Identification of the lampricide 3‐trifluoromethyl‐4‐nitrophenol as an agonist for the rainbow trout estrogen receptor

Abstract Lampricide formulations containing 3 -trifluoromethyl-4-nitrophenol (TFM) have been associated with induction of hepatic mixed function oxygenase (MFO) activity and altered levels of circulating steroids in fish. Bioassay-directed chemical fractionations have shown MFO induction to be associated with impurities in TFM field formulations. A similar toxicity identification/evaluation approach coupled to competitive binding to rainbow trout estrogen receptors (ER) was used to identify compounds associated with estrogenic responses in fish. In contrast to MFO induction, nearly all binding to the ER was associated with fractions containing TFM, TFM isomers, and p-chlorophenol.p-Chlorophenol did not show any affinity for the receptor when tested separately. Diphenyl ether impurities identified in the fractions causing MFO induction as well as analogues to dibenzo-p-dioxins suspected in these fractions also showed no affinity for the receptor when tested individually. Relative to estradiol, TFM demonstrated an affinity of 5.03 × 10−5, compared to 2.47 × 10−4 for p-nonylphenol, a reported estradiol agonist. Vitellogenin induction in primary cultures of rainbow trout hepatocytes indicated that TFM acts as an estradiol agonist.