Title: Representing the Process of Inflammation as Key Events in Adverse Outcome Pathways
Authors: VILLENEUVE DANLANDESMANN BRIGITTEALLAVENA PAOLAASHLEY NOAHPRICE ANNACORSINI EMANUELAHALAPPANAVAR SABINAHUSSELL TRACYLASKIN DEBRALAWRENCE TOBYNIKOLIC-PATERSON DAVIDPALLARDY MARCPAINI ALICIAPIETERS RAYMONDROTH ROBERTTSCHUDI-MONNET3 FLORIANNE
Citation: TOXICOLOGICAL SCIENCES vol. 163 no. 2 p. 346–352
Publisher: OXFORD UNIV PRESS
Publication Year: 2018
JRC N°: JRC109122
ISSN: 1096-6080
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC109122
DOI: 10.1093/toxsci/kfy047
Type: Articles in periodicals and books
Abstract: Inflammation is an important biological process involved in many target organ toxicities. However, there has been little consensus on how to represent inflammatory processes using the adverse outcome pathway (AOP) framework. In particular, there were concerns that inflammation was not being represented in a way that it would be recognized as a highly connected, central node within the global AOP network. The consideration of salient features common to the inflammatory process across tissues was used as a basis to propose 3 hub key events (KEs) for use in AOP network development. Each event, “tissue resident cell activation”, “increased pro-inflammatory mediators”, and “leukocyte recruitment/activation,” is viewed as a hallmark of inflammation, independent of tissue, and can be independently measured. Using these proposed hub KEs, it was possible to link together a series of AOPs that previously had no shared KEs. Significant challenges remain with regard to accurate prediction of inflammation-related toxicological outcomes even if a broader and more connected network of inflammation-centered AOPs is developed. Nonetheless, the current proposal addresses one of the major hurdles associated with representation of inflammation in AOPs and may aid fit-for-purpose evaluations of other AOPs operating in a network context.
JRC Directorate:Health, Consumers and Reference Materials

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