Effect-directed analysis of endocrine-disrupting compounds in multi-contaminated sediment: identification of novel ligands of estrogen and pregnane X receptors
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  • 作者:Nicolas Creusot (1) (2) (3)
    Hélène Budzinski (2) (3)
    Patrick Balaguer (4)
    Sa?d Kinani (1)
    Jean-Marc Porcher (1)
    Selim A?t-A?ssa (1)
  • 关键词:EDCs ; Emerging pollutants ; Multi ; contaminated sediment ; Multi ; step fractionation
  • 刊名:Analytical and Bioanalytical Chemistry
  • 出版年:2013
  • 出版时间:March 2013
  • 年:2013
  • 卷:405
  • 期:8
  • 页码:2553-2566
  • 全文大小:536KB
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  • 作者单位:Nicolas Creusot (1) (2) (3)
    Hélène Budzinski (2) (3)
    Patrick Balaguer (4)
    Sa?d Kinani (1)
    Jean-Marc Porcher (1)
    Selim A?t-A?ssa (1)

    1. Unité écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, BP2, 60550, Verneuil-en-Halatte, France
    2. Université de Bordeaux, EPOC, UMR 5805, 33405, Talence, France
    3. CNRS, EPOC, UMR 5805, 33405, Talence, France
    4. INSERM U896, IRCM-UM1-CRLC Val d’Aurelle, 34298, Montpellier, France
  • ISSN:1618-2650
文摘
Effect-directed analysis (EDA)-based strategies have been increasingly used in order to identify the causative link between adverse (eco-)toxic effects and chemical contaminants. In this study, we report the development and use of an EDA approach to identify endocrine-disrupting chemicals (EDCs) in a multi-contaminated river sediment. The battery of in vitro reporter cell-based bioassays, measuring estrogenic, (anti)androgenic, dioxin-like, and pregnane X receptor (PXR)-like activities, revealed multi-contamination profiles. To isolate active compounds of a wide polarity range, we established a multi-step fractionation procedure combining: (1) a primary fractionation step using normal phase-based solid-phase extraction (SPE), validated with a mixture of 12 non-polar to polar standard EDCs; (2) a secondary fractionation using reversed-phase-based high-performance liquid chromatography (RP-HPLC) calibrated with 33 standard EDCs; and (3) a purification step using a recombinant estrogen receptor (ER) affinity column. In vitro SPE and HPLC profiles revealed that ER and PXR activities were mainly due to polar to mid-polar compounds, while dioxin-like and anti-androgenic activities were in the less polar fractions. The overall procedure allowed final isolation and identification of new environmental PXR (e.g., di-iso-octylphthalate) and ER (e.g., 2,4-di-tert-butylphenol and 2,6-di-tert-butyl-α-methoxy-p-cresol) ligands by using gas chromatography coupled with mass spectrometry with full-scan mode acquisition in mid-polar fractions. In vitro biological activity of these chemicals was further confirmed using commercial standards, with di-iso-octylphthalate identified for the first time as a potent hPXR environmental agonist.

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