Effects of dissolved organic matter from sewage sludge on sorption of tetrabromobisphenol A by soils

Sorption of tetrabromobisphenol A (TBBPA) by soil influences its fate and transport in the environment. The presence of dissolved organic matter (DOM) may complicate the sorption process in soil. The effects of DOM from sewage sludge on TBBPA sorption by three soils were investigated using batch equilibration experiments in the study. DOM was observed to be sorbed on the soils and the isotherms could be fitted by the Langmuir model. The effects of DOM on TBBPA sorption were dependent on the characteristics ...

Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose

The present study determined the thyroid hormone interference of tetrabromobisphenol A （TBBPA） in Sprague-Dawley （SD） rats, and the derived-reference dose （RfD） of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine （T3）, thyroxine （T4）, and thyroid stimulating hormone （TSH） demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day.

Bromination of Pd Compounds during Thermal Decomposition of Tetrabromobisphenol A

We conducted thermal tests using the reagent tetrabromobisphenol A (TBBPA) and various Pd compounds to study the chemical forms of Pd obtained during the pyrolytic and oxidative decomposition of TBBPA. Thermal testing was conducted in an electric furnace at temperatures of 280°C - 800°C in an Ar or Ar-O2 (5%) atmosphere for a heating period of 40 min. Scanning electron microscopy-energy dispersive X-ray spectroscopy results revealed that Pd bromide was formed in the mixture of TBBPA and PdO after heating to 450°C in the Ar atmosphere. In addition, thermogravimetry-differential thermal analysis showed that as the heating temperature was increased from 350°C to 730°C, weight loss occurred at a nearly constant rate, indicating that Pd bromide decomposed in this temperature range.

Tetrabromobisphenol A exerts thyroid disrupting effects but has little overt impact on postnatal brain development and neurobehaviors in mice

Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.

Toxic Effects of Tetrabromobisphenol A on Human Hepatocellular Carcinoma Cells(HepG2)Evaluated Using RNA-Seq

Tetrabromobisphenol A(TBBPA)is used as a brominated flame retardant and can easily release into environment.It has been detected in a variety of environmental media and even in food,making it a new pollutant that is potentially harmful to environment and human health.However,the toxicity and underlying mechanism of TBBPA remain to be explored.TBBPA is actively metabolized in the liver,so it is vital to study the hepatocellular toxicity of TBBPA.In this study,we treated hepatocellular carcinoma cells(HepG2)with TBBPA and searched the differentially expressed genes(DEGs)triggered by TBBPA exposure.RNA-seq analysis showed that the expression of genes,such as CLIC1 and GATSL1,were significantly down-regulated and PTENP1 was significantly up-regulated after TBBPA exposure,and these genes were involved in cell proliferation and metabolism.The down-regulated genes were enriched to peroxisome proliferator-activated receptor(PPAR)signaling pathway and up-regulated genes were enriched to Janus Kinase-signal transduces and activators of transcription(JAK-STAT)signaling pathway,which play a role in regulating cell growth.Overall,our transcriptome analysis obtained for TBBPA-treated HepG2 cells implies that TBBPA affects the cell proliferation and growth.

Tetrabromobisphenol A‑bis(2,3-dibromopropyl ether)impairs Postnatal Testis Development in Mice:The Microtubule Cytoskeleton as a Sensitive Target

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether)(TBBPA-BDBPE),a widely used flame retardant,has been frequently detected in various environmental compartments,but its health hazard remains largely unknown.Here,we investigated the adverse effects of TBBPA-BDBPE(50 and 1000μg/kg/day)on postnatal testis development in CD-1 mice and the underlying mechanism.Following the first week of maternal exposure,neonatal mice in the high-dose group exhibited reduced seminiferous tubule area,fewer Sertoli cells and germ cells,and damaged microtubules in Sertoli cells;even microtubule damage was also observed in the low-dose group.When exposure extended to adulthood,male offspring in the high-dose group presented more remarkable alterations in reproductive parameters,including reduced sperm count;in the low-dose group,microtubule damage was also observable,along with blood−testis barrier impairment.Further molecular docking analysis and tubulin polymerization assay indicated that TBBPA-BDBPE could interact with tubulin and disrupt its polymerization.Moreover,we observed attenuated microtubules in mouse Sertoli cells in vitro(TM4)following TBBPABDBPE treatment,suggesting that TBBPA-BDBPE impaired testis development possibly by interfering with tubulin dynamics.This study not only highlights the male reproductive hazard of TBBPA-BDBPE but also greatly improved the understanding of the molecular mechanism for male reproductive toxicity of chemicals.

Tetrabromobisphenol A(TBBPA): A controversial environmental pollutant

Tetrabromobisphenol A(TBBPA)is one of the most widely used brominated flame retardants and is extensively used in electronic equipment,furniture,plastics,and textiles.It is frequently detected in water,soil,air,and organisms,including humans,and has raised concerns in the scientific community regarding its potential adverse health effects.Human exposure to TBBPA is mainly via diet,respiration,and skin contact.Various in vivo and in vitro studies based on animal and cell models have demonstrated that TBBPA can induce multifaceted effects in cells and animals,and potentially exert hepatic,renal,neural,cardiac,and reproductive toxicities.Nevertheless,other reports have claimed that TBBPA might be a safe chemical.In this review,we re-evaluated most of the published TBBPA toxicological assessments with the goal of reaching a conclusion about its potential toxicity.We concluded that,although low TBBPA exposure levels and rapid metabolism in humans may signify that TBBPA is a safe chemical for the general population,particular attention should be paid to the potential effects of TBBPA on early developmental stages.

Hexabromocyclododecane and tetrabromobisphenol A in sediments and paddy soils from Liaohe River Basin, China： Levels, distribution and mass inventory

Hexabromocyclododecane （HBCD） and tetrabromobisphenol A （TBBPA） are two kinds of brominated flame retardants and widely present in the environment and biota. The levels, spatial distributions and mass inventories of HBCD and TBBPA were investigated in sediments and paddy soils from the Liaohe River Basin in northeast China. The concentrations of ∑HBCD and TBBPA were in the range of not detected （nd） to 4.02 ng/g dry weight （dw） and 0.03 to 4.06 ng/g dw, respectively, y-HBCD was dominated in sediments, while the abundance of a-HBCD was relatively high in paddy soils. The spatial distributions of HBCD and TBBPA in surface sediments and paddy soils indicated that the local point-input was their major source. The significant correlation between total organic carbon （TOC） contents and the HBCD levels suggested that TOC content also exerted an influence on the distribution of HBCD in sediments. Meanwhile, it was found that the irrigation with fiver water was not the major transportation pathway of HBCD and TBBPA in paddy soils. Based on the study, it was estimated that there were about 1.67 tons HBCD and 2.20 tons TBBPA deposited into sediments of the Liaohe River system every year. The total mass inventories of HBCD and TBBPA in sediments were far higher than that in paddy soils.

Re-evaluation of thyroid hormone signaling antagonism of tetrabromobisphenol A for validating the T3-induced Xenopus metamorphosis assay

We developed the T3-induced Xenopus metamorphosis assay, which is supposed to be able to sensitively detect thyroid hormone（TH） signaling disruption of chemicals. The present study aimed to validate the T3-induced Xenopus metamorphosis assay by re-evaluating the TH signaling antagonism of tetrabromobisphenol A（TBBPA）, a known TH signaling disruptor. According to the assay we developed, Xenopus tadpoles at stage 52 were exposed to 10–500 nmol/L TBBPA in the presence of 1 nmol/L T3. After 96 hr of exposure, TBBPA in the range of 10–500 nmol/L was found to significantly inhibit T3-induced morphological changes of Xenopus tadpoles in a concentration-dependent manner in term of body weight and four morphological endpoints including head area（HA）, mouth width（MW）, unilateral brain width/brain length（ULBW/BL）, and hind-limb length/snout-vent length（HLL/SVL）.The results show that these endpoints we developed are sensitive for characterizing the antagonistic effects of TBBPA on T3-induced metamorphosis. Following a 24-hr exposure,we found that TBBPA antagonized expression of T3-induced TH-response genes in the tail,which is consistent with previous findings in the intestine. We propose that the tail can be used as an alternative tissue to the intestine for examining molecular endpoints for evaluating TH signaling disruption. In conclusion, our results demonstrate that the T3-induced Xenopus metamorphosis assay we developed is an ideal in vivo assay for detecting TH signaling disruption.

One-pot preparation of graphene oxide magnetic nanocomposites for the removal of tetrabromobisphenol A

A simple solvothermal method was used to prepare monodisperse magnetite （Fe304） nanoparticles attached onto graphene oxide （GO） sheets as adsorbents to remove tetrabromobisphenol A （TBBPA） from an aqueous solution. These Fe304/GO （MGO） nanocomposites were characterized by transmission electron microscopy. The adsorption capacity at different initial pH, contact duration, and temperature were evaluated. The kinetics of adsorption was found to fit the pseudo-second-order model perfectly. The adsorption isotherm well fitted the Langmuir model, and the theoretical maximum of adsorption capacity calculated by the Langmuir model was 27.26 mg ·g^-1 The adsorption thermodynamics of TBBPA on the MGO nanocomposites was determined at 303K, 313K, and 323 K, respectively. The results indicated that the adsorp- tion was spontaneous and endothermic. The MGO nanocomposites were conveniently separated from the media by an extemal magnetic field within several seconds, and then regenerated in 0.2 M NaOH solution. Thus, the MGO nanocomposites are a promising candidate for TBBPA removal from wastewater.

Occurrence and distribution of tetrabromobisphenol A and its derivative in river sediments from Vaal River Catchment,South Africa

Brominated flame retardants(BFRs)compounds have been widely added in a number of products to reduce their flammability.In the present study,the concentrations and distribution of tetrabromobisphenol A(TBBPA)and its derivatives,i.e.tribromophenol dibromopropyl ether(TBPDBPE),tetrabromobisphenol A bis-dibromopropyl ether(TBBPA BDBPE),tetrabromobisphenol A bis-allyl ether(TBBPA BAE)were investigated in sediment samples collected from the Vaal River catchment,South Africa.The results showed that all these pollutants were detected in sediments with TBBPA BAE being the most abundant contaminant.The TBBPA BAE concentrations ranged from 3.5 to 44.4 ng/g(mean 16 ng/g)while the concentration ranged from not detected(nd)to 2.4 ng/g(mean 0.6 ng/g),nd-21.0 ng/g(mean 6 ng/g)and nd-2.0 ng/g(mean 0.2 ng/g)for TBPDBPE,TBBPA and TBBPA BDBPE;respectively.Higher concentrations of these pollutants were found in sampling sites receiving effluents of wastewater treatment works(WWTWs)treating some industrial wastewater suggesting effluents might play an important role in the contamination of BFRs in the environment.Negative correlation between TBBPA and TBBPA BAE was observed implying different sources or environmental fates between these pollutants.Overall,the results showed a need for further studies to be undertaken in investigating the presence,fate and sources of alternative halogenated flame retardants in the environment.

Biodegradation of tetrabromobisphenol A in the sewage sludge process

Anaerobic sewage sludge capable of rapidly degrading tetrabromobisphenol A（TBBPA） was successfully acclimated in an anaerobic reactor over 280 days. During the period from 0 to 280 days, the TBBPA degradation rate（DR）, utilization of glucose, and VSS were monitored continuously. After 280 days of acclimation, the TBBPA DR of active sludge reached 96.0% after 20 days of treatment in batch experiments. Based on scanning electron microscopy（SEM） observations and denaturing gradient gel electrophoresis（DGGE） determinations,the diversity of the microorganisms after 0 and 280 days in the acclimated anaerobic sewage sludge was compared. Furthermore, eleven metabolites, including 2-bromophenol,3-bromophenol, 2,4-dibromophenol, 2,6-dibromophenol, tribromophenol and bisphenol A,were identified by gas chromatography–mass spectrometry（GC–MS）. Moreover, the six primary intermediary metabolites were also well-degraded by the acclimated anaerobic sewage sludge to varying degrees. Among the six target metabolites, tribromophenol was the most preferred substrate for biodegradation via debromination. These metabolites degraded more rapidly than monobromide and bisphenol A. The biodegradation data of the intermediary metabolites exhibited a good fit to a pseudo-first-order model.Finally, based on the metabolites, metabolic pathways were proposed. In conclusion, the acclimated microbial consortia degraded TBBPA and its metabolites well under anaerobic conditions.

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

A screening assay for thyroid hormone signaling disruption based on thyroid hormone-response gene expression analysis in the frog Pelophylax nigromaculatus

Amphibian metamorphosis provides a wonderful model to study the thyroid hormone（TH）signaling disrupting activity of environmental chemicals, with Xenopus laevis as the most commonly used species. This study aimed to establish a rapid and sensitive screening assay based on TH-response gene expression analysis using Pelophylax nigromaculatus, a native frog species distributed widely in East Asia, especially in China. To achieve this, five candidate TH-response genes that were sensitive to T3 induction were chosen as molecular markers, and T3 induction was determined as 0.2 nmol/L T3 exposure for 48 hr. The developed assay can detect the agonistic activity of T3 with a lowest observed effective concentration of 0.001 nmol/L and EC50 at around 0.118–1.229 nmol/L, exhibiting comparable or higher sensitivity than previously reported assays. We further validated the efficiency of the developed assay by detecting the TH signaling disrupting activity of tetrabromobisphenol A（TBBPA）, a known TH signaling disruptor. In accordance with previous reports, we found a weak TH agonistic activity for TBBPA in the absence of T3,whereas a TH antagonistic activity was found for TBBPA at higher concentrations in the presence of T3, showing that the P. nigromaculatus assay is effective for detecting TH signaling disrupting activity. Importantly, we observed non-monotonic dose-dependent disrupting activity of TBBPA in the presence of T3, which is difficult to detect with in vitro reporter gene assays. Overall, the developed P. nigromaculatus assay can be used to screen TH signaling disrupting activity of environmental chemicals with high sensitivity.

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.