In vitro estrogenicity of polybrominated diphenyl ethers, hydroxylated PBDEs, and polybrominated bisphenol A compounds

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as addi tive dame retardants in plastics and textile materials. PBDEs are persisten t compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic pot encies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line a ssays based on estrogen receptor (ER)-dependent luciferase reporter gene ex pression. In human T47D breast cancer cells stably transfected with an estr ogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC50) varying from 2.5 to 7.3 muM. The luciferase induction of the most po tent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of est radiol (E-2), though at concentrations 50,000 times higher. As expected, br ominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC50 values of 0.5 muM for 3-monobromobisphe nol A). In an ER alpha -specific, stably transfected human embryonic kidney cell line (293-ER alpha -Luc), the HO-PBDE 4-(2,4,6-tribromophenoxy)phenol was a highly potent estrogen with an EC50 < 0.1 <mu>M and a maximum 35- to 40-fold induction, which was similar to E-2. In an analogous ER beta -spec ific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-trib romophenoxy)phenol was much lower (maximum 50% induction compared to E-2), but EC50 values were comparable. These results indicate that several pure P BDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-me diated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.