Myelotoxicity induced in female B6C3F1 mice by inhalation of methyl isocyanate

Journal Article · Mon Jun 01 04:00:00 EDT 1987 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.8772143· OSTI ID:6061182

Hong, H L; Bucher, J R; Canipe, J; Boorman, G A

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, and 21 days following exposure. The MIC exposure was associated with myelotoxicity as evidenced by hypocellularity, suppression of pluripotent stem cells (CFU-S), granulocyte-macrophage progenitors (CFU-GM) 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. This indicates that the alterations in the bone marrow parameters persist for a relatively long period at dose levels where there are little or no changes in body weight, clinical pathology, or immunological parameters, suggesting that the bone marrow may be a sensitive endpoint for MIC exposure in mice. MIC is a highly reactive chemical that appears to exert its effect directly on the lining epithelium of the nasal cavity and major airways; there was no histological evidence of a systemic effect. The pathogenesis of the bone marrow depression is unknown; however, there were chronic bronchitis and bronchial fibrosis in the 3 ppm dose group. One possible explanation is that the cell injury induced in the lung is associated with the release of inhibitory factors for hematopoiesis, as the rodent lung is a potent source of both stimulatory and inhibitory growth factors for bone marrow progenitor cells. A second possibility is that the thymic atrophy found in MIC-exposed mice might be related to myelotoxicity. The pathogenesis of myelotoxicity in MIC exposure and its relationship with pulmonary injury require further study.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 6061182
• Journal Information: Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 72; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BLOOD FORMATION
BODY
BONE MARROW
BRONCHITIS
DISEASES
EPITHELIUM
FEMALES
FIBROSIS
HEMATOPOIETIC SYSTEM
HEMIC DISEASES
INHALATION
INTAKE
ISOCYANATES
MAMMALS
MICE
ORGANS
PATHOGENESIS
PATHOLOGICAL CHANGES
RESPIRATORY SYSTEM DISEASES
RODENTS
SOMATIC CELLS
STEM CELLS
TISSUES
TOXICITY
VERTEBRATES