Chronic toxicity of 2,3,7,8 tetrachlorodibenzo-p-dioxin in rats
- J. P. Van Miller, J. R. Allen
- Fed. Proc. 36(3);
A bioassay of 2,7-dichlorodibenzo-p-dioxin (DCDD) for possible carcinogenicity was conducted by administering the test chemical in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 35 rats of each sex were administered DCDD at one of two doses, either 5,000 or 10,000 ppm, for 110 weeks. Groups of 50 mice of each sex were administered these same doses for 90 weeks. Controls consisted of 35 untreated rats of each sex and 50 untreated mice of each sex. All surviving male rats were killed at 110 to 112 weeks, all surviving female rats at 110 to 117 weeks, all surviving male mice at 92 to 101 weeks, and all surviving female mice at 91 to 98 weeks. Mean body weights of most of the dosed groups of rats and mice were lower than those of corresponding controls both when placed on study and for much of the study period; however, survival of any group was not significantly affected by administration of the test chemical. Sufficient numbers of dosed and control rats and mice of each sex were at risk for the development of late-appearing tumors. No tumors were induced in male or female rats or female mice at incidences that were significantly higher in the dosed groups than in the corresponding control groups. Both low-and high-dose rats had toxic hepatic lesions characterized by centrilobular fatty metamorphosis and/or necrosis. In the male mice, hepatocellular adenomas or carcinomas occurred at incidences that were dose related (P=0.008), and, in direct comparisons, were higher in the low-dose group (P=0.008) and the high-dose group (P=0.010) than in the control group (controls 8/49, low-dose 20/50, high-dose 17/42). However, the historical incidence of this lesion in control male B6C3F1 mice at this laboratory does not permit a clear association of the lesion with the administration of the test compound. There were also significant increases in the incidence of combinations of leukemias and lymphomas and of hemangiosarcomas and hemangiomas in the low-dose male mice, but these findings were not supported by the high-dose animals. It is concluded that under the conditions of this bioassay, DCDD was not carcinogenic for Osborne-Mendel rats of either sex or for female B6C3F1 mice. The marginal increased incidences of combinations of leukemias and lymphomas, of hemangiosarcomas and hemangiomas, and of hepatocellular carcinomas and adenomas in male B6C3F1 mice are, however, considered as suggestive of a carcinogenic effect of 2,7-dichlorodibenzo-p-dioxin in these animals.