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Utilizing Toxicogenomic Data to Understand Chemical Mechanism of Action in Risk Assessment
Citation:
WILSON, V. S., N. Keshava, S. Euling, S. D. HESTER, D. Segal, W. Chiu, AND C. Thompson. Utilizing Toxicogenomic Data to Understand Chemical Mechanism of Action in Risk Assessment. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 271(3):299-308, (2013).
Impact/Purpose:
The goal of this article is to review some of the major regulatory and research activities that have or may impact risk assessments with focus on the largely qualitative application of toxicogenomic data to risk assessment.
Description:
A recent National Academy of Sciences report pointed to the strong potential for genomic technologies to contribute to the risk assessment process. The report, however, also acknowledged that neither has the full impact of genomic technology been realized nor has it been broadly implemented in risk assessment. Furthermore, the report added that the development of methods to understand the circuitry of toxicity pathways would " ...most likely require improved methods in bioinformatics, systems biology, and computational toxicology". With these points in mind, the goal of this article is to review some of the major regulatory and research activities that have or may impact risk assessments with focus on the largely qualitative application of toxicogenomic data to risk assessment. After a brief overview of some of the techniques and data interpretation tools, a few ofthe major efforts in the standardization and validation of genomic techniques will be highlighted along with an update on current regulatory guidance for the submission of genomic data for risk assessment purposes. The predominant role of toxicogenomic data in risk assessment thus far has been one of augmentation of other more traditional in vitro and in vivo toxicology data. As such, even though not necessarily incorporated into risk assessments, toxicogenomic data have been used to inform toxicokinetics, toxicodynamics including mode of action, identification of biomarkers, predictive potential and dose response. Furthermore, toxicogenomic data have been evaluated in a small number of specific risk assessments where they were utilized to inform mechanism of action. As for progress on bioinformatics needs, some cutting edge techniques under development are highlighted. Finally, some of the continuing challenges and limitations are discussed that must be overcome before toxicogenomic data can be fully utilized in the risk assessment process. The views expressed in this article are those of the authors and do not necessarily reflect the policies of the U.S. Environmental Protection Agency.