Welshons Wade V, Nagel Susan C, vom Saal Frederick S
Department of Biomedical Sciences, E102 Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri 65211-5120, USA.
Endocrinology. 2006 Jun;147(6 Suppl):S56-69. doi: 10.1210/en.2005-1159. Epub 2006 May 11.
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.
每年有超过60亿磅的雌激素单体双酚A（BPA）被用于制造聚碳酸酯塑料制品、金属罐装食品的内衬树脂、牙科密封剂以及与其他类型塑料制品的混合物。聚碳酸酯和树脂中连接双酚A分子的酯键会发生水解，导致游离双酚A释放到食品、饮料和环境中，众多监测研究表明，现在人类几乎普遍接触到具有生物活性水平的这种化学物质。双酚A通过经典的核雌激素受体发挥雌激素作用，并且双酚A作为一种选择性雌激素受体调节剂。然而，双酚A还可能通过与质膜相关的雌激素受体引发快速反应。与雌二醇类似，双酚A在1皮摩尔至1纳摩尔的浓度范围内会引起某些细胞功能的变化，通过多种技术在人类孕妇、胎儿、成人血液及其他组织中测得的未结合双酚A的平均和中位数范围超过了这些水平。与这些已发表的研究结果形成对比的是，双酚A制造商仍坚持将双酚A描述为一种弱雌激素，并坚称几乎无需担心人类接触水平。我们对人类接触双酚A的担忧源于以下几点：1）确定了在极低剂量下介导人类和动物组织效应的分子机制；2）在人类接触范围内的低剂量对实验动物产生的体内效应；3）人类广泛接触到对动物产生不良影响的双酚A水平。
