Comprehensive analysis of environmental exposure to hazardous trace elements and lung function: a national cross-sectional study.

BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Construction of Models To Predict the Effectiveness of E-Waste Control through Capture of Volatile Organic Compounds and Metals/Metalloids Exposure Fingerprints: A Six-Year Longitudinal Study.

The significant health implications of e-waste toxicants have triggered the global tightening of regulation on informal e-waste recycling sites (ER) but with disparate governance that requires effective monitoring. Taking advantage of the opportunity to implement e-waste control in the Guiyu ER since 2015, we investigated the temporal variations in levels of oxidative DNA damage, 25 volatile organic compound metabolites (VOCs), and 16 metals/metalloids (MeTs) in urine in 918 children between 2016 and 2021 to demonstrate the effectiveness of e-waste control in reducing population exposure risks. The hazard quotients of most MeTs and levels of 8-hydroxy-2'-deoxyguanosine in children decreased significantly during this time, indicating that e-waste control effectively reduces the noncarcinogenic risks of MeT exposure and levels of oxidative DNA damage. Using mVOC-derived indexes as a feature, a bagging-support vector machine algorithm-based machine learning model was constructed to predict the extent of e-waste pollution (EWP). The model exhibited excellent performance with accuracies >97.0% in differentiating between slight and severe EWP. Five simple functions established using mVOC-derived indexes also had high accuracy in predicting the presence of EWP. These models and functions provide a novel human exposure monitoring-based approach for assessing e-waste governance or the presence of EWP in other ERs.

Why Do People Gain Belly Fat in Rural Areas? A Study of Urinary Metal(loid)s and Abdominal Obesity in China.

Obesity is prevalent in rural areas of China, and there are inconsistent findings regarding the association between metal(loid) exposure and the risk of obesity. Abdominal obesity (AOB), which reflects visceral fat abnormity, is a crucial factor in studying obesity-related diseases. We conducted a study measuring 20 urinary metal(loid)s, 13 health indicators, and the waist circumference (WC) in 1849 participants from 10 rural areas of China to investigate their relationships. In the single exposure models, we found that urinary chromium (Cr) was significantly associated with the odds of having AOB [adjusted odds ratio (OR) = 1.81 (95% confidence interval (CI): 1.24, 2.60)]. In the mixture exposure models, urinary Cr consistently emerged as the top contributor to AOB, while the overall effect of mixed metal(loid)s was positive toward the odds of having AOB [adjusted OR: 1.33 (95% CI: 1.00, 1.77)], as revealed from the quantile g-computation model. After adjusting for the effects of other metal(loid)s, we found that the elevation of apolipoprotein B and systolic blood pressure significantly mediated the association between urinary Cr and the odds of having AOB by 9.7 and 19.4%, respectively. Our results suggest that exposure to metal(loid)s is a key factor contributing to the prevalence of AOB and WC gain in rural areas of China.

Sorption in soils and bioaccumulation potential of 2,2'-DiBBPA.

2,2'-Dibromobisphenol A (2,2'-DiBBPA) is frequently detected in the environment. However, the mobility of 2,2'-DiBBPA in the soil environment is poorly understood. The present study examined the effects of soil components such as the NaClO-resistant fraction, dithionite-citrate-bicarbonate -demineralized fraction, humin fraction, black carbon, DOC-removed fraction, exogenous dissolved organic carbon and heavy metal cations on the adsorption of 2,2'-DiBBPA on several types of agricultural soils. The adsorption isotherms on soils and soil components were well fitted to the linear isotherm equation. 2,2'-DiBBPA sorption onto soils was dominated by soil organic matter content (SOM) and affected by exogenous dissolved organic carbon. Linear regression relationships between adsorption capacity (Kd) and soil characteristics were evaluated to predict partitioning of 2,2'-DiBBPA. Black carbon played a predominant role in the adsorption of 2,2'-DiBBPA. Heavy metal ions significantly inhibited the adsorptive behavior of 2,2'-DiBBPA under alkaline conditions. Semiempirical linear relationships were observed between biota-sediment accumulation factors (1.18-2.47)/logarithm of bioconcentration factors (BCFs, 2.49-2.52) of 2,2'-DiBBPA in lugworms and Kd. These results allow for the prediction of the bioaccumulation of 2,2'-DiBBPA in other soils. Furthermore, values of log BCF > 1.0 indicate the preferential bioaccumulation of 2,2'-DiBBPA in biota. These data are of significance for understanding the migration of 2,2'-DiBBPA in agricultural soils and bioaccumulation in organisms.

Changes in molybdenum bioaccessibility in four spiked soils with respect to soil pH and organic matter.

Investigation of the inherent relationship between soil physicochemical properties and pollutant's bioaccessibility (BAc) by analyzing different soil types may produce erroneous results or bias, owing to the complexity of natural soil characteristics. However, use of single factor analysis (e.g., soil pH, organic matter) facilitates evaluation of the transition. In this study, the inherent relationship between soil properties and the BAc of molybdenum (Mo) was evaluated in two typical variable-charge soils (Ferralosol and Ferrosol) and constant-charge soils (Alfisol and Inceptisol) spiked with Mo after adjusting their pH and organic carbon content. The Unified Bioaccessibility Research Group of Europe (BARGE) Method (UBM) was applied to evaluate the BAc of Mo in the gastric and intestinal phase (GP and IP, respectively). Isothermal adsorption experiment, Tessier sequential extraction, and field emission scanning electron microscope-energy dispersive spectroscopy (FESEM-EDS) analysis were conducted on these spiked soils. The results indicated that the BAc of Mo in IP (27.42-80.41%) was significantly higher than that in GP (2.52-28.53%). A significantly lower level of BAc of Mo was found in the variable-charge soils, when compared with that in the constant-charge soils. Furthermore, significant negative correlations were identified between the BAc and adsorption of Mo, which decreased with soil pH. These negative correlations can be attributed to the increase in soil negative charge density and enhancement of Mo desorption by hydroxyl, which reinforce the repulsion between Mo and soil particles with increasing soil pH; this was further confirmed by the decrease in Mo adsorption with Alfisol pH. The Mo fractions and FESEM-EDS patterns confirmed that the BAc of Mo in GP was negatively correlated with soil organic carbon (SOC) content, possibly owing to an increase in Mo retention by SOC. These findings indicated that the health risk of Mo contamination in low pH and SOC-rich variable-charge soil is relatively low, thus providing references for rationalizing risk assessment and remediating Mo-polluted soil.

Fe3O4 loaded on ball milling biochar enhanced bisphenol a removal by activating persulfate: Performance and activating mechanism.

In this study, pristine biochar (BC), ball milling biochar (MBC), Fe3O4 modified BC (Fe3O4@BC), and Fe3O4 modified MBC (Fe3O4@MBC) were prepared to compare the Bisphenol A (BPA) removal efficiency by activating persulfate (PDS). All catalysts exhibited excellent degradation rather than adsorption in the PDS system, and Fe3O4@MBC800 had the best BPA removal efficiency, with 96.73% degradation and negligible 1.43% adsorption due to the synergistic effect between MBC800 and Fe3O4 particles. Radical quenching experiments and electron paramagnetic resonance analysis indicated radical pathways, namely, SO4∙- and ∙OH, O2∙-, and non-radical pathway (1O2) involving BPA degradation. The abundant oxygen-containing groups, increased graphitization and mesopores of MBC800, and Fe3+/Fe2+ conversion of Fe3O4 particles facilitated PDS activation to produce reactive oxygen species. In addition, the superior electrochemical performance accelerated the electron transfer between the catalyst and PDS, promoting BPA degradation in the Fe3O4@MBC800/PDS system. More importantly, Fe3O4@MBC800 is resistant to environmental interference, including pH, anions, cations, and humic acid, and has good catalytic reusability and stability, which fulfills the requirements of engineering applications. Therefore, Fe3O4 loaded on ball-milled biochar provides a convenient strategy for preparing environmentally friendly, economical, and efficient carbon-based catalysts to remove organic contaminants.

Rapid and simultaneous analysis of tetrabromobisphenol A and hexabromocyclododecane in water by direct immersion solid phase microextraction: Uniform design to explore factors.

Direct immersion solid phase microextraction (DI-SPME) coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) is of significant research interest because of its low solvent consumption, simple design, and efficient, sensitive, fast performance. In this work, a combination of these two methods (DI-SPME-LC-MS) for the determination of tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD) in water was developed. Important factors, which included temperature, stirring rate, salt concentration, pH value and adsorption time, were evaluated in for the optimization of solid phase microextraction (SPME) method. The method was developed using spiked natural waters in a concentration range of 0.1-10 ng mL-1, and showed notable linearity with regression coefficients ranging between 0.992 and 0.999. The limits of detection varied from 0.01 to 0.04 ng mL-1 (at S/N = 3) and relative standard deviation (RSD < 11%) were obtained showing that the precision of the method was reliable. Recoveries were in relatively high levels for both analytes and ranged from 88% to 108%. Moreover, in comparison with the performance time of traditional sample pretreatment methods such as solid-phase extraction (SPE), accelerated solvent extraction (ASE), and liquid-liquid extraction (LLE), DI-SPME-LC-MS takes only approximately 35 min to perform. The optimized method was successfully applied for monitoring concentrations of TBBPA and HBCD in water.

Health implication of heavy metals exposure via multiple pathways for residents living near a former e-waste recycling area in China: A comparative study.

Herein, crop (vegetables and rice, n = 30), soil (n = 14), dust (n = 12), and PM10 (n = 25) samples were collected to assess the environmental quality of a former e-waste recycling area and evaluate the related health risks. In dust and PM10, the concentrations of heavy metals (Cd, Cu, Ni, Pb, and Zn) were lower than previously reported values, although the numbers for soil, vegetables, and rice remained high. The average accumulation factors of heavy metals in crops decreased in the order of Zn > Cd > Ni > Cu > Pb, and soil was identified as the largest contributor to crop pollution. Heavy metal ingestion largely occurred via rice consumption, which accounted for a significant fraction of the total average daily dose (ADD; 75.2-86.7% in children and 78.0-91.7% in adults), especially for Cd, Cu, Ni, and Zn. However, in the case of Pb, soil ingestion accounted for 48.9% of the ADD in adults, while in children, vegetable, rice, and dust ingestion accounted for 44.7%, 28.6%, and 23.7% of the ADD, respectively. The combined exposure hazard indices at the fifth, median, and 95th percentiles for all heavy metals were determined as 2.54, 9.40, and 40.1 for adults and as 3.75, 13.7, and 58.4 for children, respectively. In terms of health risk, crop consumption was identified as the major exposure pathway for both children and adults, featuring a contribution of 99.9%. In addition, the 95th percentile carcinogenic risks for Pb exceeded the acceptable level. Thus, this work shows that to reduce the health risk for local residents in the former e-waste area, more attention should be paid to soil repair.

Bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) in wild marine fish from the coastal waters of the northern South China Sea: Risk assessment for human health.

Little data are available on polycyclic aromatic hydrocarbons (PAHs) in marine fish associated with oil and gas activities from the South China Sea (SCS). Twenty-one wild marine fish species from the northern South China Sea were collected for analysis of the presence of polycyclic aromatic hydrocarbons (PAHs). The total concentration of the PAHs (∑16PAHs) ranged from 199 to 606 ng·g-1 d.w., indicating moderate contamination. PAHs in fish species found in the Pearl River Delta (PRD) were significantly higher than those from the Yachen (YC) gas fields (p < 0.05). Planktivorous fish exhibited significantly higher concentrations of PAHs than carnivorous and omnivorous fish (p < 0.05). The PAHs were dominated by three ring compounds. Source identification analyses indicated that the PAH pollution originated from petroleum inputs. The cancer and non-cancer risk assessments concluded that the probable risk associated with the intake of PAHs via fish consumption is minimal. Long-term monitoring is necessary to determine the ecological impacts of PAHs associated with oil and gas activities.

A review of toxicity induced by persistent organic pollutants (POPs) and endocrine-disrupting chemicals (EDCs) in the nematode Caenorhabditis elegans.

Persistent organic pollutants (POPs) and endocrine disrupting compounds (EDCs) are almost ubiquitous in synthetic and natural sources; however these contaminants adversely impact ecosystems and humans. Owing to their potential toxicity, concerns have been raised about the effects of POPs and EDCs on ecological and human health. Therefore, toxicity evaluation and mechanisms actions of these contaminants are of great interest. The nematode Caenorhabditis elegans (C. elegans), an excellent model animal for environmental toxicology research, has been used widely for toxicity studies of POPs or EDCs from the whole-animal level to the single-cell level. In this review, we have discussed the toxicity of specific POPs or EDCs after acute, chronic, and multigenerational exposure in C. elegans. We have also introduced a discussion of the toxicological mechanisms of these compounds in C. elegans, with respect to oxidative stress, cell apoptosis, and the insulin/IGF-1 signaling pathway. Finally, we raised considered the perspectives and challenges of the toxicity assessments, multigenerational toxicity, and toxicological mechanisms.

Multi-generational effects and variations of stress response by hexabromocyclododecane (HBCD) exposure in the nematode Caenorhabditis elegans.

In order to understand multi-generational effects and changes of stress response by hexabromocyclododecane (HBCD) exposure, the animal model Caenorhabditis elegans was chosen for toxicity study. Multiple endpoints, including the physiological levels (growth, reproduction, and locomotion behaviors), stress-related gene expressions, reactive oxygen species (ROS) production and degree of cell apoptosis, were evaluated on exposed nematodes and their progeny. Prolonged exposure to HBCD at concentrations of 2 nM-200 nM caused adverse physiological effects in the parental generation (F0), and these effects were also observed in the offspring under HBCD-free conditions (F1). HBCD-induced toxicities could be transferred from parent to offspring. The integrated gene expressions profiles showed that exposure to HBCD at concentrations of 20-200 nM resulted in obvious changes in stress-related gene expressions, which were more increased in F0 generation than in F1 generation. The increased expressions were pronounced in several genes related to oxidative stress and cell apoptosis, e.g., hsp-16.2, hsp-16.48, sod-1, sod-3 and cep-1 genes. Exposure to 200 nM of HBCD could significantly increase ROS production and degree of cell apoptosis in the F0 and F1 generations. Therefore, it was speculated that HBCD exposure induced oxidative stress and cell apoptosis, which resulted in the adverse physiological effects. This finding is helpful for understanding the multi-generational effects and evaluating the potential risk of HBCD.

Screening and prioritization of chemical hazards for deriving human health ambient water quality criteria in China.

A two-step screening and prioritization approach of the chemical hazard to derive water quality criteria for the protection of human health in China was developed. Seventy-five potential candidate chemicals were identified in Step 1, and then were screened and scored in Step 2, based on three characteristics: detection frequency, toxicity, and human exposure. Substances with a score above 900 were considered the proposed candidates. Using this approach, 18 chemicals were successfully identified, and ranked in the following order: zinc, di(2-ethylhexyl) phthalate, dibutyl phthalate, trichloromethane, arsenic, cadmium, gamma-hexachlorocyclohexane (HCH), copper, benzo[a]pyrene, lead, benzene, fluoranthene, mercury, beta-HCH, anthracene, p,p'-DDT, and alpha-HCH. Additional chemical contaminants, including thallium, antimony, chromium (VI), and nitrobenzene, suggested by the Ministry of Environmental Protection for consideration during the development of the water quality criteria, brought the final number of proposed candidates to 22. These candidates belong to different groups: nine metals, four polycyclic aromatic hydrocarbons (PAHs), four pesticides, two phthalic acid esters, one halogenated hydrocarbon, and two monocyclic aromatic hydrocarbons. This list of pollutants will provide guidance when selecting the substances to be considered during the development of water quality criteria for the protection of human health in China.

Role of miR-155 in fluorooctane sulfonate-induced oxidative hepatic damage via the Nrf2-dependent pathway.

Studies demonstrated that perfluorooctane sulfonate (PFOS) tends to accumulate in the liver and is capable to cause hepatomegaly. In the present study, we investigated the roles of miR-155 in PFOS-induced hepatotoxicity in SD rats and HepG2 cells. Male SD rats were orally administrated with PFOS at 1 or 10mg/kg/day for 28 days while HepG2 cells were treated with 0-50 µM of PFOS for 24h or 50 µM of PFOS for 1, 3, 6, 12 or 24h, respectively. We found that PFOS significantly increased the liver weight and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in rats. Morphologically, PFOS caused actin filament remodeling and endothelial permeability changes in the liver. Moreover, PFOS triggered reactive oxygen species (ROS) generation and induced apoptosis in both in vivo and in vitro assays. Immunoblotting data showed that NF-E2-related factor-2 (Nrf2) expression and activation and its target genes were all suppressed by PFOS in the liver and HepG2 cells. However, PFOS significantly increased miR-155 expression. Further studies showed that pretreatment of HepG2 cells with catalase significantly decreased miR-155 expression and substantially increased Nrf2 expression and activation, resulting in reduction of PFOS-induced cytotoxicity and oxidative stress. Taken together, these results indicated that miR-155 plays an important role in the PFOS-induced hepatotoxicity by disrupting Nrf2/ARE signaling pathway.

Particle-Associated Ambient Benzo[a]pyrene and Levels of Urinary 1-Hydroxypyrene in a Non-occupationally Exposed Population of Adults and Children in Lanzhou, China.

Concentrations of benzo[a]pyrene (B[a]P) in ambient air from different areas in Lanzhou city in northwest of China, and its metabolite 1-hydroxypyrene (1-OHP) in the urine of resident children and adults were determined by using gas chromatography/mass spectrometry and high performance liquid chromatography. Results showed that the atmospheric environmental concentration of B[a]P varied significantly from one part of the city to another with levels of 150 ng/m(3) in the industrial area of Xigu and 73.8 ng/m(3) in the agricultural area of Yuzhong. The geometric mean urinary 1-OHP concentration was 0.42 µmol/mol-creatinine, with a range of means between 0.067 and 2.05 for the various population sub-groups. The non-occupationally exposed populations' age, gender and area of residence were the major factors that influenced urinary 1-OHP levels. The health risks of B[a]P for adults and children in Xigu and for children in Yuzhong exceeded the acceptable level (1 × 10(-4)) of the US Environmental Protection Agency.

Aged polystyrene microplastics cause reproductive impairment via DNA-damage induced apoptosis in Caenorhabditis elegans.

Although polystyrene microplastics (PS-MPs) could induce toxic effects on environmental organisms, the toxicity of aged PS-MPs with H2O2 on soil organisms remains unclear. Our study utilized Caenorhabditis elegans as model organism to examine the reproductive toxicity of pristine PS-MPs (pPS-MPs) and aged PS-MPs (aPS-MPs) at environmentally relevant concentrations (0.1-100 µg/L). Acute exposure to aPS-MPs could induce greater reproductive impairment compared to pPS-MPs, as evidenced by changes in brood size and egg release. Assessment of gonad development using the number of mitotic cells, length of gonad arm, and relative area of gonad arm as parameters revealed a high reproductive toxicity caused by aPS-MPs exposure. Furthermore, aPS-MPs exposure promoted substantial germline apoptosis. Additionally, exposure to aPS-MPs (100 µg/L) markedly altered the expression of DNA damage-induced apoptosis-related genes (e.g., egl-1, cep-1, clk-2, ced-3, -4, and -9). Alterations in germline apoptosis caused by aPS-MPs were observed in mutants of cep-1, hus-1, egl-1, ced-3, -4, and -9. Consequently, the augmentation of reproductive toxicity resulting from aPS-MPs exposure was attributed to DNA damage-triggered cellular apoptosis. Additionally, the EGL-1-CEP-1-HUS-1-CED-3-CED-4-CED-9 signaling pathway was identified as a key regulator of germline apoptosis in nematodes. Our study provides insights into potential environmental risk of aPS-MPs with H2O2 on environmental organisms.

Neurotoxicity of tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) through the GABAergic and serotonergic neurotransmission in Caenorhabditis elegans.

Tetrabromobisphenol-A-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel additive brominated flame retardant, is being developed for use in polyolefin and copolymers. Despite its emerging application, the neurotoxicity and mechanisms of action of TBBPA-BDBPE remain unexplored. Caenorhabditis elegans was utilized as the model organism to study the neurotoxic effects of TBBPA-BDBPE across environmental concentrations ranging from 0 to 100 µg/L. This investigation focused on various toxicological endpoints such as locomotive behavior, neuronal injury, neurotransmitter transmission, and the regulation of nervous system-related gene expression. Acute exposure to TBBPA-BDBPE at concentrations of 10-100 µg/L significantly impaired nematode movement, indicating potential neurotoxicity. In transgenic nematodes, this exposure also caused damage to γ-aminobutyric acid (GABAergic) and serotonergic neurons, along with notable changes in the levels of GABAergic and serotonergic neurotransmitters. Further molecular studies indicated alterations in neurotransmission-related genes (cat-4, mod-1, unc-25, and unc-47). Molecular docking analysis confirmed the binding affinity of TBBPA-BDBPE to key neurotransmission proteins-CAT-4, MOD-1, UNC-25, and UNC-47. These findings demonstrate that TBBPA-BDBPE exerts neurotoxic effects by impacting GABAergic and serotonergic neurotransmission in nematodes. This study provides new insights into the potential environmental risks of TBBPA-BDBPE.

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.

Perturbation of lipid metabolism in 3T3-L1 at different stages of preadipocyte differentiation and new insights into the association between changed metabolites and adipogenesis promoted by TBBPA or TBBPS.

Tetrabromobisphenol A (TBBPA) and tetrabromobisphenol S (TBBPS) are widely distributed brominated flame retardants. While TBBPA has been demonstrated to stimulate adipogenesis, TBBPS is also under suspicion for potentially inducing comparable effects. In this study, we conducted a non-targeted metabolomics to examine the metabolic changes in 3T3-L1 cells exposed to an environmentally relevant dose of TBBPA or TBBPS. Our findings revealed that 0.1 µM of both TBBPA and TBBPS promoted the adipogenesis of 3T3-L1 preadipocytes. Multivariate analysis showed significant increases in glycerophospholipids, sphingolipids, and steroids relative levels in 3T3-L1 cells exposed to TBBPA or TBBPS at the final stage of preadipocyte differentiation. Metabolites set composed of glycerophospholipids was found to be highly effective predictors of adipogenesis in 3T3-L1 cells exposed to TBBPA or TBBPS (revealed from the receiver operating characteristic curve with an area under curve > 0.90). The results from metabolite set enrichment analysis suggested both TBBPA and TBBPS exposures significantly perturbed steroid biosynthesis in adipocytes. Moreover, TBBPS additionally disrupted the sphingolipid metabolism in the adipocytes. Our study presents new insights into the obesogenic effects of TBBPS and provides valuable information about the metabolites associated with adipogenesis induced by TBBPA or TBBPS.

Insight into the interaction of tetrabromobisphenol A with sediment-derived dissolved organic carbon in a multiphase system by direct immersion solid phase microextraction.

Tetrabromobisphenol A (TBBPA), a ubiquitously used commercial brominated flame retardant (BFR), has been widely detected in aquatic environments, and has aroused much attention due to its potential adverse effects on aquatic organisms. However, current research on the environmental fate and transport of TBBPA in the sediment-dissolved organic carbon (DOC)-water polyphase system is lacking. In this study, the sorption behavior of TBBPA in a water-DOC-sediment system was investigated using the direct-immersion solid-phase microextraction (DI-SPME) method, and the free dissolved concentration (Cw-SPME) and DOC adsorption concentration (CDOC) of TBBPA in water were measured by applying this DI-SPME approach. In addition, the effects of pH, ionic strength, and soluble organic concentration on the adsorption of TBBPA in the multiphase system were evaluated. The adsorption kinetics experimental results show that the adsorption behavior of TBBPA on sediments conforms to a linear model, suggesting that it could be mainly absorbed by sediments. The solid-water partition coefficient (Kd) of TBBPA was artificially reduced 1.54 times using the traditional liquid-liquid extraction method because the sorption behavior of the DOC was ignored, which could be accurately corrected using the DI-SPME method. The logKd and logKOC of TBBPA in the multiphase system were 4.12 ± 0.25 and 6.48 ± 0.25, respectively. Finally, the interference experiment revealed that the sorption behavior of TBBPA was affected by the pH, ionic strength (calcium ion), and humic acid concentration, apart from the lead ion concentration itself.