title: Health impacts of estrogens in the environment, considering complex mixture effects.
abstract: BACKGROUND
  Environmental estrogens in wastewater treatment work (WwTW) effluents are well established as the principal cause of reproductive disruption in wild fish populations, but their possible role in the wider health effects of effluents has not been established.
  
  
  OBJECTIVE
  We assessed the contribution of estrogens to adverse health effects induced in a model fish species by exposure to WwTW effluents and compared effects of an estrogen alone and as part of a complex mixture (i.e., spiked into effluent).
  
  
  METHODS
  Growth, genotoxic, immunotoxic, metabolic, and endocrine (feminized) responses were compared in fathead minnows (Pimephales promelas) exposed for 21 days to a potent estrogenic effluent, a weakly estrogenic effluent before and after spiking with a steroidal estrogen [17 alpha-ethinyl-estradiol (EE2)], and to EE2 alone.
  
  
  RESULTS
  In addition to endocrine disruption, effluent exposure induced genotoxic damage, modulated immune function, and altered metabolism; many of these effects were elicited in a sex-specific manner and were proportional to the estrogenic potencies of the effluents. A key finding was that some of the responses to EE2 were modified when it was present in a complex mixture (i.e., spiked into effluent), suggesting that mixture effects may not be easily modeled for effluent discharges or when the chemicals impact on a diverse array of biological axes.
  
  
  CONCLUSIONS
  These data reveal a clear link between estrogens present in effluents and diverse, adverse, and sex-related health impacts. Our findings also highlight the need for an improved understanding of interactive effects of chemical toxicants on biological systems for understanding health effects of environmental mixtures.
authors: School of Biosciences, University of Exeter, Exeter, United Kingdom. a.l.filby@exeter.ac.uk
authors: Amy L
authors: AL
authors: Filby
authors: Teresa
authors: T
authors: Neuparth
authors: Karen L
authors: KL
authors: Thorpe
authors: Richard
authors: R
authors: Owen
authors: Tamara S
authors: TS
authors: Galloway
authors: Charles R
authors: CR
authors: Tyler
mesh_terms: D000818:Animals; D045424:Complex Mixtures / Q000633:toxicity*; D003530:Cyprinidae / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004703:Endocrine System / Q000187:drug effects; D004777:Environment; D004967:Estrogens / Q000633:toxicity*; D006262:Health; D014867:Water / Q000737:chemistry; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D045424:Complex Mixtures; D004967:Estrogens; D014874:Water Pollutants, Chemical; D014867:Water