Bladder cancer in crack testers applying azo dye-based sprays to metal bodies.

Bladder cancer may be produced by azo dyes due to the presence of carcinogenic aromatic amines. Nine cases of suspected occupational bladder cancer that were exposed to different crack test sprays in metal-related jobs were examined. A detailed occupational history was taken and, if possible, the N-acetyltransferase 2 (NAT2) status was determined. The first exposure to crack test sprays ranged from 1957 to 1986. Age at first exposure was between 14 and 33 yr. Age at first diagnosis of bladder cancer varied from 35 to 64 yr. Latency periods were between 17 and 45 yr. The maximal reported exposure period was 29 yr. Four of six genotyped cases were slow NAT2 acetylators. The handling of the crack test spray included spraying the red dye-containing matter on the metal body and washing off the spray with a rag. Thus, workers were exposed by dermal contact as well as by inhalation. The crack test spray, which makes the cracks visible after washing off the red testing spray compounds and applying an additional white spray, contained dyes such as solvent red 19 (Sudan red 7B, N-ethyl-1[[4-(phenylazo)phenyl]azo]-2-naphthylamine) or a mixture of p-phenylazoaniline-N-ethyl-2-naphthylamine and p-phenylazoaniline-N-ethyl-1-naphthylamine. The aromatic amine 2-naphthylamine is classified as human carcinogen by IARC and the national authorities and has been banned in many countries since the mid 1950s. Bladder cancer patients with metal-related jobs need to be explicitly asked about the use of crack test sprays.

Glutathione S-transferase P1 ILE105Val polymorphism in occupationally exposed bladder cancer cases.

The genotype glutathione S-transferase P1 (GSTP1) influences the risk for bladder cancer among Chinese workers occupationally exposed to benzidine. Studies of Caucasian bladder cancer cases without known occupational exposures showed conflicting results. Research was thus conducted to define the role of GSTP1 genotypes in Caucasian bladder cancer cases with an occupational history of exposure to aromatic amines. DNA from 143 cases reported to the Industrial Professional Associations (Berufsgenossenschaften) in Germany from 1996 to 2004, who had contracted urothelial cancer due to occupational exposure, and 196 patients from one Department of Surgery in Dortmund, without known malignancy in their medical history, were genotyped using real-time polymerase chain reaction (PCR) (LightCycler) in relation to GSTP1 A1578G (Ile105Val) polymorphism. Among the subjects with bladder cancer, 46% presented the AA genotype, 39% the AG genotype, and 15% the GG genotype. In the surgical (noncancer) control group analyzed, 42% presented the AA genotype, 42% the AG genotype, and 16% the GG genotype. A subgroup of bladder cancer cases, represented by 46 painters, showed a distribution of 41% of the AA genotype, 48% of the AG genotype, and 11% of the GG genotype. Data indicated that in Caucasians exposed to aromatic amines the GSTP1 A1578G polymorphism did not appear to play a significant role as a predisposing factor for bladder cancer incidence.

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.