A DOSIMETRY MODEL OF NICKEL COMPOUNDS IN THE RAT LUNG

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.