REASONED OPINION ADOPTED: 13 June 2016 doi: 10.2903/j.efsa.2016.4527
Modification of the existing maximum residue levels for zoxamide in various leafy crops European Food Safety Authority (EFSA) Abstract In accordance with Article 6 of Regulation (EC) No 396/2005, Italy, hereafter referred to as the rcio evaluating Member State (EMS), received an application from the company Gowan - Come Internacional e Servicßos Lda to modify the existing maximum residue levels (MRLs) for the active substance zoxamide in the groups ‘lettuces and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’. In order to accommodate for the intended uses of zoxamide, Italy proposed to raise the existing MRL from the limit of quantification (0.02 mg/kg) to 30 mg/kg in all crops under consideration. According to EFSA, the submitted residue trials on lettuce, rocket, endive, chicory and escarole are sufficient to derive a MRL proposal of 30 mg/kg, extrapolated to the groups ‘lettuces and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’. EFSA concludes that the intended use of zoxamide on the crops under consideration will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a concern for public health. © 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.
Keywords: zoxamide, lettuce, leafy crops, MRL application, consumer risk assessment
Requestor: European Commission Question number: EFSA-Q-2015-00078 Correspondence:
[email protected]
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EFSA Journal 2016;14(7):4527
Modification of existing MRLs for zoxamide in various leafy crops
Suggested citation: EFSA (European Food Safety Authority), 2016. Reasoned opinion on the modification of the existing maximum residue levels for zoxamide in various leafy crops. EFSA Journal 2016;14(7):4527, 13 pp. doi:10.2903/j.efsa.2016.4527 ISSN: 1831-4732 © 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union.
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EFSA Journal 2016;14(7):4527
Modification of existing MRLs for zoxamide in various leafy crops
Summary In accordance with Article 6 of Regulation (EC) No 396/2005, Italy, hereafter referred to as the rcio evaluating Member State (EMS), received an application from the company Gowan - Come Internacional e Servicßos Lda to modify the existing maximum residue levels (MRLs) for the active substance zoxamide in the groups ‘lettuces and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’. In order to accommodate for the intended uses of zoxamide, Italy proposed to raise the existing MRL to 30 mg/kg for all crops under consideration. Italy 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 28 January 2015. An updated report, addressing the data requirements set by EFSA, was submitted in April 2016. EFSA bases its assessment on the evaluation report submitted by the EMS, the DAR prepared under Directive 91/414/EEC, the Commission review report on zoxamide and the JMPR Evaluation report. The toxicological profile of zoxamide was assessed in the framework of the peer review under Directive 91/414/EEC and the data were sufficient to derive an acceptable daily intake (ADI) of 0.5 mg/kg body weight (bw) per day. The setting of an acute reference dose (ARfD) was deemed not necessary. In the framework of the peer review, the metabolism of zoxamide in primary crops was investigated for foliar applications in the fruit and root crop groups. The residue definition for enforcement and risk assessment was proposed as zoxamide. A new metabolism study on pea (pulses/ oilseeds group) was submitted under the current MRL application and confirms that zoxamide is the major component of the residues in all crop parts. As a similar metabolic pathway was demonstrated in three different crop groups, it is concluded that the residue definition initially set as zoxamide are applicable to all plant groups. Adequate analytical enforcement methods are available to control the residues of zoxamide in the crops under consideration. EFSA concludes that the submitted residue trials on lettuce, rocket, endive, chicory and escarole are sufficient to derive an MRL proposal of 30 mg/kg, extrapolated to the crops under consideration. Processing studies were not provided are not required as the total calculated theoretical maximum daily intake (TMDI) amounts to less than 10% of the ADI. Based on the available information, it is concluded that significant residues are unlikely to occur in rotational crops, provided that the active substance is used according to the proposed good agricultural practice (GAP). Residues of zoxamide in commodities of animal origin were not assessed, as the crops under consideration are normally not fed to livestock. The chronic consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo) and the median residue value (STMR) derived from the indoor residue trials. For the remaining commodities, the existing MRLs as established in Regulation (EU) No 491/2014 were used as input values. A long-term consumer intake concern was not identified for any of the European diets incorporated in the EFSA PRIMo. The highest calculated chronic intake accounted for up to 5% of the ADI (FR, general population). An acute consumer exposure assessment was not performed, since the setting of an ARfD was concluded to be unnecessary for zoxamide. EFSA concludes that the intended uses of zoxamide on the crops under consideration will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a concern for public health and proposes to amend the existing MRL as reported in the table below: Code(a)
Commodity
Enforcement residue definition: Zoxamide 0251000 Lettuces and other salad plants 0252000 Spinaches and similar leaves 0256000
Herbs and edible flowers
Existing EU MRL (mg/kg)
Proposed EU MRL (mg/kg)
Comment/justification
0.02(b) 0.02(b)
30 30
Indoor and SEU. MRL derived from indoor trials
0.02(b)
30
EU: European Union; MRL: maximum residue level. (a): Commodity code number according to Annex I of Regulation (EC) No 396/2005. (b): Indicates that the MRL is set at the limit of analytical quantification (LOQ).
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Table of contents Abstract.................................................................................................................................................... Summary.................................................................................................................................................. Background .............................................................................................................................................. The active substance and its use pattern .................................................................................................... Assessment............................................................................................................................................... 1. Method of analysis ....................................................................................................................... 1.1. Methods for enforcement of residues in food of plant origin ............................................................ 1.2. Methods for enforcement of residues in food of animal origin .......................................................... 2. Mammalian toxicology .................................................................................................................. 3. Residues...................................................................................................................................... 3.1. Nature and magnitude of residues in plant ..................................................................................... 3.1.1. Primary crops............................................................................................................................... 3.1.1.1. Nature of residues........................................................................................................................ 3.1.1.2. Magnitude of residues .................................................................................................................. 3.1.1.3. Effect of industrial processing and/or household preparation ........................................................... 3.1.2. Rotational crops ........................................................................................................................... 3.2. Nature and magnitude of residues in livestock ................................................................................ 4. Consumer risk assessment ............................................................................................................ Conclusions and recommendations ............................................................................................................. References................................................................................................................................................ Abbreviations ............................................................................................................................................ Appendix A – Good agricultural practice ...................................................................................................... Appendix B – Used compound codes ..........................................................................................................
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EFSA Journal 2016;14(7):4527
Modification of existing MRLs for zoxamide in various leafy crops
Background Regulation (EC) No 396/20051 establishes the rules governing the setting of pesticide maximum residue levels (MRLs) at the European Union (EU) level. Article 6 of that Regulation lays down that any party having a legitimate interest or requesting an authorisation for the use of a plant protection product in accordance with Council Directive 91/414/EEC,2 repealed by Regulation (EC) No 1107/20093, shall submit to a Member State, when appropriate, an application to set or to modify a MRL or to set an import tolerance in accordance with the provisions of Article 7 of that Regulation. Italy, hereafter referred to as the evaluating Member State (EMS), received an application from the rcio Internacional e Servicßos Lda4 to modify the existing MRLs for the active company Gowan - Come substance zoxamide in the groups ‘lettuces and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’. This application was notified to the European Commission and the European Food Safety Authority (EFSA) and was subsequently evaluated by the EMS in accordance with Article 8 of the Regulation. After completion, the evaluation report was submitted to the European Commission and to EFSA on 28 January 2015. The application was included in the EFSA Register of Questions with the reference number EFSA-Q-2015-00078 and the following subject: Zoxamide: Setting new MRLs in various crops Italy proposed to raise the existing MRLs of zoxamide in the groups ‘lettuces and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’ from the limit of quantification (LOQ) of 0.02–30 mg/kg. EFSA proceeded with the assessment of the application and the evaluation report as required by Article 10 of the Regulation. In accordance with Article 10 of Regulation (EC) No 396/2005, EFSA shall, based on the evaluation report provided by the EMS, provide a reasoned opinion on the risks to the consumer associated with the application. In accordance with Article 11 of that Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within 3 months (which may be extended to 6 months if more detailed evaluations need to be carried out) from the date of receipt of the application. If EFSA requests supplementary information, the time limit laid down shall be suspended until that information has been provided. On 31 January 2015 some data requirements were identified, which prevented EFSA to conclude on the consumer risk assessment. An updated evaluation report, addressing those data requirements, was submitted by the EMS in April 2016 and taken into consideration by EFSA for finalisation of this reasoned opinion.
The active substance and its use pattern Zoxamide is the ISO common name for (RS)-3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2oxopropyl)-p-toluamide (IUPAC). The S-enantiomer is the active enantiomer within zoxamide. The chemical structures of the active substance and its main metabolites are reported in Appendix B. Zoxamide was evaluated in the framework of Directive 91/414/EEC with United Kingdom (UK) designated as rapporteur Member State (RMS). It was included in Annex I of this Directive by Directive 2003/119/EC5 which entered into force on 1 April 2004 for use as a fungicide only. In accordance with Regulation (EU) No 540/20116, zoxamide is approved under Regulation (EC) No 1107/2009, repealing Council Directive 91/414/EEC. The representative uses evaluated in the peer review were foliar applications on grapes and potatoes. The draft assessment report (DAR) was not peer reviewed by EFSA and therefore, an EFSA conclusion is not available.
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2
3
4
5
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Regulation (EC) No 396/2005 of the Parliament and of the Council of 23 February 2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin and amending Council Directive 91/414/EEC. OJ L 70, 16.3.2005, p. 1–16. Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, 19.8.1991, p. 1–32. Regulation (EC) No 1107/2009 of the European Parliament and Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Directives 79/117/EEC and 91/414/EEC. OJ L 309, 24.11.2009, p. 1–50. rcio Internacional e Servicßos, Limitada, Rua Ivens n. 3 B, Edificio Dona Mecia 6, 9000 046 Funchal, Madeira, Gowan - Come Portugal. Commission Directive 2003/119/EC of 5 December 2003 amending Council Directive 91/414/EEC to include mesosulfuron, propoxycarbazone and zoxamide as active substances. OJ L 325, 12.12.2003, p. 41–43. Commission Implementing Regulation (EU) No 540/2011 of 23 May 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards the list of approved active substances. OJ L 153, 11.6.2011, p. 1–186.
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Modification of existing MRLs for zoxamide in various leafy crops
The EU MRLs for zoxamide are established in Annexes II and IIIB of Regulation (EC) No 396/2005. Since the entry into force of the above-mentioned regulation, EFSA reasoned opinions for the modification of MRLs have not been issued. Codex Alimentarius has established CXLs for zoxamide for some crops but no CXLs have been set for the crops under consideration. The review of zoxamide MRLs according to Article 12 of Regulation (EC) 396/2005 has not been initiated. The details of the intended indoor and SEU GAPs for zoxamide are given in Appendix A.
Assessment EFSA bases its assessment on the updated evaluation report submitted by the EMS (Italy, 2016), the DAR prepared under Directive 91/414/EEC (United Kingdom, 2001, 2002), the Commission review report on zoxamide (European Commission, 2004) and the JMPR Evaluation report (FAO, 2008). 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 and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (European Commission, 1997a–g, 2000, 2010a,b, 2011, 2015; OECD, 2011).
1.
Method of analysis
1.1.
Methods for enforcement of residues in food of plant origin
Analytical methods for the determination of zoxamide residues in plant commodities were assessed during the peer review under Directive 91/414/EEC. A GC-ECD method was concluded to be sufficiently validated to determine zoxamide and its ester metabolite at the LOQ of 0.02 mg/kg in potato and at the LOQ of 0.01 mg/kg in grapes (United Kingdom, 2001, 2002). According to the database of the EU Reference Laboratories for Residues (EURL), the multi-residue QuEChERS method has been validated for the determination of zoxamide residues in:
• •
dry, high water, high acid and high oil content matrices at the LOQ of 0.05 mg/kg, using GC-MS quantification. dry, high acid and high oil content matrices at the LOQ of 0.01 mg/kg and in high water content matrices at the LOQ of 0.002 mg/kg using HPLC-MS/MS quantification.
As the crops under consideration belong to the high water content matrices, EFSA concludes that sufficiently validated analytical methods are available to control zoxamide residues.
1.2.
Methods for enforcement of residues in food of animal origin
Analytical methods for the determination of residues in food of animal origin are not assessed in the current application as the crops under consideration are normally not fed to livestock.
2.
Mammalian toxicology
The toxicological profile of the active substance zoxamide was assessed in the framework of the peer review under Directive 91/414/EEC (European Commission, 2004). The data were sufficient to derive toxicological reference values as compiled in Table 1. Table 1:
Overview of the toxicological reference values Source
Year
Value
Study relied upon
Zoxamide ADI EC
2004
0.5 mg/kg bw per day
90 day, 1-year dog study
ARfD
2004
Not allocated, not necessary
EC
Safety factor 100
ADI: acceptable daily intake; ARfD: acute reference dose; EC: European Commission.
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Commission Regulation (EU) No 546/2011 of 10 June 2011 implementing Regulation (EC) No 1107/2009 of the European Parliament and of the Council as regards uniform principles for evaluation and authorisation of plant protection products. OJ L 155, 11.6.2011, p. 127–175.
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Modification of existing MRLs for zoxamide in various leafy crops
3.
Residues
3.1.
Nature and magnitude of residues in plant
3.1.1.
Primary crops
3.1.1.1. Nature of residues The metabolism in primary crops was evaluated in the framework of the peer review under Directive 91/414/EEC (United Kingdom, 2001, 2002) in the root (potato) and fruit (grape) crop groups. Additional metabolism studies on tomato and cucumber (fruit crops) were evaluated by the JMPR (FAO, 2008) and a new metabolism study on pea (pulses/oilseeds) was submitted in the framework of the current application (Italy, 2016). An overview of the available studies is presented in Table 2. Table 2:
Summary of available metabolism studies in plants
Crop group
Crops
Application
Sampling(a) (day, DAT)
Fruit
Grape
3 9 1,900 g/ha; 30-day interval
1 DAT
Cucumber Tomato
3 9 1,300 g/ha; 7-day interval 3 9 860 g/ha; 18-day interval
1 DAT 1 DAT
Potato
3 9 900 g/ha; 39, 21, 17-day interval
14 DAT
Root
Comments United Kingdom (2001), FAO (2008) FAO (2008) Not peer reviewed United Kingdom (2001); FAO (2008)
a) 2 9 140 g/ha (BBCH 60/65 and 60/69) 7, 13, 30 DAT Italy (2016) b) 2 9 286 g/ha (BBCH 60/65 and 60/69) Not peer reviewed
Pulses/oilseeds Pea
(a): DATx, days after treatment x, e.g. DAT2: day after second treatment.
Based on the metabolism study on potato and grape and considering that zoxamide was the major component of the radioactive residues in grape, the residue definitions for monitoring and risk assessment for the crop groups investigated were proposed as zoxamide in the framework of the peer review. Considering the additional studies on cucumber and tomato where zoxamide was observed as the predominant constituent of the residues, the JMPR also proposed to set the residue definitions for risk assessment and enforcement as zoxamide alone. A new metabolic study on pea (pulses/oilseeds group) was submitted in the framework of this MRL application. A study was conducted using 14C-zoxamide labelled on the phenyl ring with a total of two applications at BBCH growth stages 60/65 and 60/69 at ca. 140 g/ha and at an exaggerated rate of ca. 730 g/ha (ca. 5N). The metabolites identified at the highest application rate 7, 14 and 30 days after the second treatment are summarised in Table 3. Table 3:
Summary of identified metabolites in peas (% of TRR) following treatment with 14Czoxamide at 2 9 286 g/ha (5 9 rate)
PHI (days) Plant matrix
7
13
13
13
30
30
30
Whole plant
Straw
Pods
Fresh pea
Straw
Pods
Dry pea
TRR (mg eq/kg)
38.65
99.29
10.57
200.77
216.72
33.24
0.30
Zoxamide RH-139432
94.5 0.1
95.1 2.4
94.7 1.1
31.6 1.9
91.4 3.4
89.0 3.6
16.7 1.6
RH-129151
0.3
0.4
0.5
0.8
1.8
TRR: total radioactive residue; PHI: pre-harvest interval.
The metabolism study on peas confirms that zoxamide is the major component of the total radioactive residues (TRRs) accounting for 16.7–91.4% TRR in the different plant matrices at maturity, 30 days after the second application. The same metabolites present in the fruit and potato metabolism studies were also identified in pea.
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Modification of existing MRLs for zoxamide in various leafy crops
In conclusion, the study on pea confirms that zoxamide is the major component of the residues and therefore, the residue definition for monitoring and risk assessment initially proposed as zoxamide for the fruit and root crop groups is also applicable to the pulses/oilseeds group. Considering that the metabolism studies conducted on three different crop groups confirm a similar metabolic pathway in plants, a general residue definition as zoxamide is proposed on a temporary basis, pending the re-assessment of the active substance in the framework of the peer review for the renewal of the approval under Regulation (EC) No 1107/2009 and the review of the existing MRLs in the framework of Article 12 of Regulation (EC) No 396/2005. It is noted that the residue definition for enforcement reported under Regulation (EC) No 396/2005 is similar and limited to zoxamide only. 3.1.1.2. Magnitude of residues SEU GAP outdoor/indoor: 2 9 180 g/ha, interval 8–10 days, PHI 7 days In support to the SEU use, the applicant submitted 12 independent trials conducted on lettuce, rocket and endive in Italy, France, Spain and Greece in 2012, 2013 and 2015. In eight locations two different formulations were tested and the highest value per location was selected for MRL calculations. Four trials on head-forming lettuce varieties were disregarded as the extrapolation rules reported in the guideline 7525/VI/95-rev.10.1 (European Commission, 2015) refer to open leaf varieties. Four trials from 2015 were performed with three instead of two applications, but as residues were within overall range, these trials were accepted. Based on residues in the range of 0.68–9.46 mg/kg, an MRL proposal of 20 mg/kg was derived from this residue data set. In support to the indoor uses, the applicant submitted eight independent residue trials on lettuce, rocket, escarole and chicory performed in Italy, Spain and Greece in 2012, 2013 and 2015. In five locations two formulations were tested and the highest residue value per location was selected for MRL calculation. Assuming that rocket, escarole and chicory belong to open leaf varieties, an MRL proposal of 30 mg/kg is derived from residues in the range of 0.53–16.24 mg/kg. The residue data indicate that the indoor use is more critical than outdoor and therefore, an MRL of 30 mg/kg is proposed, extrapolated to the groups ‘lettuce and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’. The results of the residue trials are summarised in Table 4. Table 4:
Overview of the available residue trials data
Crop (GAPs)
Region/ indoor(a)
Lettuce, rocket, endive, chicory, escarole
Indoor
SEU
Residue levels observed in the Recommendations/ supervised (c) (b) comments residue trials (mg/kg) 0.53; 0.75; 2.52; Underlining: trials on rocket, 2.88; 5.68; 5.97; endive, escarole, chicory and 7.53; 16.24 open leaf lettuce MRLOECD = 25.7/30 (indoor) 0.68; 1.56; 3.16; MRL OECD = 17.2/20 (SEU) 3.18; 4.18; 4.48; MRL proposal derived from 8.94; 9.46 indoor trials Extrapolation to the groups ‘Lettuces and salad plants’, ‘Spinaches and similar leaves’ and ‘Herbs and edible flowers’
MRL proposal (mg/kg)
HR(d) (mg/ kg)
STMR(e) (mg/kg)
30
16.24
4.28
–
9.46
3.68
GAP: good agricultural practice; MRL: maximum residue level. (a): NEU: Outdoor trials conducted in northern Europe; SEU: Outdoor trials conducted in southern Europe; Indoor: indoor EU trials or Country code: if non-EU trials. (b): Individual residue levels considered for MRL calculation are reported in ascending order (2 9 < 0.01, 0.01, 6 9 0.02, 0.04, 0.08, 2 9 0.10, 0.15, 0.17). (c): Any information/comment supporting the decision and OECD MRL calculation (unrounded/rounded values). (d): HR: Highest residue level according to the residue definition for risk assessment. (e): STMR: Median residue level according to residue definition for risk assessment.
The stability of zoxamide residues in plant matrices under storage conditions prior to analysis was assessed during the peer review under Directive 91/414/EEC (United Kingdom, 2002). Residues were www.efsa.europa.eu/efsajournal
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found to be stable at ≤ 18°C for up to 24 months in high water content matrices (potato) and for 14 months in high acid content matrices (grapes). The trial samples were stored under conditions for which the integrity of the samples was demonstrated and therefore it is concluded that the residue data are valid with regard to storage stability. According to the EMS, the analytical methods used to analyse the residue trial samples have been sufficiently validated and were proved to be fit for purpose (Italy, 2016). EFSA concludes that the submitted data are sufficient to derive an MRL proposal of 30 mg/kg, extrapolated to the groups ‘lettuce and salad plants’, ‘spinaches and similar leaves’ and ‘herbs and edible flowers’, covering the indoor and SEU uses of zoxamide. 3.1.1.3. Effect of industrial processing and/or household preparation Studies investigating the effect of processing on the nature of zoxamide residues have not been provided in the framework of the peer review (United Kingdom, 2001). Studies investigating the impact of processing on the magnitude of residues in lettuces, spinaches or herbs were not submitted in the framework of the current application. However, as the total theoretical maximum daily intake (TMDI) for the individual crop amounts to less than 10% of the ADI, such studies are not required (European Commission, 1997d).
3.1.2.
Rotational crops
All crops under consideration can grow in a crop rotation and therefore the possible accumulation of zoxamide residues in rotational crops after the use of zoxamide on primary crops has to be further investigated. According to laboratory soil degradation studies, the degradation rate of zoxamide under aerobic conditions is below the trigger value of 100 days (mean DT90lab of 9.4 days). The field degradation studies were considered not necessary (United Kingdom, 2001). Based on the confined rotational crop studies where TRRs greater than 0.1 mg eq./kg were observed in immature radish and soybean hay at plant back interval of 30 days, it was concluded that significant residues are not expected in succeeding crops (United Kingdom, 2001). Moreover, as the dose rate investigated in the confined rotational crop study is a 5N rate compared to the application rate proposed on the crops under consideration, EFSA concludes that significant residue levels are unlikely to occur in rotational crops, provided that the active substance is used on crops under consideration according to the proposed GAPs.
3.2.
Nature and magnitude of residues in livestock
As the crops under consideration are normally not fed to livestock, the nature and magnitude of zoxamide residues in livestock is not assessed in the framework of this application.
4.
Consumer risk assessment
The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). This exposure assessment model contains the relevant European food consumption data for different subgroups of the EU population8 (EFSA, 2007). To calculate the chronic exposure from the intake of the crops under consideration, EFSA used median residue value (STMR) as derived from the indoor residue trials reported in Table 4. For the remaining commodities of plant and animal origin, the existing MRLs as established in Regulation (EU) No 520/20119 were used as input values. An acute consumer exposure assessment was not performed, as the setting of an ARfD was concluded to be unnecessary for zoxamide. The input values used for the dietary exposure calculation are summarised in Table 5. The results of the intake calculation using the EFSA PRIMo is a key supporting document and is made publicly available as a background document to this reasoned opinion. 8
9
The calculation of the long-term exposure (chronic exposure) is based on the mean consumption data representative for 22 national diets collected from MS surveys plus one regional and four cluster diets from the WHO GEMS Food database; for the acute exposure assessment the most critical large portion consumption data from 19 national diets collected from MS surveys is used. The complete list of diets incorporated in EFSA PRIMo is given in its reference section (EFSA, 2007). Commission Regulation (EU) No 520/2011 of 25 May 2011 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 benalaxyl, boscalid, buprofezin, carbofuran, carbosulfan, cypermethrin, fluopicolide, hexythiazox, indoxacarb, metaflumizone, methoxyfenozide, paraquat, prochloraz, spirodiclofen, prothioconazole and zoxamide in or on certain products. OJ L 140, 27.5.2011, p. 2–47.
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Table 5:
Input values for the consumer dietary exposure assessment Chronic exposure assessment
Commodity
Input (mg/kg)
Comment
Risk assessment residue definition: Zoxamide Lettuces and other salad plants Spinaches and similar leaves Herbs and edible flowers
4.28 4.28 4.28
STMR (indoor) (Table 4)
Other plant and animal commodities
MRL
MRL in Regulation (EU) 520/2011
STMR: supervised trials median residue; MRL: maximum residue level.
A long-term consumer intake concern was not identified for any of the European diets incorporated in the EFSA PRIMo. The total calculated chronic intake accounted for up to 5% of the ADI (FR, general population). The individual contribution of residues in the crops under consideration to the total consumer exposure accounted for a maximum of 0.06% of the ADI for the whole group of herbs and edible flowers, 0.6% of the ADI for spinaches (FR toddler diet) and 0.5% for lettuce (ES adult diet), being lower for all remaining crops. EFSA concludes that the intended use of zoxamide on the crops under consideration will not result in a consumer exposure exceeding the toxicological reference value and therefore is unlikely to pose a concern for public health.
Conclusions and recommendations The information submitted was sufficient to propose the MRLs summarised in the table below: Code(a)
Commodity
Enforcement residue definition: Zoxamide 0251000 Lettuces and other salad plants 0252000 Spinaches and similar leaves 0256000
Herbs and edible flowers
Existing EU MRL (mg/kg)
Proposed EU MRL (mg/kg)
0.02(b) 0.02(b)
30 30
0.02(b)
30
Comment/justification
Indoor and SEU. MRL based on indoor trials
EU: European Union; MRL: maximum residue level. (a): Commodity code number according to Annex I of Regulation (EC) No 396/2005. (b): Indicates that the MRL is set at the limit of analytical quantification (LOQ).
References EFSA (European Food Safety Authority), 2007. Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. EFSA Journal 2007;5(3):32r, 1141 pp. doi:10.2903/j.efsa.2007.32r European Commission, 1997a. Appendix A. Metabolism and distribution in plants. 7028/IV/95-rev.3. European Commission, 1997b. Appendix B. General recommendations for the design, preparation and realisation of residue trials. Annex 2. Classification of (minor) crops not listed in the Appendix of Council Directive 90/642/ EEC. 7029/VI/95-rev.6. European Commission, 1997c. Appendix C. Testing of plant protection products in rotational crops. 7524/VI/95-rev.2. European Commission, 1997d. Appendix E. Processing studies. 7035/VI/95-rev.5. European Commission, 1997e. Appendix F. Metabolism and distribution in domestic animals. 7030/VI/95-rev.3. European Commission, 1997f. Appendix H. Storage stability of residue samples. 7032/VI/95-rev.5. European Commission, 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. European Commission, 2000. Residue analytical methods. For pre-registration data requirement for Annex II (part A, section 4) and Annex III (part A, section 5 of Directive 91/414). SANCO/3029/99-rev.4. European Commission, 2004. Review report for the active substance zoxamide. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 3 October 2003 in view of the inclusion of zoxamide in Annex I of Council Directive 91/414/EEC. SANCO/10297/2003-Final, 4 February 2004, 30 pp. European Commission, 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SANCO 10634/2010 Rev. 0, finalised in the Standing Committee on the Food Chain and Animal Health at its meeting of 23–24 March 2010. European Commission, 2010b. Residue analytical methods. For post-registration control. SANCO/825/00-rev.8.1. European Commission, 2011. Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.9. www.efsa.europa.eu/efsajournal
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Modification of existing MRLs for zoxamide in various leafy crops
European Commission, 2015. Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.10.1. FAO (Food and Agriculture Organization of the United Nations), 2008. Zoxamide. In: Pesticide residues in food – 2007. Evaluations. Part I. Residues. FAO Plant Production and Protection Paper 192, 1375–1458. Italy, 2016. Updated evaluation report on the modification of MRLs for zoxamide in lettuce and other salad plants including Brassicaceae, spinach and similar (leaves) and herbs prepared by the evaluating Member State Italy under Article 8 of Regulation (EC) No 396/2005, updated in April 2016, 144 pp. OECD (Organisation for Economic Co-operation and Development), 2011. OECD MRL calculator: spreadsheet for single data set and spreadsheet for multiple data set, 2 March 2011. In: Pesticide Publications/Publications on Pesticide Residues. Available online: http://www.oecd.org United Kingdom, 2001. Draft assessment report on the active substance zoxamide prepared by the rapporteur Member State United Kingdom in the framework of Council Directive 91/414/EEC, April 2001. United Kingdom, 2002. Zoxamide: Revised list of endpoints. European Commission Peer Review Programme/ECCO/ BBA/01. 21 June 2002, 37 pp.
Abbreviations a.s. ADI ARfD BBCH bw CXL DAR DAT ECD EMS eq ES EURL FAO FR GAP GC GCPF GEMS HPLC HPLC HR ISO IUPAC JMPR LOQ MRL MS MS/MS OECD PHI PRIMo QuEChERS RMS SC SEU SMILES STMR TRR WHO
active substance acceptable daily intake acute reference dose growth stages of mono- and dicotyledonous plants body weight Codex maximum residue limit (Codex MRL) draft assessment report days after treatment electron capture detector evaluating Member State residue expressed as a.s. equivalent Spain EU Reference Laboratory (former Community Reference Laboratory (CRL)) Food and Agriculture Organization of the United Nations France good agricultural practice gas chromatography Global Crop Protection Federation (formerly International Group of National Associations of Manufacturers of Agrochemical Products (GIFAP)) Global Environment Monitoring System high performance liquid chromatography high performance liquid chromatography highest residue International Organization for Standardization International Union of Pure and Applied Chemistry Joint FAO/WHO Meeting on Pesticide Residues limit of quantification maximum residue level mass spectrometry detector tandem mass spectrometry detector Organisation for Economic Co-operation and Development pre-harvest interval Pesticide Residues Intake Model Quick, Easy, Cheap, Effective, Rugged, and Safe (analytical method) rapporteur Member State suspension concentrate southern Europe Simplified Molecular Input Line Entry System supervised trials median residue total radioactive residue World Health Organization
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F/G
F G or I(b)
Bremia lactucae, Peronospora farinose, Sclerotina
Pest or group of pests controlled(c)
Application
240 g/L Spray
Type(d),(e)
SC
BBCH 10-89
1–2/growing cycle
8–10 days
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PHI Remarks(l) (days)(k)
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1.44–9 200–1,000 144–180
g/ha min– max
Application rate per treatment
Growth Interval g/hL Water stage Method Number min– min– L/ha (f),(g) (j) and kind min–max max max min–max (i) season
Conc. a.s.(h)
Formulation
NEU: northern Europe; SEU: southern Europe; SC: suspension concentrate; a.s.: active substance. (a): For crops, EU or other classifications, e.g. Codex, should be used; where relevant, the usage situation should be described (e.g. fumigation of a structure). (b): Outdoor or field use (F), glasshouse application (G) or indoor application (I). (c): For example, biting and sucking insects, soil-born insects, foliar fungi, weeds. (d): For example, wettable powder (WP), water-soluble granule (WG). (e): GCPF Codes – GIFAP Technical Monograph No 2, 1989. (f): Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench. (g): Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants. Type of equipment used must be indicated. (h): g/kg or lg/L. (i): Growth stage at last treatment (Meier U, 2001. Growth Stages of mono- and dicotyledonous plants. BBCH Monograph, 2nd Edition, Federal Biological Research Centre of Agriculture and Forestry, Braunschweig, Germany, 2001), including where relevant, information on season at time of application. (j): The minimum and maximum number of application possible under practical conditions of use must be provided. (k): PHI – minimum pre-harvest interval. (l): Remarks may include: Extent of use/economic importance/restrictions.
SEU Lettuce and other salad plants Spinach and similar (leaves) Herbs and edible flowers
Crop and/or situation(a)
MS or NEU/SEU or country
Appendix A – Good agricultural practice
Modification of existing MRLs for zoxamide in various leafy crops
Modification of existing MRLs for zoxamide in various leafy crops
Appendix B – Used compound codes Code/trivial name
Chemical name/ SMILES notation
Zoxamide (C14H16Cl3NO2)
3,5-dichloro-N-(1-chloro3-methyl-2-oxopentan-3yl)-4-methylbenzamide
Structural formula
Cl CH3
O H3C
CH2
C N H
Cl RH-139432
C
O C
CH3
CH2
Cl
O
3,5-dichloro-p-toluamide
Cl
C NH2
H 3C Cl RH-129151
2-(3,5-dichloro-p-tolyl)-4ethyl-4-methyl-4H-1,3oxazin-5(6H)-one
CH3 CH2
CH3 O
N Cl O
H3C Cl STMR: supervised trials median residue; MRL: maximum residue level.
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