期刊
TOXICOLOGICAL SCIENCES
卷 137, 期 1, 页码 212-233出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kft235
关键词
developmental; high-throughput screening; Tox21; ToxCast
类别
资金
- National Institute of Environmental Health Sciences (NIEHS) [RC4 ES019764 P30, P30 ES000210]
- Environmental Protection Agency (EPA) STAR Grant [R835168]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P42ES016465, T32ES007060, P30ES000210, RC4ES019764] Funding Source: NIH RePORTER
Editors Highlight: The Tanguay group uses the embryonic zebrafish model to demonstrate the utility of high throughput screening for toxicology studies. The group evaluated the 1060 US EPA ToxCast Phase 1 and 2 compounds on 18 distinct outcomes. With four doses for each compound the group generated a dizzying number of data points highlighting the importance of bioinformatics analysis in these types of studies. The study shows how it is now possible to screen many of the tens of thousands of untested chemicals using a whole animal model in which one can literally see developmental malformations. uGary W. Miller.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.
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