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The Human Toxome Project

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Mounir Bouhifd1, Melvin E. Andersen2, Christina Baghdikian3, Kim Boekelheide4, Kevin M. Crofton5, Albert J. Fornace Jr.6, Andre Kleensang1, Henghong Li6, Carolina Livi7, Alexandra Maertens1, Patrick D. McMullen2, Michael Rosenberg7, Russell Thomas5, Marguerite Vantangoli4, James D. Yager8, Liang Zhao1 and Thomas Hartung1,9
1 Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA;
2 The Hamner Institute, Research Triangle Park, NC, USA;
3 ASPPH Fellow, National Center for Computational Toxicology, US EPA, Research Triangle Park, NC, USA;
4 Brown University, Pathology & Laboratory Medicine, Providence, RI, USA;
5 US EPA, National Center for Computational Toxicology, Research Triangle Park, NC, USA;
6 Georgetown University Medical Center, Washington, DC, USA;
7 Agilent Inc., Santa Clara, CA, USA;
8 Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA;
9 University of Konstanz, Center for Alternatives to Animal Testing Europe, Konstanz, Germany

Summary

The Human Toxome Project, funded as an NIH Transformative Research grant 2011-2016, is focused on developing the concepts and the means for deducing, validating and sharing molecular pathways of toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF-7 human breast cancer cells are being phenotyped by transcriptomics and mass-spectrometry-based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies and bioinformatics are being addressed. In parallel, concepts for annotation, validation and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge-base, could become a point of reference for toxicological research and regulatory test strategies.

 

Keywords: regulatory toxicology, safety sciences, transcriptomics, metabolomics, alternative methods

 

 

ALTEX 32(2), 112-124

DOI: http://dx.doi.org/10.14573/altex.1502091


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