Bioassay of 2,5-dithiobiurea for possible carcinogenicity.

A bioassay of 2,5-dithiobiurea for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 2,5-Dithiobiurea 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 high dose male rats, of which there were only 49. The dietary concentrations used in the chronic bioassay were 0.6 percent for the low dose rats and 1.2 percent for the high dose rats. The dietary concentrations used for low and high dose mice were 1.0 and 2.0 percent, respectively. After a 78-week dosing period, observation of the mice continued for an additional 16 weeks. For each species, 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-developing tumors. Compound-related mean body weight depression was observed in mice but not in rats. No consistent pattern of clinical signs was observed in either species. No tumors occurred at a significantly higher incidence in dosed rats than in their controls. Among female mice, the Cochran-Armitage test indicated a significant positive association between the incidence of hepatocellular carcinoma and dietary concentrations of 2,5-dithiobiurea. According to results of the Fisher exact test, the incidence of hepatocellular carcinoma was significantly higher in the high dose female mouse group when compared to the corresponding control group but not when compared to the laboratory historical control data. No neoplasms occurred at a significantly higher incidence in dosed male mice than in their controls. Under the conditions of this bioassay, the evidence suggested, but was insufficient to establish the carcinogenicity of 2,5-dithiobiurea for female B6C3F1 mice. The compound was not carcinogenic to male B6C3F1 mice or to male or female Fischer 344 rats.