You are here:
Comparison of trout hepatocytes and liver S9 fractions as in vitro models for predicting hepatic clearance in fish
Citation:
Fay, K., P. Fitzsimmons, A. Hoffman, AND J. Nichols. Comparison of trout hepatocytes and liver S9 fractions as in vitro models for predicting hepatic clearance in fish. setac north america, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
not applicable
Description:
Isolated hepatocytes and liver S9 fractions have been used to collect in vitro biotransformation data for fish as a means of improving modeled estimates of chemical bioaccumulation. To date, however, there have been few direct comparisons of these two methods. In the present study, cryopreserved trout hepatocytes were used to measure in vitro intrinsic clearance rates for 6 polycyclic aromatic hydrocarbons (PAHs). These rates were extrapolated to estimates of in vivo intrinsic clearance and used as inputs to a well-stirred liver model to predict hepatic clearance. Predicted rates of hepatic clearance were then evaluated by comparison to measured rates determined previously using isolated perfused livers (IPL) from well-matched animals. Hepatic clearance rates predicted using hepatocytes corresponded closely to measured values (< 2.1 fold difference for 5 of 6 compounds) under two competing binding assumptions. These findings, which may be attributed in part to high rates of PAH metabolism, are similar to those obtained previously using data from liver S9 fractions obtained from animals closely matching those used for the hepatocyte assays and IPL studies. For one compound (benzo[a]pyrene), the in vivo intrinsic clearance rate calculated using S9 data was 10-fold higher than that determined using hepatocytes, possibly due to a diffusion limitation on cellular uptake. Generally, however, there was good agreement between calculated in vivo intrinsic clearance rates obtained using either in vitro test system. These results suggest that both systems can be used to improve bioaccumulation assessments for fish, particularly when vitro rates of activity are relatively high, although additional work is needed to determine if the chemical domain of applicability for each system differs.