Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Environ Health Perspect. 2013 Jul;121(7):756-65. doi: 10.1289/ehp.1205784. Epub 2013 Apr 19.
In 2008, the National Institute of Environmental Health Sciences/National Toxicology Program, the U.S. Environmental Protection Agency's National Center for Computational Toxicology, and the National Human Genome Research Institute/National Institutes of Health Chemical Genomics Center entered into an agreement on "high throughput screening, toxicity pathway profiling, and biological interpretation of findings." In 2010, the U.S. Food and Drug Administration (FDA) joined the collaboration, known informally as Tox21.
The Tox21 partners agreed to develop a vision and devise an implementation strategy to shift the assessment of chemical hazards away from traditional experimental animal toxicology studies to one based on target-specific, mechanism-based, biological observations largely obtained using in vitro assays.
Here we outline the efforts of the Tox21 partners up to the time the FDA joined the collaboration, describe the approaches taken to develop the science and technologies that are currently being used, assess the current status, and identify problems that could impede further progress as well as suggest approaches to address those problems.
Tox21 faces some very difficult issues. However, we are making progress in integrating data from diverse technologies and end points into what is effectively a systems-biology approach to toxicology. This can be accomplished only when comprehensive knowledge is obtained with broad coverage of chemical and biological/toxicological space. The efforts thus far reflect the initial stage of an exceedingly complicated program, one that will likely take decades to fully achieve its goals. However, even at this stage, the information obtained has attracted the attention of the international scientific community, and we believe these efforts foretell the future of toxicology.
2008 年，美国国家环境卫生科学研究所/国家毒理学计划、美国环境保护署国家计算毒理学中心和美国国立人类基因组研究所/美国国立卫生研究院化学基因组学中心就“高通量筛选、毒性途径分析和研究结果的生物学解释”达成协议。2010 年，美国食品和药物管理局（FDA）加入了该合作，非正式称为 Tox21。
Tox21 的合作伙伴们一致同意制定一个愿景，并设计一个实施策略，将化学危害评估从传统的动物毒理学实验研究转移到基于目标特异性、基于机制的、主要通过体外检测获得的生物学观察上来。
在这里，我们概述了 Tox21 合作伙伴在 FDA 加入合作之前的努力，描述了为开发目前正在使用的科学技术所采取的方法，评估了当前的状况，并确定了可能阻碍进一步进展的问题，以及提出了解决这些问题的方法。
Tox21 面临着一些非常困难的问题。然而，我们正在将来自不同技术和终点的数据整合到一个有效的毒理学系统生物学方法中，这方面取得了进展。只有当我们获得了广泛的化学和生物/毒理学空间的全面知识时，才能实现这一点。迄今为止的努力反映了一个极其复杂的计划的初始阶段，这个计划可能需要几十年的时间才能完全实现其目标。然而，即使在这个阶段，所获得的信息已经引起了国际科学界的关注，我们相信这些努力预示着毒理学的未来。
