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The Journal of Biological Chemistry 2021Polychlorinated bisphenols (PCBs) continue to contaminate food chains globally where they concentrate in tissues and disrupt the endocrine systems of species throughout...
Polychlorinated bisphenols (PCBs) continue to contaminate food chains globally where they concentrate in tissues and disrupt the endocrine systems of species throughout the ecosphere. Hydroxylated PCBs (OH-PCBs) are major PCB metabolites and high-affinity inhibitors of human estrogen sulfotransferase (SULT1E1), which sulfonates estrogens and thus prevents them from binding to and activating their receptors. OH-PCB inhibition of SULT1E1 is believed to contribute significantly to PCB-based endocrine disruption. Here, for the first time, the molecular basis of OH-PCB inhibition of SULT1E1 is revealed in a structure of SULT1E1 in complex with OH-PCB1 (4'-OH-2,6-dichlorobiphenol) and its substrates, estradiol (E2), and PAP (3'-phosphoadenosine-5-phosphosulfate). OH-PCB1 prevents catalysis by intercalating between E2 and catalytic residues and establishes a new E2-binding site whose E2 affinity and positioning are greater than and competitive with those of the reactive-binding pocket. Such complexes have not been observed previously and offer a novel template for the design of high-affinity inhibitors. Mutating residues in direct contact with OH-PCB weaken its affinity without compromising the enzyme's catalytic parameters. These OH-PCB resistant mutants were used in stable transfectant studies to demonstrate that OH-PCBs regulate estrogen receptors in cultured human cell lines by binding the OH-PCB binding pocket of SULT1E1.
Topics: Enzyme Inhibitors; Estrogens; Humans; Hydroxylation; Models, Molecular; Polychlorinated Biphenyls; Receptors, Estrogen; Sulfotransferases
PubMed: 33524392
DOI: 10.1016/j.jbc.2021.100353 -
Environmental Science & Technology Jun 2022Polychlorinated biphenyls (PCBs), "famous" as persistent organic pollutants (POPs), have been managed nationally since the 1970s and globally under the Stockholm...
Polychlorinated biphenyls (PCBs), "famous" as persistent organic pollutants (POPs), have been managed nationally since the 1970s and globally under the Stockholm Convention on POPs since 2004, requiring environmentally sound management (ESM) of PCBs by 2028. At most, 30% of countries are on track to achieve ESM by 2028. Globally over 10 million tonnes of PCB-containing materials remain, mostly in countries lacking the ability to manage PCB waste. Canada (Ontario) and Czechia, both parties to the Stockholm Convention, are close to achieving the 2028 goal, having reduced their stocks of pure PCBs by 99% in the past 10 years. In contrast, the USA, not a party to the Stockholm Convention, continues to have a substantial but poorly inventoried stock of PCBs and only ∼3% decrease in mass of PCBs since 2006. PCB management, which depends on Stockholm Convention support and national compliance, portends major challenges for POP management. The failure to manage global PCB stocks >30 years after the end of production highlights the urgent need to prioritize reducing production and use of newer, more widely distributed POPs such as chlorinated paraffins and per- and polyfluorinated alkyl substances, as these management challenges are unlikely to be resolved in the coming decades.
Topics: Environmental Monitoring; Environmental Pollutants; Ontario; Paraffin; Polychlorinated Biphenyls
PubMed: 35647669
DOI: 10.1021/acs.est.2c01204 -
Environmental Science and Pollution... Mar 2020Polychlorinated biphenyls (PCBs) are environmental pollutants implicated in a variety of adverse health effects, including cancer and noncancer diseases in animals and...
Polychlorinated biphenyls (PCBs) are environmental pollutants implicated in a variety of adverse health effects, including cancer and noncancer diseases in animals and humans. PCBs are metabolized to hydroxylated compounds, and some of these PCB metabolites are more toxic than the parent PCBs. Unfortunately, most PCB metabolites needed for toxicological studies are not available from commercial sources. Moreover, it is challenging to synthesize PCB metabolites because starting materials with suitable substitution patterns are not readily available. Here, we report the novel synthesis of a variety of mono- and dimethoxyarene derivatives from commercially available fluoroarenes via nucleophilic aromatic substitution with sodium methoxide. This reaction provided good to excellent yields of the desired methoxylated products. Suzuki coupling of selected mono- and dimethoxy haloarenes with chlorinated phenylboronic acids yielded methoxylated derivatives of PCB 11, 12, 25, 35, and 36 in low to good yields. Crystal structures of 3,3'-dichloro-2,5-dimethoxy-1,1'-biphenyl and 3',5-dichloro-2,3-dimethoxy-1,1'-biphenyl confirmed the substitution pattern of both compounds. This synthesis strategy provides straightforward access to a range of mono- and dimethoxylated PCB derivatives that were not readily accessible previously.
Topics: Animals; Environmental Pollutants; Humans; Polychlorinated Biphenyls
PubMed: 31893358
DOI: 10.1007/s11356-019-07133-3 -
Environmental Science & Technology Oct 2022We conducted experiments to determine whether bioaugmentation with aerobic, polychlorinated biphenyl (PCB)-degrading microorganisms can mitigate polychlorinated biphenyl...
We conducted experiments to determine whether bioaugmentation with aerobic, polychlorinated biphenyl (PCB)-degrading microorganisms can mitigate polychlorinated biphenyl (PCB) emissions from contaminated sediment to air. strain LB400 was added to bioreactors containing PCB-contaminated site sediment. PCB mass in both the headspace and aqueous bioreactor compartments was measured using passive samplers over 35 days. Time-series measurements of all 209 PCB congeners revealed a 57% decrease in total PCB mass accumulated in the vapor phase of bioaugmented treatments relative to non-bioaugmented controls, on average. A comparative congener-specific analysis revealed preferential biodegradation of lower-chlorinated PCBs (LC-PCBs) by LB400. Release of the most abundant congener (PCB 4 [2,2'-dichlorobiphenyl]) decreased by over 90%. Simulations with a PCB reactive transport model closely aligned with experimental observations. We also evaluated the effect of the phytogenic biosurfactant, saponin, on PCB bioavailability and biodegradation by LB400. Time-series qPCR measurements of biphenyl dioxygenase () genes showed that saponin better maintained abundance, compared to the saponin-free treatment. These findings indicate that an active population of bioaugmented, aerobic PCB-degrading microorganisms can effectively lower PCB emissions and may therefore contribute to minimizing PCB inhalation exposure in communities surrounding PCB-contaminated sites.
Topics: Biodegradation, Environmental; Dioxygenases; Hydroxylamines; Polychlorinated Biphenyls
PubMed: 36178372
DOI: 10.1021/acs.est.2c01043 -
Environmental Health Perspectives Mar 2017Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are neurodevelopmental toxicants, but few studies have examined associations with autism spectrum...
Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability.
BACKGROUND
Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are neurodevelopmental toxicants, but few studies have examined associations with autism spectrum disorder (ASD).
OBJECTIVES
We aimed to determine whether prenatal exposure to PCBs and OCPs influences offspring risk of ASD and intellectual disability without autism (ID).
METHODS
We conducted a population-based case-control study among Southern California births, including children with ASD ( = 545) meeting (DSM-IV-TR) criteria and ID ( = 181), as well as general population (GP) controls ( = 418). Concentrations of 11 PCB congeners and 2 OCPs measured in banked second-trimester serum samples were compared between the diagnostic groups. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses.
RESULTS
Geometric mean levels of several PCB congeners were higher in the ASD group than in the ID and GP groups. ASD risk was elevated for a number of PCB congeners, particularly for the highest vs. lowest quartile of PCB138/158 (AOR = 1.79; 95% CI: 1.10, 2.71) and PCB153 (AOR = 1.82; 95% CI: 1.10, 3.02), and for highest deciles of other congeners in secondary analyses. PCB138/158 was also associated with increased ID (AOR = 2.41; 95% CI: 1.18, 4.91), though no trend was suggested. OCPs were not associated with increased risk of ASD in primary analyses, whereas nonmonotonic increases in risk of ID were found with ´-DDE.
CONCLUSIONS
Our results suggest higher levels of some organochlorine compounds during pregnancy are associated with ASD and ID. Citation: Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, Windham GC. 2017. Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect 125:474-480; http://dx.doi.org/10.1289/EHP277.
Topics: Adult; Autism Spectrum Disorder; California; Case-Control Studies; Child; Environmental Pollutants; Female; Humans; Hydrocarbons, Chlorinated; Intellectual Disability; Logistic Models; Male; Maternal Exposure; Odds Ratio; Pesticides; Polychlorinated Biphenyls; Pregnancy
PubMed: 27548254
DOI: 10.1289/EHP277 -
Chemosphere Feb 2022Polychlorinated biphenyls (PCBs) can provide crucial information into the bioaccumulation and biomagnification of POPs in marine mammals. Muscle tissue samples were...
Polychlorinated biphenyls (PCBs) can provide crucial information into the bioaccumulation and biomagnification of POPs in marine mammals. Muscle tissue samples were obtained for detailed PCB congener specific analysis of all 209 PCBs in 11 species of marine mammals stranded across the coast of the UK between 2010 and 2013. At least 145 PCB congeners were found in each individual. The highest concentrations of PCBs were recorded in a killer whale (318 mg/kg lipid) and the highest toxic equivalent in a Risso's dolphin (1687 pg/g TEQ wet). Concentrations of PCBs in the majority of samples exceeded toxic thresholds (9 mg/kg lipid) for marine mammals, highlighting the health risk they face from PCB exposure. Many PCB profiles did not fit typical 'Aroclor' signatures, but instead indicated patterns of congeners that are resistant to biotransformation and elimination. However, this study identified a novel PCB signature in a sei whale that has not yet been previously observed in marine mammals. The whale had a PCB profile that included lighter and inadvertent PCB congeners such as PCB 11, suggesting that the main source of exposure was through atmospheric deposition, rather than terrestrial discharges. Seven subsamples were chosen for chiral analysis of PCB 95, 136 and 149. The enantiomer fractions (EFs) of C-PCBs 95 and 149 were non racemic suggesting there may be enantiomer selective metabolism in marine mammals. Although there has been a shift in the literature towards emerging pollutants, this study acts as a stark reminder that PCBs continue to pose a significant risk to wildlife.
Topics: Animals; Atlantic Ocean; Biotransformation; Caniformia; Environmental Pollutants; Polychlorinated Biphenyls
PubMed: 34687677
DOI: 10.1016/j.chemosphere.2021.132639 -
Ecotoxicology and Environmental Safety May 2022Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated...
Exposure to environmental pollutants, including dioxin-like pollutants, can cause numerous health issues. A common exposure route to pollutants is through contaminated foods, and thus the gastrointestinal system and gut microbiota are often exposed to high amounts of pollutants. Multiple studies have focused on the imbalance in intestinal microbiota composition caused by dioxin-like pollutants. Here, we examined the effects of polychlorinated biphenyl 126 (PCB126) on the composition and functions of gut microbes through metagenomic sequencing, and explored the correlations between microflora dysbiosis and aryl hydrocarbon receptor (AHR) signaling. Adult male wild-type and Ahr mice with a C57BL/6 background were weekly exposed to 50 μg/kg body weight of PCB126 for 8 weeks. Results showed that PCB126 had the opposite effect on gut microbiota composition and diversity in the wild-type and Ahr mice. Functional prediction found that PCB126 exposure mainly altered carbon metabolism and signal regulatory pathways in wild-type mice but impacted DNA replication and lipopolysaccharide biosynthesis in Ahr mice. In wild-type mice, PCB126 exposure induced liver injury, decreased serum lipid content, and delayed gastrointestinal motility, which were significantly correlated to several specific bacterial taxa, such as Helicobacter. Following AHR knockout, however, the holistic effects of PCB126 on the host were lessened or abolished. These results suggest that PCB126 may disrupt host metabolism and gut microbiota dynamics via AHR activation. Overall, our findings provide new insight into the complex interactions between host metabolism and gut microbiota, which may contribute to grouped assessment of environmental pollutants in the future.
Topics: Animals; Dioxins; Environmental Pollutants; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Receptors, Aryl Hydrocarbon
PubMed: 35367886
DOI: 10.1016/j.ecoenv.2022.113448 -
PloS One 2023As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether...
As an animal familiar to humans, cats are considered to be sensitive to chemicals; cats may be exposed to polychlorinated biphenyls (PCBs) and decabromodiphenyl ether (BDE-209) from indoor dust, household products, and common pet food, leading to adverse endocrine effects, such as thyroid hormone dysfunction. To elucidate the general biological effects resulting from exposure of cats to PCBs and PBDEs, cats were treated with a single i.p. dose of a principal mixture of 12 PCBs and observed for a short-term period. Results revealed that the testis weight, serum albumin, and total protein of the treated group decrease statistically in comparison with those in the control group. The negative correlations suggested that the decrease in the total protein and albumin levels may be disturbed by 4'OH-CB18, 3'OH-CB28 and 3OH-CB101. Meanwhile, the serum albumin level and relative brain weight decreased significantly for cats subjected to 1-year continuous oral administration of BDE-209 in comparison to those of control cats. In addition, the subcutaneous fat as well as serum high-density lipoprotein (HDL) and triglycerides (TG) levels increased in cats treated with BDE-209 and down-regulation of stearoyl-CoA desaturase mRNA expression in the liver occurred. These results suggested that chronic BDE-209 treatment may restrain lipolysis in the liver, which is associated with lipogenesis in the subcutaneous fat. Evidence of liver and kidney cell damage was not observed as there was no significant difference in the liver enzymes, blood urea nitrogen and creatinine levels between the two groups of both experiments. To the best of our knowledge, this is the first study that provides information on the biochemical effects of organohalogen compounds in cats. Further investigations on risk assessment and other potential health effects of PCBs and PBDEs on the reproductive system, brain, and lipid metabolism in cats are required.
Topics: Male; Cats; Humans; Animals; Polychlorinated Biphenyls; Halogenated Diphenyl Ethers; Liver; Thyroid Hormones
PubMed: 36662783
DOI: 10.1371/journal.pone.0277689 -
Environmental Science. Processes &... Dec 2014Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use...
Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.
Topics: Air Pollution, Indoor; Australia; Dioxins; Dust; Female; Humans; Maternal Exposure; Polychlorinated Biphenyls; Pregnancy
PubMed: 25343442
DOI: 10.1039/c4em00383g -
Neurotoxicology Dec 2019A series of complex physiological processes underlie the development of the microbiota, gut, and brain in early life, which together communicate via the... (Review)
Review
A series of complex physiological processes underlie the development of the microbiota, gut, and brain in early life, which together communicate via the microbiota-gut-brain axis to maintain health and homeostasis. Disruption of these processes can lead to dysbiosis of the microbiota, pathophysiology of the gut and behavioral deficits including depression, anxiety and cognitive deficits. Environmental exposures, particularly in early life, can interfere with development and impact these pathways. This review will focus on the role of the microbiome and the gut in neurodevelopment and neurodegeneration as well as the impacts of environmental exposures, particularly to the neurotoxicant polychlorinated biphenyls (PCBs), given that the gut serves as the primary exposure route. There exists extensive research on the importance of the microbiome in the developing brain and connections with autism spectrum disorder (ASD) and increasing links being established between the microbiome and development of Alzheimer's disease (AD) in the elderly. Finally, we will speculate on the mechanisms through which PCBs can induce dysbiosis and dysregulate physiology of the gut and brain.
Topics: Alzheimer Disease; Animals; Autistic Disorder; Brain; Gastrointestinal Microbiome; Humans; Neurodegenerative Diseases; Neurodevelopmental Disorders; Neurogenesis; Polychlorinated Biphenyls
PubMed: 31454514
DOI: 10.1016/j.neuro.2019.08.010