Zebrafish developmental screening of the ToxCast™ Phase I chemical library

被引:245
作者
Padilla, S. [1 ]
Corum, D. [2 ]
Padnos, B. [1 ]
Hunter, D. L. [1 ]
Beam, A. [2 ]
Houck, K. A. [2 ]
Sipes, N. [2 ]
Kleinstreuer, N. [2 ]
Knudsen, T. [2 ]
Dix, D. J. [2 ]
Reif, D. M. [2 ]
机构
[1] US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA
[2] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA
关键词
Zebrafish; Development; Concentration-response; ToxCast (TM); Octanol-water partition coefficient; Chemical class; BLOOD-BRAIN-BARRIER; DANIO-RERIO; CARRIER SOLVENTS; HUMAN-DISEASE; TOXICITY; MODEL; BIOCONCENTRATION; ASSAY; EMBRYOS; FISH;
D O I
10.1016/j.reprotox.2011.10.018
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (TM) 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 mu M. 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. Published by Elsevier Inc.
引用
收藏
页码:174 / 187
页数:14
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