title: Glucocorticoid-like activity of propylparaben, butylparaben, diethylhexyl phthalate and tetramethrin mixtures studied in the MDA-kb2 cell line.
abstract: Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use - propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 μM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 μM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 μM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 μM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we include mixed exposures. This study emphasizes that risk assessment of compounds should take mixture effects into account.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Klopčič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia.
authors.forename: Katra
authors.initials: K
authors.lastname: Kolšek
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, Ljubljana 1000, Slovenia. Electronic address: marija.sollner@ffa.uni-lj.si.
authors.forename: Marija Sollner
authors.initials: MS
authors.lastname: Dolenc
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004285:Dogs; D005938:Glucocorticoids / Q000378:metabolism*; D007306:Insecticides / Q000633:toxicity*; D061985:Madin Darby Canine Kidney Cells; D010226:Parabens / Q000633:toxicity*; D010968:Plasticizers / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D011965:Receptors, Glucocorticoid / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D007306:Insecticides; D010226:Parabens; D010968:Plasticizers; D011722:Pyrethrins; D011965:Receptors, Glucocorticoid; C038091:butylparaben; D004051:Diethylhexyl Phthalate; C009424:tetramethrin; C006068:propylparaben
keywords: Effects of mixtures; Endocrine disruption; Glucocorticoid receptor; MDA-kb2 cells; Parabens; Phthalates; Pyrethroid insecticides