High-Throughput Screening and Hazard Testing Prioritization

Tox21 is a collaborative effort among the National Center for Advancing Translational Sciences, the Environmental Protection Agency, the National Toxicology Program, and the Food and Drug Administration to elucidate the toxic effects of compounds found in the environment and/or created by humans. Since 2008, this program has screened many different pathways, targets, or phenotypes (more than 70 assays) using an in vitro quantitative high-throughput screening approach. Endocrine disruption and stress-related signaling pathways have been the main focus of the Tox21 screening program. Nuclear receptors play an important role in endocrine disruption, modulating many different biological processes and metabolism. It is therefore important to classify endogenous and exogenous compounds for their ability to alter the function or quantity of these nuclear receptors. Stress-related signaling pathways are necessary for body homeostasis and are involved in many disease states as well. Identifying compounds which induce stress signaling pathways in the body is prudent to fully determine the safety of an environmental chemical. This book chapter describes an in-depth analysis of Tox21, a summary of select examples of their assays, and the future plan for the screening program.