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EPA’s HTTK Research: In vitro Data and Generic TK Models for IVIVE
Citation:
Wambaugh, J., B. Wetmore, K. Paul-Friedman, S. Davidson, M. Devito, C. Ring, M. Breen, D. Kapraun, M. Evans, AND R. Thomas. EPA’s HTTK Research: In vitro Data and Generic TK Models for IVIVE. European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) invited workshop meeting, Brussels, N/A, BELGIUM, November 09 - 10, 2021. https://doi.org/10.23645/epacomptox.19131650
Impact/Purpose:
Invited presentation to the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) workshop meeting November 2021
Description:
Chemical-specific toxicokinetic in vitro data have been collected by EPA, its collaborators, and contractors for over a decade. These data allow in vitro-in vivo extrapolation (IVIVE) of bioactivity data from high throughput screening efforts like ToxCast and Tox21. Chemical-specific in vitro measurements are now available for more than one thousand compounds. One way that EPA makes these data publicly available is through the R package “httk”, which also includes a suite of models that can be parametrized with the in vitro data to make chemical-specific predictions of tissue concentrations as a function of exposure route and time. The generic models within “httk” include both empirical and physiologically-based toxicokinetic (PBTK) approaches. The models currently cover oral, intravenous, and inhalation exposure and efforts are underway to add dermal, aerosol, and gestational exposure. Tools are available to simulate human variability using Monte Carlo based upon biometric data and tissue-specific regressions. The predictions of “httk” are evaluated on the basis of their ability to reproduce measurements of in vivo tissue concentrations over time, which are now provided publicly through EPA’s CvTdb (Concentration vs. time database). Carefully quantifying the chemical- and scenario-specific uncertainty in data and models allows decision makers to consider the use of “httk” for IVIVE as well as any other situation where extrapolation using toxicokinetics may be useful. This abstract does not necessarily represent EPA policy.
URLs/Downloads:
DOI: EPA’s HTTK Research: In vitro Data and Generic TK Models for IVIVE
EPA’s HTTK Research: In vitro Data and Generic TK Models for IVIVE (PDF, 42 pp, 3131 KB, about PDF)