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PloS One 2017Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of...
Firemaster® 550 and its components isopropylated triphenyl phosphate and triphenyl phosphate enhance adipogenesis and transcriptional activity of peroxisome proliferator activated receptor (Pparγ) on the adipocyte protein 2 (aP2) promoter.
Firemaster® 550 (FM550) is a chemical mixture currently used as an additive flame retardant in commercial products, and is comprised of 2-ethylhexyl-2,3,4,5-tertrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (IPTP). Animal and in vitro studies suggest that FM550, TPP and IPTP may have adipogenic effects and may exert these effects through PPARγ activation. Using murine 3T3-L1 preadipocytes, we investigated the detailed expression of transcription factors and adipogenic markers in response to FM550 and its components. Further we investigated the mechanism of action of the peroxisome proliferator-activated receptor gamma (PPARγ) on downstream targets of the receptor by focussing on the mature adipocyte marker, adipocyte protein 2 (aP2). In addition, we set to elucidate the components responsible for the adipogenic effects seen in the FM550 mixture. We show that FM550 and its components TPP, IPTP, and TBPH, but not TBB induced lipid accumulation in a dose-dependent manner. Interestingly, despite displaying enhanced lipid accumulation, TBPH did not alter the mRNA or protein expression of terminal differentiation markers. In contrast, FM550, TPP, and IPTP treatment enhanced lipid accumulation, and mRNA and protein expression of terminal differentiation markers. To further delineate the mechanisms of action of FM550 and its components we focussed on aP2 promoter activity. For this purpose we used the enhancer region of the mouse aP2 promoter using a 584-bp reporter construct containing an active PPRE located 5.4 kb away from the transcription start site of aP2. Exposure to FM550, IPTP, and TPP significantly increased PPARγ mediated aP2 enhancer activity. Furthermore, we show that TPP- and IPTP-dependent upregulation of aP2 was significantly inhibited by the selective PPARγ antagonist GW9662. In addition, chromatin immunoprecipitation experiments showed that IPTP and TPP treatment led to the recruitment of PPARγ to the regulatory region of aP2.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Dose-Response Relationship, Drug; Fatty Acid-Binding Proteins; Mice; Organophosphates; PPAR gamma; Polybrominated Biphenyls; Promoter Regions, Genetic; Transcription Factors; Transcriptional Activation
PubMed: 28437481
DOI: 10.1371/journal.pone.0175855 -
Chemosphere Mar 2018Some commonly consumed marine fish species are considered to display a higher risk of bio-accumulating organic environmental contaminants such as PBDEs. As part of a...
Some commonly consumed marine fish species are considered to display a higher risk of bio-accumulating organic environmental contaminants such as PBDEs. As part of a study to investigate the spatial distribution of these contaminants, data on polybrominated diphenlyethers (PBDEs) and polybrominated biphenyls (PBBs) were collected and analysed by introducing a web-based resource which enables efficient spatial, species and concentration level representations. Furthermore, hierarchical cluster analyses permits correlations within the data to be predicted. The data provide current information on levels of PBDE and PBB occurrence, allowing identification of locations that show higher contaminant levels. 135 fish samples of various species were analysed from UK marine waters, but encompassing the waters around Norway in the North and to the Algarve in the South. PBDEs were observed in all samples with the majority of measured congeners being detected. The concentrations ranged from 0.087 μg/kg to 8.907 μg/kg whole weight (ww) for the sum of all measured PBDE congeners. PBBs occurred less frequently showing a corresponding range of <0.02 μg/kg to 0.97 μg/kg ww for the sum of seven PBB congeners. Concentrations vary depending on species and locations where landed, e.g. PBBs occurred more frequently and at higher levels in grey mullet from French waters. The high frequency of PBDE occurrence makes it prudent to continue the monitoring of these commonly consumed marine fish species. The web-based resource provides a flexible and efficient tool for assessors and policy-makers to monitor and evaluate levels within caught fish species improving evidenced-based decision processes.
Topics: Animals; Environmental Monitoring; Fishes; Food Contamination; Halogenated Diphenyl Ethers; Norway; Polybrominated Biphenyls; Polychlorinated Biphenyls; Seafood; Spatial Analysis; United Kingdom
PubMed: 29289018
DOI: 10.1016/j.chemosphere.2017.11.114 -
Ecotoxicology and Environmental Safety Apr 2023Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants...
Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.
Topics: Animals; Transcriptome; Arabidopsis; Polybrominated Biphenyls; Flame Retardants
PubMed: 36905847
DOI: 10.1016/j.ecoenv.2023.114736 -
Environmental Health : a Global Access... Aug 2019Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence...
BACKGROUND
Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure's effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB.
METHODS
Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T), total triiodothyronine (T), free T, free T, thyroid stimulating hormone (TSH), and free T: free T ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry.
RESULTS
Higher PBB levels were associated with many thyroid hormones measures, including higher free T (p = 0.002), lower free T (p = 0.01), and higher free T: free T ratio (p = 0.0001). Higher PCB levels were associated with higher free T (p = 0.0002), and higher free T: free T ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T (p = 0.01) and free T (p = 0.0003), lower free T (p = 0.04), and higher free T: free T ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted.
CONCLUSIONS
This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally.
Topics: Adult; Aged; Cross-Sectional Studies; Environmental Exposure; Female; Humans; Male; Michigan; Middle Aged; Polybrominated Biphenyls; Polychlorinated Biphenyls; Thyroid Hormones
PubMed: 31443693
DOI: 10.1186/s12940-019-0509-z -
Nutrients Dec 2021Breastfeeding is the best way to feed an infant, although it can also be a source of abiotic contaminants such as heavy metals or bisphenol A (BPA). The early life...
Dietary Habits and Relationship with the Presence of Main and Trace Elements, Bisphenol A, Tetrabromobisphenol A, and the Lipid, Microbiological and Immunological Profiles of Breast Milk.
Breastfeeding is the best way to feed an infant, although it can also be a source of abiotic contaminants such as heavy metals or bisphenol A (BPA). The early life exposure to these compounds can lead to serious toxic effects in both the short and long-term. These substances can reach breast milk through the mother's habits, diet being one of the main routes of exposure. The aim of the present work was to analyse possible associations between the dietary habits of women and the content of major trace elements, BPA, fatty acids and lipids, and the microbiological and immunological profiles of human milk. Possible associations between major trace elements and BPA and the lipid, microbiological and immunological profiles were also analysed. The results of this study support that the microbiological composition of human milk is associated with the dietary habits of the women, and that the consumption of canned drinks is related to the presence of BPA in human milk. Furthermore, some relationships were found between the amount of major trace elements and the microbiological and immunological profile of the milk samples. Finally, the presence of BPA was associated with changes in the immunological profile of human milk.
Topics: Adult; Benzhydryl Compounds; Feeding Behavior; Female; Humans; Lipid Metabolism; Maternal Nutritional Physiological Phenomena; Milk, Human; Phenols; Polybrominated Biphenyls; Trace Elements
PubMed: 34959899
DOI: 10.3390/nu13124346 -
Chemosphere Sep 2020This critical review summarizes the occurrence of 63 novel brominated flame retardants (NBFRs) in indoor air, dust, consumer goods and food. It includes their EU... (Review)
Review
This critical review summarizes the occurrence of 63 novel brominated flame retardants (NBFRs) in indoor air, dust, consumer goods and food. It includes their EU registration and (potential) risks. The increasing application of NBFRs calls for more research on their occurrence, environmental fate and toxicity. This review reports which NBFRs are actually being studied, which are detected and which are of most concern. It also connects data from the European Chemical Association on NBFRs with other scientific information. Large knowledge gaps emerged for 28 (out of 63) NBFRs, which were not included in any monitoring programs or other studies. This also indicates the need for optimized analytical methods including all NBFRs. Further research on indoor environments, emission sources and potential leaching is also necessary. High concentrations of 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), decabromodiphenyl ethane (DBDPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE) were often reported. The detection of hexabromobenzene (HBB), pentabromotoluene (PBT), 1,4-dimethyltetrabromobenzene (TBX), 4-(1,2-dibromoethyl)-1,2-dibromocyclohexane (DBE-DBCH) and tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) also raises concern.
Topics: Air Pollution, Indoor; Bromobenzenes; Dust; Environmental Monitoring; Flame Retardants; Halogenated Diphenyl Ethers; Halogenation; Polybrominated Biphenyls
PubMed: 32417508
DOI: 10.1016/j.chemosphere.2020.126816 -
Aging Aug 2019Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently...
Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants' effect on aging.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Biomarkers; DNA Methylation; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Epigenesis, Genetic; Female; Humans; Male; Middle Aged; Polybrominated Biphenyls; Young Adult
PubMed: 31375641
DOI: 10.18632/aging.102134 -
Environmental Health Perspectives May 2004Six polybrominated diphenyl ethers (PBDEs), one hexabromobiphenyl [polybrominated biphenyl (PBB)], and one hexachlorobiphenyl [polychlorinated biphenyl (PCB)] were...
Six polybrominated diphenyl ethers (PBDEs), one hexabromobiphenyl [polybrominated biphenyl (PBB)], and one hexachlorobiphenyl [polychlorinated biphenyl (PCB)] were measured in 40 human serum pools collected in the southeastern United States during 1985 through 2002 and in Seattle, Washington, for 1999 through 2002. The concentrations of most of the PBDEs, which are commercially used as flame retardants in common household and commercial applications, had significant positive correlations with time of sample collection, showing that the concentrations of these compounds are increasing in serum collected in the United States. In contrast, PCB and PBB levels were negatively correlated with sample collection year, indicating that the levels of these compounds have been decreasing since their phaseout in the 1970s.
Topics: Environmental Exposure; Environmental Pollutants; History, 20th Century; Humans; Polybrominated Biphenyls; Polychlorinated Biphenyls; Retrospective Studies; United States
PubMed: 15121506
DOI: 10.1289/ehp.112-1241957 -
Environmental Research Jun 2021Biomarkers of exposure can be measured at lower and lower levels due to advances in analytical chemistry. Using these sensitive methods, some epidemiology studies report... (Review)
Review
Biomarkers of exposure can be measured at lower and lower levels due to advances in analytical chemistry. Using these sensitive methods, some epidemiology studies report associations between biomarkers and health outcomes at biomarker levels much below those associated with effects in animal studies. While some of these low exposure associations may arise from increased sensitivity of humans compared with animals or from species-specific responses, toxicology studies with drugs, commodity chemicals and consumer products have not generally indicated significantly greater sensitivity of humans compared with test animals for most health outcomes. In some cases, these associations may be indicative of pharmacokinetic (PK) bias, i.e., a situation where a confounding factor or the health outcome itself alters pharmacokinetic processes affecting biomarker levels. Quantitative assessment of PK bias combines PK modeling and statistical methods describing outcomes across large numbers of individuals in simulated populations. Here, we first provide background on the types of PK models that can be used for assessing biomarker levels in human population and then outline a process for considering PK bias in studies intended to assess associations between biomarkers and health outcomes at low levels of exposure. After providing this background, we work through published examples where these PK methods have been applied with several chemicals/chemical classes - polychlorinated biphenyls (PCBs), perfluoroalkyl substances (PFAS), polybrominated biphenyl ethers (PBDE) and phthalates - to assess the possibility of PK bias. Studies of the health effects of low levels of exposure will be improved by developing some confidence that PK bias did not play significant roles in the observed associations.
Topics: Animals; Biomarkers; Environmental Pollutants; Epidemiologic Studies; Halogenated Diphenyl Ethers; Humans; Outcome Assessment, Health Care; Polychlorinated Biphenyls
PubMed: 33887277
DOI: 10.1016/j.envres.2021.111183 -
Neurotoxicology and Teratology 2023Perfluorinated compounds (PFCs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent environmental compounds, present in humans and at higher levels in...
Perfluorinated chemicals (PFOA) can, by interacting with highly brominated diphenyl ethers (PBDE 209) during a defined period of neonatal brain development, exacerbate neurobehavioural defects.
Perfluorinated compounds (PFCs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent environmental compounds, present in humans and at higher levels in infants/children than in adults. This study shows that co-exposure to pentadecafluorooctanoic acid (PFOA) and 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) can significantly exacerbate developmental neurobehavioural defects. Neonatal male NMRI mice, 3 and 10 days old, were exposed perorally to PBDE 209 (1.4 or 8.0 μmol/kg bw), PFOA (1.4 or 14 μmol/kg bw), co-exposed to PBDE 209 and PFOA (at the given doses), or a vehicle (20% fat emulsion) and observed for spontaneous behaviour in a novel home environment when 2 and 4 months old. The behavioural defects observed included hyperactivity and reduced habituation indicating cognitive defects. This interaction appears most likely dependent on the presence of PBDE 209 and/or its metabolites together with PFOA, during a defined critical period of neonatal brain development, corresponding to the perinatal and newborn period in humans.
Topics: Humans; Animals; Mice; Pregnancy; Female; Child; Male; Infant; Halogenated Diphenyl Ethers; Animals, Newborn; Polybrominated Biphenyls; Brain; Flame Retardants
PubMed: 36584763
DOI: 10.1016/j.ntt.2022.107150