Toxicology of Industrial Compounds

304 SPECIAL POINTS IN THE TOXICITY ASSESSMENT OF COLORANTS
and mixing of the dyes and preparation of the coloring mixture by addition
of solvents. All painters we had interviewed reported that this type of work
had been regularly associated with considerable occurrence of dye dust in
the atmosphere, up to the end of the 1950s.
The very long latency period may explain why an enhanced risk of bladder
cancer in German painters (due to previous exposure to azo dyes) is
observed even today. Similar arguments have also been put forward for
other occupational groups associated with an increased risk of bladder
cancer, and where a causal connection with benzidine-based azo dyes had
been proven or suggested, e.g. for textile dyers (Jenkins, 1978), leather
dyers and shoeworkers (Decouflé, 1979), hairdressers (Guberan et al.,
1985), and tailors (Anthony and Thomas, 1970). The results of our own
survey of painters are very probably not relevant for the present working
conditions in Germany and other highly industrialized countries, because
of different materials, working methods, and hygienic standards introduced
in recent years. They are, however, quite relevant for matters of
compensation of persons who are now diseased.
Regulatory aspects (FRG)
The arguments described above have led the German Commission for
Investigation of Health Hazards of Chemical Compounds in the Work
Area (MAK-Commission) to include the following chapter in the MAKlist,
since 1988 (DFG, 1988):
Azo colorants are characterized by the azo group -N=N-. They are
made by the coupling of singly and multiply diazotized aryl amines.
Of particular toxicological importance are colorants from double
diazotized benzidine and from benzidine derivatives (3,3′dimethylbenzidine,
3,3′-dimethoxybenzidine, 3,3′-dichlorobenzidine).
In addition, aminoazo-benzene, aminonaphthalene and monocyclic
aromatic amines are encountered. Reductive fission of the azo group,
either by intestinal bacteria or by azo reductases of the liver and
extrahepatic tissues, can cause these compounds to be released. Such
breakdown products have been detected in animal experiments as
well as in man (urine). Mutagenicity, which has been observed with
numerous azo colorants in in-vitro test systems, and the
carcinogenicity in animal experiments are attributed to the release of
amines and their subsequent metabolic activation. There are now
epidemiological indications that occupational exposure to benzidinebased
azo colorants can increase the incidence of bladder carcinomas.
Thus, all azo colorants whose metabolism can liberate a carcinogenic
aryl amine are suspected of having carcinogenic potential. Due to the
large number of such dyes (several hundred) it seems neither possible