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() Polyomics: A Revolution in Mechanistic Risk Assessment?

Borgert, C1, 2, Guiney, P3, Degitz, S4, Tiege, J4, 1 Applied Pharmacology and Toxicology, Inc., Gainsville, FL, USA2 Department of Physiological Sciences, University of FL College of Veterinary Medicine, Gainsville, FL, USA3 S.C. Johnson & Son, Inc, Racine, WI, USA4 US EPA, Duluth, MN, USA

ABSTRACT- Omics technologies promise unprecedented advancements for the field of toxicology and risk assessment. Among these are new and more sensitive biomarkers of exposure and effect, identification of pre-toxicological changes, and elucidation of mechanisms of toxic action. One particularly interesting promise is the ability to recognize fundamentally similar modes of toxic action based on similar DNA, RNA, protein or metabolic profiles and categorizing chemicals accordingly. Omics technologies are beginning to make good on some of these promises, but few examples can be cited in which omics technologies alone have elucidated a mechanism or mode of toxic action. In order to understand how to best utilize omics technologies in mechanistic research, it may be helpful to consider the classic definitions of mode and mechanism of action and evaluate the types of data required to satisfy the definitions. Several conclusions follow from such an evaluation. Neither a mode nor a mechanism of action can be addressed with any single omic technology. Instead, a "polyomic" approach will be required. Polyomic approaches will augment, but not replace classical mechanistic research due to the need to understand the causal links between individual mechanistic steps and to integrate this understanding at several levels of biological organization. Informatics technology will be an essential component of evaluating polyomic data, but specific pharmacological and toxicological concepts, such as dose-response, must be incorporated to make relevant interpretations of mechanistic data. Key challenges will be the development of approaches that differentiate between pre-toxicological, compensatory and protective responses to chemicals, and that can identify dose-dependent transitions in mechanisms that are critical for risk assessments.

Key words: Omics technologies

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