Evaluation of Systemic Safety Toolbox for Risk Assessment

This technical report evaluates a systemic safety toolbox designed for use in Next Generation Risk Assessment (NGRA). The report discusses the effectiveness of non-animal data methods in safety assessments and presents findings from a pilot study and a full evaluation involving various chemicals. The pilot study involved ten chemicals and aimed to optimize experimental design, while the full evaluation included 38 chemicals to assess the toolbox's protectiveness and utility. Key components of the NGRA workflow include estimating internal exposure through physiologically-based kinetic models and calculating a Bioactivity Exposure Ratio (BER) to determine risk levels. The results indicate that the toolbox is 93% protective for high-risk scenarios and 24% effective in identifying low-risk scenarios. The report also compares the toolbox's performance with traditional in vivo data, suggesting that a higher-tier approach may be necessary for accurate risk classification. Overall, the findings support the consideration of non-animal methods in early tier safety assessments.