EPA CompTox Communities of Practice

March 26 / 10:00 AM - 11:00 AM EDT
03/26/20 10:00 AM 03/26/20 11:00 AM America/New_York EPA CompTox Communities of Practice United States

High Throughput Inhalation Toxicokinetics with the HTTK R Package

Speaker: Dr. John Wambaugh, Physical Scientist in the Center for Computational Toxicology and Exposure (CCTE)

This webinar will provide basics on in vitro-in vivo extrapolation (IVIVE) for applying in vitro toxicity screening data to real world scenarios. We will start with background material on "high throughput toxicokinetics" -- the combination of in vitro measurement of key toxicokinetic parameters and generic mathematical and physico-chemical modeling of toxicokinetics. Then we will describe the recently developed generic gas inhalation physiologically-based toxicokinetic (PBTK) model. The new model has been evaluated across 41 volatile organic chemicals (VOCs) and provides a foundation for applying IVIVE to new chemical classes.

The new gas inhalation PBTK model has been incorporated into the recently released HTTK R Package version 2.0.1. The HTTK R Package is composed of four toxicokinetic models that are designed to be parameterized using high-throughput in vitro data (plasma protein binding and hepatic clearance), as well as structure-derived physicochemical properties and species-specific physiological data. Using these models allows for the inclusion of toxicokinetics in the statistical analysis of chemicals undergoing high-throughput screening. HTTK provides free, open-source models as well as chemical-specific data on 987 chemicals in humans and 212 chemicals in rats.