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© 1994 Oxford University Press

research-article

Chronic Toxicity Studies of Piperonyl Butoxide in F344 Rats: Induction of Hepatocellular Carcinoma1

O. TAKAHASHI2, S. OISHI, T. FUJITANI, T. TANAKA and M. YONEYAMA

Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health 24-1, Hyakunincho 3-chome, Shinjuku-ku, Tokyo 169, Japan

Received May 20, 1992; accepted July 7, 1993

Male and female F344 rats (30–33 rats/group) were administered piperonyl butoxide ({alpha}-[2-(2 butoxyethoxy)ethoxy]-4-,5-methylenedioxy-2-propyltoluene) in the diet at levels of 0 (control), 0.6, 1.2, and 2.4% for nearly 2 years. Beginning at about 40 weeks, 10 rats in the 1.2% treated male group died due to cecal hemorrhages. Piperonyl butoxide induced hepatocellular carcinoma in both sexes in a dose-dependent manner. Hepatocellular carcinoma was found even in the 1.2% treated male group (incidence, 26.7%), and incidences in the 2.4% groups of males and females were 80.0 and 57.7% respectively of all those surviving. Piperonyl butoxide also caused essential thrombo cythemia with a dose-response relationship. Hemorrhages in stomach and cecum, anemia, degenerative lesions of alveoli, and nephrotoxicity were also observed related to exposure. These results indicate that piperonyl butoxide is a hepatocarcinogen to the rat.


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