Physiologically based models of metal kinetics

Many of the characteristics of metals that determine their kinetics and 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 of binding with respect to the distribution, sequestration, and mechanisms of action of a metal; mechanisms of metal uptake by cells; the possibility of metal-metal interactions; and, for some metals, the long residence times associated with incorporation into bone. In addition, exposure to metals typically includes ambient exposure, multiple exposure routes, and variable bioavailability depending on the source of the metal and its physical makeup. These features are discussed, and examples of them are given. Their incorporation into physiologically based kinetic models is illustrated for four metals for which such models have been developed or are in the process of development: arsenic, chromium, lead, and mercury.