Bioassay of ethyl tellurac for possible carcinogenicity.
A bioassay of technical-grade ethyl tellurac for possible carcinogenicity was conducted by administering the preparation in feed to F344 rats and B6C3F1 mice. Groups of 50 rats of each sex were administered ethyl tellurac at one of two doses, either 300 or 600 ppm for the males and either 150 or 300 ppm for the females, for 105 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at 105 weeks. Groups of 50 mice of each sex were administered ethyl tellurac at one of two doses, initially either 2,500 or 5,000 ppm. Due to signs of toxicity in the dosed animals, these doses were reduced to 500 and 2,000 ppm, respectively, starting at week 41 for the males and at week 38 for the females. The reduced doses were maintained for 66 weeks for the males; for the females, the reduced doses were raised after 3 weeks to 2,000 and 5,000 ppm, respectively, and maintained at these levels for 66 weeks. The time-weighted average doses for the males were either 1,255 or 3,132 ppm; for the females, either 2,132 or 4,915 ppm. Matched controls consisted of 20 untreated mice of each sex. All surviving mice were killed at 106 weeks. Mean body weights of the dosed groups of rats or mice were lower than those of corresponding controls throughout most or all of the bioassay. No other clinical signs in the rats or mice were clearly related to administration of the test chemical. Survival of the rats and the mice was not affected by the chemical, and sufficient numbers of all groups were at risk for the development of late-appearing tumors. In the male rats, mesotheliomas occurred at incidences that were dose related (P=0.012); in direct comparisons, the incidences of the tumors in the individual dosed groups were not significantly higher than that in the control group (controls 0/20, low-dose 2/49, high-dose 8/50). However, the historical-control data at this laboratory indicate an incidence of 12/416 (2.9%) in male F344 rats compared with 8/50 (16%) in the male high-dose group in this study. In the female rats, no tumors occurred at incidences that were related to administration of the test chemical. In both male and female mice, adenomas of the lacrimal (harderian) gland of the eye occurred in the dosed groups, but not in the corresponding controls (males: controls 0/17; low-dose 16/46, high-dose 10/49; females: controls 0/20, low-dose 6/50, high-dose 5/49). The incidences in the dosed groups were not high enough to show statistically significant dose-related trends. However, in direct comparisons of dosed and control groups of male mice, the incidence was statistically significant in the low-dose males (P=0.003). In female mice, direct comparisons of dosed and control groups indicated that the incidence of this tumor was not statistically significant. It is concluded that under the conditions of this bioassay, ethyl tellurac was not carcinogenic for F344 rats or B6C3F1 mice of either sex. The incidence of mesotheliomas in dosed male rats and the incidence of adenomas of the lacrimal (harderian) gland of the eye in dosed mice of either sex provided evidence which was suggestive but under the conditions of the bioassay insufficient to establish the carcinogenicity of ethyl tellurac in these animals.