Andre Kleensang
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Alexandra Maertens
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Michael Rosenberg
Agilent Technologies, Inc., Santa Clara, CA, USA
Suzanne Fitzpatrick
US Food and Drug Administration, Center for Food Safety & Applied Nutrition, College Park, MD, USA
Justin Lamb
Genometry Inc., Cambridge, MA, USA
Scott Auerbach
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Richard Brennan
Thomson Reuters Inc., Carlsbad, CA, USA
Kevin M. Crofton
U.S. Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, USA
Ben Gordon
Dept of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
Albert J. Jr. Fornace
Dept. of Biochemistry and Molecular & Cellular Biology, and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
Kevin Gaido
US Food and Drug Administration, Center for Food Safety & Applied Nutrition, College Park, MD, USA
David Gerhold
The National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA
Robin Haw
Reactome, Ontario Institute for Cancer Research, Toronto, Canada
Adriano Henney
The German Virtual Liver Network, University of Heidelberg, Heidelberg, Germany
Avi Ma’ayan
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Mary McBride
Agilent Technologies, Inc., Santa Clara, CA, USA
Stefano Monti
Section of Computational Biomedicine, Boston University School of Medicine, Boston, MA, USA
Michael F. Ochs
Johns Hopkins University, School of Medicine, Department of Oncology, Baltimore, MD, USA
Akhilesh Pandey
Institute of Genetic Medicine and Departments of Biological Chemistry, Oncology and Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA
Roded Sharan
Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel
Rob Stierum
TNO Healthy Living, Microbiology & Systems Biology, Zeist, The Netherlands
Stuart Tugendreich
Ingenuity Systems, Inc., Redwood City, CA, USA
Catherine Willett
The Humane Society of the United States, Washington, DC, USA
Clemens Wittwehr
European Commission, Joint Research Centre, Systems Toxicology Unit, Ispra, Italy
Jianguo Xia
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
Geoffrey W. Patton
U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, College Park, MD, USA
Kirk Arvidson
U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Food Additive Safety, College Park, MD, USA
Mounir Bouhifd
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Helena T. Hogberg
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Thomas Luechtefeld
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Lena Smirnova
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Liang Zhao
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA
Yeyejide Adeleye
Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire, UK
Minoru Kanehisa
Institute for Chemical Research, Kyoto University, Kyoto, Japan
Paul Carmichael
Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire, UK
Melvin E. Andersen
The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
Thomas Hartung
Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA; CAAT-Europe, University of Konstanz, Germany
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Abstract
Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation – the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as “A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants”. It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities.
