Dibutyl phthalate contributes to the thyroid receptor antagonistic activity in drinking water processes.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, P.O. Box 2871 Beijing 100085, China.
Environmental Science & Technology (Impact Factor: 5.48). 09/2010; 44(17):6863-8. DOI: 10.1021/es101254c
Source: PubMed

ABSTRACT It has long been recognized that thyroid hormone (TH) is essential for normal brain development in both humans and animals, and there is growing evidence that environmental chemicals can disrupt the thyroid system. In the present work, we used a two-hybrid yeast assay to screen for agonistic or antagonistic thyroid receptor (TR) mediated effects in drinking waters. We found no TR agonistic, but TR antagonistic activities in all samples from the drinking water processes. The TR antagonistic activities in organic extracts of water samples were then calibrated regarding to a known TR-inhibitor, NH3, and were expressed as the NH3 equivalents (TEQbio). The observed TEQbio in waters ranged from 180.8+/-24.8 to 280.2+/-48.2 microg/L NH3. To identify the specific compounds responsible for TR disrupting activities, the concentrations of potentially thyroid-disrupting chemicals including organochlorine pesticides (OCPs), phenols, and phthalates in organic extracts were quantitatively determined and their toxic equivalents with respect to NH3 (TEQcal) were estimated from their concentration-dependent relationships, respectively, using the same set of bioassays. Based on the TEQ approach, it was revealed that dibutyl phthalate (DBP) accounted for 53.7+/-8.2% to 105.5+/-16.7% of TEQbio. There was no effective removal of these potential thyroid disrupting substances throughout drinking water treatment processes.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence of estrogenic activities of source waters and drinking waters in China based on estrogen receptors (ERs) testing. However, relating such activities to retinoid X receptors (RXRs) in both drinking and source waters are lacking. To rectify this situation, we assessed 23 source water samples from six major river systems in China. We also collected samples at various stages of water processing from three drinking water treatment plants (DWTPs) using a two-hybrid RXR yeast assay with and without metabolism. No RXR agonistic activity was observed, but significant antagonistic activity was detected in all sample extracts. The RXR antagonistic activities of source water sample extracts ranged from 15.2% to 57.8% without metabolism and 11.5% to 68.3% with metabolism, respectively. In the drinking water treatment processes, RXR antagonistic activities without metabolism and with metabolism of up to 31.4% and 37.5% were removed, respectively. Nevertheless, the remaining RXR antagonists in treated drinking water from these source waters could still be harmful to human health. To the best of our knowledge, the occurrence of in vitro RXR disruption activities in source and drinking water has not been previously reported in China. Therefore, an attempt was made to conduct detailed studies investigating RXR disrupting activities and their possible risks in source and drinking water.
    Chinese Science Bulletin 57(6). · 1.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dibutyl phthalates (DBP) are widely used as plasticizers to soften and increase the flexibility of polyvinyl chloride plastics, although they can leach into the surrounding environment. Many studies have reported that changes in thyroid function are linked to a variety of chemicals in the environment. Although the mechanism is not known, DBP decreases T3 and T4, and downregulates the sodium/iodide symporter promoter in the thyroid. We undertook a genome-wide analysis of transcriptional responses in human thyroid follicular carcinoma FTC-238 cells to non-toxic doses of DBP (100 μM). Whole human genome microarrays detected a total of 4,480 genes that exhibited altered expression after exposure to non-toxic doses of DBP compared with the vehicle control. We found that 2,218 and 2,262 genes showed different expression levels following treatment with non-toxic doses of DBP (1.5-fold (p <0.01)). Significant changes in the expression levels of multiple genes potentially critical in the regulation of DBP-induced thyroid disease were found. A DBP exposure gene network was identified and established by computational analysis. The possible roles of responsive genes and their related pathways during DBP treatment are discussed. This study details how cells respond to DBP exposure via transcriptional regulation. Information from our network could provide clues for further mechanistic studies that explain how DBP exposure leads to thyroid toxicity and disease.
    Toxicology and Environmental Health Sciences. 4(2).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Some synthetic chemicals, which have been shown to disrupt thyroid hormone (TH) function, have been detected in surface waters and people have the potential to be exposed through water-drinking. Here, the presence of thyroid-active chemicals and their toxic potential in drinking water sources in Yangtze River Delta were investigated by use of instrumental analysis combined with cell-based reporter gene assay. A novel approach was developed to use Monte Carlo simulation, for evaluation of the potential risks of measured concentrations of TH agonists and antagonists and to determine the major contributors to observed thyroid receptor (TR) antagonist potency. None of the extracts exhibited TR agonist potency, while 12 of 14 water samples exhibited TR antagonistic potency. The most probable observed antagonist equivalents ranged from 1.4 to 5.6 µg di-n-butyl phthalate (DNBP)/L, which posed potential risk in water sources. Based on Monte Carlo simulation related mass balance analysis, DNBP accounted for 64.4% for the entire observed antagonist toxic unit in water sources, while diisobutyl phthalate (DIBP), di-n-octyl phthalate (DNOP) and di-2-ethylhexyl phthalate (DEHP) also contributed. The most probable observed equivalent and most probable relative potency (REP) derived from Monte Carlo simulation is useful for potency comparison and responsible chemicals screening.
    PLoS ONE 01/2013; 8(10):e73883. · 3.53 Impact Factor


Available from
May 16, 2014