Carcinogenicity of azo colorants: influence of solubility and bioavailability.
In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic to man". This is not the case for 3,3'-dichlorobenzidine-based azo pigments.
Golka
Klaus
K
Institut für Arbeitsphysiologie an der Universität Dortmund, Ardeystr. 67, D-44139 Dortmund, Germany. golka@arb-phys.uni-dortmund.de
Kopps
Silke
S
Myslak
Zdislaw W
ZW
D000818:Animals; D001391:Azo Compounds / Q000493:pharmacokinetics* / Q000633:toxicity*; D001560:Benzidines / Q000493:pharmacokinetics / Q000633:toxicity; D001682:Biological Availability; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D016273:Occupational Exposure / Q000009:adverse effects; D010860:Pigments, Biological / Q000493:pharmacokinetics / Q000633:toxicity
D001391:Azo Compounds; D001560:Benzidines; D002273:Carcinogens; D010860:Pigments, Biological