Work

P30-38 Towards phasing out acute toxicity in vivo testing in EU chemical safety assessments

Year: 2025

Type: article

Abstract: To this day, in the European Union (EU) the potential acute toxicity of chemicals is still mostly assessed based on results from in vivo testing in rodents. In July 2023, the European Commission (EC) announced the preparation of a “roadmap towards phasing out animal testing in chemical safety assessments”, expected to be published early 2026. In the context of the roadmap work, the replacement of in vivo testing with in silico predictions as the default methodology for acute oral toxicity (AOT) assessment under EU chemicals legislation has been identified as having great potential in the short term. Here, we report the outcome of this work performed by an international expert group towards this target. First, we present results of an analysis of the legal frameworks within the scope of the EC roadmap with respect to the legal requirements/regulatory needs as well as to a possible need for updating legal or guidance texts in case in silico methods were to become the new standard methodology for assessing AOT. Next, possible benchmarks for acceptable predictivity of in silico models AOT are discussed and progress with the curation of a large AOT reference data set and the subsequent performance assessment of the CATMoS in silico tool (DOI: 10.1289/EHP8495) is reported as a pilot for the validation of further in silico tools in the future. In addition, the presentation will provide an outlook on mid- to long-term activities envisaged under the roadmap, directed towards investigating potentially acceptable conditions for waiving AOT testing, towards complementing in silico methods with suitable in vitro test designs for out-of-domain chemicals and for developing animal-free strategies for the dermal and inhalation exposure routes as well.

Source: Toxicology Letters

DOI: 10.1016/j.toxlet.2025.07.899