Pathways of Toxicity

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Andre Kleensang
Alexandra Maertens
Michael Rosenberg
Suzanne Fitzpatrick
Justin Lamb
Scott Auerbach
Richard Brennan
Kevin M. Crofton
Ben Gordon
Albert J. Jr. Fornace
Kevin Gaido
David Gerhold
Robin Haw
Adriano Henney
Avi Ma’ayan
Mary McBride
Stefano Monti
Michael F. Ochs
Akhilesh Pandey
Roded Sharan
Rob Stierum
Stuart Tugendreich
Catherine Willett
Clemens Wittwehr
Jianguo Xia
Geoffrey W. Patton
Kirk Arvidson
Mounir Bouhifd
Helena T. Hogberg
Thomas Luechtefeld
Lena Smirnova
Liang Zhao
Yeyejide Adeleye
Minoru Kanehisa
Paul Carmichael
Melvin E. Andersen
Thomas Hartung

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.

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How to Cite
[1]
Kleensang, A., Maertens, A., Rosenberg, M., Fitzpatrick, S., Lamb, J., Auerbach, S., Brennan, R., Crofton, K., Gordon, B., Fornace, A., Gaido, K., Gerhold, D., Haw, R., Henney, A., Ma’ayan, A., McBride, M., Monti, S., Ochs, M., Pandey, A., Sharan, R., Stierum, R., Tugendreich, S., Willett, C., Wittwehr, C., Xia, J., Patton, G., Arvidson, K., Bouhifd, M., Hogberg, H., Luechtefeld, T., Smirnova, L., Zhao, L., Adeleye, Y., Kanehisa, M., Carmichael, P., Andersen, M. and Hartung, T. 2014. Pathways of Toxicity. ALTEX - Alternatives to animal experimentation. 31, 1 (Feb. 2014), 53-61. DOI:https://doi.org/10.14573/altex.1309261.
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