Filer Dayne, Patisaul Heather B, Schug Thaddeus, Reif David, Thayer Kristina
National Center for Computational Toxicology, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, USA.
Curr Opin Pharmacol. 2014 Dec;19:145-52. doi: 10.1016/j.coph.2014.09.021.
Identifying chemicals, beyond those already implicated, to test for potential endocrine disruption is a challenge and high throughput approaches have emerged as a potential tool for this type of screening. This review focused the Environmental Protection Agency's (EPA) ToxCast(TM) high throughput in vitro screening (HTS) program. Utility for identifying compounds was assessed and reviewed by using it to run the recently expanded chemical library (from 309 compounds to 1858) through the ToxPi(TM) prioritization scheme for endocrine disruption. The analysis included metabolic and neuroendocrine targets. This investigative approach simultaneously assessed the utility of ToxCast, and helped identify novel chemicals which may have endocrine activity. Results from this exercise suggest the spectrum of environmental chemicals with potential endocrine activity is much broader than indicated, and that some aspects of endocrine disruption are not fully covered in ToxCast.
识别除已涉及的化学物质之外的、用于检测潜在内分泌干扰的化学物质是一项挑战,高通量方法已成为这类筛选的一种潜在工具。本综述聚焦于美国环境保护局(EPA)的ToxCast™高通量体外筛选(HTS)计划。通过使用该计划,将最近扩充的化学物质库(从309种化合物增至1858种)按照ToxPi™内分泌干扰物优先排序方案进行运行,以此评估并审查其在识别化合物方面的效用。该分析涵盖了代谢和神经内分泌靶点。这种研究方法同时评估了ToxCast的效用,并有助于识别可能具有内分泌活性的新型化学物质。这项工作的结果表明,具有潜在内分泌活性的环境化学物质范围比所示的要广泛得多,而且ToxCast并未完全涵盖内分泌干扰的某些方面。