Carcinogenicity of o-ethoxybenzamide in (C57BL/6N X C3H/HeN)F1 mice

The carcinogenicity of o-ethoxybenzamide (CAS: 938-73-8), which is also called ethenzamide and which is widely used as an antipyretic anodyne in Japan, was examined in 298 (C57BL/6N X C3H/HeN)F1 mice. Groups of males and females were fed a diet containing 0 (control), 0.4, or 1.2% o-ethoxybenzamide for 96 weeks and sacrificed at the 100th week. Among the male mice fed the higher dose of the drug, the total incidence of liver cell tumors was 68%, with 18% of the mice developing hepatocellular carcinomas; both yields were significantly higher than those in the controls. In o-ethoxybenzamide-treated male mice the multiplicities of the hepatic cell tumors were also significantly higher than the multiplicity of the hepatic tumor in male control mice. A dose-response relationship with regard to both incidence and multiplicities of hepatic cell tumors in male mice was observed. In female mice fed o-ethoxybenzamide the incidence and multiplicities of the liver cell tumors were increased compared to those of the controls, but statistical significance was observed only in the multiplicity of tumors in mice given the lower dose. In both sexes hepatic cell tumors developed earlier than in the controls. These results show that o-ethoxybenzamide enhances the development of hepatic cell tumors in male (C57BL/6N X C3H/HeN)F1 mice.