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

Abstract

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.

An integrative approach combining passive sampling, bioassays, and effect‐directed analysis to assess the impact of wastewater effluent

“…Overall, our findings identified target compounds as the main contributors to the estrogen and glucocorticoid agonistic activity in the effluent extracts. These observations agree with earlier reports in which the synthetic glucocorticoids clobetasol propionate and fluticasone propionate significantly contributed to the glucocorticoid activity in WWTP effluents (Macikova et al ; Suzuki et al ; Jia et al ). Steroidal estrogens are well‐known major contributors of estrogenic activity in urban WWTP effluents (reviewed by Jarosova et al ), as again confirmed at the studied site.…”

“…Effect‐based tools have been proposed in water quality assessment because they are considered integrative techniques for the detection of bioactive compounds (Eggen et al ; Altenburger et al ). A variety of in vitro receptor‐based assays currently exists for the assessment of EDCs and many studies have reported their effectiveness for water quality assessment (i.e., for monitoring the endocrine‐disrupting potential of WWTP effluents; Schriks et al ; Creusot et al ; Macikova et al ; Jia et al ). Mechanism‐based in vivo assays using transgenic fish embryos that allow sensitive detection of EDCs within a living organism have also been recently developed (Brion et al ; Gorelick et al ).…”

Effect‐Directed Analysis of Progestogens and Glucocorticoids at Trace Concentrations in River Water

“…Both progestogens and glucocorticoids act through binding to a wide range of receptors including progesterone (PR), estrogen (ER), androgen (AR), glucocorticoid (GR), and mineralocorticoid (MR) receptors (Kumar et al 2015). The presence of progestogens and glucocorticoids in the environment can be detected by chemical trace analysis (Schriks et al 2010;Ammann et al 2014;Jia et al 2016;Shen et al 2018) or biologically via PR and GR binding using a variety of reporter gene assays (Creusot et al 2014;Jia et al 2015;Wangmo et al 2018). Because GR and PR ligands are rarely monitored (in contrast to ERs), only limited information is available on the occurrence and concentrations of these compounds in the environment (Fent 2015).…”

Application of Generalized Concentration Addition to Predict Mixture Effects of Glucocorticoid Receptor Ligands

“…In 2016 the number of prescriptions for prednisolone and dexamethasone in the United States exceeded 4 and 1 million, respectively (Kane, 2018). Furthermore, pharmaceutical glucocorticoids have also been detected in wastewater samples worldwide (Schriks et al 2010;Kolkman et al 2013;Macikova et al 2014;Suzuki et al 2015;Jia et al 2016). Humans also endogenously secrete a glucocorticoid called cortisol in response to stress.…”