Comparison of low doses of aged and freshly fractured silica on pulmonary inflammation and damage in the rat

Most previous studies of silica toxicity have used relatively high exposure doses of silica, In this study. male rats received by intratracheal instillation either vehicle. aged or freshly fractured silica at a dose of either 5 mug rat once a week for 12 weeks (total dose = 60 mug) or 20 mug/rat once a week for 12 weeks (total dose = 240 mug). One week after the last exposure. bronchoalveolar lavage (BAL) was conducted and markers of pulmonary inflammation. alveolar macrophage (AM) activation and pulmonary damage were examined. For rats exposed to a total of 60 mug silica. both aged and freshly fractured silica increased polymorphonuclear leukocytes (PMN) yield and AM activation above control to a similar degree. but no evidence of pulmonary damage. as measured by BAL fluid lactate dehdrogenase activity or albumin concentration. was detected. For rats exposed to 240 mug silica. aged or freshly fractured silica increased PMN yield and AM activation above control. However. zymosan-stimulated and L-NAME sensitive AM chemiluminescence was greater for rats exposed to freshly fractured silica compared to aged silica. Exposure to 240 mug aged or freshly fractured silica also resulted in pulmonary damage. but the extent of this damage did not differ between the two types of silica. The results suggest that exposure of rats to silica levels far lower than those previously examined can cause pulmonary inflammation. In addition. exposure to freshly fractured silica causes greater generation of reactive oxygen species from AM. measured as AM chemiluminescence. in comparison to aged silica, but there is an apparent threshold below which this difference does not Occur. Published by Elsevier Science Ireland Ltd.