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Review Advance Publication

Environ Health Perspect; DOI:10.1289/ehp.1307260

A Framework for the Next Generation of Risk Science

Daniel Krewski,1,2 Margit Westphal,1 Melvin E. Andersen,3 Gregory M. Paoli,2 Weihsueh A. Chiu,4 Mustafa Al-Zoughool,1 Maxine C. Croteau,1 Lyle D. Burgoon,4 and Ila Cote4
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1McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada; 2Risk Sciences International, Ottawa, Ontario, Canada; 3Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA; 4National Center for Environmental Assessment, U.S. Environmental Protection Agency, Washington, DC, USA
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This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. EHP Advance Publication articles are completely citable using the DOI number assigned to the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.

Citation: Krewski D, Westphal M, Andersen ME, Paoli GM, Chiu WA, Al-Zoughool M, Croteau MC, Burgoon LD, Cote I. A Framework for the Next Generation of Risk Science. Environ Health Perspect;

Received: 21 June 2013
Accepted: 9 April 2014
Advance Publication: 11 April 2014

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Objectives: In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science.

Methods: The NexGen framework was built on three cornerstones: the availability of new data on toxicity pathways made possible by fundamental advances in basic biology and toxicological science; the incorporation of a population health perspective that recognizes that most adverse health outcomes involve multiple determinants; and a renewed focus on new risk assessment methodologies designed to better inform risk management decision making.

Results: The NexGen framework has three phases. Phase I (objectives) focuses on problem formulation and scoping, taking into account the risk context and the range of available risk management decision making options. Phase II (risk assessment) seeks to identify critical toxicity pathway perturbations using new toxicity testing tools and technologies, and to better characterize risks and uncertainties using advanced risk assessment methodologies. A blueprint for pathway-based toxicity testing was provided by the 2007 U.S. National Research Council (NRC) report, Toxicity Testing in the 21st Century: A Vision and a Strategy; guidance on new risk assessment methods is provided by the 2009 NRC report, Science and Decisions, Advancing Risk Assessment. Phase III (risk management) involves the development of evidence-based population health risk management strategies of a regulatory, economic, advisory, community-based, or technological nature, using sound principles of risk management decision making.

Conclusions: Analysis of a series of case-study prototypes indicated that many aspects of the NexGen framework are already beginning to be adopted in practice.

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