© 1988 Oxford University Press
research-article |
Pulmonary Fibrosis Produced in F-344 Rats by Subchronic Inhalation of Aerosols of a 4000 Molecular Weight Ethylene Oxide/Propylene Oxide Polymer
*Bushy Run Research Center R D No. 4, Mellon Road, Export, Pennsylvania 15632
Union Carbide Corporation 39 Old Ridgebury Road, Danbury, Connecticut 06817
Received July 22, 1987; accepted December 21, 1987
Pulmonary Fibrosis Produced in F-344 Rats by Subchronic Inhalation of Aerosols of a 4000 Molecular Weight Ethylene Oxide/Propylene Oxide Polymer. KLONNE, D. R., DODD, D. E., Losco, P. E., TROUP, C. M., AND TYLER, T. R. (1988), Fundam Appl. Toxicol 10, 682–690. Inhalation of aerosols of the ethylene oxide/propylene oxide polymer (U-5100) evaluated in this study has previously been shown in acute and 2-week studies to produce toxicologic effects on the lungs, with increased lung weights and microscopic findings of congestion and hemorrhage of pulmonary alveolar capillaries and necrosis of alveolar epithelial cells (D. R. KLONNE, D. J. NACHREINER, D. E. DODD, P. E. Losco, AND T. R. TYLER, 1987, Fundam. Appl. Toxicol. 9, 7737–784). In the present studies, F-344 rats were exposed 6 hr/day, 5 day/week for 2 weeks to aerosols at mean concentrations of 0,0.9, or 5.0 mg/m3 or for 13 weeks to mean concentrations of 0, 0.3, 1.1, or 5.2 mg/m3. Following the 2-week study, minimal multifocal hemorrhage and eosinophilic proteinaceous debris in alveoli were observed in the 0.9 mg/m3 group; similar lesions plus alveolar cell necrosis were found in the 5 mg/m3 group. In the 13-week study, the 5.2 mg/m3 group had a slight decrease in body weight gain, while increases in absolute and/or relative lung weights occurred for both the 1.1 and 5.2 mg/m3 groups at the end of the exposure regimen and at the end of a 5-week recovery period. Histologic lesions of the lungs occurred in all U-5100-exposed groups and consisted of hemorrhage, alveolar histiocytosis, interstitial pneumonia, and multifocal fibrosis. The incidence and severity of the pulmonary lesions were concentration related. At the end of the 5-week recovery period, there was little change in the severity or incidence of the pulmonary lesions in the 1 and 5 mg/m3 groups when compared to rats killed the day after the termination of exposures. In conclusion, exposure to aerosols of U-5100 for 13 weeks produced generally slight but biologically significant pulmonary fibrosis in rats at all the exposure concentrations tested in this study.