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Assessment of differences in sensitivity to aromatase inhibitors among freshwater fish species
Citation:
Doering, J., G. Ankley, B. Blackwell, J. Cavallin, K. Fay, D. Feifarek, K. Jensen, M. Kahl, C. LaLone, S. Poole, E. Randolph, AND Dan Villeneuve. Assessment of differences in sensitivity to aromatase inhibitors among freshwater fish species. SETAC North America, Minneapolis, MN, November 12 - 16, 2017.
Impact/Purpose:
This is a presentation showing that intrinsic differences in sensitivity to inhibition of aromatase could be as great as 50-fold among species of fish. Further, this presentation shows that species of fish with synchronous gonadal development, such as catfish, trout, perch, and sturgeon, could be more sensitive to impairment of reproduction relative to the laboratory model species, fathead minnow, and other species with asynchronous gonadal development. 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. Results will aid prediction of in vivo effect concentrations for a wider range of species based on in vitro measures of aromatase inhibition, supporting the EDSP, pre-prioritization under TSCA, and expedited approaches to ambient water quality criteria derivation for chemicals acting through this adverse outcome pathway.
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 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, recreational, and economic importance such as catfish (Ictaluridae), trout (Salmonidae), and perch (Percidae). This study investigated in vitro inhibition of aromatase by the model inhibitor fadrozole across twenty phylogenetically diverse species of fish, including species with asynchronous oocyte development and species with synchronous oocyte development. Fathead minnow and other species with asynchronous oocyte development were the least sensitive in vitro with IC50s of 0.1 to 0.04 µM. Synchronous species that spawn annually were more sensitive with IC50s of 0.02 to 0.007 µM. Sturgeons (Acipenseridae) and paddlefish (Polyodontidae) that have synchronous oocyte development but spawn less than annually were the most sensitive with IC50s of 0.002 µM. This suggests that intrinsic differences in sensitivity to inhibition of aromatase could be as great as 50-fold among fishes. However, species with the same process of oocyte development had comparable in vitro sensitivities to inhibition. Therefore, knowledge of reproductive strategy might be predictive of relative sensitivity, with species with asynchronous oocyte development being less sensitive than species with synchronous oocyte development. Results of this study are being used in the construction of a quantitative adverse outcome pathway that incorporates species-specific differences in sensitivity to inhibition of aromatase for application to the regulation and risk assessment of EDCs that can inhibit aromatase. The content of this presentation neither constitute nor necessarily reflect US EPA policy.