Statement on the BfR opinion regarding the toxicity of 2-chloroethanol.

In accordance with Art. 31(1) of Regulation (EC) No 178/2002, the Commission asked EFSA to provide a scientific review on the BfR opinion on the 'Health risk assessment of ethylene oxide residues in sesame seeds' (Opinion No 024/2021) regarding the toxicity of 2-chloroethanol. In addition, EFSA was asked to clarify under which circumstances the use of the MOE approach is considered appropriate. Based on the information available to EFSA, i.e. the studies assessed in the frame of the BfR opinion and additional data provided by stakeholders not assessed by BfR, EFSA considers the genotoxicity of 2-chloroethanol as inconclusive. On this basis, EFSA would not recommend setting reference points for risk assessment or health-based guidance values until the genotoxic potential of 2-chloroethanol is clarified. EFSA therefore recommends performing new in vitro gene mutation and in vitro micronucleus tests with 2-chloroethanol following the recommendations of the most recent OECD technical guidelines to clarify its genotoxic potential. If the result of any of the test is positive, the recommendations of the EFSA Scientific Committee (2011) should be followed. If the genotoxic potential of 2-chloroethanol is finally clarified and overall negative, EFSA would recommend setting the reference point for deriving health-based guidance values based on existing toxicity studies on 2-chloroethanol.

Peer review of the pesticide risk assessment of the active substance sheep fat.

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the Czech Republic (CZ) and co-rapporteur Member State France (FR) for the pesticide active substance sheep fat 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 sheep fat as a repellent on deciduous and coniferous trees in forestry. 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.

Peer review of the pesticide risk assessment for the active substance propyzamide in light of confirmatory data submitted.

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State Sweden, for the pesticide active substance propyzamide are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information in the areas of mammalian toxicology and residues. The conclusions were reached on the basis of the evaluation of the representative uses of propyzamide as an herbicide on lettuce and winter oilseed rape. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Concerns are identified.

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

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State the Czech Republic and co-rapporteur Member State France for the pesticide active substance fish oil 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 fish oil as a game repellent on deciduous and coniferous trees in forestry. 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.

Peer review of the pesticide risk assessment for the active substance penthiopyrad in light of confirmatory data submitted.

The conclusions of EFSA following the peer review of the initial risk assessment carried out by the competent authority of the original rapporteur Member State United Kingdom supported by the new rapporteur Member State Sweden, for the pesticide active substance penthiopyrad are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information in the area of mammalian toxicology. The European Commission mandated EFSA to arrange a further peer review of the confirmatory data. The conclusions were reached on the basis of the evaluation of the representative uses of penthiopyrad as a fungicide on pome fruit, tomato, aubergines, cucurbits, cucumbers, courgettes and cereals. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Concerns are identified.

Peer review of the pesticide risk assessment of the active substance Bacillus thuringiensis subsp. kurstaki strain ABTS-351.

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, Denmark, and co-rapporteur Member State, the Netherlands, for the pesticide active substance Bacillus thuringiensis subsp. kurstaki strain ABTS-351 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 Bacillus thuringiensis subsp. kurstaki strain ABTS-351 as an insecticide on cabbage (field use) and tomato (permanent greenhouse and walk-in tunnel 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 identified.

Updated peer review of the pesticide risk assessment of the active substance asulam (variant evaluated asulam-sodium).

The conclusions of EFSA following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, the United Kingdom (France after Brexit), for the pesticide active substance asulam 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 use of asulam (variant evaluated asulam-sodium) as a herbicide on spinach and tulip, hyacinth and lily for bulb production. MRLs were assessed in spinach. The conclusions were updated with regard to the endocrine-disrupting properties following a mandate received from the European Commission in February 2019. In addition, the peer review also provided considerations on whether exposure to humans and the environment from the representative uses of asulam-sodium can be considered negligible, taking into account the European Commission's draft guidance on this topic. 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 identified. An evaluation of data concerning the necessity of asulam-sodium as a herbicide to control a serious danger to plant health which cannot be contained by other available means, including non-chemical methods is also presented.

Peer review of the pesticide risk assessment of the active substance Spodoptera exigua multicapsid nucleopolyhedrovirus (SeMNPV).

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, Spain, for the pesticide active substance Spodoptera exigua multicapsid nucleopolyhedrovirus 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 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 Spodoptera exigua multicapsid nucleopolyhedrovirus as an insecticide on pepper and leafy vegetables (lettuce crops) (field, greenhouse and walk-in tunnel uses). 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 identified.

Peer review of the pesticide risk assessment of the active substance benthiavalicarb (variant assessed benthiavalicarb-isopropyl).

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, Poland, and co-rapporteur Member State, France, for the pesticide active substance benthiavalicarb (variant assessed benthiavalicarb-isopropyl) 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 benthiavalicarb-isopropyl as a fungicide on potato (field use). The peer review also provided considerations on whether exposure to humans and the environment from the representative uses of benthiavalicarb-isopropyl can be considered negligible, taking into account the European Commission's draft guidance on this topic. 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. An evaluation of data concerning the necessity of benthiavalicarb-isopropyl as a fungicide to control a serious danger to plant health which cannot be contained by other available means, including non-chemical methods, is also presented.

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

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, Sweden, and co-rapporteur Member State, Italy, for the pesticide active substance bifenazate 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 bifenazate as an acaricide on strawberry, fruiting vegetables (tomatoes, peppers, aubergines, cucumbers, courgettes, melons, watermelons), flowering and ornamental plants and nursery ornamentals and updated following the request to peer review the exposure and risk assessments for bifenazate. 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.

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

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, Spain, and co-rapporteur Member State, the Netherlands, for the pesticide active substance clofentezine 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, 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 clofentezine as an acaricide on citrus, pome fruits, strawberry, tomatoes and aubergine. The peer review also provided considerations on whether exposure to humans and the environment from the representative uses of clofentezine can be considered negligible, taking into account the European Commission's draft guidance on this topic. 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. An evaluation of data concerning the necessity of clofentezine as acaricide to control a serious danger to plant health which cannot be contained by other available means, including non-chemical methods is also presented.

Peer review of the pesticide risk assessment of the active substance pelargonic acid (nonanoic acid).

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, Greece, and co-rapporteur Member State, Austria, for the pesticide active substance pelargonic acid (nonanoic acid) 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 use of pelargonic acid as a herbicide on vineyards, potatoes, paths and places with woody plants, ornamental shrubs, ornamentals lawn, home gardens and allotments, paths and open areas with tree growth, woody ornamentals, decorative lawns, turf (field use). The reliable end points appropriate for use in regulatory risk assessment are presented. Assessments not finalised and missing information identified as being required by the regulatory framework are listed.

Peer review of the pesticide risk assessment for the active substance acibenzolar-S-methyl in light of confirmatory data submitted.

The conclusions of the EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State, France, for the pesticide active substance acibenzolar-S-methyl are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the endocrine disruption potential of the substance. The conclusions were reached on the basis of the evaluation of the representative uses of acibenzolar-S-methyl as a plant activator on pome fruit, tomato and tobacco. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and literature in the dossier peer reviewed, are presented. Assessments not finalised together with the missing information identified as being required by the regulatory framework are listed.

Studies on articular and general toxicity of orally administered ozenoxacin in juvenile rats and dogs.

AIM: Ozenoxacin is a nonfluorinated quinolone antibacterial approved for topical treatment of impetigo. Because quinolones have known chondrotoxic effects in juvenile animals, the potential toxicity of ozenoxacin was assessed in preclinical studies. MATERIALS & METHODS: Ozenoxacin or ofloxacin (300 mg/kg/day for 5 days, for each compound) was orally administered to juvenile rats, and oral ozenoxacin (10-100 mg/kg/day for 14 days) was administered to juvenile dogs. RESULTS: In juvenile rats, ozenoxacin showed no chondrotoxicity, whereas ofloxacin produced typical quinolone-induced lesions in articular cartilage in three of ten rats. Oral ozenoxacin administration to juvenile dogs showed no chondrotoxicity or toxicologically relevant findings in selected target organs. CONCLUSION: Ozenoxacin was generally well-tolerated in juvenile rats and dogs, with no evidence of quinolone-induced arthropathy.

Evaluation of the genotoxic potential of the natural neurotoxin Tetrodotoxin (TTX) in a battery of in vitro and in vivo genotoxicity assays.

The genotoxic potential of the natural neurotoxin Tetrodotoxin (TTX) was evaluated in a battery of in vitro and in vivo genotoxicity assays. These comprised a bacterial reverse-mutation assay (Ames test), an in vitro human lymphocyte chromosome-aberration assay, an in vivo mouse bone-marrow micronucleus assay and an in vivo rat-liver UDS assay. Maximum test concentrations in in vitro assays were determined by the TTX limit of solubility in the formulation vehicle (0.02% acetic acid solution). In the Ames test, TTX was tested at concentrations of up to 200 microg/plate. In the chromosome-aberration assay human lymphocytes were exposed to TTX at concentrations of up to 50 microg/ml for 3 and 20 h in the absence of S9, and for 3h in the presence of S9. For the in vivo assays, maximum tested dose levels were determined by the acute lethal toxicity of TTX after subcutaneous administration. In the mouse micronucleus assay TTX dose levels of 2, 4 and 8 microg/kg were administered to male and female animals, and bone-marrow samples taken 24 and 48 h (high-dose animals only) after administration. In the UDS assay, male rats were given TTX on two occasions with a 14-h interval at dose levels of 2.4 and 8 microg/kg, the last dose being administered 2h before liver perfusion and hepatocyte culturing. Relevant vehicle and positive control cultures and animals were included in all assays. TTX was clearly shown to lack in vitro or in vivo genotoxic activity in the assays conducted in this study. The results suggest that administration of TTX as a therapeutic analgesic agent would not pose a genotoxic risk to patients.

Assessment of heavy metal levels in Almendares River sediments--Havana City, Cuba.

The Almendares River watershed covers a large portion of Havana, Cuba and is centrally important to both recreational and other activities in the region. In order to assess current water quality conditions prior to planned remediation efforts, the spatial distribution of six heavy metals and other compounds were determined in river sediments at fifteen sampling stations in the watershed. Metal concentrations in sediments ranged from 86.1 to 708.8 for Zn, 39.3 to 189.0 for Pb, 71.6 to 420.8 for Cu, 84.4 to 209.7 Cr, 1.5 to 23.4 for Co, and 1.0 to 4.3 for Cd microg/g dry weight sediment. Calculated enrichment factors (EF; measured metal versus background mineral conditions) were almost always greater than 1.0, suggesting significant anthropogenic impact on metal levels in the river. The highest EF values were seen immediately below Cotorro (EF>10 for Pb, Cu, and Cd), a suburban town that has an active secondary smelter, and below the largest municipal landfill in Havana (EF>10 for Pb, Cu, Cd, and Zn). Further, three sampling stations had multiple metals at concentrations higher than probable effects concentrations (PEC), implying possible local ecotoxicological impacts. Finally, sequential extractions of the sediments indicated that heavy metals were largely associated with the organic fraction, and it was estimated that up to 62% of metals in the sediments would be susceptible to release back into the water column if hydraulic or other changes occurred in the river. These data are being used to prioritize decisions related to the remediation of the river system.

Comparative genotoxic evaluation of 2-furylethylenes and 5-nitrofurans by using the comet assay in TK6 cells.

The genotoxicity of three 2-furylethylene derivatives and four 5-nitrofurans was evaluated by using the comet assay in human lymphoblastoid cultured TK6 cells. The 2-furylethylene derivatives were 2-furyl-1-nitroethene, 1-(5-bromofur-2-yl)-2-nitroethene and 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene, while the 5-nitrofurans were nitrofurantoin, nitrofurazone, furazolidone and 5-nitro-2-furanacrolein. The treatments lasted for 3 h in the absence of metabolic activation. No genotoxic effects were observed for two of the 2-furylethylene compounds, while the derivative 1-(5-bromofur-2-yl)-2-nitroethene showed a statistically significant response mainly at the highest concentration tested; this effect was considered biologically relevant and the compound was classified as slightly genotoxic. On the other hand, for the classical 5-nitrofurans tested there is a tendency towards a dose-related increase of the DNA damage in the comet assay and the observed increases for the parameters analysed (Olive tail moment, tail % DNA and tail length) were significant for all compounds. Then, the four 5-nitrofurans tested were considered genotoxic. These results show that the position of the nitro group influences the genotoxicity of the assayed compounds. Thus, in this comet assay, the 2-furylethylene derivatives having the nitro group attached outside the furan ring appear to be much less genotoxic than the 5-nitrofurans.

In vivo genotoxic evaluation of the furylethylene derivative 1-(5-bromofur-2-yl)-2-nitroethene in mouse bone marrow.

The genotoxic potential of the compound 1-(5-bromofur-2-yl)-2-nitroethene (2-ßNF) has been tested by using the in vivo mouse bone marrow micronucleus assay. Its ability to induce clastogenicity or aneugenicity, through the induction of micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow cells has been evaluated. Treatment groups of five CD-1 male mice were administered once intraperitoneally at the doses of 10, 20, and 30mg/kg, and their bone marrows were sampled at 24 and 48h after the administration, at the first sampling time animals administered with the three doses were used, and in the second sampling time, only animals administered with the highest dose were used. All animals treated with the highest dose of the test compound (30mg/kg) showed evident clinical symptoms of toxicity such as irritation, hunched posture, slight ataxia, dyspnoea, piloerection, and palpebral ptosis. However, no marked depression of bone marrow cell proliferation was observed, and no significant increases in the frequency of MNPCE were obtained in any of the concentrations tested at any sampling times. The positive control treated-animals were administered with cyclophosphamide at the dose of 40mg/mL. The compound caused a significant increase in the number of MNPCE in all treated animals, demonstrating the sensitivity of the mouse strain used. From the results obtained, it is concluded that the compound 2-ßNF is neither clastogenic nor aneugenic in the erythrocytes from the bone marrow of treated mice at the doses tested.

Genotoxicity testing of the furylethylene derivative 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene in cultured human lymphocytes.

The genotoxic potential of the compound 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene (G-1) was evaluated in peripheral blood lymphocytes cultured in vitro, at concentrations ranging from 1 to 20 microg/ml. Micronuclei (MN) and sister-chromatid exchanges (SCE) were scored as biomarkers of genotoxic effects. To detect the role of metabolic enzymes on the genotoxicity of this furylethylenic derivative, cultures for MN and SCE demonstrations were treated for 3 h with and without the S9 microsomal fraction as well as for 48 h without S9. Under the conditions of the study, the test agent did not induce significant increases in the frequency of micronucleated cells, irrespective of the presence/absence of the metabolic fraction. Nevertheless, a slight/moderate increase in the SCE frequency was observed in those cultures treated without the S9 mix. In addition, cytotoxic/cytostatic effects of the G-1 compound were observed mainly in cultures without S9 fraction, as indicated by the reduction of cell proliferation measured by the cytokinesis block proliferation index (CBPI) and the proliferative rate index (PRI).

In vitro genotoxicity testing of the furylethylene derivative UC-245 in human cells.

The possible genotoxic potential of the 2-furylethylene derivative UC-245 has been evaluated in vitro using human cells as a test system. This compound was synthesized at the Centro de Bioactivos Químicos, Universidad Central de Las Villas (Cuba) and it appears to be effective against leishmaniosis. The induced genetic damage was determined by scoring the frequency of micronuclei (MN) and the frequency of sister chromatid exchanges (SCE) in primary lymphocyte cultures set up from two different donors. The DNA breakage level was also evaluated by the Comet assay, using an established human lymphoblastoid cell line (TK6). For the MN and SCE studies, to detect eventual metabolic modification in the genotoxicity of this compound, the cultures were treated with S9 microsomal fraction. The results obtained indicate that, under the experimental conditions used, the test agent does not induce significant increases in the frequency of micronucleated cells, irrespective of presence/absence of the metabolic fraction, which would indicate a lack of clastogenic and/or aneugenic potential. Nevertheless, a clear and significant increase in the SCE frequency was observed in the treatments without S9. This would support the 2-furylethylene derivative UC-245 inducing DNA primary damage. In addition, the results obtained in the Comet assay also show that UC-245 induces a significant increase in the level of DNA breakage, which would confirm its genotoxicity.