Abstract
The aim of this study was to compare in silico data with results obtained in two alternative in vitro methods; and to investigate the potential endocrine activity of bisphenol A analogues. This article contributes to recent findings and brings up-to-date information on development of EU legislation and in vitro testing methods of endocrine disruption.
In silico approach based on the OECD QSAR Toolbox was used for prediction of potential ligands of human estrogen receptor α. Estrogen Receptor Transactivation in vitro Assay to Detect Estrogen Receptor Agonists and Antagonists (OECD TG 455/457) using the VM7Luc4E2 (formerly designated BG1Luc4E2) cell line was performed for measurement of transactivation activity of the tested substances.
Commercially available yeast-based microplate assay (XenoScreen YES/YAS, Xenometrix, Switzerland) for detection of compounds with estrogenic and androgenic agonistic/antagonistic activity was used as a comparative test to estrogen receptor transactivation assay (OECD TG 455/457) and for screening of the agonistic/antagonistic potential of human estrogen receptor and agonistic/antagonistic activity of tested compounds on human androgen receptor. The study showed good correlation between the two in vitro assays and significant correlation with in silico data.
All tested substances were identified as agonists for human estrogen receptor α by methods in silico and in vitro, four substances showed a potentially higher estrogenic activity comparing to bisphenol A, two substances were identified as very weak antagonists of human androgen receptor and one compound showed a potential of agonistic activity to human androgen receptor. The study contributes to recent findings and brings new in silico and in vitro data of bisphenol A analogues, revealing that these analogous substances should be further tested as they may show similar or higher activity in vivo comparing to bisphenol A, which has been recently legislatively regulated.