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Coronary artery disease (CAD) is often accompanied by abnormal cardiac structure and function, leading to an increased prognostic risk. However, less is known about the associations of mixed metals with abnormal cardiac structure and function in CAD patients. Here, we aimed to investigate the associations of exposure to metal mixtures with cardiac structure and function and potential interactions in a CAD population. We conducted a cross-sectional study from Southwest China that included 1555 CAD patients. The blood concentrations of 14 metals were measured via inductively coupled plasma spectrometry. CAD was defined as at least one vessel having stenosis ≥50% the vessel diameter. Echocardiography was used for cardiac structural and functional measurements. Bayesian kernel machine regression was applied to explore the overall effect, metal weight, and dose effect. Linear regression analysis was used to analyze the effects of single metals, metal‒metal interactions and metal‒traditional interactions. Finally, we found that the negative associations of mixed metals with cardiac structure was significant when the levels of all metals were below the 60th percentile. For cardiac function, changes in metals from 50th to 75th were associated with 0.954% and 0.683% decrease in left ventricular ejection fraction and left ventricular fractional shortening, respectively. Negative associations of copper and manganese with cardiac structure and function, whereas positive associations of titanium, selenium and molybdenum with several parameters were found. Antagonistic interactions between copper and tin and between selenium and several metals (manganese, copper and aluminum) (all P interaction terms < 0.05) were found. In conclusion, mixed metal exposure was negatively associated with cardiac structure and function in CAD patients. The main metals contributing to this negative associations were copper and manganese. Selenium or tin supplementation may reduce the adverse associations of copper and manganese with cardiac structure and function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood., Methods: We investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype., Results: Carotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: -0.25, -0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: -0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: -0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively., Conclusions: We observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Bile acids (BAs) play a crucial role in lipid metabolism of children. However, the association between per- and polyfluoroalkyl substance (PFAS) exposure and BAs in children is scarce. To address this need, we selected 252 children from the Maoming Birth Cohort and measured 32 PFAS, encompassing short- and long-chain perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs) in the cord blood. Additionally, we analyzed nine primary and eight secondary BAs in the serum of three-year-old children. Generalized linear models with FDR-adjusted and Bayesian kernel machine regression (BKMR) were used to explore the associations of individual and mixture effects of PFAS and BAs. We found negative associations between cord blood long-chain PFCAs exposure and serum primary BAs in three-year-old children. For example, one ln-unit (ng/mL) increase of perfluoro-n-tridecanoic acid (PFTrDA), perfluoro-n-undecanoic acid (PFUnDA) and perfluoro-n-decanoic acid (PFDA) were associated with decreased taurochenodeoxycholic acid, with estimated percentage change of -24.28% [95% confidence interval (CI): -36.75%, -9.35%], -25.84% (95% CI: -39.67%, -8.83%), and -22.97% (95% CI: -34.45%, -9.47%) respectively. Notably, the observed associations were more pronounced in children with lower vegetable intake. Additionally, the BKMR model also demonstrated a monotonical decline in primary BAs as the PFAS mixture increased. We provided the first evidence of the association between intrauterine exposure to PFAS and its mixture with BAs in children. Further large-sample-size studies are needed to verify this finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing exposure to environmental chemicals calls for comprehensive non-targeted analysis to detect unrecognized substances in human samples. We examined human serum samples to classify compounds as endogenous or exogenous using public databases and to explore the relationships between exposure markers and metabolic patterns. Serum samples from 84 pregnant women at 32 weeks gestation were analyzed using LC-QToFMS. Using the PubChemLite for Exposomics database, we annotated and classified 106 compounds (51 endogenous, 55 exogenous). The compound patterns were analyzed using three dimensional reduction methods: Principal Component Analysis (PCA), regularized Generalized Canonical Correlation Analysis (rGCCA), and Uniform Manifold Approximation and Projection (UMAP). OPTICS clustering applied to these methods revealed two distinct clusters, with 89 % of significant compounds overlapping between clusters. The detected exogenous compounds included dietary substances, phthalates, nitrogenous compounds, and parabens. Pathway enrichment analysis showed that chemical exposure was linked to changes in amino acid metabolism, protein and mineral transport, and energy metabolism. While we found associations between exposure and metabolite changes, we could not establish causality. Our approach of analyzing both exogenous and endogenous chemicals from the same dataset using PubChemLite database presents a new method for exposome research, despite limitations in sample size and peak annotation accuracy. These findings contribute to understanding multiple chemical exposures and their metabolic effects in human biomonitoring., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akifumi Eguchi reports financial support was provided by Environmental Restoration and Conservation Agency. Akifumi Eguchi reports financial support was provided by Japan Society for the Promotion of Science. Chisato Mori reports financial support was provided by Japan Science and Technology Agency. Chisato Mori reports financial support was provided by Yamada Bee Company. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with half-lives in humans in the range of years in case of the long-chain compounds, leading to accumulation and measurable levels in plasma. In contrast, short-chain and "alternative" PFAS have lower levels or are not detectable in humans with background exposure. This may be due to lower exposure, but also due to much shorter half-lives compared to long-chain compounds. To get better data on kinetics, a healthy volunteer orally ingested a mixture of fifteen predominantly 13 C-labeled PFAS ("MPFAS") in a pilot investigation (MPFBA, MPFPeA, MPFHxA, MPFHpA, MPFOA, MPFNA, MPFDA, MPFUdA, MPFDoA, PFBS, MPFHxS, MPFOS, DONA, HFPO-DA, 6:2FTS). After application, concentrations were measured over 450 days in plasma, urine and feces, using UHPLC-MS/MS analysis after extraction. The compounds were absorbed quickly and almost completely. Data analysis revealed volumes of distribution between 110 and 177 mL/kg bw for most compounds, but higher values for MPFDA, MPFUdA and MPFDoA (maximum of 354 mL/kg bw). Half-lives were found to vary extremely, from 0.5 days (MPFPeA) and 1.5 days (MPFHxA) to 51 days (PFBS) and 152 days (MPFHpA) in case of the short-chain and "alternative" compounds. For the long-chain compounds, half-lives in the range of several years were confirmed for MPFOA, MPFNA, MPFHxS and MPFOS, but with even higher chain-lengths of the carboxylic acids, the half-lives were found to decrease, with the shortest half-life for MPFDoA (295 days). Elimination from the body was completely explained by the urinary losses in case of the short-chain and "alternative" PFAS, and in part by the fecal losses in case of the long-chain PFCA. Overall, elimination kinetics seem to be determined by several different renal and gastrointestinal factors (fraction unbound in plasma, binding affinity to organic anion transporters causing netto secretion or reabsorption, fecal loss with mechanisms to be clarified)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, β-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, β-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yudong Pu reports financial support was provided by Songshan Lake Central Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) have attracted increasing attention due to their persistence in the environment and potential adverse effects on human and animal health. The detection and quantification of PFASs in livestock could substantially contribute to monitoring their presence within the food chain. We developed a targeted quantification method for 34 PFASs in livestock serum by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). We used protein precipitation for serum sample extraction and accurate mass measurement of targeted PFAS compounds for quantification. We validated the method with various analytical parameters, achieving accuracy of 70-120% and precision of <20%. The method also demonstrated good analytical sensitivity, with a limit of detection of <0.051 ng/mL and a limit of quantification of <0.175 ng/mL. When applying the developed method to actual serum samples from a variety of livestock, we successfully identified and quantified various PFASs in different livestock species. Our method has the potential to be a valuable tool for veterinary laboratory analysis of PFAS contamination in livestock., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Longitudinal trends in per- and polyfluoroalkyl substances (PFAS) serum concentrations across pregnancy have not been thoroughly examined, despite evidence linking prenatal PFAS exposures with adverse birth outcomes., Objectives: We sought to characterize longitudinal PFAS concentrations across pregnancy and to examine the maternal-fetal transfer ratio among participants in a study of risk and protective factors for adverse birth outcomes among African Americans., Methods: In the Atlanta African American Maternal-Child cohort (2014-2020), we quantified serum concentrations of four PFAS in 376 participants and an additional eight PFAS in a subset of 301 participants during early (8-14 weeks gestation) and late pregnancy (24-30 weeks gestation). Among these, PFAS concentrations were also measured among 199 newborns with available dried blood spot (DBS) samples. We characterized the patterns, variability, and associations in PFAS concentrations at different time points across pregnancy using intraclass correlation coefficients (ICCs), maternal-newborn pairs transfer ratios, linear mixed effect models, and multivariable linear regression, adjusting for socioeconomic and prenatal predictors., Results: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) were detected in > 95 % of maternal samples, with PFHxS and PFOS having the highest median concentrations. We observed high variability in PFAS concentrations across pregnancy time points ( ICC = 0.03 - 0.59 ). All median PFAS concentrations increased from early to late pregnancy, except for PFOA and N-methyl perfluorooctane sulfonamido acetic acid (NMFOSAA), which decreased [paired t -test for all PFAS p < 0.05 except for PFOA and perfluorobutane sulfonic acid (PFBS)]. Prenatal serum PFAS were weakly to moderately correlated with newborn DBS PFAS ( - 0.05 < rho < 0.49 ). The median maternal-fetal PFAS transfer ratio was lower for PFAS with longer carbon chains. After adjusting for socioeconomic and prenatal predictors, in linear mixed effect models, the adjusted mean PFAS concentrations significantly increased during pregnancy, except for PFOA. In multivariable linear regression, PFAS concentrations in early pregnancy significantly predicted the PFAS concentrations in late pregnancy and in newborns., Discussion: We found that the concentrations of most PFAS increased during pregnancy, and the magnitude of variability differed by individual PFAS. Future studies are needed to understand the influence of within-person PFAS variability during and after pregnancy on birth outcomes. https://doi.org/10.1289/EHP14334.

Environmental exposure to toxic chemicals including cadmium (Cd), lead (Pb), and mercury (Hg), are known risk factors for cardiovascular (CVD) and kidney disease. In people living with HIV (PLWH), CVD and kidney disease are the leading cause of death. Neither traditional risk factors nor markers of HIV infection fully explain such an increased risk. It is of paramount importance to establish the epidemiology of toxic chemicals exposure in PLWH, to inform screening and prevention interventions in this vulnerable population. This cross-sectional study compares toxic chemical levels (T-Cd, T-Pb, and T-Hg) among PLWH and HIV-uninfected adults in Northwestern Tanzania. A total of 495 PLWH and 505 HIV-uninfected subjects were analyzed. Spearman's rank correlations were used to examine the relationship between toxic chemical elements by HIV status. Linear regression models were used to determine the association between exposures and outcomes of interest among study participants. In both PLWH and HIV-uninfected adults, blood T-Cd, T-Pb, and T-Hg levels were frequently found at levels above the reference value of 5, 50, and 20 μg/L, respectively. Overall, factors associated with blood toxic chemical levels included vegetable servings per week, obesity, untreated water sources, use of alcohol, and HIV. Among PLWH, weekly vegetable intake provided a protective effect against T-Cd (Coeff = -0.03, 95%CI = -0.06, -0.01) and T-Pb (Coeff = -0.05, 95%CI = -0.09, -0.01) exposure among PLWH. Alcohol intake (Coeff = 0.10, 95%CI = 0.06, 0.13), obesity (Coeff = 0.08, 95%CI = 0.02, 0.13), longer duration to indoor smoke exposure (Coeff = 0.003, 95%CI = 0.001, 0.004), and HIV infection (Coeff = 0.11, 95%CI = 0.07, 0.15) were associated with increased individuals blood T-Hg levels. Individuals in northwestern Tanzania, including PLWH, have high blood levels for T-Cd, T-Pb, and T-Hg. Factors associated with higher blood levels include water sources, obesity, use of alcohol, exposure to indoor smoke, and HIV infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Per- and poly-fluoroalkyl substances (PFAS), ubiquitous environmental pollutants, have been reported as possible contributors to human dyslipidemia. However, evidence for emerging PFAS remains scarce. Using a nested case-control study (n = 357) in a middle-aged and elderly population from Beijing, we investigated the serum concentrations of eight traditional and fourteen emerging PFAS and their potential links with dyslipidemia. Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were found to be the dominant PFAS. Serum levels of perfluorohexanesulfonic acid (PFHxS) and 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA/F53B) were associated with higher risk of elevated low-density lipoprotein cholesterol (LDL-C) with odds ratios (OR) of 3.88 (95% CI: 1.44-10.51) and 2.71 (95% CI: 1.11-6.57), respectively. These compounds also positively correlated with high total cholesterol (TC). PFOA, perfluorodecanoic acid (PFDA), and 6:2 Fluorotelomer phosphate monoester (6:2 PAP) were linked to increased risk of high triglycerides (TG) with OR of 2.79 (95% CI: 1.30-6.01), 2.41 (95% CI: 1.27-4.60), and 1.53 (95% CI: 1.05-2.22), respectively. Conversely, perfluorooctane sulfonamidoacetic acid (FOSAA) was negatively associated with high TG levels. These findings indicate that both traditional and emerging PFAS may induce dyslipidemia, emphasizing the potentially serious impact of emerging PFAS on human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Exposure to perfluoroalkyl substances (PFAS) are reported to have numerous negative health effects and children are especially vulnerable. The aim of this study was to investigate whether maternal and infant PFAS burden have any impact on prenatal and postnatal growth, liver and lipid parameters in infants at age six months. Data on diet and growth parameters, as well as blood samples were collected from healthy pregnant women in week 18 and in the women and their infants at six months postpartum. The blood samples were analysed for liver enzymes, blood lipids and PFAS. Maternal perfluoroalkyl carboxylic acids (PFCA) and fish for dinner ≥ 3 days per week in pregnancy week 18 were associated with reduced birth weight and increased percent weight gain the first six months of life. Infant PFCA concentrations were positively associated with serum alanine aminotransferase and total- and LDL-cholesterol concentrations at six months of age. Our data demonstrate that prenatal and postnatal PFAS exposure are associated with an unfavourable metabolic profile at a very young age. This pattern is concerning as it may be linked to early conditioning of later metabolic disease. It is vital to reduce PFAS exposure in women of fertile age in order to prevent development of metabolic disease in the next generation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants previously associated with elevated liver enzymes in human cohorts and steatotic liver disease in animal models. We aimed to evaluate the associations between PFAS exposures, and liver enzymes and vibration controlled transient elastography (VCTE) biomarkers of metabolic dysfunction associated steatotic liver disease (MASLD) in adult National Health and Nutrition Examination Survey (NHANES) 2017 to 2018. VCTE was determined by FibroScan. Serum PFAS (n = 14), measured by mass spectrometry, were analyzed individually and by principal component (PC). Univariate and multivariable associations were determined between PFAS exposures and liver disease outcome variables: alanine aminotransferase (ALT), controlled attenuation parameter (CAP), liver stiffness measurement (LSM), FibroScan-based Score (FAST), using R. About 1,400 participants including 50% women with a mean age of 48 ± 19 years and a mean BMI of 29 ± 7 kg/m2 were analyzed. Four PFAS clustered to PC1, whereas 3 PFAS clustered to PC2. PC1 was significantly associated with ALT (β = 0.028), CAP (β = 0.041), LSM (β = 0.025), and FAST (β = 0.198) in univariate analysis. Individual PFAS exposures were oftentimes inversely associated with these measurements in multivariate analysis. In adult NHANES 2017-2018, PFAS may not be a significant burden for MASLD, because of the inconsistent associations between the environmental PFAS exposures and biomarkers of liver steatosis, inflammation, and fibrosis. More data are required to better understand the relationships between PFAS exposures and liver disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in children. We hypothesized environmental toxins could drive progression to metabolic dysfunction-associated steatohepatitis (MASH), and assayed serum toxins and metabolites in children with histologically characterized MASLD/MASH., Methods: Environmental chemicals, common in household items, perfluoroalkyl substances (PFAS), polybrominated flame retardants (polybrominated diphenyl ethers [PBDEs]), and metabolic profiles were assayed in children enrolled in the multicenter NASH Clinical Research Network Pediatric Database 2. Mixture models, using repeated holdout weighted quantile sum regression (WQS rh ) were run in addition to single chemical/metabolite logistic regression. For metabolomic analyses, random subset version of WQS rh was used for the large number of predictors versus participants. Nominal and false discovery rate (FDR) p-values (two-sided) were computed., Results: Four hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Mean (standard deviation) for Nonalcoholic Steatohepatitis Score (NAS) and alanine aminotransferase (ALT) for MASLD were 3.1 (1.0), 67.9 (43.4), and for MASH 4.2 (1.4), 144 (121). There was an inverse association between PFAS/PBDE mixture and MASH versus MASLD, lobular inflammation (p = 0.026), NAS (p = 0.009, FDR p = 0.04), and log-transformed ALT (p = 0.005, FDR p = 0.025) driven by perfluorohexane sulfonate (PFHXS). Metabolites from positive hydrophilic interaction liquid chromatography mode, biliverdin (p = 0.002) and 1-methylhistidine (associated with meat ingestion, p = 0.02) and reverse phase negative mode, hippuric acid (solvent exposure, p = 0.022) significantly associated with MASH., Conclusions: Significant negative PFAS/PBDE mixture effect and odds of MASH were dominated by PHFXS. Several metabolites are significantly associated with MASH which inform mechanistic pathways and could drive key therapeutic and diagnostic strategies in children., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous chemicals routinely detected in personal care products (PCPs). However, few studies have evaluated the impact of PCP use on PFAS concentrations in pregnant and lactating populations., Objective: We investigated associations between PCP use and PFAS concentrations in prenatal plasma and human milk., Methods: We leveraged the Maternal-Infant Research on Environmental Chemicals (MIREC) Study to evaluate the contribution of PCP use on PFAS concentrations in prenatal plasma (6 to 13 weeks' gestation; n = 1,940) and human-milk (2 to 10 weeks' postpartum; n = 664). Participants reported frequency of use across 8 PCP categories during the 1st and 3rd trimesters, 1 to 2 days postpartum, and 2 to 10 weeks' postpartum. We used adjusted linear regression models to quantify percent differences and corresponding 95 % confidence intervals., Results: In 1st trimester pregnant people, we found higher use of nailcare products (≥once a week vs. never: perfluorooctanoic acid (PFOA): 21 % [9.7 %, 32 %]; perfluorooctane-sulfonic acid (PFOS): 11 % [0.3 %, 23 %]), fragrances (daily vs. never: PFOA: 14 % [7.8 %, 21 %]; PFOS: 7.8 % [1.3 %, 15 %]), makeup (daily vs. never: PFOA: 14 % [5.8 %, 23 %]), hair dyes (never vs. 1-2 times during pregnancy: PFOA: 8.3 % [2.4 %, 15 %]), and hair sprays or gels (daily vs. never: PFOA: 12 % [5.0 %, 19 %], PFOS: 7.1 % [0.2 %, 15 %]) were associated with higher plasma PFAS concentrations. Similar results were observed for 3rd trimester PCP use and 2 to 10 weeks' postpartum human-milk PFAS concentrations. In addition, we also found that people using colored-permanent dye 1 to 2 days postpartum had higher Sm-PFOS (18 % [2.7 %, 35 %]), PFOA (16 % [4.3 %, 29 %]), and perfluorononanoic acid (17 % [3.6 %, 33 %]) postpartum human-milk concentrations., Conclusions: Our results show that PCP use may be a modifiable source of PFAS exposure in pregnant and lactating populations. These results along with growing scientific evidence can help inform PFAS regulation and guide individual choices to reduce PFAS exposure., Competing Interests: Declaration of competing interest Dr. Joseph Braun was compensated for serving as an expert witness on behalf of plaintiffs in litigation related to PFAS-contaminated drinking water. No other authors have any conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The ubiquity of Per- and polyfluoroalkyl substances (PFAS) in various consumer and industrial products poses a significant public health challenge, but effective strategies to reduce human exposure to PFAS are limited., Objectives: This study aims to evaluate the association between dietary patterns, specifically low-salt diets and salt-free cooking, and serum PFAS levels in the general population., Methods: The study analyzed data from 11,137 participants from the National Health and Nutrition Examination Survey (NHANES) using weighted linear regression. We assessed associations between low-salt or low-sodium dietary patterns and the way salt was used during cooking or food preparation and serum levels of five highly detectable PFAS compounds: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). Since consuming fish and shellfish is a major source of PFAS exposure in humans, the intake status of these foods was adjusted for in the sensitivity analysis. Additionally, other sensitivity analyses, including propensity score matching, were conducted., Results: The analyses showed a significant negative association between low-salt or low-sodium diet and serum levels of the five PFAS compounds. In contrast, regular use of salt in cooking or food preparation was significantly and positively associated with higher serum levels of PFAS. These findings were consistent across all models. Also consistent were the results of sensitivity analyses based on participants' consumption of fish and shellfish and propensity score matching., Conclusions: Low-salt or low-sodium dietary patterns, and salt-free cooking may be are associated with a reduced risk of PFAS exposure in the general population. While this study offers new insights into mitigating PFAS exposure, further validation in additional datasets is necessary, along with confirmation through intervention studies designed based on this hypothesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Perfluoroalkyl and polyfluoroalkyl(PFAS) substances are the most common environmental pollutants, which has an inconsistent association with hyperuricemia across different populations. This study explored the relationship between hyperuricemia and different gender PFAS and PFAS mixtures, using data from two cycles of the NHANES from 2015-2018. Weighted logistic regression results showed that the correlation between individual PFAS and hyperuricemia was significant only in men. Compared to the reference quartile, the fourth quartile of n-PFOA increased the risk of hyperuricemia in men (OR: 2.79, 95% CI: 1.50, 5.18). The Qgcomp model results showed that each quartile increase in the serum concentration of PFAS mixtures was associated with an increased likelihood of hyperuricemia in the total population, with odds ratios (OR) for men and women being 1.74 (95% CI: 1.26, 2.40), and 2.04 (95% CI: 1.35, 3.16), respectively. we concluded that PFAS might increase the risk of hyperuricemia in adults.

Per- and polyfluoroalkyl substances (PFAS) are known as persistent and bioaccumulative chemicals. The present paper describes the analysis of 969 human blood samples collected in South Germany aiming to determine whether there are statistic significant differences in internal PFAS burden between three regions with known PFAS releases in the environment (study regions) and three regions without known PFAS releases in the environment (control regions). Nine environmental relevant PFAS were analyzed, including the perfluorooctanoic acid (PFOA) substitute 3H-perfluoro-3-[(3-methoxy-propoxy)propanoic acid] ammonium salt (ADONA). We found that concentrations of PFOA and perfluorooctane sulfonate (PFOS) were higher than for all other PFAS in all of the six regions, but all medians of PFOA (between 0.8 and 0.9 ng/ml for the study and control regions) and PFOS (between 1.3 and 1.5 ng/ml for the study regions and between 1.4 and 1.5 ng/ml for the control regions) were below the human biomonitoring values (HBM) I for PFOA (2 ng/ml) und for PFOS (5 ng/ml) derived by the German HBM Commission. Concentrations of ADONA were below the limit of quantification in all samples. Minor differences were observed in PFAS blood levels between study and control regions. Especially for PFOS and PFOA the medians for women are slightly lower compared to men. In summary, individuals living in regions with known environmental PFAS contaminations show no higher internal PFAS exposure to controls and in comparison to other studies in the literature., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Over the years eastern Slovakia has been subject to consistent monitoring of high levels of polychlorinated biphenyls (PCBs) in both the environment and human populations attributed to the former production of PCBs at the Chemko Strážske plant. We aimed to investigate the extent to which dietary habits and residential location could affect the concentrations of PCBs in the blood serum samples of subjects., Methods: We enrolled 602 adult subjects from eastern Slovakia with an average age of 45.14 (±8.49) years. To determine the concentrations of 21 PCB congeners, we used solid phase extraction along with gas chromatography coupled with high-resolution mass spectrometry. Based on questionnaire data, the assessment of dietary habits and residential location was performed using score calculations and creating a map., Results and Discussion: Through principal component analysis, the 20 PCB congeners were classified into three groups: PC1, comprising highly chlorinated PCBs, and PC2 and PC3, consisting primarily of low chlorinated PCBs. Stepwise multivariate regression revealed positive and negative associations between PCB congeners represented by PC1-3 and scores related to the residential location and scores related to food consumption, respectively. We confirmed that levels of PCBs represented by PC1-3 increased with age. The geographical proximity to pollution sources proved to be a key contributing factor to the observed PCB levels in individuals residing in eastern Slovakia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hlisníková, Kolena, Trnovec, Richterová Bagratuni, Patayová, Čonka, Drobná, Rausová, Tihányi, Wimmerová, Petrovičová, Nagyová and Palkovičová Murínová.)

Background: The developing kidney is vulnerable to prenatal environmental factors such as metal exposure, potentially altering the risk of later-life kidney dysfunction. This study examines the relationship between prenatal metal exposures, individually and as mixtures, and adolescent kidney function in Project Viva, a prospective longitudinal birth cohort in Massachusetts, USA., Methods: We used data on metals measured in blood during pregnancy including 15 in the first trimester and four in the second trimester. We calculated estimated glomerular filtration rate (eGFR) in adolescents (mean: 17.7 years) using cystatin C- (eGFRcys) and creatinine-based (eGFRcreat) equations for children. We used linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses, adjusting for relevant covariates. To account for multiple comparisons in the single metal analyses, we applied the Holm-Bonferroni procedure to control the false discovery rate., Results: This study included 371 participants with first trimester metals and adolescent eGFR, and 256 with second trimester metals. Each doubling in first trimester cadmium concentration was associated with lower adolescent eGFRcys (β:-1.51; 95% CI:-2.83, -0.18). Each doubling in first trimester chromium (β:-1.45; 95% CI:-2.71, -0.19), nickel (β:-1.91; 95% CI:-3.65, -0.16), and vanadium (β:-1.69; 95% CI:-3.21, -0.17) was associated with lower adolescent eGFRcreat. After adjusting for multiple comparisons, p-values for associations between adolescent eGFR and chromium, nickel, vanadium and cadmium did not meet the criteria for significance. Metal mixture analyses did not identify statistically significant associations with adolescent eGFR., Conclusions: These findings have important implications for future studies investigating the potential mechanisms through which prenatal metal exposures affect long-term kidney health in children., (© 2024. The Author(s).)

Current-use pesticides (CUPs), including insecticides, fungicides, and herbicides, are extensively employed in agriculture to manage pests, diseases, and weeds. Nonetheless, their widespread application raises significant concerns regarding potential impacts on human health, particularly with reproductive health. This study focuses on exploring the landscape of CUP exposure among pre-pregnancy women. Based on a cohort study comprising 354 pre-pregnancy women of reproductive age in Beijing, China, we measured the concentrations of 94 CUPs in serum and conducted an in-depth analysis of exposure profiles, health risks, and contributing factors. The results revealed that the serum of pre-pregnancy women was contaminated with CUPs, of which the median concentrations ranged from 0.114 (fenamiphos-sulfone) to 61.2 ng/L (mefenacet). Among the 94 CUPs, 54 exhibited detection rates higher than 50 %, including 26 insecticides, 14 fungicides, and 14 herbicides. The exposure concentration profile highlighted that the insecticides contributed 56 % to the total CUP concentration percentages, with organophosphate insecticides being the primary contributors within this category (63.0 %). The average daily intake (ADI) of CUPs ranged from 2.23 to 16,432.28 ng/kg, while diflubenzuron had the highest ADI. Health risk assessments showed that exposure to a combination of total insecticides or herbicides poses a moderate risk for 15.8 % and 30.2 % of women, with mefenacet being the most significant, which showed moderate hazard in 29.4 % of participants. The overlap analysis showed that methiocarb-sulfone, diflubenzuron, and mefenacet were the dominant pesticides. In addition, maternal age, annual income level, smoking, and vitamin B12 supplementation were associated with serum CUP concentrations. Our study contributes a novel and comprehensive exposure profile of CUPs in pre-pregnancy women in northern China, providing valuable insights for evaluating the potential consequences of pre-pregnancy exposure on reproductive health. SYNOPSIS: We provided a comprehensive exposure landscape, health effects, and influential factors of 94 current-use pesticides among pre-pregnancy women in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread and excessive use of pesticides in modern agricultural practices has caused pesticide contamination of the environment, animals, and humans, with confirmed serious health consequences. This study aimed to identify the 20 most critical substances based on an analysis of detection frequency (DF) and median concentrations (MC) across environmental and biological matrices. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina, each encompassing conventional and organic farming systems. We analysed 209 active substances in a total of 4609 samples. All substances ranked among the 20 most critical were detected in silicon wristbands worn by humans and animals and indoor dust from both farming systems. Five of them were detected in all environmental matrices. Overall, higher values of DF and MC, including in the blood plasma of animals and humans, were recorded in samples of conventional compared to organic farms. The differences between farming systems were greater in the environmental samples and less in animal and human samples. Ten substances were detected in animal blood plasma from conventional farms and eight in animal blood plasma from organic farms. Two of those, detected in both farming systems, are classified as hazardous for mammals (acute). Five substances detected in animal blood plasma from organic farms and seven detected in animal blood plasma from conventional farms are classified as hazardous for mammals (dietary). Three substances detected in human blood plasma are classified as carcinogens. Seven of the substances detected in human blood plasma are classified as endocrine disruptors. Six substances, of which five were detected in human blood plasma, are hazardous for reproduction/development. Efforts are needed to elucidate the unknown effects of mixtures, and it is crucial that such research also considers biocides and banned substances, which constitute a baseline of contamination that adds to the effect of substances used in agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Endocrine function in patients with type 2 diabetes (T2DM) typically differs from those with normal glucose tolerance (NGT). However, few epidemiologic studies have explored how these differences impact the association between exposure to polychlorinated biphenyls (PCBs) and vitamin D levels., Methods: This study included 1,705 subjects aged 18-79 years from the Henan Rural Cohort [887 NGT and 818 T2DM]. Linear regression was applied to evaluate the associations between PCB exposure and vitamin D levels. Quantile g-computation regression (QG) and Bayesian kernel machine regression (BKMR) were applied to evaluate the impact of PCB mixtures on vitamin D levels. Interaction effects of ΣPCBs with HOMA2-%β and HOMA2-IR on vitamin D levels were assessed., Results: Plasma ΣPCBs was positively associated with 25(OH)D2 in the NGT group (β = 0.060, 95% CI: 0.028, 0.092). Conversely, in T2DM group, ΣPCBs was negatively associated with 25(OH)D3 and 25(OH)D (β = -0.049, 95% CI: -0.072, -0.026; β = -0.043, 95% CI: -0.063, -0.023). Similarly, both QG and BKMR analysis revealed a negative association between PCB mixture exposure and vitamin D levels in the T2DM group, contrary to the results observed in the NGT groups. Furthermore, the negative association of ΣPCBs with 25(OH)D2 and 25(OH)D disappeared or changed to a positive association with the increase of HOMA2-%β levels., Conclusions: These findings suggest that decreased β cell function may exacerbate the negative effects of PCB exposure on vitamin D levels. Recognizing T2DM patients' sensitivity to PCBs is vital for protecting chronic disease health., (© 2024. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that persist in the environment and can accumulate in humans, leading to adverse health effects. MicroRNAs (miRNAs) are emerging biomarkers that can advance the understanding of the mechanisms of PFAS effects on human health. However, little is known about the associations between PFAS exposures and miRNA alterations in humans., Objective: To investigate associations between PFAS concentrations and miRNA levels in children., Methods: Data from two distinct cohorts were utilized: 176 participants (average age 17.1 years; 75.6% female) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort in the United States, and 64 participants (average age 6.5 years, 39.1% female) from the Rhea study, a mother-child cohort in Greece. PFAS concentrations and miRNA levels were assessed in plasma samples from both studies. Associations between individual PFAS and plasma miRNA levels were examined after adjusting for covariates. Additionally, the cumulative effects of PFAS mixtures were evaluated using an exposure burden score. Ingenuity Pathways Analysis was employed to identify potential disease functions of PFAS-associated miRNAs., Results: Plasma PFAS concentrations were associated with alterations in 475 miRNAs in the Teen-LABs study and 5 miRNAs in the Rhea study (FDR p < 0.1). Specifically, plasma PFAS concentrations were consistently associated with decreased levels of miR-148b-3p and miR-29a-3p in both cohorts. Pathway analysis indicated that PFAS-related miRNAs were linked to numerous chronic disease pathways, including cardiovascular diseases, inflammatory conditions, and carcinogenesis., Conclusion: Through miRNA screenings in two independent cohorts, this study identified both known and novel miRNAs associated with PFAS exposure in children. Pathway analysis revealed the involvement of these miRNAs in several cancer and inflammation-related pathways. Further studies are warranted to enhance our understanding of the relationships between PFAS exposure and disease risks, with miRNA emerging as potential biomarkers and/or mediators in these complex pathways., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vaia Lida Chatzi reports financial support was provided by The National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics., Methods: We conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998-2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline-June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption)., Results: Prostate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88-1.59)] and PFOS [HR (95% CI): 1.18 (0.89-1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02-2.31) and PFOS 1.62 (1.08-2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage., Conclusions: Our findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response., Objective: We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion., Methods: We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers., Results: Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively., Conclusions: Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited., Objectives: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar., Methods: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels., Results: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 μg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 μg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 μg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72)., Discussion: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitously environmental contaminant, leads to the development of major toxic effects on human health, such as carcinogenic and immunosuppressive alterations reported for the most studied PAH, i.e., benzo(a)pyrene (B(a)P). In order to assess the risk associated with this exposure, it is necessary to have predictive biomarkers. Thus, extracellular vesicles (EVs) and their microRNA (miRNA) contents, have recently been proposed as potentially interesting biomarkers in Toxicology. Our study here explores the use of vesicles secreted and found in blood fluids, and their miRNAs, as biomarkers of exposure to B(a)P alone and within a realistic occupational mixture. We isolated EVs from primary human cultured blood mononuclear cells (PBMCs) and rat plasma after PAH exposure and reported an increased EV production by B(a)P, used either alone or in the mixture, in vitro and in vivo. We then investigated the association of this EV release with the blood concentration of the 7,8,9,10-hydroxy (tetrol)-B(a)P reactive metabolite, in rats. By performing RNA-sequencing (RNA-seq) of miRNAs in PBMC-derived EVs, we analyzed miRNA profiles and demonstrated the regulation of the expression of miR-342-3p upon B(a)P exposure. We then validated B(a)P-induced changes of miR-342-3p expression in vivo in rat plasma-derived EVs. Overall, our study highlights the feasibility of using EVs and their miRNA contents, as biomarkers of PAH exposure and discusses their potential in environmental Toxicology., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lydie SPARFEL reports financial support was provided by National Agency for Food Environmental and Occupational Health and Safety. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Concentrations of plasma per and poly-fluoroalkyl substances (PFAS) are elevated in the Inuit population of Nunavik and may be causing adverse health effects. Respiratory health outcomes have been associated with PFAS, but have not been explored in Inuit communities. The aim of the study was to examine the association between PFAS and respiratory health outcomes, and the moderating role of nutritional biomarkers., Methods: We included up to 1298 participants of the Qanuilirpitaa? 2017 survey aged 16-80 years. Generalized regression models were used to estimate the associations between six individual PFAS congeners and four self-reported symptoms, four spirometry measures, and physician-diagnosed asthma. Outcomes associated with PFAS from single chemical models were further explored using Bayesian Kernel Machine Regression (BKMR). The modifying effect of n-3 PUFA in red blood cell quartiles and vitamin D deficiency were examined on the associations between PFAS and respiratory outcomes., Results: PFNA and PFOS were associated with asthma (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12, 2.32; OR 1.45 95% CI 1.04, 2.03). PFOA, PFNA, PFDA and PFHxS were associated with a decrease in the ratio between the forced expiratory volume in the first second and forced vital capacity (FEV1/FVC). No associations were observed with self-reported respiratory symptoms. No associations were observed between a PFAS mixture and asthma. Some associations were modified by nutritional factors, namely, stronger associations between PFOA and PFHxS and asthma with lower n-3 PUFA levels and stronger associations between PFDA, PFUnDA and PFOS and FEV1/FVC with vitamin D deficiency., Conclusion: These findings add to the growing literature on the impacts of PFAS on respiratory health, and the importance of their global regulation. Associations were modified by nutritional factors pointing to the nutritional value of traditional Inuit foods., (© 2024. The Author(s).)

Background: Research on the correlation between exposure to per- and polyfluoroalkylated substances (PFASs)/heavy metals and bone health during childhood and adolescence is limited. Considering their role as endocrine disruptors, we examined relationships of six PFASs and three heavy metals with bone mineral density (BMD) in children and adolescents using representative samples from the National Health and Nutrition Examination Survey (NHANES)., Methods: The study included 622 participants aged 12-19. The relationship between single pollutant and lumbar spine and total BMD was studied using linear regression analyses. Additionally, Bayesian Kernel Machine Regression (BKMR) models were applied to assess the joint effects of multiple PFASs and heavy metals exposure on the lumbar spine and total BMD., Results: Statistically significant differences were noted in the serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), blood lead (Pb), and blood manganese (Mn) between male and female participants (all p < 0.05). Single-exposure studies have shown that Mn was negatively correlated with lumbar spine BMD and total BMD. Multivariate linear regression models revealed that, in the male group, total bone density decreased as the blood PFOA levels [95% CI = (-0.031, -0.001), p = 0.040] and blood manganese levels [95% CI = (-0.009, -0.002), p = 0.004] increased. Similarly, lumbar spine bone density decreased as the blood manganese levels [95% CI = (-0.011, -0.002), p = 0.009] increased. In the female group, total bone density decreased as the serum PFNA levels [95% CI = (-0.039, 0.000), p = 0.048] increased. As shown in the BKMR model, the joint effects of pollutant mixtures, including Mn, were negatively associated with both the lumbar spine and total BMD. Among the pollutants analyzed, Mn appeared to be the primary contributor to this negative association., Conclusion: This study suggests that exposure to certain PFASs and heavy metals may be associated with poor bone health. Childhood and adolescence are crucial stages for bone development, and improper exposure to PFASs and heavy metals during these stages could potentially jeopardize future bone health, consequently raising the risk of osteoporosis in adulthood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Zhang, Ji, Yang and Yang.)

Background: Although studies have assessed the association of metals and bisphenols with lipid metabolism, the observed results have been controversial, and limited knowledge exists about the combined and interactive effects of metals and bisphenols exposure on lipid metabolism., Methods: Plasma metals and serum bisphenols concentrations were evaluated in 888 participants. Multiple linear regression and logistic regression models were conducted to assess individual associations of 18 metals and 3 bisphenols with 5 lipid profiles and dyslipidemia risk, respectively. The dose-response relationships of targeted contaminants with lipid profiles and dyslipidemia risk were captured by applying a restriction cubic spline (RCS) function. The bayesian kernel machine regression (BKMR) model was used to assess the overall effects of metals and bisphenols mixture on lipid profiles and dyslipidemia risk. The interactive effects of targeted contaminants on interested outcomes were explored by constructing an interaction model., Results: Single-contaminant analyses revealed that exposure to iron (Fe), nickel (Ni), copper (Cu), arsenic (As), selenium (Se), strontium (Sr), and tin (Sn) was associated with elevated lipid levels. Cobalt (Co) showed a negative association with high density lipoprotein cholesterol (HDL-C). Bisphenol A (BPA) and bisphenol AF (BPAF) were associated with decreased HDL-C levels, with nonlinear associations observed. Vanadium (V), lead (Pb), and silver (Ag) displayed U-shaped dose-response relationships with most lipid profiles. Multi-contaminant analyses indicated positive trends between contaminants mixture and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C). The interaction analyses showed that Se-Fe exhibited synergistic effects on LDL-C and non-HDL-C, and Se-Sn showed a synergistic effect on HDL-C., Conclusions: Our study suggested that exposure to metals and bisphenols was associated with changes in lipid levels, and demonstrated their combined and interactive effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified., Methods: We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol., Results: The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports., Conclusions: Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature., Competing Interests: Competing interests: Support sources: This work was supported by 3M. 3M previously used PFOA, PFHxS, and precursors to PFOS in manufacturing, and has more recently used perfluorobutanesulfonyl fluoride (PBSF), which can degrade to perfluorobutanesulfonate (PFBS). Role of sponsor or funder: 3M requested a scoping review of gestational diabetes mellitus and PFAS but was not involved in the preparation of the manuscript. The authors retained sole control of the manuscript content and the findings, and statements in this paper are those of the authors and not those of the funder, the author’s employer, or the sponsors. No authors were directly compensated by 3M. This project was funded through a contract between 3M and Ramboll U.S. Consulting, Inc., an international science and engineering company that provided compensation to the authors. None of the authors are currently engaged to testify as experts in litigation related to the compounds discussed in this manuscript, nor have they done so in the past. Authors’ conflicts of interest: GA, SH and FS declared they have no conflicts of interest. AKP and MPL work for Ramboll U.S. Consulting, Inc., which has a contract with 3M. See sections on support sources and role of sponsor or funder for more information., (Copyright: © 2024 Aali G et al.)

Polychlorinated biphenyls (PCBs) and their metabolites are linked to developmental neurotoxicity, but their levels in the gestational and lactational environment remain unexplored. This study investigated the effects of dietary exposure to the Fox River Mixture (FRM) on serum levels of PCBs and their metabolites in female C57BL/6 J mice. Mice were exposed to 0.1, 1.0, or 6.0 mg/kg body weight/day of FRM beginning two weeks before mating and throughout gestation and lactation. Serum samples collected from the dams at weaning were analyzed using gas chromatograph-tandem mass spectrometry and nontarget liquid chromatography-high resolution mass spectrometry. Results showed complex and dose-dependent differences in PCB and metabolite profiles. Untargeted metabolomics revealed alterations in metabolites involved in glucuronidation. Network analysis suggested disturbances in heme and amino acid metabolism associated with higher chlorinated PCBs. These findings suggested that PCBs and metabolites present in the gestational and lactation environment of mice may contribute to developmental neurotoxicity in rodents., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Pamela J. Lein reports a relationship with Friedman Rubin (Seattle, WA) that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: Lead (Pb) is a toxic heavy metal and pervasive environmental contaminant, and a class 2 A carcinogen according to the IARC classification, yet its link with cancer at several body sites remains uncertain. Here, we aimed at summarizing the scientific evidence regarding its association with cancer risk and mortality, focusing on studies that carried out Pb measurements in biological samples., Methods: We reviewed articles published in PubMed and EMBASE until January 2nd, 2024, that quantified the epidemiological association between Pb measured in blood, urine, nails, and other biological media, and cancer risk and mortality (overall and by cancer site/type)., Results: We included 46 articles (out of 8022 screened) published in 1995-2023 and reporting on investigations conducted in fifteen countries. In terms of design, 20 were prospective, 24 were retrospective case-control studies, and 2 were cross-sectional. Pb levels were determined in blood in the majority of studies (n=28). The most consistent evidence was for the association of Pb with cancer of the gastrointestinal tract, particularly the oesophagus, stomach (RR ranging from 0.80 to 2.66), colon-rectum, and pancreas; and of the bladder and urinary tract (RR from 1.10 to 2.89). For other specific malignancies, the data were conflicting or too limited to draw reliable conclusions. Finally, increased Pb concentration in blood and urine was consistently associated with higher overall cancer incidence and mortality., Conclusions: Lead is a widespread and highly persistent environmental pollutant associated with cancer at multiple body sites. Comprehensive primary prevention interventions aiming at reducing opportunities for Pb exposure need to be continuously promoted and implemented., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metal exposure has been reported to be associated with metabolic syndrome (MetS), however, the evidence remains inconclusive, particularly in elderly individuals. From May to July 2016, serum levels of 16 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) in 852 elderly individuals (≥65 years) residing in Wuhan, China. Biological detection and disease recognition were based on individual surveys conducted during health check-ups. Spearman's rank correlation analysis was performed to identify the correlation among serum metals. The data were Ln-transformed to fit a normal distribution for further analyses. Linear and logistic regression were applied to explore the associations between metals and diseases. Restricted cubic spline (RCS) analysis was utilized to examine dose-response relationships. The Weighted Quantile Sum (WQS) score was applied to determine the empirical weights of each heavy metal in the context of their combined effect on metabolic diseases. The prevalence of MetS, hypertension, diabetes, and hyperlipidemia were 46.36 %, 68.90 %, 24.65 %, and 21.60 %, respectively. Serum metal mixture was positively associated with the prevalence of MetS (OR = 1.92, 95 % CI: 1.30-2.82), hypertension (OR = 1.50, 95 % CI: 1.01-2.23), and diabetes (OR = 2.18, 95 % CI: 1.48-3.22). In single metal models, we found that serum zinc levels were associated with an increased risk of MetS, while rubidium had a protective effect against MetS. Interestingly, different metals had distinct effects on specific diseases in this study: lithium and barium were more likely to influence blood pressure, while selenium had a more significant effect on blood glucose. Lipids were more susceptible to the effects of zinc, selenium, and strontium. Platelet count (PLT) and lymphocyte count (LYM) mediated the association between selenium exposure and hyperlipidemia, while neutrophil count (NEU) mediated the relationship between serum rubidium exposure and MetS. Our findings offer valuable etiological insights into the relationship between serum heavy metals and the prevalence of MetS, suggesting that peripheral blood cells may play a mediating role in this association., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhang rong reports financial support was provided by National Natural Science Foundation of China. Pang yaxian reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Many epidemiological studies use a single blood sample per participant to assess exposure, but it is unclear how well a single sample represents longer term exposure. We performed a simulation study using summary statistics for repeated serum PFOA measurements from several previous studies in men to generate plausible serum concentrations over time, taking within-subject correlations into account. Simulated serum concentrations for controls were categorized into quintiles at each time point, and used to determine the extent of misclassification at each time point compared to the "true" long-term average exposure. We then generated case counts by quintile needed to produce an odds ratio (OR) of 1.5 for the highest vs. lowest quintile categorized based on long term exposure, and used the same misclassification rates observed in the controls to simulate misclassified exposure quintiles for cases. Comparing long term vs. single baseline exposure measures for repeated serum samples collected within about 5-13 years of each other revealed similar effect estimates, although there was a small bias to the null. Trend tests across quintiles were mostly significant using either baseline or long-term exposure. For the general population sample of men in Norway, with 5 repeated measurements over 28 years, serum PFOA was substantially lower prior to 1987, and using either of the two earliest samples as the exposure metric, compared to the long term average, produced larger bias to the null and non-significant trend tests; however using later time points as the exposure metric resulted in only a small bias. Using data based on studies of men, single baseline serum samples represented rather well the mean of repeated samples collectedup to 13 years apart, but were not always reliable surrogates for average exposure over 3 decades, during which time PFOA exposure levels in the general population have changed substantially., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Scott M. Bartell has served as a compensated expert witness for PFOA medical monitoring lawsuits in New Hampshire. The terms of this arrangement were reviewed and approved by the University of California, Irvine in accordance with its conflict-of-interest policies. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A growing percentage of diabetes-related deaths has been attributed to cancer, with environmental factors playing important contributions. Thus, we studied the potential relationship between endocrine disruptors polychlorinated biphenyls (PCBs) and cancer risk in diabetes. We aimed to evaluate the association between serum seven indicator-PCB (PCB-28/52/101/118/138/153/180) levels and incident cancer, and further explore the possible modifying role of lifestyle. A total of 2806 type 2 diabetes mellitus (T2DM) cases were included from the Dongfeng-Tongji cohort at the baseline in 2008 and tracked until December 2018, and 320 incident cancers were identified during about 10-year follow-up. Cox proportional hazards models and competing risk regression models were used to reveal associations of baseline concentrations of PCBs with total cancer and specific cancer, respectively. Lifestyle score was determined by body mass index, waist circumference, physical activity, smoking, alcohol drinking, and diet. Each interquartile range (IQR) increment of non-dioxin-like PCBs (NDL-PCBs) generated an 8%-30% increase in cancer incidence. Individuals in the highest quartile for PCB-52, PCB-101, PCB-138, and lowly chlorinated PCBs had 1.44- to 1.68-fold higher cancer risk compared to those in the lowest quartile. Restricted cubic spline analyses and the quantile g-computation model showed similar results. Significant interactions were found between PCBs and fasting blood glucose or simplified insulin resistance assessment indicators. NDL-PCBs were positively and significantly associated with gastrointestinal cancer and respiratory cancer, especially with liver cancer, colorectal cancer, and lung cancer. Higher PCBs showed a significant increase in total cancer risk among participants with an unhealthy lifestyle, however, no associations were observed in those with a relatively healthy lifestyle (P interaction < 0.05). Our findings indicated an increased cancer risk associated with NDL-PCBs, highlighted the role of a healthy lifestyle in potentially reducing adverse impact, and provided preliminary data for environmental and public health interventions to alleviate the risk of cancer among diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55-93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; P trend  = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; P trend  = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR <1997  = 1.00, 95 % CI = 0.82, 1.21; OR ≥1997  = 0.65, 95 % CI = 0.53, 0.79; P interaction  = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead., Objectives: We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase ( MTHFR ) 677C>T genotype., Methods: We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between log 2 -transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression., Results: Third-trimester BLLs were associated with increased SRS-2 scores [ β a d j = 3.3 ; 95% confidence interval (CI): 1.1, 5.5] among participants with low ( < 10 th percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null ( β a d j = - 0.3 ; 95% CI: - 1.2 , 0.5) among those in the middle category ( ≥ 10 th and < 80 th percentiles) ( p -interaction < 0.001 ). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP ( β a d j = 0.9 ; 95% CI: - 1.2 , 3.1) than those without the T allele ( β a d j = - 0.3 ; 95% CI: - 1.3 , 0.7), but the difference was not statistically significant ( p -interaction = 0.28 )., Discussion: Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.

Background: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited., Objective: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents., Methods: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively., Results: The multivariable-adjusted β-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted β = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all P interation  < 0.001)., Conclusion: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9-16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure., Methods: Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately., Results: Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8-10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models., Conclusion: This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data., (© 2023. The Author(s).)

Increased cardiometabolic risk is associated with abnormalities in blood biomarkers profile and adiposity measurements. Some substances found in the food matrix and the environment, called endocrine-disrupting chemicals, may impair cardiometabolic health in the early and later stages of life. Bisphenol A (BPA) is a food contaminant that migrates from food contact materials and may act as an endocrine disruptor, negatively affecting human health. The present work aims to longitudinally assess the association between BPA exposure and cardiometabolic outcomes, considering data from Portuguese population-based birth cohort Generation XXI. Blood insulin (0.06stdβ; 95 %CI:0.03,0.09) and insulin resistance (0.05stdβ; 95 %CI:0.02,0.08) presented a significant longitudinal association with BPA daily exposure after adjustment for important variables and energy. The same findings were observed for fat mass (0.03stdβ; 95 %CI 0.01,0.06) and waist circumference (0.06stdβ; 95 %CI:0.04,0.08). For z-BMI, a significant cross-sectional (0.03stdβ; 95 %CI:0.01,0.04) and longitudinal (0.02stdβ; 95 %CI:0.00,0.04) association was found. This was the first study assessing the association between BPA exposure and health outcomes from childhood to adolescence. We found an association between BPA exposure and increased blood insulin level, insulin resistance, fat mass percentage, waist circumference and z-BMI. Our results point to the need to reduce exposure to BPA in the early stages of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)