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Experimental data from inhalation studies in rats were used to develop mathematical models of deposition, clearance, and retention kinetics for inhaled Ni compounds (high-temperature [green] NiO, Ni3S2, and NiSO4*6H2O) in the rat lung. For deposition, an updated version of an earlier model (Yu & Xu, 1986) was used in this study. Three major mechanisms of airway deposition-impaction, sedimentation, and diffusion-were considered in the deposition model. In the development of a clearance model, a single compartment model in the lung was used and a general assumption was made that the clearance of the insoluble and moderately soluble nickel compounds (high-temperature [green] NiO and Ni3S2, respectively) depends highly on the volume of retained particles in the lungs. For the highly soluble nickel compound (NiSO4 *6H2O), the clearance rate coefficient was assumed to depend on the retained particle mass and total alveolar surface. The retention half-time, however, was found to increase with the lung burden for high-temperature (green) NiO and NiSO4*6H2O particles but decrease with the lung burden for Ni3S2 particles.

Existing experimental data on pulmonary clearance of low-toxicity, poorly soluble particles in several mammalian species including the rat, mouse, guinea pig, dog, monkey, and human have been analyzed using a two-exponential time-decay function with one exponential representing the fast clearance phase and the other for the slow clearance phase. Mass fractions of both clearance phases and the corresponding clearance rates were determined from the lung burden data for different specific initial lung burdens (initial lung burden/ lung weight). It was found that the slow clearance mass fraction increased with lung burden for all species, and it approached almost 100% when the specific initial lung burden exceeded 1 mg/ g lung. However, the slow clearance mass fraction at low lung burdens was found to be much higher for the slow-clearing species (guinea pig, dog, monkey, and human) than for the fast-clearing species (rat and mouse). It was also found that the fast clearance rate was nearly a constant, but the...