Sublethal effects of DBE-DBCH diastereomers on physiology, behavior, and gene expression of Daphnia magna.

1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH) is a brominated flame retardant used in commercial and industrial applications. The use of DBE-DBCH containing products has resulted in an increased release into the environment. However, limited information is available on the long-term effects of DBE-DBCH and its effects in aquatic invertebrates.

Androgen receptor modulation following combination exposure to brominated flame-retardants.

Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists.

Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages.

The glucocorticoid (GC) receptor (GR) suppresses inflammation by activating anti-inflammatory and repressing pro-inflammatory genes. GR-interacting protein-1 (GRIP1) is a GR corepressor in macrophages, however, whether GRIP1 mediates GR-activated transcription, and what dictates its coactivator versus corepressor properties is unknown. Here we report that GRIP1 loss in macrophages attenuates glucocorticoid induction of several anti-inflammatory targets, and that GC treatment of quiescent macrophages globally directs GRIP1 toward GR binding sites dominated by palindromic GC response elements (GRE), suggesting a non-redundant GRIP1 function as a GR coactivator.

TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer.

Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the ART877A mutation, which is frequently detected mutation in PCa tumors and the ARW741C that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide.

The brominated flame retardants TBP-AE and TBP-DBPE antagonize the chicken androgen receptor and act as potential endocrine disrupters in chicken LMH cells.

Increased exposure of birds to endocrine disrupting compounds has resulted in developmental and reproductive dysfunctions. We have recently identified the flame retardants, allyl-2,4,6-tribromophenyl ether (TBP-AE), 2-3-dibromopropyl-2,4,6-tribromophenyl ether (TBP-DBPE) and the TBP-DBPE metabolite 2-bromoallyl-2,4,6-tribromophenyl ether (TBP-BAE) as antagonists to both the human androgen receptor (AR) and the zebrafish AR. In the present study, we aimed at determining whether these compounds also interact with the chicken AR.

In silico and biological analysis of anti-androgen activity of the brominated flame retardants ATE, BATE and DPTE in zebrafish.

The brominated flame retardants (BFRs) 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH or DBE-DCBH) and allyl 2,4,6-tribromophenyl ether (ATE or TBP-AE) are alternative BFRs that have been introduced to replace banned BFRs. TBECH is a potential endocrine disrupter in human, chicken and zebrafish and in a recent study we showed that ATE, along with the structurally similar BFR 2,3-dibromopropyl 2,4,6-tribromophenyl ether (DPTE or TBP-DBPE) and its metabolite 2-bromoallyl 2,4,6-tribromophenyl ether (BATE or TBP-BAE) are potential endocrine and neuronal disrupters in human. In this study we analyzed ATE, BATE and DPTE for zebrafish androgen receptor (zAR) modulating properties.

Identification of a group of brominated flame retardants as novel androgen receptor antagonists and potential neuronal and endocrine disrupters.

Brominated flame-retardants (BFRs) are used in industrial products to reduce the risk of fire. However, their continuous release into the environment is a concern as they are often persistent, bioaccumulating and toxic. Information on the impact these compounds have on human health and wildlife is limited and only a few of them have been identified to disrupt hormone receptor functions.

Mixtures of chemical pollutants at European legislation safety concentrations: how safe are they?

The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels.

The brominated flame retardant TBECH activates the zebrafish (Danio rerio) androgen receptor, alters gene transcription and causes developmental disturbances.

Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been shown to be a potent agonist to the human androgen receptor (AR). However, while it is present in the environment, it is not known if it interacts with AR from aquatic species. The present study was therefore aimed at improving our understanding of how TBECH affects aquatic animals using zebrafish as a model organism.