‐[(1,1,1,3,3,3‐hexafluoropropan‐2‐yl)oxy]‐3‐oxoprop‐1‐en‐1‐yl}‐2,2‐dimethylcyclopropane‐1‐carboxylate CC1(C)[C@@H]([C@@H]1\C=C/C(=O)OC(C(F)(F)F)C(F)(F)F)C(=O)O[C@@H](C#N)c1cccc(Oc2ccccc2)c1 YLFSVIMMRPNPFK‐UTFPFDPTSA‐N

The complete list of acrinathrin isomers is reported in the Evaluation Report (Spain, 2020).

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

^bACD/Name 2018.2.2 ACD/Labs 2018 Release (File version N50E41, Build 103230, 21 Jul 2018).

^cACD/ChemSketch 2018.2.2 ACD/Labs 2018 Release (File version C60H41, Build 106041, 07 Dec 2018).

Suggested citation: European Food Safety Authority (EFSA) , Anastassiadou M, Bernasconi G, Brancato A, Carrasco Cabrera L, Ferreira 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 modification of the existing maximum residue level for acrinathrin in lettuce. EFSA Journal 2020;18(7):6218, 24 pp. 10.2903/j.efsa.2020.6218