ABSTRACT
One of the major challenges in the field of toxicology is the dependence upon surrogate species as predictors of toxic response. Implicit in the value of crossspecies extrapolations is the assumption that a chemical produces its adverse effects through a common mechanism. However, seldom does a chemical have only a single biochemical or molecular target within a cell, and many toxicokinetic and toxicodynamic events within an organism, tissue, or cell can greatly alter the disposition of a toxic substance prior to its ultimate interaction with a molecular target. Omics technologies hold the promise of being able to capture an integrated snapshot of the entire biology of response to a toxic substance (at least in a given tissue) at a given dose and a given time point. Comparisons of such snapshots across species could yield great insights into shared pathways of toxicity, identification of potential molecular biomarkers of effects or susceptibility, and identification of important differences in response that could greatly affect how surrogate species are used in the risk assessment process.
