vom Saal Frederick S, Hughes Claude
Division of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA.
Environ Health Perspect. 2005 Aug;113(8):926-33. doi: 10.1289/ehp.7713.
Bisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 microg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10(-12) M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice; and d) recent epidemiologic evidence that BPA is related to disease in women.
双酚A（BPA）是用于制造聚碳酸酯塑料、罐装树脂内衬及其他产品的单体，其全球年产能超过64亿磅。由于这些基于双酚A的聚合物中的酯键易发生水解，双酚A的浸出导致人类广泛接触。由哈佛风险分析中心编写并由美国塑料协会资助的一份近期报告，在仅对19项研究进行审查的基础上得出结论，即双酚A低剂量效应的证据不足；该报告在延迟2.5年后发布。当前对文献的全面审查表明事实恰恰相反。截至2004年12月，有115项关于双酚A低剂量效应的体内研究发表，其中94项报告了显著效应。在31项涉及脊椎动物和无脊椎动物的出版物中，在低于预测的“安全”或参考剂量50微克/千克/天双酚A的情况下出现了显著效应。双酚A的雌激素作用模式已通过体外实验得到证实，这些实验描述了在10⁻¹²摩尔/升或0.23皮克/升时细胞功能的破坏。尽管如此，化学制造商继续对这些已发表的研究结果不予理会，因为没有行业资助的研究报告低剂量双酚A的显著效应，尽管超过90%的政府资助研究报告了显著效应。一些行业资助的研究忽略了阳性对照的结果，许多报告无显著效应的研究使用了一种不适用于雌激素反应研究的大鼠品系。我们建议基于以下几点对双酚A进行新的风险评估：a）大量新文献报告了在低于当前参考剂量的情况下动物出现的不良反应；b）双酚A从食品和饮料容器中的高浸出率，导致人类广泛接触；c）报告称人类血液和组织（包括人类胎儿血液）中的双酚A中位数水平高于对小鼠产生不良反应的水平；d）近期的流行病学证据表明双酚A与女性疾病有关。
