Serum Concentrations Of Polychlorinated Biphenyls Research Articles

Changes in Adipose Tissue and Circulating Concentrations of Persistent Organic Pollutants in Midlife Women.

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are persistent organic pollutants (POPs) that bioaccumulate in adipose tissue. We investigated the relationship between change in central adiposity and changes in circulating concentrations of POPs over a 12-year period during the midlife. Serum concentrations of 34 PCBs and 19 OCPs were measured at four time points (1999/2000, 2002/03, 2005/06, 2009/11) in a cohort of midlife women, the Study of Women's Health Across the Nation. Linear mixed models were used to test the association between a change in waist circumference and a change in serum POP concentrations. Sixty-five women contributed 181 PCB observations. Fifty-nine women contributed 151 OCP observations. After adjustment for covariates (study site, race and ethnicity, age at baseline, parity), a one-inch (2.54 cm) increase in the change in waist circumference between visits was associated with a 4.9% decrease in the change in serum concentration of PCB 194 (95% CI: -8.0%, -1.6%). No associations were observed for other PCB congeners or the presence of OCPs. An increase in the difference in waist circumference over time was not associated with a change in the difference in serum concentrations of PCBs and OCPs except for PCB 194, possibly due to the high lipophilicity.

Mixture Effects of Polychlorinated Biphenyls (PCBs) and Three Organochlorine Pesticides on Cognitive Function in Mohawk Adults at Akwesasne.

The Mohawks at Akwesasne have been highly exposed to polychlorinated biphenyls (PCBs), via releases from three aluminum foundries located near the reserve. They are also exposed to organochlorine pesticides, namely hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex. Previous studies have demonstrated reduced cognition in relation to total PCBs, but the effects of the mixtures of different PCB congener groups, HCB, DDE, and mirex on cognitive function have not been studied. Therefore, cognitive performance for executive function, scored via the digit symbol substitution test (DSST), in Mohawk adults aged 17-79 years (n = 301), was assessed in relation to serum concentrations of low-chlorinated PCBs, high-chlorinated PCBs, total PCBs, HCB, DDE, and mirex. We used mixture models employing the quantile-based g-computation method. The mixture effects of low-chlorinated PCBs, high-chlorinated PCBs, HCB, DDE, and mirex were significantly associated with 4.01 DSST scores decrements in the oldest age group, 47-79 years old. There were important contributions to mixture effects from low-chlorinated PCBs, high-chlorinated PCBs, and total PCBs, with smaller contributions of HCB and DDE. Our findings indicate that exposures to both low- and high-chlorinated PCBs increase the risk of cognitive decline in older adults, while DDE and HCB have less effect.

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment

BackgroundGestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. ObjectivesWe aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. MethodsWe measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. ResultsPCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. ConclusionsPlacental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

Polychlorinated biphenyl serum levels in subjects with hepatocellular carcinoma as compared with the general population

Background. Polychlorinated biphenyls (PCBs) have been recognized as human carcinogens and cause liver cancer in animal experimental studies. However, no study investigated their association with hepatocellular carcinoma (HCC) so far. This study aimed to evaluate the serum PCB concentration in HCC patients and in healthy subjects of the general population living in Brescia, North Italy, a highly industrialized area with heavy PCB environmental pollution due to the presence of a PCB producing factory.
 Methods. Lipid-adjusted PCB concentrations, computed as the sum of 24 congeners, were measured in the serum of 101 HCC patients and in 101 healthy subjects of the same age and gender.
 Results. Hepatitis B and C virus infection and history of heavy alcohol intake were found, alone and combined, in 87% of HCC patients. No difference was found in PCB serum concentration of HCC patients with and without, and according to, the major risk factors for liver disease. No significant difference was observed in serum total PCB concentration between HCC patients (median: 1081; range: 287.0-3182.0 ng/g lipid) and healthy subjects (median: 1199.3; range: 225.7-22825 ng/g lipid). PCB congeners 118, 138, 153, 156, 180 and 194 were the only ones found over the detection limit in at least 30% of HCC patients. The serum level of PCB 118, but not that of other congeners, was higher in HCC patients than in healthy subjects.
 Conclusion. These findings do not support the hypothesis that PCBs play an important role in HCC development, although a contribution by some specific congeners cannot be ruled out

Associations of concurrent PCB and PBDE serum concentrations with executive functioning in adolescents

Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental chemicals that have long half-lives. Humans are exposed to PCBs and PBDEs mainly through diet, and relative to other populations, those who consume sport-caught fish generally have elevated body burdens. Numerous studies have found associations between prenatal exposure to these chemicals and neurodevelopmental deficits, but there are few studies assessing the impact of exposure during adolescence, a period of rapid development of executive functions. We assessed executive functions in adolescents at risk for exposure to PCBs and PBDEs through consumption of fish from the Lower Fox River and other contaminated waters in northeastern Wisconsin. Between 2007 and 2012, a sample of 115 12–18-year-old children was recruited from households in the Green Bay, WI area in which at least one parent held a WI fishing license. We assessed associations of total PCBs and total PBDEs, as well as the predominant individual congeners (PBDE 47 and 153; PCB 138/163, 153 and 180) with performance on four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intradimensional/Extradimensional Set-Shifting (ID/ED) which assesses cognitive flexibility, Delayed Matching to Sample (DMS) which assesses visual recognition memory, Spatial Working Memory (SWM), and Stockings of Cambridge (SOC) which assess planning and working memory. In addition to the exposure and outcome variables, multivariable regression models included the child's age, sex and IQ score as well as a sex by exposure interaction term. All of the children were non-Hispanic whites and most parents were married, employed, and had at least some college. After adjusting for serum lipids, the GM (GSD) for total PCBs (ng/g) was 30.83 (2.46), and the GM (GSD) for the predominant PCB congeners PCB 138/163, PCB 153, and PCB 180 were 4.60 (2.39), 5.43 (2.37), and 1.01 (2.71), respectively. The GM (GSD) for total PBDEs (ng/g) was 26.82 (3.30), and the GM (GSD) for the predominant PBDE congeners PBDE 47 and PBDE 153 were 16.64 (2.94) and 3.95 (3.43), respectively. For both chemicals, the primary finding of the negative binomial regression analyses was that higher blood serum concentrations were associated with poorer cognitive flexibility as measured on the ID/ED task. In particular, the PCB x sex interaction p-value was 0.08, and stratifying by sex demonstrated that males with higher blood serum total PCB concentrations (β = 2.20, 95% CL: 1.16, 4.16, p = 0.02) took more trials to complete the ID/ED task, while both males and females with higher total PBDE concentrations (β = 1.74, 95% CL: 1.25, 2.42, p = 0.001) took more total trials to complete the task. Higher serum total PCB concentrations were also associated with more errors on the DMS task (β = 1.15, 95% CL: 1.00, 1.31, p < 0.05). These findings suggest that exposure to PCBs or PBDEs during adolescence may be associated with impaired cognitive flexibility and that adolescent PCB exposure may be associated with visual recognition memory deficits.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013–2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and “Dana Dwek” Children’s Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4–6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes—allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence.

BackgroundChronic exposure to low-dose persistent organic pollutants (POPs) can induce mitochondrial dysfunction. This study evaluated the association between serum POP concentrations and oxygen consumption rate (OCR) as a marker of mitochondrial function in humans and in vitro cells.MethodsSerum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in 323 adults. The OCRs of platelets and peripheral blood mononuclear cells (PBMCs) were assessed in 20 mL of fresh blood using a Seahorse XF analyzer. Additionally, the in vitro effects of Arochlor-1254, β-hexachlorocyclohexane, and p,p′-dichlorodiphenyltrichloroethane at concentrations of 0.1 pM to 100 nM were evaluated in human platelets, human PBMCs, and Jurkat T-cells.ResultsThe association between serum POP concentrations and OCR differed depending on the cell type. As serum OCP concentrations increased, basal platelet OCR levels decreased significantly; according to the OCP quintiles of summary measure, they were 8.6, 9.6, 8.2, 8.0, and 7.1 pmol/min/μg (P trend=0.005). Notably, the basal PBMC OCR levels decreased remarkably as the serum PCB concentration increased. PBMC OCR levels were 46.5, 34.3, 29.1, 16.5, and 13.1 pmol/min/μg according to the PCB quintiles of summary measure (P trend <0.001), and this inverse association was consistently observed in all subgroups stratified by age, sex, obesity, type 2 diabetes mellitus, and hypertension, respectively. In vitro experimental studies have also demonstrated that chronic exposure to low-dose POPs could decrease OCR levels.ConclusionThe findings from human and in vitro studies suggest that chronic exposure to low-dose POPs can induce mitochondrial dysfunction by impairing oxidative phosphorylation.

PCBs in indoor air and human blood in Pittsfield, Massachusetts

Concentrations of polychlorinated biphenyls (PCBs) and three chlorinated pesticides were determined in serum from 21 residents of Pittsfield, MA and in the basement, living room and outdoor air of the 10 homes in which they lived. Median serum PCB levels were 4.2 ng/g, which are at least four times the average level in the US population, and consisted primarily of more highly chlorinated, persistent congeners. This reflects contamination with PCBs coming from the local General Electric facility. Median basement air concentration was 20.3 ng/m3, while the median living room air was 11.4 ng/m3 and median outdoor air concentration was 3.0 ng/m3. The PCB congeners detected in air were primarily low chlorinated (four and fewer) congeners, reflecting the greater volatility of PCBs with fewer chlorines. The congener pattern between basement and living room air showed a 95% correlation, while correlation with outdoor air was much less. While the congener pattern in air is very different from that of the PCB products used in Pittsfield (Aroclors 1254 and 1260), low chlorinated PCBs are detected in the vapor phase after air is blown across the commercial mixtures. The human serum samples did not show detectible levels of many of the congeners seen in the basement air samples, reflecting rapid metabolism of lower chlorinated PCBs by the human body. However, with continuous inhalation of indoor air, especially in the living room, the exposure to these non-persistent congeners may still have adverse health effects. Cellular studies of some of these non-persistent, low chlorinated congeners indicate that they are neurotoxic, mutagenic and cytotoxic. These results demonstrate the importance of consideration of inhalation of PCBs as a route of exposure, especially in indoor sites, and suggest that monitoring serum PCB concentration may not always provide a good measurement of exposure, especially to congeners that are relatively rapidly metabolized but have significant toxicity.

Persistent organic pollutants in pregnant women potentially affect child development and thyroid hormone status

BackgroundPotentially harmful effects of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) on prenatal development and the endocrine system have been controversially discussed.MethodsWorking with a German cohort of 324 pregnant women, we assessed POP levels and used robust linear regression models to determine potential associations between maternal POP concentrations and pre- and postnatal development in the children, as well as the thyroid hormone status of the mother and child.ResultsMaternal p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and most measured PCBs positively correlated with postnatal weight gain. We detected no correlation between newborn birth weight and head circumference, respectively, and maternal PCB and p,p′-DDE serum levels, while body length at birth was negatively associated with the maternal serum concentration of PCB 183. Maternal p,p′-DDE and nearly all PCB serum levels showed a negative correlation with maternal free triiodothyronine (FT3). p,p′-DDE and PCB 74 and 118 were negatively associated with maternal thyroid-stimulating hormone levels. In addition, we identified significant associations between maternal POP levels and thyroid hormone parameters of the child.ConclusionsThese results indicate that POP exposure likely affects different aspects of pre- and postnatal development and impacts the thyroid hormone status of both mother and child.ImpactPregnant women in a German cohort display a substantial accumulation of POPs.Body mass index and age influence maternal serum POP levels.Maternal POP levels show correlations with the child’s length at birth and weight gain, and FT3 levels in the mother and child.Our data provide additional evidence for the potentially harmful influence of POPs.Our data indicate that POPs influence pre- and postnatal development.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Quantification of PCB in the serum of patients with breast cancer and its correlation in the soil of their place of residence.

Polychlorinated biphenyls (PCB) are highly lipophilic compounds and persistent in the environment, which converts them into substances able to accumulate in the food chain and persistent contaminants in soil, air, and water. Our objective was to determine the concentration of PCB in the serum of patients with Breast Cancer (BC) and its correlation with PCB in the soil of their homes in different areas of the Comarca Lagunera region in Mexico. With non-probabilistic sampling, we selected the homes of subjects with and without BC. In 20% of cases, the diagnosis was carried out 25 and 39 years of age. Sample analysis was by Gas-mass Chromatography (GC). The concentration of the different congeners was similar between the samples of household soil in cases and controls, with a sole exception with marginal significance (p=0.056), that is, congener 52, was greater in the cases. The highest concentrations found in soil in the study were for congeners 118 and 138. The highest risk found for BC was congener 195; however, it was not statistically significant, similar to the other congener quantified in soil. The correlation analysis between PCB serum concentrations and that of the soil exhibited a low concentration, the highest being for congener 101. The concentrations in serum of the 13 congener were significantly greater between cases and controls. No risk association was found among the individual concentrations of the 41 congeners’ PCB or among total PCB neither in soil nor with BC.

Type II diabetes status, adipokines, and dioxin-like compounds in the Anniston Community Health Survey II

Background/Aim: A polychlorinated biphenyl (PCB) production facility operated in Anniston, AL for several decades. Serum PCB concentrations were found to be about 3 times higher than the general U.S. population, and the Anniston Community Health Survey (ACHS 2005-07) found significant associations between PCBs and type II diabetes (T2D) prevalence. We also noted an inverse relationship between insulin and dioxin-like compounds in a subset of participants where the novel liver damage biomarker – cytokeratin 18 (CK-18) indicated non-alcoholic toxicant-associated steatohepatitis (TASH). Using data on serum concentration of dioxin-like compounds collected in the 2014 follow-up study (ACHS II), we investigated the association between dioxin-like compounds, insulin, measured cytokines, and adipokines as related to T2D status. Methods: T2D status was defined as previous physician diagnosis, measured glucose &gt;125 mg/dL, or being on any glycemic medication; 135 (39.9%) of 338 participants were classified as diabetic. Adipokines were measured on HADK2MAG-61K and HADK1MAG-61K bead arrays (EMD Millipore, Billerica, MA). The polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF), and non-ortho PCBs were measured using high-resolution gas chromatography/high-resolution mass spectrometry and expressed as dioxin toxic equivalents (TEQs, pg/g lipid). Linear regression models adjusted for age, sex, ethnicity, BMI, family history of diabetes, and smoking status.Results/Conclusion: We found significant associations between total dioxin concentration and insulin, leptin, and adiponectin for the total 338 participants. For insulin and leptin, this was primarily driven by PCDD/PCDF TEQ in those with diabetes (β=-0.31, p-value 0.034; β=-0.010, p-value 0.003). For adiponectin, these associations were stronger in those without diabetes (β=0.27, p-value 0.017). Participants with TASH saw a similar inverse relationship between PCDD/PCDF and insulin, and those with both diabetes and TASH had the largest measure of effect (β=-1.08, p-value 0.01). These findings suggest that these chemicals may affect concentrations of compounds regulating glucose levels as well as lipid metabolism and energy balance.

Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Thyroid Cancer in Women

Background: Both polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) have been associated with thyroid hormone disruption, but their relationship to thyroid cancer is not known. Methods: We investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010-2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, and body mass index. Sub-analyses included stratification by tumor size (&lt;=1 cm and &gt;1 cm) and birth cohort (born before or in 1960 and born after 1960). We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with exposures to multiple PCB/OCPs. Results: No PCB/OCPs were positively associated with PTC risk in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the younger birth cohort based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. Conclusions: Our results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC risk, but some associations in the younger birth cohort suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Exposure to polychlorinated biphenyls and organochlorine pesticides and thyroid cancer in connecticut women

BackgroundThyroid cancer incidence has increased substantially over the past decades, and environmental risk factors have been suggested to play a role. Polychlorinated biphenyls (PCB) and organochlorine pesticides (OCP) are established thyroid hormone disruptors, but their relationship to thyroid cancer is not known. MethodsWe investigated the relationship between serum PCB and OCP concentrations and papillary thyroid cancer (PTC) in 250 incident female PTC cases and 250 female controls frequency-matched on age, all residing in Connecticut. Interviews and serum samples were collected from 2010 to 2013. Samples were analyzed for 32 different chemicals using gas chromatography with isotope dilution high resolution mass spectrometry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using single pollutant logistic regression models for concentrations (per interquartile range) of individual PCB/OCP and summed groups of structurally or biologically similar PCB/OCP, adjusted for education, family history of cancer, alcohol consumption, age, and body mass index. Sub-analyses included stratification by tumor size (≤ and >1 cm) and birth before or during peak PCB production (born in 1960 or earlier and born after 1960), as exposures during early life may be important. We also applied three multi-pollutant approaches (standard multi-pollutant regression, hierarchical Bayesian modeling, principal components regression analysis) to investigate associations with co-exposures to multiple PCB/OCPs. ResultsNo PCB/OCPs were positively associated with PTC in primary analyses. Statistically significant associations were observed for 9 of the 32 chemicals and 3 summed groups of similar chemicals in the those born during peak production based on single-pollutant models. Multi-pollutant analyses suggested null associations overall. ConclusionsOur results using single and multi-pollutant modeling do not generally support an association between PCB or OCP exposure and PTC, but some associations in those born during peak production suggest that additional investigation into early-life exposures and subsequent thyroid cancer risk may be warranted.

Cardiovascular Effects of Polychlorinated Biphenyls and Their Major Metabolites.

Background:Xenobiotic metabolism is complex, and accounting for bioactivation and detoxification processes of chemicals remains among the most challenging aspects for decision making with in vitro new approach methods data.Objectives:Considering the physiological relevance of human organotypic culture models and their utility for high-throughput screening, we hypothesized that multidimensional chemical-biological profiling of chemicals and their major metabolites is a sensible alternative for the toxicological characterization of parent molecules vs. metabolites in vitro.Methods:In this study, we tested 25 polychlorinated biphenyls (PCBs) [PCB 3, 11, 52, 126, 136, and 153 and their relevant metabolites (hydroxylated, methoxylated, sulfated, and quinone)] in concentration–response () for effects in human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) and endothelial cells (ECs) (iPSC-derived and HUVECs). Functional phenotypic end points included effects on beating parameters and intracellular flux in CMs and inhibition of tubulogenesis in ECs. High-content imaging was used to evaluate cytotoxicity, mitochondrial integrity, and oxidative stress.Results:Data integration of a total of 19 physicochemical descriptors and 36 in vitro phenotypes revealed that chlorination status and metabolite class are strong predictors of the in vitro cardiovascular effects of PCBs. Oxidation of PCBs, especially to di-hydroxylated and quinone metabolites, was associated with the most pronounced effects, whereas sulfation and methoxylation of PCBs resulted in diminished bioactivity.Discussion:Risk characterization analysis showed that although in vitro derived effective concentrations exceeded the levels measured in the general population, risks cannot be ruled out due to the potential for population variability in susceptibility and the need to fill data gaps using read-across approaches. This study demonstrated a strategy for how in vitro data can be used to characterize human health risks from PCBs and their metabolites. https://doi.org/10.1289/EHP7030

Prediagnostic serum polychlorinated biphenyl concentrations and primary liver cancer: A case-control study nested within two prospective cohorts

BackgroundPolychlorinated 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. MethodsThis 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. ResultsConcentrations 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, ORtertile 3vs1 = 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. DiscussionWe 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.

Association Between Leukocyte Telomere Length and Serum Concentrations of PCBs and Organochlorine Pesticides.

Exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) through food, water, and air occurred during the life, which may change telomere length (TL) in peripheral blood leukocytes. The present study was designed to investigate the association between TL and serum levels of PCBs and OCPs in Tehran male's population. Whole blood samples were randomly taken from 300 adult males, aged between 25 and 40years. TL was determined by real-time PCR to measure the number of the telomere (T) repeats to the number of a single-copy gene (S). We applied the multivariate linear regression model to compare the effect of each lipid adjusted serum levels of PCBs and OCPs congener on the TL, with adjustment for age, body mass index, education, smoking, and food patterns. Each doubling of the nondioxin-like PCBs, dioxin-like PCBs, and OCPs levels were associated with 1.9% [95% confidence interval (CI) - 0.70 to 5.40%], 2.5% (95% CI 0.30-8.3%), and - 2.4% (95% CI - 0.70 to - 6.2%) variation in the TL, respectively. The percent difference in the TL with exposure to nondioxin-like PCBs, dioxin-like PCBs, and OCPs for participants with older than age 37years were 6.45% (95% CI 2.81-16.50%), 4.52% (95% CI 1.60-10.54%), and - 7.44% (95% CI - 1.55 to - 15.51%), respectively. Exposures to nondioxin-like PCBs (except for PCB 28 and 52) with high chlorine in structure and dioxin-like PCBs were related to longer TLs. Conversely, serum levels of OCPs can be associated with oxidative stress and systemic inflammation that lead to telomere shortening.

Polychlorinated biphenyls (PCBs) and risk of hypertension: A population-based cohort study in a North Italian highly polluted area

This study aimed to assess the longitudinal association between PCB exposure and the subsequent occurrence of hypertension in a highly polluted area. The study subjects had at least one PCB serum measurement between 2003 and 2014 and were followed up to the end of 2017. Hypertension cases were obtained from the Brescia Health Protection Agency database. Risk ratios of hypertension for total PCBs, high-, middle- and low-chlorinated groups and some common congeners were estimated using Poisson regression models. 1031 subjects were included (43.4% males, mean age 45.3 years). 229 subjects developed hypertension during the follow-up. Total PCBs, middle- and high-chlorinated PCBs, and particularly PCB congeners 138, 153 and 180 were associated with an about 2-fold increased risk of hypertension comparing the third with first tertile of distribution. After lipid-standardization of PCB serum values, the excess risk showed only a slight attenuation. A dose-response linear relationship of the risk of hypertension by PCB serum concentrations as continuous variables was also observed. The PCBs-hypertension association was stronger in overweight/obese subjects than those with normal body mass index. In this prospective cohort study the serum levels of total and middle to high chlorinated (≥6 Cl) PCBs were associated with an increased risk of hypertension, particularly among overweight/obese subjects.

Serum concentrations of DDE, PCBs, and other persistent organic pollutants and mammographic breast density in Triana, Alabama, a highly exposed population

IntroductionAlthough some persistent organic pollutants (POPs) are considered human carcinogens, results from studies evaluating exposures and breast cancer risk have been inconsistent, potentially related to varying ages at exposure. Additionally, few studies evaluated the association between POPs exposure and mammographic breast density (MBD), an intermediate biomarker of breast cancer risk. We carried out a cross-sectional study to investigate associations between serum POPs concentrations and MBD measured in 1998 in female residents of Triana, Alabama, in a predominately African American population with high POPs exposures, particularly to p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane). MethodsWe measured lipid-adjusted serum concentrations (ng/g lipid) of p,p'-DDT and its main metabolite p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), polychlorinated biphenyls (PCBs), β-hexachlorocyclohexane (β-HCCH), heptachlor epoxide, oxychlordane, trans-nonachlor, mirex, and aldrin for each woman in our study (n = 210). We also measured two MBD metrics, percent MBD (%MBD) and area of MBD (aMBD). Using adjusted Spearman correlation coefficients (rs) we evaluated correlations between %MBD and aMBD with individual POPs in the overall population and by age group (19–40, 41–54, and 55–91 years) and also estimated adjusted mean measures of MBD with 95% confidence intervals across tertiles of analytes using generalized linear models (GLM). We calculated p-values for multiplicative interaction by age group using GLM. Additional analyses excluded women with current hormone replacement therapy (HRT) use and evaluated early-life exposure (prior to age 18) during the heaviest contamination period in Triana (1947–90). ResultsAmong all women, we found no correlation between p,p’-DDE and %MBD, but after age stratification and exclusion of HRT users, there was a suggestion of a difference by age group, with younger women having a weak positive correlation (rs = 0.12, p = 0.37) and older women having a weak negative correlation (rs = −0.12, p = 0.43); pinteraction = 0.06. In contrast, PCBs were weakly positively correlated with %MBD among all women, with the correlation magnitudes increasing after excluding current HRT users (rs-total PCBs = 0.17, p = 0.03). After age stratification and exclusion of HRT users, correlations for PCBs were higher among younger and middle-age women, with only a handful of these correlations being statistically significant. For β-HCCH, the strongest finding was a negative correlation among older women (rs = −0.26, p = 0.07). Correlations were positive predominantly in the younger age group for heptachlor epoxide (rs = 0.27, p = 0.04), oxychlordane (rs = 0.35, p = 0.006), and trans-nonachlor (rs = 0.37, p = 0.003), and largely null for the middle and older age groups; pinteraction range: 0.03–0.05. Similar patterns were found in GLM analyses using tertiles of exposure and aMBD as the metric for MBD. Women exposed during the heaviest chemical contamination period in Triana prior to age 18 had positive correlations between %MBD and PCBs, heptachlor epoxide, mirex, oxychlordane, and trans-nonachlor. ConclusionsIn this population, despite high exposures to p,p’-DDT and thus high serum concentrations of its main metabolite, p,p’-DDE, we did not find strong evidence of a positive association with MBD. In fact, there was some evidence of a negative association among older women for p,p’-DDE; a similar pattern was found for β-HCCH. However, younger women with higher serum levels of PCBs, heptachlor epoxide, oxychlordane, and trans-nonachlor, who were likely exposed in early life, had higher MBD. These findings should be replicated in larger studies.

Exploring the associations of serum concentrations of PCBs, PCDDs, and PCDFs with walking speed in the U.S. general population: Beyond standard linear models

Studies have shown that persistent organic pollutants (POPs) can have various health effects. However, little is known about the effects of multiple chemicals with possible common sources of exposure on walking speed, a proxy index reflecting lower limb neuromuscular function and physical function. We simultaneously applied multiple linear and nonlinear statistical models to explore the complex exposure-response relationship between a mixture of 22 selected POPs and walking speed. A total of 14 polychlorinated biphenyls (PCBs), 3 polychlorinated dibenzo-p-dioxins (PCDDs), and 5 polychlorinated dibenzofurans (PCDFs) were measured in the serum of participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002. Walking speed was measured during a physical examination. Linear regression (LR), least absolute shrinkage and selection operator (LASSO), and group LASSO were used to evaluate the linearity of mixtures, while restricted cubic spline (RCS) regression, random forest (RF), and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Potential confounders were adjusted in the above models. A total of 436 subjects were included in our final analysis. The results of the LR model did not identify any POP exposure that was significantly associated with walking speed. The LASSO results revealed an inverse association of one PCDD congener and two PCDF congeners with walking speed, while the group LASSO analysis identified PCDFs at the exposure level and at the group level. In the RCS analysis, two PCB congeners presented significant overall associations with walking speed. The PCB congener PCB194 showed statistically significant effects on the outcome (P = 0.01) when a permutation-based RF was used. The BKMR analysis suggested that PCBs and PCDFs (probabilities = 0.887 and 0.909, respectively) are potentially associated with walking speed. Complex statistical models, such as RCS regression, RF and BKMR models, can detect the nonlinear and nonadditive relationships between PCBs and walking speed, while LASSO and group LASSO can identify only the linear relationships between PCDFs and walking speed. Fully considering the influence of collinearity in each method during modelling can increase the comprehensiveness and reliability of conclusions in studies of multiple chemicals.