Evaluation of confirmatory data following the Article 12 MRL review for pyraclostrobin

Abstract

The applicant BASF SE submitted a request to the competent national authority in Germany to evaluate the confirmatory data that were identified for pyraclostrobin in the framework of the MRL review under Article 12 of Regulation (EC) No 396/2005 as not available. To address the data gaps, residues trials supporting the existing use of pyraclostrobin on table grapes authorised in southern EU Member States and an analytical method for analysing residues of pyraclostrobin in coffee beans were submitted. The data gap for coffee beans was considered satisfactorily addressed. The new residue trials in table grapes give an indication that the existing MRL for table grapes should be raised. However, since a potential acute consumer health risk for table grapes could not be excluded, EFSA recommend the lowering of the existing MRL.

Summary

In 2011, when the European Food Safety Authority (EFSA) reviewed the existing maximum residue levels (MRLs) for pyraclostrobin according to Article 12 of Regulation (EC) No 396/2005, EFSA identified some information as unavailable (data gaps) and derived tentative MRLs for those uses which were not fully supported by data but for which no risk to consumers was identified. The following data gaps were noted:

1. Eight residues trials complying with the import tolerance GAP on cotton seed;

2. Eight trials supporting the southern FR GAP on grapes (data gap resulting from a fall back GAP);

3. Four residues trials complying with the import tolerance GAP on celery;

4. A validated method for enforcement of pyraclostrobin in coffee beans.

Tentative MRL proposals have been implemented in the MRL legislation by Commission Regulation (EU) No 668/2013, including footnotes related to data gaps number 2 (related to table grapes), 3 and 4, indicating the type of confirmatory data that should be provided by a party having an interest in maintaining the proposed tentative MRL by 13 July 2015. Data gap number 1 was not implemented in the MRL regulation, because risk managers decided to set an alternative MRL that was sufficiently supported by data. The footnote related to data gap number 3 was deleted by Commission Regulation (EU) No 2017/1016, since the requested confirmatory data were provided in the framework of a MRL application and were found to be sufficient to address the data gap (EFSA, 2017).

In accordance with the agreed procedure set out in the working document SANTE/10235/2016, BASF SE submitted an application to the competent national authority in the Germany (rapporteur Member State (RMS)) to evaluate the confirmatory data identified during the MRL review. The RMS assessed the new information in an evaluation report, which was submitted to the European Commission and forwarded to EFSA on 26 April 2018. When assessing the evaluation report, EFSA identified points which needed further clarifications. On 13 September 2018, the evaluating Member State (EMS) submitted a revised evaluation report which addressed the points for clarification.

The summary table below provides an overview of the assessment of confirmatory data and the recommended MRL modifications to Regulation (EU) No 396/2005.

Codea	Commodity	Existing MRLb	Proposed MRL	Conclusion/recommendation
Enforcement residue definition: PyraclostrobinF
0151010	Table grapes	1 (ft.1)	0.01*	A sufficient number of residue trials representative for the SEU use were submitted, providing evidence that the existing MRL needs to be raised to 1.5 mg/kg. However, since an acute consumer health risk could not be excluded, EFSA suggests lowering the MRL to the LOQ. Data for alternative GAPs that would allow deriving a safe fall‐back MRL are not available to EFSA
0620000	Coffee beans	0.3 (ft.2)	0.3	The data submitted were sufficient to address the data gap identified in the framework of the MRL review. The footnote related to the existing MRL for coffee beans can be deleted. The risk assessment performed for coffee beans in the framework of the MRL review is still valid

MRL: maximum residue level; SEU: southern Europe; LOQ: limit of quantification; GAP: Good Agricultural Practice.

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

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

b Existing EU MRL and corresponding footnote on confirmatory data.

Ft.1: The European Food Safety Authority identified some information on residue trials as unavailable. When reviewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 July 2015, or, if that information is not submitted by that date, the lack of it (Footnote related to data gap No 2).

Ft.2: The European Food Safety Authority identified some information on analytical methods as unavailable. When reviewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 July 2015, or, if that information is not submitted by that date, the lack of it (Footnote related to data gap No 4).

F Fat‐soluble.

Assessment

The review of existing maximum residue levels (MRLs) for pyraclostrobin according to Article 12 of Regulation (EC) No 396/20051 (MRL review) has been performed in 2011 (EFSA, 2011). The European Food Safety Authority (EFSA) identified some information as unavailable (data gaps) and derived tentative MRLs for those uses not fully supported by data but for which no risk to consumers was identified. The list of Good Agricultural Practices (GAPs) assessed in the framework of the MRL review that were not fully supported by data and for which confirmatory data were requested are listed in Appendix A.

Following the MRL review, MRLs have been modified by Commission Regulation (EU) No 668/20132, including footnotes that specified for the relevant MRLs the type of information that was identified as missing. Any party having an interest in maintaining the proposed tentative MRL was requested to address the confirmatory data by 13 July 2015.

In accordance with the specific provisions set out in the working document of the European Commission SANTE/10235/2016 (European Commission, 2016), the applicant, BASF SE, submitted an application to the competent national authority in Germany (designated rapporteur Member State, RMS) to evaluate the confirmatory data identified during the MRL review. To address the data gaps identified by EFSA, the applicant provided (i) residues trials supporting the GAP on grapes (south EU) and (ii) a validated method for enforcement of pyraclostrobin in coffee beans.

The RMS assessed the new information in an evaluation report, which was submitted to the European Commission and forwarded to EFSA on 26 April 2018 (Germany, 2018). EFSA proceeded with the assessment of the application as requested by the European Commission in accordance with Article 9 of the Regulation. During the detailed assessment, EFSA identified points which needed further clarifications. On 13 September 2018, the RMS submitted a revised evaluation report which addressed the points for clarification (Germany, 2018).

EFSA based its assessment on the evaluation report submitted by the RMS (Germany, 2018), the reasoned opinion on the MRL review according to Article 12 of Regulation (EC) No 396/2005 and additional assessments of pyraclostrobin performed after the MRL review (EFSA, 2011, 2012, 2013, 2014a,b, 2016, 2017, 2018).

For this application, the data requirements established in Regulation (EU) No 544/20113 and the relevant guidance documents at the date of implementation of the confirmatory data requirements by Regulation (EU) No 668/2013 are applicable. 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 546/20114.

An updated list of end points, including the end points of relevant studies assessed previously and the confirmatory data evaluated in this application, is presented in Appendix B.

The process on the renewal of the approval of the active substance pyraclostrobin in accordance with Regulation (EC) No 1107/2009 is ongoing; thus, the conclusions reported in this reasoned opinion might need to be reconsidered in the light of the outcome of the peer review.

The evaluation report submitted by the RMS (Germany, 2018) is considered a supporting document to this reasoned opinion and, thus, is made publicly available as a background document 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

Not relevant for the current assessment.

1.1.2. Nature of residues in rotational crops

Not relevant for the current assessment.

1.1.3. Nature of residues in processed commodities

Not relevant for the current assessment.

1.1.4. Methods of analysis in plants

In order to address data gap number 4, the applicant provided a validated analytical method, including independent laboratory validation, for enforcement of pyraclostrobin in coffee beans. Details on the analytical method are presented in Appendix B.1.1.1.

EFSA concluded that the data gap identified in the framework of the MRL review was addressed.

1.1.5. Stability of residues in plants

Not relevant for the current assessment.

1.1.6. Proposed residue definitions

The previously derived residue definitions are still applicable (EFSA, 2011).

1.2. Magnitude of residues in plants

In order to address data gap number 2, the applicant provided 26 residue trials performed in grapes. Among the submitted trials, 10 outdoor trials on grapes compliant with the southern Europe (SEU) GAP (3 × 100 g/ha, preharvest interval (PHI) 35 days) were identified. The number of the studies is sufficient for the purpose of MRL setting in table grapes. All samples were analysed for the parent compound, using sufficiently validated analytical methods. The samples of these residue trials were stored under conditions for which integrity of the samples has been demonstrated (Germany, 2018).

Based on the GAP‐compliant residue trials, a MRL proposal of 1.5 mg/kg was calculated using the OECD calculator, hence, suggesting that the existing MRL which was derived from residue trials that reflected a more critical GAP (i.e. 4 × 160 g/ha, PHI 35 days) should be raised. The applicant and the RMS did not provide any further explanations for the unexpected result of the residue trials.

Furthermore, the trials were used to derive the risk assessment values; while the highest residue (HR) derived from the GAP‐compliant residue trials was higher than the HR derived from the overdosed trials, the supervised trials median residue (STMR) value comparable. The results of the risk assessment are presented in Section 3.

2. Residues in livestock

The confirmatory data assessed in this evaluation do not have an impact on pesticide residues expected in livestock. Thus, the previous assessment of residues in livestock (EFSA, 2018) is still valid.

3. Consumer risk assessment

EFSA updated the previous risk assessment for table grapes, taking into account the new data submitted under this application.

3.1.

3.1.1.

3.1.1.1.

Short‐term (acute) dietary risk assessment

The short‐term exposure assessment was performed for table grapes in accordance with the internationally agreed methodology. The calculation was based on the HR derived from the GAP‐compliant residue trials submitted as confirmatory data (Appendix D.1).

The calculated short‐term exposure exceeded the ARfD (113.9% of the ARfD) for table grapes assessed in this application (see Appendix B.3). Based on these results, EFSA concluded that for the existing SEU use in table grapes a potential short‐term intake concern cannot be excluded.

Long‐term (chronic) dietary risk assessment

EFSA updated the chronic risk assessment, including the STMR value derived from the residue trials submitted in support of this MRL application for table grapes; in addition, STMR values derived in EFSA opinions published after the MRL review (2011, 2012, 2013, 2014a, 2014b, 2016, 2017, 2018) were included in the dietary exposure assessment (scenario 1). The input values used in the exposure calculations are summarised in Appendix D.1. In scenario 1, the estimated long‐term dietary intake was in the range of 1.8–14% of the acceptable daily intake (ADI).

In scenario 2 of the chronic risk assessment, table grapes were excluded; taking into account that for the critical SEU use in table grapes an acute intake concern was identified. In this scenario, the estimated long‐term dietary intake was in the range of 1.8–12.5% of the ADI. EFSA concluded that the long‐term intake of residues of pyraclostrobin resulting from the existing and the intended uses in table grapes is unlikely to present a risk to consumer health.

4. Conclusion and Recommendations

To address data gaps identified in the framework of the MRL review (EFSA, 2011), the applicant provided GAP‐compliant residues trials supporting the SEU GAP (France) on table grapes and a validated method for enforcement of pyraclostrobin in coffee beans. The data gaps were sufficiently addressed.

The submitted residue trials in grapes led to a higher MRL (1.5 mg/kg) than the tentative one (1 mg/kg) which was derived from overdosed residue trials; furthermore, the risk assessment values derived from these residue trials suggest that the residue trials had a higher HR value. However, EFSA does not recommend raising the current tentative MRL since a risk to consumer health cannot be excluded for short‐term dietary exposure to table grapes. The calculated short‐term exposure exceeded the ARfD (113.9% of the ARfD).

The overview of the assessment of confirmatory data and the recommended MRL modifications are summarised in Appendix B.4.

Abbreviations

a.s.

pyraclostrobin

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

FAO

Food and Agriculture Organization of the United Nations

GAP

Good Agricultural Practice

HPLC‐UVD

high performance liquid chromatography with ultra‐violet detector

HR

highest residue

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ILV

independent laboratory validation

InChiKey

International Chemical Identifier Key.

ISO

International Organisation for Standardisation

IUPAC

International Union of Pure and Applied Chemistry

LC

liquid chromatography

LOQ

limit of quantification

Mo

monitoring

MRL

maximum residue level

MS

Member States

MS/MS

tandem mass spectrometry detector

NEU

northern Europe

OECD

Organisation for Economic Co‐operation and Development

PBI

plant‐back interval

PHI

preharvest interval

PRIMo

(EFSA) Pesticide Residues Intake Model

RA

risk assessment

RD

residue definition

RMS

rapporteur Member State

SE

Suspo‐emulsion

SEU

southern Europe

SMILES

simplified molecular‐input line‐entry system

STMR

supervised trials median residue

WG

water‐dispersible granule

Appendix A – Summary of GAPs assessed in the evaluation of confirmatory data

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)	kg a.s./hL min–max	Water L/ha min‐max	Rate	Unit
Critical SEU GAP assessed in the framework of the MRL review (EFSA, 2011 )
Table grapes	SEU	F	Fungal diseases	SE	40 g/L	Foliar treatment – spraying	n.d.	3	n.d.	n.d.	n.d.	100	g a.s./ha	35
Additional GAPs reported in ER (Germany, 2018 )
Grapes	IT, ES	F	Fungal diseases	WG	50 g/kg	Spraying	BBCH 09‐83	3	8–12 days	8.3–50	200–1,200	100	g a.s./ha	35
Grapes	BG	F	Fungal diseases	WG	50 g/kg	Spraying	BBCH 09‐83	2	7‐ to 10‐day spray intervals for 75 g/ha and 10–14 days for 100 g/ha	8.3–50	200–1,200	100	g a.s./ha	28	75–100 g as/ha for Plasmopara and 100 g as/ha for Uncinula
Grapes	FR	F	Fungal diseases	WG	50 g/kg	Spraying	BBCH 09‐83	2	10 days	25–75	100–300	75	g a.s./ha	35
Grapes	PT	F	Fungal diseases	WG	50 g/kg	Spraying	BBCH 09‐83	2	12 days	6.25–37.5	200–1,200	75	g a.s./ha	56
Grapes	ES, GR, IT	F	Fungal diseases		67 g/kg	Spraying	BBCH 15‐81	3	12 days	10–20	500–1,000	100	g a.s./ha	35
Grapes	ES, IT	F	Fungal diseases		250 g/kg	Spraying	BBCH 53‐83	3	12 days	8.3–100	100‐1,200	100	g a.s./ha	35
Grapes	FR	F	Fungal diseases		40 g/kg	Spraying	BBCH 09‐83	1	n.a.	20–66.7	150–500	100	g a.s./ha	35	No application later than BBCH 69 in table grapes

NEU: northern European Union; SEU: southern European Union; MS: Member State; a.s.: active substance; WG: water‐dispersible granule; SE: Suspo‐emulsion.

^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				No new information provided under the current application. The residue definitions derived in the framework of the MRL review (EFSA, 2011) are still applicable
	Root crops
	Leafy crops
	Cereals/grass
	Pulses/oilseeds
	Miscellaneous

Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/source
	Root/tuber crops				No new information provided under the current application. The residue definitions derived in the framework of the MRL review (EFSA, 2011) are still applicable
	Leafy crops
	Cereal (small grain)
	Other

Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/source
	Pasteurisation (20 min, 90°C, pH 4)		No new information provided under the current application. The residue definitions derived in the framework of the MRL review (EFSA, 2011) are still applicable
	Baking, brewing and boiling (60 min, 100°C, pH 5)
	Sterilisation (20 min, 120°C, pH 6)
	Other processing conditions

B.1.1.2. Stability of residues in plants

No new information has been submitted under the current application.

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
Table grapes (0151010)	SEU	0.11, 0.17, 0.22, 0.23, 0.30, 0.40, 0.42, 0.44, 0.85, 0.87	GAP‐compliant residue trials on grapes (3 × 100 g/ha, PHI 35 days).	1.5	0.87	0.35	–
		0.13, 2 × 0.14, 0.16, 0.18, 0.2, 0.21, 2 × 0.23, 0.27, 0.28, 0.34, 0.37, 0.38, 0.39, 0.4, 0.45, 0.47, 0.48, 0.56, 2 × 0.59, 2 × 0.72	Overdosed residues trials assessed in the framework of MRL review GAP (4 × 160 g/ha) (EFSA, 2011)	1	0.72	0.36	–

MRL: maximum residue level; GAP: Good Agricultural Practice; PHI: preharvest interval.

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

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

^dConversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment.

B.1.2.2. Residues in rotational crops

B.1.2.3. Processing factors

No processing studies were submitted in the framework of the current MRL application.

B.2. Residues in livestock

The submitted information does not trigger the re‐assessment of the livestock dietary burden.

B.3. Consumer risk assessment

B.4. Recommended MRLs

Codea	Commodity	Existing MRLb	Proposed MRL	Conclusion/recommendation
Enforcement residue definition: PyraclostrobinF
0151010	Table grapes	1 (ft.1)	0.01*	A sufficient number of residue trials representative for the SEU use were submitted, providing evidence that the existing MRL needs to be raised to 1.5 mg/kg. However, since an acute consumer health risk could not be excluded, EFSA suggests lowering the MRL to the LOQ Data for alternative GAPs that would allow deriving a safe fall‐back MRL are not available to EFSA
0620000	Coffee beans	0.3 (ft.2)	0.3	The data submitted were sufficient to address the data gap identified in the framework of the MRL review. The footnote related to the existing MRL for coffee beans can be deleted. The risk assessment performed for coffee beans in the framework of the MRL review is still valid

MRL: maximum residue level; SEU: southern Europe; LOQ: limit of quantification; GAP: Good Agricultural Practice.

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

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

b Existing EU MRL and corresponding footnote on confirmatory data.

Ft.1: The European Food Safety Authority identified some information on residue trials as unavailable. When reviewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 July 2015, or, if that information is not submitted by that date, the lack of it (Footnote related to data gap No 2).

Ft.2: The European Food Safety Authority identified some information on analytical methods as unavailable. When reviewing the MRL, the Commission will take into account the information referred to in the first sentence, if it is submitted by 13 July 2015, or, if that information is not submitted by that date, the lack of it (Footnote related to data gap No 4).

F Fat‐soluble.

Appendix C – Pesticide Residue Intake Model (PRIMo)

1.

Appendix D – Input values for the exposure calculations

D.1. Consumer risk assessment

Commodity	Chronic risk assessment		Acute risk assessment
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Risk assessment residue definition: Pyraclostrobin
Table grapes	0.35	Scenario 1: STMR (see Table B.1.2.1)	0.87	Scenario 1: :HR (see Table B.1.2.1)
	–	Scenario 2: No input value included, assuming that the use of table grapes is withdrawn	–	Scenario 2: No input value included, assuming that the use of table grapes is withdrawn
Other commodities		See input values derived during the Article 12 MRL review (EFSA, 2011) and the latest MRL applications under Art 10 of the EU regulation 396/2005 (EFSA, 2011, 2012, 2013, 2014a,b, 2016, 2017, 2018)	–	Acute risk assessment is performed only for crop for which confirmatory data were requested

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

Appendix E – Used compound codes

1.

Code/trivial namea	IUPAC name/SMILES notation/InChiKeyb	Structural formulac
Pyraclostrobin	methyl 2‐[1‐(4‐chlorophenyl)‐1H‐pyrazol‐3‐yloxymethyl]‐N‐methoxycarbanilate O=C(OC)N(OC)c1ccccc1COc1ccn(n1)c1ccc(Cl)cc1 HZRSNVGNWUDEFX‐UHFFFAOYSA‐N

IUPAC: International Union of Pure and Applied Chemistry; SMILES: simplified molecular‐input line‐entry system; InChiKey: International Chemical Identifier Key.

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

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

^cACD/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, Erdos Z, Ferreira L, Greco L, Jarrah S, Kardassi D, Leuschner R, Lostia A, Lythgo C, Medina P, Miron I, Molnar T, Pedersen R, Reich H, Sacchi A, Santos M, Stanek A, Sturma J, Tarazona J, Theobald A, Vagenende B and Villamar‐Bouza L, 2018. Evaluation of confirmatory data following the Article 12 MRL review for pyraclostrobin. EFSA Journal 2018;16(11):5472, 21 pp. 10.2903/j.efsa.2018.5472