Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-α-p-chlorophenoxyisobutyrate (clofibrate) in rats

Abstract

Ethyl-alpha-p-chlorophenoxyisobutyrate), a hypolipidaemic drug which induces hepatomegaly and proliferation of peroxisomes in liver cells of rats and mice, was fed to 15 male F344 rats at a dietary concentration of 0.5% (v/w) for up to 28 months. Hepatocellular carcinomas developed in 10/11 (91%) rats killed between 24 and 28 months. Other tumours included carcinoma of the pancreas (2 rats), leiomyoma of the small intestine (1 rat) and a large dermatofibrosarcoma (1 rat). Clofibrate is the third hypolipidaemic peroxisome proliferator demonstrated to be hepatocarcinogenic in rats. These studies suggest that hypolipidaemic agents which are capable of producing a sustained hepatomegalic and peroxisome-proliferative effect also induce liver tumours.