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Drug Delivery and Translational Research Jun 2018Despite production having stopped in the 1970s, polychlorinated biphenyls (PCBs) represent persistent organic pollutants that continue to pose a serious human health... (Review)
Review
Despite production having stopped in the 1970s, polychlorinated biphenyls (PCBs) represent persistent organic pollutants that continue to pose a serious human health risk. Exposure to PCBs has been linked to chronic inflammatory diseases, such as cardiovascular disease, type 2 diabetes, obesity, as well as hepatic disorders, endocrine dysfunction, neurological deficits, and many others. This is further complicated by the PCB's strong hydrophobicity, resulting in their ability to accumulate up the food chain and to be stored in fat deposits. This means that completely avoiding exposure is not possible, thus requiring the need to develop intervention strategies that can mitigate disease risks associated with exposure to PCBs. Currently, there is excitement in the use of nutritional compounds as a way of inhibiting the inflammation associated with PCBs, yet the suboptimal delivery and pharmacology of these compounds may not be sufficient in more acute exposures. In this review, we discuss the current state of knowledge of PCB toxicity and some of the antioxidant and anti-inflammatory nanocarrier systems that may be useful as an enhanced treatment modality for reducing PCB toxicity.
Topics: Animals; Antioxidants; Cardiovascular Diseases; Environmental Exposure; Environmental Pollutants; Humans; Nanomedicine; Oxidative Stress; Polychlorinated Biphenyls
PubMed: 28975503
DOI: 10.1007/s13346-017-0429-9 -
Microbial Ecology Oct 2023Polychlorinated biphenyls (PCBs) are recognized as persistent organic pollutants and accumulate in organisms, soils, waters, and sediments, causing major health and...
Polychlorinated biphenyls (PCBs) are recognized as persistent organic pollutants and accumulate in organisms, soils, waters, and sediments, causing major health and ecological perturbations. Literature reported PCB bio-transformation by fungi and bacteria in vitro, but data about the in situ impact of those compounds on microbial communities remained scarce while being useful to guide biotransformation assays. The present work investigated for the first time microbial diversity from the three-domains-of-life in a long-term contaminated brownfield (a former factory land). Soil samples were ranked according to their PCB concentrations, and a significant increase in abundance was shown according to increased concentrations. Microbial communities structure showed a segregation from the least to the most PCB-polluted samples. Among the identified microorganisms, Bacteria belonging to Gammaproteobacteria class, as well as Fungi affiliated to Saccharomycetes class or Pleurotaceae family, including some species known to transform some PCBs were abundantly retrieved in the highly polluted soil samples.
Topics: Polychlorinated Biphenyls; Soil Pollutants; Biodegradation, Environmental; Soil Microbiology; Bacteria; Soil
PubMed: 36646913
DOI: 10.1007/s00248-022-02161-y -
Environmental Research Aug 2020Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the...
BACKGROUND
Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the 1970s, they are highly persistent in the environment and bioaccumulate. Whether PCBs are associated with liver cancer risk at general population levels is unknown.
METHODS
This study consisted of 136 incident liver cancer cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the Norwegian Janus cohort. Sera collected in the 1960s-1980s were measured for 37 PCB congeners and markers of hepatitis B (HBV) and C (HCV) infection. Odds ratios (OR) and 95% confidence intervals (CI) for tertiles of each lipid-adjusted PCB were estimated from conditional logistic regression. We also examined the molar sum of congeners in groups: total PCBs; low, medium, and high chlorination; and Wolff functional groups.
RESULTS
Concentrations of individual congeners from the 1960s/1970s sera ranged from 1.3-123.0 and 1.4-116.0 ng/g lipid among MHC cases and controls, respectively, and from 1.9-258.0 and 1.9-271.0 ng/g lipid among Janus cases and controls, respectively. Among MHC participants with sera from the 1960s, collected an average of 27 years before diagnosis among cases, the top tertile of PCBs 151, 170, 172, 177, 178, 180, and 195 was significantly associated with elevated odds of liver cancer (OR range = 2.01-2.38); most of these congeners demonstrated exposure-response trends. For example, OR = 2.38 (95% CI: 1.22-4.64, p-trend = 0.01) for PCB 180. As a group, Wolff group 1b congeners, which are biologically persistent and weak phenobarbital inducers, were associated with increased odds. In MHC participants, ever vs. never HBV or HCV infection modified the PCB-liver cancer associations. There was little evidence of an association between PCBs and odds of liver cancer among the Janus cohort.
DISCUSSION
We observed associations between a number of PCB congeners and increased odds of liver cancer among MHC, but not Janus, participants with sera from the 1960s/1970s.
Topics: Case-Control Studies; Environmental Pollutants; Europe; Humans; Liver Neoplasms; Norway; Polychlorinated Biphenyls; Prospective Studies
PubMed: 32474310
DOI: 10.1016/j.envres.2020.109690 -
International Journal of Environmental... Dec 2021Dietary acid load (DAL) may be associated with all-cause mortality (ACM) and breast cancer-specific mortality (BCM), and these associations may be modified by serum...
Dietary acid load (DAL) may be associated with all-cause mortality (ACM) and breast cancer-specific mortality (BCM), and these associations may be modified by serum polychlorinated biphenyl (PCB) levels. Participants included 519 women diagnosed with first primary in situ or invasive breast cancer in 1996/1997 with available lipid-corrected PCB data. After a median of 17 years, there were 217 deaths (73 BCM). Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from a baseline food frequency questionnaire estimated DAL. Cox regression estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PRAL and NEAP with mortality. We evaluated effect measure modification by total serum PCB levels (>median vs. ≤median). PRAL quartile 4 versus quartile 1 was associated with an ACM HR of 1.31 (95%CI = 0.90-1.92). In the upper median of PCBs, ACM HRs were 1.43 (95%CI = 0.96-2.11) and 1.40 (95%CI = 0.94-2.07) for PRAL and NEAP upper medians, respectively. In the lower median of PCBs, the upper median of NEAP was inversely associated with BCM (HR = 0.40, 95%CI = 0.19-0.85). DAL may be associated with increased risk of all-cause mortality following breast cancer among women with high total serum PCB levels, but inversely associated with breast cancer mortality among women with low PCB levels.
Topics: Acids; Breast Neoplasms; Diet; Female; Humans; Polychlorinated Biphenyls; Proportional Hazards Models
PubMed: 35010632
DOI: 10.3390/ijerph19010374 -
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 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 2023The gut microbiota plays an important role throughout the lifespan in maintaining host health, and several factors can modulate microbiota composition including diet,...
The gut microbiota plays an important role throughout the lifespan in maintaining host health, and several factors can modulate microbiota composition including diet, exercise, and environmental exposures. Maternal microbiota is transferred to offspring during early life; thus, environmental exposures before gestation may also modulate offspring microbiota. Here we aimed to investigate the effects of maternal exposure to dioxin-like polychlorinated biphenyls (PCBs) on the microbiota of aged offspring and to determine if lifestyle factors, including maternal exercise or offspring high-fat feeding alter these associations. To test this, dams were exposed to PCB 126 (0.5 μmole/kg body weight) or vehicle oil by oral gavage during preconception, gestation, and during lactation. Half of each group was allowed access to running wheels for ≥ 7 days before and during pregnancy and up through day 14 of lactation. Female offspring born from the 4 maternal groups (PCB exposure or not, with/without exercise) were subsequently placed either on regular diet or switched to a high-fat diet during adulthood. Microbiota composition was quantified in female offspring at 49 weeks of age by 16 S rRNA sequencing. Maternal exposure to PCB 126 resulted in significantly reduced richness and diversity in offspring microbiota regardless of diet or exercise. Overall compositional differences were largely driven by offspring diet, but alterations in specific taxa due to maternal PCB 126 exposure, included the depletion of Verrucomicrobiaceae and Akkermansia muciniphila, and an increase in Anaeroplasma. Perturbation of microbiota due to PCB 126 may predispose offspring to a variety of chronic diseases later in adulthood.
Topics: Pregnancy; Female; Humans; Aged; Polychlorinated Biphenyls; Maternal Exposure; Gastrointestinal Microbiome; Diet, High-Fat; Prenatal Exposure Delayed Effects
PubMed: 37061048
DOI: 10.1016/j.reprotox.2023.108384 -
Environmental Health Perspectives Nov 2016Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty.
BACKGROUND
Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty.
OBJECTIVES
We examined the association of peripubertal serum levels of these compounds [and their toxic equivalents (TEQs)] with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years.
METHODS
At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [genitalia (G), pubarche (P), and testicular volume (TV)]. Three hundred fifteen subjects completed the follow-up visit at 17-18 years of age. Pubertal onset was defined as TV > 3 mL, G2, or P2. Sexual maturity was defined as TV ≥ 20 mL, G5, or P5. Multivariable interval-censored models were used to evaluate associations of lipid-standardized concentrations with pubertal timing.
RESULTS
Medians (interquartile ranges) of the sum of dioxin-like compounds, TEQs, and non-dioxin-like PCBs were 362 pg/g lipid (279-495), 21.1 pg TEQ/g lipid (14.4-33.2), and 250 ng/g lipid (164-395), respectively. In adjusted models, the highest compared to lowest TEQ quartile was associated with later pubertal onset [TV = 11.6 months (95% CI: 3.8, 19.4); G2 = 10.1 months (95% CI: 1.4, 18.8)] and sexual maturity [TV = 11.6 months (95% CI: 5.7, 17.6); G5 = 9.7 months (95% CI: 3.1, 16.2)]. However, the highest compared to the lowest quartile of non-dioxin-like PCBs, when co-adjusted by TEQs, was associated with earlier pubertal onset [TV = -8.3 months (95% CI:-16.2, -0.3)] and sexual maturity [TV = -6.3 months (95% CI:-12.2, -0.3); G5 = -7.2 months (95% CI:-13.8, -0.6)]; the non-dioxin-like PCB associations were only significant when adjusted for TEQs. TEQs and PCBs were not significantly associated with pubic hair development.
CONCLUSIONS
Our results suggest that TEQs may delay, while non-dioxin-like PCBs advance, the timing of male puberty. Citation: Burns JS, Lee MM, Williams PL, Korrick SA, Sergeyev O, Lam T, Revich B, Hauser R. 2016. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ Health Perspect 124:1801-1807; http://dx.doi.org/10.1289/EHP154.
Topics: Adolescent; Child; Dioxins; Environmental Exposure; Humans; Longitudinal Studies; Male; Polychlorinated Biphenyls; Russia; Sexual Maturation; Time Factors
PubMed: 27187981
DOI: 10.1289/EHP154 -
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 -
Toxicology in Vitro : An International... Jun 2023Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2',5,5'-tetrachorobiphenyl), is found at...
Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2',5,5'-tetrachorobiphenyl), is found at high levels in school air. Hydroxylation of PCB52 to 4-OH-PCB52 (4-hydroxy-2,2',5,5'-tetrachorobiphenyl) may increase its toxicity. To understand PCB52's role in causing adipose dysfunction, we exposed human preadipocytes to PCB52 or 4-OH-PCB52 across a time course and assessed transcript changes using RNAseq. 4-OH-PCB52 caused considerably more changes in the number of differentially expressed genes as compared to PCB52. Both PCB52 and 4-OH-PCB52 upregulated transcript levels of the sulfotransferase SULT1E1 at early time points, but cytochrome P450 genes were generally not affected. A set of genes known to be transcriptionally regulated by PPARα were consistently downregulated by PCB52 at all time points. In contrast, 4-OH-PCB52 affected a variety of pathways, including those involving cytokine responses, hormone responses, focal adhesion, Hippo, and Wnt signaling. Sets of genes known to be transcriptionally regulated by IL17A or parathyroid hormone (PTH) were found to be consistently downregulated by 4-OH-PCB52. Most of the genes affected by PCB52 and 4-OH-PCB52 were different and, of those that were the same, many were changed in an opposite direction. These studies provide insight into how PCB52 or its metabolites may cause adipose dysfunction to cause disease.
Topics: Humans; Polychlorinated Biphenyls; Hydroxylation; Cytochrome P-450 Enzyme System; Gene Expression
PubMed: 36804509
DOI: 10.1016/j.tiv.2023.105568