title: Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents.
abstract: The widespread occurrence of feminized male fish downstream of some UK Wastewater Treatment Works (WwTWs) has been associated with exposure to estrogenic and potentially antiandrogenic (AA) contaminants in the effluents. In this study, profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC in combination with in vitro androgen receptor transcription screens. Analysis of extracts of wastewater effluents revealed complex profiles of AA activity comprising 21-53 HPLC fractions. Structures of bioavailable antiandrogens were identified by exposing rainbow trout to a WwTW effluent and profiling the bile for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen receptor transcription screens. The predominant fractions with AA activity in both androgen receptor screens contained the germicides chlorophene and triclosan, and together these contaminants accounted for 51% of the total anti-YAS activity in the fish bile. Other AA compounds identified in bile included chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol, and bisphenol A. Pure standards of these compounds were active in the androgen receptor screens at potencies relative to flutamide of between 0.1 and 13.0. Thus, we have identified, for the first time, a diverse range of AA chemicals in WwTWs that are bioavailable to fish and which need to be assessed for their risk to the reproductive health of these organisms and other aquatic biota.
authors: Department of Biology and Environmental Science, University of Sussex, BN1 9QG Brighton, U.K.
authors: Pawel
authors: P
authors: Rostkowski
authors: Julia
authors: J
authors: Horwood
authors: Janice A
authors: JA
authors: Shears
authors: Anke
authors: A
authors: Lange
authors: Francis O
authors: FO
authors: Oladapo
authors: Harrie T
authors: HT
authors: Besselink
authors: Charles R
authors: CR
authors: Tyler
authors: Elizabeth M
authors: EM
authors: Hill
mesh_terms: D000726:Androgen Antagonists / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001681:Biological Assay; D052244:Endocrine Disruptors / Q000032:analysis / Q000378:metabolism; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D005399:Fishes / Q000378:metabolism*; D008297:Male; D014865:Waste Disposal, Fluid; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000378:metabolism*
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D014874:Water Pollutants, Chemical