Pulmonary fibrosis produced in F-344 rats by subchronic inhalation of aerosols of a 4000 molecular weight ethylene oxide/propylene oxide polymer.
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, 773-784). 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 histocytosis, interstitial pneumonia, and multifocal fibrosis. The incidence and severity of the pulmonary lesions were concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)
Klonne
D R
DR
Bushy Run Research Center, Export, Pennsylvania 15632.
Dodd
D E
DE
Losco
P E
PE
Troup
C M
CM
Tyler
T R
TR
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D005027:Ethylene Oxide / Q000633:toxicity*; D005260:Female; D008168:Lung / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011108:Polymers; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344
D000336:Aerosols; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D011108:Polymers; D005027:Ethylene Oxide; C009068:propylene oxide