Isocyanates used in the production of polyurethanes were investigated for mutagenic action in Salmonella typhimurium. These investigations showed that the most commonly used isocyanates, toluene diisocyanate (TDI) and 4,4'-methylene-diphenylisocyanate (MDI), are mutagenic. This effect can be ascribed to the amine analogues formed during the hydrolysis of isocyanates: TDI is mutagenic in TA 1538 and TA 98 after metabolic activation. This finding agrees with the results obtained with the amine analogue 2,4-toluenediamine. MDI, like the amine analogue 4,4'-methylenedianiline, is mutagenic in TA 100 after metabolic activation by rat liver enzymes (S-9 mix). A prepolymerized polyisocyanate of the MDI type is also mutagenic in assays using TA 100 and S-9 mix. It is concluded that isocyanates are potentially mutagenic and carcinogenic to man. In view of their widespread use in the work environment and in light of the high production figures for polyurethanes in industrialized countries, isocyanates must be considered to represent a serious health hazard.

Key terms Salmonella typhimurium; 4,4´-methylenediphenylisocyanate; aromatic amine; carcinogen; isocyanate; MDI; mutagene; mutagenic action; polyurethane; TDI; toluene diisocyanate