Setting of import tolerance for tricyclazole in rice

Abstract

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Corteva Agriscience submitted a request to the competent national authority in Italy to set an import tolerance for the active substance tricyclazole in rice. The data submitted in support of the request were found to be sufficient to derive an maximum residue level (MRL) proposal for rice. Adequate analytical methods for enforcement are available to control the residues of tricyclazole in rice at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short‐term and long‐term intake of residues resulting from the use of tricyclazole according to the reported agricultural practice is unlikely to present a risk to consumer health.

Summary

In accordance with Article 6 of Regulation (EC) No 396/2005, Corteva Agriscience submitted an application to the competent national authority in Italy (rapporteur Member State, RMS) to set an import tolerance for the active substance tricyclazole in rice. The RMS 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 26 April 2018. The RMS proposed to establish maximum residue level (MRL) for rice imported from Brazil at the level of 0.09 mg/kg.

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified data gaps, which were requested from the RMS. On 7 October 2022, the RMS submitted a revised evaluation report, which replaced the previously submitted evaluation report.

Based on the conclusions derived by EFSA in the framework of Regulation (EC) No 1107/2009, the data evaluated under previous MRL assessment and the additional data provided by the RMS in the framework of this application, the following conclusions are derived.

The metabolism of tricyclazole following foliar application was investigated in rice belonging to the groups of cereals. The compounds identified in rice grain, hulls and straw were parent tricyclazole and its alcohol metabolite tricyclazole‐OH. During the peer review, it was postulated that the fused 3‐ring structure of tricyclazole is likely impending the release of triazole derivative metabolites (TDMs) and that with the available data, it cannot be excluded that tricyclazole is adding to the pool of compounds able to produce TDMs.

Studies investigating the effect of processing on the nature of tricyclazole (hydrolysis studies) demonstrated that tricyclazole is stable. As the proposed use of tricyclazole is on imported crops, investigations of residues in rotational crops are not required.

EFSA concluded that for the crops assessed in this application, metabolism of tricyclazole in primary crops, and the possible degradation in processed products has been sufficiently addressed.

Based on the metabolic pattern identified in the metabolism studies, hydrolysis studies, the toxicological significance of metabolites, the residue definitions for plant products were proposed as ‘tricyclazole’ for enforcement and is provisionally proposed as ‘tricyclazole and tricyclazole‐OH’ for risk assessment. These residue definitions are applicable to primary crops and processed products. However, the residue definition for risk assessment was not finalised during the peer review because the genotoxicity and carcinogenicity potential were still to be defined for parent.

A sufficiently validated analytical methods based on gas chromatography with gas chromatography mass spectrometry (GC‐MS) methods are available to quantify residues in rice according to the enforcement residue definition at the limit of quantification (LOQ) of 0.02 mg/kg. A lower LOQ of 0.01 mg/kg is achievable with a validated liquid chromatography with tandem mass spectrometry (LC–MS/MS) method in the crops assessed in this application; however, it is to be noted that the peer review identified a data gap for its extraction efficiency.

The available residue trials are sufficient to derive an MRL proposal of 0.09 mg/kg for rice.

Specific studies investigating the magnitude of tricyclazole residues in processed commodities are in principle not required, as the total theoretical maximum daily intake (TMDI) is below the trigger value of 10% of the acceptable daily intake (ADI); however, three new processing trials were provided and considered.

Processing factors (PF) for the crops under assessment were derived from processing studies provided and are recommended to be included in Annex VI of Regulation (EC) No 396/2005.

When considering the existing residue definition for risk assessment, PFs are calculated as follows:

– Paddy rice/husks: PF: 4.35 – Paddy rice/brown rice: PF: 0.09

– Paddy rice/brown rice by‐products: PF:1.52 – Paddy rice/brown rice bran: PF: 0.39

– Paddy rice/white rice: PF: 0.05 – Paddy rice/white rice by‐products: PF: 0.22

– Paddy rice/parboiled rice: PF: 0.81 – Brown rice/brown rice bran: PF: 3.28

When considering the existing residue definition for enforcement, PFs are calculated as follows:

– Paddy rice/husks: PF: 4.48 – Paddy rice/brown rice: PF: 0.09

– Paddy rice/brown rice by‐products: PF: 1.51 – Paddy rice/brown rice bran: PF: 0.38

– Paddy rice/white rice: PF: 0.05 – Paddy rice/white rice by‐products: PF: 0.21

– Paddy rice/parboiled rice: PF: 0.82 – Brown rice/brown rice bran: PF: 3.22

An investigation for the occurrence of tricyclazole residues in rotational crops was not triggered in the context of this import tolerance application.

As by‐products from (husked) rice, rice bran may be used for feed purposes, a potential carry‐over into food of animal origin was assessed. The calculated livestock dietary burden did not exceed the trigger value of 0.1 mg/kg dry matter (DM) for all relevant animal species. The relative contribution of tricyclazole residues from rice hulls to the total livestock exposure was insignificant, and therefore, animal commodities were not further considered in this application.

The toxicological profile of tricyclazole was assessed in the framework of the EU pesticides peer review under Regulation (EC) No 1107/2009 and based on new data provided in the context of this application. The data were sufficient to derive an ADI of 0.05 mg/kg body weight (bw) per day and an acute reference dose (ARfD) of 0.05 mg/kg bw. The OH‐metabolite included in the residue definition was considered to be of similar toxicity as the parent active substance.

The consumer risk assessment was performed with revision 3.1 of the EFSA Pesticide Residues Intake Model (PRIMo). The calculations were based on the supervised trials median residue (STMR) value derived from supervised field trials. The acute short‐term consumer exposure did not exceed the ARfD for rice assessed in this application which represented 0.8% of ARfD.

The long‐term exposure assessment was performed, considering the STMR value derived from the residue trials submitted in support of this MRL application for rice. Other uses on tricyclazole are not authorised in Europe. For rice based on the import tolerance assessed in this application, 0.1% of the ADI (GEMS/Food G06 diet) was calculated.

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal for rice. EFSA concluded that the proposed use of tricyclazole on rice will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

EFSA emphasises that the above assessment does not yet take into consideration TDMs. As 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 in the context of the confirmatory data requested for triazole compounds in the framework of Regulation (EC) No 1107/2009, which have been evaluated and a general methodology on the risk assessment of triazole compounds and their TDMs is available.

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

Full details of all end points and the consumer risk assessment can be found in Appendices Appendix B – List of end points, Appendix C – Pesticide Residue Intake Model (PRIMo)–D.1

Code (a)	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Tricyclazole
0500060	Rice	0.01*	0.09	The submitted data are sufficient to derive an import tolerance (Brazilian GAP). Risk for consumers unlikely.

MRL: maximum residue level; NEU: northern Europe; SEU: southern Europe; GAP: Good Agricultural Practice.

^*Indicates that the MRL is set at the limit of analytical determination (LOD).

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

Assessment

The European Food Safety Authority (EFSA) received an application to set an import tolerance for the active substance tricyclazole in rice. The detailed description of the intended use of tricyclazole authorised in Brazil on rice, which is the basis for the current MRL application, is reported in Appendix A.

Tricyclazole is the ISO common name for 5‐methyl‐1,2,4‐triazolo[3,4‐b]benzothiazole (IUPAC). The chemical structures of the active substance and its main metabolites are reported in Appendix E.

Tricyclazole was evaluated in the framework of Regulation (EC) No 1107/20092 with Italy designated as rapporteur Member State (RMS) for the representative use as hydraulic spraying fungicide treatment on rice. The draft assessment report (DAR) prepared by the RMS has been peer reviewed by EFSA (EFSA, 2015). Tricyclazole was not approved.3

The EU MRLs for tricyclazole are established in Annex IIIA of Regulation (EC) No 396/20054. The review of existing MRLs according to Article 12 of Regulation (EC) No 396/2005 (MRL review) was deemed unnecessary. EFSA prepared a statement explaining the reasons why in a reason opinion (EFSA, 2017). EFSA has issued one reasoned opinion on the setting of an import tolerance for tricyclazole in rice (EFSA, 2013). All MRLs for tricyclazole are currently set at the limit of determination (LOD).

In accordance with Article 6 of Regulation (EC) No 396/2005, Corteva Agriscience submitted an application to the competent national authority in Italy (rapporteur Member State, RMS) to set an import tolerance for the active substance tricyclazole in rice. The RMS 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 EFSA on 26 April 2018. The RMS proposed to establish maximum residue level (MRL) for rice imported from Brazil at the level of 0.09 mg/kg.

EFSA assessed the application and the evaluation report as required by Article 10 of the MRL regulation. EFSA identified data gaps, which were requested from the RMS. On 7 October 2022, the RMS submitted a revised evaluation report (Italy, 2018), which replaced the previously submitted evaluation report.

EFSA based its assessment on the evaluation report submitted by the RMS (Italy, 2018), the draft assessment report (DAR) and its addendum (Italy, 2014a,b) prepared under Regulation (EC) 1107/2009, the Commission review report on tricyclazole (European Commission, 2016), the conclusion on the peer review of the pesticide risk assessment of the active substance tricyclazole (EFSA, 2015), as well as the conclusions from a previous EFSA opinion on tricyclazole (EFSA, 2013).

For this application, the data requirements established in Regulation (EU) No 283/20135 and the guidance documents applicable at the date of submission of the application to the RMS are applicable (European Commission, 2000, 2010a,b, 2017; OECD, 2007a,b,c,d,e,f,g,h, 2008a,b, 2009a,b, 2011, 2013, 2016, 2018).

It is noted that tricyclazole is currently not approved for use in the EU ³ . The applicant recently submitted a new dossier for the approval of tricyclazole under Regulation (EC) No 1107/2009; thus, the conclusions derived in this reasoned opinion might be reconsidered taking into account the additional information provided for the active substance in a new dossier.

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 546/20116.

A selected list of end points of the studies assessed by EFSA in the framework of this MRL application including the end points of relevant studies assessed previously is presented in Appendix B.

The evaluation report submitted by the RMS (Italy, 2018) and the exposure calculations using the EFSA Pesticide Residues Intake Model (PRIMo) are considered as supporting documents to this reasoned opinion and, thus, are made publicly available as background documents to this reasoned opinion.

1. Mammalian toxicology

Tricyclazole and its alcohol metabolite (tricyclazole‐OH)

EFSA assessed the toxicological profile of tricyclazole during the EU pesticide peer review process. During the peer review process, the available long‐term toxicity and carcinogenicity study in rats available at that time was not considered acceptable and the genotoxic and carcinogenic potential of tricyclazole were considered inconclusive. This led to an inconclusive risk assessment since the setting of reference values was not considered appropriate (EFSA, 2015).

Under the current MRL assessment, the applicant has provided additional data to address data gaps identified during the peer review process as well as data to address the endocrine disruption potential according to the ECHA/EFSA guidance on endocrine disruptors (2018). Additional data7 critical for the risk assessment (genotoxicity and carcinogenicity) and cut‐off criteria (endocrine disruption) have been discussed with Member States experts during the TC 193 (EFSA, 2018b) and TC 89 (EFSA, 2022).

The experts agreed that tricyclazole is considered unlikely to be genotoxic and that no carcinogenic potential has been identified in the new acceptable rat and existing mice long‐term toxicity and carcinogenicity studies.

The agreed acceptable daily intake (ADI) is 0.05 mg/kg body weight (bw) per day, based on the relevant developmental no observed adverse effect level (NOAEL) of 5 mg/kg bw per day in the developmental rat toxicity study based on embryo/fetal toxicity at 20 mg/kg bw per day. An uncertainty factor (UF) of 100 is applied. The NOAEL of 5.9 mg/kg bw per day found in the new and acceptable 2‐year rat study supported the ADI value.

The agreed acute reference dose (ARfD) is 0.05 mg/kg based on the relevant developmental NOAEL of 5 mg/kg bw per day in the developmental rat toxicity study based on embryo/foetal toxicity at 20 mg/kg bw per day. An UF of 100 is applied.

As a regards classification and labelling tricyclazole has not harmonised classification and labelling for carcinogenicity, germ cell mutagenicity or reproductive toxicity (CMR) endpoints.8 The RMS proposed to keep the existing harmonised classification and labelling as regards CMR endpoints. Classification and labelling of tricyclazole was not further discussed under this MRL opinion.9

As regards endocrine disruption criteria for human health, the experts considered the data set for the thyroidal (T)‐modality complete. Overall, no T‐mediated adverse effects were observed in a sufficiently investigated data set. The scenario 1a of the ECHA/EFSA guidance is applicable. The experts concluded that tricyclazole does not meet the ED criteria for the T‐modality in humans according to point 3.6.5 of Annex II of Regulation 1107/2009. The data set for the estrogenic, androgenic and steroidogenic (EAS)‐modalities was considered complete by considering additional data submitted by the applicant under the current MRL opinion. No evidence of a pattern of EAS‐mediated adversity was observed in the data set. The scenario 1a is applicable. The experts concluded that tricyclazole does not meet the endocrine disruption (ED) criteria for the EAS‐modalities in humans according to point 3.6.5 of Annex II of Regulation 1107/2009.

Under the current MRL opinion, further studies to fulfil data requirements were provided including a comparative in vitro metabolism study using liver microsomes. The comparative in vitro metabolism study using liver microsomes from F344/DuCrl Rats, Beagle Dogs and Human indicated no significant differences between animal laboratory species and human liver microsomes. EFSA noted that the study does not follow the recent recommendations of the EFSA Panel on Plant Protection Products and their Residues (PPR) Opinion on comparative in vitro metabolism studies (EFSA PPR, 2021).

In addition, a comparative in vitro metabolism study with metabolite tricyclazole‐OH and a combined repeated dose oral toxicity study with the reproduction/developmental toxicity screening test with tricyclazole and tricyclazole‐OH in rats were provided. The studies confirmed the conclusions reached at the TC 193 (EFSA, 2018b) where the experts agreed that the metabolite can be considered as covered by the parent tricyclazole. According to the RMS, the overall evidence indicates that metabolite tricyclazole‐OH has a similar toxicity profile and is equally or less toxic than tricyclazole parent compound. EFSA agrees with the RMS. In addition, experimental genotoxicity studies indicated that that the metabolite tricyclazole‐OH is unlikely to be genotoxic.

2. Residues in plants

2.1. Nature of residues and methods of analysis in plants

2.1.1. Nature of residues in primary crops

The plant metabolism of tricyclazole in rice was evaluated during a previous import tolerance application and during the EU pesticide peer review (EFSA, 2013, 2015).

Tricyclazole was labelled on the triazole ring in one study and in another study on the phenyl‐UL‐¹⁴C‐tricyclazole in the benzene ring of the molecule which was considered only as supporting information because it is not fully according to the required standards for a metabolism study (EFSA, 2015). The main compounds identified in rice grain, hulls and straw were tricyclazole and its alcohol metabolite tricyclazole‐OH (EFSA, 2015).

2.1.2. Nature of residues in rotational crops

Investigations of residues in rotational crops are not required for imported crops. Therefore, for the proposed use assessed in this application, no further information is required.

2.1.3. Nature of residues in processed commodities

The effect of processing on the nature of tricyclazole was investigated in a standard hydrolysis study. Tricyclazole was stable under conditions representative for pasteurisation, boiling and sterilisation (EFSA, 2013). As for tricyclazole‐OH, no data was available; however, if processing data will be triggered according to current guidance (theoretical maximum daily intake (TMDI) reaching 10% ADI) a study on the nature of residues in processed commodities has also to be submitted for the tricyclazole‐OH metabolite (EFSA, 2015). Nevertheless, in this application, the effect of household processing on aqueous samples containing the alcohol metabolite of tricyclazole has been investigated (Italy, 2018). The results demonstrated tricyclazole‐OH was stable to hydrolysis in samples processed to simulate pasteurisation, baking, brewing, boiling and sterilisation.

2.1.4. Analytical methods for enforcement purposes in plant commodities

Analytical methods for the determination of tricyclazole and tricyclazole alcohol metabolite10 in rice were assessed in the draft assessment report (DAR) drafted for the peer review under Directive 91/414/EEC (France, 2007). A gas chromatography with mass spectrometry (GC‐MS) method was considered sufficiently validated for the determination of tricyclazole and its alcohol metabolite at an individual limit of analytical quantification (LOQ) of 0.02 mg/kg in rice grain and at the individual LOQ of 0.05 mg/kg in rice green plant and straw. An independent laboratory validation (ILV) was also performed and confirmed the applicability of the analytical method for analysing both compounds in rice grain at the individual LOQ of 0.02 mg/kg (EFSA, 2013).

The applicability of the multiresidue method DFG S 19 was also tested for the determination of tricyclazole in rice grain. It was concluded that the multiresidue method using GC‐MS is fully validated for the determination of tricyclazole in rice grain at a LOQ of 0.02 mg/kg (EFSA, 2013).

During the previous assessment, the RMS Italy informed that Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) multiresidue method (using high‐performance liquid chromatography with tandem mass spectrometry (HPLC‐MS/MS)) has been sufficiently validated for the determination of residues of tricyclazole and its alcohol metabolite in agricultural commodities representative of the four crop groupings and five animal matrices. The method was validated at the individual LOQ of 0.01 mg/kg. However, detailed validation data have not been provided (EFSA, 2013).

During the peer review, it was concluded that a suitable liquid chromatography with tandem mass spectrometry (LC–MS/MS) method with a validated LOQ of 0.01 mg/kg for tricyclazole and for its alcohol metabolite was available. However, it was noted that this method is open for extraction efficiency (EFSA, 2015).

New data were not provided in the context of this application. However, the RMS resubmitted the nature of residue studies assessed during the peer review where extraction efficiency was demonstrated. Noting the similarity of the extraction procedure in the metabolism studies and the LC–MS/MS method proposed for method of official controls, the RMS suggested to apply read‐across to bridge the data gap (Italy, 2018).

EFSA concludes that adequate analytical enforcement methods are available to control tricyclazole residues in rice at the LOQ of 0.01 mg/kg. EFSA, however, recommends providing data on extraction efficiency specifically for the LC‐MS/MS method proposed for official controls noting new guidance on extraction efficiency (European Commission, 2017).

2.1.5. Storage stability of residues in plants

The storage stability of tricyclazole and of its tricyclazole‐OH metabolite in plants stored under frozen conditions was investigated in the framework of the EU pesticides peer review (EFSA, 2015). It was demonstrated that in the crop assessed, residues of both compounds were stable for at least 12 months when stored at −18°C.

2.1.6. Proposed residue definitions

During the previous EFSA assessments, no reference values could be set for tricyclazole and the toxicological profile of tricyclazole‐OH was not addressed. Therefore, the residue definition for risk assessment could not be finalised (EFSA, 2015).

The new toxicological information provided in response to the toxicological data and following its assessment by EFSA (see Section 1), EFSA derived toxicological reference values for tricyclazole and concluded that metabolite tricyclazole‐OH has a similar toxicity profile and is equally or less toxic than the parent compound.

Based on the metabolic pattern identified in metabolism studies, the results of hydrolysis studies, the new toxicological data on tricyclazole and its alcohol metabolite tricyclazole‐OH and the capabilities of enforcement analytical methods, the following residue definitions can now be proposed:

• residue definition for enforcement: tricyclazole

• residue definition for risk assessment: sum of tricyclazole and tricyclazole‐OH, expressed as tricyclazole11 The residue definitions are appropriate for the crop under assessment and are also applicable to processed products.

The residue definition for enforcement set in Regulation (EC) No 396/2005 is identical with the above‐mentioned residue definition.

2.2. Magnitude of residues in plants

2.2.1. Magnitude of residues in primary crops

Rice (husked rice)

Authorised Brazilian good agricultural practices (GAP) on rice: outdoor foliar application 2 × 225 g a.s./ha, interval 15 or 20 days, PHI 30 days (Appendix A).

In support of the authorised critical GAP (cGAP) of tricyclazole in Brazil, the applicant submitted 16 residue trials on rice including eight decline trials (up to 39–42 days) performed in Brazil during the 2002–2003 growing season (one trial), during the 2006–2007 growing season (two trials), during the 2010–2011 growing season (eight trials) and during the 2014–2015 growing season (five trials) (Italy, 2018).

The residue trials on rice performed during the 2002–2003 and 2006–20/07 growing seasons were analysed for parent tricyclazole only. The residue trial during the 2002–2003 season was not considered because the second treatment was performed at grain filling, it was not driving the MRL and was not analysed according to the residue definition for risk assessment. The trials performed during 2006–2007 were not GAP compliant because the first application was performed as a seed treatment.

The residue trials performed during the 2010–2011 and 2014–2015 growing seasons were analysed simultaneously according to the residue definitions for monitoring and risk assessment and sufficient in number to derive an MRL proposal and corresponding values for risk assessment.

The eight trials performed during 2010–20/11 growing season included four duplicates, and therefore, only four independent trials were considered in support of the GAP. Four of the five residue trials performed during the 2014/15 growing season were overdosed. However, in four of these trials, residues were found to remain below the combined LOQ of 0.02 mg/kg (0.01 mg/kg for each analyte (tricyclazole and tricyclazole‐OH)). In the trial where residues were above the LOQ, the result could be scaled according to the proportionality principle (EFSA, 2018c; Italy, 2018).

Overall, sufficient independent residue trials (nine) compliant with the cGAP and analysed simultaneously according to the residue definitions for enforcement and risk assessment (tricyclazole and tricyclazole‐OH) are available. The samples of these residue trials were stored under conditions for which integrity of the samples is demonstrated. According to the assessment of the RMS, the methods used were sufficiently validated and fit for purpose (Italy, 2018).

The provided residue data are sufficient to derive an MRL proposal of 0.09 mg/kg for rice in support of the authorised Brazilian outdoor GAP of tricyclazole on rice. The tolerance established in the Brazil12 for tricyclazole in rice is 3 mg/kg.

2.2.2. Magnitude of residues in rotational crops

Investigations of residues in rotational crops are not required for imported crops. Therefore, for the proposed use assessed in this application, no further information is required.

2.2.3. Magnitude of residues in processed commodities

During the EU pesticide peer review, an available processing study investigating the magnitude of tricyclazole residues and tricyclazole‐OH in processed rice commodities was considered not fully relied upon by the RMS and a mass balance study was requested (EFSA, 2015).

This processing study was re‐submitted in the context of the present assessment and was assessed by the RMS (Italy, 2018). However, noting that residue levels in paddy rice and husked rice were close of below the individual LOQ of 0.02 mg/kg for tricyclazole and of OH‐tricyclazole, the study did not allow to derive processing factors for any processed commodities of rice. Furthermore, no data were available for rice bran, which may be used as a feed item in Europe. Therefore, this study was not deemed relevant by EFSA for the present assessment.

In the framework of the present application, three new processing trials were provided which include (husked) rice and bran and their processed products (Italy, 2018). In these trials, the magnitude of tricyclazole and its metabolite OH‐tricyclazole was quantified above the individual LOQ for both compounds. A concentration of residues was observed in brown rice by‐products and husks, whereby reduction of residues was reported for (husked) brown rice, white rice, white rice by‐products and parboiled rice. Detailed summary of the processing factors derived from these trials is available in Appendix B.2.2.3.

Noting that in this assessment an import tolerance for (husked) rice is requested, (husked) rice is considered as the imported product. EFSA, derived a median processing factor, however, used the highest processing factor of 7 for rice bran based on the reported residues according to the residue definitions for monitoring and risk assessment for the animal dietary burden calculation. It is to be noted that this calculation indicated a concentration of residues in rice bran and to a lesser content in white rice by‐products.

2.2.4. Proposed MRLs

The available data are considered sufficient to derive an MRL proposal as well as risk assessment values for the commodity under evaluation (see Appendix B.2.2.1). In Section 4, EFSA assessed whether residues in rice and its by‐products resulting from the intended uses or the uses authorised in Brazil is likely to pose a consumer health risk.

3. Residues in livestock

Rice is usually not fed to livestock in Europe; however, its by‐product rice bran represents a feed item according to the OECD guidance (OECD, 2013).

Therefore, considering the case that rice bran derived from imported hushed rice might enter the feed chain, it was necessary to estimate whether the residues in rice bran from the import tolerance under evaluation would have an impact on the residues expected in food of animal origin. EFSA considered residues in brown rice and derived a highest worse case processing factor for rice bran.

EFSA calculated the expected livestock dietary burden calculations for different groups of livestock according to OECD guidance (OECD, 2013). The calculated dietary burden did not exceed the trigger values for any livestock group and further consideration on animal commodities were not required within the context of this import tolerance application.

The results of the livestock dietary burden calculation are presented in Section B.2.

4. Consumer risk assessment

EFSA performed a dietary risk assessment using revision 3.1 of the EFSA PRIMo (EFSA, 2018a, 2019). This exposure assessment model contains food consumption data for different subgroups of the EU population and allows the acute and chronic exposure assessment to be performed in accordance with the internationally agreed methodology for pesticide residues (FAO, 2016).

Based on the new toxicological data provided in the context of this assessment, EFSA could derive an ADI of 0.05 mg/kg bw per day and an ARfD of 0.05 mg/kg bw for tricyclazole (see Section 1).

The new toxicological data also allowed to conclude that the metabolite tricyclazole‐OH included in the risk assessment residue definition was of similar toxicity to that of the parent compound (see Section 1).

Short‐term (acute) dietary risk assessment

The short‐term exposure assessment was performed only for the commodity assessed in this application in accordance with the internationally agreed methodology (FAO, 2016). The calculations were based on the supervised trials median residue (STMR) value derived from supervised field trials (see Appendix C).

The short‐term consumer exposure for rice was calculated and represents 0.8% of ARfD, thus not exceeding the ARfD (see Appendix B.5).

Long‐term (chronic) dietary risk assessment

The long‐term exposure assessment was performed, considering the STMR value derived from the residue trials submitted in support of this MRL import tolerance application for rice; for the remaining commodities covered by the MRL legislation, no other uses are authorised and the existing EU MRLs13 are lowered the respective LOQs. Currently, for tricyclazole, no CXLs are set.

The complete list of input values is presented in Appendix D.2.

The contribution of rice based on the import tolerance assessed in this application to the overall long‐term exposure was 0.1% of the ADI (GEMS/Food G06 diet) (see Appendix D.2)

EFSA concluded that the long‐term intake of residues of tricyclazole resulting from the authorised Brazilian use reported in Appendix A on rice is unlikely to present a risk to consumer health.

For further details on the exposure calculations, a screenshot of the Report sheet of the PRIMo is presented in Appendix C.

5. Conclusion and recommendations

The data submitted in support of this MRL application were found to be sufficient to derive an MRL proposal for rice.

EFSA concluded that the proposed use of tricyclazole on rice will not result in a consumer exposure exceeding the toxicological reference values and therefore is unlikely to pose a risk to consumers' health.

The MRL recommendations are summarised in Appendix B.5.

Abbreviations

a.s.

active substance

ADI

acceptable daily intake

AR

applied radioactivity

ARfD

acute reference dose

BBCH

growth stages of mono‐ and dicotyledonous plants

bw

body weight

CAC

Codex Alimentarius Commission

CF

conversion factor for enforcement to risk assessment residue definition

cGAP

critical GAP

CXL

Codex maximum residue limit

DAR

draft assessment report

DAT

days after treatment

DM

dry matter

EC

emulsifiable concentrate

ECD

electron capture detector

EDI

estimated daily intake

EAS

oestrogen, androgen and steroidogenesis

ECHA

European Chemicals Agency

ED

endocrine disruption

EMS

evaluating Member State

eq

residue expressed as a.s. equivalent

EURL

EU Reference Laboratory (former Community Reference Laboratory (CRL))

FAO

Food and Agriculture Organisation of the United Nations

GAP

Good Agricultural Practice

GC

gas chromatography

GC‐ECD

gas chromatography with electron capture detector

GC‐MS

gas chromatography with mass spectrometry

GC‐MS/MS

gas chromatography with tandem mass spectrometry

HPLC

high‐performance liquid chromatography

HPLC‐MS

high‐performance liquid chromatography with mass spectrometry

HPLC‐MS/MS

high‐performance liquid chromatography with tandem mass spectrometry

IEDI

international estimated daily intake

IESTI

international estimated short‐term intake

ILV

independent laboratory validation

IPCS

International Programme of Chemical Safety

ISO

International Organisation for Standardisation

IUPAC

International Union of Pure and Applied Chemistry

LC

liquid chromatography

LOD

limit of detection

LOQ

limit of quantification

MRL

maximum residue level

MS

Member States

MS

mass spectrometry detector

MS/MS

tandem mass spectrometry detector

NEU

northern Europe

NOAEL

no observed adverse effect level

OECD

Organisation for Economic Co‐operation and Development

PBI

plant back interval

PF

processing factor

PHI

preharvest interval

PPR

Panel on Plant Protection Products and their Residues

PRIMo

(EFSA) Pesticide Residues Intake Model

QuEChERS

Quick, Easy, Cheap, Effective, Rugged, and Safe (analytical method)

RA

risk assessment

RAC

raw agricultural commodity

RD

residue definition

RMS

rapporteur Member State

SANCO

Directorate‐General for Health and Consumers

SEU

southern Europe

STMR

supervised trials median residue

TMDI

theoretical maximum daily intake

WHO

World Health Organization

WP

wettable powder

Appendix A – Summary of intended GAP triggering the amendment of existing EU MRLs

Crop and/or situation	NEU, SEU, MS or country	F, G or I(a)	Pests or Group of pests controlled	Preparation		Application				Application rate per treatment				PHI (days)(d)	Remarks
				Type(b)	Conc. a.s. (g/kg)	Method kind	Range of growth stages & season(c)	Number min–max	Interval between application (days) min–max	g a.s./hL min–max	Water (L/ha) min–max	Rate min–max	Unit
Rice	Brazil	F	Rice Blast PYRIOR	WP	750 g/kg	foliar spray		2	15–20		200–400 L/ha (ground)/30–50 L/ha (aerial)	150–225 g/ha	g a.i./ha	30	Application timings (Foliar application): Leaf blast: – 1st application: in the phase of complete tillering. – 2nd application minimum of 20 days after the first application in areas where disease pressure is high. Neck and panicle blast: – 1st application: at the end of the boot stage, or when 5% of the panicles are emerged. – 2nd application: minimum of 15 days after the first application, or when 75% of the panicles are emerged See explanatory note below.

MRL: maximum residue level; GAP: Good Agricultural Practice; NEU: northern European Union; SEU: southern European Union; MS: Member State; a.s.: active substance; WP: Wettable powder. Explanatory note: if the first application is performed at the end of the boot stage or when 5% of panicles are emerged, the second application is performed 15 days later; if the first application is performed in the phase of complete tillering, the second application is done a minimum of 20 days afterwards.

^(a)Outdoor or field use (F), greenhouse application (G) or indoor application (I).

^(b)CropLife International Technical Monograph no 2, 7th Edition. Revised March 2017. Catalogue of pesticide formulation types and international coding system.

^(c)Growth stage range from first to last treatment (BBCH Monograph, Growth Stages of Plants, 1997, Blackwell, ISBN 3–8,263–3,152‐4), including, where relevant, information on season at time of application.

^(d)PHI – minimum preharvest interval.

Appendix B – List of end points

B.1 Impact on human and animal health

Genotoxicity (Regulation (EU) No 283/2013, Annex IIA, point 5.4) | Tricyclazole

Long term toxicity and carcinogenicity (Regulation (EU) No 283/2013, Annex IIA, point 5.5) |Tricyclazole

Other toxicological studies (Regulation (EU) No 283/2013, Annex IIA, point 5.8)

Summary (Regulation (EU) No 283/2013, Annex IIA, point 5.10) Value Study Uncertainty factor

Value

Study

Uncertainty factor

Classification and proposed labelling with regard to toxicological data (Annex IIA, point 10)

B.2 Residues in plants

B.2.1 Nature of residues and analytical methods for enforcement purposes in plant commodities

B.2.1.1 Metabolism studies, analytical methods and residue definitions in plants

Primary crops (available studies)	Crop groups	Crop(s)	Application(s)	Sampling (DAT)	Comment/Source
	Cereals/grass	Rice	Foliar: 2 × (0.508 kg a.s./ha; 0.986 a.s./ha); 35 days interval (BBCH 23 and BBCH 50–52)	Immature crop: 0, 14, 30 days after 1st appl. and 0, 14 DAT following the last treatment; Mature crop (rice and straw): 82 days after last treatment	Radiolabelled tricyclazole: triazole‐UL‐14C‐tricyclazole (2‐position of the triazole ring) Plot I (Italy, 2014a,b); (EFSA, 2015)
		Rice	Foliar: 1 × 0.933 g a.s./ha at BBCH 52	Immature crop: 0, 14 DAT following the last treatment; Mature crop (rice and straw): 82 days after last treatment	Radiolabelled tricyclazole: triazole‐UL‐14C‐tricyclazole (2‐position of the triazole ring) Plot II (Italy, 2014a,b); (EFSA, 2015)
	Cereals/grass	Rice	Foliar: 2 × 0.28 kg a.s./ha; 30 days interval	Mature crop (rice and hulls): 79 days after last treatment	Radiolabelled tricyclazole: phenyl‐UL‐14C‐tricyclazole in the benzene ring; study from 1976 considered as supporting evidence only (Italy, 2014a,b); (EFSA, 2015)
Rotational crops (available studies)	Crop groups	Crop(s)	Application(s)	PBI (DAT)	Comment/Source
	Not relevant for import tolerance applications.

Processed commodities (hydrolysis study)	Conditions	Stable?	Comment/Source
	Pasteurisation (20 min, 90°C, pH 4)	Yes	Radiolabelled tricyclazole: triazole‐UL‐14C‐tricyclazole (2‐position of the triazole ring) (EFSA 2013); Radiolabelled tricyclazole: triazole‐UL‐14C‐tricyclazole‐OH (2‐position of the triazole ring) (Italy, 2018)
	Baking, brewing and boiling (60 min, 100°C, pH 5)	Yes
	Sterilisation (20 min, 120°C, pH 6)	Yes

B.2.1.2 Stability of residues in plants

Plant products (available studies)	Category	Commodity	T (°C)	Stability period		Compounds covered	Comment/Source
				Value	Unit
	High water content	Rice, whole plant	−18	365	days	tricyclazole and tricyclazole‐OH metabolite	The storage stability of tricyclazole and its tricyclazole‐OH metabolite has been determined in rice whole plant, grain and straw. The results of the study indicate that tricyclazole and tricyclazole‐OH metabolite in rice whole plant, grain and straw matrices from field studies can be stored frozen for at least 363 days without significant decline of residues (EFSA, 2015).
	Dry/High starch	Rice, grain	−18	365	days
	Others	Rice, straw	−18	365	days

B.2.2 Magnitude of residues in plants

B.2.2.1 Summary of residues data from the supervised residue trials

Commodity	Region/(a)	Residue levels observed in the supervised residue trials (mg/kg)	Comments/Source	Calculated MRL (mg/kg)	HR (b) (mg/kg)	STMR (c) (mg/kg)	CF (d)
Rice	Import (BR)	Grain without husk Mo: 0.04(e); 0.02(f); 0.02(f); 0.02(g) Triazole‐OH metabolite: < 0.01; < 0.01; < 0.01; < 0.01 RA: 0.05(e); 0.03; 0.03; 0.03(g)	Residue trials on rice compliant with GAP performed in 2010–2011 in Brazil with last treatments at BBCH 69–87. Analysed for parent tricyclazole and its alcohol metabolite according to the provisional residue definition for risk assessment (Italy, 2018).	–			–
		Grain without husk Mo: 0.0284; 0.06(h); < 0.01; < 0.01; < 0.01 Triazole‐OH metabolite: < 0.01; 0.01(h); < 0.01; < 0.01; < 0.01 RA: 0.0384; 0.07(h); < 0.02; < 0.02; < 0.02	Residue trial on rice performed in 2014/15 in Brazil. Analysed for parent tricyclazole and its alcohol metabolite according to the provisional residue definition for risk assessment with last treatments at BBCH 61–63. Trials exceeded in the 1st application the upper 25% tolerance of 281 g a.s./ha (up to 305.25 g a.s./ha). Since the 2nd application was considered more significant for the final residues, scaling was performed based on the 2nd application rate where an exceedance of the application rate was applicable in case that residues were above the LOQ (Italy, 2018).	–			–
		Grain without husk Mo: 3 × < 0.01; 3 × 0.02; 0.0284; 0.04; 0.06 RA: 3 × < 0.02; 3 × 0.03; 0.0384; 0.05; 0.07	Combined data set of residue trials on rice grain presented in the rows above without husks analysed simultaneously according to the residue definitions for monitoring and risk assessment	0.09	Mo: 0.06 RA: 0.07	Mo: 0.02 RA: 0.03	1

MRL: maximum residue level; GAP: Good Agricultural Practice; Mo: monitoring; RA: risk assessment; BR: Brazil.

^(a)NEU: Outdoor trials conducted in northern Europe, SEU: Outdoor trials conducted in southern Europe, EU: indoor EU trials or Country code: if non‐EU trials.

^(b)Highest residue. The highest residue for risk assessment refers to the whole commodity and not to the edible portion.

^(c)Supervised trials median residue. The median residue for risk assessment refers to the whole commodity and not to the edible portion.

^(d)Conversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment. A CF of 1 is derived because the metabolite was below or in one case at the LOQ of 0.01 mg/kg.

^(e)Higher value at a longer PHI of 42 days.

^(f)Higher value in the residue trial with two applications of 206 and 216.7 g a.s./ha.

^(g)Higher value at a longer PHI of 35 days.

^(h)Residue data scaled by a factor of 0.78 (225/286.88 = 0.7843) (Italy, 2018).

B.2.2.2 Residues in rotational crops

B.2.2.3 Processing factors

New processing studies were submitted in the framework of the present MRL application.

Processed commodity	Number of valid studies (a)	Processing Factor (PF)				CF (b)	Comment/Source
		Individual values based on RDMo	Median PF	Individual values based on RDRA	Median PF
Paddy rice	4	1; 1; 1; 1	1	1; 1; 1; 1	1	1	Residues in husked rice and polished rice (except 1st trial where 0.03 mg/kg for tricyclazole) were all below the individual LOQ of 0.02 mg/kg; residues in by‐products were all below the individual LOQ of 0.05 mg/kg (Italy, 2014a,b, 2018).
Husked rice	4	< 1; < 0.5; < 2; < 1	< 1	< 1.33; < 0.67; < 2; < 0.57	< 1	1
Husk	4	5; 5; 5.5, 6	5.3	5; 5.14, 5.33; 5.83;	5.2	1
Polished rice	4	< 0.25; < 2; < 1, 1.5	< 1.3	< 0.5; < 2; < 0.57, 1.67	< 1.1	1
By‐products	4	< 2.5; < 1.25; < 5; < 2.5	< 2.5	< 3.33; < 1.67; < 5; < 1.43	< 2.5	1
Paddy rice before drying	3	1; 1; 1	1	1; 1; 1	1	1	New processing study provided for this assessment (Italy, 2018)
Paddy rice after drying	3	1.02, 1.06; 1.29	1.06	1.01, 1.05; 1.28	1.1	1
Rice, husks	3	3.48; 4.48, 5.08	4.5	3.46; 4.35, 4.95	4.4	1
Brown rice	3	0.05; 0.09; 0.21	0.09	0.06; 0.09; 0.21	0.09	1
Brown rice, by‐products	3	0.84, 1.51; 2.85	1.5	0.83, 1.52; 2.8;	1.5	1
Bran from paddy rice	3	0.26; 0.38; 0.68	0.38	0.26; 0.39; 0.68	0.39	1
White rice	3	0.03; 0.05; 0.11	0.05	0.03; 0.05; 0.11	0.05	1
White rice, by‐products	3	0.11; 0.21; 0.37	0.11	0.11; 0.22; 0.37	0.22	1
Parboiled rice	3	0.62; 0.82; 0.98	0.82	0.61; 0.81; 0.97	0.81	1
	Calculation of a PF for rice bran considering residues in brown imported rice
Brown (husked) rice	3	1; 1; 1	1	1; 1; 1	1	1	Highest PF of 7 for rice bran based of residue values for monitoring and risk assessment in brown rice vs. bran.
Bran from husk rice	3	2.81; 3.22, 7.22;	3.22	2.81; 3.28, 6.83	3.28	1

PF: processing factor. RD_Mo: Residue definition for monitoring; RD_RA: Residue definition risk assessment

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

^(b)Conversion factor to recalculate residues according to the residue definition for monitoring to the residue definition for risk assessment.

B.3 Residues in livestock

Dietary burden calculation according to OECD, 2013.

Relevant groups (subgroups)	Dietary burden expressed in				Most critical subgroup (a)	Most critical commodity (b)	Trigger exceeded (Y/N)
	mg/kg bw per day		mg/kg DM
	Median	Maximum	Median	Maximum
Cattle (all)	0.002	0.002	0.05	0.05	Dairy cattle	Rice, bran/pollard	N
Cattle (dairy only)	0.002	0.002	0.05	0.05	Dairy cattle	Rice, bran/pollard	N
Sheep (all)	0.003	0.003	0.07	0.07	Lamb	Rice, bran/pollard	N
Sheep (ewe only)	0.002	0.002	0.07	0.07	Ram/Ewe	Rice, bran/pollard	N
Swine (all)	0.001	0.001	0.02	0.02	Swine (breeding)	Rice, bran/pollard	N
Poultry (all)	0.002	0.002	0.02	0.02	Poultry broiler	Rice, bran/pollard	N
Poultry (layer only)	0.001	0.001	0.01	0.01	Poultry layer	Rice, bran/pollard	N
Fish	N/A

bw: body weight; DM: dry matter.

^(a)When one group of livestock includes several subgroups (e.g. poultry ‘all’ including broiler, layer and turkey), the result of the most critical subgroup is identified from the maximum dietary burdens expressed as ‘mg/kg bw per day’.

^(b)The most critical commodity is the major contributor identified from the maximum dietary burden expressed as ‘mg/kg bw per day’.

B.4 Consumer risk assessment

B.5 Recommended MRLs16

Code(a)	Commodity	Existing EU MRL (mg/kg)	Proposed EU MRL (mg/kg)	Comment/justification
Enforcement residue definition: Tricyclazole
0500060	Rice 16	0.01*	0.09	The submitted data are sufficient to derive an import tolerance (Brazilian GAP). Risk for consumers unlikely.

MRL: maximum residue level; NEU: northern Europe; SEU: southern Europe; GAP: Good Agricultural Practice.

^*Indicates that the MRL is set at the limit of analytical determination (LOD).

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

Appendix C – Pesticide Residue Intake Model (PRIMo)

Appendix D – Input values for the exposure calculation

D.1 Livestock dietary burden calculations

Feed item	Median dietary burden		Maximum dietary burden
	Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
Rice bran	0.21	STMR‐RACxPF(7)(a)	0.21	STMR‐RACxPF(7)(a)

STMR: supervised trials median residue; PF: processing factor

^(a)For rice bran, a worst‐case PF of 7 was considered (Appendix B.2.2.3).

D.2 Consumer risk assessment

Code	Commodity	Existing/proposed MRL	Source/type of MRL	Chronic risk assessment (1)		Acute risk assessment (1)
				Input value (mg/kg)	Comment	Input value (mg/kg)	Comment
0500060	Rice	0.09	Proposed	0.03	STMR‐RAC	0.03	STMR‐RAC

⁽¹⁾Refined calculation mode; STMR‐RAC: supervised trials median residue in raw agricultural commodity; LOQ: Limit of quantification according to Regulation (EC) No 2017/983

Appendix E – Used compound codes

Code/trivial name(a)	IUPAC name/SMILES notation/InChiKey(b)	Structural formula(c)
Tricyclazole	5‐methyl‐1,2,4‐triazolo[3,4‐b]benzothiazole DQJCHOQLCLEDLL‐UHFFFAOYSA‐N Cc1cccc2sc3nncn3c12
Tricyclazole‐OH Alcohol metabolite (metabolite X355227)	([1,2,4]triazolo[3,4‐b][1,3]benzothiazol‐5‐yl)methanol QHFZNYBHZQCEOU‐UHFFFAOYSA‐N OCc1cccc2sc3nncn3c12

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

^(a)The metabolite name in bold is the name used in the conclusion.

^(b)ACD/Name 2021.1.3 ACD/Labs 2021.1.3 (File Version N15E41, Build 123,232, 07 July 2021).

^(c)ACD/ChemSketch 2021.1.3 ACD/Labs 2021.1.3 (File Version C25H41, Build 123,835, 28 August 2021).

Suggested citation: EFSA (European Food Safety Authority) , Bellisai G, Bernasconi G, Brancato A, Carrasco Cabrera L, Castellan I, Del Aguila M, Ferreira L, Giner Santonja G, Greco L, Jarrah S, Leuschner R, Magrans JO, Miron I, Nave S, Pedersen R, Reich H, Robinson T, Ruocco S, Santos M, Scarlato AP, Theobald A and Verani A, 2023. Reasoned Opinion on the setting of import tolerance for tricyclazole in rice. EFSA Journal 2023;21(1):7757, 27 pp. 10.2903/j.efsa.2023.7757