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Ecotoxicology and Environmental Safety Jul 2024Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high...
Tetrabromobisphenol A (TBBPA), a widely-used brominated flame retardant, has been revealed to exert endocrine disrupting effects and induce adipogenesis. Given the high structural similarities of TBBPA analogues and their increasing exposure risks, their effects on lipid metabolism are necessary to be explored. Herein, 9 representative TBBPA analogues were screened for their interference on 3T3-L1 preadipocyte adipogenesis, differentiation of C3H10T1/2 mesenchymal stem cells (MSCs) to brown adipocytes, and lipid accumulation of HepG2 cells. TBBPA bis(2-hydroxyethyl ether) (TBBPA-BHEE), TBBPA mono(2-hydroxyethyl ether) (TBBPA-MHEE), TBBPA bis(glycidyl ether) (TBBPA-BGE), and TBBPA mono(glycidyl ether) (TBBPA-MGE) were found to induce adipogenesis in 3T3-L1 preadipocytes to different extends, as evidenced by the upregulated intracellular lipid generation and expressions of adipogenesis-related biomarkers. TBBPA-BHEE exhibited a stronger obesogenic effect than did TBBPA. In contrast, the test chemicals had a weak impact on the differentiation process of C3H10T1/2 MSCs to brown adipocytes. As for hepatic lipid formation test, only TBBPA mono(allyl ether) (TBBPA-MAE) was found to significantly promote triglyceride (TG) accumulation in HepG2 cells, and the effective exposure concentration of the chemical under oleic acid (OA) co-exposure was lower than that without OA co-exposure. Collectively, TBBPA analogues may perturb lipid metabolism in multiple tissues, which varies with the test tissues. The findings highlight the potential health risks of this kind of emerging chemicals in inducing obesity, non-alcoholic fatty liver disease (NAFLD) and other lipid metabolism disorders, especially under the conditions in conjunction with high-fat diets.
Topics: Polybrominated Biphenyls; Lipid Metabolism; 3T3-L1 Cells; Animals; Mice; Adipogenesis; Humans; Flame Retardants; Hep G2 Cells; Cell Differentiation; Mesenchymal Stem Cells; Endocrine Disruptors; Adipocytes
PubMed: 38870736
DOI: 10.1016/j.ecoenv.2024.116577 -
Environment International Jul 2024Arctic Monitoring and Assessment Programme (AMAP) monitors persistent organic pollutant (POP) levels in the Arctic populations and assesses health effects related to...
INTRODUCTION
Arctic Monitoring and Assessment Programme (AMAP) monitors persistent organic pollutant (POP) levels in the Arctic populations and assesses health effects related to exposure to them. Many internationally regulated POPs persist in humans and biota, while new Emerging Contaminants of Arctic Concern (ECAC), many of which are unregulated, present additional challenges. Biomonitoring offers valuable insights into temporal trends within human matrices, revealing critical information not only about the efficacy of international regulations but also serving as an early warning system for exposure and risks for human health.
METHODS
Data analyzed in this study is aggregated data presented in the AMAP Human Health in the Arctic assessments, which provide data on contaminant concentrations measured in human matrices from adults, and children across various population studies conducted in the Arctic since the 1980 s. Linear regression analyses were used to assess trends of various POPs including organochlorine (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and per- and polyfluoroalkyl substances (PFAS), measured over time from the Arctic populations in Finland, Norway, Sweden, Denmark, Iceland, Canada and Alaska (USA).
RESULTS
Overall, decreasing trends were observed for PCBs and OCPs. Regulated PFAS showed decreasing trends, but increasing trends were observed for unregulated PFAS in certain populations. PBDEs showed decreasing or inconsistent trends in certain Arctic populations.
CONCLUSIONS
Decreasing trends are observed for legacy POPs, but the trends for new emerging contaminants are inconsistent. More focus is needed on biomonitoring the new emerging contaminants of concern in the Arctic and their implications on human health.
Topics: Humans; Arctic Regions; Environmental Monitoring; Environmental Pollutants; Adult; Child; Halogenated Diphenyl Ethers; Environmental Exposure; Polychlorinated Biphenyls; Hydrocarbons, Chlorinated; Persistent Organic Pollutants; Biological Monitoring
PubMed: 38838491
DOI: 10.1016/j.envint.2024.108777 -
Chemosphere Aug 2024Brominated flame retardants (BFRs) are synthetic chemicals incorporated into a wide variety of products, both for industrial applications and everyday use, with the... (Review)
Review
Brominated flame retardants (BFRs) are synthetic chemicals incorporated into a wide variety of products, both for industrial applications and everyday use, with the primary aim of reducing their flammability or reducing the material burning rate. These compounds find widespread use in plastics, textiles, and electrical/electronic devices. However, BFRs can be released from products and, thus are determined in many environmental matrices such as soil, water and air.This review discuss the potential health implications of selected BFRs (PBDEs and TBBPA) exposure arising from their impact on the epigenetic mechanisms. Epigenetic modifications, such as DNA methylation and histone acetylation or methylation, as well as changes in miRNA pattern, play significant roles in gene expression and cell function and can be influenced by environmental factors.The studies indicate that PBDEs exposure can lead to global DNA hypomethylation, disrupting normal gene regulation and contributing to genomic instability. In animal models, PBDEs have been associated with adverse effects on neurodevelopment, including impairments in memory and learning. TBBPA exposure has also been linked to changes in DNA methylation patterns, alterations in histone posttranslational modifications and non-coding RNA expression. These epigenetic changes may contribute to health issues related to growth, development, and endocrine functions.The growing evidence of epigenetic modifications induced by BFRs exposure highlights the importance of understanding their potential risks to human health. Further investigations are needed to fully elucidate the long-term consequences of altered epigenetic marks and their impact on human health.
Topics: Flame Retardants; Epigenesis, Genetic; Humans; Halogenated Diphenyl Ethers; Polybrominated Biphenyls; DNA Methylation; Animals; Environmental Exposure; Environmental Pollutants
PubMed: 38821124
DOI: 10.1016/j.chemosphere.2024.142488 -
JAMA Network Open May 2024Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied...
IMPORTANCE
Prenatal exposure to ubiquitous endocrine-disrupting chemicals (EDCs) may increase the risk of metabolic syndrome (MetS) in children, but few studies have studied chemical mixtures or explored underlying protein and metabolic signatures.
OBJECTIVE
To investigate associations of prenatal exposure to EDC mixtures with MetS risk score in children and identify associated proteins and metabolites.
DESIGN, SETTING, AND PARTICIPANTS
This population-based, birth cohort study used data collected between April 1, 2003, and February 26, 2016, from the Human Early Life Exposome cohort based in France, Greece, Lithuania, Norway, Spain, and the UK. Eligible participants included mother-child pairs with measured prenatal EDC exposures and complete data on childhood MetS risk factors, proteins, and metabolites. Data were analyzed between October 2022 and July 2023.
EXPOSURES
Nine metals, 3 organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 5 perfluoroalkyl substances (PFAS), 10 phthalate metabolites, 3 phenols, 4 parabens, and 4 organophosphate pesticide metabolites measured in urine and blood samples collected during pregnancy.
MAIN OUTCOMES AND MEASURES
At 6 to 11 years of age, a composite MetS risk score was constructed using z scores of waist circumference, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and insulin levels. Childhood levels of 44 urinary metabolites, 177 serum metabolites, and 35 plasma proteins were quantified using targeted methods. Associations were assessed using bayesian weighted quantile sum regressions applied to mixtures for each chemical group.
RESULTS
The study included 1134 mothers (mean [SD] age at birth, 30.7 [4.9] years) and their children (mean [SD] age, 7.8 [1.5] years; 617 male children [54.4%] and 517 female children [45.6%]; mean [SD] MetS risk score, -0.1 [2.3]). MetS score increased per 1-quartile increase of the mixture for metals (β = 0.44; 95% credible interval [CrI], 0.30 to 0.59), organochlorine pesticides (β = 0.22; 95% CrI, 0.15 to 0.29), PBDEs (β = 0.17; 95% CrI, 0.06 to 0.27), and PFAS (β = 0.19; 95% CrI, 0.14 to 0.24). High-molecular weight phthalate mixtures (β = -0.07; 95% CrI, -0.10 to -0.04) and low-molecular weight phthalate mixtures (β = -0.13; 95% CrI, -0.18 to -0.08) were associated with a decreased MetS score. Most EDC mixtures were associated with elevated proinflammatory proteins, amino acids, and altered glycerophospholipids, which in turn were associated with increased MetS score.
CONCLUSIONS AND RELEVANCE
This cohort study suggests that prenatal exposure to EDC mixtures may be associated with adverse metabolic health in children. Given the pervasive nature of EDCs and the increase in MetS, these findings hold substantial public health implications.
Topics: Humans; Female; Pregnancy; Prenatal Exposure Delayed Effects; Metabolic Syndrome; Child; Male; Endocrine Disruptors; Risk Factors; Environmental Pollutants; Adult; Maternal Exposure; Cohort Studies; Birth Cohort
PubMed: 38780942
DOI: 10.1001/jamanetworkopen.2024.12040 -
Folia Neuropathologica 2024Polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) are dominant environmental and food contaminants. Tetrabromobisphenol A (TBBPA) is the most...
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.
Topics: Animals; Microglia; Polybrominated Biphenyls; Rats; Chlorodiphenyl (54% Chlorine); Neurotoxicity Syndromes; Brain; Male; Flame Retardants; Rats, Wistar
PubMed: 38741432
DOI: 10.5114/fn.2023.133796 -
Antioxidants (Basel, Switzerland) Apr 20242,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans...
Protective Effects of Isoliquiritigenin and Licochalcone B on the Immunotoxicity of BDE-47: Antioxidant Effects Based on the Activation of the Nrf2 Pathway and Inhibition of the NF-κB Pathway.
2,2',4,4'-Tetrabrominated biphenyl ether (BDE-47) is a polybrominated diphenyl ether (PBDE) homologue that is ubiquitous in biological samples and highly toxic to humans and other organisms. Prior research has confirmed that BDE-47 can induce oxidative damage in RAW264.7 cells, resulting in apoptosis and impaired immune function. The current study mainly focused on how Isoliquiritigenin (ISL) and Licochalcone B (LCB) might protect against BDE-47's immunotoxic effects on RAW264.7 cells. The results show that ISL and LCB could increase phagocytosis, increase the production of , and decrease the production of inflammatory factors (TNF-α, IL-6, and IL-1β) and co-stimulatory factors (, , and ), alleviating the immune function impairment caused by BDE-47. Secondly, both ISL and LCB could reduce the expressions of the proteins Bax and Caspase-3, promote the expression of the protein Bcl-2, and reduce the apoptotic rate, alleviating the apoptosis initiated by BDE-47. Additionally, ISL and LCB could increase the levels of antioxidant substances (SOD, CAT, and GSH) and decrease the production of reactive oxygen species (ROS), thereby counteracting the oxidative stress induced by BDE-47. Ultimately, ISL and LCB suppress the NF-κB pathway by down-regulating IKBKB and up-regulating IκB-Alpha in addition to activating the Nrf2 pathway and promoting the production of HO-1 and NQO1. To summarize, BDE-47 causes oxidative damage that can be mitigated by ISL and LCB through the activation of the Nrf2 pathway and inhibition of the NF-κB pathway, which in turn prevents immune function impairment and apoptosis. These findings enrich the current understanding of the toxicological molecular mechanism of BDE-47 and the detoxification mechanism of licorice.
PubMed: 38671893
DOI: 10.3390/antiox13040445 -
Environment & Health (Washington, D.C.) Apr 2024Halogenated natural products (HNPs) are considered to be emerging contaminants whose environmental distribution and fate are only incompletely known. Therefore, several...
Halogenated natural products (HNPs) are considered to be emerging contaminants whose environmental distribution and fate are only incompletely known. Therefore, several persistent and bioaccumulative HNP groups, together with man-made polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), were quantified in the blubber of nine sperm whales () stranded on the coast of the Mediterranean Sea in Italy. The naturally occurring polybrominated hexahydroxanthene derivatives (PBHDs; sum of TetraBHD and TriBHD) were the most prominent substance class with up to 77,000 ng/g blubber. The mean PBHD content (35,800 ng/g blubber) even exceeded the one of PCBs (28,400 ng/g blubber), although the region is known to be highly contaminated with man-made contaminants. Based on mean values, Q1 ∼ PBDEs > MeO-BDEs ∼ 2,2'-diMeO-BB 80 and several other HNPs followed with decreasing amounts. All blubber samples contained an abundant compound whose molecular formula (CHBrO) was verified using high-resolution mass spectrometry. The only plausible matching isomer was (2,4',9,9')-2,7-dibromo-4'-bromomethyl-1,1-dimethyl-2,3,4,4',9,9'-9,9'-hexahydro-1-xanthen-9-ol (OH-TriBHD), a hydroxylated secondary metabolite previously detected together with TriBHD and TetraBHD in a sponge known to be a natural producer of PBHDs. The estimated mean amount of the presumed OH-TriBHD was 3000 ng/g blubber, which is unexpectedly high for hydroxylated compounds in the lipids of marine mammals.
PubMed: 38660428
DOI: 10.1021/envhealth.3c00182 -
Environmental Epidemiology... Apr 2024Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as...
BACKGROUND
Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as polybrominated biphenyl (PBB), during fetal development and early life has been suspected to impact neurological development. This study aims to investigate the association between prenatal and early life exposure to PBB and the development of ADHD and autism later in life.
METHODS
Data from the Michigan PBB Registry, a cohort of Michigan residents who had been exposed to PBB in a mass contamination event in 1973, was leveraged for this nested case-control analysis among two distinct samples: (1) Those who self-reported ADHD or autism diagnosis, and (2) mothers who reported their child's ADHD or autism diagnosis. PBB exposure was measured in participants of the PBB Registry, and the mother's PBB level was used in mother-reported analyses. Cases were matched with controls by sex and year of birth. Conditional logistic regression models were used to estimate the association between PBB level and case status.
RESULTS
PBB levels were higher among those who were exposed in early life compared with those exposed in utero (geometric mean: 0.300 ng/ml vs. 0.016 ng/ml). Among women in this cohort, a higher than expected proportion of self-reported ADHD diagnosis (11.11%), compared with population estimates. PBB was not associated with ADHD or autism in either self-reported or mother-reported analyses.
CONCLUSIONS
This study adds to the sparse literature about prenatal and early life exposure to PBB-153 and ADHD and autism. Future studies should examine potential effect modification by sex.
PubMed: 38617420
DOI: 10.1097/EE9.0000000000000304 -
Environment International Apr 2024The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the...
The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T] and thyroxine [T]), and their metabolites reverse T and 3,5-diiodothyronine [3,5-T]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T, rT and 3,5-T. Specifically, there was a weak significant negative association between T and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T and ΣPBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.
Topics: Animals; Female; Male; Water Pollutants, Chemical; Hydrocortisone; Thyroid Hormones; Beluga Whale; Estuaries; Halogenated Diphenyl Ethers; Polychlorinated Biphenyls; Environmental Monitoring; Flame Retardants; Stress, Physiological; Endangered Species; Triiodothyronine; Hydrocarbons, Halogenated; Thyroxine
PubMed: 38615542
DOI: 10.1016/j.envint.2024.108647 -
Journal of Chromatography. A May 2024Birds are excellent bioindicators of environmental pollution, and blood provides information on contaminant exposure, although its analysis is challenging because of the...
Optimization and uncertainty assessment of a gas chromatography coupled to Orbitrap mass spectrometry method to determine organic contaminants in blood: A case study of an endangered seabird.
Birds are excellent bioindicators of environmental pollution, and blood provides information on contaminant exposure, although its analysis is challenging because of the low volumes that can be sampled. The objective of the present study was to optimize and validate a miniaturized and functional extraction and analytical method based on gas chromatography coupled to Orbitrap mass spectrometry (GCOrbitrap-MS) for the trace analysis of contaminants in avian blood. Studied compounds included 25 organochlorine pesticides (OCPs), 6 polychlorinated biphenyls (PCBs), 8 polybrominated diphenyl ethers (PBDEs) and 15 polycyclic aromatic hydrocarbons (PAHs). Four extraction and clean-up conditions were optimized and compared in terms of efficiency, accuracy, and uncertainty assessment. Extraction with hexane:dichloromethane and miniaturized Florisil pipette clean-up was the most adequate considering precision and accuracy, time, and costs, and was thereafter used to analyse 20 blood samples of a pelagic seabird, namely the Bermuda petrel (Pterodroma cahow). This species, endemic to the Northwest Atlantic, is among the most endangered seabirds of the region that in the '60 faced a decrease in the breeding success likely linked to a consistent exposure to dichloro-diphenyl-trichloroethane (DDT). Indeed, p,p'-DDE, the main DDT metabolite, was detected in all samples and ranged bewteen 1.13 and 6.87 ng/g wet weight. Other ubiquitous compounds were PCBs (ranging from 0.13 to 6.76 ng/g ww), hexachlorobenzene, and mirex, while PAHs were sporadically detected at low concentrations, and PBDEs were not present. Overall, the extraction method herein proposed allowed analysing very small blood volumes (∼ 100 µL), thus respecting ethical principles prioritising the application of less-invasive sampling protocols, fundamental when studying threatened avian species.
Topics: Animals; Gas Chromatography-Mass Spectrometry; Pesticides; Birds; Hydrocarbons, Chlorinated; Polychlorinated Biphenyls; Halogenated Diphenyl Ethers; Polycyclic Aromatic Hydrocarbons; Endangered Species; Environmental Monitoring; Environmental Pollutants
PubMed: 38604058
DOI: 10.1016/j.chroma.2024.464870