Advancing systemic toxicity risk assessment: Evaluation of a NAM-based toolbox approach

• DOI: 10.1093/toxsci/kfae159
• Publication Date: 2024-12-18T16:41:15Z
• Authors: Sophie Cable; Maria Teresa Balt...; Fazila Bunglawala; Paul L Carmichael; Leonardo Contreas; Matthew Philip Dent; Jade Houghton; Predrag Kukic; Sophie Malcomber; Beate Nicol; Katarzyna R Przyb...; Ans Punt; Georgia Reynolds; Joe Reynolds; Sharon Scott; Dawei Tang; Alistair M Middleton
• Keywords: Toolbox; Animal testing

Abstract For many years, a method that allowed systemic toxicity safety assessments to be conducted without generating new animal test data, seemed out of reach. However, several different research groups and regulatory authorities are beginning use variety in silico, chemico vitro techniques inform decisions. To manage this transition animal-free responsibly, it is important ensure the level protection offered by assessment based on approach methodologies (NAMs), at least as high provided traditional studies. end, we have developed an evaluation strategy assess both utility NAM-based ‘toolbox’. The toolbox comprises physiologically-based kinetic (PBK) models predict internal exposures, bioactivity NAMs designed give broad coverage across modes action. output calculation bioactivity: Exposure ratio (analogous margin exposure), which can used decision-making. In work expanded upon initial pilot study 10 chemicals with additional 38 70 consumer exposure scenarios. We found that, for majority these (>90%), workflow protective human health, enabling us make decisions preventing unnecessary use. also identified critical areas improvement further increase our confidence robustness approach.