Proinflammatory microglial response is a common mechanism of Aroclor 1254- and Tetrabromobisphenol-A-induced neurotoxicity in immature chronically exposed rats.

Polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) are dominant environmental and food contaminants. Tetrabromobisphenol A (TBBPA) is the most widely used BFR in the world to improve the fire safety of laminates in electrical and electronic equipment. Aroclor 1254, one of the PCBs, is widely distributed in the environment due to its extensive use in industrial applications around the world. Both groups of substances are potent toxicants. There is also increasing evidence that they have neurotoxic effects. In this study we tested the pro-inflammatory effects of Aroclor 1254 and TBBPA based on markers of microglial reactivity and levels of pro-inflammatory factors in the brain of immature rats. Aroclor 1254 or TBBPA were administered to the rats by oral gavage for two weeks at a dose of 10 mg/kg b.w. Both light and electron microscopy studies revealed features indicative of microglia activation in brains of exposed rats. Morphological changes were associated with overexpression of pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Analysis of cytokine/chemokine array revealed significant secretion of inflammatory mediators following exposure to both TBBPA and Aroclor 1254, which was stronger in the cerebellum than in the forebrain of exposed immature rats. The results indicate a pro-inflammatory profile of microglia activation as one of the neurotoxic mechanisms of both examined toxicants.

Exposure to synthesized tribromobisphenol A and critical effects: Metabolic pathways, disease signature, and benchmark dose derivation.

2,2',6-Tribromobisphenol A (Tri-BBPA), the main debrominated congener of tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and human body but with unknown toxicity. Tri-BBPA was synthesized and applied to investigate its sub-chronic exposure effects on 28 organ coefficients and clinical health indicators related to liver function, kidney function, and cardiovascular system function in female mice. Results showed that the liver was the targeted organ of Tri-BBPA exposure. Compared to the control group, the changes in liver coefficient, cholinesterase, total protein, albumin, γ-glutamyl transpeptidase, lactate dehydrogenase, and creatine kinase levels ranged from -61.2 % to 35.5 % in the high-exposed group. Creatine kinase was identified as a critical effect indicator of Tri-BBPA exposure. Using the Bayesian benchmark dose derivation method, a lower reference dose than TBBPA was established for Tri-BBPA (10.6 µg/kg-day). Serum metabolomics revealed that Tri-BBPA exposure may primarily damage the liver by disrupting tryptophan metabolism related to L-alanine, tryptamine, 5-hydroxyindoleacetic acid, and 5-methoxyindoleacetate in liver cells and leading to liver dysfunction. Notably, epilepsy, schizophrenia, early preeclampsia, and late-onset preeclampsia were the top six enriched diseases, suggesting that the nervous system may be particularly affected by Tri-BBPA exposure. Our findings hinted a non-negligible health risk of exposure to debrominated products of TBBPA.

Evaluating effects of tetrabromobisphenol A and microplastics on anaerobic granular sludge: Physicochemical properties, microbial metabolism, and underlying mechanisms.

Tetrabromobisphenol A (TBBPA) and microplastics are emerging contaminants of widespread concern. However, little is known about the effects of combined exposure to TBBPA and microplastics on the physicochemical properties and microbial metabolism of anaerobic granular sludge. This study investigated the effects of TBBPA, polystyrene microplastics (PS MP) and polybutylene succinate microplastics (PBS MP) on the physicochemical properties, microbial communities and microbial metabolic levels of anaerobic granular sludge. The results showed that chemical oxygen demand (COD) removal of sludge was lowest in the presence of TBBPA alone and PS MP alone with 33.21% and 30.06%, respectively. The microorganisms promoted the secretion of humic substances under the influence of TBBPA, PS MP and PBS MP. The lowest proportion of genes controlling glycolytic metabolism in sludge was 1.52% when both TBBPA and PS MP were added. Microbial reactive oxygen species were increased in anaerobic granular sludge exposed to MPS. In addition, TBBPA treatment decreased electron transfer of the anaerobic granular sludge and disrupted the pathway of anaerobic microorganisms in acquiring adenosine triphosphate, and MPs attenuated the negative effects of TBBPA on the acetate methanogenesis process of the anaerobic granular sludge. This study provides a reference for evaluating the impact of multiple pollutants on anaerobic granular sludge.

Complete biodegradation of tetrabromobisphenol A through sequential anaerobic reductive dehalogenation and aerobic oxidation.

Tetrabromobisphenol A (TBBPA), a common brominated flame retardant and a notorious pollutant in anaerobic environments, resists aerobic degradation but can undergo reductive dehalogenation to produce bisphenol A (BPA), an endocrine disruptor. Conversely, BPA is resistant to anaerobic biodegradation but susceptible to aerobic degradation. Microbial degradation of TBBPA via anoxic/oxic processes is scarcely documented. We established an anaerobic microcosm for TBBPA dehalogenation to BPA facilitated by humin. Dehalobacter species increased with a growth yield of 1.5 × 108 cells per µmol Br- released, suggesting their role in TBBPA dehalogenation. We innovatively achieved complete and sustainable biodegradation of TBBPA in sand/soil columns columns, synergizing TBBPA reductive dehalogenation by anaerobic functional microbiota and BPA aerobic oxidation by Sphingomonas sp. strain TTNP3. Over 42 days, 95.11 % of the injected TBBPA in three batches was debrominated to BPA. Following injection of strain TTNP3 cells, 85.57 % of BPA was aerobically degraded. Aerobic BPA degradation column experiments also indicated that aeration and cell colonization significantly increased degradation rates. This treatment strategy provides valuable technical insights for complete TBBPA biodegradation and analogous contaminants.

Single and combined association between brominated flame retardants and cardiovascular disease: a large-scale cross-sectional study.

Introduction: The single and combined association between brominated flame retardants (BFRs) and cardiovascular diseases (CVD) has remained unelucidated. This research aimed at exploring the associations between mixture of BFRs and CVD. Methods: This research encompassed adult participants from the National Health and Nutrition Examination Survey in 2005-2016. The weighted quantile sum (WQS) model and quantile g-computation (QGC) model were applied to examine the combined effects of BFRs mixture on CVD. Results: In this research, overall 7,032 individuals were included. In comparison with the lowest quartile, the highest quartile of PBB153 showed a positive association with CVD, with odds ratio (OR) values and 95% confidence intervals (CI) of 19.2 (10.9, 34.0). Furthermore, the acquired data indicated that PBB153 (OR: 1.23; 95% CI: 1.02, 1.49), PBB99 (OR: 1.29; 95% CI: 1.06, 1.58), and PBB154 (OR: 1.29; 95% CI: 1.02, 1.63) were linked to congestive heart failure. PBB153 was also related to coronary heart disease (OR: 1.29; 95% CI: 1.06, 1.56). Additionally, a positive correlation between the BFRs mixture and CVD (positive model: OR: 1.23; 95% CI: 1.03, 1.47) was observed in the weighted quantile sum (WQS) model and the quantile g-computation (QGC) model. Discussion: Therefore, exposure to BFRs has been observed to heighten the risk of cardiovascular disease in US adults, particularly in the case of PBB153. Further investigation is warranted through a large-scale cohort study to validate and strengthen these findings.

Mechanism of tartaric acid mediated dissipation and biotransformation of tetrabromobisphenol A and its derivatives in soil.

Biotransformation is a major dissipation process of tetrabromobisphenol A and its derivatives (TBBPAs) in soil. The biotransformation and ultimate environmental fate of TBBPAs have been widely studied, yet the effect of root exudates (especially low-molecular weight organic acids (LMWOAs)) on the fate of TBBPAs is poorly documented. Herein, the biotransformation behavior and mechanism of TBBPAs in bacteriome driven by LMWOAs were comprehensively investigated. Tartaric acid (TTA) was found to be the main component of LMWOAs in root exudates of Helianthus annus in the presence of TBBPAs, and was identified to play a key role in driving shaping bacteriome. TTA promoted shift of the dominant genus in soil bacteriome from Saccharibacteria_genera_incertae_sedis to Gemmatimonas, with a noteworthy increase of 24.90-34.65% in relative abundance of Gemmatimonas. A total of 28 conversion products were successfully identified, and ß-scission was the principal biotransformation pathway for TBBPAs. TTA facilitated the emergence of novel conversion products, including 2,4-dibromophenol, 3,5-dibromo-4-hydroxyacetophenone, para-hydroxyacetophenone, and tribromobisphenol A. These products were formed via oxidative skeletal cleavage and debromination pathways. Additionally, bisphenol A was observed during the conversion of derivatives. This study provides a comprehensive understanding about biotransformation of TBBPAs driven by TTA in soil bacteriome, offering new insights into LMWOAs-driven biotransformation mechanisms.

Association of tetrabromobisphenol A (TBBPA) with micro/nano-plastics: A review of recent findings on ecotoxicological and health impacts.

Despite the diverse research into the environmental impact of plastics, several stones have yet to be unraveled in terms of their ecotoxicological potential. Moreover, their detrimental impacts have become terrifying in recent years as the understanding of their tendency to associate and form cohorts with other emerging contaminants grew. Despite the hypothesis that microplastics may potentially adsorb organic pollutants, sequestering and making them not bioavailable for enhanced toxicity, evidence with pollutants such as Tetrabromobisphenol A (TBBPA) defers this assertion. TBBPA, one of the most widely used brominated flame retardants, has been enlisted as an emerging contaminant of serious environmental and human health concerns. Being also an additive to plasticware, it is not far to suspect that TBBPA could be found in association with micro/nanoplastics in our environment. Several pieces of evidence from recent studies have confirmed the micro/nanoplastics-TBBPA association and have exposed their compounded detrimental impacts on the environment and human health. This study, therefore, presents a comprehensive and up-to-date review of recent findings regarding their occurrence, factors that foster their association, including their sorption kinetics and isotherms, and their impacts on aquatic/agroecosystem and human health. The way forward and prospects for future studies were presented. This research is believed to be of significant interest to the readership due to its relevance to current environmental challenges posed by plastics and TBBPA. The study not only contributes valuable insights into the specific interaction between micro/nanoplastics and TBBPA but also suggests the way forward and prospects for future studies in this field.

Insights into the influence of polystyrene microplastics on the bio-degradation behavior of tetrabromobisphenol A in soil.

Soil contamination by emerging pollutants tetrabromobisphenol A (TBBPA) and microplastics has become a global environmental issue in recent years. However, little is known about the effect of microplastics on degradation of TBBPA in soil, especially aged microplastics. In this study, the effect of aged polystyrene (PS) microplastics on the degradation of TBBPA in soil and the mechanisms were investigated. The results suggested that the aged microplastics exhibited a stronger inhibitory effect on the degradation of TBBPA in soil than the pristine microplastics, and the degradation efficiency of TBBPA decreased by 21.57% at the aged microplastic content of 1%. This might be related to the higher TBBPA adsorption capacity of aged microplastics compared to pristine microplastics. Aged microplastics strongly altered TBBPA-contaminated soil properties, reduced oxidoreductase activity and affected microbial community composition. The decrease in soil oxidoreductase activity and relative abundance of functional microorganisms (e.g., Bacillus, Pseudarthrobacter and Sphingomonas) caused by aged microplastics interfered with metabolic pathways of TBBPA. This study indicated the importance the risk assessment and soil remediation for TBBPA-contaminated soil with aged microplastics.

Tourmaline-enhanced bioremediation of Cd/BDE-153 co-contaminated soil: Migration, soil microorganism structure and enzyme activities.

The efficient remediation of the soil co-contaminated with heavy metals and polybrominated diphenyl ethers (PBDEs) from electronic disassembly zones is a new challenge. Here, we screened a fungus of F. solani (F.s) can immobilize Cd and remove PBDEs. wIt combined with tourmaline enhances the remediation of co- pollutants in the soil. Furthermore, the environment risks of the enhanced technology were assessed through the amount of Cd/BDE-153 in Amaranthus tricolor L. (amaranth) migrated from soil, as well as the changes of soil microorganism communities and enzyme activities. The results showed the combined treatment of tourmaline and F.s made the removal percentage of BDE-153 in rhizosphere soil co-contaminated with BDE-153 and Cd reached 46.5%. And the weak acid extractable Cd in rhizosphere soil decreased by 33.7% compared to control group. In addition, the combined remediation technology resulted in a 32.5% (22.8%), 45.5% (37.2%), and 50.7% (38.1%) decrease in BDE-153 (Cd) content in the roots, stems, and leaves of amaranth, respectively. Tourmaline combined with F.s can significantly increase soil microorganism diversity, soil dehydrogenase and urease activities, further improving the remediation rate of Cd and BDE-153co-pollutants in soil and the biomass of amaranth. This study provides the remediation technology of soil co-contaminated with heavy metal and PBDEs and ensure the maintenance of food security.

Green tea polyphenols inhibit TBBPA-induced lung injury via enhancing antioxidant capacity and modulating the NF-κB pathway in mice.

Tetrabromobisphenol A (TBBPA) is a global pollutant. When TBBPA is absorbed by the body through various routes, it can have a wide range of harmful effects on the body. Green tea polyphenols (GTPs) can act as antioxidants, resisting the toxic effects of TBBPA on animals. The effects and mechanisms of GTP and TBBPA on oxidative stress, inflammation and apoptosis in the mouse lung are unknown. Therefore, we established in vivo and in vitro models of TBBPA exposure and GTP antagonism using C57 mice and A549 cells and examined the expression of factors related to oxidative stress, autophagy, inflammation and apoptosis. The results of the study showed that the increase in reactive oxygen species (ROS) levels after TBBPA exposure decreased the expression of autophagy-related factors Beclin1, LC3-II, ATG3, ATG5, ATG7 and ATG12 and increased the expression of p62; oxidative stress inhibits autophagy levels. The increased expression of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α decreased the expression of the anti-inflammatory factor IL-10 and activation of the NF-κB p65/TNF-α pathway. The increased expression of Bax, caspase-3, caspase-7 and caspase-9 and the decreased expression of Bcl-2 activate apoptosis-related pathways. The addition of GTP attenuated oxidative stress levels, restored autophagy inhibition and reduced the inflammation and apoptosis levels. Our results suggest that GTP can attenuate the toxic effects of TBBPA by modulating ROS, reducing oxidative stress levels, increasing autophagy and attenuating inflammation and apoptosis in mouse lung and A549 cells. These results provide fundamental information for exploring the antioxidant mechanism of GTP and further for studying the toxic effects of TBBPA.

Influence of polystyrene nanoparticles on the toxicity of tetrabromobisphenol A in human intestinal cell lines.

Research and regulatory efforts in toxicology are increasingly focused on the development of suitable non-animal methodologies for human health risk assessment. In this work we used human intestinal Caco-2 and HT29/MTX cell lines to address the potential risks of mixtures of the emerging contaminants tetrabromobisphenol A (TBBPA) and commercial polystyrene nanoparticles (PSNPs). We employed different in vitro settings to evaluate basal cytotoxicity through three complementary endpoints (metabolic activity, plasmatic, and lysosomal membrane integrity) and the induction of the oxidative stress and DNA damage responses with specific endpoints. Although no clear pattern was observed, our findings highlight the predominant impact of TBBPA in the combined exposures under subcytotoxic conditions and a differential behavior of the Caco-2 and HT29/MTX co-culture system. Distinctive outcomes detected with the mixture treatments include reactive oxygen species (ROS) increases, disturbances of mitochondrial inner membrane potential, generation of alkali-sensitive sites in DNA, as well as significant changes in the expression levels of relevant DNA and oxidative stress related genes.

Environmentally Relevant Concentrations of Tetrabromobisphenol A Exposure Impends Neurovascular Formation through Perturbing Mitochondrial Metabolism in Zebrafish Embryos and Human Primary Endothelial Cells.

Tetrabromobisphenol A (TBBPA), the most extensively utilized brominated flame retardant, has raised growing concerns regarding its environmental and health risks. Neurovascular formation is essential for metabolically supporting neuronal networks. However, previous studies primarily concerned the neuronal injuries of TBBPA, its impact on the neurovascularture, and molecular mechanism, which are yet to be elucidated. In this study, 5, 30, 100, 300 µg/L of TBBPA were administered to Tg (fli1a: eGFP) zebrafish larvae at 2-72 h postfertilization (hpf). The findings revealed that TBBPA impaired cerebral and ocular angiogenesis in zebrafish. Metabolomics analysis showed that TBBPA-treated neuroendothelial cells exhibited disruption of the TCA cycle and the Warburg effect pathway. TBBPA induced a significant reduction in glycolysis and mitochondrial ATP production rates, accompanied by mitochondrial fragmentation and an increase in mitochondrial reactive oxygen species (mitoROS) production in neuroendothelial cells. The supplementation of alpha-ketoglutaric acid, a key metabolite of the TCA cycle, mitigated TBBPA-induced mitochondrial damage, reduced mitoROS production, and restored angiogenesis in zebrafish larvae. Our results suggested that TBBPA exposure impeded neurovascular injury via mitochondrial metabolic perturbation mediated by mitoROS signaling, providing novel insight into the neurovascular toxicity and mode of action of TBBPA.

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, 500 µg/(kg·day)) to male mice following maternal and direct exposure through drinking water, with the anti-thyroid 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 500 µg/(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 TBBPA-treated 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.

Functional Melanin Nanoparticles-Assisted Laser Desorption Ionization Mass Spectrometry for High-Sensitivity Detection of TBBPA and TBBPS Contaminations in Animal-Derived Foodstuffs.

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) have been widely used as additives in various products; however, their residues damage human health mainly via dietary ingestion. The current detection techniques remain challenging in directly and sensitively identifying TBBPA and TBBPS from food samples. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has great potential as an alternative tool for the analysis of low-mass environmental pollution. Herein, we successfully screened and optimized COOH-MNP-COOH as a novel MALDI matrix to enhance deprotonation for the analysis of TBBPA and TBBPS from animal-derived food samples in negative-ion mode. Notably, COOH-MNP-COOH was synthesized by a facile self-assembly strategy and characterized by TEM, FT-IR, UV-vis, and zeta potential analysis. Compared with conventional and control matrices, the COOH-MNP-COOH matrix exhibited excellent performance of TBBPA and TBBPS with high chemical stability, favorable reproducibility, remarkable salt and protein tolerance, and high sensitivity owing to abundant active groups, stronger UV-vis absorption at 355 nm, and better hydrophilicity and biocompatibility. TBBPA and TBBPS were detected with the assistance of an internal standard with limits of detection (LODs) of 300 and 200 pg/mL, respectively. Moreover, this method was applied to directly identify the residues of TBBPA and TBBPS in milk products, followed by basa catfish and meat. This research may provide a promising approach for the analysis of environmental pollutants in foodstuffs.

Influence of humic acid on the bioaccumulation, elimination, and toxicity of PFOS and TBBPA co-exposure in Mytilus unguiculatus Valenciennes.

Tetrabromobisphenol A (TBBPA) and Perfluorooctane sulfonate (PFOS) are emerging contaminants which coexist in marine environments, posing significant risks to ecosystems and human health. The behavior of these contaminants in the presence of dissolved organic matter (DOM), specifically the co-contamination of TBBPA and PFOS, is not well understood. The bioaccumulation, distribution, elimination, and toxic effects of TBBPA and PFOS on thick-shell mussels (Mytilus unguiculatus V.), with the absence and presence of humic acid (HA), a typical DOM, were studied. The results showed that the uptake of TBBPA decreased and the uptake of PFOS increased when exposed to 1 mg/L HA. However, at higher concentrations of HA (5 and 25 mg/L), the opposite effect was observed. Combined exposure to HA, TBBPA, and PFOS resulted in oxidative stress in the digestive gland, with the severity of stress dependent on exposure time and HA dose. Histological analysis revealed a positive correlation between HA concentration and tissue damage caused by TBBPA and PFOS. This study provides insights into the influence of HA on the bioaccumulation-elimination patterns and toxicity of TBBPA and PFOS in marine bivalves, offering valuable data for ecological and health risk assessments of combined pollutants in aquatic environments rich in DOM.

Neurodevelopmental toxicity and molecular mechanism of environmental concentration of tetrabromobisphenol A bis (2- hydroxyethyl) ether exposure to sexually developing male SD rats.

Tetrabromobisphenol A bis (2- hydroxyethyl) ether (TBBPA-DHEE), as one of the main derivatives of Tetrabromobisphenol A, been attracted attention for its health risks. In this study, the neurotoxicity, mechanism, and susceptivity of TBBPA-DHEE exposure to sexually developing male rats were systematically studied. Neurobehavioral research showed that TBBPA-DHEE exposure could significantly affect the behavior, learning,and memory abilities of male-developing rats, and aggravate their depression. TBBPA-DHEE exposure could inhibit the secretion of neurotransmitters. Transcriptomics studies show that TBBPA-DHEE can significantly affect gene expression, and a total of 334 differentially expressed genes are enriched. GO function enrichment analysis shows that TBBPA-DHEE exposure can significantly affect the expression of genes related to synapses and cell components. KEGG function enrichment analysis shows that TBBPA-DHEE exposure can significantly affect the expression of signal pathways related to nerves, nerve development, and signal transduction. Susceptibility analysis showed that female rats were more susceptible to TBBPA-DHEE exposure than male rats. Therefore, TBBPA-DHEE exposure has neurodevelopmental toxicity to male developmental rats, and female developmental rats are more susceptible than male developmental rats. Its possible molecular mechanism is that TBBPA-DHEE may inhibit the secretion of neurotransmitters and affect signal pathways related to neurodevelopment and signal transduction.

Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.

Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Bisphenols and brominated bisphenols induced endothelial dysfunction via its disruption of endothelial nitric oxide synthase.

Emerging literatures have concentrated on the association between cardiovascular diseases risk of typical endocrine disruptor bisphenols, which also put forward the further studies need respect to the potential mechanism. Herein, we investigated the endothelial dysfunction effects of bisphenols and brominated bisphenols involved in aortic pathological structure, endothelial nitric oxide synthase (eNOS) protein phosphorylation, synthase activity and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice. Bisphenol A (BPA) and bisphenol S (BPS) increased NO production by 85.7% and 68.8% at 10-6 M level in vitro and 74.3%, 41.5% in vivo, respectively, while tetrabromobisphenol S (TBBPS) significantly inhibited NO by 55.7% at 10-6 M in vitro and 28.9% in vivo at dose of 20 mg/kg BW/d. Aortic transcriptome profiling revealed that the process of 'regulation of NO mediated signal transduction' was commonly induced. The mRNA and protein expression of phosphorylated eNOS at Ser1177 were promoted by BPA and BPS but decreased by TBBPA and TBBPS in HUVECs. Phosphorylation and enzymatic activity of eNOS were significantly increased by 43.4% and 13.8% with the treatment of BPA and BPS at 10-7 M, but decreased by 16.9% after exposure to TBBPS at 10-6 M in vitro. Moreover, only TBBPS was observed to increase aorta thickness significantly in mice and induce endothelial dysfunction. Our work suggests that bisphenols and brominated bisphenols may exert adverse outcome on vascular health differently in vitro and in vivo, and emphasizes areas of public health concern similar endocrine disruptors vulnerable on the vascular endothelial function.

Debromination of novel brominated flame retardants using Zn-based additives: A viable thermochemical approach in the mitigation of toxic effects during e-waste recycling.

Brominated flame retardants (BFRs) are bromine-bearing additives added to the polymeric fraction in various applications to impede fire ignition. The Stockholm Convention and various other legislations abolished legacy BFRs usage and hence, the so-called novel BFRs (NBFRs) were introduced into the market. Recent studies spotlighted their existence in household dust, aquifers and aquatic/aerial species. Co-pyrolysis of BFRs with metal oxides has emerged as a potent chemical recycling approach that produces a bromine-free stream of hydrocarbon. Herein, we investigate the debromination of two prominent two NBFRs; namely tetrabromobisphenol A 2,3-dibromopropyl ether (TD) and tetrabromobisphenol A diallyl ether (TAE) through their co-pyrolysis with zinc oxide (ZnO) and franklinite (ZnFe2O4). Most of the zinc content in electrical arc furnace dust (EAFD) exists in the form of these two metal oxides. Conversion of these metal oxides into their respective bromides could also assist in the selective extraction of the valuable zinc content in EAFD. The debromination potential of both oxides was unveiled via a multitude of characterization studies to analyze products (char, gas and condensates). The thermogravimetric analysis suggested a pyrolytic run up to 500 °C and the TAE treatment with ZnO produced only a trivial amount of brominated compounds (relative area, 0.83%). Phenol was the sole common compound in condensable products; potentially formed by the ß-scission debromination reaction from the parental molecular skeleton. Inorganic compounds and methane were the major constituents in the gaseous products. The pyrochar analyses confirmed the presence of metal bromides retained in the residue, averting the bromine release into the atmosphere. The ion chromatography analysis portrayed <8% of HBr gas release into the atmosphere upon pyrolysis with ZnO. The ZnO dominance herein envisaged further probes into other spinel ferrites in combating brominated polymers.