Hepatic Clearance Binding Terms of Hydrophobic Organic Chemicals in Rainbow Trout: Application of a Streamlined Sorbent-Phase Dosing Method

Knowledge of the freely dissolved chemical fraction in liver S9 incubation medium (ϕ S9 ) and blood plasma (ϕ P ), often expressed as the ϕ P /ϕ S9 ratio or f U, plays a central role in in vitro–in vivo extrapolation of biotransformation rates for hydrophobic organic chemicals (HOCs) in fish. However, there are very few empirical f U data for adequately assessing the bioaccumulation potential of HOCs (i.e., log K OW ≥ 4) from in vitro biotransformation rates. In this study, we present a novel streamlined approach for obtaining the f U values of HOCs and produce some of the first empirical f U data for rainbow trout. We show that f U is relatively constant for substances with a log K OW of ≥4 and appears to be largely controlled by the relative differences in protein and lipid contents in blood plasma and liver S9 incubation media. Predictive f U models are in reasonable agreement with empirical observations. Empirical f U values for HOCs with a log K OW of ≥4 ranged between 0.015 and 0.096 with an average f U value of 0.044 at an S9 protein concentration of 1 mg/mL. This range of f U values may provide reasonable preliminary estimates for the extrapolation of biotransformation rates measured in trout liver S9 bioassays.