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Quantitative response-response relationships linking aromatase inhibition to decreased fecunditiy are conserved across three fishes with asynchronous oocyte development
Citation:
Doering, J., D. Villeneuve, S. Poole, B. Blackwell, K. Jensen, M. Kahl, A. Kittelson, D. Feifarek, C. Tilton, C. Lalone, AND G. Ankley. Quantitative response-response relationships linking aromatase inhibition to decreased fecunditiy are conserved across three fishes with asynchronous oocyte development. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 53(17):10470-10478, (2019). https://doi.org/10.1021/acs.est.9b02606
Impact/Purpose:
This publication shows that a previously developed quantitative adverse outcome pathway (qAOP) for inhibition of aromatase leading to decreased fecundity developed from a single laboratory model test species, the fathead minnow, could have immediate regulatory applications that include several laboratory model test species as well as regionally important native indicator species and economically valuable species. Specifically, this study demonstrated that response-response predictions from the qAOP could accurately simulate plasma estradiol, plasma vitellogenin, and fecundity measured in female fathead minnow, Japanese medaka, and zebrafish exposed to serial concentrations of the model aromatase inhibitor, fadrozole, for 21 days. This work supports aims of CSS project 17.01 toward enabling predictive, adverse outcome pathway-driven ecological risk assessments for native species of regulatory concern.
Description:
Quantitative adverse outcome pathways (qAOPs) describe quantitative response-response relationships that can predict the probability or severity of an adverse outcome for a given magnitude of chemical interaction with a molecular initiating event. However, the taxonomic domain of applicability for these predictions is largely unknown. Therefore, the present study began defining this applicability for a qAOP describing inhibition of aromatase leading to decreased fecundity which was developed from studies of fathead minnow (Pimephales promelas). Quantitative response-response relationships describing plasma 17β-estradiol (E2) as a function of fadrozole water concentration, plasma vitellogenin (VTG) as a function of plasma E2, and fecundity as a function of plasma VTG accurately predicted plasma E2, plasma VTG, and fecundity measured in female fathead minnow and zebrafish (Danio rerio) exposed to serial concentrations of fadrozole for 21 days. But, responses measured in female Japanese medaka (Oryzias latipes) were different. However, Japanese medaka had different basal levels of plasma E2, plasma VTG, and fecundity. Normalizing basal levels to equal those in the qAOP enabled the relationships to accurately predict plasma E2, plasma VTG, and fecundity measured in female Japanese medaka. This suggests that quantitative response-response relationships are conserved across these three fishes when considering relative change rather than absolute measurements.
URLs/Downloads:
DOI: Quantitative response-response relationships linking aromatase inhibition to decreased fecunditiy are conserved across three fishes with asynchronous oocyte development
09/01/2019