Peer review of the pesticide risk assessment of the active substance lenacil.

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, Belgium, and co-rapporteur Member State, Austria, for the pesticide active substance lenacil are reported. 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 lenacil as a herbicide on sugar and fodder beet (field use). 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 reported where identified.

Peer review of the pesticide risk assessment of the active substance paraffin oil (CAS 8042-47-5, chain lengths C17-C31).

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, Greece, and co-rapporteur Member State, France, for the pesticide active substance paraffin oil are reported. 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 paraffin oil as an acaricide and insecticide on potatoes, ornamentals (flower bulbs) and orchards (pear/apple), on pome fruit and stone fruit, on field and permanent protected fruiting vegetables and on field and permanent protected roses and on citrus. 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 reported where identified.

Statement on the toxicological properties and maximum residue levels of acetamiprid and its metabolites.

Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the EFSA PPR Panel published a statement following a request from the European Commission to advise on human health or the environment based on new scientific evidence presented by France during the decision-making phase. In July 2022, by means of a further mandate received from the European Commission, EFSA was requested to provide advice if new information and any other scientific evidence that has become available since the assessment conducted for the renewal in 2018 warrant re-evaluation of (i) toxicological parameters used for the risk assessment of acetamiprid during the renewal process, including toxicological endpoints; (ii) the residue definition for acetamiprid in products of plant origin; and (iii) the safety of existing maximum residue levels (MRLs). Meanwhile, the applicant of acetamiprid in the EU submitted new toxicology studies regarding the toxicological profile of the metabolite IM-2-1. Furthermore, the European Commission was made aware that several recent publications in scientific literature were made available after the literature searches conducted by EFSA. As the new data could affect the advice that EFSA was expected to deliver through the 2022 mandate, EFSA was further requested to consider this information by means of a revised mandate received in September 2023. As regards re-evaluation of point (i) in this statement, this was addressed by an EFSA Working Group integrating all the available evidence. The results of the weight of evidence indicated that there are major uncertainties in the body of evidence for the developmental neurotoxicity (DNT) properties of acetamiprid and further data are therefore needed to come to a more robust mechanistic understanding to enable appropriate hazard and risk assessment. In view of these uncertainties, the EFSA WG proposed to lower the acceptable daily intake (ADI) and acute reference dose (ARfD) from 0.025 to 0.005 mg/kg body weight (per day). A revised residue definition for risk assessment was proposed for leafy and fruit crops as sum of acetamiprid and N-desmethyl-acetamiprid (IM-2-1), expressed as acetamiprid. Regarding pulses/oilseeds, root crops and cereals, the new data received did not indicate a need to modify the existing residue definition for risk assessment, which therefore remains as parent acetamiprid. Regarding the residue definition for enforcement, the available data did not indicate a need to modify the existing definition because acetamiprid is still a sufficient marker of the residues in all crop groups. Considering the new health-based guidance values derived in the present statement, a risk for consumer has been identified for 38 MRLs currently in place in the EU Regulation. Consequently, EFSA recommended to lower the existing MRLs for 38 commodities based on the assessment of fall-back Good Agricultural Practices received within an ad hoc data call. Some fall-back MRLs proposals require further risk management considerations.

Peer review of the pesticide risk assessment of the active substance clove oil.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Malta, for the pesticide active substance clove oil are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions for the amendment of approval were reached on the basis of the evaluation of the representative use of clove oil as a preharvest nematicide on tomatoes and cucumbers (permanent greenhouse use). The representative use evaluated for the renewal of approval of clove oil was as post-harvest fungicide and bactericide on apples, pears and peaches (indoor uses). The reliable endpoints appropriate for use in regulatory risk assessment are presented. Endpoints not relevant to the scope of the proposed amendment of approval conditions will be addressed in the context of the renewal of approval procedure of clove oil running in parallel (AIR IV, EFSA Q-2016-00809). Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance quinolin-8-ol.

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, Spain, and co-rapporteur Member State, the Netherlands, for the pesticide active substance quinolin-8-ol are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative use of quinolin-8-ol as a fungicide and bactericide against soil-borne pathogens in tomato cultivation in permanent greenhouses applied by drip irrigation. 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 reported where identified.

Updated peer review of the pesticide risk assessment of the active substance dichlorprop-P and variant dichlorprop-P-2-ethylhexyl.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Ireland, and co-rapporteur Member State, Poland, for the pesticide active substance dichlorprop-P and the variant dichlorprop-P-2-ethylhexyl and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of dichlorprop-P as a herbicide on cereals, grassland and grass seed crops and of the variant dichlorprop-P-2-ethylhexyl as a plant growth regulator on citrus. MRLs were assessed in mandarin and lemon. The conclusions from 2018 were updated in 2024 following the request from the European Commission with regard to the endocrine-disrupting properties. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Determination of in vitro immunotoxic potencies of a series of perfluoralkylsubstances (PFASs) in human Namalwa B lymphocyte and human Jurkat T lymphocyte cells.

Exposure to PFASs is associated to several adverse health effects, such as immunotoxicity. Immunotoxic effects of PFOA and PFOS, including a reduced antibody response in both experimental animals and humans, have been reported. However, there is limited understanding of the underlying mechanisms involved. Moreover, there is only a restricted amount of immunotoxicity data available for a limited number of PFASs. In the current study the effects of 15 PFASs, including short- and long-chain perfluorinated carboxylic and sulfonic acids, fluorotelomer alcohols, and perfluoralkyl ether carboxylic acids were studied on the expression of recombinant activating gene 1 (RAG1) and RAG2 in the Namalwa human B lymphoma cell line, and on the human IL-2 promotor activity in Jurkat T-cells. Concentration-response data were subsequently used to derive in vitro relative potencies through benchmark dose analysis. In vitro relative potency factors (RPFs) were obtained for 6 and 9 PFASs based on their effect on RAG1 and RAG2 gene expression in Namalwa B-cells, respectively, and for 10 PFASs based on their inhibitory effect on IL-2 promotor activity in Jurkat T-cells. The most potent substances were HFPO-TA for the reduction of RAG1 and RAG2 gene expression in Namalwa cells (RPFs of 2.1 and 2.3 respectively), and PFDA on IL-2 promoter activity (RPF of 9.1). RAG1 and RAG2 play a crucial role in V (D)J gene recombination, a process for acquiring a varied array of antibodies crucial for antigen recognition. Hence, the effects observed in Namalwa cells might indicate a PFAS-induced impairment of generating a diverse range of B-cells essential for antigen recognition. The observed outcomes in the Jurkat T-cells suggest a possible PFAS-induced reduction of T-cell activation, which may contribute to a decline in the T-cell dependent antibody response. Altogether, the present study provides potential mechanistic insights into the reported PFAS-induced decreased antibody response. Additionally, the presented in vitro models may represent useful tools for assessing the immunotoxic potential of PFASs and prioritization for further risk assessment.

Updated peer review of the pesticide risk assessment of the active substance pydiflumetofen.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, France, and co-rapporteur Member State, Austria, for the pesticide active substance pydiflumetofen and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses of pydiflumetofen as a fungicide field application on pome fruits, grapes, potato, fruiting vegetables, cucurbits and Brassica vegetables and updated following the request from Commission to consider additional information submitted and review the risk assessment. The reliable endpoints, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment.

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8440/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full.

Peer review of the pesticide risk assessment of the active substance dimoxystrobin.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Hungary, and co-rapporteur Member State, Ireland, for the pesticide active substance dimoxystrobin as well as the assessment of maximum residue levels (MRLs) and confirmatory data following the review of the existing MRLs of dimoxystrobin according to Article 12 of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. In June 2023, the European Commission sent a mandate confirming the need to adopt and publish a conclusion on the peer review of the pesticide risk assessment of the active substance dimoxystrobin excluding the full assessment of endocrine-disrupting properties, containing all the results of the peer review process related to the renewal of approval as well as the assessment of the application for MRL for oilseed rapeseed, poppy seed, mustard seed and gold of pleasure seed, and the MRL application addressing the confirmatory data identified during the MRL review under Article 12 of Regulation (EC) No 396/2005. The conclusions were reached on the basis of the evaluation of the representative uses of dimoxystrobin as a fungicide on oilseed rape and sunflower. MRLs were assessed in rapeseeds, poppy seed, mustard seed and Gold of pleasure seed. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are presented where identified.

Peer review of the pesticide risk assessment of the active substance metalaxyl-M (amendment of approval conditions).

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, Greece, for the pesticide active substance metalaxyl-M are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative uses for the amendment to the conditions of approval of metalaxyl-M as a fungicide seed treatment for sunflower and spinach seeds intended to be sown in field and on the basis of data submitted to update the specified level of an impurity in the technical active substance. The reliable endpoints, appropriate for use in regulatory risk assessment are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance metribuzin.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Estonia, and co-rapporteur Member State, Germany, for the pesticide active substance metribuzin and the assessment of application to amend existing residue definition are reported. 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 use of metribuzin as a herbicide on potato and soybean (field use). 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 reported where identified.

Peer review of the pesticide risk assessment of the active substance metconazole.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, the United Kingdom, for the pesticide active substance are reported. 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 metconazole as a fungicide on cereals and oilseed rape and as a plant growth regulator on oilseed rape. 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 reported where identified.

Peer review of the pesticide risk assessment of the active substance folpet.

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 Austria and co-rapporteur Member State Italy for the pesticide active substance folpet and of confirmatory data following the MRL review under Article 12 of Regulation (EC) No 396/2005. 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 folpet as a fungicide on barley, wheat and wine grape (field uses) and tomato (field and greenhouse uses). The reliable end points, appropriate for use in regulatory risk assessment and the confirmatory data, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are reported where identified.

Peer review of the pesticide risk assessment of the active substance urea.

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 Greece and co-rapporteur Member State Finland for the pesticide active substance urea and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. 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 urea as an attractant of fruit fly Bactrocera oleae on olive crops. 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 reported where identified.

Peer review of the pesticide risk assessment of the active substance tritosulfuron.

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, Slovenia, and co-rapporteur Member State, Austria, for the pesticide active substance tritosulfuron are reported. 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 tritosulfuron as a herbicide on spring and winter cereals, spring cereals with undersown grasses and maize (field uses). 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 reported where identified.

Updated peer review of the pesticide risk assessment of the active substance mepanipyrim.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, Belgium, and co-rapporteur Member State, Greece, for the pesticide active substance mepanipyrim are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of mepanipyrim as a fungicide on table and wine grapes and in field and protected strawberries and tomatoes. The conclusions were updated with regard to the endocrine-disrupting properties following a mandate received from the European Commission in January 2019. 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 reported where identified.

Peer review of the pesticide risk assessment of the active substance milbemectin.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authorities of the rapporteur Member State, Germany, and co-rapporteur Member State, the Netherlands, for the pesticide active substance milbemectin are reported. 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 milbemectin as an acaricide and insecticide in strawberry (field and greenhouse), berries and black and white currant (field and greenhouse), apple, pear, cherry and plum (field) and ornamentals (field and greenhouse). 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 reported where identified.

Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells.

Per- and polyfluoroalkyl substances (PFASs) are omnipresent and have been shown to induce a wide range of adverse health effects, including hepatotoxicity, developmental toxicity, and immunotoxicity. The aim of the present work was to assess whether human HepaRG liver cells can be used to obtain insight into differences in hepatotoxic potencies of a series of PFASs. Therefore, the effects of 18 PFASs on cellular triglyceride accumulation (AdipoRed assay) and gene expression (DNA microarray for PFOS and RT-qPCR for all 18 PFASs) were studied in HepaRG cells. BMDExpress analysis of the PFOS microarray data indicated that various cellular processes were affected at the gene expression level. From these data, ten genes were selected to assess the concentration-effect relationship of all 18 PFASs using RT-qPCR analysis. The AdipoRed data and the RT-qPCR data were used for the derivation of in vitro relative potencies using PROAST analysis. In vitro relative potency factors (RPFs) could be obtained for 8 PFASs (including index chemical PFOA) based on the AdipoRed data, whereas for the selected genes, in vitro RPFs could be obtained for 11-18 PFASs (including index chemical PFOA). For the readout OAT5 expression, in vitro RPFs were obtained for all PFASs. In vitro RPFs were found to correlate in general well with each other (Spearman correlation) except for the PPAR target genes ANGPTL4 and PDK4. Comparison of in vitro RPFs with RPFs obtained from in vivo studies in rats indicate that best correlations (Spearman correlation) were obtained for in vitro RPFs based on OAT5 and CXCL10 expression changes and external in vivo RPFs. HFPO-TA was found to be the most potent PFAS tested, being around tenfold more potent than PFOA. Altogether, it may be concluded that the HepaRG model may provide relevant data to provide insight into which PFASs are relevant regarding their hepatotoxic effects and that it can be applied as a screening tool to prioritize other PFASs for further hazard and risk assessment.

A computational study on the biotransformation of alkenylbenzenes by a selection of CYPs: Reflections on their possible bioactivation.

Alkenylbenzenes are aromatic compounds found in several vegetable foods that can cause genotoxicity upon bioactivation by members of the cytochrome P450 (CYP) family, forming 1'-hydroxy metabolites. These intermediates act as proximate carcinogens and can be further converted into reactive 1'-sulfooxy metabolites, which are the ultimate carcinogens responsible for genotoxicity. Safrole, a member of this class, has been banned as a food or feed additive in many countries based on its genotoxicity and carcinogenicity. However, it can still enter the food and feed chain. There is limited information about the toxicity of other alkenylbenzenes that may be present in safrole-containing foods, such as myristicin, apiole, and dillapiole. In vitro studies showed safrole as mainly bioactivated by CYP2A6 to form its proximate carcinogen, while for myristicin this is mainly done by CYP1A1. However, it is not known whether CYP1A1 and CYP2A6 can activate apiole and dillapiole. The present study uses an in silico pipeline to investigate this knowledge gap and determine whether CYP1A1 and CYP2A6 may play a role in the bioactivation of these alkenylbenzenes. The study found that the bioactivation of apiole and dillapiole by CYP1A1 and CYP2A6 is limited, possibly indicating that these compounds may have limited toxicity, while describing a possible role of CYP1A1 in the bioactivation of safrole. The study expands the current understanding of safrole toxicity and bioactivation and helps understand the mechanisms of CYPs involved in the bioactivation of alkenylbenzenes. This information is essential for a more informed analysis of alkenylbenzenes toxicity and risk assessment.