Furukawa F, Nishikawa A, Mitsui M, Sato M, Suzuki J, Imazawa T, Takahashi M
Eisei Shikenjo Hokoku. 1994(112):89-96.
A 13-week subchronic toxicity study of bisphenol A (BPA) was performed in male and female B6C3F1 mice at dose levels of 0, 0.2, 0.5, 1.0, 2.0 and 4.0% in the diet, to facilitate dose selection for a subsequent carcinogenicity study. Mice were randomly allocated to 6 groups, each consisting of 10 males and 10 females. Two 0.2% group males and two 4.0% group females died during the experimental period. Suppression of body weight gain and increase in food consumption were observed in males and females of the 4.0% groups. Hematological examination revealed decrease in number of erythrocytes, volume of hemoglobin and value of hematocrit in males and females of the groups receiving 1.0% or above, and an increase in number of platelets in males of 4.0% group. Decrease in number of erythrocytes and hematocrit value was also noticed in females of 0.5% group. Histopathologically, cystic dilatation, degeneration or regeneration of renal tublues were found in males and females of 1.0% or higher groups, multinucleated hepatocytes were increased in mice of both sexes treated with any dose of BPA, and fibrous osteodystrophy was observed in males and females of the 4.0% groups. Based on the results of the present study, it was concluded that the maximum tolerance dose (MTD) of BPA is 0.2% in diet, because the dose level of 0.5% proved to exert significant hematological toxicity.
在雄性和雌性B6C3F1小鼠中开展了一项为期13周的双酚A(BPA)亚慢性毒性研究,饲料中BPA的剂量水平分别为0%、0.2%、0.5%、1.0%、2.0%和4.0%,以便为后续致癌性研究选择剂量。小鼠被随机分为6组,每组由10只雄性和10只雌性组成。实验期间,0.2%组的两只雄性小鼠和4.0%组的两只雌性小鼠死亡。4.0%组的雄性和雌性小鼠均出现体重增加受抑制和食物消耗量增加的情况。血液学检查显示,接受1.0%及以上剂量的组中,雄性和雌性小鼠的红细胞数量、血红蛋白量和血细胞比容值均下降,4.0%组的雄性小鼠血小板数量增加。0.5%组的雌性小鼠红细胞数量和血细胞比容值也有所下降。组织病理学检查发现,1.0%及以上剂量组的雄性和雌性小鼠肾 tubules 出现囊性扩张、变性或再生,任何剂量BPA处理的两性小鼠多核肝细胞均增多,4.0%组的雄性和雌性小鼠出现纤维性骨营养不良。基于本研究结果,得出结论:BPA在饲料中的最大耐受剂量(MTD)为0.2%,因为0.5%的剂量水平已证明会产生显著的血液学毒性。