Modification of the existing maximum residue levels for tebuconazole in rye and wheat

Transcription

1 REASOED OPIIO APPROVED: 06 October 2015 PUBLISHED: 20 October 2015 doi: /j.efsa Modification of the existing maximum residue levels for tebuconazole in rye and wheat European Food Safety Authority (EFSA) Abstract In accordance with Article 6 of Regulation (EC) o 396/2005, the evaluating Member State (EMS), Denmark, received an application from Sumitomo Chemical Agro Europe S.A.S to modify the existing maximum residue levels (MRLs) for the active substance tebuconazole in rye and wheat. In order to accommodate for the intended uses of tebuconazole, Denmark proposed to raise the existing MRLs from 0.1 mg/kg to 0.3 mg/kg for rye and wheat. Denmark drafted an evaluation report in accordance with Article 8 of Regulation (EC) o 396/2005, which was submitted to the European Commission and forwarded to EFSA. According to EFSA the data are sufficient to derive MRL proposals of 0.3 mg/kg for the proposed use on wheat and rye. Based on the risk assessment results, EFSA concludes that the proposed use of tebuconazole on wheat and rye will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a consumer health risk. European Food Safety Authority, 2015 Keywords: tebuconazole, rye, wheat, MRL application, consumer risk assessment Requestor: European Commission Question number: EFSA-Q Correspondence: pesticides.mrl@efsa.europa.eu EFSA Journal 2015;13(10):4262

2 Suggested citation: EFSA (European Food Safety Authority), Modification of the existing maximum residue levels for tebuconazole in rye and wheat. EFSA Journal 2015;13(10):4262, 20 pp. doi: /j.efsa ISS: European Food Safety Authority, 2015 Reproduction is authorised provided the source is acknowledged. The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. 2 EFSA Journal 2015;13(10):4262

3 Summary In accordance with Article 6 of Regulation (EC) o 396/2005, the evaluating Member State (EMS) Denmark, received an application from Sumitomo Chemical Agro Europe S.A.S to modify the existing maximum residue levels (MRLs) for the active substance tebuconazole in rye and wheat (triticale). In order to accommodate for the intended EU uses of tebuconazole, Denmark proposed to raise the existing MRLs from 0.1 mg/kg to 0.3 mg/kg for rye and wheat. Denmark drafted an evaluation report in accordance with Article 8 of Regulation (EC) o 396/2005, which was submitted to the European Commission and forwarded to the European Food Safety Authority (EFSA) on 3 June EFSA bases 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 tebuconazole, the conclusion on the peer review of the pesticide risk assessment of the active substance tebuconazole, the JMPR Evaluation report as well as the conclusions from previous EFSA opinions on tebuconazole. The toxicological profile of tebuconazole 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) value of 0.03 mg/kg bw per day and an acute reference dose (ARfD) of 0.03 mg/kg bw. The metabolism of tebuconazole in primary crops was investigated in the fruit (grape), cereal (wheat), and pulses/oilseeds (peanut) crop groups. Residue definitions for monitoring and risk assessment in plant products were provisionally proposed as tebuconazole (sum of enantiomers), pending the submission of additional information on the triazole derivative metabolites (TDMs). The peer review concluded that a separate risk assessments have to be performed for triazole compounds and TDMs once a global risk assessment approach for TMDs is developed. EFSA concludes that the submitted residue trials on wheat are sufficient to derive a MRL proposal of 0.3 mg/kg for tebuconazole in wheat extrapolated to rye. Data on the magnitude of TDMs were not provided. Adequate analytical enforcement methods are available to monitor the residues of tebuconazole in cereals at the validated LOQ of 0.02 mg/kg. Studies investigating the nature of tebuconazole residues under standard hydrolysis conditions were assessed during peer review and showed the active substance to be hydrolytically stable. ew processing studies have not been submitted under the current application and are not requested. The occurrence of tebuconazole residues in rotational crops was investigated in the framework of the peer review. The metabolites identified in rotational crops were in accordance with the metabolic pathway observed in primary crops and it was concluded that the uptake by plants is not expected to lead to residues of tebuconazole in rotational crops above the LOQ. In contrast, triazole derivative metabolites might be of concern in rotational crops and this situation will be reconsidered as soon as a global approach on TDMs will be defined. The supported uses of tebuconazole on wheat and rye do not result in a change of the livestock dietary intakes estimated in framework of the Article 12 MRL review. Thus, EFSA concluded that a modification of the current MRL values is not required. The consumer risk assessment was performed with revision 2 of the EFSA Pesticide Residues Intake Model (PRIMo). The risk assessment performed in the last issued reasoned opinion of EFSA was now updated with the median (STMR) and highest (HR) residue levels derived from the residue trials conducted on wheat according to the supported GAP. o chronic or acute intake concern was identified for the consumers, since the highest long-term intake was calculated to be 14 % of the ADI (WHO Cluster B) and the highest acute intake was calculated to be 8 % of the ARfD for wheat. EFSA concludes that the intended use of tebuconazole on wheat and rye in Europe will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a health risk to consumers. However, EFSA emphasises that the above assessment does not yet take into consideration triazole derivative metabolites. Since these metabolites may be generated by several pesticides belonging to 3 EFSA Journal 2015;13(10):4262

4 the group of triazole fungicides, EFSA recommends that a separate risk assessment is performed for TDMs as soon as the confirmatory data requested for triazole compounds in the framework of Regulation (EC) o 1107/2009 have been evaluated and a general methodology on the risk assessment of triazole compounds and their triazole derivative metabolites is available. EFSA proposes to amend the existing MRLs as reported in the summary table below. Code (a) Commodity Existing EU MRL Proposed EU MRL Comment/Justification Enforcement residue definition: Tebuconazole Rye Extrapolation from wheat Wheat SEU and EU uses. (a): Commodity code number according to Annex I of Regulation (EC) o 396/ EFSA Journal 2015;13(10):4262

5 Table of contents Abstract... 1 Summary... 3 Background... 6 The active substance and its use pattern... 6 Assessment Method of analysis Methods for enforcement of residues in food of plant origin Methods for enforcement of residues in food of animal origin Mammalian toxicology Residues ature and magnitude of residues in plant Primary crops Rotational crops ature and magnitude of residues in livestock Consumer risk assessment Conclusions and recommendations References Abbreviations Appendix A Good Agricultural Practice (GAPs) Appendix B Pesticide Residue Intake Model (PRIMo) Appendix C Used compound code(s) EFSA Journal 2015;13(10):4262

6 Background Regulation (EC) o 396/ establishes the rules governing the setting of pesticide maximum residue levels (MRLs) at European Union (EU) level. Article 6 of the 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) o 1107/2009, 3 shall submit to a Member State, when appropriate, an application to modify a MRL in accordance with the provisions of Article 7 of the Regulation. Denmark, hereafter referred to as the evaluating Member State (EMS), received an application from the company Sumitomo Chemical Agro Europe S.A.S 4 to modify the existing MRLs for the active substance tebuconazole in rye and wheat. 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 3 June The application was included in the EFSA Register of Questions with the reference number EFSA-Q and the following subject: Tebuconazole - Modification of the existing MRLs in rye and wheat (triticale) Denmark proposed to raise the existing MRLs of tebuconazole in rye and wheat from 0.1 mg/kg to 0.3 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) o 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 the Regulation, the reasoned opinion shall be provided as soon as possible and at the latest within three months (which may be extended to six 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. The active substance and its use pattern Tebuconazole is the ISO common name for (RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1- ylmethyl)-pentan-3-ol (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix C. Tebuconazole has been approved for the uses as fungicide and has systemic properties. Tebuconazole was evaluated in the framework of Directive 91/414/EEC with Denmark designated as rapporteur Member State (RMS). It was included in Annex I of this Directive by Commission Directive 2008/125/EC 5 which entered into force on 1 September 2009 for use as fungicide only. In accordance with Commission Implementing Regulation (EU) o 540/ tebuconazole is approved under Regulation (EC) o 1107/2009, repealing Council Directive 91/414/EEC. The representative uses 1 Regulation (EC) o 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, , p Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market. OJ L 230, , p Regulation (EC) o 1107/2009 of the European Parliament and of the Council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. OJ L 309, , p Sumitomo Chemical Agro Europe, 2 Rue Claude Chappe, Saint-Didier-au-Mont-d'Or, France 5 Commission Directive 2008/125/EC of 19 December 2008 amending Council Directive 91/414/EEC to include aluminium phosphide, calcium phosphide, magnesium phosphide, cymoxanil, dodemorph, 2,5-dichlorobenzoic acid methylester, metamitron, sulcotrione, tebuconazole and triadimenol as active substances, OJ L 344, , p Commission Implementing Regulation (EU) o 540/2011 of 23 May 2011 implementing Regulation (EC) o 1107/2009 of the European Parliament and of the Council as regards the list of approved active substances. OJ L 153, , p EFSA Journal 2015;13(10):4262

7 evaluated in the peer review were foliar applications on wheat, barley, oat, rye and grape and seed dressing for barley. The draft assessment report (DAR) has been peer reviewed by EFSA (EFSA, 2008, 2014). The EU MRLs for tebuconazole are established in Annex II of Regulation (EC) o 396/2005. Since the entry into force of this regulation, EFSA has issued several reasoned opinions on the modification of MRLs for tebuconazole. The review of the existing tebuconazole MRLs according to Article 12 of Regulation (EC) o 396/2005 (hereafter - Article 12 MRL review) has been finalized and EFSA opinion has been issued (EFSA, 2011b). The proposals from these reasoned opinions have been considered in the preparation of EU legislation. The MRL changes that were reported in the EU legislation after the Article 12 MRL review are summarised in Table 1. Table 1: Overview of the MRL changes after the Article 12 MRL review Procedure (a) Considered by Regulation Remarks Art. 12 (EFSA, 2011b) and Implementation of CXLs o 61/ Existing MRL review and implementation of the CXLs adopted by the CAC 2012 Art. 10 (EFSA, 2013) (EU) 2015/401 8 Poppy seed Art. 10 (EFSA, 2015) ot yet legally implemented Cucumbers and courgettes (a): Art. 10: Assessment of MRL application according to Article 6 to 10 of Regulation (EC) o 396/2005 Art. 12: Review of the existing MRLs according to Article 12 of Regulation (EC) o 396/2005 Codex Alimentarius has established maximum residue limits (CXL) for a wide range of commodities, including wheat and rye for which the CXLs are set at 0.15 mg/kg. The details of the intended GAPs for tebuconazole on wheat and rye are given in Appendix A. Assessment EFSA bases its assessment on the evaluation report submitted by the EMS (Denmark, 2015), the DAR (and its addendum) prepared under Directive 91/414/EEC (Denmark, 2007, 2012), the Commission review report on tebuconazole (European Commission, 2008, 2014), the conclusion on the peer review of the pesticide risk assessment of the active substance tebuconazole (EFSA, 2008, 2014), the JMPR Evaluation report (FAO, 2011) as well as the conclusions from previous EFSA opinions on tebuconazole (EFSA, 2011b, 2012, 2013, 2015). 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) o 546/ and the currently applicable guidance documents relevant for the consumer risk assessment of pesticide residues (European Commission, 1996, 1997a g, 2000, 2010a, b, 2011; OECD, 2011). 1. Method of analysis 1.1. Methods for enforcement of residues in food of plant origin Analytical methods for the determination of tebuconazole residues in plant commodities were assessed during the peer review under Directive 91/414/EEC (EFSA, 2008, 2014). The multi-residue method DFG-S19 using GC-MS quantification and its ILV were evaluated and adequately validated for the determination of tebuconazole in plant matrices with high water content (tomato, onion, 7 Commission Regulation (EU) o 61/2014 of 24 January 2014 amending Annexes II and III to Regulation (EC) o 396/2005 of the European Parliament and of the Council as regards maximum residue levels for cyromazine, fenpropidin, formetanate, oxamyl and tebuconazole in or on certain products. OJ L 22, , p Commission Regulation (EU) 2015/401 of 25 February 2015 amending Annexes II and III to Regulation (EC) o 396/2005 of the European Parliament and of the Council as regards maximum residue levels for acetamiprid, chromafenozide, cyazofamid, dicamba, difenoconazole, fenpyrazamine, fluazinam, formetanate, nicotine, penconazole, pymetrozine, pyraclostrobin, taufluvalinate and tebuconazole in or on certain product. OJ L 71, , p Commission Regulation (EU) o 546/2011 of 10 June 2011 implementing Regulation (EC) o 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, , p EFSA Journal 2015;13(10):4262

8 cauliflower), high oil content (rape), acidic (orange) and dry/starch (wheat) commodities, with a LOQ of 0.02 mg/kg. Since cereals belong to dry/starch commodities crop group, EFSA concludes that sufficiently validated analytical methods are available to control tebuconazole residues in cereals Methods for enforcement of residues in food of animal origin Analytical methods for the determination of tebuconazole residues in animal commodities were assessed during the peer review under Directive 91/414/EEC (EFSA, 2014). The monitoring residue definition for food of animal origin was set as the sum of tebuconazole and hydroxy-tebuconazole and their conjugates expressed as tebuconazole. According to the peer review, currently none of the analytical methods evaluated are completely validated to enforce the residue in animal matrices according to the proposed residue definition. A data gap has been identified (EFSA, 2014). However, as new MRLs for tebuconazole in food of animal origin are not proposed under the current application, the submission of a validated enforcement method for food of animal origin is not required. 2. Mammalian toxicology The toxicological profile of the active substance tebuconazole was assessed in the framework of the peer review under Directive 91/414/EEC (EFSA, 2014). The data were sufficient to derive toxicological reference values compiled in Table 2. Metabolism studies in both mammalians and plants have shown the active substances belonging to the chemical class of triazoles to be degraded/metabolised to common metabolites known as triazole derivative metabolites (TDMs), the major ones being the metabolites 1,2,4-triazole, triazole alanine, triazole lactic acid and triazole acetic acid. These TDMs were initially considered of no toxicological concerns, but further evaluations indicated their toxicological relevance. The toxicological profile of TMDs was discussed in the peer review of another triazole compound difenoconazole (EFSA, 2011a). The agreed toxicological reference values are compiled in the table below. Table 2: Overview of the toxicological reference values Source Year Value Study Safety factor Tebuconazole ADI EFSA mg/kg bw per day 1 year dog study supported by developmental mouse study (LOAEL) 100 (dog) 300 (mouse) ARfD EFSA mg/kg bw Developmental mouse study (LOAEL) 300 Metabolites: 1,2,4-triazole, triazole acetic acid (a), triazole lactic acid (a) ADI EFSA mg/kg bw per day Rat, multigeneration study 1000 ARfD EFSA mg/kg bw Rat, developmental study 500 Metabolite: triazole alanine ADI EFSA mg/kg bw per day Rat, developmental study 1000 ARfD EFSA mg/kg bw Rat, developmental study 1000 (a): The same value as for 1,2,4 triazole due to limited database available (EFSA, 2011a) 8 EFSA Journal 2015;13(10):4262

9 3. Residues 3.1. ature and magnitude of residues in plant Primary crops ature of residues The metabolism of tebuconazole in primary crops was evaluated in the framework of the peer review under Directive 91/414/EEC in the fruit, cereals and pulses/oilseeds crop groups (EFSA, 2014). An overview of the available metabolism studies is presented in Table 3. Table 3: Summary of available metabolism studies in plants Crop group Crops Application Fruit Grape Foliar (1x 280 g/ha) 0, 3, 7, 14, 28 DAT Cereals/Grass Pulses/Oilseeds (a): DAT, days after treatment Sampling (a) (day, DAT) Wheat Foliar (1x 500 g/ha) 0, 7, 14, 21, 28 and 50 DAT Seed (11 g/100 kg) 38 and 66 d after planting Peanut Foliar (3x 250 g/ha) 7 weeks after last application Foliar (3x 250 g/ha) Foliar (7x 593 g/ha) 14 weeks after application 14 weeks after application Comments Based on these metabolism studies, the residue definition for monitoring in plant commodities was proposed as tebuconazole (sum of enantiomers) in the conclusions of the peer review (EFSA, 2014). For risk assessment, the experts of the peer review agreed that separate risk assessments have to be performed for the parent compound and the TDM S respectively, and therefore, separate residue definitions were proposed, one for the parent tebuconazole and the second covering the TDMs. However, since TDMs may be generated by several active substances belonging to the group of triazole fungicides, a general methodology on the risk assessment of triazole compounds and their triazole derivative metabolites would need to be developed, taking into account all triazole active substances. The residue definitions were therefore set provisionally, pending the submission of additional information on TDMs and the development of a common approach for the assessment of the TDMs. The current enforcement residue definition in Regulation (EC) o 396/2005 is parent tebuconazole. For the uses on cereals, EFSA concludes that the metabolism of tebuconazole is sufficiently addressed and the residue definitions for enforcement and risk assessment agreed in the peer review are applicable Magnitude of residues Wheat, rye (EU and SEU GAP: 1 x 128 g/ha, BBCH 69) In support of the intended use, the applicant submitted residue trials on wheat. Samples were analysed for tebuconazole only and data on the occurrence of TDMs were not provided. The applicant submitted a total 8 residue trials on wheat performed in northern European countries (France, Germany, Hungary, Poland, Belgium and The United Kingdom) and 8 residue trials conducted in southern European countries (France, Italy and Spain) during the growing season The application of tebuconazole was done according to the proposed GAP, at BBCH 69 and samples were taken days after application. Since the SEU trials result in a higher residue levels, an MRL proposal of 0.3 mg/kg is derived from the SEU dataset, where residues in grains were observed in the range of <0.01 to 0.16 mg/kg. The applicant proposes residue data extrapolation from wheat to rye, which is acceptable according to EU guidelines (European Commission, 2011). The data allow deriving a MRL of 0.3 mg/kg. 9 EFSA Journal 2015;13(10):4262

10 The results of the residue trials, the related risk assessment input values (highest residue, median residue) and the MRL proposals are summarised in Table 4. When more than one use has been assessed for a crop, EFSA proposes the MRL derived from the more critical residue situation and highlighted in bold in Table 4. The stability of tebuconazole residues in plant matrices under storage conditions prior to analysis was assessed during the peer review under Directive 91/414/EEC (EFSA, 2014). Residues of tebuconazole in wheat grain, straw and forage were found to be stable at -18 C for up to 30 months and in wheat flour and wheat bran for 24 months. As the trial samples were stored for a maximum period of 6 months under conditions for which integrity of the samples was demonstrated, 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 proven to be fit for the purpose (Denmark, 2015). EFSA concludes that the data are sufficient to derive the following MRL proposal: 0.30 mg/kg wheat (SEU and EU), extrapolation to rye 10 EFSA Journal 2015;13(10):4262

11 Table 4: Overview of the available residues trials data Crop (GAPs) Wheat (1x 128 g/ha, BBCH 69) Region/ Indoor (a) Residue levels observed in the supervised residue trials (b) SEU Grain: 2x <0.01; 0.01; 0.02; 0.04; 0.09; 0.10; 0.16 Straw: 0.14; 0.61; 0.88; 1.20; 1.30; 1.90; 2.10; 2.30 EU Grain: 4x <0.01; 2x 0.01; 0.02; 0.03 Recommendations/comments (c) Underlined values: mean from three analytical replicates. MRL derived from the SEU dataset since resulting in a higher MRL proposal. MRL OECD : 0.28/0.30 (SEU) MRL OECD : 0.04/0.05 (EU) MRL proposal HR (d) 0.30 Grain: 0.16 Straw: Grain: 0.03 STMR (e) Grain: 0.03 Straw: 1.25 Grain: 0.01 Straw: 0.20; 0.27; 0.44; 0.57; 1.30; 1.90; 2.30; 3.50 Extrapolation to rye Straw: 3.50 Straw: 0.94 (a): EU: 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 (c): Any information/comment supporting the decision and OECD MRL calculation (unrounded/rounded values) (d): HR: Highest residue level (e): STMR: Median residue level 11 EFSA Journal 2015;13(10):4262

12 Effect of industrial processing and/or household preparation The effect of processing on the nature of tebuconazole was investigated in the framework of the peer review and it was concluded that tebuconazole is hydrolytically stable under standard hydrolysis conditions and that no formation of toxicologically relevant metabolites occurs (Denmark, 2008; EFSA, 2014). In the framework of the peer review and of Article 12 MRL review, several studies investigating the effect of processing on tebuconazole residues in barley, grapes, citrus fruit and passion fruit were assessed and the various processing factors were derived (EFSA, 2011b, 2014). ew studies on the processing of wheat or rye have not been submitted under the current application Rotational crops Cereals are grown in rotation with other plants and therefore the possible occurrence of residues in succeeding crops resulting from the use on primary crops has to be assessed. The soil degradation studies demonstrated that the degradation rate of tebuconazole is slow, with maximum DT 90 values exceeding 100 days (EFSA, 2014). Thus, further studies on the nature and magnitude of tebuconazole in rotational crops are required (European Commission, 1997c). The nature of tebuconazole in rotational crops was investigated in the framework of the peer review using 14 C-labelled tebuconazole in either the triazole or the phenyl ring on various rotational crops at a dose rates ranging from 560 to 2500 g/ha (3 to 19 the intended GAP on cereals) (Denmark, 2008; EFSA, 2014). These studies are reported in detail in the EFSA reasoned opinion on the Article 12 MRL review (EFSA, 2011b). The metabolites identified in rotational crops were in accordance with the metabolic pathway observed in primary crops and it was concluded that the uptake by plants is not expected to lead to residues of tebuconazole in rotational crops above the LOQ. In contrast, a significant uptake of the triazole derivative metabolites was observed and therefore the peer review recommended reconsidering the residue in rotational crops once a general methodology on the risk assessment of triazole compounds and their triazole derivative metabolites is available (EFSA, 2014). Additional data on rotational crops were not provided in the framework of this MRL application. Based on the available information, EFSA concludes that residues of tebuconazole are not expected to be present in significant levels in rotational crops when the active substance is applied on cereals according to the proposed GAPs. In contrast, the magnitude of the TDM residue levels in rotational crops could not be addressed ature and magnitude of residues in livestock Cereals and/or their by-products are fed to livestock and therefore the nature and magnitude of tebuconazole residues in livestock has to be investigated. The nature of tebuconazole in livestock was investigated in the framework of the peer review. Based on the submitted metabolism studies on goats and hens, the residue definition for monitoring and risk assessment in livestock was set as the sum of tebuconazole, hydroxy-tebuconazole and their conjugates, expressed as tebuconazole (EFSA, 2014). This residue definition is set on a provisional basis, as TDM residues in livestock have not been investigated. A comprehensive livestock dietary burden calculation was performed in the framework of the Article 12 MRL review considering all existing uses of tebuconazole. MRLs for products of animal origin were proposed (EFSA, 2011b) and taken over in the EU legislation by Regulation (EU) o 61/2014. o change was observed in the calculated livestock intake considering the uses on wheat and rye supported in the current MRL application, since residue intakes from cereals are mainly driven by the uses authorised on barley, which result in significantly higher residues in straw (17 mg/kg) and in grains (0.68 mg/kg) (EFSA, 2011b). It is therefore concluded that the intended new uses of tebuconazole on wheat and rye will not affect the existing livestock dietary burden and will not trigger a need to change the current MRLs set in food commodities of animal origin EFSA Journal 2015;13(10):4262

13 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 sub-groups of the EU population 10 (EFSA, 2007). In the framework of the review of the existing MRLs for tebuconazole according to Article 12 of Regulation (EC) o 396/2005, a comprehensive long-term exposure assessment was performed taking into account the existing uses at the EU level and the acceptable CXLs (EFSA, 2011b). This consumer exposure assessment has been recently updated in EFSA reasoned opinions on the modification of existing MRLs for cucumbers and courgettes (EFSA, 2015) and the CXLs adopted by Codex Alimentarius (FAO, 2011) and implemented in the EU legislation. EFSA now updated the chronic risk assessment performed in the last issued reasoned opinion of EFSA with the STMR derived from the residue trials conducted on wheat according to the use supported in this MRL application. The acute exposure assessment was performed only with regard to wheat and rye assuming the consumption of a large portion of the food items as reported in the national food surveys and that these items contained residues at the highest residue level (HR) as observed in supervised field trials. A variability factor accounting for the inhomogeneous distribution on the individual items consumed was included in the calculation, when required (EFSA, 2007). The input values used for the dietary exposure calculation are summarised in Table 5. Table 5: Input values for the consumer dietary exposure assessment Commodity Input Chronic exposure assessment Comment Input Acute exposure assessment Comment Risk assessment residue definition (plant commodities): Tebuconazole Wheat 0.03 STMR (Table 4) 0.16 HR (Table 4) Rye 0.03 STMR (Table 4) 0.16 HR (Table 4) Other plant commodities STMR see Table 4-1 in previous EFSA reasoned opinion (EFSA, 2015) Acute risk assessment undertaken only with regard to the crops under consideration Risk assessment residue definition (animal commodities): sum of tebuconazole, hydroxy-tebuconazole and their conjugates expressed as tebuconazole Animal commodities STMR see Table 4-1 in previous EFSA reasoned opinion (EFSA, 2015) Acute risk assessment undertaken only with regard to the crops under consideration The estimated exposure was then compared with the toxicological reference values derived for tebuconazole (see Table 1). The results of the intake calculation are presented in Appendix B of this reasoned opinion. A long-term consumer intake concern was not identified for any of the European diets incorporated in the EFSA PRIMo. The highest estimated chronic intake accounted for 14 % of the ADI (WHO Cluster B). The contribution of residues to the total consumer exposure accounted for a maximum of ca. 1 % of the ADI (WHO Cluster B) for wheat. An acute consumer risk was not identified in relation to the MRL proposals for wheat and rye. The highest acute consumer exposure was calculated to be 8 % of the ARfD for wheat. EFSA concludes that the intended use of tebuconazole on wheat and rye in Europe will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a health risk to consumers. 10 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 1 regional and 4 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) EFSA Journal 2015;13(10):4262

14 evertheless, EFSA emphasises that the above assessment does not yet take into consideration triazole derivative metabolites (TDMs). Since these metabolites may be generated by several pesticides belonging to the group of triazole fungicides, EFSA recommends that a separate risk assessment should be performed for TDMs as soon as the confirmatory data requested for triazole compounds in the framework of Regulation (EC) o 1107/2009 have been evaluated and a general methodology on the risk assessment of triazole compounds and their triazole derivative metabolites is available. Conclusions and recommendations The information submitted was sufficient to propose the MRLs summarised in the table below: Code (a) Commodity Existing EU MRL Proposed EU MRL Comment/Justification Enforcement residue definition: Tebuconazole Rye Extrapolation from wheat Wheat Cover SEU and EU uses. (a): Commodity code number according to Annex I of Regulation (EC) o 396/2005 References Denmark, Draft assessment report on the active substance tebuconazole prepared by the rapporteur Member State Denmark in the framework of Council Directive 91/414/EEC, February Available online: Denmark, Addendum to the draft assessment report on the active substance active substance prepared by the rapporteur Member State Denmark in the framework of Council Directive 91/414/EEC, September Available online: Denmark, Compiled addendum to the Draft Assessment Report (DAR) on the active substance tebuconazole prepared by the rapporteur Member State Denmark in the framework of Regulation (EC) o 1107/2009, July Available online: Denmark, Addendum to Compiled addendum to the Draft Assessment Report on the active substance tebuconazole prepared by the rapporteur Member State Denmark in the framework of Regulation (EC) o 1107/2009, October Available online: Denmark, Evaluation report on the modification of MRLs for tebuconazole in rye and wheat prepared by the evaluating Member State Denmark under Article 8 of Regulation (EC) o 396/2005, 28 March 2015, 38 pp. European Commission, Appendix G. Livestock Feeding Studies. 7031/VI/95-rev.4. 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 EFSA Journal 2015;13(10):4262

15 European Commission, 1997g. Appendix I. Calculation of maximum residue level and safety intervals. 7039/VI/95. European Commission, 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). SACO/3029/99- rev.4. European Commission, Review report for the active substance tebuconazole. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 28 October 2008 in view of the inclusion of tebuconazole in Annex I of Council Directive 91/414/EEC. SACO/171/08 rev. 1, 9 September 2008, 9 pp. European Commission, Review report for the active substance tebuconazole. Finalised in the Standing Committee on the Food Chain and Animal Health at its meeting on 28 October 2008 in view of the inclusion of tebuconazole in Annex I of Council Directive 91/414/EEC. SACO/171/08 rev. 2, 11 July 2014, 9 pp. European Commission, 2010a. Classes to be used for the setting of EU pesticide Maximum Residue Levels (MRLs). SACO 10634/2010 Rev. 0, finalised in the Standing Committee on the Food Chain and Animal Health at its meeting of March European Commission, 2010b. Residue analytical methods. For post-registration control. SACO/825/00-rev.8.1. European Commission, Appendix D. Guidelines on comparability, extrapolation, group tolerances and data requirements for setting MRLs. 7525/VI/95-rev.9. EFSA (European Food Safety Authority), Reasoned opinion on the potential chronic and acute risk to consumers health arising from proposed temporary EU MRLs. The EFSA Journal 2007, 32r, doi: /j.efsa r EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance tebuconazole EFSA Scientific Report (2008) 176, 1-109, doi: /j.efsa r EFSA (European Food Safety Authority), 2011a. Conclusion of EFSA prepared by PRAPeR on the peer review of pesticide risk assessment of the active substance difenoconazole. EFSA Journal 2011;9(1):1967, 71 pp. doi: /j.efsa EFSA (European Food Safety Authority), 2011b. Reasoned opinion on the modification of the existing MRLs for tebuconazole according to Article 12 of Regulation (EC) o 396/2005. EFSA Journal 2011;9(8):2339, 96 pp. doi: /j.efsa EFSA (European Food Safety Authority), Reasoned opinion on the modification of the existing MRLs for tebuconazole in poppy seed. EFSA Journal 2013;11(5):3248, 31 pp, doi: /j.efsa EFSA (European Food Safety Authority), Conclusion on the peer review of the pesticide risk assessment of the active substance tebuconazole. EFSA Journal 2014;12(1):3485, 98 pp. doi: /j.efsa EFSA (European Food Safety Authority), Reasoned opinion on the modification of the existing MRL for tebuconazole in cucumbers and courgettes. EFSA Journal 2015;13(1):4000, 24 pp. doi: /j.efsa FAO (Food and Agriculture Organization of the United ations), Tebuconazole. In: Pesticide residues in food Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 211, OECD (Organisation for Economic Co-operation and Development), OECD MRL calculator: spreadsheet for single data set and spreadsheet for multiple data set, 2 March In: Pesticide Publications/Publications on Pesticide Residues. Available online: EFSA Journal 2015;13(10):4262

16 Abbreviations a.s. ADI AR ARfD BBCH bw CAC CF CXL DAR DAT EC EMS eq FAO GAP GC GLP HR ILV IUPAC JMPR LOQ LOAEL MRL MS MS MW EU OECD PHI PRIMo RD RMS SEU STMR TDM active substance acceptable daily intake applied radioactivity acute reference dose growth stages of mono- and dicotyledonous plants body weight Codex Alimentarius Commission conversion factor for enforcement to risk assessment residue definition Codex maximum residue limit (Codex MRL) draft assessment report days after treatment emulsifiable concentrate evaluating Member State residue expressed as a.s. equivalent Food and Agriculture Organization of the United ations good agricultural practice gas chromatography Good Laboratory Practice highest residue independent laboratory validation International Union of Pure and Applied Chemistry Joint FAO/WHO Meeting on Pesticide Residues limit of quantification lowest observed adverse effect level maximum residue level Member States mass spectrometry detector molecular weight northern Europe Organisation for Economic Co-operation and Development pre-harvest interval (EFSA) Pesticide Residues Intake Model residue definition rapporteur Member State southern Europe supervised trials median residue triazole derivative metabolite 16 EFSA Journal 2015;13(10):4262

17 Appendix A Good Agricultural Practice (GAPs) Crop and/or situation (a) MS or EU /SEU or Country F G or I (b) Pest or group of pests controlled (c) Formulation Application Application rate per treatment type (d-f) conc. a.s. (i) Method kind (f-h) Growth stage & season (j) umber minmax (k) Interval min-max g/hl min-max Water L/ha min-max g/ha min-max PHI (days) (l) Remarks (m) Wheat, rye EU and SEU F Erysiphe graminis, Septoria nodorum, Septoria tritici, Puccinia recondite, Fusarium spp. EC 107 g/l Foliar spray BBCH Remarks: (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) e.g. biting and sucking insects, soil-born insects, foliar fungi, weeds (d) e.g. wettable powder (WP), water soluble granule (WG) (e) GCPF Codes - GIFAP Technical Monograph o 2, 1989 (f) all abbreviations must be explained (g) Method, e.g. high volume spraying, low volume spraying, spreading, dusting, drench (h) Kind, e.g. overall, broadcast, aerial spraying, row, individual plant, between the plants. type of equipment used must be indicated (i) g/kg or µg/l (j) Growth stage at last treatment (Meier U, Growth Stages of mono- and dicotyledonous plants. BBCH Monograph, 2 nd Ed., Federal Biological Research Centre of Agriculture and Forestry, Braunschweig, Germany, 2001), including where relevant, information on season at time of application (k) The minimum and maximum number of application possible under practical conditions of use must be provided (l) PHI - minimum pre-harvest interval (m) Remarks may include: Extent of use/economic importance/restrictions 17 EFSA Journal 2015;13(10):4262

18 Appendix B Pesticide Residue Intake Model (PRIMo) Tebuconazole Status of the active substance: Approved Code no. LOQ (mg/kg bw): 0,02 proposed LOQ: Toxicological end points ADI (mg/kg bw/day): 0,03 ARfD (mg/kg bw): 0,03 Source of ADI: EFSA Source of ARfD: EFSA Year of evaluation: 2008 Year of evaluation: 2008 Prepare workbook for refined calculations Undo refined calculations Highest calculated TMDI values in % of ADI MS Diet TMDI (range) in % of ADI minimum - maximum 3 14 o of diets exceeding ADI: --- Highest contributor to MS diet (in % of ADI) Chronic risk assessment - refined calculations Commodity / group of commodities 2nd contributor to MS diet (in % of ADI) Commodity / group of commodities 3rd contributor to MS diet (in % of ADI) Commodity / group of commodities 14 WHO Cluster diet B 2 Tomatoes 2 Wine grapes 1 Wheat 1,0 14 DE child 5 Apples 1 Milk and milk products: Cattle 1 Tomatoes 1,3 14 IE adult 3 Barley 2 Wine grapes 1 Grapefruit 1,0 13 L child 3 Apples 2 Milk and milk products: Cattle 1 Beans (with pods) 2,6 11 WHO cluster diet E 2 Wine grapes 2 Barley 0 Beans (with pods) 0,7 9 FR toddler 2 Beans (with pods) 1 Carrots 1 Apples 0,5 8 FR all population 5 Wine grapes 0 Tomatoes 0 Wheat 0,3 8 FR infant 2 Milk and milk products: Cattle 1 Beans (with pods) 1 Carrots 2,1 8 PT General population 3 Wine grapes 1 Rice 1 Tomatoes 0,5 8 WHO regional European diet 1 Tomatoes 1 Barley 0 Swine: Meat 0,7 7 WHO Cluster diet F 1 Barley 1 Wine grapes 1 Tomatoes 0,6 7 ES child 1 Milk and milk products: Cattle 1 Tomatoes 0 Apples 1,0 7 L general 1 Barley 1 Wine grapes 1 Apples 0,7 7 WHO cluster diet D 1 Tomatoes 1 Wheat 1 Rice 0,8 6 ES adult 1 Barley 1 Tomatoes 1 Wine grapes 0,5 6 UK Toddler 2 Sugar beet (root) 1 Apples 1 Rice 1,8 6 SE general population 90th percentile 1 Milk and milk products: Cattle 1 Tomatoes 0 Apples 1,3 6 DK child 1 Apples 1 Oats 1 Carrots 0,2 5 UK Infant 1 Apples 1 Sugar beet (root) 1 Carrots 1,1 4 DK adult 2 Wine grapes 0 Apples 0 Tomatoes 0,1 4 UK vegetarian 1 Wine grapes 0 Tomatoes 0 Rice 0,4 4 IT kids/toddler 1 Tomatoes 1 Wheat 0 Apples 0,2 4 UK Adult 1 Wine grapes 0 Rice 0 Tomatoes 0,4 4 LT adult 1 Apples 0 Tomatoes 0 Swine: Meat 0,5 4 IT adult 1 Tomatoes 0 Wheat 0 Apples 0,1 3 PL general population 1 Apples 1 Tomatoes 0 Potatoes 0,3 3 FI adult 0 Wine grapes 0 Tomatoes 0 Oats 0,1 ptmrls at LOQ (in % of ADI) Conclusion: The estimated Theoretical Maximum Daily Intakes (TMDI), based on ptmrls were below the ADI. A long-term intake of residues of Tebuconazole is unlikely to present a public health concern EFSA Journal 2015;13(10):4262

19 Processed commodities Unprocessed commodities Acute risk assessment /children - refined calculations Acute risk assessment / adults / general population - refined calculations The acute risk assessment is based on the ARfD. For each commodity the calculation is based on the highest reported MS consumption per kg bw and the corresponding unit weight from the MS with the critical consumption. If no data on the unit weight was available from that MS an average European unit weight was used for the IESTI calculation. In the IESTI 1 calculation, the variability factors were 10, 7 or 5 (according to JMPR manual 2002), for lettuce a variability factor of 5 was used. In the IESTI 2 calculations, the variability factors of 10 and 7 were replaced by 5. For lettuce the calculation was performed with a variabilty factor of 3. Threshold MRL is the calculated residue level which would leads to an exposure equivalent to 100 % of the ARfD. o of commodities for which ARfD/ADI is exceeded (IESTI 1): o of commodities for which o of commodities for which o of commodities for which ARfD/ADI is --- ARfD/ADI is exceeded (IESTI 2): --- ARfD/ADI is exceeded (IESTI 1): --- exceeded (IESTI 2): --- IESTI 1 *) **) IESTI 2 *) **) IESTI 1 *) **) IESTI 2 *) **) Highest % of ARfD/ADI ptmrl/ threshold MRL ptmrl/ threshold MRL ptmrl/ threshold MRL ptmrl/ threshold MRL Highest % of Highest % of Highest % of Commodities ARfD/ADI Commodities ARfD/ADI Commodities ARfD/ADI Commodities 8 Wheat 0,16 / - 8 Wheat 0,16 / - 4 Wheat 0,16 / - 4 Wheat 0,16 / - 3 Rye 0,16 / - 3 Rye 0,16 / - 3 Rye 0,16 / - 3 Rye 0,16 / - o of critical MRLs (IESTI 1) --- o of critical MRLs (IESTI 2) --- o of commodities for which ARfD/ADI is exceeded: Highest % of ARfD/ADI Processed commodities o of commodities for which --- ARfD/ADI is exceeded: --- ***) ***) ptmrl/ ptmrl/ threshold MRL Highest % of Processed threshold MRL ARfD/ADI commodities *) The results of the IESTI calculations are reported for at least 5 commodities. If the ARfD is exceeded for more than 5 commodities, all IESTI values > 90% of ARfD are reported. **) ptmrl: provisional temporary MRL ***) ptmrl: provisional temporary MRL for unprocessed commodity Conclusion: For Tebuconazole IESTI 1 and IESTI 2 were calculated for food commodities for which ptmrls were submitted and for which consumption data are available. o exceedance of the ARfD/ADI was identified for any unprocessed commodity. For processed commodities, no exceedance of the ARfD/ADI was identified EFSA Journal 2015;13(10):4262

20 Appendix C Used compound codes Code/Trivial name Chemical name (a) Structural formula (a) tebuconazole (RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H- 1,2,4-triazol-1-ylmethyl)-pentan-3-ol HO C H 3 CH3 CH 3 MW: Cl hydroxy-tebuconazole 5-(4-chlorophenyl)-2,2-dimethyl-3-(1H-1,2,4- triazol-1-ylmethyl)pentane-1,3-diol HO OH Cl Triazole derivative metabolites 1,2,4-triazole triazole alanine 1H-1,2,4-triazole (free triazole) (CAS number ) (RS)-2-amino-3-(1H-1,2,4 triazol-1-yl) propanoic acid or 3-(1H-1,2,4-triazol-1-yl)-D,L-alanine H 2 H O (CAS number ) OH triazole acetic acid 1H-1,2,4-triazol-1-ylacetic acid HO O (CAS number ) triazole lactic acid or triazole hydroxy propionic acid (R,S)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl) propanoic acid HO O HO 20 EFSA Journal 2015;13(10):4262