[A 13-week subchronic toxicity study of bisphenol A in B6C3F1 mice].

F Furukawa, A Nishikawa, M Mitsui, M Sato, J Suzuki, T Imazawa, M Takahashi
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Abstract

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.

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双酚A对B6C3F1小鼠13周的亚慢性毒性研究
本研究对雄性和雌性B6C3F1小鼠进行了为期13周的亚慢性毒性研究,其剂量水平分别为0、0.2、0.5、1.0、2.0和4.0%,以便为后续的致癌性研究选择剂量。将小鼠随机分为6组,每组雄性10只,雌性10只。0.2%组雄鼠2只,4.0%组雌鼠2只,试验期死亡。在4.0%组中,雄性和雌性的体重增加受到抑制,食物消耗增加。血液学检查显示,1.0%及以上各组男性和女性红细胞数量、血红蛋白体积和红细胞压积值减少,4.0%组男性血小板数量增加。0.5%组女性红细胞数量和红细胞压积值也明显下降。病理组织学上,1.0%及以上双酚a组雌雄小鼠均出现囊性扩张、肾小管变性或再生,多核肝细胞增多,4.0%双酚a组雌雄小鼠均出现纤维性骨营养不良。根据本研究结果,BPA在日粮中的最大耐受剂量(MTD)为0.2%,因为0.5%的剂量水平证明会产生显著的血液毒性。
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