Mounir Bouhifd
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Melvin E. Andersen
The Hamner Institute, Research Triangle Park, NC, USA
Christina Baghdikian
ASPPH Fellow, National Center for Computational Toxicology, US EPA, Research Triangle Park, NC, USA
Kim Boekelheide
Brown University, Pathology & Laboratory Medicine, Providence, RI, USA
Kevin M. Crofton
US EPA, National Center for Computational Toxicology, Research Triangle Park, NC, USA
Albert J. Fornace Jr.
Georgetown University Medical Center, Washington, DC, USA
Andre Kleensang
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Henghong Li
Georgetown University Medical Center, Washington, DC, USA
Carolina Livi
Agilent Inc., Santa Clara, CA, USA
Alexandra Maertens
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Patrick D. McMullen
The Hamner Institute, Research Triangle Park, NC, USA
Michael Rosenberg
Agilent Inc., Santa Clara, CA, USA
Russell Thomas
US EPA, National Center for Computational Toxicology, Research Triangle Park, NC, USA
Marguerite Vantangoli
Brown University, Pathology & Laboratory Medicine, Providence, RI, USA
James D. Yager
Johns Hopkins Bloomberg School of Public Health, Department of Environmental Health Sciences, Baltimore, MD, USA
Liang Zhao
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Thomas Hartung
Johns Hopkins Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA; University of Konstanz, Center for Alternatives to Animal Testing Europe, Konstanz, Germany
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Abstract
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.