Chapter 5: Transcriptomic Dose–Response Analysis for Mode of Action and Risk Assessment

Microarray and RNA-seq technologies can play an important role in assessing the health risks associated with environmental exposures. The utility of gene expression data to predict hazard has been well documented. Early toxicogenomics studies used relatively high, single doses with minimal replication. Thus, they were not useful in understanding health risks at environmentally relevant doses. Until the past decade, application of toxicogenomics in dose–response assessment and determination of chemical mode of action has been limited. New transcriptomic biomarkers have evolved to detect chemical hazards in multiple tissues together with pathway methods to study biological effects across the full dose–response range and critical time course. Comprehensive low-dose datasets are now available and with the use of transcriptomic benchmark dose estimation techniques within a mode-of-action framework, the ability to incorporate informative genomic data into human health risk assessment has substantially improved. The key advantage to applying transcriptomic technology to risk assessment is both the sensitivity and comprehensive examination of direct and indirect molecular changes that lead to adverse outcomes.