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Toxicol Sci. 2014 Jan;137(1):212-33. doi: 10.1093/toxsci/kft235. Epub 2013 Oct 17.

Multidimensional in vivo hazard assessment using zebrafish.

Author information

1
* Department of Environmental and Molecular Toxicology, the Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center at Oregon State University, Corvallis, Oregon 97333.

Abstract

There are tens of thousands of man-made chemicals in the environment; the inherent safety of most of these chemicals is not known. Relevant biological platforms and new computational tools are needed to prioritize testing of chemicals with limited human health hazard information. We describe an experimental design for high-throughput characterization of multidimensional in vivo effects with the power to evaluate trends relating to commonly cited chemical predictors. We evaluated all 1060 unique U.S. EPA ToxCast phase 1 and 2 compounds using the embryonic zebrafish and found that 487 induced significant adverse biological responses. The utilization of 18 simultaneously measured endpoints means that the entire system serves as a robust biological sensor for chemical hazard. The experimental design enabled us to describe global patterns of variation across tested compounds, evaluate the concordance of the available in vitro and in vivo phase 1 data with this study, highlight specific mechanisms/value-added/novel biology related to notochord development, and demonstrate that the developmental zebrafish detects adverse responses that would be missed by less comprehensive testing strategies.

KEYWORDS:

Tox21; ToxCast.; developmental; high-throughput screening

PMID:
24136191
PMCID:
PMC3871932
DOI:
10.1093/toxsci/kft235
[Indexed for MEDLINE]
Free PMC Article

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