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Zebrafish Developmental Screening of the ToxCast™ Phase I Chemical Library
PADILLA, S. J., D. CORUM, B. K. PADNOS, D. L. HUNTER, A. BEAM, K. A. HOUCK, N. SIPES, N. KLEINSTREUER, T. B. KNUDSEN, D. J. DIX, AND D. M. REIF. Zebrafish Developmental Screening of the ToxCast™ Phase I Chemical Library . REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 33(2):174-187, (2012).
Use of integrative model organisms such as the zebrafish as test systems provide the biological complexity of a vertebrate embryo but the simplicity of a moderate throughput platform. More detailed work is required to understand which types of toxicity are within the domain of applicability for this approach, particularly using a larger and more diverse chemical collection with many known toxicants and diverse mechanisms of action, as well as an analysis comparing general and specific effects across the concentration-response. This is a significant next step toward further validating this approach.
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.