Analysis of the ToxCast Chemical-Assay Space Using the Comparative Toxicogenomics Database

Autor: Eric Gifford, Huijun Wang, Bingjie Hu, Timothy E. Johnson, Wendy J. Bailey
Rok vydání: 2015
Předmět:
Zdroj: Chemical research in toxicology. 28(11)
ISSN: 1520-5010
Popis: Many studies have attempted to predict in vivo hazards based on the ToxCast in vitro assay results with the goal of using these predictions to prioritize compounds for conventional toxicity testing. Most of these conventional studies rely on in vivo end points observed using preclinical species (e.g., mice and rats). Although the preclinical animal studies provide valuable insights, there can often be significant disconnects between these studies and safety concerns in humans. One way to address these concerns, for an admittedly more limited set of compounds, is to explore relationships between the in vitro data from human cell lines and observations from human related studies. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org ) is a rich source of data linking chemicals to human diseases/adverse events and pathways. In this study we explored the relationships between ToxCast chemicals, their ToxCast in vitro test results, and their annotations of human disease/adverse event end points as captured in the CTD database. We mined these associations to identify potentially interesting, statistically significant in vitro assay and in vivo toxicity correlations. To the best of our knowledge, this is one of the first studies analyzing the relationships between the ToxCast in vitro assays results and the CTD disease/adverse event end point annotations. The in vitro profiles identified in this analysis may prove useful for prioritizing compounds for toxicity testing, suggesting mechanisms of toxicity, and forecasting potential in vivo human drug induced injury.
Databáze: OpenAIRE