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Comparison of low doses of aged and freshly fractured silica on pulmonary inflammation and damage in the rat.
Porter-DW; Barger-M; Robinson-VA; Leonard-S; Landsittel-D; Castranova-V
Toxicology 2002 Jun; 175(1-3):63-71
Most previous studies of silica toxicity have used relatively high doses of silica. In this study, rats received by intratracheal instillation either vehicle, aged or freshly fractured silica at a dose of either 5 ug per rat once a week for 12 weeks (total dose of 60 ug) or 20 ug per rat once a week for 12 weeks (total dose of 240 ug). One week after the last exposure, bronchoalveolar lavage (BAL) was conducted and pulmonary inflammation, alveolar macrophage (AM) activation and pulmonary damage were examined. Specifically, pulmonary inflammation was assessed by BAL polymorphonuclear leukocyte (PMN) yields, AM chemiluminescence was measured as an indicator of AM activation, and first acellular BAL fluid lactate dehydrogenase activity and serum albumin concentration were determined as markers of pulmonary damage. For rats exposed to a total of 60 ug silica, both aged and freshly fractured silica increased PMN yield and AM chemiluminescence above control to a similar degree, but no evidence of pulmonary damage was detected. For rats exposed to 240 ug silica, aged or freshly fractured silica increased PMN yield and AM chemiluminescence above control. However, total and NO-dependent AM chemiluminescence was greater for rats exposed to freshly fractured silica compared to aged silica. Exposure to 240 ug 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 to silica levels far lower than those previously examined can cause pulmonary inflammation and damage. In addition, exposure to freshly fractured silica causes greater generation of reactive oxygen and nitrogen species from AMs (measured as total and NO-dependent AM chemiluminescence) in comparison to aged silica, but there is an apparent threshold below which this difference does not occur.
Silica-dusts; Pulmonary-system-disorders; Animal-studies; Alveolar-cells; Exposure-levels; Laboratory-animals; Respiratory-system-disorders; Aerosols
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