Results of in vitro and in vivo genetic toxicity tests on method isocyanate

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

DOI:https://doi.org/10.1289/ehp.8772183· OSTI ID:5898224

Shelby, M D; Allen, J W; Caspary, W J; Haworth, S; Ivett, J; Kligerman,; Luke, C A; Mason, J M; Myhr, B; Tice, R R; Valencia, R; Zeiger, E

Methyl isocyanate (MIC) was tested for genetic toxicity in a variety of in vitro and in vivo assays. Negative results were obtained in the Salmonella/mammalian microsome assay using five bacterial strains in a preincubation protocol. The Drosophila sex-linked recessive lethal test also gave negative results in studies that involved three routes of administration: inhalation, feeding, and injection. Reproducible, dose-related increases in trifluorothymidine-resistant clones were induced in L5178Y mouse lymphoma cells, and the frequencies of both SCE and chromosomal aberrations increased in Chinese hamster ovary cells. These effects were independent of exogenous metabolism. In mice exposed to methyl isocyanate by inhalation, cytogenetic analyses were carried out on bone marrow, blood, and lung cells. A single, 2-hr exposure to concentrations of 0, 3, 10, and 30 ppm MIC produced no evidence of chromosomal effects in the bone marrow, although significant cell cycle delay was observed. From these results, it appears that methyl isocyanate has the capacity to affect chromosomal structure but not to induce gene mutations. Furthermore, in vitro tests show that the induction of chromosomal effects is not dependent on an exogenous source of metabolism. Based on these results and on what is known about the binding of carbamoylating agents to cellular macromolecules, methyl isocyanate may exert its genetic toxicity by binding to nuclear proteins rather than by binding to DNA.

• Research Organization: National Institute of Environmental Health Sciences, Research Triangle Park, NC
• OSTI ID: 5898224
• Journal Information: Environ. Health Perspect.; (United States), Vol. 72
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ISOCYANATES
CONFIGURATION INTERACTION
GENETIC EFFECTS
NUCLEOPROTEINS
BONE MARROW
CHO CELLS
CHROMOSOMAL ABERRATIONS
DNA
DROSOPHILA
IN VITRO
IN VIVO
LYMPHOCYTES
MICE
SALMONELLA TYPHIMURIUM
SISTER CHROMATID EXCHANGES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ARTHROPODS
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DIPTERA
FLIES
FRUIT FLIES
HEMATOPOIETIC SYSTEM
INSECTS
INVERTEBRATES
LEUKOCYTES
MAMMALS
MATERIALS
MICROORGANISMS
MUTATIONS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SALMONELLA
SOMATIC CELLS
TISSUES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology