Mutagenicity of Methylisocyanate and Its Reaction Products to Cultured Mammalian Cells

Mutat Res. 1986 Aug;174(4):285-93. doi: 10.1016/0165-7992(86)90049-7.

Abstract

Methylisocyanate (MIC) induced mutagenic responses in the absence of exogenous activation in the mouse lymphoma cell forward mutation assay at concentrations as low as 8-24 microM. MIC produced predominantly small mutant colonies, suggesting the possibility of clastogenic activity. The intermediate hydrolysis product, methylamine, was also mutagenic without exogenous activation but required several hundred-fold higher concentrations (ca. 3 mM). N,N'-Dimethylurea, the final product in the reaction of methylisocyanate and water, was totally refractory in either the presence or absence of S9 for concentrations up to 57 mM (5 mg/ml). The ethyl ester of N-methylcarbamic acid was also tested since it was the only available analogue to the highly reactive N-methylcarbamic acid intermediate. This compound was mutagenic only in the presence of S9 at doses exceeding 5-40 microM, which suggested the possibility that the free acid, produced by enzymatic hydrolysis, is also mutagenic. The mutagenic activity of the ester resulted solely in the production of small mutant colonies.

MeSH terms

  • Animals
  • Biotransformation
  • Cells, Cultured
  • Cyanates / pharmacology*
  • Isocyanates*
  • Leukemia L5178
  • Methylurea Compounds / pharmacology
  • Mice
  • Microsomes, Liver / metabolism
  • Mutagenicity Tests
  • Rats
  • Urethane / analogs & derivatives
  • Urethane / pharmacology

Substances

  • Cyanates
  • Isocyanates
  • Methylurea Compounds
  • N-methylcarbamic acid, ethyl ester
  • Urethane
  • methyl isocyanate
  • 1,1-dimethylurea