胡椒基丁醚对F344大鼠的慢性毒性研究：肝细胞癌的诱发

Chronic toxicity studies of piperonyl butoxide in F344 rats: induction of hepatocellular carcinoma.

作者信息

Takahashi O, Oishi S, Fujitani T, Tanaka T, Yoneyama M

机构信息

Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.

出版信息

Fundam Appl Toxicol. 1994 Feb;22(2):293-303. doi: 10.1006/faat.1994.1033.

DOI:10.1006/faat.1994.1033

PMID:7911767

Abstract

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.

摘要

将雄性和雌性F344大鼠（每组30 - 33只大鼠）置于含胡椒基丁醚（α-[2-(2 - 丁氧基乙氧基)乙氧基]-4,5 - 亚甲基二氧基 - 2 - 丙基甲苯）的饲料中，含量分别为0（对照）、0.6%、1.2%和2.4%，持续近2年。从大约40周开始，1.2%处理组的雄性大鼠中有10只因盲肠出血死亡。胡椒基丁醚以剂量依赖的方式诱导两性肝细胞癌。在1.2%处理组的雄性大鼠中也发现了肝细胞癌（发生率为26.7%），2.4%处理组的雄性和雌性大鼠中肝细胞癌的发生率分别为所有存活大鼠的80.0%和57.7%。胡椒基丁醚还导致原发性血小板增多症，存在剂量 - 反应关系。与接触相关，还观察到胃和盲肠出血、贫血、肺泡退行性病变以及肾毒性。这些结果表明胡椒基丁醚是大鼠的一种肝癌致癌物。