Improvement of the quantitativeness of the thermal desorption-GC/MS method and development of polystyrene certified reference material for the quantification of decabromodiphenyl ether (BDE 209) by using isotope dilution mass spectrometry.

A polystyrene (PS) certified reference material (CRM) for the analysis of decabromodiphenyl ether (BDE 209) was issued. PS disk was prepared by injection molding of the mixture of versine PS and BDE 209. The certification of the PS CRM was conducted by two analytical methods with different sample preparation methods using isotope dilution mass spectrometry (IDMS). The certified value, wCRM, was 978 mg/kg, and this value coincided with the regulation value of BDE 209 in the Restriction of Hazardous Substances directive (1000 mg/kg). The uncertainties related to certification, uwmean, inhomogeneity, uhom, and long- and short-term instability, usts and ults, respectively, were evaluated based on the mass fraction of BDE 209. The uwmean, uhom, usts, and ults were 0.0265, 0.0046, 0.0061, and 0.0099 (relative), respectively, and the expanded uncertainty for this CRM was determined as 57 mg/kg (coverage factor is 2). Additionally, the quantitative capability of the thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) method was evaluated. In TD-GC/MS, the analytical values of the developed CRM obtained by the external and internal standard methods with matrix-free calibrants were out of the range of the wCRM (almost 10% larger or smaller), whereas those with matrix-matched calibrants agreed with the wCRM. In contrast to these results, the analytical values obtained by TD-GC/MS using IDMS were consistent with the wCRM no matter if matrix-free or matrix-matched calibrants were used. These results indicated that, for quantification of BDE 209 in PS, the trueness and precision of TD-GC/MS can be enhanced by applying IDMS without matrix-matched calibrants.

ROS suppression and oocyte quality restoration: NMN intervention in decabromodiphenyl ether-exposed mice.

Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.

Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice.

The environmental presence of decabromodiphenyl ether (BDE-209), which is toxic to the male reproductive system, is widespread. The current study investigated its mechanism of toxicity in mice. The results showed, that BDE-209 induced DNA damage, decreased the expression of the promoter of meiosis spermatogenesis- and oogenesis-specific basic helix-loop-helix 1 (Sohlh1), meiosis related-factors Lethal (3) malignant brain tumor like 2 (L3MBTL2), PIWI-like protein 2 (MILI), Cyclin-dependent kinase 2 (CDK2), Cyclin A, synaptonemal complex protein 1 (SYCP1) and synaptonemal complex protein 3 (SYCP3), and caused spermatogenic cell apoptosis, resulting in a decrease in sperm quantity and quality. Furthermore, BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome (APC/C), increased the expression of PIWI-like protein 1 (MIWI) in the cytoplasm of elongating spermatids, and decreased the nuclear levels of RING finger protein 8 (RNF8), ubiquitinated (ub)-H2A/ub-H2B, and Protamine 1 (PRM1)/Protamine 2 (PRM2), while increasing H2A/H2B nuclear levels in spermatids. The reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 exposure. The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1. Furthermore, the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines, by preventing RNF8 from entering nuclei, which affected the evolution of spermatids into mature sperm.

Hepatotoxicity evaluation and possible mechanisms of decabrominated diphenyl ethers (BDE-209) in broilers: Oxidative stress, inflammatory, and transcriptomics.

Decabrominated diphenyl ether (BDE-209), a persistent organic pollutant, is linked to a great number of health problems, the most severe of which impact the liver due to its role in the elimination and degradation of exogenous harmful substances. Though the hepatotoxicity of BDE-209 has been observed, its underlying mechanism is yet unknown. The purpose of this study is to thoroughly investigate the hepatotoxicity of BDE-209 and its molecular processes in broilers by subjecting 120 male broilers to varied concentrations of BDE-209 for 42 days. We observed that the bioaccumulation of BDE-209 in the liver in a dose-dependent manner, and that BDE-209 exposure can raise the concentrations of ALT, AST, and GGT, accompanied by hepatocyte fatty degeneration and inflammatory foci. In the hepatic homogenates, oxidative stress was evidenced by elevated levels of MDA and ROS and decreased activies of SOD and CAT. Additionally, pro-inflammatory cytokines including IL-1, IL-1ß, TNF-α, IL-8 levels were increased, whereas anti-inflammatory cytokine IL-4 level was declined. Furthermore, RNA sequencing revealed that genes involved in inflammation were considerably dysregulated, and real-time PCR verified the expressed alterations of numerous genes related to the MAPK and WNT signaling pathways. The protein concentrations of NF-κB, ß-catenin, and WNT5A, and the phosphorylation levels of JNK and ERK were all dramatically enhanced. The current study indicates that BDE-209 exposure can cause hepatotoxicity in broilers via bioaccumulation and oxidative stress, which then activates the MAPK and WNT signaling pathways, subsequently generating inflammation and hepatic injury.

Ferroptosis mediates decabromodiphenyl ether-induced liver damage and inflammation.

Decabromodiphenyl ether (BDE-209) is an environmental toxin. Increasing evidence showed that BDE-209 exposure induced liver injury, but the mechanism still remains unknown. The present study explored the effect and mechanism of ferroptosis on hepatotoxicity triggered by BDE-209 in vivo and in vitro. In vivo experiment, ICR mice were exposed to BDE-209 for 50 days, and then recovered for 50 days; HepG2 and L02 cells were treated with BDE-209 or/and ferrostatin-1 (Fer-1) for establishing in vitro model. In vivo, the results showed that BDE-209 accumulated in liver and induced liver damage, increased Fe2+ and MDA contents, and blocked the activation of SLC7A11/GSH/GPX4 pathway in liver; BDE-209 also activated IKK/IκB/NF-κB pathway and elevated inflammatory cytokines levels in liver after exposure for 50 days. After BDE-209 stopping exposure 50 days, the severity of liver damage, ferroptosis and inflammatory response were still higher than the corresponding control group. In vitro, ferroptosis inhibitor Fer-1 rescued ferroptotic damage and attenuated cell death in BDE-209-treated HepG2 and L02 cells. In addition, Fer-1 reversed the activation of IKK/IκB/NF-κB pathway and the increase of pro-inflammatory cytokines levels in BDE-209-treated HepG2 and L02 cells. Together, the above results suggested that BDE-209 induced tissue damage and inflammatory response by activating ferroptosis through increasing iron-dependent lipid peroxidation and blocking the activation of SLC7A11/GSH/GPX4 pathway in liver, indicating that ferroptosis is a potential mechanism for BDE-209-induced hepatotoxicity.

New Insights into Human Biotransformation of BDE-209: Unique Occurrence of Metabolites of Ortho-Substituted Hydroxylated Higher Brominated Diphenyl Ethers in the Serum of e-Waste Dismantlers.

Extremely high levels of decabromodiphenyl ether (BDE-209) are frequently found in the serum of occupationally exposed groups, such as e-waste dismantlers and firefighters. However, the metabolism of BDE-209 in the human body is not adequately studied. In this study, 24 serum samples were collected from workers at a typical e-waste recycling workshop in Taizhou, Eastern China, and the occurrence and fate of these higher brominated diphenyl ethers (PBDEs) were investigated. The median concentration of the total PBDEs in the serum was 199 ng/g lipid weight (lw), ranging from 125 to 622 ng/g lw. Higher brominated octa- to deca-BDEs accounted for more than 80% of the total PBDEs. Three ortho-hydroxylated metabolites of PBDEs─6-OH-BDE196, 6-OH-BDE199, and 6'-OH-BDE206─were widely detected with a total concentration (median) of 92.7 ng/g lw. The concentrations of the three OH-PBDEs were significantly higher than their octa- and nona-PBDE homologues, even exceeding those of the total PBDEs in several samples, indicating that the formation of OH-PBDEs was a major metabolic pathway of the higher brominated PBDEs in occupationally exposed workers. An almost linear correlation between 6-OH-BDE196 and 6-OH-BDE199 (R = 0.971, P < 0.001) indicates that they might undergo a similar biotransformation pathway in the human body or may be derived from the same precursor. In addition, the occurrence of a series of penta- to hepta- ortho-substituted OH-PBDEs was preliminarily identified according to their unique "predioxin" mass spectral profiles by GC-ECNI-MS. Taken together, the tentative metabolic pathway for BDE-209 in e-waste dismantlers was proposed. The oxidative metabolism of BDE-209 was mainly observed at the ortho positions to form 6'-OH-BDE-206, which later underwent a consecutive loss of bromine atoms at the meta or para positions to generate other ortho-OH-PBDEs. Further studies are urgently needed to identify the chemical structures of these ortho-OH-PBDE metabolites, and perhaps more importantly to clarify the potentially toxic effects, along with their underlying molecular mechanisms.

Toxicokinetics and edible tissues-specific bioaccumulation of decabrominated diphenyl ethers (BDE-209) after exposure to the broilers.

Decabromodiphenyl ether (BDE-209), the primary constituent of a widely used flame retardant formulation, is often present in high levels in avian derived products and could be transferred to humans through consumption. The purpose of this study was to investigate the toxicokinetics and bioaccumulation patterns of BDE-209 in different tissues of broilers, which would benefit the evaluation of chicken product safety. Male broilers received a single oral administration of BDE-209 at 25 mg/kg.BW and then BDE-209 concentrations in the plasma, liver, leg muscle, breast muscle, and other tissues were measured using gas chromatography-electron capture detection (GC-ECD). The changes of BDE-209 concentrations in the plasma were fitted to a non-compartmental model for kinetic analysis. Peak values were observed at 24 h (t1/2 =168.28 h), and trace levels remained for four weeks. Additionally, Cmax in the liver was much higher than that in leg and breast muscles, and Tmax from the liver and muscle were 12 and 24 h, respectively. Residual BDE-209 was detected in all broiler tissues after 2 weeks, and concentrations were ranked as follows: fat > liver > thymus gland > heart > testis > thigh muscle > skin > lung > kidney > breast muscles > spleen (wet weight (ww)). Our results suggested that BDE-209 was widely distributed in different tissues after intestinal absorption, and preferentially accumulated in adipose and liver tissues. Observations of bioaccumulation and slow elimination in the liver and muscles provide critical insight into the toxicity of BDE-209 and risk assessment of edible tissues from broilers.

Gestational exposure to BDE-209 induces placental injury via the endoplasmic reticulum stress-mediated PERK/ATF4/CHOP signaling pathway.

Several epidemiological studies have reported significant associations between prenatal polybrominated diphenyl ethers (PBDEs) exposure and adverse birth outcomes. Placental injury is thought to mediate these associations. However, few study has investigated the adverse effects of PBDEs exposure on placental growth and development. We examined the impacts of gestational exposure to BDE-209, the most abundant PBDE conger detected in human samples, on placental structure and function, and its model of action in vivo and in vitro. Pregnant mice were exposed to 0, 2, 20, 200 mg/kg/day of BDE-209 by gavages from gestational day (GD) 0 to GD18. Results showed that gestational BDE-209 exposure significantly reduced placental weight, impaired placental vascular development and induced placental cell apoptosis. In addition, gestational BDE-209 exposure impaired placental transport and endocrine function as demonstrated by markedly downregulated expression of Glut1, Znt1, Pgf and Igf2 in BDE-209-treated placentas. Mechanistically, gestational exposure to BDE-209 upregulated the expression of GRP78, and 3 downstream proteins (p-eIF2α, ATF4 and CHOP) of the PERK signaling, suggesting the activation of endoplasmic reticulum (ER) stress and PERK signaling pathway in mouse placentas. Further in vitro study showed that PERK siRNA pretreatment markedly reversed BDE-209-induced cell apoptosis in human JEG-3 cells. Collectively, our results suggest that the activation of the ER stress-mediated PERK/ATF4/CHOP signaling pathway played a role in BDE-209-induced placental injury. Our findings provide new insight into the mechanisms of BDE-209 induced reproductive and developmental toxicity.

Vitamin C supplementation rescued meiotic arrest of spermatocytes in Balb/c mice exposed to BDE-209.

Deca-brominated diphenyl ether (BDE-209) is a ubiquitous industrial chemical as brominated flame retardant (BFRs). Exposure to BDE-209 has been clearly associated with male reproductive disorders. However, the meiotic arrest mechanism of spermatocytes exposed to BDE-209 is still unclear. The present work aimed to explore the protective effect of vitamin C on BDE-209-induced meiotic arrest of spermatocytes and its possible mechanism. Vitamin C (100 mg/kg BW) was administered to BDE-209-exposed (80 mg/kg BW) male Balb/c mice once daily by intraperitoneal injection for 2 weeks. Our results showed that vitamin C played male reproductive protection effects as showed by attenuated BDE-209-induced testicular damage, and reduced sperm abnormality rate. Vitamin C also attenuated BDE-209-induced increase in SOD and MDA in testes and GC-2 spd cells. Moreover, vitamin C promoted meiotic prophase in BDE-209-induced mice, with suppressed γ-H2AX, restored DMC1, RAD51, and crossover marker MLH1 levels, and prevented BDE-209-induced DNA impairment. In addition, vitamin C supplementation also interfered with BDE-209-induced upregulation of testicular H3K4me3 through inhibition of KDM5s capacity and decreasing ferrous ion concentration. Furthermore, ferrous sulfate pretreatment could partially restore the expression of H3K4me3 via maintaining the concentration of ferrous ions. Taken together, vitamin C exerts a potential therapeutic agent for preventing BDE-209-induced reproductive toxicity with meiotic arrest, which is attributed to its antioxidant and electron donor properties, as well as, modulation of ferrous ion levels and demethylation of H3K4me3.

Decabromodiphenyl Ether versus Decabromodiphenyl Ethane: Source, Fate, and Influencing Factors in a Coastal Sea Nearing Source Region.

Both decabromodiphenyl ether (BDE 209) and decabromodiphenyl ethane (DBDPE) are still produced in large quantities in China, especially in the Shandong Province closed to the Bohai Sea (BS). This study conducted a comprehensive investigation of the distribution and budget of brominated flame retardants (BFRs) in the BS. BDE 209 was the predominant BFR in most of the investigated rivers flowing into the BS, although DBDPE exceeded BDE 209 in certain rivers as a result of the replacement of BDE 209 with DBDPE in North China. The spatial distributions of BFRs in the rivers were controlled by the proximity of the BFR manufacturing base and the extent of urbanization. BFRs' spatial distribution in the BS was influenced by a combination of land-based pollution sources, environmental parameters (e.g., suspended particulate matter, particulate organic carbon, and particulate black carbon), and hydrodynamic conditions. The spatial variation trend of BDE 209/DBDPE ratios in various environmental media provided useful information. Vertically, the BDE 209/DBDPE ratio decreased from the seawater surface layer to the sediment, indicating their differential transport in the BS. A multi-box mass balance model and analysis of BDE 209 showed that degradation was the primary sink of BFRs in seawater (∼68%) and surface sediment (∼72%) in the BS.

Decabromodiphenyl ether (BDE-209) exposure to lactating mice perturbs steroidogenesis and spermatogenesis in adult male offspring.

Decabromodiphenyl ether (BDE-209) is widely used as a flame retardant in many products like electronic equipments, plastics, furniture and textiles. BDE-209, a thyroid hormones (THs)-disrupting chemical, affects male reproductive health through altered THs status in mouse model. The present study was designed in continuation to our earlier work to elucidate whether early life exposure to BDE-209 has a long term potential risk to male reproductive health. This study, therefore, aimed to evaluate the effect of maternal BDE-209 exposure during lactation and to elucidate possible mechanism(s) of its action on male reproduction in adult Parkes mice offspring. Lactating female Parkes mice were orally gavaged with 500, and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 1 to PND 28 along with 6-propyl-2-thiouracil (PTU)-treated positive controls and vehicle-treated controls. Male pups of lactating dams were euthanized at PND 75. Maternal BDE-209 exposure during lactation markedly affected histoarchitecture of testis and testosterone production with concomitant down-regulation in the expression of various steroidogenic markers in adult offspring. Maternal exposure to BDE-209 during lactation also interfered with germ cell dynamics and oxidative status in testes of adult mice offspring. A decreased expression of connexin 43 and androgen receptor was also evident in testes of these mice offspring; further, number, motility and viability of spermatozoa were also adversely affected in these mice. The results thus provide evidences that maternal exposure to BDE-209 during lactation causes reproductive toxicity in adult mice offspring.

Nephrotoxicity and possible mechanisms of decabrominated diphenyl ethers (BDE-209) exposure to kidney in broilers.

The flame retardant decabrominated diphenyl ether (BDE-209) is a widely used chemical in a variety of products and exists extensively in the environment. BDE-209 has been reported to induce kidney injury and dysfunction. However, the causes and mechanisms of its nephrotoxicity are still under investigation. In this study, 150 male broilers were exposed to BDE-209 concentrations of 0, 0.004, 0.04, 0.4, 4.0 g/kg for 42 days. The relative kidney weight, histopathology, markers of renal injury, oxidative stress, inflammation, apoptosis and the expression of MAPK signaling pathways-related proteins were assessed. The results showed that the concentrations of blood urea nitrogen (BUN), creatinine (CRE) and the neutrophil gelatinase-associated lipocalin (NGAL), significantly increased after exposure to BDE-209 with the doses more than 0.04 g/kg. Similarly, severe damage of renal morphology was observed, including atrophy and necrosis of glomeruli, and swelling and granular degeneration of the renal tubular epithelium. In the renal homogenates, the oxidative stress was evidenced by the elevated concentrations of MDA and NO, and decreased levels of GSH-Px, GSH and SOD. Due to the inflammatory response, the level of NF-κB and the pro-inflammatory cytokines TNF-α, IL-1ß, IL-18 were remarkably upregulated, while the content of the anti-inflammatory cytokine IL-10 decreased. Additionally, the apoptotic analysis showed notable upregulations of Bax/Bcl-2 ratio, the relative expression of p-ERK1/2 and p-JNK1/2, and the expression of Bax, cytochrome c and caspase 3. The present study indicates that BDE-209 exposure can cause nephrotoxicity in broilers through oxidative stress and inflammation, which activate the phosphorylation of key proteins of the MAPK signaling pathways, and subsequently induce mitochondria-mediated kidney apoptosis.

DNA methylation changes induced by BDE-209 are related to DNA damage response and germ cell development in GC-2spd.

Decabrominated diphenyl ether (BDE-209) is generally utilized in multiple polymer materials as common brominated flame retardant. BDE-209 has been listed as persistent organic pollutants (POPs), which was considered to be reproductive toxin in the environment. But it still remains unclear about the effects of BDE-209 on DNA methylation and the induced-male reproductive toxicity. Due to the extensive epigenetic regulation in germ line development, we hypothesize that BDE-209 exposure impacts the statue of DNA methylation in spermatocytes in vitro. Therefore, the mouse GC-2spd (GC-2) cells were used for the genome wide DNA methylation analysis after treated with 32 µg/mL BDE-209 for 24 hr. The results showed that BDE-209 caused genomic methylation changes with 32,083 differentially methylated CpGs in GC-2 cells, including 16,164 (50.38%) hypermethylated and 15,919 (49.62%) hypomethylated sites. With integrated analysis of DNA methylation data and functional enrichment, we found that BDE-209 might affect the functional transcription in cell growth and sperm development by differential gene methylation. qRT-PCR validation demonstrated the involvement of p53-dependent DNA damage response in the GC-2 cells after BDE-209 exposure. In general, our findings indicated that BDE-209-induced genome wide methylation changes could be interrelated with reproductive dysfunction. This study might provide new insights into the mechanisms of male reproductive toxicity under the environmental exposure to BDE-209.

AM fungi increase uptake of Cd and BDE-209 and activities of dismutase and catalase in amaranth (Amaranthus hypochondriacus L.) in two contaminants spiked soil.

Soil co-contaminated with cadmium (Cd) and decabromodiphenyl ether (BDE-209) is a widespread environmental problem, especially in electronic waste contaminated surroundings. Accumulation of Cd and BDE-209 in crops has possibly harmful effects on local human health. In order to assess the potential of arbuscular mycorrhizal (AM) fungi and amaranth (Amaranthus hypochondriacus L.) in remediation of soil co-contaminated with Cd and BDE-209, pot trials were performed to investigate interactive effects of AM fungi, Cd and BDE-209 on growth of amaranth, uptake of Cd and BDE-209, distribution of chemical forms of Cd and activities of antioxidant enzymes in shoots and dissipation of BDE-209 in soil. The present results showed that shoot biomass of non-mycorrhizal plants was significantly inhibited by increasing of Cd addition (5-15 mg kg-1), but were only slightly declined with BDE-209 addition (5 mg kg-1). The interaction of Cd and BDE-209 reduced the proportions of ethanol- and d-H2O-extractable Cd in shoots, consequently alleviated Cd toxicity to plants and enhanced root uptake of Cd and BDE-209. Inoculation of AM fungi resulted in significantly greater shoot biomass as well as higher concentrations of Cd and BDE-209 compared with non-mycorrhizal treatment. Moreover, AM fungi played a beneficial role in relieving oxidative stress on amaranth by increasing the activities of dismutase (SOD) and catalase (CAT) in shoots and significantly improved the dissipation of BDE-209 in soil. The present study suggested that combination of AM fungi and amaranth may be a potential option for remediation of Cd and BDE-209 co-contaminated soils.

Effects of Decabromodiphenyl Ether and Elevated Carbon Dioxide on Rice (Oryza sativa L.).

We assessed the effects of carbon dioxide (CO2) and decabromodiphenyl ether (BDE-209, 0, 3 and 30 mg/kg) on rice (Oryza sativa L. cv. Wuyunjing) in field free-air CO2 enrichment system. Rice at elevated (580 ppm) CO2 had increased net photosynthetic rate, intercellular CO2 concentration, shoot biomass, yield and phosphorus content in grains. However, there were no significant changes in such parameters observed on rice at elevated CO2 combined with BDE-209 (3 and 30 mg/kg). Elevated CO2 alone had no significant effects on sugar or starch content in rice grains, whereas its combination with BDE-209 (3 mg/kg) significantly decreased grain sugar and starch content. In conclusion, rice reared in soil polluted by BDE-209 under elevated CO2 modulates the effects in grain feature.

Decarbromodiphenyl ether (BDE-209) promotes monocyte-endothelial adhesion in cultured human aortic endothelial cells through upregulating intercellular adhesion molecule-1.

There is growing evidence that exposure to persistent organic pollutants (POPs) is statistically associated with incidence of cardiovascular disease (CVD) or its risk factors. Decarbromodiphenyl ether (BDE-209) is a new POP which exists extensively in human tissues, but its potential effects on CVD have so far received less focus. The adhesion of circulating monocytes to endothelial cells is one of the critical underlying steps in the initiation and development of CVD. In the present study, we investigated the effect of BDE-209 on the adhesion of THP-1 monocytes to human aortic endothelial cells (HAECs) and identified the molecular mechanisms involved. Our results showed that 6.25, 12.5 and 25 µM of BDE-209 exposures caused significant increases in monocyte-endothelial cell adhesion, in a dose-dependent manner. Mechanistically, BDE-209 exposure increased the expression of intercellular adhesion molecule-1 (ICAM-1). Moreover, the up-regulation of ICAM-1 was accompanied by a decrease in the expression of microRNA-141 (miR-141). Furthermore, the up-regulation of ICAM-1 and the increased adhesion induced by BDE-209 could be reversed by miR-141 supplement. Taken together, our results show that BDE-209 potentiates monocyte-endothelial cell interaction via miR-141/ICAM-1 pathway in HAECs.

The degradation of decabromodiphenyl ether in the e-waste site by biochar supported nanoscale zero-valent iron /persulfate.

Biochar supported nano zero-valent iron (BC-nZVI) synthesized through liquid phase reduction method was used to activate persulfate (PS) for the removal of decabromodiphenyl ether (BDE209) in the soil. The morphology, structure and composition of BC-nZVI were determined by SEM, XRD, XPS and FTIR. Batch experiments were carried out to investigate the effect of different factors, such as the molar ratio of PS to BC-nZVI, pH value of PS solution and reaction temperature, on the degradation efficiency of BDE209. Results showed that when the molar ratio of PS/BC-nZVI was 3:1, pH value was 3, reaction temperature was 40 °C, 82.06% of BDE209 could be removed within 240 min. The process fitted pseudo-first-order kinetics model well and the apparent activation energy (Ea) was 48.92 kJ mol-1, indicating that the process was controlled by surface reaction. The quenching experiments showed that ·SO4- was predominate radical species in the degradation process in acid and neutral condition. However, ·OH played more important role in alkaline condition. GC-MS was used to determine the reaction products for inferring the degradation pathway of BDE209 in soil by BC-nZVI/PS system.

Insight into the tolerance, biochemical and antioxidative response in three moss species on exposure to BDE-47 and BDE-209.

Responses of Hypnum plumaeforme, Thuidium cymbifolium, and Plagiomnium cuspidatum to short-term (96 h) BDE-47 and BDE-209(0, 0.005, 0.05, 0.5, and 5 µM, respectively) stress were investigated. Both BDE-47 and BDE-209 increased the lipid peroxidation in the three moss species, malondialdehyde (MDA) content increased with the elevated concentration of contaminants, and followed the order: P. cuspidatum > H. plumaeforme > T. cymbifolium on exposure to different concentrations. BDE-47 and BDE-209 stimulated the superoxide dismutase (SOD) and peroxidase (POD) activity of the three moss species, indicating that they played an important role in preventing oxidative stress. Reactive oxygen species (ROS) accumulation was positively correlated with the level of contaminants. The response of anti-oxidative enzymes to BDE-47 and BDE-209 stress differed among the three species. At 5  µM BDE-47 and BDE-209 treatment, the chlorophyll content of T. cymbifolium was even a little higher than the control group. Proline played an important role for the scavenging of ROS in P. cuspidatum and T. cymbifolium. In summary, BDE-47 was more toxic to the three moss species than BDE-209. P. cuspidatum was the most sensitive and T. cymbifolium was the most tolerant species to BDE-47 and BDE-209 stress. The strong resistance and tolerance of T. cymbifolium, combined with sensitive/moderate anti-oxidative response could elucidate its potential use as bio-indicator in the ecological risk assessment of BDE-47 and BDE-209 contamination.

Toxicological, gene expression and histopathological evaluations of environmentally realistic concentrations of polybrominated diphenyl ethers PBDE- 47, PBDE-99 and PBDE-209 on zebrafish embryos.

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Biomonitoring studies have shown widespread presence of PBDEs in humans and their accumulation in food chain cause concern to human health, especially for foetus and infant development. The early-life stages are generally considered more sensitive to exposure to toxic compounds than juvenile or adults. For this reason the aim of this study was to evaluate the effects of the three most environmentally relevant BDE (BDE- 47, 99 and 209) on zebrafish embryos. The fish embryo toxicity (FET) OECD tests on zebrafish were performed followed by histopathogical examination to assess morphological changes. The gene expression of the thyroid stimulating hormone ß (Tshß), the transport proteins transthyretin (Ttr) and thyroxine-binding globulin (Tbg) as well as the enzyme iodothyronine deiodinase 1 (Dio1) was also assessed by Real-time PCR. BDE-47 and BDE-99 showed an increase of the severity of the effects at the lower concentrations while for the BDE-209 the effects were higher to the high concentrations. Although all compounds did not show any acute toxicity for none of the concentrations tested, they reported interesting sub-acute lesions, including yolk and pericardial edema, tail and head malformation, reduced and extremely reduced heart beat rate, blood stasis and spinal curvature, with the highest percentage recorded for BDE-209. Cardiac edema, damage of eye structure and hydrocephaly were confirmed also by histophatological examination. Furthermore, a toxic and dose-dependent liver vacuolization in BDE-209 was observed in all experimental groups. Although no statistically significant difference in gene expression was observed, BDE-209 up-regulated only Dio1 while the other congeners induced Tshß, Ttr, Tbg and Dio1. Overall, this research highlighted that exposure to BDE-47, BDE-99 and BDE-209 at realistic concentrations caused lethal and sub-lethal alterations and impaired genes involved in thyroid hormones homeostasis leading to abnormal development of zebrafish embryos.

Roles of mtDNA damage and disordered Ca2+ homeostasis in the joint toxicities of cadmium and BDE209.

Cadmium, a typical heavy metal, causes serious toxicities on many organs and tissues. As the last partially controlled class of polybrominated diphenyl ethers (PBDEs), BDE209 can also induce various health issues. Although apoptosis mediated by mitochondria has been known to be a key player in inducing toxicities by cadmium, the detailed mechanisms are incompletely understood. Moreover, co-existence of cadmium and PBDEs has been found in various environment context and human body. However, studies on the joint toxicity of cadmium and PBDEs are still limited with largely unknown mechanisms. In the present study, we investigated the adverse effects and mechanisms of single or combined treatment of CdCl2 and BDE209 on hepatocytes. We observed that apoptosis were significantly induced by CdCl2, and the combined treatment of CdCl2 and BDE209 greatly promoted the progression of apoptosis. BDE209 induced mild apoptosis. Mitochondria was the pivot of several mechanisms to induce apoptosis, including ROS production, decreased mitochondrial membrane potential (MMP), mtDNA damage and disordered calcium (Ca2+) homeostasis. However, we found that mtDNA damage and disordered Ca2+ homeostasis were the main mechanisms for CdCl2-induced apoptosis while ROS production played important roles in BDE209-induced apoptosis. Less mtDNA damage occurred in BDE209-treated cells. In the cells with combined treatment, CdCl2 and BDE209 exhibited a complementary pattern for the underlying mechanisms of apoptosis, leading to the joint toxicities, in which CdCl2 showed more contributions. In a conclusion, our results demonstrated that combined exposure to cadmium and BDE209 causes joint adverse effects on hepatocytes through diverse mechanisms as mediated by mitochondria.