APPLICATION OF TOXICOKINETIC MODELS TO ESTABLISH BIOLOGICAL EXPOSURE INDICATORS

This article is a critical review of the application of toxicokinetic models to the biological monitoring of occupational exposure to industrial chemicals. The experimentally based toxicokinetic models are used to determine the elimination half-lives, the metabolic clearance, the elimination rate constants and the volume of distribution. The physiologically based multicompartmental simulation models, which describe the uptake, distribution and elimination of inhaled or percutaneously absorbed organic solvents, contributed to the understanding of the transport of the xenobiotics in the body. They are used for describing and predicting the dependence of concentrations of indicators of exposure in biological specimens on the extent of exposure and time (duration of exposure and sampling time), and for depicting the contribution of various biological and exposure factors to differences in biological response to the exposure. In biological monitoring, toxicokinetic models are used for matching biological concentrations and body burden of indicators of exposure with extent of inhalation or dermal exposure, and for predicting half-lives. They lay the grounds for the strategy used in collecting biological specimens and controlling external and internal factors which alter the biological concentrations and possibly increase the health risk from the exposure. Elimination half-lives are used as guidelines in selecting the appropriate indicators of exposure, in designing the procedure for the collection of biological specimens, and in interpreting the measured data. Predictive models are needed for heavy metals, particulates and compounds undergoing binding to constituents of tissues.