Schug T T, Abagyan R, Blumberg B, Collins T J, Crews D, DeFur P L, Dickerson S M, Edwards T M, Gore A C, Guillette L J, Hayes T, Heindel J J, Moores A, Patisaul H B, Tal T L, Thayer K A, Vandenberg L N, Warner J, Watson C S, Saal F S Vom, Zoeller R T, O'Brien K P, Myers J P
Green Chem. 2013 Jan;15(1):181-198. doi: 10.1039/C2GC35055F.
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 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.
绿色化学的一个核心目标是在新化学品设计过程中避免危害。若能在设计过程中尽早获取有关化学品潜在危害影响的信息，就能最好地实现这一目标。内分泌干扰是一种危害类型，迄今为止，工业科学和监管科学都未对其予以充分关注。为帮助化学家避免此类危害，我们提出了一种内分泌干扰测试方案，供化学家在新化学品设计中使用。内分泌干扰分层方案（TiPED）是在一个由绿色化学和环境卫生科学领域的主要代表组成的科学咨询委员会监督下制定的。TiPED被设想为新化学品设计的工具，因此理论上它从化学家“在绘图板前”开始。它由五个测试层级组成，从广泛评估到基于特定细胞和整个生物体的检测。为有效检测内分泌干扰，测试方案必须能够测量化学品潜在的类激素或激素抑制作用，以及此类化学品与基于细胞的受体可能产生的许多相互作用和信号后遗症。因此，我们设计了这个方案以广泛地探究内分泌系统。由于对这些现象的科学理解正在迅速发展，所提议的方案无法检测到内分泌干扰的所有可能机制。为确保该方案与时俱进，我们制定了一项计划，随着科学的进步将新的检测方法纳入该方案。在本文中，我们阐述了指导新化学品内分泌干扰检测科学的原则，以及评估单个检测方法适用性和实验室可靠性的原则。在一次“原理验证”测试中，我们依据已发表的文献，让6种通过不同内分泌机制起作用的内分泌干扰化学物质（EDCs）通过该方案进行测试。每种物质都在一个或多个层级中被确定为具有内分泌活性。我们相信，这个自愿性测试方案将成为一个动态工具，有助于高效且早期地识别潜在有问题的化学品，同时最终降低对公众健康的风险。
