Tumorigenicity of the hypolipidaemic peroxisome proliferator ethyl-alpha-p-chlorophenoxyisobutyrate (clofibrate) in rats.
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.
D000818:Animals; D002994:Clofibrate / Q000633:toxicity*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008854:Microscopy, Electron; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344
D002994:Clofibrate