title: Developmental exposure to valproate and ethanol alters locomotor activity and retino-tectal projection area in zebrafish embryos.
abstract: 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 retino-tectal projection area in the optic tectum. Developmental ethanol exposure also affected retino-tectal projection area at concentrations below those concentrations causing malformations. As both valproate and ethanol are known human developmental neurotoxicants, these results add to the growing body of evidence showing the potential utility of zebrafish in screening compounds for mammalian developmental neurotoxicity.
authors.affiliation: Integrated Systems Toxicology Division United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. cowden.john@epamail.epa.gov
authors.forename: John
authors.initials: J
authors.lastname: Cowden
authors.forename: Beth
authors.initials: B
authors.lastname: Padnos
authors.forename: Deborah
authors.initials: D
authors.lastname: Hunter
authors.forename: Robert
authors.initials: R
authors.lastname: MacPhail
authors.forename: Karl
authors.initials: K
authors.lastname: Jensen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Padilla
mesh_terms: D000014:Abnormalities, Drug-Induced; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology; D000431:Ethanol / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D013477:Superior Colliculi / Q000187:drug effects / Q000473:pathology; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D014635:Valproic Acid / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D013723:Teratogens; D000431:Ethanol; D014635:Valproic Acid