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The presence of polybrominated flame retardants in the environment seems to be increasing in the past decade. Considering the toxic effects of these pollutants, it is important evaluating the potential interaction with biological membranes for a risk assessment. In this study low and high brominated biphenyls and biphenyl ethers were used to investigate their interaction with biological membrane models constituted by liposomes, using differential scanning calorimetry (DSC) technique. The medium influence on membrane absorption was also assessed. The findings indicate that membrane interaction is controlled by compound structural characteristics. The membrane absorption is allowed by lipophilic medium; instead hydrophilic medium prevents membrane permeation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) are photolytically unstable flame retarding chemicals. Here, photocatalyzed byproducts of TeDB-DiPhOBz and BDE-209 (i.e Br(8)- to Br(11)-PB-DiPhOBz congeners from TeDB-DiPhOBz, and Br(6)- to Br(8)-BDE congeners from BDE-209), formed after 21 days of natural sunlight irradiation (SI), were assessed for exposure effects on cytotoxicity and mRNA expression levels of selected genes in chicken embryonic hepatocytes (CEH). CEHs were exposed for 36 h to concentrations of SI- and nonirradiated (NI)-TeDB-DiPhOBz and BDE-209. Cytotoxic effects were observed only in CEH exposed to 50 μM SI-BDE-209. Results from a custom-designed Avian ToxChip polymerase chain reaction array showed that NI-TeDB-DiPhOBz and NI-BDE-209, up to maximum concentrations of 1.9 and 9 μM, respectively, caused limited changes in mRNA levels of 27 genes from toxicologically relevant pathways, including phase I/II metabolism, the thyroid hormone pathway, lipid/cholesterol metabolism, oxidative stress, immune response, and cell death. In contrast, 12 and 14 of the 27 genes were altered after exposure to 25 μM SI-TeDB-DiPhOBz or 10 μM SI-BDE-209, respectively. Aryl hydrocarbon receptor (AhR)-related CYP1A4 mRNA levels were the most altered on the PCR array with an induction of 560- and 5200-fold after exposure to 1 or 25 μM SI-TeDB-DiPhOBz, respectively, and 2500- and 2300-fold after exposure to 1 or 10 μM SI-BDE-209, respectively. A dioxin-responsive luciferase reporter gene assay confirmed that the CYP1A4 inductions were independent of the dissolution solvents used (tetrahydrofuran/n-hexane, n-hexane, or methanol) during photolysis. Overall, degradation of TeDB-DiPhOBz and BDE-209 by natural sunlight generates byproducts that affect in vitro expression of genes, especially the AhR-mediated CYP1A4.

The widespread occurrence of polybrominated diphenyl ethers (PBDEs) in the environment has attracted considerable attention, leading to concerns about the extent and magnitude of wildlife and human exposure. In this work, we focus on the occurrence and fate of PBDEs in a Norwegian air-plant-herbivore-carnivore system. Specifically, we have analysed for PBDEs in moss, livers from various terrestrial herbivores (moose, grouse, and European roe deer) and, for the first time, livers from the top predator lynx. The samples were collected from different sites and time periods (1990-2004) to identify possible spatial and temporal trends in contaminant levels and patterns. The general finding was that PBDEs were found in all (biotic) samples, although at lower concentrations than previously observed in mammals from the marine environment. The PBDE levels in the herbivores ranged from less than 0.5 ng/g lipid weight to 9.4 ng/g lipid weight as the highest. The median PBDE concentration in lynx was approximately one order of magnitude higher than in the herbivores. In the lynx samples there was a predominance of BDE-153 whereas BDE-47 and 99 dominated in the herbivores. This probably reflects different bioaccumulation properties or metabolic transformation processes of the BDE-congeners, and food choice. Levels of PBDEs in both moss and herbivores showed a general decline towards the northern parts of Norway. No clear temporal trends were observed. The PBDE levels observed in this study were low and are probably of limited toxicological significance.

The debromination pathways of seven polybrominated diphenyl ethers (PBDEs) by three different cultures of anaerobic dehalogenating bacteria were investigated using comprehensive two-dimensional gas chromatography (GC x GC). The congeners analyzed were the five major components of the industrially used octa-BDE mixture (octa-BDEs 196, 203, and 197, hepta-BDE 183, and hexa-BDE 153) as well as the two most commonly detected PBDEs in the environment, penta-BDE 99 and tetra-BDE 47. Among the dehalogenating cultures evaluated in this study were a trichloroethene-enriched consortium containing multiple Dehalococcoides species, and two pure cultures, Dehalobacter restrictus PER-K23 and Desulfitobacterium hafniense PCP-1. PBDE samples were analyzed by GC x GC coupled to an electron capture detector to maximize separation and identification of the product congeners. All studied congeners were debrominated to some extent by the three cultures and all exhibited similar debromination pathways with preferential removal of para and meta bromines. Debromination of the highly brominated congeners was extremely slow, with usually less than 10% of nM concentrations of PBDEs transformed after three months. In contrast, debromination of the lesser brominated congeners, such as penta 99 and tetra 47, was faster, with some cultures completely debrominating nM levels of tetra 47 within weeks.

Surprisingly high levels of PBDEs (polybrominated diphenyl ethers) in fish from Lake Mjøsa watercourse initialized a more detailed study of PBDE contamination in the Lake Mjøsa region as well as fish from other lakes in southeast Norway. With exception of the fish from Lake Mjøsa, the sum concentration of PBDEs in trout was, on a wet weight (ww) basis, in the range of 0.3-40 ng/g (21-1215 ng/g lipid weight (lw)) in fish fillet and 39-446 ng/g (125-915 ng/g lw) in burbot liver. The PBDE levels in fish from Lake Mjøsa, was found in the range of 72-1120 ng/g ww (2348-16,753 ng/g lw) in trout and 156-2265 ng/g ww (4201-45,144 ng/g lw) in burbot. It was later confirmed that the elevated levels in Lake Mjøsa were mainly caused by the release of PBDEs to the water from a textile manufacturer in the town of Lillehammer. In addition to PBDE levels in fish we also present information on the spatial distribution of PBDEs in air around the Mjøsa watercourse, based on the complementary use of passive air samples and analysis of moss, including data on measured air concentrations. The results confirm the presence of an active source of atmospheric PBDEs in the region of Lillehammer. Although this source appears to have a limited impact on atmospheric levels towards the southern reaches of the lake, it could still be a significant source of PBDEs to the lake as a whole. However, more research is needed to better understand and quantify the relative importance of various sources and pathways for which PBDEs enter Lake Mjøsa in order to support the development of future control strategies.

Small-scale geographical variation in the occurrence of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) was investigated using the eggs of a terrestrial residential songbird species, the great tit (Parus major). In addition, we investigated the influence of the type of sampling location on the presence of these pollutants. To achieve this, 10 different sampling locations in Flanders (Belgium) were classified into 3 groups based on the extent of urbanisation, industrialisation and agriculture. The higher variance among sampling locations for the levels and profiles of PCBs and OCPs, suggests that local contamination sources are more important for the PCBs and OCPs compared to the PBDEs. Levels of PCBs and PBDEs were significantly higher in the industrialised sampling locations compared to the other locations. Sum PCB and sum PBDE levels reached up to 6050 and 79 ng/g lipid weight, respectively. PCBs and PBDEs were highly positively correlated for all groups, suggesting similar exposure pathways and/or mechanisms of accumulation. Significantly higher levels of OCPs (sum OCPs up to 2683 ng/g lipid weight) were detected in the rural sampling locations situated in a residential area. This suggests that local historical usage of OCPs by inhabitants may be an important source of contamination in Flanders. Contamination profiles differed also among the sampling locations. The rural sampling locations had a higher contribution of lower brominated BDE congeners, whereas the industrialised locations had a higher contribution of higher brominated congeners. The differences in contamination profiles among the sampling locations are probably due to differences in exposure. In conclusion, our results showed that the characteristics of a sampling location influence both the levels and profiles of PCBs, OCPs and PBDEs.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in numerous products. These compounds have been found to enter the marine environment where they have the potential to bioaccumulate in biota. Limited information is currently available concerning the levels of PBDEs in Australian marine wildlife. This study presents baseline information on PBDE levels in a variety of marine species from Queensland, Australia and considers the influence of species-specific factors on contaminant levels and tissue distribution in marine turtles. Overall, the PBDE levels measured in this study are relatively low compared to marine biota from the northern hemisphere, indicating low level input into the marine system of Queensland. This is in general agreement with global estimates which suggest low PBDE usage in Australia. Previous studies, however, have found relatively high PBDE levels in Australian human milk and sera. This discrepancy in contamination trends between terrestrial and marine biota suggests that future transport of PBDEs may occur to the marine system in Australia.

Decabromodiphenyl ether (BDE-209) is a high production volume flame retardant. To date, regulation and control of its environmental release have been minimal. Once in the environment, BDE-209 may encounter conditions favoring debromination, potentially forming congeners with greater toxicity, bioaccumulation potential, and persistence. However, (photolytic and in vivo) debromination has only been demonstrated under laboratory scenarios. To examine whether debromination was likely in the field, PBDE congener profiles were tracked from a wastewater treatment plant (sludge) to receiving stream sediments and associated aquatic biota. BDE-209 and 23 additional PBDEs were detected. Sludge congener profiles resembled the commercial penta- and deca- formulations, suggesting minimal -209 debromination during wastewater treatment. Similar profiles were observed in surficial sediments at the outfall and downstream. However, sunfish (Lepomis gibbosus), creek chub (Semotilus atromaculatus), and crayfish (Cambarus puncticambarus sp. c) collected near the outfall contained tri- through deca-PBDEs, including congeners not detected in the commercial deca-mixture, sludges or sediments (BDE-179, -184, -188, -201, and -202). A previous in vivo laboratory study identified these as -209 debromination products. This supports the hypothesis that metabolic debromination of -209 does occur in the aquatic environment under realistic conditions. Hence assessments that assume no BDE-209 debromination may underestimate associated bioaccumulation and toxicity attributable to the less brominated congeners produced.

Decabromodiphenyl ether (BDE-209) isthe major component in the flame-retardant formulation DecaBDE which is incorporated into numerous consumer goods ranging from upholsteries to electronics. Because of the high volume of DecaBDE produced, its presence in consumer products and the environment, and the finding of BDE-209 in the blood of exposed workers, the extent of bioavailability, persistence, and potential debromination are important issues. To measure the bioconcentration, distribution, reductive debromination, and whole-body half-lives of BDE-209 after multiple low doses in an animal model, we dosed rats with a commercial DecaBDE (0.3 microg/g of diet) for 21 days and measured tissue polybrominated diphenyl ether levels during a 21 day withdrawal period. BDE-209, three nona-BDEs, and four octa-BDEs accumulated in the rats and distributed proportionately throughout the body. Only 5% of the total BDE-209 dose was present as parent compound in the rats after 21 days of dosing and <4% in the feces, suggesting extensive metabolism. A nona-BDE (BDE-207) and two octa-BDEs (BDEs-201 and -197) appeared to form via meta-debromination(s) of BDE-209 to a minimal extent (1% of the total BDE-209 dose). The wholebody half-lives tended to increase with decreasing bromination; however, two octa-BDEs, presumably forming from debromination, increased in the rats after 21 days of withdrawal and demonstrated the potential for BDE-209 to form more persistent lipophilic compounds in vivo.

Concentrations of organochlorines (OCs) and brominated flame-retardants (BFRs) were determined in guillemot (Uria aalge) eggs from the island of Stora Karlsö in the Baltic Sea where 10 eggs/year were collected in the years 2000, 2001 and 2002. The dominating contaminant in egg was p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with a geometric mean (GM) concentration of 18200 ng/g lipid weight (lw). The GM concentration in egg of hexabromocyclododecane (HBCD) of 140 ng/glw, was significantly higher than that of polybrominated diphenyl ether (summation operatorPBDE) of 77 ng/glw. For the evaluation of the data multivariate data analysis techniques namely principal components analysis (PCA), partial least squares regression (PLS), soft independent modelling of class analogy (SIMCA classification), and PLS discriminant analysis (PLS-DA), were used. We investigated whether the eggs' biological characteristics co-varied with egg concentrations of OCs and BFRs, and found e.g., significant negative correlations between egg weight and concentrations of HCB and p,p'-DDE. A PLS model with analyzed BFRs as the Y matrix and OCs as the X matrix could, with varying accuracy, calculate the concentrations of BFRs in the individual egg from their concentrations of OCs (e.g., R(2)Y of 0.89 for BDE47, and of 0.50 for HBCD). Lastly, we compared the contaminant concentrations in the eggs to those in previously analyzed pectoral muscles from adult guillemots from Stora Karlsö, from the year 2000. A PLS-DA model, showed that some of the contaminants (e.g., HBCD and CB28) had significantly higher concentrations in egg than in muscle, although 7 of the 14 contaminants showed no difference in concentrations between the two matrices.

Polybrominated diphenyl ethers (PBDEs), widely used as flame-retardants, are now recognized as globally distributed pollutants, and are detected in most environmental and biological samples, including human blood, adipose tissue, and breast milk. Due to their wide use in commercial products and their persistent nature, long-term exposure to PBDEs may pose a human health risk, especially to children. Our previous reports showed that the commercial PBDE mixture, DE-71, affected protein kinase C (PKC) and calcium homeostasis in a similar way to those of a structurally-related polychlorinated biphenyl (PCB) mixture. These intracellular signaling events are associated with neuronal development and learning and memory function. The objectives of the present study were to test whether environmentally relevant PBDE congeners, with different position and number of bromines, affected PKC translocation in cerebellar granule neuronal cultures and compare the potency and efficacy of PBDE congeners with their 14C-accumulation. All the tested PBDE congeners increased 3H-phorbol ester (PDBu) binding, and a significant effect was seen as low as 10 microM. Among the congeners tested, 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) increased 3H-PDBu binding in a concentration-dependent manner and to a greater extent than other congeners. These effects were seen at concentrations and exposure times where no cytotoxicity was observed. The efficacy of PBDE congeners varied with their structural composition, and the effects seen on 3H-PDBu binding with some PBDE congeners are similar to those of PCB congeners. Cerebellar granule neurons accumulated all three PBDE congeners (PBDEs 47, 99, and 153) following exposure. At the lowest concentration (0.67 microM), about 13-18% of the total dose of 14C-PBDE congeners was accumulated by these neurons. There were distinct differences in the pattern of 14C-PBDE accumulation among the PBDE congeners. The 14C-PBDE accumulation, either represented as percent basis or nanomole basis, was much lower for the 30.69 microM PBDE 99 and 10.69-30.69 microM PBDE 153 than at the lower concentrations, which may be due to low solubility of these congeners. The accumulation pattern with PBDE 47 did not vary with concentration. On a nanomole accumulation basis, PBDEs 47, 99, and 153 accumulation was linear with time. While the nanomole accumulation was linear with concentration for PBDE 47, it is nonlinear for PBDEs 99 and 153. The pattern of PBDE accumulation seems to correlate with the effects on PKC translocation, with regression values of 0.773-0.991. These results indicate that PBDEs affected PKC translocation in neurons in a similar way to those of other organohalogens, some PBDE congeners are equally efficacious as the respective PCB congeners, and PBDE accumulation correlated well with PKC translocation, suggesting a common mode of action for this group of chemicals.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants and are increasingly turning up in the environment. Their structural similarities to polychlorinated biphenyls and thyroid hormones suggest they may be a risk to human health. The present study examines the reactivity of brominated diphenyl ethers (BDEs) on the basis of the electronic structures as calculated by semiempirical AM1 self-consistent field molecular orbital (SCF-MO) method. Frontier orbital energies were used to elucidate the reactivity of BDEs in electrophilic, nucleophilic and photolytic reactions. From an examination of the frontier electron densities, the regioselectivity, or orientation, of metabolic reactions of BDEs was predicted. Furthermore, satisfactory quantitative structure-activity (property) relationship (QSAR and QSPR) models were derived to calculate gas chromatographic and ultraviolet spectral properties and luciferase induction activities from the AM1-computed electronic parameters.

The environmental safety of decabromodiphenyl ether (BDE-209), a widely used flame retardant, has been the topic of controversial discussions during the past several years. Degradation of BDE-209 into lower brominated diphenyl ether congeners, exhibiting a higher bioaccumulation potential, has been a critical issue. Here, we report on the degradation of BDE-209 and the formation of octa- and nonabromodiphenyl ether congeners under anaerobic conditions. Sewage sludge collected from a mesophilic digester was used as the inoculum and incubated up to 238 days with and without a set of five primers. Following Soxhlet extraction and a liquid chromatography cleanup procedure, parent compounds and debromination products were analyzed by GC/HRMS. In experiments with primers, concentrations of BDE-209 decreased by 30% within 238 days. This corresponds to a pseudo-first-order degradation rate constant of 1 x 10(-3) d(-1). Without primers, the degradation rate constant was 50% lower. Formation of two nonabromodiphenyl ether and six octabromodiphenyl ether congeners proved that BDE-209 underwent reductive debromination in these experiments. Debromination occurred at the para and the meta positions, whereas debromination at the ortho position was not statistically significant. All three nonabromodiphenyl ether congeners (BDE-206, BDE-207, and BDE-208) were found to undergo reductive debromination as well. No significant change of the BDE-209 concentration and no formation of lower brominated congeners was observed in sterile control experiments. To our knowledge, this is the first report demonstrating microbially mediated reductive debromination of BDE-209 under anaerobic conditions.

Brominated flame retardants (BFRs) were investigated for toxic effects both in vivo and in vitro in two invertebrate bioassays. Subchronic effects of tetrabromobisphenol A (TBBPA), tribromophenol (TBP), and four polybrominated diphenyl ethers ([PBDEs]; BDE-28, BDE-47, BDE-99, and BDE-100) on larval development of the marine copepod Acartia tonsa were studied. For TBBPA and TBP 5-d effective median concentration (EC50) values for inhibition of the larval development rate were 125 and 810 microg/L, respectively, whereas the PBDEs were much more potent with 5-d EC50 in the low microg/L range (1.2 microg/L for BDE-100; 4.2 microg/L for BDE-99; 13 microg/L for BDE-28; and 13 microg/L for BDE-47). These concentrations were up to two orders of magnitude below the 48-h LC50 for acute adult toxicity (108 microg/L for BDE-28; 400 microg/L for TBBPA; 520 microg/L for BDE-100; 705 microg/L for BDE-99; 1,500 microg/L for TBP; and 2,370 microg/L for BDE-47). To distinguish between general toxicological and endocrine-mediated toxic effects, the BFRs were assessed in vitro for ecdysteroid agonistic/antagonistic activity with the ecdysteroid-responsive Drosophila melanogaster B(II)-cell line. The pentabrominated diphenyl ethers BDE-99 and BDE-100 showed weak ecdysteroid antagonistic activity. Thus, these PBDEs may be regarded as potential endocrine disrupters in invertebrates. The combination of in vitro assays and subchronic biotests with ecologically important crustacean species is a rapid and cost-effective tool when screening for sublethal effects of BFRs and other chemicals.

Polybrominated diphenyl ethers (PBDEs) have been used worldwide as additive flame retardants in polymeric materials. Commercial products consist predominantly of deca-, octa-, and pentabromodiphenyl ether mixtures. PBDEs are resistant to degradation in the natural environment and Penta-BDE in particular accumulates in the fatty tissues of fish, birds and mammals (including humans). Several toxic effects on the thyroid system or on neurodevelopment have been reported in experimental animals exposed to PBDEs. It is likely that human exposure is predominantly through the ingestion of contaminated food and/or mother's milk. The potential health effects of dietary exposure to PBDEs have now become a great concern because of the increasing PBDE levels in the biosphere. In this review, published information on the toxicology of PBDEs, levels in foodstuffs and human milk, and analytical methods has been compiled.

PBDEs are being released to the environment in wastes from their production facilities, degradation, or leaching and volatilization from products that contain PBDEs during the product's useful life. Brominated diphenyl ether congeners BDE-47, -99, and -153 are ubiquitous in the environment and are regarded as the most dominant congeners present in wildlife and humans. The tetra- to hexa-BDE are most likely the congeners to which humans are exposed through food consumption. Knowledge of PBDE uptake, metabolism, elimination, and enzyme induction is restricted largely to rodents (rats and mice) in vitro and in vivo. Feeding studies have shown that excretion of higher brominated BDEs is much greater than lower brominated BDEs. Penta-BDE is more toxic than octa- and deca-BDE following oral administration (oral LD50 in rats, 0.5-5 g/kg). In rodents, repeated exposure to PBDEs results in thyroid hormone disruption, developmental neurotoxicity, some changes of fetal development, and hepatotoxic effects. The observed chronic NOELs depend upon the technical mixture type (i.e., deca-, octa-, or penta- and their congener composition), animal species, and study protocol. Values range from 0.6 to 100 mg/kg in rats and from I to 100 mg/kg in mice. PBDEs are neither mutagenic nor genotoxic. Immunotoxicity in mice is observed following exposure to BDE-47 at 18 mg/kg/d, where splenocyte number decreased. Mice exposed neonatally to a single oral dose of BDE-47(10.5 mg/kg) or BDE-99 (12 mg/kg) on Pnd10 (period of rapid brain growth and development) show permanent impairment of spontaneous motor behavior when reaching adulthood. BDE-99 also induced adverse effects on learning and memory functions of mice. The estimated daily intake based on food consumption for PBDEs ranges from 44 to 51 ng/d, with fish contributing almost one-half. The BDE-99 body burden from a human milk survey can be estimated at 0.64 microg/kg, well below the experimental body burden of 0.4 mg/kg BDE-99 associated with behavioral alterations in neonatal mice. When considering the outlier value for PBDE-99 at 229 ng/g, this would result in an estimated PBDE-99 body burden of 46 microg/kg, or a MOS of only 9. However, no toxicokinetics data are available for humans, and the actual margin of safety may be much smaller if based on levels in critical target organs or tissues.

Polybrominated diphenyl ethers (PBDEs) are used as flame-retardants and have recently been shown to be increasing in the environment and in human mother's milk. We have recently reported that neonatal exposure to 2,2',4,4',5-pentaBDE (PBDE 99) can induce persistent aberrations in spontaneous behavior and also affect learning and memory functions in the adult animal. The present study indicates that the cholinergic system, in its developing stage, may be a target of and sensitive to PBDEs. Neonatal exposure of male NMRI mice on postnatal day 10, to 2,2',4,4',5-pentaBDE (8 mg/kg bw) was shown to alter the response to a cholinergic agent, nicotine, at an adult age. The nicotine-induced behavior test revealed a hypoactive response to nicotine in PBDE 99-treated animals, whereas the response of controls was an increased activity. These findings show similarities to observations made from neonatal exposure to PCBs and nicotine, compounds shown to affect cholinergic nicotinic receptors. This indicates that PBDE 99 can affect the cholinergic system and might thereby interact with other environmental toxicants.