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Evaluating High Throughput Toxicokinetics and Toxicodynamics for IVIVE (WC10)
Wambaugh, J., R. Pearce, G. Honda, M. Hughes, C. Ring, L. Pham, B. Wetmore, AND Woodrow Setzer. Evaluating High Throughput Toxicokinetics and Toxicodynamics for IVIVE (WC10). Presented at World Congress on Alternatives and Animal Use in the Life Sciences, Washington, Seattle, August 20 - 24, 2017.
This is a presentation for the World Congress on Alternatives and Animal Use in the Life Sciences. This is an invited presentation to session on "In Vitro to In Vivo Extrapolation (IVIVE): New Approaches, Considerations, and Implementation".
High-throughput screening (HTS) generates in vitro data for characterizing potential chemical hazard. TK models are needed to allow in vitro to in vivo extrapolation (IVIVE) to real world situations. The U.S. EPA has created a public tool (R package “httk” for high throughput toxicokinetics) for TK and physiologically-based TK (PBTK). We are now able to rapidly parameterize generic PBPK models using in vitro data to allow IVIVE for 543 chemicals. We evaluate using four R’s: We have (1) Reused existing TK data by compiling a library of TK time course data in, this data has (2) Refined the design of in vivo TK studies, allowing us to perform new, informative experiments for high value chemicals using a (3) Reduced (n=6) study design. Careful evaluation of the existing and new data allows comparison of the results of in vitro HTS bioactivity assays with previously collected in vivo toxicity studies. In some cases, we may be able to (4) Replace in vivo animal studies with HTS and HTTK. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:WAMBAUGH-HTTK-DRAFT3_FINAL.PDF (PDF,NA pp, 1231.808 KB, about PDF)
WCA-HTTK2.PDF (PDF,NA pp, 74.992 KB, about PDF)