Progression of lung inflammation and damage in rats after cessation of silica inhalation.
Porter DW; Hubbs AF; Mercer R; Robinson VA; Ramsey D; McLaurin J; Khan A; Battelli L; Brumbaugh K; Teass A; Castranova V
Toxicol Sci 2004 Mar; 79(2):370-380
Human epidemiologic studies have found that silicosis may develop or progress even after occupational exposure has ended, suggesting that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure. We previously described the time course of rat pulmonary responses to silica inhalation as biphasic, the initial phase characterized by increased but controlled pulmonary inflammation and damage. However, after a threshold lung burden was exceeded, rapid progression of silica-induced pulmonary disease occurred. To test the hypothesis that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure we initiated a study to investigate the relationship between silica exposure, the initiation and progression of silica-induced pulmonary disease, and recovery. Rats were exposed to silica (15 mg/m3, 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were maintained without further exposure for 36 days to examine recovery. The major findings of this study are: (1) silica-exposed rats were not in pulmonary overload, and lung silica burden decreased with recovery; (2) pulmonary inflammation, damage and lipidosis increased with recovery for rats exposed to silica for 40 and 60 days, but not 20 days; (3) histopathology revealed changes in silica-induced alveolitis, epithelial hypertrophy and hyperplasia, and alveolar lipoproteinosis consistent with bronchoalveolar lavage (BAL) endpoints; and (4) pulmonary fibrosis developed even when exposure was stopped prior to its initial development.
Silicosis; Silicates; Silica-dusts; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-function; Respiratory-infections; Respiratory-irritants; Respiratory-system-disorders; Lung-disorders; Lung-disease; Lung-burden;
Author Keywords: silica inhalation; pulmonary inflammation; silica lung burden; recovery
Dale W. Porter, Health Effects Laboratory Division, National Insitute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown WV, 26505