Publications : 2019

Doering JA, Villeneuve DL, Poole ST, Blackwell BR, Jensen KM, Kahl MD, Kittelson AR, Feifarek DJ, Tilton CB, LaLone CA, Ankley GT. 2019. Quantitative response-response relationships linking aromatase inhibition to decreased fecundity are conserved across three fishes with asynchronous oocyte development. Environ Sci Technol 53(17):10470–10478.


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.