Modeling of Deposition and Clearance of Inhaled Ni Compounds in the Human Lung

Abstract

By extrapolation from the rat study, a mathematical model of deposition, clearance, and retention kinetics for inhaled Ni compounds (high-temperature (green) NiO, Ni(3)S(2), and NiSO(4). 6H(2)O) in the alveolar region of the human lung has been developed. For human deposition, an updated version of an earlier model (C. P. Yu and C. K. Diu, 1982, Am. Ind. Hyg. Assoc. J.) was used in this study. Because of the profound differences in physiological and ventilation conditions between humans and rats, humans were found to have a higher alveolar deposition fraction than rats when exposed to the same Ni compounds. However, when normalized to the lung weight, the deposition rate per gram of lung in humans is much smaller than in rats. 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 Ni(3)S(2), respectively) depends highly on the volume of retained particles in the lungs. As for the highly soluble nickel compound (NiSO(4). 6H(2)O), the clearance rate coefficient was assumed to depend on the retained particle mass and total alveolar surface. These clearance rate coefficients were extrapolated from the rat data. The retention half-times for high temperature (green) NiO and Ni(3)S(2) particles in humans were found to be much longer than in rats, whereas the retention half-time for NiSO(4). 6H(2)O particles was about the same for both species. The lung burden results in humans for various exposure conditions are predicted and the equivalent exposure concentrations for humans which lead to the same lung burdens found in rats were calculated.