Plasma Persistent Organic Pollutants Research Articles

Construction, evaluation, and AOP framework-based application of the EpPRS as a genetic surrogate for assessing environmental pollutants

BackgroundEnvironmental pollutant measurement is essential for accurate health risk assessment. However, the detection of humans’ internal exposure to pollutants is cost-intensive and consumes time and energy. Polygenic risk scores (PRSs) have been widely applied in genetic studies of complex trait diseases. It is important to construct a genetically relevant environmental surrogate for pollutant exposure and to explore its utility for disease prediction and risk assessment. ObjectivesThis study enrolled 714 individuals with complete genomic data and exposomic data on 22 plasma-persistent organic pollutants (POPs). MethodsWe first conducted 22 POP genome-wide association studies (GWAS) and constructed the corresponding environmental pollutant-based PRS (EpPRS) by clumping and P value thresholding (C + T), lassosum, and PRS-CS methods. The best-fit EpPRS was chosen by its regression R2. An adverse outcome pathway (AOP) framework was developed to assess the effects of contaminants on candidate diseases. Furthermore, Mendelian randomization (MR) analysis was performed to explore the causal association between POPs and cancer risk. ResultsThe C + T method produced the best-performing EpPRSs for 7 PCBs and 4 PBDEs. EpPRSs replicated the correlations of environmental exposure measurements based on consistent patterns. The diagnostic performance of type 2 diabetes mellitus (T2DM) PRS was improved by the combined model of T2DM-EpPRS of PCB126/BDE153. Finally, the AKT1-mediated AOP framework illustrated that PCB126 and BDE153 may increase the risk of T2DM by decreasing AKT1 phosphorylation through the cGMP-PKG pathway and promoting abnormal glucose homeostasis. MR analysis showed that digestive system tumors, such as colorectal cancer and biliary tract cancer, are more sensitive to POP exposure. ConclusionsEpPRSs can serve as a proxy for assessing pollutant internal exposure. The application of the EpPRS to disease risk assessment can reveal the toxic pathway and mode of action linking exposure and disease in detail, providing a basis for the development of environmental pollutant control strategies.

Biomarkers of Oxidative Stress and Persistent Organic Pollutants in Plasma and Eggs of Chelonia mydas Nesting in the Southern Gulf of Mexico

The major nesting sites for the endangered green turtle (Chelonia mydas) are in Campeche, Mexico: Carmen, Isla Aguada, and Sabancuy. Although they are in a natural reserve, these nesting sites are threatened by agricultural activities and oil extraction. This study aimed to determine the presence and concentration of organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons (PAHs) in plasma and eggs and to assess the antioxidant response in plasma of nesting C. mydas from the southern Gulf of Mexico. Using censored statistics allowed us to do a realistic calculation incorporating the presence of non-detects in the analysis. A few contaminants (α+β+γ-HCH, trans-chlordane, 4,4′-DDE, 4,4′-DDT, methoxychlor, naphthalene, acenaphthylene, 2-Bromo naphthalene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, and dibenz[a,h]anthracene) were detected in plasma and their corresponding eggs, but correlations were not-significant. Spatial differences in concentrations of persistent organic pollutants (POPs) among nesting sites may reflect differences in foraging areas. Approximately 30% of the POPs in plasma and 60% of the POPs in eggs correlated with the biomarkers of oxidative stress. Detection of POPs in C. mydas indicated that plasma and eggs are suitable matrices to assess POPs concentrations.

Relationships of First-Trimester Body Mass Index and Weight Change with Persistent Organic Pollutant Concentrations in Pregnant Canadian Individuals

Persistent organic pollutants (POPs) are toxic chemicals with demonstrable effects on pregnancy and neonatal outcomes. The associations of early pregnancy body mass index (BMI) and antenatal weight changes with circulating POP concentrations are poorly understood in the Canadian context. The aim of this study was to explore the relationship between maternal BMI in the first trimester, weight change from pre-pregnancy to 6–13 weeks of pregnancy, and first-trimester plasma POP concentrations among Canadian pregnant women. We analyzed data collected as part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study and evaluated POP concentrations based on first-trimester BMI and early gestational weight change categories. We tested for overall differences using Kruskal-Wallis tests. The associations between first-trimester maternal BMI, weight change, and plasma concentrations of 41 POPs were evaluated using censored regression models. After controlling for potential confounders, first-trimester plasma levels of multiple POPs differed significantly across BMI categories, with the highest concentrations in underweight/normal-weight individuals and the lowest in class III obese individuals. Our findings provide preliminary evidence of higher circulating POP levels in individuals with obesity and align with previous findings of an inverse relationship between circulating POP concentrations and BMI in pregnancy. Future studies should prospectively evaluate the interplay between weight change and POP concentrations throughout pregnancy to inform gestational weight gain recommendations for pregnant individuals with obesity.

Chlorinated persistent organic pollutants in plasma and risk of cardiovascular disease: a prospective nested case-control study in two Swedish cohorts

BACKGROUND AND AIM: Cardiovascular toxic effects derived from high exposures to persistent organic pollutants (POPs) are well documented. Evidence in general population with low-dose and long-term exposures is limited. To analyze the association of chlorinated POP plasma levels, which include polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), with risk of composite cardiovascular disease (CVD) and separate ischemic stroke and myocardial infarction (MI) in a general Swedish population. METHODS: Within the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Old (60YO), we conducted a population-based nested case-control study with first incident stroke (n=708) and MI (n=820) ascertained via linkage. Controls were matched by age, sex, and sampling date. Baseline blood sampling occurred during 2003-2009 and 1997-1999 with follow-up through 2017 and 2014 for the SMC-C and the 60YO, respectively. POP levels were evaluated as cohort-specific tertiles based on controls. Multivariable adjusted logistic regressions were conducted to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS:Mean age was 72 (±7) years in SMC-C and 61 (±0.1) years in 60YO. The individual chlorinated POPs found in highest concentrations (ng/ml) were by far PCB-153 [1016 (721–1365) in controls and 1072 (816–1366) in cases] and pp-DDE [1889 (1057–3240) in controls and 2348 (1296–3724) in cases]. Sum of standardized chlorinated POP levels associated with composite CVD, OR (95% CI) 1.40 (1.03-1.92), and with stroke 1.62 (1.01-2.59) but not with MI, 1.24 (0.77-1.98), comparing extreme tertiles. These associations were mainly driven by OCPs, which associated with composite CVD 1.45 (1.07-1.99), and with MI 1.91 (1.16-1.37), but less clear with stroke 1.52 (0.92-2.50). CONCLUSIONS:These findings indicate that high levels of OCPs in human blood might increase the risk of both stroke and MI, while the cardiovascular risk associated with PCBs was less clear. More evidence from studies using biological samples is needed. KEYWORDS: Chlorinated persistent organic pollutants, endocrine disrupting chemicals, prospective nested case-control study, Swedish cohorts, cardiovascular disease

Persistent organic pollutants in plasma and stable isotopes in red blood cells of Caretta caretta, Chelonia mydas and Lepidochelys olivacea sea turtles that nest in Brazil

Studies of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), in sea turtles are reported, but there are still spatial data gaps worldwide. POP contamination of live female blood plasma from Caretta caretta (n = 28), Chelonia mydas (n = 31) and Lepidochelys olivacea (n = 19), which nest in Brazil and feed along the South Atlantic Ocean, was investigated. Carbon and nitrogen stable isotopes from red blood cells (RBC) were also evaluated to obtain information about trophic ecology. C. caretta had the highest POP concentrations, followed by L. olivacea and C. mydas. PCBs predominated in all species, and the major OCPs were the DDTs (dichlorodiphenyltrichloroethane and derivatives) and Lindane. POPs and stable isotopes revealed intra- and interspecific variations, which reflect the high plasticity in the use of habitat and food resources, making individuals within the same population susceptible to different exposures to pollutants.

Maternal plasma concentrations of persistent organic pollutants and placental DNA methylation

Background/Aim: Prenatal maternal plasma persistent organic pollutants (POPs) concentrations have been associated with neonatal outcomes; however, the underlying mechanisms remain unknown. Placental epigenetics may be involved but no prior epigenome-wide studies have investigated such mechanisms. We studied the association between POPs in early pregnancy and epigenome-wide placental DNA methylation among 262 pregnant women from the NICHD Fetal Growth Studies. Methods: Epigenome-wide analyses using robust adjusted linear regression models were performed for each POP with more than 80% plasma concentration above the limit of quantification; including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p’-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180) and 6 poly-and-perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Genes annotated to the differentially methylated CpGs were tested for enrichment of molecular pathways. Results: At 5% false discovery rate, POPs concentrations were associated with a total of 193 differentially methylated CpGs in the placenta (nominal p-values ranging from 8.37x10-21 to 1.52x10-7). Among them, 21 CpGs were significantly correlated with placental expression of 18 unique genes (p-values<0.05). Notably, PFUnDA was associated with higher methylation of 3 CpGs (cg13996963, cg12089439, cg18145877) annotated to TUSC3. Higher methylation at the three CpGs was correlated with decreased expression of TUSC3 in placenta; and decreased expression of TUSC3 was correlated with smaller birth length. Pathway analysis found that genes annotated to CpGs differentially methylated with PBDE 47 were enriched in birthweight (p-value = 2.06x10-5) and differentiation of embryonic cells (p-value = 2.25x10-5), while genes annotated to CpGs associated with PFASs were enriched in brain size (p-value = 4.09x10-4) and morphology (p-value = 7.29x10-3). Conclusions: The findings give insight into the potential for placental DNA methylation and gene expression mechanism to be involved in the prenatal toxicity of POPs and their associations with fetal growth outcomes.

Association of Maternal Exposure to Persistent Organic Pollutants in Early Pregnancy With Fetal Growth

Prenatal exposure to persistent organic pollutants (POPs) has been associated with birth size, but data on fetal growth and among racially/ethnically diverse pregnant women remain scarce. To assess the association between maternal plasma POPs in early pregnancy and fetal growth and by infant sex and maternal race/ethnicity. This cohort study used the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, which recruited nonobese, low-risk pregnant women before 14 weeks' gestation between July 1, 2009, and January 31, 2013, in 12 community-based clinics throughout the United States. Participants self-identified their race/ethnicity, self-reported their behavioral risk factors, and were followed up throughout their pregnancy. Data were analyzed from July 31, 2018, to June 3, 2019. Levels of 76 POPs in early gestation plasma were measured: 11 perfluoroalkyl and polyfluoroalkyl substances, 1 polybrominated biphenyl, 9 polybrominated diphenyl ethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 organochlorine pesticides (OCPs). The bayesian kernel machine regression method was used to examine chemical class mixtures, and generalized additive mixed model was used to analyze individual chemicals. Fourteen fetal biometrics were measured, including head circumference, abdominal circumference, and femur length, within 5 ultrasonography appointments. A total of 2284 low-risk pregnant women were included: 606 women (26.5%) self-identified as white with a mean (SD) age of 30.3 (4.4) years, 589 (25.8%) as black with a mean (SD) age of 25.5 (5.5) years, 635 (27.8%) as Hispanic with a mean (SD) age of 27.1 (5.5) years, and 454 (19.9%) as Asian with a mean (SD) age of 30.5 (4.5) years. A comparison between the 75th and 25th percentile of exposure revealed that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% CI, -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2 mm) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. Higher exposure to the PBDE mixture was associated with reduced abdominal circumference (-2.4 mm; 95% CI, -4.0 to -0.5 mm) and femur length (-0.5 mm; 95% CI, -1.0 to -0.1 mm), and the dioxin-like PCB mixture was associated with reduced head circumference (-6.4 mm; 95% CI, -8.4 to -4.3 mm) and abdominal circumference (-2.4 mm; 95% CI, -3.9 to -0.8 mm). Associations with individual chemicals were less consistent. There were some interactions by fetal sex, although most of the results did not vary by maternal race/ethnicity. For example, oxychlordane (-0.98 mm; 95% CI, -1.60 to -0.36 mm; P for interaction <.001), trans-nonachlor (-0.31 mm; 95% CI, -0.54 to -0.08 mm; P for interaction = .005), and p,p'-dichlorodiphenyldichloroethylene (-0.19 mm; 95% CI, -0.22 to -0.09 mm; P for interaction = .006) were associated with shorter femur length among boys only. This study found that, among pregnant women with low POP levels, a mixture of OCPs was negatively associated with most fetal growth measures and that mixtures of PBDEs and dioxin-like PCBs were associated with reduced abdominal circumference. These findings suggested that, although exposures may be low, associations with fetal growth are apparent.

Joint Analysis of Metabolite Markers of Fish Intake and Persistent Organic Pollutants in Relation to Type 2 Diabetes Risk in Swedish Adults

There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish. The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults. In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression. We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ=0.37, P<0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P=0.07). This component mainly consisted of metabolites reflecting fatty fish intake. Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.

High plasma concentrations of organic pollutants negatively impact survival in amyotrophic lateral sclerosis

ObjectiveTo determine whether persistent organic pollutants (POP) affect amyotrophic lateral sclerosis (ALS) survival.MethodsALS participants seen at the University of Michigan (Ann Arbor, MI, USA) provided plasma samples for measurement of...

Predicting human plasma concentrations of persistent organic pollutants from dietary intake and socio-demographic information in the Norwegian Women and Cancer study

BackgroundConcentrations of persistent organic pollutants (POPs) in humans are influenced by a large number of factors including birth year, reproductive history and diet. Accordingly, information on dietary habits and socio-demographic variables may predict plasma concentrations of POPs, thus enabling studies on health effects in large epidemiological studies, without performing time consuming and expensive chemical analyses on entire cohorts. AimsTo develop and evaluate statistical models for predicting concentrations of POPs in participants of the Norwegian Women and Cancer (NOWAC) study, using questionnaire information and measured plasma POP concentrations. Materials and methodsInformation on estimated dietary intakes and socio-demographic variables from four different questionnaires (in 1991, 1994, 2004 and 2005) were obtained from participants in the NOWAC study. We measured POP concentrations in a total of 367 blood samples from 2005 and built multivariable linear regression models for p,p′-DDE, PCB-118, -138, -153, -180 and summed PCB concentrations in one subsample (N = 259) and evaluated the models in another subsample (N = 108). Measured and predicted values were compared using correlation coefficients and inter-method agreement was evaluated using weighted Cohen's κ for tertile categorization. ResultsMedian POP concentrations in the population ranged from 13 ng/g lipid to 162 ng/g lipid (lowest for PCB-118 and highest for p,p′-DDE). Common predictors for all POPs were birth year, breastfeeding and the weight-related variables (BMI or weight change), whereas influential dietary variables differed and were of varying importance. The predicted plasma concentrations were significantly correlated with the measured values (rs = 0.24, 0.33, 0.41, 0.50, 0.56, and 0.54 for p,p′-DDE, PCB-118, -138, 153, -180 and summed PCBs, respectively). Tertiles of predicted plasma concentrations displayed significant, but varying agreement with measured concentrations (Weighted Cohen's κ = 0.19, 0.22, 0.33, 0.42, 0.45, and 0.50 respectively). ConclusionPredicted plasma concentrations of certain PCBs showed good precision (Kw > 0.4) when compared to measured concentrations. Thus, the models can be used to classify NOWAC participants into high, medium and low PCB exposure groups.

A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction

The objective of this study was to develop and validate a 96-well plate solid phase extraction method for analysis of 23 lipophilic persistent organic pollutants (POPs) in low-volume plasma and serum samples which is applicable for biomonitoring and epidemiological studies. The analysis of selected markers for internal exposure: 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and polybrominated diphenylether 47 (BDE 47) was evaluated by comparing two SPE sorbents and GC-HRMS or GC–MS/MS detection. The final method extracted 23 POPs from 150 μL of serum and plasma using a 96-well extraction plate containing 60 mg Oasis HLB sorbent per well prior to GC-HRMS magnetic sector analysis. The extraction method was applied to 40 plasma samples collected for an epidemiological study. The recovery of selected POPs ranged from 31% to 63% (n = 48), and detection limits ranged from 2.2 to 45 pg/mL for PCBs, 4.2 to 167 pg/mL for OCPs, 7.8 pg/mL for OCDD and 6.1 pg/mL for BDE 47. This method showed good precision with relative standard deviations of selected POP concentrations in quality control samples (n = 48) ranging from 11% to 25%. The trueness was determined with standard reference material serum (n = 48) and the deviation from certified values ranged from 1 to 27%. Of the 23 POPs analyzed, 18 were detected in 43% to 100% of plasma samples collected for the epidemiological study. The method showed good robustness with low inter-well plate variation (11–31%) determined by twelve 96-well plate extractions, and can extract 96 samples, including quality controls and procedural blanks in 2–3 days. Comparison with GC–MS/MS analysis showed that similar concentrations (within 0.5% to 30%) of most POPs could be obtained with GC-APCI-MS/MS. Larger deviations were observed for PCB 194 (60%) and trans-nonachlor (43%). The developed method produces accurate concentrations of low-level marker POPs in plasma and serum, providing a suitable high-throughput sample preparation procedure for biomonitoring and epidemiological studies involving large sample size and limited sample volume. GC-HRMS was chosen over GC–MS/MS, however the latter showed promising results, and could be used as an alternative to GC-HRMS analysis for most POPs.

Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II

BackgroundExposure to persistent organic pollutants (POPs) may predispose to the development of type 2 diabetes (T2D), but prospective human evidence is scarce. ObjectivesWe investigated the association between plasma-POP concentrations in the late 1990s and incident T2D over 11 years of follow-up in the Nurses' Health Study II. DiscussionThree organochlorine pesticides and 20 polychlorinated biphenyls (PCBs) were measured in banked plasma from 793 case–control pairs of T2D. In a multiviarate-adjusted model, T2D ORs (95%CIs) comparing extreme POP tertiles (high vs. low) were 1.67 (1.24, 2.23; Ptrend < 0.001) for hexachlorobenzene (HCB), 3.62 (2.57, 5.11; Ptrend < 0.001) for β-hexachlorocyclohexane (β-HCH), 1.55 (1.13, 2.13; Ptrend = 0.05) for p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and 1.95 (1.42, 2.69; Ptrend < 0.001) for total dioxin-like PCBs (DL-PCBs) which included 5 mono-ortho congeners, PCB-105, 118, 156, 157, and 167. Adjustment for previous weight change and body mass index (BMI) at blood draw attenuated these associations, but that for DL-PCBs remained (OR[95% CI] = 1.78[1.14, 2.76]; Ptrend = 0.006). Age, breastfeeding history, previous weight change and BMI at blood draw were significant predictors of plasma POP concentrations. In addition, we found significant interactions of POPs and weight change before blood draw on T2D risk. ORs (95%CIs) of T2D comparing extreme (high vs. low) POP groups were 2.00 (1.02, 3.92; Ptrend = 0.01) for HCB, 2.69 (1.34, 5.40; Ptrend < 0.001) for β-HCH, and 2.41 (1.22, 4.77; Ptrend < 0.001) for DL-PCBs in the lowest weight gain group, whereas these values were 1.29 (0.73, 2.28; Ptrend = 0.46; Pinteraction = 0.04) for HCB, 1.41 (0.77, 2.60; Ptrend = 0.24; Pinteraction = 0.003) for β-HCH, and 0.90 (0.50, 1.63; Ptrend = 0.61; Pinteraction = 0.01) for DL-PCBs in the highest weight-gain group. ConclusionsOur findings suggest that elevated POP exposure may have diabetogenic potential. These data also highlight the impact of lifestyle factors, especially history of weight gain, on circulating POP concentrations and their associations with subsequent T2D risk.

Steroid hormones and persistent organic pollutants in plasma from North-eastern Atlantic pilot whales

Persistent organic pollutants (POPs) are known to have endocrine disruptive effects, interfering with endogenous steroid hormones. The present study examined nine steroid hormones and their relationships with the concentrations of selected POPs in pilot whales (Globicephala melas) from the Faroe Islands, NE Atlantic. The different steroids were detected in 15 to all of the 26 individuals. High concentrations of progesterone (83.3–211.7pmol/g) and pregnenolone (PRE; 4.68–5.69pmol/g) were found in three adult females indicating that they were pregnant or ovulating. High androgen concentrations in two of the males reflected that one was adult and that one (possibly) had reached puberty. In males a significant positive and strong correlation between body length and testosterone (TS) levels was identified. Furthermore, positive and significant correlations were found between 4-OH-CB107/4’-OH-CB108 and 17β-estradiol in males. In adult females significant positive correlations were identified between PRE and CB149 and t-nonachlor, between estrone and CB138, -149, -187 and p,p’-DDE, between androstenedione and CB187, and between TS and CB-99 and -153. Although relationships between the POPs and the steroid hormones reported herein are not evidence of cause-effect relationships, the positive correlations between steroids and POPs, particularly in females, suggest that POPs may have some endocrine disrupting effects on the steroid homeostasis in this species.

Sea ice-associated decline in body condition leads to increased concentrations of lipophilic pollutants in polar bears (Ursus maritimus) from Svalbard, Norway

Global climate changes are magnified in the Arctic and are having an especially dramatic effect on the spatial and temporal distribution and the thickness traits of sea ice. Decline of Arctic sea ice may lead to qualitative and/or quantitative changes in diet and reduced body condition (i.e. adipose tissue stores) of ice-associated apex predators such as polar bears (Ursus maritimus). This may further affect their tissue concentrations of lipophilic pollutants. We determined how variations in adipose tissue stores associated to both breeding status and spatial changes in sea ice conditions and diet influence concentrations and biotransformation of lipophilic persistent organic pollutants (POPs). We collected 112 blood and fat samples from female polar bears (Ursus maritimus) of different breeding status (alone, with cubs of the year, or with yearlings) during two seasons (April and September) in 2012 and 2013 at three locations of Svalbard, Norway, with contrasted sea ice conditions. We inferred diet from nitrogen and carbon stable isotope ratios in red blood cells and fatty acid composition in adipose tissue. Relative to diet, body condition, which was negatively related to sea ice extent at both temporal and spatial scales, was the most important predictor for concentrations of POPs in plasma and fat, whereas diet showed a minor influence. Additionally, fatter females were more efficient at biotransforming PCBs than were leaner ones. Breeding status influenced the concentrations of less lipophilic compounds such as β-hexachlorocyclohexane, which were lower in females with yearlings, probably due to excretion into milk and subsequent offloading to young. In conclusion, our results indicate that declining sea ice indirectly leads to increased concentrations of lipophilic pollutants in polar bears mediated through reduced feeding opportunities and declining body condition rather than changes in diet composition.

The Metabolically Healthy But Obese Phenotype Is Associated With Lower Plasma Levels of Persistent Organic Pollutants as Compared to the Metabolically Abnormal Obese Phenotype

Although obesity is strongly linked to insulin resistance and type 2 diabetes, a subset of obese individuals termed metabolically healthy but obese (MHO) appears relatively protected from the development of cardiometabolic complications. The origins of this metabolically healthy phenotype remain unclear. Recently, persistent organic pollutants (POPs) have emerged as potential endocrine disruptors. The aim of this study was to test the hypothesis that the MHO phenotype presents lower circulating levels of POPs as compared to the metabolically abnormal obese (MAO) phenotype. We conducted a cross-sectional study of 76 nondiabetic obese (body mass index ≥30 kg/m(2)) postmenopausal women. Plasma concentrations of 21 POPs as well as cardiometabolic risk factors were analyzed. For similar age, body mass index, and fat mass index, MHO women (n = 40) showed higher insulin sensitivity levels and a more favorable cardiometabolic profile than MAO women (n = 36), as evidenced by a 2-fold increase in glucose disposal rates measured by the hyperinsulinemic-euglycemic clamp (P = .001). Among 18 detectable pollutants measured, MAO women had higher plasma concentrations of 12 POPs (fold increase, 1.4-2.9; P < .001-.036). Logistic regression analyses showed that the prevalence of the MAO phenotype was significantly associated with higher levels of total dioxin- and non-dioxin-like polychlorinated biphenyls (odds ratio, 4.7; 95% confidence interval, 1.8-12.5; P = .002), as well as trans-nonachlor (odds ratio, 6.1; 95% CI, 2.2-16.4; P < .001). Our study demonstrates that the metabolically healthy and abnormal phenotypes have distinct plasma POP profiles.

Associations between plasma persistent organic pollutants and type II diabetes in Canadians: a nationally-representative, cross-sectional study.

Background: There is increasing evidence from epidemiological and toxicological studies that persistent organic pollutants (POPs) contribute to the pathogenesis of type II diabetes. Aims: To quantify the associations between plasma POPs and diabetes in cycle 1 (2007-2009) of the Canadian Health Measures Survey, a cross-sectional multistage sample representing 96% of Canadians. Methods: Our sample included 1669 participants aged 20 to 79. We used logistic regression with bootstrap resampling to analyze 19 POPs detectable in at least 60% of plasma samples. Diabetes was defined as any of self-reported doctor diagnosis, use of diabetic medication, fasting HbA1C &gt;=6.5% or fasting glucose &gt;=7.0 mmol/L. Results: The relative odds of diabetes (OR, 95% CI) for interquartile increases in log-transformed and lipid-normalized POPs after adjustment for BMI, waist-to-hip ratio (WHR), BMI-WHR interaction, daily leisure energy expenditure and age (sex was not a confounder) were 2.0 (1.2-3.3) for Arochlor 1260; 1.7 (1.1-2.9) for PCB 138; 2.1 (1.2-3.5) for PCB 153; 1.9 (1.0-3.4) for PCB 163; 1.9 (1.2-3.0) for PCB 170; 1.8 (1.2-2.8) for PCB 180; 1.7 (1.0-2.9) for PCB 187; 1.5 (1.1-2.1) for betahexachlorohexane; 1.4 (1.0-1.8) for hexachlorobenzene and 2.1 (1.0-4.6) for oxychlordane. Adjusted interquartile ORs with 2-sided p value &gt;0.05 were 1.6 (0.9-2.7) for PCB 118; 1.6 (1.0-2.6) for PCB 146; 1.6 (0.9-2.7) for PCB 156; 1.3 (0.9-1.9) for PCB 194; 1.4 (0.9-2.1) for PCB 201; 1.3 (0.9-1.9) for PCB 203; 1.5 (0.9-2.3) for pp-DDE; 1.9 (0.7-4.8) for transnonachlor; and 1.1 (0.8-1.5) for PBDE 47. Conclusions: Most POPs were positively associated with the odds of diabetes in this sample although some estimates had insufficient precision. Our results add to the weight of evidence that POPs contribute to the pathogenesis of type II diabetes.

Plasma concentrations of organohalogenated pollutants in predatory bird nestlings: Associations to growth rate and dietary tracers

The extent to which persistent organic pollutants (POPs) with different physicochemical properties originated from the food (dietary input) was assessed in raptor nestlings. Lipophilic polychlorinated biphenyl (PCB) 153, 1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB), and protein-bound perfluorooctane sulfonate (PFOS), were measured repeatedly in blood plasma of individual goshawk (Accipiter gentilis) and white-tailed eagle (Haliaeetus albicilla) nestlings, 1 to 3 wk after hatching and near fledging. Maternally derived POPs dilute as nestlings grow (growth dilution), and increasing plasma concentrations would indicate dietary input. First, plasma concentrations given no dietary input were estimated, and concentrations of p,p'-DDE, HCB, and notably PFOS were significantly higher than predicted from a growth-dilution scenario (approximately 1.5-fold to 2.5-fold higher; p < 0.001). In contrast, PCB 153 declined in both species, although concentrations were still higher than predicted in white-tailed eagle nestlings (p < 0.05). Second, the relationships between plasma POP concentrations and trophic position (δ(15) N) and dietary carbon source (δ(13) C) were analyzed, controlling for growth rate. Both δ(15) N and δ(13) C (measured in body feathers) were significantly associated to the accumulation of most POPs, except PFOS. In conclusion, pollutant data acquired in plasma of nestling raptors should be interpreted and further investigated in the light of individual feeding ecology, and the use of raptor nestlings as sentinels for POP monitoring could be optimized by correcting for different factors such as body condition, brood size, and age.

Circulating levels of persistent organic pollutants in relation to visceral and subcutaneous adipose tissue by abdominal MRI

We and others have shown relationships between circulating levels of persistent organic pollutants (POPs) and different measures of obesity in both cross-sectional and prospective studies. Since viscerally located fat seems to be the most harmful type, we investigated whether plasma POP levels were more closely related to visceral adipose tissue (VAT) than to subcutaneous adipose tissue (SAT). Thousand hundred and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study; 23 POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry. Abdominal magnetic resonance imaging, measuring VAT and SAT, respectively, was performed in a representative subsample of 287 subjects. The less chlorinated polychlorinated biphenyl (PCB) congeners (105 and 118), and the pesticides dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and trans-nonachlordane (TNC) were positively related to both VAT and SAT, whereas the more highly chlorinated PCBs (153, 156, 157, 169, 170, 180, 194, 206, and 209) were inversely related to both VAT and SAT. PCB189 was related to the VAT/SAT ratio in an inverted U-shaped manner (P = 0.0008). In conclusion, the results were in accordance with our previous studies using waist circumference and fat mass as obesity measure. However, the novel finding that PCB189 was related to the VAT/SAT ratio deserves further investigation since exposure to this PCB congener, which has previously been linked to diabetes development, might thereby play a role in the distribution of abdominal adipose tissue.

Persistent Organic Pollutants and Type 2 Diabetes: A Prospective Analysis in the Nurses’ Health Study and Meta-analysis

Background: Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies.Objectives: We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis.Methods: Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989–1990 and participated in two case–control studies in the Nurses’ Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results.Results: After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, ptrend = 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I2 = 21.4%, pheterogeneity = 0.28) and 1.70 (95% CI: 1.28, 2.27; I2 = 16.3%, pheterogeneity = 0.30) for HCB and total PCBs, respectively.Conclusions: These findings support an association between POP exposure and the risk of T2D.

Dysregulation of Cytokine Response in Canadian First Nations Communities: Is There an Association with Persistent Organic Pollutant Levels?

In vitro and animal studies report that some persistent organic pollutants (POPs) trigger the secretion of proinflammatory cytokines. Whether POP exposure is associated with a dysregulation of cytokine response remains to be investigated in humans. We studied the strength of association between plasma POP levels and circulating cytokines as immune activation markers. Plasma levels of fourteen POPs and thirteen cytokines were measured in 39 Caucasians from a comparator sample in Québec City (Canada) and 72 First Nations individuals from two northern communities of Ontario (Canada). Caucasians showed significantly higher levels of organochlorine insecticides (β-HCH, p,p′-DDE and HCB) compared to First Nations. Conversely, First Nations showed higher levels of Mirex, Aroclor 1260, PCB 153, PCB 170, PCB 180 and PCB 187 compared to Caucasians. While there was no difference in cytokine levels of IL-4, IL-6, IL-10 and IL-22 between groups, First Nations had significantly greater average levels of IFNγ, IL-1β, IL-2, IL-5, IL-8, IL-12p70, IL-17A, TNFα and TNFβ levels compared to Caucasians. Among candidate predictor variables (age, body mass index, insulin resistance and POP levels), high levels of PCBs were the only predictor accounting for a small but significant effect of observed variance (∼7%) in cytokine levels. Overall, a weak but significant association is detected between persistent organochlorine pollutant exposure and elevated cytokine levels. This finding augments the already existing information that environmental pollution is related to inflammation, a common feature of several metabolic disorders that are known to be especially prevalent in Canada's remote First Nations communities.