Carbromal, a mild central nervous system depressant, was selected for bioassay by the National Cancer Institute because of the similarity of the biological activity of this compound to that of urethan, which is known to induce leukemia in mice and is an initiator of skin carcinogenesis in mice, and the widespread exposure to this compound among the general population via deliberate ingestion for medicinal purposes.
A bioassay for the possible carcinogenicity of carbromal was conducted using Fischer 344 rats and B6C3F1 mice. Carbromal was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species with the exception of 49 low dose male mice and high dose female mice. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of carbromal were, respectively, 2,500 and 1,250 ppm for rats and 2,500 and 1,250 ppm for mice. The compound was administered for 103 weeks to rats and for 78 weeks to mice. The period of compound administration was followed by an observation period of 1 week for rats and 26 weeks for mice.
There was no significant positive associations between the concentrations of carbromal administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Slight dose-related mean body weight depression was observed for male rats and for females of both species and the mean body weight among dosed male mice was lower than that for controls, indicating that the concentrations of carbromal administered to the animals in this bioassay may have approximated the maximum tolerated concentrations.
None of the statistical tests for any site in female rats or in mice of either sex indicated a significant positive association between compound administration and tumor incidence. There was a significant positive association between the concentrations administered and the incidences of adrenal pheochromocytomas in male rats; however, the Fisher exact comparisons were not significant.
Under the conditions of this bioassay, dietary administration of carbromal was not carcinogenic in Fischer 344 rats or B6C3F1 mice.