Details

Autor(en) / Beteiligte

• Skledar, Darja Gramec
• Schmidt, Jan
• Fic, Anja
• Klopčič, Ivana
• Trontelj, Jurij
• Dolenc, Marija Sollner
• Finel, Moshe
• Mašič, Lucija Peterlin

Titel

Influence of metabolism on endocrine activities of bisphenol S

Ist Teil von

• Chemosphere (Oxford), 2016-08, Vol.157, p.152-159

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2016

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative–conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10−5 M and 6.7 × 10−4 M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10−5 M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. •BPS is primarily metabolized by glucuronidation, to BPS glucuronide.•BPS glucuronide has no activity on either estrogen, androgen or thyroid hormone receptors.•Hydroxylation to BPSM1, through CYP3A4 and CYP2C9, is a minor metabolic pathway for BPS.•BPSM1 has agonistic estrogenic (EC50 6.7 × 10−4 M) and antagonistic thyroid hormone (IC50 4.3 × 10−5 M) activities.•Glucuronidation is the main detoxification pathway for BPS.