Methyl isocyanate: an evaluation of in vivo cytogenetic activity

Journal Article · Thu Jan 01 04:00:00 EST 1987 · Environ. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2860090106· OSTI ID:6692649

Tice, R R; Luke, C A; Shelby, M D

The ability of inhaled methyl isocyanate (MIC) to induce genotoxic and cytotoxic damage in vivo was evaluated by assessing the induction of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in bone marrow metaphase cells, the induction of micronuclei in polychromatic erythrocytes (MN-PCEs), and the inhibition of bone marrow cellular proliferation and erythropoiesis. B6C3F1 mice were exposed to MIC by two exposure regiments: a) in two experiments, male mice only were exposed to 3, 10, and 30 ppm for 2 hr; b) in four experiments, male and female mice were exposed to 1 and 3 ppm (in one experiment, to 6 ppm, also), 6 hr per day for 4 consecutive days. The various cytogenetic endpoints were analyzed in bone marrow and peripheral blood (4-day exposure regimen only) samples taken from bromodeoxyuridine tablet-implanted animals killed 11 to 22 hr after cessation of the exposure to MIC. Exposure to MIC for 2 hr induced a significant delay in cellular proliferation but did not induce a significant increase in CAs, SCEs or in bone marrow MN-PCEs. Following exposure to MIC for 4 days, a weak but significant increase in CAs and SCEs was observed in male and in female mice. Delay in bone marrow cell proliferation was observed in male mice beginning at 3 ppm and in female mice at 6 ppm. The 4-day exposure regimen resulted also in a depressed rate of erythropoiesis, with male mice appearing to exhibit greater depression than female mice. The results demonstrate that exposure to MIC by inhalation results in bone marrow damage, indicating the systemic genotoxic/cytotoxic activity of MIC and/or reactive metabolites.

• Research Organization: Brookhaven National Lab., Upton, NY
• DOE Contract Number: AC02-76CH00016
• OSTI ID: 6692649
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 9:1; ISSN ENMUD
• 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
ANIMALS
BIOLOGICAL EFFECTS
BLOOD FORMATION
BONE MARROW CELLS
CELL PROLIFERATION
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
ERYTHROPOIESIS
GENETIC EFFECTS
IN VIVO
INHALATION
INTAKE
ISOCYANATES
MAMMALS
MICE
MUTATIONS
RODENTS
SISTER CHROMATID EXCHANGES
SOMATIC CELLS
VERTEBRATES