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首页> 外文期刊>Chemical research in toxicology >Update on EPA's ToxCast program: Providing high throughput decision support tools for chemical risk management
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Update on EPA's ToxCast program: Providing high throughput decision support tools for chemical risk management

机译：EPA ToxCast计划的更新：提供用于化学风险管理的高通量决策支持工具

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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.
机译：在如何评估化学品的安全性和危害对人类健康和环境的潜在影响方面，毒理学领域正处于重大变革的前沿。由于认识到当前范式在成本，时间和通量方面的局限性，再加上现代生物学工具以越来越高的分辨率探测化学-生物相互作用机制的能力日益增强，21世纪的毒理学是快速成型。新方法的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。通过以这种方式理解毒性，我们开始学习化学物质如何引起毒性，而不仅仅是化学物质可能引起什么疾病或健康影响。这种更深入的了解导致人们对确定哪些人群可能处于危险之中，重大的易感性因素以及对剂量反应曲线形状的关键影响具有更大的信心。美国环境保护署（EPA）于5年前启动了ToxCast计划，即“毒性预测仪”，旨在通过对相当大数量的化学药品进行相同数量的测试，从而了解新方法的优势和局限性生物学测定的数量。 EPA正在使用计算方法来构建基于ToxCast体外筛选结果的决策支持工具，以帮助确定化学品的优先级以进行进一步研究，并为许多健康结果开发预测模型。此观点提供了ToxCast的初始概念验证（第一阶段）的摘要，该阶段为该程序的下一阶段和未来方向奠定了基础。

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