The Role of Genomics in Mode-of-Action Based Risk Assessment

Classical toxicology is traditionally focused on understanding of xenobiotic metabolism, the dose-response relationships between chemicals and adverse health effects, and mode-of-action evaluation for toxicant-induced disease. Novel molecular, biochemical, genetic and genomics approaches are increasingly used to understand the mechanisms of environmental agent-related organ injury and carcinogenesis. Toxicogenomics is a rapidly maturing field which provides the ability to define in greater detail the underlying molecular events preceding or accompanying toxicity. The incorporation of this new information requires careful validation and altered gene expression patterns should be corroborated with conventional indices of toxicity in a dose- and time-dependent manner.  Recent efforts by the US EPA advance the process of regulatory acceptance of such data whereby toxicogenomics data is being applied in mode of action analysis. This talk will illustrate the potential steps in risk assessment process that may benefit from the availability of more granular molecular information on toxicity mechanisms, as well as address the challenges inherent in changing the regulatory paradigms.