US EPA

Uncertainties in risk assessment arise from sparse or inadequate data including gaps in our understanding of mode of action, the exposure-dose-response pathway, cross-species toxicokinetic and toxicodynamic information, and/or exposure data. There is an expectation that toxicogenomic data will address issues to help improve risk assessment by reducing uncertainty about the mechanisms of toxicity as well as in the source to outcome continuum in the quantitative processes in ecological and human health risk assessments. Two major concerns about the use of toxicogenomics data in risk assessment are: 1) demonstration of linkage between the gene expression data (i.e., patterns of gene expression or the expression of single key genes) to an outcome of concern; and 2) identification of precursor events at low dose, doses lower than those at which effects are observed. While there are numerous examples of the use of toxicogenomics data in the published literature, there are hardly any examples descnbing approaches to incorporating these data in the risk assessment process, in part because of the stringent requirements for use of new technologies in risk assessment. The purpose of this workshop is to discuss the current status of the application of toxicogenomics in regulatory decision making. A case study approach will be used to descnbe the application of toxicogenomics in the various steps of the accepted risk assessment paradigm (i.e., hazard identification, dose-response assessment and exposure assessment). Each presentation will discuss the study design, outcome, research gaps/needs and future directions.

This workshop will seek to highlight issues and research recommendations needed for toxicogenomics to be used successfully in risk assessment in the future.