Balancing the Budget: Accounting for Glucocorticoid Bioactivity and Fate during Water Treatment.

Numerous studies have identified the presence and bioactivity of glucocorticoid receptor (GR) active substances in water; however, the identification and activity-balance of GR compounds remained elusive. This study determined the occurrence and attenuation of GR bioactivity and closed the balance by determining those substances responsible. The observed in vitro GR activity ranged from 39 to 155 ng dexamethasone-equivalent/L (ng Dex-EQ/L) in the secondary effluents of four wastewater treatment plants. Monochromatic ultraviolet light of 80 mJ/cm(2) disinfection dose was efficient for GR activity photolysis, whereas chlorination could not appreciably attenuate the observed GR activity. Ozonation was effective only at relatively high dose (ozone/TOC 1:1). Microfiltration membranes were not efficient for GR activity attenuation; however, reverse osmosis removed GR activity to levels below the limits of detection. A high-sensitivity liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was then developed to screen 27 GR agonists. Twelve were identified and quantified in effluents at summed concentrations of 9.6-21.2 ng/L. The summed Dex-EQ of individual compounds based on their measured concentrations was in excellent agreement with the Dex-EQ obtained from bioassay, which demonstrated that the detected glucocorticoids can entirely explain the observed GR bioactivity. Four synthetic glucocorticoids (triamcinolone acetonide, fluocinolone acetonide, clobetasol propionate, and fluticasone propionate) predominantly accounted for GR activity. These data represent the first known publication where a complete activity balance has been determined for GR agonists in an aquatic environment.

[1]  T. Isobe,et al.  Occurrence of glucocorticoids discharged from a sewage treatment plant in Japan and the effects of clobetasol propionate exposure on the immune responses of common carp (Cyprinus carpio) to bacterial infection , 2016, Environmental toxicology and chemistry.

[2]  Z. Gong,et al.  Glucocorticoid activity detected by in vivo zebrafish assay and in vitro glucocorticoid receptor bioassay at environmental relevant concentrations. , 2016, Chemosphere.

[3]  Daniel Schlenk,et al.  Interlaboratory comparison of in vitro bioassays for screening of endocrine active chemicals in recycled water. , 2015, Water research.

[4]  H. Takigami,et al.  Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan. , 2015, The Science of the total environment.

[5]  S. Snyder,et al.  On-line sensor monitoring for chemical contaminant attenuation during UV/H2O2 advanced oxidation process. , 2015, Water research.

[6]  Erin M. Snyder,et al.  In vitro bioassays to evaluate complex chemical mixtures in recycled water. , 2015, Water research.

[7]  S. Tanabe,et al.  Determination of natural and synthetic glucocorticoids in effluent of sewage treatment plants using ultrahigh performance liquid chromatography-tandem mass spectrometry , 2015, Environmental Science and Pollution Research.

[8]  E. Kristiansson,et al.  Waterborne beclomethasone dipropionate affects the physiology of fish while its metabolite beclomethasone is not taken up. , 2015, The Science of the total environment.

[9]  Ksenia J. Groh,et al.  Endocrine disrupting compounds affecting corticosteroid signaling pathways in Czech and Swiss waters: potential impact on fish. , 2014, Environmental science & technology.

[10]  Ksenia J. Groh,et al.  LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters , 2014, Analytical and Bioanalytical Chemistry.

[11]  Tomohiko Isobe,et al.  Uptake and biological effects of synthetic glucocorticoids in common carp (Cyprinus carpio). , 2014, Marine pollution bulletin.

[12]  Rolf Altenburger,et al.  Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays. , 2014, Environmental science & technology.

[13]  Trang Trinh,et al.  Assessment of the application of bioanalytical tools as surrogate measure of chemical contaminants in recycled water. , 2014, Water research.

[14]  B. Wols,et al.  Degradation of 40 selected pharmaceuticals by UV/H2O2. , 2013, Water research.

[15]  Merijn Schriks,et al.  Occurrence of glucocorticogenic activity in various surface waters in The Netherlands. , 2013, Chemosphere.

[16]  T. Runnalls,et al.  Metabolic and reproductive effects of relatively low concentrations of beclomethasone dipropionate, a synthetic glucocorticoid, on fathead minnows. , 2013, Environmental science & technology.

[17]  C. Deal,et al.  Prevalence of oral glucocorticoid usage in the United States: A general population perspective , 2013, Arthritis care & research.

[18]  G. Hager,et al.  Prevalent Glucocorticoid and Androgen Activity in US Water Sources , 2012, Scientific Reports.

[19]  H. Salem,et al.  New developed spectrophotometric method for simultaneous determination of salmeterol xinafoate and fluticasone propionate in bulk powder and Seritide® diskus inhalation , 2012 .

[20]  Daniel L Villeneuve,et al.  Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development , 2012, Environmental toxicology and chemistry.

[21]  F. Borrull,et al.  Determination of glucocorticoids in sewage and river waters by ultra-high performance liquid chromatography-tandem mass spectrometry. , 2012, Journal of chromatography. A.

[22]  Zhanlan Fan,et al.  Behaviors of glucocorticoids, androgens and progestogens in a municipal sewage treatment plant: comparison to estrogens. , 2011, Environmental science & technology.

[23]  John P Sumpter,et al.  Synthetic glucocorticoids in the environment: first results on their potential impacts on fish. , 2011, Environmental science & technology.

[24]  John P. Sumpter,et al.  Pharmaceuticals in the Aquatic Environment: Steroids and Anti-Steroids as High Priorities for Research , 2010 .

[25]  Annemarie P van Wezel,et al.  High-resolution mass spectrometric identification and quantification of glucocorticoid compounds in various wastewaters in the Netherlands. , 2010, Environmental science & technology.

[26]  Jianying Hu,et al.  Determination and source apportionment of five classes of steroid hormones in urban rivers. , 2009, Environmental science & technology.

[27]  Yi-Wen Liu,et al.  Crosstalk between activated forms of the aryl hydrocarbon receptor and glucocorticoid receptor. , 2009, Toxicology.

[28]  Z. Dvořák,et al.  Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. , 2009, Chemico-biological interactions.

[29]  Bart Van der Burg,et al.  Detection of multiple hormonal activities in wastewater effluents and surface water, using a panel of steroid receptor CALUX bioassays. , 2008, Environmental science & technology.

[30]  J. Gauvrit,et al.  Development and optimisation of a single extraction procedure for the LC/MS/MS analysis of two pharmaceutical classes residues in sewage treatment plant. , 2008, Talanta.

[31]  Abraham Brouwer,et al.  Glucocorticoid-enhanced expression of dioxin target genes through regulation of the rat aryl hydrocarbon receptor. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  Jianying Hu,et al.  Occurrence of natural and synthetic glucocorticoids in sewage treatment plants and receiving river waters. , 2007, Environmental science & technology.

[33]  Anamika Gupta,et al.  Photochemistry of clobetasol propionate, a steroidal anti- inflammatory drug , 2006 .

[34]  P. Högger,et al.  Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate. , 2004, Journal of pharmaceutical sciences.

[35]  Andrea I. Schäfer,et al.  Particle interactions and removal of trace contaminants from water and wastewaters , 2002 .

[36]  J. Gallego,et al.  Spectrophotometric determination of hydrocortisone, nystatin and oxytetracycline in synthetic and pharmaceutical preparations based on various univariate and multivariate methods , 2002 .

[37]  M. Cayen,et al.  Bioavailability and Metabolism of Mometasone Furoate following Administration by Metered‐Dose and Dry‐Powder Inhalers in Healthy Human Volunteers , 2000, Journal of clinical pharmacology.

[38]  R. Schleimer,et al.  A Mass Balance Study to Evaluate the Biotransformation and Excretion of [14C]‐Triamcinolone Acetonide following Oral Administration , 2000, Journal of clinical pharmacology.

[39]  R. Newton Molecular mechanisms of glucocorticoid action: what is important? , 2000, Thorax.

[40]  J. Florini,et al.  Plasma half-life, tissue distribution, and excretion of triamcinolone-H3. , 1961, The Journal of pharmacology and experimental therapeutics.

[41]  Z. Dvořák,et al.  Effects of glucocorticoids on cytochrome P450 1A1 (CYP1A1) expression in isolated human placental trophoblast , 2013 .

[42]  S. Kugathas Synthetic glucocorticoids in the aquatic environment : their potential impacts on fish , 2011 .

[43]  A. Miyamoto,et al.  Determination of Selected Corticosteroids in Sewage-treatment-plant Samples by Liquid Chromatography-mass Spectrometry , 2010 .

[44]  S. Umland,et al.  Review of the molecular and cellular mechanisms of action of glucocorticoids for use in asthma. , 2002, Pulmonary pharmacology & therapeutics.