Bioassays of DDT, TDE, and p,p'-DDE for possible carcinogenicity.
Bioassays of technical-grade DDT, TDE, and p,p'-DDE for possible carcinogenicity were conducted using Osborne-Mendel rats and B6C3F1 mice. Each compound was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each species and sex were placed on test as controls for the bioassay of each compound. The time-weighted average high and low dietary concentrations of DDT were, respectively, 642 and 321 ppm for male rats, 420 and 210 ppm for female rats, 44 and 22 ppm for male mice, and 175 and 87 ppm for female mice. The time-weighted average high and low dietary concentrations of TDE were, respectively, 3,294 and 1,647 ppm for male rats, 1,700 and 850 ppm for female rats, and 822 and 411 ppm for male and female mice. The time-weighted average high and low dietary concentrations of DDE were, respectively, 839 and 437 ppm for male rats, 462 and 242 ppm for female rats, and 261 and 148 ppm for male and female mice. After the 78-week dosing period there was an additional observation period of up to 35 weeks for rats and 15 weeks for mice. There were significant positive associations between increased chemical concentration and accelerated mortality in female mice dosed with DDT and in both sexes of rats and in female mice dosed with DDE. This association was not demonstrated in other groups. There was, however, poor survival among control and dosed male mice used in the bioassays of DDT and DDE. In all cases adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. When those male rats receiving TDE and their controls were combined within each group so that the numerators of the tumor incidences represented those animals with either a follicular-cell carcinoma or a follicular-cell adenoma of the thyroid, the incidence in the low dose group was significantly higher than that in the controls. There was a significant positive association between the concentration of DDE administered and the incidences of hepatocellular carcinomas in male and female mice. Among dosed rats and mice no other neoplasms occurred in statistically significant incidences when compared to their respective control groups. Under the conditions of these bioassays there was no evidence for the carcinogenicity of DDT in Osborne-Mendel rats or B6C3F1 mice, of TDE in female Osborne-Mendel rats or B6C3F1 mice of either sex, or of p,p'-DDE in Osborne-Mendel rats, although p,p'-DDE was hepatotoxic in Osborne-Mendel rats. The findings suggest a possible carcinogenic effect of TDE in male Osborne-Mendel rats, based on the induction of combined follicular-cell carcinomas and follicular-cell adenomas of the thyroid. Because of the variation of these tumors in control male rats in this study, the evidence does not permit a more conclusive interpretation of these lesions. p,p'-DDE was carcinogenic in B6C3F1 mice, causing hepatocellular carcinomas in both sexes.