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Heavy metals in our direct environment have profound effects on human health and while some are essential for life, others can be toxic. In vivo studies often focus on clinical features caused by overexposure to, or by deprivation of a heavy metal. However, to understand the cellular impact of heavy metals on health, studies in healthy volunteers before symptom onset are needed. Here, we explored the impact of mercury, lead and selenium in over 800 British female twins on multi-tissue gene expression levels as an intermediate phenotype. Total mercury, lead and selenium concentrations were determined in plasma as a proxy for heavy metal exposure. We identified significant associations between total mercury levels measured in plasma, that fall within normal ranges, and expression of 873 genes within skin tissue, including PUSL1, SAMD10, ERCC1, MRPL17, NDUFB8, SELENOH, SEC31A, and KAT7P1. Functional analysis of genes associated with total mercury levels in plasma show a strong link to the mitochondrial oxidative phosphorylation pathway (p-value = 3.02 × 10 -10 ). Analysis of mitochondrial-specific gene expression supported involvement of genes of oxidative phosphorylation complexes (MT-ND4L, and MT-ND5), which are encoded in mitochondrial DNA. These results suggest that mercury is likely detrimental to the energy metabolism of mitochondria. We also tested for associations between total mercury levels in plasma and gene expression in adipose and whole blood samples, but did not identify significant associations in these tissues, nor with lead or selenium in any tissue. Our results demonstrate that subtoxic mercury exposure leaves a clear molecular signature. It also underscores the necessity of conducting tissue-specific association studies to accurately capture the molecular impact of environmental exposures, as only relevant tissues will manifest a response to environmental exposures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcel van de Streek is currently an employee of Genome Diagnostics B.V., Utrecht, the Netherlands. Co-authors: Tim D. Spector is a co-founder and shareholder of ZOE Ltd. Ana M. Valdes, reported serving as a scientific consultant for ZOE Ltd. The remaining 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: While a number of studies have examined the effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on childhood obesity, the results reported have been inconsistent and few studies have integrated biological markers. The aim of this study was to investigate the associations between prenatal exposure to PFAS and cardiometabolic health parameters at age 12, taking pubertal stage into consideration., Method: This study included 394 mother-child pairs enrolled in the PELAGIE mother-child cohort (France). Nine PFAS were measured in umbilical cord blood, and the children attended a clinical examination at age 12. Anthropometry, blood metabolic markers, and blood pressure were measured and used to build an internal cardiometabolic score. Linear regression and Quantile G-computation models were used to evaluate individual and mixture PFAS effects, adjusting for confounders and stratifying by sex and pubertal stage., Results: No statistically significant association was observed between prenatal exposure to PFAS and cardiometabolic score at age 12. In post-menarche girls, perfluorohexane sulfonate (PFHxS) and perfluorodecanoic acid (PFDA) were statistically significantly associated with a decrease in a number of adiposity parameters (e.g., Body mass index z-score: beta [95%CI] = -0.37 [-0.67; -0.07]), as well as a decrease in low-density lipoproteins (LDL) and leptin levels. Similar results were observed with PFAS mixture, with statistically significantly decreased tricipital skinfolds (beta [95%CI] = -1.30 [(-2.54;-0.06)]). Isolated associations, including higher systolic blood pressure, changes in cholesterol levels, and lower adiponectin levels were observed in specific subgroups., Conclusion: There is no clear evidence of an association between prenatal exposure to PFAS and the cardiometabolic health at earlier stage of pubertal development. However, inverse associations between PFAS and anthropometric measures have been observed in post-menarche girls. While the literature on this topic is scarce in pre-adolescents, these results suggest the importance of considering sex and pubertal stage in these associations., 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.)

Per- and polyfluoroalkyl substances (PFAS) are a class of ubiquitously detected chemicals, some of which are highly persistent and bioaccumulative in humans. Within the general population, dietary ingestion is considered a primary pathway for PFAS exposure, and seafood consumption specifically has been associated with higher serum PFAS concentrations. Proximity of residence to the ocean may influence dietary habits, particularly seafood consumption, and exposure to geographically specific PFAS sources such as sea spray aerosols (SSA). The objective of this study was to evaluate potential spatial trends in serum PFAS concentrations between Australian coastal and island populations compared to those with inland residency. Human sera were obtained from deidentified surplus pathology samples and pooled with respect to geographical location, sex (male or female), and age group (males: ≥15-<45 years, ≥45 years; females: ≥15-<45 years, ≥45-<60 years, ≥60 years) stratification criteria. Serum samples were then analysed for PFAS using High Performance Liquid Chromatography-Mass Spectrometry (HP LC-MS). A total of 13 of the 45 targeted PFAS were quantifiable in at least one pooled sample, including the detection of perfluorooctane sulfonate (PFOS) replacement compounds 5:3 fluorotelomer carboxylic acid (5:3 FTCA) and potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl-F53B). Significant spatial trends were observed in males aged ≥45 years, with serum concentrations of PFOS, perfluorobutanoic acid (PFBA), perfluorodecanoic acid (PFDA) and perfluoroheptane sulfonic acid (PFHpS) demonstrated to be 32-77% higher in pooled samples from island locations compared with inland. A similar trend was observed for PFHpS in coastal locations. Whilst deidentification of samples limited inferences about exposure pathways associated with the observed trends, this study indicated the feasibility of utilising pooled samples for assessing spatial variations in serum PFAS concentrations between geographically distinct subpopulations., 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: Female sexual function is important for sexual well-being, general health, fertility, and relationship satisfaction. Distressing impairments in sexual function, clinically recognized as female sexual dysfunction (FSD), can manifest as issues with interest/desire, arousal, orgasm, and pain during vaginal penetration. Some evidence suggests that exposure to endocrine-disrupting chemicals may adversely affect female sexual function, but associations for per- and polyfluoroalkyl substances (PFAS) have not been previously evaluated., Objective: We investigated associations between serum PFAS concentrations and female sexual function among U.S. pregnancy planners., Methods: We used cross-sectional data from participants from Pregnancy Study Online (PRESTO), a prospective preconception cohort study. Participants reported sexual function and distress at baseline on two validated measures: a modified version of the Female Sexual Function Index-6 (FSFI-6) and the Female Sexual Distress Scale (FSDS). We quantified PFAS serum concentrations in samples collected in the preconception period (i.e., at baseline) using solid phase extraction-high performance liquid chromatography-isotope-dilution-mass spectrometry. Participants reported sociodemographic information on structured baseline questionnaires. We included 78 participants with complete PFAS and sexual function data and fit multivariable linear regression models to estimate mean differences in FSFI-6 scores (β) or percent differences (%) in FSDS scores per interquartile range (IQR) increase in PFAS concentrations, adjusting for age, annual household income, years of education, parity, and body mass index. We further investigated effect measure modification by parity (parous vs. nulliparous) in stratified models., Results: An IQR increase in perfluorohexanesulfonic acid was associated with a 1.0-point decrease (95% CI = -1.8, -0.1) in reported FSFI-6 scores, reflecting poorer sexual function. PFAS were consistently associated with lower FSFI-6 scores among parous participants. PFAS were also associated, though imprecisely, with greater sexual distress., Conclusion: Some PFAS were associated with poorer sexual function among U.S. pregnancy planners, but future studies are needed to clarify the extent to which PFAS influences female sexual 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 Inc. All rights reserved.)

Recent evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of different cancer types, such as kidney and testicular cancers. Instead, evidence for lung, head and neck, and thyroid cancer is sparse. Hence, we aimed to summarize available literature on the topic. We searched Pubmed and Scopus in January 2024 to retrieve relevant studies and estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) for lung, head and neck, and thyroid cancers according to PFAS exposure using restricted maximum likelihood method. Pooled RRs for occupational or environmental PFAS exposure were 1.20 (95% CI: 1.12-1.28; I 2  = 0.0%, p het  = 0.9; n. studies = 9), 1.15 (95% CI: 0.96-1.37; I 2  = 0.0%, p het  = 0.7; n. studies = 3), and 1.54 (95% CI: 0.86-2.78; I 2  = 69.0%, p het  = 0.02; n. studies = 4) for lung, head and neck, and thyroid cancer, respectively. We did not find compelling evidence of publication bias for lung cancer (p = 0.3). Studies on statistically modelled serum PFAS levels did not support associations with these cancers. We found no positive associations between measured serum levels of 6 different types of PFAS and thyroid cancer. However, the pooled RR of two case-control studies nested within cohorts on the association between natural log-unit increase of perfluorooctanesulfonic acid (PFOS) and thyroid cancer was 1.51 (95% CI: 1.11-2.05; I 2  = 21.1%, p het  = 0.3). PFAS exposure may be associated with lung and thyroid cancer. Due to the limited number of studies and their limitations, further prospective studies with appropriate account of co-exposure with other carcinogens and detailed exposure assessment are needed to establish causality of observed associations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Paolo Boffetta acted as an expert in litigation involving PFAS exposure, unrelated to the present work. 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: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results., Objectives: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort., Methods: We measured cord blood concentrations of eight PFAS in a sample of 430 mother-child pairs from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. We assessed autistic traits using the Social Responsiveness Scale Second Edition (SRS-2) and its sub-scores, in which higher scores indicate more autistic traits. We estimated covariate-adjusted associations between the PFAS and SRS-2 scores using Bayesian weighted quantile sum (BWQS) regression models for the PFAS mixtures and multivariable regressions for single PFAS. We additionally evaluated effect modification by biological sex., Results: We observed a positive association between the PFAS mixture and SRS-2 cognition sub-scores (β per SD increase = 1.25 points, 95% CI -0.03, 2.40). Perfluorononanoic acid (PFNA) was the strongest contributor to the mixture effect. In single PFAS models, exposure to PFNA was associated with a higher SRS-2 total score (β = 0.93 points, 95% CI 0.29, 1.58), cognition sub-score (β = 1.26 points, 95% CI 0.55, 1.97), communication sub-score (β = 0.88 points, 95% CI 0.20, 1.56), and restrictive and repetitive behaviors sub-score (β = 0.93 points, 95% CI 0.23, 1.63). We also observed evidence of effect modification by sex for perfluoroundecanoic acid (PFUnDA) for the total score (p-effect modification [EM] = 0.03), cognition sub-score (p-EM = 0.03), and communication sub-score (p-EM = 0.04), with negative associations seen in females and null associations in males., Discussion: Cord blood PFAS concentrations were positively associated with autistic traits measured by SRS-2., 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 © 2025 Elsevier Ltd. All rights reserved.)

The present study investigated the clinical and hematological effects of chronic lead exposure in the population residing in Shadi Pura, a small industrial zone in Lahore, Pakistan. A cross-sectional analysis of 149 participants recruited through health camps was conducted to explore the hematological manifestations of environmental lead exposure, focusing on various red blood cell (RBC) indices and morphology. Moreover, the study examined the differences in the impact of lead exposure on RBC indices and morphology between men, women, and children. Participants exhibited symptoms of lead poisoning, including fatigue, muscle pain, and headache, with a significant percentage of women (44%) reporting miscarriages. Iron deficiency anemia was highly prevalent among all sub-groups of the study population, with adult females showing a significantly higher prevalence than adult males. Male children were the most affected subgroup, with 93% displaying anemia. The RBC count in children remained unchanged, while 31% of male and 7% of female participants displayed elevated RBC counts. RBC indices, mainly mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), were below normal levels, with children being more affected than adults and adult males being the least affected group. Furthermore, RBC morphology was severely affected, with a considerable proportion of females and children displaying hypochromic microcytic morphology. Our results highlight variations in the hematological impacts of lead exposure in different sex and age cohorts. Overall, our findings underscore the urgency of addressing the issue of environmental lead exposure in similar industrial zones. It is critical to implement appropriate measures to reduce lead exposure and enhance the infrastructure for safe drinking water and waste disposal to protect the health of populations in such areas., Competing Interests: Declarations. Ethics approval: This study was conducted following the Helsinki Declaration and approved by the Cancer Research Center Ethics Committee at the University of the Punjab. Before sample and data collection, informed consent (with WMA Declaration of Helsinki-Ethics principles for research involving human subjects) was obtained from each participant, and for minors, consent was obtained from their guardians. Consent for publication: Not applicable. Competing interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

DNA methylation is a critical step in brain development, 5-Methyl-2'-deoxycytidine (5mdC) is one of the global DNA methylation markers. Arsenic and lead exposures have been associated with neurotoxicity, which may be linked to epigenetic changes. Our research sought to investigate the correlation between 5mdC and developmental delay (DD) among preschoolers. Additionally, we assessed whether 5mdC modified the impacts of blood lead and total urinary arsenic levels on DD. We analyzed the concentrations of 5mdC, blood cadmium and lead, and total urinary arsenic in 174 children with DD and 88 healthy children. Global DNA methylation levels are expressed as the ratio 5mdC/2'-dexyguanosine (dG), called 5mdC (%). In our findings, elevated levels of blood lead and total urinary arsenic were significantly associated with DD risk among preschoolers. Furthermore, high 5mdC (%) was related with reduced risk of DD, with an odds ratio (OR) and 95% confidence interval (CI) of 0.14 (0.06 - 0.32). A notable multiplicative interaction was observed between low 5mdC (%) and elevated blood lead levels to increase OR of DD, with OR and 95% CI was 9.51 (4.18 - 21.64). The findings provide evidence of the combined effects of reduced 5mdC (%) and high blood lead concentrations, increasing the OR of DD., Competing Interests: Declarations. Competing interests: No actual or potential competing financial interests., (© 2025. The Author(s).)

Background: Childhood obesity is significantly influenced by maternal exposure to Per and Poly-Fluoroalkyl Substances (PFAS) during pregnancy. PFAS exposure occurs through the Peroxisome Proliferator-Activated Receptor (PPAR-γ) receptor, leading to increased fat deposition and profound health effects in child growth and development. Despite ongoing investigations, the relationship between maternal serum PFAS concentration and child obesity requires further exploration., Objective: This study aimed to review the possible effects of Per and poly-fluoroalkyl substances exposure and their mechanism in overweight/obese children from pregnant ladies., Methods: A detailed literature survey was conducted using online databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study focused on the diverse effects of PFAS on maternal and child health, with particular emphasis on neurological complications., Results: Child growth development depends upon breastfeeding and placenta health, which is disrupted by PFAS exposure, ultimately destroying the body mass index of the child. Neurotoxicity testing utilized the SH-SY5Y human-derived cell line as an in vitro model, revealing PFAS-induced increases in adipocyte number, reduced cell size, altered lipid conglomeration, increased adiposity, and changes in liver function. in vivo studies in mice and human cell lines indicated PPAR-γ and ER-α activation, leading to adiposity and weight gain through Estrogen signaling and Lipid metabolism. PFAS concentrations positively correlated in maternal sera, analyzed by liquid chromatography/quadrupole mass spectrometry., Conclusion: PFAS, with a long half-life of 3.5-8.5 years, is commonly found in the serum of pregnant women, crossing the placenta barrier. This exposure disrupts placental homeostasis, negatively impacting mechanisms of action and potentially leading to deterioration in pregnancy and child health. Further research is needed to comprehensively understand the complex interplay between PFAS exposure and its implications for maternal and child well-being., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: A relatively well-established link was observed between metal mixtures exposure and neurodegenerative diseases. However, the relationship between metal mixtures exposure and serum neurofilament light chain (sNfL) concentrations, a valuable non-invasive biomarker of neurodegenerative diseases, in general adult populations remains understudied and unclear., Objective: This study seeks to elucidate the potential impact of metal mixtures exposure on sNfL concentrations in a representative sample of U.S. general adults., Methods: Twelve urinary metal levels, including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), tin (Sn), strontium (Sr), thallium (Tl), tungsten (W) and uranium (U), were analyzed in U.S. general adults recruited from the 2013-2014 National Health and Nutrition Examination Survey using inductively coupled plasma mass spectrometry (ICP-MS) after a simple dilution step. Urine samples are diluted with 2 % concentrated nitric acid (1:9). We employed a two-pronged approach, combining weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models, to examine the association between the multiple-metals effect and sNfL concentrations. Survey-weighted multivariate linear regression was used to explore the correlation between single-metal effect and sNfL concentrations., Results: With the increasing quartiles of log-transformed sNfL (log-sNfL) concentrations, the fourth quartile had a higher proportion of smokers and hypertensive individuals (P < 0.001). Cd (69.6 %) and Pb (8.9 %) were the primary drivers of the association between metal mixtures exposure and sNfL concentrations. Analysis of WQS and BKMR models showed a positive association between metal mixtures exposure and sNfL concentrations, especially in older, and male participants., Conclusion: In the U.S. general adult, a significant correlation between metal mixtures exposure and increased sNfL concentrations was observed, and urinary Cd levels play a pivotal role in this positive correlation. Notably, stronger risk associations were observed among elderly, males, smokers, and hypertensive individuals. The results could be significant for detecting and tracking the beginning of neurodegenerative diseases early, as well as helping to pinpoint individuals at high 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may impact postnatal growth trajectories, increasing the risk of various diseases later in life. This issue is of particular concern in industrially contaminated areas, where environmental matrices contain mixtures of pollutants. This study aimed to evaluate the associations between cord serum concentrations of organochlorine pollutants (hexachlorobenzene-HCB and polychlorinated biphenyls-PCBs) and essential elements (EEs), and weight growth trajectories during the first year of life. We analyzed data from 237 infants enrolled in the Neonatal Environment and Health Outcomes (NEHO) cohort. Using the Group-Based Multivariate Trajectory modeling approach, we identified three distinct growth trajectories from birth to 12 months, classified as "Higher," "Normal," and "Lower." Multinomial regression models were then applied to the whole sample and stratified by sex to assess the associations between individual exposures and the identified child growth trajectories. HCB exposure was associated with an increased risk of reduced growth during the first year of life in both the overall sample and among males [higher vs normal: OR Male  = 0.33 (95 % CI Male :0.12;0.87); lower vs normal: OR Male  = 2.17 (95 % CI Male :0.94;5.00)]. Conversely, PCB-180 exposure was linked to higher growth only in females [higher vs normal: OR Female  = 24.10 (95 % CI Female :1.33;438.24)]. Elevated levels of selenium in cord serum were negatively associated with excessive growth [higher vs normal: OR Overall  = 0.50 (95 % CI Overall : 0.26;0.97)]. These findings suggest sex-specific effects on the growth profile during the first year of life, with different chemical exposures contributing to different outcomes., 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.)

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) may linked to thyroid cancer (TC) risk, but inconsistent findings and a lack of studies on mixed exposures exist, especially regarding novel PFAS compounds. Additionally, little is known about the potential mechanisms underlying the association., Objectives: Explore the effects of PFAS exposure on the serum metabolome and its correlation with TC., Methods: A 1:1 age- and sex-matched case-control study was administered with 746 TC cases and healthy controls. Liquid chromatography-high resolution mass spectrometry determined serum 11 PFAS and untargeted metabolome profile. ENET and LightGBM models were used to explore the exposure patterns and perform variable selection. The mixed exposure effects were assessed using Weighted quantile sum regression and Bayesian kernel machine regression. Metabolome-wide association analyses were performed to assess metabolic dysregulation associated with PFAS, and a structural synthesis analysis was used to detect latent groups of individuals with TC based on PFAS levels and metabolite patterns., Results: Ten of the 11 PFAS were detected in > 80 % of the population. PFHxA and PFDoA exposure associated with increased TC risk, while PFHxS and PFOA associated with decreased TC risk in single compound models (all P < 0.05). Machine learning algorithms identified PFHxA, PFDoA, PFHxS, PFOA, and PFHpA as the key PFAS influencing the development of TC, and mixed exposures have an overall positive effect on TC risk, with PFHxA making the primary contribution. A novel integrative analysis identified a cluster of TC patients characterized by increased PFHxA, PFDoA, PFHpA and decreased PFOA, PFHxS levels, and altered metabolite patterns highlighted by the upregulation of free fatty acids., Conclusions: PFAS exposure is linked to a higher risk of TC, possibly through changes in fatty acid metabolism. Larger, prospective studies are needed to confirm these findings, and the role of short-chain PFAS requires more attention., 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.)

Background: The organophosphate pesticide chlorpyrifos was widely used in the European Union before its ban in 2020 and was associated with neurodevelopmental disorders. However, within the concept of Developmental Origins of Health and Disease, in utero exposure to chlorpyrifos can lead to neurodevelopmental effects in developing children., Objective: The aim of this study was to estimate fetal exposure to chlorpyrifos using biomonitoring data measured in Elfe pregnant women and a physiologically based pharmacokinetic (PBPK) approach and compare exposure to toxicological reference values., Methods: A pregnancy-PBPK model was developed based on an existing adult chlorpyrifos model and a new toxicological reference value was proposed for neurodevelopmental effects. The pregnant women exposure was estimated based on dialkylphosphate (DAP) levels in urine assuming constant exposure to chlorpyrifos and compared to both the existing toxicological reference value and the new proposed draft toxicological reference value. Fetal internal concentrations in target tissues were then predicted using the developed pregnancy-PBPK model. Urinary concentrations of the chlorpyrifos-specific metabolite (TCPy) were also predicted for comparison with other biomonitoring data., Results: The median daily exposure to chlorpyrifos for the French pregnant women from the Elfe cohort was estimated at 6.3x10 -4  μg/kg body weight/day. The predicted urinary excretion of TCPy, the chlorpyrifos-specific metabolite, is in the same range as observed in other European cohorts (mean: 2.13 μg/L). Predicted brain chlorpyrifos levels were similar in pregnant women and their fetus and were 10-fold higher than the predicted blood chlorpyrifos levels. It was estimated that 6% and 20% of the pregnant women population had been exposed to levels exceeding the general population and draft toxicological reference values, respectively., Conclusions: Prenatal exposure to chlorpyrifos was estimated for the French population based on data from the Elfe cohort. Internal chlorpyrifos concentrations in target tissues (brain and blood) were predicted for fetuses at the end of the pregnancy. Under a conservative assumption, a small percentage of the population was identified as being exposed to levels exceeding the toxicological reference values., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Environmental pollution is of global concern. In Southeast Sweden, historical glass production has contaminated communities with toxic metals. Long-term residency in these communities and high consumption of local foods may constitute a risk for cardiovascular disease (CVD) or stroke. The current study investigates if residency in these contaminated sites and long-term consumption of local foods is associated with self-reported CVD and stroke. In addition, the body burden of the toxic metals arsenic, cadmium, and lead, as well as inflammatory protein markers, were studied for association with CVD and stroke. From an existing questionnaire cohort and biomonitoring sub cohort (n = 2290/882) of people living in the contaminated areas, self-reported CVD cases (n = 366/166) and stroke cases (n = 78/25) were identified. Individuals were grouped based on their residency within a 2 km radius of glassworks with historical high, moderate, or low air-borne lead emissions. Body burden of arsenic, cadmium, and lead was analyzed using ICP-MS. Inflammatory markers were investigated using electrochemiluminescence. Long-term residency near glassworks with historically high levels of lead emissions, and high consumption of local foods, were associated with CVD. The risk was increasing for each year of residency in high emission areas. Increased body burden of arsenic in blood, and lead in urine, were associated with stroke. Five and two inflammatory markers, respectively, were elevated in CVD and stroke cases after adjusting for confounders. An increased risk for CVD was found in areas with historically high emissions of lead but possibly also other toxic metals. Interestingly, there was an indication of a dose-response relationship with increasing risk for CVD per year of residency time. Inhalation and consumption of local food may constitute major pathways for this association. The study shows that long-term exposure to toxic metals in these contaminated areas is associated with CVD and that there is a need to limit exposure in the general population., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Phenols and parabens, as endocrine-disrupting chemicals (EDCs), are prevalent in daily consumer products and industrial applications. Folate, a vital vitamin, plays a crucial role in numerous metabolic processes. The interaction between EDCs and folate is not well understood and warrants investigation. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Since many pollutants are co-exposed congeners, with interactive effects between pollutants, we employed multivariate linear regression model, weighted quantile sum regression, and Bayesian kernel machine regression (BKMR) to quantify the impact of folate levels in serum and red blood cell (RBC) and the overall effects of combined exposures. The study included 4395 children and adolescents. A negative correlation was observed between RBC folate concentrations and urinary concentrations of Bisphenol A (BPH), Triclosan (TRS), Methyl paraben (MPB), Propyl paraben (PPB), and Butyl paraben (BUP), in children and adolescents. Specifically, an increase in RBC folate levels was linked to a decrease in urinary BPH, TRS, MPB, PPB, and BUP concentrations. Similar associations were found with serum folate. The weighted quantile sum index showed a decrease in both RBC and serum folate levels with an increase in the mixture of phenols and parabens. BKMR further supported the overall negative impact of the chemical mixture on folate levels. This study provides evidence of an inverse relationship between exposure to phenols and parabens and folate concentrations in children and adolescents, which would be of significance in providing guidance for clinical interventions and calling for remediation actions to be prioritized during 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: In response to substantial lead exposure, the autonomous republic of Adjara in Georgia initiated complementary blood lead level (BLL) testing for pregnant women as part of their antenatal care services in 2020., Objectives: To study the background BLLs in pregnant and breastfeeding women in Adjara and explore the time-trends of BLLs from September 2020 to July 2023., Methods: We used data on BLLs during pregnancy or postpartum from the lead screening program in Adjara, combined with data from the Georgian Birth Registry, totaling 9,510 women. To study the temporal changes in BLLs, we used independent samples t-tests and chi-square tests., Results: In 2020, the mean (standard deviation [SD]) BLL was 8.8 (5.4) μg/dL, declining annually by 1.0-2.2 μg/dL to reach 3.6 (2.5) μg/dL in 2023. The prevalence of pregnant women with BLLs ≥3.5, ≥5.0, and ≥10.0 μg/dL also decreased from 2020 to 2023. Specifically, 21.2% of women in their first trimester had BLLs ≥10 μg/dL in 2020, compared with 2.3% in 2023. Similarly, 73.5% had BLLs ≥5.0 μg/dL in 2020, which declined to 20.4% in 2023. Lastly, 89.1% had BLLs ≥3.5 μg/dL in 2020, decreasing to 38.6% in 2023., Discussion: In 2023, nearly 40% of women in their first trimester had BLLs of ≥3.5 μg/dL, a level considered the reference value in the United States (US) and corresponding to the 97.5th percentile among US children. From 2020 to 2023, the mean BLL in pregnant women decreased by 59%, accompanied by a considerable decline in the prevalence of women with BLLs ≥3.5, ≥5.0, and ≥10.0 μg/dL. Despite the encouraging downward trend in BLLs throughout the study period, our data indicate that a considerable number of fetuses continue to be exposed to harmful levels of lead and that lead exposure remains a significant public health challenge in Adjara., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Several organic pollutants, including dioxins, furans, and coplanar polychlorinated biphenyls (PCBs), have become a growing concern due to their significant capacity for accumulation and migration across regions, as well as their extended half-lives and relatively high toxicity. Our study aimed to assess the impact of these pollutants on mortality, inflammatory states, and chronic diseases. Exposure was quantified in serum through high-resolution gas chromatography and isotope-dilution high-resolution mass spectrometry. Statistical analyses employed multivariate Cox regression, multivariate logistic regression, restricted cubic splines and subgroup analysis. The results indicated a significant increase in mortality (p < 0.05) associated with the seven substances classified as dioxins, furans, and PCBs. Moreover, these pollutants were linked to a higher incidence of chronic diseases, including hematological disorders, chronic kidney disease, hypertension, and diabetes (p < 0.05). Additionally, a robust correlation was observed between serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) concentrations and these substances, revealing their proinflammatory effects at specific concentrations. Consequently, our research unmasked that exposure to dioxins, furans, and coplanar PCBs could be associated with an elevated mortality rate, increased inflammatory conditions, and a higher incidence of chronic diseases. We proposed that exposure to these pollutants may initiate various afflictions by activating the inflammatory system, ultimately resulting in increased mortality. However, this hypothesis requires further empirical investigation to validate its assertions., Competing Interests: Declaration of Competing Interest The authors hereby verify the absence of any financial or personal affiliations that may have the potential to impact the credibility of the findings articulated in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low., Objective: To measure contamination by arsenic, lead, 4,4'-dichlorodiphenyldichloroethylene (4,4'-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population., Methods: In the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4'-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC)., Results: The PCBs 180, -153 and -138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4'-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes., Conclusions: Our results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure., Competing Interests: Declaration of competing interest The authors declare that there is no competing interest regarding the publication of this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Anticoagulant rodenticides (ARs) are widely used for pest control, resulting in their pervasive presence in the environment and posing significant toxicological risks to a range of predatory and scavenging species. Our study mainly aimed to evaluate AR exposure and effects in nestlings of eagle owl (Bubo bubo) from the Region of Murcia (southeastern Spain). We analysed ARs in blood samples (n = 106) using high-performance liquid chromatography-triple quadrupole (HPLC-TQ), assessed the influence of potential anthropogenic (presence of livestock farms, landfills and human population density) and environmental (land uses and proximity to watercourses) variables, and measured prothrombin time (PT) and plasma biochemical parameters as biomarkers of effects. Our results showed the presence of AR residues in 91.5% of the nestlings, with 70.8% exhibiting multiple ARs (up to six compounds in a single individual). Second-generation ARs (SGARs) were the most prevalent compounds. The analysis of biochemical parameters indicated that the sampled individuals were in good physiological condition. Although PT was positively correlated with total AR concentration (ΣARs), the relationship was not significant (Rho = 0.04; p = 0.49). Regarding environmental factors, higher ΣARs were associated with the most urbanised study site and the presence of landfills, likely due to the increased availability of rodent prey. The prevalence of two SGARs (brodifacoum and difenacoum) was linked to closer proximity to riverbeds, suggesting a contamination pathway associated with inland aquatic ecosystems, where these AR compounds may concentrate due to water scarcity. This study underscores the widespread exposure of eagle owls to ARs and highlights the importance of effective monitoring and management of these pollutants to protect conservation-concern wildlife in Mediterranean semiarid regions., 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: Phthalate exposures have been shown to be inversely associated with reproductive success among women undergoing assisted reproductive technology (ART). However, the underlying mechanisms are unknown., Objectives: To explore blood coagulation function as the mediating role of associations between exposure to phthalates and ART outcomes., Methods: A total of 735 women from the Tongji Reproductive and Environmental (TREE) study were included. Urine samples collected at recruitment were quantified for 8 phthalate metabolites, and blood clotting time and platelet indices were also determined. Generalized linear regression, logistic regression, weighted quantile sum (WQS) regression, or Bayesian kernel machine regression (BKMR) models were applied to investigate the associations among individual and mixture of phthalate metabolites, blood coagulation parameters, and ART outcomes. The mediation role of blood coagulation parameters was estimated by mediation analysis., Results: Mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and molar sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) were positively associated with platelet indices. Phthalate metabolite mixture was also positively associated with platelet count (PLT), mean platelet volume (MPV), and plateletcrit (PCT), whereas inversely associated with international normalized ratio (INR). Meanwhile, PLT and PCT were inversely associated with the odds of implantation success and live birth, while prothrombin time and INR were positively associated with the odds of implantation success. Mediation analyses showed indirect effects of above-mentioned phthalate metabolites and phthalate mixture on the odds of implantation success and live birth through PLT or PCT, with the proportion mediated ranging from 3.44% to 8.96%., Conclusions: Phthalates may increase the risks of ART failure through enhancing blood coagulation function. More studies are warranted to verify the findings., 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.)

Background: Per- and polyfluoroalkyl substances (PFAS) are a class of widespread persistent chemicals, which may have obesogenic effects during the fetal period. This study investigated the long-term association of maternal plasma PFAS concentrations at delivery and their mixture with child body mass index (BMI) and the risk of Overweight or Obesity (OWO) at the age of 2-18 years., Methods: The study included 1189 mother-child dyads from the prospective Boston Birth Cohort. Eight PFAS were measured in maternal plasma samples collected 24-72 h after delivery. Outcomes were BMI Z-score and OWO status of children at 2-18 years. The exposure-outcome associations were evaluated with linear and modified Poisson mixed-effects regression for individual PFAS and Bayesian kernel machine regression and quantile-based g-computation models for PFAS mixture. We explored the effect modification by maternal pre-pregnancy OWO, child age, sex, and race., Results: Maternal plasma samples had PFAS detection frequencies from 87 % to 100 % and geometric means ranging from 0.11 to 3.67 ng/mL. PFHpS and PFHxS were associated with higher child BMI Z-score. Such associations were stronger in children aged 6-12 years and 13-18 years than in 2-5 years. Stratified by maternal pre-pregnancy OWO, significant associations of the PFAS mixture with child BMI Z-score were only found in children of non-OWO mothers. In children aged 13-18 years, children with both high maternal plasma PFDeA, PFNA, and PFOA concentrations and maternal OWO had the highest risks of OWO compared to children with either only. Such synergistic effects were not found in younger children., Conclusions: Early life exposure to individual PFAS and their mixture were associated with a higher risk of childhood OWO, with stronger associations observed in older child age groups and in children of non-OWO mothers. Synergistic effects of PFAS exposures and maternal pre-pregnancy OWO became evident in adolescence., Competing Interests: Declaration of competing interest Dr. Braun has been compensated for services as an expert witness to plaintiffs involved in litigation related to PFAS-contaminated drinking water., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) have been detected worldwide, from the deep seas to polar regions. A previous review showed that PFAS are risk drivers of the chemical mixture present in human blood. This study focused on establishing the PFAS exposure of a Swedish subpopulation and investigated whether the exposure poses a risk of adverse health effects. Human serum from 60 blood donors in Stockholm, Sweden, was analyzed. A target method including 32 PFAS analytes and over 270 suspect features was used to detect and quantify PFAS. Twenty-six PFAS were quantified, and 7 suspect PFAS features (6 H-PFCAs and PFECHS) were semi-quantified. Nine mixture risk assessment (MRA) strategies were used to assess the risk of health outcomes. Fifteen effect levels were derived and used, along with 15 already established values. The certainty of various derivation techniques was discussed. The MRAs showed that the entire studied population exceeded some of the risk thresholds, with effects including high cholesterol and immune suppression. However, the certainty was lower when deriving these two effect levels. The MRA, using human biomonitoring guidance values (high certainty), concluded that for 63 % of the individuals, a risk for adverse health effects cannot be excluded. This study has demonstrated that there is a reason for concern regarding PFAS exposure in the general population of Sweden. To our knowledge, this is the first time the H-PFCAs have been semi-quantified in human blood using a reference standard., 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.)

Background and Aim: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have demonstrated potential toxicity in skeletal development. However, the relationship between prenatal PFAS exposure and offspring bone health remains unclear in epidemiological studies. Therefore, we aim to investigate whether prenatal exposure to PFAS is associated with bone mineral density (BMD) in offspring., Method: This study population included 182 mother-child pairs in the Shanghai Obesity and Allergy Cohort, enrolled during 2012-2013. 10 PFAS were measured by liquid chromatography-mass spectrometry (LC-MS) in cord plasma. The child's spinal BMD was measured using a dual-energy X-ray absorptiometry (DXA) scanner at the age of 8. Multivariable linear regression models were used to estimate the associations between individual PFAS concentrations (as a continuous variable or categorized into quartiles) and child BMD. Bayesian kernel machine regression (BKMR) was employed to explore the joint effects of PFAS mixtures on BMD., Results: Among the 10 PFAS, 8 of them had a detection rate >90% and were included in the subsequent analysis. We observed no significant associations between individual PFAS (as a continuous variable) and spinal BMD in 8-year-old children using the multivariable linear regression model. When treated as quartile categories, the second and fourth quartiles of perfluorobutane sulfonate (PFBS) was associated with higher BMD in the first lumbar vertebra, compared with the lowest quartile. BKMR analysis revealed no association between the PFAS mixture and child BMD., Conclusion: We observed no associations of prenatal PFAS exposure with child BMD at 8 years of age. Given the inconsistent epidemiological evidence, further research is needed to confirm these findings from other studies or elucidate the potentially toxic effects of PFAS on bone., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Living in urban environments presents many challenges to wildlife, including exposure to potentially toxic pollutants. For example, the heavy metal lead (Pb) introduces numerous health problems to all animals, including humans. The little work that has been conducted on lead toxicity in reptiles suggests that lizards may be extraordinarily resilient to very high levels of lead pollution, by either avoiding or mitigating the toxicity. To assess the impact of lead exposure, we measured field blood levels and tested for the effects on ecologically-relevant performance measures in common wall lizards (Podarcis muralis) - a small reptile particularly capable of thriving in urban environments. We captured lizards from roadside and park habitats across Cincinnati, Ohio, USA and quantified the concentration of lead in blood samples (n = 71 adult lizards). Lizards from roadside populations had higher blood lead concentrations than lizards from park populations, and females had higher blood lead concentrations than males regardless of habitat type. We then tested two aspects of lizard performance important for survival: (1) balance, a cognitively-demanding task, to assess the effect of lead on cognition (n = 41), and (2) running endurance, an aerobic exercise dependent on oxygen (n = 43), to assess the impact of lead on blood oxygen-carrying capacity. We then used correlation analyses to quantify the relationship between lead levels and these ecologically-relevant performance measures. There was no effect of blood lead levels on running endurance, but contrary to our predictions there was a slight positive effect on balance performance, whereby lizards with higher blood lead concentrations slipped less often than lizards with lower blood lead concentrations. Understanding the effects of lead toxicity and resilience in a particularly resistant animal could help us better respond to public health and environmental pollution concerns., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Eric Gangloff reports financial support was provided by National Science Foundation. 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: Recent evidence suggests that cumulative low-level lead exposure has adverse effects on cognitive function in the elderly. To date, the few studies that have measured bone lead exposure relied on K-X-ray fluorescence (KXRF), methods that are mostly unavailable in large community-based studies. Here, we employ a methylation-based estimation method for bone and blood lead in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort., Methods: Tibia, patella, and blood lead levels were estimated using blood DNA methylation (DNAm) biomarkers in 625 participants from the ADNI cohort. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Longitudinal analyses were conducted using linear mixed-effect regression models. Participants had different years of baseline (2010-2014) and follow-up visits (2014-2015)., Results: DNAm derived tibia and patella lead levels were negatively associated with MoCA scores throughout follow-up, while DNAm derived blood lead level was not associated with MoCA scores. On average, we observed lower MoCA scores with increasing DNAm tibia lead (per interquartile range (IQR): β = -0.23; 95% CI: -0.44, -0.03) and DNAm patella lead, albeit the latter was weaker (per IQR: β = -0.19; 95% CI: -0.41, 0.04). When stratifying by gender, women showed a stronger decrease in cognitive function with increasing DNAm tibia lead (per IQR β = -0.34; 95% CI: -0.65, -0.04) than men (per IQR β = -0.15; 95% CI: -0.42, 0.13). The estimated decrease in MoCA scores per DNAm tibia lead IQR increase was stronger among participants with one or two APOE4 alleles (per IQR β = -0.37; 95% CI: -0.74, -0.01) than those with zero alleles (per IQR β = -0.14; 95% CI: -0.38, 0.10)., Conclusion: These findings strengthen the evidence that cumulative long-term lead exposure levels are associated with decreased cognitive function in the elderly, especially among women and carriers of one or two APOE4 alleles. These findings based on whole blood methylation data corroborate previous epidemiologic studies that used KXRF for measuring bone lead., 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 per- and polyfluoroalkyl substances (PFAS) is ubiquitous and may be associated with neurodevelopmental toxicity. However, epidemiological studies report mixed results on the risks of gestational PFAS exposure for children's neurobehavioral impairment. We aimed to examine the associations between prenatal PFAS exposure and children's neurobehavioral and social problems. We measured plasma concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulphonate (PFHxS) in first-trimester blood from 757 women from the Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study. Children were assessed at 3-4 years with the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2) (n = 756 and 496, respectively). We used multivariable linear regression to examine associations between individual and summed log 2 -transformed PFAS and scores on these assessments. Effect modification by sex was evaluated through interaction terms and stratified analyses. In the sample combining both sexes, a doubling of maternal PFOA was significantly associated with lower T-scores on the following SRS-2 scales: Social Motivation, DSM-Social Communication, and SRS Total score (B ranging from -1.08 to -0.78), suggesting lesser impairments with higher exposure. In sex-stratified analysis, PFOA was related to significantly lower T-scores in boys for these BASC-2 scales: Behavioral Symptoms Index, Externalizing Problems, Aggression, and Hyperactivity (B ranging from -1.32 to -1.03). In girls, however, PFAS were associated with more problem behaviors, but most associations were small and the CIs included the null, with the exception of PFOA being significantly associated with higher T-scores for the BASC-2Anxiety scale (B = 1.84, 95% CI: 0.36, 3.32). In conclusion, we did not observe strong associations between prenatal exposure to the PFAS evaluated and children's neurobehavioral and social development in this population with low exposure levels. The results show mixed findings, depending on children's sex, neurodevelopmental outcome, and specific PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The increasing role of environmental pollutants and nutrients in the development of myopia. Further longitudinal evidence is needed to elucidate the effects of early-life environmental pollutants on myopia and nutrients to protect against pollutant-induced myopia. We used mother-child dyads from the Ma'anshan Birth Cohort (n = 2028) to explore the modifying effects of maternal vitamin D status of prenatal and childhood arsenic exposure with refractive parameters and myopia. We measured serum or plasma arsenic concentrations during three trimesters, in cord blood, in childhood (5-year-old), and performed cycloplegic refraction in children aged 7-9 years (n = 1616). Primary outcomes were myopia and refractive parameters including axial length (AL), corneal radius of curvature, and spherical equivalent refraction error. Linear regression, logistic regression, and multiple informant models were performed for the association of prenatal and childhood arsenic exposure with vision health. Sex- and vitamin D status stratification analyses were also conducted. Cord serum arsenic was positively associated with AL (β = 0.15, 95%CI: 0.01, 0.29) and the risk of developing myopia (OR = 1.72, 95%CI: 1.07,， 2.75). Among boys, a 1 ng/L increase in cord serum log 10 -transformed arsenic resulted in larger AL and a higher risk of myopia. In the vitamin D deficient group (<20 ng/mL), cord serum arsenic showed positive associations with AL (0.26 [0.06, 0.46]) and the risk of myopia (1.99 [1.01, 3.90]). Late pregnancy arsenic exposure likely affects offspring development of myopia, especially in boys. Maternal sufficient vitamin D may confer protective effects against the development of myopia., 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.)

Heavy metals and metalloids are increasingly recognised as a threat to avian health, especially in species at the top of the food chain such as vultures. Griffon Vultures (Gyps fulvus) are ideal bioindicators for studying environmental contamination due to their scavenging habits and territorial behavior. In this study, we analysed the concentrations of six trace elements (Cd, Pb, Cr, Sb, Ni, and Cu) in feathers, pectoral plumage, and blood samples of Griffon Vultures from a captive environment in Sicily, Southern Italy, using an ICP-MS method. Significant differences in the levels of trace elements were observed between different matrices (p < 0.05). The ramigal feathers were divided into rachis (basal, medial, apical), calamus, and barbs (basal, medial apical). The Principal Component Analysis (PCA) demonstrated a clear differentiation in metal accumulation between the sections of feather matrices and between pectoral plumage and blood, reflecting the diverse pathways and time of exposure and deposition. No significant differences in heavy metal concentrations were observed between sexes and age classes. This work highlights the effectiveness of using feather matrices for monitoring environmental exposure to toxic elements and highlight the importance of continuous surveillance of heavy metal contamination in reintroduced vulture populations., Competing Interests: Declarations. Ethics approval: The study was carried out in accordance with ethical considerations on animal welfare and under the supervision of a veterinary. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Bioaccumulation of trace element contaminants with endocrine disruptive (ED) potential has been noted in European brown bears, though evidence of their effects is lacking. Generalized linear models were employed to assess circulating levels of reproductive, stress, and thyroid hormones in relation to arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb) and thallium (Tl) in 53 free-ranging brown bears (Ursus arctos) from two European populations (Carpathian and Dinara-Pindos). Other potential drivers of hormone variation, such as essential elements, ecological factors, physiological variables, and capture methods, were included as predictors. The models demonstrated a positive association between cortisol and Cd, and a negative association with Tl. In addition, Tl and Pb were identified as key factors in explaining variation in thyroid hormones (free triiodothyronine, fT3 and free thyroxine, fT4). Trap type was significant in explaining variation in fT3 concentrations, while sex was an important predictor of progesterone levels. The essential elements, cobalt (Co) and copper (Cu) accounted for 41 % of testosterone variation, while Cu and selenium (Se) were negatively associated with fT4. Other notable predictors of investigated hormone variation included body condition index (important for cortisol), age (for fT4), year (for fT3), capture day (for fT4 and fT4:fT3 ratio) and population (fT4:fT3 ratio). This study evidenced trace elements as important factors to consider when studying hormonal variation in terrestrial wildlife (Tl for cortisol and fT3, Cd for cortisol, Cu for testosterone and fT4, Co for testosterone, Pb and Se for fT4). To gain a more definitive understanding of the effects of exposure to element contaminants on endocrine status, it is recommended to include more sensitive and specific endocrine disruption-related endpoints in a larger sample size. Doing so will further enhance our understanding of the potential adverse endocrine effects of environmental pollutants on these bear populations and other large mammalian wildlife species., 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.)

Mercury pollution, including from its use during gold mining and refining, remains an important problem worldwide. In particular, methylmercury, a microbial alteration of mercury released into the environment, is a major environmental neurotoxicant. Although there has been growing concern about the health hazards of exposure to low levels of mercury, the effects of prenatal mercury exposure on neurodevelopmental outcomes in children have remained controversial. In the Japan Environment and Children's Study, a large-scale nationwide birth cohort study, we measured methylmercury and inorganic mercury concentrations in cord blood and conducted developmental scoring tests at ages 2 and 4 years. We then analyzed the associations between mercury levels in cord blood and neurodevelopmental outcomes. Measurements of cord blood obtained from 3822 participants revealed median values of 7.39 ng/ml (5th percentile: 2.95, 95th percentile: 18.1) and 0.25 ng/ml (5th percentile: 0.10, 95th percentile: 0.58) for methylmercury and inorganic mercury, respectively. Analyzing the association with fish consumption, bonito-tuna was most strongly correlated with both methylmercury and inorganic mercury in cord blood. Although the association between cord blood mercury and neurodevelopmental scores was subsequently examined in 3083 individuals, we found no significant association with either methylmercury or inorganic mercury. Further quartile group analysis based on methylmercury concentrations in cord blood revealed no concentration-dependent association between a prenatal mercury exposure and neurodevelopment in children. However, various factors influence neurodevelopment, and long-term observational studies that consider those covariates are necessary for a more definitive conclusion. Although the findings of our study provide important insights into the association between prenatal mercury exposure and neurodevelopment, further research is needed to make recommendations for safe mercury intake thresholds during pregnancy., 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.)

Background: The adverse effects of environmental toxic metal exposure on human health are well-documented. However, the specific influence of heavy metal exposure on stroke prevalence remains underexplored., Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2011 to 2018 to investigate the association between blood metal concentrations and the incidence of stroke. Four analytical approaches-logistic regression, Restricted Cubic Splines (RCS), Weighted Quantile Sum regression (WQS), and Bayesian Kernel Machine Regression (BKMR)-were employed to assess the relationship, with a mediation analysis conducted to explore the role of inflammatory markers in Pb exposure-induced stroke., Results: Among the 9,399 participants in this project, 421 (4.4%) were diagnosed with stroke. After adjusting for covariates, a multivariable logistic regression model identified a positive association between the logarithmic concentration of Pb and the incidence of stroke. Besides, the analysis conducted using both WQS and BKMR methodologies found a consistent positive association between the composite exposure to heavy metals and the frequency of stroke cases, with Pb emerging as the predominant factor in this relationship. An evident saturation phenomenon was noted in the correlation between lead exposure and the risk of stroke. Additionally, the interplay between Pb exposure and stroke manifestation was found to be partially mediated by inflammatory markers, which were responsible for 6.9% of the observed effect (95%CI:0.01, 0.24, P = 0.03)., Conclusion: These findings indicate a notable contribution of Pb exposure to stroke risk, highlighting inflammation as a significant intermediary mechanism in the Pb exposure-stroke association., Competing Interests: Declarations. Ethics approval and consent to participate: All NHANES participants provided informed consent prior to undergoing health examinations. The study’s protocols received approval from the Research Ethics Review Board at the National Center for Health Statistics, part of the Centers for Disease Control and Prevention (NHANES, 2022). Consent for publication: Publication consent has been obtained from all authors. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The objective of this study is to evaluate the impact of low blood lead levels (BLLs) on the red blood cell folate concentrations in U.S. children aged 2-17 years. All data were obtained from the National Health and Nutrition Examination Survey (NHANES) over six consecutive cycles from 2007-2008 to 2017-2018. A total of 12,739 children with BLLs lower than 10 µg/dL (geometric mean: 0.66 µg/dL) were included in the dataset. BLLs were categorized into three tertiles (tertile 1: <0.55 µg/dL; tertile 2: 0.55-0.95 µg/dL; and tertile 3: ≥0.95 µg/dL). The multivariate linear regression model analysis indicates a negative relationship between BLLs and red blood cell folate concentrations. After adjusting for potential confounding factors, red blood cell folate concentrations were lower in children in the BLL tertile 2 (β-coefficient = -0.0450; 95% CI: -0.0676, -0.0224) and BLL tertile 3 groups (β-coefficient = -0.0775; 95% CI: -0.1032, -0.0517) compared to children in the BLL tertile 1 group. When stratified by age, gender, and race/Hispanic origin, the subgroup analysis consistently revealed a negative relationship between BLLs and red blood cell folate concentrations, with red blood cell folate concentrations being lower ( p < 0.05) in children in the BLL tertile 3 group compared to children in the tertile 1 group. Further investigation is needed to explore the mechanism underlying the potential relationship between BLLs and red blood cell folate concentrations and determine whether folate plays an active role beneficial for preventing the harmful effects of lead on children.

Top-predators serve as sentinels of ecosystem health due to their sensitivity to environmental contamination. However, our understanding on how contaminants affect individual fitness is still scarce, especially for long-lived species. Here, we measured blood concentrations of 4 metals (Cd, Cu, Pb, and Zn) and one metalloid (As) in black kite (Milvus migrans) adults from Doñana National Park (SW Spain) following a major mine spill. Besides temporal variation (1998-2001) in metal and As concentrations, we tested how metal and As profiles changed across individuals in relation to their sex, age or breeding status, and examined whether metal and As concentrations affected individuals' fitness (breeding success and mortality). We found that, overall, blood concentrations of Pb, Cd and As increased throughout the study period in black kites, mirroring the progressive increase previously reported for their main prey. Both sex (Cu and Zn) and breeding status (Zn and Pb) affected element concentrations. Non-breeding (floater) females had higher levels of Zn than their breeding counterparts. The same pattern of higher contamination in floaters was observed for Pb, which might be related to differences in diet and foraging activity between breeders and floaters. The percentage of the individuals with Pb concentrations that exceeded toxicity thresholds (> 200 μg/L) was relatively high (15.4 %). Moreover, Pb concentrations were negatively correlated to males' breeding success. We found no clear evidence to support metal and As effects on survival or life expectancy after accounting for environmental and individual sources of variation. Our results highlight the importance of long-term studies of marked individuals in wild populations; detailed knowledge of ecological processes relevant to these populations, combined with measures of contaminant exposure at individual level, provides opportunities to enhance our understanding of its fitness effects and potential demographic consequences., 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.)

Environmental exposure of preschool children to mercury can elevate blood mercury levels (BML) and negatively affect their health. This study aimed to determine BML in preschool children from Brazil's largest city and explore potential associated risk factors. Blood samples were collected in 2013 from 2436 children (age 1-5 years) attending 50 daycare centers (DCC) located in São Paulo, Brazil. Parents or guardians answered questionnaires collecting information on sociodemographics and potential risk factors. BML was determined by Cold Vapor Atomic Absorption Spectrophotometry (CV-AAS) and categorized using a cutoff point of 2.77 μg L⁻ 1 , corresponding to the 75 th percentile. Multiple logistic regression was performed (p < 0.05). Data were georeferenced and associations with air pollution, wind frequency and direction were evaluated. The results showed a geometric mean for BML of 1.65 μg L⁻ 1 (95% CI: 1.60-1.70), arithmetic mean of 2.15 μg L⁻ 1 (95% CI: 2.09-2.22), 75 th percentile of 2.77 μg L⁻ 1 (95% CI: 2.67-2.91) and 95 th percentile of 5.51 μg L⁻ 1 (95% CI: 5.18-5.92). DCCs located in the Northwest and East zones (p < 0.001) and fish consumption in the past two days (p = 0.04) were associated with high BML. The elevated BML observed in children living in the eastern zone might be attributed to the southeasterly winds passing through a petrochemical complex located nearby. The 95 th percentile of BML in this study exceeded the U.S. 95 th percentile by five times. BML in São Paulo preschool children was associated with individual and environmental risk factors. This finding highlights the need to identify and control hot spots in São Paulo, Brazil, especially in peripheral and surrounding areas, where individuals are more vulnerable. Further research is needed in Latin America to identify additional sources of urban environmental mercury exposure and guide interventions for protecting the environment and safeguarding children's 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.)

Introduction: Effects of environmental contaminants (ECs) on endocrine systems have been reported, but few studies assessed associations between ECs and sex hormones (SH) in elderly. Aim of this study was to investigate whether blood concentrations of four classes of ECs were associated with SH concentrations in elderly., Methods: Samples from participants of the cross-sectional population-based Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 70-year-old men and women, n = 1016) were analyzed using validated mass spectrometry-based methods for SH (testosterone (T), dihydrotestosterone (DHT), estrone and estradiol (E2)); 23 persistent organic pollutants (POPs); 8 perfluoroalkyl substances (PFAS); 4 phthalates and 11 metals. SH binding globulin (SHBG) was analyzed using immunoassay. The measured concentrations were normalized, and the values converted to a z-scale. Linear regression analyses were conducted to assess association between concentration of the SH, SHBG and E2/T (aromatase enzyme index, AEI) with the ECs. Multiple linear regression analyses were performed to model the relationships., Results: The strongest associations were observed with the polychlorinated biphenyls (PCBs). In men, the strongest associations with concentrations of SH and SHBG were seen for PCBs containing >5 chlorine, monoethyl phthalate (MEP), Ni and Cd; and in women, with PCBs, MEP, several of the PFAS, Cd, Co, and Ni. Difference in the effect of ECs on AEI between men and women were observed. Area under the ROC curve for the models predicting abnormal values of SH and SHBG >0.75 due to the effects of ECs was observed for T, DHT, and E2 in men, and for E2 and SHBG in women., Conclusions: Results of this study suggest that in elderly subjects, concentrations of many ECs associated with concentrations of SH and SHBG, and AEI. Further studies are needed to confirm the findings and to assess effect of the pollutants on endocrine system function in elderly., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark Kushnir reports a relationship with ARUP Institute for Clinical and Experimental Pathology that includes: employment. The other authors declared 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.)

The rapidly rising risk of cognitive decline is a serious challenge for the elderly. As the wide-distributed environmental chemicals, the effects of metals exposure on cognitive function have attracted much attention, but the results remain inclusive. This study aimed to investigate the roles of multiple metals co-exposure on cognition. We included a total of 6112 middle-aged and older participants, detected their plasma levels of 23 metals by using inductively coupled plasma mass spectrometry, and assessed their cognitive function by using the Mini-Mental State Examination (MMSE). The results showed that increased plasma levels of iron (Fe) and zinc (Zn) were positively associated with MMSE score, but the increased levels of nickel (Ni) and lead (Pb) were associated with decreased MMSE score (all FDR < 0.05). Subjects exposed to both high levels of Ni and Pb showed the lowest MMSE score [β (95% CI) = -0.310 (-0.519, -0.100)], suggesting that Ni and Pb had a synergistic toxic effect on cognitive function. In addition, the hazardous roles of Ni and Pb were mainly found among subjects with low plasma level of Zn, but were not significant among those with high-Zn level [Ni: β (95% CI) = -0.281 (-0.546, -0.015) vs. -0.146 (-0.351, 0.058); Pb: β (95% CI) = -0.410 (-0.651, -0.169) vs. -0.060 (-0.275, 0.155)], which suggested that Zn could attenuate the adverse effects of Pb and Ni on cognitive function. The cognitive function was gradually decreased among subjects with increased number of adverse exposures to the above four metals (P trend < 0.001). In conclusion, our findings revealed the individual, interactive, and combined effects of Fe, Ni, Pb, and Zn on cognitive function, which may provide new perspectives on cognitive protection, but further prospective cohort studies and biological researches are needed to validate these findings., 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.)

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver 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: Epidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association., Methods: The study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation., Results: One ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects., Conclusion: Our findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators., 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.)

In Arctic seabirds, positive correlations between per- and polyfluoroalkyl substances (PFAS) and thyroid hormones (THs) and resting metabolic rate (RMR) have been documented. Herein we investigated levels and patterns of PFAS in Arctic terns (Sterna paradisaea) nesting in Kongsfjorden, Svalbard (Norway), and if circulating concentrations of PFAS correlated with their circulating concentrations of TH, and the RMR of the birds. The hypothesis was that there will be positive correlations between PFAS, TH, and RMR, indicating that PFAS-induced increases in plasma THs could be responsible for the increased RMR. The dominating PFAS in the terns were perfluorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA) and perfluorotridecanoate (PFTrDA). The PFAS pattern was similar to what has been found in other seabirds in Kongsfjorden. There were positive correlations between several PFAS and total triiodothyronine (TT 3 ) concentrations in the terns. When sex was accounted for there were significant correlations in female terns, but not in males. There were no correlations between PFAS and RMR or between TT 3 and RMR. This indicates that there is no link between a PFAS-induced increase in plasma TT 3 concentrations and a resultant increased RMR. The positive associations between blood PFAS concentrations and plasma TT 3 concentrations may be a passive association, as both PFAS and T 3 bind to thyroid hormone binding proteins (THBP). We recommend that interrelationships between circulating concentrations of PFAS, THs and THBP are investigated further to identify the role of PFAS as TH disrupting chemicals and chemicals that may affect the RMR in birds., 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: Per- and polyfluoroalkyl substances (PFAS), synthetic chemicals with adverse health effects, are used extensively in consumer products. Ski waxes, applied to the base of skis, contain up to 100% PFAS by mass, but exposure and health effects are poorly characterized., Objectives: Our objectives were to quantify serum PFAS concentrations among skiers and explore associations with reported ski wax use and biomarkers of cardiometabolic, thyroid, and immune health., Methods: We recruited 30 active adult skiers to provide non-fasting blood samples and complete questionnaires. We quantified 18 PFAS using mass spectrometry, and measured serum lipids, thyroid hormones, and immunoglobulins. We explored associations of individual and aggregate measures of serum PFAS with wax use indicators and health biomarkers using multivariable regression models, adjusted for age and gender identity., Results: Nine PFAS (PFBS, PFHpS, PFHxS, Sm-PFOS, n-PFOS, PFDA, PFNA, PFUnDA, n-PFOA) were detected in 100% of participants, and MeFOSAA in 93%. Compared to NHANES, median serum concentrations (ng/ml) were similar, but higher in coaches (e.g., PFOA all : 1.1, PFOA coaches : 2.7, PFOA NHANES : 1.2; PFNA all : 0.5, PFNA coaches : 1.7, PFNA NHANES : 0.4). Factors reflecting wax exposure were positively associated with PFAS: e.g., >10 years as a snow sport athlete, compared to ≤10 years, was associated with 3.2 (95% CI: 0.7, 5.6) ng/ml higher aggregate PFAS, as defined by National Academies of Science, Engineering, and Medicine (NASEM). An IQR (6.3 ng/ml) increase in NASEM PFAS was associated with 32.1 (95% CI: 7.0, 57.2), 35.5 (13.5, 57.5), and 12.8 (0.6, 25.1) mg/dl higher total cholesterol, LDL-C, and sdLDL-C, respectively., Discussion: Our study provides early evidence that recreational skiers, particularly coaches, are exposed to PFAS through ski wax. Several PFAS were associated with higher serum lipids among these physically active adults. Interventions to remove PFAS from fluorinated wax could decrease direct exposure to skiers and reduce PFAS release into the environment., 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.)

With the soaring use of rare earth elements (REEs) worldwidely in high-technology and clean energy industries, there were growing concerns for adverse health effect from the REEs exposure. However, there is a lack of biomonitoring research concerning both urine and blood in population with definite exposure. We performed a biomonitoring study that involved 103 REEs exposed males and 110 males as non-REEs exposed controls. We measured the levels of REEs in environment and urine and blood samples from participants, and explored the exposure-response relationship between REEs in environment and body fluids. The effects of exposure duration and smoking status on the internal exposure level of REEs were also investigated. The results showed environmental REEs level of exposure group was significantly higher than that of control group (range of geometric mean of exposure vs. control: 1.08-4.07 × 10 4  ng/m 3 vs. 2  ng/m 3 ). Six elements with detection rates higher than 60% in blood or urine samples were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), samarium (Sm), gadolinium (Gd). We found the REEs concentrations both in urine and blood of exposure population were significantly higher than controls, median range of the above 6 elements of urine and blood was 0.02-1.06 μmol/mol vs.

Per- and polyfluoroalkyl substances (PFAS) have been detected in the blood of humans and animals worldwide. Exposure to some PFAS are associated with multiple adverse pregnancy outcomes. Existing literature has identified a strong association with PFAS exposure and metabolic dysfunction in humans, including modification of lipid metabolism. Using a subset of the Michigan Mother-Infant Pairs cohort (n = 95), this study investigated associations between first trimester plasma levels of PFAS and maternal lipids and metabolites in the first trimester (T1), at the time of delivery (T3), and in the infant cord blood (CB) using untargeted shotgun lipidomics and metabolomics. Identifying PFAS-induced alterations in the maternal lipid- or metabolome at specific timepoints may help elucidate windows of susceptibility to adverse pregnancy outcomes. Out of 9 PFAS measured, 7 were detected in at least 20% of samples and were used for further analyses. PFOS and PFHxS were measured at the highest concentrations with medians of 5.76 ng/mL and 3.33 ng/mL, respectively. PFOA, PFNA, and PFDA had lower measured values with medians of <1.2 ng/mL. PFHxS concentrations were positively associated with monounsaturated sphingomyelins (SMs) in T1 maternal plasma in adjusted models, determined by an adjusted p-value (q) < 0.1. PFHxS was positively associated with saturated and polyunsaturated SMs and inversely associated with saturated diacylglycerols in T1. Following metabolite-specific analysis, two mono-unsaturated diacylglycerols with carbon chain lengths of 32 and 35 were inversely associated with PFHxS in T1. In T3, only the association between PFHxS and SMs remained, but was attenuated. In addition, PFDA was associated with an increase in polyunsaturated plasmenyl-phosphatidylethanolamines in T3. No associations were identified between PFAS and infant cord blood lipids. Continued research into PFAS associated disruptions in lipid metabolism at sensitive stages of gestation may provide insight into the mechanisms that lead to adverse birth and pregnancy outcomes., 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.)

Intensive use of synthetic pesticides in conventional agriculture may harm non-target organisms through sublethal effects on life-history traits. Farmland birds are exposed throughout their life cycle, but the fate of non-persistent pesticide mixtures in wild birds remains unknown. In this study, we investigated changes in pesticide contamination levels in Montagu's harrier (Circus pygargus) nestlings during their growth. In total, 35 chicks were sampled twice during the rearing period, and blood was tested for 116 pesticides to assess pesticide load through two proxies; the number of pesticides detected and the sum of pesticide concentrations. Body mass and tarsus length were also measured to estimate body condition. Across the two sampling times, nine herbicides, five insecticides and four fungicides were detected. Contamination levels decreased significantly with nestling age irrespective of sampling date, and there was no relationship between pesticide load and body condition. Moreover, concentrations of chlorpyrifos-methyl, fenpropidin, metamitron, picloram and S-metolachlor, all detected throughout the rearing period, were unrelated to any of the explanatory variables. However, ethofumesate concentrations decreased significantly with chick age. This study provides the first evidence that non-persistent pesticide mixtures can decrease with age in wild nestlings. This has implications for understanding how chicks are contaminated and provides new insights on pesticide fate within organisms., 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 relationship between body levels of heavy metals and the risk of schizophrenia remains unclear. This study investigates the relationship between plasma levels of toxic heavy metals and the risk of schizophrenia among adults in Guangxi, China. Plasma concentrations of lead (Pb), cadmium (Cd), arsenic (As), and chromium (Cr) were measured using inductively coupled plasma mass spectrometry (ICP-MS). To evaluate both the single and combined effects of metal exposure on the risk of schizophrenia, we employed multivariate logistic regression, Bayesian Kernel Machine Regression (BKMR), and generalized Weighted Quantile Sum (gWQS) models. Additionally, we employed the Comparative Toxicogenomics Database (CTD) to analyze the mechanistic pathways through which metal mixtures may induce schizophrenia. Relative mRNA expression levels were measured using Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict potential biological functions. In logistic regression models, compared to the lowest exposure group (Q1), the odds ratios (ORs) for Pb in groups Q2, Q3, and Q4 were 2.18 (95% CI: 1.20-3.94), 4.74 (95% CI: 2.52-8.95), and 3.62 (95% CI: 1.80-7.28), respectively. Both BKMR and gWQS models indicated a positive correlation between the combined effects of toxic heavy metal mixtures and the risk of schizophrenia, with Pb demonstrating the most substantial impact, particularly in older adults and females. Elevated levels of tumor necrosis factor (TNF) and interleukin-1 beta (IL-1β) were observed in patients with schizophrenia, while the expression of tumor protein p53 (TP53) was significantly reduced. These findings underscore the critical need to avoid exposure to toxic heavy metals to prevent schizophrenia, highlighting significant public health implications., 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.)

Despite numerous studies, the associations between per- and polyfluoroalkyl substances (PFAS) exposure and various lipid levels in pregnant women remain ambiguous, especially concerning the association with cord blood lipids. This analysis included 20,960 pregnant women enrolled in the Japan Environment and Children's Study, recruited between 2011 and 2014. Non-fasting plasma samples collected before 22 weeks of gestation were examined for PFAS concentrations. Additionally, non-fasting serum samples collected before, at and after 22 weeks of gestation, at birth, and from cord blood were used to measure total cholesterol (TC) and triglycerides (TG). Linear regression models were applied to quantify the association between each PFAS and various lipid metrics. Among the 28 PFAS analyzed, 7 were quantifiable in more than 80% of participants. Of these, 6 PFAS showed positive associations with TC in maternal blood before 22 weeks of gestation, a trend that remained mostly consistent for maternal blood samples in later stages. However, no associations were found with TC levels in cord blood. Regarding TG, 3 PFAS demonstrated a negative association with TG levels in maternal blood before 22 weeks of gestation, with these relationships generally persisting in later stages, while 4 PFAS were positively associated with TG in cord blood. In summary, this study identified associations between PFAS concentrations in maternal blood and lipid levels in both maternal and cord blood, with differing patterns observed between the two., 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.)

Background: Early-life lead exposure affects cognitive development and emerging evidence suggests similar effects of cadmium and fluoride., Objective: To assess the impact of gestational and childhood exposure to lead, cadmium, and fluoride on cognitive abilities and behavioral and social communication problems., Methods: We studied 470 pregnant women (gestational week 29) and their 4-year-old children from the NICE cohort in northern Sweden. Concentrations of erythrocyte lead and cadmium and urinary cadmium were measured using inductively coupled plasma mass spectrometry and urinary fluoride with an ion-selective electrode. Urinary concentrations were specific-gravity adjusted. Associations of log 2 -transformed exposure concentrations with cognitive abilities (full-scale IQ and verbal comprehension by Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition), behavioral problems (Child Behavior Checklist), and social communication (Social Responsiveness Scale-Second Edition) were evaluated with multivariable-adjusted linear regression analysis., Results: Both gestational and cord erythrocyte lead concentrations were non-significantly inversely associated with child cognitive abilities (full-scale IQ: B [95%CI]: -1.2 [-2.9, 0.5] and -1.6 [-3.7, 0.4], respectively; per doubling of exposure). Similarly, both gestational and child urinary cadmium were inversely associated with cognitive abilities (full-scale IQ: -1.1 [-2.5, 0.3] and -1.1 [-2.5, 0.4], verbal comprehension: -1.2 [-3.1, 0.6] and -1.4 [-3.4, 0.6], respectively). Urinary fluoride concentrations showed no association with cognitive abilities. However, gestational fluoride was associated with increasing externalizing problems (0.9 [-0.3, 2.0]) and ADHD raw scores (0.3 [0.0, 0.6]). Childhood erythrocyte lead and urinary cadmium were non-significantly associated with increased behavioral problems (lead with total problems: 1.2 [-0.4, 2.9] and internalizing problems: 1.5 [-0.4, 3.4]; cadmium with externalizing problems: 1.1 [-0.2, 2.4])., Conclusion: Despite non-significant associations, both lead and cadmium exposure showed consistent inverse associations with cognitive abilities at 4 years, whereas associations with behavioral problems were less conclusive, especially for cadmium. Results on fluoride indicated association with externalizing problems, including ADHD, but prevalence of behavioral problems was low, increasing uncertainty., 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 and Objectives: Diet plays critical roles in modulating maternal metabolic health in pregnancy, but is also a source of metabolic-disrupting phthalates and their replacements. We aimed to evaluate whether the effects of better diet quality on favorable maternal metabolic outcomes could be partially explained by lower exposure to phthalates/replacements., Methods: At 13 weeks gestation, 295 Illinois women (enrolled 2015-2018) completed a three-month food frequency questionnaire that we used to calculate the Alternative Healthy Eating Index (AHEI)-2010 to assess diet quality. We quantified 19 metabolites, reflecting exposure to 10 phthalates/replacements, in a pool of five first-morning urine samples collected monthly across pregnancy. We measured 15 metabolic biomarkers in fasting plasma samples collected at 17 weeks gestation, which we reduced to five uncorrelated principal components (PCs), representing adiposity, lipids, cholesterol, inflammation, and growth. We used linear regression to estimate associations of diet quality with [1] phthalates/replacements and [2] metabolic PCs, as well as [3] associations of phthalates/replacements with metabolic PCs. We estimated the proportion of associations between diet quality and metabolic outcomes explained by phthalates/replacements using a causal mediation framework., Results: Overall, every 10-point improvement in AHEI-2010 score was associated with -0.15 (95% CI: -0.27, -0.04) lower adiposity scores, reflecting lower glucose, insulin, C-peptide, leptin, C-reactive protein, but higher adiponectin biomarker levels. Every 10-point increase in diet quality was also associated with 18% (95%CI: 7%, 28%) lower sum of di-2-ethylhexyl terephthalate urinary metabolites (∑DEHTP). Correspondingly, each 18% increase in ∑DEHTP was associated with 0.03 point (95% CI: 0.01, 0.05) higher adiposity PC scores. In mediation analyses, 21% of the inverse relationship between diet quality and adiposity PC scores was explained by lower ∑DEHTP., Conclusions: The favorable impact of diet quality on maternal adiposity biomarkers may be partially attributed to lower metabolite concentrations of DEHTP, a plasticizer allowed to be used in food packaging materials., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Braun served as an expert witness in litigation related to perfluorooctanonic acid contamination in drinking water in New Hampshire. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies., Methods: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies., Results: Of the 18 studies published between 2006 and 2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR = 1.18, 95% CI 1.02-1.37 at 2.0 μg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 μg/L, reaching a RR of 1.48 (95% CI 1.17-1.86) at 2.0 μg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 μg/g creatinine., Conclusions: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lauren Wise receives in-kind donations from Kindara.com (fertility apps) and Swiss Precision Diagnostics (home pregnancy tests). She also serves as consultant for Gates Foundation and AbbVie, Inc. All of these relationships are for work unrelated to this manuscript. All other authors have nothing to disclosure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cadmium is a common environmental pollutant associated with various health risks. Its neurotoxic, muscle-damaging, and pro-inflammatory properties may be related to overactive bladder (OAB), though few studies have assessed its impact on urinary function. This study aimed to examine the potential link between cadmium exposure and OAB. Using data from the 2007-2020 National Health and Nutrition Examination Survey (NHANES), we analyzed adults aged 40 and older (n = 15,467) in a cross-sectional design. OAB was defined by the refined Overactive Bladder Symptom Score (OABSS). Weighted multivariate logistic regression examined the associations between blood cadmium levels and OAB and its components. Age and gender stratifications were performed, and restricted cubic splines (RCS) were used to explore non-linear associations between blood cadmium and OAB. Sensitivity analyses and co-exposure analyses with other pollutants were conducted to assess OAB definition stability, subgroup differences, and exposure collinearity. The prevalence of OAB was 26.2%. While blood cadmium showed a small, non-significant positive association with overall OAB, it was inversely associated with nocturia severity (OR = 0.85, 95% CI 0.74-0.98, p < 0.05). Blood cadmium was also linked to more severe urinary incontinence in the 50-59 age group and among non-Hispanic Black adults. A non-linear association between blood cadmium and OAB was observed (p for nonlinearity = 0.016, p < 0.05). In co-exposure analyses, cadmium remained a dominant and independent factor. These findings suggest that cadmium exposure may have a complex association with OAB and may relate differently to its various components. Further research is needed to explore these relationships., 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: The reproductive hormone homeostasis is crucial for child development. Exposure to metals during pregnancy may have adverse effects on offspring health. However, the association between prenatal exposure to metals and infant reproductive hormone levels remains unknown., Methods: This study involved 812 mother-infant pairs from Wuhan, China, assessing prenatal exposure to 13 metals in maternal plasma during early pregnancy and measuring five reproductive hormones in urine samples of one-month-old infants. Generalized linear models were employed to investigate the associations between individual metal exposures and urinary hormone levels in infants. Additionally, weighted quantile sum (WQS) regression and quantile g-computation were employed to evaluate the impact of metal mixtures., Results: Most of the detected metals in maternal plasma were associated with lower levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in infants. Each interquartile range (IQR) increase in manganese (Mn), barium (Ba), thallium (Tl), vanadium (V), cobalt (Co), nickel (Ni), and lead (Pb) was significantly associated with an approximately 9.87 % to 38.24 % decrease in FSH or LH. WQS and quantile g-computation models confirmed a significant association between prenatal metal mixtures and reduced FSH and LH in male infants, and WQS indicated a significant association between metal mixtures and decreased FSH in female infants., Conclusions: Maternal exposure to mixed metals during early pregnancy was associated with lower levels of FSH and LH in infants, suggesting that prenatal exposure to metals may disrupt the balance of infant reproductive hormones. Further research is warranted to confirm these associations and explore 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 B.V. All rights reserved.)