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Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.9 %, 93.9 % and 97.6 % for ERα dataset and 91.9 %, 90.9 % and 92.7 % for ERβ dataset. The areas under the ROC curves, constructed with the training set data, were found to be 0.985 and 0.987 for the two models. Predictions made by models I and II correctly classified 84.0 % and 88.0 % of the test set compounds and 89.8 % and 85.8% of the cross-validation set compounds respectively. The two classification-based QSAR models proposed in this paper are considered robust and reliable for rapid identification of ERα and ERβ agonists among OH-PCB congeners.

Some adverse effects of hydroxylated polychlorinated biphenyls (OH-PCBs) in humans are presumed to be initiated via thyroid hormone receptor (TR) binding. Due to the trial-and-error approach adopted for OH-PCB selection in previous studies, experiments designed to test the TR binding hypothesis mostly utilized inactive OH-PCBs, leading to considerable waste of time, effort and other material resources. In this paper, linear discriminant analysis (LDA) and binary logistic regression (LR) were used to develop classification models to group OH-PCBs into active and inactive TR agonists using radial distribution function (RDF) descriptors as predictor variables. The classifications made by both LDA and LR models on the training set compounds resulted in an accuracy of 84.3%, sensitivity of 72.2% and specificity of 90.9%. The areas under the ROC curves, constructed with the training set data, were found to be 0.872 and 0.880 for LDA and LR models, respectively. External validation of the models revealed that 76.5% of the test set compounds were correctly classified by both LDA and LR models. These findings suggest that the two models reported in this paper are good and reliable for classifying OH-PCB congeners into active and inactive TR agonists. [ABSTRACT FROM AUTHOR]

Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.9 %, 93.9 % and 97.6 % for ERα dataset and 91.9 %, 90.9 % and 92.7 % for ERβ dataset. The areas under the ROC curves, constructed with the training set data, were found to be 0.985 and 0.987 for the two models. Predictions made by models I and II correctly classified 84.0 % and 88.0 % of the test set compounds and 89.8 % and 85.8% of the cross-validation set compounds respectively. The two classification-based QSAR models proposed in this paper are considered robust and reliable for rapid identification of ERα and ERβ agonists among OH-PCB congeners., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development. [ABSTRACT FROM AUTHOR]

Highlights: [•] We studied the mechanism of inhibition of hSULT2A1 by hydroxylated PCBs (OHPCBs). [•] The OHPCBs studied bind at the sulfuryl-acceptor binding site of hSULT2A1. [•] This binding may occur with different orientations of the OHPCB. [•] The results suggest binding of OHPCBs to more than one form of hSULT2A1. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) can be metabolized into hydroxylated PCBs (OH-PCBs) that exhibit greater toxicity than their parent compounds. In particular, 2,2',4,5,5'-pentachlorobiphenyl (PCB 101) is commonly found in chicken feeds and breeding environments, although information on the biotransformation of this PCB in chickens is lacking. In this study, the hydroxylation metabolization of PCB 101 was assessed based on in vitro trials with Sanhuang chicken liver microsomes and in vivo experiments with Hy-Line Brown hens. The para -substituted metabolite 4'-OH-PCB 101 is the predominant metabolite of PCB 101. 4'-OH-PCB 101 is preferentially retained in the chicken bloodstream and partly distributed into different tissues of laying hens. The blood-brain barrier can effectively prevent the OH-PCB from entering the brain, and the adipose tissue contains a relatively low residue concentration of the OH-PCB. The laying hen can deplete the OH-PCB via laying eggs and excrement. The ratio of 4'-OH-PCB 101/PCB 101 in egg yolk is about 1:2. These results first provide definite evidence for the previous hypothesis of the PCB 101 metabolism by chickens. They could assist in predicting the environmental fate of PCBs, and in the risk assessment of PCBs and OH-PCBs in chicken-based foodstuffs.

Three hydroxylated derivatives of PCBs, 2′-hydroxy-4-chlorobiphenyl (2′-OH-4-CB), 3′-hydroxy-4-chlorobiphenyl (3′-OH-4-CB), and 4′-hydroxy-4-chlorobiphenyl (4′-OH-4-CB), were transformed by the PCB degrader, Burkholderia xenovorans. When the bacterium was growing on biphenyl (biphenyl pathway-inducing conditions), all three hydroxylated isomers were transformed. However, only 2′-OH-4-CB was transformed by the bacterium growing on succinate (conditions non-inductive of the biphenyl pathway). Gene expression analyses showed a strong induction of key genes of the biphenyl pathway ( bph) when cells were grown on biphenyl, which is consistent with the transformation of the three isomers by biphenyl-grown cells. When cells were grown on succinate, only exposure to 2′-OH-4-CB resulted in expression of biphenyl pathway genes, which suggests that this isomer was capable of inducing the biphenyl pathway. These results provide the first evidence that bacteria are able to metabolize PCB derivatives hydroxylated on the non-chlorinated ring. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are environmental pollutants that have been associated with numerous adverse health effects in human and animals. Hydroxylated PCBs (HPCBs) are the product of the oxidative metabolism of PCBs. The presence of hydroxyl groups in HPCBs makes these compounds more hydrophilic than the parent PCBs. One of the best approaches to break down and remove these contaminants is bioremediation; an environmentally friendly process that uses microorganisms to degrade hazardous chemicals into non-toxic ones. In this study, we investigated the cellular accumulation and toxicity of selected PCBs and HPCBs in Gram-negative bacteria, using Escherichia coli as a model organism. We found that none of the five PCBs tested were toxic to E. coli, presumably due to their limited bioavailability. Nevertheless, different HPCBs tested showed different levels of toxicity. Furthermore, we demonstrated that the primary multidrug efflux system in E. coli, AcrAB-TolC, facilitated the efflux of HPCBs out of the cell. Since AcrAB-TolC is constitutively expressed in E. coli and is conserved in all sequenced Gram-negative bacterial genomes, our results suggest that the efflux activities of multidrug resistant pumps may affect the accumulation and degradation of PCBs in Gram-negative bacteria. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

As the active metabolites of polychlorinated biphenyl (PCBs), hydroxylated polychlorinated biphenyls (OH-PCBs) are found in wildlife and human tissues. They have been proposed as main contributors for endocrine disruption of PCBs in living organisms. In this study, mono-ortho PCB 156 and its hydroxylated metabolites 4'-OH-PCB 159, 4'-OH-PCB 121, and 4'-OHPCB 72 were selected to investigate the toxic effects on rat hepatoma H4IIE cell line and rat thyroid follicle FRTL-5 cell line at concentrations of 1, 10², 104 nM. 7-Ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) activities were determined with micro-EROD/PROD to indicate cytochrome P4501A1 (CYP1A1) and cytochrome P4502B (CYP2B) induction in the H4IIE cell after exposure for 72 h. To assess thyroid disruption of these compounds, thyroglobulin concentrations also were detected inside FRTL-5 cell with immunocellularchemistry and in its medium with radioimmunoassay after exposure for 24 h. Significant inductions of EROD activity by PCB156 at 10² and 104 nM (p < 0.05) were observed, but no effects by the three OHPCBs in H4IIE cell line. 7-Pentoxyresorufin-O-dealkylase activities were induced only by 104 nM of PCB156 and the three OHPCBs (p < 0.05). Meanwhile, significant increases of thyroglobulin concentrations were observed in the medium of FRTL-5 cell exposed to 4'-OH-PCB 121 and 4'-OH-PCB 72 at all of the test concentrations (p < 0.05), but not to the other compounds. The results demonstrated that mono-ortho PCBs mainly could be metabolized to hydroxylated metabolites through CYP1A1 instead of CYP2B. Moreover, after being metabolized, OH-PCBs still sustained the ability to induce PROD activity and did exhibit the disruption on thyroglobulin synthesis/excretion in rat cells. [ABSTRACT FROM AUTHOR]

We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

Background: The production ban of polychlorinated biphenyl (PCB) technical mixtures has left the erroneous impression that PCBs exist only as legacy pollutants. Some lower-chlorinated PCBs are still being produced and contaminate both indoor and ambient air., Objectives: To inform PCB risk assessment, we characterized lung uptake, distribution, metabolism and excretion of PCB11 as a signature compound for these airborne non-legacy PCBs., Methods: After delivering [(14)C]PCB11 to the lungs of male rats, radioactivity in 34 major tissues and 5 digestive matter compartments was measured at 12, 25, 50, 100, 200 and 720min postexposure, during which time the excreta and exhaled air were also collected. [(14)C]PCB11 and metabolites in lung, liver, blood, digestive matter, urine, feces, and adipose tissues were extracted separately to establish the metabolic profile of the disposition., Results: [(14)C]PCB11 was distributed rapidly to all tissues after 99.8% pulmonary uptake and quickly underwent extensive metabolism. The major tissue deposition of [(14)C]PCB11 and metabolites translocated from liver, blood and muscle to skin and adipose tissue 200min postexposure, while over 50% of administered dose was discharged via urine and feces within 12h. Elimination of the [(14)C]PCB11 and metabolites consisted of an initial fast phase (t½=9-33min) and a slower clearance phase to low concentrations. Phase II metabolites dominated in liver blood and excreta after 25min postexposure., Conclusions: This study shows that PCB11 is completely absorbed after inhalation exposure and is rapidly eliminated from most tissues. Phase II metabolites dominated with a slower elimination rate than the PCB11 or phase I metabolites and thus can best serve as urine biomarkers of exposure., (Copyright © 2013 Elsevier Ltd. All rights reserved.)