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=== Uncertainties or Inconsistencies === | === Uncertainties or Inconsistencies === |
Revision as of 16:59, 16 June 2016
Contents
Key Event Relationship Overview
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Description of Relationship
Upstream Event | Downstream Event/Outcome |
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Endothelial network, Impairment | Vascular, Insufficiency |
AOPs Referencing Relationship
AOP Name | Type of Relationship | Weight of Evidence | Quantitative Understanding |
---|---|---|---|
VEGF Signaling and Vascular Disruption Leading to Adverse Developmental Outcomes | Indirectly Leads to | Moderate | Weak |
Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
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How Does This Key Event Relationship Work
In utero vascular disruptions are thought to be associated with a variety of developmental defects [Husain et al. 2008]. Vascular disruption was identified as one of 6 teratogenic mechanisms linked with medications [van Gelder et al. 2010].
Weight of Evidence
Biological Plausibility
In humans, the most common apparent cause of limb deficiencies was found to be vascular disruption defects [Gold et al. 2011]. Many genetic and environmental factors alter molecular pathways regulating angiogenesis [Knudsen and Kleinstreuer, 2011].
Empirical Support for Linkage
Include consideration of temporal concordance here
Susceptibility to Thalidomide linked to the disruption of immature angiogenic network at time of exposure [Therapontos et al. 2009]. Predicted vascular disrupting chemicals in ToxCast correlate with developmental toxicity [Kleinstreuer et al. 2011].
Uncertainties or Inconsistencies
Quantitative Understanding of the Linkage
Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?