title: Zebrafish developmental screening of the ToxCast™ Phase I chemical library.
abstract: Zebrafish (Danio rerio) is an emerging toxicity screening model for both human health and ecology. As part of the Computational Toxicology Research Program of the U.S. EPA, the toxicity of the 309 ToxCast™ Phase I chemicals was assessed using a zebrafish screen for developmental toxicity. All exposures were by immersion from 6-8 h post fertilization (hpf) to 5 days post fertilization (dpf); nominal concentration range of 1 nM-80 μM. On 6 dpf larvae were assessed for death and overt structural defects. Results revealed that the majority (62%) of chemicals were toxic to the developing zebrafish; both toxicity incidence and potency was correlated with chemical class and hydrophobicity (logP); and inter-and intra-plate replicates showed good agreement. The zebrafish embryo screen, by providing an integrated model of the developing vertebrate, compliments the ToxCast assay portfolio and has the potential to provide information relative to overt and organismal toxicity.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27712, USA. Padilla.Stephanie@epa.gov
authors.forename: S
authors.initials: S
authors.lastname: Padilla
authors.forename: D
authors.initials: D
authors.lastname: Corum
authors.forename: B
authors.initials: B
authors.lastname: Padnos
authors.forename: D L
authors.initials: DL
authors.lastname: Hunter
authors.forename: A
authors.initials: A
authors.lastname: Beam
authors.forename: K A
authors.initials: KA
authors.lastname: Houck
authors.forename: N
authors.initials: N
authors.lastname: Sipes
authors.forename: N
authors.initials: N
authors.lastname: Kleinstreuer
authors.forename: T
authors.initials: T
authors.lastname: Knudsen
authors.forename: D J
authors.initials: DJ
authors.lastname: Dix
authors.forename: D M
authors.initials: DM
authors.lastname: Reif
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D023421:Models, Animal; D010575:Pesticides / Q000633:toxicity*; D054852:Small Molecule Libraries; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods; D015027:Zebrafish
chemical_list: D004785:Environmental Pollutants; D010575:Pesticides; D054852:Small Molecule Libraries; D013723:Teratogens