Use of Genomics in Mechanism Based Risk Assessment

Recent advances in genomic and proteomic research, coupled with the availability of novel tools and methods with which to analyze the products of altered gene expression, are providing new insights into the study of mechanistic toxicology. One of the short-term needs is to establish a body of publicly available knowledge to serve as a foundation for applying the data generated by these new methods to risk assessment. The ILSI Health and Environmental Sciences Institute is providing a scientific forum to facilitate further development and advances in genomics and proteomics methodologies toward the goal of increasing the utility of gene expression data for mechanism-based risk assessment. A collaborative research effort has been undertaken to help establish appropriate experimental methodologies for measuring alterations in gene expression and to relate genomic and proteomic expression data to toxic endpoints characterized by established methods under standardized conditions. Through this collaboration, data are being generated in government, industry and research laboratories on a series of prototype compounds across a broad range of available microarray platforms. This paper describes the initial phase of this project which has focused on nephrotoxicity, hepatotoxicity, and genotoxicity as important endpoints for the risk assessment of many chemicals. In addition, the challenges associated with drawing correlations between patterns of gene expression with biological and toxicological parameters, the influence of experimental conditions on data variability and reproducibility, and other issues associated with interpretation and application of data from these types of studies for risk assessment are identified.