MATHEMATICAL MODELING TO PREDICT THE RESPONSES TO POORLY SOLUBLE PARTICLES IN RAT LUNGS

Rat inhalation experiments with titanium dioxide (TiO2) and barium sulfate (BaSO4), at concentrations calculated to produce similar volumetric lung burden for both dusts, showed overload with TIO2 but not for BaSO4 “Overload,” occurring in rats exposed to “low-toxicity” dusts at high concentrations, is characterized by a rapid deterioration in clearance and onset of inflammation. Impairment of alveolar macrophage (AM) mediated clearance, dust translocation to the lymph nodes, and neutrophil (PMN) recruitment for both dusts were better predicted by the lung burden expressed as surface area rather than mass or volume. A mathematical model describing the translocation (in terms of particulate mass) of inhaled particles in various physiologically based pulmonary compartments was used to calculate pulmonary clearance when effective and also when impairment by overload leads to increased dust translocation to the lymph nodes. Our objectives were: (I) to modify this model to include the influence of particle sur...