Pathologic changes following acute methyl isocyanate inhalation and recovery in B6C3F1 mice

Male and female mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 91-day recovery period. Sixteen of 80 (20%) male mice in the 30-ppm group died following exposure with seven deaths occurring in the first 24 hr. Two female mice died, one each in the 30- and 10-ppm concentration groups. Five mice/sex/group were examined at 2 hr and at 1, 3, 7, 14, 28, 49, and 91 days following exposure. Treatment-related changes were restricted to the respiratory system. At 30 ppm there was extensive necrosis and erosion of the respiratory and olfactory epithelia in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Epithelialization occurred rapidly and most of the denuded turbinates were covered by flattened epithelium by Day 3. On the turbinates, recovery was essentially complete with the exception of small areas in the olfactory epithelia where lesions were present in the male mice through Day 91. In the trachea and major bronchi, fibrin and cellular debris were present in the airways, which in some cases had organized and formed intraluminal fibrotic projections. These projections became covered by respiratory epithelium. The intraluminal projections and bronchial fibrosis persisted to Day 91. In the males, where the fibrosis was more severe, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, there appeared to be complete recovery. These inhalation studies indicate that methyl isocyanate exposure of mice at or near lethal concentrations causes reversible lesions in the nose and persistent intraluminal and mural fibrosis of the major bronchi.