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All of life’s great journeys start with a goal in mind! The 2007 NAS report, Toxicity Testing in the 21st Century – A Vision and A Strategy, has proposed a clear goal. This report envisions a not-so-distant future where all routine toxicity testing for environmental agents will be conducted in human cells in vitro evaluating perturbations of cellular responses in a suite of toxicity pathway assays. Dose response modeling would utilize computational systems biology models of the circuitry underlying each toxicity pathway; in vitro to in vivo extrapolations would use pharmacokinetic models, ideally physiologically based pharmacokinetic models, to predict human blood and tissue concentrations under specific exposure conditions. Results from these toxicity pathway assays and associated dose response modeling tools rather than those from high dose studies in animals would represent the new gold standard for chemical risk assessment. This talk focuses on some of the scientific challenges required to make this vision a reality, including characteristics of assay design, prospects for mapping and modeling toxicity pathways, assay validation, and biokinetic modeling. All of these tools necessary for this transformation of toxicity testing to an in vitro platform are either available or in advanced development. Science must lead the transformation. The scientific community, animal alternatives groups, regulatory agencies, and funding organizations will also have to muster the resolve to work together to make this vision a reality.


open access article