Doses Of Polychlorinated Biphenyls Research Articles

Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers

BackgroundExposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. ObjectivesThe purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. MethodsThe Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. ResultsA 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06–2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05–2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02–2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. ConclusionsThis study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Enantiomeric Fractions Reveal Differences in the Atropselective Disposition of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) in Wildtype, Cyp2abfgs-Null, and CYP2A6-Humanized Mice.

Polychlorinated biphenyls (PCBs) are environmental contaminants that can cause neurotoxicity. PCBs, such as PCB 95 (2,2',3,5',6-pentachlorobiphenyl), can be metabolized by cytochrome P450 enzymes into neurotoxic metabolites. To better understand how the metabolism of PCB 95 affects neurotoxic outcomes, we conducted a study on the disposition of PCB 95 in transgenic mouse models. The mice were given a single oral dose of PCB 95 (1.0 mg/kg) and were euthanized 24 h later for analysis. PCB 95 levels were highest in adipose tissue, followed by the liver, brain, and blood. Adipose tissue levels were significantly higher in wild-type (WT) mice than in Cyp2abfgs-null (KO) or CYP2A6-transgenic (KI) mice. We also observed genotype-dependent differences in the enrichment of aS-PCB 95 in female mice, with a less pronounced enrichment in KO than WT and KI mice. Ten hydroxylated PCB 95 metabolites were detected in blood and tissue across all exposure groups. The metabolite profiles differed across tissues, while sex and genotype-dependent differences were less pronounced. Total OH-PCB levels were highest in the blood, followed by the liver, adipose tissue, and brain. Total OH-PCB blood levels were lower in KO than in WT mice, while the opposite trend was observed in the liver. In male mice, total OH-PCB metabolite levels were significantly lower in KI than in WT mice in blood and the liver, while the opposite trend was observed in female mice. In conclusion, the study highlights the differences in the atropselective disposition of PCB 95 and its metabolites in different types of mice, demonstrating the usefulness of these transgenic mouse models for characterizing the role of PCB metabolism in PCB neurotoxicity.

Air Monitoring of Polychlorinated Biphenyls and Organochlorine Pesticides in Eastern Siberia: Levels, Temporal Trends, and Risk Assessment

In this study, we evaluate the long-term and seasonal variations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), α-, γ-hexachlorocyclohexanes (HCH), and p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT) and its metabolites through a passive air sampling method at two (urban and suburban) stations in Eastern Siberia, Russia, in 2011–2017. The median levels of HCB, ∑HCHs, ∑DDTs, ∑PCB39, and ∑PCB6 in the air were 116, 84, 55, 128, and 41 pg/m3 and 83, 21, 11, 52, and 16 pg/m3 at the urban and suburban stations, respectively. PCB and HCH levels in the air of Irkutsk decreased considerably in the 2000s, in comparison to the late 1980s and early 1990s, while an increasing trend was observed for HCB during the 2010s. The seasonality of air concentrations (with summer concentrations higher than winter concentrations) was well exhibited by PCB, HCH, and DDT, but not HCB. Significant correlations were observed between approximately all studied persistent organic pollutants and the average air temperature, quantity of precipitation, and frequency of the prevailing wind direction during the sampling period. The daily doses of PCBs, DDTs, HCHs, and HCB under human exposure by inhalation amounted to 38, 21, 27, and 35 and 17, 6, 7, and 27 pg/kg body weight per day in urban and suburban areas, respectively.

Effect of PCBs Extracted from Offshore Sediment of South China Sea (Zhanjiang) on Histological Structure and Inflammation of Zebrafish Intestine

As ubiquitous environmental pollutants, polychlorinated biphenyls (PCBs) can cause significant health risks to various organisms, including humans. Meanwhile, PCBs exhibit various properties such as biological toxicity, high fat solubility, and accumulation in sediments and bioaccumulation in the food chain. In this study, the concentration of PCBs in Zhanjiang offshore sediment and the histopathological changes and the mRNA expression of cytokines in intestines of zebrafish (Danio rerio) exposed to environmentally relevant concentrations of PCBs were investigated. Among the six sites selected, PCB28 was found in the sediments of Lakeside Park (BHP) and Seashore Park (HBP), with concentrations of 35.0 and 27.0 μg/kg, respectively. On the other hand, PCB81 was discovered in the sediments of Jinsha Bay (JSW) with a total amount of 29.0 μg/kg. Adult zebrafish were exposed to different PCB concentrations through water, with control (no PCB exposure), positive control (PCB 81 at 10 μg/L), low (5 μg/L), medium (10 μg/L), and high (15 μg/L) PCB doses. The fish were euthanized on days 1, 3, 5, and 7. The intestinal epithelial cells of the zebrafish exposed to PCB extracts proved the dose-responsive lesions. With the increase of concentration and time (P < 0.05), the relative expression of IL-1β, IL-8, and TNF-α mRNA increased significantly. The results showed that intestinal lesions and inflammation were dependent on exposure dose.

The disposition of polychlorinated biphenyls (PCBs) differs between germ-free and conventional mice

The disposition of toxicants, such as polychlorinated biphenyls (PCBs), in germ-free (GF) vs. conventional (CV) mice has received little attention to date. Here, we investigate PCB levels in three-month-old female CV and GF mice exposed orally daily for 3 days to 0, 6, or 30 mg/kg body weight of the Fox River Mixture (FRM), an environmental PCB mixture. We euthanized animals 24 h after the final dose. PCB profiles in tissues differed from the FRM profile but were similar in tissues across all 4 PCB exposure groups. PCB levels in CV but not GF mice followed the difference in PCB dose. Importantly, PCB levels were higher in CV than GF mice exposed to the same dose. Hepatic cytochrome P450 enzyme or lipid levels did not explain these trends in PCB tissue levels. Thus, toxicity studies with CV and GF animals need to assess the toxicokinetics of the toxicant investigated. CapsulePCB levels are typically higher in conventional than germ-free mice exposed to the same dose of PCBs.

Sex and Genotype Modulate the Dendritic Effects of Developmental Exposure to a Human-Relevant Polychlorinated Biphenyls Mixture in the Juvenile Mouse.

While many neurodevelopmental disorders (NDDs) are thought to result from interactions between environmental and genetic risk factors, the identification of specific gene-environment interactions that influence NDD risk remains a critical data gap. We tested the hypothesis that polychlorinated biphenyls (PCBs) interact with human mutations that alter the fidelity of neuronal Ca2+ signaling to confer NDD risk. To test this, we used three transgenic mouse lines that expressed human mutations known to alter Ca2+ signals in neurons: (1) gain-of-function mutation in ryanodine receptor-1 (T4826I-RYR1); (2) CGG-repeat expansion in the 5′ non-coding portion of the fragile X mental retardation gene 1 (FMR1); and (3) a double mutant (DM) that expressed both mutations. Transgenic and wildtype (WT) mice were exposed throughout gestation and lactation to the MARBLES PCB mix at 0.1, 1, or 6 mg/kg in the maternal diet. The MARBLES mix simulates the relative proportions of the twelve most abundant PCB congeners found in serum from pregnant women at increased risk for having a child with an NDD. Using Golgi staining, the effect of developmental PCB exposure on dendritic arborization of pyramidal neurons in the CA1 hippocampus and somatosensory cortex of male and female WT mice was compared to pyramidal neurons from transgenic mice. A multilevel linear mixed-effects model identified a main effect of dose driven by increased dendritic arborization of cortical neurons in the 1 mg/kg PCB dose group. Subsequent analyses with genotypes indicated that the MARBLES PCB mixture had no effect on the dendritic arborization of hippocampal neurons in WT mice of either sex, but significantly increased dendritic arborization of cortical neurons of WT males in the 6 mg/kg PCB dose group. Transgene expression increased sensitivity to the impact of developmental PCB exposure on dendritic arborization in a sex-, and brain region-dependent manner. In conclusion, developmental exposure to PCBs present in the gestational environment of at-risk humans interfered with normal dendritic morphogenesis in the developing mouse brain in a sex-, genotype- and brain region-dependent manner. Overall, these observations provide proof-of-principle evidence that PCBs interact with heritable mutations to modulate a neurodevelopmental outcome of relevance to NDDs.

In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder

Bladder dysfunction, including incontinence, difficulty emptying the bladder, or urgency to urinate is a pervasive health and quality of life concern. However, risk factors for developing these symptoms are not completely understood, and the influence of exposure to environmental chemicals, especially during development, on the formation and function of the bladder is understudied. Environmental contaminants such as polychlorinated biphenyls (PCBs) are known to pose a risk to the developing brain; however, their influence on the development of peripheral target organs, such as bladder, are unknown. To address this data gap, C57Bl/6J mouse dams were exposed to an environmentally-relevant PCB mixture at 0, 0.1, 1 or 6 mg/kg daily beginning two weeks prior to mating and continuing through gestation and lactation. Bladders were collected from offspring at postnatal days (P) 28–31. PCB concentrations were detected in bladders in a dose-dependent manner. PCB effects on the bladder were sex- and dose-dependent. Overall, PCB effects were observed in male, but not female, bladders. PCBs increased bladder volume and suburothelial βIII-tubulin-positive nerve density compared to vehicle control. A subset of these nerves were sensory peptidergic axons indicated by increased calcitonin gene-related protein (CGRP) positive nerve fibers in mice exposed to the highest PCB dose compared to the lowest PCB dose. PCB-induced increased nerve density was also positively correlated with the number of mast cells in the bladder, suggesting inflammation may be involved. There were no detectable changes in epithelial composition or apoptosis as indicated by expression of cleaved caspase 3, suggesting PCBs do not cause overt toxicity. Bladder volume changes were not accompanied by changes in bladder mass or epithelial thickness, indicating that obstruction was not likely involved. Together, these results are the first to suggest that following developmental exposure, PCBs can distribute to the bladder and alter neuroanatomic development and bladder volume in male mice.

Exercise influences the impact of polychlorinated biphenyl exposure on immune function.

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1β concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1β concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.

Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.

Polychlorinated biphenyls (PCBs) are ubiquitously detected and have been linked to metabolic diseases. Gut microbiome is recognized as a critical regulator of disease susceptibility; however, little is known how PCBs and gut microbiome interact to modulate hepatic xenobiotic and intermediary metabolism. We hypothesized the gut microbiome regulates PCB-mediated changes in the metabolic fingerprints and hepatic transcriptome. Ninety-day-old female conventional and germ-free mice were orally exposed to the Fox River Mixture (synthetic PCB mixture, 6 or 30 mg/kg) or corn oil (vehicle control, 10 ml/kg), once daily for 3 consecutive days. RNA-seq was conducted in liver, and endogenous metabolites were measured in liver and serum by LC-MS. Prototypical target genes of aryl hydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor were more readily upregulated by PCBs in conventional conditions, indicating PCBs, to the hepatic transcriptome, act partly through the gut microbiome. In a gut microbiome-dependent manner, xenobiotic, and steroid metabolism pathways were upregulated, whereas response to misfolded proteins-related pathways was downregulated by PCBs. At the high PCB dose, NADP, and arginine appear to interact with drug-metabolizing enzymes (ie, Cyp1-3 family), which are highly correlated with Ruminiclostridium and Roseburia, providing a novel explanation of gut-liver interaction from PCB-exposure. Utilizing the Library of Integrated Network-based Cellular Signatures L1000 database, therapeutics targeting anti-inflammatory and endoplasmic reticulum stress pathways are predicted to be remedies that can mitigate PCB toxicity. Our findings demonstrate that habitation of the gut microbiota drives PCB-mediated hepatic responses. Our study adds knowledge of physiological response differences from PCB exposure and considerations for further investigations for gut microbiome-dependent therapeutics.

The influence of sex, genotype, and dose on serum and hippocampal cytokine levels in juvenile mice developmentally exposed to a human-relevant mixture of polychlorinated biphenyls

Polychlorinated biphenyls (PCBs) are pervasive environmental contaminants implicated as risk factors for neurodevelopmental disorders (NDDs). Immune dysregulation is another NDD risk factor, and developmental PCB exposures are associated with early life immune dysregulation. Studies of the immunomodulatory effects of PCBs have focused on the higher-chlorinated congeners found in legacy commercial mixtures. Comparatively little is known about the immune effects of contemporary, lower-chlorinated PCBs. This is a critical data gap given recent reports that lower-chlorinated congeners comprise >70% of the total PCB burden in serum of pregnant women enrolled in the MARBLES study who are at increased risk for having a child with an NDD. To examine the influence of PCBs, sex, and genotype on cytokine levels, mice were exposed throughout gestation and lactation to a PCB mixture in the maternal diet, which was based on the 12 most abundant PCBs in sera from MARBLES subjects. Using multiplex array, cytokines were quantified in the serum and hippocampus of weanling mice expressing either a human gain-of-function mutation in ryanodine receptor 1 (T4826I mice), a human CGG premutation repeat expansion in the fragile X mental retardation gene 1 (CGG mice), or both mutations (DM mice). Congenic wildtype (WT) mice were used as controls. There were dose-dependent effects of PCB exposure on cytokine concentrations in the serum but not hippocampus. Differential effects of genotype were observed in the serum and hippocampus. Hippocampal cytokines were consistently elevated in T4826I mice and also in WT animals for some cytokines compared to CGG and DM mice, while serum cytokines were usually elevated in the mutant genotypes compared to the WT group. Males had elevated levels of 19 cytokines in the serum and 4 in the hippocampus compared to females, but there were also interactions between sex and genotype for 7 hippocampal cytokines. Only the chemokine CCL5 in the serum showed an interaction between PCB dose, genotype, and sex. Collectively, these findings indicate differential influences of PCB exposure and genotype on cytokine levels in serum and hippocampal tissue of weanling mice. These results suggest that developmental PCB exposure has chronic effects on baseline serum, but not hippocampal, cytokine levels in juvenile mice.

Toxicokinetics of Chiral PCB 136 and Its Hydroxylated Metabolites in Mice with a Liver-Specific Deletion of Cytochrome P450 Reductase.

Exposure to polychlorinated biphenyls (PCBs) has been implicated in adverse human health effects, including developmental neurotoxicity. Several neurotoxic PCBs are chiral and undergo atropisomeric enrichment in vivo due to atropselective metabolism by cytochrome P450 enzymes. Here we study how the liver-specific deletion of the cytochrome P450 reductase ( cpr) gene alters the toxicokinetics of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice. Male and female mice with a liver-specific deletion of cpr (KO) and congenic wild-type (WT) mice were exposed to a single oral dose of racemic PCB 136 (6.63 mg/kg). Levels and chiral signatures of PCB 136 and its hydroxylated metabolites were determined 1-48 h after PCB exposure in whole blood. Blood levels of PCB 136 were typically higher in M-WT compared to F-WT mice. At the later time points, F-KO mice had significantly higher PCB 136 levels than F-WT mice. 2,2',3',4,6,6'-Hexachlorobiphenyl-3-ol (3-150), 2,2',3,3',6,6'-hexachlorobiphenyl-4-ol (4-136), 2,2',3,3',6,6'-hexachlorobiphenyl-5-ol (5-136), and 4,5-dihydroxy-2,2',3,3',6,6'-hexachlorobiphenyl (4,5-136) were detected in blood, with 5-136 and 4-136 being major metabolites. At later time points, the sum of HO-PCB (∑HO-PCB) levels exceeded PCB 136 levels in the blood; however, higher ∑HO-PCB than PCB 136 levels were observed later in KO than WT mice. PCB 136 and its major metabolites displayed atropisomeric enrichment in a manner that depended on the time point, sex, and genotype. Toxicokinetic analysis revealed sex and genotype-dependent differences in toxicokinetic parameters for PCB 136 atropisomers and its metabolites. The results suggest that mice with a liver-specific deletion of the cpr gene can potentially be used to assess how an altered metabolism of neurotoxic PCB congeners affects neurotoxic outcomes following exposure of the offspring to PCBs via the maternal diet.

Characterization of 209 polychlorinated biphenyls in street dust from northern Vietnam: Contamination status, potential sources, and risk assessment

A full congener-specific determination of polychlorinated biphenyls (PCBs) was conducted for street dusts in some areas in northern Vietnam. Total 209 PCB concentrations (median and range) of 14 (2.2–120), 11 (6.6–32), and 0.25 (0.10–0.97) ng g−1 were measured in the street dusts from an industrial park, an urban area, and a rural commune, respectively, suggesting environmental loads of PCBs related to industrialization and urbanization in northern Vietnam. PCB patterns of street dusts from the industrial park were dominated by lightly chlorinated homologs (tri- and tetra-CBs), while more highly chlorinated homologs (penta- and hexa-CBs) were the major contributors to total PCBs in the urban samples, indicating different emission sources. Linear correlations of log-transformed sum of 7 indicator congeners with total PCBs and sum of dioxin-like PCBs were observed. PCB-11, an inadvertently produced congener of pigment manufacturing processes, was detected in all the samples with more elevated proportions in the urban and rural areas than industrial park. Our results have revealed complex emission sources of PCBs in the study areas, including both historical (e.g., the past usage of imported PCB-containing oils and old electric equipment) and current sources such as releases from industrial activities and increasing use of new consumer products. Occupationally exposed persons (e.g., street sweepers, street vendors, and traffic policemen) and children in the urban and industrial areas were estimated to receive much higher doses of dust-bound PCBs than general population, suggesting the need for appropriate protection conditions.

Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure

Polychlorinated biphenyls (PCBs) are persistent organic pollutants ubiquitously detectable in the environment and in the food chain. Prenatal exposure to PCBs negatively affects fetal development and produces long-term detrimental effects on child health. The present study sought to evaluate the cytotoxic and genotoxic effects of chronic PCB exposure on fetal cells during pregnancy. To this aim, sheep embryonic fibroblasts (SEF) and amniocytes (SA) were cultured in vitro in the presence of low doses of PCBs for a period of 120days, comparable to the full term of ovine pregnancy. Cellular proliferation rates, global DNA methylation, chromosome integrity, and markers of DNA damage were evaluated at different time points. Moreover, SEF treated with PCBs for 60days were left untreated for one further month and then examined in order to evaluate the reversibility of PCB-induced epigenetic defects. PCB-treated SEF were more sensitive than SA treated with PCBs, in terms of low cell proliferation, and increased DNA damage and global DNA methylation, which were still detectable after interruption of PCB treatment. These data indicate that chronic exposure of fetal cells to PCBs causes permanent genomic and epigenetic instability, which may influence both prenatal and post-natal growth up to adulthood. Our in vitro model offer a simple and controlled means of studying the effects of different contaminants on fetal cells - one that could set the stage for targeted in vivo studies.

Skeletal and dental effects on rats following in utero/lactational exposure to the non-dioxin-like polychlorinated biphenyl PCB 180.

Polychlorinated biphenyls (PCBs) are a large class of persistent organic pollutants that are potentially harmful to human and wildlife health. Although a small number of dioxin-like (DL) PCBs are well characterized, the majority of PCBs have non-dioxin-like (NDL) modes of action and biological effects that are less understood. We conducted a dose-response study of the skeletal and dental effects of in utero/lactational exposure to 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB 180), a NDL PCB congener that is abundantly present in the environment and foods, including mother’s milk. In a sample of 35- and 84-day-old male and female offspring from pregnant rats exposed to different doses of PCB 180 (0, 10, 30, 100, 300, and 1000 mg/kg bw), we measured the three-dimensional (3D) coordinates of 27 landmarks on the craniofacial skeleton with a Microscribe G2X system, the buccolingual width of all molars with digital sliding calipers, and a variety of tibial parameters with peripheral quantitative computed tomography (pQCT) and a biomechanical testing apparatus. The landmark coordinates were analyzed for variation in size, shape, and fluctuating asymmetry (FA) using MorphoJ software, showing no effects on cranial size, on FA in females only (i.e., decreased asymmetry), and on shape in both sexes (i.e., decreased facial length and shift in the palatal suture). In the maxillary teeth, females in the highest dose group showed a significant decrease of 0.1 mm (p = 0.033) of the second molar only, whereas males in most dose groups showed average increases of 0.1 mm (p = 0.006–0.044) in all three molars. In the mandibular teeth, the only significant response to PCB 180 exposure was the average increase of 0.1 mm (p = 0.001–0.025) in the third molars of males only. Males also shower greater sensitivity in postcranial effects of increased tibial length and decreased cortical bone mass density, although only females showed significant effects on tibial bone area and thickness. These results demonstrate marked sex differences in effects of PCB 180, which can be attributed to differences in their underlying biological mechanisms of toxicity. Furthermore, although tooth and bone development are targets of both DL and NDL compounds, this study shows that there are marked differences in their mechanisms and effects.

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

To characterize polychlorinated biphenyls (PCBs) action on Leydig cells, PCBs congeners, low-chlorinated (delor 103; d103) and high-chlorinated ones (delor 106; d106) were selected. The cells were treated according to PCBs dose (d103 or d106 0.2 ng/ml in low doses:, or 2 ng/ml in high doses) and type (d103 + d106 in low doses or 103 + 106 in high doses). After 24 h treatment with PCBs, a distinct increase in estrogen-related receptors (ERRs type α, β and γ) expression was revealed. However, the dose- and type-dependent PCBs effect was mostly exerted on ERRα expression. A similar increase in ERRs expression was demonstrated by estradiol but not testosterone, which was without an effect on ERRs. PCBs caused no decrease in the membrane potential status of Leydig cells (either in dose or type schedule) but had severe effects on the mitochondria number and structure. Moreover, PCBs markedly increased calcium (Ca2+) concentration and sex steroid secretion (both androgens and estrogens were elevated). These findings suggest a similar estrogenic action of PCBs congeners (d103 and d106) on Leydig cell function. We report dose- and type-specific effects of PCBs only on Leydig cell ERRs expression. Both delors showed common effects on the mitochondria ultrastructural and functional status. Based on our results, ERRα seems to be the most sensitive to hormonal modulation. The increases in Ca2+ and sex steroid secretion may be due to the activation of ERRs by PCBs binding and/or direct effect of PCBs on ERRs mRNA/protein expression. Nevertheless, to confirm the existence of possible relationships between ERRs signaling (including PCBs as ligands) and mitochondria function in Leydig cells, further intensive studies are needed.

PCBs, PBDEs and dioxin-related compounds in floor dust from an informal end-of-life vehicle recycling site in northern Vietnam: contamination levels and implications for human exposure

Floor dusts from Vietnamese end-of-life vehicle (ELV)-processing households were investigated to elucidate the contamination levels and exposure risk of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and dioxin-related compounds (DRCs). The concentrations were in order of PBDEs (260–11,000, median 280 ng/g overall) > PCBs (19–2200, median 140 ng/g) > dioxin-like PCBs (8.8–450, median 22 ng/g) ≫ polybrominated dibenzo-p-dioxin/dibenzofurans (PBDD/Fs, 2000–28,000, median 8500 pg/g) > polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs, 440–4100, median 1800 pg/g) > MoBPCDD/Fs (1.9–1200, median 250 pg/g). Concentrations of PCBs and DRCs were higher than those reported for Vietnamese urban houses, indicating ELV processing as a significant source of these contaminants. Higher concentrations of PCBs relative to PBDEs suggest the abundance of old electrical capacitors/transformers in ELVs. The PBDD/F and PCDD/F profiles were indicative of DecaBDE-containing materials and combustion sources, respectively. PBDFs, PCDFs and DL-PCBs were the most important dioxin-like toxic equivalent (TEQ) contributors. The estimated PCB and TEQ intake doses from dust ingestion approached or exceeded the reference doses for children living in some ELV-processing households, indicating potential health risk. More comprehensive risk assessment of the exposure to PCBs and DRCs is required for residents of informal ELV recycling sites.

Lactational exposure of polychlorinated biphenyls downregulates critical genes in Leydig cells of F1 male progeny (PND21).

Polychlorinated biphenyls (PCBs) are environmental contaminants. The present study was aimed to test the effect of lactational exposure of PCBs on Leydig cellular mRNA and protein expressions of 5α-reductase, aromatase and androgen receptor (AR) in F1 male offspring. Lactating dams were orally gavaged with different doses of PCBs (Aroclor 1254) 0, 1, 2 and 5mgkg b.wt-1 day-1 , respectively, from PND1 to PND21. Male offsprings were sacrificed at PND21. Testes were used to isolate Leydig cells. Blood was collected. Serum testosterone (T) and oestradiol (E2 ) were measured. Anogenital distance was measured. Dams' milk lipid and serum lipids of male pups were estimated. PCB (Aroclor 1254) concentration of dams' milk and serum of male pups were analysed by GC-ECD. Leydig cellular mRNA and protein expressions of 5α-reductase, aromatase and AR were significantly decreased. Our data suggest that lactational exposure of PCBs downregulates selected genes in Leydig cells of F1 generation on post-natal day 21.

A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose.The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk. Liver and brain PCB toxicities were investigated by evaluating oxidative stress status and mitochondrial function. PCB toxicity in the liver was also estimated by transaminase enzymatic activity.This study shows that even at low doses, chronic PCB exposure resulted in a statistically significant reduction of mitochondrial function in liver and brain. In the liver, oxygen consumption in the condition of adenosine triphosphate (ATP) production (state 3) decreased by 22–29% (p < 0.01), according to the respiratory substrates. In the brain, respiratory chain complexes II and III were reduced by 24% and 39%, respectively (p < 0.005). The exposed rats presented higher lipid peroxidation status (+20%, p < 0.05) and transaminase activity (+30%, p < 0.05) in the blood.Thus, our study showed that exposure of rats to a daily realistic dose of PCBs (twice the TDI in a food complex mixture of environmental origin) resulted in multiple disruptions in the liver and brain.

Responses of hepatic biochemical markers in bream Abramis brama L. to dietary administered polychlorinated biphenyls

An experimental study of the effects of dietary administered polychlorinated biphenyls (PCBs) on bream (Abramis brama L.) is reported in the present article. Responses of xenobiotic biotransformation system (ethoxyresorufin-O-deethylase and glutathione-S-transferase activities), antioxidant system (superoxide dismutase and catalase activities), and lipid peroxidation system (levels of conjugated dienes and malonic dialdehyde) are investigated. A PCB dose of 2 mg/kg feed does not cause irreversible physiological transformations in bream after 14 days of administration. The defense systems appear to efficiently suppress the effects of the xenobiotic and maintain stable and low intensity of the destructive processes at the exposure conditions used.

Environmental Polychlorinated Biphenyl Exposure and Breast Cancer Risk: A Meta-Analysis of Observational Studies.

BackgroundAssociation between polychlorinated biphenyl (PCB) exposure and breast cancer risk has been widely studied, but the results remain controversial. We performed a meta-analysis to evaluate the evidences from observational studies on PCB exposure and breast cancer risk.MethodsRelevant studies with data on internal PCB dose were identified from PubMed, EMBASE, CBM and CNKI databases through November 2014. Multivariable-adjusted odds ratio (OR) with 95% confidence intervals (CIs) were applied to assess the association between PCB exposure and breast cancer risk. Heterogeneity test, sensitivity analysis, subgroup analysis and publication bias test were also performed. To further explore the association between specific groups of PCB congeners and breast cancer, we examined the PCB congeners classified, according to their structural, biological and pharmacokinetics properties, as group I (potentially estrogenic), group II (potentially anti-estrogenic and immunotoxic, dioxin-like), and group III (phenobarbital, CYP1A and CYP2B inducers, biologically persistent).ResultsOf 660 studies screened, 25 studies which met criteria were selected, involving a total of 12866 participants (6088 cases and 6778 controls) from eight countries. The results showed that the risk of breast cancer was associated with group II (OR = 1.23, 95% CI: 1.08–1.40) and group III (OR = 1.25, 95% CI: 1.09–1.43) PCBs, but not with group I (OR = 1.10, 95%CI: 0.97–1.24) PCBs or total PCB exposure (OR = 1.09, 95%CI: 0.97–1.22).ConclusionsOur meta-analysis based on the selected studies found group II and group III PCB exposure might contribute to the risk of breast cancer. More studies in developing countries with higher PCB levels are needed, as well as studies to explore the relationships between mixtures of organochlorine compounds and breast cancer risk.