title: Mixtures of estrogenic chemicals enhance vitellogenic response in sea bass.
abstract: BACKGROUND
  The potential impact of natural and synthetic estrogens on aquatic ecosystems has attracted considerable attention because it is currently accepted that their joint effects are more severe when they are present in mixtures. Although it is well-known that they occur as mixtures in the marine environment, there is little information about the combined effects of estrogenic chemicals on marine biota.
  
  
  OBJECTIVE
  In 14-day tests with juvenile sea bass, we analyzed singly and in combination the estrogenic activity of estradiol (E(2)), ethynylestradiol (EE(2)), and bisphenol A (BPA) using vitellogenin induction as an end point.
  
  
  METHODS
  Fish were exposed to each compound, and on the basis of these concentration-response data, we predicted mixture effects by applying the model of concentration addition. The mixtures were tested using a fixed-ratio design, and the resulting mixture effects were compared to the predictions.
  
  
  RESULTS
  EE(2) was the most potent steroid, with an EC(50) (median effective concentration) of 0.029 microg/L, 3.6 times more potent than E(2) (EC(50) = 0.104 microg/L); BPA was the least potent chemical, with an EC(50) of 77.94 microg/L. The comparative assessment yielded a good agreement between observed and predicted mixture effects.
  
  
  CONCLUSIONS
  This study demonstrates the potential hazard of these compounds to seawater life by their ability to act together in an additive manner. It provides evidence that concentration addition can be used as a predictive tool for assessing the combined effects of estrogenic chemicals in marine ecosystems.
authors.affiliation: CIIMAR-Centre of Marine and Environmental Research, Environmental Toxicology Laboratory, Porto, Portugal. anacorreia@ciimar.up.pt
authors.forename: Ana D
authors.initials: AD
authors.lastname: Correia
authors.forename: Sandro
authors.initials: S
authors.lastname: Freitas
authors.forename: Martin
authors.initials: M
authors.lastname: Scholze
authors.forename: José F
authors.initials: JF
authors.lastname: Goncalves
authors.forename: Petra
authors.initials: P
authors.lastname: Booij
authors.forename: Marja H
authors.initials: MH
authors.lastname: Lamoree
authors.forename: Evaristo
authors.initials: E
authors.lastname: Mañanós
authors.forename: Maria A
authors.initials: MA
authors.lastname: Reis-Henriques
mesh_terms: D000818:Animals; D001492:Bass; D001559:Benzhydryl Compounds; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004784:Environmental Monitoring / Q000379:methods; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity; D004967:Estrogens / Q000008:administration & dosage / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity; D018570:Risk Assessment; D014819:Vitellogenins / Q000096:biosynthesis / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004958:Estradiol; D004967:Estrogens; D004997:Ethinyl Estradiol; D010636:Phenols; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; C006780:bisphenol A; D000098826:Bisphenol A Compounds