Nyska Abraham, Hayashi Shim-Mo, Koyanagi Mihoko, Davis Jeffrey P, Jokinen Micheal P, Ramot Yuval, Maronpot Robert R
Sackler School of Medicine, Tel Aviv University, Toxicologic Pathology, Timrat, Israel.
Global Scientific and Regulatory Affairs, San-Ei Gen, F.F.I., Inc., Osaka, Japan.
Food Chem Toxicol. 2016 Nov;97:354-366. doi: 10.1016/j.fct.2016.09.030. Epub 2016 Sep 28.
alpha-Glycosyl isoquercitrin (AGIQ) is highly absorbable and has been shown to possess antioxidative properties. Based on a favorable safety profile, it has been confirmed as generally recognized as safe (GRAS) compound by the FDA. Nevertheless, safety and toxicity information for AGIQ is still sparse. Therefore, the aim of this study was to test the safety and toxicokinetics of AGIQ in a 90-day study in 60 male and 60 female Sprague-Dawley rats at dietary doses up to 5%. All animals survived until scheduled euthanasia with no clinical signs of toxicity in any animal. AGIQ was rapidly absorbed with metabolism to quercetin and quercetin glucuronide at all dose levels. Statistically significant changes were noted in some tissue weights and clinical chemistry analytes, without evidence of systemic toxicity. The most prominent finding was systemic dose dependent yellow discoloration of bones of treated animals. However, no changes were observed microscopically, and this observation was concluded as toxicologically insignificant. The overall lack of adverse clinical signs, changes in body weight, feed consumption, clinical pathology parameters, and histopathological endpoints in animals administered AGIQ supports no observable adverse effect levels (NOAEL) of 5.0% in diet for both male and female rats (3461 mg/kg/day and 3867 mg/kg/day, respectively).
α-糖基异槲皮苷（AGIQ）具有高度可吸收性，且已被证明具有抗氧化特性。基于良好的安全性，它已被美国食品药品监督管理局（FDA）确认为一般认为安全（GRAS）的化合物。然而，关于AGIQ的安全性和毒性信息仍然稀少。因此，本研究的目的是在一项为期90天的研究中，对60只雄性和60只雌性斯普拉格-道利大鼠进行测试，膳食剂量高达5%，以检验AGIQ的安全性和毒代动力学。所有动物均存活至预定安乐死，任何动物均无毒性临床症状。在所有剂量水平下，AGIQ均被迅速吸收并代谢为槲皮素和槲皮素葡萄糖醛酸苷。在一些组织重量和临床化学分析物中发现了具有统计学意义的变化，但没有全身毒性的证据。最显著的发现是处理过的动物骨骼出现全身剂量依赖性的黄色变色。然而，显微镜下未观察到变化，这一观察结果在毒理学上被认为无显著意义。在给予AGIQ的动物中，总体缺乏不良临床症状、体重变化、饲料消耗、临床病理学参数和组织病理学终点变化，这支持了雄性和雌性大鼠在饮食中5.0%的剂量水平（分别为3461毫克/千克/天和3867毫克/千克/天）下无明显不良作用水平（NOAEL）。
