ToxSci Advance Access originally published online on September 12, 2008
Toxicological Sciences 2008 106(2):312-318; doi:10.1093/toxsci/kfn190
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Systems Biology and Mode of Action Based Risk Assessment
National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
1 To whom correspondence should be addressed at 109 TW Alexander Dr. (MD B305-01), Research Triangle Park, NC 27711. Fax: (919) 685-3221. E-mail: edwards.stephen{at}epa.gov.
Received May 1, 2008; accepted August 29, 2008
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Abstract |
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The applications of systems biology approaches have 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 and pharmaceutical realm for diagnostic purposes and target identification. During this same period, the use of mode of action (MOA) for risk assessment has been increasing and there is a 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 MOA and an information base for subsequent evaluation of MOA when conducting a risk assessment. These genome-wide measurements are not chosen based on the hypothesized MOA and therefore represent an unbiased check of the comprehensiveness of an 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.
Key Words: systems biology; toxicity testing; mode of action; risk assessment; biologically based dose-response modeling.
This manuscript has been reviewed and approved for publication by the Environmental Protection Agency but does not necessarily reflect the views of the Agency. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.
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