“Next Generation Risk Assessment” (NGRA) to assess the genotoxicity of chemical compounds without the use of experimental animals. (FWOSB107)

Worldwide, the development of new strategic tools to test chemicals for human health adverse effects is high on the agenda. One of the reasons is the increasing ethical, economic and scientific pressure to reduce the use of experimental animals. In Europe, a regulatory testing and marketing ban even exists for dermato-cosmetic products. “New Generation Risk Assessment” (NGRA) frameworks that put more emphasis on exposure and mechanistic information can help to address the challenges associated with this “paradigm shift”. Consequently, interest to apply NGRA for different toxicological endpoints is rapidly growing. In this project, the applicability of an NGRA without the use of animals will be investigated for genotoxicity. Mechanistic information obtained with innovative non-animal methods, also known as new approach methodologies (NAMs, e.g. in chemico, in silico and in vitro), will be integrated in an NGRA, based on the available “Adverse Outcome Pathways” (AOPs) for genotoxicity. Focus will be put on the possible role of transcriptomicsbased biomarkers, and more specifically, on the GENOMARK tool. This biomarker in human-derived metabolically competent cells can provide important mechanistic insights and will therefore be further optimized. The practical applicability of the NGRA framework enriched with mechanistic information within the risk assessment process will be investigated by means of two case studies using data-rich dermato-cosmetic substances

Keywords:next generation risk assessment, genotoxicity, transcriptomics, adverse outcome pathways, new approach methodologies

Disciplines:Biomarker evaluation, In vitro testing, Drug discovery and development not elsewhere classified, Toxicogenomics