Modification of the existing maximum residue levels for mandestrobin in apricots, cherries, peaches/nectarines and plums

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Sumitomo Chemical Agro Europe S.A.S. submitted a request to the competent national authority in France, to modify the existing maximum residue levels (MRL) for the active substance mandestrobin in apricots, cherries, peaches/nectarines and plums. The data submitted in support of the request were found to be sufficient to derive MRL proposals for apricots, cherries, peaches/nectarines and plums. Adequate analytical methods for enforcement are available to control the residues of mandestrobin in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. A short‐term dietary risk assessment was not required. Based on the long‐term risk assessment results, EFSA concluded that the long‐term intake of residues resulting from the use of mandestrobin according to the agricultural practices reported in the good agricultural practice (GAP) for applications at growth stages BBCH 77–87 is unlikely to present a risk to consumer health. The GAP for applications at growth stages BBCH 57–69 is not adequately supported by residue trials data. The reliable end points appropriate for use in regulatory risk assessment are presented.

Summary

In accordance with Article 6 of Regulation (EC) No 396/2005, Sumitomo Chemical Agro Europe S.A.S. submitted an application to the competent national authority in France (evaluating Member State, EMS), to modify the existing maximum residue levels (MRLs) for the active substance mandestrobin in apricots, cherries, peaches/nectarines and plums. France 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 29 August 2017. To accommodate the intended uses of mandestrobin, the EMS proposed to raise the existing MRLs from the limit of quantification (LOQ) of 0.01 mg/kg–2 mg/kg for apricots and peaches, 3 mg/kg for cherries and 0.5 mg/kg for plums.

EFSA assessed the application and the evaluation report as required by Article 10 of Regulation 396/2005. Taking into account the conclusions derived by EFSA in the framework of the European Union (EU) pesticide peer review of the active substance mandestrobin under Regulation (EC) No 1107/2009 and the additional data provided by the EMS in the framework of the present application, the following conclusions are derived.

The metabolism of mandestrobin following foliar application was investigated in crops belonging to the pulses/oilseeds (oilseed rape), cereals/grasses (wheat) and leafy (lettuce) crop groups. Studies investigating the effect of processing on the nature of mandestrobin (hydrolysis studies) demonstrated that the active substance is stable. Studies on the effects of processing on the nature of the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200 and 2‐CH₂OH‐S‐2200 have not been submitted. As the proposed uses of mandestrobin are on permanent crops, investigations of residues in rotational crops are not required.

Based on the metabolic pattern identified in metabolism studies, hydrolysis studies, the toxicological significance of metabolites and/or degradation products, the residue definitions for plant products were proposed as mandestrobin for enforcement and sum of mandestrobin, De‐Xy‐S‐2200, 4‐OH‐S‐2200 conjugate, 2‐CH₂OH‐S‐2200 conjugate, expressed as mandestrobin for risk assessment. These residue definitions are applicable to primary crops and processed products.

EFSA concluded that for the crops assessed in this application, the metabolism of mandestrobin in primary crops and the possible degradation in processed products have been sufficiently addressed and that the previously derived residue definitions are applicable.

A sufficiently validated analytical method based on liquid chromatography‐ tandem mass spectrometry detector (LC‐MS/MS) is available to quantify residues in the crops assessed in this application according to the enforcement residue definition. The methods enable quantification of residues at or above 0.01 mg/kg in the crops assessed (LOQ).

The available residue trials are sufficient to derive MRL proposals of 3 mg/kg for cherries, 0.5 mg/kg for plums and a common MRL proposal of 2 mg/kg for apricots and peaches/nectarines, on the basis of the good agricultural practice (GAP) for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 is not adequately supported by residue trials data.

Specific processing factors (PFs) for the crops under assessment are not available. Specific studies investigating the magnitude of mandestrobin residues in processed commodities are not required in this case because the contribution of mandestrobin residues in the commodities under consideration to the theoretical maximum daily intake (TMDI) is less than 10% of the acceptable daily intake (ADI), and the metabolite 2‐CH₂OH‐S‐2200 (not covered by the toxicological studies) was at levels below the LOQ. If processing factors were to be required by risk managers, in particular for enforcement purposes, then additional processing studies would be needed.

Residues of mandestrobin in commodities of animal origin were not assessed since the crops under consideration in this MRL application are normally not fed to livestock.

The toxicological profile of mandestrobin 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 ADI of 0.19 mg/kg body weight (bw) per day. An acute reference dose (ARfD) was deemed not necessary on the basis of the low acute toxicity profile of mandestrobin.

The toxicological properties of the metabolites included in the residue definition for risk assessment were assessed in the framework of the EU pesticides peer review and the metabolites De‐Xy‐S‐2200 and 4‐OH‐S‐2200 are covered by the toxicological profile of the parent mandestrobin. The metabolite 2‐CH₂OH‐S‐2200 (also included as conjugate in the residue definition for risk assessment) is not covered by the toxicological studies; however, this metabolite was not detected at levels at or above the LOQ in the supervised crop field trials for the commodities under consideration. In case the metabolite 2‐CH₂OH‐S‐2200 is detected in commodities assessed in future MRL applications then additional studies addressing the toxicological properties of this metabolite may be required.

The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). The long‐term exposure assessment was performed taking into account the supervised trials median residue (STMR) values derived for the commodities assessed in this application; for the remaining commodities covered by the MRL regulation, the existing EU MRLs were selected as input values. The highest estimated long‐term dietary intake was 0.6% of the ADI.

EFSA concluded that the proposed uses of mandestrobin on apricots, cherries, peaches/nectarines and plums will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a risk to consumers' health.

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

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

Codea	Commodity	Existing EU MRLb (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: mandestrobin
140010	Apricots	0.01*	2	The combined submitted data on apricots and peaches are sufficient to derive a common MRL proposal for apricots and peaches/nectarines on the basis of the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140020	Cherries	0.01*	3	The MRL proposal reflects the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140030	Peaches/nectarines	0.01*	2	The combined submitted data on apricots and peaches are sufficient to derive a common MRL proposal for apricots and peaches/nectarines on the basis of the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140040	Plums	0.01*	0.5	The MRL proposal reflects the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.

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

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

^bExisting EU MRLs established in Commission Regulation (EU) 2016/486.

Assessment

The detailed description of the intended uses of mandestrobin in apricots, cherries, peaches/nectarines and plums, which are the basis for the current maximum residue level (MRL) application, is reported in Appendix A.

Mandestrobin is the ISO common name for (RS)‐2‐methoxy‐N‐methyl‐2‐[α‐(2,5‐xylyloxy)‐o‐tolyl]acetamide (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Mandestrobin is a new active substance and was evaluated in the framework of Regulation (EC) No 1107/20091 with Austria designated as rapporteur Member State (RMS) for the representative use as a spray application to oilseed rape. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by European Food Safety Authority (EFSA) (EFSA, 2015).

Mandestrobin was approved2 for use as a fungicide on 9 December 2015.

The European Union (EU) MRLs for mandestrobin are established in Annexes II of Regulation (EC) No 396/2005.3 The MRL review required under Article 12 of Regulation (EC) No 396/2005 was addressed by the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance mandestrobin (EFSA, 2015). Currently, Codex MRLs have not been established for mandestrobin.

EFSA based its assessment on the evaluation report submitted by the evaluating Member State (EMS; France, 2017), the DAR and its revision (Austria, 2014, 2015) prepared under Regulation (EC) 1107/2009, and the EFSA Conclusion on the peer review of the pesticide risk assessment of the active substance mandestrobin (EFSA, 2015).

For this application, the data requirements established in Regulation (EU) No 283/20134 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 2017; OECD, 2011). 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, submitted in support of the current MRL application, are presented in Appendix B.

The evaluation report submitted by the EMS (France, 2017) 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

1.1.1. Nature of residues in primary crops

The metabolism of mandestrobin in primary crops was assessed in the EU peer review on the basis of studies performed with foliar application in crops belonging to the pulses/oilseeds (oilseed rape), cereals/grasses (wheat) and leafy (lettuce) crop groups (EFSA, 2015). Mandestrobin was a major component of the residue in all crops. The R/S ratio of mandestrobin remained approximately 1:1 indicating no R/S isomerisation in all tested crops. Major metabolites (> 10% total radioactive residue (TRR)) were identified as 4‐OH‐S‐2200 (conjugated), 2‐CH₂OH‐S‐2200 (conjugated) and De‐Xy‐S‐2200. No additional studies on crop metabolism were submitted in the present application. For the intended uses, the metabolic behaviour in primary crops is sufficiently addressed.

1.1.2. Nature of residues in rotational crops

As the proposed uses of mandestrobin are on permanent crops, investigations of residues in rotational crops are not required.

1.1.3. Nature of residues in processed commodities

The effects of industrial processing and/or household preparation were assessed in the EU peer review. Studies on the nature of the residue during processing showed that mandestrobin was stable under conditions representing pasteurisation, baking/brewing/boiling and sterilisation (EFSA, 2015). Studies on the effects of processing on the nature of the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200 and 2‐CH₂OH‐S‐2200 have not been submitted.

1.1.4. Methods of analysis in plants

Methods of analysis for monitoring of residues in plants were assessed in the EU peer review and the liquid chromatography‐tandem mass spectrometry detector (LC‐MS/MS) method is validated for quantification of residues in the crops assessed (high water content matrices) with a limit of quantification (LOQ) of 0.01 mg/kg (EFSA, 2015).

1.1.5. Stability of residues in plants

Studies on the storage stability of mandestrobin and the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200, 2‐CH₂OH‐S‐2200 performed on oilseed rape seed (high oil content commodity), lettuce (high water content commodity), barley grain (dry commodity) and straw were assessed in the EU peer review and stability was demonstrated to be at least 12 months when stored at < −18^°C (EFSA, 2015). Additional storage stability studies on orange (whole fruit; high acid commodity) and dried bean (white seeds; high protein commodity) have been submitted in the present MRL application and the stability of mandestrobin and the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200 and 2‐CH₂OH‐S‐2200 were demonstrated to be at least 9 months in samples stored at < −18^°C (France, 2017).

1.1.6. Proposed residue definitions

Based on the metabolic pattern identified in metabolism studies, the results of hydrolysis studies, the toxicological significance of metabolites and degradation products and the capabilities of enforcement analytical methods, the following residue definitions were proposed in the EFSA Conclusion on the EU peer review (EFSA, 2015):

• residue definition for enforcement: mandestrobin;

• residue definition for risk assessment: sum of mandestrobin, De‐Xy‐S‐2200, 4‐OH‐S‐2200 conjugate, 2‐CH₂OH‐S‐2200 conjugate, expressed as mandestrobin.

The same residue definitions are applicable to processed products. The residue definition for enforcement set in Regulation (EC) No 396/2005 is identical with the above‐mentioned residue definition. Taking into account the proposed use assessed in this application, EFSA concluded that these residue definitions are appropriate for the crops under assessment and no modification is required.

1.2. Magnitude of residues in plants

1.2.1. Magnitude of residues in primary crops

The proposed uses on apricot, cherry, peach/nectarine and plum are based on two common Good Agricultural Practices (GAPs) for distinct use patterns, by application of the pesticide product during the growth stage range of either BBCH 57–69 or BBCH 77–87. In support of the MRL application, the applicant submitted residue trials performed in apricot, cherry, peach and plum during the 2015 growing season. For apricot, cherry and peach, the residue trials were conducted for each crop at five geographically independent sites located in southern France, Greece, Italy and Spain. For plum, 10 residue trials were conducted at geographically independent sites in southern France, Greece, Italy and Spain. All trials were performed with two foliar spray applications of a suspension concentrate formulation with an interval of 6 or 7 days.

The submitted residue trials were performed with applications in apricot at BBCH 78–85 and 85–87, in cherry at BBCH 81–85 and 85–87, in peach at BBCH 77–85 and 85–87 and in plum at BBCH 81–87 and 85–87 and are sufficiently compliant with the southern Europe (SEU) GAP for applications in the growth stage range BBCH 77–87 (2 × 262.5 g a.s./ha). The samples in all the submitted residue trials are reported to have been stored under the conditions, for which integrity of residues has been demonstrated. The portion analysed was the flesh after removal of the stone and residues were calculated as whole fruit assuming no residue in stone, in accordance with the parts of the products to which the EU MRLs for stone fruit apply.6 In all submitted residue trials, the samples were analysed for the parent compound, in accordance with the residue definition for enforcement, and for the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200 conjugate, 2‐CH₂OH‐S‐2200 conjugate, which are included in the residue definition for risk assessment. According to the assessment of the EMS, the methods used were sufficiently validated and fit for purpose, with individual LOQs of 0.01 mg/kg for each component of the residue definition.

The metabolite 4‐OH‐S‐2200 was present at levels at or above the LOQ in all trials performed on cherry, in one trial on apricot (at all five preharvest intervals (PHIs)), and in one trial on plum (at two PHIs); this metabolite was at levels below the LOQ in all other trials on apricot and plum and in all trials on peach. Metabolite De‐Xy‐S‐2200 was present at the level of the LOQ in samples from two trials on cherry (at four distinct PHIs); the levels of this metabolite were below the LOQ in all other submitted residue trials. Metabolite 2‐CH₂OH‐S‐2200 was at levels below the LOQ in all submitted residue trials. Where peak residues were detected after the GAP minimum PHI, the highest residue value was selected for the purpose of MRL calculation, and the highest summed residue value was selected for the purpose of risk assessment.

The GAP for applications at earlier growth stages (BBCH 57–69; 2 × 225 g a.s./ha) is not supported by the submitted residue trials. It may be expected that the GAP for applications of the active substance at earlier growth stages, before the formation of fruit and at a lower application rate than performed in the submitted residues trials would likely lead to lower residues of the parent mandestrobin in the fruit at time of harvest; however, for longer PHIs (i.e. for applications at growth stages earlier than BBCH 77), the potential for the metabolite 2‐CH₂OH‐S‐2200 (included in the risk assessment residue definition but not covered by the toxicological studies; see also Section 3) to be present at levels higher the LOQ in the fruit at time of harvest cannot be excluded on the basis of the available residue trials data. It therefore cannot be concluded that the GAP for applications at earlier growth stage would lead to the less critical residues situation with regard to residue levels of the metabolite 2‐CH₂OH‐S‐2200 and the potential risk to consumer health.

1.2.2. Magnitude of residues in rotational crops

As the proposed uses of mandestrobin are on permanent crops, investigations of residues in rotational crops are not required.

1.2.3. Magnitude of residues in processed commodities

Specific processing factors (PFs) for the crops under assessment are not available. Processing studies in plum (juice, puree, canned and dried) were submitted in the present MRL application and gave an indication that residue levels are reduced; but the studies did not allow for the derivation of robust processing factors because the analytical method used has not been validated for the processed commodities (France, 2017). Processing of stone fruit by cooking, canning, juicing and pureeing is not expected to lead to a concentration of residues of mandestrobin or a significant increase in the levels of the metabolites De‐Xy‐S‐2200, 4‐OH‐S‐2200 conjugate, 2‐CH₂OH‐S‐2200 conjugate. However, the processing of stone fruits to dried fruits and jamming may result in a concentration of the residues resulting from loss of water in the processed product. Nevertheless, specific processing studies are not required in this case because the contribution of mandestrobin residues in the commodities under consideration to the theoretical maximum daily intake (TMDI) is less than 10% of the acceptable daily intake (ADI) and the metabolite 2‐CH₂OH‐S‐2200 (not covered by the toxicological studies) was at levels below the LOQ. If processing factors were to be required by risk managers, in particular for enforcement purposes, then additional processing studies would be needed.

1.2.4. Proposed MRLs

The available data are sufficient to derive MRL proposals as well as risk assessment values for the commodities under evaluation on the basis of the GAP for applications at growth stages BBCH 77–87 (see Appendix B.4). It is proposed to derive a common MRL for apricots and peaches/nectarines on the basis of the combined residues data from trials performed on apricot and peach, in accordance with the guidance (European Commission, 2017).

The GAP for applications at growth stages BBCH 57–69 is not supported by residue trials data and the information available was not sufficient to derive MRL proposals or risk assessment values on the on the basis of this GAP.

In Section 3, EFSA assessed whether residues on these crops resulting from the intended uses in accordance with the GAP for applications at growth stages BBCH 77–87 are likely to pose a consumer health risk.

2. Residues in livestock

The assessment of potential residues in livestock in not required because the crops under consideration in this MRL application are normally used for feed purposes.

3. Consumer risk assessment

EFSA performed a dietary risk assessment using revision 2 of the EFSA PRIMo (EFSA, 2007). This exposure assessment model contains food consumption data for different subgroups of the EU population and allows the chronic exposure assessment to be performed in accordance with the internationally agreed methodology for pesticide residues.

The toxicological reference value for mandestrobin used in the risk assessment (i.e. ADI value) was derived in the framework of the EU pesticides peer review (EFSA, 2015). The derivation of an acute reference dose (ARfD) was deemed not necessary on the basis of the low acute toxicity profile of mandestrobin.

The toxicological properties of the metabolites included in the residue definition for risk assessment were assessed in the framework of the EU pesticides peer review. The metabolites De‐Xy‐S‐2200 and 4‐OH‐S‐2200 are covered by the toxicological profile of the parent active substance. It was concluded that the metabolite 2‐CH₂OH‐S‐2200 (also included as conjugate in the residue definition for risk assessment) is not covered by the toxicological studies (EFSA, 2015). However, the metabolite 2‐CH₂OH‐S‐2200 was not detected at levels at or above the LOQ in the supervised crop field trials for the commodities under consideration in the present application (compliant with the GAP for applications at growth stages BBCH 77–87), and therefore, further consideration is not required in the framework of the current MRL application. In case the metabolite 2‐CH₂OH‐S‐2200 is detected in commodities assessed in future MRL applications then additional studies addressing the toxicological properties of this metabolite may be required.

A short‐term dietary risk assessment was not required considering the toxicological profile of the active substance mandestrobin and the metabolites De‐Xy‐S‐2200 and 4‐OH‐S‐2200, and considering that the metabolite 2‐CH₂OH‐S‐2200 (included in the residue definition for risk assessment but not covered by the toxicological studies) was not found at or above the LOQ in the supervised crop field trials for the commodities under consideration.

The long‐term exposure assessment was performed taking into account the supervised trials median residue (STMR) values derived for the commodities assessed in this application; for the remaining commodities covered by the MRL regulation, the existing EU MRLs were selected as input values. A conversion factor (CF) for enforcement to risk assessment was not necessary because currently all existing EU MRLs are set at the LOQ. The complete list of input values is presented in Appendix D.2.

The highest estimated long‐term dietary intake was 0.6% of the ADI. The contribution of residues expected in the commodities assessed in this application to the overall long‐term exposure is presented in more detail in Appendix B.3. EFSA concluded that the long‐term intake of residues of mandestrobin resulting from the intended uses is unlikely to present a risk to consumer health.

4. Conclusion and Recommendations

The data submitted in support of this MRL application were found to be sufficient to derive MRL proposals for cherries and plums and to derive a common MRL proposal for apricots and peaches/nectarines.

EFSA concluded that the proposed uses of mandestrobin on apricots, cherries, peaches/nectarines and plums will not result in a consumer exposure exceeding the toxicological reference value and therefore are unlikely to pose a risk to consumers' health.

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

CF

conversion factor for enforcement to risk assessment residue definition

DAR

draft assessment report

DAT

days after treatment

EMS

evaluating Member State

GAP

Good Agricultural Practice

GC

gas chromatography

GC‐MS

gas chromatography with mass spectrometry

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ISO

International Organisation for Standardisation

IUPAC

International Union of Pure and Applied Chemistry

LC

liquid chromatography

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

MS

mass spectrometry detector

MS/MS

tandem mass spectrometry detector

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

QuEChERS

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

RA

risk assessment

RD

residue definition

RMS

rapporteur Member State

SANCO

Directorate‐General for Health and Consumers

SC

suspension concentrate

SEU

southern Europe

STMR

supervised trials median residue

TAR

total applied radioactivity

TMDI

theoretical maximum daily intake

TRR

total radioactive residue

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			Unit	PHI (days)d	Remarks
				Typeb	Conc. a.s.	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
Stone fruits (peach, nectarine, apricot, plum, cherry)	SEU	F	Monilinia laxa	SC	250 g/L	Foliar spray	57–69	2	7	Max. 15	500–1500	225	g a.s./ha	n.a.	At flowering
Stone fruits (peach, nectarine, apricot, plum, cherry)	SEU	F	Monilinia sp.	SC	250 g/L	Foliar spray	77–87	2	7	Max. 17.5	500–1500	262.5	g a.s./ha	1	Preharvest

NEU: northern European Union; SEU: southern European Union; MS: Member State; n.a.: not applicable.

^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 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
	Leafy crops	Lettuce	Foliar; 2 × 800 g a.s./ha	5 DAT1, 5 DAT2	[phenoxy‐14C]‐mandestrobin EFSA, 2015
	Cereals/grass	Wheat	Foliar; 1 × 300 g a.s./ha	7, 14, 104	[phenoxy‐14C]‐mandestrobin [benzyl‐14C]‐mandestrobin EFSA, 2015
	Pulses/oilseeds	Oilseed rape	Foliar; 2 × 400 g a.s./ha Foliar; 1 × 400 g a.s./ha	14, 40 14, 54	[phenoxy‐14C]‐mandestrobin [benzyl‐14C]‐mandestrobin EFSA, 2015
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Carrot	Soil; 1 × 1.6 kg a.s./ha	30, 120, 365	[phenoxy‐14C]‐mandestrobin [benzyl‐14C]‐mandestrobin EFSA, 2015
	Leafy crops	Lettuce	Soil; 1 × 1.6 kg a.s./ha	30, 120, 365	[phenoxy‐14C]‐mandestrobin [benzyl‐14C]‐mandestrobin EFSA, 2015
	Cereal (small grain)	Wheat	Soil; 1 × 1.6 kg a.s./ha	30, 120, 365	[phenoxy‐14C]‐mandestrobin [benzyl‐14C]‐mandestrobin EFSA, 2015
					As the proposed uses of mandestrobin in the present MRL application are on permanent crops, investigations of residues in rotational crops are not required
Processed commodities (hydrolysis study)	Conditions		Stable?		Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)		Yes		Parent mandestrobin only. Metabolites 2‐CH2OH‐S‐2200, 4‐OH‐S‐2200 and De‐Xy‐S‐2200 not investigated. EFSA, 2015
	Baking, brewing and boiling (60 min, 100°C, pH 5)		Yes		Parent mandestrobin only. Metabolites 2‐CH2OH‐S‐2200, 4‐OH‐S‐2200 and De‐Xy‐S‐2200 not investigated. EFSA, 2015
	Sterilisation (20 min, 120°C, pH 6)		Yes		Parent mandestrobin only. Metabolites 2‐CH2OH‐S‐2200, 4‐OH‐S‐2200 and De‐Xy‐S‐2200 not investigated. EFSA, 2015

DAT₁: Days after first treatment; DAT₂: Days after second treatment.

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	Lettuce	≤ −18	12	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	EFSA, 2015
	High oil content	Oilseed rape seed	≤ −18	12	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	EFSA, 2015
	High protein content	Dried bean, white seeds	≤ −18	9	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	France, 2017
	Dry/High starch	Barley grain	≤ −18	12	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	EFSA, 2015
	High acid content	Orange	≤ −18	9	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	France, 2017
	Others	Straw	≤ −18	12	month	Mandestrobin De‐Xy‐S‐2200 4‐OH‐S‐2200 2‐CH2OH‐S‐2200	EFSA, 2015

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)b	Comments/Source	Calculated MRL (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)	CFd
Apricots, peaches/nectarines	SEU	Apricots Mo: 0.11, 0.25, 0.35e, 0.48, 1.1e RA: 0.14, 0.28, 0.39e, 0.51, 1.13e Peaches Mo: 0.41, 0.51, 0.64, 0.83, 1.2 RA: 0.44, 0.54, 0.67, 0.86, 1.23	Residue trials compliant with the GAP for applications at BBCH growth stages 77–87 only. The trials on apricot and peach were combined to derive a common MRL for apricots and peaches/nectarines. The metabolite 4‐OH‐S‐2200 was present at levels at or above the LOQ of 0.01 mg/kg in one trial on apricot (at all five PHIs) and below the LOQ in all other trials. Metabolites 2‐CH2OH‐S‐2200 and De‐Xy‐S‐2200 were below the LOQs of 0.01 mg/kg in all trials on apricot and peach.	2	Mo: 1.20 RA: 1.23	Mo: 0.50 RA: 0.53	1.13
Cherries	SEU	Mo: 0.38, 0.45, 0.52, 1.1, 1.4 RA: 0.41, 0.49, 0.58, 1.16, 1.43	Residue trials compliant with the GAP for applications at BBCH growth stages 77–87 only. The metabolite 4‐OH‐S‐2200 was present at levels at or above the LOQ of 0.01 mg/kg in all trials. Metabolite De‐Xy‐S‐2200 was present at the level of the LOQ of 0.01 mg/kg in samples from two trials (at four distinct PHIs) and below the LOQ in all other trials. Metabolite 2‐CH2OH‐S‐2200 was below the LOQ of 0.01 mg/kg in all trials.	3	Mo: 1.40 RA: 1.43	Mo: 0.52 RA: 0.58	1.09
Plums	SEU	Mo: 0.06, 0.07, 0.07e, 0.08, 0.09, 0.11e, 0.17, 0.20, 0.20, 0.29e , f RA: 0.09, 0.10, 0.10e, 0.11, 0.12, 0.14e, 0.20, 0.23, 0.23, 0.32e , f	Residue trials compliant with the GAP for applications at BBCH growth stages 77–87 only. The metabolite 4‐OH‐S‐2200 was present at levels at or above the LOQ of 0.01 mg/kg in one trial (at two PHIs) and below the LOQ in all other trials. Metabolites 2‐CH2OH‐S‐2200 and De‐Xy‐S‐2200 were below the LOQs of 0.01 mg/kg in all trials.	0.5	Mo: 0.29 RA: 0.32	Mo: 0.10 RA: 0.13	1.40

^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.

^dCF: Conversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment.

^ePeak residue detected after the GAP minimum PHI.

^fValue identified as an outlier according to Dixon test but included in the MRL and risk assessment calculations since no further explanation is given in study reports.

B.1.2.2. Residues in rotational crops

B.1.2.3. Processing factors

Processing studies submitted in the framework of the present MRL application did not allow for the derivation of robust processing factors.

B.2. Residues in livestock

Not relevant as stone fruits are not used for feed purposes.

B.3. Consumer risk assessment

B.4. Recommended MRLs

Codea	Commodity	Existing EU MRLb (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: mandestrobin
140010	Apricots	0.01*	2	The combined submitted data on apricots and peaches are sufficient to derive a common MRL proposal for apricots and peaches/nectarines on the basis of the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140020	Cherries	0.01*	3	The MRL proposal reflects the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140030	Peaches/nectarines	0.01*	2	The combined submitted data on apricots and peaches are sufficient to derive a common MRL proposal for apricots and peaches/nectarines on the basis of the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57‐69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.
140040	Plums	0.01*	0.5	The MRL proposal reflects the SEU GAP for applications at growth stages BBCH 77–87. The GAP for applications at growth stages BBCH 57–69 was not supported by sufficient data to derive an MRL proposal. Risk for consumers unlikely.

MRL: maximum residue level; SEU: southern Europe; BBCH: growth stages of mono‐ and dicotyledonous plants.

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

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

^bExisting EU MRLs established in Commission Regulation (EU) 2016/486.

Appendix C – PESTICIDE Residue Intake Model (PRIMo)

1.

Appendix D – Input values for the exposure calculations

D.1. Livestock dietary burden calculations

Not relevant as apricots, cherries, peaches, nectarines and plums are not used for feed purposes.

D.2. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: sum of mandestrobin, De‐Xy‐S‐2200, 4‐OH‐S‐2200 conjugate, 2‐CH2OH‐S‐2200 conjugate, expressed as mandestrobin
140010 Apricots	0.53	STMR RA (apricot, peach)	A short‐term dietary risk assessment was not required due to the toxicological profile of the active substance mandestrobin and because the metabolite 2‐CH2OH‐S‐2200 (included in the risk assessment residue definition but not covered by the toxicological studies) was not detected at levels at or above the LOQ in the supervised crop field trials for the commodities under consideration.
140020 Cherries	0.58	STMR RA
140030 Peaches	0.53	STMR RA (apricot, peach)
140040 Plums	0.13	STMR RA
Other commodities	MRL	MRLs in Commission Regulation (EU) 2016/486.a A conversion factor (CF) for enforcement to risk assessment was not necessary because all MRLs are set at the LOQ.

MRL: maximum residue level; LOQ: limit of quantification; STMR: supervised trials median residue; RA: risk assessment.

^aCommission Regulation (EU) 2016/486 of 29 March 2016 amending Annexes II and III to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards maximum residue levels for cyazofamid, cycloxydim, difluoroacetic acid, fenoxycarb, flumetralin, fluopicolide, flupyradifurone, fluxapyroxad, kresoxim‐methyl, mandestrobin, mepanipyrim, metalaxyl‐ M, pendimethalin and tefluthrin in or on certain products. C/2016/1707. OJ L 90, 6.4.2016, p. 1–66.

Appendix E – Used compound codes

1.

Code/trivial name	Chemical name/SMILES notationa	Structural formulaa
mandestrobin (R‐isomer of mandestrobin) S‐2167	(R)‐2‐methoxy‐N‐methyl‐2‐[α‐(2,5‐xylyloxy)‐o‐tolyl]acetamide CNC(=O)[C@H](OC)c2ccccc2COc1cc(C)ccc1C
mandestrobin (S‐isomer of mandestrobin) S‐2354	(S)‐2‐methoxy‐N‐methyl‐2‐[α‐(2,5‐xylyloxy)‐o‐tolyl]acetamide CNC(=O)[C@@H](OC)c2ccccc2COc1cc(C)ccc1C
2‐CH 2 OH‐S‐2200	(2RS)‐2‐[2‐(2‐hydroxymethyl‐5‐ methylphenoxymethyl)phenyl]‐2‐methoxy‐N‐methylacetamide CNC(=O)C(OC)c2ccccc2COc1cc(C)ccc1CO
4‐OH‐S‐2200	(2RS)‐2‐[2‐(4‐hydroxy‐2,5‐dimethylphenoxymethyl)phenyl)‐2‐methoxy‐N‐methylacetamide CNC(=O)C(OC)c2ccccc2COc1cc(C)c(O)cc1C
De‐Xy‐S‐2200	(2RS)‐2‐(2‐hydroxymethylphenyl)‐2‐methoxy‐N‐methylacetamide OCc1ccccc1C(OC)C(=O)NC

^a(ACD/ChemSketch, Advanced Chemistry Development, Inc., ACD/Labs Release: 12.00 Product version: 12.00 (Build 29305, 25 Nov 2008).

Suggested citation: EFSA (European Food Safety Authority) , Brancato A, Brocca D, De Lentdecker C, Erdos Z, Ferreira L, Greco L, Jarrah S, Kardassi D, Leuschner R, Lythgo C, Medina P, Miron I, Molnar T, Nougadere A, Pedersen R, Reich H, Sacchi A, Santos M, Stanek A, Sturma J, Tarazona J, Theobald A, Vagenende B, Verani A and Villamar‐Bouza L, 2018. Reasoned Opinion on the modification of the existing maximum residue levels for mandestrobin in apricots, cherries, peaches/nectarines and plums. EFSA Journal 2018;16(1):5148, 21 pp. 10.2903/j.efsa.2018.5148