Chromosome aberrations and sister-chromatid exchanges induced by technical grade toluene diisocyanate and methylenediphenyl diisocyanate in cultured human lymphocytes.

Technical-grade toluene diisocyanate (TDI; 80% 2,4-isomer and 20% 2,6-isomer) and 4,4'-methyl-enediphenyl diisocyanate (MDI; about 45% MDI, 25% 4,4'-methylenediphenyl triisocyanate and 30% unspecified compounds of higher molecular weight), used as hardeners in the production of polyurethane, induced chromosome aberrations after a 24 h treatment in the absence of metabolic activation in human whole-blood lymphocyte cultures, MDI at all doses tested (0.54-4.30 microliter/ml) and TDI (0.019-0.150 microliter/ml) at the highest two doses (0.075 and 0.150 microliter/ml). In the presence of rat liver S9 mix (1.5 h treatment), both mixtures significantly increased aberrations at only one of the doses used, MDI at the highest dose (4.30 microliter/ml) and TDI at the second highest dose (0.038 microliter/ml). MDI also marginally increased sister-chromatid exchanges at the highest dose available (2.17 microliter/ml) with and without (48 h treatment) S9 mix. On addition to culture medium, both TDI and MDI formed polymers, which were seen as small particles on the microscopic slides. At high doses the presence of these polymers made metaphase analysis impossible.