title: Bioassay of ethionamide for possible carcinogenicity.
abstract: A bioassay of the chemotherapeutic drug ethionamide for possible carcinogenicity was conducted by administering the test chemical in feed to Fischer 344 rats and B6C3F1 mice. Groups of 35 rats and 34 or 35 mice of each sex were administered ethionamide at one of the following doses, either 1,500 or 3,000 ppm for the rats and either 1,000 or 2,000 ppm for the mice. The animals were treated 5 days per week for 78 weeks, then observed for an additional 25 or 26 weeks. Matched controls consisted of groups of 15 untreated rats and 15 untreated mice of each sex. All surviving animals were killed at 103 or 104 weeks. Mean body weights of the treated rats and mice were lower than those of the corresponding matched controls during most or all of the study. Survival in the rats was sufficient to allow development of late-appearing tumors. In the mice, survival of the high-dose males (27%), matched-control males (7%), and low-dose females (37%) to the end of the study was low, and the deaths were associated with suppurative lung lesions. However, tests for dose-related trend in mortality were not significant in either sex, and 47% or more of all groups of mice except control males were alive at 78 weeks. In the rats, a variety of neoplasms were observed in treated and control groups of each sex. The lesions were of types commonly found in Fischer 344 rats, and none of the incidences of tumors in dosed animals were statistically significant when compared with controls. In the mice, the incidences of malignant lymphoma were slightly higher in dosed than in control mice (males: controls 2/15, low-dose 8/34, high-dose 4/34; females: controls 2/15, low-dose 4/31, high-dose 10/34). The incidences were not significant by any of the statistical tests used, including the Tarone and Cox tests using the life-table method. It is concluded that under the conditions of this bioassay, ethionamide was not carcinogenic in either Fischer 344 rats or B6C3F1 mice.