Eighty-Five Day Postexposure Follow-Up Study in Fischer 344 Rats after Repeated Exposures to Methyl Isocyanate Vapor

• Published in: Environmental health perspectives 1987-06, Vol.72, p.125-132
• Main Authors: Fowler, Edward H., Dodd, Darol E.
• Format: Article
• Language: English
• Subjects: Acrolein - toxicity; Animals; Body weight; Body Weight - drug effects; Bronchioles; Cyanates - administration & dosage; Cyanates - toxicity; Epithelium; Female; Inhalation; Isocyanates; Lesions; Lungs; Male; Metaplasia; Rats; Rats, Inbred F344; Respiratory congestion; Respiratory System - drug effects; Respiratory System - pathology; The Toxicity of Methyl Isocyanate. March 12-13, 1986. Research Triangle Park, NC; Time Factors; Vapors
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8772125

The objectives of this study were to describe the microscopic lesions in the respiratory tract of Fischer 344 rats as a result of 4- or 8-days exposure (6 hr/day) of 3 ppm MIC and to characterize the postexposure development of these lesions up to day 85. All rats survived the exposure regimen, although significant decreases in body weight and encrustation of the eyes, nose, or mouth were observed. During the first 15 days of postexposure, the rats were hypoactive and had increased respirtory rates. Male mortality was as high as 63%; only 5% of the MIC-exposed females died. The cause of death was interpreted to be respiratory compromise complicated by anorexia and probably dehydration as well. During the next 28 postexposure days, 48% of the male survivors died, while only 3% of the female survivors died. Throughout the 85-day postexposure period, body weight gains in the MIC-treated groups were consistently below control values. Inflammatory and squamous metaplastic lesions of the respiratory tract, observed the day following completion of either the 4- or 8-day exposure regimen, decreased in both frequency and/or severity in survivors of the 85-day postexposure period, indicating recovery from the cytotoxic and irritating effects of MIC vapor. The squamous metaplastic epithelium was replaced by regenerative epithelium beginning in the deeper portion of the respiratory tract. Maturation of collagen occurred in the areas of submucosal fibroplasia.