Cho Y-M, Onodera H, Ueda M, Imai T, Hirose M
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo 158-8501, Japan.
Food Chem Toxicol. 2006 Jun;44(6):891-7. doi: 10.1016/j.fct.2005.12.002. Epub 2006 Jan 25.
A subchronic toxicity study of a flavonoid morin was performed in both sexes of F344 rats with dietary administration at concentrations of 0%, 0.625%, 1.25%, 2.5% and 5% (w/w) for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any group. Although a slight tendency for increase in food intake was noted in both sexes of the 2.5% and 5.0% groups, slight non-significant body weight decrease was observed in 5.0% males. Significant increases in alanine transaminase (ALT; over 2.5%), alkali phosphatase (ALP; 1.25% and 5.0%) and relative liver weights (1.25% and 2.5%) in males and in gamma-glutamyl transpeptidase (gamma-GT), aspartate transaminase (AST), ALT, relative liver weights in the 2.5% and 5.0% females and ALP in 5.0% females were noted. Increased urea nitrogen and relative kidney weights at dose of 1.25% and above and creatinine at 5.0% were observed also in females. On histopathological observation, hepatocyte hypertrophy was detected in 3 of 10 5.0% females. Based on the above findings, the no-observed-adverse-effect level (NOAEL) for both sexes was estimated to be 0.625% (299 and 356 mg/kg b.w./day for males and females, respectively).
对F344大鼠进行了一项关于黄酮类化合物桑色素的亚慢性毒性研究，以0%、0.625%、1.25%、2.5%和5%（w/w）的浓度通过饮食给药，持续13周。在整个实验期间，任何组均未观察到死亡或异常临床体征。虽然在2.5%和5.0%组的雌雄大鼠中均注意到食物摄入量有轻微增加趋势，但在5.0%的雄性大鼠中观察到体重略有下降但无统计学意义。雄性大鼠中丙氨酸转氨酶（ALT；超过2.5%）、碱性磷酸酶（ALP；1.25%和5.0%）以及相对肝脏重量（1.25%和2.5%）显著增加，雌性大鼠在2.5%和5.0%组中γ-谷氨酰转肽酶（γ-GT）、天冬氨酸转氨酶（AST）、ALT、相对肝脏重量以及5.0%雌性大鼠中的ALP也显著增加。在雌性大鼠中，还观察到在1.25%及以上剂量时尿素氮和相对肾脏重量增加，以及在5.0%剂量时肌酐增加。组织病理学观察发现，在10只5.0%的雌性大鼠中有3只检测到肝细胞肥大。基于上述结果，估计雌雄两性的未观察到有害作用水平（NOAEL）均为0.625%（雄性和雌性分别为299和356 mg/kg体重/天）。
