Citation:

Ring, C., R. Pearce, Woodrow Setzer, AND J. Wambaugh. Inter-individual variability in high-throughput risk prioritization of environmental chemicals (IVIVE). Presented at IVIVE for HT Prioritization and Decision Making, Durham, NC, February 17 - 18, 2016. https://doi.org/10.23645/epacomptox.5063248

Impact/Purpose:

Invited presentation at IVIVE workshop for HT Prioritization and Decision Making in RTP, NC

Description:

We incorporate inter-individual variability into an open-source high-throughput (HT) toxicokinetics (TK) modeling framework for use in a next-generation risk prioritization approach. Risk prioritization involves rapid triage of thousands of environmental chemicals, most which have little or no existing TK data. Chemicals are prioritized based on model estimates of hazard and exposure, to decide which chemicals should be first in line for further study. Hazard may be estimated with in vitro HT screening assays, e.g., U.S. EPA’s ToxCast program. Bioactive ToxCast concentrations can be extrapolated to doses that produce equivalent concentrations in body tissues using a reverse TK approach in which generic TK models are parameterized with 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with physiological parameters for a virtual population. Here we draw physiological parameters from estimates of distributions of demographic and anthropometric quantities in the modern U.S. population based on the most recent CDC NHANES data. A Monte Carlo approach, accounting for the correlation structure of physiological parameters, is used to estimate ToxCast equivalent doses for the most sensitive portion of the population. For risk prioritization, ToxCast equivalent doses are compared to population estimates of exposure rates based on Bayesian inferences drawn from NHANES urinary analyte biomonitoring data. The inclusion of inter-individual variability in the TK modeling framework allows targeted risk prioritization for potentially sensitive sub-populations. (This abstract does not necessarily represent U.S. EPA policy.)

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