The translocation of inhaled silicon dioxide: an empirically derived compartmental model

The movement of inhaled silicon dioxide particles was studied by measuring the amounts in alveolar fluid and cells, lung tissue, and lymphoid tissue during the 6 months following short-term aerosol exposure of Fischer 344 rats. A variety of first-order compartmental models were fit to data from nine exposure experiments to identify the most feasible biologic pathways for the transfer of material among these sites and out of the body. A multivariate least-squares approach was used to simultaneously fit the data from several compartments. The results indicate that transfer between alveolar cells and lung tissue occurs in both directions, suggesting that silica can reenter the alveolar space from the lung tissue. This feature has not been included in previously published models. The results also indicate that transfer from lung tissue to the mediastinal lymph nodes and thymus is indirect; there are one or more unidentified extrapulmonary compartments that receive silica from the lung. Rates of transfer among compartments were dependent on mineral type (quartz or cristobalite), heat treatment, and exposure dose. There was no evidence for direct clearance from the alveolar space via the tracheobronchial tract.