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.

Effect of bariatric surgery in the body burden of persistent and non-persistent pollutants: longitudinal study in a cohort of morbidly obese patients.

Introduction: Obesity is a pathological state that involves the dysregulation of different metabolic pathways and adipose tissue cells, constituting a risk factor for the development of other diseases. Bariatric surgery is the most effective treatment. The study of the behavior of pollutants in situations of extreme weight loss can provide biomonitoring information and tools to manage diseases of environmental etiology. Aim: To determine the prevalence of serum persistent and non-persistent pollutants in obese patients subjected to bariatric surgery and analyze the impact of sociodemographic variables on these changes. Methods: GC-MS/MS and UHPLC-MS/MS were utilized to determine the detection rates and concentrations of 353 compounds, including persistent organic pollutants (POPs), pesticides, pharmaceuticals, and rodenticide, in serum samples of 59 obese patients before and after undergoing bariatric surgery. Results: Detection rates of p,p'-DDE, HCB, ß-HCH, naphthalene, phenanthrene and PCB congeners 138, 153 and 180 significantly increased due to surgery-induced weight loss. Serum levels of p,p'-DDE, PCB-138, PCB-153 and PCB-180 also increased after surgery. Correlations between naphthalene levels, weight loss, variation of total lipids and time after surgery were found. Additionally, correlations were observed between concentrations of PCB-138 and weight loss, and between phenanthrene levels and reduction of total lipids. No statistically significant differences were observed for other groups of contaminants, pharmaceuticals and other chemicals included in the quantification methods. Conclusions: Increment of POPs was observed after bariatric surgery. Serum concentrations of POPs after surgery were influenced by adiposity-related variables. Although biomonitoring studies show a decreasing tendency of exposure, rapid weight loss leads to an increase of circulating POPs. Further research on the interplay between adipose tissue, POPs and peripheral organs is required.

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 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.

Suspect and non-target screening of chemicals of emerging Arctic concern in biota, air and human serum.

Contaminants of emerging concern receive increasing attention in the Arctic environment. The aim of this study was to screen for chemicals of emerging Arctic concern (CEACs) in different types of Arctic samples including biota, air and human serum. We used a combination of gas chromatography (GC) and liquid chromatography (LC) with high resolution mass spectrometry (HRMS) for suspect and non-target screening (NTS). Suspect screening of 25 CEACs was based on published in-silico approaches for the identification of CEACs and revealed tetrabromophthalic anhydride (TBPA) in pilot whale and air, albeit with low detection frequencies (17 and 33%, respectively). An NTS workflow detected 49, 42, 31 and 30 compounds in pilot whale, ringed seal, air, and human serum, respectively, at confidence level 2 and 3. Although legacy POPs still dominated the samples, 64 CEACs were tentatively identified and further assessed for persistence (P), bioaccumulation (B), mobility (M), toxicity (T), and long-range transport potential (LRTP). While four PBT compounds were identified, 37 PMT substances dominated among these 64 compounds. Our study indicated that many chemicals of potential risk might be present in Arctic samples and would benefit from confirmation and further studies of their transport to and accumulation in the Arctic environment.

Blood levels of persistent organic pollutants among women in France in the 90's: Main profiles and individual determinants.

CONTEXT AND OBJECTIVES: Persistent organic pollutants (POPs) are a group of organic chemical compounds potentially toxic to human health. The objectives of this study were 1) to describe the levels of POPs biomarkers in blood samples from French women collected during the 1990s and to compare them with levels measured in two more recent French studies, 2) to identify POPs exposure profiles, and 3) to explore their main determinants. METHODS: 73 POPs biomarkers were measured in the blood of 468 women from the French E3N cohort (aged 45-73 years), collected between 1994 and 1999: 28 per- and polyfluoroalkyl substances, 27 organochlorine pesticides, 14 polychlorinated biphenyls and 4 polybrominated diphenyl ethers. POPs biomarker levels were described and compared with levels measured in two more recent French studies conducted by the French National Public Health Agency, the ENNS and Esteban studies. Principal component analysis was performed on POPs quantified in at least 75% of samples to identify the main exposure profiles. Linear regression models were used to estimate the associations between anthropometric, socio-demographic and lifestyle characteristics and exposure to these profiles. RESULTS: Among the 73 biomarkers measured, 41 were quantified in more than 75% of samples. Levels of most pollutants that were also measured in the Esteban of ENNS studies have decreased over time. Six POPs exposure profiles were revealed, explaining 62.1% of the total variance. Most of the characteristics studied were associated with adherence to at least one of these profiles. CONCLUSION: This study highlighted that most of the pollutants for which a comparison was possible decreased over the 10 or 20 years following the E3N blood collection, and identified those which, on the contrary, tended to increase. The health effects of the profiles identified could be assessed in future studies. The determinants identified should be confirmed in larger populations.

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.

Blood and tissue levels of persistent organic pollutants and genetic susceptibility in patients with breast cancer.

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR. However, the GSTT1 null polymorphism represented a significant risk for breast cancer when OR adjusted for age and smoking status. CYP1A1 polymorphism was a significant risk factor for breast cancer, regardless of whether the OR was adjusted. These results suggest that exposure to certain POPs, GSTT1 and CYP1A1 polymorphisms, age, and smoking status are risk factors for breast cancer. In addition, the blood concentrations of some POPs represent surrogates for breast tissue concentrations.

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.

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.

Associations between human internal chemical exposure to Persistent Organic Pollutants (POPs) and In Vitro Fertilization (IVF) outcomes: Systematic review and evidence map of human epidemiological evidence.

The impact of environmental chemicals like persistent organic pollutants (POPs) on reproductive health is still poorly understood, despite the high societal and economical costs. The aim of the present study was to systematically review and evaluate the human evidence on the associations between internal levels of POPs and in vitro Fertilization (IVF) outcomes among women. We applied a protocol based on the National Toxicology Program Office of Health Assessment and Translation's guidelines for the study search, selection and quality assessment. Fifteen studies were finally retained in the present work. The results showed that main families of POPs are still pervasive in follicular fluid and serum of women undergoing IVF treatments. Globally, we found inconsistent findings across studies for specific exposure-outcome dyads, suggesting that adverse effects of POPs on IVF outcomes cannot be ruled out. Specifically, there is evidence that POPs, notably some polychlorinated biphenyls and organochlorine pesticides, may impair embryo quality and pregnancy rates. Most studies have been performed in small cohorts (n<50) and focused on PCBs and OCPs, whereas major research gaps remain for emerging compounds (e.g. perfluoroalkylated substances) and the most clinically relevant outcome, live birth rate. The overall evidence presented 'serious' or 'very serious' risk of bias, mainly due to the lack of consideration of relevant confounding variables, low sample size or underreporting of methods. Globally, we judged the level of evidence being "low". Given the high economical and societal costs associated to infertility and IVF, further well-designed research is urged to fill the highlighted gaps.

A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) differentially affect glutamate induced excitotoxic responses in chicken cerebellum granule neurons (CGNs) in vitro.

Primary cultures of cerebellar granule neurons (CGNs) derived from chicken embryos were used to explore the effects on developmental neurotoxicity by a complex defined mixture of persistent organic pollutants (POPs). Its chemical composition and concentrations were based on blood levels in the Norwegian/Scandinavian population. Perfluorooctane sulfonic acid (PFOS) alone, its most abundant compound was also evaluated. Different stages of CGNs maturation, between day in vitro (DIV) 1, 3, and 5 were exposed to the POP mixture, or PFOS alone. Their combination with glutamate, an excitatory endogenous neurotransmitter important in neurodevelopment, also known to cause excitotoxicity was evaluated. Outcomes with the mixture at 500x blood levels were compared to PFOS at its corresponding concentration of 20 µM. The POP mixture reduced tetrazolium salt (MTT) conversion at earlier stages of maturation, compared to PFOS alone. Glutamate-induced excitotoxicity was enhanced above the level of that induced by glutamate alone, especially in mature CGNs at DIV5. Glutathione (GSH) concentrations seemed to set the level of sensitivity for the toxic insults from exposures to the pollutants. The role of N-methyl-D-aspartate receptor (NMDA-R) mediated calcium influx in pollutant exposures was investigated using the non-competitive and competitive receptor antagonists MK-801 and CGP 39551. Observations indicate a calcium-independent, but still NMDA-R dependent mechanism in the absence of glutamate, and a calcium- and NMDA-R dependent one in the presence of glutamate. The outcomes for the POP mixture cannot be explained by PFOS alone, indicating that other chemicals in the mixture contribute its overall effect.

Exposure to human relevant mixtures of halogenated persistent organic pollutants (POPs) alters neurodevelopmental processes in human neural stem cells undergoing differentiation.

Halogenated persistent organic pollutants (POPs) like perfluorinated alkylated substances (PFASs), brominated flame retardants (BFRs), organochlorine pesticides and polychlorinated biphenyls (PCBs) are known to cause cancer, immunotoxicity, neurotoxicity and interfere with reproduction and development. Concerns have been raised about the impact of POPs upon brain development and possibly neurodevelopmental disorders. The developing brain is a particularly vulnerable organ due to dynamic and complex neurodevelopmental processes occurring early in life. However, very few studies have reported on the effects of POP mixtures at human relevant exposures, and their impact on key neurodevelopmental processes using human in vitro test systems. Aiming to reduce this knowledge gap, we exposed mixed neuronal/glial cultures differentiated from neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) to reconstructed mixtures of 29 different POPs using concentrations comparable to Scandinavian human blood levels. Effects of the POP mixtures on neuronal proliferation, differentiation and synaptogenesis were evaluated using in vitro assays anchored to common key events identified in the existing developmental neurotoxicity (DNT) adverse outcome pathways (AOPs). The present study showed that mixtures of POPs (in particular brominated and chlorinated compounds) at human relevant concentrations increased proliferation of NSCs and decreased synapse number. Based on a mathematical modelling, synaptogenesis and neurite outgrowth seem to be the most sensitive DNT in vitro endpoints. Our results indicate that prenatal exposure to POPs may affect human brain development, potentially contributing to recently observed learning and memory deficits in children.

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.

Prenatal exposure to a mixture of persistent organic pollutants (POPs) and child reading skills at school age.

BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined. METHODS: We estimated associations of prenatal serum concentrations of 17 POPs, namely 5 polybrominated diphenyl ethers (PBDEs), 6 polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and 4 per- and polyfluoroalkyl substances (PFAS), with Wide Range Achievement Test-4 reading composite scores at age 8 years in 161 children from a pregnancy and birth cohort (Health Outcomes and Measures of the Environment [HOME] Study, 2003-present) in Cincinnati, OH. We applied 6 statistical methods: least absolute shrinkage and selection operator (LASSO), elastic net (ENET), Sparse Principal Component Analysis (SPCA), Weighted Quantile Sum (WQS) regression, Bayesian Kernel Machine Regression (BKMR), and Bayesian Additive Regression Trees (BART), to estimate covariate-adjusted associations with individual and their mixtures in multi-pollutant models. RESULTS: Both LASSO and ENET models indicated inverse associations with reading scores for BDE-153 and BDE-28, and positive associations for CB-118, CB-180, perfluoroctanoate (PFOA), and perfluorononanoate (PFNA). The SPCA identified inverse associations for BDE-153 and BDE-100 and positive associations for perfluorooctane sulfonate (PFOS), PFOA, and PFNA, as parts of different principal component scores. The WQS regression showed the highest weights for BDE-100 (0.35) and BDE-28 (0.16) in the inverse association model and for PFNA (0.29) and CB-180 (0.21) in the positive association model. The BKMR model identified BDE-100 and BDE-153 for inverse associations and CB-118, CB-153, CB-180, PFOA, and PFNA for positive associations. The BART method found dose-response functions similar to the BKMR model. No interactions between POPs were identified. CONCLUSIONS: Despite some inconsistency among biomarkers, these analyses revealed inverse associations between prenatal PBDE concentrations and children's reading scores. Positive associations of PCB congeners and PFAS with reading skills were also found.

DNA methylation level in blood and relations to breast cancer, risk factors and environmental exposure in Greenlandic Inuit women.

Several studies have found aberrant DNA methylation levels in breast cancer cases, but factors influencing DNA methylation patterns and the mechanisms are not well understood. This case-control study evaluated blood methylation level of two repetitive elements and selected breast cancer-related genes in relation to breast cancer risk, and the associations with serum level of persistent organic pollutants (POPs) and breast cancer risk factors in Greenlandic Inuit. DNA methylation was determined using bisulphite pyrosequencing in blood from 74 breast cancer cases and 80 controls. Using first tertile as reference, the following was observed. Positive associations for ATM in second tertile (OR: 2.33, 95% CI: 1.04; 5.23) and ESR2 in third tertile (OR: 2.22, 95% CI: 0.97; 5.05) suggest an increased breast cancer risk with high DNA methylation. LINE-1 methylation was lower in cases than controls. In third tertile (OR: 0.42, 95% CI: 0.18; 0.98), associations suggest in accordance with the literature an increased risk of breast cancer with LINE-1 hypomethylation. Among controls, significant associations between methylation levels and serum level of POPs and breast cancer risk factors (age, body mass index, cotinine level) were found. Thus, breast cancer risk factors and POPs may alter the risk through changes in methylation levels; further studies are needed to elucidate the mechanisms.

Veterinary utility of dried blood spots for detailed analysis of chlorinated pesticides and polychlorinated biphenyls by gas chromatography tandem mass spectrometry.

Persistent organic pollutants (POPs) are organic compounds of anthropogenic origin that resist atmospheric and microbial degradation and thus persist in the environment and in food chains for exceptionally long periods of time. Veterinarians and wildlife researchers need simple methodologies for monitoring and measuring such compounds including two large and diverse categories, organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs), compounds that have been largely banned from production and use except for specific exceptions. We present development of methodologies for detection and quantitation of 22 OCs and 10 PCB congeners by tandem quadrupole gas chromatography-mass spectrometric analysis of Dried Blood Spots (DBS). Development was enabled by (1) optimization of suspension and extraction methodologies for DBS; (2) strategic streamlining and condensation of Multiple Reaction Monitoring (MRM) settings on GC/MS/MS; and (3) improvement of GC settings to accommodate all 32 compounds in a single chromatographic run per sample. The method was validated for parameters of linearity, limits of detection and quantitation, recovery and precision, and results from blood were shown to correlate well with those from DBS despite both being only 50 uL in volume. The method was applied successfully to blood samples from nine avian specimens submitted to the MSU Veterinary Diagnostic Lab, and all were shown to bear the burden of varying levels of OCs and/or PCB compounds.

Blood screening for heavy metals and organic pollutants in cancer patients exposed to toxic waste in southern Italy: A pilot study.

In Italy, in the eastern area of the Campania region, the illegal dumping and burning of waste have been documented, which could potentially affect the local population's health. In particular, toxic waste exposure has been suggested to associate with increased cancer development/mortality in these areas, although a causal link has not yet been established. In this pilot study, we evaluated blood levels of toxic heavy metals and persistent organic pollutants (POPs) in 95 patients with different cancer types residing in this area and in 27 healthy individuals. While we did not find any significant correlation between the blood levels of POPs and the provenance of the patients, we did observe high blood concentrations of heavy metals in some municipalities, including Giugliano, where many illegal waste disposal sites have previously been documented. Our results showed that patients with different cancer types from Giugliano had higher blood levels of heavy metals than healthy controls. Despite the obvious limitations of this exploratory study, our preliminary observations encourage further research assessing the possible association between exposure to hazardous waste, increased blood metals, and increased risk of cancer.