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In vitro to In vivo extrapolation of hepatic metabolism in fish: An inter-laboratory comparison of In vitro methods
Citation:
Fay, K., M. Embry, M. Bernard, I. Bischof, J. Davis, J. Domoradzki, M. Halder, X. Han, K. Johanning, H. Laue, D. Nabb, J. Nichols, C. Schlechtriem, H. Segner, L. van der Wal, AND J. Weeks. In vitro to In vivo extrapolation of hepatic metabolism in fish: An inter-laboratory comparison of In vitro methods. SETAC North America, Salt Lake City, UT, November 01 - 05, 2015.
Impact/Purpose:
not applicable
Description:
Chemical biotransformation represents the single largest source of uncertainty in chemical bioaccumulation assessments for fish. In vitro methods employing isolated hepatocytes and liver subcellular fractions (S9) can be used to estimate whole-body rates of chemical metabolism, required as inputs to established in silico models of chemical accumulation. Predicted levels of accumulation obtained in this manner are generally closer to measured values than predictions obtained assuming no metabolism, suggesting that these methods could provide critical information as part of a tiered approach to bioaccumulation assessment. Regulatory use of these procedures, however, requires that they be evaluated to determine their reproducibility within and among laboratories. Building on previous work, a multi-laboratory ring-trial was coordinated by the ILSI Health and Environmental Sciences Institute (HESI). This ring-trial was initiated to support the development of an OECD Test Guideline, led by the United States and European Commission. The approach uses substrate depletion methods to determine the rate at which the in vitro test systems (S9 fractions and cryopreserved hepatocytes) metabolize selected test chemicals. This information can then be extrapolated to the whole liver to provide a direct basis (i.e., ml/h/g liver) for comparison which can then be extrapolated to whole organism bioaccumulation. The specific aims of the ring trial were to compare the performance of two in vitro methods based on rainbow trout S9 and cryopreserved hepatocytes within and across participating laboratories. The ring-trial involved seven laboratories in Europe and North America (The Dow Chemical Company, DuPont, Fraunhofer IME, Givaudan Schweiz AG, The Procter & Gamble Company, SC Johnson / KJ Scientific, and the US Environmental Protection Agency). Six chemicals (pyrene, 4-n-nonylphenol, fenthion, methoxychlor, deltamethrin, and cyclohexyl salicylate) were evaluated in both test systems. This presentation will summarize the results of the ring-trial.