You are here:
In Vitro to In Vivo Extrapolation Incorporating Toxicokinetics (EMGS 2021)
Citation:
Paul-Friedman, K. AND M. Beal. In Vitro to In Vivo Extrapolation Incorporating Toxicokinetics (EMGS 2021). Environmental Mutagenesis & Genomics Society (EMGS) Virtual Annual Meeting 2021, NA (Virtual), Virtual, September 22 - 25, 2021. https://doi.org/10.23645/epacomptox.17311475
Impact/Purpose:
Presentation to the Environmental Mutagenesis and Genomics Society meeting September 2021. The purpose of this presentation is to share information with the EMGS community on case studies that incorporate in vitro to in vivo extrapolation of dose for point of departure estimates as well as training on how this is done operationally using high-throughput toxicokinetic data and models in the httk R package.
Description:
Thousands of chemicals exist in commerce internationally with constant introduction of new and complex substances, highlighting the ongoing importance of innovative approaches to identify emerging genotoxicants of concern. For many chemicals, there is an absence of genotoxicity data from traditional animal studies, and recent modernization efforts are seeking alternative testing strategies that minimize animal use. New approach methodologies (NAMs), consisting of in vitro toxicology tests and computational models, hold great promise in modernizing and accelerating the pace of chemical risk assessment. In order to apply NAM data for quantitative risk assessment, in vitro to in vivo extrapolation (IVIVE) models are required to account for chemical disposition. One approach to IVIVE being used for large numbers of chemicals with limited data utilizes chemical-specific screening data and generalized, high-throughput toxicokinetic models. These IVIVE models estimate external doses required to achieve genotoxic concentrations in the plasma that are equivalent to the concentrations where genotoxicity occurs in the test model following exposure. Thus, IVIVE provides points of departure (PODs) useful for deriving margins of exposure. This presentation will focus on collaborative case studies applying IVIVE to demonstrate the utility of in vitro toxicity data in quantitative assessments and prioritization efforts. The results of these studies suggest that NAM-based PODs are protective of human health relative to traditional PODs. Through this presentation, the concepts of IVIVE and HTTK modeling will be introduced, while lessons learned from the case studies and lingering uncertainties will be discussed. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: In Vitro to In Vivo Extrapolation Incorporating Toxicokinetics (EMGS 2021)
PAUL-FRIEDMAN_EMGS_PRESENTATION_V7.PDF (PDF, NA pp, 3681.46 KB, about PDF)