Embryonic vascular disruption adverse outcomes: Linking HIGH throughput signaling signatures with functional consequences.
- Robert G Ellis-Hutchings,
- Raja S Settivari,
- Alene T McCoy,
- Nicole Kleinstreuer,
- Jill Franzosa,
- Thomas B Knudsen,
- Edward W Carney
Reprod Toxicol 2017 May 17. Epub 2017 May 17.
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, United States.
Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Read More