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https://www.readbyqxmd.com/read/28552772/pcb-28-metabolites-elimination-kinetics-in-human-plasma-on-a-real-case-scenario-study-of-hydroxylated-polychlorinated-biphenyl-oh-pcb-metabolites-of-pcb-28-in-a-highly-exposed-german-cohort
#1
Natalia Quinete, André Esser, Thomas Kraus, Thomas Schettgen
Polychlorinated biphenyls (PCBs) are suspected of carcinogenic, neurotoxic and immunotoxic effects in animals and humans. Although background levels of PCBs have been slowly decreased after their ban, they are still among the most persistent and ubiquitous pollutants in the environment, remaining the subject of great concern. PCB 28 is a trichlorinated PCB found in high concentrations not only in human plasma but also in indoor air in Europe, yet little is known about its metabolic pathway and potential metabolites in humans...
July 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28510766/detection-of-3-3-dichlorobiphenyl-in-human-maternal-plasma-and-its-effects-on-axonal-and-dendritic-growth-in-primary-rat-neurons
#2
Sunjay Sethi, Kimberly P Keil, Hao Chen, Keri Hayakawa, Xueshu Li, Yanping Lin, Hans-Joachim Lehmler, Birgit Puschner, Pamela J Lein
3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is increasingly detected in environmental samples. While more highly chlorinated PCB congeners are known developmental neurotoxicants, nothing is known about the potential developmental neurotoxicity of PCB 11. To address this critical data gap, we measured PCB 11 levels in human maternal plasma and quantified the effects of PCB 11 and its major metabolites on morphometric parameters of neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of plasma from 241 pregnant women enrolled in the MARBLES study (University of California, Davis) detected PCB 11 in all samples at concentrations ranging from 0...
May 16, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28477162/polychlorinated-biphenyls-and-their-hydroxylated-metabolites-in-the-serum-of-e-waste-dismantling-workers-from-eastern-china
#3
Shengtao Ma, Guofa Ren, Xiangying Zeng, Zhiqiang Yu, Guoying Sheng, Jiamo Fu
A number of studies have reported on the exposure of e-waste dismantling workers to significantly high concentrations of halogenated organic pollutants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers. Such exposure can have adverse health effects. However, little information on the metabolites of these contaminants exists. In this study, we investigated PCBs levels and their hydroxylated metabolites (OH-PCB) in the serum of e-waste workers in Taizhou in eastern China. Our results indicate elevated PCB and OH-PCB levels in the serum of the workers, with medians of 443...
May 5, 2017: Environmental Geochemistry and Health
https://www.readbyqxmd.com/read/28431184/congener-specific-disposition-of-chiral-polychlorinated-biphenyls-in-lactating-mice-and-their-offspring-implications-for-pcb-developmental-neurotoxicity
#4
Izabela Kania-Korwel, Tracy Lukasiewicz, Christopher D Barnhart, Marianna Stamou, Haeun Chung, Kevin M Kelly, Stelvio Bandiera, Pamela J Lein, Hans-Joachim Lehmler
Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of two environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8 weeks old) were fed daily, beginning two weeks prior to conception and continuing throughout gestation and lactation, with 3...
April 14, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28038482/microsomal-metabolism-of-prochiral-polychlorinated-biphenyls-results-in-the-enantioselective-formation-of-chiral-metabolites
#5
Eric Uwimana, Anna Maiers, Xueshu Li, Hans-Joachim Lehmler
Polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substituents and their metabolites exist as stable rotational isomers, or atropisomers, that are nonsuperimposable mirror images of each other. Additionally, the oxidation of certain axially prochiral PCBs, such as 2,2',4,6'-tetrachlorobiphenyl (PCB 51) and 2,2',4,5,6'-pentachlorobiphenyl (PCB 102), in the meta position of the symmetrically substituted phenyl ring is expected to form axially chiral hydroxylated metabolites (OH-PCBs); however, the formation of chiral OH-PCBs from prochiral PCBs has not been demonstrated experimentally...
February 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/27989147/2-2-3-5-6-pentachlorobiphenyl-pcb-95-is-atropselectively-metabolized-to-para-hydroxylated-metabolites-by-human-liver-microsomes
#6
Eric Uwimana, Xueshu Li, Hans-Joachim Lehmler
Exposure to neurotoxic, chiral PCBs has been associated with neurodevelopmental disorders, but their metabolism in humans remains unexplored. We investigated the enantioselective metabolism of PCB 95 by human liver microsomes (HLMs) to potentially neurotoxic, hydroxylated metabolites (OH-PCBs). OH-PCB profiles formed in experiments with HLMs differed from metabolite profiles reported for rodent species. The second eluting atropisomer of 2,2',3,5',6-pentachlorobiphenyl-4'-ol, the major metabolite, was preferentially formed by all HLM preparations investigated...
December 19, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27710904/polychlorinated-biphenyl-exposure-and-deiodinase-activity-in-young-infants
#7
Shalini D Soechitram, Sietske A Berghuis, Theo J Visser, Pieter J J Sauer
BACKGROUND: Several studies have shown effects of polychlorinated biphenyls (PCBs) on serum thyroid hormone levels in pregnant woman and their infants, while other studies did not find such effects. How PCBs might affect thyroid hormone metabolism, is still unclear. Potential mechanisms are direct influence on the thyroid gland, binding to thyroid binding proteins, increased excretion or metabolism of thyroid hormones by deiodinases or sulfatases. It is also not well known whether the effect on thyroid hormone levels is caused by PCBs themselves, or by their hydroxylated metabolites (OH-PCBs)...
October 3, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27649311/detoxification-of-hydroxylated-polychlorobiphenyls-by-sphingomonas-sp-strain-n-9-isolated-from-forest-soil
#8
Satomi Mizukami-Murata, Futa Sakakibara, Katsuhide Fujita, Makiko Fukuda, Masato Kuramata, Kazuhiro Takagi
To examine the biodegradation of hydroxylated polychlorobiphenyls (OH-PCBs), we isolated Sphingomonas sp. strain N-9 from forest soil using mineral salt medium containing 4-hydroxy-3-chlorobiphenyl (4OH-3CB) at the concentration of 10 mg/L. Following incubation with strain N-9, the concentration of 4OH-3CB decreased in inverse proportion to strain N-9 proliferation, and it was converted to 3-chloro-4-hydroxybenzoic acid (4OH-3CBA) after 1 day. We observed that strain N-9 efficiently degraded lowly chlorinated OH-PCBs (1-4 Cl), while highly chlorinated OH-PCBs (5-6 Cl) were less efficiently transformed...
December 2016: Chemosphere
https://www.readbyqxmd.com/read/27622755/determination-of-hydroxylated-polychlorinated-biphenyls-oh-pcbs-in-human-urine-in-a-highly-occupationally-exposed-german-cohort-new-prospects-for-urinary-biomarkers-of-pcb-exposure
#9
Natalia Quinete, André Esser, Thomas Kraus, Thomas Schettgen
The present study evaluates for the first time the determination of 20 hydroxylated polychlorinated biphenyl (OH-PCB) congeners and their glucuronide and sulfate conjugates in urine as a biomarker of exposure to PCBs in humans. Thereby, a fast, sensitive and selective online solid phase extraction (SPE) method coupled to LC-MS/MS was validated for the determination of OH-PCBs in human urine, being previously successfully developed and applied for the separation and quantitation of OH-PCBs in human plasma. The lowest limit of quantification (LLOQ) ranged from 0...
December 2016: Environment International
https://www.readbyqxmd.com/read/27352881/serum-polychlorinated-biphenyls-and-their-hydroxylated-metabolites-are-associated-with-demographic-and-behavioral-factors-in-children-and-mothers
#10
Wen Xin Koh, Keri C Hornbuckle, Kai Wang, Peter S Thorne
Factors contributing to the inter-individual variation in body burden of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have not been fully elucidated. We examined associations between total serum concentrations of 209 PCBs, 64 OH-PCBs, and frequently detected individual congeners with demographic characteristics (age, gender, ethnicity and community of residence), body mass index (BMI or BMI percentile), and breastfeeding history in children and their mothers from 83 U.S. households...
September 2016: Environment International
https://www.readbyqxmd.com/read/27267742/concentrations-and-patterns-of-hydroxylated-polybrominated-diphenyl-ethers-and-polychlorinated-biphenyls-in-arctic-foxes-vulpes-lagopus-from-svalbard
#11
Heli Routti, Martin S Andersen, Eva Fuglei, Anuschka Polder, Nigel G Yoccoz
Concentrations and patterns of hydroxylated (OH) polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were investigated in liver from arctic foxes (Vulpes lagopus) sampled from Svalbard 1997-2011 (n = 100). The most important OH-PBDE in the arctic foxes was 6-OH-BDE47 detected in 24% of the samples. Relationships between 6-OH-BDE47, δ(13)C and BDE47 suggest that 6-OH-BDE47 residues in arctic foxes are related to marine dietary input, while the relative importance of the metabolic/natural origin of this compound remains unclear...
September 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27116425/sulfation-of-lower-chlorinated-polychlorinated-biphenyls-increases-their-affinity-for-the-major-drug-binding-sites-of-human-serum-albumin
#12
Eric A Rodriguez, Xueshu Li, Hans-Joachim Lehmler, Larry W Robertson, Michael W Duffel
The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin...
May 17, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/26774304/hydroxylated-polychlorinated-biphenyls-in-human-sera-from-adolescents-and-their-mothers-living-in-two-u-s-midwestern-communities
#13
Wen Xin Koh, Keri C Hornbuckle, Rachel F Marek, Kai Wang, Peter S Thorne
Hydroxylated polychlorinated biphenyls (OH-PCBs) have been detected in human specimens and some are suspected as being more toxic than their parent compounds. We compared 58 OH-PCB congeners (in 51 chromatographic peaks) in serum samples from participants in the AESOP Study, a longitudinal cohort study of adolescents and their mothers living in urban and rural areas in the United States. We hypothesized that adolescents would have lower levels of OH-PCBs than their mothers and that serum concentration of OH-PCBs would be stable over a 3-year period...
March 2016: Chemosphere
https://www.readbyqxmd.com/read/26630569/organohalogen-compounds-in-pet-dog-and-cat-do-pets-biotransform-natural-brominated-products-in-food-to-harmful-hydroxlated-substances
#14
Hazuki Mizukawa, Kei Nomiyama, Susumu Nakatsu, Hisato Iwata, Jean Yoo, Akira Kubota, Miyuki Yamamoto, Mayumi Ishizuka, Yoshinori Ikenaka, Shouta M M Nakayama, Tatsuya Kunisue, Shinsuke Tanabe
There are growing concerns about the increase in hyperthyroidism in pet cats due to exposure to organohalogen contaminants and their hydroxylated metabolites. This study investigated the blood contaminants polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PCBs, OH-PBDEs, and MeO-PBDEs), in pet dogs and cats. We also measured the residue levels of these compounds in commercially available pet foods. Chemical analyses of PCBs and OH-PCBs showed that the OH-PCB levels were 1 to 2 orders of magnitude lower in cat and dog food products than in their blood, suggesting that the origin of OH-PCBs in pet dogs and cats is PCBs ingested with their food...
January 5, 2016: Environmental Science & Technology
https://www.readbyqxmd.com/read/26598992/3d-qsar-studies-of-hydroxylated-polychlorinated-biphenyls-as-potential-xenoestrogens
#15
Patricia Ruiz, Kundan Ingale, John S Wheeler, Moiz Mumtaz
Mono-hydroxylated polychlorinated biphenyls (OH-PCBs) are found in human biological samples and lack of data on their potential estrogenic activity has been a source of concern. We have extended our previous in silico 2D QSAR study through the application of advance techniques such as docking and 3D QSAR to gain insights into their estrogen receptor (ERα) binding. The results support our earlier findings that the hydroxyl group is the most important feature on the compounds; its position, orientation and surroundings in the structure are influential for the binding of OH-PCBs to ERα...
February 2016: Chemosphere
https://www.readbyqxmd.com/read/26463278/subacute-nicotine-co-exposure-has-no-effect-on-2-2-3-5-6-pentachlorobiphenyl-disposition-but-alters-hepatic-cytochrome-p450-expression-in-the-male-rat
#16
Marianna Stamou, Eric Uwimana, Brenna M Flannery, Izabela Kania-Korwel, Hans-Joachim Lehmler, Pamela J Lein
Polychlorinated biphenyls (PCBs) are metabolized by cytochrome P450 2B enzymes (CYP2B) and nicotine is reported to alter CYP2B activity in the brain and liver. To test the hypothesis that nicotine influences PCB disposition, 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and its metabolites were quantified in tissues of adult male Wistar rats exposed to PCB 95 (6mg/kg/d, p.o.) in the absence or presence of nicotine (1.0mg/kg/d of the tartrate salt, s.c.) for 7 consecutive days. PCB 95 was enantioselectively metabolized to hydroxylated (OH-) PCB metabolites, resulting in a pronounced enrichment of E1-PCB 95 in all tissues investigated...
December 2, 2015: Toxicology
https://www.readbyqxmd.com/read/26271003/effect-of-pregnancy-on-the-disposition-of-2-2-3-5-6-pentachlorobiphenyl-pcb-95-atropisomers-and-their-hydroxylated-metabolites-in-female-mice
#17
Izabela Kania-Korwel, Christopher D Barnhart, Pamela J Lein, Hans-Joachim Lehmler
Chiral PCBs, such as PCB 95, are developmental neurotoxicants that undergo atropisomeric enrichment in nonpregnant adult mice. Because pregnancy is associated with changes in hepatic cytochrome P450 enzyme activity as well as lipid disposition and metabolism, this study investigates the effect of pregnancy on the maternal disposition of chiral PCBs. Female C57BL/6 mice (8 weeks old) were dosed daily beginning 2 weeks prior to conception and continuing throughout gestation and lactation (56 days total) with racemic PCB 95 (0, 0...
September 21, 2015: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/26165989/mechanistic-insights-into-the-specificity-of-human-cytosolic-sulfotransferase-2a1-hsult2a1-for-hydroxylated-polychlorinated-biphenyls-through-the-use-of-fluoro-tagged-probes
#18
E J Ekuase, T J van 't Erve, A Rahaman, L W Robertson, M W Duffel, G Luthe
Determining the relationships between the structures of substrates and inhibitors and their interactions with drug-metabolizing enzymes is of prime importance in predicting the toxic potential of new and legacy xenobiotics. Traditionally, quantitative structure activity relationship (QSAR) studies are performed with many distinct compounds. Based on the chemical properties of the tested compounds, complex relationships can be established so that models can be developed to predict toxicity of novel compounds...
February 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/25743931/organohalogens-and-their-hydroxylated-metabolites-in-the-blood-of-pigs-from-an-open-waste-dumping-site-in-south-india-association-with-hepatic-cytochrome-p450
#19
Hazuki Mizukawa, Kei Nomiyama, Tatsuya Kunisue, Michio X Watanabe, Annamalai Subramanian, Hisato Iwata, Mayumi Ishizuka, Shinsuke Tanabe
The concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and their hydroxylated metabolites (OH-PCBs and OH-PBDEs) were measured in the blood of Eurasian wild pigs (Sus scrofa) from a municipal waste open dumping site (DS) and a reference site (RS) in South India. We showed that contamination with OH-PCBs was higher in female pigs from the DS than in all other adult pigs. The highest OH-PCB concentrations were found in piglets from the DS. Moreover, the hepatic expression levels of CYP1A and CYP2B were higher in piglets than in their dam, implying metabolism of PCBs by cytochrome P450 (CYP) enzymes...
April 2015: Environmental Research
https://www.readbyqxmd.com/read/25659948/residue-profiles-of-organohalogen-compounds-in-human-serum-from-e-waste-recycling-sites-in-north-vietnam-association-with-thyroid-hormone-levels
#20
Akifumi Eguchi, Kei Nomiyama, Nguyen Minh Tue, Pham Thi Kim Trang, Pham Hung Viet, Shin Takahashi, Shinsuke Tanabe
This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam. Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300pgg(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200pgg(-)(1) wet wt, respectively)...
February 2015: Environmental Research
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