Chronic toxicity studies of piperonyl butoxide in F344 rats: induction of hepatocellular carcinoma.
Male and female F344 rats (30-33 rats/group) were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy]-4,5-methylenedioxy-2-propylto luene) 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 thrombocythemia 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.
Takahashi
O
O
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Oishi
S
S
Fujitani
T
T
Tanaka
T
T
Yoneyama
M
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001772:Blood Cell Count / Q000187:drug effects; D001806:Blood Urea Nitrogen; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000473:pathology; D004032:Diet; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010882:Piperonyl Butoxide / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013920:Thrombocythemia, Essential / Q000097:blood / Q000139:chemically induced; D015430:Weight Gain / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000097:blood
D005723:gamma-Glutamyltransferase; D010882:Piperonyl Butoxide