Predicting azo dye toxicity

Abstract

Literature regrading azo dye carcinogenicity was examined to establish, if possible, guidelines to predict the human health risks of new azo dyes. Three different mechanisms for azo dye carcinogenicity were identified, all involving metabolic activation to reactive electrophilic intermediates that covalently bind DNA. In the order of decreasing number of published references, these mechanisms are

1. Azo dyes that are toxic only after reduction and cleavage of the azo linkage to give aromatic amines, mostly via intestinal anaerobic bacteria. The aromatic amines are met‐abolically oxidized to reactive electrophilic species that covalently bind DNA.

2. Azo dyes with structures containing free aromatic amine groups that can be meta‐bolically oxidized without azo reduction.

3. Azo dyes that may be activated via direct oxidation of the azo linkage to highly reactive electrophilic diazonium salts.

Each mechanism may be compound specific, thus azo toxicity is probably caused by more than one mechanism. Although it is not possible to predict azo dye carcinogenicity with absolute certainty, it is possible to establish certain guidelines. Because some species of intestinal anaerobic bacteria (and in some cases, hepatic azo reductases) may reduce any azo compound to aromatic amines, those containing aromatic amine subgroups known to be carcinogenic, such as benzidines, must be suspect. Information about human carcinogenicity of other specific aromatic amines is scant, and various short‐term mutagenicity tests may provide some guidance. Other in vitro tests can directly assay new azo dyes. Although it is unlikely that azo dyes can be developed that can be guaranteed not to generate constituent aromatic amines, it may be possible to select aromatic amines that are not toxic.

Key words:

• azo
• dye
• toxicity
• azo reduction
• carcinogenicity
• metabolism