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Critical Evaluation of a Human In Vitro Biotransformation Rate Database
Citation:
Foster, K., A. Looky, J. Armitage, M. Embry, J. Nichols, B. Wetmore, AND J. Arnot. Critical Evaluation of a Human In Vitro Biotransformation Rate Database. 2017 SETAC North America Annual Meeting, MN, Minneapolis, November 12 - 16, 2017.
Impact/Purpose:
Chemical toxicokinetics is a research area that facilitates a link between high-throughput toxicity testing data and an exposure metric for margin of exposure-based approaches, which can be used during risk-based prioritization. Chemical biotransformation, or the conversion of a parent chemical to a metabolized form is critical information in the understanding of how a chemical may elicit health effects in humans or in the environment. Despite the fundamental value of these data, very relatively few measured in vivo data are available for humans compared to the thousands of chemicals requiring evaluation. Human in vitro biotransformation rate data are available for thousands of chemicals; but there is a high degree of variability in assay methods and in the reporting of complementary data, which may impact biotransformation rates extrapolated to the organ or whole body level and/or data utility. The objective of this effort has been to develop a new database that captures human in vitro biotransformation rate estimates that can be used in in vitro-in vivo extrapolation approaches. Data quality assessment methods consistent with those proposed within OECD testing guidance (OECD 2017a,b,c) were employed to assess this newly created database with the goal of identifying critical needs in study design and data reporting specifically relevant to in vitro hepatic clearance and biotransformation data. This work is consistent with related efforts being conducted as a part of the Chemical Safety for Sustainability program and will aid in increasing the availability of additional toxicokinetic data to toxicologists and exposure scientists while also providing a discussion on the need for a harmonized approach in the curation of such data and supporting information.
Description:
Chemical biotransformation is critical information in the understanding of how a chemical may elicit health effects in humans or in the environment. Despite the fundamental value of these data, very relatively few measured in vivo data are available for humans compared to the thousands of chemicals requiring evaluation. Human in vitro biotransformation rate data are available for thousands of chemicals; but there is a high degree of variability in assay methods and in the reporting of complementary data, which may impact biotransformation rates extrapolated to the organ or whole body level and/or data utility. The objective of this effort has been to develop a new database that captures human in vitro biotransformation rate estimates that can be used in in vitro-in vivo extrapolation approaches. Data quality assessment methods consistent with those proposed within OECD testing guidance (OECD 2017a,b,c) were employed to assess this newly created database with the goal of identifying critical needs in study design and data reporting specifically relevant to in vitro hepatic clearance and biotransformation data.
