Physiological and pathophysiological pulmonary responses to inhaled nuisance-like or fibrogenic dusts.
A short-term bioassay has been developed to assess pulmonary toxicity and predict pathological effects in animals exposed to aerosolized particulates. To test the reliability and predictive value of our bioassay, we have exposed rats to 2 materials with different biological activities. Rats were exposed for 1 or 3 days to selected concentrations of crystalline silica (a known fibrogenic dust), or to carbonyl iron (CI) particles (a material with activity reputedly similar to nuisance dusts). Pulmonary cells and tissues were evaluated at several time points after exposure. In a companion manuscript we reported that brief exposures of silica produced a sustained pulmonary inflammatory response, characterized by increases in biochemical indicators, whereas no significant effects were measured in CI-exposed animals. In the current study, our results showed that although deposition patterns for the 2 dusts were similar (i.e., at alveolar duct bifurcations), brief doses of silica produced a sustained granulocytic inflammatory response at the sites of particle deposition, while CI particles were phagocytized and cleared from the lung by normal pulmonary macrophage mechanisms which included transport via the airway mucociliary escalator. Light, scanning, and transmission electron microscopy of silica-exposed lung tissue revealed a chronically active pulmonary inflammatory response characterized by hyperplasia of type II alveolar epithelial cells and the infiltration of pulmonary macrophages and neutrophils into interstitial tissues and alveoli. The lesions were progressive leading to a granulomatous pneumonitis within 2 months postexposure. In contrast to the alterations in pulmonary tissues produced by silica, no CI-related lesions were detected at any time postexposure. The results justify the utility of this bioassay as a reliable approach to evaluating the pulmonary toxicity of inhaled particulates.
Warheit
D B
DB
Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Co., Newark, Delaware 19714.
Hansen
J F
JF
Hartsky
M A
MA
D000280:Administration, Inhalation; D000818:Animals; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D007249:Inflammation / Q000139:chemically induced*; D054354:Iron Carbonyl Compounds; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012822:Silicon Dioxide / Q000633:toxicity*
D009942:Organometallic Compounds; D054354:Iron Carbonyl Compounds; D012822:Silicon Dioxide