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International Agency for Research on Cancer (IARC) - Summaries & Evaluations

BENZIDINE AND ITS SULPHATE, HYDROCHLORIDE
AND DIHYDROCHLORIDE

VOL.: 29 (1982) (p. 149)

5. Summary of Data Reported and Evaluation

5.1 Experimental data

Benzidine and its dihydrochloride were tested in mice, rats and hamsters by oral administration, in mice and rats by subcutaneous administration and in rats by inhalation and intraperitoneally. Following its oral administration to mice of different strains, both sexes, newborn and adult, and following its subcutaneous administration, it significantly increased the incidence of liver-cell tumours (benign and malignant). In female rats, it markedly increased the incidence of mammary tumours; and in male and female hamsters, it increased the incidence of liver tumours following its oral administration. The subcutaneous administration of benzidine or its sulphate to rats produced a high incidence of Zymbal-gland tumours; colonic tumours were also reported. The results of the inhalation study in rats could not be interpreted. The intraperitoneal administration of benzidine to rats resulted in a marked increase in the incidence of mammary and Zymbal-gland tumours. It was also tested in dogs by oral administration, producing bladder carcinomas. Studies in fish, rabbits and frogs could not be evaluated.

The metabolites of benzidine, N,N'-diacetylbenzidine and N-hydroxy-N,N'-diacetylbenzidine, produced mammary and Zymbal-gland tumours in rats following their intraperitoneal injection.

Benzidine and urine from rats fed benzidine are mutagenic to Salmonella typhimurium with metabolic activation. Benzidine is mutagenic to Drosophila melanogaster. It inhibits DNA synthesis in HeLa cells and in renal and hepatic cells in mice in vivo. It induces unscheduled DNA synthesis in HeLa cells and in rat hepatocytes. Benzidine transformed Syrian hamster embryo cells and was positive in the BHK21 clone-13 cell system.

The data were inadequate to assess the teratogenicity of this compound to experimental animals.

5.2 Human data

Occupational exposure to benzidine or its dihydrochloride has and probably still does occur during their manufacture and conversion to derived dyes and during the use of those dyes. When benzidine is used for blood testing or to enhance fingerprints, laboratory or field workers may be exposed. Environmental exposure can occur under certain conditions, when benzidine-based dyes are converted to benzidine in streams into which dye-containing wastes have been discharged.

No data were available to assess the mutagenicity or teratogenicity of benzidine to man.

Occupational exposure to benzidine has been strongly associated with bladder cancer in numerous case reports from many countries. The association has also been observed in several epidemiological studies. In one extreme instance, all five of a group of workers continuously employed in benzidine manufacture for 15 years or more developed bladder cancer.

5.3 Evaluation

There is sufficient evidence that benzidine is carcinogenic to mice, rats, hamsters and dogs.

There is sufficient evidence that benzidine is carcinogenic to man.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 1 (1972)

Subsequent evaluation: Suppl. 7 (1987)


Last updated: 9 April 1998






















    See Also:
       Toxicological Abbreviations
       Benzidine (ICSC)