Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5857947 | Reproductive Toxicology | 2016 | 38 Pages |
Abstract
The 2011 EPA trichloroethylene (TCE) IRIS assessment, used developmental cardiac defects from a controversial drinking water study in rats (Johnson et al. [51]), along with several other studies/endpoints to derive reference values. An updated literature search of TCE-related developmental cardiac defects was conducted. Study quality, strengths, and limitations were assessed. A putative adverse outcome pathway (AOP) construct was developed to explore key events for the most commonly observed cardiac dysmorphologies, particularly those involved with epithelial-mesenchymal transition (EMT) of endothelial origin (EndMT); several candidate pathways were identified. A hypothesis-driven weight-of-evidence analysis of epidemiological, toxicological, in vitro, in ovo, and mechanistic/AOP data concluded that TCE has the potential to cause cardiac defects in humans when exposure occurs at sufficient doses during a sensitive window of fetal development. The study by Johnson et al. [51] was reaffirmed as suitable for hazard characterization and reference value derivation, though acknowledging study limitations and uncertainties.
Keywords
DCAMouse Genome InformaticsBMDSWOEBMDLCHDMGIBMRBMDTCAAOPEPAPODNTPTCEU.S. Environmental Protection Agencydichloroacetic acidtrichloroacetic acidMalformationsNational Toxicology ProgramTrichloroethylenebenchmark doseIntegrated Risk Information SystemIrisconfidence intervalCardiacadverse outcome pathwaybenchmark responseCongenital heart defectsPoint of departure
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Susan L. Makris, Cheryl Siegel Scott, John Fox, Thomas B. Knudsen, Andrew K. Hotchkiss, Xabier Arzuaga, Susan Y. Euling, Christina M. Powers, Jennifer Jinot, Karen A. Hogan, Barbara D. Abbott, E. Sidney III, Michael G. Narotsky,