Adverse Outcome Pathway on Aryl hydrogen receptor activation leading to early life stage mortality, via reduced VEGF

Abstract

This Adverse Outcome Pathway (AOP) on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF, has been developed under the auspices of the OECD AOP Development Programme, overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST), which is an advisory group under the Working Group of the National Coordinators for the Test Guidelines Programme (WNT). The AOP has been reviewed internally by the EAGMST, externally by experts nominated by the WNT, and has been endorsed by the WNT and the Working Party on Hazard Assessment (WPHA) in May 2019. Through endorsement of this AOP, the WNT and the WPHA express confidence in the scientific review process that the AOP has undergone and accept the recommendation of the EAGMST that the AOP be disseminated publicly. Endorsement does not necessarily indicate that the AOP is now considered a tool for direct regulatory application. The Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology agreed to declassification of this AOP on 26 June 2019. This document is being published under the responsibility of the Joint Meeting of the Chemicals Committee and the Working Party on Chemicals, Pesticides and Biotechnology. The outcome of the internal and external reviews are publicly available respectively in the AOP Wiki and the eAOP Portal of the AOP Knowledge Base at the following links: [internal review] [external review].

Systems Toxicology Approach for Testing Chemical Cardiotoxicity in Larval Zebrafish

“…The in-depth curation based on literature, directionality of edges between nodes, and inclusion of nodes that represent diverse levels of biological organization make our method similar to the approach taken in developing AOPs. , Therefore, it is not surprising that some of the AOPs recently released by the OECD (Organisation for Economic Co-operation and Development)AOP 21 and AOP 150can also be found in our network. , This similarity makes the curated functional layer of the network a useful resource for future AOP development. In effect, the network may be thought of as a network of putative AOPs that share key events.…”

“…Zebrafish larvae deficient in mylk3 develop cardiac edema . Additionally, the network describes two adverse outcome pathways (AOPs) currently under development in the AOP database AOPwiki () (Figure b): “Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF” (AOP 150) and “Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2” (AOP 21). , …”