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APCRA Case Study: High Throughput Toxicokinetics for In Vitro-In Vivo Extrapolation
Citation:
Wambaugh, J., T. Barton-Maclaren, M. Beal, M. Devito, J. Dorne, S. Ferguson, M. Hughes, R. Judson, A. Long, I. Moffat, K. Paul-Friedman, S. Stavroula, R. Thomas, AND B. Wetmore. APCRA Case Study: High Throughput Toxicokinetics for In Vitro-In Vivo Extrapolation. APCRA 7, Helsinki, FINLAND, April 25 - 27, 2023. https://doi.org/10.23645/epacomptox.22647385
Impact/Purpose:
A PowerPoint slide presentation has been prepared by John Wambaugh for the APCRA 7 meeting in Helsinki, Finland. Accelerating the Pace of Chemical Risk Assessment (APCRA) Is an international governmental collaborative initiative focused on translating new approach methodologies (NAMs) into chemical risk decision making. The seventh APCRA meeting is being hosted by the European Food Safety Authority (EFSA). This presentation is entitled “APCRA Case Study: High Throughput Toxicokinetics for In Vitro-In Vivo Extrapolation”. The case study being presented will eventually result in a peer reviewed manuscript. The presentation has been internally reviewed by Dr. Katie Paul Friedman (EPA).
Description:
This product will investigate how HTTK, with appropriately propagated uncertainty, enhances new approach methodology (NAM)-based prediction of in vivo points of departure to inform regulatory decision making. Since 2017 a series of Accelerating the Pace of Chemical Risk Assessment (APCRA) workshops been regularly convened "to examine how NAMs can contribute to the transformation of the regulatory evaluation of chemicals and pragmatically tackle barriers to acceptance." APCRA includes participants from United States, Australia, Japan, Korea, Singapore, Canada, and Europe. This product is an official APCRA case study that will describe a framework for decision makers to make use of HTTK. HTTK combines chemical-specific in vitro measures of TK with reproducible, transparent, and open-source TK models that place data generated by NAMs in a public health risk context and enhance interpretation of biomonitoring data. The product will develop a tiered framework that is two dimensional contrasting the decision context against chemical-specific considerations. Complexity is constrained by the limited data available to calibrate and test TK models and the need to justify both the model assumptions and predictions. Different levels of certainty are needed for prioritization, risk evaluation, and for protecting susceptible populations. This product will develop a table of what can be measured and modeled with HTTK, describing the decision context, applicable chemistry, scientific motivation, impact on models, and whether quantitative structure-property relationship (QSPR) models exist and when they are appropriate. We will provide a series of examples potentially including generic vs. bespoke (that is, chemical-specific) model, data rich chemicals, handling chemicals as a class, and biomonitoring. The resulting product is intended to serve as a guide to regulators who are interested to know when and where HTTK might be used for chemical safety decision making.
URLs/Downloads:
DOI: APCRA Case Study: High Throughput Toxicokinetics for In Vitro-In Vivo Extrapolation
APCRAHTTKCASESTUDY-DRAFT2.PDF (PDF, NA pp, 1168.415 KB, about PDF)