Characterization of Individual Isopropylated and tert-Butylated Triarylphosphate (ITP and TBPP) Isomers in Several Commercial Flame Retardant Mixtures and House Dust Standard Reference Material SRM 2585.

Since the phase-out of pentaBDE in the early 2000s, replacement flame-retardant mixtures including Firemaster 550 (FM 550), Firemaster 600 (FM 600), and organophosphate aryl ester technical mixtures have been increasingly used to treat polyurethane foam in residential upholstered furniture. These mixtures contain isomers of isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs), which have similar or greater neuro- and developmental toxicity compared to BDE 47 in high-throughput assays. Additionally, human exposure to ITPs and TBPPs has been demonstrated to be widespread in several recent studies; however, the relative composition of these mixtures has remained largely uncharacterized.

Impacts of Unregulated Novel Brominated Flame Retardants on Human Liver Thyroid Deiodination and Sulfotransferation.

The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and β-tetrabromoethylcyclohexane (β-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations. Only DBDPE showed inhibition of both outer and inner ring deiodination (O and IRD) of T3 and 3,3'-T2 formation from T4, respectively, with an estimated IC of 160 nM; no statistically significant inhibition of SULT activity was observed.

Characterization and Biological Potency of Mono- to Tetra-Halogenated Carbazoles.

This paper deals with the characterization and aryl hydrocarbon receptor (AhR) agonist activities of a series of chlorinated, brominated, and mixed bromo/chlorocarbazoles, some of which have been identified in various environmental samples. Attention is directed here to the possibility that halogenated carbazoles may currently be emitted into the environment as a result of the production of carbazole-containing polymers present in a wide variety of electronic devices. We have found that any carbazole that is not substituted in the 1,3,6,8 positions may be lost during cleanup of environmental extracts if a multilayer column is utilized, as is common practice for polychlorinated dibenzo-p-dioxin (dioxin) and related compounds.

Aryl phosphate esters within a major PentaBDE replacement product induce cardiotoxicity in developing zebrafish embryos: potential role of the aryl hydrocarbon receptor.

Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model.

Cytochrome P4501A induction in avian hepatocyte cultures exposed to polychlorinated biphenyls: comparisons with AHR1-mediated reporter gene activity and in ovo toxicity.

Avian-specific toxic equivalency factors (TEFs) were developed by the World Health Organization to simplify environmental risk assessments of dioxin-like compounds (DLCs), but TEFs do not account for differences in the toxic and biochemical potencies of DLCs among species of birds. Such variability may be due to differences in species sensitivity to individual DLCs. The sensitivity of avian species to DLCs was recently associated with the identity of amino acids 324 and 380 in the aryl hydrocarbon receptor 1 (AHR1) ligand binding domain.

A luciferase reporter gene assay and aryl hydrocarbon receptor 1 genotype predict the LD50 of polychlorinated biphenyls in avian species.

Birds differ in sensitivity to the embryotoxic effects of polychlorinated biphenyls (PCBs), which complicates environmental risk assessments for these chemicals. Recent research has shown that the identities of amino acid residues 324 and 380 in the avian aryl hydrocarbon receptor 1 (AHR1) ligand binding domain (LBD) are primarily responsible for differences in avian species sensitivity to selected dibenzo-p-dioxins and furans. A luciferase reporter gene (LRG) assay was developed in our laboratory to measure AHR1-mediated induction of a cytochrome P450 1A5 reporter gene in COS-7 cells transfected with different avian AHR1 constructs.

Induction of cytochrome P4501A by highly purified hexachlorobenzene in primary cultures of ring-necked pheasant and Japanese quail embryo hepatocytes.

Primary cultures of ring-necked pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica) embryo hepatocytes were used to compare the potencies of highly purified hexachlorobenzne (HCB-P), reagent-grade HCB (RG-HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as inducers of ethoxyresorufin O-deethylase (EROD) activity, cytochrome P4501A (CYP1A4) messenger ribonucleic acid (mRNA) and CYP1A5 mRNA. HCB-P, RG-HCB and TCDD all induced EROD activity and up-regulated CYP1A4 and CYP1A5 mRNA. Induction was not caused by contamination of HCB with polychlorinated dibenzo-p-dioxins, dibenzofurans or biphenyls.

Highly purified hexachlorobenzene induces cytochrome P4501A in primary cultures of chicken embryo hepatocytes.

Some uncertainty exists regarding the purity of hexachlorobenzene (HCB) used in past toxicity studies. It has been suggested that reported toxic and biochemical effects initially attributed to HCB exposure may have actually been elicited by contamination of HCB by polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Herein, primary cultures of chicken embryo hepatocytes (CEH) were used to compare the potencies of two lots of reagent-grade hexachlorobenzene (HCB-old [HCB-O] and HCB-new [HCB-N]), highly purified HCB (HCB-P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as inducers of ethoxyresorufin O-deethylase (EROD) activity, cytochrome P4501A4 (CYP1A4) messenger ribonucleic acid (mRNA) and CYP1A5 mRNA.

Alternate and new brominated flame retardants detected in U.S. house dust.

Due to the voluntary withdrawals and/or bans on the use of two polybrominated diphenyl ether (PBDE) commercial mixtures, an increasing number of alternate flame retardant chemicals are being introduced in commercial applications. To determine if these alternate BFRs are present in indoor environments, we analyzed dust samples collected from 19 homes in the greater Boston, MA area during 2006. Using pure and commercial standards we quantified the following brominated flame retardant chemicals using GC/ECNI-MS methods: hexabromocyclododecane (sigma HBCD), bis(2,4,6,-tribromphenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), and the brominated components found in Firemaster 550 (FM 550): 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) and (2-ethylhexyl)tetrabromophthalate (TBPH), the latter compound being a brominated analogue of di(2-ethylhexyl)phthalate (DEHP).

4,5,6,7-Tetra-bromo-1,1,3-trimethyl-3-(2,3,4,5-tetra-bromo-phen-yl)indane.

The title compound (OctaInd), C(18)H(12)Br(8), is a commercial brominated flame retardant (BFR). In the mol-ecule, the five-membered ring has a slight envelope conformation, with a deviation of 0.317 (9) Å for the flap C atom from four essentially planar C atoms.

In vivo and in vitro debromination of decabromodiphenyl ether (BDE 209) by juvenile rainbow trout and common carp.

Decabromodiphenyl ether (BDE 209), the major congener in the high volume industrial flame retardant mixture "DecaBDE", has recently been shown to be metabolized by carp. To further explore this phenomenon, juvenile rainbow trout were exposed to BDE 209 via the diet for a five month period. Analysis of the whole body homogenate, liver, serum, and intestinal tissues revealed that BDE 209 accumulated in rainbow trout tissues and was most concentrated in the liver.

Structure-dependent Ah receptor agonist activities of chlorinated biphenylenes.

Polychlorinated biphenylenes (PCBP) have been identified as combustion by-products that bind the aryl hydrocarbon receptor (AhR) and exhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like activity. This study investigates the Ah-responsiveness of 2,3,6,7-tetrachlorobiphenylene (2,3,6,7-CBP), 2,3,6-CBP, 2,3-CBP and 2-CBP in breast cancer cells. MCF-7 or ZR-75 cells were treated with different concentrations (1-100 nM) of the compounds alone to determine their activity as inducers of CYP1A1 protein expression or luciferase activity in cells transfected with a construct (pDRE(3)) containing three tandem dioxin responsive elements (DREs) linked to a luciferase reporter gene.