Maruyama H, Williams G M
American Health Foundation, Valhalla, NY 10595.
Arch Toxicol. 1988;62(6):465-9. doi: 10.1007/BF00288351.
To evaluate the degree of toxicity to the liver of chronic administration of acetaminophen, the slides from two independent previously reported experiments using different strains of mouse were reviewed and compared. One experiment was performed using B6C3F1 mice of both sexes which were fed 0.3, 0.6 or 1.25% acetaminophen in the diet for 41 weeks. The other was conducted with NIH general purpose mice of both sexes which were fed 1.1% acetaminophen in the diet for 48 weeks. In both experiments, at the levels of 1.1 or 1.25%, the drug produced severe liver injury characterized by centrilobular necrosis which was comparable in both males and females at the end of the experiments. The findings show that ingestion of dietary levels of greater than 1% leads to chronic hepatotoxicity to mice. The import of these findings in interpretation of carcinogenicity studies of acetaminophen is discussed.
为评估长期服用对乙酰氨基酚对肝脏的毒性程度，回顾并比较了此前两项分别使用不同品系小鼠进行的独立实验的玻片。一项实验使用了雌雄皆有的B6C3F1小鼠，在其饮食中添加0.3%、0.6%或1.25%的对乙酰氨基酚，持续41周。另一项实验使用了雌雄皆有的NIH通用小鼠，在其饮食中添加1.1%的对乙酰氨基酚，持续48周。在这两项实验中，当剂量为1.1%或1.25%时，该药物均产生了以小叶中心坏死为特征的严重肝损伤，在实验结束时，雌雄小鼠的损伤情况相当。研究结果表明，摄入超过1%的饮食水平会导致小鼠慢性肝毒性。本文还讨论了这些发现对解释对乙酰氨基酚致癌性研究的意义。
