m-Cresidine, an aromatic amine and dyestuff intermediate, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer associated with exposure to aromatic amines and several other classes of chemicals among workers in the dye manufacturing industry.
A bioassay of technical-grade m-cresidine for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. m-Cresidine in corn oil was administered by gavage five days a weeks at either of two dosages, to groups of 50 male and 49 or 50 female animals of each species. The dosages used in the chronic bioassay for low and high dose rats were 0.08 and 0.16 gm/kg/day, respectively. The time-weighted average dosages used for low and high dose mice were 0.06 and 0.11 gm/kg/day, respectively. After a 77-week dosing period observation of rats continued for an additional 32 to 33 weeks. After a 53-week dosing period, observation of mice continued for an additional observation period of up to 41 weeks. For each species, 50 animals of each sex were placed on test as untreated controls and 25 animals of each sex were placed on test as vehicle controls.
The urinary bladder and the kidney were the target organs of m-cresidine toxicity in male and female rats. Papillary transitional-cell carcinomas of the urinary bladder occurred in 0/45 low dose males, 5/44 (11 percent) high dose males, 1/46 (2 percent) low dose females, and 2/44 (5 percent) high dose females but did not occur in any untreated control or vehicle control rats. Although the incidences in each dosed rat group were not statistically significant when compared to vehicle controls, comparison with historical controls indicates that these bladder carcinomas are rare and are, therefore, considered to be compound-related in both sexes.
Among mice, dose-related nonneoplastic lesions were observed at higher incidences for males than females in the kidneys, spleen and thymus. Dose-related toxic effects were also observed in testes of male mice. No neoplasms occurred in male mice at statistically significant incidences.
Under the conditions of this bioassay, m-cresidine was carcinogenic to Fischer 344 rats, causing papillary transitional-cell carcinomas of the urinary bladder in both sexes. No convincing evidence was provided for carcinogenicity in female B6C3F1 mice. Poor survival of male B6C3F1 mice receiving m-cresidine precluded evaluation of the possible carcinogenicity of the compound in these animals.
|Male Mice:||Inadequate Study|