Chronic toxicity tests of pyrilamine maleate and methapyrilene hydrochloride in F344 rats.

Methapyrilene hydrochloride was administered at levels of 125 or 250 ppm in the diet to groups of male and female F344 rats. The closely analogous antihistaminic drug pyrilamine, as the maleate, was given at 2000 ppm in the diet or at 2 g/litre drinking-water to groups of male and female F344 rats. Almost all of the rats given the higher dose of methapyrilene had either carcinomas or neoplastic nodules of the liver, whereas at 125 ppm 40% of the rats had neoplastic nodules in the liver. Among the 20 male and 20 female rats treated with pyrilamine maleate mixed into the diet, two males and two females had hepatocellular carcinomas and, in addition, five males and eight females had neoplastic nodules in the liver. The incidence of liver neoplasms in the rats given pyrilamine in the drinking-water did not differ from that in the untreated controls, of which five males and three females had neoplastic nodules in the liver.