Toxicokinetics of organic solvents

Organic solvents, because of their small molecules and large solubility in fat, water, or both, are expected to be readily absorbed through the skin or by inhalation. Toxicokinetic models (empirical, pharmacokinetic, and simulation) are used to describe the time course of their absorption and elimination. Special attention is given in this review to simulation models in which rate constants are derived from physiological parameters of the exposed subject (alveolar ventilation, tissue perfusion, body build) and from physicochemical properties of the inhaled chemical (partition coefficient, metabolic clearance). Such a simulation model is used to gain insight into the uptake, distribution, and elimination of inhaled vapors of organic solvents. Large differences between kinetic patterns of hydrophobic and hydrophilic solvents are indicated by the effects of biosolubility, metabolic clearance, changes in physiological parameters, exposure duration, and concentration fluctuation on the uptake, distribution, and elimination of solvents. Because kinetics is the basis for interindividual and intraindividual differences in pulmonary uptake and bioavailability and in the development of toxic effects, simulation models have practical application in the biological exposure monitoring and medical surveillance of exposed workers.