Clofibrate (ethyl chlorophenoxyisobutyrate, Atromid-S), because it contains a chlorinated phenoxy moiety and is the most commonly used hypolipidemic drug in the United States and Europe, was fed at a concentration of 0.5% in the diet of 25 male F344 rats for 72 to 97 weeks, and the animals were inspected for tumors up to a maximum of 129 weeks. Between 72 and 129 weeks, there were 10 rats with a total of 16 tumors. These included 4 hepatocellular carcinomas, an adenocarcinoma of the glandular stomach, papillary carcinoma of the urinary bladder, acinar cell carcinoma of the pancreas, lymphosarcoma involving pancreas, acinar cell adenomas of the pancreas, renal carcinoma, and sarcomas of the lung and parotid gland. Although the number of experimental animals was small, none of these tumors were present in 25 controls, and systematic examination of available literature dealing with spontaneous tumors in several thousand rats indicated that the tumors in clofibrate-fed rats were not spontaneous. A number of the tumors were transplanted through several generations. Clofibrate, like two other hypolipidemic drugs that are carcinogenic, causes peroxisome proliferation. It is speculated that some drugs that cause peroxisome proliferation may represent a new class of chemical carcinogens and that there may be a relationship between peroxisome proliferation and malignant transformation.
This study was supported in part by Grant CA-5680 awarded by the National Cancer Institute and by Grant GM-15956 from the National Institutes of General Medical Sciences, Department of Health, Education and Welfare.