Update on EPA's ToxCast Program: Providing High Throughput Decision Support Tools for Chemical Risk Management
Update on EPA's ToxCast Program: Providing High Throughput Decision Support Tools for Chemical Risk Management
复制标题
DOI：
10.1021/tx3000939
复制
发表时间：
2012-07-01
影响因子：
4.1
通讯作者：
Dix, David
中科院分区：
文献类型：
--
作者：
Kavlock, Robert;Chandler, Kelly;Dix, David
毒理学领域正处于如何评估化学品的安全性和危险性对人类健康和环境的潜在影响的重大变革的风口浪尖。由于人们认识到当前模式在成本、时间和产量方面的局限性，加上现代生物学工具在越来越精细的分辨率下探索化学-生物相互作用机制的能力不断增强，21世纪毒理学正在迅速形成。新方法的一个关键要素是关注作为化学相互作用目标的分子和细胞途径。通过以这种方式了解毒性，我们开始了解化学品是如何引起毒性的，而不仅仅是它们可能导致什么疾病或健康影响。这种更深入的理解使人们在确定哪些人群可能处于危险之中、显著的易感因素以及对剂量-反应曲线形状的关键影响方面增加了信心。5年前，美国环境保护署(EPA)发起了ToxCast或“毒性预测者”计划，通过开始对相对大量(数百种)的化学物质进行同等数量的生物测试，以了解新方法的优势和局限性。利用计算方法，美国环保局正在根据ToxCast的体外筛查结果建立决策支持工具，以帮助确定进一步研究的化学品的优先顺序，并开发一些健康结果的预测模型。这一观点提供了ToxCast的初始概念验证第一阶段的摘要，该阶段为该计划的下一阶段和未来方向奠定了基础。
The field of toxicology is on the cusp of a major transformation in how the safety and hazard of chemicals are evaluated for potential effects on human health and the environment. Brought on by the recognition of the limitations of the current paradigm in terms of cost, time, and throughput, combined with the ever increasing power of modern biological tools to probe mechanisms of chemical-biological interactions at finer and finer resolutions, 21st century toxicology is rapidly taking shape. A key element of the new approach is a focus on the molecular and cellular pathways that are the targets of chemical interactions. By understanding toxicity in this manner, we begin to learn how chemicals cause toxicity, as opposed to merely what diseases or health effects they might cause. This deeper understanding leads to increasing confidence in identifying which populations might be at risk, significant susceptibility factors, and key influences on the shape of the dose-response curve. The U. S. Environmental Protection Agency (EPA) initiated the ToxCast, or "toxicity forecaster", program 5 years ago to gain understanding of the strengths and limitations of the new approach by starting to test relatively large numbers (hundreds) of chemicals against an equally large number of biological assays. Using computational approaches, the EPA is building decision support tools based on ToxCast in vitro screening results to help prioritize chemicals for further investigation, as well as developing predictive models for a number of health outcomes. This perspective provides a summary of the initial, proof of concept, Phase I of ToxCast that has laid the groundwork for the next phases and future directions of the program.