High-resolution mass spectrometric identification and quantification of glucocorticoid compounds in various wastewaters in the Netherlands.

In the past two decades much research effort has focused on the occurrence, effects, and risks of estrogenic compounds. However, increasing emissions of new emerging compounds may also affect the action of hormonal pathways other than the estrogenic hormonal axis. Recently, a suite of novel CALUX bioassays has become available that enables looking further than estrogenic effects only. By employing these bioassays, we recently showed high glucocorticogenic activity in wastewaters collected at various sites in The Netherlands. However, since bioassays provide an integrated biological response, the identity of the responsible biological compounds remained unknown. Therefore, our current objective was to elucidate the chemical composition of the wastewater extracts used in our previous study by means of LC-high-resolution Orbitrap MS/MS and to determine if the compounds quantified could account for the observed glucocorticoid responsive (GR) CALUX bioassay response. The mass spectrometric analysis revealed the presence of various glucocorticoids in the range of 13-1900 ng/L. In extracts of hospital wastewater-collected prior to sewage treatment-several glucocorticoids were identified (cortisol 275-301 ng/L, cortisone 381-472 ng/L, prednisone 117-545 ng/L, prednisolone 315-1918 ng/L, and triamcinolone acetonide 14-41 ng/L) which are used to treat a great number of human pathologies. A potency balance calculation based on the instrumental analyses and relative potencies (REPs) of the individual glucocorticoids supports the conclusion that triamcinolone acetonide (REP = 1.3), dexamethasone (REP = 1), and prednisolone (REP = 0.2) are the main contributors to the glucocorticogenic activity in the investigated wastewater extracts. The action of these compounds is concentration additive and the overall glucocorticogenic activity can be explained to a fairly large extent by their contribution.

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

[2]  Saskia S Sterk,et al.  Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays. , 2009, Analytica chimica acta.

[3]  Hogenboom,et al.  Accurate mass screening and identification of emerging contaminants in environmental samples by liquid chromatography-hybrid linear ion trap Orbitrap mass spectrometry. , 2009, Journal of chromatography. A.

[4]  A. Odermatt,et al.  Glucocorticoid and mineralocorticoid action: why should we consider influences by environmental chemicals? , 2008, Biochemical pharmacology.

[5]  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.

[6]  Jeanne Garric,et al.  Human pharmaceuticals in surface waters. Implementation of a prioritization methodology and application to the French situation. , 2008, Toxicology letters.

[7]  Gerald T Ankley,et al.  Repeating history: pharmaceuticals in the environment. , 2007, Environmental science & technology.

[8]  K. Cooper,et al.  Matrix metalloproteinase-13 is required for zebra fish (Danio rerio) development and is a target for glucocorticoids. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[9]  Karen A Kidd,et al.  Collapse of a fish population after exposure to a synthetic estrogen , 2007, Proceedings of the National Academy of Sciences.

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

[11]  Donald P. McDonnell,et al.  International Union of Pharmacology. LXV. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Glucocorticoid, Mineralocorticoid, Progesterone, and Androgen Receptors , 2006, Pharmacological Reviews.

[12]  A. Odermatt,et al.  Disruption of glucocorticoid action by environmental chemicals: Potential mechanisms and relevance , 2006, The Journal of Steroid Biochemistry and Molecular Biology.

[13]  R. Schwarzenbach,et al.  The Challenge of Micropollutants in Aquatic Systems , 2006, Science.

[14]  M. Lamoree,et al.  Biological validation of a sample preparation method for ER-CALUX bioanalysis of estrogenic activity in sediment using mixtures of xeno-estrogens. , 2006, Environmental science & technology.

[15]  Andrew C Johnson,et al.  Lessons from endocrine disruption and their application to other issues concerning trace organics in the aquatic environment. , 2006, Environmental science & technology.

[16]  A. D. Vethaak,et al.  An integrated assessment of estrogenic contamination and biological effects in the aquatic environment of The Netherlands. , 2005, Chemosphere.

[17]  C. A. Harris,et al.  Accurate Prediction of the Response of Freshwater Fish to a Mixture of Estrogenic Chemicals , 2005, Environmental health perspectives.

[18]  R. Kookana,et al.  Occurrence and fate of hormone steroids in the environment. , 2002, Environment international.

[19]  Erin M. Snyder,et al.  Identification and quantification of estrogen receptor agonists in wastewater effluents. , 2001, Environmental science & technology.

[20]  A. Kortenkamp,et al.  Prediction and assessment of the effects of mixtures of four xenoestrogens. , 2000, Environmental health perspectives.

[21]  A D Vethaak,et al.  Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  A. D. Vethaak,et al.  Analysis and occurrence of estrogenic hormones and their glucuronides in surface water and waste water in The Netherlands. , 1999, The Science of the total environment.

[23]  J. Sumpter Xenoendorine disrupters--environmental impacts. , 1998, Toxicology letters.

[24]  R J Kavlock,et al.  Endocrine disruptors and reproductive development: a weight-of-evidence overview. , 1997, The Journal of endocrinology.

[25]  J. Baxter,et al.  Glucocorticoid receptors: relations between steroid binding and biological effects. , 1972, Journal of molecular biology.

[26]  J. Boer,et al.  Efficacy of Wastewater Treatment Plants in the Netherlands for Removal of Estrogens and Xenoestrogens , 2006 .

[27]  Willem G Schoonen,et al.  Comparison of in vitro and in vivo screening models for androgenic and estrogenic activities. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  L. Shore,et al.  Naturally produced steroid hormones and their release into the environment , 2003 .