Application of NAM-based Systemic Safety Toolbox

This technical report presents the application of a NAM-based systemic safety toolbox focusing on the bioactive food component sulforaphane. The report outlines methods for estimating internal exposure through PBK modeling, comparing in silico and in vitro data to refine predictions of maximum plasma concentration (Cmax). It details the evaluation of bioactivity exposure ratios (BER) for sulforaphane and benchmark chemicals, highlighting the relationship between points of departure (PODs) and bioactivity. The findings indicate that the NAM-based toolbox aims to enhance human health protection by integrating various data sources, including pharmacological profiling and transcriptomics. The report concludes that while the toolbox has been refined, further studies are necessary to clarify the risk categories of benchmark chemicals and the implications for sulforaphane's safety profile. The results suggest that the risk of sulforaphane remains uncertain, necessitating additional refinement of exposure scenarios and risk assessments.