title: Bioassay of trimethylthiourea for possible carcinogenicity.
abstract: A bioassay for the possible carcinogenicity of trimethylthiourea was conducted using Fischer 344 rats and B6C3F1 mice. A mixture containing 80 percent trimethylthiourea and 15 percent dimethylthiourea 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 sex and species were placed on test as controls. The high and low dietary concentrations of trimethylthiourea were, respectively, 500 and 250 ppm for rats and 1,000 and 500 ppm for mice. The compound was administered in the diet for 77 weeks, followed by an observation period of 29 weeks for rats and 14 weeks for mice. There were no significant positive associations between the dosage of trimethylthiourea administered and mortality in rats or mice of either sex. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. For high dose female rats and for dosed mice of both sexes, compound-related mean body weight depression was observed, indicating that the dosages of trimethylthiourea administered to these animals may have approximated the maximum tolerated dosages. Since no mean body weight depression relative to controls, no significant accelerated mortality, and no other signs of toxicity were associated with administration of trimethylthiourea to male rats, it is possible that these animals may have been able to tolerate a higher dietary concentration. The incidences of follicular-cell carcinomas of the thyroid in female rats were dose-related, and there was a significant difference between the incidences in the high dose and control. This same relationship was established for the combination of follicular-cell carcinomas and follicular-cell adenomas in female rats. Under the conditions of this bioassay, dietary administration of trimethylthiourea was carcinogenic in female Fischer 344 rats, inducing follicular-cell carcinomas of the thyroid. There was not sufficient evidence for the carcinogenicity of the compound in male Fischer 344 rats or in B6C3F1 mice of either sex.