Predictors of PCP,OH-PCBs,PCBs and chlorinated pesticides in a general female Norwegian population

The aims of the current study were to assess plasma concentrations and predictors of halogenated phenolic compounds (HPCs), polychlorinated biphenyls (PCBs) and chlorinated pesticides in a representative group of postmenopausal Norwegian women (n = 311, mean age: 56 years). In addition to delivering a blood sample, the participants had also filled out a detailed questionnaire regarding their current health status, use of medication and dietary habits, etc. The association between a large number of dietary variables, lifestyle factors and plasma concentration of organic pollutants were investigated using multivariate statistics.Within the current study group, p,p′-DDE (median: 903 ng/L w.w.) and pentachlorophenol (PCP, median: 711 ng/L w.w.) were the dominating compounds on a wet weight basis and were present in considerable higher concentrations than the PCBs, the hydroxylated PCBs (OH-PCBs) and the remaining chlorinated pesticides. Of the PCBs, PCB 153 was detected in highest concentrations, whereas 4-OH-PCB187 was present in highest concentration of the selected OH-PCBs. The ratio of ΣOH-PCB to ΣPCB varied between 0.06 and 0.77 ng/L and were significantly lower in individuals with higher ΣPCB concentration. PCP did not co-vary with the other contaminants, indicating a different route of exposure. No clear food cluster was positively associated with PCP exposure; however intake of marine food was negatively linked to PCP concentration and age and being a non-smoker were positive predictors of PCP. The other investigated contaminants co-varied and were positively associated with age, plasma concentrations of marine derived omega-3 fatty acids and a traditional Norwegian fish and bread based diet. The difference in contaminant concentration between high, medium and low consumers of total marine food were however marginal for the dominating PCBs and chlorinated pesticides. The current results indicate however that marine food in itself could be a source of some of the OH-PCBs, regardless of their PCB precursors.As PCP is one of the dominating organic contaminants within the general female Norwegian population, future research on human concentrations, exposure routes and potential health effects of PCP is encouraged. Continued monitoring of human OH-PCB levels should also be performed as they could be present at levels almost as high as the PCBs and they are expected to be more toxic than their mother substances.     

Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men — A population-based prospective cohort study

BackgroundMajor food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored.Methods and resultsWe assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12 years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113 ng/day), men in the highest quintile (median 436 ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30–2.33; p-trend < 0.001) for total and 1.97 (95% CI 1.42–2.75; p-trend < 0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction = 0.03).ConclusionsExposure to PCBs via diet was associated with increased risk of myocardial infarction in men.     

Associations between blood persistent organic pollutants and 25-hydroxyvitamin D3 in pregnancy

Persistent organic pollutants (POPs) are suggested to contribute to lower vitamin D levels; however, studies in humans are scarce and have never focused on pregnancy, a susceptibility period for vitamin D deficiency. We investigated whether serum levels of POPs were associated with circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration in pregnancy. Cross-sectional associations of serum concentrations of eight POPs with plasma 25(OH)D3 concentration were analyzed in 2031 pregnant women participating in the Spanish population-based cohort INfancia y Medio Ambiente (INMA) Project. Serum concentrations of POPs were measured by gas chromatography and plasma 25(OH)D3 concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.3 ± 1.5 weeks of gestation). Multivariable regression models were performed to assess the relationship between blood concentrations of POPs and 25(OH)D3. An inverse linear relationship was found between serum concentration of PCB180 and circulating 25(OH)D3. Multivariate linear regression models showed higher PCB180 levels to be associated with lower 25(OH)D3 concentration: quartile Q4 vs. quartile Q1, coefficient = − 1.59, 95% CI − 3.27, 0.08, p trend = 0.060. A non-monotonic inverse relationship was found between the sum of predominant PCB congeners (PCB 180, 153 and 138) and 25(OH)D3 concentration: coefficient (95% CI) for quartile Q2 vs. Q1 [− 0.50 (− 1.94, 0.94)], quartile Q3 vs. Q1 [− 1.56 (− 3.11, − 0.02)] and quartile Q4 vs. Q1 [− 1.21 (− 2.80, 0.38)], p trend = 0.081. No significant associations were found between circulating 25(OH)D3 and serum levels of p,p′-DDE, p,p′-DDT, HCB, and ß-HCH. Our results suggest that the background exposure to PCBs may result in lower 25(OH)D3 concentration in pregnant women.     

Hydroxylated PCB metabolites (OH-PCBs) in archived serum from 1950–60s California mothers: A pilot study

We are studying participants selected from the Child Health and Development Studies (CHDS), a longitudinal birth cohort of over 20,000 California pregnancies between 1959 and 1967, for associations between maternal body burden of organochlorine contaminants and thyroid function. We designed a pilot study using 30 samples selected among samples with high and low PCB concentrations to evaluate the feasibility of measuring OH-PCBs in the larger study population. GC-ECD and GC-NCI/MS were used to determine PCBs and OH-PCBs as methyl derivatives, respectively. Maternal serum levels of Σ₁₁PCBs and Σ₈OH-PCB metabolites varied from 0.74 to 7.99 ng/mL wet wt. with a median of 3.05 ng/mL, and from 0.12 to 0.98 ng/mL wet wt. with a median of 0.39 ng/mL, respectively. Average concentrations of Σ₈OH-PCB metabolites in the high PCB group were significantly higher than those in the low PCB group (p < 0.05). The levels of OH-PCB metabolites were dependent on PCB levels (r = 0.58, p < 0.05) but approximately an order of magnitude lower (p < 0.05). The average ratio of Σ₈OH-PCBs to Σ₁₁PCBs was 0.14 ± 0.08. The primary metabolite was 4-OH-CB187 followed by 4-OH-CB107. Both of these metabolites interfere with the thyroid system in in vitro, animal, and human studies. OH-PCBs were detectable in all archived sera analyzed, supporting the feasibility to measure OH-PCB metabolites in the entire cohort.     

Persistent organic pollutants in the Scheldt estuary: Environmental distribution and bioaccumulation

Levels of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs) were determined in the sediment and several species (European flounder, Platichthys flesus; common sole, Solea solea; Chinese mitten crab, Eriocheir sinensis; shore crab, Carcinus maenas; brown shrimp, Crangon crangon; blue mussel, Mytilus edulis and bristle worms, Polychaeta) from 7 locations in the Scheldt estuary (SE, the Netherlands–Belgium). Overall POP levels in the sediment were low. The average PCB and PBDE concentrations were respectively 31.5 and 115 ng/g dry weight (dw). Highest sediment loads were measured in the vicinity of Antwerp (368 ng PCBs/g dw), a location with intense harbor and industrial activities. Pollution concentrations in the tissues of biota were species-specific. Blue mussels contained the highest lipid concentrations (2.74 ± 0.55%) and reached the highest contamination levels (from 287 to 1688 ng PCBs/g ww, from 2.09 to 12.4 ng PBDEs/g ww). Lowest tissue loads were measured in brown shrimp (from 3.27 to 39.9 ng PCBs/g ww, from 0.05 to 0.47 ng PBDEs/g ww). The PCB congener profile in most of the species was similar with the pattern found in the sediment. PCB 153 was the most abundant congener (16.5–25.7% in biota, 10.4% in sediment). In the sediment, the total amount of PBDEs consisted for more than 99% of BDE 209. Congener BDE 47 had the highest concentrations in all sampled species (38.5–70.1%). Sediment POP loadings and tissue concentrations were poorly correlated, indicating that a simple linear or non-linear relationship is insufficient to describe this relationship, possible caused by the complexity of the bioaccumulation processes and the variability in exposure. Because of the high PCB levels, regular consumption of fish and seafood, especially mussels, from the Scheldt estuary should be avoided.     

Historical intake and elimination of polychlorinated biphenyls and organochlorine pesticides by the Australian population reconstructed from biomonitoring data

Quantifying the competing rates of intake and elimination of persistent organic pollutants (POPs) in the human body is necessary to understand the levels and trends of POPs at a population level. In this paper we reconstruct the historical intake and elimination of ten polychlorinated biphenyls (PCBs) and five organochlorine pesticides (OCPs) from Australian biomonitoring data by fitting a population-level pharmacokinetic (PK) model. Our analysis exploits two sets of cross-sectional biomonitoring data for PCBs and OCPs in pooled blood serum samples from the Australian population that were collected in 2003 and 2009. The modeled adult reference intakes in 1975 for PCB congeners ranged from 0.89 to 24.5 ng/kg bw/day, lower than the daily intakes of OCPs ranging from 73 to 970 ng/kg bw/day. Modeled intake rates are declining with half-times from 1.1 to 1.3 years for PCB congeners and 0.83 to 0.97 years for OCPs. The shortest modeled intrinsic human elimination half-life among the compounds studied here is 6.4 years for hexachlorobenzene, and the longest is 30 years for PCB-74. Our results indicate that it is feasible to reconstruct intakes and to estimate intrinsic human elimination half-lives using the population-level PK model and biomonitoring data only. Our modeled intrinsic human elimination half-lives are in good agreement with values from a similar study carried out for the population of the United Kingdom, and are generally longer than reported values from other industrialized countries in the Northern Hemisphere.     

Distribution of persistent organic pollutants in two different fat compartments from obese individuals

There are only few studies defining persistent organic pollutant (POP) concentrations in various fat compartments from living obese individuals. The present study has therefore determined the concentrations of various classes of organohalogenated compounds, such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in visceral fat (VF: n = 52) and subcutaneous abdominal fat (SF: n = 52) samples collected in 2010–2012 from obese individuals in Belgium. Organohalogen compounds were detected in all fat samples in the decreasing order of their concentrations: PCBs > DDTs > HCHs > CHLs > HCB > HBCDs > PBDEs, suggesting that Belgians have been widely exposed to these contaminants. The levels and the patterns of POP distribution in VF and SF tissue depots were not significantly different. Concentrations of PCBs (VF/SF; median: 285/275 ng/g lw) and DDTs (VF/SF; median: 150/155 ng/g lw) were the major POPs in all fat samples. Concerning PCBs, PCB 153 (VF/SF: 27/26%) was the most dominant congener, followed by PCB 180 (VF/SF: 17/18%), PCB 138 (VF/SF: 15/14.5%) and PCB 170 (VF/SF: 8.1/8.4%) to the sum PCBs, respectively. Levels of HBCDs (VF/SF; median: 4.0/3.7 ng/g lw) and PBDEs (VF/SF; median: 2.6/2.7 ng/g lw) were 1–2 orders of magnitude lower than those of PCBs and DDTs. Among PBDEs, BDE 153 (VF/SF: 31/34%) was the dominant congener, followed by BDE 47 (VF/SF: 26/23%), BDE 154 (VF/SF: 16/16%), BDE 100 (VF/SF: 10/11%) and BDE 99 (VF/SF: 9/9%). To our knowledge, this is the first report on HBCD concentrations in Belgian human fat tissues. Total PBDE and HBCD levels in human fat samples could not be correlated with age. In agreement with the literature, a significant correlation (p < 0.05) between age and the concentration of PCBs (r = 0.828), DDTs (r = 0.640), HCHs (r = 0.666), CHLs (r = 0.534) and HCB (r = 0.754), was observed in the present study. Levels of DDTs, HCHs, HCB and CHLs were also significantly correlated to each other, suggesting that they share similar exposure routes. Correlation with computed tomography (CT) scan data revealed that VF and VF/SF ratios are positive for most of the POPs, such as PCBs, PBDEs, p,p′DDE, CHLs, β-HCH, and HCB. To our knowledge, this study is the first to assess the relationship between POP levels in adipose tissue and markers of abdominal adiposity, determined by CT.     

Mechanistic polychlorinated biphenyl exposure modeling of mothers in the Canadian Arctic: the challenge of reliably establishing dietary composition

BackgroundTraditional food (TF) consumption represents the main route of persistent organic pollutant (POP) exposure for indigenous Arctic Canadians. Ongoing dietary transitions away from TFs and toward imported foods (IFs) may contribute to decreasing POP exposures observed in these groups.MethodsTo explore this issue, we combined the global fate and transport model GloboPOP and the human food chain bioaccumulation model ACC-Human Arctic to simulate polychlorinated biphenyl (PCB) exposure in two indigenous Arctic Canadian communities from the Inuvik region, Northwest Territories and Baffin region, Nunavut. Using dietary survey information from initial (1996–98) and follow-up (2005–07) biomonitoring campaigns in Inuvik and Baffin, we simulated PCB exposures (PCB-118, -138, -153, and -180) for each individual study participant and also whole study populations.ResultsTF intake rates, particularly of marine mammals (MMs), were the most important predictors of modeled PCB exposure, while TF consumption did not associate consistently with measured PCB exposures. Further, reported mean TF intake increased from baseline to follow-up in both Inuvik (from 8 to 183 g d^− 1) and Baffin (from 60 to 134 g d^− 1), opposing both the expected dietary transition direction and the observed decrease in human PCB exposures in these communities (ΣPCB Inuvik: from 43 to 29 ng g lipid^− 1, ΣPCB Baffin: from 213 to 82 ng g lipid^− 1). However dietary questionnaire data are frequently subject to numerous biases (e.g., recall, recency, confirmation), and thus casts doubt on the usefulness of these data.ConclusionsUltimately, our model's capability to reproduce historic PCB exposure data in these two groups was highly sensitive to TF intake, further underscoring the importance of accurate TF consumption reporting, and clarification of the role of dietary transitions in future POP biomonitoring of indigenous Arctic populations.     

Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population

Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p = 0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p = 0.009) only in subjects with one G-allele (n = 103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p′-DDE were related to DNA hypermethylation (p = 0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p′-DDE were related to global DNA hypermethylation in a cross-sectional analysis.     

Can polychlorinated biphenyl (PCB) signatures and enantiomer fractions be used for source identification and to age date occupational exposure?

Detailed polychlorinated biphenyl (PCB) signatures and chiral Enantiomer Fractions (EFs) of CB-95, CB-136 and CB-149 were measured for 30 workers at a transformer dismantling plant. This was undertaken to identify sources of exposure and investigate changes to the PCB signature and EFs over different exposure periods. Approximately 1.5 g of serum was extracted and PCB signatures were created through analysis by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC–TOFMS) and EFs calculated following analysis by gas chromatography with high resolution mass spectrometry (GC–HRMS). A total of 84 PCBs were identified in the serum samples with concentrations of the 7 indicator PCBs ranging from 11–350 ng g^− 1 of serum (1.2–39 μg g^− 1 lipid). The PCB signatures were interpreted using principal component analysis (PCA) which was able to distinguish workers with background or recent minimal exposure from those with prolonged occupational exposure. Occupationally exposed individuals had a similar PCB profile to Aroclor A1260. However, individuals with prolonged exposure had depleted proportions of several PCB congeners that are susceptible to metabolism (CB-95, CB-101 and CB-151) and elevated proportions of PCBs that are resistant to metabolism (CB-74, CB-153, CB-138 and CB-180). The results also identified a third group of workers with elevated proportions of CB-28, CB-60, CB-66, CB-74, CB-105 and CB-118 who appeared to have been exposed to an additional source of PCBs. The results show near complete removal of the CB-95 E2 enantiomer in some samples, indicating that bioselective metabolism or preferential excretion of one enantiomer occurs in humans. By considering PCB concentrations along with detailed congener specific signatures it was possible to identify different exposure sources, and gain an insight into both the magnitude and duration of exposure.     

Development and validation of prediction models for blood concentrations of dioxins and PCBs using dietary intakes

BackgroundDioxins and PCBs accumulate in the food chain and might exert toxic effects in animals and humans. In large epidemiologic studies, exposure estimates of these compounds based on analyses of biological material might not be available or affordable.ObjectivesTo develop and then validate models for predicting concentrations of dioxins and PCBs in blood using a comprehensive food frequency questionnaire and blood concentrations.MethodsPrediction models were built on data from one study (n = 195), and validated in an independent study group (n = 66). We used linear regression to develop predictive models for dioxins and PCBs, both sums of congeners and 33 single congeners (7 and 10 polychlorinated dibenzo-p-dioxins and furans (PCDDs/PCDFs), 12 dioxin-like polychlorinated biphenyls (PCBs: 4 non-ortho and 8 mono-ortho), sum of all the 29 dioxin-like compounds (total TEQ) and sum of 4 non dioxin-like PCBs (∑ CB-101, 138, 153, 183 = PCB₄). We used the blood concentration and dietary intake of each of the above as dependent and independent variables, while sex, parity, age, place of living, smoking status, energy intake and education were covariates. We validated the models in a new study population comparing the predicted blood concentrations with the measured blood concentrations using correlation coefficients and Weighted Kappa (К_W) as measures of agreement, considering К_W > 0.40 as successful prediction.ResultsThe models explained 78% (sum dioxin-like compounds), 76% (PCDDs), 76% (PCDFs), 74% (no-PCBs), 69% (mo-PCBs), 68% (PCB₄) and 63% (CB-153) of the variance. In addition to dietary intake, age and sex were the most important covariates.The predicted blood concentrations were highly correlated with the measured values, with r = 0.75 for dl-compounds 0.70 for PCB₄, (p < 0.001) and 0.66 (p < 0.001) for CB-153. К_W was 0.68 for sum dl-compounds 0.65 for both PCB₄ and CB-153. Out of 33 congeners 16 (13 dl-compounds and 3 ndl PCBs) had К_W > 0.40.ConclusionsThe models developed had high power to predict blood levels of dioxins and PCBs and to correctly rank subjects according to high or low exposure based on dietary intake and demographic information. These models underline the value of dietary intake data for use in investigations of associations between dioxin and PCB exposure and health outcomes in large epidemiological studies with limited biomaterial for chemical analysis.     

Development of a synthetic PCB mixture resembling the average polychlorinated biphenyl profile in Chicago air

Studies of environmental and toxic effects of polychlorinated biphenyls (PCBs) are ideally performed with PCB mixtures reflecting the composition of environmental PCB profiles to mimic actual effects and to account for complex interactions among individual PCB congeners. Unfortunately, only a few laboratory studies employing synthetic PCB mixtures have been reported, in part because of the challenges associated with the preparation of complex PCB mixtures containing many individual PCB congeners. The objective of this study was to develop a PCB mixture that resembles the average PCB profile recorded from 1996 to 2002 at a satellite station of the Integrated Atmospheric Deposition Network located at the Illinois Institute of Technology (IIT) in Chicago, Illinois, using commercial PCB mixtures. Initial simulations, using published Aroclor profiles, showed that a mixture containing 65% Aroclor 1242 and 35% Aroclor 1254 was a good approximation of the target profile. A synthetic Chicago air mixture (CAM) was prepared by mixing the respective Aroclors in this ratio, followed by GC/MS/MS analysis. Comparison of the PCB profile of the synthetic mixture with the target profile suggests that the synthetic PCB mixture is a good approximation of the average IIT Chicago air profiles (similarity coefficient cos θ = 0.82; average relative percent difference = 84%). The synthetic CAM was also a reasonable approximation of the average of 184 PCB profiles analyzed in 2007 at 37 sites throughout Chicago as part of the University of Iowa Superfund Basic Research Program (isbrp), with a cos θ of 0.70 and an average relative percent difference of 118%. While the CAM and the two Chicago air profiles contained primarily di- to pentachlorobiphenyls, higher chlorinated congeners, including congeners with seven or eight chlorine atoms, were underrepresented in the synthetic CAM. The calculated TCDD toxic equivalency quotients of the synthetic CAM (2.7 ng/mg PCB) and the IIT Chicago air profile (1.6 ng/mg PCB) were comparable, but lower by two orders of magnitude than the isbrp Chicago air profile (865 ng/mg PCB) due to surprisingly high PCB 126 levels in Chicago air. In contrast, the calculated neurotoxic equivalency quotients of the CAM (0.33 mg/mg PCB) and the two Chicago air profiles (0.44 and 0.30 mg/mg PCB, respectively) were similar. This study demonstrates the challenges and methods of creating and characterizing synthetic, environmental mixtures of PCBs.     

Analysis of human milk to assess exposure to PAHs,PCBs and organochlorine pesticides in the vicinity Mediterranean city Mersin,Turkey

Assessment of human exposure to environmental persistent organic pollutants such as organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and polycyclic aromatic hydrocarbons (PAHs) based on the levels in human breast milk provides a reasonable tool not only to assess the contaminant burden in mothers but also to assess potential exposure of breast-fed neonates. There are limited data on levels of PCBs and OCPs in humans but no previous reports from Turkey on chemically determined levels PAHs in human milk. The aim of this study was to report the levels and accumulation profiles of OCPs, PCBs and PAHs in 47 breast milk samples obtained from a Mediterranean city, Mersin. High resolution analyses were performed by a gas chromatography coupled with mass spectrometer (GC–MS). Dichlorodiphenyldichloroethane (4.4′-DDE) was the dominant pollutant. Beta-hexachlorocyclohexane (ß-HCH), dichlorodiphenyltrichloroethane (4.4′-DDT), dieldrin, hexachlorobenzene, oxy-chlordane, cis-heptachlorepoxide were the other main OCPs detected. Mean levels of ΣPCB congeners and WHO_PCB-TEQ were 9.94 and 0.001 ng/g lipid, respectively. PCB 153 showed the highest concentration (3.37 ng/g lipid), followed by PCB 138 and 180. For the dioxin-like PCBs, PCB 118 was the dominant (0.97 ng/g lipid). Naphthalene, phenanthrene, pyrene and fluoranthene were the major PAHs among the 16 PAHs detected. The estimated daily intakes of DDTs, PCBs, HCHs and HCB were not exceeded the tolerable daily intake (TDI) proposed by the Health Canada Guideline. These results indicate that the neonates of Mersin city are exposed to persistent organic pollutants analyzed in this study. However, neonates born in Mersin province are less exposed than the ones born in other regions, considering OCP and PCB levels in breast milk.     

Pharmacokinetics of bisphenol A in humans following a single oral administration

BackgroundHuman exposures to bisphenol A (BPA) are widespread. The current study addresses uncertainties regarding human pharmacokinetics of BPA.ObjectiveTo reduce uncertainties about the metabolism and excretion of BPA in humans following oral administration.MethodsWe exposed six men and eight women to 100 μg/kg bw of deuterated BPA (d6-BPA) by oral administration and conducted blood and urine analysis over a three day period. The use of d6-BPA allowed administered d6-BPA to be distinguished from background native (unlabeled) BPA. We calculated the rate of oral absorption, serum elimination, half-life, area under the curve (AUC), urinary excretion, and metabolism to glucuronide and sulfate conjugates.ResultsMean serum total (unconjugated and conjugated) d6-BPA C_max of 1711 nM (390 ng/ml) was observed at T_max of 1.1 ± 0.50 h. Unconjugated d6-BPA appeared in serum within 5–20 min of dosing with a mean C_max of 6.5 nM (1.5 ng/ml) observed at T_max of 1.3 ± 0.52 h. Detectable blood levels of unconjugated or total d6-BPA were observed at 48 h in some subjects at concentrations near the LOD (0.001–0.002 ng/ml). The half-times for terminal elimination of total d6-BPA and unconjugated d6-BPA were 6.4 ± 2.0 h and 6.2 ± 2.6 h, respectively. Recovery of total administered d6-BPA in urine was 84–109%. Most subjects (10 of 14) excreted > 90% as metabolites within 24 h.ConclusionsUsing more sensitive methods, our study expands the findings of other human oral pharmacokinetic studies. Conjugation reactions are rapid and nearly complete with unconjugated BPA comprising less than 1% of the total d6-BPA in blood at all times. Elimination of conjugates into urine largely occurs within 24 h.     

Concentrations of chlorinated and brominated contaminants and their metabolites in serum of harbour seals and harbour porpoises

Harbour seals (Phoca vitulina) and harbour porpoises (Phocoena phocoena) are top predators in the North Sea and consequently accumulate a variety of pollutants in their tissues. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (HO-PCBs and HO-PBDEs) were measured in serum of wild harbour seals (n = 47) and captive harbour porpoises (n = 21). Both species exhibit long life spans and do not have extreme situations, such as complete fasting during periods of lactation, in their annual cycles. For PCBs, concentrations in adult males were slightly higher than in juveniles and lowest in juvenile females. For PBDEs, juveniles have higher levels than adult males and females, probably as a consequence of lactational transfer. However, differences between these age–gender groups were not statistical significant, indicating that individual variation was limited within each species, even without knowing the feeding status of the animals. Body condition, particularly emaciation, has a major influence on the levels of chlorinated and brominated contaminants in serum. Profiles of PCBs were CB 153 > CB 138 > CB 187 > CB 180 and CB 153 > CB 138 > CB 149 > CB 187 > CB 180 for harbour seals and porpoises respectively. For PBDEs, BDE 47 was the predominant congener followed by BDE 100 and 99 in both species. In harbour seals, concentrations of sum PCBs (median: 39,200 pg/ml) were more than 200 times higher than levels of sum PBDEs (median: 130 pg/ml) and almost 10 times higher than concentrations of sum HO-PCBs (4350 pg/ml). In harbour porpoises, concentrations of sum PCBs (median: 24,300 pg/ml) were about 20 times higher than concentrations of PBDEs (median: 1300 pg/ml). HO-PCBs were detected in only 4 harbour porpoises and this at very low concentrations. Naturally-produced MeO-PBDEs were only found in harbour porpoises at concentrations ranging from 120 to 810 pg/ml. HO-PBDEs were not found in any species. In general, harbour seals accumulate less compounds and have mostly lower concentrations than harbour porpoises possibly as a result of a better developed metabolism.     

Fish ingestion and congener specific polychlorinated biphenyl and p,p'-dichlorodiphenyldichloroethylene serum concentrations in a great lakes cohort of pregnant African American women

A cohort of low income, city dwelling, pregnant African American Women (delivered from 1994–1999) was assembled to identify factors related to organochlorine exposure through consumption of Great Lakes resources. The cohort is known as the Great Lakes Cohort of Pregnant African American Women (GLCPAAW). Pregnant women from metropolitan Chicago, IL area clinics were administered a questionnaire on diet, demographics, and health history. Weight, height, and serum lipids were measured at delivery along with serum organochlorines such as PCBs and DDE. Congener specific concentrations of PCBs and p,p'-DDE found in the maternal serum are reported. Dominant PCB congeners found in the serum of the pregnant women at delivery included PCB 101, 118, 138, 153, and 180. The high prevalence and magnitude of PCB 101 (greater than the limit of detection in > 80% of the women in the cohort) are unique characteristics of this cohort.Great Lakes fish has been identified as a source of exposure to organochlorines in several studies. Spearman correlations and robust regression models were utilized to identify the impact of Great Lakes fish ingestion on cohort serum organochlorine concentrations. Several potential confounders of the relationship between serum organochlorines and Great Lakes fish consumption were identified. Covariates related to organochlorines in correlations as well as regression models included age, body surface area, fish ingestion, lipids, parity, race and smoking. Lower chlorinated PCB congeners do not follow the same trends as the higher chlorinated congeners and DDE. The higher chlorinated PCB congeners (PCB 138, 153, and 180) and DDE were correlated with age while the lower chlorinated congeners were not. PCB 153 and 180 regression models included age as a significant covariate. None of the higher chlorinated congeners correlated to race, while both lower chlorinated congeners were correlated to race. Race was also significant in both lower chlorinated congeners' regression models. PCB 101, a lower chlorinated congener seldom found in human serum, is readily found in the cohort. Airborne PCB exposure as well as diminished metabolism of PCB 101 in African Americans may explain the increased presence of PCB 101 and it's correlation with race.High end sport fish consumers (≥ 1meal per week) carried elevated levels of DDE and higher chlorinated PCB congeners (138, 153, and 180) compared to non-sport fish eaters. Unexpectedly, DDE was correlated more consistently with fish ingestion and age (a marker of bioaccumulation) in comparison to PCBs. Small correlations were found between serum PCBs and fish ingestion (Spearman correlation = 0.19 for total PCBs and fish meals per year). Additionally, Serum PCBs in low end Great Lakes sport fish consumers were not higher than non-consumers. These findings suggest the women of the cohort are being exposed to PCBs through other routes in addition to Great lakes sport fish. One major route of exposure may be Chicago air. The observed trends amongst individual PCB congeners has important ramifications because lower chlorinated congeners or their metabolites may be mediators of toxicity. Organochlorine exposure through Great Lakes fish ingestion was clearly identified in high end fish consumers while associations with race, metabolism, and possible airborne exposures pose new questions.     

Maternal dietary intake of dioxins and polychlorinated biphenyls and birth size in the Norwegian Mother and Child Cohort Study (MoBa)

Maternal diet not only provides essential nutrients to the developing fetus but is also a source of prenatal exposure to environmental contaminants. We investigated the association between dietary intake of dioxins and PCBs during pregnancy and birth size. The study included 50,651 women from the Norwegian Mother and Child Cohort Study (MoBa). Dietary information was collected by FFQs and intake estimates were calculated by combining food consumption and food concentration of dioxins, dioxin-like PCBs and non-dioxin-like PCBs. We used multivariable regression models to estimate the association between dietary intake of dioxins and PCBs and fetal growth. The contribution of fish and seafood intake during pregnancy was 41% for dietary dioxins and dioxin-like PCBs and 49% for dietary non-dioxin-like PCBs. Further stratified analysis by quartiles of seafood intake during pregnancy was conducted. We found an inverse dose–response association between dietary intake of dioxins and PCBs and fetal growth after adjustment for confounders. Newborns of mothers in the upper quartile of dioxin and dioxin-like PCBs intake had 62 g lower birth weight (95% CI: − 73, − 50), 0.26 cm shorter birth length (95% CI: − 0.31, − 0.20) and 0.10 cm shorter head circumference (95% CI: − 0.14, − 0.06) than newborns of mothers in the lowest quartile of intake. Similar negative associations for intake of dioxins and dioxin-like PCBs were found after excluding women with intakes above the tolerable weekly intake (TWI = 14 pg TEQ/kg bw/week). The negative association of dietary dioxins and PCBs with fetal growth was weaker as seafood intake was increasing. No association was found between dietary dioxin and PCB intake and the risk for small-for-gestational age neonate. In conclusion, dietary intakes of dioxins and PCBs during pregnancy were negatively associated with fetal growth, even at intakes below the TWI.     

Prenatal and early-life polychlorinated biphenyl (PCB) levels and behavior in Inuit preschoolers

BackgroundWhereas it is well established that prenatal exposure to polychlorinated biphenyls (PCBs) can disrupt children's behavior, early postnatal exposure has received relatively little attention in environmental epidemiology.ObjectivesTo evaluate prenatal and postnatal exposures to PCB-153, a proxy of total PCB exposure, and their relation to inattention and activity in 5-year-old Inuits from the Cord Blood Monitoring Program.MethodsPrenatal exposure to PCBs was informed by cord plasma PCB-153 levels. We used a validated pharmacokinetic model to estimate monthly infants' levels across the first year of life. Inattention and activity were assessed by coding of video recordings of children undergoing fine motor testing. We used multivariable linear regression to evaluate the association between prenatal and postnatal PCB-153 levels and inattention (n = 97) and activity (n = 98) at 5 years of age.ResultsCord plasma PCB-153 was not associated with inattention and activity. Each interquartile range (IQR) increase in estimated infant PCB-153 levels at 2 months was associated with a 1.02% increase in the duration of inattention (95% CI: 0.04, 2.00). Statistical adjustment for the duration of breastfeeding slightly increased regression coefficients for postnatal level estimates, some of which became statistically significant for inattention (months: 2–4) and activity (months: 2–5).ConclusionsOur study adds to the growing evidence of postnatal windows of development during which children are more susceptible to neurotoxicants like PCBs.     

The influence of maternal dietary exposure to dioxins and PCBs during pregnancy on ADHD symptoms and cognitive functions in Norwegian preschool children

BackgroundPolychlorinated dibenzo-p-dioxins/dibenzofurans (dioxins) and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) with potentially adverse impact on child neurodevelopment. Whether the potential detrimental effects of dioxins and PCBs on neurodevelopment are of specific or unspecific character is not clear.ObjectivesThe purpose of the current study was to examine the influence of maternal dietary exposure to dioxins and PCBs on ADHD symptoms and cognitive functioning in preschoolers. We aimed to investigate a range of functions, in particular IQ, expressive language, and executive functions.Material and methodsThis study includes n = 1024 children enrolled in a longitudinal prospective study of ADHD (the ADHD Study), with participants recruited from The Norwegian Mother and Child Cohort Study (MoBa). Boys and girls aged 3.5 years participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview (PAPA), Stanford-Binet 5th revision (SB-5), Child Development Inventory (CDI), and Behavior Rating Inventory of Executive Function, Preschool version (BRIEF-P). Maternal dietary exposure to dioxins and PCBs was estimated based on a validated food frequency questionnaire (FFQ) answered mid-pregnancy and a database of dioxin and PCB concentrations in Norwegian foods. Exposure to dioxins and dioxin-like PCBs (dl-compounds) was expressed in total toxic equivalents (TEQ), and PCB-153 was used as marker for non-dioxin-like PCBs (ndl-PCBs). Generalized linear and additive models adjusted for confounders were used to examine exposure-outcome associations.ResultsExposure to PCB-153 or dl-compound was not significantly associated with any of the outcome measures when analyses were performed for boys and girls together. After stratifying by sex, adjusted analyses indicated a small inverse association with language in girls. An increase in the exposure variables of 1 SD was associated with a reduction in language score of − 0.2 [CI − 0.4, − 0.1] for PCB-153 and − 0.2 [CI − 0.5, − 0.1] for dl-compounds in girls. For boys, exposure to PCB-153 or dl-compounds was not associated with language skills. The difference between sex-specific associations was not statistically significant (p-value = 0.13). No sex-specific effects were observed for ADHD-symptoms, IQ scores, or executive functions.ConclusionsWe found no indications that variation in current low-level exposure to PCB-153 or dl-compounds in Norway is associated with variation ADHD-symptoms, verbal/non-verbal IQ, or executive functions including working memory in preschoolers. However, our findings indicated that maternal dietary exposure to PCB-153 or dl-compounds during pregnancy was significantly associated with poorer expressive language skills in preschool girls, although the sex-specific associations were not significantly different.     

Relative effect potency estimates of dioxin-like activity for dioxins,furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood

BackgroundIn the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates.ObjectivesWe sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways.MethodsWe used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia.ResultsWe calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ = 0.85; p < 0.001) and serum FT4 (ρ = 0.77; p = 0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r = 0.63; p = 0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r = 0.80; p = 0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r = 0.77; p = 0.001) and log WHO-TEFs (r = 0.81; p < 0.001).ConclusionsREPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways.