Designing Endocrine Disruption Out of the Next Generation of Chemicals.
Designing Endocrine Disruption Out of the Next Generation of Chemicals.
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DOI：
10.1039/c2gc35055f
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发表时间：
2013-01
期刊：
影响因子：
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通讯作者：
Myers JP
中科院分区：
文献类型：
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作者：
Schug TT;Abagyan R;Blumberg B;Collins TJ;Crews D;DeFur PL;Dickerson SM;Edwards TM;Gore AC;Guillette LJ;Hayes T;Heindel JJ;Moores A;Patisaul HB;Tal TL;Thayer KA;Vandenberg LN;Warner J;Watson CS;Saal FS;Zoeller RT;O'Brien KP;Myers JP
绿色化学的中心目标是在设计新化学品时避免危险。如果在设计过程中尽可能早地获得关于化学品潜在危险影响的信息，就能最好地实现这一目标。内分泌干扰是一种迄今为止工业和管理科学都没有充分解决的危害。为了帮助化学家避免这种危害，我们提出了一种内分泌干扰测试协议，供化学家在设计新化学品时使用。内分泌干扰分层方案（TiPED）是在一个科学咨询委员会的监督下创建的，该委员会由绿色化学和环境健康科学的主要代表组成。TIPED被认为是一种新的化学设计工具，因此它从理论上的化学家开始“绘图板”。它由五个测试层组成，从广泛的计算机模拟评估到特定的细胞和整个生物体检测。为了有效地检测内分泌干扰，测试方案必须能够测量化学品的潜在的类内分泌干扰或抑制内分泌干扰的作用，以及这些化学品可能与细胞受体发生的许多可能的相互作用和信号传导。因此，我们设计了这个协议，广泛询问内分泌系统。拟议的方案不会检测到内分泌干扰的所有可能机制，因为对这些现象的科学理解正在迅速发展。为了确保方案保持最新，我们已经制定了一项计划，随着科学的进步，将新的检测方法纳入方案中。在本文中，我们提出的原则，应指导科学的测试新的化学品内分泌干扰，以及原则，以评估个别测定的适用性，和实验室的可靠性。在“原理验证”测试中，我们使用已发表的文献通过协议运行了6种通过不同内分泌机制起作用的内分泌干扰物（EDCs）。每一种都被确定为一个或多个层次的内分泌活性。我们认为，这一自愿检测议定书将是一个有力的工具，有助于有效和及早查明可能存在问题的化学品，同时最终减少对公众健康的风险。
A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical’s potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at “the drawing board.” It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a ‘proof-of-principle’ test, we ran 6 endocrine disrupting chemicals (EDCs) that act via different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health.