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Objectives: Lead (Pb) and manganese (Mn) are confirmed neurotoxins but it is unclear to what extent low-level exposure produces a unique behavioral signature. The objective of this study was to investigate latent cognitive profiles among children (6-8 years) from Montevideo, Uruguay co-exposed to these metals., Method: Among 345 children, blood Pb and hair Mn were measured using atomic absorption spectroscopy and ICP-MS, respectively. Sixteen measures, reflecting multiple domains of cognitive functioning were gathered: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (WM): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task. Scores were modeled using latent profile analysis (LPA). Association between blood Pb and hair Mn on performance profiles was assessed using ordinal regression, controlling for confounders. An interaction between Pb and Mn was tested., Results: Mean ± SD of blood Pb was 4.1 ± 2.1 μg/dL and 35% of children had blood Pb ≥ 5 μg/dL. Median [5%, 95%] hair Mn level was 0.8 [0.3, 4.1] ppb. Three latent cognitive performance profiles were identified: high (n = 46, 13%), average (n = 209, 61%) and low (n = 90, 26%). Each one-unit increase in blood Pb was associated with a 28% greater likelihood of belonging to a poorer-performing profile. The association was non-linear, with the effect of Pb on profile membership strongest at lower levels of exposure. There was no meaningful interaction between Pb and Mn., Conclusions: A behavioral signature for low-level Pb & Mn exposure was not identified, but the likelihood of membership in low-performing profile was higher at lowest levels of blood Pb. There was no effect measure modification between Pb and Mn. Future research should address how complex environments created by chemical exposures and the social context relate to cognitive performance in young children., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chronic lead exposure frequently brings about increased blood pressure and other cardiovascular diseases associated with autonomic nervous dysfunction. Purinergic signaling is involved in the development of abnormal sympathoexcitatory response due to myocardial ischemic injury. However, the potential implication of P2X7 receptor in altered sympathoexcitatory response caused by chronic lead exposure and the underlying mechanisms remain unclear. In this study, a rat model of chronic lead exposure was used to explore the changes in sympathoexcitatory response and possible involvement of P2X7 receptor in the superior cervical ganglion (SCG). Rats were divided into three groups called control, low lead and high lead groups according to daily lead exposure levels, i.e. 0, 0.5 and 2 g/L respectively. One year later, changes in P2X7 receptor expression in SCG, sympathetic nerve activity and myocardial function were measured for these rats. Our results showed that increased blood pressure and heart rate, decreased heart rate variability, enhanced cervical sympathetic nerve discharge, higher phosphorylation of ERK1/2, and up-regulated protein and mRNA levels of P2X7 expression in SCG occurred after lead exposure. In addition, double-label immunofluorescence staining of P2X7 receptor and glutamine synthetase (GS) revealed activation of the satellite glial cells of SCG by lead exposure. Moreover, knockdown of P2X7 could effectively relief the effect of lead exposure on enhanced expression of P2X7 receptor and GS. Thus our data suggest that the up-regulation of P2X7 receptor activity in satellite glial cells of SCG may contribute to the raised sympathoexcitatory response due to chronic lead exposure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Electron radiotherapy is a labor-intensive treatment option that is complicated by the need for field shaping blocks. These blocks are typically made from casting Cerrobend alloys containing lead and cadmium. This is a highly toxic process with limited precision. This work aims to provide streamlined and more precise electron radiotherapy by 3D using printing techniques., Methods: The 3D printed electron cutout consists of plastic shells filled with 2 mm diameter tungsten ball bearings. Five clinical Cerrobend defined field were compared to the planned fields by measuring the light field edge when mounted in the electron applicator on a linear accelerator. The dose transmitted through the 3D printed and Cerrobend cutouts was measured using an IC profiler ion chamber array with 6 MeV and 16 MeV beams. Dose profiles from the treatment planning system were also compared to the measured dose profiles. Centering and full width half maximum (FWHM) metrics were taken directly from the profiler software., Results: The transmission of a 16MeV beam through a 12 mm thick layer of tungsten ball bearings agreed within 1% of a 15 mm thick Cerrobend block (measured with an ion chamber array). The radiation fields shaped by ball bearing filled 3D printed cutout were centered within 0.4 mm of the planned outline, whereas the Cerrobend cutout fields had shift errors of 1-3 mm, and shape errors of 0.5-2 mm. The average shift of Cerrobend cutouts was 2.3 mm compared to the planned fields (n = 5). Beam penumbra of the 3D printed cutouts was found to be equivalent to the 15 mm thick Cerrobend cutout. The beam profiles agreed within 1.2% across the whole 30 cm profile widths., Conclusions: This study demonstrates that with a proper quality assurance procedure, 3D-printed cutouts can provide more accurate electron radiotherapy with reduced toxicity compared to traditional Cerrobend methods., Competing Interests: The authors have declared that no competing interests exist.

After decades of accumulation of lead aerosols in cities from additives in gasoline, in 1975 catalytic converters (which are ruined by lead) became mandatory on all new cars. By 1 January 1986 the rapid phase-down banned most lead additives. The study objective is to review temporal changes of environmental lead and children's blood lead in communities of metropolitan New Orleans. In 2001, a soil lead survey of 287 census tracts of metropolitan New Orleans was completed. In August-September 2005 Hurricanes Katrina and Rita storm surges flooded parts of the city with sediment-loaded water. In April-June 2006, 46/287 (16%) of the original census tracts were selected for resurvey. A third survey of 44/46 (15%) census tracts was completed in 2017. The census tract median soil lead and children's median blood lead decreased across surveys in both flooded and unflooded areas. By curtailing a major urban source of lead aerosols, children's lead exposure diminished, lead loading of soil decreased, and topsoil lead declined. Curtailing lead aerosols is essential for primary prevention. For the sake of children's and ultimately societal health and welfare, the long-term habitability of cities requires terminating all remaining lead aerosols and cleanup of legacy-lead that persists in older inner-city communities.

Lead (Pb) is an environmental pollutant and can damage organisms. Selenium (Se) can alleviate Pb poisoning. The present study aimed to investigate the alleviative effect of Se on Pb-induced immune toxicity in chicken hearts. One-hundred-and-eighty Hy-line male chickens were randomly divided into four groups at 7 days of age. The control group was offered a standard commercial diet (SD) and drinking water (DW); the Se group was offered SD supplemented with sodium selenite (SeSD) and DW; the Pb + Se group was offered SeSD and DW supplemented with lead acetate (PbDW); and the Pb group was offered SD and PbDW. Relative mRNA expression of inducible nitric oxide synthase (iNOS), interleukins (IL-2, IL-4, IL-6, IL-12β, IL-17 and IFN-γ), and heat shock proteins (HSP27, HSP40, HSP60, HSP70, and HSP90) were determined by means of quantitative real-time PCR. Relative protein expression of iNOS, HSP60, HSP70, and HSP90 was assessed, as well as nitric oxide (NO) content and iNOS activity in heart tissue. The results indicated a down-regulation of interleukin (IL)-2 and IFN-γ and an up-regulation of NO, iNOS, interleukins (IL-4, IL-6, IL-12β, IL-17), and heat shock proteins (HSP27, HSP40, HSP60, HSP70, and HSP90) in Pb-damaged hearts. Se alleviated all of the above Pb-induced changes. There were time-dependent effects on NO content, iNOS activity, and mRNA levels of iNOS, IL-2, IL-4, IL-6, IL-17, HSP27, HSP40, HSP60, HSP70, and HSP90 after Pb treatment in the chicken hearts. Se alleviated Pb-induced immune toxicity in the chicken hearts.

Aims: The present study aimed to investigate the potential therapeutic effect of diallyl sulfide (DAS), a natural component of garlic (Allium sativum), in the improvement of lead (Pb)-induced testicular toxicity and its underlying mechanisms., Materials and Methods: Thirty-two male albino rats were randomly divided into control, PbAc (20 mg lead acetate/kg bwt, orally), DAS (200 mg/kg bwt, orally), and PbAc + DAS groups for 49 successive days. The investigation based on the following criteria: Paired testes and epididymides weights, epididymal sperm analysis, level of serum sex hormones (Testosterone and17β-estradiol (E2)), aromatase (CYP19) expression, Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD) enzyme, reduced glutathione (GSH), testicular histopathology, spermatogenesis score and apoptosis detection (Caspase-3 immunoexpression)., Key Findings: Pb caused significant decline in epididymal sperm count and motility, testes and epididymes weights, spermatogenesis score and serum testosterone and1E2, as well as a significant decrease in SOD and GSH level, and a significant elevation of MDA and NO compared to a control group. In addition, Pb induced significant downregulation of CYP19 gene expression, increase of Caspase-3 immunoreactivity, various testicular degenerative and necrotic changes. Whereas, co-treatment of rats with DAS improved sperm analysis, and testicular histology and antioxidative status. Furthermore, DAS co-administration regulated testicular CYP19 and Caspase-3 expressions., Significance: Collectively, DAS seemed to be a promising agent for protection against Pb-induced testicular toxicity through antioxidative properties, beside regulation of testicular apoptosis and aromatase expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Before a lead compound goes through a clinical trial, preclinical studies utilize two-dimensional (2D) in vitro models and animal models to study the pharmacodynamics and pharmacokinetics of that lead compound. However, these current preclinical studies may not accurately represent the efficacy and safety of a lead compound in humans, as there has been a high failure rate of drugs that enter clinical trials. All of these failures and the associated costs demonstrate a need for more representative models of human organ systems for screening in the preclinical phase of drug development. In this study, we review the recent advances in in vitro modeling including three-dimensional (3D) organoids, 3D microfabrication, and 3D bioprinting for various organs including the heart, kidney, lung, gastrointestinal tract (intestine-gut-stomach), liver, placenta, adipose, retina, bone, and brain as well as multiorgan models. The availability of organ-on-chip models provides a wealth of opportunities to understand the pathogenesis of human diseases and provide a potentially better model to screen a drug, as these models utilize a dynamic 3D environment similar to the human body. Although there are limitations of organ-on-chip models, the emergence of new technologies have refined their capability for translational research as well as precision medicine., (© 2018 Wiley Periodicals, Inc.)

Early exposure to lead (Pb) has been associated with an elevated risk of developing neurodegenerative diseases. There is evidence that neuronal damage in chronic Pb exposure can be caused by the convergence of glial damage. Apoptosis may be a possible mechanism of Pb-induced cell death in the central nervous system. We tested cellular damage and apoptosis in the spinal cord of Wistar rats treated with Pb. Twelve rats were divided into two groups (n = 6): the control group was treated with only drinking water and the other group received 500 ppm of Pb acetate. After 3 months of Pb treatment, all animals were euthanized and spinal cords were extracted. Morphology was evaluated by Nissl and Kluver-Barrera stainings. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Specific antibodies were used to evaluate Pb damage in oligodendrocytes, astrocytes, and microglia. A large number of apoptotic bodies was observed in the white matter of the Pb-treated group. The Pb-treated group also showed a reduced number of neurons and oligodendrocytes but had an increased number of astrocytes compared with the nontreated group. Our results demonstrate that chronic Pb treatment induces neurodegeneration, demyelination, and astrogliosis in the rat spinal cord., (© 2019 International Federation for Cell Biology.)

Objective: To observe the correlation between the oxidative stress index and cardiovascular system damage in a population with lead exposure., Methods: Two populations (144 manufacturing workers and 94 administrators) from a lead-acid battery manufacturer in Shandong Province in China were recruited. The blood lead level, oxidative stress index, blood pressure, electrocardiogram findings, and their correlations were analyzed in both groups., Results: The blood lead level was significantly higher in manufacturing workers than administrators (254.34 vs. 65.32 µg/L, respectively). The differences in the oxidative stress index, serum total superoxide dismutase (T-SOD) concentration, and malondialdehyde (MDA) concentration between the two populations were statistically significant. The rates of abnormal blood pressure and electrocardiogram findings were significantly higher in manufacturing workers than administrators. Workers with middle- and high-dose lead exposure had lower T-SOD and higher MDA concentrations than those with low-dose lead exposure. Significant correlations were found between the blood lead level and the MDA concentration, systolic pressure, diastolic pressure, and electrocardiogram findings. Linear multiple regression analysis showed that T-SOD was negatively associated with blood lead, electrocardiogram findings, and MDA., Conclusion: Lead exposure can lead to oxidative stress, increased blood pressure, and abnormal electrocardiogram findings and may impact cardiovascular diseases through oxidative stress.

Background: Numerous studies suggested that occupational or environmental exposure to lead adversely affects renal function. However, most studies lost relevance because of the substantially lower current environmental lead exposure and all relied on serum creatinine to estimate glomerular filtration. We investigated the association of estimated glomerular filtration rate (eGFR), estimated from serum creatinine, cystatin C or both, with blood lead (BPb) using the baseline measurements of the ongoing Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) in newly hired workers prior to significant occupational lead exposure., Methods: Among 447 men (participation rate, 82.7%), we assessed the association of eGFR and the urinary albumin-to-creatinine ratio (ACR) with BPb across thirds of the BPb distribution using linear regression analysis. Fully adjusted models accounted for age, blood pressure, body mass index, the waist-to-hip ratio, smoking, the total-to-high-density-lipoprotein ratio, plasma glucose, serum γ-glutamyltransferase and antihypertensive drug treatment., Results: Age averaged 28.7 (SD, 10.2) years (range, 19.1-31.8). Geometric mean BPb concentration was 4.34 μg/dL (5th-95th percentile interval, 0.9-14.8). In unadjusted and adjusted analyses, eGFR estimated from serum creatinine [mean (SD), 105.26 (15.2) mL/min/1.73 m2], serum cystatin C [mean (SD), 127.8 (13.8) mL/min/1.73 m2] or both [mean (SD), 111.9 (14.8) mL/min/1.73 m2] was not associated with BPb (P  ≥  0.36), whereas ACR [geometric mean, 4.32 mg/g (5th-95th percentile interval, 1.91-12.50)] was lower with higher BPb., Conclusions: At the BPb levels observed in this study, there was no evidence for an association between renal function and lead exposure., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.)

The increment of eryptosis in lead-exposed workers has been associated with oxidative stress, having as the main mediator [Ca 2+ ] i . However, other molecules could participate as signals, such as PLA 2 and SMase, which have been proposed to increase PGE 2 and ceramides, both involved in the increment of PS externalization due to osmotic stress. To study the role of these enzymes in lead intoxication, we studied 30 lead exposed workers and 27 non-lead exposed individuals. We found, compared to non-exposed subjects, lead intoxication characterized by high blood lead concentration (median = 39.1 μg/dL), and low δ-ALAD activity (median = 348 nmol of porphobilinogen/h/mL); oxidative stress with high lipid peroxidation (median = 1.31 nmol of malondialdehyde/mL) and low TAC (median = 370 mM Trolox equivalents); a higher enzymatic activity of PLA 2 (median = 518 AFU/mg) and SMase (median = 706 AFU/mg) and higher eryptosis (median = 0.92% PS externalization). Correlation and conditional probability analyses permit to associate oxidative stress and eryptosis with high PLA 2 activity. However, high SMase activity was only associated with PLA 2 activity. The role of these enzymes in the signal path to eryptosis induced by oxidative stress in lead-exposed workers is discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The effects of lead exposure on cognitive function have been studied intensively over the past decade, but less attention has focused on its impact on auditory function. This study is aimed at investigating the effect of lead on the cochlea and the molecular mechanisms responsible for its actions., Methods: 0.2% lead acetate was administered to rats in drinking water for 30, 60, and 90 days. Brainstem auditory evoked responses (ABR) were recorded, and morphological changes in the hair cells were observed. We also measured glutathione (GSH) and malondialdehyde (MDA) concentrations and antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities in the cochlea., Results: Lead exposure increased the ABR threshold and slightly prolonged the latencies of wave II and wave IV in rats. Abnormally shaped hair cells and loss of hair cells were found in the cochlea basilar membrane, together with degenerative changes in spiral ganglion neurons following lead exposure. The activities of some antioxidant enzymes were also reduced in association with upregulation of MDA expression. These effects may be caused by impaired catalytic function of the enzymes as a result of lead interaction., Conclusion: The antioxidant system of the cochlea in the immature rat brain is highly vulnerable to developmental lead exposure. Oxidative stress may therefore represent a possible mechanism for lead-induced auditory deficits.

Objectives: Bone lead and past blood lead levels may be more strongly associated with current health effects than current blood lead, representing recent exposure. We examined whether current bone lead was correlated with maximum past blood lead and compared how three lead measures predicted current blood pressure (BP) and kidney function among workers with past occupational lead exposure., Methods: Adult men in a lead surveillance programme residing near New York City were enrolled. Current bone and blood lead, BP and estimated glomerular filtration rate (eGFR) were measured. Maximum past blood lead was obtained from surveillance data. Regression models were used to determine associations of health with different lead measures., Results: Among 211 participants, median (IQR) bone, maximum past blood and current blood leads were 13.8 (9.4-19.5) µg lead per bone mineral gram, 29.0 (14.0-38.0) µg/dL and 2.5 (1.5-4.4) µg/dL, respectively. Maximum past and current blood lead were significantly associated with current bone lead in adjusted analyses (both p<0.0001), with associations driven by high blood lead. Bone lead was associated with increased continuous systolic BP (coefficient=0.36; 95% CI 0.05 to 0.67; p=0.02); categorical analyses indicated this was driven by the top two bone lead quartiles. Bone lead was non-significantly associated with decreased (worse) eGFR (coefficient=-0.15; 95% CI -0.36 to 0.07; p=0.18)., Conclusions: Bone lead was significantly associated with past maximum and current blood lead. The association between bone and current blood lead was possibly driven by bone lead resorption into blood. Bone lead, but not past or current blood lead, was associated with elevated systolic BP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Lead represents a highly prevalent metal toxicant with potential to alter human biology in lasting ways. A population segment that is particularly vulnerable to the negative consequences of lead exposure is the human fetus, as exposure events occurring before birth are linked to varied and long-ranging negative health and behavioral outcomes. An area that has yet to be addressed is the potential that lead exposure during pregnancy alters brain development even before an individual is born. Here, we combine prenatal lead exposure information extracted from newborn bloodspots with the human fetal brain functional MRI data to assess whether neural network connectivity differs between lead-exposed and lead-naïve fetuses. We found that neural connectivity patterns differed in lead-exposed and comparison groups such that fetuses that were not exposed demonstrated stronger age-related increases in cross-hemispheric connectivity, while the lead-exposed group demonstrated stronger age-related increases in posterior cingulate cortex (PCC) to lateral prefrontal cortex (PFC) connectivity. These are the first results to demonstrate metal toxicant-related alterations in human fetal neural connectivity. Remarkably, the findings point to alterations in systems that support higher-order cognitive and regulatory functions. Objectives for future work are to replicate these results in larger samples and to test the possibility that these alterations may account for significant variation in future child cognitive and behavioral outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Lead is a ubiquitous dietary contaminant that occurs in food because of natural and anthropogenic sources and pathways of exposure. Lead adversely affects a number of tissues and organ systems and the severity of effect on each is dependent on the level and duration of exposure. The most sensitive and notable effects are those that occur on the nervous system. This is particularly the case in the exposure to the fetus, infant and child. Infants and children generally have higher lead exposures on a body weight basis. While lead exposure can come from many sources, a major source of exposure for at least some individuals comes from food. Estimates for the impact of dietary lead on IQ were developed from published total diet studies. While most of these were designed to characterize intake of chemical contaminants on a national basis, some sampled market baskets from a single city. To develop global estimates, default ranges were created for countries with no data which encompassed the values encountered elsewhere. Blood lead levels and IQ decrements were estimated using functions previously developed by the WHO Joint Expert Committee for Food Additives. Since both the exposure and dose response components were variable and uncertain, a two dimensional Monte-Carlo simulation was used to develop the estimates for the impact of dietary lead on IQ. In addition to estimating blood lead and IQ decrements attributable to dietary lead from those countries with published market basket data, simulations were also run for WHO regions that sampled in the variability dimension based on the population size of the individual countries in each region. Dietary exposure to lead occurs throughout the world. The global average IQ decrement attributable to dietary lead was 1.1. The total number of Disability-Adjusted Life Years (DALYs) arising from those IQ decrements were estimated to be 5.2 million DALYs, with an uncertainty range of 0-31 million DALYs. Significant uncertainties regarding exposure and dose-response relationships, however, warrant continued investigation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives Higher than contemporary exposure levels and advanced age of study participants have limited the interpretation of previous studies relating neurocognitive function to lead exposure. We reassessed this association in young American men prior to chronic occupational exposure at lead recycling plants, using baseline measurements of the Study for Promotion of Health in Recycling Lead (NCT02243904). Methods We administered the Stroop test (ST) and the digit-symbol test (DST) to 339 men (mean age, 28.6 years; participation rate 82.7%). Whole blood lead (BL) was determined by inductively coupled plasma mass spectrometry and related ST and DST test results using multivariable-adjusted regression. Results Average values were 4.26 μg/dL for BL, 1624 ms and 1474 ms for mean reaction time in incongruent and congruent ST trials, and 109 sec for mean total latency in DST. The number of participants with fully correct answers amounted to 281 (82.9%) and 334 (98.5%) in incongruent and congruent ST trials, respectively, and to 198 (58.4%) in the DST. In multivariable-adjusted analyses, there was no association between cognitive performance and BL except for a weak but opposite association in DST; for a 10-fold BL increment, mean total latency was 5.4% (95% confidence interval, -0.4‒11.5%; P=0.066) higher, whereas the error score was 42% (-10‒69%; P=0.096) lower. To exclude an effect of the cumulative lead dose, sensitivity analyses restricted to workers <40, 35 and 30 years were confirmatory. Conclusions At the exposure levels in our current study, we failed to demonstrate a consistent inverse association of BL with neurocognitive performance in young American men.

Introduction: The aim of the study was to identify the places that could pose a threat to children's health due to the significant concentration of heavy metals in the top layer of soil on which they actively spend their time., Materials and Methods: The research material consisted of 144 topsoil samples from 10 randomly selected playgrounds and 10 sports fields located in two cities in Poland. The content of cadmium (Cd), lead (Pb) and zinc (Zn) in the analyzed samples was determined by atomic absorption using the INTEGRA XL ICP spectrometer with inductively coupled plasma., Results: From the 144 collected soil samples 48 (33%) exceeded the normative value for at least one of the three analyzed heavy metals. The maximum permissible concentration of all three elements was exceeded in the case of 15 samples. The heavy metals concentrations determined in the soil samples taken from the sports fields and playgrounds were in the following ranges, respectively: 0.3-43.0 mg/kg d. w. - Cd; 1.3-1393.8 mg/kg d. w.- Pb; 12.5-4315.8 mg/kg d. w. - Zn. Estimated children's exposure to heavy metals (Cd and Pb) via non-nutrient route indicates a significant risk which can be a place of recreation of the youngest children, as a result of secondary dusting during activity and games., Conclusions: In one-third of the analyzed soil samples from playgrounds and sport fields significant contamination with heavy metals (Cd, Pb, Zn) was indicated. In extreme cases, the maximum permissible concentration was exceeded over 20-fold, constituting an important risk factor for children's health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Surface soil contamination has been long recognized as an important pathway of human lead exposure, and is now a worldwide health concern. This study estimates the causal effects of exposure to lead in topsoil on cognitive ability among 5-year-old children. We draw on individual level data from the 2000 U.S. Census, and USGS data on lead in topsoil covering a broad set of counties across the United States. Using an instrumental variable approach relying on the 1944 Interstate Highway System Plan, we find that higher lead in topsoil increases considerably the probability of 5-year-old boys experiencing cognitive difficulties such as learning, remembering, concentrating, or making decisions. Living in counties with topsoil lead concentration above the national median roughly doubles the probability of 5-year-old boys having cognitive difficulties. Nevertheless, it does not seem to affect 5-year-old girls, consistent with previous studies. Importantly, the adverse effects of lead exposure on boys are found even in counties with levels of topsoil lead concentration considered low by the guidelines from the U.S. EPA and state agencies. These findings are concerning because they suggest that legacy lead may continue to impair cognition today, both in the United States and in other countries that have considerable lead deposition in topsoil., (Copyright © 2019 Elsevier B.V. All rights reserved.)

: Lead (Pb) exposure is associated with a wide range of neurological deficits. Environmental exposures may impact epigenetic changes, such as DNA methylation, and can affect neurodevelopmental outcomes over the life-course. Mating mice were obtained from a genetically invariant C57BL/6J background agouti viable yellow A vy strain. Virgin dams (a / a) were randomly assigned 0 ppm (control), 2.1 ppm (low), or 32 ppm (high) Pb-acetate water two weeks prior to mating with male mice ( A vy / a ), and this continued through weaning. At age 10 months, cortex neuronal nuclei were separated with NeuN⁺ antibodies in male mice to investigate neuron-specific genome-wide promoter DNA methylation using the Roche NimbleGen Mouse 3x720K CpG Island Promoter Array in nine pooled samples (three per dose). Several probes reached p-value < 10 -5 , all of which were hypomethylated: 12 for high Pb (minimum false discovery rate (FDR) = 0.16, largest intensity ratio difference = -2.1) and 7 for low Pb (minimum FDR = 0.56, largest intensity ratio difference = -2.2). Consistent with previous results in bulk tissue, we observed a weak association between early-life exposure to Pb and DNA hypomethylation, with some affected genes related to neurodevelopment or cognitive function. Although these analyses were limited to males, data indicate that non-dividing cells such as neurons can be carriers of long-term epigenetic changes induced in development., Competing Interests: The authors declare no conflict of interest.

Objectives: Previous research has indicated links between lead (Pb) exposure and increased risk of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). In this study, we evaluated the association between occupational Pb exposures and ALS., Methods: ALS cases were ascertained through the Danish National Patient Registry from 1982 to 2013 and age and sex-matched to 100 controls. Using complete employment history since 1964 from the Danish Pension Fund, cumulative Pb exposure was estimated for each subject via a Danish job exposure matrix. Associations were evaluated using conditional logistic regression analyses and stratified by sex., Results: For men with >50% probability of exposure, there was an increase in odds of ALS for exposures in the 60th percentile or higher during any time 5 years prior to diagnosis (aOR: 1.35; 95% CI 1.04 to 1.76) and 10 years prior to diagnosis (aOR: 1.33; 95% CI 1.03 to 1.72). No significant associations were observed in women, and there were no linear trends seen for Pb exposures for either sex., Conclusions: Our study indicates an association between consistently higher occupational Pb exposures and ALS. These findings support those of previously reported associations between ALS and specific occupations that commonly experience Pb exposure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Environmental justice (EJ) is the concept that all people and communities, regardless of their race and socioeconomic status, are entitled to enjoy an equally clean environment and resources. Communities where residents face environmental injustice and a higher risk of being exposed to environmental hazards due to their race, ethnicity, and socioeconomic status are called EJ communities. The purpose of this manuscript is to provide an example of nurses' involvement in observation, assessment, and intervention of an EJ community using a community-based participatory research (CBPR) model. Utilizing a multistage CBPR approach along with a mixed methods design, the project was carried out in three stages. Within the three stages, we conducted a thorough observation of the community, identified possible environmental issues, and collected health data and drinking water samples. Citizens' complaints included coal ash, failed sewer system, health issues, including kidney disorders and neuropathy. Drinking water samples (n = 59) showed lead levels higher than the health limits in 10.4% of samples. We intervened based on our short-term goal, reducing citizens' exposure to lead by education, and our long-term goal, reducing disparities, and exposures. We recommend that nurses increase their knowledge about EJ communities and environmental exposures and their health effects and be advocates for EJ communities., (© 2019 Wiley Periodicals, Inc.)

Importance: Millions of adults now entering middle age were exposed to high levels of lead, a developmental neurotoxin, as children. Although childhood lead exposure has been linked to disrupted behavioral development, the long-term consequences for adult mental and behavioral health have not been fully characterized., Objective: To examine whether childhood lead exposure is associated with greater psychopathology across the life course and difficult adult personality traits., Design, Setting, and Participants: This prospective cohort study was based on a population-representative birth cohort of individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, the Dunedin Multidisciplinary Health and Development Study. Members were followed up in December 2012 when they were 38 years of age. Data analysis was performed from March 14, 2018, to October 24, 2018., Exposures: Childhood lead exposure ascertained as blood lead levels measured at 11 years of age. Blood lead levels were unrelated to family socioeconomic status., Main Outcomes and Measures: Primary outcomes were adult mental health disorder symptoms assessed through clinical interview at 18, 21, 26, 32, and 38 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology and internalizing, externalizing, and thought disorder symptoms (all standardized to a mean [SD] of 100 [15]) and adult personality assessed through informant report using the Big Five Personality Inventory (assessing neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) at 26, 32, and 38 years of age (all scores standardized to a mean [SD] of 0 [1]). Hypotheses were formulated after data collection; an analysis plan was posted in advance., Results: Of 1037 original study members, 579 (55.8%) were tested for lead exposure at 11 years of age (311 [53.7%] male). The mean (SD) blood lead level was 11.08 (4.96) μg/dL. After adjusting for study covariates, each 5-μg/dL increase in childhood blood lead level was associated with a 1.34-point increase (95% CI, 0.11-2.57; P = .03) in general psychopathology, driven by internalizing (b = 1.41; 95% CI, 0.19-2.62; P = .02) and thought disorder (b = 1.30; 95% CI, 0.06-2.54; P = .04) symptoms. Each 5-μg/dL increase in childhood blood lead level was also associated with a 0.10-SD increase in neuroticism (95% CI, 0.02-0.08; P = .02), a 0.09-SD decrease in agreeableness (95% CI, -0.18 to -0.01; P = .03), and a 0.14-SD decrease in conscientiousness (95% CI, -0.25 to -0.03; P = .01). There were no statistically significant associations with informant-rated extraversion (b = -0.09; 95% CI, -0.17 to 0.004; P = .06) and openness to experience (b = -0.07; 95% CI, -0.17 to 0.03; P = .15)., Conclusions and Relevance: In this multidecade, longitudinal study of lead-exposed children, higher childhood blood lead level was associated with greater psychopathology across the life course and difficult adult personality traits. Childhood lead exposure may have long-term consequences for adult mental health and personality.

Background : Environmental factors determine children's health. Quantifying the health impacts related to environmental hazards for children is essential to prioritize interventions to improve health in Europe. Objective : This study aimed to assess the burden of childhood disease due to environmental risks across the European Union. Methods : We conducted an environmental burden of childhood disease assessment in the 28 countries of the EU (EU28) for seven environmental risk factors (particulate matter less than 10 micrometer of diameter (PM 10 ) and less than 2.5 micrometer of diameter (PM 2.5 ), ozone, secondhand smoke, dampness, lead, and formaldehyde). The primary outcome was disability-adjusted life years (DALYs), assessed from exposure data provided by the World Health Organization, Global Burden of Disease project, scientific literature, and epidemiological risk estimates. Results : The seven studied environmental risk factors for children in the EU28 were responsible for around 211,000 DALYs annually. Particulate matter (PM 10 and PM 2.5 ) was the main environmental risk factor, producing 59% of total DALYs (125,000 DALYs), followed by secondhand smoke with 20% of all DALYs (42,500 DALYs), ozone 11% (24,000 DALYs), dampness 6% (13,000 DALYs), lead 3% (6200 DALYs), and formaldehyde 0.2% (423 DALYs). Conclusions : Environmental exposures included in this study were estimated to produce 211,000 DALYs each year in children in the EU28, representing 2.6% of all DALYs in children. Among the included environmental risk factors, air pollution (particulate matter and ozone) was estimated to produce the highest burden of disease in children in Europe, half of which was due to the effects of PM 10 on infant mortality. Effective policies to reduce environmental pollutants across Europe are needed.

This review evaluates the sources of lead exposure worldwide. Studies from searches relating to sources of lead exposure in various countries within different regional zones were reviewed. Results indicated that in Nigeria, exposure sources include electronic waste, paint and batteries. In Mexico exposure sources include glazed ceramics, lead contaminated utensils and lead contaminated water, for India lead sources include cosmetics and traditional medicines. Sources of lead exposure in China include e-waste, traditional medicines and industrial emissions. In France, exposure sources included lead paint from older homes, imported ceramics and cosmetics and industrial emissions. Australia's exposure sources include paint, dust, imported toys and traditional medicines. Finally, in the United States exposure sources included paint, the industrial legacy of lead exposure and batteries. In high-income countries (HICs) the legacy of lead exposure keeps populations continuously exposed. In lower- and middle-income countries (LMICs), in addition to the legacy of lead exposure, lack of regulations or the inability to enforce regulations keeps populations exposed. In all, evidence suggests that lead exposure remains an issue of public health significance in both HIC and LMIC.

Animal personalities, as defined by repeatable among individual differences in behavior, can vary across urbanization gradients. However, how urbanization affects personalities remains incompletely understood, especially because different urban stressors could affect personality traits in opposing ways, whereas most previous studies have considered only one urban disturbance factor. For instance, novel habitat features could favor reduced neophobia, whereas exposure to pollutants could increase risk sensitivity through neurotoxic or hormonal effects. To address this contingency, we studied object neophobia in four urban populations of great tits (Parus major) that vary in exposure to metal pollution and anthropogenic disturbance, as quantified by proximity to roads and pathways. We measured the return latency of incubating females when flushed from the nest and presented with up to two different novel objects, allowing quantification of behavioral repeatability and plasticity. To separate neophobia from sensitivity to disturbance, we also conducted baseline trials, in which females were flushed but no object was presented. We additionally measured exploration behavior and aggression (hissing) during nest defense, to explore whether suites of behaviors covary with urbanization, and examined whether neophobia affects reproductive success. Sensitivity to disturbance and neophobia were repeatable, and thus represent personality traits. Moreover, females occupying territories near roads and pathways had shorter return latencies during novel object but not baseline trials, suggesting a specific reduction in neophobia in disturbed areas. Plasticity in neophobia also increased with disturbance level. In contrast, metal exposure did not affect neophobia or sensitivity to disturbance, despite negatively correlating with exploration behavior. Neophobia correlated with exploration behavior, but not aggression or reproductive success. Results suggest that shifts in personality types in urbanized areas might involve specific reductions in neophobia, rather than general reductions in sensitivity to disturbance, and unexpectedly indicate no effect of toxic metals on risk sensitivity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 μg/dL, higher than the 3.47 μg/dL blood lead level in Haojiang children (P <  0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 μg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 μg/dL) were higher than those in the low blood lead level group (blood lead < 5 μg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Vultures and condors (hereafter vultures) make up one the most threatened avian guilds in the world due to a variety of human-mediated impacts and disturbances. In fact, 70% of vulture species are currently suffering impacted by significant conservation threats, with lead contamination being particularly important. Unfortunately, lead contamination in vulture species remains poorly studied in many regions of the world. We reviewed the existing scientific knowledge about this threat to vultures. We found 62 scientific articles studying lead contamination in vultures. Seventy-two percent of these articles were from North America and Europe, with the rest corresponding to Asia (13%), South America (8%), and Africa (7%). Most (92%) were published recently (2001-2018). Published articles included information on 13 vulture species out of a total of 23 from both the Old (9) and New World (4). Eighty-eight percent of the articles showed individuals with lead concentrations above threshold levels in some tissues sampled, with New World (Cathartidae) vultures more affected than Old World vultures (Accipitridae). The most suspected but rarely probed source of lead was lead ammunition, but other sources such as pollution or industry were also reported. It is concerning that lead contamination is considered a major threat for just 8% (2/23) of the vulture species categorized by the IUCN Red list. Our review shows that lead contamination is an important threat for several vulture species worldwide, but remains undiagnosed and not well-recognized in some species and geographical areas. The effect of this contaminant on vulture demography is not well known but merits particular attention since it may be leading to population declines in several species., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate the associations between blood heavy metal concentrations and dry eye disease using a Korean population-based survey., Methods: This study included 23,376 participants >40 years of age who participated in the Korean National Health and Nutrition Examination Survey from 2010 to 2012. Blood concentrations of lead, cadmium, and mercury were measured in all participants. The associations between blood heavy metal concentrations and dry eye disease were assessed using multivariate logistic regression analyses., Results: After adjusting for potential confounders, including age, sex, lifestyle behaviors and sociodemographic factors, the analyses revealed an increased odds ratio (OR) for dry eye disease with higher blood mercury concentrations (tertile 2: OR, 1.22; 95% confidence interval [CI], 0.91 to 1.64; tertile 3: OR, 1.39; 95% CI, 1.02 to 1.89; p = 0.039). The prevalence of dry eye disease was not associated with blood lead (tertile 2: OR, 1.15; 95% CI, 0.87 to 1.51; tertile 3: OR, 0.83; 95% CI, 0.59 to 1.16; p = 0.283) or cadmium (tertile 2: OR, 1.05; 95% CI, 0.77 to 1.44; tertile 3: OR, 1.15; 95% CI, 0.84 to 1.58; p = 0.389) concentrations. There were no significant associations between any of the three heavy metals and dry eye disease in males after adjusting for potential confounding factors, but blood mercury concentrations in females were associated with dry eye disease (tertile 2: OR, 1.18; 95% CI, 0.83 to 1.69; tertile 3: OR, 1.58; 95% CI, 1.12 to 2.24; p = 0.009)., Conclusions: Mercury concentrations in blood were associated with dry eye disease. Our results suggested that controlling environmental exposure to mercury may be necessary to reduce the incidence of dry eye disease., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2019 The Korean Ophthalmological Society.)

The etiology of Attention-Deficit/Hyperactivity Disorder (ADHD) is complex and multifactorial. Although the development of ADHD symptoms remains to be elucidated, in recent years, epigenetic processes have emerged as candidate mechanisms. Lead is one of the most dangerous environmental pollutants, and it is suspected to be associated with ADHD. The aim of the present study was to review the epidemiological literature currently available on the relation between lead exposure and the diagnosis of ADHD. The PubMed and EMBASE databases were searched from 1 July 2018 up to 31 July 2018. The authors included observational studies (cohort, case⁻control and cross-sectional studies) published in English carried out on children within the last 5 years, measuring lead exposure and health outcomes related to ADHD. Seventeen studies met the inclusion criteria: 5 of these studies found no association between lead exposure and ADHD whereas the remaining 12 studies showed positive associations, even though not all of them were homogeneous in terms of exposure periods considered or ADHD diagnosis. To conclude, the evidence from the studies allowed us to establish that there is an association between lead and ADHD and that even low levels of lead raise the risk. However, there is still a lack of longitudinal studies about the relationship between lead exposure and the development of ADHD. Given the potential importance for public health, further research that includes the entire potential risk factors for ADHD in children must be encouraged.

Lead exposure causes or aggravates hearing damage to human or animal, but the detailed effects of lead exposure on auditory system including injury sites of the cochlea in mammal remain controversy. To investigate the effect of chronic lead exposure on auditory system, 40 adult guinea pigs with normal hearing were randomly divided into five groups. They were fed 2 mmol/L lead acetate in drinking water for 0, 15, 30, 60, and 90 days (n = 8), respectively. Lead concentrations in blood, cochlea, and brainstem were measured. Auditory function was measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). The morphology of cochlea and brainstem was observed, and expression of autophagy-related protein in brainstem was also assessed. The blood lead concentration reached a high level at the 15th day and kept stable, but the lead level in brainstem and cochlear tissue increased obviously at the 60th day and 90th day of lead exposure, respectively. There was no significant difference in the morphology of hair cells and stria vascularis (SV) among these five groups, but the number of spiral ganglion neuron (SGN) gradually decreased after 60 days. The differences of ABR thresholds and DPOAE amplitudes were not statistically significant among each group, but I wave latency, III latency, and I-III wave interval of ABR were delayed with the prolonging of time of lead exposure. The expressions of autophagy-related protein ATG5, ATG6, and LC3B in brainstem were increased after 30 days. These results suggest that the key target of lead toxicity was the auditory nerve conduction pathway including SGNs and brainstem, rather than cochlear hair cells and SV. Autophagy may play a very important role in lead toxicity to auditory nervous system.

Purpose: An ongoing health crisis across a large area of Northern Nigeria has resulted in hundreds of deaths and thousands of cases of lead poisoning from artisanal small-scale gold mining. Occupational Knowledge International (OK International) and Doctors Without Borders/Médecins Sans Frontières (MSF) have formed a partnership to conduct a pilot project to introduce safer mining practices in selected communities. The primary objective was to reduce lead exposures among artisanal small-scale miners and minimize take home exposures by reducing dust contamination on clothing and body surfaces., Methods: Personal air samples were collected from miners and ore processors before and after the introduction of wet spray misting in mine processing activities to crush and grind gold ore. We measured reductions in total airborne lead and respirable silica dust levels. A total of 44 air samples were collected for airborne lead using NIOSH method 7082 and 29 air samples for respirable silica dust with NIOSH method 7500., Results: Low-cost interventions to convert dry ore processing to wet methods with spray misting were effective at reducing arithmetic mean airborne lead levels by 95%. Mean airborne respirable silica (quartz) was reduced by 80% following the introduction of wet spray misting. Differences in geometric means between wet and dry ore processing methods were statistically significant for both airborne lead and respirable silica., Conclusions: This pilot project has been successful in working cooperatively with miners to provide them with the necessary information and tools to reduce exposures in mining and processing, and minimize off-site contamination. As silica dust is a significant risk factor for silicosis and tuberculosis (TB), this intervention could provide public health benefits to small-scale mining communities even in areas without significant lead concentrations in the ore. Significant reductions in respirable silica and lead exposures are feasible in low-resource, small-scale mining communities.

Lead (Pb 2+ ) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb 2+ -induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb 2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb 2+ -exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60-90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb 2+ -exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb 2+ -exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb 2+ -exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.

The Centers for Disease Control and Prevention's (CDC's) Childhood Lead Poisoning Prevention Program (CLPPP) serves as the nation's public health leader and resource on strategies, policies, and practices aimed at preventing lead exposure in young children. CDC supports and advises state and local public health agencies and works with other federal agencies and partners to achieve the Healthy People 2020 objective of eliminating childhood lead exposure as a public health concern. Primary prevention-the removal of lead hazards from the environment before a child is exposed-is the most effective way to ensure that children do not experience the harmful effects of lead exposure. Blood lead screening tests and secondary prevention remain an essential safety net for children who may be exposed to lead. CDC's key programmatic strategy is to strengthen blood lead surveillance by supporting state and local programs to improve blood lead screening test rates, identify high-risk populations, and ensure effective follow-up for children with elevated blood lead levels. Surveillance plays a central role in helping measure the collective progress of federal, state, and local public health agencies in protecting children from lead, as well as enhancing our ability to target population-based interventions for primary prevention to those areas at highest risk. The CDC CLPPP has been at the front line of efforts to protect children from lead exposure and the resulting adverse health effects over the last 3 decades. As we chart our path for the future, we will continue to learn from past successes and challenges, incorporate new evidence and lessons learned, and work closely with federal, state, local, and nonprofit partners, experts in academia, and the community to advance the overarching goal of eliminating lead exposure in children.

There is mounting concern about the effects of early-life exposure to chemical substances on children's health and development. We summarize the past and ongoing birth cohort studies carried out worldwide on the association between environmental exposure and children's health. Our PubMed search with the keywords 'birth cohort' revealed that the number of articles jumped from 200-300 in the 1980s to over 1,000 in the 1990s. Many of these articles reported elevated risks to children's health posed by chemical exposure owing their vulnerability. At the same time, policies implemented to reduce exposure to lead and dioxins were successful in the past few decades. Research also demonstrated that intervention to reduce exposure to certain chemicals whose exposure routes were well documented was also successful. We summarize the effects of early-life exposure to chemical substances on children's health and development. Our findings will hopefully help safeguard the environment in which future generations grow and live.

Background: Alzheimer's Dementia (AD) has a complex pathophysiology that is incompletely understood. Chronic, low-level environmental lead (Pb) exposure is associated with cognitive impairment, hypertension and mortality, and has been proposed as a potential cause of AD., Objective: We aimed to review the literature to clarify the potential role of Pb in AD and to guide future research., Methods: Through a series of systematic reviews, we identified case-control studies comparing AD to controls on 6 measures of Pb exposure or accumulation: blood, bone, cerebrospinal fluid, hair/nail, postmortem pathology, and urine. We completed meta-analyses where possible., Results: The number of identified case-control studies of AD, by measurement method, was: 15 by blood, 0 by bone, 5 by Cerebrospinal Fluid (CSF), 3 by hair/nail, 3 by postmortem, and 1 by urine. Two meta-analyses were possible for 7 studies reporting whole blood Pb and for 8 studies of serum Pb. Both were negative. The largest study of CSF Pb showed lower levels in AD. Similarly, lower hair Pb levels were found in AD., Conclusion: The available case-control studies are insufficient to draw conclusions on the role of Pb in AD. Most methods do not address long-term or early-life exposure. The preferred measure of chronic Pb is in bone, which has not been utilized in case-control AD studies. Future research should measure bone Pb in AD, together with other biomarkers, such as amyloid and tau imaging, and markers of cerebrovascular pathology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

There is currently a lack of risk assessments around Pb and Cd in prescription food for special medical purposes (FSMPs) and modified milk products available in from pharmacies in Poland. This article describes and evaluates a toxicological analysis of lead and cadmium in prescription FSMPs (n = 6) and modified milk products (n = 6) available in Polish pharmacies. The metals were determined using electrothermal atomisation atomic absorption spectrometry. To make the appropriate risk assessment, we considered (1) the levels of lead and cadmium in a powdered product, (2) the amount of the metals consumed in one portion (single exposure), (3) the daily dose depending on age (months) and body weight and (4) the weekly intake of Pb and Cd in samples in comparison to provisional tolerable weekly intake (PTWI). The results demonstrated that the samples analysed do not represent a health hazard to newborns and infants. This study is important because of the concerns around the complex risk assessment of prescription FSMP's and modified milk products available in Polish pharmacies related to lead and cadmium., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Context: During the past 45 years, exposure to lead has declined dramatically in the United States. This sustained decline is measured by blood and environmental lead levels and achieved through control of lead sources, emission reductions, federal regulations, and applied public health efforts., Objective: Explore regulatory factors that contributed to the decrease in exposure to lead among the US population since 1970., Design/setting: We present historical information about the control of lead sources and the reduction of emissions through regulatory and selected applied public health efforts, which have contributed to decreases in lead exposure in the United States. Sources of lead exposure, exposure pathways, blood lead measurements, and special populations at risk are described., Results: From 1976-1980 to 2015-2016, the geometric mean blood lead level (BLL) of the US population aged 1 to 74 years dropped from 12.8 to 0.82 μg/dL, a decline of 93.6%. Yet, an estimated 500 000 children aged 1 to 5 years have BLLs at or above the blood lead reference value of 5 μg/dL established by the Centers for Disease Control and Prevention. Low levels of exposure can lead to adverse health effects. There is no safe level of lead exposure, and child BLLs less than 10 μg/dL are known to adversely affect IQ and behavior. When the exposure source is known, approximately 95% of BLLs of 25 μg/dL or higher are work-related among US adults. Despite much progress in reducing exposure to lead in the United States, there are challenges to eliminating exposure., Conclusions: There are future challenges, particularly from the inequitable distribution of lead hazards among some communities. Maintaining federal, state, and local capacity to identify and respond to populations at high risk can help eliminate lead exposure as a public health problem. The results of this review show that the use of strong evidence-based programs and practices, as well as regulatory authority, can help control or eliminate lead hazards before children and adults are exposed.

Background: Neonates may be exposed to lead (Pb) through blood transfusions from donors. Pb exposure has neurological, cardiovascular, renal, and other adverse effects. The study aimed to (i) determine the blood lead levels (BLLs) in different blood product units (whole blood, packed red blood cells (pRBCs), platelets, and plasma transfused to neonates) and (ii) estimate the proportion of units with high BLLs., Methods: Residual blood from blood bank bags that were used for neonatal transfusion were collected: 25 samples from each type of blood product except for whole blood (10 samples). The Pb analysis was performed using the atomic absorption method. The study was conducted at the Suez Canal University Hospital, Egypt., Results: The mean of BLL in pRBCs, platelets, plasma, and whole blood were 136, 199, 108, and 130 µg/L, respectively; 60% contained Pb above 50 µg/L. The highest BLLs were in platelet units., Conclusions: The present study showed for the first time that platelets and plasma in addition to whole blood and pRBCs used for neonatal transfusions are sources of Pb. Re-evaluation of the guidelines is mandatory for the safety of the neonates. Long-term neurodevelopment assessment of neonates exposed to high Pb is warranted.

Lead (Pb 2+ ) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb 2+ -exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb 2+ -exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb 2+ -exposure with no gender differences observed. However, Pb 2+ -exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.

Background and Objective: Host responses in periodontitis span a range of local and emigrating cell types and biomolecules. Accumulating evidence regarding the expression of this disease across the population suggests some component of genetic variation that controls onset and severity of disease, in concert with the qualitative and quantitative parameters of the oral microbiome at sites of disease. However, there remains little information regarding the capacity of accruing environmental stressors or modifiers over a lifespan at both the host genetic and microbial ecology levels to understand fully the population variation in disease. This study evaluated the impact of environmental lead exposure on the responses of oral epithelial cells to challenge with a model pathogenic oral biofilm., Methods and Results: Using NanoString technology to quantify gene expression profiles of an array of 511 host response-associated genes in the epithelial cells, we identified an interesting primary panel of basal responses of the cells with numerous genes not previously considered as major response markers for epithelial cells, eg, interleukin (IL)-32, CTNNB1, CD59, MIF, CD44 and CD99. Even high levels of environment lead had little effect on these constitutive responses. Challenge of the cells with the biofilms (Streptococcus gordonii/Fusobacterium nucleatum/Porphyromonas gingivalis) resulted in significant increases in an array of host immune-related genes (134 of 511). The greatest magnitude in differential expression was observed with many genes not previously described as major response genes in epithelial cells, including IL-32, CD44, NFKBIA, CTSC, TNFAIP3, IL-1A, IL-1B, IL-8 and CCL20. The effects of environmental lead on responses to the biofilms were mixed, although levels of IL-8, CCL20 and CD70 were significantly decreased at lead concentrations of 1 and/or 5 μmol/L., Conclusion: The results provided new information on a portfolio of genes expressed by oral epithelial cells, targeted substantial increases in an array of immune-related genes post-biofilm challenge, and a focused impact of environmental lead on these induced responses., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Much evidence demonstrates the adverse effects of lead ammunition on wildlife, their habitats and human health, and confirms that the use of such ammunition has no place within sustainable hunting. We identify the provisions that define sustainable hunting according to European law and international treaties, together with their guidance documents. We accept the substantial evidence for lead's actual and potential effects on wildlife, habitats and health as persuasive and assess how these effects relate to stated provisions for sustainability and hunting. We evaluate how continued use of lead ammunition negatively affects international efforts to halt loss of biodiversity, sustain wildlife populations and conserve their habitats. We highlight the indiscriminate and avoidable health and welfare impacts for large numbers of exposed wild animals as ethically unsustainable. In societal terms, continued use of lead ammunition undermines public perceptions of hunting. Given the existence of acceptable, non-toxic alternatives for lead ammunition, we conclude that hunting with lead ammunition cannot be justified under established principles of public/international policy and is not sustainable. Changing from lead ammunition to non-toxic alternatives will bring significant nature conservation and human health gains, and from the hunter's perspective will enhance societal acceptance of hunting. Change will create opportunities for improved constructive dialogue between hunting stakeholders and others engaged with enhancing biodiversity and nature conservation objectives.

Iron mining activities in the Bruche valley (Vosges Mountains, France) date historically from the Roman period to the mid-nineteenth century. The geochemical and palynological study of a core from the peat bog of Le Champ du Feu allows highlighting impacts of these activities over the past millennium. Trace metal contamination is recorded for lead (Pb), arsenic, zinc, and antimony during the Middle Ages, the sixteenth century, and from cal. AD 1750-1900, with several sources distinguished by Pb isotope analyses. Forest exploitation is attested by the palynological analysis of the core, with exploitation of Fagus for smelting processes and cutting of Abies for agro-pastoralism. This approach highlights several patterns of contamination, corresponding to the mixing sources and the contamination intensity, which can be linked to the pollen assemblage zones. Hence, anthropogenic activities such as mining and farming led to long-term modification of the landscape composition in this mountainous area.

Individual susceptibility to the toxic effects induced by exposure to lead (Pb) may be affected by several variables, such as environmental factors, as well as intrinsic variations among the individuals, which are hypothetically associated to genetic differences in enzymes metabolizing the metal. Aim of the present study was to evaluate the effects of polymorphisms of glutathione (GSH)-genes related to the antioxidant status and Pb metabolism (GCLC, rs17883901 and GCLM, rs41303970) on Pb levels in blood (B-Pb) and plasma (P-Pb), as well as Pb-related effects on activity of glutathione-peroxidase (GPX) and on GSH concentrations. A cross-sectional study with 236 adults (men, >18 years old) was carried out with workers from automotive battery factories, Brazil. B-Pb and P-Pb were determined by ICP-MS; blood GPX and GSH were determined by spectrophotometry and qPCR TaqMan assays were used for genotyping. A questionnaire was applied in order to collect socio-demographic, lifestyle and time of exposure. The mean B-Pb level was 211 ± 118 μg/L and P-Pb was 6.05 ± 7.13 μg/L. GCLM are associated with changes of B-Pb and P-Pb; individuals who carry at least one polymorphic allele for GCLM gene had lower metal levels in the blood and plasma (β = -1.5; p = 0.0080; β = -0.12 and p = 0.050). In addition, individuals carrying at least one polymorphic allele for the GCLC gene had higher concentrations of GSH than the non-polymorphic ones, as a function of B-Pb (β = 0.072; p = 0.029). Significant associations were also observed with GCLC polymorphism on GSH concentrations (as a function of P-Pb), that is, polymorphic individuals tended to have higher concentrations of GSH than non-polymorphic ones (β = 0.072; p = 0.030), while those individuals who are polymorphic for GCLM had higher activities of GPX, compared to the non-variant genotype (β = 0.19; p = 0.028). Taken together, our data indicate that polymorphisms related to Pb toxicokinetics modify the metal body burden and Pb-related antioxidant effects., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Outdated federal and state occupational lead standards leave workers and their families vulnerable to the adverse effects of lead. Standards should be updated to reflect the best available scientific and medical evidence, which documents harm to multiple organ systems even at low levels of exposure. This commentary will review the inadequacies of existing policies, highlight susceptible populations, and briefly summarize state revision efforts to date. Federal policies must be strengthened to protect all workers and their families from this well-documented hazard., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: It is argued that breakdown of β-amyloid in the brain causes deposition of senescent plaques and therefore Alzheimer's disease (AD). One of the influential factors for increasing level of this protein is exposure to lead. Our aim was to compare blood lead levels (BLLs) between patients with AD and healthy controls., Methods: This case-control study was performed on all patients with cognitive impairment who were referred to the Neurological Clinic of Birjand in 2016 to 2017. Patients were referred to the laboratory for measurement of their serum levels of lead. The controls and patients were matched by age and sex., Results: In the AD case group, the average BLL was 22.22 ± 28.57 μg/dL. Mann-Whitney U test showed that BLLs were significantly higher in the patients than in the controls. The unadjusted odds ratio for BLL among the patients was 1.05 (95% confidence interval: 1.01-1.09; P = .01) compared to the controls., Conclusion: In the present study, BLL was associated with AD.

Importance: Contrast sensitivity (CS) is an important indicator of visual function that affects daily life, including mobility, visually intensive tasks, safety, and autonomy. Understanding the risk factors for CS impairment could prevent decreases in visual function., Objective: To determine the incidence of and factors associated with CS impairment in a large cohort., Design, Setting, and Participants: The Beaver Dam Offspring Study is an ongoing longitudinal cohort study of aging involving adults in Beaver Dam, Wisconsin. Participants who were free of CS impairment in both eyes at baseline were included (N = 1983). Baseline data collection occurred from June 8, 2005, through August 4, 2008, when the participants ranged from 21 to 84 years of age. Two follow-up examinations occurred at 5-year intervals: one was conducted between July 12, 2010, and March 21, 2013, and the other between July 1, 2015, and November 13, 2017. Data analysis was performed from November 27, 2017, to February 27, 2018., Main Outcomes and Measures: Contrast sensitivity testing was conducted with Pelli-Robson letter sensitivity charts, and incident impairment was defined as a log CS score less than 1.55 in either eye at any follow-up examination. Cadmium and lead levels were measured in whole blood with inductively coupled plasma mass spectrometry. Associations between baseline characteristics and CS impairment incidence were examined using Cox proportional hazard models and quantified as hazard ratios (HRs) with 95% CI., Results: Of the 1983 participants included, 1028 (51.8%) were female and 955 (48.2%) were male, with a mean (SD) age of 48 (9.3) years. The 10-year cumulative incidence of CS impairment was 24.8% (95% CI, 22.9-26.8), similar in women (24.9%) and men (24.6%), and highest in the oldest age group (65-84 years) at 66.3%. In multivariable models, cadmium level in the highest quintile (HR, 1.35; 95% CI, 1.02-1.78), older age (HR, 1.36; 95% CI, 1.25-1.47), larger waist circumference (HR, 1.06; 95% CI, 1.01-1.11), and more plaque sites (1-3 sites: HR, 1.43; 95% CI, 1.07-1.92; 4-6 sites: HR, 2.75; 95% CI, 1.26-6.05) were among the factors associated with increased risk, while male sex (HR, 0.77; 95% CI, 0.60-0.98) and any alcohol consumption (HR, 0.61; 95% CI, 0.43-0.88) were associated with decreased risk. Results were similar when smoking status replaced cadmium exposure in the models. Lead level was not associated with increased risk., Conclusions and Relevance: This study's findings suggest that incident CS impairment was common in the 10-year follow-up, with cadmium, but not lead, exposure associated with increased risk. The associations of diminished CS with other modifiable risk factors found appear to imply that changes in behavior may reduce future incidence of CS impairment.

Growing evidence suggests that environmental exposures can influence blood pressure over the course of a lifetime. Exposure to toxic metals, such as lead (Pb) and arsenic (As), has been associated with increased blood pressure in adults, but few studies have examined the impacts of in utero and early life toxic metals exposure on blood pressure in childhood. As subclinical vascular changes are thought to begin early in life, it is possible that in utero toxic metals exposure may play a role in blood pressure homeostasis. In the ongoing New Hampshire Birth Cohort Study, we investigated whether in utero exposure to Pb and As was associated with measures of blood pressure in a total of 323 young children (mean age 5.5 years, SD 0.4). Pb and As were measured in maternal toenail samples collected at ~28 weeks gestation (n = 257) and/or 6 weeks postpartum (n = 285), which represent exposures ~6 to 12 months prior to collection and therefore reflect the early prenatal and late prenatal exposures, respectively. Five measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were averaged for each child using a standardized technique. In linear regression analyses, where log 2 -transformed prenatal toenail Pb and As were modeled jointly and adjusted for child age, sex, height, weight and maternal smoking during pregnancy, we observed that a doubling of maternal prenatal toenail Pb was associated with statistically significant increases in child SBP (β: 0.58 mm Hg, 95% CI: 0.05, 1.11). We did not observe any association of prenatal or postpartum As, or postpartum Pb, with SBP or DBP. Exploratory sex-stratified analyses suggest that associations of prenatal Pb with BP may be stronger among boys (SBP β: 0.72 mm Hg: 95% CI: -0.01, 1.44; DBP β: 0.37; 95% CI: -0.09, 0.84), compared to girls (SBP β: 0.48 mm Hg: 95% CI: -0.31, 1.26; DBP β: -0.05; 95% CI: -0.52, 0.41), though tests for interaction did not reach statistical significance (p-interaction SBP = 0.059; DBP = 0.057). Our preliminary results suggest that in utero toxic metals exposures may be associated with early life increases in blood pressure in children, which could have consequences for long-term health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Most of studies assessed the effect of Pb-exposure on serum total magnesium (tMg). The hypomagnesium condition depended on protein concentration in the sample and influence of lifestyle factors. This study assessed the effect of Pb- exposure on serum tMg, corrected Mg (cMg), ionized Mg (iMg), percentage of iMg from tMg, and percentage of iMg from cMg with contemplation of lifestyle factors., Study Design: Case control study., Methods: The serum magnesium fractions were assessed in 176 male Pb-exposed workers in the year 2015 at Tamil nadu in India and 80 control subjects with no occupational exposure of Pb. The serum tMg and albumin concentrations were estimated using diagnostic kit methods. Blood lead levels (BLLs) were estimated using atomic absorbtion spectrophotometer method. The fraction of cMg and iMg were calculated from serum tMg and albumin concentration among individual subjects., Results: The BLLs was significantly (P<0.001) increased in the study group as compared to control. Serum tMg, cMg, iMg, % of iMg from tMg and % of iMg from cMg concentrations were not significantly decreased in the study group as compared to control. Pb-exposure was significantly associated with abnormal frequency distribution of serum iMg (P=0.048) and % of iMg from tMg (P=0.016). Smoking habit was significantly associated with cMg (P=0.039) and % of iMg from cMg concentration (P=0.018). The alcohol consumption was significantly (P=0.049) associated with cMg., Conclusion: The Pb-exposure and lifestyle factor such as smoking and alcohol consumption were associated with alteration of serum magnesium fractions.