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In Vitro to In Vivo Extrapolation

A key issue with high-throughput in vitro testing methods is how to accurately relate concentrations of substances that induce in vitro responses to in vivo exposure concentrations that could result in human or animal illness or injury. This relationship is established through in vitro to in vivo extrapolation (IVIVE), the focus of a NICEATM webinar series and following workshop during February 2016.

Scientists interested in the use of IVIVE for substance screening and risk decision-making met at the 2016 workshop to develop best practices and identify areas for further research. The workshop, co-organized by NICEATM and the U.S. Environmental Protection Agency, was summarized in a 2018 publication in the journal Toxicology In Vitro (Bell et al. 2018).

NICEATM's computational toxicologists are developing methods for conducting IVIVE analyses, described in a publication in the journal Applied In Vitro Toxicology (Chang et al. 2014). Current work is focused on understanding the impact of various parameters, such as using free plasma concentration as a surrogate for total plasma concentration, and comparing multiple modeling approaches.

Application of these IVIVE approaches to predict the potential of substances to cause developmental toxicity and to interact with the endocrine system was described in a poster presented at the 2017 SOT Annual Meeting (Chang et al.). A workflow for conducting these analyses is planned for a future release of the Integrated Chemical Environment resource.