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Building shared experience to advance practical application of pathway-based toxicology: Liver toxicity mode-of-action

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Catherine Willet1, Jessica Caverly Rae2, Katy O. Goyak3, Gary Minsavage3, Carl Westmoreland4, Melvin Andersen5, Mark Avigan6, Daniel Duché7, Georgina Harris8,Thomas Hartung8, Hartmut Jaeschke9, Andre Kleensang8, Brigitte Landesmann10, Suzanne Martos8, Marilyn Matevia1, Colleen Toole11, Andrew Rowan1, Terry Schultz12, Jennifer Seed13, John Senior6, Imran Shah14, Kalyanasundaram Subramanian15, Mathieu Vinken16 and Paul Watkins17
1 The Humane Society of the United States, Washington, DC, USA;
2 DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE, USA;
3 ExxonMobil Biomedical Sciences, Inc., Annandale, NJ, USA;
4 Safety & Environmental Assurance Centre, Unilever Research and Development, Sharnbrook, Bedford, UK;
5 The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA;
6 Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;
7 L’Oréal Research & Innovation, Aulnay sous Bois, France;
8 Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing (CAAT), Baltimore, MD, USA and CAAT-Europe, University of Konstanz, Germany;
9 University of Kansas Medical Center, Kansas City, KS, USA;
10 Joint Research Centre, Institute for Health and Consumer Protection, European Commission, Ispra, Italy;
11 CeeTox, Inc., Kalamazoo, MI, USA;
12 University of Tennessee, Knoxville, TN, USA, and OECD Secretariat, Paris, France;
13 Risk Assessment Division, Office of Pollution Prevention and Toxics, Environmental Protection Agency, Washington, DC, USA;
14 National Center for Computational Toxicology, Environmental Protection Agency, Research Triangle Park, NC, USA;
15 Strand Life Sciences, Bangalore, India;
16 Vrije Universiteit Brussels, Brussels, Belgium;
17 The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA and University of North Carolina, Institute for Drug Safety Sciences, Chapel Hill, NC, USA

Summary


A workshop sponsored by the Human Toxicology Project Consortium (HTPC), “Building Shared Experience to Advance Practical Application of Pathway-Based Toxicology: Liver Toxicity Mode-of-Action” brought together experts from a wide range of perspectives to inform the process of pathway development and to advance two prototype pathways initially developed by the European Commission Joint Research Center (JRC): liver-specific fibrosis and steatosis. The first half of the workshop focused on the theory and practice of pathway development; the second on liver disease and the two prototype pathways. Participants agreed pathway development is extremely useful for organizing information and found that focusing the theoretical discussion on a specific AOP is helpful. It is important to include several perspectives during pathway development, including information specialists, pathologists, human health and environmental risk assessors, and chemical and product manufacturers, to ensure the biology is well captured and end use is considered.

 

Keywords: systems toxicology, pathways of toxicity, adverse outcome pathways, in vitro toxicology, liver toxicity

 

 

ALTEX (31)4: 500-519

DOI: http://dx.doi.org/10.14573/altex.1401281


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