OECD Series on Adverse Outcome Pathways

ISSN: 
2415-170X (online)
DOI: 
10.1787/2415170X
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An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a chemical and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude the regular update or new contributions to a given AOP in the AOP Wiki. While the AOP Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP. The number 1 in the OECD Series on Adverse Outcome Pathways is the Users’ Handbook, which is a supplement to the Guidance Document for developing and assessing AOPs. This handbook contains an updated template for AOP development and provides focused and practical instructions for both AOP developers and reviewers.
 

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis You or your institution have access to this content

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    http://oecd.metastore.ingenta.com/content/5jlsvwl6g7r5-en.pdf
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Author(s):
Brigitte Landesmann1
Author Affiliations
  • 1: European Commission, Belgium

04 Aug 2016
Bibliographic information
No.:
2
Pages:
72
DOI: 
10.1787/5jlsvwl6g7r5-en

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Liver fibrosis is an important human health issue associated with chemical exposure. It is a typical result of chronic toxic injury and one of the considered endpoints for regulatory purposes. This AOP describes the linkage between hepatic injury caused by protein alkylation and the formation of liver fibrosis. Fibrogenesis is a long-term and complex process for which an adequate cell model is not available and an in vitro evaluation of fibrogenic potential is therefore not feasible yet. This systematic and coherent display of currently available mechanistic-toxicological information can serve as a knowledge-based repository for identification/selection/development of in vitro methods suitable for measuring key events and their relationships along the AOP and to facilitate the use of alternative data for regulatory purposes. Identified uncertainties and knowledge gaps can indicate priorities for future research.
Keywords:
protein alkylation, liver fibrosis, hepatotoxicity
 
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