Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice
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 eight (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.
- Research Organization:
- National Institute of Environmental Health Sciences, Research Triangle Park, NC
- OSTI ID:
- 6061037
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 72
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ISOCYANATES
BIOLOGICAL EFFECTS
INHALATION
LUNGS
FIBROSIS
BIOLOGICAL RECOVERY
EPITHELIUM
HISTOLOGY
MICE
MORTALITY
NECROSIS
ANIMAL TISSUES
ANIMALS
BODY
INTAKE
MAMMALS
ORGANS
PATHOLOGICAL CHANGES
RECOVERY
RESPIRATORY SYSTEM
RODENTS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology