Bioassay of nithiazide for possible carcinogenicity.

The bioassay of nithiazide for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. Nithiazide was administered in the diet, at either of two concentrations, to groups of 50 male and 50 female animals of each species. The high and low concentrations of nithiazide utilized were, respectively, 1,250 and 625 ppm for rats and 5,000 and 2,500 ppm for mice. Dosed rats received feed containing nithiazide for 38 weeks, and as a result of a shortage of nithiazide, the animals were not fed the dosed feed for the next 9 weeks. The dosed feed diet was then resumed and continued for 56 weeks, after which time a 1-week observation period followed. Dosed mice received feed containing nithiazide for 61 weeks and, due to a shortage of nithiazide, the animals were not fed dosed feed for the next 9 weeks. The dosed feed diet was then resumed and continued for 33 weeks, followed by a 1-week observation period. Twenty animals of each sex and species were placed on test as controls. In both species, adequate numbers of animals survived sufficiently long to be at risk from late-developing tumors. There was no significant positive association between dosage and mortality for either rats or mice. Compound-related mean body weight depression occurred in both sexes of each species. Statistically significant incidences of hepatocellular adenomas and carcinomas were found in high dose male mice but not in female mice. Although the increased incidences of these tumors in dosed female mice were not statistically significant, the evidence presented was strongly suggestive of carcinogenicity to the liver in female B6C3F1 mice. Statistically significant increased incidences of a combination of mammary and skin fibroadenomas and cystadenomas NOS were found in the high dose female rats. No unusual tumors were observed in either species. Under the conditions of this bioassay, nithiazide was carcinogenic in male and probably female B6C3F1 mice, causing a combination of hepatocellular carcinomas and hepatocellular adenomas. Nithiazide was also carcinogenic in female Fischer 344 rats, causing an increase in the incidence of mammary neoplasms. The compound was not carcinogenic in male Fischer 344 rats.