Hydroxylated Polychlorinated Biphenyls Are Emerging Legacy Pollutants in Contaminated Sediments.

We measured the concentrations of 837 hydroxylated polychlorinated biphenyls (OH-PCBs, in 275 chromatographic peaks) and 209 polychlorinated biphenyls (PCBs, in 174 chromatographic peaks) in sediments from New Bedford Harbor in Massachusetts, Altavista wastewater lagoon in Virginia, and the Indiana Harbor and Ship Canal in Indiana, USA and in the original commercial PCB mixtures Aroclors 1016, 1242, 1248, and 1254. We used the correlation between homologues and the peak responses to quantify the full suite of OH-PCBs including those without authentic standards available. We found that OH-PCB levels are approximately 0.4% of the PCB levels in sediments and less than 0.0025% in Aroclors. The OH-PCB congener distributions of sediments are different from those of Aroclors and are different according to sites. We also identified a previously unknown compound, 4-OH-PCB52, which together with 4'-OH-PCB18 made up almost 30% of the OH-PCBs in New Bedford Harbor sediments but less than 1.2% in the Aroclors and 3.3% in any other sediments. This indicates site-specific environmental transformations of PCBs to OH-PCBs. We conclude that the majority of OH-PCBs in these sediments are generated in the environment. Our findings suggest that these toxic breakdown products of PCBs are prevalent in PCB-contaminated sediments and present an emerging concern for humans and ecosystems.

Machine Learning-Assisted Identification and Quantification of Hydroxylated Metabolites of Polychlorinated Biphenyls in Animal Samples.

Laboratory studies of the disposition and toxicity of hydroxylated polychlorinated biphenyl (OH-PCB) metabolites are challenging because authentic analytical standards for most unknown OH-PCBs are not available. To assist with the characterization of these OH-PCBs (as methylated derivatives), we developed machine learning-based models with multiple linear regression (MLR) or random forest regression (RFR) to predict the relative retention times (RRT) and MS/MS responses of methoxylated (MeO-)PCBs on a gas chromatograph-tandem mass spectrometry system. The final MLR model estimated the retention times of MeO-PCBs with a mean absolute error of 0.55 min (n = 121). The similarity coefficients cos θ between the predicted (by RFR model) and experimental MS/MS data of MeO-PCBs were >0.95 for 92% of observations (n = 96). The levels of MeO-PCBs quantified with the predicted MS/MS response factors approximated the experimental values within a 2-fold difference for 85% of observations and 3-fold differences for all observations (n = 89). Subsequently, these model predictions were used to assist with the identification of OH-PCB 95 or OH-PCB 28 metabolites in mouse feces or liver by suggesting candidate ranking information for identifying the metabolite isomers. Thus, predicted retention and MS/MS response data can assist in identifying unknown OH-PCBs.

In vitro effects of polychlorinated biphenyls and their hydroxylated metabolites on the synthesis and metabolism of iodothyronines in the chicken (Gallus domesticus) thyroid gland.

To assess the effect of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) on thyroid hormone [TH: thyroxine (T4) and triiodothyronine (T3)] secretion, the concentrations of iodothyronine deiodinases (DIO1, DIO2, DIO3), and mRNA expression of genes involved in TH synthesis (TSHR, NIS, TPO, TG), metabolism (DIO1, DIO2, DIO3), and transport (OATP1C1, MCT8, MCT10, LAT1), chicken thyroid explants were incubated in medium supplemented with TSH (250 mU/ml), PCB118, PCB153, 4-OH-PCB107, and 3-OH-PCB153 (0.5 × 10-8 M), and TSH together with each PCB and OH-PCB. The results of the in vitro experiment revealed that, except for 4-OH-PCB107, all applied PCBs and OH-PCBs inhibited basal and TSH-stimulated T4 secretion. Moreover, they increased basal and reduced TSH-stimulated T3 secretion. PCBs and OH-PCBs decreased the TSH-stimulated TSHR expression. Following PCB and OH-PCB exposure, significant changes in mRNA expression of NIS, TPO, and TG were observed. PCBs and OH-PCBs affected DIO1 and DIO3 transcript levels and protein abundances of each DIO. Furthermore, PCB-dependent effects on OATP1C1, MCT8, and MCT10 mRNA expression were found. In conclusion, both PCB118 and PCB153 and their OH-PCBs affect TH synthesis and deiodination processes in the chicken thyroid gland and influence TH transport across the thyrocyte membrane. In addition, the effects of PCBs and OH-PCBs depended mainly on the type of PCB congener and the exposure time. These results indicate that not only parental PCBs but also OH-PCBs are hazardous for the thyroid gland and may disrupt its endocrine function. Further studies are necessary to explain a mechanism of PCB and OH-PCB action in the avian thyroid gland.

Response to the note to editor: Comments on "transcriptomic response of Arabidopsis thaliana exposed to hydroxylated polychlorinated biphenyls (OH-PCBs)".

In response to Dr. Yang et al.'s comments on our article "Transcriptomic response of Arabidopsis thaliana exposed to hydroxylated polychlorinated biphenyls (OH-PCBs)", additional details were provided regarding the analysis of the gene expression level (One-Way Between-Subject ANOVA) and correction for false discovery rate (FDR) (Benjamini-Hochberg). The gene expression analysis was performed again using the new release of the Transcriptome Analysis Console™ (version 4.0.1, Life Technologies - not available at the time our initial study was conducted), which integrates the Limma differential expression portion of the Bioconductor package. Overall similar results were obtained regarding the number of genes differentially expressed and the enrichment of genes in different Gene Ontology (GO) categories. The transcriptomic profiles induced in response to the three OH-derivatives were shown, again, to be similar to those induced by inhibitors of the brassinosteroid synthesis (i.e., brassinazole, propiconazole, and uniconazole), potentially resulting in iron deficiency in exposed plants. The new (and improved) method used for the selection of differentially expressed genes did not change the conclusion of our initial study, which suggested that the higher phytotoxicity of OH-derivatives, as compared to the parent compound 2,5-dichlorobiphenyl (2,5-DCB), may be explained by the inhibition of the brassinosteroid synthesis pathway.

Transcriptomic response of Arabidopsis thaliana exposed to hydroxylated polychlorinated biphenyls (OH-PCBs).

Hydroxylated polychlorinated biphenyls (OH-PCBs) are toxic contaminants produced by biotic or abiotic transformation of PCBs. In this study, we have tested the toxicity of 2,5-dichlorobiphenyl (2,5-DCB) and three of its OH-derivatives, 2'-OH-, 3'-OH-, and 4'-OH-2,5-DCB toward the model plant, Arabidopsis thaliana. Toxicity tests showed that the parent 2,5-DCB (5 mg L-1) had little effect on the plants, while all three OH-metabolites (5 mg L-1) exhibited a significant toxicity, with 4'-OH-2,5-DCB being the most potent (inhibition concentration 50%-IC50 in germination tests = 9.8 mg L-1 for 2'-OH-2,5-DCB, 9.5 mg L-1 for 3'-OH-2,5-DCB, and 4.8 mg L-1 for 4'-OH-2,5-DCB). Whole-genome expression microarrays (Affymetrix) showed that exposure to the three OH-PCBs resulted in rather similar expression patterns, which were distinct from the one developing in response to 2,5-DCB. Searching an Arabidopsis microarray database (Genevestigator) revealed that, unlike the parent compound, the three OH-derivatives induced expression profiles similar to inhibitors of brassinosteroid synthesis (i.e., brassinazole, propiconazole, and uniconazole), resulting in severe iron deficiency in exposed plants. Our results suggest that the higher phytotoxicity of OH-derivatives as compared to 2,5-DCB is at least partly explained by the inhibition of the brassinosteroid pathway.

New Perspectives on the Risks of Hydroxylated Polychlorinated Biphenyl (OH-PCB) Exposure: Intestinal Flora α-Glucosidase Inhibition.

Polychlorinated biphenyls (PCBs) are a group of colorless and odorless environmental pollutants with a wide range of toxic effects. Some PCBs, especially less chlorinated ones, will rapidly undergo phase I metabolism after entering the body, and hydroxylated polychlorinated biphenyls (OH-PCBs) are the main metabolites of PCBs. Intestinal flora α-glucosidase is a common carbohydrate-active enzyme which is ubiquitous in human intestinal flora. It can convert complex dietary polysaccharides into monosaccharides, assisting the body in degrading complex carbohydrates and providing energy for the survival and growth of bacterial flora. The present study aims to investigate the inhibition of the activity of intestinal flora α-glucosidase by OH-PCBs. 4-Nitrophenyl-α-D-glucopyranoside (PNPG) was used as a probe substrate for α-glucosidase, and in vitro incubation experiments were conducted to study the inhibition of 26 representative OH-PCBs on α-glucosidase. Preliminary screening of in vitro incubation was performed with 100 µM of OH-PCBs. The results showed that 26 OH-PCBs generally exhibited strong inhibition of α-glucosidase. The concentration-dependent inhibition and half inhibition concentrations (IC50s) of OH-PCBs on α-glucosidase were determined. 4'-OH-PCB 86 and 4'-OH-PCB 106 were chosen as representative OH-PCBs, and the inhibition kinetic parameters (Kis) of inhibitors for α-glucosidase were determined. The inhibition kinetic parameters (Kis) of 4'-OH-PCB 86 and 4'-OH-PCB 106 for α-glucosidase are 1.007 µM and 0.538 µM, respectively. The silico docking method was used to further analyze the interaction mechanism between OH-PCBs and α-glucosidase. All these results will help us to understand the risks of OH-PCB exposure from a new perspective.

Comparative transcriptomic analysis reveals reproductive impairments caused by PCBs and OH-PCBs through the dysregulation of ER and AR signaling.

Reports have highlighted the presence of PCBs and their metabolites, OH-PCBs, in human serum as well as their endocrine-disrupting effects on reproductive function through direct interactions with the androgen receptor (AR) and estrogen receptor (ER). However, the molecular mechanisms directly linking the actions of PCBs and OH-PCBs on the AR and ER to induce reproductive impairment remain poorly understood. In this study, we characterized the cellular response to PCBs and OH-PCBs acting on AR and ER transactivation at the transcriptome level coupled with bioinformatics analysis to identify the downstream pathways of androgen and estrogen signaling that leads to reproductive dysfunction. We first confirmed the agonistic and antagonistic effects of several PCBs and OH-PCBs on AR- and ER-mediated reporter gene activity using the androgen-responsive LNCaP and estrogen-responsive MCF-7 cell lines, respectively. Anti-estrogenic activity was not detected among the tested compounds; however, we found that in addition to anti-androgenic and estrogenic activity, PCB 28 and PCB 138 exhibited androgenic activity, while most of the tested OH-PCBs showed a synergistic effect on DHT-mediated transactivation of the AR. Bioinformatics analysis of transcriptome profiles from selected PCBs and OH-PCBs revealed various pathways that were dysregulated depending on their agonistic, antagonistic, or synergistic effects. The OH-PCBs with estrogenic activity affected pathways including vitamin metabolism and calcium transport. Other notable dysregulated pathways include cholesterol transport in response to androgenic PCBs, thyroid hormone metabolism in response to anti-androgenic PCBs, and antioxidant pathways in response to androgen-synergistic OH-PCBs. Our results demonstrate that PCBs and OH-PCBs directly alter specific pathways through androgen- or estrogen-mediated signaling, thereby providing additional insights into the mechanisms by which these compounds cause reproductive dysfunction.

Inhibition of hydroxylated polychlorinated biphenyls (OH-PCBs) on sulfotransferases (SULTs).

Polychlorinated biphenyls (PCBs) have been demonstrated as a kind of the persistent organic pollutants (POPs) that could exert complicated influences towards metabolism in human bodies. Since hydroxylated polychlorinated biphenyls (OH-PCBs) are important metabolites of PCBs, our study focuses on investigating the potential inhibitory capability of OH-PCBs on four human sulfotransferase (SULT) isoforms. P-nitrophenol (PNP) was utilized as nonselective probe substrate for this study, and recombinant SULT isoforms were utilized as the enzyme resources. Ultra-performance liquid chromatography (UPLC)-UV detecting system was used to analyze PNP and its metabolite PNP-sulfate. As result, 100 µM of most tested OH-PCBs significantly inhibited the activity of four SULT isoforms. Concentration-dependent inhibition of OH-PCBs towards SULTs was found, and half inhibition concentration values (IC50) of some inhibition processes were determined. Inhibition kinetics (inhibition kinetic type and parameters) were determined using 4'-OH-PCB106 as the representative OH-PCB, SULT1B1 and SULT1E1 as representative SULT isoforms. The inhibition kinetic parameters (Ki) were 1.73 µM and 1.81 µM for the inhibition of 4'-OH-PCB106 towards SULT1B1 and SULT1E1, respectively. In silico docking simulation was utilized to analyze the inhibition capability of 2'-OH-PCB5, 4'-OH-PCB9, 2'-OH-PCB12 towards SULT1A3.All these results obtained in this study are helpful for further understanding the toxicity of PCBs.

A semi-target analytical method for quantification of OH-PCBs in environmental samples.

Hydroxylated polychlorinated biphenyls (OH-PCBs) are oxidative metabolites of PCBs and residuals found in original Aroclors. OH-PCBs are known to play a role as genotoxicants, carcinogens, and hormone disruptors, and therefore it is important to quantify their presence in human tissues, organisms, and environmental matrices. Of 837 possible mono-OH-PCBs congeners, there are only ~ 70 methoxylated PCB (MeO-PCB) standards commercially available. Hence, a semi-target analytical method is needed for unknown OH-PCBs. The mass concentrations of these unknowns are sometimes determined by assuming the peak responses of other available compounds. This can bias the results due to the choices and availabilities of standards. To overcome this issue, we investigated the peak responses of all commercially available MeO-PCB standards with gas chromatography (GC) coupling with triple quadrupole (QqQ) mass spectrometry (MS) system, with positive electron impact (EI) ionization at 20-70 eV in selected ion monitoring (SIM) mode. We found correlations between the relative peak responses (RRFs) and the number of chlorine (#Cl) in the molecules of MeO-PCBs. Among the studied models, the quadratic regression of #Cl is the most suitable model in the RRF prediction (RRF = ß1 × #Cl^2 + ß0) when the peak responses are captured at 30 eV. We evaluated the performance of the model by analyzing 12 synthesized MeO-PCB standards and a PCB-contaminated sediment collected from a wastewater lagoon. We further demonstrate the utility of the model using a different chromatography column and GC-EI-MS system. We found the method and associated model to be sufficiently simple, accurate, and versatile for use in quantifying OH-PCBs in complex environmental samples.

Estrogen-related receptor γ is a novel target for Lower-Chlorinated Polychlorinated Biphenyls and their hydroxylated and sulfated metabolites.

Airborne lower-chlorinated PCBs are vulnerable to metabolization to PCB sulfates through further sulfation of the hydroxylated metabolites (OH-PCBs). However, studies on the toxic effects and mechanisms of PCB sulfates are still very limited. Here, we investigated for the first time the potential endocrine disruption effects of PCB sulfates through estrogen-related receptor γ (ERRγ) in comparison with their OH-PCBs precursors and PCB parent compounds. The binding affinity of thirteen PCBs/OH-PCBs/PCB sulfates was measured by using fluorescence competitive binding assays based on fluorescence polarization (FP). All of the tested chemicals could bind to ERRγ with the Kd (dissociation constant) values ranging from not available (NA) to 3.2 µM 4'-OH-PCB 12 showed the highest binding affinity with Kd value of 3.2 µM, which was comparable to that of a synthetic ERRγ agonist GSK4716. The effects of the thirteen chemicals on the ERRγ transcriptional activity were determined by using the luciferase reporter gene assay. We found the PCBs/OH-PCBs/PCB sulfates acted as agonists for ERRγ, with the lowest observed effective concentration reaching 3 µM. The binding affinity and agonistic activity of PCBs towards ERRγ were both enhanced after hydroxylation, while further sulfation of OH-PCBs decreased the activity instead. Molecular docking simulation showed that OH-PCBs had lower binding energy than the corresponding PCBs and PCB sulfates, indicating that OH-PCBs had higher binding affinity theoretically. In addition, OH-PCBs could form hydrogen bonds with amino acids Glu316 and Arg247 while PCBs and PCB sulfates could not, which might be the main factor impacting the binding affinity and agonistic activity. Overall, ERRγ is a novel target for lower-chlorinated PCBs and their metabolites.

Effects of PCB exposure on serum thyroid hormone levels in dogs and cats.

Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) might disrupt thyroid function. However, there is no clear evidence of PCB exposure disrupting thyroid hormone (TH) homeostasis in dogs and cats. The present study conducted in vivo experiments to evaluate the effects of a mixture of 12 PCB congeners (CB18, 28, 70, 77, 99, 101, 118, 138, 153, 180, 187 and 202, each congener 0.5 mg/kg BW, i.p. administration) on serum TH levels in male dogs (Canis lupus familiaris) and male cats (Felis silvestris catus). In PCB-exposed dogs, the time courses of higher-chlorinated PCBs and L-thyroxine (T4)-like OH-PCBs (4-OH-CB107 and 4-OH-CB202) concentrations were unchanged or tended to increase, whereas those of lower-chlorinated PCBs and OH-PCBs tended to decrease after 24 h. In PCB-exposed cats, concentrations of PCBs increased until 6 h and then remained unchanged. The levels of lower-chlorinated OH-PCBs including 4'-OH-CB18 increased until 96 h and then decreased. In PCB-exposed dogs, free T4 concentrations were higher than those in the control group at 48 and 96 h after PCB administration and positively correlated with the levels of T4-like OH-PCBs, suggesting competitive binding of T4 and T4-like OH-PCBs to a TH transporter, transthyretin. Serum levels of total T4 and total 3,3',5-triiodo-L-thyronine (T3) in PCB-exposed dogs were lower than in the control group at 24 and 48 h and negatively correlated with PCB concentrations, implying that PCB exposure enhanced TH excretion by increasing TH uptake and TH conjugation enzyme activities in the dog liver. In contrast, no obvious changes in TH levels were observed in PCB-exposed cats. This could be explained by the lower levels of T4-like OH-PCBs and lower hepatic conjugation enzyme activities in cats compared with dogs. Different effects on serum TH levels in PCB-exposed dogs and cats are likely to be attributable to species-specific PCB and TH metabolism.

Monitoring OH-PCBs in PCB transport worker's urine as a non-invasive exposure assessment tool.

In this study, we analyzed hydroxylated polychlorinated biphenyls (OH-PCBs) in urine of both PCB transport workers and PCB researchers. A method to monitor OH-PCB in urine was developed. Urine was solid-phase extracted with 0.1% ammonia/ methanol (v/v) and glucuronic acid/sulfate conjugates and then decomposed using ß-glucuronidase/arylsulfatase. After alkaline digestion/derivatization, the concentration of OH-PCBs was determined by HRGC/HRMS-SIM. In the first sampling campaign, the worker's OH-PCB levels increased several fold after the PCB waste transportation work, indicating exposure to PCBs. The concentration of OH-PCBs in PCB transport workers' urine (0.55~11 µg/g creatinine (Cre)) was higher than in PCB researchers' urine (< 0.20 µg/g Cre). However, also a slight increase of OH-PCBs was observed in the researchers doing the air sampling at PCB storage area. In the second sampling, after recommended PCB exposure reduction measures had been enacted, the worker's PCB levels did not increase during handling of PCB equipment. This suggests that applied safety measures improved the situation. Hydroxylated trichlorobiphenyls (OH-TrCBs) were identified as a major homolog of OH-PCBs in urine. Also, hydroxylated tetrachlorobiphenyls (OH-TeCBs) to hydroxylated hexachlorobiphenyls (OH-HxCBs) were detected. For the sum of ten selected major indicators, a strong correlation to total OH-PCBs were found and these can possibly be used as non-invasive biomarkers of PCB exposure in workers managing PCB capacitors and transformer oils. We suggest that monitoring of OH-PCBs in PCB management projects could be considered a non-invasive way to detect exposure. It could also be used as a tool to assess and improve PCB management. This is highly relevant considering the fact that in the next 10 years, approx. 14 million tons of PCB waste need to be managed. Also, the selected populations could be screened to assess whether exposure at work, school, or home has taken place.

Effect of lower chlorinated hydroxylated-polychlorobiphenyls on development of PC12 cells.

Hydroxylated polychlorobiphenyls (OH-PCBs) are major metabolites of PCBs that are widely distributed in the environment. While the effects of penta- to hepta-chlorinated OH-PCBs on neuronal differentiation have been widely reported, those of lower chlorinated OH-PCBs have not been extensively studied. To investigate the effects of lower chlorinated OH-PCBs on neuronal development, we studied the effects of mono- to hexa-chlorinated OH-PCBs on PC12 cells. Morphological changes were examined using an automatic system IN Cell Analyzer. Seventeen of the 20 OH-PCBs investigated promoted neuronal elongation in an OH-PCB concentration-dependent manner, while three OH-PCB congeners suppressed neuronal elongation based on Dunnett's analysis. In particular, the top five OH-PCBs (4OH-PCB2, 4'OH-PCB3, 4'OH-PCB25, 4'OH-PCB68, and 4'OH-PCB159), which have hydroxyl groups at the para-position and chlorine substitutions at the 2, 4, or 3' positions, significantly promoted neuronal elongation. Moreover, these neuronal elongations were suppressed by U0126, and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was observed in PC12 cells treated with 4OH-PCB2, 4'OH-PCB25, and 4'OH-PCB159. Taken together, our results indicate that the effect of OH-PCB on neuronal development is not dependent on the number of chlorine groups but on the chemical structure, and the mitogen-activated kinase kinase (MEK)-ERK1/2 signaling pathway is involved in this process.

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) exhibit inhibitory effects on UDP-glucuronosyltransferases (UGTs).

Hydroxy metabolites of polychlorinated biphenyls (OH-PCBs) are important substance basis for the toxicity of PCBs. This study aims to investigate the inhibition of OH-PCBs on the activity of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of PCBs from a new perspective. In vitrohuman recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used as the probe reaction. The number of chlorine atom can affect the inhibition potential of OH-PCBs towards different isoforms of UGTs, and complex structure-activity relationship was found for the inhibition of OH-PCBs on the activities of UGT isoforms. For the inhibition kinetic determination, 2'OHPCB106 and 4'OHPCB106 were selected as the representative OH-PCBs, and UGT1A1, 1A7, and 2B7 were chosen as the representative UGT isoforms. Competitive inhibition of 2'OHPCB106 and 4'OHPCB106 on the activities of UGT1A1, UGT1A7, and UGT2B7 was found. For 2'OHPCB106, the inhibition kinetic parameters (Ki) were calculated to be 0.4 µM for UGT1A1, 1.3 µM for UGT1A7, and 2.7 µM for UGT2B7, respectively. For 4'OHPCB106, Ki values were calculated to be 0.7 µM for UGT1A1, 6.8 µM for UGT1A7, and 4.8 µM for UGT2B7, respectively. In silico docking method was utilized to elucidate the inhibition difference of UGT1A1 by four OH-PCBs with similar structures (4'OHPCB9, 4'OHPCB26, 4'OHPCB112 and 4'OHPCB165). In conclusion, these data will be helpful for understanding the toxicity mechanisms of PCBs from a view of metabolic interference.

Determination of phenolic organohalogens in human serum from a Belgian population and assessment of parameters affecting the human contamination.

Many in vitro or in vivo studies highlighted the potential deleterious effects of phenolic organohalogenated compounds (POHs) on the health, particularly on the thyroid system homeostasis, however few large scale human epidemiological studies have been carried out, especially in Europe. Further studies monitoring the human contamination by POHs, the sources of exposure and the influence of these compounds on thyroid health are still needed. Therefore we determined the concentrations of 16 POHs (pentachlorophenol (PCP), tetrabromobisphenol A (TBBPA), 4 bromophenols (BPs), 3 hydroxy-polybromodiphenylethers (OH-PBDEs) and 7 hydroxy-polychlorobiphenyls (OH-PCBs)) in serum from 274 people aged from 18 to 76years old living in Liege (Belgium) and the surrounding area. A questionnaire about their alimentary habits, life style and home environment was also administered to the volunteers. The predominant compound measured in the population was PCP (median concentration of 593.0pgmL-1). 4-OH-CB 107, 4-OH-CB 146 and 4-OH-CB 187 were detected in all samples and contributed for 75% of the sum of OH-PCBs (ΣOH-PCBs). The median measured in our population for ΣOH-PCBs was 143.7pgmL-1. TBBPA and 2,4,6-tribromophenol were detected in 31% and 63.8% of the samples respectively while the detection frequency observed for the other BPs and the OH-PBDEs was close to zero. We computed multivariate regression models in order to assess the influence of demographic and lifestyle parameters on the PCP and ΣOH-PCBs contamination levels. Significant correlation was found between the PCP concentration and sex, smoker status, sea fish consumption and level of education, although the model seemed to be a poor (R2=0.14) predictor of the PCP concentration. The model computed for ΣOH-PCBs was more explanatory (R2=0.61) and involved age, BMI and sea fish consumption. Finally, we assessed the parameters affecting the ΣOH-PCBs/ΣPCBs ratio. The model proposed involved age, BMI, smoker status and parent PCB level, and explained 41% of the variability of the ΣOH-PCBs/ΣPCBs ratio.

3D QSAR studies of hydroxylated polychlorinated biphenyls as potential xenoestrogens.

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. This study has also revealed the following additional interactions that influence estrogenicity of these chemicals (a) the aromatic interactions of the biphenyl moieties with the receptor, (b) hydrogen bonding interactions of the p-hydroxyl group with key amino acids ARG394 and GLU353, (c) low or no electronegative substitution at para-positions of the p-hydroxyl group, (d) enhanced electrostatic interactions at the meta position on the B ring, and (e) co-planarity of the hydroxyl group on the A ring. In combination the 2D and 3D QSAR approaches have led us to the support conclusion that the hydroxyl group is the most important feature on the OH-PCB influencing the binding to estrogen receptors, and have enhanced our understanding of the mechanistic details of estrogenicity of this class of chemicals. Such in silico computational methods could serve as useful tools in risk assessment of chemicals.

Carbon nanotubes based electrochemical aptasensing platform for the detection of hydroxylated polychlorinated biphenyl in human blood serum.

A novel strategy to sense target molecules in human blood serum is achieved by immobilizing aptamers (APTs) on multi-walled carbon nanotubes (MWCNT) modified electrodes. In this work, the aminated aptamer selected for hydroxylated polychlorinated biphenyl (OH-PCB) was covalently immobilized on the surface of the MWCNT-COOH modified glassy carbon electrode through amide linkage. The aptamers function as recognition probes for OH-PCB by the binding induced folding of the aptamer. The developed aptasensing device was characterized by electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR). The aptasensor displayed excellent performance for OH-PCB detection with a linear range from 0.16 to 7.5 µM. The sensitivity of the developed aptasensing platform is improved (1×10(-8) M) compared to the published report (1×10(-6) M) for the determination of OH-PCB (Turner et al., 2007). The better performance of the sensor is due to the unique platform, i.e. the presence of APTs onto electrodes and the combination with nanomaterials. The aptamer density on the electrode surface was estimated by chronocoulometry and was found to be 1.4×10(13) molecules cm(-2). The validity of the method and applicability of the aptasensor was successfully evaluated by the detection of OH-PCB in a blood serum sample. The described approach for aptasensing opens up new perspectives in the field of biomonitoring providing a device with acceptable stability, high sensitivity, good accuracy and precision.

Blood levels of polychlorinated biphenyls and their hydroxylated metabolites in Baikal seals (Pusa sibirica): emphasis on interspecies comparison, gender difference and association with blood thyroid hormone levels.

We have previously demonstrated that Baikal seals (Pusa sibirica) are still being exposed to polychlorinated biphenyls (PCBs), and the population is at risk. In the present study, we measured the residue levels of PCBs and their hydroxylated metabolites (OH-PCBs) in the blood of Baikal seals and assessed the impact of OH-PCBs on the thyroid function. Blood concentrations of PCBs and OH-PCBs were in the range of 2.8-130 ng g(-1)wet wt. and 0.71-4.6 ng g(-1)wetwt., respectively. Concentrations of higher-chlorinated OH-PCBs (hexa- to octa-PCBs) were more than 70% to total OH-PCB concentrations, indicating Baikal seals are mostly risked by higher-chlorinated OH-PCBs. High levels of 4OH-CB146 and 4OH-CB187 and low levels of 4OH-CB107/4'OH-CB108 found in Baikal seals were different from those in other phocidae species, suggesting the unique drug-metabolizing enzyme activities and/or contamination sources in this species. Concentrations of some OH-PCBs in males were significantly higher than those in females. These results suggest that these isomers may be preferentially transferred from mother to pup via cord blood. However, concentrations of almost all the isomers were not significantly correlated with the levels of blood total T3 and T4, implying less impact of PCB-related compounds on the thyroid hormone circulation.