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A screening approach using zebrafish for the detection and characterization of developmental neurotoxicity.
Citation:
COWDEN, J., B. K. PADNOS, D. L. HUNTER, R. C. MACPHAIL, K. F. JENSEN, AND S. J. PADILLA. A screening approach using zebrafish for the detection and characterization of developmental neurotoxicity. Presented at Fourth Aquatic Animal Models of Human Diseases, Durham, NC, January 31 - February 03, 2008.
Impact/Purpose:
To support criteria for MYP
Description:
Thousands of chemicals have little or no data to support developmental neurotoxicity risk assessments. Current developmental neurotoxicity guideline studies mandating mammalian model systems are expensive and time consuming. Therefore a rapid, cost-effective method to assess developmental neurotoxicity potential is needed for risk assessment prioritization. In an effort to prioritize chemicals based on developmental neurotoxicity potential, we are developing an alternative species approach for high throughput in vivo screening using zebrafish. Zebrafish are small fresh-water fish that reproduce by external fertilization. The embryos develop rapidly (3-4 days) in an optically clear chorion, allowing visual inspection of the embryo throughout development. We chose a multi-faceted approach to developmental neurotoxicity screening, assessing lethality, teratology, histology, and behavioral as endpoints. Sensitivity of the screen was examined using developmental exposure to ethanol, a known human developmental neurotoxicant that has been shown to affect zebrafish development. We exposed zebrafish embryos in a 96-well plate format to various concentrations of ethanol (0.25% - 5%) from 0-4 days post fertilization, assessing endpoints at either 2 days post fertilization (histology) or 6 days post fertilization (lethality, teratogenicity, behavior). Our data are consistent with previous reports regarding the lethal and teratogenic doses of developmental ethanol exposure on zebrafish embryos. We also find that subteratogenic doses of ethanol produce effects on motor activity in zebrafish fry as well as changes in the staining patterns of a nervous system marker anti-acetylated -tubulin. These data suggest that zebrafish are amenable to high-throughput approaches for in vivo developmental neurotoxicity screening and could provide a rapid method for chemical prioritization for further testing. This abstract is for a proposed presentation; the information does not necessarily reflect Agency policy.