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.

The brominated flame retardant tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) as well as hexabromocyclododecane lead to lipid disorders in mice.

The brominated flame retardant tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) is a recommended substitute for hexabromocyclododecane (HBCD), a banned persistent organic pollutant, yet its potential toxicities remains largely unexplored. Here, we investigated the effects of a long-term exposure to TBBPA-DBMPE at nominal doses of 50 and 1000 µg/kg/d on lipid homeostasis in CD-1 mice, in comparison with 50 µg/kg/d HBCD as a positive control. Male pups received chemical treatments through maternal administration via drinking water from postnatal day 0-21, followed by direct administration through drinking water after weaning. On the 23rd week after treatment, the oral lipid tolerance test revealed that low-dose TBBPA-DBMPE as well as HBCD affected lipid tolerance, although the fasting serum triglyceride (TG) levels were not altered. When chemical treatment was extended to the 32nd week, TBBPA-DBMPE-treated animals displayed adipocyte hypertrophy in both white adipose tissue (eWAT) and brown adipose tissue (BAT) and hepatic steatosis, which was largely consistent with the effects of HBCD. These findings indicate that like HBCD, TBBPA-DBMPE led to increased lipid load in mice. Interestingly, we also observed intestinal histological changes, coupled with increased expression of lipid absorption-related genes in both HBCD and TBBPA-DBMPE treatments, suggesting increased lipid absorption. This was supported by in vitro findings that both HBCD and TBBPA-DBMPE promoted lipid accumulation in IEC-6 cells under the stress of oleic acid for 6 h, implying that altered lipid absorption by the intestine may partly contributed to increased lipid load in mice. Overall, the effects of 50 µg/kg/d TBBPA-DBMPE in terms of some parameters were comparable with 50 µg/kg/d HBCD, suggesting that TBBPA-DBMPE may not be an ideal substitute of HBCD.

Novel Insights into Uptake, Translocation, and Transformation Mechanisms of 2,2',4,4'-Tetra Brominated Diphenyl Ether (BDE-47) in Wheat (Triticum aestivum L.): Implication by Compound-Specific Stable Isotope and Transcriptome Analysis.

The uptake, translocation, and transformation of 2,2',4,4'-tetra brominated diphenyl ether (BDE-47) in wheat (Triticum aestivum L.) were comprehensively investigated by hydroponic experiments using compound-specific stable isotope analysis (CSIA) and transcriptome analysis. The results indicated that BDE-47 was quickly adsorbed on epidermis of wheat roots and then absorbed in roots via water and anion channels as well as an active process dependent on energy. A small fraction of BDE-47 in roots was subjected to translocation acropetally, and an increase of δ13C values in shoots than roots implied that BDE-47 in roots had to cross at least one lipid bilayer to enter the vascular bundle via transporters. In addition, accompanied by the decreasing concentrations, δ13C values of BDE-47 showed the increasing trend with time in shoots, indicating occurrence of BDE-47 transformation. OH-PBDEs were detected as transformation products, and the hydroxyl group preferentially substituted at the ortho-positions of BDE-47. Based on transcriptome analysis, genes encoding polybrominated diphenyl ether (PBDE)-metabolizing enzymes, including cytochrome P450 enzymes, nitrate reductases, and glutathione S-transferases, were significantly upregulated after exposure to BDE-47 in shoots, further evidencing BDE-47 transformation. This study first reported the stable carbon isotope fractionation of PBDEs during translocation and transformation in plants, and application of CSIA and transcriptome analysis allowed systematically characterize the environmental behaviors of pollutants in plants.

Spatial and temporal change of tetrabromobisphenol A and hexabromocyclododecane in mangrove sediments from the Pearl River Estuary, South China.

Spatial and temporal trends of tetrabromobisphenol (TBBPA) and hexabromocyclododecane (HBCD) in mangrove sediments from the Pearl River Estuary (PRE) in South China were evaluated. Concentrations of TBBPA and HBCD in mangrove sediments ranged from 0.23 to 13.3 and 0.36 to 54.7 ng g-1 dry weight. The highest TBBPA concentration was seen in Guangzhou mangrove wetland near a dockyard and a ferry terminal where TBBPA is utilized in the coatings for the shipbuilding industry. The rapid development of building might elucidate the higher concentrations of HBCD in Shenzhen mangrove sediments. γ-HBCD and α-HBCD was the two main diastereoisomer of HBCD in mangrove sediments with contributions of 56.1 % and 34.0 %. Sediments from the three PRE mangrove ecosystems were selectively enriched for (-)-γ-HBCD. TBBPA concentrations in mangrove sediments from Guangzhou rose during 2012-2015 and declined from 2015 to 2021. HBCD concentrations in the PRE mangrove sediments exhibited an increasing trend from 2012 to 2021.

Serum levels of polychlorinated biphenyls and polybrominated diphenyl ethers in early pregnancy and their associations with gestational diabetes mellitus.

Polychlorinated Biphenyls (PCBs) and Polybrominated Diphenyl Ethers (PBDEs) are extensively present in humans and may disturb glucose metabolism during pregnancy. However, previous reports on the associations between PCBs/PBDEs levels and gestational diabetes mellitus (GDM) have been inconsistent. We performed a nested case-control study to measure the serum levels of 6 PCB and 7 PBDE congeners in early pregnancy, and to assess their associations with GDM risk and blood glucose levels. Totally, 208 serum samples (104 GDM cases and 104 controls) were included based on a prospective cohort which was carried out in Jiangsu province, China, from 2020 to 2022. The results showed that PCB-153 was the major PCB congener, whereas PBDE-47 was the predominant PBDE congener. The continuous concentrations of PCB-153, PBDE-28, and total PCB were significantly related to an increased risk of GDM, with adjusted ORs (95%CI) of 1.25 (1.04-1.50), 1.19 (1.02-1.39), and 1.37 (1.05-1.79), respectively. Potential dose-response relationships were also observed between serum levels of PCB-153 (P = 0.011), PBDE-28 (P = 0.028), total PCB (P = 0.048), and total PCB/PBDE (P = 0.010) and GDM risk. Moreover, PCB-153, PBDE-28 and total PCB levels were positively related to 1-h OGTT blood glucose (adjusted ßPCB-153: 0.14, 95%CI: 0.00-0.28; adjusted ßPBDE-28: 0.20, 95%CI: 0.08-0.32; adjusted ßtotal PCB: 0.30, 95%CI: 0.09-0.50), whereas none of the PCBs/PBDEs were statistically related to fasting blood glucose and 2-h OGTT blood glucose (all P > 0.05). Further meta-analysis also supported the association of PCBs exposure with GDM risk. Our study provides further evidence that PCBs/PBDEs exposure may increase GDM risk during pregnancy.

Sensitive method for simultaneous determination of TBBPA and its ten derivatives.

Tetrabromobisphenol A (TBBPA) and its derivatives are regarded as new contaminants, raising much attention on their environmental occurrence and fates. However, the sensitive detection of TBBPA and its main derivatives is still a great challenge. This study investigated a sensitive method for simultaneous detection of TBBPA and its ten derivatives using high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (HPLC-MS/MS) with atmospheric pressure chemical ionization (APCI) source. The method exhibited much better performance than previously reported methods. Furthermore, it was successfully applied in determining complicated environmental samples, including sewage sludge, river water and vegetable samples with concentration range from undetected (n.d.) to 25.8 ng g-1 dry weight (dw). For sewage sludge, river water and vegetable samples, the spiking recoveries of TBBPA and its derivatives ranged from 69.6 ± 7.0% to 86.1 ± 12.9%, 69.5 ± 13.9% to 87.5 ± 6.6%, and 68.2 ± 5.6% to 80.2 ± 8.3%, respectively; the accuracy ranged from 94.9 ± 4.6% to 113 ± 5%, 91.9 ± 10.9% to 112 ± 7%, and 92.1 ± 5.1% to 106 ± 6%, and the method quantitative limits ranged from 0.00801 to 0.224 ng g-1 dw, 0.0104-0.253 ng L-1, and 0.00524-0.152 ng g-1 dw, respectively. Moreover, the present manuscript describes for the first time the simultaneous detection of TBBPA and ten derivatives from various environmental samples, providing fundamental work for further research on their environmental occurrences, behaviors and fates.

Sensitive Instrumental Method for Quantitative Determination of High-Brominated Flame Retardants in Human Serum Samples.

BACKGROUND: High-brominated flame retardants (BFRs) can be released into the environment from consumer products, such as electric and electronic equipment, and enter the human body by different pathways. Because of their toxicity and the regulations, it is very relevant to know their levels and trends in human samples. However, chromatographic serum analysis of some of these compounds represents nowadays a challenge in the general population. OBJECTIVE: To optimize and validate an instrumental method based on gas chromatography coupled to mass spectrometry, which, together with a simple sample preparation procedure, allows the analysis of decabromodiphenyl ether (BDE-209), decabromodiphenyl ethane (DBDPE), and tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-DBPE) in human serum samples from the general population. METHOD: To minimize the high degradation during instrumental analysis, GC parameters such as injection volumes, carrier flow rates, and column lengths were assessed and optimized. This instrumental approach in combination with solid-phase extraction (SPE) followed by multilayer silica gel column purification allowed satisfactory analysis using only 1 mL of serum. RESULTS: The performance of the complete method was evaluated at three spiking levels, 0.01, 0.05, and 0.2 ng/mL. Recoveries in the range 87-108% were obtained whereas the relative standard deviation in interday measurements, were, in general, lower than 19%. Limits of detection were in the range of 0.0045-0.0070 ng/mL. The optimized procedure was successfully applied to the determination of the investigated pollutants in real human samples of general population. CONCLUSIONS: The proposed method could contribute to the inclusion of these environmental pollutants in human biomonitoring (HBM) studies, increasing the knowledge of levels and trends in the general population. HIGHLIGHTS: GC-MS parameters optimization to minimize instrumental analytes degradation. Successful application to human serum samples from the general population. Tetrabromobisphenol A bis(2,3-dibromopropyl ether) human serum levels are reported for the first time.

Identification of lower brominated bisphenol A analogs as the photooxidation products of tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE).

The transformation products and mechanism of tetrabromobisphenol A (TBBPA) derivatives are still largely unknown compared with TBBPA. In this paper, sediment, soil and water samples (15 sites, 45 samples) collected in a river flowing through brominated flame retardant manufacturing zone were analyzed to determine TBBPA derivatives, byproducts, and transformation products. TBBPA derivatives and byproducts were detected with concentrations ranging from none detection to 1.1 × 104 ng/g dw and with detection frequencies of 0-100 % in all samples. The concentrations of TBBPA derivatives such as TBBPA bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) and TBBPA bis(allyl ether) in sediment and soil samples were higher than that of TBBPA. In addition, the occurrence of various unknown bromobisphenol A allyl ether analogs in the samples was further confirmed by using 11 synthesized analogs, which might be produced during the waste treatment process of the factories. The possible transformation pathways of TBBPA-BDBPE were revealed for the first time by using UV/base/persulfate (PS) as designed photooxidation waste treatment system in the laboratory. Ether bond cleavage, debromination, and ß-scission contributed to the transformation of TBBPA-BDBPE and the occurrence of transformation products in the environment. The concentrations of the transformation products of TBBPA-BDBPE ranged from none detection to 3.4 × 102 ng/g dw. These data provide new insights into the fate of TBBPA derivatives in environmental compartments.

Prediction of Thermogravimetric Data in Bromine Captured from Brominated Flame Retardants (BFRs) in e-Waste Treatment Using Machine Learning Approaches.

The principal objective in the treatment of e-waste is to capture the bromine released from the brominated flame retardants (BFRs) added to the polymeric constituents of printed circuits boards (PCBs) and to produce pure bromine-free hydrocarbons. Metal oxides such as calcium hydroxide (Ca(OH)2) have been shown to exhibit high debromination capacity when added to BFRs in e-waste and capturing the released HBr. Tetrabromobisphenol A (TBBA) is the most commonly utilized model compound as a representative for BFRs. Our coauthors had previously studied the pyrolytic and oxidative decomposition of the TBBA:Ca(OH)2 mixture at four different heating rates, 5, 10, 15, and 20 °C/min, using a thermogravimetric (TGA) analyzer and reported the mass loss data between room temperature and 800 °C. However, in the current work, we applied different machine learning (ML) and chemometric techniques involving regression models to predict the TGA data at different heating rates. The motivation of this work was to reproduce the TGA data with high accuracy in order to eliminate the physical need of the instrument itself, so that this could save significant experimental time involving sample preparation and subsequently minimizing human errors. The novelty of our work lies in the application of ML techniques to predict the TGA data from e-waste pyrolysis since this has not been conducted previously. The significance of our work lies in the fact that e-waste is ever increasing, and predicting the mass loss curves faster will enable better compositional analysis of the e-waste samples in the industry. Three ML models were employed in our work, namely Linear, random forest (RF), and support vector regression (SVR), out of which the RF method exhibited the highest coefficient of determination (R2) of 0.999 and least error of prediction as estimated by the root mean squared error (RMSEP) at all 4 heating rates for both pyrolysis and oxidation conditions. An 80:20 split was used for calibration and validation data sets. Furthermore, for showing versatility and robustness of the best-predicting RF model, it was also trained using all the data points in the lower heating rates of 5 and 10 °C/min and predicted on all the data points for the higher heating rates of 15 and 20 °C/min to again obtain a high R2 of 0.999. The excellent performance of the RF model showed that ML techniques can be used to eliminate the physical use of TGA equipment, thus saving experimental time and potential human errors, and can further be applied in other real-time e-waste recycling scenarios.

A Review on Tetrabromobisphenol A: Human Biomonitoring, Toxicity, Detection and Treatment in the Environment.

Tetrabromobisphenol A (TBBPA) is a known endocrine disruptor employed in a range of consumer products and has been predominantly found in different environments through industrial processes and in human samples. In this review, we aimed to summarize published scientific evidence on human biomonitoring, toxic effects and mode of action of TBBPA in humans. Interestingly, an overview of various pretreatment methods, emerging detection methods, and treatment methods was elucidated. Studies on exposure routes in humans, a combination of detection methods, adsorbent-based treatments and degradation of TBBPA are in the preliminary phase and have several limitations. Therefore, in-depth studies on these subjects should be considered to enhance the accurate body load of non-invasive matrix, external exposure levels, optimal design of combined detection techniques, and degrading technology of TBBPA. Overall, this review will improve the scientific comprehension of TBBPA in humans as well as the environment, and the breakthrough for treating waste products containing TBBPA.

Binding of Tetrabromobisphenol A and S to Human Serum Albumin Is Weakened by Coexisting Nanoplastics and Environmental Kosmotropes.

Human serum albumin (HSA) was used as a model protein to explore the effects of brominated flame retardant (BFR) binding and the corona formation on polystyrene nanoplastics (PNs). Under physiological conditions, HSA helped to disperse PNs but promoted the formation of aggregates in the presence of tetrabromobisphenol A (TBBPA, ΔDh = 135 nm) and S (TBBPS, ΔDh = 256 nm) at pH 7. At pH 4, these aggregates became larger with fewer electrostatic repulsion effects (ΔDh = 920 and 691 nm for TBBPA and TBBPS, respectively). However, such promotion effects as well as BFR binding are different due to structural differences of tetrabromobisphenol A and S. Environmental kosmotropes efficiently stabilized the structure of HSA and inhibited BFR binding, while the chaotropes favored bioconjugated aggregate formation. Such effects were also verified in natural seawater. The newly gained knowledge may help us anticipate the behavior and fate of plastic particles and small molecular pollutants in both physiological and natural aqueous systems.

First insight into accumulation of characteristics and tissue distribution of PCBs, PBDEs, and other BFRs in the living Indonesian coelacanth (Latimeria menadoensis).

Persistent organic pollutants, including polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and other brominated flame retardants, were detected in the liver, muscle, and ovary tissues of the Indonesian coelacanth (Latimeria menadoensis) incidentally caught around Gangga Island, North Sulawesi Province, Indonesia, on November 5, 2014. Concentrations of total PCBs (209 congeners, 300-2600 ng g-1 lipid weight) in all tissues showed higher than those of PBDEs (41 congeners, 3.9-6.3 ng g-1 lw) and BTBPE (1.1-3.6 ng g-1 lw). The tissue-specific PCB and PBDE profiles were likely due to differences in the lipid composition. Toxic equivalent (TEQ) values of dioxin-like PCBs in coelacanth tissues were lower than the benchmark values for early-life fish. However, compared with the data reported for deep-sea fishes in the Pacific and Indian Oceans, the relatively high concentrations of PCBs detected in this study raise concerns regarding Indonesian coelacanth conservation and habitat conditions.

Utility of an alternative method (to USEPA Method 1613) for analysis of priority persistent organic pollutants in soil from mixed industrial-suburban areas of Durban, South Africa.

This study evaluates the adequacy of a USEPA Method 1613 alternative analytical method for analysis of persistent organic pollutants (POPs) in soil from the immediate vicinity of industrialized areas in the eThekwini municipal area in South Africa. The objective of this study is in line with the Stockholm Convention Article 11 on research, development, and monitoring. Furthermore, it became imperative to find an alternative analytical procedure to USEPA Method 1613 that could cater to studies conducted in Africa where recent reviews have indicated that most African countries lack the technical and instrumental capacity for performing analysis of dioxin-like compounds according to USEPA Method 1613, which entails the use of high-resolution chromatography and high-resolution mass spectrometry instrumentation. The study aimed to ascertain the utility of an alternative two-dimensional gas chromatography-time of flight mass spectrometry method for analysis of trace-level priority POPs in soil, along with a fast single quadrupole gas chromatography-mass spectrometry method. The analytical methods were applied to the analysis of POPs on soil samples from industrial areas with oil refineries and a pulp and paper manufacturing company, while other samples were collected near the electricity substations and a landfill site. Analytical results showed BDE 209 as the dominant contaminating polybrominated diphenyl ether (concentration ranges from 0.006 to 5.71 ng g-1 ). Polybrominated biphenyls (PBBs) 9, 10, and 49 were the dominant PBBs detected in 78% of the sites tested, although their concentrations were below the limit of quantification (LOQ). Polychlorinated dibenzo-p-dioxins and furans and dioxin-like polychlorinated biphenyls detected could not be quantified above their respective LOQs, indicating that the Durban area has low priority pollutant contamination levels compared to other regions around the world. The methods developed are a starting point that will inform considerations for routine evaluation and management of soil contamination, which plays a vital role in environmental management. Integr Environ Assess Manag 2023;19:749-762. © 2022 SETAC.

A transcriptomic-based analysis predicts the neuroendocrine disrupting effect on adult male and female zebrafish (Danio rerio) following long-term exposure to tetrabromobisphenol A bis(2-hydroxyethyl) ether.

Endocrine-disrupting chemicals (EDCs) are now ubiquitously distributed in the environment. Tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) pollution in environment media poses a significant threat to humans and aquatic organisms as a result of its potential neurotoxicity and endocrine-disrupting effect. The endocrine-disrupting effects of TBBPA-DHEE on aquatic organisms, however, have received limited attention. In this study, the neurotoxicity and reproductive endocrine-disruptive effect of TBBPA-DHEE was evaluated by observing the neurobehavioral changes, vitellogenin (VTG), testosterone, 17ß-estradiol and gene expression levels in adult male and female zebrafish exposed to TBBPA-DHEE (0.05, 0.2 and 0.3 mg/L) for 100 days. Furthermore, transcriptomic analysis was conducted to unravel other potential neuroendocrine-disrupting mechanism. Our result showed TBBPA-DHEE significantly (p < 0.05) altered the locomotor behavior and motor coordination abilities in both sexes. Steroid hormone and VTG levels were also altered indicating the neuroendocrine-disrupting effect of TBBPA-DHEE on the hypothalamic-pituitary-gonadal-axis. A total of 1568 genes were upregulated and 542 genes downregulated in males, whereas, 1265 upregulated and 535 downregulated genes were observed in females. The KEGG enrichment analysis showed that cell cycle and p55 signaling pathways were significantly enriched due to TBBPA-DHEE exposure. These pathways and its component genes are potential target of EDCs. The significant upregulation of genes in these pathways could partly explain the neuroendocrine disrupting effect of TBBPA-DHEE. The observed toxic effects of TBBPA-DHEE observed in this study is confirmation of the endocrine-disrupting toxicity of this chemical which would be valuable in biosafety evaluation and biomonitoring of TBBPA-DHEE for public health purposes.

The potential mechanisms of TBBPA bis(2-hydroxyethyl) ether induced developmental neurotoxicity in juvenile zebrafish (Danio rerio).

TBBPA bis(2-hydroxyethyl) ether (TBBPA-DHEE), one of the main derivatives of TBBPA, has been widely detected in environmental samples and been discovered to be potential neurotoxic. In this study, the juvenile zebrafish were selected as the research subject to explore the neurotoxicity and its mechanism of low-dose TBBPA-DHEE exposure, and to reveal the neurotoxicity susceptibility in different sexes. Behavioral studies revealed that TBBPA-DHEE could significantly reduce the swimming velocity, maximum acceleration and cumulative duration of high-speed mobility, significantly increasing the cumulative duration of low-speed mobility and average social distance. It significantly reduced the contents of ATP, glutamate and Ca2+ in the whole brain. The histopathological study demonstrated that TBBPA-DHEE could cause brain tissue damage in female and male juvenile zebrafish. The comprehensive data analysis indicated that female zebrafish were more susceptible to TBBPA-DHEE exposure than male zebrafish. Transcriptomic analysis showed that TBBPA-DHEE could significantly affect the expressions of behavioral and development-related genes. Furthermore, female and male juvenile zebrafish have different molecular mechanisms of neurotoxicity. For female juvenile zebrafish, the potential mechanism of neurotoxicity could be that it interfered with the feedback regulation of nerves by affecting the related genes expressions in the signaling pathways such as Ca2+ signaling, Wnt signaling and synapses. For male juvenile zebrafish, the potential mechanism of neurotoxicity may be through affecting the expression of related genes in hormones and neuro-related genes. This research could reveal the potential neurotoxicity of TBBPA-DHEE to aquatic organisms, which will be helpful to reveal the health effects of the emerging environmental pollutants.

Pristina longiseta reproduction test: chronic exposure to environmental contaminants.

Aquatic worms are considered a suitable group to evaluate the effects of contaminants on the environment, although one of the main challenges is to use the species of local occurrence. Recently, Pristina longiseta was suggested to be used in acute bioassays. In this context, this study aimed to establish a chronic exposure for ecotoxicological bioassays using the cosmopolitan species of occurrence in Brazilian freshwater P. longiseta. Firstly, we tested three exposure times (4, 7, and 10 days) under the presence or absence of aeration for reproduction outputs. After determining the best configuration (7 days without aeration), we assessed the effects of the chronic exposures using the standardized reference substance potassium chloride (KCl), the antibiotic sulfamethoxazole (SMX), the flame retardant tetrabromobisphenol A (TBBPA), and the sugarcane vinasse. Our results showed suitability for applying the chronic exposure using P. longiseta and indicated the sensitivity of the offspring to KCl (EC50-7d = 0.51 g/L). Sulfamethoxazole and TBBPA caused a significant decrease in the offspring of P. longiseta (EC50-7d = 59.9 µg/L and < 62.5 µg/L, respectively). Sugarcane vinasse showed high toxicity for the species, and 4.26% of vinasse was calculated as EC50-7d. Therefore, the described protocol was successfully applied as an ecotoxicological bioassay to evaluate the effects of environmental contaminants on the reproduction rate of the freshwater worm P. longiseta.

Breast adipose metabolites mediates the association of tetrabromobisphenol a with breast cancer: A case-control study in Chinese population.

Studies exploring the association of tetrabromobisphenol A (TBBPA) with breast cancer and related mechanisms are limited. To investigate the relationship between TBBPA levels in breast adipose and breast cancer, we carried out case-control research. As well as further examine the mediating role of adipose metabolites between TBBPA and breast cancer using the metabolomics approach. In this study, the concentration of TBBPA was determined utilizing ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after a solid phase extraction (SPE) pretreatment. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was employed to analyze adipose metabolomics. Evaluation of metabolites linked to TBBPA exposure and breast cancer was performed utilizing mediation analysis. With an estimated OR (95%CI) of 1.153 (1.023, 1.299), TBBPA was firmly linked with breast cancer. We also used propensity score matching analysis and sensitivity analysis to reduce the effect of confounding factors on the results. Metabolomics of adipose suggested significant perturbation in the linoleic acid metabolism pathway. In addition, for PC (16:0/16:0) as phospholipids, a mediation effect on the associations of TBBPA exposure with breast cancer risks was observed (estimated mediation percentage: 56.58%). Understanding the relationship between TBBPA exposure and the risk of breast cancer may be facilitated by the findings, which point to potential mediation metabolites.

Determination of Apoptotic Mechanism of Action of Tetrabromobisphenol A and Tetrabromobisphenol S in Human Peripheral Blood Mononuclear Cells: A Comparative Study.

BACKGROUND: Tetrabromobisphenol A (TBBPA) is the most commonly used brominated flame retardant (BFR) in the industry. TBBPA has been determined in environmental samples, food, tap water, dust as well as outdoor and indoor air and in the human body. Studies have also shown the toxic potential of this substance. In search of a better and less toxic BFR, tetrabromobisphenol S (TBBPS) has been developed in order to replace TBBPA in the industry. There is a lack of data on the toxic effects of TBBPS, while no study has explored apoptotic mechanism of action of TBBPA and TBBPS in human leukocytes. METHODS: The cells were separated from leucocyte-platelet buffy coat and were incubated with studied compounds in concentrations ranging from 0.01 to 50 µg/mL for 24 h. In order to explore the apoptotic mechanism of action of tested BFRs, phosphatidylserine externalization at cellular membrane (the number of apoptotic cells), cytosolic calcium ion and transmembrane mitochondrial potential levels, caspase-8, -9 and -3 activation, as well as PARP-1 cleavage, DNA fragmentation and chromatin condensation in PBMCs were determined. RESULTS: TBBPA and TBBPS triggered apoptosis in human PBMCs as they changed all tested parameters in the incubated cells. It was also observed that the mitochondrial pathway was mainly involved in the apoptotic action of studied compounds. CONCLUSIONS: It was found that TBBPS, and more strongly TBBPA, triggered apoptosis in human PBMCs. Generally, the mitochondrial pathway was involved in the apoptotic action of tested compounds; nevertheless, TBBPS more strongly than TBBPA caused intrinsic pathway activation.

Transcriptomic sequencing reveals the potential molecular mechanism by which Tetrabromobisphenol A bis (2-hydroxyethyl ether) exposure exerts developmental neurotoxicity in developing zebrafish (Danio rerio).

Tetrabromobisphenol A bis (2-hydroxyethyl ether) (TBBPA-DHEE) is a derivative of Tetrabromobisphenol A (TBBPA) used as an intermediate flame retardant in engineering polymers. The mechanism of neurodevelopmental toxicity of TBBPA-DHEE remains unclear due to limited toxicological data. We performed behavioral and transcriptomic analyses to assess the neurodevelopmental effects of TBBPA-DHEE on developing zebrafish and potential toxicity mechanisms. Our result shows that exposure to TBBPA-DHEE significantly increased mortality, deformity rate, and reduction in hatch rate, hatchability, and body length relative to the DMSO control. The behavior analysis indicates that TBBPA-DHEE significantly reduced the spontaneous movement of larva compared to the control. The TSH and GH levels were significantly reduced in all the exposure groups in a concentration-dependent manner relative to the DMSO control. TBBPA-DHEE exhibited a significant reduction in locomotor activity across all the exposure groups in the light/dark locomotion test. The transcriptomic analysis result shows that 579 genes were differentially expressed. KEGG analysis shows the enrichment of complement cascade, JAK-STAT signaling pathway, cytokine-cytokine interaction, and phototransduction pathway resulting in a change in mRNA expression of their genes. These observed changes in developmental endpoints, hormonal level, and alteration in mRNA expression of component genes involved in neurodevelopmental pathways could be part of the possible mechanism of the observed toxic effects of TBBPA-DHEE exposure on zebrafish. This study could reveal the possible neurodevelopmental toxicity of TBBPA-DHEE to aquatic species, which could help uncover the health implications of emerging environmental contaminants.

Characterization and Interpolation of Sediment Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers in Resident Killer Whale Habitat along the Coast of British Columbia, Canada.

The northeastern Pacific northern and southern resident killer whale (Orcinus orca) populations are listed as threatened and endangered in Canada, respectively, with persistent, bioaccumulative contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), posing threats to their recovery. Concentrations of PCBs and PBDEs in subtidal surface sediments collected from 97 sites along the British Columbia (BC) coast were used to identify their distribution and profiles, and to assess killer whale habitat quality. Victoria Harbour (VH3(site ID: 1) ) sediments exhibited the highest PCB and PBDE concentrations. For PCBs, PCB-138 was found at the highest concentration, followed by PCB-153, PCB-110, PCB-149, PCB-101, and PCB-118. For PBDEs, individual congeners were ranked as follows: BDE-209 > BDE-207 > BDE-206 > BDE-208 > BDE-47 > BDE-99. Principal component analyses (PCA) illustrated the variations in contaminant profiles, with PC1 for PCBs and PBDEs correlated with the octanol-water partition coefficient (log KOW , p < 0.003). Based on the PCA, sediment particle size, total organic carbon (TOC), and water depth at collection were other factors associated with the distribution of PBDEs, while PCB profiles were associated with TOC. Total PCB and PBDE concentrations at 100% and 34% of the sites, respectively, exceeded the recently adopted British Columbia's Ministry of Environment and Climate Change Strategy Working Sediment Quality Guidelines (PCBs 3.7 pg/g dry wt and PBDEs 1000 pg/g dry wt), considered protective of killer whales. Our findings suggest that the legacy of banned PCBs and PBDEs has the potential to constrain the recovery of killer whales as a result of their mobilization from sediments and consequent uptake by marine food webs. Environ Toxicol Chem 2022;41:2139-2151. © 2022 SETAC.