title: Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan.
abstract: Glucocorticoids (GCs) are widely used as anti-inflammatory drugs. Our previous study demonstrated that several GCs such as cortisol and dexamethasone (Dex) were frequently detected in effluents collected from Japanese sewage treatment plants (STPs) in 2012. In this study, we used the GC-Responsive Chemical-Activated LUciferase gene eXpression (GR-CALUX) assay to elucidate GC receptor (GR) agonistic activities of ten pure synthetic GCs and selected STP effluents in Japan for assessment of the risks associated with the presence of GR agonists. The tested GCs demonstrated dose-dependent agonistic effects in the GR-CALUX assay and their EC50 values were calculated for estimation of relative potencies (REPs) compared to Dex. The GR agonistic potency was in the rank of: clobetasol propionate > clobetasone butyrate > betamethasone 17-valerate > difluprednate > betamethasone 17,21-dipropionate > Dex > betamethasone > 6α-methylprednisolone > prednisolone > cortisol. The GR agonistic activity in STP effluents as measured in Dex-equivalent (Dex-EQ) activities ranged from < 3.0-78 ng L(-1) (median: 29 ng L(-1), n = 50). To evaluate the contribution of the target GCs, theoretical Dex-EQs were calculated by multiplying the concentrations of each GC by its respective REP. Our calculation of Dex-EQ contribution for individual GR agonists indicated that the well-known GCs cortisol and Dex should not be given priority for subsequent in vivo testing, monitoring and removal experiments, but rather the highly potent synthetic GCs clobetasol propionate and betamethasone 17-valerate (REP = 28 and 3.1) as well as other unidentified compounds are important GR agonists in STP effluents in Japan.
authors.affiliation: Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. Electronic address: g-suzuki@nies.go.jp.
authors.forename: Go
authors.initials: G
authors.lastname: Suzuki
authors.affiliation: Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sato
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Isobe
authors.affiliation: Center for Material Cycles and Waste Management Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takigami
authors.affiliation: BioDetection Systems, 1098 XH Amsterdam, The Netherlands.
authors.forename: Abraham
authors.initials: A
authors.lastname: Brouwer
authors.affiliation: Center for Marine Environmental Studies, Ehime University, Matsuyama 790-8577, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D004784:Environmental Monitoring; D007564:Japan; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D012722:Sewage / Q000737:chemistry*; D014865:Waste Disposal, Fluid; D062065:Wastewater / Q000737:chemistry; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D011965:Receptors, Glucocorticoid; D012722:Sewage; D062065:Wastewater; D014874:Water Pollutants, Chemical
keywords: Effluent; GR agonism; Glucocorticoid; Glucocorticoid receptor (GR); Sewage treatment plant