You are here:
A conceptual framework to support exposure science research and complete the source-to-outcome continuum for risk assessment
Teeguarden, J., C. Tan, S. Edwards, P. Egeghy, J. Leonard, K. Anderson, R. Corley, A. Harding, M. Kile, S. Simonich, D. Stone, R. Tanguay, K. Waters, S. Harper, D. Williams, J. Orme-Zavaleta, AND T. Bahadori. A conceptual framework to support exposure science research and complete the source-to-outcome continuum for risk assessment. ISES 2016 Annual Meeting, Utrecht, NETHERLANDS, October 09 - 13, 2016.
This work involves the introduction of the aggregate exposure pathway (AEP) concept. This concept includes following the concentrations and changes of a chemical from source (e.g., manufacture), throughout various environmental media, and finally to an internal molecular target. Such an approach will allow linkages to be established between a chemical and its respective biological health outcomes, especially when the AEP can be integrated with the adverse outcome pathway framework. The topics discussed in this presentation will aid in advancing both the fields of exposure science and toxicology, as they relate to critical considerations during decision-making processes.
While knowledge of exposure is fundamental to assessing and mitigating risks, exposure information has been costly and difficult to generate. Driven by major scientific advances in analytical methods, biomonitoring, computational tools, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition that allows it to be more agile, predictive, and data- and knowledge-driven. A necessary element of this evolved paradigm is an organizational and predictive framework for exposure science that furthers the application of systems-based approaches. To enable such systems-based approaches, we proposed the Aggregate Exposure Pathway (AEP) concept to organize data and information emerging from an invigorated and expanding field of exposure science. The AEP framework is a layered structure that describes the elements of an exposure pathway, as well as the relationship between those elements. The basic building blocks of an AEP adopt the naming conventions used for Adverse Outcome Pathways (AOPs): Key Events (KEs) to describe the measurable, obligate steps through the AEP; and Key Event Relationships (KERs) describe the linkages between KEs. Importantly, the AEP offers an intuitive approach to organize exposure information from sources to internal site of action, setting the stage for predicting stressor concentrations at an internal target site. These predicted concentrations can help inform the relevance of biological effects observed or expected at the target site. We envision the AEP as a natural and complementary companion in exposure science to the AOP concept used in the toxicological sciences. The coupling of these frameworks will ensure that (a) biologically relevant exposure information is integrated into toxicity testing strategies; (b) models of adverse outcomes are informed by exposure information at the appropriate levels of biology; and (c) effects of multiple, cumulative, and chronic low dose exposures can be evaluated. Together, the AEP and AOP concepts form and inform a flexible framework with the flexibility for risk-based, hazard-based, and exposure-based decision making. Disclaimer: Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL EXPOSURE RESEARCH LABORATORY
COMPUTATIONAL EXPOSURE DIVISION
HUMAN EXPOSURE & DOSE MODELING BRANCH