Endocrine Disruption Activity of 30-day Dietary Exposure to Decabromodiphenyl Ethane in Balb/C Mouse

Objective This study aimed to evaluate the hepatotoxicity, metabolic disturbance activity and endocrine disrupting activity of mice treated by Decabromodiphenyl ethane （DBDPE）. Methods In this study, Balb/C mice were treated orally by gavage with various doses of DBDPE. After 30 days of treatment, mice were sacrificed; blood, livers and thyroid glands were obtained, and hepatic microsomes were isolated. Biochemical parameters including 8 clinical chemistry parameters, blood glucose and hormone levels including insulin and thyroid hormone were assayed. The effects of DBDPE on hepatic cytochrome P450 （CYP） levels and activities and uridinediphosphate-glucuronosyltransferase （UDPGT） activities were investigated. Liver and thyroid glands were observed. Results There were no obvious signs of toxicity and no significant treatment effect on body weight, or liver-to-body weight ratios between treatment groups. The levels of ALT and AST of higher dose treatment groups were markedly increased. Blood glucose levels of treatment groups were higher than those of control group. There was also an induction in TSH, T3, and f T3. UDPGT, PROD, and EROD activities were found to have been increased significantly in the high dose group. Histopathologic liver changes were characterized by hepatocyte hypertrophy and cytoplasmic vacuolization. Our findings suggest that DBDPE can cause a certain degree of mouse liver damage and insufficiency. Conclusion DBDPE has the activity of endocrine disruptors in Bal/C mice, which may induce drug-metabolizing enzymes including CYPs and UDPGT, and interfere with thyroid hormone levels mediated by Ah R and CAR signaling pathways. Endocrine disrupting activity of DBDPE could also affect the glucose metabolism homeostasis.

Cytotoxicity and Apoptosis Induction in Human HepG2 Hepatoma Cells by Decabromodiphenyl Ethane

Abstract Objective To investigate the toxic effects of decabromodiphenyl ethane （DBDPE）, used as an alternative to decabromodiphenyl ether in vitro. Methods HepG2 cells were cultured in the presence of DBDPE at various concentrations （3.125-100.0 mg/L） for 24, 48, and 72 h respectively and the toxic effect of DBDPE was studied. Results As evaluated by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assays and nuclear morphological changes, DBDPE inhibited HepG2 viability in a time- and dose-dependent manner within a range of 12.5 mg/L to 100 mg/L and for 48 h and 72 h. Induction of apoptosis was detected at 12.5-100 mg/L at 48 h and 72 h by propidium iodide staining, accompanied with overproduction of reactive oxygen species （ROS）. Furthermore, N-acetyI-L-cysteine, a widely used ROS scavenger, significantly reduced DBDPE-induced ROS levels and increased HepG2 cells viability. Conclusion DBDPE has cytotoxic and anti-proliferation effect and can induce apoptosis in which ROS plays an important role

Subacute Effect of Decabromodiphenyl Ethane on Hepatotoxicity and Hepatic Enzyme Activity in Rats

Information regarding decabromodiphenyl ethane （DBDPE） effects on hepatotoxicity and metabolism is limited. In the present study, Wistar rats were given oral DBDPE at different doses. DBDPE induced oxidative stress, elevated blood glucose levels, increased CYP2B2 mRNA, CYP2B1/2 protein, 7-pentoxyresorufin O-depentylase （PROD） activity, and induced CYP3A2 mRNA, CYP3A2 protein, and luciferin benzylether debenzylase （LBD） activity. UDPGT activity increased with its increasing exposure levels, suggesting that oral DBDPE exposure induces drug-metabolizing enzymes in rats via the CAR/PXR signaling pathway. The induction of CYPs and co-regulated enzymes of phase II biotransformation may affect the homeostasis of endogenous substrates, including thyroid hormones, which may, in turn, alter glucose metabolism.

Profiling kidney microRNAs from juvenile grass carp(Ctenopharyngodon idella) after 56 days of oral exposure to decabromodiphenyl ethane

Grass carp（Ctenopharyngodon idella） is one of the most important species in China.Decabromodiphenyl ethane（DBDPE） is a brominated flame retardant that has been used widely in industry, and has been observed to accumulate in the tissues of fish from South China. Evidence has shown that DBDPE is toxic to aquatic animals, but the molecular response has been unclear. MicroRNAs（miRNAs） are small noncoding and negative regulatory RNAs that are 20–24 nucleotides in length, which are involved in a wide range of biological processes. We took advantage of deep-sequencing techniques to accurately and comprehensively profile the kidney mi RNA expression of grass carp after 8 weeks of oral exposure to DBDPE. After mapping sequencing data to the genome and Expressed Sequence Tags（ESTs） of grass carp, we identified 493 miRNAs in the sequenced grass carp samples, which included 51 new miRNAs. The results indicated that 5 miRNAs were significantly down-regulated and 36 miRNAs were significantly up-regulated（FDR 〈 0.001,1.5-fold change） after DBDPE exposure. Real-time quantitative PCR（RT-qPCR） was performed on 4 miRNAs from the two samples, and the sequencing and RT-qPCR data were consistent. This study provides the first comprehensive identification of grass carp miRNAs, and the first expression analysis of grass carp miRNAs following DBDPE exposure.The results indicated that miRNAs have potential for use as biomarkers.

Temporal trends in concentrations of legacy and novel brominated flame retardants in house dust from Birmingham in the United Kingdom

Concentrations of polybrominated diphenyl ethers(PBDEs),hexabromocyclododecane(HBCDD),tetrabromobisphenol-A(TBBPA)and two potential replacements decabromodiphenylethane(DBDPE)and 1,2-bis(2,4,6-tribromophenoxy)ethane(BTBPE)were measured in dust samples collected from 14 homes across Birmingham(UK).Concentrations were compared with those from the same city in previous studies to ascertain any temporal changes and to assess the effects of legislative restrictions.The average PHBCDDs concentration(46,000 ng/g;median=280 ng/g)included the highest dust concentration recorded globally(570,000 ng/g).This is despite the listing of HBCDD under the Stockholm Convention in 2013,demonstrating that decreases in indoor contamination will likely be slow as existing sources are gradually discarded.In contrast,concentrations of BDE-47(mean=5.7 ng/g;median=0.93 ng/g)and BDE-99(mean=11 ng/g;median=2.9 ng/g)were significantly lower than in all previous(p<0.01)studies in the same city since 2006,suggesting restrictions on the Penta-BDE formulation have been effective.The average BDE-209 concentration(4800 ng/g;median=1600 ng/g)is lower than the peak average concentration,which was observed in 2007(280,000 ng/g),however this is not a significant decline,probably due to the later imposition of Deca-BDE restrictions compared to those on Penta-BDE.Decreases in PBDE concentrations have coincided with a significant(p<0.01)increase in DBDPE concentrations(average=1500 ng/g;median=660 ng/g)since 2014,suggesting its use as a replacement flame retardant for Deca-BDE.While no significant change was detected for BTBPE(average 11 ng/g;median=0.84 ng/g in this study);concentrations of TBBPA(average=34 ng/g;median=35 ng/g)were significantly lower(p<0.05)than in 2007(average 62 ng/g).The decreases observed in PBDE concentrations,demonstrates that legislation has been effective in reducing the commercial use of PBDEs,however this has coincided with increases of alternative flame retardants such as DBDPE.