Aze Y, Toyoda K, Imaida K, Hayashi S, Imazawa T, Hayashi Y, Takahashi M
Eisei Shikenjo Hokoku. 1991(109):48-54.
A 13-week subchronic oral toxicity study of stevioside was carried out in F344 rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5% in diet, to determine appropriate dose levels for a 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Between the control and treated groups, there were no differences in body weight gain during the administration period and in food consumption in the later period of the study. LDH on biochemical investigation and single cell necrosis in the liver revealed by histopathological examination were increased in all male treated groups. These were not considered specific changes, because of the lack of any clear dose response, the relatively low severity and the limitation to males. Other parameters that were found to demonstrate significant differences on hematological and biochemical investigations were of minor toxicological significance. From these results, a concentration of 5% in diet was concluded to be a suitable maximum tolerable dose of stevioside for a 2-year carcinogenicity study in rats.
在F344大鼠中开展了甜菊糖苷的13周亚慢性经口毒性研究，饲料中甜菊糖苷的剂量水平分别为0%、0.31%、0.62%、1.25%、2.5%和5%，以确定2年致癌性研究的合适剂量水平。大鼠被随机分为6组，每组由10只雄性和10只雌性大鼠组成。给药期间无动物死亡。在给药期间，对照组和治疗组之间的体重增加以及研究后期的食物消耗量均无差异。生化检查中的乳酸脱氢酶以及组织病理学检查显示的肝脏单细胞坏死在所有雄性治疗组中均增加。由于缺乏明确的剂量反应、严重程度相对较低且仅限于雄性，这些变化不被视为特异性变化。在血液学和生化检查中发现显示出显著差异的其他参数具有较小的毒理学意义。根据这些结果，得出结论，饲料中5%的浓度是大鼠2年致癌性研究中甜菊糖苷合适的最大耐受剂量。
