Bioassay of emetine for possible carcinogenicity.

Abstract

A bioassay of emetine, an amebicide and anticancer drug, for possible carcinogenicity was conducted by administering the test material by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice. Groups of 35 rats of each sex were administered emetine at one of two doses, either 0.5 or 1 mg/kg body weight, three times per week for 52 weeks, and then observed for an additional 31 or 32 weeks. Control groups of each sex consisted of 10 untreated rats (untreated controls) and 10 rats injected with buffered saline (vehicle controls). Pooled-control groups, used for statistical evaluation, consisted of the vehicle-control rats of each sex for this study combined with 15 vehicle-control rats of each sex from a similar bioassay of another test chemical. All surviving rats were killed at 83 or 84 weeks. Initially, groups of 35 mice of each sex were administered emetine at one of two doses, either 3.2 or 6.4 mg/kg body weight (mid- and high-dose), three times per week. Control groups of each sex consisted of 15 untreated mice (untreated controls) and 15 mice injected with buffered saline (vehicle controls). Due to high mortality rates in the initial treated groups, additional groups of 35 mice of each sex were later put on study at 1.6 mg/kg (low-dose), together with 10 untreated-control and 10 vehicle-control mice of each sex. The high-dose males were treated for 28 weeks and the mid- and high-dose females for 40 and 33 weeks, respectively. Mid- and low-dose male mice and low-dose female mice were treated for 52 weeks, and then observed for an additional 20 or 26 weeks. All surviving mice were killed at 78-83 weeks. Emetine was toxic to male rats at the high dose, to both sexes of mice at the high and mid doses and to a lesser extent at the low dose, as shown by the low survival in these groups. Twenty-six percent of the high-dose male rats and 69% of the high-dose female rats, but none of the high- and mid-dose mice of either sex, survived to the end of the study. In the low-dose mice, 30/35 males and 21/35 females lived at least 1 year, and the median time on study was 72 weeks for males and 59 weeks for females. No tumors occurred at a statistically significant incidence in treated rats or mice compared with controls; however, it should be noted that in this study, treatment of both species was stopped at week 52 and the studies were terminated by week 83, which is earlier than in current bioassays where animals are treated until termination of the studies at 2 years. In addition, there was poor survival among the treated mice. It is concluded that the results of this study do not allow evaluation of the possible carcinogenicity of emetine.