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

Groups of ten male and ten female Fischer 344 rats were exposed by inhalation 3.1, 0.6, 0.15, or 0.0 (control) ppm of methyl isocyanate (MIC) vapor 6 hr per day for 8 days (two 4-day sessions separated by a 2-day rest). Evaluation of toxic effects included body weight, food consumption, organ weights, and selected hematologic, ophthalmic, neurologic, gross anatomic, and histologic examinations. There were no deaths during the study. Rats of the 3.1 ppm exposure group had decreased body weights, food consumption, and blood oxygen saturation (males only). An increase in hemoglobin concentration (males only) and in lung weights (absolute and as a percentage of body weight) were also observed in the 3.1 ppm rats. Ophthalmic or neurofunctional behavior evaluations were negative for all MIC exposure groups. Only 3.1 ppm of MIC vapor resulted in lesions in the respiratory tract, 0.6 or 0.15 ppm did not. The types of lesions observed were inflammation and squamous metaplasia in the nasal cavity, trachea, and bronchi; inflammation of the bronchioles and alveoli; and submucosal fibroplasia of the bronchioles. No significant lesions were observed in tissues other than those of the respiratory tract in all MIC exposure groups. The results of this study indicate the current 0.02 ppm threshold limit value for MIC is not too high regarding toxicity.