Upstream eventIncrease, Plasma vitellogenin concentrations
Increase, Renal pathology due to VTG deposition
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Directness||Weight of Evidence||Quantitative Understanding|
|Estrogen receptor agonism leading to reproductive dysfunction||directly leads to||Strong|
Life Stage Applicability
How Does This Key Event Relationship Work
Weight of Evidence
High level of biological plausibility in fish.
Empirical Support for Linkage
Laboratory in vivo aquatic exposures of fish (fathead minnow) to 17alpha-ethinylestradiol led to renal pathology within 16 weeks, concomitant with macroscopic evidence of osmoregulatory dysfunction and morbidity (Laenge et al., 2001).
Uncertainties or Inconsistencies
None that the author of this entry is aware of.
Quantitative Understanding of the Linkage
Published studies include 17beta-estradiol and 17alpha-ethinylestradiol as known modulators of this relationship in fish. Model fish species (eg fathead minnow) have been used to study this biological effect and while there are no quantitative extrapolation models published to date, empirical data suggests renal pathology occurs in juvenile or male fish when plasma VTG levels are >1000-fold above baseline for a period of several weeks.
Evidence Supporting Taxonomic Applicability
Publish studies specifically relate to fish, although it is plausible that the same response may occur in the aquatic life-stages of amphibians.
Herman, R.L., Kincaid, H.L. (1988) Pathological effects of orally administered 17beta-estradiol to rainbow trout. Aquaculture 72:165–172
Länge, R., Hutchinson, T.H., Croudace, C.P., Siegmund, F., Schweinfurth, H., Hampe, P., Panter, G.H., Sumpter, J.P. (2001) Effects of the synthetic estrogen 17 alpha-ethinylestradiol on the life-cycle of the fathead minnow (Pimephales promelas). Environ Toxicol Chem 20:1216-1227