PHYSIOLOGICALLY-BASED MODELS OF METAL KINETICS

Many of the characteristics of metals that determine their kinetics an d disposition are quite different from those that control the kinetics and disposition of volatile organic chemicals. Particularly important characteristics include binding to macromolecules and the functions o f binding with respect to the distribution, sequestration, and mechani sms of action of a metal; mechanisms of metal uptake by cells; the pos sibility of metal-metal interactions; and, for some metals, the long r esidence times associated with incorporation into bone. In addition, e xposure to metals typically includes ambient exposure, multiple exposu re routes, and variable bioavailability depending on the source of the metal and its physical makeup. These features are discussed, and exam ples of them are given. Their incorporation into physiologically based kinetic models is illustrated for four metals for which such models h ave been developed or are in the process of development: arsenic, chro mium, lead, and mercury.