Deposition and Clearance Models of Ni Compounds in the Mouse Lung and Comparisons with the Rat Models

Experimental data from inhalation studies in mice were used to develop mathematical models of deposition, clearance, and retention kinetics in the respiratory tract for inhaled Ni compounds (high temperature (green) NiO,Ni₃S₂, and NiSO₄.6H₂O) in the mouse lung. For deposition, a new model was developed using the experimental data on nasal deposition and lung morphometry by Phalen (1991). Three major mechanisms of airway deposition, including impaction, sedimentation, and diffusion, were considered in the deposition model. Because of the differences in physiological and ventilation conditions, it was found that mice have a lower alveolar deposition fraction than rats when exposed to the same Ni compounds. 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 Ni compounds (high temperature (green) NiO and Ni₃S₂, respectively) depends highly on the volume of retained particles in the lungs. As for the highly soluble Ni 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 to decrease with the lung burden for Ni₃S₂ particles. The retention half times for high temperature (green) NiO and Ni₃S₂ particles in mice are shorter than in rats, whereas the retention half time for NiSO₄.6H₂O particles is the same for both species.