Tox21

Tox21

旋转臂，旋转臂

Thousands of chemical substances exist in the world，but only asmall fraction of these have been adequately assessed for their potential toxicity to humans。The Toxicology in the 21st Century program，or Tox21，is a unique collaboration between several federal agencies to develop new ways to rapidly test whether substances adversely affect human health。Substances assayed in Tox21include a diverse range of products such as:commercial chemicals，pesticides，food additives/contaminants，and medical compounds。

The following four government agencies bring their unique expertise，resources，and tools to the Tox21 collaboration:

  • National Institute of Environmental Health Sciences（NIEHS）/National Toxicology Program（NTP）单击功能区上，
    National Institutes of Health（NIH），U.S.Department of Health and Human Services
  • 高级翻译方案（NCATS）单击功能区上，
    National Institutes of Health（NIH）
  • U.S.Food and Drug Administration（FDA）单击功能区上，
    U.S.Department of Health and Human Services
  • 计算机辅助中心单击功能区上，
    Office of Research and Development，U.S.Environmental Protection Agency（EPA）
后退到顶部

Goals of the Tox21 Program

The goal of Tox21is to research，develop，evaluate，and translate innovative test method that will better predict how substances may affect humans and the environment。This includes the use of robotics in high-throughput screening（HTS）in Tox21as well as the use of other new approach methodologies to evaluate substance toxicity。

The use of robotics in HTS is important because of the ability to increase the volume and speed of testing。While many conventional pre-clinical tests use animals，these approaches are often slow and expensive。In addition，they provide no guarantee of predicting toxic health effects on humans later observed in clinical trial settings。Automated，“high-throughput”screening serves an important role asan alternative method foranimal use，as well asan efficient and forward-thinking use of scientific resources。

Tox21aims to：

  • 第一次全方位定位
  • Identify mechanisms of action for further investigation（e.g.，toxicity-associated and disease-associated pathways）
  • 去极化电流检测器predict how substances will affect biological responses（predictive toxicology）
  • Employ测试methods using human cells（in vitroapproaches）
  • 冗余时间、effort和cost associated with测试
  • 内容到修复、修复和修复
后退到顶部

Research Phases

Since2008，NIEHS and collaborating agencies have created a three-phase plan。Today，Tox21is in the Phase III stage of the collaboration。

Phase I&II

Some milestones achieved during Phase I and Phase III:

Phase Milestones
Phase I
  • Demonstrate robotic testing could produce high-quality test results for thousands of substances，with the goal of reduction in animal testing。
  • By2010，the use of robotics for high-throughput screening yielded high quality data on environmental substances in a fraction of the time required with traditional animal testing。
Phase II
  • The quantity of compounds tested and types of assays（methods or testing）used were greatly increased。
  • The chemical library was expanded to more than10000compounds，including industrial and consumer products，food additives，drugs，and chemical mixtures。
  • Tox21partners are pursuing additional cell-based experiments to further define and clarify chemical exposure effects。

Phase III

In Phase III，the Tox21federal partners developed a document entitled“The US Federal Tox21Program:Astrategic and operational plan for continued leadership”that was recently published（Thomas et al.，ALTEX2018Mar8。DOI:10.14573/altex.1803011.）。Focus were identified for moving forward in Phase III，which were：

  • 开发试验系统that are predictive of human toxicity and dose response
  • 预应力检测系统in vitro测试系统
  • Curate and characterize legacyin vivotoxicity studies
  • Establish scientific confidence inin vitro测试系统和集成的assay batteries
  • Refine and deployin vitro测量和测量in vitro分度，分度，分度

In one Phase III project，Tox21 partners have identified approximately2800human genes that can serve as“Sentinel”genes（the S150+gene set）to interrogate responses in cells and tissues to toxic substances。Identification of similar gene sets for rats，mice，and zebrafish are in process。anew test using these genes will study changes in levels of ribonucleic acid（RNA）messages（or transcripts），which may ultimately reveal the effect of substances on our genes。

Phase III will also attempt to predict human disease by assessing the effects of substances on cells more like those in human organs，such as the liver，heart，or brain。Phase III will test substances in3-D organ-like models，as well as organisms，like zebrafish，that have shared biological complexity with humans。

Scientists can already predict toxicity，if a substance's structure is similar to that of aknown toxicant，using a process referred to as“read across.”Ultimately，researchers hope to create better computational models，including biological response read across apaches，to better redight humans。

安装在Tox21and its testing phases are available in theTox21 Fact Sheet。

后退到顶部

联络，联络

For further information on NTP’s Tox21 program，contact:

  • David M.Reif，Ph.D。
  • Chief，Predictive Toxicology Branch
  • 530 Davis Dr Durham，NC27713
  • 984-287-3195