Integration Of Data

A key objective in toxicogenomics is to integrate data from different studies and analytical platforms to produce a richer and biologically more refined understanding of the toxicological response of a cell, organ, or organism. For example, one would like to describe the interplay between protein function and gene expression, or between the activity of certain metabolizing enzymes and the excretion into serum or urine of populations of small metabolites. The integration of data from different...

Toxicogenomics Evolution Of The Field

Toxicogenomics evolved from early gene expression studies on the response of a biological system to a particular toxicant or panel of reference agents, toward more mature investigations that integrate several -omics domains with toxicology and pathology data (see Table 5.1). Exposure-specific and outcome-specific patterns of gene, protein, and metabolite profiles have been used to identify molecular changes that serve as biomarkers of toxicity 23,38-44 and provide insights into mechanisms of...

Extrapolation across Doses Routes of Exposure and Species

PBPK modeling can play an essential role in three common types of extrapolation used in classical toxicology dose to dose (usually high dose in animals to low dose for realistic exposure scenarios), route to route (e.g., ingestion vs. inhalation), and species to species (animal or cell culture to human). Each of these types of extrapolation is described in some detail below. Dose to Dose PBPK modeling permits reasonable extrapolation from one dose to another, if adequate information on...