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Challenges of In Vitro Disposition Modeling: First Insights from the Tox21 Project
Citation:
Wambaugh, J., B. Savage, G. Honda, D. Crizer, M. Devito, S. Ferguson, M. Feshuk, J. Harrill, N. Sipes, R. Thomas, AND K. Paul-Friedman. Challenges of In Vitro Disposition Modeling: First Insights from the Tox21 Project. Society of Toxicology Annual Meeting, Nashville, TN, March 19 - 23, 2023. https://doi.org/10.23645/epacomptox.22263784
Impact/Purpose:
A PowerPoint presentation has been prepared by John Wambaugh for presentation to the Society of Toxicology annual meeting as part of a symposium on “Challenges in the development of in vitro-in vivo extrapolation models for next generation risk assessment”. The presentation is entitled “Challenges of In Vitro Disposition Modeling: First Insights from the Tox21 Project."
Description:
Next Generation Risk Assessment (NGRA) hinges on quantitative determination of surrogate points of departure (PODs) using in vitro-in vivo extrapolation (IVIVE). Understanding in vitro disposition is critical for IVIVE since the free, effective concentration might be a hundredth or a hundred times the nominal test concentration. While mathematical models exist for predicting in vitro disposition from physico-chemical properties, the data for evaluating these predictions represent limited chemical structure diversity. The chemical library of the U.S. Federal Tox21 screening program contains thousands of diverse chemicals. The Tox21 library has already been screened in concentration-response mode for diverse bioactivities using high-throughput in vitro assays. In some cases of PODs -- based on nominal in vitro tested concentration -- have been identified. This presentation will describe how Tox21 has been collecting new data characterizing in vitro disposition of sentinel chemicals to assess any differences between nominal and free concentration. These data permit evaluation of a variety of mathematical models for in vitro disposition across a wider range of physico-chemical properties, including key chemical classes found in commerce and the environment. Accurate prediction of in vitro disposition will enhance the predictive power of quantitative NGRA.
URLs/Downloads:
DOI: Challenges of In Vitro Disposition Modeling: First Insights from the Tox21 Project
SOT2023-WAMBAUGH-INVITRODIST-3.PDF (PDF, NA pp, 3457.898 KB, about PDF)