National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
National Center for Environmental Assessment, U.S. Environmental Protection Agnecy, Washington, D.C. 20004.
Toxicol Sci. 2019 Jun 1;169(2):317-332. doi: 10.1093/toxsci/kfz058.
The U.S. Environmental Protection Agency (EPA) is faced with the challenge of efficiently and credibly evaluating chemical safety often with limited or no available toxicity data. The expanding number of chemicals found in commerce and the environment, coupled with time and resource requirements for traditional toxicity testing and exposure characterization, continue to underscore the need for new approaches. In 2005, EPA charted a new course to address this challenge by embracing computational toxicology (CompTox) and investing in the technologies and capabilities to push the field forward. The return on this investment has been demonstrated through results and applications across a range of human and environmental health problems, as well as initial application to regulatory decision-making within programs such as the EPA's Endocrine Disruptor Screening Program. The CompTox initiative at EPA is more than a decade old. This manuscript presents a blueprint to guide the strategic and operational direction over the next 5 years. The primary goal is to obtain broader acceptance of the CompTox approaches for application to higher tier regulatory decisions, such as chemical assessments. To achieve this goal, the blueprint expands and refines the use of high-throughput and computational modeling approaches to transform the components in chemical risk assessment, while systematically addressing key challenges that have hindered progress. In addition, the blueprint outlines additional investments in cross-cutting efforts to characterize uncertainty and variability, develop software and information technology tools, provide outreach and training, and establish scientific confidence for application to different public health and environmental regulatory decisions.
美国环境保护署（EPA）面临着有效且可信地评估化学安全性的挑战，而通常情况下，其可用的毒性数据有限或没有。商业和环境中发现的化学物质数量不断增加，加上传统毒性测试和暴露特征描述所需的时间和资源，这使得我们继续强调需要新的方法。2005 年，EPA 通过采用计算毒理学（CompTox）并投资于推动该领域发展的技术和能力，开辟了新的途径来应对这一挑战。这一投资的回报已通过一系列人类健康和环境健康问题的结果和应用得到证明，并且已初步应用于 EPA 的内分泌干扰物筛选计划等计划中的监管决策中。EPA 的 CompTox 计划已经有十余年的历史。本文档提供了一个蓝图，以指导未来 5 年的战略和运营方向。主要目标是获得更广泛的认可，将 CompTox 方法应用于更高层次的监管决策，例如化学品评估。为了实现这一目标，蓝图扩大并完善了高通量和计算建模方法的使用，以改变化学风险评估中的各个组成部分，同时系统地解决阻碍进展的关键挑战。此外，蓝图还概述了在跨领域工作中的额外投资，以描述不确定性和可变性，开发软件和信息技术工具，提供宣传和培训，并为不同的公共卫生和环境监管决策中的应用建立科学信心。
