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Toxicity of Vascular Disrupting Chemicals to Developing Zebrafish
Citation:
Hemmer, M., T. Tal, P. Harris, AND S. Padilla. Toxicity of Vascular Disrupting Chemicals to Developing Zebrafish. Presented at SETAC North America 34th Annual Meeting, Nashville, TN, November 17 - 21, 2013.
Impact/Purpose:
Information provided by these studies will assist in anchoring specific toxicity pathways to development for integration into predictive virtual tissue models.
Description:
Vascular development is integral to proper embryonic development and disruption of that process can have serious developmental consequences. We performed static 48-hr exposures of transgenic TG(kdr:EGFP)s843 zebrafish (Danio rerio) embryos with the known vascular inhibitors Vatalanib dihydrochloride (PTK787) and Tyrophostin (AG1478) followed by a 28 day grow-out period in clean untreated water. Exposures starting with 24 hr old dechorinated embryos were conducted at nominal concentrations of 0.07, 0.12, 0.22, 0.7 µM PTK787, 0.17, 0.98, 1.76, 3.14 µM AG1478 or a 4% DMSO solvent control with 3 replicates per exposure concentration and 15 fish per replicate. Embryos and larval fish were assessed for mortality, morbidity and normal development daily with growth parameters determined on day 30. Moderate to severe pericardial and yolk sac edema were observed in fish exposed to 0.22 and 0.7 µM PTK787, with significantly higher larval mortality occurring in the 0.7 µM treatment. Fish standard length and body weight were not affected by exposure to PTK787. Moderate to severe edema of the pericardium and yolk sac were also evident in fish treated with 1.76 and 3.14 µM AG1478 as well as structural abnormalities of the pectoral fins and vertebral column. Exposure AG1478 reduced survival while significantly increasing body weight at higher exposure levels while significantly decreasing standard length at the lowest concentration tested. Information provided by these studies will assist in anchoring specific toxicity pathways to development for integration into predictive virtual tissue models.