Decabrominated Diphenyl Ether Research Articles

Correlation of total and free thyroid hormones in rats after subacute exposure to decabrominated diphenyl ether

Correlation of total and free thyroid hormones in rats after subacute exposure to decabrominated diphenyl ether

Effect of Bromine Substitution on Human Dermal Absorption of Polybrominated Diphenyl Ethers.

Human dermal absorption of eight mono- to deca-brominated diphenyl ethers (PBDEs) was investigated for the first time using EPISKIN human skin equivalent tissue. Using a standard in vitro protocol, EPISKIN tissues mounted in specially designed diffusion cells were exposed to the target PBDEs for 24 h. Estimated steady-state flux (Jss) and permeation coefficients (Papp) across the skin increased with decreasing bromine substitution from BDE-153 (Papp = 4.0 × 10(-4) cm/h) to BDE-1 (Papp = 1.1 × 10(-2) cm/h). This was accompanied by an increase in the time required to traverse the skin tissue into the receptor fluid (lag time) from 0.25 h for BDE-1 to 1.26 h for BDE-153. Papp values for the studied PBDEs were correlated significantly (P < 0.05) with physicochemical parameters like water solubility and log KOW. While less brominated congeners achieved faster dermal penetration, higher PBDEs displayed greater accumulation within the skin tissue. The PBDEs thus accumulated represent a contaminant depot from which they may be slowly released to the systemic circulation over a prolonged period. Maximal percutaneous penetration was observed for BDE-1 (∼ 30% of the applied 500 ng/cm(2) dose). Interestingly, BDE-183 and BDE-209 showed very low dermal absorption, exemplified by a failure to reach the steady state within the 24 h exposure period that was studied.

Polybrominated diphenyl ethers in articles: a review of its applications and legislation.

Polybrominated diphenyl ethers (PBDEs), especially commercial decabrominated diphenyl ethers (c-decaBDE), have been widely produced and applied to numerous materials because of their highly effective flame-retardant capabilities. The production of commercial pentaBDE (c-pentaBDE) and commercial octaBDE (c-octaBDE) ended in 2004 because they are persistent, bioaccumulative, and toxic to both humans and the environment, but decaBDE production and use continue. Furthermore, many congeners of PBDEs are still prevalent in consumer products and articles that they pose enormous threat to both the environment and human health. PBDEs have been detected in the casing of electrical and electronic equipment, textile materials, automotive interiors, polyurethane foam (PUF) in seat cushions, children's toys, kitchenware, and other products. With increasing evidence about PBDE pollution and the adoption of international conventions, many developed countries have drawn more public attention to PBDEs and developed sound strategies for their management. This review summaries the utilization and management of PBDEs in a number of countries and reaches the conclusion that PBDEs are still prevalent in consumer articles, while specific regulations or policies for articles containing PBDEs are rare. Public awareness should be raised on the importance of sound management of articles containing PBDEs.

The effects of PBDE-209 exposure during pregnancy on placental ET-1 and eNOS expression and the birth weight of offspring

Decabrominated diphenyl ether (PBDE-209) is a persistent organic pollutant. Gestational exposure to PBDE-209 can accumulate in pregnant women and fetuses via the placenta and umbilical cord, affecting perinatal outcome. In this study, pregnant Sprague–Dawley (SD) rats were randomly divided into five groups and intragastrically administered peanut oil (vehicle) 1, 5 and 10mg/kg by body weight (b.w.) of PBDE-209, or nothing (control) from day 0 (G0) to day 21 (G21) gestation, respectively. Placental samples were collected on G21 by cesarean section. The mRNA and protein expressions of ET-1, eNOS and iNOS in the placenta were examined using qRT-PCR and Western blot, respectively. Total nitric oxide (NO) in the placenta was measured using a specific ELISA kit. Compared with the control and vehicle groups, the mRNA expression of ET-1 and iNOS in the placenta was gradually and significantly increased after exposure to increasing concentrations of PBDE-209 (P<0.05), while the mRNA level of eNOS in the placenta was gradually and significantly reduced after exposure to increasing concentrations of PBDE-209 (P<0.05). The expression trends of ET-1, eNOS and iNOS proteins were consistent with those of mRNA expression. Interestingly, the production of total NO was significantly increased after exposure to 5 and 10mg/kg b.w. PBDE-209 (P<0.05). Finally, the birth weight of the offspring rats was significantly reduced after maternal exposure to 5 and 10mg/kg b.w. PBDE-209 compared with the control and vehicle groups (P<0.05). These results suggest that PBDE-209 exposure during pregnancy upregulates ET-1 and iNOS expression, but decreases eNOS expression in the placenta, as well as reduces the birth weight of offspring.

In vitro human metabolism of the flame retardant resorcinol bis(diphenylphosphate) (RDP).

Resorcinol bis(diphenylphosphate) (RDP) is widely used as a flame retardant in electrical/electronic products and constitutes a suitable alternative to decabrominated diphenyl ether. Due to its toxicity and its recently reported ubiquity in electronics and house dust, there are increasing concerns about human exposure to this emerging contaminant. With the aim of identifying human-specific biomarkers, the in vitro metabolism of RDP and its oligomers was investigated using human liver microsomes and human liver cytosol. Mono- and dihydroxy-metabolites, together with glucuronidated and sulfated metabolites, were detected. Regarding RDP oligomers, only a hydroxy-metabolite of the dimer could be detected. RDP and its oligomers were also readily hydrolyzed, giving rise to a variety of compounds, such as diphenyl phosphate, para-hydroxy-triphenyl phosphate, and para-hydroxy RDP, which were further metabolized. These degradation products or impurities are possibly of environmental importance in future studies.

Simulating long-term occupational exposure to decabrominated diphenyl ether using C57BL/6 mice: Biodistribution and pathology

Decabrominated biphenyl ether (BDE-209) is a fully brominated diphenyl ether compound used widely as an additive brominated flame retardant in a variety of consumer products. In recent years, BDE-209 has been reported to be abundant and persistent in the environment, and comparatively high burdens have been found in occupational environmental compartments and exposed individuals. In the present study, an animal model for simulating long-term occupational exposure to BDE-209 was set up. Female C57BL/6 mice (n=10) were intragastrically administered BDE-209 at a dose of 800mgkg−1bw at 2-d intervals for 2years with an internal blood level of approximately 200ngmL−1, which was comparable to the high level of BDE-209 detected in the occupational population, and the biodistribution and biological effects were evaluated systematically. The results showed that large amounts of the chemical accumulated in most tissues, and the preferential organs were the ovary and uterus, liver and lung. Decreased survival was observed in the exposed mice. The subsequent pathological analysis revealed hepatomegaly in the exposed mice, accompanied by obvious histopathological changes in the liver, lung, brain, spleen, kidney and ovary. No neoplastic lesions were observed in this lifetime exposure study. Although the number of experimental mice was limited, our observations offer a comprehensive understanding of the chronic toxicology of BDE-209 after continuous high-dose exposure.

Brominated flame retardants in Korean river sediments, including changes in polybrominated diphenyl ether concentrations between 2006 and 2009

Brominated flame retardants were analyzed in sediment samples from the Nakdong River basin, Korea. The total concentrations of the 27 polybrominated diphenyl ethers (PBDEs), including decabrominated diphenyl ether (BDE 209), analyzed were 0.55–300ngg−1 dry weight (dw), the BDE 209 concentrations were 0.39–190ngg−1dw, the tetrabromobisphenol A (TBBPA) concentrations were 0.05–150ngg−1dw, and the total hexabromocyclododecane (sum of α-, β-, γ-HBCDs) concentrations were 0.11–19ngg−1dw. The PBDE and HBCD concentrations were comparable to or lower than the concentrations found in sediments from other countries, whereas the TBBPA concentrations were comparable to or higher than the concentrations found in other countries. The TBBPA concentrations were similar to or lower than the PBDE concentrations, even though more than twice as much TBBPA as total PBDEs is consumed in Korea, and this phenomenon was probably caused by TBBPA and PBDEs being used differently during the manufacture of products, and their different half-lives in sediment and affinities for the particle phase in aquatic environments. Sediment samples from several sampling sites close to facilities where expandable polystyrene, epoxy, and polycarbonate resins are manufactured and handled had relatively high TBBPA and HBCD concentrations. Temporal changes in the PBDE concentration strongly correlated with temporal variations in the geochemical compositions such as total organic carbon content and grain size value of the sediment. The PBDE and HBCD distribution profiles in the sediment samples indicated that commercial PBDE and HBCD products were released locally.

Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats

Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1;000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose-response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. After the application of 1,000,2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 x external dose (mg/kg bw/day) + 0.0622. Hepatotoxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDLs of 0.07228 mg BDE-209 /kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely exposed rats. The results of the present work add up to the issue ofBDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/ day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent substances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely deined than the effect established based on external dose, particularly.

Determination of eight polybrominated diphenyl ethers in marine sediments by ultrasonically assisted alkaline degradation extraction and gas chromatography-electron capture detection

For determination of the eight polybrominated diphenyl ethers (PBDEs) in marine sediments based on gas chromatography-electron capture detection (GC-ECD), a rapid and effective method for simultaneous sample extraction and purification was developed, in which ultrasonically assisted alkaline hydrolysis was combined with solvent extraction. The sediment sample was processed in an ultrasonic bath in 2. 00 mol/L NaOH-methanol solution for 30 min, and subsequently extracted by n-hexane. The organic phase was then separated and purified by silica column and concentrated to 100 µL for GC-ECD analysis. Under the optimized conditions, the recoveries and relative standard deviations (RSDs) for eight PBDE congeners ranged from 63.6% to 110.3% and from 1.7% to 10.5% (n = 5), respectively. The limits of detection (LODs, S/N = 3) ranged from 0.002 to 0.011 ng/g except for deca-brominated diphenyl ether (BDE-209), which was 0.097 ng/g. With high accuracy, good stability and adequate recovery, the established method was successfully applied to the analysis of PBDEs in the surface sediments from Bohai Sea. The concentrations of ∑8PBDEs (sum of 2,4,4'-tribromodiphenyl ether (BDE-28), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2, 2', 4, 4', 5-pentabromodiphenyl ether (BDE-99), 2, 2', 4, 4', 6-pentabromodiphenyl ether (BDE100), 2, 2', 4, 4', 5, 5'- 1.566 to 6.760 ng/g and from 1.461 to 6.438 ng/g, respectively. A decreasing gradient of concentration was basically observed with increasing distance off the shore, indicating that anthropogenic activities, surface runoff and river inputs may be the sources of PBDEs in the sediments from Bohai Sea.

Determination of atmospheric polybrominated diphenyl ethers and polybrominated biphenyl 153 using isotope dilution-high resolution gas chromatography/high resolution mass spectrometry

Considering the features and demands of the environmental monitoring, an isotope dilution-high resolution gas chromatography/high resolution mass spectrometry method was developed for the determination of polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls 153 (BB153) in the ambient air. PBDEs and BB153 were extracted using an accelerated solvent extraction apparatus with a mixture of hexane-dichloromethane (v/v, 1:1) and hexane, respectively. The concentrated extracts were loaded on the composite silica gel column for cleanup. The mean recoveries of native compounds at 10% and 90% of the highest levels of calibration curves were 100% and 104% with 5% and 6% of the mean relative standard deviations (n = 7), respectively. The recoveries of 13C labeled surrogates for di- to deca-brominated diphenyl ethers and BB153 were in the range of 36.5%-133%. However, the recoveries of 13C-monobrominated diphenyl ethers were relatively low, maybe due to the different physicochemical properties compared with the other homologues. No breakthrough of pollutants was estimated under real sampling volume of 300 m3. The limits of detection were lower than 2 x 10(-4) ng/Nm3. The recoveries of 13C labeled surrogates were between 56% and 126%, except monoBDEs. The results demonstrated that the method is suitable for the analysis of di- to decabrominated diphenyl ethers and BB153 in the ambient air with precise quantification.

Feasibility Study of Feces for Noninvasive Biomonitoring of Brominated Flame Retardants in Toddlers

This study investigated the feasibility of using feces as a noninvasive matrix to estimate serum concentrations of brominated flame retardants (BFRs) in toddlers for biomonitoring purposes. Tri- to decabrominated diphenyl ethers (tri-decaBDEs), isomer-specific hexabromocyclododecanes, and 16 emerging BFRs were determined in feces from 22 toddlers (11-15 months of age), and results were compared to previously analyzed matched serum samples. BDE-47, -153, -196, -197, -203, -206, -207, -208, and -209 were detected in the feces creating a matched data set (feces-serum, n = 21). Tetra-octaBDE concentrations were significantly higher (Student's paired comparisons t test, α = 0.05) in serum versus feces with BDE-153 having the highest mean difference between the sample matrices. BDE-209 was found in significantly higher concentrations in feces compared to serum. Significant correlations (Pearson's, α = 0.05) between congener-specific concentrations in feces and serum were found for all BDEs except BDE-197 and -203. The feces-serum associations found can be used to estimate serum concentrations of tetra-decaBDEs from feces concentrations and enable a noninvasive sampling method for biomonitoring BDEs in toddlers.

Prenatal Exposure to Persistent Organic Pollutants and Sex Hormone Levels in Cord Blood

Prenatal Exposure to Persistent Organic Pollutants and Sex Hormone Levels in Cord BloodAbstract Number:1921 Charline Warembourg*, Anne Debost-Legrand, Catherine Massart, Ronan Garlantézec, Christine Monfort, Eric Gaudreau, Cécile Chevrier, and Sylvaine Cordier Charline Warembourg* National Institute of Health and Medical Research (INSERM IRSET U1085) University of Rennes 1, France, E-mail Address: [email protected] Search for more papers by this author , Anne Debost-Legrand Genetic medical unit, university hospital of Clermont-Ferrand, France, E-mail Address: [email protected] Search for more papers by this author , Catherine Massart Laboratoire Hormonologie, Centre d Investigation Clinique, National Institute of Health and Medical Research (INSERM U0203), France, E-mail Address: [email protected] Search for more papers by this author , Ronan Garlantézec National Institute of Health and Medical Research (INSERM IRSET U1085) School of Public Health (EHESP), France, E-mail Address: [email protected] Search for more papers by this author , Christine Monfort National Institute of Health and Medical Research (INSERM IRSET U1085) University of Rennes 1, France, E-mail Address: [email protected] Search for more papers by this author , Eric Gaudreau Centre de Toxicologie du Québec of the National Institute of Public Health, Canada, E-mail Address: [email protected] Search for more papers by this author , Cécile Chevrier National Institute of Health and Medical Research (INSERM IRSET U1085) University of Rennes 1, France, E-mail Address: [email protected] Search for more papers by this author , and Sylvaine Cordier National Institute of Health and Medical Research (INSERM IRSET U1085) University of Rennes 1, France, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Persistent organic pollutants (POP) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides are known to cause endocrine disruption but few studies have examined the effects of such prenatal exposures on sex hormone levels in cord blood. Aim: To explore associations between prenatal exposure to POP and sex hormones in cord blood.Methods: Sex hormones levels were measured in 283 cord blood samples from the PELAGIE mother-child cohort (Brittany, France): sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (TT), free androgen index (FAI=TT/SHBG), testosterone:estradiol ratio (TT/E) and anti-Müllerian hormone (AMH; male newborns only). Pesticide concentrations of alpha endosulfan, beta hexachlorocyclohexane (ßHCH), pp’-dichlorodiphenyldichloroethylene (pp’DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE) as well as PCBs (congeners 153, 187 and sum of anti-estrogenic PCB 118, 138, 170) and decabrominated diphenyl ether 209 (PBDE209) were also measured in cord blood. Associations between sex hormones and POP exposures treated in categories were explored by multiple linear regressions. Statistical significance was defined as p<0.05.Results: High pesticide levels were associated with an increase of SHBG, and E2, and a decrease of TT/E and FAI, for several compounds especially alpha endosulfan, HCE and HCB. High PCB levels were associated with an increase of SHBG and AMH, and a decrease of TT/E and FAI. Several of these associations were stronger, or specific, for male or female newborns. No association was found for PBDE209 or with TT.Conclusion: Prenatal exposure to a number of persistent pollutants is associated with disruption of hormone levels at birth. The clinical significance of these findings on a longer term remains to be established.

Exploring the interactions of decabrominateddiphenyl ether and tetrabromobisphenol A with human serum albumin

Decabrominateddiphenyl ether (deca-BDE) and tetrabromobisphenol A (TBBPA) are known as brominated flame-retardants, which are commonly found in the environment. The binding mechanisms of deca-BDE and TBBPA with human serum albumin (HSA) are still unknown. In this report, the interactions of deca-BDE and TBBPA with HSA were investigated using different spectroscopic methods and molecular modeling. The experimental results indicated the formation of complexes between deca-BDE/TBBPA and HSA with different affinity. These interactions affected the secondary structure of HSA. Thermodynamic investigations revealed that hydrophobic forces mainly drove the binding interactions of deca-BDE/TBBPA with HSA. For TBBPA, hydrogen-bonding interactions were also involved in the binding process of TBBPA with HSA. According to the analysis of experimental and theoretical data, we concluded that the binding site of deca-BDE to HSA located in the subdomain IB, while TBBPA was near to subdomain IIA and Trp-214. The binding interactions of deca-BDE and TBBPA with the most prominent carrier protein in the human circulatory system could influence mechanisms of their biochemical processes. Thus, these binding interactions can play central roles in studying the distribution and toxicity mechanisms of brominated flame-retardants.

Cadmium and decabrominated diphenyl ether mixture: In vitro evaluation of cytotoxic, prooxidative and genotoxic effects

In order to look into the combined effects of Cd and BDE-209 in vitro, this study was aimed at examining cytotoxic and genotoxic effects using the human colon carcinoma cell line (SW 480) as a biological test system as well as to determine if ROS production was one of the possible mechanisms of their mixture action. This cell line was chosen since ingestion of contaminated food/water represents an important route of exposure to both Cd and BDE-209, which is why intestinal cells are a common target for the contaminants present in food and water. Cells were treated with single Cd in concentrations of 2.5, 7.5 or 15μg Cd/mL (corresponding to 22, 67 or 134μM), single BDE-209 in concentrations of 2.5, 5 or 10μg BDE209/mL (corresponding to 2.5, 5 or 10μM), and their mixtures (design 3×3).Mixture of Cd and BDE-209 has shown clear potential to reduce the viability of SW 480 cells, as evidenced by cytotoxicity associated with ROS generation. Factorial regression models used to identify type of interaction revealed synergism related to mixture citotoxicity and additive interaction for the effect on ROS production. The results from this introductory study could contribute to the issue of possible adverse effects associated with co-exposure and body burden with two persistent environmental pollutants, Cd and BDE-209.

Decabrominated diphenyl ether and methylmercury impair fetal nervous system development in mice at documented human exposure levels.

The central nervous system (CNS) is extremely vulnerable to the toxic effects of environmental pollutants during development. Polybrominated diphenyl ethers (PBDEs) are persistent contaminants, increasingly present in the environment and in human tissues. Recent investigations identified a correlation between maternal exposure to PBDEs and impairment in fetal neurobehavioral development, suggesting that these contaminants pose a potential risk for children. We investigated on the potential effects of environmental decabrominated diphenyl ether (decaBDE, the fully brominated congener) on key neurodevelopmental molecules (e.g., synaptic proteins and immature neuron markers) in fetal mouse neurons. Methylmercury was used as reference neurotoxic contaminant and to evaluate its possible synergism with decaBDE. The neurotoxic effects of decaBDE and methylmercury were determined in developing cultured neurons from mouse fetal hippocampus and cerebellum. Neuron death, dendritic branching, synaptic protein expression, markers of immature neurons, and microglia activation were evaluated by immunocytochemistry. Brain samples from prenatally treated embryos were also examined for neurotoxicity signs by immunoblotting and histochemistry. DecaBDE significantly affected (down to 0.4 nM) the number of dendritic branches, and the levels of synaptic proteins and doublecortin in cultured neurons. Prenatal exposure to decaBDE decreased the synaptic proteins and increased the expression of the immature neuron and microglial markers in mouse fetuses. In conclusion, prenatal exposure to realistic (relevant for human exposure) concentrations of decaBDE induces impairment of fetal CNS development in mice, suggesting a potential risk of fetotoxicity in humans.

Long-term exposure to decabrominated diphenyl ether impairs CD8 T-cell function in adult mice

Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants that accumulate to high levels in human populations that are subject to occupational or regional industry exposure. PBDEs have been shown to affect human neuronal, endocrine and reproductive systems, but their effect on the immune system is not well understood. In this study, experimental adult mice were intragastrically administered 2,2′,3,3′,4,4′,5,5′,6,6′-decabromodiphenyl ether (BDE-209) at doses of 8, 80 or 800 mg/kg of body weight (bw) at 2-day intervals. Our results showed that continuous exposure to BDE-209 resulted in high levels of BDE-209 in the plasma that approached the levels found in people who work in professions with high risks of PDBE exposure. Reduced leukocytes, decreased cytokine (IFN-γ, IL-2 and TNF-α) production and lower CD8 T-cell proliferation were observed in the mice exposed to BDE-209. Additionally, mice with long-term BDE-209 exposure had lower numbers of antigen-specific CD8 T cells after immunization with recombinant Listeria monocytogenes expressing ovalbumin (rLm-OVA) and the OVA-specific CD8 T cells had reduced functionality. Taken together, our study demonstrates that continuous BDE-209 exposure causes adverse effects on the number and functionality of immune cells in adult mice.

Prenatal exposure to decabrominated diphenyl ether impairs learning ability by altering neural stem cell viability, apoptosis, and differentiation in rat hippocampus.

Background:Polybrominated diphenyl ether (PBDE) levels in children and teenagers were higher than those of the adults and the highest levels were found in infants and toddlers. 2,2',3,3',4,4',5,5',6,6'-Decabrominated diphenyl ether (BDE-209) readily crosses the placental barrier and produces toxicity in the developing fetus, particularly to the developing brain.Objectives:This present study aims to investigate the potential effects of prenatal BDE-209 exposure on regulation of neurogenesis and learning function in an experimental rat model.Methods:Pregnant rats received BDE-209 (10, 30, or 50 mg kg-1 day-1) or vehicle (arachis oil) through gastric gavage from gestation day 1 to 14 (n = 10 per group). The embryonic hippocampal neural stem cells (NSCs) from five pregnant rats in each group were collected on day 14 and cultured in vitro to determine the cell viability, apoptosis, and differentiation of NSCs using cell counting kit 8 assay, flow cytometry, and immunofluorescence staining, respectively. In total, 20 male offspring on postnatal day 25 from each group were chosen to evaluate learning ability using a Morris water navigation task assay.Results:The data showed that prenatal exposure to BDE-209 decreased cell viability and differentiation of NSCs but promoted apoptosis in a dose-dependent manner. Prenatal BDE-209 exposure also impaired rat-learning acquisition in a dose-dependent manner.Conclusions:Prenatal BDE-209 exposure impairs rat-learning acquisition, possibly by affecting neurogenesis in the hippocampus during embryonic development.

Neuromodulatory role of Bacopa monnieri on oxidative stress induced by postnatal exposure to decabromodiphenyl ether (PBDE -209) in neonate and young female mice.

Bacopa monnieri (BM), a traditional ayurvedic medicine, is a well-known memory enhancer. We have explored the role of BM against decabrominated diphenyl ether (PBDE-209)-induced alterations in neonate and young female mice. Mice were orally administered with B. monnieri at the doses of 40, 80 or 120 mg/kg body weight along with PBDE-209 (20 mg/kg body weight) from postnatal day (PND) 3-10. Levels of malondialdehyde, protein carbonyl and activities of superoxide dismutase and glutathione peroxidase were measured at both ages. The correct choices and reference/working memory errors of young mice were evaluated by Morris water and radial arm maze. The results showed that BM at the dose of 120 mg/kg significantly (P<0.05) restored the levels of oxidants and the activities of antioxidant enzymes in frontal cortex and hippocampus of neonates against PBDE-209-induced toxicity. BM plays a neuroprotective role against PBDE-209-induced alterations in oxidative status.

Decabrominated diphenyl ether (BDE-209) and/or BDE-47 exposure alters protein expression in purified neural stem/progenitor cells determined by proteomics analysis

Polybrominateddiphenyl ethers (PBDEs) are widely utilized as the additive brominated flame retardants in electronic devices, furniture, plastics, rubber foam, and textiles, which exhibit many negative biological effects, especially potential toxic effects on neurodevelopment. In the present study, we applied a proteomics approach to study the effects of decabromodiphenyl ether (BDE-209) and/or tetrabromodiphenyl ether (BDE-47) on the expression of proteins extracted from neural stem/progenitor cells and further explored mechanisms on neurodevelopmental toxicity. We sub-cultured 3–4 generations of neural stem/progenitor cells which were exposed to BDE-209 and/or BDE-47. After a 72-h exposure, we applied two-dimensional gel (2-DE) to identify differentially expressed proteins and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS) to determine the protein identity of 25 spots. Western blot analysis was applied to determine the expression of cofilin-1 and vimentin. A total of 39 differential expression protein spots were identified by 2-DE after BDE-209 and/or BDE-47 exposure in the neural stem/progenitor cells, and 19 differentially expressed proteins were identified by MALDI-TOF-MS. Western blot analysis revealed that cofilin-1 and vimentin were differentially expressed in all groups. Expression of both proteins was decreased when the neural stem/progenitor cells were exposed to BDE-209 and were absent when exposed to both BDE-47 and BDE-209. BDE-209 and/or BDE-47 might alter the expression of some proteins of neural stem/progenitor cells. Nineteen proteins were identified by MALDI-TOF-MS, which will provide a useful basis for further study of the mechanisms underlying PBDE-mediated neurotoxicity.

Emissions of two phthalate esters and BDE 209 to indoor air and their impact on urban air quality

Estimated emissions of decabrominated diphenyl ether (BDE 209) and the two phthalate esters diethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP) to indoor air in the Stockholm conurbation, Sweden were used to assess the contribution of chemical outflows from the indoor environment to urban outdoor air pollution for these substances, by applying the recently developed Stockholm MUltimedia URban fate (SMURF) model. Emission rates of DINP from PVC materials were measured and published emission rates of DEHP were adapted to Swedish conditions. These were used as input to the model, as well as recently reported estimates of BDE 209 emissions to indoor air in Stockholm. Model predicted concentrations were compared to empirical monitoring data obtained from the literature and from additional measurements of phthalates in ventilation outlets and urban air performed in the current study. The predicted concentrations of the phthalates DINP and DEHP in indoor air and dust were within a factor of 1.5–10 of the measured concentrations. For BDE 209, predicted indoor concentrations were within the measured ranges, but measured concentrations showed a much larger variability. An adjusted emission scenario to better fit observed concentrations indoors was employed for DEHP and final outcomes resulted in estimated indoor emissions of 250 (50–1250), 2.9 (0.58–15), and 0.068 (0.014–0.34) kg year−1 for DEHP, DINP and BDE 209. These emissions could not explain the observed concentrations in urban air of the phthalates, suggesting an underestimation of background inflow or existence of additional sources in the outdoor environment. For BDE 209, the assessment indicates that the Stockholm indoor environment contributes about 25% to the air pollution load in inflowing background air, but additional monitoring data in urban air are needed to confirm this conclusion.