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Epidemiology (Cambridge, Mass.) Jul 2021Polychlorinated biphenyls (PCBs), a diverse class of chemicals, are hypothesized mammary carcinogens. We examined plasma levels of 17 PCBs as individual congeners and as...
BACKGROUND
Polychlorinated biphenyls (PCBs), a diverse class of chemicals, are hypothesized mammary carcinogens. We examined plasma levels of 17 PCBs as individual congeners and as a mixture in association with breast cancer using a novel approach based on quantile g-computation.
METHODS
This study included 845 White and 562 Black women who participated in the population-based, case-control Carolina Breast Cancer Study Phase I. Cases (n = 748) were women with a first diagnosis of histologically confirmed, invasive breast cancer residing in 24 counties in central and eastern North Carolina; controls (n = 659) were women without breast cancer from the same counties. PCBs were measured in plasma samples obtained during the study interview. We estimated associations [covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs)] between individual PCB congeners and breast cancer using multivariable logistic regression. We assessed PCB mixtures using quantile g-computation and examined effect measure modification by race.
RESULTS
Comparing highest and lowest tertiles of PCBs resulted in ORs of 1.3 (95% CI = 0.95, 1.8) for congener 74, 1.4 (95% CI = 1.0, 1.9) for 99, 1.3 (95% CI = 0.91, 1.8) for 194, and 1.2 (95% CI = 0.90, 1.7) for 201. Among all women, we estimated a joint effect of the PCB mixture with an OR of 1.3 (95% CI = 0.98, 1.6) per tertile change. In race-stratified analyses, associations for tertiles of PCB mixtures were stronger among Black women (OR = 1.5; 95% CI = 1.0, 2.3) than among White women (OR = 1.1; 95% CI = 0.81, 1.6).
CONCLUSION
Our results are consistent with the hypothesis that exposure to PCB mixtures increase the risk of breast cancer, but studies of populations with different exposure profiles are needed.
Topics: Black or African American; Breast Neoplasms; Case-Control Studies; Environmental Pollutants; Female; Humans; North Carolina; Polychlorinated Biphenyls
PubMed: 33788793
DOI: 10.1097/EDE.0000000000001356 -
Environmental Health : a Global Access... Oct 2022Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for...
Systematic review of associations of polychlorinated biphenyl (PCB) exposure with declining semen quality in support of the derivation of reference doses for mixture risk assessments.
BACKGROUND
Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon Receptor (AhR)-agonists and Androgen Receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to systematically gather data from animal and human studies to derive a reference dose for declines in semen quality for individual PCB.
METHODS
We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners.
RESULTS
Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day.
CONCLUSIONS
We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other antiandrogenic chemicals.
Topics: Animals; Humans; Male; Polychlorinated Biphenyls; Receptors, Androgen; Risk Assessment; Semen; Semen Analysis
PubMed: 36217156
DOI: 10.1186/s12940-022-00904-5 -
Environmental Health Perspectives Jan 2022Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs...
BACKGROUND
Polychlorinated biphenyl (PCB) exposures have been associated with liver injury in human cohorts, and steatohepatitis with liver necrosis in model systems. MicroRNAs (miRs) maintain cellular homeostasis and may regulate the response to environmental stress.
OBJECTIVES
We tested the hypothesis that specific miRs are associated with liver disease and PCB exposures in a residential cohort.
METHODS
Sixty-eight targeted hepatotoxicity miRs were measured in archived serum from 734 PCB-exposed participants in the cross-sectional Anniston Community Health Survey. Necrotic and other liver disease categories were defined by serum keratin 18 (K18) biomarkers. Associations were determined between exposure biomarkers (35 ortho-substituted PCB congeners) and disease biomarkers (highly expressed miRs or previously measured cytokines), and Ingenuity Pathway Analysis was performed.
RESULTS
The necrotic liver disease category was associated with four up-regulated miRs (miR-99a-5p, miR-122-5p, miR-192-5p, and miR-320a) and five down-regulated miRs (let-7d-5p, miR-17-5p, miR-24-3p, miR-197-3p, and miR-221-3p). Twenty-two miRs were associated with the other liver disease category or with K18 measurements. Eleven miRs were associated with 24 PCBs, most commonly congeners with anti-estrogenic activities. Most of the exposure-associated miRs were associated with at least one serum hepatocyte death, pro-inflammatory cytokine or insulin resistance bioarker, or with both. Within each biomarker category, associations were strongest for the liver-specific miR-122-5p. Pathways of liver toxicity that were identified included inflammation/hepatitis, hyperplasia/hyperproliferation, cirrhosis, and hepatocellular carcinoma. Tumor protein p53 and tumor necrosis factor were well integrated within the top identified networks.
DISCUSSION
These results support the human hepatotoxicity of environmental PCB exposures while elucidating potential modes of PCB action. The MiR-derived liquid liver biopsy represents a promising new technique for environmental hepatology cohort studies. https://doi.org/10.1289/EHP9467.
Topics: Circulating MicroRNA; Cross-Sectional Studies; Humans; Liver Diseases; MicroRNAs; Polychlorinated Biphenyls; Public Health
PubMed: 34989596
DOI: 10.1289/EHP9467 -
General and Comparative Endocrinology Mar 2022To assess the effect of polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) on thyroid hormone [TH: thyroxine (T) and triiodothyronine (T)]...
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 (T) and triiodothyronine (T)] 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 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 T secretion. Moreover, they increased basal and reduced TSH-stimulated T 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.
Topics: Animals; Chickens; Polychlorinated Biphenyls; Thyroid Gland; Thyroxine; Triiodothyronine
PubMed: 35151725
DOI: 10.1016/j.ygcen.2022.113989 -
Environmental Health Perspectives Mar 2022Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains...
BACKGROUND
Miscellaneous cardiovascular risk factors have been defined, but the contribution of environmental pollutants exposure on cardiovascular disease (CVD) remains underappreciated.
OBJECTIVE
We investigated the potential impact of typical environmental pollutant exposure on atherogenesis and its underlying mechanisms.
METHODS
We used human umbilical vein endothelial cells (HUVECs) and apolipoprotein E knockout () mice to investigate how 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ, a toxic polychlorinated biphenyl metabolite) affects atherogenesis and identified early biomarkers of CVD associated with PCB29-pQ exposures. Then, we used long noncoding RNAs (lncRNAs) -overexpressing mice and apolipoprotein E/caveolin 1 double-knockout () mice to address the role of these early biomarkers in PCB29-pQ-induced atherogenesis. Plasma samples from patients with coronary heart disease (CHD) were also used to confirm our findings.
RESULTS
Our data indicate that lncRNA bound to via argonaute 2 in PCB29-pQ-challenged HUVECs. Our mRNA sequencing assay identified transforming growth () as a possible target gene of ; sponged and inhibited the binding of to . The effect of PCB29-pQ-induced endothelial injury, vascular inflammation, development of plaques, and atherogenesis in mice was greater with -mediated inhibition, whereas -overexpressing mice and mice showed the opposite effect. Consistently, plasma levels of and were found to be significantly associated individuals diagnosed with CHD.
DISCUSSIONS
These findings demonstrated that a mechanism-based, integrated-omics approach enabled the identification of potentially clinically relevant diagnostic indicators and therapeutic targets of CHD mediated by environmental contaminants using and models of HUVECs and and mice. https://doi.org/10.1289/EHP9833.
Topics: Animals; Atherosclerosis; Biomarkers; Human Umbilical Vein Endothelial Cells; Humans; Mice; Polychlorinated Biphenyls; RNA, Long Noncoding
PubMed: 35349355
DOI: 10.1289/EHP9833 -
Mini Reviews in Medicinal Chemistry 2023A class of organic chemicals known as polychlorinated biphenyls (PCBs) consists of chlorine, hydrogen, and carbon atoms. High boiling points, chemical stability,... (Review)
Review
A class of organic chemicals known as polychlorinated biphenyls (PCBs) consists of chlorine, hydrogen, and carbon atoms. High boiling points, chemical stability, non-flammability, and insulating properties have enabled them to be used in various industries. Because of their high toxicity, PCBs were one of the first industrial compounds to be banned from production. These compounds have high-fat solubility with bioaccumulation and biomagnification properties in the environment, food chain, and individuals. Hence, they may have an impact not only on individual organisms but ultimately on whole ecosystems. The main sources of PCB exposure are food and environmental pollutants. In the toxicology of PCBs, oxidative stress plays the most influential function. The induction of CYP1A1 due to the high affinity of PCBs for aryl hydrocarbon receptors is considered a trigger for oxidative stress. Production of reactive oxygen species and depletion of glutathione occur due to phase Ⅰ and Ⅱ metabolism, respectively. Thus, cellular redox balance may be disrupted in the presence of PCBs and their metabolites. Chronic and long-term exposure to these compounds can often lead to life-threatening diseases, like diabetes, obesity, cardiovascular and neurological diseases, cancer, and reproductive and endocrine disorders. We present the current knowledge of the routes of PCB exposure and bioaccumulation, the outlook regarding environmental and food safety, the potential role of PCBs in various diseases, the principal mechanisms responsible for PCB toxicity, and the main detection techniques used for PCBs.
Topics: Humans; Polychlorinated Biphenyls; Ecosystem; Neoplasms; Environmental Monitoring; Food Safety
PubMed: 36515022
DOI: 10.2174/1389557523666221213091445 -
Alcohol, Clinical & Experimental... Jan 2023The prevalence of alcohol-associated liver disease (ALD), a subtype of fatty liver disease (FLD), continues to rise. ALD is a major cause of preventable death....
BACKGROUND
The prevalence of alcohol-associated liver disease (ALD), a subtype of fatty liver disease (FLD), continues to rise. ALD is a major cause of preventable death. Polychlorinated biphenyl (PCB) 126 is an environmentally relevant, dioxin-like pollutant whose negative metabolic effects have been well documented. In human and animal studies, PCB has been associated with the severity of nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated whether exposures to environmental toxicants can worsen ALD. Thus, the objective of the current study was to develop an alcohol-plus-toxicant model to study how an environmental pollutant, PCB 126, impacts rodent ALD pathology.
METHODS
Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB 126 or corn oil vehicle four days prior to ethanol feeding using the chronic-binge (10-plus-one) model.
RESULTS
Concentrations of macromolecules, including hepatic lipids, carbohydrates, and protein (albumin) were impacted. Exposure to PCB 126 exacerbated hepatic steatosis and hepatomegaly in mice exposed to the chemical and fed an ethanol diet. Gene expression and the analysis of blood chemistry showed a potential net increase and retention of hepatic lipids and reductions in lipid oxidation and clearance capabilities. Depletion of glycogen and glucose was evident, which contributes to disease progression by generating systemic malnutrition. Granulocytic immune infiltrates were present but driven solely by ethanol feeding. Hepatic albumin gene expression and plasma levels were decreased by ~50% indicating a potential compromise of liver function. Finally, gene expression analyses indicated that the aryl hydrocarbon receptor and constitutive androstane receptor were activated by PCB 126 and ethanol, respectively.
CONCLUSIONS
Various environmental toxicants are known to modify or enhance FLD in high-fat diet models. Findings from the present study suggest that they interact with other lifestyle factors such as alcohol consumption to reprogram intermediary metabolism resulting in exacerbated ethanol-associated systemic malnutrition in ALD.
Topics: Humans; Male; Mice; Animals; Polychlorinated Biphenyls; Environmental Pollutants; Rodentia; Mice, Inbred C57BL; Liver; Non-alcoholic Fatty Liver Disease; Liver Diseases, Alcoholic; Diet, High-Fat; Ethanol; Lipids; Malnutrition
PubMed: 36377258
DOI: 10.1111/acer.14976 -
Environmental Research May 2022Most functional microorganisms cannot be cultivated due to entering a viable but non-culturable (VBNC) state, which limits the characterization and application of...
Most functional microorganisms cannot be cultivated due to entering a viable but non-culturable (VBNC) state, which limits the characterization and application of polychlorinated biphenyl (PCB)-degrading strains. Resuscitating VBNC bacteria could provide huge candidates for obtaining high-efficient PCB degraders. However, limited studies have focused on the ability of resuscitated strains for PCBs degradation. In the present study, whole-genome analysis of a resuscitated strain SPC0, and its performances in degradation of three prevalent PCB congeners (PCBs 18, 52 and 77) were investigated. The results indicate that the strain SPC0 belonged to the genus Streptococcus, possessed the degradation potential for aromatic xenobiotics. The SPC0 could effectively degrade PCBs 18 and 52, but exhibited lower degradation efficiency of PCB 77. Degradation of PCBs 18 and 52 could be fitted well by zero-order model, whereas the fittest model for PCB 77 degradation was pseudo second-order kinetics. The bph genes expression, chloride ions release and degradation metabolites identification, suggest that SPC0 possessed the capability of oxidative dehalogenation and mineralization of PCBs. Interestingly, SPC0 can degrade PCBs via the bph-encoded biphenyl pathway, and further mineralize metabolite dichlorobenzoate via protocatechuate pathway. This study is the first to show that a strain belonging to genus Streptococcus possessed PCB-degrading capability, which uncovered the powerful potential of resuscitated strains for bioremediation of PCB-contaminated sites.
Topics: Biodegradation, Environmental; Oxidative Stress; Polychlorinated Biphenyls; Soil Microbiology; Streptococcus
PubMed: 34990605
DOI: 10.1016/j.envres.2021.112648 -
Environmental Science & Technology Jun 2023Persistent organic pollutants (POPs) are recognized as pollutants of global concern, but so far, information on the trends of legacy POPs in the waters of the world has...
Persistent organic pollutants (POPs) are recognized as pollutants of global concern, but so far, information on the trends of legacy POPs in the waters of the world has been missing due to logistical, analytical, and financial reasons. Passive samplers have emerged as an attractive alternative to active water sampling methods as they accumulate POPs, represent time-weighted average concentrations, and can easily be shipped and deployed. As part of the AQUA-GAPS/MONET, passive samplers were deployed at 40 globally distributed sites between 2016 and 2020, for a total of 21 freshwater and 40 marine deployments. Results from silicone passive samplers showed α-hexachlorocyclohexane (HCH) and γ-HCH displaying the greatest concentrations in the northern latitudes/Arctic Ocean, in stark contrast to the more persistent penta (PeCB)- and hexachlorobenzene (HCB), which approached equilibrium across sampling sites. Geospatial patterns of polychlorinated biphenyl (PCB) aqueous concentrations closely matched original estimates of production and use, implying limited global transport. Positive correlations between log-transformed concentrations of ΣPCB, ΣDDTs, Σendosulfan, and Σchlordane, but not ΣHCH, and the log of population density ( < 0.05) within 5 and 10 km of the sampling sites also supported limited transport from used sites. These results help to understand the extent of global distribution, and eventually time-trends, of organic pollutants in aquatic systems, such as across freshwaters and oceans. Future deployments will aim to establish time-trends at selected sites while adding to the geographical coverage.
Topics: Polychlorinated Biphenyls; Environmental Monitoring; Hexachlorobenzene; Fresh Water; Environmental Pollutants; Air Pollutants; Pesticides; Hydrocarbons, Chlorinated
PubMed: 37294896
DOI: 10.1021/acs.est.3c01866 -
Chemosphere Oct 2019Different countries produce varying amounts of polychlorinated biphenyls (PCBs), have distinct patterns of use, and regulations for treatment and disposal. Therefore,...
Different countries produce varying amounts of polychlorinated biphenyls (PCBs), have distinct patterns of use, and regulations for treatment and disposal. Therefore, long-term countermeasures require an understanding of historical and future emission trends at the national scale. In this study, we estimate historical PCB emissions from products containing PCBs, unintentional production related thermal processes, and disposal processes for products containing PCBs from 1950 to 2030 in Japan. In addition, in order to validate the results, we estimated PCB concentrations in environmental media using an environmental fate model and a sensitivity analysis was conducted. Our results show that total PCB emissions were approximately 2.6 tons in 2017, which was a dramatic decrease from peak emissions of 68.9 tons in 1970. We suggest that PCB emissions may continue to decrease, reaching 0.707 tons in 2030. This trend might be due to a change in the emission source; it was estimated that the main emission source in past and recent years was volatilization from large products containing PCBs. However, it is predicted that the main emission sources in the future will be unintentional PCB production from thermal processes and volatilization from small untreated products containing PCBs, although the estimation of environmental PCB levels suggested that there might be unknown emission sources. Additionally, the sensitivity analysis indicated that some parameters greatly influenced the estimation of recent and future emissions. In particular, there was no detailed information concerning the applications for PCBs, which potentially had a large influence on the estimation of future emissions.
Topics: Air Pollutants; Conservation of Natural Resources; Environmental Monitoring; History, 20th Century; History, 21st Century; Japan; Models, Theoretical; Polychlorinated Biphenyls; Volatilization
PubMed: 31158633
DOI: 10.1016/j.chemosphere.2019.04.206