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Incorporating High-Throughput In Vitro Bioactivity and Toxicokinetics with Predicted Exposure to Advance Screening-Level Human Health Risk Assessment
Citation:
Paul-Friedman, K. AND R. Thomas. Incorporating High-Throughput In Vitro Bioactivity and Toxicokinetics with Predicted Exposure to Advance Screening-Level Human Health Risk Assessment. Presented at SETAC NA Annual Meeting, Minneapolis, Minnesota, November 12 - 16, 2017. https://doi.org/10.23645/epacomptox.6861992
Impact/Purpose:
Advancement toward the goal of accelerated risk assessment by incorporated high-throughput predictions of bioactivity, toxicokinetics, and exposure for risk assessment is discussed using a case study.
Description:
Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year, but only a small fraction of chemicals have been adequately evaluated for potential human health effects due to resource-intensive methods. Use of high-throughput, in vitro bioactivity data to estimate point-of-departures (PODs) has the potential to accelerate human health risk assessments. In the U.S. EPA’s ToxCast program, high-throughput in vitro assays broadly characterized the biological activity and potential mechanisms of ~1,800 chemicals. In vitro toxicokinetic assays and in vitro-to-in vivo extrapolation modeling enable conversion of in vitro bioactive concentrations to estimated administered dose equivalents (mg/kg/day). The U.S. EPA’s ExpoCast project uses key aspects of chemical production, fate, transport, and personal use to predict human exposure. Advancement toward the goal of accelerated risk assessment by incorporated high-throughput predictions of bioactivity, toxicokinetics, and exposure for risk assessment will be discussed using a case study. PODs predicted using high-throughput methods and PODs from traditional animal toxicology studies were compared to high-throughput predictions of exposure for ~400 chemicals. The results demonstrate the feasibility, and continuing challenges, of using high-throughput predictions of bioactivity to estimate PODs in screening level assessments. This abstract does not necessarily reflect U.S. EPA policy.
URLs/Downloads:
DOI: Incorporating High-Throughput In Vitro Bioactivity and Toxicokinetics with Predicted Exposure to Advance Screening-Level Human Health Risk Assessment
NEW TECHNOLOGIES FOR 21ST CENTURY RISK ASSESSMENT_SETAC_NOV_2017.PDF (PDF, NA pp, 2178.296 KB, about PDF)