Genotoxicity evaluation of trimethylbenzenes

The three trimethyl isomers of benzene (hemimellitene, 1,2,3-TMB; pseudocumene, 1,2,4-TMB and mesitylene, 1,3,5-TMB) were investigated for different genotoxicity endpoints: in vitro, in the Ames test with Salmonella typhimurium TA97a, TA98, TA100 and TA102 strains in the presence and absence of rat liver S9 metabolic activation; in vivo, in the micronucleus and sister chromatid exchange (SCE) tests with bone marrow cells of Imp:Balb/c mice. Only the isomer of benzene with the methyl-group at position 1, 2, 3 was found to have mutagenic effect on S. typhimurium cells. Increase in bacterial reversions was observed in four conventional strains used in this study, but most clearly in TA97a. The mutagenic responses of 1,2,3-TMB with the SalmonellaL tester strains were observed in the experiments performed in the absence of enzymatic activation. None of the compounds had an influence on the frequency of micronucleated polychromatic erythrocytes in bone marrow cells of mice. However, all the three compounds were observed to have a cytogenetic potential of increasing the SCE level in these cells. Significant responses in SCE induction, compared with the level of those changes in corresponding solvent-administered controls, were obtained at three test doses of 1,2,3-TMB (730, 1470, 2200 mg/kg) and 1,2,4-TMB (900, 1800, 2700 mg/kg) and at two doses of 1,3,5-TMB (1800, 2700 mg/kg). These data provided a limited evidence for the genotoxic activity of 1,2,3-TMB and inadequate evidence for genotoxic activity of 1,2,4-TMB and 1,3,5-TMB.