Polychlorinated Biphenyls Mixture Research Articles

Spatial and seasonal variations, sources, air-soil exchange, and carcinogenic risk assessment for PAHs and PCBs in air and soil of Kutahya, Turkey, the province of thermal power plants.

Atmospheric and concurrent soil samples were collected during winter and summer of 2014 at 41 sites in Kutahya, Turkey to investigate spatial and seasonal variations, sources, air-soil exchange, and associated carcinogenic risks of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). The highest atmospheric and soil concentrations were observed near power plants and residential areas, and the wintertime concentrations were generally higher than ones measured in summer. Spatial distribution of measured ambient concentrations and results of the factor analysis showed that the major contributing PAH sources in Kutahya region were the coal combustion for power generation and residential heating (48.9%), and diesel and gasoline exhaust emissions (47.3%) while the major PCB sources were the coal (thermal power plants and residential heating) and wood combustion (residential heating) (45.4%), and evaporative emissions from previously used technical PCB mixtures (34.7%). Results of fugacity fraction calculations indicated that the soil and atmosphere were not in equilibrium for most of the PAHs (88.0% in winter, 87.4% in summer) and PCBs (76.8% in winter, 83.8% in summer). For PAHs, deposition to the soil was the dominant mechanism in winter while in summer volatilization was equally important. For PCBs, volatilization dominated in summer while deposition was higher in winter. Cancer risks associated with inhalation and accidental soil ingestion of soil were also estimated. Generally, the estimated carcinogenic risks were below the acceptable risk level of 10-6. The percentage of the population exceeding the acceptable risk level ranged from <1% to 16%, except, 32% of the inhalation risk levels due to PAH exposure in winter at urban/industrial sites were >10-6.

Polyurethane foam (PUF) disk passive samplers derived polychlorinated biphenyls (PCBs) concentrations in the ambient air of Bursa-Turkey: Spatial and temporal variations and health risk assessment

Polyurethane foam (PUF) passive samplers were employed to assess air concentrations of polychlorinated biphenyls (PCBs) in background, agricultural, semi-urban, urban and industrial sites in Bursa, Turkey. Samplers were deployed for approximately 2-month periods from February to December 2014 in five sampling campaign. Results showed a clear rural-agricultural-semi-urban-urban-industrial PCBs concentration gradient. Considering all sampling periods, ambient air concentrations of Σ43PCBs ranged from 9.6 to 1240 pg/m3 at all sites with an average of 24.1 ± 8.2, 43.8 ± 24.4, 140 ± 190, 42.8 ± 24.6, 160 ± 280, 84.1 ± 105, 170 ± 150 and 280 ± 540 pg/m3 for Mount Uludag, Uludag University Campus, Camlica, Bursa Technical University Osmangazi Campus, Hamitler, Agakoy, Kestel Organised Industrial District and Demirtas Organised Industrial District sampling sites, respectively. The ambient air PCB concentrations increased along a gradient from background to industrial areas by a factor of 1.7–11.4. 4-Cl PCBs (31.50–81.60%) was the most dominant homologue group at all sampling sites followed by 3-Cl, 7-Cl, 6-Cl and 5-Cl homologue groups. Sampling locations and potential sources grouped in principal component analysis. Results of PCA plots highlighted a large variability of the PCB mixture in air, hence possible related sources, in Bursa area. Calculated inhalation risk levels in this study indicated no serious adverse health effects. This study is one of few efforts to characterize PCB composition in ambient air seasonally and spatially for urban and industrial areas of Turkey by using passive samplers as an alternative sampling method for concurrent monitoring at multiple sites.

Enrichment, isolation and biodegradation potential of psychrotolerant polychlorinated-biphenyl degrading bacteria from the Kongsfjorden (Svalbard Islands, High Arctic Norway)

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), have been detected in abiotic Arctic matrices: surface sediments and seawater from coastal areas in the Kongsfjorden were collected and analyzed. Levels of PCBs varied depending on the sampling site. Total PCB concentrations were between 11.63 (site C2W) and 27.69pgl−1 (site AW). These levels were comparable to those reported previously in lake sediments from the northern Svalbard.The occurrence and biodegradation potential of cold-adapted PCB-oxidizing bacteria in seawater and sediment along the fjord was also evaluated. After enrichment with biphenyl, 246 isolates were obtained with 45 of them that were able to grow in the presence of the PCB mixture Aroclor 1242, as the sole carbon source. The catabolic gene bphA was harbored by 17 isolates with affiliates to the genera Algoriphagus, Devosia and Salinibacterium that have been never reported as able to utilize PCBs, thus deserving further investigation. The total removal of Aroclor 1242 and selected PCB congeners was evaluated at 4 and 15°C for eight bphA-harboring isolates and Gelidibacter sp. DS-10. With few exceptions, tested strains showed greater efficiency at 15 than at 4°C. Isolates were able to reduce most chromatographic peaks by >50%, with some di- and trichlorobiphenyls that were quite totally removed (>90%).

Microbial-Catalyzed Reductive Dechlorination of Polychlorinated Biphenyls in Hudson and Grasse River Sediment Microcosms: Determination of Dechlorination Preferences and Identification of Rare Ortho Removal Pathways.

Biodegradation of polychlorinated biphenyls (PCBs) is an important transformation and detoxification route in the environment. To better understand the influence of PCB congener compositions on dechlorination, sediments from two rivers, Hudson and Grasse, and two PCB mixtures (PCB 5/12, 64/71, 105/114, and 149/153/170 in Mixture 1 and PCB 5/12, 64/71, 82/97/99, and 144/170 in Mixture 2) were used for this microcosm study. The Grasse River sediment microcosms exhibited more extensive dechlorination than the Hudson River sediment microcosms. The extent of dechlorination was predominantly controlled by sediment itself, not by the PCB compositions. Rare ortho dechlorination, targeting mono-ortho PCB congeners was observed in Grasse sediment, indicating a potential for full dechlorination of some PCBs in this sediment. The identified ortho dechlorination pathways were PCB 28 (24-4-CB) to PCB 15 (4-4-CB) and PCB 25 (24-3-CB) to PCB 13(3-4-CB). The relative abundances of Dehalococcoides were much higher in both sediments spiked with PCBs. An apparent increase of Dehalococcoides 16S rRNA genes coincided with the commencement of dechlorination. The dechlorination preferences were identified using a modified data analysis approach focusing on chlorine neighboring conditions. In both sediments, the overall dechlorination preferred meta > para > ortho. Specially, ortho-/double-flanked meta-chlorines were primarily targeted followed by single-/double-flanked para-chlorines.

Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero

Exposure to polychlorinated biphenyls (PCBs), a class of endocrine-disrupting chemicals, can result in altered reproductive behavior in adulthood, especially when exposure occurs during critical periods of brain sexual differentiation in the fetus. Whether PCBs alter other sexually dimorphic behaviors such as those involved in anxiety is poorly understood. To address this, pregnant rat dams were injected twice, on gestational days 16 and 18, with the weakly estrogenic PCB mixture Aroclor 1221 (A1221) at one of two low dosages (0.5mg/kg or 1.0mg/kg, hereafter 1.0 and 0.5), estradiol benzoate (EB; 50μg/kg) as a positive estrogenic control, or the vehicle (3% DMSO in sesame oil). We also conducted a comprehensive assessment of developmental milestones of the F1 male and female offspring. There were no effects of treatment on sex ratio at birth and age at eye opening. Puberty, assessed by vaginal opening in females and preputial separation in males, was not affected in females but was advanced in males treated with A1221 (1.0). Males and females treated with A1221 (both dosages) were heavier in early adulthood relative to controls. The earliest manifestation of this effect developed in males prior to puberty and in females slightly later, during puberty. Anxiety-like behaviors were tested using the light:dark box and elevated plus maze tests in adulthood. In females, anxiety behaviors were unaffected by treatment. Males treated with A1221 (1.0) showed reduced indices of anxiety and increased activity in the light:dark box but not the elevated plus maze. EB failed to replicate the phenotype produced by A1221 for any of the developmental and behavioral endpoints. Collectively, these results indicate that PCBs increase body weight in both sexes, but their effects on anxiety-like behaviors are specific to males. Furthermore, differences between the results of A1221 and EB suggest that the PCBs are likely acting through mechanisms distinct from their estrogenic activity.

Biological degradation of 4-chlorobenzoic acid by a PCB-metabolizing bacterium through a pathway not involving (chloro)catechol.

Cupriavidus sp. strain SK-3, previously isolated on polychlorinated biphenyl mixtures, was found to aerobically utilize a wide spectrum of substituted aromatic compounds including 4-fluoro-, 4-chloro- and 4-bromobenzoic acids as a sole carbon and energy source. Other chlorobenzoic acid (CBA) congeners such as 2-, 3-, 2,3-, 2,5-, 3,4- and 3,5-CBA were all rapidly transformed to respective chlorocatechols (CCs). Under aerobic conditions, strain SK-3 grew readily on 4-CBA to a maximum concentration of 5mM above which growth became impaired and yielded no biomass. Growth lagged significantly at concentrations above 3mM, however chloride elimination was stoichiometric and generally mirrored growth and substrate consumption in all incubations. Experiments with resting cells, cell-free extracts and analysis of metabolite pools suggest that 4-CBA was metabolized in a reaction exclusively involving an initial hydrolytic dehalogenation yielding 4-hydroxybenzoic acid, which was then hydroxylated to protocatechuic acid (PCA) and subsequently metabolized via the β-ketoadipate pathway. When strain SK-3 was grown on 4-CBA, there was gratuitous induction of the catechol-1,2-dioxygenase and gentisate-1,2-dioxygenase pathways, even if both were not involved in the metabolism of the acid. While activities of the modified ortho- and meta-cleavage pathways were not detectable in all extracts, activity of PCA-3,4-dioxygenase was over ten-times higher than those of catechol-1,2- and gentisate-1,2-dioxygenases. Therefore, the only reason other congeners were not utilized for growth was the accumulation of CCs, suggesting a narrow spectrum of the activity of enzymes downstream of benzoate-1,2-dioxygenase, which exhibited affinity for a number of substituted analogs, and that the metabolic bottlenecks are either CCs or catabolites of the modified ortho-cleavage metabolic route.

Toxic effects of polychlorinated biphenyls (Aroclor 1254) on human sperm motility.

Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent a considerable risk to reproductive toxicity in exposed human populations. Although some experimental studies have suggested an association between the levels of PCBs and semen quality, the direct effects of PCBs on human sperm parameters remain largely unexplored. To this aim, a short-term in vitro incubation experiment that better imitated the putative exposure of sperm to Aroclor 1254 (a commercial PCB mixture) in male reproduction tissue was conducted. Human sperm were incubated with various concentrations (0, 1, 5, or 25 mg l−1) of Aroclor 1254 for different amounts of time (3 and 6 h) in vitro. Sperm motility parameters were analyzed with computer-assisted sperm analysis (CASA). The proportion of sperm with high mitochondrial membrane potential (ΔΨm) and the levels of intracellular reactive oxygen species (ROS) were detected to explore the probable cause of sperm impairment. Human sperm exposed to continuous Aroclor 1254 exhibited: (i) reduced sperm motility and kinematic parameters, (ii) a proportion of sperm with high ΔΨm that decreased in a dose-dependent manner (P < 0.05), and (iii) increased levels of ROS compared with controls (P < 0.05). In conclusion, Aroclor 1254 can decrease sperm motility, which may culminate in increased ROS and general mitochondrial dysfunction, thus affecting the fertilization potential of sperm. Our findings suggest a broader understanding of the effect of Aroclor 1254 on human sperm.

Polychlorinated biphenyls in agricultural soils from the Yangtze River Delta of China: Regional contamination characteristics, combined ecological effects and human health risks

The current contamination status of polychlorinated biphenyls (PCBs) was studied in the agricultural soils of the Yangtze River Delta (YRD), one of the largest economic zones in China. The concentrations of PCBs ranged from <0.1 to 130 ng/g dry weight. Higher concentrations of PCBs were observed in the 0–30 cm surface layers relative to the subsurface soils. A distinct spatial distribution was observed with a declining concentration gradient from the northwest to the southeast of the region. The composition of PCBs in the soils was consistent with the Chinese commercial PCB mixtures, but different from the compositions in global background soil. Local sources including large-scale use and disposal of PCB-containing products were the main potential sources to soil. The ecological effects and human health risks associated with combined persistent organic pollutants, including PCBs, organochlorine pesticides (OCPs), phthalate esters (PAEs) and polybrominated diphenyl ethers (PBDEs), were further estimated. The four toxic organic compounds and seven physicochemical parameters together could only explain 12.7% of the variation in microbial community composition, suggesting the soil ecosystem function was not strongly influenced by the combined pollution at low concentrations. However, the potential health risks to residents via multiple pathways were notably higher for PCBs than other chemicals. The potential risks were mainly derived from PCB-126, 81, and 169.

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.

Developmental exposure to PCBs alters the activation of the auditory cortex in response to GABAA antagonism

Developmental exposure of rats to polychlorinated biphenyls (PCBs) causes impairments in hearing and in the functioning of peripheral and central auditory structures. Additionally, recent work from our laboratory has demonstrated an increase in audiogenic seizures. The current study aimed to further characterize the effects of PCBs on auditory brain structures by investigating whether developmental exposure altered the magnitude of activation in the auditory cortex (AC) in response to electrical stimulation of thalamocortical afferents. Long-Evans female rats were fed cookies containing either 0 or 6mg/kg of an environmental PCB mixture daily from 4 weeks prior to breeding until postnatal day 21. Brain slices containing projections from the thalamus to the AC were collected from adult female offspring and were bathed in artificial cerebrospinal fluid (aCSF) alone, aCSF containing a gamma-aminobutyric acid (GABA) receptor antagonist (200nM SR95531), and aCSF containing an and N-methyl-d-aspartate (NMDA) receptor antagonist (50μM AP5). During each of these drug conditions, electrical stimulations ranging from 25 to 600μA were delivered to the thalamocortical afferents. Activation of the AC was measured using flavoprotein autofluorescence imaging. Although there were no differences seen between treatment groups in the aCSF condition, there were significant increases in the ratio of aCSF/SR95531 activation in slices from PCB-exposed animals compared to control animals. This effect was seen in both the upper and lower layers of the AC. No differences in activation were noted between treatment groups when slices were exposed to AP5. These data suggest that developmental PCB exposure leads to increased sensitivity to antagonism of GABAA receptors in the AC without a change in NMDA-mediated intrinsic excitability.

Polychlorinated biphenyls: New evidence from the last decade.

Millions of pounds of polychlorinated biphenyl (PCB) compounds have been produced in multiple countries for industrial applications over the last several decades. PCB exposure induces various adverse health effects in animals and humans. Environmental and occupational exposures to PCBs have been associated with liver, kidney, endocrine, and neurodevelopmental adverse effects. We have collected and reviewed animal and human data cited in the US National Library of Medicine from 2000 to 2010. In brief, our review shows new evidence, that is, in animal studies, exposure to one of the PCBs, A1221, induces a significant alteration of serum luteinizing hormone. The effects were more profound in the F2 generation, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. Morphological analyses of brain tissue from rats exposed to A1254 confirmed the results of an earlier work which showed that the relative size of the intra- and infrapyramidal (II-P) mossy fibers was smaller than that in the controls and also reduction in growth was selective for the II-P mossy fibers. PCB exposure increased anogenital distance and prostate size but decreased epididymal weight, epididymal sperm count, and motile epididymal sperm count. No effects were observed on testicular weight or size. The epidemiological data showed an association between diabetes mellitus prevalence and elevated concentrations of PCB 153. Additionally, prenatal PCB exposure studies were associated with a smaller thymic index at birth and could adversely affect immune responses to childhood vaccinations and resistance to respiratory infections. PCB exposure was also reported to adversely affect enamel development in children in a dose-dependent manner. Because PCBs and their metabolites are potential health hazards, understanding the risk factors associated with individual PCBs, PCB mixtures, and PCB metabolites is important. PCB exposures of vulnerable populations (pregnant women, fetuses, infants, and children) are of particular concern because of heightened sensitivity during this period of brain development.

Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition.

Polychlorinated biphenyls (PCBs) are ubiquitous legacy persistent pollutants and epidemiological data showed that PCB burdens were associated with failed implantation in human. However, the mechanism how PCB exposure affects the embryo implantation is not clear. Using an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial cell line Ishikawa, we have shown that PCB mixture Aroclor 1254 at environmental-relevant concentrations (2.5, 12.5, and 62.5μM) dose-dependently impaired the endometrial receptivity by reducing the adhesion of JAR spheroid attachment and increasing the spheroid outgrowth. The receptive-up-regulated micro-RNA, mir-30d was also down-regulated in endometrial cells by the exposure. Following transient transfection of mir-30d mimic, the disrupted attachment and outgrowth of JAR spheroids was partially restored in the model. By measurement of cadherin switch and vimentin expression, the PCB exposure also activated epithelial mesenchymal transition (EMT) in endometrial cells. In accordance, mir-30d mimic suppressed the EMT markers induced by PCBs. Luciferase reporter assay confirmed that the EMT regulator Snai1 was targeted by mir-30d, and the expression of Snai1 was dose-dependently up-regulated by PCB exposure. Taken together, our study revealed that PCBs may affect the receptivity of endometrial cells by impairing the interaction between receptivity-up-regulated microRNA and EMT process.

Tracing the biotransformation of polychlorinated biphenyls (PCBs) in common carp (Cryprinus carpio): Enantiomeric fraction and compound-specific stable carbon isotope analyses

Metabolites of polychlorinated biphenyls (PCBs) in fish are difficult to detect in vivo due to the complexity of biometabolism. In the present study, atropisomeric fraction analysis of chiral PCB congeners and compound-specific isotopic analysis (CSIA) were applied to trace the biotransformation of PCBs in fish by exposure of common carp (Cryprinus carpio) to the commercial PCB mixture Aroclor 1242. Stereoselective elimination of the chiral PCB congeners 91, 95, and 136 was observed, indicating a stereoselective biotransformation process. The δ13C values of PCBs 5/8, 18, and 20/33 in fish were increased compared with those in the spiked food, while PCBs 47/48 and 49 showed significant heavy isotope depletion. These results suggested a significant biotransformation of the corresponding individual PCB congeners although the potential PCB metabolites, hydroxylated PCBs (OH-PCBs) and methylsulfone PCBs (MeSO2-PCBs), were not detected in the fish tissue samples throughout this experiment. The results of the present study demonstrated that a combination of chiral analysis and CSIA is a promising new approach for investigating the biotransformation of PCBs in biota.

Indirect Evidence Link PCB Dehalogenation with Geobacteraceae in Anaerobic Sediment-Free Microcosms.

Although polychlorinated biphenyls (PCBs) production was brought to a halt 30 years ago, recalcitrance to degradation makes them a major environmental pollutant at a global scale. Previous studies confirmed that organohalide-respiring bacteria (OHRB) were capable of utilizing chlorinated congeners as electron acceptor. OHRB belonging to the Phyla Chloroflexi and Firmicutes are nowadays considered as the main PCB-dechlorinating organisms. In this study, we aimed at exploring the involvement of other taxa in PCB dechlorination using sediment-free microcosms (SFMs) and the Delor PCB mixture. High rates of congener dehalogenation (up to 96%) were attained in long-term incubations of up to 692 days. Bacterial communities were dominated by Chloroflexi, Proteobacteria, and Firmicutes, among strictly simplified community structures composed of 12 major phyla only. In a first batch of SFMs, Dehalococcoides mccartyi closely affiliated with strains CG4 and CBDB1 was considered as the main actor associated with congener dehalogenation. Addition of 2-bromoethanesulfonate (BES), a known inhibitor of methanogenic activity in a second batch of SFMs had an adverse effect on the abundance of Dehalococcoides sp. Only two sequences affiliated to this Genus could be detected in two (out of six) BES-treated SFMs, contributing to a mere 0.04% of the communities. BES-treated SFMs showed very different community structures, especially in the contributions of organisms involved in fermentation and syntrophic activities. Indirect evidence provided by both statistical and phylogenetic analysis validated the implication of a new cluster of actors, distantly affiliated with the Family Geobacteraceae (Phylum δ-Proteobacteria), in the dehalogenation of low chlorinated PCB congeners. Members of this Family are known already for their dehalogenation capacity of chlorinated solvents. As a result, the present study widens the knowledge for the phylogenetic reservoir of indigenous PCB dechlorinating taxa.

Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases

Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) is correlated with multiple vascular complications including endothelial cell dysfunction and atherosclerosis. PCB-induced activation of the vasculature subsequently leads to oxidative stress and induction of pro-inflammatory cytokines and adhesion proteins. Gene expression of these cytokines/proteins is known to be regulated by small, endogenous oligonucleotides known as microRNAs that interact with messenger RNA. MicroRNAs are an acknowledged component of the epigenome, but the role of environmentally-driven epigenetic changes such as toxicant-induced changes in microRNA profiles is currently understudied. The objective of this study was to determine the effects of PCB exposure on microRNA expression profile in primary human endothelial cells using the commercial PCB mixture Aroclor 1260. Samples were analyzed using Affymetrix GeneChip® miRNA 4.0 arrays for high throughput detection and selected microRNA gene expression was validated (RT-PCR). Microarray analysis identified 557 out of 6658 microRNAs that were changed with PCB exposure (p<0.05). In-silico analysis using MetaCore database identified 21 of these microRNAs to be associated with vascular diseases. Further validation showed that Aroclor 1260 increased miR-21, miR-31, miR-126, miR-221 and miR-222 expression levels. Upregulated miR-21 has been reported in cardiac injury while miR-126 and miR-31 modulate inflammation. Our results demonstrated evidence of altered microRNA expression with PCB exposure, thus providing novel insights into mechanisms of PCB toxicity.

Development of an in vitro test battery model based on liver and colon cancer cell lines to discriminate PCB mixtures by transcription factors gene expression analysis

The combined exposure to chemical mixtures, especially of persistent compounds like polychlorinated biphenyls (PCBs), prompts to the development of sound methods to evaluate their cumulative effects. With the aim to discriminate among different PCB mixtures (one dioxin-like and two non-dioxin-like), at human real internal levels, three human cell lines from tissues of the digestive system (HuH6 and HepG2 for the liver and DLD-1 for the colon) were selected as targets of toxicological effects. A panel of nine transcription factors (ERα, ERβ, AR, AhR, CAR, PXR, PPARγ, RARα and THRα) was assessed at gene expression level by real time PCR.Marked differences were observed in the responsiveness of the three cell lines to each mixture as well as in the patterns of modulation induced by the three mixtures, strongly supporting the subdivision of non-dioxin-like congeners in at least two groups.On the basis on Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) we propose the combination of six target genes (AhR, AR, PXR, PPARγ, ERβ and THRα) and two cell lines (HepG2 and DLD1) as a suitable tool to discriminate PCB mixtures effects also considering cell-type specific modulations.

Growth and reproductive effects from dietary exposure to Aroclor 1268 in mink (Neovison vison), a surrogate model for marine mammals.

Polychlorinated biphenyls (PCBs) from the commercial mixture Aroclor 1268 were historically released into the Turtle-Brunswick River estuary (southeastern Georgia, USA) from industrial operations. Sum PCBs (ΣPCBs) in blubber samples from Turtle-Brunswick River estuary bottlenose dolphins (Tursiops truncatus) have been reported at concentrations more than 10-fold higher than those observed in dolphins from adjacent regional estuaries. Given that toxicity data specific to Aroclor 1268 and applicable to marine mammals are limited, predicting the toxic effects of Aroclor 1268 in dolphins is uncertain, particularly because of its unique congener profile and associated physiochemical characteristics compared with other PCB mixtures. American mink (Neovison vison) were chosen as a surrogate model for cetaceans to develop marine mammalian PCB toxicity benchmarks. Mink are a suitable surrogate species for cetaceans in toxicity studies because of similarities in diet and taxonomic class, and a characteristic sensitivity to PCBs provides a potential safety factor when using mink toxicology data for cross-species extrapolations. Effects of dietary exposure to Aroclor 1268 on reproduction, growth, and mortality in mink were compared with both a negative control and a positive control (3,3',4,4',5-pentachlorobiphenyl, PCB 126). Aroclor 1268 dietary ΣPCB concentrations ranged from 1.8 µg/g feed wet weight to 29 µg/g feed wet weight. Whelp success was unaffected by Aroclor 1268 exposure at any level. Treatment mean litter size, kit growth, and kit survival were adversely affected relative to the negative control at dietary ΣPCB concentrations of 10.6 µg/g feed wet weight and greater.

Enzyme induction and histopathology elucidate aryl hydrocarbon receptor-mediated versus non-aryl hydrocarbon receptor-mediated effects of Aroclor 1268 in American mink (Neovison vison).

Polychlorinated biphenyl (PCB) concentrations reported in preferred prey and blubber of bottlenose dolphins from the Turtle-Brunswick River estuary (Georgia, USA) suggest the potential for adverse effects. However, PCBs in Turtle-Brunswick River estuary dolphins are primarily derived from Aroclor 1268, and predicting toxic effects of Aroclor 1268 is uncertain because of the mixture's unique composition and associated physiochemical characteristics. These differences suggest that toxicity benchmarks for other PCB mixtures may not be relevant to dolphins exposed to Aroclor 1268. American mink (Neovison vison) were used as a surrogate model for cetaceans to characterize mechanisms of action associated with Aroclor 1268 exposure. Mink share similarities in phylogeny and life history with cetaceans and are characteristically sensitive to PCBs, making them an attractive surrogate species for marine mammals in ecotoxicity studies. Adult female mink and a subsequent F1 generation were exposed to Aroclor 1268 through diet, and effects on enzyme induction, histopathology, thyroid hormone regulation, hematology, organ weights, and body condition index were compared to a negative control and a 3,3',4,4',5-pentachlorobiphenyl (PCB 126)-positive control. Aroclor 1268 dietary exposure concentrations ranged from 1.8 µg/g wet weight to 29 µg/g wet weight. Anemia, hypothyroidism, and hepatomegaly were observed in mink exposed to Aroclor 1268 beyond various dietary thresholds. Cytochrome P450 induction and squamous epithelial proliferation jaw lesions were low in Aroclor 1268 treatments relative to the positive control. Differences in enzyme induction and the development of squamous epithelial proliferation jaw lesions between Aroclor 1268 treatments and the positive control, coupled with effects observed in Aroclor 1268 treatments not observed in the positive control, indicate that mechanisms additional to the aryl hydrocarbon receptor-mediated pathway are associated with Aroclor 1268 exposure.

Effects of embryonic exposure to polychlorinated biphenyls (PCBs) on anxiety-related behaviors in larval zebrafish

The zebrafish (Danio rerio) is an excellent model system for assessing the effects of toxicant exposure on behavior and neurodevelopment. In the present study, we examined the effects of sub-chronic embryonic exposure to polychlorinated biphenyls (PCBs), a ubiquitous anthropogenic pollutant, on anxiety-related behaviors. We found that exposure to the PCB mixture, Aroclor (A) 1254, from 2 to 26h post-fertilization (hpf) induced two statistically significant behavioral defects in larvae at 7 days post-fertilization (dpf). First, during 135min of free swimming, larvae that had been exposed to 2ppm, 5ppm or 10ppm A1254 exhibited enhanced thigmotaxis (edge preference) relative to control larvae. Second, during the immediately ensuing 15-min visual startle assay, the 5ppm and 10ppm PCB-exposed larvae reacted differently to a visual threat, a red ‘bouncing’ disk, relative to control larvae. These results are consistent with the anxiogenic and attention-disrupting effects of PCB exposure documented in children, monkeys and rodents and merit further investigation.

Polychlorinated Biphenyl-Xenobiotic Nuclear Receptor Interactions Regulate Energy Metabolism, Behavior, and Inflammation in Non-alcoholic-Steatohepatitis.

Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis.