You are here:
Effects of the azole fungicide imazalil on the fathead minnow (Pimephales promelas) steroidogenesis pathway
Citation:
Feifarek, D., R. Milsk, K. Jensen, B. Blackwell, E. Randolph, J. Cavallin, T. Saari, M. Kahl, G. Ankley, W. Cheng, AND Dan Villeneuve. Effects of the azole fungicide imazalil on the fathead minnow (Pimephales promelas) steroidogenesis pathway. Midwest SETAC, Madison, WI, March 14 - 16, 2016.
Impact/Purpose:
not applicable
Description:
Azole fungicides, used for both agriculture and human therapeutic applications may disrupt endocrine function of aquatic life. Azole fungicides are designed to inhibit the fungal enzyme lanosterol 14 á-demethylase (cytochrome P450 [CYP] 51). However, they can also interact with and inhibit other CYPS, including those involved in steroid biosynthesis, through competitive binding to the heme moiety. High throughput screening in US EPA’s Toxcast program identified imazalil as an endocrine active chemical capable of inhibiting mammalian aromatase (CYP19A1) and likely 17á-hydroxylase/17,20 lyase (CYP17A1). The present study confirmed this endocrine activity in fish. Exposure of reproductively mature female P. promelas to 100, 500 and 1580 µg/L imazalil for 24 h significantly reduced both testosterone (T) and 17â-estradiol (E2) production by ovary tissue collected from the fish. Likewise, plasma E2 concentrations in reproductively mature female P. promelas were significantly reduced following exposure to 80 and 250 µg imazalil/L, but not 2.5, 8, and 25 µg/L, for 24 h. The in vivo impacts of imazalil on fathead minnow steroid production were further supported by in vitro ovarian steroidogenesis assay in which ovary tissue exposed to the 200 µg imazalil/L in vitro synthesized significantly less E2 than tissue exposed to 0, 0.2, 2, or 20 µg imazalil/L. The present results support the use of an adverse outcome pathway linking aromatase inhibition to reproductive impairment in fish treatments and control, as a means to predict hazards, and potentially risk associated with exposures to this compound.