Citation:

Bell, S., X. Chang, J. Wambaugh, D. Allen, M. Bartels, K. Brouwer, W. Casey, N. Choksi, S. Ferguson, G. Fraczkiewicz, A. Jarabek, A. Ke, A. Lumen, S. Lynn, A. Paini, Paul S Price, C. Ring, T. Simon, N. Sipes, C. Sprankle, J. Strickland, J. Troutman, B. Wetmore, AND N. Kleinstreuer. In vitro to in vivo extrapolation for high throughput prioritization and decision making. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, 47:213-227, (2018). https://doi.org/10.1016/j.tiv.2017.11.016

Impact/Purpose:

This review is the outcome of a workshop held in RTP in February 2016 entitled “In Vitro to In Vivo Extrapolation for High Throughput Prioritization and Decision Making. In vitro to in vivo extrapolation requires a model to relate active in vitro concentrations to an in vivo response-inducing dose. Models for regulatory use will vary depending on needs: prioritization vs. hazard assessment. Transparency and reporting standards for models are critical during implementation.

Description:

Human-based in vitro chemical safety testing methods provide efficient and economical tools with the potential to provide relevant assessments of human health risk. Realizing this potential requires the availability of methods to relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). A variety of IVIVE approaches have been developed but need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop webinar series. Here, we integrate content from the webinars and workshop to discuss key aspects contributing to successful inclusion of IVIVE in regulatory decision-making. We discuss key aspects of models that can successfully generate predictions of external in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making and prioritization.

URLs/Downloads:

Record Details: