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The National Academies of Sciences 2007 report, "Toxicity Testing in the 21 st Century: A Vision and A Strategy" envisions toxicity testing using human cells in vitro to evaluate perturbations of cellular response networks and coupling results from these assays with computational systems biology and in vitro-in vivo extrapolations (IVIVE) to complete human safety assessments.To support this transition in toxicity testing, our laboratory is evaluating key cell response networks to develop proof of concept safety assessments for a series of prototype compounds and networks, including the DNA damage response pathway.