Modification of the existing maximum residue levels for isofetamid in tomatoes, peppers, aubergines, okra and cucurbits with edible peel

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant ISK Biosciences Europe N.V. submitted a request to the competent national authority in Belgium, to modify the existing maximum residue levels (MRL) for the active substance isofetamid in tomatoes, sweet peppers/bell peppers, aubergines/eggplants, okra/lady's fingers and the whole subgroup of cucurbits with edible peel. The data submitted in support of the request were found to be sufficient to derive MRL proposals for the commodities under evaluation. Adequate analytical methods for enforcement are available to control the residues of isofetamid in the commodities 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 isofetamid according to the reported agricultural practices is unlikely to present a risk to consumer health. 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, ISK Biosciences Europe N.V. submitted an application to the competent national authority in Belgium (evaluating Member State, EMS) to modify the existing maximum residue levels (MRLs) for the active substance isofetamid in tomatoes, sweet peppers/bell peppers, aubergines/eggplants, okra/lady's fingers and the whole subgroup of cucurbits with edible peel. Belgium 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 25 January 2018. To accommodate for the intended uses of isofetamid, the EMS proposed to raise the existing MRLs from the limit of quantification (LOQ; 0.01 mg/kg) to 1.5 mg/kg for tomatoes and aubergines/eggplants, 3 mg/kg for sweet peppers/bell peppers and okra/lady's fingers, and 1 mg/kg for the whole subgroup of cucurbits with edible peel.

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified points which needed further clarification, which were requested from the EMS. On 21 March 2018, the EMS submitted a revised evaluation report, which replaced the previously submitted evaluation report. Based on the conclusions derived by EFSA in the framework of the European Union (EU) peer review under Regulation (EC) No 1107/2009 and the additional data provided by the EMS in the framework of this application, the following conclusions are derived.

The metabolism of isofetamid following foliar application was investigated in crops belonging to the groups of fruit crops, leafy crops, pulses/oilseeds. Studies investigating the effect of processing on the nature of isofetamid (hydrolysis studies) demonstrated that the active substance is stable. In rotational crops, parent isofetamid was detected in lower amounts and proportions than in primary crops and the residues mainly composed of the metabolites GPTC and GPTC‐malonyl. Overall, the peer review concluded that the metabolic pathways in rotational crops are similar to those observed in primary crops.

Based on the metabolic pattern identified in metabolism studies, the results of hydrolysis studies, the toxicological significance of metabolites and/or degradation products and the capabilities of enforcement analytical methods, the following residue definitions were proposed: plant residue for risk assessment: sum of isofetamid and metabolite GPTC, expressed as isofetamid; residue definition for enforcement: isofetamid. These residue definitions are applicable to primary crops, rotational crops and processed products.

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

Sufficiently validated analytical methods based on liquid chromatography with tandem mass spectrometry (LC‐MS/MS) are 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 proposal for the commodities under evaluation.

Processing studies with tomatoes were submitted in the present MRL application; however, the number of studies was insufficient to derive robust‐processing factors.

The occurrence of isofetamid residues in rotational crops was investigated in the framework of the EU pesticides peer review. The available field rotational crop study was underdosed in comparison with the proposed uses under consideration, and the results cannot be scaled because the residues levels were at or below the LOQ. However, based on the available information on the nature and magnitude of residues, it was concluded that significant residues are not expected in succeeding crops, provided that the active substance is applied according to the proposed good agricultural practice (GAP).

Residues of isofetamid 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 isofetamid 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 0.02 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 1 mg/kg bw. The toxicological reference values for isofetamid are considered to be applicable to the metabolite GPTC included in the risk assessment residue definition.

The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). The estimated short‐term exposure did not exceed the ARfD for any of the crops assessed in this application. The estimated long‐term dietary intake was in the range from 2% to 20% of the ADI.

EFSA concluded that the proposed uses of isofetamid on tomatoes, peppers, aubergines, okra and cucurbits with edible peel will not result in a consumer exposure exceeding the toxicological reference values 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 MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: isofetamid
0231010	Tomatoes	0.01*	1.5	The submitted data are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231020	Sweet peppers/bell peppers	0.01*	3	The submitted data are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231030	Aubergines/eggplants	0.01*	1.5	The submitted data on tomatoes are sufficient to derive a CMRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231040	Okra/lady's fingers	0.01*	3	The submitted data on peppers are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0232000	Cucurbits with edible peel	0.01*	1	The submitted data on cucumbers are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely

EU MRL: European Union maximum residue level.

*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.

Assessment

The detailed description of the intended uses of isofetamid in tomatoes, peppers, aubergines, okra and cucurbits with edible peel, which are the basis for the current maximum residue level (MRL) application, is reported in Appendix A.

Isofetamid is the ISO common name for N‐[1,1‐dimethyl‐2‐(4‐isopropoxy‐o‐tolyl)‐2‐oxoethyl]‐3‐methylthiophene‐2‐carboxamide (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Isofetamid was evaluated in the framework of Regulation (EC) No 1107/20091 with Belgium designated as rapporteur Member State (RMS) for the representative uses as field uses on peaches, plums, apricots, cherries, grapes, strawberries, lettuces and oilseed rapes and glasshouse uses on strawberries and lettuces. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by European Food Safety Authority (EFSA) (EFSA, 2015). Isofetamid was approved2 for the use as fungicide on 15 September 2016. The process of renewal of the first approval has not yet been initiated.

The European Union (EU) MRLs for isofetamid are established in Annexes II of Regulation (EC) No 396/2005.3 The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) has not yet been completed. There are currently no Codex Maximum Residue Limits (CXLs) for isofetamid available yet, although draft CXLs were discussed at the 49th Codex Committee for Pesticides Residues (CCPR) meeting in 2017. The proposed Regulation transposing CXLs, for which the EU had not reserved its position in the CCPR, into EU legislation has not yet been published.

EFSA based its assessment on the evaluation report submitted by the EMS (Belgium, 2017), the draft DAR (and its addendum) (Belgium, 2014, 2015) prepared under Regulation (EC) 1107/2009, the Commission review report on isofetamid (European Commission, 2016) and the conclusion on the peer review of the pesticide risk assessment of the active substance isofetamid (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, 2017; OECD, 2008, 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.

As the review of the existing MRLs under Article 12 of Regulation 396/2005 is not yet finalised, the conclusions reported in this reasoned opinion should be taken as provisional and might need to be reconsidered in the light of the outcome of the MRL review.

A selected list of end points of the studies assessed by EFSA in the framework of the this MRL application, review, 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 (Belgium, 2017; as revised in March 2018) 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 isofetamid in primary crops belonging to the group of fruit crops, leafy crops and pulses/oilseeds following foliar application has been investigated in the framework of the EU pesticides peer review (EFSA, 2015). In all plant matrices, isofetamid was by far the major component of the residues, accounting for 18–73% of the total radioactive residues (TRR), except in bean seeds at harvest where isofetamid was only 1% of the TRR and the residues mainly composed of polar fractions representing all 22–51% TRR. In addition, metabolite GPTC was observed up to 10% TRR in grape and lettuce, all other identified metabolites being below 7% TRR. The metabolic pathway was seen to be similar in the three plant groups (EFSA, 2015). For the intended use, the metabolic behaviour in primary crops is sufficiently addressed.

1.1.2. Nature of residues in rotational crops

Isofetamid 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, the DT₉₀ value of isofetamid ranged from 96 to 174 days (EFSA, 2015). The trigger value of 100 days was exceeded, and therefore, studies investigating the nature and magnitude of residues in rotational crops are required. In the confined rotational crop studies assessed in the framework of the peer review, parent isofetamid was detected in lower amounts and proportions than in primary crops and the residues mainly composed of the metabolites GPTC and GPTC‐malonyl, accounting together up to ca 40% TRR in carrot roots and up to ca 60% TRR in lettuce at the 120‐day plant back interval (EFSA, 2015). Overall, the peer review concluded that the metabolic pathways in rotational crops are similar to those observed in primary crops. For the proposed uses assessed in the present application, no further information is required.

1.1.3. Nature of residues in processed commodities

The effect of processing on the nature of isofetamid was investigated in the framework of the EU pesticides peer review (EFSA, 2015). The available hydrolysis studies showed that isofetamid is hydrolytically stable under standard processing conditions representative of pasteurisation, boiling/cooking and sterilisation. The metabolite GPTC, included together with isofetamid in the plant residue definition for risk assessment, is a glucoside conjugate of isofetamid, and therefore, possible hydrolytic decomposition of GPTC to the aglycone is covered by the available hydrolysis studies on isofetamid.

1.1.4. Methods of analysis in plants

Analytical methods for the determination of residues of isofetamid and the metabolite GPTC in food/feed of plant origin were assessed during the EU pesticides peer review (EFSA, 2015). The methods allow for the quantification of residues at or above the limit of quantification (LOQ) of 0.01 mg/kg for each analyte in crops belonging to the high water content, high acid content and dry groups of commodities; however, the methods were not validated for residues in high oil content commodities (Belgium, 2014). The methods are sufficiently validated for residues of isofetamid and the metabolite GPTC in the crops under consideration in the present MRL application.

1.1.5. Stability of residues in plants

The storage stability of isofetamid and the metabolite GPTC in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review (EFSA, 2015). It was demonstrated that for the crops assessed in the framework of this application, residues were stable for at least 12 months when stored at −20 °C.

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/or degradation products and the capabilities of enforcement analytical methods, the following residue definitions were proposed:

• plant residue for risk assessment: sum of isofetamid and metabolite GPTC, expressed as isofetamid

• residue definition for enforcement: isofetamid

The same residue definitions are applicable to rotational crops and 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 no further information is required.

1.2. Magnitude of residues in plants

1.2.1. Magnitude of residues in primary crops

In support of the MRL application, the applicant submitted four residue trials and four residue decline trials each for tomatoes, peppers and cucumbers. The trials were conducted under greenhouse conditions in Italy, the Netherlands and Spain and were performed with two foliar spray applications after formation of the edible parts at a nominal rate of 480 g a.s./ha with an application interval of 7–10 days, whereas the critical good agricultural practices (GAPs) for the intended uses are a minimum application interval of 7 days.6 That the application interval in a number of residue trials is longer than the application interval in the critical GAPs is a source of additional uncertainty in the MRL calculations and in the risk assessment; however, this deficiency in the residues trials data is judged to be a minor deviation which is expected to have no material impact on the results of the MRL calculation or the risk assessment.

For tomatoes, the residue trials and the residue decline trials were conducted with half of the trials performed on standard‐sized varieties and half of the trials performed on cherry tomato varieties. The applicant proposed to extrapolate the results of the residue trials performed on tomatoes to aubergines, to extrapolate the results of the residue trials on peppers to okra and to extrapolate the results of the residue trials on cucumbers to the whole subgroup of cucurbits with edible peel, in accordance with the EU extrapolation rules (European Commission, 2017). Overall, the trials are considered sufficiently representative of the GAPs for the intended uses on the crops under consideration.

The residue trial samples were stored under conditions for which integrity has been demonstrated. The samples were analysed for the parent compound and the metabolite GPTC, in accordance with the requirements of the residue definitions for enforcement (isofetamid only) and risk assessment (isofetamid and GPTC). According to the assessment of the EMS, the methods used were sufficiently validated and fit for purpose. The levels of metabolite GPTC were below the LOQ in all residue trials samples, and therefore, the LOQ value of 0.01 mg/kg was used in calculations of the supervised trials median residue (STMR) and highest residue (HR) values for risk assessment purposes. The residues data from the supervised residue trials in primary crops are summarised in Appendix B.1.2.1.

1.2.2. Magnitude of residues in rotational crops

The possible transfer of isofetamid residues to crops that are grown in crop rotation has been assessed in EU pesticides peer review (EFSA, 2015). The available field rotational crop studies demonstrated that no significant residues (residues of isofetamid and GPTC below 0.01 mg/kg and residues of GPTC‐malonyl at or below 0.02 mg/kg) are expected in the edible parts of succeeding crops (spinach, radish and winter barley) planted in soil following foliar applications to primary crop (lettuce) treated at 2 × 400 g a.s./ha (Belgium, 2014). The total seasonal application rate for the crops under consideration is 960 g a.s./ha, and therefore, the field rotational crop study was underdosed (0.83N) and the results cannot be scaled because the residues levels were at or below the LOQ. However, considering the total seasonal application rates for the proposed uses (GAPs) and that the levels of residues observed in the field rotational crop study were not only below the LOQ (0.01 mg/kg) but, in most instances, also below the limit of detection (LOD) (0.004 mg/kg), it was concluded that significant residues are not expected to occur in succeeding crops, provided that the active substance is applied according to the proposed GAPs.

1.2.3. Magnitude of residues in processed commodities

Processing studies in grapes were assessed in EU pesticides peer review and processing factors were derived for wine, juice and raisin (EFSA, 2015). Two processing studies (one balance and one follow‐up) with tomatoes were submitted in the present MRL application which indicate that drying of tomatoes leads to a concentration of isofetamid and metabolite GPTC residues in the processed product, whereas juicing, pureeing, processing to ketchup and canning lead to a reduction of residues in the processed products (Belgium, 2014). However, the submitted processing studies gave variable results for the same processes, not enabling the waiving of further studies, and therefore, in accordance with the data requirements, the number of studies was insufficient to derive robust‐processing factors. Further processing studies would be required to propose processing factors for inclusion in Annex VI of Regulation (EC) No 396/2005 (European Commission, 1997d; OECD, 2008).

1.2.4. Proposed MRLs

The available data are considered sufficient to derive MRL proposals as well as risk assessment values for the commodities under evaluation (see Appendix B.1.2.1). In Section 3, EFSA assessed whether residues on these crops resulting from the intended uses are likely to pose a consumer health risk.

2. Residues in livestock

An assessment of potential residues in livestock is not required because the commodities under consideration are not 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 acute and chronic exposure assessment to be performed in accordance with the internationally agreed methodology for pesticide residues (FAO, 2016a).

The toxicological reference values for isofetamid used in the risk assessment (i.e. acceptable daily intake (ADI) and acute reference dose (ARfD) values) were derived in the framework of the EU pesticides peer review (EFSA, 2015). The toxicological reference values for isofetamid are considered to be applicable to the metabolite GPTC included in the risk assessment residue definition (EFSA, 2015).

The short‐term exposure assessment was performed for the commodities assessed in this application in accordance with the internationally agreed methodology. The calculations were based on the HR derived from the supervised field trials and the complete list of input values can be found in Appendix D.2. The estimated short‐term exposure did not exceed the ARfD for any of the crops assessed in this application (see Appendix B.3).

The long‐term exposure assessment was performed, taking into account the STMR values derived for the commodities assessed in this application; for the remaining commodities covered by the MRL regulation, the existing EU MRLs and where relevant the STMR values derived by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) were selected as input values (FAO, 2016b). The complete list of input values is presented in Appendix D.2. The estimated long‐term dietary intake was in the range from 2% to 20% 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 isofetamid resulting from the existing and the intended uses is unlikely to present a risk to consumer health.

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 MRL proposals for tomatoes, sweet peppers/bell peppers, aubergines/eggplants, okra/lady's fingers and the whole subgroup of cucurbits with edible peel.

EFSA concluded that the proposed uses of isofetamid on tomatoes, peppers, aubergines, okra and cucurbits with edible peel will not result in a consumer exposure exceeding the toxicological reference values and therefore is 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

CCPR

Codex Committee on Pesticide Residues

CF

conversion factor for enforcement to risk assessment residue definition

CXL

Codex maximum residue limit

DALA

days after last application

DAR

draft assessment report

DAT

days after treatment

DT₉₀

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

EMS

evaluating Member State

FAO

Food and Agriculture Organization of the United Nations

GAP

Good Agricultural Practice

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

JMPR

Joint FAO/WHO Meeting on Pesticide Residues

LC‐MS/MS

liquid chromatography with tandem mass spectrometry

LOD

limit of detection

LOQ

limit of quantification

LWA

Leaf Wall Area

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

RA

risk assessment

RAC

raw agricultural commodity

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

TRR

total radioactive residue

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.	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
Cucurbits, edible peel	UK; BE; NL; DE; LU; CZ; PL; HU; RO; SK; SI	G	Botrytis cinerea anamorph of Botryotinia fuckeliana; Sclerotinia sp.	SC	400 g/L	Foliar spray	From BBCH 51 to BBCH 89	2	7 days	40–64	750–1,200	480	g a.s./ha	1	360 g a.s./ha Leaf Wall Area (LWA) (to be evaluated by efficacy)
Tomato	UK; BE; NL; DE; LU; CZ; PL; HU; RO; SK; SI	G	Botrytis cinerea anamorph of Botryotinia fuckeliana; Sclerotinia sp.	SC	400 g/L	Foliar spray	From BBCH 51 to BBCH 89	2	7 days	40–64	750–1,200	480	g a.s./ha	1	360 g a.s./ha Leaf Wall Area (LWA) (to be evaluated by efficacy)
Aubergine/eggplant	UK; BE; NL; DE; LU; CZ; PL; HU; RO; SK; SI	G	Botrytis cinerea anamorph of Botryotinia fuckeliana; Sclerotinia sp.	SC	400 g/L	Foliar spray	From BBCH 51 to BBCH 89	2	7 days	40–64	750–1,200	480	g a.s./ha	1	360 g a.s./ha Leaf Wall Area (LWA) (to be evaluated by efficacy)
Peppers	UK; BE; NL; DE; LU; CZ; PL; HU; RO; SK; SI	G	Botrytis cinerea anamorph of Botryotinia fuckeliana; Sclerotinia sp.	SC	400 g/L	Foliar spray	From BBCH 51 to BBCH 89	2	7 days	40–64	750–1,200	480	g a.s./ha	1	360 g a.s./ha Leaf Wall Area (LWA) (to be evaluated by efficacy)
Okra/lady's fingers	UK; BE; NL; DE; LU; CZ; PL; HU; RO; SK; SI	G	Botrytis cinerea anamorph of Botryotinia fuckeliana; Sclerotinia sp.	SC	400 g/L	Foliar spray	From BBCH 51 to BBCH 89	2	7 days	40–64	750–1,200	480	g a.s./ha	1	360 g a.s./ha Leaf Wall Area (LWA) (to be evaluated by efficacy)

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

^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
	Fruit crops	Grape	3 × 750 g/ha foliar spray, 13‐14 day intervals, BBCH 67–69, 71–75 and 77–79	43 DALA	Radiolabelled active substance: [14C‐phenyl]‐isofetamid or [14C‐(C2)‐thiophene]‐isofetamid Belgium (2014)
	Leafy crops	Lettuce	3 × 750 g/ha foliar spray, 14 day intervals	18 DALA	Radiolabelled active substance: [14C‐phenyl]‐isofetamid or [14C‐(C2)‐thiophene]‐isofetamid Belgium (2014)
	Pulses/oilseeds	French bean	3 × 750 g/ha foliar spray, 8 day intervals, first application at BBCH 60–61	0, 14, 68 DALA	Radiolabelled active substance: [14C‐phenyl]‐isofetamid or [14C‐(C2)‐thiophene]‐isofetamid Belgium (2014)
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Root/tuber crops	Carrot	1 × 2,134 to 2,152 g/ha, bare soil application	30, 120 and 365	Radiolabelled active substance: [14C‐phenyl]‐isofetamid Belgium (2014)
	Leafy crops	Lettuce	1 × 2,134 to 2,152 g/ha, bare soil application	30, 120 and 365	Radiolabelled active substance: [14C‐phenyl]‐isofetamid Belgium (2014)
	Cereal (small grain)	Wheat	1 × 2,134 to 2,152 g/ha, bare soil application	30, 120 and 365	Radiolabelled active substance: [14C‐phenyl]‐isofetamid Belgium (2014)
Processed commodities (hydrolysis study)	Conditions		Stable?		Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)		Yes		EFSA (2015)
	Baking, brewing and boiling (60 min, 100°C, pH 5)		Yes		EFSA (2015)
	Sterilisation (20 min, 120°C, pH 6)		Yes		EFSA (2015)

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	Lettuces	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	High water content	Potatoes	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	High oil content	Almonds	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	High oil content	Oilseed rape	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	High protein content	Beans	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	High starch	–	–	–	–	–	–
	High acid content	Grapes	−20	12	Month	Isofetamid, GPTC	EFSA (2015)
	Processed products	–	–	–	–	–	–
	Others	–	–	–	–	–	–

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)	CFd
Tomatoes,Aubergines/eggplants	Indoor	Mo: 0.17, 0.22, 0.44, 0.45, 0.49, 0.52, 0.58, 0.93RA: 0.18, 0.23, 0.45, 0.46, 0.50, 0.53, 0.59, 0.94	Residue trials on tomatoes compliant with GAP. Extrapolation to aubergines/eggplants possible. Levels of metabolite GPTC were below the LOQ, and therefore, the LOQ value of 0.01 mg/kg was used multiplied by the molecular mass conversion factor of 0.75	1.5	Mo: 0.93RA: 0.94	Mo: 0.47RA: 0.48	1.02
Sweet peppers/bell peppers,Okra/lady's fingers	Indoor	Mo: 0.14, 0.20, 0.25, 0.44, 0.69, 0.71, 0.74, 1.65RA: 0.15, 0.21, 0.26, 0.45, 0.70, 0.72, 0.75, 1.66	Residue trials on peppers compliant with GAP. Extrapolation to okra/lady's fingers possible. Levels of metabolite GPTC were below the LOQ, and therefore, the LOQ value of 0.01 mg/kg was used multiplied by the molecular mass conversion factor of 0.75	3	Mo: 1.65RA: 1.66	Mo: 0.57RA: 0.57	1.01
Cucurbits with edible peel	Indoor	Mo: 0.04, 0.05, 0.10, 2 × 0.12, 0.13, 0.44, 0.55RA: 0.05, 0.06, 0.11, 2 × 0.13, 0.14, 0.45, 0.56	Residue trials on cucumbers compliant with GAP. Extrapolation to cucurbits with edible peel possible. Levels of metabolite GPTC were below the LOQ, and therefore, the LOQ value of 0.01 mg/kg was used multiplied by the molecular mass conversion factor of 0.75	1	Mo: 0.55RA: 0.56	Mo: 0.12 RA: 0.13	1.06

^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. RA: The median residue for risk assessment refers to the whole commodity and not to the edible portion. Mo: Supervised trials median residue according to the residue definition for monitoring. Minor difference in the STMR‐RA value for peppers in the evaluation report is due to rounding of residue values (Belgium, 2017).

^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

Processed commodity	Number of valid studiesa	Processing Factor (PF)		CFP b	Comment/Source
		Individual values	Median PF
Tomato, juice	2	0.17, 0.07	–	–	Insufficient number of studies to derive robust‐processing factors (Belgium, 2017)
Tomato, puree	2	0.11, 0.06	–	–	Insufficient number of studies to derive robust‐processing factors (Belgium, 2017)
Tomato, ketchup	2	0.23, 0.12	–	–	Insufficient number of studies to derive robust‐processing factors (Belgium, 2017)
Tomato, canned fruit	2	0.11, 0.03	–	–	Insufficient number of studies to derive robust‐processing factors (Belgium, 2017)
Tomato, dried	2	8.3, 2.0	–	–	Insufficient number of studies to derive robust‐processing factors (Belgium, 2017)

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

^bConversion factor for risk assessment in the processed commodity; median of the individual conversion factors for each processing residues trial.

B.2. Residues in livestock

Not relevant as the commodities under consideration are not used for feed purposes.

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: isofetamid
0231010	Tomatoes	0.01*	1.5	The submitted data are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231020	Sweet peppers/bell peppers	0.01*	3	The submitted data are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231030	Aubergines/eggplants	0.01*	1.5	The submitted data on tomatoes are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0231040	Okra/lady's fingers	0.01*	3	The submitted data on peppers are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely
0232000	Cucurbits with edible peel	0.01*	1	The submitted data on cucumbers are sufficient to derive a MRL proposal for indoor/greenhouse use. Risk for consumers unlikely

EU MRL: European Union maximum residue level.

*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.

Appendix C – Pesticide Residue Intake Model (PRIMo)

1.

Appendix D – Input values for the exposure calculations

D.1. Livestock dietary burden calculations

Feed commodity	Median dietary burden		Maximum dietary burden
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Commodities under assessment are not fed to livestock.

D.2. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Plant residue definition for risk assessment: Sum of isofetamid and metabolite GPTC, expressed as isofetamid
0231010 Tomatoes	0.48	STMR	0.94	HR
0231020 Sweet peppers/bell peppers	0.57	STMR	1.66	HR
0231030 Aubergines/eggplants	0.48	STMR tomatoes	0.94	HR tomatoes
0231040 Okra/lady's fingers	0.57	STMR peppers	1.66	HR peppers
0232010 Cucumbers	0.13	STMR	0.56	HR
0232020 Gherkins	0.13	STMR cucumbers	0.56	HR cucumbers
0232030 Courgettes	0.13	STMR cucumbers	0.56	HR cucumbers
0232990 Other cucurbits with edible peel	0.13	STMR cucumbers	0.56	HR cucumbers
0140010 Apricots	0.017	STMR, ‘no‐residue situation’ EFSA (2015)	Acute risk assessment was undertaken only with regard to the crops under consideration.
0140020 Cherries	0.017	STMR, ‘no‐residue situation’ EFSA (2015)
0151010 Table grapes	0.710	STMR EFSA (2015)
0151020 Wine grapes	0.710	STMR EFSA (2015)
0152000 Strawberries	0.500	STMR(JMPR) × CF (0.49 × 1.02) FAO (2016b); EFSA (2015)a
0154020 Cranberries	0.500	STMR(JMPR) × CF (0.49 × 1.02) FAO (2016b); EFSA (2015)b
0251020 Lettuces	0.047	EFSA (2015)
0252000 Spinaches and similar leaves	0.047	EFSA (2015)
0256000 Herbs and edible flowers	0.047	EFSA (2015)
0401010 Linseeds	0.017	STMR rapeseeds EFSA (2015)
0401030 Poppy seeds	0.017	STMR rapeseeds EFSA (2015)
0401060 Rapeseeds/canola seeds	0.017	STMR, ‘no‐residue situation’ EFSA (2015)c
0401080 Mustard seeds	0.017	STMR rapeseeds EFSA (2015)
0401130 Gold of pleasure seeds	0.017	STMR rapeseeds EFSA (2015)
Other plant commodities	MRL	MRLs in Commission Regulation (EU) 2017/171. A conversion factor (CF) for enforcement to risk assessment was not necessary because MRLs for all other plant commodities are set at the LOQ
Animal residue definition for risk assessment: Sum isofetamid and metabolite PPA, expressed as isofetamid (provisional)
Animal commodities	MRL	MRLs in Commission Regulation (EU) 2017/171.d A conversion factor (CF) for enforcement to risk assessment was not necessary because MRLs for all animal commodities are set at the LOQ	Acute risk assessment was undertaken only with regard to the crops under consideration

^aJMPR STMR value based on more critical Canada and USA GAPs. JMPR residue definition for risk assessment for plant commodities: Isofetamid. EFSA derived a CF of 1.02 and an STMR value of 0.362 mg/kg on the basis of a less critical EU GAP and indoor residue trials. Outdoor EU trials resulted in lower residues.

^bJMPR STMR value based on Canada and USA GAPs. JMPR residue definition for risk assessment for plant commodities: Isofetamid. EFSA derived a CF of 1.02 for strawberries on the basis of an EU GAP.

^cIt is noted that the JMPR derived an STMR value of 0.01 mg/kg on the basis of more critical Canada and USA GAPs (FAO, 2016b). JMPR residue definition for risk assessment for plant commodities: Isofetamid.

^dCommission Regulation (EU) 2017/171 of 30 January 2017 amending Annexes II, III and IV to Regulation (EC) No 396/2005 of the European Parliament and of the Council as regards maximum residue levels for aminopyralid, azoxystrobin, cyantraniliprole, cyflufenamid, cyproconazole, diethofencarb, dithiocarbamates, fluazifop‐P, fluopyram, haloxyfop, isofetamid, metalaxyl, prohexadione, propaquizafop, pyrimethanil, Trichoderma atroviride strain SC1 and zoxamide in or on certain products. C/2017/0401. OJ L 30, 3.2.2017, p. 45–111.

Appendix E – Used compound codes

1.

Code/trivial name	IUPAC name/SMILES notation/InChIKeya	Structural formulab
Isofetamid IKF‐5411	N‐[1,1‐dimethyl‐2‐(4‐isopropoxy‐o‐tolyl)‐2‐oxoethyl]‐3‐methylthiophene‐2‐carboxamide O=C(NC(C)(C)C(=O)c1 ccc(OC(C)C)cc1C)c2sccc2C WMKZDPFZIZQROT‐UHFFFAOYSA‐N
PPA	(2RS)‐2‐{3‐methyl‐4‐[2‐methyl‐N‐(3‐methylthiophene‐2‐carbonyl)alanyl]phenoxy}propanoic acid O=C(NC(C)(C)C(=O)c1ccc(OC(C)C(=O)O)cc1C)c2sccc2C CFZWEHRXSMYLPD‐UHFFFAOYSA‐N
GPTC	N‐{1‐[4‐(D‐glucopyranosyloxy)‐2‐methylphenyl]‐2‐methyl‐1‐oxopropan‐2‐yl}‐3‐methylthiophene‐2‐carboxamide O=C(NC(C)(C)C(=O)c2ccc(O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)cc2C)c3sccc3C AJMFCWXRIDCDDN‐XHCNLMPISA‐N
GPTC‐malonyl	3‐methyl‐4‐[2‐methyl‐N‐(3‐methylthiophene‐2‐carbonyl)alanyl]phenyl 6‐O‐(carboxyacetyl)‐D‐glucopyranoside O=C(NC(C)(C)C(=O)c2ccc(OC1O[C@H](COC(=O)CC(=O)O)[C@@H](O)[C@H](O)[C@H]1O)cc2C)c3sccc3C HAKKTWCXWDYAPF‐VVHFXJRLSA‐N
IBA	2‐methyl‐4‐(propan‐2‐yloxy)benzoic acid CC(C)Oc1cc(C)c(cc1)C(=O)O FTZOSZBGDBNSEM‐UHFFFAOYSA‐N
3‐MTCAM	3‐methylthiophene‐2‐carboxamide NC(=O)c1sccc1C QZDTWJRYMXQXBX‐UHFFFAOYSA‐N
3‐MTCA	3‐methylthiophene‐2‐carboxylic acid O=C(O)c1sccc1C IFLKEBSJTZGCJG‐UHFFFAOYSA‐N

^aACD/Name 2015 ACD/Labs 2015 Release (File version N20E41, Build 75170, 19 December 2014).

^bACD/ChemSketch 2015 ACD/Labs 2015 Release (File version C10H41, Build 75059, 17 December 2014).

Suggested citation: EFSA (European Food Safety Authority) , Brancato A, Brocca D, Carrasco Cabrera L, De Lentdecker C, 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, and Villamar‐Bouza L, 2018. Reasoned Opinion on the modification of the existing maximum residue levels for isofetamid in tomatoes, peppers, aubergines, okra and cucurbits with edible peel. EFSA Journal 2018;16(5):5264, 24 pp. 10.2903/j.efsa.2018.5264