Weight of Evidence Frameworks in Evaluation of Adverse Outcome Pathways

2018 ◽  
pp. 303-316 ◽  
Author(s):  
Taylor Rycroft ◽  
Olivia Massey ◽  
Christy M. Foran ◽  
Igor Linkov
Keyword(s):  
Adverse Outcome ◽  
Weight Of Evidence ◽  
Adverse Outcome Pathways

scholarly journals Increasing Scientific Confidence in Adverse Outcome Pathways: Application of Tailored Bradford-Hill Considerations for Evaluating Weight of Evidence

2015 ◽  
Vol 72 (3) ◽  
pp. 514-537 ◽  
Author(s):  
Richard A. Becker ◽  
Gerald T. Ankley ◽  
Stephen W. Edwards ◽  
Sean W. Kennedy ◽  
Igor Linkov ◽  
...  
Keyword(s):  
Adverse Outcome ◽  
Weight Of Evidence ◽  
Bradford Hill ◽  
Adverse Outcome Pathways

scholarly journals Capturing a Comprehensive Picture of Biological Events From Adverse Outcome Pathways in the Drug Exposome

2021 ◽  
Vol 9 ◽  
Author(s):  
Qier Wu ◽  
Youcef Bagdad ◽  
Olivier Taboureau ◽  
Karine Audouze
Keyword(s):  
Health Effects ◽  
Drug Safety ◽  
Safety Assessment ◽  
Drug Exposure ◽  
Adverse Outcome ◽  
Information Loss ◽  
Weight Of Evidence ◽  
Bipartite Network ◽  
Biological Organization ◽  
Adverse Outcome Pathways

Background: The chemical part of the exposome, including drugs, may explain the increase of health effects with outcomes such as infertility, allergies, metabolic disorders, which cannot be only explained by the genetic changes. To better understand how drug exposure can impact human health, the concepts of adverse outcome pathways (AOPs) and AOP networks (AONs), which are representations of causally linked events at different biological levels leading to adverse health, could be used for drug safety assessment.Methods: To explore the action of drugs across multiple scales of the biological organization, we investigated the use of a network-based approach in the known AOP space. Considering the drugs and their associations to biological events, such as molecular initiating event and key event, a bipartite network was developed. This bipartite network was projected into a monopartite network capturing the event–event linkages. Nevertheless, such transformation of a bipartite network to a monopartite network had a huge risk of information loss. A way to solve this problem is to quantify the network reduction. We calculated two scoring systems, one measuring the uncertainty and a second one describing the loss of coverage on the developed event–event network to better investigate events from AOPs linked to drugs.Results: This AON analysis allowed us to identify biological events that are highly connected to drugs, such as events involving nuclear receptors (ER, AR, and PXR/SXR). Furthermore, we observed that the number of events involved in a linkage pattern with drugs is a key factor that influences information loss during monopartite network projection. Such scores have the potential to quantify the uncertainty of an event involved in an AON, and could be valuable for the weight of evidence assessment of AOPs. A case study related to infertility, more specifically to “decrease, male agenital distance” is presented.Conclusion: This study highlights that computational approaches based on network science may help to understand the complexity of drug health effects, with the aim to support drug safety assessment.

A weight of evidence assessment approach for adverse outcome pathways

2016 ◽  
Vol 75 ◽  
pp. 46-57 ◽  
Author(s):  
Zachary A. Collier ◽  
Kurt A. Gust ◽  
Benette Gonzalez-Morales ◽  
Ping Gong ◽  
Mitchell S. Wilbanks ◽  
...  
Keyword(s):  
Adverse Outcome ◽  
Weight Of Evidence ◽  
Assessment Approach ◽  
Adverse Outcome Pathways

Adverse outcome pathways: A conceptual framework to support ecotoxicology research and risk assessment

2011 ◽  
pp. n/a-n/a ◽  
Author(s):  
Gerald T. Ankley ◽  
Richard S. Bennett ◽  
Russell J. Erickson ◽  
Dale J. Hoff ◽  
Michael W. Hornung ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Conceptual Framework ◽  
Adverse Outcome ◽  
Adverse Outcome Pathways

scholarly journals An Update on Adverse Outcome Pathways Leading to Liver Injury

2017 ◽  
Vol 3 (4) ◽  
pp. 283-285 ◽  
Author(s):  
Eva Gijbels ◽  
Mathieu Vinken
Keyword(s):  
Liver Injury ◽  
Adverse Outcome ◽  
Adverse Outcome Pathways

Adverse outcome pathways, key events, and radiation risk assessment

2020 ◽  
pp. 1-18
Author(s):  
R. Julian Preston ◽  
Werner Rühm ◽  
Edouard I. Azzam ◽  
John D. Boice ◽  
Simon Bouffler ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Adverse Outcome ◽  
Radiation Risk ◽  
Key Events ◽  
Adverse Outcome Pathways
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