“…Previous studies show that 4-NP sequesters in the liver, brain, gills, gonads, and tissues of fish (Ahel et al, 1994;Lewis and Lech, 1996;Coldham et al, 1998) and can cause negative consequences for reproduction and development (Colborn et al, 1993;Jobling et al, 1996;Christiansen et al, 1998;Tabata et al, 2001;Chandrasekar et al, 2011). Male fish exposed to 4-NP, for instance, have been found to exhibit a suite of defects including altered testicular structure, decreased sperm counts, intersex gonads, disrupted reproductive cycles, liver damage, and reduced growth (e.g., Christiansen et al, 1998;Servos, 1999;Tanaka and Grizzle, 2002;Kaptaner and € Unal, 2011;El-Sayed Ali et al, 2014;Traversi et al, 2014). And, even though 4-NP is approximately 1500 times less potent than E2 (Butwell et al, 2002), exposure to 4-NP either at concentrations in the range found commonly in sewage effluents or for only a brief duration of exposure is capable of activating intracellular ERs and inducing the expression of estrogen-regulated genes in juvenile and male fish (e.g., Soto et al, 1991;White et al, 1994;Arukwe et al, 2001Arukwe et al, , 2002Ackermann et al, 2002;Genovese et al, 2011;Brander et al, 2012).…”