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People are paying more and more attention to the effects of environmental factors such as heavy metals on depression, and heavy metals may destroy the homeostasis of vitamin D in the body by affecting human metabolism, and the lack of vitamin D will increase the risk of depression. There are few studies on vitamin D deficiency in depression caused by heavy metals, and it is not deep enough. Therefore, this study used logistic regression, restricted cubic spline curve, weighted quantile and Quantile g-computation model to analyze the effects of heavy metal exposure alone and in combination on vitamin D and depression, as well as the potential role of vitamin D deficiency in the process of heavy metal-induced depression. The results showed that cadmium exposure alone or in combination increased the risk of depression (P < 0.05). When Cd increased by 1 unit, the risk of depressive symptoms increased by 1.178 units. Arsenic and its compounds and lead affected vitamin D levels in the body and contributed the second highest or highest weight in the mixture (P < 0.05). It is worth noting that after grouping according to vitamin D deficiency, compared with the normal group, the mixed exposure of heavy metals in the vitamin D deficiency group had more types of metals related to depression and contributed more weight (P < 0.05). This study found that single metal or multi-metal mixed exposure is associated with depression. Vitamin D deficiency may increase the risk of depression. Vitamin D may be a potential factor in the treatment of depression caused by metal, and the specific mechanism of action needs further study., 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.)

Context: Federal law requires property owners to disclose the presence of known lead-based paint and/or lead hazards to potential home buyers and renters in homes built before 1978., Objective: Using 2015-2016 randomized survey data, we measured lead and radon knowledge, awareness, and exposure avoidance practices., Setting: Home buyers from 4 US states (Illinois, Minnesota, North Carolina, and Ohio)., Participants: 477 recent, single-family pre-1978 dwelling home buyers., Main Outcome Measure(s): Predictors of the home buyer decision to purchase the home during the entire home buying experience based on their understanding of health issues related to lead-based paint and radon exposure., Results: Personal networks (22%) and real estate agents (21%) were the most common sources of health-related lead information. Many home buyers (77%) reported that their awareness of lead did not affect their purchasing decision, and 78% could not confirm that their homes were tested for lead. Respondents who understood lead-related health effects were 5.4 times more likely (95% CI, 1.7-17.5) to have their decision to buy a home affected when their real estate agent discussed lead-based paint issues. Many home buyers reported either they did not remember (37%) or did not sign (20%) the federal law requirement that property owners reveal known lead paint hazards to prospective buyers before a property is sold. Home buyers with awareness of health issues caused by radon were 1.7 times (95% CI, 1.4-2.1) more likely than those who understood lead-related health issues to have their decision to buy the home affected., Conclusion: Real estate agents play an important role to increase awareness of potential lead-based paint health issues when people buy older homes. Home buyer knowledge, awareness, and practice of radon exposure prevention was greater compared to lead exposure prevention. More than half of home buyers did not sign or remember signing lead disclosure paperwork., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Special education enrollment increased in Flint following the 2014-2015 Flint Water Crisis, but lead exposure is not plausibly responsible. Labeling Flint children as lead poisoned and/or brain damaged may have contributed to rising special education needs (ie, nocebo effect). To better document this possibility, we surveyed schoolteachers and reviewed neuropsychological assessments of children for indications of negative labeling., Methods: A survey of Flint and Detroit (control) public schoolteachers using a modified Illness Perception Questionnaire was conducted 5 years post-crisis. We also examined neuropsychological assessments from a recently settled class lawsuit., Results: Relative to Detroit (n = 24), Flint teachers (n = 11) believed that a higher proportion of their students had harmful lead exposure (91.8% Flint vs 46% Detroit; P = 0.00034), were lead poisoned (51.3% vs 24.3%; P = 0.018), or brain damaged (28.8% vs 12.9%; P = 0.1), even though blood lead of Flint children was always less than half of that of Detroit children. Neuropsychological assessments diagnosed lead poisoning and/or brain damage from water lead exposure in all tested children (n = 8), even though none had evidence of elevated blood lead and a majority had prior learning disability diagnoses., Conclusion: Teachers' responses and neuropsychological assessments suggest Flint children were harmed by a nocebo effect.

Purpose of Review: While high levels of lead exposure, as occurs accidentally or occupationally, can cause toxicity across multiple organ systems, the hazard of commonly encountered levels of lead in the environment remains unresolved. Challenges to researching the health effects of lead include its complex interplay with renal function, rendering analyses at risk of unaccounted confounding, and the likely small effect size of environmental levels of exposure. While children are known to be disproportionately susceptible to lead toxicity, resulting in appropriately more stringent regulatory surveillance for those under 5 years old, emerging evidence suggests that those with chronic kidney disease (CKD) similarly are at a greater risk. This review summarizes the role of environmental lead toxicity as a potential cause and consequence of CKD., Recent Findings: Whether environmental lead exposure causes CKD remains debatable, with little recent research advancing the conflicting, mostly cross-sectional, analyses from years ago. However, an emerging body of evidence suggests that CKD increases the susceptibility to lead toxicity. Higher circulating lead levels and lower urinary excretion result in greater lead accumulation in CKD, with simultaneous greater risk of clinically meaningful disease. Recent studies suggest that levels of lead found commonly in the United States drinking water supply, and currently permissible by the Environmental Protection Agency, associate with hematologic toxicity in those with advanced CKD. Whether environmental lead contamination may have additional negative health impact among this at-risk population, including cardiovascular and neurocognitive disease, warrants further study., Summary: The underlying pathophysiology of kidney disease synergizes the susceptibility to environmental lead toxicity for those with CKD. Low levels of exposure, as found commonly in the United States water supply, may have adverse health impact in CKD. Further research will be needed to determine if more stringent environmental regulations are warranted to protect the health of all., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a recognized neurodevelopmental disorder with a complex, multifactorial origin. Lead (Pb) and mercury (Hg) are highly toxic substances that can potentially impair brain development and have been implicated in the development of ADHD. This systematic review aims to analyze the epidemiological literature regarding the association between Pb and Hg exposure and the diagnosis of ADHD., Methods: From November 1983 to June 2, 2023, a comprehensive search was conducted in multiple databases and search engines, including PubMed, Web of Science, Scopus, and Google Scholar. Observational studies (case-control, cohort, and cross-sectional) measuring Pb and Hg levels in various biological samples (blood, hair, urine, nail, saliva, teeth, and bone) of children with ADHD or their parents and their association with ADHD symptoms were included., Results: Out of 2059 studies, 87 met the inclusion criteria and were included in this systematic review. Approximately two-thirds of the 74 studies investigating Pb levels in different biological samples reported associations with at least one subtype of ADHD. However, most studies examining Hg levels in various biological samples found no significant association with any ADHD subtype, although there were variations in exposure periods and diagnostic criteria., Conclusion: The evidence gathered from the included studies supports an association between Pb exposure and the diagnosis of ADHD, while no significant association was found with Hg exposure. Importantly, even low levels of Pb were found to elevate the risk of ADHD. Further research is needed to explore the comprehensive range of risk factors for ADHD in children, considering its significance as a neurodevelopmental disorder., (© 2024. The Author(s).)

Background: Brownfields consist of abandoned and disused sites, spanning many former purposes. Brownfields represent a heterogenous yet ubiquitous exposure for many Americans, which may contain hazardous wastes and represent urban blight. Neonates and pregnant individuals are often sensitive to subtle environmental exposures. We evaluate if residential exposure to lead (Pb) brownfields is associated with birth defects., Methods: Using North Carolina birth records from 2003 to 2015, we sampled 169,499 births within 10 km of a Pb brownfield with 3255 cardiovascular, central nervous, or external defects identified. Exposure was classified by binary specification of residing within 3 km of a Pb brownfield. We utilized multivariable logistic regression models adjusted for demographic covariates available from birth records and 2010 Census to estimate odds ratios (OR) and 95% confidence intervals (CI). Effect measure modification was assessed by inclusion of interaction terms and stratification for the potential modifiers of race/ethnicity and diabetes status., Results: We observed positive associations between cardiovascular birth defects and residential proximity to Pb brownfields, OR (95%CI): 1.15 (1.04, 1.26), with suggestive positive associations for central nervous 1.16 (0.91, 1.47) and external defects 1.19 (0.88, 1.59). We did observe evidence of effect measure modification via likelihood ratio tests (LRT) for race/ethnicity for central nervous and external defect groups (LRT p values 0.08 and 0.02). We did observe modification by diabetes status for the cardiovascular group (LRT p value 0.08)., Conclusions: Our results from this analysis indicate that residential proximity to Pb brownfields is associated with cardiovascular birth defects with suggestive associations for central nervous and external defects. In-depth analyses of individual defects and other contaminants or brownfield site functions may reveal additional novel associations., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Childhood exposure to polycyclic aromatic hydrocarbons (PAHs) or lead (Pb) is associated with epigenetic modifications. However, the effects of their co-exposures on IGF1 (Insulin-like growth factor 1) methylation and the potential role in child physical growth are unclear., Methods: From our previous children study (N = 238, ages of 3-6), 75 children with higher total concentrations of urinary ten hydroxyl PAH metabolites (∑ 10 OH-PAHs) from an e-waste recycling area, Guiyu, and 75 with lower ∑ 10 OH-PAHs from Haojiang (reference area) were included. Pb and IGF1 P2 promoter methylation in peripheral blood were also measured. Multivariable linear regression analyses were performed to estimate individual associations, overall effects and interactions of co-exposure to OH-PAHs and Pb on IGF1 methylation were further explored using Bayesian kernel machine regression., Results: Methylation of IGF1 (CG-232) was lower (38.00 vs. 39.74 %, P < 0.001), but of CG-207 and CG-137 were higher (59.94 vs. 58.41 %; 57.60 vs. 56.28 %, both P < 0.05) in exposed children than the reference. The elevated urinary 2-OHPhe was associated with reduced methylation of CG-232 (B = -0.051, 95 % CI: -0.096, -0.005, P < 0.05), whereas blood Pb was positively associated with methylation of CG-108 (B = 0.106, 95 %CI: 0.013, 0.199, P < 0.05), even after full adjustment. Methylations of CG-224 and 218 significantly decreased when all OH-PAHs and Pb mixtures were set at 35th - 40th and 45th - 55th percentile compared to when all fixed at 50th percentile. There were bivariate interactions of co-exposure to the mixtures on methylations of CG-232, 224, 218, and 108. Methylations correlated with height, weight, were observed in the exposed children., Conclusions: Childhood co-exposure to high PAHs and Pb from the e-waste may be associated with IGF1 promoter methylation alterations in peripheral blood. This, in turn, may interrupt the physical growth of preschool children., 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.)

This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures., 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: This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA., Methods: Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 μg/dL) and high (≥ 5 μg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level., Results: The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted., Conclusions: These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Lead exposure has been linked to a myriad of cardiovascular diseases. Utilizing data from the 2019 Global Burden of Disease Study, we quantified age-standardized lead exposure-related mortality and disability-adjusted life years (DALYs) in the United States between 1990 and 2019. Our analysis revealed a substantial reduction in age-standardized cardiovascular disease (CVD) mortality attributable to lead exposure by 60 % (from 7.4 to 2.9 per 100,000), along with a concurrent decrease in age-standardized CVD DALYs by 66 % (from 143.2 to 48.7 per 100,000)., 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.)

Diabetes is a global health concern with significant implications for individuals and societies. Diabetes results from a complex interaction between genes and environmental factors, including metal exposure. Lead or plumbum (Pb) is a heavy metal pollutant and is predicted to be associated with the morbidity of diabetes. The aim of this study was to assess the relationship between blood Pb level and possible risk factors (body mass index insulin resistance, carbohydrate intake, sugar intake, and physical activity) with fasting blood sugar (FBS) level in women living in the mining area. A cross-sectional study was conducted in a mining area of Indonesia located in Pemali District, Bangka Belitung Regency, involving women aged 30-49, selected through purposive sampling. Logistic regression was used to assess the relationship between the risk factors and FBS level, while the Spearman correlation was used to analyze the correlations between the risk factors and FBS level. Our data indicated that blood Pb concentration and other risk factors (carbohydrate intake, sugar intake and physical activity) were neither associated nor correlated with FBS level. However, as predicted, insulin resistance was associated with FBS level with OR: 9.66; 95%CI: 1.13-82.29; p =0.038. In addition, the Homeostatic Model Assessment Insulin Resistance (HOMA-IR) score was also correlated with FBS level ( r =0.316, p =0.002). This study highlights the level of Pb is not associated with the risk of diabetes in women living in mining area., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 by the authors.)

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 μg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Dental caries has declined over the years, but it remains a major public health issue. This review aimed to investigate the association between lead (Pb) and caries experience in either deciduous or permanent teeth., Methods: A comprehensive search of PubMed, Embase, and Google Scholar was conducted to identify relevant studies published up until December 2022. Included were human observational studies that investigated the association between Pb exposure and dental caries. The review adhered to the PRISMA guideline., Results: Sixteen studies were included in this review, with nine focusing on deciduous teeth, thirteen on permanent teeth, and six examining both types of teeth. Most of the studies (5 of 6) found a positive association between blood lead (PbB) levels and caries in deciduous teeth, while the findings for permanent teeth were less conclusive, with only 3 of 10 studies finding an association. One of the two studies assessing salivary lead levels found a weak association for permanent teeth. All four studies that measured Pb concentration from teeth found a positive association for both deciduous and permanent teeth., Conclusion: Many published studies have indicated a positive association between Pb exposure and caries experience in deciduous dentition. Children with elevated PbB level should be considered having higher caries experience. Due to lack of consensus on measurement and examination technique, there remains insufficient evidence to make any definitive conclusions, especially in permanent dentition, and so more studies are warranted., (© 2024 S. Karger AG, Basel.)

Lead is a heavy, toxic metal and its exposure to humans can lead to increased risk of cardiovascular disease development and mortality. Lead exposure has been shown to induce hyperhomocysteinemia (HHCy) which may be a major pathogenic risk for the risk of CVDs. The aim of this study was to investigate whether homocysteine (Hcy) mediates the effect of lead on cardiovascular mortality. A total of 17,915 adults aged ≥ 20 who participated in the National Health and Nutrition Examination Survey (1999 to 2006). Information on mortality was ascertained via probabilistic matching to the death certificates from the National Death Index recorded up to December 31, 2015. Cox proportional hazards regression was performed to assess the association between blood lead levels and mortality. Mediation via Hcy was examined using a logit model. During a mean follow-up of 11.6 years, the incidences of CVD mortality were 0.73, 2.18, 3.03 and 4.94 per 1000 person-years across quarterlies of blood lead levels from low to high. Following multivariable adjustment, blood lead levels were strongly associated with CVD mortality in all mortality models (p-trend < 0.001). This association remained statistically significant after further adjusting for quartiles of homocysteine (model 3; HR 1.38 (95% CI 1.01-1.89) p-trend < 0.001). Furthermore, blood lead levels increased the odds of CVD mortality via homocysteine (indirect effect) (OR 1.42 (95% CI 1.30-1.55)), demonstrating the mediatory effect of homocysteine. This the first study that demonstrates that increased homocysteine mediates nearly half of CVD mortality related to blood lead levels., (© 2024. The Author(s).)

Background: Exposure to lead (Pb) is a major public health problem that could occur through contaminated soil, air, food, or water, either during the course of everyday life, or while working in hazardous occupations. Although Pb has long been known as a neurodevelopmental toxicant in children, a recent and growing body of epidemiological research indicates that cumulative, low-level Pb exposure likely drives age-related neurologic dysfunction in adults. Environmental Pb exposure in adulthood has been linked to risk of late-onset Alzheimer's disease (AD) and dementia., Objective: Although the biological mechanism underlying this link is unknown, it has been proposed that Pb exposure may increase the risk of AD via altering the expression of AD-related genes and, possibly, by activating the molecular pathways underlying AD-related pathology., Methods: We investigated Pb exposure using a line of genetically modified mice with AD-causing knock-in mutations in the amyloid precursor protein and presenilin 1 (APPΔNL/ΔNL x PS1P264L/P264L) that had been crossed with Leprdb/db mice to impart vulnerability to vascular pathology., Results: Our data show that although Pb exposure in adult mice impairs cognitive function, this effect is not related to either an increase in amyloid pathology or to changes in the expression of common AD-related genes. Pb exposure also caused a significant increase in blood pressure, a well known effect of Pb. Interestingly, although the increase in blood pressure was unrelated to genotype, only mice that carried AD-related mutations developed cognitive dysfunction, in spite of showing no significant change in cerebrovascular pathology., Conclusions: These results raise the possibility that the increased risk of dementia associated with Pb exposure in adults may be tied to its subsequent interaction with either pre-existing or developing AD-related neuropathology.

Objective: To investigate the effect of lead (Pb) exposure on Aβ 1-42 -induced microglial activation and copper ion accumulation in microglial cells and explore the regulatory mechanism of Pb-induced aggravation of Alzheimer's disease (AD)-like pathology., Methods: Cultured microglial BV2 cells were treated with different concentrations of Aβ 1-42 , lead acetate or their combination for 12 h, and the changes in cell viability and morphology were evaluated. Immunofluorescence assay was performed to detect iNOS and oxidative stress level in the treated cells, and the release of inflammatory factors was detected using ELISA. Western blotting and inductively coupled plasma-mass spectrometry (ICP-MS) were used to detect the expressions of CTR1 and ATP7A proteins and copper content in the cells., Results: Treatment with 15 and 20 μmol/L Aβ 1-42 for 12 h significantly lowered the viability of BV2 cells. Treatment with Aβ 1-42 at 10 μmol/L for 12 h obviously increased the release of iNOS, TNF-α and IL-6 in the cells ( P <0.05), and its combination with 15 or 20 μmol/L lead acetate more strongly lowered BV2 cell viability ( P <0.05). Compared with 10 μmol/L Aβ 1-42 treatment alone, 10 μmol/L Aβ 1-42 combined with 10 μmol/L lead acetate for 12 h caused more obvious microglial activation, as manifested by enlarged cell bodies, increased cell protrusions and elongation, enhanced release of iNOS, TNF-α, IL-6, IL-1β and ROS, and increased intracellular copper ion accumulation and expression of copper transporter CTR1 ( P <0.05). Compared with the conditioned medium from activated BV2 cells, which caused obvious injuries in hippocampal neuron HT22 cells ( P <0.001), the medium from BV2 cells treated with NAC and the copper ion chelating agent TM caused milder injuries in HT22 cells ( P <0.05)., Conclusion: Lead exposure aggravates neuronal damage caused by Aβ 1-42 -treated microglial cells by increasing copper ion accumulation, oxidative stress, and inflammatory factor release to trigger microglial activation.

Purpose: The purpose of this study was to determine the association between prenatal and early life exposure to lead and the presence of molar hypomineralization (MH) in a group of Mexican children. Methods: A subset of participants of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENTS) cohort study was examined for the presence of molar hypomineralization using European Academy of Pedi- atric Dentistry (EAPD) criteria. Prenatal lead exposure was assessed by K-ray fluorescence measurements of patella and tibia lead and by maternal blood lead levels by trimester and averaged over trimesters. Postnatal exposure was assessed by levels of maternal blood lead at delivery and child blood lead at 12 and 24 months. Results: A subset of 506 subjects from the ELEMENT cohorts (nine to 18 years old) were examined for MH; 87 subjects (17.2 percent) had MH. Maternal blood lead levels in the third trimester (odds ratio [OR] equals 1.08; 95 percent confidence interval [95% CI] equals 1.02 to 1.15) and averaged over three trimesters (OR equals 1.10; 95% CI equals 1.02 to 1.19) were significantly associated with MH status. None of the maternal bone lead or the child's blood lead parameters was significantly associated with the presence of MH (P>0.05). Conclusions: This study documents a significant association between prenatal lead exposure especially in late pregnancy and the odds of molar hypomineralization.

Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Exposure to environmental pollutants is linked to increased risk of cardiovascular disease. Beyond the extensive evidence for particulate air pollution, accumulating evidence supports that exposure to nonessential metals such as lead, cadmium, and arsenic is a significant contributor to cardiovascular disease worldwide. Humans are exposed to metals through air, water, soil, and food and extensive industrial and public use. Contaminant metals interfere with critical intracellular reactions and functions leading to oxidative stress and chronic inflammation that result in endothelial dysfunction, hypertension, epigenetic dysregulation, dyslipidemia, and changes in myocardial excitation and contractile function. Lead, cadmium, and arsenic have been linked to subclinical atherosclerosis, coronary artery stenosis, and calcification as well as to increased risk of ischemic heart disease and stroke, left ventricular hypertrophy and heart failure, and peripheral artery disease. Epidemiological studies show that exposure to lead, cadmium, or arsenic is associated with cardiovascular death mostly attributable to ischemic heart disease. Public health measures reducing metal exposure are associated with reductions in cardiovascular disease death. Populations of color and low socioeconomic means are more commonly exposed to metals and therefore at greater risk of metal-induced cardiovascular disease. Together with strengthening public health measures to prevent metal exposures, development of more sensitive and selective measurement modalities, clinical monitoring of metal exposures, and the development of metal chelation therapies could further diminish the burden of cardiovascular disease attributable to metal exposure.

Introduction: Drinking lead contaminated water during pregnancy is associated with infant mortality. All women of reproductive age are advised by health agencies to adhere to healthy behaviors due to the chance of unintended pregnancy. Our objectives are to understand knowledge, confidence, and reported behaviors that promote safe water drinking and prevent lead exposure among women of reproductive age., Methods: A survey among females of reproductive age from the University of Michigan - Flint was administered. A total of 83 females who wished to become pregnant one day participated., Results: Low levels of knowledge, confidence, and reported preventative health behaviors related to safe water drinking and lead exposure prevention existed. Specifically, 71.1% of respondents (59 of 83) were not at all or were somewhat confident in their ability to choose an appropriate lead water filter. Most participants rated their knowledge on how to decrease exposure to lead during pregnancy as poor/fair. No statistically significant differences were detected between respondents residing inside and outside of the city of Flint, Michigan for most variables assessed., Conclusion: While the small sample size is a limitation, the study adds to an area of scarce research. Despite widespread media attention and resources directed toward reducing the negative health effects of lead exposure following the Flint Water Crisis, significant gaps in knowledge related to safe water drinking remain. Interventions are needed to increase knowledge, confidence, and healthy behaviors that promote safe water drinking among women of reproductive age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kodjebacheva, Lapeyrouse, Okungbowa-Ikponmwosa, Walker, Campbell and Cupal.)

Background: The independent effect of lead exposure and parental education on children's neurocognition is well-documented. However, few studies have examined the combined effect of childhood lead exposure and parental education on adolescent neurocognition, especially in China., Objective: Examine both the combined and interactive effect of childhood blood lead levels (BLLs) and parental education on early adolescent neurocognition., Methods: 417 children from a longitudinal cohort study in Jintan, China had BLLs measured at 3-5 years and 12 years, parental education levels assessed at 3-5 years, and neurocognitive outcomes tested at 12 years., Results: BLLs at 3-5 years were inversely associated with adolescent IQ (β -0.55 95% CI: -0.97, -0.13) but not working memory (β -0.06 95% CI: -0.23, 0.11) and parental education was positively associated with adolescent IQ (β 0.68 95% CI: 0.19, 1.17) and working memory (β 0.24 95% CI: 0.04, 0.44). BLLs and parental education evidenced combined effects on neurocognition, where children with higher BLLs and lower fathers' education had mean IQ scores 7.84 (95% CI: -13.15, -2.53) points lower than children with lower BLLs and higher fathers' education. There were significant associations between parental education and working memory, however, not with BLLs. The interaction between mother and father high school education and BLLs was insignificant for effects on IQ and working memory., Significance: Childhood lead exposure and parental education levels have a combined and long-term impact on IQ, evidence that may partially explain disparities in lead exposure associated outcomes and highlight those children at greatest risk for neurocognitive deficits., Impact Statement: Children continue to be exposed to low-levels of environmental lead in China and globally, warranting examination of the impact of such exposures. This paper demonstrates that even relatively low-level lead exposure in early childhood significantly influences adolescent neurocognitive functioning. Furthermore, co-existing social determinant of health-related variables, measured here as parental education, have a combined impact on neurocognition. These results highlight children at greater risk for neurocognitive deficits and demonstrate the need to examine the influence of lead exposure within the broader socio- ecological environment, as these factors work in tandem to influence longer-term neurocognitive outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Lead is an environmental hazard that should be addressed worldwide. Over time, human lead exposure in the western world has decreased drastically to levels comparable to those among humans living in the preindustrial era, who were mainly exposed to natural sources of lead. To re-evaluate the potential health risks associated with present-day lead exposure, a two-pronged approach was applied. First, recently published population metrics describing the adverse health effects associated with lead exposure at the population level were critically assessed. Next, the key results of the Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) were summarized and put in perspective with those of the published population metrics. To our knowledge, SPHERL is the first prospective study that accounted for interindividual variability between people with respect to their vulnerability to the toxic effects of lead exposure by assessing the participants' health status before and after occupational lead exposure. The overall conclusion of this comprehensive review is that mainstream ideas about the public and occupational health risks related to lead exposure urgently need to be updated because a large portion of the available literature became obsolete given the sharp decrease in exposure levels over the past 40 years., (© 2022. The Author(s).)

Background: Gunshot emissions contain toxic elements that can harm those frequently exposed, such as police officers. Several years ago, police indoor firing ranges were closed by the Berlin municipality in response to police officer health complaints, and an investigation was launched into the possible respiratory health risks of frequent gunshot emission exposure. We, therefore, conducted an exploratory cross-sectional study to investigate clinical and functional parameters of respiratory health as well as the burden of trace elements in policemen with long-term high exposure to indoor gunshot emissions, compared to low-exposure and control groups., Methods: We conducted lung function tests and collected blood and urine samples from Berlin police officers and government employees who were divided into three subject groups based on exposure to gunshot emissions: high exposure (n = 53), low exposure (n = 94) and no exposure (n = 76). Lung function was examined using body plethysmography. Blood and urine samples were tested via inductively coupled plasma mass spectrometry for the presence of common gunshot powder elements (antimony, lead and manganese). Exposure and symptoms were assessed using records as well as questionnaires., Results: Higher exposure was associated with more respiratory symptoms during gun shooting practice (64% vs. 21%, P < 0.001) compared to the low-exposure group. Headache, cough, discoloured mucous and shortness of breath were also more common as were some other symptoms. The cough symptomatology of the high-exposure group also persisted significantly longer (median: 0.67 vs. 0.01 days, range: 0 to 5 days, P = 0.029) compared to the low-exposure group. They also showed a lower forced expiratory volume in 1 s/forced vital capacity quotient (Tiffeneau index), P = 0.018 between the three groups and P = 0.005 for the high-exposure group, a possible marker of early, subclinical bronchial obstruction. We observed increased blood lead concentrations depending on subject's age (+1.2% per year, 95% confidence interval: 0.5-1.9%, P < 0.001) and cumulative gunshot exposure (+0.34% per 100 000 shots, 0.02-0.66%, P = 0.037)., Conclusions: These first results suggest that long-term exposure to indoor gunshot emissions induces bronchitic reactions due to repeated irritation of the airways. Higher levels of exposure lead to more negatively impacted lung function and higher blood lead levels with the possible reason that more frequent exposure may mean shorter regeneration phases for the respiratory mucous membrane. We recommend a reduction of exposure to gunshot emissions in order to decrease symptoms and avoid any-even small-deterioration in spirometry., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Lead is an environmental hazard that should be addressed worldwide. Over time, human exposure to lead in the Western world has fallen drastically to the levels comparable to those in humans living in the pre-industrial era, who were mainly exposed to natural sources of lead. To re-evaluate the health risks possibly associated with present-day lead exposure, a three-pronged approach was applied. First, we critically assessed the recently published population metrics describing the adverse health effects associated with lead exposure at the population level. Next, we summarized the key results of the Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) and analyzed these results in the context of the published population metrics. Last but not least, we performed a brief literature review on the present-day lead exposure level in Poland. To our best knowledge, SPHERL is the first prospective study that accounted for interindividual variation in vulnerability to the toxic effects of lead exposure by assessing the participants' health status before and after occupational lead exposure, with blood pressure and hypertension as the primary outcomes. The overall conclusion of this comprehensive review on blood pressure and hypertension is that mainstream ideas about the public and occupational health risks related to lead exposure need to be urgently updated because a large part of the available literature has become obsolete given present-day exposure levels that sharply declined over the past 40 years.

Background: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy., Methods: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions., Results: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses., Discussion/conclusion: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor 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 © 2022 Elsevier B.V. All rights reserved.)

Background Lead is a cardiotoxic metal with a variety of adverse health effects. In the absence of data on bone lead exposure, epigenetic biomarkers can serve as indicators of cumulative lead exposure and body burden. Herein, we leveraged novel epigenetic biomarkers of lead exposure to investigate their association with cardiovascular disease (CVD) incidence and mortality. Methods and Results Blood DNA methylation was measured using the Illumina MethylationEPIC BeadChip among 2231 participants of the Strong Heart Study (SHS) at baseline (1989-1991). Epigenetic biomarkers of lead levels in blood, patella, and tibia were estimated using previously identified cytosine-guanine dinucleotide (CpG) sites. CVD incidence and mortality data were available through 2017. Median concentrations of lead epigenetic biomarkers were 13.8 μg/g, 21.3 μg/g, and 2.9 μg/dL in tibia, patella, and blood, respectively. In adjusted models, the hazard ratio (HR) (95% CI) of CVD mortality per doubling increase in lead epigenetic biomarkers were 1.42 (1.07-1.87) for tibia lead, 1.22 (0.93-1.60) for patella lead, and 1.57 (1.16-2.11) for blood lead. The corresponding HRs for incident CVD were 0.99 (0.83-1.19), 1.07 (0.89-1.29), and 1.06 (0.87-1.30). The association between the tibia lead epigenetic biomarker and CVD mortality was modified by sex (interaction P value: 0.014), with men at increased risk (HR, 1.42 [95% CI, 1.17-1.72]) compared with women (HR, 1.04 [95% CI, 0.89-1.22]). Conclusions Tibia and blood epigenetic biomarkers were associated with increased risk of CVD mortality, potentially reflecting the cardiovascular impact of cumulative and recent lead exposures. These findings support that epigenetic biomarkers of lead exposure may capture some of the disease risk associated with lead exposure.

Background: The relationship between maternal lead level and risk of preterm birth (PTB) remained controversial. Therefore, herein we performed this meta-analysis to investigate the association of maternal blood, urine and cord blood lead level with the risk of PTB using observational studies., Methods: A systematic search was conducted in PubMed, EMBASE and Ovid Medline databases from inception to August 2019, and sixteen studies with 65600 participants investigating the association between maternal lead level and PTB were included in our meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the highest versus lowest lead level by random-effects model., Results: Overall, the pooled OR of all included articles for the highest versus lowest PTB score was 1.29 (95% CI = 1.14-1.46; I2 = 80.4%, p  < .001), and the results revealed a direct and significant relationship between second and third trimester blood lead level (BLL) and PTB (OR 2nd trimester= 1.61, 95% CI = 1.08-2.40, OR 3rd trimester= 1.57, 95% CI = 1.11-2.23)., Conclusion: Results of this meta-analysis showed that maternal BLL is directly associated with the risk of PTB.

Background and Aim: An association between lead (Pb) exposure and antisocial behaviors has been documented, but findings have been inconclusive. We aimed to estimate the association between prenatal, early childhood, and preadolescent/adolescent (periadolescent) Pb exposure and aggression and conduct problems in periadolescent residents of Mexico City., Methods: Using information from the ELEMENT cohort study, we assessed prenatal Pb exposure through maternal patella Pb (MPPb) measurement during the puerperium, early childhood (birth to 5 years of age) exposure through a cumulative blood lead index (CBLI), and periadolescent exposure through a blood Pb (BPb) measurement concurrent with the evaluation of the outcomes. Outcomes were assessed during periadolescence using the parent-reported scales of aggression and conduct problems of the Behavioral Assessment System for Children-2nd version (BASC-2). We modeled the association between Pb exposure at each stage and each outcome (defined as a T-score ≥60 in the corresponding behavioral scale) using logistic regression, adjusting for sex, maternal age at delivery, maternal education, and household socioeconomic status (SES). The differential effect by sex was assessed with an interaction term in the models., Results: 743, 704, and 595 participants were respectively eligible for inclusion in final models of prenatal, early childhood, and periadolescent Pb exposure. Median Pb exposure at each stage was 9.9 µg/g for MPPb (prenatal), 5.19 µg/dl for CBLI (early childhood), and 2.62 µg/dl for concurrent BPb (periadolescence). 12 % of participants met the criterion for aggression, and 15 % for conduct problems. In adjusted models, a one interquartile range increase in MPPb increased the odds of conduct problems (OR:1.31; 95 % CI: 1.01, 1.70) and aggression (OR=1.24; 95 % CI: 0.93, 1.65) during periadolescence. Pb exposure during early childhood or periadolescence was not associated with either outcome. We found no evidence of interactions by sex., Conclusions: Exposure to Pb during the prenatal stage was associated with aggression and conduct problems during periadolescence., 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 © 2022 Elsevier B.V. All rights reserved.)

It is well documented that childhood lead exposure is associated with long-term decreases in intelligence quotients (IQ). Lesser known is the relationship with neurobehavioral domains, especially in adolescence. This study sought to identify cross-sectional and longitudinal associations between lead exposure and adolescent executive and visual-motor functioning and examine sex-based differences. Participants were 681 children from Jintan, China who had their blood lead levels (BLLs) assessed at age 3-5 years and 12 years old and neurobehavioral functioning assessed through the University of Pennsylvania Computerized Neurocognitive Battery (PennCNB) platform http://www.med.upenn.edu/bbl at 12 years old. Mean BLLs were 6.41 mcg/dl at age 3-5 years and 3.10 mcg/dl at 12. BLLs at 3-5 years and 12 years were used as predictors for the individual neurobehavioral domains in general linear models while controlling for father and mother occupation and education, residence location, age, and adolescent IQ. Models were run separately for males and females. In adjusted models, males BLLs at 3-5 years were associated with increased time to correctly complete tasks in multiple domains including abstraction/flexibility (β = 19.90, 95% CI( 4.26, 35.54) and spatial processing (β = 96.00, 95% CI 6.18, 185.82) at 12 years. For females in adjusted models, BLLs at 3-5 years were associated with increasing time to correctly complete tasks on the episodic memory domain task (β = 34.59, 95% CI 5.33, 63.84) at 12 years. Two adolescent cross-sectional relationships remained in the adjusted models for males only, suggesting a positive association between BLLs and increasing time for correct responses on the attentional domain task (β = 15.08, 95% CI 0.65, 29.51) and decreasing time for correct responses on the episodic memory task (β = -73.49, 95% CI -138.91, -8.06) in males at 12 years. These associations remained with and without controlling for IQ. These results suggest that lead exposure is associated with overall deficits in male and female neurobehavioral functioning, though in different domains and different timing of exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors have no competing interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The relationship between lead exposure and neurological disorders has been extensively studied, but the effects of lead exposure on hepatotoxicity are unknown. Metabolically related fatty liver disease (MAFLD) is an update of previous non-alcoholic fatty liver disease (NAFLD). It redefines the diagnostic conditions and emphasizes metabolic factors while considering non-alcoholic factors. Lead can affect the endocrine system and metabolism, so we believe that lead exposure may contribute to MAFLD. 41,723 individuals who had undergone blood lead testing from 2005 to 2018 in the National Health and Nutrition Examination Survey (NHANES) database were selected for this study. The characteristics of population lead exposure in the last decade or so, the effect of lead exposure on liver function and whether lead exposure can cause MAFLD were analyzed. Co-variates were adjusted according to age, ethnicity, body mass index (BMI), waist circumference, visceral adiposity index (VAI), poverty indices (PIR), diabetes, hypertension, and hyperlipidemia. The results showed that blood lead concentrations stabilized at a low level after a decreasing trend from year to year. The differences in blood lead concentrations were associated with differences in age, sex, race, education level, and PIR. Lead exposure was an independent risk factor for MAFLD, and lead and nine other factors were used as independent risk factors for MAFLD, so a nomogram was established to predict the prevalence probability of MAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Li, Ding, Xing, Wang and Zhang.)

Concerns are growing regarding the presence of toxic elements such as arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in the ingredients and prepared foods for infants and young children. There are few clear, evidence-based, guidelines on the maximum tolerable limits of toxicants in foods and little understanding of toxicant exposure or adverse health effects attributable to dietary exposure. Caregivers are faced with the burden of making decisions about which foods to select, how often to feed them to their children, and what foods to limit. This article reviews the current literature and existing recommendations on dietary exposure to toxic elements in children under 2 years of age, and their health effects in early childhood-focusing on growth, neurodevelopment, and immune function. The article also outlines best practices for healthcare providers to address the concerns of toxic element exposure through the diet in young children. Several foods consistently appear in the literature as potential sources of toxic element exposure. Contaminated drinking and cooking water, including water used to prepare infant formula, could also be a major exposure source. In the absence of stronger evidence on effects of dietary modification, exclusive breastfeeding until six months of age, followed by a diverse diet are some strategies to reduce dietary toxic element exposure while ensuring an adequate and balanced nutrient intake. Healthcare providers can support families by sharing information and encouraging blood Pb testing, the only element for which such testing is currently recommended., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Earlier studies have reported increased risks of lung, kidney and brain cancers for exposure to lead. The International Agency for Research on Cancer (IARC) Working Group evaluated inorganic lead and its compounds probably carcinogenic to humans. This study aimed to assess the association between blood lead level in occupational exposure and risk of lung cancer., Methods: The study was based on the follow-up of lung cancer incidence during 1973-2014 among 20 729 employees biologically monitored for their occupational lead exposure in 1973-1983. Duration of employment in the monitored work was assessed using records from the Finnish Centre for Pensions; and potential confounding by other occupational carcinogens using longitudinal information on the occupation in censuses and the Finnish National Job-Exposure Matrix (FINJEM). Occupation- and gender-specific prevalence of regular tobacco smoking and the socioeconomic status were also utilized in the adjustments for potential confounding., Results: Positive trends were found for the elevated blood lead levels on the lung cancer risk. Among employees with the duration of employment of ≥60 months, the relative risk (RR) of lung cancer was 1.72 [95% confidence interval (CI) 1.28-2.31] for mean blood lead 1.0-1.9 µmol/L and RR 2.63 (95% CI 1.71-4.05) for mean blood lead ≥2.0 µmol/L, compared with mean lead <0.5 µmol/L. The studied potential confounders did not explain the findings on the increased risk for lead exposure., Conclusions: The current study lends support to the findings that exposure to lead increases lung cancer risk. Increased risks were seen already at rather low blood lead levels.

Lead (Pb) is ubiquitous in environment that accumulates in teeth and calcified tissues from where it releases gradually with aging and adversely affects dental health. This study aimed to determine the effect of Pb exposure on odontogenic differentiation potential of isolated human dental pulp stem cells and investigate the possible underlying epigenetic factors. In the absence of Pb exposure, stem cells displayed significant odontogenic markers including elevated Alkaline Phosphatase (ALP) activity, Alizarin red staining intensity, and increased expression of odontogenic DMP1 and DSPP genes. Exposure to 60 μM Pb resulted in reduced ALP activity and calcium deposition. Also, diminished expression of RUNX2, DMP1, and DSPP, as well as Wnt signaling mediators including WNT1, and β-catenin were detected. The expression of Wnt signaling related microRNAs, miRNA-139-5p and miRNA-142-3p, on the other hand, were shown to have a significant increase. We concluded that Pb could adversely affect the odontogenic differentiation potential of dental pulp stem cell. The underlying mechanism might related to Pb-induced epigenetic dysregulation of WNT1/β-catenin pathway-related miRNAs leading to down-regulation of Wnt/β-catenin related odontogenic genes and eventually impaired odontogenic differentiation process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To assess associations of single and combined exposures to lead and stress during different stages of pregnancy with offspring neurodevelopment., Methods: We measured prenatal lead (maternal blood-lead in early-pregnancy and umbilical-cord-blood-lead) and maternal stress levels in Shanghai-Birth-Cohort from 2013 to 2016. Maternal stress was assessed using Center-for-Epidemiological-Studies-Depression-Scale and Self-Rating-Anxiety-Scale during mid-pregnancy. The Ages-Stages-Questionnaires-3 (at 6/12-months-of-age) and Bayley-III (at 24-months-of-age) were both used to assess neurodevelopment., Results: A total of 2132 mother-child pairs with both prenatal lead and stress measurements were included. The geometric-means of blood-lead in early-pregnancy and cord-blood-lead were 1.46 μg/dL and 1.33 μg/dL, respectively. Among the study women, 1.89 % and 0.14 % were screened positive for depression and anxiety. Adjusting for related confounders, the combined exposures had stronger adverse associations with offspring social-emotional skills than single exposures; and the combined exposure in early-pregnancy was associated with greater neurodevelopmental differences than combined exposure around-birth, especially in social-emotion at 24 months-of-age [β (95 %CI): - 10.48(-17.42, -3.54) vs. - 5.95(-11.53, -0.36)]., Conclusions: Both single and combined prenatal exposures to lead/stress impaired infant neuro-development, and the effects of combined exposure may be more profound than single exposures. Combined exposure in early-pregnancy may be associated with worse neurodevelopmental outcomes than combined exposure around-birth, especially in social-emotional development., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective : To identify occupational risk factors for ALS using well-characterized participants with ALS (P-ALS), sibling controls (S-controls), and matched population controls (P-controls) within the National ALS Registry. We also compared oxidative stress (OS) biomarkers between groups. Methods : P-ALS were recruited over 4 years. Demographic, socioeconomic, and medical data were ascertained from medical records and structured interviews. P-ALS were followed prospectively for 2 years or until death, whichever came sooner. S-controls and age-, sex-, race/ethnicity-, and residential location-matched P-controls were recruited over 3 years. Occupational exposure to lead and agricultural chemicals (ACs) were assigned by an occupational hygienist, blinded to case status. OS biomarkers in urine were measured. Results: P-ALS (mean age 62.8 years; 63% males) resided across the United States. Demographic and socioeconomic variables did not differ among P-ALS, S-controls, and P-controls. P-ALS were more likely to report occupations with exposure to lead (adjusted OR (aOR)=2.3, 95% CI 1.1, 4.6) and ACs (aOR = 2.4, 95% CI 1.2, 4.6) compared to pooled controls. Among those with occupations with exposure to both lead and ACs, aOR was 7.2 (95% CI 2.0, 26.1). Urinary 8-oxo-dG was significantly elevated among P-ALS (11.07 ± 5.42 ng/mL) compared to S-controls, P-controls, or pooled controls (pooled 7.43 ± 5.42 ng/mL; p  < 0.0001) but was not associated with occupational exposure to either lead or ACs. Conclusions : Findings reveal increased risk of ALS diagnosis among those with occupational exposure to lead and ACs and increased OS biomarkers among cases compared to controls. OS may be an important pathogenic mechanism in ALS.

Background: Although those with kidney disease may have heightened susceptibility to heavy metal toxicity, whether low levels of drinking water lead contamination have clinical consequence is unknown., Methods: Given that lead toxicity is known to associate with iron deficiency, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information and United States Renal Data Systems to examine whether municipal 90th percentile drinking water lead levels associate with iron deficiency among incident dialysis patients. Iron deficiency was defined across thresholds of transferrin saturation (<10% and 20%) and ferritin (<100 and <200 ng/ml), and simultaneous transferrin saturation <20% and ferritin <200 ng/ml, all obtained within 30 days of dialysis initiation. The average 90th percentile of drinking water lead samples per patient city of residence over a 5-year period before dialysis initiation was examined at the <1 μ g/L level of detection, and at the 25th, 50th, and 100th percentile of the EPA's actionable level (15 μ g/L)., Results: Among 143,754 incident ESKD patients, those in cities with drinking water lead contamination had 1.06 (95% CI, 1.03 to 1.09), 1.06 (95% CI, 1.02 to 1.10), and 1.07 (95% CI, 1.03 to 1.11) higher adjusted odds of a transferrin saturation <20%, ferritin <200 ng/ml, and simultaneous transferrin saturation <20% and ferritin <200 ng/ml, respectively. These associations were apparent across the range of lead levels found commonly in the United States and were significantly greater among Black patients (multiplicative interaction P values between lead and race <0.05)., Conclusions: Even exposure to low levels of lead contamination, as commonly found in US drinking water, may have adverse hematologic consequence in patients with advanced kidney disease. These associations are particularly evident among Black people and, although consistent with other environmental injustices facing minorities in the United States, might reflect a greater susceptibility to lead intoxication., Competing Interests: J. Danziger reports consultancy for Healthmap Solutions; ownership interest in Healthmap Solutions; and is the regional medical director at Healthmap Solutions. K.J. Mukamal reports other interests or relationships with US Highbush Blueberry Council and Wolters Kluwer., (Copyright © 2022 by the American Society of Nephrology.)

SignificanceConsiderable effort is expended to protect today's children from lead exposure, but there is little evidence on the harms past lead exposures continue to hold for yesterday's children, who are victims of what we term legacy lead exposures. We estimate that over 170 million Americans alive today were exposed to high-lead levels in early childhood, several million of whom were exposed to five-plus times the current reference level. Our estimates allow future work to plan for the health needs of these Americans and to inform estimation of the true contributions of lead exposure to population health. We estimate population-level effects on IQ loss and find that lead is responsible for the loss of 824,097,690 IQ points as of 2015.

Background: Although blood lead levels (BLLs) in children are gradually decreasing, low-concentration lead exposure can still exert adverse effects. We studied the factors that affect BLLs in children in Shenyang, China., Methods: We conducted a cross-sectional study by administering structured questionnaires on family demographics and food intake. The concentrations of lead in venous blood were determined by graphite furnace atomic absorption spectrometry., Results: A total of 273 children aged 1-6 years were enrolled. The geometric mean (geometric standard deviation) of BLLs was 24.94 (12.70) μg/L in boys and 23.75 (11.34) μg/L in girls. The prevalence of BLLs of ≥35 μg/L was 22.7% and was mainly observed in children aged under 3 years. Often hand washing before meals was protective against BLLs ≥20 μg/L (adjusted OR: 0.427, 95%CI: 0.238-0.767, p = 0.004). Consumption of puffed grains and eggs had an adjusted OR (95%CI) for BLLs ≥20 μg/L of 1.714 (1.012-2.901) (p = 0.045) and 1.787 (1.000-3.192) (p = 0.050), respectively., Conclusions: BLLs of children in Shenyang are still higher than in developed countries. Consumption of puffed grains and eggs is associated with higher BLLs. Often hand washing before meals may be protective against high BLLs., (© 2022. The Author(s).)

Abstract: Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7 days after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development., Objectives: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA)., Methods: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression., Results: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = -0.79 (95%CI = -1.51, -0.08) and β = -0.29 (95%CI = -0.62, -0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3., Discussion: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action., 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 © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to elucidate the relationship between environmental exposure to lead (Pb), mercury (Hg), and cadmium (Cd) which were measured in blood and the kidney function of adolescents., Methods: Cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey from 2010 to 2017. Statistical procedures were performed to analyze the Korean population of adolescents aged 12-17 years. Regression analysis was performed, and covariates included age, sex, body mass index, smoking status, and other heavy metal levels., Results: The median blood levels of Pb, Hg, and Cd were 1.165 μg/dL, 1.805 μg/L, and 0.304 μg/L, respectively. Adolescents with Pb levels in the highest quartile (> 1.454 μg/dL) had a 3.35 mL/min/1.73 m 2 -lower estimated glomerular filtration rate using creatinine (eGFR cr ) (95% confidence interval (CI), -6.03 to -0.68 mL/min/1.73 m 2 ) compared to those in the lowest quartile (< 0.856 μg/dL) in the unadjusted model. However, there was no association between the blood Pb level and eGFR cr in the adjusted model. Levels of Hg and Cd were not associated with eGFR cr in either model. High blood levels of all three heavy metals were not associated with the risk of hypertension., Conclusions: There was no association between increased blood levels of Pb, Hg, and Cd; eGFR cr ; and increased risk of hypertension in Korean adolescents who were exposed to relatively low levels of heavy metals., (© 2021. IPNA.)

Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I 2 statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I 2  > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure., (© 2022. The Author(s).)

Recent evidences suggest the role of chronic lead (Pb) exposure in altering immunological parameters. Present study aimed to systematically review existing literature and synthesize quantitative evidence on the association between chronic Pb exposure and changes in immunological markers. Observational studies reporting immunological markers such as leukocyte derivative counts (CD3 + , CD4 + , CD8 + , CD45 + , CD56 + , lymphocyte, and total leukocyte), cytokine, Immunoglobulin (Igs), C-reactive protein (CRP) among Pb-exposed and unexposed controls were systematically searched from PubMed, Scopus and Embase digital databases from inception to January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered during systematic review. Mean differences in the immunological markers between Pb-exposed and control groups were pooled using random-effects model. The heterogeneity was assessed using Cochran-Q test and I 2 statistic. The review included forty studies reporting immunological markers in Pb-exposed and unexposed control groups. The occupational Pb-exposed group exhibited significantly higher BLL, impaired immunological markers, characterized by a marginal lowering in lymphocyte count, lymphocyte subsets (CD3 + , CD4 + , CD4 + /CD8 + ratio), IFN-γ and IgG levels, while CD8 + , IgM, IgA, IgE, and cytokines (IL-4, IL-6, IL-10, and TNF-α) exhibited a trend of higher values in comparison to the control group. Further, inflammatory marker viz., total leukocyte count was significantly higher among Pb-exposed. The included studies exhibited high levels of heterogeneity. In conclusion, Occupational Pb exposure alters the immunological markers such as the circulating cytokines and leukocyte counts. However, high-quality, multicentered studies are required to strengthen present observations and further understand the Pb's role on the immune system. Prospero Registration ID: CRD42021228252., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Though Lippia javanica (Burm.f.) Spreng antioxidant activity has been demonstrated, its effect in protecting the brain from lead (Pb)-induced oxidative damage is unknown. This study investigated the effect of L. javanica against Pb-induced oxidative stress, inflammation, apoptosis and acetylcholinesterase activity in rat's brain., Methods: L. javanica herbal tea infusion was prepared, its phytochemical constituent was revealed by liquid chromatography-Mass spectrometer (LC-MS) and was administered simultaneously with Pb. Four groups of male Wistar rats (n = 5/group) were used: control received distilled water; Pb-acetate group received 50 mg Pb/ Kg bodyweight (bw), treatment group received 50 mg Pb/ Kg Pb-acetate + 5 ml/kg bw L. javanica and L. javanica group received 5 ml/Kg bw of L. javanica tea infusion only. After 6 weeks of treatment, oxidative status, acetylcholinesterase activity, inflammation and apoptosis was assessed in brain tissue which was also histologically examined., Results: Mean brain and heart weight was reduced (p < 0.05) while liver and spleen weights were increased (p < 0.05) in Pb exposed animals but were prevented by L. juvanica treatment. Treatment with L. javanica increased (p < 0.05) overall brain antioxidant status (glutathione and superoxide dismutase activities) and reduced lipid peroxidation (p < 0.05) compared to the Pb exposed animals. Pro-inflammatory cytokine tumour necrotic factor-alpha, pro-apoptosis Bax protein and anticholinesterase activity were reduced (p < 0.05) in Pb-L. javanica treated animals compared to the Pb exposed group. Histological examination confirmed neuroprotective effects of L. javanica as evidenced by reduced apoptosis/necrosis and inflammation-induced vacuolization and oedema in the hippocampus. The L. javanica treatment alone had no detrimental effects to the rats. LC-MS analysis revealed L. javanica to be rich in phenolics., Conclusions: This study demonstrated that L. javanica, rich in phenolics was effective in reducing Pb-induced brain oxidative stress, inflammation, apoptosis, acetylcholinesterase activity and neuronal damage., (© 2022. The Author(s).)

Environmental factors have been associated with the etiology of autism spectrum disorder ASD in recent times. The involvement of toxic metals in the generation of reactive oxygen species and their epigenetics effects have been implicated in ASD. This systemic review examines the association of toxic metals with autism in children. A systematic literature search was performed in scientific databases such as PubMed, Google scholar, and Scopus. Case-control studies evaluating toxic metal levels in different tissues of ASD children and comparing them to healthy children (control group) were identified. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of the included studies. Six case-control studies with 425 study subjects met our inclusion criteria. A total of four studies indicated higher levels of As, Pb, Hg, Cd, Al, Sn, Sb, Ba, TI, W, and Zr in whole blood, RBC, in whole blood, RBC, and hair samples of children with autism compared with control suggestive of a greater toxic metal exposure (immediate and long-term). Three studies identified significantly higher concentrations of Cd, Pb and Hg in urine and hair samples of autistic children compared to control suggesting decreased excretion and possible high body burden of these metals. The findings from this review demonstrate that high levels of toxic metals are associated with ASD, therefore, critical care is necessary to reduce body burden of these metals in children with ASD as a major therapeutic strategy., (Copyright © 2021. Published by Elsevier Inc.)

Recent studies have shown that melatonin is an important molecule in plant physiology. It seems that the most important is that melatonin effectively eliminates oxidative stress (direct and indirect antioxidant) and switches on different defence strategies (preventive and interventive actions) during environmental stresses. In the presented report, exogenous melatonin potential to protect Nicotiana tabacum L. line Bright Yellow 2 (BY-2) exposed to lead against death was examined. Analyses of cell proliferation and viability, the level of intracellular calcium, changes in mitochondrial membrane potential ( ΔΨm ) as well as possible translocation of cytochrome c from mitochondria to cytosol and subsequent caspase-like proteolytic activity were conducted. Our results indicate that pretreatment BY-2 with melatonin protected tobacco cells against mitochondrial dysfunction and caspase-like activation caused by lead. The findings suggest the possible role of this indoleamine in the molecular mechanism of mitochondria, safeguarding against potential collapse and cytochrome c release. Thus, it seems that applied melatonin acted as an effective factor, promoting survival and increasing plant tolerance to lead.

Polycystic ovary syndrome (PCOS) is a global health concern for women of reproductive age, as 6.5% of women worldwide are affected by this syndrome. PCOS is marked by hyperandrogenism, anovulation, menstrual abnormalities, and polycystic ovaries. Metals such as arsenic, cadmium, lead and mercury are considered to be systemic toxicants/human carcinogens and seem to have devastating effects on humans, even at minimal exposures. One of the probable aetiological factors for PCOS has been identified as oxidative stress. In view of the probable associations among oxidative stress, metal toxicity and PCOS, the present study examined the role of heavy metals in the generation of oxidative stress among females. This prospective study included 106 women (56 women diagnosed with PCOS and 50 women who were not diagnosed with PCOS as control women). There were no significant differences in the sociodemographic characteristics between the two groups except for the irregularity of menses and the presence of acne. The serum As, Cd, Pb, and Hg levels increased and the serum glutathione (GSH) and superoxide dismutase (SOD) levels diminished significantly in the PCOS group compared to the control group at P < 0.001. The SOD levels were negatively correlated with the As and Pb levels at P < 0.05. Additionally, the PCOS group exhibited a strong negative correlation between the GSH and As levels (P < 0.01), GSH and Pb levels (P < 0.05) and GSH and Hg levels (P < 0.01). Furthermore, the As levels were positively correlated with increased levels of Cd, Pb and Hg among PCOS women. Significant positive correlations were observed between Pb and Cd and between Cd and Hg at P < 0.001. The outcome of the study provides clear insight into the role of metal-induced oxidative stress, which plays a vital role in the pathophysiology underlying PCOS and suggests the use of these markers as prognostic tools to reduce the consequences of high-risk exposure to these metals among females., (© 2021. The Author(s).)