Peer review of the pesticide risk assessment of the active substance buprofezin

Abstract

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Italy and co‐rapporteur Member State Austria for the pesticide active substance buprofezin. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative uses of buprofezin as an insecticide on ornamental plants in greenhouse via spray application. The reliable end points, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

SUMMARY

Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659, lays down the procedure for the renewal of the approval of active substances submitted under Article 14 of Regulation (EC) No 1107/2009. The list of those substances is established in Commission Implementing Regulation (EU) No 686/2012 as amended by Commission Implementing Regulation (EU) No 2016/183. Buprofezin is one of the active substances listed in that Regulation.

In accordance with Article 1 of Regulation (EU) No 844/2012, the rapporteur Member State (RMS), Italy, and co‐rapporteur Member State (co‐RMS), Austria, received an application from Nihon Nohyaku Co., Ltd. for the renewal of approval of the active substance buprofezin.

An initial evaluation of the dossier on buprofezin was provided by the RMS in the renewal assessment report (RAR) and subsequently, a peer review of the pesticide risk assessment on the RMS evaluation was conducted by EFSA in accordance with Article 13 of Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The following conclusions are derived.

The uses of buprofezin according to the representative uses as an insecticide on ornamental plants in permanent protected structures (high/low technology) and non‐permanent protected structures (low technology) via spray application, as proposed at EU level result in a sufficient insecticidal efficacy against the target whitefly.

The assessment of the data package revealed no issues that could not be finalised or that need to be included as critical areas of concern or issues that could not be finalised with respect to the identity, physical, chemical and technical properties of buprofezin or the formulation for representative uses and analytical methods.

Regarding mammalian toxicology, critical areas of concern or issues that could not be finalised were not identified.

In the area of residues, data gaps were identified and the consumer risk assessment could not be finalised for all representative uses unless specific risk mitigation measures are considered.

In the area of environmental fate and behaviour no issues that could not be finalised or that need to be included as critical areas of concern were identified.

Regarding the ecotoxicology, high reproductive risk for mammals was identified. Moreover, the risk assessment for aquatic organisms could not be finalised. For the uses in non‐permanent greenhouses the risk for bees and other non‐target arthropods could not be finalised.

Regarding the assessment of the endocrine disruption (ED) properties, for humans buprofezin meets the ED criteria as laid down in point 3.6.5 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605. For non‐target organisms, the assessment of the endocrine disruption potential of buprofezin according to point 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, cannot be concluded.

BACKGROUND

Commission Implementing Regulation (EU) No 844/2012, ¹ as amended by Commission Implementing Regulation (EU) No 2018/1659, ² (hereinafter referred to as ‘the Regulation’), lays down the provisions for the procedure of the renewal of the approval of active substances, submitted under Article 14 of Regulation (EC) No 1107/2009. ³ This regulates for the European Food Safety Authority (EFSA) the procedure for organising the consultation of Member States, the applicant(s) and the public on the initial evaluation provided by the rapporteur Member State (RMS) and/or co‐rapporteur Member State (co‐RMS) in the renewal assessment report (RAR), and the organisation of an expert consultation where appropriate.

In accordance with Article 13 of the Regulation, unless formally informed by the European Commission that a conclusion is not necessary, EFSA is required to adopt a conclusion on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009 within 5 months from the end of the period provided for the submission of written comments, subject to an extension of an additional 3 months where additional information is required to be submitted by the applicant(s) in accordance with Article 13(3). Furthermore, in accordance with Article 13(3a), where the information available in the dossier is not sufficient to conclude the assessment on whether the approval criteria for endocrine disruption are met, additional information can be requested to be submitted in a period of minimum 3 months, not exceeding 30 months, depending on the type of information requested.

In accordance with Article 1 of the Regulation, the RMS Italy and co‐RMS Austria received an application from Nihon Nohyaku Co., Ltd. for the renewal of approval of the active substance buprofezin. Complying with Article 8 of the Regulation, the RMS checked the completeness of the dossier and informed the applicant, the co‐RMS (Austria), the European Commission and EFSA about the admissibility.

The RMS provided its initial evaluation of the dossier on buprofezin in the RAR, which was received by EFSA on 9 September 2021 (Italy, 2021).

In accordance with Article 12 of the Regulation, EFSA distributed the RAR to the Member States and the applicant, Nihon Nohyaku Co., Ltd. for consultation and comments on 9 June 2022. EFSA also provided comments. In addition, EFSA conducted a public consultation on the RAR. EFSA collated and forwarded all comments received to the European Commission on 16 August 2022. At the same time, the collated comments were forwarded to the RMS for compilation and evaluation in the format of reporting table. In addition, the applicant was invited to respond to the comments received. The comments and the applicant's response were evaluated by the RMS in column 3.

The need for expert consultation and the necessity for additional information to be submitted by the applicant in accordance with Article 13(3) of the Regulation were considered in a telephone conference between EFSA, the RMS on 17 October 2022. On the basis of the comments received, the applicant's response to the comments and the RMS's evaluation thereof, it was concluded that additional information should be requested from the applicant, and that EFSA should conduct an expert consultation in the areas of mammalian toxicology, residues, environmental fate and behaviour, and ecotoxicology.

In addition, in accordance with the provisions of Commission Implementing Regulation (EU) No 2018/1659, following a consultation with Member States in the Pesticides Peer Review Expert meeting TC 110 (June 2023), the applicant was given the opportunity to submit, within a period of 3 months, additional information to address the approval criteria set out in point 3.6.5 and/or point 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, ⁴ and/or documentary evidence demonstrating that buprofezin may be used such that exposure is negligible, or the conditions for the application of the derogation under Article 4(7) of Regulation (EC) No 1107/2009 are met.

The outcome of the telephone conference, together with EFSA's further consideration of the comments, is reflected in the conclusions set out in column 4 of the reporting table. All points that were identified as unresolved at the end of the comment evaluation phase and which required further consideration, including those issues to be considered in an expert consultation, were compiled by EFSA in the format of an evaluation table.

The conclusions arising from the consideration by EFSA, and as appropriate by the RMS, of the points identified in the evaluation table, together with the outcome of the expert consultation and the written consultation on the assessment of additional information, where these took place, were reported in the final column of the evaluation table. The applicant did not provide a negligible exposure assessment nor an argumentation regarding Article 4(7) of Regulation (EC) No 1107/2009. Although not provided by the applicant, the RMS included a negligible non‐dietary exposure assessment in the revised RAR.

A final consultation on the conclusions arising from the peer review of the risk assessment took place with Member States via a written procedure in March 2025.

This conclusion report summarises the outcome of the peer review of the risk assessment of the active substance and the formulation for representative uses, evaluated on the basis of the representative uses of buprofezin as an insecticide on ornamental plants via spray application, as proposed by the applicant. In accordance with Article 12(2) of Regulation (EC) No 1107/2009, risk mitigation options identified in the RAR and considered during the peer review, if any, are presented in the conclusion.

A list of the relevant end points for the active substance and the formulation is provided in Appendix B. In addition, the considerations as regards the cut‐off criteria for buprofezin according to Annex II of Regulation (EC) No 1107/2009 are summarised in Appendix A.

A key supporting document to this conclusion is the peer review report (EFSA, 2025), which is a compilation of the documentation developed to evaluate and address all issues raised in the peer review, from the initial commenting phase to the conclusion. The peer review report comprises the following documents, in which all views expressed during the course of the peer review, including minority views, where applicable, can be found:

• the comments received on the RAR;

• the reporting table (17 October 2022 and 30 May 2024 ⁵ );

• the evaluation table (26 March 2025);

• the reports of the scientific consultation with Member State experts (where relevant);

• the comments received on the assessment of the additional information (where relevant);

• the comments received on the draft EFSA conclusion.

Given the importance of the RAR, including its revisions (Italy, 2024), and the peer review report, both documents are considered as background documents to this conclusion and thus are made publicly available.

It is recommended that this conclusion and its background documents would not be accepted to support any registration outside the EU for which the applicant has not demonstrated that it has regulatory access to the information on which this conclusion report is based.

THE ACTIVE SUBSTANCE AND THE FORMULATION FOR REPRESENTATIVE USES

Buprofezin is the ISO common name for (Z)‐2‐(tert‐butylimino)‐3‐isopropyl‐5‐phenyl‐1,3,5‐thiadiazinan‐4‐one (IUPAC). The formulation for representative uses for the evaluation was ‘Applaud 25 SC’, a suspension concentrate (SC) containing 250 g/L of pure buprofezin.

The information on the active substance and the formulation for representative uses, including the co‐formulants in this formulation, was considered in the overall assessment during the peer review. None of the co‐formulants with known composition is an unacceptable co‐formulant listed in Annex III of Regulation (EC) No 1107/2009, ⁶ however one co‐formulant is a currently approved active substance under Regulation (EC) 1107/2009, ⁷ and another co‐formulant is a not approved active substance under Regulation (EC) 1107/2009⁷. Details on the composition of the formulations cannot be reported in conclusions because of the provisions in Article 63(2)(d) of Regulation (EC) No 1107/2009, however this information was fully available and evaluated during the peer review. A proposal for classification of the formulation(s) according to Regulation (EC) 1272/2008 was provided by the applicant and assessed by the RMS (please see Volumes 3 CP of the RAR).

The proposed uses evaluated were spray applications in greenhouse (permanent) and non‐permanent protected structures with ornamental crops against whitefly. Full details of the Good Agricultural Practices (GAPs) can be found in the list of end points in Appendix B.

Data were submitted to conclude that the representative uses of buprofezin proposed at EU level result in a sufficient insecticidal effect following the guidance document SANCO/2012/11251‐rev. 4 (European Commission, 2014b).

CONCLUSIONS OF THE EVALUATION

General aspects

With regard to the mammalian toxicity information available for the formulation for representative uses ‘Applaud 25 SC’, studies were performed for acute toxicity endpoints. With regard to the co‐formulants contained in ‘Applaud 25 SC’, sufficient toxicological data were available for all components, but four (present in limited or well below 10% in the final formulation). For these four co‐formulants, the RMS considered and the peer review experts agreed that the available toxicological information did not sufficiently address the genotoxicity and repeated dose toxicity potential over the short‐ and long‐term and that they might be considered for further assessment. The collected information (not covering all endpoints), including information from the existing uses other than plant protection products, under regulated EU frameworks, did not highlight any concern (see Section 10). ⁸

For the ecotoxicology, the available acute data (see Section 5) did not indicate that the formulation for representative uses is more acutely toxic than the active substance. The need to assess the ecotoxicity of the formulation for representative uses was highlighted at the experts' meeting TC 109 ⁹ (see Section 5). Subsequently, the RMS performed a data retrieval exercise (not covering all endpoints) from regulatory frameworks other than plant protection products, based on which no concern was highlighted on the environmental safety of the co‐formulants.

1. IDENTITY, PHYSICAL/CHEMICAL/TECHNICAL PROPERTIES AND METHODS OF ANALYSIS

The following guidance documents were followed in the production of this conclusion: European Commission, 2000a, 2000b, 2010.

The proposed minimum purity of the active substance as manufactured is 985 g/kg. New impurities, at levels below 1 g/kg, were identified in the active substance batch data, from industrial plant production, submitted in support of the renewal of approval process. A data gap is set on detailed information on the origin of those impurities (see Section 10). The RMS proposed to maintain the current reference specification for buprofezin and could not conclude on the equivalence of the submitted batch data against the current reference specification due to the new impurities identified. EFSA proposes to maintain the current reference specification pending the assessment of the toxicological, ecotoxicological and environmental relevance of the new impurities identified in the provided batch data (see data gap in Sections 2 and 5). The current reference specification is supported from the toxicological point of view (see Section 2). The batches used in the ecotoxicological studies support the current reference specification (see Section 5). No FAO specification is currently published for buprofezin.

The main data regarding the identity of buprofezin and its physical and chemical properties are given in Appendix B. In general, adequate methods are available for the generation of data required for the risk assessment, except for the method used in the acute inhalation toxicity study of ‘Applaud 25 SC’ for which validation data are required (see Section 10). Appropriate methods of analysis are available for the determination of the active substance and impurities in the technical material except for the newly identified impurities. Appropriate analytical method is available for the determination of the active substance in the formulation for representative uses.

Buprofezin was set as a provisional residue definition for monitoring in honey and in food and feed of plant origin (see Section 3), while no residue definition was proposed for monitoring in food of animal origin (see Section 3). Consequently, pending the finalisation of these residue definitions, validated monitoring methods might be required. Validated liquid chromatography with tandem mass spectrometry (LC–MS/MS) methods are available for monitoring buprofezin residues in soil with limit of quantification (LOQ) of 0.01 mg/kg, and drinking water and surface water with LOQ of 0.1 μg/L. A validated gas chromatography–mass spectrometry (GC–MS) method is available for monitoring buprofezin residues in air with LOQ of 0.27 μg/m³. A data gap is set for a method that covers the residue definition for monitoring in body fluids and tissues (see Sections 2 and 10).

2. MAMMALIAN TOXICITY

The toxicological profile of the active substance buprofezin was discussed at the Pesticides Peer Review Teleconferences (TC) 106 (23–26 May 2023) and 110 (19–26 June 2023). The assessment is based on the following guidance documents: European Commission (2003, 2012a, 2015), EFSA PPR Panel (2017), EFSA (2014b).

The current reference specification for the active substance and associated impurities is supported from the toxicological point of view. No relevant impurities are identified in the current specification. A data gap is set on the assessment of the toxicological relevance of the new impurities identified in the provided batch data (see Sections 1 and 10).

The analytical methods used in feed, body fluids and tissues, air and any additional matrices used in support of the critical ¹⁰ toxicity studies are overall considered fit‐for‐purpose (see Section 1).

In the toxicokinetic studies, the oral absorption of buprofezin is estimated to account for 40% of the administered dose, based on urinary and biliary excretion within 24 h. There is no potential for accumulation. Excretion was predominantly through faeces and urine. Distribution was primarily associated with blood, urinary bladder, liver, kidney and adipose tissues. Buprofezin was extensively metabolised in rats. The metabolic pathway included phenyl ring hydroxylation, oxidation of the t‐butyl groups, thiadiazin ring opening and conjugation. Based on comparative in vitro metabolism, the metabolic profile is similar between species and no unique human metabolites were identified. The residue definition for body fluids and tissues includes buprofezin, BF‐13, BF‐23 and BF‐28.

Buprofezin has moderate acute toxicity by oral exposure and low acute toxicity by dermal and inhalation exposure. It is neither a skin irritant nor skin sensitiser. It is a minimal and transient eye irritant.

Short‐term oral toxicity studies were provided for rats and dogs. The critical effects in short‐term oral toxicity studies included liver and thyroid changes in rats and dogs. No observed adverse effect levels (NOAELs) of 10 and 13 mg/kg bw per day were identified in the 90‐day dietary studies in dogs and rats, respectively. In the 2‐year dog study, a NOAEL of 2 mg/kg bw per day was identified.

Based on the available genotoxicity studies, the majority of experts considered buprofezin unlikely to be genotoxic. This is in line with the advice of the EFSA cross‐cutting Working group (ccWG) on Genotoxicity. ¹¹

Based on its UV–vis spectra, testing for phototoxicity and photomutagenicity is not required for buprofezin.

Long‐term toxicity was examined in rats, dogs and mice. The target organ of toxicity was the liver in rats and mice and the thyroid in rats. The rat was the most sensitive species with a NOAEL for systemic toxicity of 0.9 mg/kg bw per day. The relevant NOAEL for carcinogenicity of 17.9 mg/kg bw per day was set in female mouse based on increased incidence of liver adenomas and carcinomas. ¹² No evidence of carcinogenicity was observed in rats. EFSA noted that evidence of carcinogenicity in mice may trigger the criteria for classification as carcinogenic category 2 as proposed by the RMS. ¹³

With regard to reproductive toxicity studies, fertility and overall reproductive performance were not affected. In the multigeneration rat study, the parental NOAEL is 6 mg/kg bw per day based on organ weight changes (liver, kidney and adrenals). The offspring NOAEL is 7.9 mg/kg bw per day based on decreased body weight gain. Finally, the reproductive NOAEL is 100 mg/kg bw per day based on absence of effects on reproductive parameters (no effects seen at the top dose). In the rat developmental toxicity study, the maternal and developmental NOAEL is 50 mg/kg bw per day. For the rabbit developmental toxicity studies, the slight majority of the experts agreed to set the NOAEL for developmental toxicity at 50 mg/kg bw per day based on increased incidence of enlarged aortic arch at 250 mg/kg bw per day. The RMS and some MSs did not agree and proposed the NOAEL at the top dose level (i.e. 250 mg/kg bw per day). ¹⁴ The rabbit maternal NOAEL is 50 mg/kg bw per day. EFSA noted that evidence of developmental toxicity (i.e. increased incidence of enlarged aortic arch) may trigger the criteria for classification as developmental toxicant category 2 as proposed by the RMS. ¹⁵ In the thyroid comparative assay, a NOAEL of 10 mg/kg bw per day for thyroid‐mediated toxicity in pups was identified (see Section 6). In this assay, a lowest observable adverse effect level (LOAEL) of 10 mg/kg bw per day (lowest dose level tested) for offspring toxicity was identified based on body weight and body weight gain (PND 0–7) reduction in Segment B PND 21 pups.

With respect to neurotoxicity, buprofezin did not show any potential for neurotoxic effects in the standard regulatory toxicity studies nor in the repeated neurotoxicity studies in rats. In the 28‐day immunotoxicity study in rats, immunotoxicity effects occurred at the same dose level where other toxicological effects were observed (the relevant NOAEL for immunotoxicity is 15.4 mg/kg bw per day).

The experts agreed on the following reference values: The acceptable daily intake (ADI) is 0.01 mg/kg bw per day, based on the NOAEL of 0.9 mg/kg bw per day in the 2‐year rat study based on increased incidence of eosinophilic foci of hepatocellular alteration in females and thyroid follicular cell hypertrophy in males at 8.71 mg/kg bw per day. The standard uncertainty factor (UF) of 100 was applied. The ADI does not differ from the previous peer review (EFSA, 2010; European Commission, 2017).

The acute reference dose (ARfD) is 0.1 mg/kg bw based on the NOAEL of 10 mg/kg bw per day based on clinical signs (i.e. subdue mood observed after 1 h of treatment during the early part of week one) in the 90‐day dog study, by applying a standard uncertainty factor of 100. This value differs from the previous peer review where the ARfD of 0.5 mg/kg bw (rat developmental toxicity) was set by EFSA (EFSA, 2010; European Commission, 2017).

The acceptable operator exposure level (AOEL) is 0.013 mg/kg bw per day, based on the LOAEL of 10 mg/kg bw per day for offspring from the thyroid comparative assay in which the critical effect was body weight and body weight gain (PND 0–7) reduction (see Section 6). The standard UF of 100 was applied plus an additional UF of 3 for LOAEL to NOAEL extrapolation, using a correction for oral absorption of 40%. This value differs from the previous peer review where the AOEL of 0.04 mg/kg bw per day (90‐day dog) was set by EFSA (EFSA, 2010; European Commission, 2017).

The acute acceptable operator exposure level (AAOEL) is 0.04 mg/kg bw per day. The same basis as for setting the ARfD has been used for setting the AAOEL but with a correction for oral absorption of 40%. An AAOEL was not set during the previous peer review in 2010 (not discussed) (EFSA, 2010).

No data or assessment on metabolites of buprofezin that could be relevant for the consumer dietary risk assessment (see Section 3) were provided for re‐evaluation during the renewal peer review process.

Non‐dietary exposure considered the representative uses of ‘Applaud 25 SC’ as insecticide in ornamentals. The exposure considered hand‐held application in indoor scenarios. The EFSA model from 2022 is not applicable to the dossier on buprofezin (submission before 1 January 2023). ¹⁶ Dermal absorption values of buprofezin in the representative product ‘Applaud 25 SC’ are 0.75% for the concentrate and 5.6% for the spray dilution. Operator exposure is below the (A)AOEL with the use of Personal Protective Equipment (PPE) based on the Dutch Greenhouse (gloves and coverall) or EFSA 2014 model (coverall). Considering an application rate of 3 × 0.25 kg a.s./ha, re‐entry worker exposure is below the AOEL with the use of PPE (workwear and gloves) and with a re‐entry period restriction of 26 days, according to Greenhouse EUROPOEM Model. Considering an application rate of 1 × 0.25 kg a.s./ha, a re‐entry period restriction is not needed. Bystander and resident exposure are below the (A)AOEL according to the EFSA 2014 Model (5 meter‐buffer strip considered).

Buprofezin met the criteria for endocrine disruption for T‐modality for humans (Scenario 1b) (see Section 6). The applicant did not provide a negligible exposure assessment nor an argumentation regarding Article 4(7) of Regulation (EC) No 1107/2009. The RMS included in the revised RAR an assessment to prove the non‐dietary negligible exposure, using the margin of exposure (MoE) between the relevant critical NOAEL and the actual estimated exposure (see Appendix B). The critical NOAEL is 10 mg/kg bw per day for thyroid‐mediated toxicity in pups in the comparative thyroid assay (See Section 6). The MoE for long‐term exposure ranged from 80 (operator exposure, high crop, intensive manual‐hand held – workwear + Personal Protective Equipment/Respiratory Protective Equipment) to 4000 (Sum of all routes – adult resident). The Margin of Exposure for acute exposure ranged from 133 (operator exposure, high crop, standard, manual‐hand held – workwear + Personal Protective Equipment/Respiratory Protective Equipment) to 5000 (Vapour – child bystander).

According to the representative uses (i.e. non‐edible crops), there are no metabolites found in groundwater and/or livestock or plant metabolites.

3. RESIDUES

Buprofezin was discussed at the Pesticides Peer Review Teleconferences (TC) 108 (30–31 May 2023).

The representative uses of buprofezin on ornamental plants do not lead to direct residue exposure for consumers or livestock. However, there is potential for indirect dietary exposure due to possible residues in honey and in following crops.

In low echnology ¹⁷ or non‐permanent protected structures, honeybees may access treated ornamental plants. Ornamentals may include melliferous and non‐melliferous plants. Consequently, residues from treated ornamentals could appear in pollen and bee‐derived products, including honey, necessitating a specific residue definition for these items.

No data on buprofezin metabolism specific to ornamental plants was provided. Instead, it was proposed to extrapolate the residues from available crop metabolism studies to establish the necessary residue definition for pollen and bee products. While this approach is theoretically acceptable, the relevant crop metabolism studies were not included in the RAR (Italy, 2024) and, therefore, were not reviewed as part of the renewal process. Consequently, the use of the residue definitions established in the previous peer review (EFSA, 2010) ¹⁸ for crops and honey is provisional, pending a review of data related to buprofezin uses on food and feed crops, including toxicity data on metabolites, that is up to date.

Tunnel residue trials at the critical GAP rate confirmed the presence of significant residues of buprofezin in honey. Among the analysed compounds – buprofezin, BF‐9, BF‐12 and aniline – only aniline was not quantifiable. However, due to lack of storage stability data for the pertinent analytes in honey (see Section 9.1), the submitted residue data are considered unreliable for setting maximum residue levels (MRLs) in honey or conducting a consumer risk assessment (see Section 9.1).

Furthermore, the potential formation of metabolites, including aniline in processed foods containing honey and not investigated compounds such as BF‐25 during honey pasteurisation should be investigated (see Section 9.1). The available data showed that under standard hydrolysis conditions simulating pasteurisation, boiling and sterilisation, buprofezin was significantly degraded, yielding substantial amounts of BF‐25 (up to 43% total radioactive residue (TRR)), aniline (up to 19% TRR) and metabolite BF‐12 (up to 31% TRR).

The representative uses on ornamentals do not prevent food or feed crops from being planted in soil or substrate that was previously used to grow treated ornamentals, nor does it preclude the recycling of such soil or substrate for growing food or feed items. Data to evaluate potential uptake of residues into succeeding crops were not reviewed as part of the renewal process. The RMS argued that production of ornamental plants is a specialist industry, and ornamental plants are not rotated with edible crops. However, no such evidence was provided for the EU (see Section 10).

The previous peer review (EFSA, 2010) flagged a possible concern regarding crop rotation in greenhouses and proposed a waiting period of 1 year between the use of buprofezin in greenhouses before sowing or planting a succeeding crop. However, it was not assessed whether this proposal is still suitable for the representative use that is the subject of the renewal review. To mitigate potential residues in food or feed until a thorough up‐to‐date review of the available data including the previous mitigation proposal is conducted (see Section 10), risk managers may consider the feasibility of the following measure: the active substance should not be used on ornamental plants that may be rotated with crops intended for food or feed production, nor should exposed greenhouse soil or substrate be reused for growing food or feed.

Even with these restrictions in place a consumer dietary risk assessment, considering potential residues in honey, could still not be finalised for the representative uses in low technology permanent and non‐permanent protected structures due to the reasons outlined above (see Section 9.1).

Regarding the outcome of the assessment of the criteria for endocrine disruption (see Section 2) it is noted that the applicant has not provided a negligible exposure assessment for dietary exposure, nor has the RMS.

4. ENVIRONMENTAL FATE AND BEHAVIOUR

Buprofezin was discussed at the Pesticides Peer Review Meeting Teleconference (TC) 107 in May 2023.

The rates of dissipation and degradation in the environmental matrices investigated were estimated using FOCUS (2006) kinetics guidance.

In soil laboratory incubations under aerobic conditions in the dark, buprofezin exhibited moderate to medium persistence, forming no major (> 10% applied radioactivity (AR)) metabolites. However, a soil degradation study on buprofezin in acidic soil was not available leading to the identification of a data gap (see Section 10). Mineralisation of the phenyl ¹⁴C radiolabel to carbon dioxide accounted for 19–51% AR after 90–91 days. The formation of unextractable residues (not extracted acetonitrile/water) for this radiolabel accounted for 23%–33% AR after 91–98 days. In anaerobic soil incubations, buprofezin degraded more slowly than under aerobic conditions with the route of degradation being the same as in the aerobic investigations. In soil photolysis conditions, buprofezin was stable. Buprofezin exhibited slight mobility to immobility in soil. In satisfactory field dissipation studies carried out at seven sites from North Caroline, California, Germany, France and Spain (spray application to the soil surface on bare soil plots), buprofezin exhibited moderate to medium persistence. Sample analyses were carried out for the parent buprofezin. Field study DegT50 values were derived following normalisation to FOCUS reference conditions (20°C and pF2 soil moisture) following the EFSA (2014a) DegT50 guidance. The field data endpoints were not combined with lab values to derive modelling endpoints for buprofezin.

In laboratory incubations in dark aerobic natural sediment water systems, buprofezin exhibited low persistence, forming no major metabolites. The unextractable sediment fraction (not extracted by acetonitrile/water) was a limited sink for the phenyl ¹⁴C radiolabel, accounting for 35%–36% AR at study end (101 days). Mineralisation of this radiolabel accounted for 24%–26% AR at the end of the study. The rate of decline of buprofezin in a laboratory sterile aqueous photolysis experiment was slow relative to that occurred in the aerobic sediment water incubations. Chromatographically resolved components accounting for > 10% AR was metabolite U‐2 (max. 16% AR).

The necessary surface water and sediment exposure assessments (predicted environmental concentrations (PEC) calculations) were carried out for buprofezin and metabolite U‐2 using the FOCUS (FOCUS, 2001) step 1 and step 2 approach (version 3.2 of the Steps 1–2 in FOCUS calculator).

For the active substance buprofezin and metabolite U‐2, appropriate step 3 (FOCUS, 2001) and step 4 calculations were available ¹⁹ for the representative uses on non‐permanent protected structures. The step 4 calculations appropriately followed the FOCUS (FOCUS, 2007) guidance, with drift reducing nozzles being implemented for the drainage scenarios (representing a 90% spray drift reduction), and no‐spray buffer zones with vegetative buffer strips of up to 20 m (reducing solute flux in run‐off by 80% and erosion run‐off of mass adsorbed to soil by 95%) being implemented for the run‐off scenarios. The SWAN tool (version 5.0) was appropriately used to implement these mitigation measures in the simulations. However, risk managers and others may wish to note that whilst run‐off mitigation is included in the step 4 calculations available, the FOCUS (FOCUS, 2007) report acknowledges that for substances with KFoc < 2000 mL/g (i.e. metabolite U‐2), the general applicability and effectiveness of run‐off mitigation measures had been less clearly demonstrated in the available scientific literature, than for more strongly adsorbed compounds.

Following the EFSA (2014b) guidance on emissions from protected structures, appropriate step 3 (FOCUS, 2001) calculations were available ²⁰ for the representative uses in permanent greenhouses (when application is done with all the openings closed) considering only exposure via drainage. Appropriate step 3 (FOCUS, 2001) and step 4 calculations were available¹⁹ for the representative uses in permanent greenhouses (when application is done with all the openings opened) considering exposure via drainage and spray drift. The step 4 calculations appropriately followed the FOCUS (FOCUS, 2007) guidance, with drift reducing nozzles being implemented for the drainage scenarios (representing a 90% spray drift reduction).

The necessary groundwater exposure assessments were appropriately carried using FOCUS (European Commission, 2014a) scenarios and the models PEARL 4.4.4, PELMO 5.5.3 and MACRO 5.5.4.¹⁹ The potential for groundwater exposure from the representative uses by buprofezin above the parametric drinking water limit of 0.1 μg/L was concluded to be low in geoclimatic situations that are represented by all 9 FOCUS groundwater scenarios.

The applicant provided appropriate information to address the effect of water treatments processes on the nature of the residues that might be present in surface water, when surface water is abstracted for drinking water. The conclusion of this consideration was that neither buprofezin nor any of its degradation products that trigger assessment would be expected to undergo any substantial transformation due to oxidation at the disinfection stage of usual water treatment processes.

The PEC in soil, surface water, sediment and groundwater covering the representative uses assessed can be found in Appendix B of this conclusion. A key to the wording used to describe the persistence and mobility of the compounds assessed can be found in Appendix C of this conclusion.

5. ECOTOXICOLOGY

The risk assessment was based on the following documents: European Commission (2002), SETAC (2001), EFSA (2009, 2013) and EFSA PPR Panel (2013).

Buprofezin was discussed at the Pesticides Peer Review meeting teleconference 109 in May 2023 and teleconferences 110 and 113 in June 2023.

The batches used in the ecotoxicity studies were shown to be sufficiently comparable to the current and new reference specifications. A data gap is set on the assessment of the ecotoxicological and environmental relevance of the new impurities identified in the provided batch data (see Sections 1 and 10).

Acute and reproductive toxicity studies with birds and wild mammals with the active substance were available. The reproductive endpoint selection for birds ²¹ and mammals ²² was discussed at the meeting. The acute toxicity to birds with the formulation for representative uses was not investigated (data gap, see Section 10). The risk for birds and mammals was concluded as low in permanent greenhouses, considering the low likelihood of exposure resulting from these uses. For the uses in non‐permanent protected structures, the acute dietary risk for birds and mammals was assessed as low at the screening step. The reproductive risk was concluded as low for birds, but not for mammals, for which Tier 1 calculations indicated a high risk from non‐permanent greenhouse uses. Buprofezin has a log K _ow > 3 indicating a potential for bioaccumulation. As such, the risk for birds and mammals due to secondary poisoning was assessed. Specifically, the risk for fish‐eating birds and mammals was assessed as low based on the illustrative risk assessment agreed at the meeting. ²³ The risk for earthworm‐eating mammals, but not birds, was indicated as high at Tier‐1 for the non‐permanent greenhouse uses. A valid quantitative risk assessment for birds and mammals consuming plant metabolites was not provided (data gap, see Section 10).

Sufficient valid studies were submitted for the acute and chronic hazard assessment of buprofezin, for aquatic organisms. Furthermore, acute studies with the formulation for representative uses were provided with fish, aquatic invertebrates and algae. The acute endpoint for aquatic invertebrates, ²⁴ the long‐term endpoints for fish ²⁵ and aquatic invertebrates ²⁶ were agreed at the peer review meeting. Particularly, the interpretation of the results from the life‐cycle study with fathead minnow study was discussed among experts. Despite acknowledging the uncertainty resulting from the variability in the dataset and the absence of a clear dose–response, the experts did not exclude that effects on reproduction across all tested concentrations were treatment‐related. Consequently, no no observed effect concentration (NOEC) could be set for use in risk assessment which would be protective of potential reproductive effects. ²⁷ Another full life‐cycle study was available yielding a higher endpoint. However, this study was conducted with a different species and exposure duration. As such, it did not sufficiently address the concerns related to the potential reproductive effects observed in the fathead minnow. Therefore, the risk assessment for aquatic organisms could not be finalised (data gap, see Section 9.1). Toxicity data with the only relevant metabolite U2 were not available. Since the risk assessment for buprofezin could not be finalised due to the absence of a sufficiently protective fish chronic endpoint, a screening risk assessment assuming 10 times higher toxicity than the parent was not possible (data gap and issue not finalised, see Section 9.1).

Acute contact and oral tests with worker honey bees were available with buprofezin and the formulation for representative uses. Furthermore, a chronic test with adults and a repeated exposure study with larvae were available with buprofezin. The chronic toxicity of the formulation for representative uses to bee workers and larvae was not investigated (data gap, see Section 10). A semi‐field colony feeder study with honey bees was submitted, but it was not used in the risk assessment due to major design drawbacks. ²⁸ For the uses in permanent greenhouses, a low risk to bees was concluded, considering their low exposure. For the non‐permanent greenhouse uses, a risk assessment according to European Commission (2002) was presented, indicating a low acute risk. A screening risk assessment according to EFSA (2013) was also provided indicating low acute and chronic risk to honey bee adults and low risk to honey bee larvae. However, given the mode of action of buprofezin, an investigation of ovicidal effects beyond the available data was considered necessary¹⁶ (data gap and assessment not finalised, see Section 9.1). A quantitative risk assessment for honey bees from the relevant plant metabolites was not available (data gap, see Section 10). A suitable assessment of accumulative and sublethal effects was not provided (see Section 10). Toxicity data with bumble bees or solitary bees were not available.

To evaluate the risk to non‐target arthropods other than bees, glass plate tests with Typhlodromus pyri and Aphidius rhopalosiphi investigating mortality and reproduction were available. Based on these tests, the in‐ and off‐field risk was quantified as low. However, experts at the meeting raised concerns that the testing strategy mighy not have been sufficient to address the potential ovicidal effects of buprofezin. This was identified as a data gap and assessment that was not finalised (see Section 9.1).

Tests on soil micro‐ and macro‐organisms with the active substance but not the formulation for representative uses (data gap, see Section 10) were available. Using the available data, a low risk was identified for earthworms, soil meso‐ and macro‐fauna other than earthworms, and? soil microorganisms.

The risk for non‐target terrestrial plants was assessed as low based on screening data.

Low risk to organisms involved in biological methods for sewage treatment could also be concluded for all representative uses.

6. ENDOCRINE DISRUPTION PROPERTIES

The endocrine disruption properties of buprofezin for humans and non‐target organisms were discussed at the Pesticides Peer Review Experts' Teleconferences number 109, 110, 113 (May–June 2023) and 152 (November 2024).

With regard to the assessment of the endocrine disruption potential of buprofezin for humans according to the ECHA/EFSA guidance (2018), in determining whether buprofezin interacts with the oestrogen, androgen and steroidogenesis (EAS)‐ and thyroid (T)‐mediated pathways, the number and type of effects induced, and the magnitude and pattern of responses observed across studies were considered. Additionally, the conditions under which effects occur were considered, in particular, whether or not endocrine‐related responses occurred at dose(s) that also resulted in overt toxicity. The assessment is therefore providing a weight‐of‐evidence analysis of the potential interaction of buprofezin with the EAS and T signalling pathways using the available evidence in the data set.

For the EAS‐modality, a pattern of EAS‐mediated adversity was not identified in a sufficiently investigated dataset. Therefore, the ED criteria for humans for the EAS‐modality are not met and scenario 1a of the ECHA/EFSA ED Guidance (2018) is applicable.

The T‐modality was considered sufficiently investigated and a pattern of T‐mediated adversity, i.e. increased thyroid weight and changes in thyroid histopathology, was observed in rats in studies of different durations and when considering the time and the dose concordance across the studies, the effect was reproducible. In dogs, a perturbation of the thyroid axis cannot be excluded based on increased in thyroid weight and changes in T4 levels. In addition, the Comparative Thyroid Assay (CTA) conducted in the rat, support the conclusion that there is a perturbation of the Hypothalamic–Pituitary–Thyroid (HPT) axis in the sensitive population. This was observed in dams at gestation day (GD) 20, in non‐pregnant females, but also in the sensitive population (i.e. at PND21 pups showed a dose related thyroid‐mediated effect starting from the dose of 80 mg/kg bw per day, NOAEL 10 mg/kg bw/day). The critical NOAEL for thyroid‐mediated toxicity is 10 mg/kg bw per day.

The postulated mode of action (MOA) indicated CAR/PXR induction as the plausible molecular initiating event (MIE) and phase I/II enzymes induction as the plausible key events (KE). Based on the available and sufficiently investigated dataset and on the MOA analysis, the ED criteria for the T‐modality are met for buprofezin (Scenario 1b of the ECHA/EFSA ED Guidance, 2018).¹

For the EAS‐modalities, the outcome of the assessment reported above for humans also applies to wild mammals as non‐target organisms. ²⁹ For the T‐modality, the population relevance of the adversity observed in mammals and relevant for humans (i.e. change in thyroid weight and thyroid histopathology) was discussed. ³⁰ Based on the current knowledge, no effects that could be clearly linked to the thyroidal MoA identified in mammals were observed. However, some concerns remain regarding the potential trigger of neurodevelopmental effects in pups, especially considering that no DNT study is available. Overall, it could not be concluded whether the observed adversity in mammals could be relevant at the population level for wild mammals as non‐target organisms.

For non‐target organisms other than mammals, no relevant studies were available and thus the endocrine activity and adversity for the EATS‐modalities were not sufficiently investigated (data gap leading to an issue not finalised, see section 9).

Overall, for humans, according to point 3.6.5 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, it can be concluded that buprofezin is an endocrine disruptor. For non‐target organisms, based on the available information, the assessment of the endocrine disruption potential of buprofezin according to point 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, cannot be concluded (data gap and issue not finalised, see Section 9).

7. OVERVIEW OF THE RISK ASSESSMENT OF COMPOUNDS LISTED IN RESIDUE DEFINITIONS TRIGGERING ASSESSMENT OF EFFECTS DATA FOR THE ENVIRONMENTAL COMPARTMENTS (TABLES 1, 2, 3, 4)

TABLE 1.

Soil.

Compound (name and/or code)	Ecotoxicology
Buprofezin	Low risk to soil organisms

TABLE 2.

Groundwater. ^a

Compound (name and/or code)	> 0.1 μg/L at 1 m depth for the representative uses b step 2	Biological (pesticidal) activity/relevance step 3a	Hazard identified steps 3b and 3c	Consumer RA triggered steps 4 and 5	Human health relevance
Buprofezin	No	Yes	–	–	Yes

^a Assessment according to European Commission guidance of the relevance of groundwater metabolites (2003).

^b FOCUS scenarios or relevant lysimeter. Ranges indicated for FOCUS scenarios include the result from the model giving the highest concentration at each scenario, as needed to comply with European Commission (2014a) guidance.

TABLE 3.

Surface water and sediment.

Compound (name and/or code)	Ecotoxicology
Buprofezin	Data gap to address the long‐term risk to aquatic organisms
U‐2	Data gap to address the long‐term risk to aquatic organisms

TABLE 4.

Air.

Compound (name and/or code)	Toxicology
Buprofezin	Not acutely toxic by inhalation route (> 4.57 mg/L air/4 h (whole body))

8. PARTICULAR CONDITIONS PROPOSED TO BE TAKEN INTO ACCOUNT BY RISK MANAGERS

Risk mitigation measures (RMMs) identified following consideration of Member State (MS) and/or applicant's proposal(s) during the peer review, if any, are presented in this section. These measures applicable for human health and/or the environment leading to a reduction of exposure levels of operators, workers, bystanders/residents, environmental compartments and/or non‐target organisms for the representative uses are listed below. The list may also cover any RMMs as appropriate, leading to an acceptable level of risks for the respective non‐target organisms.

It is noted that final decisions on the need of RMMs to ensure the safe use of the plant protection product containing the concerned active substance will be taken by risk managers during the decision‐making phase. Consideration of the validity and appropriateness of the RMMs remains the responsibility of MSs at product authorisation, taking into account their specific agricultural, plant health and environmental conditions at national level (Table 5).

TABLE 5.

Risk mitigation measures proposed for the representative uses assessed.

Representative use	Ornamentals (G)	Ornamentals (G)
	3 × 0.25 kg a.s./ha	1 × 0.25 kg a.s./ha
	Hand‐held application	Hand‐held application
Operator risk	Use of PPE is required a	Use of PPE is required a
Worker exposure	Use of PPE and re‐entry period restriction are required b	Use of PPE is required b
Bystander/resident exposure	RMM equivalent to 5 m no‐spray buffer zone	RMM equivalent to 5 m no‐spray buffer zone
Dietary exposure	The active substance should not be used on ornamental plants that may be rotated with crops intended for food or feed production, nor should exposed greenhouse soil or substrate be reused for growing food or feed

^a Operator exposure is below the (A)AOEL with the use of Personal Protective Equipment (PPE) based on the Dutch Greenhouse (gloves and coverall) or EFSA 2014 model (coverall).

^b Considering an application rate of 3 × 0.25 kg a.s./ha, re‐entry worker exposure is below the AOEL with the use of PPE (workwear and gloves) and with a re‐entry period restriction of 26 days, according to Greenhouse EUROPOEM Model. Considering an application rate of 1 × 0.25 kg a.s./ha, a re‐entry period restriction is not needed.

9. CONCERNS AND RELATED DATA GAPS

9.1. Issues that could not be finalised

An issue is listed as ‘could not be finalised’ if there is not enough information available to perform an assessment, even at the lowest tier level, for one or more of the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/2011 ³¹ and if the issue is of such importance that it could, when finalised, become a concern (which would also be listed as a critical area of concern if it is of relevance to all representative uses).

An issue is also listed as ‘could not be finalised’ if the available information is considered insufficient to conclude on whether the active substance can be expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

The following issues or assessments that could not be finalised have been identified, together with the reasons including the associated data gaps where relevant, which are reported directly under the specific issue to which they are related:

1. A consumer dietary risk assessment, considering potential residues in honey, could not be finalised (relevant for the representative uses in low technology permanent or non‐permanent protected structures; see Section 3).

   1. The overall information presented is not sufficient to allow for setting a risk assessment residue definition for honey. A re‐evaluation of the crop metabolism studies and toxicological data on the pertinent plant metabolites to modern standards should be provided.
   2. Storage stability data for all analytes which were investigated in the study with honey are necessary to validate the results.
   3. The formation of metabolites, including aniline in processed foods containing honey, and not investigated compounds such as BF‐25 during honey pasteurisation should be investigated.

   Further, the consumer dietary risk assessment could not be finalised regarding possible residues in succeeding crops unless specific restrictions are put in place that have not been part of the representative GAPs (relevant for all representative uses; see Section 3).

   The overall information presented is not sufficient to allow for setting a risk assessment residue definition for rotational crops, to assess the levels of residues taken up from soil into succeeding crops and to conduct a dietary risk assessment on such residues.

2. The risk for aquatic organisms exposed to buprofezin and its metabolite U2 is not finalised (relevant for all representative uses evaluated, see Section 5) due to the:

   1. Absence of a long‐term fish endpoint (NOEC) protective of the observed effects on reproduction;
   2. Absence of a hazard characterisation for the metabolite U2.
3. The risk for bees and other non‐target arthropods for the uses in non‐permanent greenhouses could not be finalised.

   1. An investigation of ovo‐larvicidal effects (i.e. also covering effects on egg laying) of buprofezin beyond the available data was considered necessary for bees and other non‐target arthropods.

4. For non‐target organisms other than mammals, no relevant data, in line with the testing strategy of the ECHA/EFSA ED Guidance (2018) were available to conduct the assessment for the endocrine disrupting properties. ³²

9.2. Critical areas of concern

An issue is listed as a critical area of concern if there is enough information available to perform an assessment for the representative uses in line with the uniform principles in accordance with Article 29(6) of Regulation (EC) No 1107/2009 and as set out in Commission Regulation (EU) No 546/2011, and if this assessment does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater, or any unacceptable influence on the environment.

An issue is also listed as a critical area of concern if the assessment at a higher tier level could not be finalised due to lack of information, and if the assessment performed at the lower tier level does not permit the conclusion that, for at least one of the representative uses, it may be expected that a plant protection product containing the active substance will not have any harmful effect on human or animal health or on groundwater, or any unacceptable influence on the environment.

An issue is also listed as a critical area of concern if, in the light of current scientific and technical knowledge using guidance documents available at the time of application, the active substance is not expected to meet the approval criteria provided for in Article 4 of Regulation (EC) No 1107/2009.

The following critical areas of concern are identified, together with any associated data gaps, where relevant, which are reported directly under the specific critical area of concern to which they are related:

• 5Buprofezin is considered to meet the criteria for endocrine disruption for humans according to point 3.6.5 of Annex II of Regulation No 1107/2009, as amended by Commission Regulation (EU) 2018/605 (see Section 6).

9.3. Overview of the concerns identified for each representative use considered (Table 6)

TABLE 6.

Overview of concerns reflecting the issues not finalised, critical areas of concerns and the risks identified that may be applicable for some but not for all uses or risk assessment scenarios.

Representative use		Ornamental plants
		Permanent greenhouse protected structures (high technology)		Permanent greenhouse protected structures (low technology)		Non‐permanent greenhouse protected structures (low technology)
		1 × 0.25 kg a.s./ha	1–3 × 0.25 kg a.s./ha	1 × 0.25 kg a.s./ha	1–3 × 0.25 kg a.s./ha	1 × 0.25 kg a.s./ha	1–3 × 0.25 kg a.s./ha
Operator risk	Risk identified
	Assessment not finalised
Worker risk	Risk identified
	Assessment not finalised
Resident/bystander risk	Risk identified
	Assessment not finalised
Consumer risk	Risk identified
	Assessment not finalised			X1	X1	X1	X1
Risk to wild non‐target terrestrial vertebrates	Risk identified					X b , c	X b , c
	Assessment not finalised
Risk to wild non‐target terrestrial organisms other than vertebrates	Risk identified
	Assessment not finalised					X3	X3
Risk to aquatic organisms	Risk identified
	Assessment not finalised	X2	X2	X2	X2	X2	X2
Groundwater exposure to active substance	Legal parametric value breached
	Assessment not finalised
Groundwater exposure to metabolites	Legal parametric value breached
	Parametric value of 10 μg/L a breached
	Assessment not finalised

Note: In addition to the issues indicated below, buprofezin is considered to meet the criteria for endocrine disruption for humans for the T‐modality according to point 3.6.5 of Annex II of Regulation No 1107/2009, as amended by Commission Regulation (EU) 2018/605, whilst the assessment of the endocrine disrupting properties for non‐target organisms according to the scientific criteria for the determination of endocrine disrupting properties as set out in point 3.8.2 of Annex II to Regulation (EC) No 1107/2009, as amended by Commission Regulation (EU) 2018/605, could not be finalised based on the available information. The superscript numbers relate to the numbered points indicated in Sections 9.1 and 9.2 Where there is no superscript number, see Sections 2, 7 for further information.

^a Value for non‐relevant metabolites prescribed in SANCO/221/2000‐rev. 10 final, European Commission (2003).

^b High reproductive risk identified for wild mammals based on TER calculations.

^c High risk for earthworm‐eating mammals Based on TER calculations.

(If a particular condition proposed to be taken into account to manage an identified risk, as listed in Section 8, has been evaluated as being effective, then ‘risk identified’ is not indicated in Table 6.)

10. LIST OF OTHER OUTSTANDING ISSUES

Remaining data gaps not leading to critical areas of concern or issues not finalised but considered necessary to comply with the data requirements, and which are relevant for some or all of the representative uses assessed at EU level. Although not critical, these data gaps may lead to uncertainties in the assessment and are considered relevant.

These data gaps refer only to the representative uses assessed and are listed in the order of the sections:

• For four of the components of the formulation for representative uses ‘Applaud 25 SC’ genotoxicity and repeated dose toxicity information over the short‐ and long‐term was not available; therefore, in order to allow a final conclusion on the safety assessment of ‘Applaud 25 SC’, genotoxicity and repeated dose toxicity data for these components (short‐ and long‐term) might be considered for further assessment (to be confirmed by Member States when assessing applications for PPP authorisation; relevant for all representative uses evaluated; see Section ‘General aspects’).

• A validated method that covers the residue definition for monitoring in body fluids and tissues was not available (see Section 1, relevant for all representative uses).

• Validation data for the method used in the acute inhalation toxicity study of ‘Applaud 25 SC’ were not available (see Sections 1, 2 and 5, relevant for all representative uses).

• Detailed information on the origin of the new impurities identified in the batch data submitted in support of the renewal of approval process, the assessment of their toxicological, ecotoxicological and environmental relevance and validated method(s) for their analysis was not available (see Sections 1, 2 and 5, relevant for all representative uses).

• Acute inhalation toxicity of ‘Applaud 25 SC’ to be further addressed since the analytical method used in the available acute inhalation toxicity study of ‘Applaud 25 SC’ was not acceptable (relevant for all representative uses evaluated; see Sections 1 and 2).

• As regards the equivalence of the submitted batch data against the current reference specification a data gap is identified to address the relevance of new impurities (see Section 2, relevant for all representative uses).

• A complete assessment of the potential of uptake of residues into succeeding crops that could be food or feed items, including data to derive a residue definition for risk assessment to modern standards, or reliable and representative evidence that in the EU it is not a practice that food or feed items are grown following ornamental plants and soil/substrate used to grow ornamental plants is not recycled to grow feed or feed items (relevant for all representative uses evaluated, see Section 3).

• Soil degradation study on buprofezin in acidic soil (pH < 6) (relevant for all representative uses evaluated; see Section 4).

• The risk assessment for birds, mammals and bees from the relevant plant metabolites should be addressed (relevant for the non‐permanent greenhouse uses evaluated, see Section 5).

• A suitable assessment of sublethal effects for bees was not provided (relevant for the non‐permanent greenhouse uses evaluated; see Section 5).

• The acute toxicity to birds, the chronic toxicity to bee workers and larvae and the toxicity to earthworms and other soil macro‐ and microorganisms was not investigated with the formulation for representative uses (relevant for all representative uses evaluated; see Section 5).

ABBREVIATIONS

AAOEL

acute acceptable operator exposure level

ADI

acceptable daily intake

AOEL

acceptable operator exposure level

AR

applied radioactivity

ARfD

acute reference dose

bw

body weight

ccWG

cross‐cutting Working group

CFU

colony forming units

CI

confidence interval

CTA

comparative thyroid assay

DT₅₀

period required for 50% dissipation (define method of estimation)

DT₉₀

period required for 90% dissipation (define method of estimation)

EAS

oestrogen, androgen and steroidogenesis modalities

ECHA

European Chemicals Agency

ED

endocrine disruption

EUROPOEM

European Predictive Operator Exposure Model

FAO

Food and Agriculture Organization of the United Nations

FOCUS

Forum for the Co‐ordination of Pesticide Fate Models and their Use

GAP

Good Agricultural Practice

GC

gas chromatography

HPT

hypothalamic–pituitary–thyroid

ISO

International Organization for Standardization

IUPAC

International Union of Pure and Applied Chemistry

K _doc

organic carbon linear adsorption coefficient

KE

key events

K _Foc

Freundlich organic carbon adsorption coefficient

LC–MS/MS

liquid chromatography with tandem mass spectrometry

LOQ

limit of quantification

MIE

molecular initiating event

MOA

mode of action

MoE

margin of exposure

MRL

maximum residue level

MS

mass spectrometry

NOAEL

no observed adverse effect level

NOEC

no observed effect concentration

NOEL

no observed effect level

PEC

predicted environmental concentration

PPE

personal protective equipment

RAC

regulatory acceptable concentration

RAR

Renewal Assessment Report

RMMs

risk mitigation measures

SC

suspension concentrate

SFO

single first‐order

SMILES

simplified molecular‐input line‐entry system

TER

toxicity exposure ratio

TRR

total radioactive residue

WHO

World Health Organization

REQUESTOR

European Commission

QUESTION NUMBER

EFSA‐Q‐2020‐00723

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NOTE/UPDATE

This scientific output, approved on 01 April 2025, supersedes the previous output published on 3 June 2010 (EFSA, 2010).

Supporting information

List of end points for the active substance and the formulation for representative uses.

APPENDIX A. Consideration of cut‐off criteria for buprofezin according to Annex II of Regulation (EC) No 1107/2009 of the European Parliament and of the Council

Properties		Conclusion a
CMR	Carcinogenicity (C)	No proposal for harmonised classification and labelling of buprofezin for carcinogenicity has ever been submitted to ECHA EFSA noted that evidence of carcinogenicity in mice may trigger the criteria for classification as carcinogenic category 2 as proposed by the RMS
	Germ cell mutagenicity (M)	No proposal for harmonised classification and labelling of buprofezin for germ cell mutagenicity has ever been submitted to ECHA. EFSA noted that during the EU peer review buprofezin was considered unlikely to be genotoxic
	Toxic for Reproduction (R)	No proposal for harmonised classification and labelling of buprofezin for reproductive toxicity has ever been submitted to ECHA EFSA noted that evidence of developmental toxicity may trigger the criteria for classification as developmental toxicant category 2 as proposed by the RMS
Endocrine disrupting properties		According to points 3.6.5 and 3.8.2 of Annex II of Regulation No 1107/2009, as amended by Commission Regulation (EU) 2018/605, buprofezin Meet the criteria for endocrine disruption for human health according to points 3.6.5 of Annex II of Regulation No 1107/2009, as amended by Commission Regulation (EU) 2018/605
POP	Persistence	Buprofezin is not considered to be a persistent organic pollutant (POP) according to point 3.7.1 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation
	Long‐range transport
PBT	Persistence	Buprofezin is not considered to be a persistent, bioaccumulative and toxic (PBT) substance according to point 3.7.2 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation
	Toxicity
vPvB	Persistence	Buprofezin is not considered to be a very persistent, very bioaccumulative substance according to point 3.7.3 of Annex II of Regulation (EC) 1107/2009
	Bioaccumulation

^a Origin of data to be included where applicable (e.g. EFSA, ECHA RAC, Regulation).

APPENDIX B. List of end points for the active substance and the formulation for representative uses

Appendix B can be found in the online version of this output (‘Supporting information’ section): https://doi.org/10.2903/j.efsa.2025.9392.

APPENDIX C. Wording EFSA used in section 4 of this conclusion, in relation to DT and Koc ‘classes’ exhibited by each compound assessed

Wording	DT50 normalised to 20°C for laboratory incubations 33 or not normalised DT50 for field studies (SFO equivalent, when biphasic, the DT90 was divided by 3.32 to estimate the DT50 when deciding on the wording to use)
Very low persistence	< 1 day
Low persistence	1 to < 10 days
Moderate persistence	10 to < 60 days
Medium persistence	60 to < 100 days
High persistence	100 days to < 1 year
Very high persistence	A year or more

Note: These classes and descriptions are unrelated to any persistence class associated with the active substance cut‐off criteria in Annex II of Regulation (EC) No 1107/2009. For consideration made in relation to Annex II, see Appendix A.

Wording	K oc (either K Foc or K doc) mL/g
Very high mobility	0 to 50
High mobility	51 to 150
Medium mobility	151 to 500
Low mobility	501 to 2000
Slight mobility	2001 to 5000
Immobile	> 5000

Note: Based on McCall et al. (1980).

APPENDIX D. Used compound codes

Code/trivial name a	IUPAC name/SMILES notation/InChiKey b	Structural formula c
Buprofezin	(2Z)‐2‐(tert‐butylimino)‐5‐phenyl‐3‐(propan‐2‐yl)‐1,3,5‐thiadiazinan‐4‐one CC(C)(C)\N=C1/SCN(C(=O)N1C(C)C)c1ccccc1 PRLVTUNWOQKEAI‐VKAVYKQESA‐N
U‐2	4‐methyl‐1phenyl‐1H‐imidazole Cc1cn(cn1)c1ccccc1 TZFGLMGQQDEFMH‐UHFFFAOYSA‐N
BF‐13	1‐(4‐hydroxyphenyl)‐3‐(propan‐2‐yl)urea CC(C)NC(=O)Nc1ccc(O)cc1 PAGUMFRLNPFKGJ‐UHFFFAOYSA‐N
BF‐23	N‐(4‐hydroxyphenyl)acetamide Oc1ccc(NC(=O)C)cc1 RZVAJINKPMORJF‐UHFFFAOYSA‐N
BF‐28	2‐methyl‐N‐[{[(methylsulfonyl)methyl](phenyl)carbamoyl}(propan‐2‐yl)carbamoyl]alanine CS(=O)(=O)CN(C(=O)N(C(=O)NC(C)(C)C(=O)O)C(C)C)c1ccccc1 OPGMOZYBBSEYHZ‐UHFFFAOYSA‐N
Aniline	Aniline Nc1ccccc1 PAYRUJLWNCNPSJ‐UHFFFAOYSA‐N

^a The name in bold is the name used in the conclusion.

^b ACD/Name 2023.2.4, ACD/Labs 2023.2.4 (File Version N25E41, Build 137185, 30 Jan 2024).

^c ACD/ChemSketch 2023.2.4, ACD/Labs 2023.2.4 (File Version C45H41, Build 137017, 18 Jan 2024).

EFSA (European Food Safety Authority) , Álvarez, F. , Arena, M. , Auteri, D. , Leite, S. B. , Binaglia, M. , Castoldi, A. F. , Chiusolo, A. , Colagiorgi, A. , Colas, M. , Crivellente, F. , De Lentdecker, C. , De Magistris, I. , Egsmose, M. , Fait, G. , Ferilli, F. , Broussard, M. F. , Santonja, G. G. , Gouliarmou, V. , … Villamar‐Bouza, L. (2025). Peer review of the pesticide risk assessment of the active substance buprofezin. EFSA Journal, 23(4), e9392. 10.2903/j.efsa.2025.9392