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饲以 hinokitiol 的 F344 大鼠 13 周亚慢性毒性研究。

A 13-week subchronic toxicity study of hinokitiol administered in the diet to F344 rats.

机构信息

Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan.

出版信息

Food Chem Toxicol. 2011 Aug;49(8):1782-6. doi: 10.1016/j.fct.2011.04.027. Epub 2011 May 1.

DOI:10.1016/j.fct.2011.04.027
PMID:21557982
Abstract

Myocarditis has been reported in male F344 rats given a diet containing hinokitiol (HT). A subchronic toxicity study was here performed to re-evaluate toxic effects of HT in both sexes of F344 rats with dietary administration at concentrations of 0%, 0.02%, 0.07% and 0.2% for 13 weeks. Significant reduction of body weight gain was noted in 0.2% males and 0.07% and above females. Significant decrease in RBC counts, hemoglobin and hematocrit was detected in 0.07% and 0.2% females. Significant increase in MCV was observed in 0.07% and above males and 0.2% females. In the rats given 0.07% and 0.2%, significant increase in total protein and albumin were detected in males, and in total cholesterol in females. Significant increases in total cholesterol, urea nitrogen and creatinine were also detected in the 0.2% males. Significant increase in relative liver weights was detected in the 0.07% and above males and females. Absolute and relative heart weights were significantly decreased in the 0.07% and above males. Based on the above findings the no-observed-adverse-effect level (NOAEL) of HT for both male and female rats was estimated to be 0.02%, translating into 12.7 and 14.8 mg/kg b.w./day, respectively. Myocarditis was not evident in the present study.

摘要

已有报道称,饲以含有桧木醇(HT)的饮食可导致雄性 F344 大鼠发生心肌炎。本研究进行了一项亚慢性毒性试验,以重新评估 HT 在 F344 大鼠中的毒性作用,雄性和雌性大鼠分别饲以 0%、0.02%、0.07%和 0.2%的 HT 饮食 13 周。0.2%雄性大鼠的体重增长显著减少,0.07%和以上雌性大鼠的体重增长显著减少。0.07%和 0.2%雌性大鼠的 RBC 计数、血红蛋白和血细胞比容显著降低。0.07%和以上雄性大鼠和 0.2%雌性大鼠的 MCV 显著增加。0.07%和 0.2%雄性大鼠的总蛋白和白蛋白显著增加,0.2%雌性大鼠的总胆固醇显著增加。0.2%雄性大鼠的总胆固醇、尿素氮和肌酐也显著增加。0.07%和以上雄性和雌性大鼠的相对肝重显著增加。0.07%和以上雄性大鼠的绝对和相对心脏重量显著降低。基于上述发现,HT 对雄性和雌性大鼠的无观察不良效应水平(NOAEL)估计为 0.02%,分别相当于 12.7 和 14.8mg/kg bw/day。本研究中未观察到心肌炎。

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