B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm
methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eighty (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive
necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe
necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial
fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal
fibrosis persisted to day 91. In males with severe bronchial
fibrosis, chronic alveolitis and
atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that
methyl isocyanate inhalation at or near lethal concentrations can cause persistent
fibrosis of the major bronchi in mice.