Development and performance of an analytical method for polychlorinated naphthalenes and other persistent organic pollutants in dried blood spots.

BACKGROUND: Dried blood spots (DBSs) collected and archived in newborn screening programs (NSP) represent a potentially valuable resource for assessing exposure to a range of organic and inorganic chemicals in newborns. This study develops and optimizes a method to measure polychlorinated naphthalenes (PCNs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs) in DBS using the isotope dilution technique, ultrasonic-assisted liquid-liquid extraction, simple cleanup, triple quadrupole GC-MS/MS analysis, and background correction. RESULTS: We minimize the number of extraction repetitions and the volume of solvent, which helps increase throughput while minimizing the potential for contamination. We obtained high recovery and precision for most compounds, and method detection limits (MDLs) were sufficiently low to detect the more prevalent compounds based on representative sample of the US population. MDLs averaged 0.020 ng/mL (recovery: 107 %, precision: 4 %) for PCNs, 0.021 ng/mL (recovery: 97 %, precision: 4 %) for PCBs, 0.021 ng/mL (recovery: 117 %, precision: 2 %) for OCPs, and 0.021 ng/mL (recovery: 96 %, precision: 3 %) for PBDEs. SIGNIFICANCE AND NOVELTY: To our knowledge, this is the first study presenting an analytical method and for PCNs in DBS, and one of the few studies providing an assessment of method performance for persistent organic pollutants in DBS. The optimized method can be applied to a wide range of applications, including exposure assessment, environmental epidemiology, forensics, environmental surveillance, and ecological monitoring.

Polychlorinated biphenyls and incident coronary heart disease-related outcomes in Great Lakes fish consumers.

BACKGROUND: Exposure to polychlorinated biphenyls (PCBs) has been linked to risk factors for cardiovascular disease such as increased inflammation, accelerated atherosclerosis, diabetes, and sex hormone dysregulation. Furthermore, there is increasing evidence suggesting associations between internal dose of PCBs and cardiovascular outcomes. OBJECTIVES: The purpose of this study is to investigate longitudinal associations of PCBs with coronary heart disease (CHD)-related outcomes in a cohort of Great Lakes sport fish consumers. METHODS: The Great Lakes Sport Fish Consumer cohort was established in the early 1990's. Eight hundred nineteen participants were followed from 1993 to 2017. Serum PCBs were measured in 1994/1995 (baseline), in 2001, and in 2004, while health history questionnaires were administered in 1996, 2003, 2010, and 2017. Cox models were used to prospectively investigate associations of total PCBs and PCB groupings, based on aryl hydrocarbon receptor activity, with incident self-reported physician diagnosis of coronary heart disease (CHD), myocardial infarction (MI), and angina pectoris. RESULTS: A 2-fold increase in phenobarbital-type PCBs was associated with a 72% increase in likelihood of self-reported incident diagnosis of CHD (HR=1.72, 95% CI: 1.06-2.81; p=0.0294). Similar results were observed for total PCBs (HR=1.68, 95% CI: 1.05-2.69; p=0.0306) and mixed methacholine/phenobarbital type (mixed-type) PCBs (HR=1.60, 95% CI: 1.02-2.52; p=0.0427), but not methacholine-type PCBs. PCBs were not strongly associated with risk of MI or angina. CONCLUSIONS: This study presents evidence that exposure to PCBs increases the risk of developing coronary heart disease. Given the large number of risk factors and causal pathways for CHD, future research is required to better understand biological mechanisms of action for PCBs on CHD.

Thyroid cancer and endocrine disruptive chemicals: a case-control study on per-fluoroalkyl substances and other persistent organic pollutants.

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort. Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods. Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180. Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Systematic investigation of organochlorine pesticides and polychlorinated biphenyls blood levels in Greek children from the Rhea birth cohort suggests historical exposure to DDT and through diet to DDE.

The blood levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been thoroughly investigated in Greek children from the Rhea birth cohort study. This investigation aimed to assess exposure levels, explore their possible relationship with children's age and sex, and indicate potential sources of exposure. Exposure patterns and common sources of PCBs and OCPs were analyzed using bivariate and multivariate statistics. A total of 947 blood samples from study participants were analyzed for OCP and PCB exposure, with 375 samples collected at 4 years old, 239 at 6.5 years old, and 333 at 11 years old. Elevated levels of DDE were observed in 6.5-year-old children compared to corresponding levels in other European countries. Higher levels of DDE were found in 4-year-old children, with the lowest concentrations in the 11-year-old group. The DDT/DDE ratio was consistently less than 1 among all the examined subjects. These results indicate exposure to DDT and DDE both in utero and through breastfeeding and dietary intake. For the entire cohort population, the highest concentration was determined for PCB 28, followed by PCBs 138, 153, and 180. The sum of the six indicator PCBs implied low exposure levels for the majority of the cohort population. Spearman correlations revealed strong associations between PCBs and OCPs, while principal component analysis identified two different groupings of exposure. DDE exhibited a correlation with a series of PCBs (153, 156, 163, 180), indicating a combined OCP-PCB source, and an anticorrelation with others (52, 28, 101), implying a separate and competing source.

Optimization and uncertainty assessment of a gas chromatography coupled to Orbitrap mass spectrometry method to determine organic contaminants in blood: A case study of an endangered seabird.

Birds are excellent bioindicators of environmental pollution, and blood provides information on contaminant exposure, although its analysis is challenging because of the low volumes that can be sampled. The objective of the present study was to optimize and validate a miniaturized and functional extraction and analytical method based on gas chromatography coupled to Orbitrap mass spectrometry (GCOrbitrap-MS) for the trace analysis of contaminants in avian blood. Studied compounds included 25 organochlorine pesticides (OCPs), 6 polychlorinated biphenyls (PCBs), 8 polybrominated diphenyl ethers (PBDEs) and 15 polycyclic aromatic hydrocarbons (PAHs). Four extraction and clean-up conditions were optimized and compared in terms of efficiency, accuracy, and uncertainty assessment. Extraction with hexane:dichloromethane and miniaturized Florisil pipette clean-up was the most adequate considering precision and accuracy, time, and costs, and was thereafter used to analyse 20 blood samples of a pelagic seabird, namely the Bermuda petrel (Pterodroma cahow). This species, endemic to the Northwest Atlantic, is among the most endangered seabirds of the region that in the '60 faced a decrease in the breeding success likely linked to a consistent exposure to dichloro-diphenyl-trichloroethane (DDT). Indeed, p,p'-DDE, the main DDT metabolite, was detected in all samples and ranged bewteen 1.13 and 6.87 ng/g wet weight. Other ubiquitous compounds were PCBs (ranging from 0.13 to 6.76 ng/g ww), hexachlorobenzene, and mirex, while PAHs were sporadically detected at low concentrations, and PBDEs were not present. Overall, the extraction method herein proposed allowed analysing very small blood volumes (∼ 100 µL), thus respecting ethical principles prioritising the application of less-invasive sampling protocols, fundamental when studying threatened avian species.

Exposure of an endangered seabird species to persistent organic pollutants: Assessing levels in blood and link with reproductive parameters.

Ocean contamination, particularly from persistent organic pollutants (POPs), remains a significant threat to marine predators that occupy high trophic positions. Long-lived procellariform seabirds are apex predators in marine ecosystems and tend to accumulate contaminants. Prolonged exposure to pollutants negatively affects their fitness including reproductive success. Low breeding success may represent a hurdle for the restoration of small and endangered seabird populations, including several highly threatened gadfly petrels. Here we investigated the annual variation (2019 and 2022) in organochlorine pesticide (OCP), polychlorinated biphenyl ether (PCB), polybrominated diphenyl ether (PBDE), and polycyclic aromatic hydrocarbon (PAH) exposure in the endangered Bermuda petrel (Pterodroma cahow), and the relationship between female contaminant burden and breeding parameters. We found that petrels were exposed to a wide range of pollutants (33 out of 55 showed measurable levels) with PCBs dominating the blood contaminant profiles in both years. Only 9 compounds were detected in >50 % of the birds. Specifically, among OCPs, p, p'-DDE and hexaclorobenzene were the most frequently detected while fluorene and acenaphthene were the most common PAH. The concentrations of ∑5PCBs and ∑7POPs were higher in older birds. Furthermore, females with greater contaminant burdens laid eggs with a lower probability of hatching. However, female investment in egg production (size and volume) was unrelated to their blood contaminant load. Overall, this study highlights the presence of a wide range of contaminants in the petrel's food web, and it sheds light on the potential impact of chronic exposure to sub-lethal levels of PCBs on the breeding success of seabirds. We claim that toxicological testing should be a practice integrated in the management of seabirds, particularly of endangered species to monitor how past and present anthropogenic activities impact their conservation status.

Variations in thyroid hormone levels in endangered St. Lawrence Estuary belugas: Potential linkage with stress and organohalogen contaminant exposure.

The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and their metabolites reverse T3 and 3,5-diiodothyronine [3,5-T2]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T4, rT3 and 3,5-T2. Specifically, there was a weak significant negative association between T4 and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T3 and Σ34PBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.

Associations of polychlorinated biphenyls exposure, lifestyle, and genetic susceptibility with dyslipidemias: Evidence from a general Chinese population.

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. Herein we explored the associations of PCBs with dyslipidemia and further assessed the modification effect of genetic susceptibility and lifestyle factors. Six serum PCBs (PCB-28, 101, 118, 138, 153, 180) were determined in 3845 participants from the Wuhan-Zhuhai cohort. Dyslipidemia, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were determined, and lipid-specific polygenic risk scores (PRS) and healthy lifestyle score were constructed. We found that all six PCB congeners were positively associated with the prevalence of dyslipidemias, and ΣPCB level was associated with HyperTC, HyperTG, and HyperLDL-C in dose-response manners. Compared with the lowest tertiles of ΣPCB, the odds ratios (95% confidence intervals) in the highest tertiles were 1.490 (1.258, 1.765) for HyperTC, 1.957 (1.623, 2.365) for HyperTG, and 1.569 (1.316, 1.873) for HyperLDL-C, respectively. Compared with those with low ΣPCB, healthy lifestyle, and low genetic risk, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC, HyperTG, and HyperLDL-C. Our study provided evidence that high PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

PCB plasma level in different occupational groups in Iran.

Despite the ban of polychlorinated biphenyls (PCBs) some decades ago, concerns regarding their adverse health effects are continuing, because the workers employed for installation and repair of electrical equipment may be still exposed to PCBs. This study aimed to assess serum PCBs levels in workers in different industries. To do this, we determined the serum concentrations of 9 non-dioxin-like PCBs and 12 dioxin-like PCBs in 147 workers from seven occupational groups and 35 housewives. An electrical distribution company, paint manufacturer, and pesticide manufacturer were categorized as high probability exposure jobs, whereas turning and casting operations, polymer plastic manufacturing, professional driving, and office work were categorized as low probability exposure jobs. In addition, the average of PCB 138, 153, and 180 and PCB sums were observed to be significantly higher in paint manufacture workers compared to the another groups. In addition, the average PCB 118 level was higher in electrical distribution workers and housewives. Following the adjustment for age, blood lipid, residency place, and seafood in the regression model, the association of PCB 118 in electrical distribution workers and PCB 153 in paint manufacture workers remained significant. The results of this study served as further support for the hypothesis for an occupational basis for bioaccumulation of some PCB types. However, the plasma levels of almost all PCB congeners in Iran were found to be lower than many other countries.

Adverse health effects of PCBs on fine motor performance - Analysis of a neurophysiological pathway in the HELPcB surveillance program.

Since research literature indicates neurotoxic health effects of polychlorinated biphenyls (PCBs), it is necessary to identify by which mechanism PCBs might affect the human central nervous system and human behavior. In the present study, a neurophysiological pathway is assumed to explain the negative association of PCB exposure and performance in fine motor tasks mediated by the level of the dopamine (DA) metabolite homovanillic acid (HVA). A total of 113 occupationally PCB exposed workers and their relatives from an occupational health monitoring program were examined (89.4 % men). PCBs were analyzed in plasma via human biomonitoring and HVA was assessed in urine. The motor performance series was used to measure two dimensions of fine motor skills with 5 subgroups (accuracy: steadiness, line tracking accuracy; speed: line tracking speed, aiming, tapping). The direct effects of PCBs on fine motor performance and the indirect effects of PCBs on fine motor performance via DA metabolite HVA were tested with multiple regressions. We found significant effects for the accuracy dimension, namely a negative direct effect of PCBs on line tracking accuracy mediated by HVA. Further, an indirect effect could be found for PCBs with steadiness accuracy through HVA. There were no significant effects related to fine motor performances in the speed dimension. These results provide first indications for an underlying neurochemical pathomechanism involving the dopamine system of PCB-related deterioration of fine motor performance regarding accuracy.

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

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: 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. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Serum levels of polychlorinated biphenyls and stroke risk among Chinese: a hospital-based case-control study.

Previous studies have revealed the serious human health risk effects of organic pollutants-polychlorinated biphenyls (PCBs). However, the roles of circulating PCBs on stroke risk have not been elucidated. The purpose of this study was to examine whether serum PCBs could increase the risk for stroke among Chinese participants. A total of 241 patients with stroke and age- (5-year interval) and gender-matched controls were recruited in Tianjin, China. Concentrations of 17 PCB congeners were measured by using high-resolution gas chromatography with mass spectrometric detection. Conditional logistic regression models were applied to assess the odds ratio (OR) and 95% confidential interval (CI). Significant positive associations were observed between serum total PCBs and dioxin-like PCBs and the risk for stroke (all p trends < 0.05), and the adjusted ORs for the highest tertile (T3) of serum concentration compared with the lowest tertile (T1) were 1.704 (1.073, 2.506) and 1.846 (1.156, 2.949). However, no significant association was found for non-dioxin-like PCBs (OR for T3 vs. T1: 1.388, 95%CIs: 0.850, 2.266; p trend: 0.118). Stratified analysis by stroke subtypes (ischemic or hemorrhagic strokes) showed no significant heterogeneity (OR for T3 vs. T1: 1.644 vs. 1.824; p for interaction: 0.458). The results suggest detrimental roles of PCBs, mainly dioxin-like PCBs, in stroke risk, irrespective of stroke subtypes. Further well-designed prospective studies with larger sample size are invited to confirm these associations.

[Serum polychlorinated biphenyls in workers of a second-smelting steel mill]. / Policlorobifenili sierici nei lavoratori di una acciaieria di seconda fusione.

SUMMARY: In the steel industry polychlorodibenzodioxins (PCDD), polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCBs) may be present deriving from the fusion of ferrous and non-ferrous scrap, as well as for the thermal decomposition of the plastic materials (thermoplastic and thermosetting resins) contained therein and not removed before melting at high temperatures. The aim of the study was to assess in 52 workers of a secondmelting steel plant the PCBs exposure deriving from the manual handling of ferrous scrap waste eventually contaminated. The population was divided by production department (scrap, casting and office). Static air sampling of PCDD, PCDF, PCBs and biological monitoring of serum dioxin-like PCBs (DL-PCBs) were performed. The comparison of serum DL-PCB values between workers from the scrap department and those from the casting did not find any statistically significant differences (Mann- Whitney U test). The range of serum DL-PCBs was 7.74-78.55 ng/g lipids with an average of 24.21 ng/g lipids, much lower than the reference values measured in the Italian general population in 2011. Mean and median TEQ WHO 1998 of DL-PCBs were 0.22 pg/g lipids and 0.15 pg/g lipids respectively. The low concentrations of serum DL-PCBS in the studied population can be explained by the progressive reduction of environmental PCBs contamination.

Congener-specific determination of hydroxylated polychlorinated biphenyls by polar-embedded reversed-phase liquid chromatography-tandem mass spectrometry.

This paper reports the development of an LC-ESI-MS2 method for the sensitive determination of hydroxylated polychlorinated biphenyls (OH-PCBs) in human serum samples. Congener-specific separation was achieved by using a polar-embedded stationary phase, previously optimized for the working group, which provided better separation of isobaric compounds than the common octadecylsilane phases. MS fragmentation patterns and energies showed differences among OH-PCB congeners, mainly depending on the position of OH-group and the number of chlorine atoms in the molecule, although the most intense transitions were always those corresponding to the neutral loss of an HCl group from the quasi-molecular ion cluster. The method allowed the determination of OH-PCBs with good linearity (dynamic linear range of four orders of magnitude with R2 higher than 0.995) and precision (relative standard deviations of absolute areas lower than 10%), and with better sensitivity than other similar methods previously described in the literature. Matrix effect has been evaluated and reduced to less than 10% by the addition of isotopically labeled standards and a 10-fold dilution of the final sample extract. The low iLODs provided by the developed method (from 1.2 to 5.4 fg µL-1 for all the OH-PCBs studied, except 4'-OHCB108, whose iLOD was 61 fg µL-1) allows dilution without losses of detected peaks. Finally, the applicability of the method has been demonstrated by analyzing human serum samples belonging to an interlaboratory exercise.

Concentration of polychlorinated biphenyls in serum from New Jersey biomonitoring study: 2016-2018.

The first statewide New Jersey Biomonitoring (NJBM) of serum polychlorinated biphenyls (PCBs) was conducted from 2016 to 2018. Forty ortho-substituted PCBs were measured in serum samples collected from 920 NJ residents in compliance with the CDC method. The lipid adjusted geometric mean (GM) of ∑40PCB concentration for all the 920 measured subjects was 65.5 ng/g lipid (95% CIs: 56.9-75.4 ng/g lipid). Age stratified serum concentration showed that the lowest GM (33.3 ng/g lipid) was observed in the 20-39 years age group (n = 282), followed by a concentration of 76.05 ng/g lipid (n = 382) in the 40-59 years age group, and the highest GM (168.4 ng/g lipid) was found in the 60-74 years age group (n = 256). A survey regression model revealed that ∑40PCBs was significantly associated with age, moderately associated with geographic region, and not significantly associated with sex. The comparison of serum PCB levels in NJBM with the sequential National Health and Nutrition Examination Survey (NHANES) data suggested that the serum PCBs in NJ adults declined 52-59% at all age groups over the last decade. Positive Matrix Factorization (PMF) suggests that ongoing and recent exposure to lower molecular weight PCBs contributes about 15% to total serum PCB levels and more in younger subjects, while higher molecular weight PCBs contribute 52% of the total serum PCB levels and more in older subjects.

Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study.

BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation.

BACKGROUND: Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. RESULTS: Our analysis focused on POPs with more than 80% plasma concentrations 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)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10-21 to 2.11 × 10-7). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). CONCLUSIONS: DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

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

BACKGROUND: Serum polychlorinated biphenyls (PCBs) have been associated with some chronic diseases, but little evidence exists on their possible relationship with neurodegenerative diseases. We aimed to assess the relationship between PCB exposure and the occurrence of dementia and Parkinson disease in a prospective cohort study in a highly polluted area (Brescia-Caffaro). METHODS: PCB exposure was assessed by measuring serum levels of 24 congeners. Data on the onset of dementia and Parkinson disease were retrieved by the Brescia Health Protection Agency Database. We used Poisson regression models adjusted for possible confounders to calculate rate ratios (RRs). A mediation analysis was performed to evaluate the mediatory role of cardiovascular diseases. RESULTS: 699 subjects without neurologic diseases at baseline were enrolled (48.1% males, 63.2 years of mean age) in 2001-2013 and followed up to 2018. During a mean follow-up of 8.8 years, 36 and 20 subjects developed dementia and Parkinson disease. Subjects in the 2nd and 3rd tertiles of the total PCBs distribution, compared with those in the 1st tertile, had a higher risk of dementia (RR = 2.30 and RR = 4.35). The estimates for Parkinson disease included the null value with wide confidence intervals. In the mediation analysis, the association between PCB exposure and dementia was dominated by the direct pathway and not by the hypertension-mediated pathway. CONCLUSIONS: We observed a positive association between total PCBs serum levels and the onset of dementia not mediated by hypertension. For Parkinson, the unstable risk estimates did not allow to draw a conclusion on a possible association.

Risk factors associated with developing anxiety in Inuit adolescents from Nunavik.

This study aimed to examine the relation between anxiety among the at-risk population of Inuit adolescents and diverse developmental risk factors including exposure to environmental chemicals, a subject of concern in Nunavik. Anxiety was assessed in 89 Inuit participants (mean age = 18.4 years; range = 16.2-21.9) with the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the State-Trait Anxiety Inventory (STAI). Potential risk factors for anxiety were documented at birth, 11 years of age and 18 years of age, including blood levels of chemicals (mercury, lead, PCBs) and nutrients, as well as age, sex, estimated IQ, drug and alcohol use, bullying, exposure to domestic violence, food insecurity, crowding and socio-economic status. Results showed that participants scored high on both measures of anxiety, particularly the SCARED, for which the mean score was above the clinical threshold. Multiple regression results show that significant risk predictors obtained from the SCARED scores were female sex (ß = 0.32), higher current blood mercury concentration (ß = 0.26), food insecurity (ß = 0.26) and bullying experiences in the last year (ß = 0.21). The significant predictors for the STAI trait anxiety were food insecurity (ß = 0.25) and lower estimated IQ (ß = -0.31), whereas food insecurity (ß = 0.21), lower blood levels of vitamin E (ß = -0.25) and higher cord blood mercury concentrations (ß = 0.25) were found for STAI situational anxiety. Further regression analyses suggested that the adolescent-related variables were the most important risk factors. Our findings show that Inuit adolescents are at risk for anxiety via multiple contributing factors, particularly current exposure to mercury, food insecurity and female sex.