Protectiveness of NAM-based hazard assessment - which testing scope is required?

Hazard assessment requires toxicity tests to allow deriving protective points of departure (PoDs) for risk assessment irrespective of a compound’s mode of action (MoA). The scope of in vitro test batteries (ivTB) needed to assess systemic toxicity is still unclear. We explored the protectiveness regarding systemic toxicity of an ivTB with a scope that was guided by previous findings from rodent studies, where examining six main targets, including liver and kidney, was sufficient to predict the guideline scope-based PoD with high probability.

Model-based translation of DNA damage signaling dynamics across cell types.

Interindividual variability in DNA damage response (DDR) dynamics may evoke differences in susceptibility to cancer. However, pathway dynamics are often studied in cell lines as alternative to primary cells, disregarding variability. To compare DDR dynamics in the cell line HepG2 with primary human hepatocytes (PHHs), we developed a HepG2-based computational model that describes the dynamics of DDR regulator p53 and targets MDM2, p21 and BTG2.