Modification of the existing maximum residue level for cymoxanil in beans without pods

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the competent national authority in Belgium, Federal Public Service of Health, Food Chain Safety and Environment, submitted a request to modify the existing maximum residue level (MRL) for the active substance cymoxanil in beans without pods. The data submitted in support of the request were found to be sufficient to derive a MRL proposal for beans without pods. Adequate analytical methods for enforcement are available to control the residues of cymoxanil in beans without pods 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 cymoxanil according to the reported agricultural practice is unlikely to present a risk to consumer health.

Summary

In accordance with Article 6 of Regulation (EC) No 396/2005, the competent national authority in Belgium, Federal Public Service (FPS) of Public Health, Food Chain Safety and Environment, compiled an application to modify the existing maximum residue level (MRL) for the active substance cymoxanil in beans without pods. Belgium (evaluating Member State (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 8 February 2017. To accommodate for the intended use of cymoxanil, the EMS proposed to raise the existing MRL from the limit of quantification (LOQ) of 0.01 to 0.05 mg/kg.

EFSA based its assessment on the evaluation report submitted by the EMS, the draft assessment report (DAR) (and its addendum) prepared under Council Directive 91/414/EEC, the Commission review report on cymoxanil, the conclusion on the peer review of the pesticide risk assessment of the active substance cymoxanil, as well as the conclusions from the previous EFSA opinion on the review of the existing maximum residue levels for cymoxanil according to Article 12 of Regulation (EC) No 396/2005.

Based on the metabolic pattern identified in primary and rotational crops, the residue definition for plant products was proposed as cymoxanil for enforcement and risk assessment. Studies investigating the nature and magnitude of cymoxanil residues in processed commodities were not provided, but are not required. EFSA concluded that for the use on beans without pods assessed in this application, the previously derived residue definition is applicable.

Adequate analytical methods for enforcement are available to control the residues of cymoxanil in beans without pods at the validated LOQ of 0.01 mg/kg. The available residue trials are sufficient to derive a MRL proposal at the LOQ of 0.05 mg/kg for beans without pods.

Residues of cymoxanil in commodities of animal origin were not assessed since beans without pods are normally not fed to livestock.

The toxicological profile of cymoxanil was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.013 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.08 mg/kg bw.

The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). EFSA concludes that the long‐term intake of residues of cymoxanil resulting from the existing and the intended uses is unlikely to present a risk to consumer health. The estimated long‐term dietary intake accounted for up to 4.8% of the ADI for WHO Cluster diet B. The contribution of residues expected in beans without pods according to the intended use to the overall long‐term exposure is up to 0.07% of the ADI. The short‐term exposure is low (international estimated short‐term intake (IESTI) is 0.4% of the ARfD for UK toddler). Based on these calculations, EFSA concludes that the proposed use of cymoxanil on beans without pods is unlikely to pose a risk for the consumers.

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

Full details of all endpoints and the consumer dietary risk assessment can be found in Appendices Appendix B – List of end points, Appendix C – Pesticide Residue Intake Model (PRIMo), Appendix D – Input values for the exposure calculations.

Codea	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: cymoxanil
260020	Beans without pods	0.01*	0.05*	The submitted data are sufficient to derive a MRL proposal for the NEU use. Risk for consumers unlikely

MRL: maximum residue level; NEU: northern Europe.

* 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.

Background

Regulation (EC) No 396/20051 (hereinafter referred to as ‘the MRL regulation’) establishes the rules governing the setting of pesticide maximum residue levels (MRLs) at European Union (EU) level. In accordance with Article 6(3) of the MRL regulation, the competent authority in Belgium, Federal Public Service (FPS) Public Health, Food Chain Safety and Environment2 hereafter referred to as the evaluating Member State (EMS), compiled an application to modify the existing MRL for the active substance cymoxanil in beans without pods. This application was notified to the European Commission and the European Food Safety Authority (EFSA) and was subsequently evaluated in accordance with Article 8 of the MRL regulation.

The EMS submitted an evaluation report to the European Commission which was forwarded to EFSA on 8 February 2017. The application was included in the EFSA Register of Questions with the reference number EFSA‐Q‐2017‐00096 and the following subject:

Cymoxanil – MRL in beans without pods

Belgium proposed to raise the existing MRL of cymoxanil in beans without pods from the limit of quantification (LOQ) 0.01 to 0.05 mg/kg.

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

Terms of Reference

In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall assess the application and the evaluation report and give a reasoned opinion on the risks to the consumer and where relevant to animals associated with the setting of the requested MRLs. The opinion shall include:

• an assessment of whether the analytical method for routine monitoring proposed in the application is appropriate for the intended control purposes;

• the anticipated LOQ for the pesticide/product combination;

• an assessment of the risks of the acceptable daily intake (ADI) and acute reference dose (ARfD) being exceeded as a result of the modification of the MRL;

• the contribution to the intake due to the residues in the product for which the MRLs was requested;

• any other element relevant to the risk assessment.

In accordance with Article 11 of the MRL regulation, EFSA shall give its reasoned opinion as soon as possible and at the latest within 3 months from the date of receipt of the application.

The evaluation report submitted by the EMS (Belgium, 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.

The active substance and its use pattern

The detailed description of the intended use of cymoxanil in beans without pods, which is the basis for the current MRL application, is reported in Appendix A.

Cymoxanil is the ISO common name for 1‐[(E/Z)‐2‐cyano‐2‐methoxyiminoacetyl]‐3‐ethylurea (IUPAC). The chemical structure of the active substance is reported in Appendix E.

Cymoxanil was evaluated in the framework of Directive 91/414/EEC3 with Austria designated as rapporteur Member State (RMS) for the representative uses as a fungicide on lettuce and potato. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (2008). The peer review of renewal of the first approval has not yet been initiated.

Cymoxanil was approved4 for the use as a fungicide on 1 September 2009.

The EU MRLs for cymoxanil are established in Annex II A of Regulation (EC) No 396/2005. 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.5

Assessment

EFSA has based its assessment on the evaluation report submitted by the EMS (Belgium, 2017), the DAR (and its addendum) prepared under Directive 91/414/EEC (Austria, 2007, 2008), the European Commission review report on cymoxanil (European Commission, 2008), the conclusion on the peer review of the pesticide risk assessment of the active substance cymoxanil (EFSA, 2008), as well as the conclusions from the previous EFSA opinion on the review of the existing maximum residue levels for cymoxanil according to Article 12 of Regulation (EC) No 396/2005 (EFSA, 2015).

For this application, the data requirements established in Regulation (EU) No 544/20116 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, 2016; 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 546/20117.

A selected list of end points of the studies assessed by EFSA in the framework of the MRL review, including the end points of studies submitted in support of the current MRL application, are presented in Appendix B.

1. Residues in plants

1.1. Nature of residues and methods of analysis in plants

1.1.1. Nature of residues in primary crops

The metabolism of cymoxanil following foliar treatment in primary corps belonging to the group of fruit crops (tomato, grapes), root crops (potato) and leafy crops (lettuce) has been investigated in the framework of the EU pesticides peer review (EFSA, 2008) and MRL review (EFSA, 2015). According to these studies, in all crop groups the main component of the residue is parent cymoxanil only.

1.1.2. Nature of residues in rotational crops

Beans can be grown in rotation with other plants. The maximum DT₉₀ observed in the field dissipation studies ranged between 0.5 and 33.3 days (EFSA, 2008). As soil degradation studies demonstrated that cymoxanil is not persistent further investigation was not required. Nonetheless, a rotational crop study was evaluated during the peer review, and based on this study, it was confirmed that significant residues of cymoxanil are not expected in rotational crops (EFSA, 2008). Therefore, it is concluded the possible occurrence of residues in rotational crops resulting from the use on primary crops is not expected.

1.1.3. Nature of residues in processed commodities

Studies investigating the effect of processing on the nature of cymoxanil (hydrolysis studies) are not available. Nevertheless, as residues of cymoxanil exceeding 0.1 mg/kg are not expected in beans without pods and the chronic exposure does not exceed 10% of the ADI (theoretical maximum daily intake (TMDI) is up to 4.8% of the ADI), there is no need to investigate the effect of industrial and/or household processing on the nature of the residues.

1.1.4. Methods of analysis in plants

Adequate analytical methods for enforcement are available to control the residues of cymoxanil in beans without pods at the validated LOQ of 0.01 mg/kg (EFSA, 2015).

1.1.5. Stability of residues in plants

The storage stability of cymoxanil in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review (EFSA, 2008). According to these studies, in beans without pods (high water content matrix) residues are stable at −18°C for a period of 18 months.

1.1.6. Proposed residue definitions

Based on the metabolic pattern identified in primary crops and in rotational crops, the residue definition for plant products was proposed as cymoxanil for enforcement and risk assessment (EFSA, 2015). EFSA concludes that for the use on beans without pods assessed in this application, the proposed residue definition is still applicable.

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

Four residue trials performed in beans without pods were submitted in support of the MRL application. Samples were stored in compliance with the demonstrated storage conditions and analysed for the parent compound. According to the assessment of the EMS, the methods used were sufficiently validated and fit for purpose.

Three trials could not be considered independent as they were carried out in the same month at nearby locations. Therefore, having only two independent residue trials, on their own these trials are not sufficient to derive an MRL. Nevertheless, the following considerations should also be taken into account:

• residues were always below the level of quantification (LOQ) of 0.05 mg/kg in the above trials;

• residues were below the LOQ of 0.05 mg/kg in residue trials on peas without pods performed according to the same Good Agricultural Practice (GAP) and evaluated in the framework of the MRLs review (EFSA, 2015);

• according to the current guidance document extrapolation from peas without pods to beans without pods is possible (European Commission, 2016).

Altogether, the available data are considered sufficient to derive an MRL proposal of 0.05 mg/kg.

1.2.2. Magnitude of residues in rotational crops

Significant residues of cymoxanil are not expected in rotational crops (see Section 1.1.2).

1.2.3. Magnitude of residues in processed commodities

No processing studies were submitted in the present assessment and they are not required as significant residues of cymoxanil are not expected in processed commodities (see Section 1.1.2).

1.2.4. Proposed MRLs

The available residue trials are sufficient to derive a MRL proposal for beans without pods (see Appendix B.1.2.1).

2. Residues in livestock

Not relevant as beans without pods are not used for feed purposes.

3. Consumer risk assessment

The toxicological profile of cymoxanil was assessed in the framework of the EU pesticides peer review under Directive 91/414/EEC and the data were sufficient to derive an ADI of 0.013 mg/kg body weight (bw) per day and an ARfD of 0.08 mg/kg bw. The consumer risk assessment was performed with revision 2 of the EFSA PRIMo (EFSA, 2007).

3.1. Short‐term (acute) dietary risk assessment

The short‐term exposure assessment was performed for beans without pods in accordance with the internationally agreed methodology. The calculations were based on the highest residue (HR) derived from supervised field trials on beans without pods and peas without pods and the international estimated short‐term intake (IESTI) accounted for 0.4% of the ARfD for UK toddler. The complete list of input values can be found in Appendix D.2.

3.2. Long‐term (chronic) dietary risk assessment

The long‐term exposure assessment was performed, taking into account the existing uses at EU level (EFSA, 2015). EFSA updated the calculation with the supervised trials median residue (STMR) value derived for beans without pods. The input values used in the exposure calculations are summarised in Appendix D.2.

The estimated long‐term dietary intake accounted for up to 4.8% of the ADI for WHO Cluster diet B. The contribution of residues expected in beans without pods according to the intended use to the overall long‐term exposure is up to 0.07% of the ADI for IE adult (see Appendix C).

Based on these calculations, EFSA concludes that the proposed use of cymoxanil on beans without pods is unlikely to pose a risk for the consumers.

Conclusions and recommendations

The data submitted in support of this MRL application were found to be sufficient to derive MRL proposals for beans without pods.

Adequate analytical methods for enforcement are available to control the residues of cymoxanil in beans without pods.

Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of cymoxanil according to the reported agricultural practice is unlikely to present a risk to consumer health.

The MRL recommendations are summarised in Appendix B.4.

Abbreviations

a.s.

active substance

ADI

acceptable daily intake

AR

applied radioactivity

ARfD

acute reference dose

BBCH

growth stages of mono‐ and dicotyledonous plants

bw

body weight

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

FPS

Federal Public Service

GAP

Good Agricultural Practice

GC‐NPD

gas chromatography with nitrogen/phosphorous detector

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 Organization for Standardization

IUPAC

International Union of Pure and Applied Chemistry

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

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

SEU

southern Europe

SMILES

simplified molecular‐input line‐entry system

STMR

supervised trials median residue

TAR

total applied radioactivity

TMDI

theoretical maximum daily intake

WG

water‐dispersible granule

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 and seasonc	Number min–max	Interval between application (min)	g a.s./hL min–max	Water L/ha min–max	g a.s./ha min–max
Beans, fresh without pods	Belgium (NEU)	F	Mildew	WG	4%	Spraying		1	–			0.1125	14

NEU: northern European Union; SEU: southern European Union; MS; Member State; GAP: Good Agricultural Practice; MRL: maximum residue level; a.s.: active substance; WG: water‐dispersible granule.

^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)
	Fruit crops	Tomatoes(a)	Foliar, 3 × 0.63 kg a.s./ha	3
			Foliar, 4 × 0.24 kg a.s./ha	13
			Foliar, 7 × 0.14 kg a.s/ha	7, 14, 21, 35
		Grapes(a)	Foliar, 8 × 0.21 kg a.s./ha	0, 1, 4, 10,18
	Root crops	Potatoes(b)	Foliar, 8 × 0.24 kg a.s./ha	10
			Foliar, 3 × 0.40 kg a.s./ha	3
	Leafy crops	Lettuce(b)	Foliar, 3 × 0.24 kg a.s./ha	11
			Foliar, 4 × 0.84 kg a.s./ha	3
	Reference: a) EFSA (2015); b) EFSA (2008)

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)
	Root/tuber crops	Sugar beet	Bare soil, 1.2 kg a.s./ha	30, 120
	Leafy crops	Lettuce	Bare soil, 1.2 kg a.s./ha	30, 120
	Cereal (small grain)	Wheat	Bare soil, 1.2 kg a.s./ha	30, 120
	Comments: A ‘no residue’ situation in rotational crops was established Reference: EFSA (2008)

Processed commodities (hydrolysis study)	Conditions	Investigated?
	Pasteurisation (20 min, 90°C, pH 4)	No
	Baking, brewing and boiling (60 min, 100°C, pH 5)	No
	Sterilisation (20 min, 120°C, pH 6)	No
	Comment: Not triggered for the present application

DAT: days after treatment; a.s.: active substance; PBI: plant‐back interval.

B.1.1.2. Stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)	Stability (months/years)
	High water content	Tomatoes(a)	−18	≤ 18 months
	High oil content	Sunflower seed	−18	18 months
	High acid content	Grapes	−18	24 months
	(a): Study performed on several crops investigating storage periods of up to 873 days. However, an unexplained decline of residues was observed in tomatoes between 18 and 24 months. Reference: EFSA (2015)

B.1.2. Magnitude of residues in plants

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

Crop	Region/indoora	Residue levels observed in the supervised residue trials (mg/kg)	Comments	MRL proposals (mg/kg)	HRb (mg/kg)	STMRc (mg/kg)
Beans (fresh, without pods)	NEU	Beans (fresh, without pods): 2× < 0.05* Peas (fresh, without pods): 4× < 0.05	The MRL proposal is based on the combined data set of the trials with beans without pods (Belgium, 2017) and peas without pods performed according to the same GAP (EFSA, 2015)	0.05*	0.05	0.05

MRL: maximum residue level; GAP: Good Agricultural Practice.

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

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

^bHighest residue.

^cSupervised trials median residue.

B.1.2.2. Conversion factors for risk assessment in plant products

Not relevant.

B.1.2.3. Residues in succeeding crops

B.1.2.4. Processing factors

Not relevant.

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: cymoxanil
0260020	Beans without pods	0.01*	0.05*	The submitted data are sufficient to derive a MRL proposal for the NEU use. Risk for consumers is unlikely

MRL: maximum residue level; NEU: northern Europe.

* 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)

Appendix D – Input values for the exposure calculations

D.1. Livestock dietary burden calculations

Not relevant.

D.2. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Beans (fresh, without pods)	0.05*	STMR	0.05*	HR
Table grapes	0.05	STMR (EFSA, 2015)	Acute risk assessment only for the crops under consideration
Wine grapes	0.05	STMR (EFSA, 2015)
Potatoes	0.01*	STMR (EFSA, 2015)
Garlic	0.01*	STMR (EFSA, 2015)
Onions	0.01*	STMR (EFSA, 2015)
Tomatoes	0.01*	STMR (EFSA, 2015)
Aubergines (egg plants)	0.05*	STMR (EFSA, 2015)
Cucumbers	0.01*	STMR (EFSA, 2015)
Gherkins	0.01*	STMR (EFSA, 2015)
Courgettes	0.01*	STMR (EFSA, 2015)
Melons	0.002	STMR × PF (EFSA, 2015)
Pumpkins	0.002	STMR × PF (EFSA, 2015)
Watermelons	0.002	STMR × PF (EFSA, 2015)
Broccoli	0.01*	STMR (EFSA, 2015)
Cauliflower	0.01*	STMR (EFSA, 2015)
Lettuce	0.01*	STMR (EFSA, 2015)
Spinach	0.02	STMR (EFSA, 2015)
Beans (fresh, with pods)	0.05*	STMR (EFSA, 2015)
Peas (fresh, with pods)	0.05*	STMR (EFSA, 2015)
Peas (fresh, without pods)	0.05*	STMR (EFSA, 2015)
Globe artichokes	0.01*	STMR (EFSA, 2015)
Leek	0.01*	STMR (EFSA, 2015)
Beans (dry)	0.02	STMR (EFSA, 2015)
Lentils (dry)	0.02	STMR (EFSA, 2015)
Peas (dry)	0.02	STMR (EFSA, 2015)
Lupins (dry)	0.02	STMR (EFSA, 2015)
Sunflower seed	0.1	EU MRL
Soya bean	0.5	EU MRL
Herbal infusions (dried, flowers)	0.01*	STMR (EFSA, 2015)
Hops (dried), including hop pellets and unconcentrated powder	0.05*	STMR (EFSA, 2015)

STMR: supervised trials median residue; HR: highest residue; PF: processing factor; MRL: maximum residue level.

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

Appendix E – Used compound code(s)

1.

Code/trivial name	Chemical name/SMILES notationa	Structural formulaa
Cymoxanil	1‐[(EZ)‐2‐Cyano‐2‐methoxyiminoacetyl]‐3‐ethylurea N#C\C(=N\OC)C(=O)NC(=O)NCC

SMILES: simplified molecular‐input line‐entry system.

^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, 2017. Reasoned opinion on the modification of the existing maximum residue level for cymoxanil in beans without pods. EFSA Journal 2017;15(12):5066, 19 pp. 10.2903/j.efsa.2017.5066