Upstream eventAgonism, Estrogen receptor
Increase, Vitellogenin synthesis in liver
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Estrogen receptor agonism leading to reproductive dysfunction||adjacent||High|
|fathead minnow||Pimephales promelas||High||NCBI|
Life Stage Applicability
Key Event Relationship Description
Evidence Supporting this KER
High degree of plausibility in fathead minnow, zebrafish and other cyprinid species.
A wide range of studies using adult fish show that induction of plasma vitellogenin (VTG) occurs within 21 days in vivo aquatic exposure to estrogen receptor agonists (eg 17beta-estradiol and 4-tert pentylphenol) as shown during the successful validation of the OECD Test Guideline 229 and related protocols. A smaller number of experiment studies with fish have shown that within the OECD Test Guideline 2010, larval fish can also show induction of whole body VTG levels within 21 days aquatic exposure to estrogen receptor agonists.
Uncertainties and Inconsistencies
There are generally few inconsistencies for experimental studies using model fish species dervied from pathogen-free laboratory cultures. However, there can some uncertainties where wild fish have been used for experimental purposes.
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Navas, J.M., Segner, H. (2006) Vitellogenin synthesis in primary cultures of fish liver cells as endpoint for in vitro screening of the (anti)estrogenic activity of chemical substances. Aquatic Toxicology 80: 1-22
Thorpe, K.L., Benstead, R., Hutchinson, T.H., Tyler, C.R. (2007). Associations between altered vitellogenin concentrations and adverse health effects in fathead minnow (Pimephales promelas). Aquatic Toxicology 85: 176-183