MYELOTOXICITY INDUCED IN B6C3F1 MICE BY METHYL ISOCYANATE INHALATION EXPOSURE

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The effects of a 4-day inhalation exposure (6 hr/day) to 0, 1 and 3 ppm methyl isocyanate (MIC) on bone marrow parameters in female mice were examined at 5, 8, 21 days and 1 year following exposure. The MIC exposure was associated with the bone marrow as evidenced by hypocellularity, suppression of pluripotent stem cells (CFU-S), granulocyte-macrophage progenitors (CFU-C) and erythroid precursors (CFU-E) in both dose groups. Hematopoietic parameters returned to normal by 21 days in the 1 ppm dose group, but not in the 3 ppm dose group. MIC is a highly reactive chemical that appears to exert its effect directly on the lining epithelium of the nasal cavity and major airways, and there was no histological evidence of a systemic effect. There was no significant effect on bone marrow cellularity and CFU-C in mice 1 year following acute exposure at the doses of 3 and 10 ppm for 2 hours. In conclusion, MIC exposure appears to cause acute cell death of lining epithelium of the nasal passages and major airways with transient alterations of bone marrow parameters that are likely related to the pulmonary injury either directly or secondary through the thymus. These results were publicated in Environ. Health Persp. 72, p. 143-148, 1987.