Pulmonary response and intrapulmonary lipids in rats exposed to bismuth orthovanadate dust by inhalation.
Rats were exposed to 0, 1.2, or 0.11 mg/liter of uncoated bismuth orthovanadate (BOV), 1.3 or 0.15 mg/liter of silica-coated BOV, or 1.9 mg/liter of silica-coated TiO2 for 2 weeks. Rats were killed 0, 1, 3, 6, and 12 months postexposure (PE). After the rats were exposed for 2 weeks their pulmonary response to silica-coated TiO2 was characterized by dust-laden macrophage (dust cell) response with hyperplasia of type II pneumocytes. The lung reaction to uncoated BOV or silica-coated BOV was both similar to that of silica-coated TiO2 and dose-related. After the rats were exposed for 3 months, foamy macrophage infiltration in silica-coated TiO2 was evident. Alveolar proteinosis, foamy macrophages with cholesterol clefts, and hyperplastic type II pneumocytes were observed in rats exposed to uncoated BOV or silica-coated BOV. By 6 months PE, the lung exposed to silica-coated TiO2 was restored to essentially normal architecture with removal of most dust cells. In the silica-coated BOV or uncoated BOV exposure groups, alveolar proteinosis and cholesterol granulomas became obvious with degenerative foamy macrophages. After 1 year PE, the lungs exposed to silica-coated TiO2 were almost normal with only a few dust cell aggregates remaining. The pulmonary lesions of silica-coated or uncoated BOV were reduced but alveolar proteinosis and cholesterol granulomas still persisted. Electron microscopy revealed massive accumulation of intraalveolar phospholipid material with hyperplastic type II pneumocytes showing overloaded myelin figures after 2 weeks exposure. The increase in phospholipid at 1 month PE and sterol content at 3 months PE in the lungs correlated with the accumulation of intraalveolar myelin figures and lamellar structure, foamy macrophage infiltration, and occurrence of cholesterol clefts.
D000818:Animals; D001273:Atmosphere Exposure Chambers; D001729:Bismuth / Q000633:toxicity*; D004347:Drug Interactions; D004391:Dust; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D012822:Silicon Dioxide / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity; D014639:Vanadium / Q000633:toxicity*; D017968:Vanadium Compounds
D004391:Dust; D010743:Phospholipids; D017968:Vanadium Compounds; D014639:Vanadium; C009495:titanium dioxide; C049019:bismuth orthovanadate; D012822:Silicon Dioxide; D014025:Titanium; D001729:Bismuth