title: Bioassay of daminozide for possible carcinogenicity.
abstract: A bioassay of daminozide, a plant growth regulator, for possible carcinogenicity was conducted by administering the test chemical in the diet to Fischer 344 rats and B6C3F1 mice. Groups of 50 rats and 50 mice of each sex were administered daminozide at one of two doses, either 5,000 or 10,000 ppm, for 104 weeks, then observed for an additional week. Matched controls consisted of 20 untreated males and 20 untreated females of each species. All surviving rats and mice were killed at 105 weeks. Mean body weights of the high-dose female mice were appreciably lower than those of the corresponding controls, while mean body weights of all other dosed groups of rats and mice were essentially unaffected. No other clinical signs related to administration of daminozide were observed. Sufficient numbers of animals in all groups of rats and mice were at risk for development of late-appearing tumors. In the male rats, no tumors occurred at incidences that were significantly higher in dosed groups than in controls, except for interstitial-cell tumors of the testis (controls 13/20, low-dose 49/50, high-dose 47/50). These tumors occurred, however, at a high spontaneous rate (182/220) in the historical-control male rats; thus, the association of the interstitial-cell tumors with administration of the chemical is doubtful. In the female rats, adenocarcinomas of the endometrium and leiomyosarcomas of the uterus occurred only in the dosed groups (adenocarcinomas: controls 0/19, low-dose 5/50, high-dose 3/50; leiomyosarcomas: controls 0/19, low-dose 1/50, high-dose 3/50). The incidences in the dosed groups were too low to be statistically significant; however, the low incidence of these tumors in historical-control female rats (2/220 adenocarcinoma and 0/220 leiomyosarcoma) indicate that the occurrence of these tumors in the dosed female rats was associated with the administration of daminozide. In the male mice, there was a dose-related trend (P=0.008) in the incidence of hepatocellular carcinomas; also, the incidence in the high-dose group was significant (P=0.020) compared with that in the controls (controls 0/14, low-dose 7/50, high-dose 13/46). The incidence of these tumors in the historical-control male mice was, however, 21/216; thus, the association of the hepatocellular carcinomas with administration of daminozide is not clear. In female mice, only three such tumors occurred. It is concluded that under the conditions of this bioassay, daminozide was not carcinogenic in the male Fischer 344 rats or in the female B6C3F1 mice. In male B6C3F1 mice, the induction of hepatocellular carcinomas may have been associated with the administration of the test chemical. Daminozide was carcinogenic in female Fischer 344 rats, inducing adenocarcinomas of the endometrium of the uterus and leiomyosarcomas of the uterus.