Eighty-five day postexposure follow-up study in Fischer 344 rats after repeated exposures to methyl isocyanate vapor.

Abstract

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 respiratory 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.

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. I. Study Objectives and Inhalation Exposure Design

“…A discussion of the results of these MIC studies have been included in this issue of Environmental Health Perspectives (7)(8)(9). There was good agreement between the results of the studies performed in the 1960s and the studies conducted in the 1980s (4).…”

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

“…We can speculate that, had animals been allowed to survive, reparative processes would have occurred, some of which would have produced fibrosis. A previous MIC repeated exposure study in rats (3,13) indicated that intraluminal airway fibrosis matured and contracted during the 85 days of postexposure and that interstitial fibrosis was minimal and multifocal in small areas of the lung. No morphologic studies beyond 2 weeks postexposure have been conducted in the guinea pig.…”

Methyl isocyanate eight-day vapor inhalation study with Fischer 344 rats.

“…To describe more fully the lesions in the rat respiratory tract as a result of either 4 or 8 days of exposure to 3 ppm of MIC and to characterize the subsequent development of these lesions during a 3-month recovery period, an additional repeated exposure study was performed (4,5). Recovery from the necrotizing and irritating effects of MIC vapor was observed.…”

“…As the 6-hr LC50 value for Fischer 344 rats was 6.1 ppm MIC (1), the target MIC concentrations selected for the repeated (8-day) exposure study were 3.0, 0.6, 0.12, and 0.0 (control) ppm. A second repeated exposure study was conducted to describe more fully the lesions in the rat respiratory tract as a result of either 4 or 8 days of exposure to MIC at similar exposure concentrations and to characterize subsequent development of lesions during a 3-month recovery period (4,5).…”