Vandenberg Laura N, Maffini Maricel V, Sonnenschein Carlos, Rubin Beverly S, Soto Ana M
Tufts University School of Medicine, Department of Anatomy and Cellular Biology, 136 Harrison Avenue, Boston, Massachusetts 02111, USA.
Endocr Rev. 2009 Feb;30(1):75-95. doi: 10.1210/er.2008-0021. Epub 2008 Dec 12.
In 1991, a group of 21 scientists gathered at the Wingspread Conference Center to discuss evidence of developmental alterations observed in wildlife populations after chemical exposures. There, the term "endocrine disruptor" was agreed upon to describe a class of chemicals including those that act as agonists and antagonists of the estrogen receptors (ERs), androgen receptor, thyroid hormone receptor, and others. This definition has since evolved, and the field has grown to encompass hundreds of chemicals. Despite significant advances in the study of endocrine disruptors, several controversies have sprung up and continue, including the debate over the existence of nonmonotonic dose response curves, the mechanisms of low-dose effects, and the importance of considering critical periods of exposure in experimental design. One chemical found ubiquitously in our environment, bisphenol-A (BPA), has received a tremendous amount of attention from research scientists, government panels, and the popular press. In this review, we have covered the above-mentioned controversies plus six additional issues that have divided scientists in the field of BPA research, namely: 1) mechanisms of BPA action; 2) levels of human exposure; 3) routes of human exposure; 4) pharmacokinetic models of BPA metabolism; 5) effects of BPA on exposed animals; and 6) links between BPA and cancer. Understanding these topics is essential for educating the public and medical professionals about potential risks associated with developmental exposure to BPA and other endocrine disruptors, the design of rigorously researched programs using both epidemiological and animal studies, and ultimately the development of a sound public health policy.
1991年,21位科学家齐聚温斯普雷德会议中心,讨论化学品暴露后野生动物种群中观察到的发育改变证据。在那里,人们商定了“内分泌干扰物”一词,用以描述一类化学物质,包括那些作为雌激素受体(ERs)、雄激素受体、甲状腺激素受体等的激动剂和拮抗剂的物质。自那时起,这一定义不断演变,该领域也已发展到涵盖数百种化学物质。尽管在内分泌干扰物研究方面取得了重大进展,但仍出现并持续存在一些争议,包括关于非单调剂量反应曲线的存在、低剂量效应的机制以及在实验设计中考虑关键暴露期的重要性的争论。一种在我们环境中普遍存在的化学物质双酚A(BPA),受到了科研人员、政府小组和大众媒体的极大关注。在本综述中,我们涵盖了上述争议以及在BPA研究领域使科学家产生分歧的另外六个问题,即:1)BPA的作用机制;2)人类暴露水平;3)人类暴露途径;4)BPA代谢的药代动力学模型;5)BPA对暴露动物的影响;6)BPA与癌症之间的联系。了解这些主题对于向公众和医学专业人员宣传与发育暴露于BPA和其他内分泌干扰物相关的潜在风险、设计同时使用流行病学和动物研究的经过严格研究的项目以及最终制定合理的公共卫生政策至关重要。