Bioassay of Hydrazobenzene for Possible Carcinogenicity (CAS No. 122-66-7)
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Chemical Formula: C12H12N2
Hydrazobenzene is a hydrazine derivative selected for bioassay by the National Cancer Institute because of the documented carcinogenicity of the parent compound hydrazine and of certain substituted hydrazines. Treatment of hydrazobenzene with hot mineral acid results in the production of benzidine (the so-called "benzidine rearrangement") and hydrazobenzene finds application in the dye manufacturing industry as a precursor of this important dye intermediate and potent carcinogen.
A bioassay of technical-grade hydrazobenzene for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Hydrazobenzene was administered in the feed, at either of two concentrations, to groups of 50 male and 47 to 50 females animals of each species. The time-weighted average dietary concentrations used in the rat bioassay were 0.008, 0.03, 0.004, and 0.01 percent for low dose males, high dose males, low dose females, and high dose females, respectively. The time-weighted average dietary concentrations used in the mouse bioassay were 0.008, 0.04, 0.004, and 0.04 percent for low dose males, high dose males, low dose females, and high dose females, respectively. After a 78-week period of compound administration, observation of the rats continued for an additional 28 to 30 weeks and observation of the mice continued for an additional 17 or 18 weeks. For each species, 47 to 50 animals of each sex were placed on test as controls.
In both, species, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-appearing tumors.
The incidence of hepatocellular carcinomas was significantly increased in dosed male rats and the incidence of neoplastic nodules of the liver was significantly increased in dosed female rats. A significant increase in the combined incidence of squamous-cell carcinomas or squamous-cell papillomas of the Zymbal's gland, the ear canal, or the skin of the ear was observed among high dose male rats. A significant increase in mammary adenocarcinomas was observed among dosed female rats.
The incidence of hepatocellular carcinomas was significantly increased among female mice, but no significant increase in liver tumors was observed among male mice.
Under the conditions of this bioassay, hydrazobenzene was carcinogenic to Fischer 344 rats of both sexes, causing increased incidences of hepatocellular carcinoma and Zymbal's gland squamous-cell neoplasms in male rats, neoplastic nodules of the liver in female rats, and mammary adenocarcinomas in female rats. Hydrazobenzene was also carcinogenic to female B6C3F1 mice, causing an increased incidence of hepatocellular carcinomas. The compound was not carcinogenic to male B6C3F1 mice.
Report Date: 1978