Bioassay of tris (2,3-dibromopropyl) phosphate for possible carcinogenicity.
A bioassay of technical-grade tris (2,3-dibromopropyl) phosphate (TBP) for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. TBP was administered in the feed, at either of two concentrations, to groups of 55 male and 55 female rats, and 50 male and 50 female mice. The high and low dietary concentrations of TBP administered were, respectively, 100 and 50 ppm for the male and female rats, and 1,000 and 500 ppm for the male and female mice. After a 103-week dosing period, observation of the rats and mice continued for 1 or 2 additional weeks. For each species, 55 animals of each sex were placed on test as controls. No TBP was added to their diet. In both species, adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Kidney tubular-cell adenomas were observed at incidences which were significant for dosed rats of both sexes by all statistical tests applied. For male rats there was a significant positive association between the incidence of kidney tubular-cell adenocarcinomas and dietary concentration of TBP. Other neoplastic lesions appearing in the treated rats were not statistically significant when compared with the control groups. Among mice, a number of malignant and benign tumors were associated with TBP administration. These tumors included renal tubular-cell carcinoma and adenoma; squamous-cell papilloma and carcinoma of the forestomach; hepatocellular carcinoma and adenoma; and bronchiolar/alveolar adenoma and carcinoma. Renal tubular-cell carcinomas were observed at a statistically significant incidence in male mice but none were observed in females. Tubular-cell adenomas were observed in treated mice of both sexes, but not in their respective controls. The incidence of tubular-cell adenomas was significant in male mice but not in females. Squamous-cell carcinomas were observed in forestomachs of mice of both sexes but not in their respective controls. The incidence was significant in females but not in males. The incidences of squamous-cell papillomas of the forestomach were significant in mice of both sexes. Incidences of hepatocellular carcinoma and hepatocellular adenoma were each significant in female mice. Tumor incidence among male mice was not significant for hepatocellular carcinomas or hepatocellular adenomas. The proportion of mice of each sex having bronchiolar/alveolar adenoma or carcinoma or both had a significant positive dose-related trend. The incidence of bronchiolar/alveolar carcinomas exhibited a significant positive dose-related trend for males, but not for females. It is concluded that under the conditions of this study orally administered TBP was carcinogenic to B6C3F1 mice, causing increased incidences of tumors in livers, lungs, and stomachs of female mice and in kidneys, lungs, and stomachs of male mice. TBP was also carcinogenic in Fischer 344 rats, causing an increased incidence of kidney tumors in both sexes.