title: Pathways of Toxicity.
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. To this end, a workshop was organized to explore one key aspect of this transformation - the development of Pathways of Toxicity 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 Pathway of Toxicity (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.
authors.affiliation: Johns Hopkins University, Bloomberg School of Public Health, Center for Alternatives to Animal Testing, Baltimore, MD, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Kleensang
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maertens
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenberg
authors.forename: Suzanne
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authors.lastname: Fitzpatrick
authors.forename: Justin
authors.initials: J
authors.lastname: Lamb
authors.forename: Scott
authors.initials: S
authors.lastname: Auerbach
authors.forename: Richard
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authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
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authors.forename: Albert J
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authors.lastname: Fornace
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authors.lastname: Gaido
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authors.lastname: Gerhold
authors.forename: Robin
authors.initials: R
authors.lastname: Haw
authors.forename: Adriano
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authors.lastname: Henney
authors.forename: Avi
authors.initials: A
authors.lastname: Ma'ayan
authors.forename: Mary
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authors.lastname: McBride
authors.forename: Stefano
authors.initials: S
authors.lastname: Monti
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Roded
authors.initials: R
authors.lastname: Sharan
authors.forename: Rob
authors.initials: R
authors.lastname: Stierum
authors.forename: Stuart
authors.initials: S
authors.lastname: Tugendreich
authors.forename: Catherine
authors.initials: C
authors.lastname: Willett
authors.forename: Clemens
authors.initials: C
authors.lastname: Wittwehr
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xia
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Patton
authors.forename: Kirk
authors.initials: K
authors.lastname: Arvidson
authors.forename: Mounir
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authors.lastname: Bouhifd
authors.forename: Helena T
authors.initials: HT
authors.lastname: Hogberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Luechtefeld
authors.forename: Lena
authors.initials: L
authors.lastname: Smirnova
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Yeyejide
authors.initials: Y
authors.lastname: Adeleye
authors.forename: Minoru
authors.initials: M
authors.lastname: Kanehisa
authors.forename: Paul
authors.initials: P
authors.lastname: Carmichael
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.forename: Thomas
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authors.lastname: Hartung
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D016208:Databases, Factual; D015386:Hazardous Substances / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D011237:Predictive Value of Tests; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D015386:Hazardous Substances