T2 AM 'Omic' Technologies: Current and Future Application to Environmental Toxicology (Part 1)
Tuesday, 15 November 2005: 8:00 AM - 11:40 AM in Ballroom 2

(ZAC-1117-821525) Incorporation of Toxicogenomics into Quantitative Risk Assessment.

Zacharewski, T¹, ¹ Michigan State University, East Lansing, MI, USA

ABSTRACT- In order to fully assess the potential adverse health effects of chronic and subchronic exposure to environmental contaminants and commerce chemicals, as well as their mixtures, a more comprehensive understanding of their molecular, cellular and physiological effects is required within the context of the exposed organism, its genome, proteome and metabolome. Emerging omic technologies, novel computational approaches, and the availability of genome sequence information for a variety of species, including environmentally relevant models, has provided unprecedented opportunities to further elucidate mechanisms of toxicity and identify mechanistically-based biomarkers. However, our ability to extract meaningful biological information from toxicogenomic data to support quantitative risk assessment has been elusive. This presentation will attempt to separate hype from reality by describing the resources, infrastructure and technical skills that toxicologists, risk/hazard assessors and policy analysts will require to facilitate the incorporation of toxicogenomic data into regulatory decision-making. More specifically, the development of dbZach (http://dbzach.fst.msu.edu) a MIAME compliant toxicogenomic supportive relational database, the construction of orthologous human, mouse and rat cDNA microarrays, study design issues, and approaches for comprehensive data analysis and interpretation will be described. Examples from the systematic integration of computational, microarray, and histopathology data from comparative in vitro and in vivo dose response and time course studies examining the mechanisms of toxicity of dioxin and estrogenic endocrine disruptors will be used to demonstrate the support toxicogenomics can provide to mechanistically-based risk assessment. Moreover, factors impeding the incorporation of toxicogenomic data into mechanistically-based ecologically relevant quantitative risk assessment will also be presented. This work is supported by the United States Environmental Protection Agency (826301), the National Institutes of Health (ES11271 and ES12245) and the Superfund Program (ES 4911).

Key words: toxicogenomics, microarrays, endocrine disruptors, risk assessment