Bioconcentration Assessment in Fish Based on In Vitro Intrinsic Clearance: Predictivity of an Empirical Model Compared to In Vitro–In Vivo Extrapolation Models

To estimate the bioconcentration factor (BCF), the in vitro intrinsic clearance (CLIN VITRO,INT) from rainbow trout liver S9 fractions (RT-S9) can be applied to in vitro–in vivo extrapolation (IVIVE) models, yet uncertainties remain in model parameterization. An alternative model approach is evaluated: a regression model was built in the form log BCF = a × log K ow + b × log CLIN VITRO,INT. The coefficients a and b were fitted based on a training set of 40 chemicals. A high robustness of the coefficients and good accuracy of BCF prediction were found on independent datasets of neutral organic chemicals (measured log K ow 3.3–6.2). BCF predictions were similar to or in better agreement with in vivo BCFs compared to IVIVE models (2.4- to 2.9- vs 2.8- to 3.6-fold misprediction) for training and test sets. Species-matched models (trout, carp) did not result in improvements. This study presents the largest dataset on CLIN VITRO,INT and BCFs to assess predictivity of the RT-S9 assay. The robustness of the regression statistics on different datasets and the high statistical weight of the CLIN VITRO,INT term illustrate the predictive power of the RT-S9 assay as an important step toward regulatory acceptance to replace animal experiments.