Citation:

Doering, J., G. Ankley, B. Blackwell, K. Fay, D. Feifarek, K. Jensen, M. Kahl, C. LaLone, S. Poole, E. Randolph, C. Tilton, AND Dan Villeneuve. Assessing differences in sensitivity to aromatase inhibitors among freshwater fish species. SETAC Europe, Rome, ITALY, May 13 - 17, 2018.

Impact/Purpose:

This is a presentation showing that intrinsic differences in sensitivity to inhibition of aromatase could be greater than 60-fold among species of fish. Further, this presentation shows that species of fish of significant ecological or economic importance in the US, such as catfish, trout, perch, and sturgeon, could be more sensitive to impairment of reproduction relative to the laboratory model species, fathead minnow. This work supports aims of CSS project 17.01 toward understanding cross-species differences in sensitivity to anthropogenic contaminants and the mechanisms that drive those differences in order to guide more objective ecological risk assessments.

Description:

There is significant concern regarding potential impairment of fish reproduction associated with exposure to endocrine disrupting chemicals (EDCs). Aromatase is a steroidogenic enzyme involved in the conversion of androgens to estrogens. Inhibition of aromatase activity by exposure to chemicals can reduce levels of circulating estrogen leading to reduced synthesis of vitellogenin and production of fewer eggs by females. This mechanism has been extensively studied in the laboratory model species, fathead minnow (Pimephales promelas). However, differences in sensitivity to inhibition of aromatase among species of fish is largely unknown. This is particularly true for species that are not routinely studied in short-term reproduction assays, including many fishes of significant ecological and economic importance such as catfish (Ictaluridae), eel (Anguillidae), and perch (Percidae). This study investigated in vitro inhibition of aromatase by the model inhibitor, fadrozole, across eighteen phylogenetically diverse species of freshwater fish. Concentrations of fadrozole that result in 50 % inhibition of in vitro aromatase activity range from 0.0014 to 0.088 nM among these species. This suggests that intrinsic differences in sensitivity to inhibition of aromatase could be greater than 60-fold among fishes. Paddlefish (Polyodontidae), white sucker (Catostomidae), rainbow trout (Salmonidae), and fathead minnow (Cyprinidae) were investigated for sensitivity to in vitro inhibition of aromatase by four additional inhibitors. Potencies of letrozole, imazalil, prochloraz, and propiconazole relative to fadrozole were comparable among paddlefish, white sucker, rainbow trout, and fathead minnow despite up to 40-fold difference in sensitivity to fadrozole. This suggests that relative potencies generated for a model species, such as fathead minnow, could be applicable across diverse species, despite great differences in relative sensitivity. Results of this study are being used in the construction of a cross-species quantitative adverse outcome pathway (qAOP) that incorporates in vitro sensitivity data as a relative-sensitivity adjustment for prediction of impacts at the individual and population level. This information could guide more objective ecological risk assessments of native species to EDCs that inhibit aromatase.

Record Details: