A DOSIMETRY MODEL OF NICKEL COMPOUNDS IN THE RAT LUNG

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Abstract
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.