International Agency for Research on Cancer (IARC) - Summaries & Evaluations
BENZIDINE AND ITS SULPHATE, HYDROCHLORIDE
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
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