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Developmental Exposure to Valproate or Ethanol Alters Locomotor Activity and Retino-Tectal Projection Area in Zebrafish Embryos
COWDEN, J., B. K. PADNOS, D. L. HUNTER, R. C. MACPHAIL, K. F. JENSEN, AND S. J. PADILLA. Developmental Exposure to Valproate or Ethanol Alters Locomotor Activity and Retino-Tectal Projection Area in Zebrafish Embryos. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 33(2):165-73, (2012).
What is the study? This is a study of the effects of two different developmental neurotoxicants on the neuronal development and behavior of very young zebrafish. Why was it done? It was done to determine if a simple zebrafish toxicity screening test could predict developmental neurotoxicity of human neurotoxicants. What is the impact on the field and to the Agency? Impact on the field: We have shown in a very limited way that embryonic zebrafish are sensitive to the human neurotoxicants. Impact on the Agency: This is a proof-of-principle study showing that zebrafish embyo screening assays may be able to identify human developmental neurotoxicants
Given the minimal developmental neurotoxicity data available for the large number of new and existing chemicals, there is a critical need for alternative methods to identify and prioritize chemicals for further testing. We outline a developmental neurotoxicity screening approach using zebrafish embryos. Embryos were exposed to nominal concentrations of either valproate or ethanol then examined for lethality, malformation, nervous system structure and locomotor activity. Developmental valproate exposure caused locomotor activity changes at concentrations that did not result in malformations and showed a concentration-dependent decrease in retinotectaI projection area in the optic tectum. Developmental ethanol exposure also affected retinotectaI projection area at concentrations below those concentrations causing malformations.. As both valproate and ethanol are known human developmental neurotoxicants, these results offer preliminary evidence that zebrafish may be useful in screening compounds for mammalian developmental neurotoxicity.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
GENETIC AND CELLULAR TOXICOLOGY BRANCH