RP8 Ecotoxicology of Agrochemicals and Pharmaceuticals
Thursday, 17 November 2005: 8:00 AM - 6:30 PM in Exhibit Hall

(KAH-1117-746048) Effects of three fungicides on reproductive success and endocrinology of the fathead minnow.

Kahl, M.¹, Villeneuve, D.¹, Jensen, K.¹, Durhan, E.¹, Makynen, E.¹, Linnum, A.¹, Ankley, G.¹, ¹ U.S. EPA Mid-Continent Ecology Division, Duluth, MN

ABSTRACT- The toxic mechanism of action of several current-use fungicides involves inhibition of ergosterol formation by 14-demethylase, a cytochrome P450-based enzyme. However, many of these fungicides can inhibit a variety of P450s, including some involved in vertebrate steroidogenesis. A companion paper by Villeneuve et al. describes the effects of three fungicides, prochloraz, fenarimol and ketoconazole, on in vitro steroid synthesis by fathead minnow ovarian tissue. The studies in this presentation describe in vivo effects of the three pesticides on fathead minnow reproductive success (fecundity) and a suite of diagnostic measures of endocrine system status, including gonadal histopathology and plasma concentrations of vitellogenin and sex steroids (testosterone, 11-ketotestosterone, 17-estadiol). Exposure to the fungicides for 21 d significantly inhibited fecundity of the fish at water concentrations greater than 0.1 (prochloraz), 1.0 (fenarimol) and 0.4 (ketoconazole) mg/L. The suite of diagnostic responses in the fish varied among the three fungicides. Some, but not all, observed effects were suggestive of inhibition of steroid synthesis. For example, prochloraz depressed both androgen (testosterone, 11-ketotestosterone) and 17-estradiol concentrations. This was associated with decreased concentrations of vitellogenin (an estrogen-responsive protein) observed in exposed females. In contrast, fenarimol also decreased vitellogenin concentrations in female fathead minnows but the effect was not associated with a significant decrease in 17-estradiol concentrations. Results of the in vivo studies confirm that the three fungicides broadly act as endocrine-disrupting chemicals (EDCs), but suggest that they operate via modes/mechanisms of action in addition to disruption of steroid synthesis. This highlights the importance of complementary in vivo and in vitro studies to assess the mechanistic basis of adverse effects of EDCs.

Key words: steroidogenesis, endocrine disruption, Pimephales promelas, fungicides