Cote Ila, Andersen Melvin E, Ankley Gerald T, Barone Stanley, Birnbaum Linda S, Boekelheide Kim, Bois Frederic Y, Burgoon Lyle D, Chiu Weihsueh A, Crawford-Brown Douglas, Crofton Kevin M, DeVito Michael, Devlin Robert B, Edwards Stephen W, Guyton Kathryn Z, Hattis Dale, Judson Richard S, Knight Derek, Krewski Daniel, Lambert Jason, Maull Elizabeth Anne, Mendrick Donna, Paoli Gregory M, Patel Chirag Jagdish, Perkins Edward J, Poje Gerald, Portier Christopher J, Rusyn Ivan, Schulte Paul A, Simeonov Anton, Smith Martyn T, Thayer Kristina A, Thomas Russell S, Thomas Reuben, Tice Raymond R, Vandenberg John J, Villeneuve Daniel L, Wesselkamper Scott, Whelan Maurice, Whittaker Christine, White Ronald, Xia Menghang, Yauk Carole, Zeise Lauren, Zhao Jay, DeWoskin Robert S
National Center for Environmental Assessment, U.S. Environmental Protection Agency (EPA), Washington, District of Columbia, USA.
Environ Health Perspect. 2016 Nov;124(11):1671-1682. doi: 10.1289/EHP233. Epub 2016 Apr 19.
The Next Generation (NexGen) of Risk Assessment effort is a multi-year collaboration among several organizations evaluating new, potentially more efficient molecular, computational, and systems biology approaches to risk assessment. This article summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions.
Our specific objectives were to test whether advanced biological data and methods could better inform our understanding of public health risks posed by environmental exposures.
New data and methods were applied and evaluated for use in hazard identification and dose-response assessment. Biomarkers of exposure and effect, and risk characterization were also examined. Consideration was given to various decision contexts with increasing regulatory and public health impacts. Data types included transcriptomics, genomics, and proteomics. Methods included molecular epidemiology and clinical studies, bioinformatic knowledge mining, pathway and network analyses, short-duration in vivo and in vitro bioassays, and quantitative structure activity relationship modeling.
NexGen has advanced our ability to apply new science by more rapidly identifying chemicals and exposures of potential concern, helping characterize mechanisms of action that influence conclusions about causality, exposure-response relationships, susceptibility and cumulative risk, and by elucidating new biomarkers of exposure and effects. Additionally, NexGen has fostered extensive discussion among risk scientists and managers and improved confidence in interpreting and applying new data streams.
While considerable uncertainties remain, thoughtful application of new knowledge to risk assessment appears reasonable for augmenting major scope assessments, forming the basis for or augmenting limited scope assessments, and for prioritization and screening of very data limited chemicals. Citation: Cote I, Andersen ME, Ankley GT, Barone S, Birnbaum LS, Boekelheide K, Bois FY, Burgoon LD, Chiu WA, Crawford-Brown D, Crofton KM, DeVito M, Devlin RB, Edwards SW, Guyton KZ, Hattis D, Judson RS, Knight D, Krewski D, Lambert J, Maull EA, Mendrick D, Paoli GM, Patel CJ, Perkins EJ, Poje G, Portier CJ, Rusyn I, Schulte PA, Simeonov A, Smith MT, Thayer KA, Thomas RS, Thomas R, Tice RR, Vandenberg JJ, Villeneuve DL, Wesselkamper S, Whelan M, Whittaker C, White R, Xia M, Yauk C, Zeise L, Zhao J, DeWoskin RS. 2016. The Next Generation of Risk Assessment multiyear study-highlights of findings, applications to risk assessment, and future directions. Environ Health Perspect 124:1671-1682; http://dx.doi.org/10.1289/EHP233.
下一代风险评估计划是多个组织之间开展的一项为期多年的合作项目，旨在评估新的、可能更高效的分子、计算和系统生物学方法在风险评估中的应用。本文总结了我们的研究结果，提出了在风险评估中的应用建议，并确定了战略研究方向。
我们的具体目标是测试先进的生物学数据和方法是否能更好地帮助我们理解环境暴露所带来的公共卫生风险。
应用并评估新的数据和方法，以用于危害识别和剂量反应评估。还对暴露和效应生物标志物以及风险特征进行了研究。考虑了具有越来越大监管和公共卫生影响的各种决策背景。数据类型包括转录组学、基因组学和蛋白质组学。方法包括分子流行病学和临床研究、生物信息知识挖掘、通路和网络分析、短期体内和体外生物测定以及定量构效关系建模。
下一代风险评估计划提升了我们应用新科学的能力，能够更快速地识别潜在关注的化学物质和暴露因素，有助于描述影响因果关系、暴露 - 反应关系、易感性和累积风险结论的作用机制，并阐明新的暴露和效应生物标志物。此外，下一代风险评估计划促进了风险科学家和管理人员之间的广泛讨论，并增强了对解释和应用新数据流的信心。
尽管仍存在相当多的不确定性，但将新知识审慎地应用于风险评估，对于扩大主要范围评估、形成有限范围评估的基础或对其进行补充，以及对数据非常有限的化学物质进行优先级排序和筛选而言，似乎是合理的。引文：科特 I，安德森 M.E.，安克利 G.T.，巴龙 S，伯恩鲍姆 L.S.，博克尔海德 K，布瓦 F.Y.，布尔贡 L.D.，邱 W.A.，克劳福德 - 布朗 D，克罗夫顿 K.M.，德维托 M，德夫林 R.B.，爱德华兹 S.W.，盖顿 K.Z.，哈蒂斯 D，贾德森 R.S.，奈特 D，克鲁斯凯 D，兰伯特 J，莫尔 E.A.，门德里克 D，保利 G.M.，帕特尔 C.J.，珀金斯 E.J.，波耶 G，波蒂埃 C.J.，鲁辛 I，舒尔特 P.A.，西梅诺夫 A，史密斯 M.T.，塞耶 K.A.，托马斯 R.S.，托马斯 R，蒂斯 R.R.，范登伯格 J.J.，维伦纽夫 D.L.，韦塞尔坎珀 S，惠兰 M，惠特克 C，怀特 R，夏 M，约克 C，蔡斯 L，赵 J，德沃斯金 R.S. 2016. 下一代风险评估多年研究——研究结果亮点、在风险评估中的应用及未来方向。《环境健康展望》124:1671 - 1682；http://dx.doi.org/10.1289/EHP233。
