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Systems Biology and Mode of Action Based Risk Assessment.
EDWARDS, S. W. AND J. PRESTON. Systems Biology and Mode of Action Based Risk Assessment. TOXICOLOGICAL SCIENCES. Society of Toxicology, 106(2):312-318, (2008).
The application of systems biology approaches has greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnostic purposes and target identification. During this same period, risk assessment approaches have also been transformed by a variety of factors including a much greater emphasis on mode of action (MOA) in defining risk and the need for quantitative risk assessments on an ever-growing number of environmental chemicals. Genome-wide (i.e. global) measurements provide both a discovery engine for identifying the MOA and a framework for subsequent evaluation of the MOA during the conduct of a risk assessment. This framework is important as these measurements are not chosen based on the hypothesized MOA and therefore represent an unbiased check of the comprehensiveness of the MOA. In addition, optimal design for MOA studies is critical to provide the time and dose dependent data required for quantitative model building. Finally, identification of biomarkers and bioindicators of disease in humans provides a viable way to extrapolate from disease outcomes measured at high exposure levels to those at low exposure levels and thus provide the opportunity to reduce or perhaps eliminate in vivo animal testing. To realize the full potential of these approaches, larger integrated projects which include all these individual components are necessary.
The focus of this review is on the application of systems biology thus defined to risk assessment to aid in mode of action (MOA) definition, species extrapolation, in vitro to in vivo extrapolation, and providing a mechanistic basis for describing the susceptibility of certain subpopulations.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ASSOCIATE DIRECTOR FOR HEALTH