Lack of carcinogenicity of oxprenolol, a β-adrenergic blocking agent

Abstract

Because of an early report that pronethalol, a β -adrenergic blocking agent, produced lymphoreticular tumors in mice, all β -blocking agents as a class came under suspicion. For this reason, several carcinogenicity studies were conducted on the β -blocker, oxprenolol. Drug diet studies in Carworth CF/1 mice were conducted in two separate laboratories, one in which the drug was fed in a commercial diet at 15, 50, and 150 mg/kg/day for 18 months and observed for an additional 3 months, and the other in which the drug was fed in a semisynthetic diet at 150 mg/kg/day for 18 months. Pronethalol (150 mg/kg/day) was used in the semisynthetic diet studies for comparison, and 2-acetylaminofluorine (2-AAF) was fed in the diet at a level of 0.03% for 12 months as a positive carcinogen control. Oxprenolol was also tested in Charles River CD rats for 18 months by admixing in a commercial diet at dosages of 15, 50, and 150 mg/kg/day. Definite evidence of hepatocarcinogenicity was found in mice given 2-AAF for 12 months. In contrast, neither oxprenolol nor pronethalol gave any indication of carcinogenic potential after 18–21 months in either mice or rats. These findings suggest that the initial observation of a carcinogenic response in mice to pronethalol was possibly fortuitous or perhaps related to the specific strain of mouse used and that β -adrenergic blocking agents as a class should not be considered carcinogenic.