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Systems Biology and Mode of Action Based Risk Assessment
Citation:
EDWARDS, S. W. Systems Biology and Mode of Action Based Risk Assessment . Presented at InnovationWell Community of Practice Interaction Meeting, Philadephia, PA, October 14 - 17, 2008.
Impact/Purpose:
Presentation to describe need for MOA projects.
Description:
The application of systems biology has 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 has also been transformed by a variety of factors including a much greater emphasis on mode of action (MOA) in defining risk. MOA is defined as “a brief description of the sequence of measured events” from chemical administration to adverse outcome. Genome-wide measurements provide both a discovery engine for identifying the MOA and a framework for 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. [This abstract does not reflect EPA policy.]