Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure
Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure
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DOI：
10.1210/en.2005-1159
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发表时间：
2006-06-01
期刊：
影响因子：
4.8
通讯作者：
Saal, Frederick S. vom
中科院分区：
文献类型：
--
作者：
Welshons, Wade V.;Nagel, Susan C.;Saal, Frederick S. vom
每年有超过60亿磅的雌激素单体双酚A（BPA）用于制造聚碳酸酯塑料产品，金属罐内衬树脂，牙科密封剂以及与其他类型塑料产品的混合物。聚碳酸酯和树脂中连接BPA分子的酯键发生水解，导致游离BPA释放到食品、饮料和环境中，许多监测研究现在显示，几乎无处不在的人类暴露于这种化学物质的生物活性水平。BPA通过经典的核雌激素受体发挥雌激素作用，BPA作为一种选择性雌激素受体调节剂。然而，BPA也通过推测与质膜相关的雌激素受体启动快速反应。与雌二醇类似，BPA在1 pM和1 nM之间的浓度下会引起某些细胞功能的变化，并且通过多种技术在人类孕妇、胎儿和成人血液和其他组织中测量的未结合BPA的平均值和中位数范围超过这些水平。与这些发表的研究结果相反，BPA制造商坚持将BPA描述为弱雌激素，并坚持认为人体暴露水平几乎没有问题。我们对人类暴露于BPA的关注源于：1）确定了介导极低剂量对人类和动物组织影响的分子机制，2）在人类暴露范围内的低剂量对实验动物造成的体内影响，以及3）人类广泛暴露于导致动物不良反应的BPA水平。
Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.