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

Abstract

Polybrominated diphenyl ethers (PBDEs) are used in large quantities as additive flame retardants in plastics and textile materials. PBDEs are persistent compounds and have been detected in wildlife and in human adipose tissue and plasma samples. In this study, we investigated the (anti)estrogenic potencies of several PBDE congeners, three hydroxylated PBDEs (HO-PBDEs), and differently brominated bisphenol A compounds in three different cell line assays based on estrogen receptor (ER)-dependent luciferase reporter gene expression. In human T47D breast cancer cells stably transfected with an estrogen-responsive luciferase reporter gene construct (pEREtata-Luc), 11 PBDEs showed estrogenic potencies, with concentrations leading to 50% induction (EC(50)) varying from 2.5 to 7.3 microM. The luciferase induction of the most potent HO-PBDE [2-bromo-4-(2,4,6-tribromophenoxy)phenol] exceeded that of estradiol (E(2)), though at concentrations 50,000 times higher. As expected, brominated bisphenol A compounds with the lowest degree of bromination showed highest estrogenic potencies (EC(50) values of 0.5 microM for 3-monobromobisphenol 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 EC(50) < 0.1 microM and a maximum 35- to 40-fold induction, which was similar to E(2). In an analogous ER beta-specific 293-ER betas-Luc cell line, the agonistic potency of the 4-(2,4,6-tribromophenoxy)phenol was much lower (maximum 50% induction compared to E(2)), but EC(50) values were comparable. These results indicate that several pure PBDE congeners, but especially HO-PBDEs and brominated bisphenol A-analogs, are agonists of both ER alpha and ER beta receptors, thus stimulating ER-mediated luciferase induction in vitro. These data also suggest that in vivo metabolism of PBDEs may produce more potent pseudoestrogens.

Review of risk from potential emerging contaminants in UK groundwater

“…Polybrominated diphenyl ether (PBDE) flame retardants have been found to bioaccumulate and have potential endocrine disrupting properties (Hooper and McDonald, 2000;Meerts et al, 2001;Rahman et al, 2001). Tris-(2-chloroethyl) phosphate (TRCP), which is used in industrial and consumer products, appears to be responsible for brain damage (Matthews et al, 1993).…”

Endocrine disruptive chemicals: mechanisms of action and involvement in metabolic disorders

“…Another example are brominated flame retardants (BFRs) that have been reported to disrupt thyroid, androgen, and estrogenic signaling, both in vivo and in vitro (reviewed in Legler & Brouwer (2003)), some of them by directly binding to the ERs (Meerts et al 2001).…”

Graphene-assisted matrix solid-phase dispersion for extraction of polybrominated diphenyl ethers and their methoxylated and hydroxylated analogs from environmental samples

“…These compounds have also been identified in human milk and blood [19,20]. Due to the associated health risks such as thyroid disruption and cytotoxicity of these PBDE analogs [21,22], it is important to understand the sources and biotransformation processes of these compounds in the environment. However, this is not a straightforward task partly because there is still a lack of reliable and efficient methods for simultaneous analysis of PBDEs and their MeO-and OH-analogs in environmental and biological matrices.…”