THE ESTROGENICITY OF BISPHENOL A-RELATED DIPHENYLALKANES WITH VARIOUSSUBSTITUENTS AT THE CENTRAL CARBON AND THE HYDROXY-GROUPS

The chemical structure of hydroxylated diphenylalkanes or bisphenols c onsists of two phenolic rings joined together through a bridging carbo n. This class of endocrine disrupters that mimic estrogens is widely u sed in industry, particularly in plastics. Bisphenol F, bisphenol A, f luorine-containing bisphenol A (bisphenol AF), and other diphenylalkan es were found to be estrogenic in a bioassay with MCF7 human breast ca ncer cells in culture (E-SCREEN assay). Bisphenols promoted cell proli feration and increased the synthesis and secretion of cell type-specif ic proteins. When ranked by proliferative potency, the longer the alky l substituent at the bridging carbon, the lower the concentration need ed for maximal cell yield; the most active compound contained two prop yl chains at the bridging carbon. Bisphenols with two hydroxyl groups in the para position and an angular configuration are suitable for app ropriate hydrogen bonding to the acceptor site of the estrogen recepto r. Our data suggest that estrogenicity is influenced not only by the l ength of the substituents at the bridging carbon but also by their nat ure. Because diphenylalkane derivatives are widespread and their produ ction and use are increasing, potential exposure of humans to estrogen ic bisphenols is becoming a significant issue. The hazardous effects o f inadvertent exposure to bisphenol-releasing chemicals in professiona l workers and the general populations therefore deserve investigation.