PARAMETER VARIABILITY AND THE INTERPRETATION OF PHYSIOLOGICALLY-BASEDPHARMACOKINETIC MODELING RESULTS

For the past several years we have been working with models of benzene distribution and metabolism principally in the rat, but more recently in humans. Our biologically related objectives have been primarily to assist our laboratory-based colleagues in their quest for understandi ng of the mechanisms by which benzene exerts its toxic action. A secon dary goal has been to develop or adapt models useful in risk assessmen t applications. We have also had methodological goals that relate to a pplications oi sensitivity analysis on the one hand, but more fundamen tally to the connection between experimental data and model structure and parameterization. This paper presents an overview of our work in t hese areas