Persistent endocrine-disrupting chemicals and incident uterine leiomyomata: A mixtures analysis.

BACKGROUND: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL. METHODS: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders. RESULTS: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (ß comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (ß for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (ß = -0.06, 95 % CrI: -0.21, 0.10 and ß = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs. CONCLUSION: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions.

Utilizing machine learning to classify persistent organic pollutants in the serum of pregnant women: a predictive modeling approach.

Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), and per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants (POPs) that remain detrimental to critical subpopulations, namely pregnant women. Required tests for biomonitoring are quite expensive. Moreover, statistical models aiming to discover the relationships between pollutants levels and human characteristics have their limitations. Therefore, the objective of this study is to use machine learning predictive models to further examine the pollutants' predictors, while comparing them. Levels of 33 congeners were measured in the serum of 269 pregnant women, from whom data was collected regarding sociodemographic, dietary, environmental, and anthropometric characteristics. Several machine learning algorithms were compared using "Python" for each pollutant: support vector machine (SVM), random forest, XGBoost, and neural networks. The aforementioned characteristics were included in the model as features. Prediction, accuracy, precision, recall, F1-score, area under the ROC curve (AUC), sensitivity, and specificity were retrieved to compare the models between them and among pollutants. The highest performing model for all pollutants was Random Forest. Results showed a moderate to acceptable performance and discriminative power among all POPs, with OCPs' model performing slightly better than all other models. Top related features for each model were also presented using SHAP analysis, detailing the predictors' negative or positive impact on the model. In conclusion, developing such a tool is of major importance in a context of limited financial and research resources. Nevertheless, machine learning models should always be interpreted with caution by exploring all evaluation metrics.

Genetic variants reduced POPs-related colorectal cancer risk via altering miRNA binding affinity and m6A modification.

Exposure to persistent organic pollutants (POPs) may contribute to colorectal cancer risk, but the underlying mechanisms of crucial POPs exposure remain unclear. Hence, we systematically investigated the associations among POPs exposure, genetics and epigenetics and their effects on colorectal cancer. A case-control study was conducted in the Chinese population for detecting POPs levels. We measured the concentrations of 24 POPs in the plasma using gas chromatography-tandem mass spectrometry (GC-MS/MS) and evaluated the clinical significance of POPs by calculating the area under the receiver operating characteristic curve (AUC). To assess the associations between candidate genetic variants and colorectal cancer risk, unconditional logistic regression was used. Compared with healthy control individuals, individuals with colorectal cancer exhibited higher concentrations of the majority of POPs. Exposure to PCB153 was positively associated with colorectal cancer risk, and PCB153 demonstrated superior accuracy (AUC=0.72) for predicting colorectal cancer compared to other analytes. On PCB153-related genes, the rs67734009 C allele was significantly associated with reduced colorectal cancer risk and lower plasma levels of PCB153. Moreover, rs67734009 exhibited an expression quantitative trait locus (eQTL) effect on ESR1, of which the expression level was negatively related to PCB153 concentration. Mechanistically, the risk allele of rs67734009 increased ESR1 expression via miR-3492 binding and m6A modification. Collectively, this study sheds light on potential genetic and epigenetic mechanisms linking PCB153 exposure and colorectal cancer risk, thereby providing insight into the accurate protection against POPs exposure.

A decade of data and hundreds of analytes: Legacy and emerging chemicals in North American herring gull plasma.

Between 2010 and 2021, 199 herring gull serum samples were collected from Lake Michigan, Lake Huron, and Lake Erie, including two Areas of Concern: Saginaw Bay and the River Raisin. They were analyzed for 21 polybrominated diphenyl ether congeners, 10 non-PBDE flame retardants, 85 polychlorinated biphenyls, 17 legacy organochlorine pesticides, and 36 per- and polyfluoroalkyl substances. Σ36PFAS, Σ85PCB, Σ21PBDE, and Σ17Pesticide concentrations comprised 41-74%, 17-50%, 3-4%, and 5-9% of the total concentration, respectively. Median concentrations of the chemical groups ranged from 81.5 to 129 ng/g ww for PFAS, 26.3-158 ng/g ww for PCBs, 4.26-8.89 ng/g ww for PBDEs, and 8.08-23.0 ng/g ww for pesticides. The regional concentrations of all four classes of compounds are significantly decreasing when sites are combined with halving times of 11.3 ± 4.8, 8.2 ± 4.3, 5.9 ± 3.1, and 8.3 ± 4.2 years for the Penta-BDE mixture, ΣDDTs, Σ85PCBs and Σ36PFAS, respectively. These results suggest that, while PFAS has emerged as the dominant group of chemicals in the plasma, legacy pollutants continue to represent a threat to herring gulls and wildlife in the Great Lakes basin. PCBs were the largest contributors to the chemical load in plasma of birds whose colonies are located near the River Raisin, and continue to pose a threat to herring gulls within the two Areas of Concern.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos.

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Impact of antenatal exposure to a mixture of persistent organic pollutants on intellectual development.

OBJECTIVE: Strong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child's cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects. We examined here the impact of a prenatal exposure to a mixture of persistent organic pollutants (POPs) on intellectual abilities in preschool children, and compared their effects to those described in the literature. METHODS: Sixty-two children were included in a longitudinal cohort. Four organochlorine pesticides, four polychlorinated biphenyls (PCBs) and seven perfluorinated compounds (PFCs) were measured in cord blood. Intellectual abilities were assessed at 6 years of age using the Wechsler Preschool and Primary Scale of Intelligence 4th ed. (WPPSI-IV). We examined the associations between a mixture of POPs and cognitive performances using principal components approach (PCA) and weighted quantile sum (WQS) regression taking sex difference into account. RESULTS: No negative correlation was found when analyses were performed on boys and girls together. In sex-stratified analyses, lower scores in full scale intelligence quotient (FSIQ) and fluid reasoning index (FRI) were observed in boys most exposed to a mixture of POPs. Increase of the WQS index was also associated with lower verbal comprehension index (VCI) scores in girls only. No other negative correlation was found using both WQS and PCA models. CONCLUSION: Our study suggests deleterious associations between antenatal exposure to a mixture of POPs and sex-specific cognitive level, clarifying some trends described in the literature.

Healthy dietary patterns are associated with exposure to environmental chemicals in a pregnancy cohort.

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory efforts aimed at lowering environmental chemical exposure.

Possible associations between prenatal exposure to environmental pollutants and neurodevelopmental outcome in children.

This study aimed to evaluate associations between prenatal and childhood exposure to phthalates and prenatal exposure to polychlorinated biphenyls (PCBs) and the development of 4-year-old children. Urinary metabolites of five phthalates were measured in women upon delivery, as well as serum concentrations of four PCB congeners. Postnatal phthalate metabolites were measured from children's urine obtained at the time of developmental assessment. The primary outcome was cognitive function as evaluated by the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) administered at 4 years. Secondary outcomes were motor function and response to sensory stimuli as evaluated by the Developmental Coordination Disorder Questionnaire (DCDQ) and Short Sensory Profile (SSP) that the mothers filled out, respectively. The study included 57 mother-child pairs. Higher maternal phthalate metabolite concentrations were inversely associated with WPPSI-III scores among boys and not among girls. After using linear regression models and controlling for confounding variables, we found that higher levels of monobenzyl phthalate (MBzP) were the ones associated with lower WPPSI-III scores (p=0.004, 95 %CI [-14.18; -3.16]), lower DCDQ scores (p=0.007, 95 %CI [-6.08; -1.17] and lower SSP scores (p=0.004, 95 %CI [-7.47; -1.79]). No association was found between child urinary phthalate metabolite concentrations or maternal PCB blood concentrations and developmental function. These findings indicate that higher prenatal phthalate metabolite levels may be associated with deficits in neurologic development of young boys.

Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights in Sanliurfa, Turkey.

BACKGROUND: Controversy surrounds the impact of persistent organic pollutants (POPs) on fetal development. This study aimed to investigate levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in umbilical cord blood from Sanliurfa mothers in Turkey, exploring associations with gestational age and birth weight. METHODS: Participants included voluntary mothers pregnant with a single fetus, providing details on maternal factors. Cord blood samples were collected immediately after delivery. Samples were extracted with a modified QuEChERS method, and OCPs (17 pesticides) and PCBs (11 congeners) compound levels were analyzed with a gas chromatograph/mass spectrometry. Detection frequencies and levels of POPs by single pollutant type and pollutant groups were calculated and compared according to gestational duration and birth weight. We used partial least squares discriminant analysis to identify the key chemicals and distinguish their respective statuses. RESULTS: Among 120 infants, 35 were preterm but appropriate for gestational age, 35 were term but small for gestational age (SGA), and 50 were term and appropriate for gestational age (AGA). Beta HCH, Oxy-Chlordan, and PCB 28, were not detected in cord blood samples. Half of the samples contained at least 4 types of OCPs, with a median OCP level of 38.44 ng/g. Among the DDT, 2,4'-DDE was found at the highest concentration in cord plasma samples. The PCB congeners with a frequency exceeding 50% were ranked in the following order: 151, 149, 138, 146. The median level of ∑PCBs was 5.93 ng/g. Male infants born at term with SGA status exhibited lower levels of ∑DDTs, ∑OCPs compared to male infants born preterm or at term with AGA status. Di-ortho-substituted PCBs and hexachlorinated PCBs were higher in male infants born at term with SGA status than male infants born preterm with AGA status. CONCLUSION: Overall, exposure to DDT and PCBs demonstrates varying effects depending on gestational duration and birth weight, with exposure levels also differing by gender. This underscores the necessity for studies across diverse populations that investigate the combined effects of multiple pollutant exposures on gestational age, birth weight, and gender simultaneously.

Associations of exposure to organochlorine pesticides and polychlorinated biphenyls with chronic kidney disease among adults: the modifying effects of lifestyle.

Exposure to organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) has been reported to be associated with renal impairment and chronic kidney disease (CKD). Nevertheless, the research results thus far have exhibited inconsistency, and the effect of lifestyle on their association is not clear. In this study, we assessed the correlation between serum OCPs/PCBs and CKD and renal function indicators including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among 1721 Chinese adults. In order to further investigate the potential impact of lifestyle, we conducted joint associations of lifestyle and OCPs/PCBs on CKD. We found a negative correlation between p,p'-DDE and eGFR, while logistic regression results showed a positive correlation between PCB-153 and CKD (OR, 1.92; 95% CI, 1.21, 3.06). Quantile g-computation regression analyses showed that the association between co-exposure to OCPs/PCBs and CKD was not significant, but p,p'-DDE and PCB-153 were the main contributors to the negative and positive co-exposure effects of eGFR and CKD, respectively, which is consistent with the regression results. Participants with both relatively high PCB-153 exposure and an unhealthy lifestyle had the highest risk of CKD, in the joint association analysis. The observed associations were generally supported by the FAS-eGFR method. Our research findings suggest that exposure to OCPs/PCBs may be associated with decreased eGFR and increased prevalence of CKD in humans, and a healthy lifestyle can to some extent alleviate the adverse association between PCB-153 exposure and CKD.

Associations of serum persistent organic pollutant concentrations with incident diabetes in midlife women: The Study of Women's Health Across the Nation Multi-Pollutant Study.

BACKGROUND: Organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that can negatively impact metabolic health through pathways including endocrine disruption. Few studies have evaluated diabetes risk associated with PBDEs. Little is known about the joint effect of exposure to POP mixtures on diabetes risk. OBJECTIVES: We investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women. METHODS: We measured lipid-standardized serum concentrations of 34 PCBs, 19 OCPs, and 14 PBDEs in 1040 midlife women aged 45-56 years from the Study of Women's Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC). RESULTS: For most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB 123. A doubling of PBDE 47 was associated with 1.11 (1.00, 1.24) times the risk of T2D. QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR = 1.04 [0.53, 2.07]). CONCLUSION: Exposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.

Brain gray matter volume of reward-related structures in Inuit adolescents pre- and postnatally exposed to lead, mercury and polychlorinated biphenyls.

This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures.

Spatial and cumulative organochlorine and mercury exposure assessments in Steller Sea lions of Alaska: Emphasizing pups.

Steller sea lions (SSL) are sentinels for monitoring environmental contaminants in remote areas of the Aleutian Islands, Alaska. Therefore, concentrations of several organochlorines (OCs) were measured in blood from 123 SSL pups sampled from 3 regions; the western Aleutian Islands (WAI), central Aleutian Islands (CAI), and the central Gulf of Alaska. Blood, blubber, and milk from 12 adult female SSL from WAI, CAI and southeast Alaska also were analyzed. Findings included the following. SSL pups had higher concentrations of some OCs and mercury (Hg) on rookeries in the WAI than those more easterly. Pups had significantly higher blood concentrations of many OC classes than adult females sampled within the same region; some pups had PCB concentrations exceeding thresholds of concern (∑PCBs >8600 ng/g lw). ∑PCB concentration in pup whole blood was positively correlated with the trophic marker, δ15N within the regions sampled, along with two PCB congeners (PCB138 and PCB153). This suggests that the dams of pups with higher ∑PCBs, PCB138, and PCB153 concentrations were feeding on more predatory prey. Adult female blubber ∑DDT and hexachlorocyclohexane concentrations were also positively correlated with δ15N values. Several pups (mostly from WAI) had blood Hg concentrations and/or blood PCB concentrations (surrogate for overall OC exposures) of concern. The finding that WAI SSL pups have been exposed to multiple contaminants calls for future investigation of their cumulative exposure to a mixture of contaminants especially their transplacental and then transmammary exposure routes.

Relationships between pesticides, polychlorinated biphenyls, blood parameters and oxidative stress of white stork Ciconia ciconia chicks in Poland.

The white stork Ciconia ciconia is a bird species located at the top of the trophic pyramid in grassland and wetland ecosystems. This charismatic species is susceptible to pesticides and their environmental residues. In 2016, we collected blood samples from 114 white stork chicks across Western and Southern Poland. Chicks were sexed by molecular analysis and aged by development pattern. We studied the relationship between the concentration of pesticides (beta-HCH, heptachlor, aldrin, endrin, 4.4'-DDD, 4.4'-DDE and 4.4'-DDT) and of PCB in the chicks' blood with blood morphology and biochemistry parameters in the blood. The mean (± SD) values of concentrations of above detection level pesticides were: for (1) beta-HCH 4.139 ± 19.205; (2) 4.4'-DDE 9.254 ± 91.491 and additionally (3) PCB 16.135 ± 44.777 ppb. We found negative relationships between beta-HCH and oxidative stress enzyme activity in the blood, between beta-HCH and leukocyte concentration and between 4.4'-DDE and catalase activity. We also found a positive relationship between the concentration of pesticides in blood and the age of chicks. Interestingly, we found a higher concentration of PCB in the blood of male stork chicks than in female stork chicks. We provide more evidence that the presence of pesticides in the environment can be a strong stress factor, shaping the health status of birds.

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.

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.

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.

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.