Comparison of three physiologically based pharmacokinetic models of benzene disposition

We assess the goodness of fit of three physiologically based models of benzene pharmacokinetics to experimental data in Fischer-344 rats. These models were independently developed and published. Large differences in the quality of the fit are observed. In addition, the parameter values leading to acceptable fits are spread over the entire range of physiologically plausible values and can be quite different from average or standard values. On the other hand, choosing standard values for the parameters does not ensure good predictions of all tissue levels. These results emphasize the difficulty of a rigorous calibration of physiological models, and the need for further research in this area, including precise experimental determination of parameter values. Physiological models are powerful tools, but for risk assessment purposes simpler models, making equivalent use of the crucial data, are probably preferable.