Physiologically Based Models of Metal Kinetics

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Abstract
The issues confronting the modeler of metals kinetics are somewhat different from those with which the modeler of organic chemical behavior is faced. Particularly important features of metals kinetics include metal-protein binding and metal-metal interactions. Reduction, and for some metals oxidation, is frequently an intrinsic part of metal metabolism. Alkylation/dealkylation reactions may or may not render the metal less active, and the behavior of alkylated or dealkylated metabolites must often be included in a complete kinetic model. Despite these complexities, the kinetics of metals are as amenable to the techniques of physiologically based modeling as are the kinetics of organic chemicals. Like all models, those for metals kinetics have the potential to organize a variety of observations, sometimes including apparently inconsistent observations, into a coherent framework of behavior, to identify needs for more complete experimental information, and to assist the risk assessor in making judgments concerning dose-response relationships. Development of physiologically based models of the kinetic behavior of metals is in its very early stages. The kinetics of only four metals, arsenic, chromium, mercury, and lead, have been modeled with any degree of completeness. Of these, the lead model is the most fully realized at the present time. The chromium and mercury models are still in the process of development, and experimental data are being gathered to support further development and refinement of the arsenic model. We may expect to see continued progress made on these models and their practical applications, as well as the development of new models for other toxicologically significant metals such as cadmium, manganese, nickel, and aluminum.