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Integrating tools for non-targeted analysis research and chemical safety evaluations at the US EPA
Sobus, J., J. Wambaugh, K. Isaacs, A. Williams, A. McEachran, A. Richard, Chris Grulke, E. Ulrich, J. Rager, M. Strynar, AND S. Newton. Integrating tools for non-targeted analysis research and chemical safety evaluations at the US EPA. Journal of Exposure Science and Environmental Epidemiology . Nature Publishing Group, London, Uk, 28:411-426, (2018). https://doi.org/10.1038/s41370-017-0012-y
The last decade has witnessed pronounced transformations in approaches for linking chemical exposures to human and ecological health. Toxicity testing methods that support chemical safety evaluations have evolved rapidly, ushering in an era defined by high-throughput screening (HTS) and chemical prioritization (Collins et al. 2008; NRC 2007). Two US-based testing programs – the Toxicity Testing in the 21st Century (Tox21) Federal Consortium and the EPA Toxicity Forecaster (ToxCast) project – have together evaluated over 8,000 chemical substances across hundreds of bioassays (Kavlock et al. 2012; Richard et al. 2016; Tice et al. 2013). Efforts are underway to map the derived bioactivity data to key events along adverse outcome pathways (AOPs) in support of 21st century risk assessments and regulatory decisions (Edwards et al. 2016; Kleinstreuer et al. 2016). Risk-based decisions, however, are weakened without quantitative knowledge of exposure, processes that link exposure and target dose, and the impact of target dose on AOPs (Escher et al. 2017; Hubal 2009; NRC 2012; 2017). Noting this challenge, the exposure science community has mirrored recent advances in toxicity testing, developing both predictive and empirical methods for rapid acquisition of chemical exposure data (Cohen Hubal et al. 2010; Egeghy et al. 2016; NRC 2012; 2017). Many measurement-based methods are borne out of successes in the metabolomics field over recent decades. For example, high-resolution mass spectrometry (HRMS), a common metabolomics tool, now allows for the rapid characterization of hundreds to thousands of compounds in a given environmental (e.g., surface water, house dust) or biological (e.g., serum, urine) sample. Whereas metabolomics has mostly eyed endogenous compounds, the emerging field of “exposomics” has broadened the analytical focus to include xenobiotic compounds (Neveu et al. 2017; Wishart et al. 2015). Popular open metabolomics databases, in fact, are expanding to include large lists of man-made compounds (Warth et al.). Furthermore, instrument and software vendors are adapting existing tools, and developing new tools, to better meet the needs of the growing exposomics community. In time, these adaptations will enable fully integrated research workflows that seamlessly bridge empirical knowledge of stressors and biological adaptations to those stressors (Escher et al. 2017; Warth et al. ).
Tens-of-thousands of chemicals are registered in the U.S. for use in countless processes and products. Recent evidence suggests that many of these chemicals are measureable in environmental and/or biological systems, indicating the potential for widespread exposures. Traditional public health research tools, including in vivo studies and targeted analytical chemistry methods, have been unable to meet the needs of screening programs designed to evaluate chemical safety. As such, new tools have been developed to enable rapid assessment of potentially harmful chemical exposures and their attendant biological responses. One group of tools, known as “non-targeted analysis” (NTA) methods, allows the rapid characterization of thousands of never-before-studied compounds in a wide variety of environmental, residential, and biological media. This article discusses current applications of NTA methods, challenges to their effective use in chemical screening studies, and ways in which shared resources (e.g., chemical standards, databases, model predictions, and media measurements) can advance their use in risk-based chemical prioritization. A brief review is provided of resources and projects within EPA’s Office of Research and Development (ORD) that provide benefit to, and receive benefits from, NTA research endeavors. A summary of EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT) is also given, which makes direct use of ORD resources to benefit the global NTA research community. Finally, a research framework is described that shows how NTA methods will bridge chemical prioritization efforts within ORD. This framework exists as a guide for institutions seeking to understand the complexity of chemical exposures, and the impact of these exposures on living systems.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL EXPOSURE RESEARCH LABORATORY
EXPOSURE METHODS & MEASUREMENT DIVISION