Low-level Lead Research Articles

Lasting Adverse Effects of Low-Level Lead Exposure on Cognition and Heritable Susceptibilities

Lasting Adverse Effects of Low-Level Lead Exposure on Cognition and Heritable Susceptibilities

Association of low-level lead exposure with all-cause and cardiovascular disease mortality in US adults with hypertension: evidence from the National Health and Nutrition Examination Survey 2003–2010

BackgroundTo explore the association of low-level lead exposure with all-cause mortality and cardiovascular disease (CVD) mortality among hypertensive patients.MethodsThis cohort study enrolled 6453 adults with hypertension from the National Health and Nutrition Examination Survey 2003–2010 and followed mortality information through December 31, 2019. The baseline population were divided into four groups based on quartiles of blood lead levels (Q1: < 1.2 μg/dL, Q2: 1.2–1.6 μg/dL, Q3: 1.7–2.4 μg/dL, Q4: 2.5–4.9 μg/dL). The correlation of blood lead levels to mortality was investigated by Kaplan–Meier survival curves, restricted cubic spline (RCS), proportional hazard regression model, and subgroup analysis.ResultsDuring a median follow-up period of 136 (interquartile range 113, 164) months, a total of 1943 (30.1%) deaths were documented, among which 553 (28.5%) were due to CVD. Blood lead showed a linear dose–response relationship with all-cause and CVD mortality. After adequate adjusting for confounders, the risk of all-cause death rose by 23% for each unit increase in continuous variable blood lead (hazard ratio (HR): 1.23; 95% confidence interval (CI):1.16–1.30). When blood lead was a quartile group variable, participants in the Q 4 group had a 73% higher risk of death than those in the Q 1 group (HR:1.73; 95% CI: 1.43–2.10; P for trend < 0.001). The association for CVD mortality was analogous. The concordant results were achieved in the subgroup analysis.ConclusionElevated blood lead levels were strongly associated with an increased all-cause and CVD mortality in adults with hypertension, even at the reference range of blood lead.

Stability of blood lead levels in children with low-level lead absorption.

Current child blood lead (Pb) screening guidelines assume that blood lead levels (BLLs) are relatively stable over time, and that only youngest children are vulnerable to the damaging effects of lower-range BLLs. This study aimed to test the stability of lower-range (≤ 10 μg/dL) child BLLs over time, and whether lower-range BLLs diminished with age among children aged 6 months to 16 years living in a lower-income neighborhood with a density of pre-1986 housing and legacy contamination. Age, sex, family income, age of residence, and/or residence proximity to point sources of Pb, were tested as potential additional factors. Capillary blood samples from 193 children were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Multiple imputation was used to simulate missing data for 3 blood tests for each child. Integrated Growth Curve models with Test Wave as a random effect were used to test BLL variability over time. Among N = 193 children tested, at Time 1 testing, 8.7% had the BLLs ≥ 5 μg/dL (CDC "elevated" BLL reference value at the time of data collection) and 16.8% had BLLs ≥ 3.5 μg/dL (2021 CDC "elevated" BLL reference value). Modeling with time as a random effect showed that the variability of BLLs were attributable to changes within children. Moreover, time was not a significant predictor of child BLLs over 18 months. A sex by age interaction suggested that BLLs diminished with age only among males. Of the additional environmental factors tested, only proximity to a major source of industrial or vehicle exhaust pollution predicted child BLL variability, and was associated with a small, but significant BLL increase (0.22 μg/dL). These findings suggest that one or two BLL tests for only infants or toddlers are insufficient for identifying children with Pb poisoning.

Temporal transition trends of cord blood lead levels in various human development index countries and in the Taipei metropolitan area

Since low-level lead exposure is still of concern for neonates, it is worth further characterizing the temporal transition trends of cord blood lead levels (CBLLs) globally and locally in Taipei, Taiwan, after the cessation of leaded gasoline use. A literature review on CBLLs around the world was performed by searching three databanks, i.e., PubMed, Google Scholar and Web of Science, with the search keywords “cord blood” combined with “lead” or “Pb” for studies published from 1975 to May 2021. In total, 66 articles were included. Linear regressions for the reciprocal of sample size weighed CBLLs against calendar year presented a high r2 value (0.722) for the very high Human Development Index (HDI) countries and a moderate r2 value (0.308) for the combined high and medium HDI countries. The predicted CBLLs in 2030 and 2040 were 6.92 (95% CI: 6.02–7.81) μg/L and 5.85 (95% CI: 5.04–6.66) μg/L, respectively, for the very high HDI countries and 13.10 (95% CI: 7.12–19.09) μg/L and 10.63 (95% CI: 5.37–15.89) μg/L, respectively, for the combined high and medium HDI countries. To characterize the CBLL transitions in the Great Taipei metropolitan area, data from five studies conducted from 1985 to 2018 were employed. Although the results of the early four studies indicated that the Great Taipei metropolitan area did not reach the pace in CBLL reduction among the very high HDI countries, the CBLLs of the latest study during 2016–2018 were pretty low (8.1 ± 4.5 μg/L), approximately 3 years in advance of the very high HDI countries as one group to reach this low CBLL. In conclusion, further effective reduction in environmental lead exposure is challenging and must be based on the efforts from the aspects reflected by the HDI index compositions, i.e., economics, education and health, mostly implying health disparity and inequality.

Analisis Kadar Timbal (Pb) Darah dan Malondialdehid (MDA) Pada Manusia Silver di Kota Semarang

The danger of lead in paint that is coated on the human body, silver can enter through the skin and will interact with proteins, DNA, RNA and oxidative stress. Formation of Reactive Oxygen Species (ROS) by lead can cause oxidative stress and is characterized by an increase in the enzymes catalase, malondialdehyde (MDA) and Oxidized glutathione (GSSG). The aim of this study was to analyze blood lead levels against Malondealdehyde (MDA) in silver humans in Semarang City. This study used an observational analytic study with a cross sectional approach to analyze the effect of lead levels on Malondialdehyde levels in silver humans in Semarang City using a t test to see differences in results based on length of work, length of exposure and age on lead levels, and the effect of lead on MDA. The results showed that from 20 human samples, the lowest lead level was 23.9 g/dl and the highest was 61.9 g/dl with an average blood lead level of 37.3 g/dl with an average blood lead level of 37.3 g/dl, and the lowest MDA level was 0.4 mg/L and the highest level is 1.74 mg/L with an average of 1.2 mg/L. Based on the data obtained from the t test, it shows a significant value (P-Value) of 0.610 which means 0.05, this indicates that the decision taken is to reject H1 which means that there is no effect between the results of lead levels on the results of MDA levels.

Effect of lead, calcium, iron, zinc, copper and magnesium on anemia in children with BLLs ≥ 100 μg/L

ObjectiveAdverse effects of lead exposure on children's health have been demonstrated. While studies have examined the relationship between iron status and low-level lead exposure in children with blood lead levels (BLLs) < 100 μg/L, few have investigated the association between blood lead and other trace elements and anemia in children with BLLs ≥ 100 μg/L. This study aimed to assess the levels of lead, iron, copper, zinc, magnesium, and calcium in children aged 0–14 with BLLs≥ 100 μg/L between 2009 and 2021, and to examine the relationship between blood lead, trace elements and anemia. MethodsA total of 11,541 children with BLLs ≥ 100 μg/L were included in this study. Venous blood samples were collected to measure blood lead levels, hemoglobin levels, and trace element levels. According to the World Health Organization standard, outpatients with hemoglobin levels < 110 g / L were defined as having anemia. ResultsThe study results found that high BLLs and blood calcium had a negative influence on Hb with odds ratios (95% confidence interval) of 1.411(1.208, 1.649) and 1.219(1.043, 1.424). High blood iron had a positive influence on Hb with odds ratios of 0.421(0.355, 0.499). ConclusionThe results suggest that the risk of anemia rose significantly with higher BLLs, blood copper, and blood calcium levels, and decreases considerably with higher blood iron levels.

Cognitive outcomes caused by low-level lead, cadmium, and mercury mixture exposure at distinct phases of brain development.

Contaminated water and food are the main sources of lead, cadmium, and mercury in the human body. Long-term and low-level ingestion of these toxic heavy metals may affect brain development and cognition. However, the neurotoxic effects of exposure to lead, cadmium, and mercury mixture (Pb+Cd+Hg) at different stages of brain development are rarely elucidated. In this study, different doses of low-level Pb+Cd+Hg were administered to Sprague-Dawley rats via drinking water during the critical stage of brain development, late stage, and after maturation, respectively. Our findings showed that Pb+Cd+Hg exposure decreased the density of memory- and learning-related dendritic spines in the hippocampus during the critical period of brain development, resulting in hippocampus-dependent spatial memory deficits. Only the density of learning-related dendritic spines was reduced during the late phase of brain development and a higher-dose of Pb+Cd+Hg exposure was required, which led to hippocampus-independent spatial memory abnormalities. Exposure to Pb+Cd+Hg after brain maturation revealed no significant change in dendritic spines or cognitive function. Further molecular analysis indicated that morphological and functional changes caused by Pb+Cd+Hg exposure during the critical phase were associated with PSD95 and GluA1 dysregulation. Collectively, the effects of Pb+Cd+Hg on cognition varied depending on the brain development stages.

Lead pollution-related health of children in China: Disparity, challenge, and policy

Lead (Pb) is a neurotoxic metal, and no level of lead exposure is safe for children. China has still experienced problems on child lead poisoning even though the Chinese government has phased out leaded gasoline since 2000. The underlying problem affecting the lead pollution-related health of children in China remains to be comprehensively investigated. It is found that although the significant decline of BLLs, as the Geometric Mean (GM), from 91.40 μg/LGM in 2001 to 37.52 μg/LGM in 2018 is observed, the average BLLs of children are still above 50 μg/L or more [average 59.70 (60.50–65.02, 95 % CI) μg/LGM] after phasing out leaded gasoline since 2000 in China. Lead exposure causes 29.67 MID per 1000 children with a loss of 98.23 (59.40–146.21, 95 % CI) DALYs per 1000 in China, which is greater than the levels reported from the Western Pacific Region and other low- and middle-income countries. A significant correlation is observed between the number of child crimes (NoCCs) and the outcomes of long-term lead exposure for children in China. Although the disparities in BLLs in China are strongly influenced by unequal distributions of potential multi-lead related sources (soil lead, PM2.5 lead, dust lead), unbalance development of local industrialization and economies, as well as incorrect health care for younger children, the notable emissions from coal combustion (CC) and non-ferrous metals (NMS) exploitation dominate the crucial sources of low-level lead exposure to children after phasing out leaded gasoline in China currently. Faced with the unequal and disparate distribution of BLLs in China, the big bottleneck is to decrease the BLLs exertions of 36–45 μg/L in the next few decades. The Chinese government needs to make more efforts on developing more strict guidelines, implementing more policy strategies on prevention and management of blood Pb poisoning, and monitoring the nationwide changes in children's BLLs continuously.

Lead induced differences in bone properties in osteocalcin +/+ and −/− female mice

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodeling and is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly increased turnover in OC+/+ and in OC−/− bones producing increased total volume, area and marrow area/total area with decreased BV/TV compared to controls. The increased turnover decreased mineral/matrix vs. Oc+/+ and increased mineral/matrix and crystallinity vs. OC−/−. PbOC−/− had increased bone formation, cross-sectional area (Imin) and decreased collagen maturity compared OC−/− and PbOC+/+. Imbalanced turnover in PbOC−/− confirmed the role of osteocalcin as a coupler of formation and resorption. Bone strength and stiffness were reduced in OC−/− and PbOC−/− due to reduced material properties vs. OC+/+ and PbOC+/+ respectively. The PbOC−/− bones had increased area to compensate for weaker material properties but were not proportionally stronger for increased size. However, at low lead levels osteocalcin plays the major role in bone strength suggesting increased fracture risk in low Pb2+ exposed elderly could be due to reduced osteocalcin as well. Years of low lead exposure or higher blood lead levels may have an additional effect on bone strength.

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs)

BackgroundTobacco-free nicotine pouches is a novel category of oral nicotine-delivery products. Among current tobacco users such pouches may serve as a low-risk alternative to cigarettes or conventional, tobacco-based oral products e.g., snus and moist snuff. In the United States (U.S.), the market leading nicotine-pouch brand is ZYN®. However, no data on the chemical characteristics of ZYN have been published.MethodsWe screened for 43 compounds potentially present in tobacco products in seven oral nicotine-delivery products: ZYN (dry and moist), snus (General®), moist snuff (CRP2.1 and Grizzly Pouches Wintergreen), and two pharmaceutical, nicotine replacement therapy products (NRTs, Nicorette® lozenge and Nicotinell® gum). Thirty-six of the tested compounds are classified as harmful and potentially harmful constituents (HPHCs) by the Center for Tobacco Products at the U.S. Food and Drug Administration (FDA-CTP). Five additional compounds were included to cover the GOTHIATEK® product standard for Swedish snus and the last two compounds were chosen to include the four primary tobacco specific nitrosamines (TSNAs).ResultsThe tested products contained nicotine at varying levels. The two ZYN products contained no nitrosamines or polycyclic aromatic hydrocarbons (PAHs) but low levels of ammonia, chromium, formaldehyde, and nickel. In the NRT products we quantified low levels of acetaldehyde, ammonia, cadmium, chromium, lead, nickel, uranium-235, and uranium-238. The largest number (27) and generally the highest levels of HPHCs were quantified in the moist snuff products. For example, they contained six out of seven tested PAHs, and seven out of ten nitrosamines (including NNN and NNK). A total of 19 compounds, none of which were PAHs, were quantified at low levels in the snus product. NNN and NNK levels were five to 12-fold lower in snus compared to the moist snuff products.ConclusionsNo nitrosamines or PAHs were quantified in the ZYN and NRT products. Overall, the number of quantified HPHCs were similar between ZYN and NRT products and found at low levels.

Analysis and Preliminary Design of Primary Heat Exchanger Failure Testing Facility for Lead-Cooled Fast Reactors

This paper presents an assessment aimed at evaluating primary heat exchanger (PHE) failure of the Westinghouse Electric Company Lead-cooled Fast Reactor (LFR) and at designing a facility for testing phenomena involved in such failure. The system thermal-hydraulic code RELAP5/MOD3.3 was used to develop a transient analysis simulation at reactor scale. Because of RELAP5/MOD3.3’s inability to mix working fluids, the steam injection effect was evaluated using the SIMMER-III code. The limits and strengths of both codes are highlighted throughout the paper. The reactor-scale steady-state results are in good agreement with the nominal operating condition. The transient results show that lead pool surface level variation and primary system pressurization during the PHE failure event are limited. The PHE failure testing facility was characterized, and a preliminary layout was developed. A separate-effects transient inside the vessel was analyzed with SIMMER-III and RELAP5/MOD3.3 runs. The simulation outcomes have provided useful data to inform subsequent design stages for the test facility. Different configurations of the facility have been assessed, highlighting the strengths and weaknesses of each design. The most important issue was identified to be lead pool swelling, reaching the vessel’s lid and blocking the pressure relief vent. This poses a safety hazard that must be addressed and has been raised for resolution in subsequent design stages. The so-called V4 configuration is suggested as a starting point for further improvement of the facility. Furthermore, a smaller failure opening and lower lead level in the vessel are suggested.

Association between toxic metals, vitamin D and preterm birth in the Maternal-Infant research on environmental chemicals study.

Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB. In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations. We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal-Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first-trimester plasma 25-hydroxyvitamin D (25OHD) concentrations. Of 1851 live births, 6.1% (n= 113) were PTBs and 4.9% (n= 89) were spontaneous PTB. A 1μg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1μg/L. Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D-deficient populations.

Predicting Low-Level Childhood Lead Exposure in Metro Atlanta Using Ensemble Machine Learning of High-Resolution Raster Cells.

Low-level lead exposure in children is a major public health issue. Higher-resolution spatial targeting would significantly improve county and state-wide policies and programs for lead exposure prevention that generally intervene across large geographic areas. We use stack-ensemble machine learning, including an elastic net generalized linear model, gradient-boosted machine, and deep neural network, to predict the number of children with venous blood lead levels (BLLs) ≥2 to <5 µg/dL and ≥5 µg/dL in ~1 km2 raster cells in the metro Atlanta region using a sample of 92,792 children ≤5 years old screened between 2010 and 2018. Permutation-based predictor importance and partial dependence plots were used for interpretation. Maps of predicted vs. observed values were generated to compare model performance. According to the EPA Toxic Release Inventory for air-based toxic release facility density, the percentage of the population below the poverty threshold, crime, and road network density was positively associated with the number of children with low-level lead exposure, whereas the percentage of the white population was inversely associated. While predictions generally matched observed values, cells with high counts of lead exposure were underestimated. High-resolution geographic prediction of lead-exposed children using ensemble machine learning is a promising approach to enhance lead prevention efforts.

Maternal Low Level Lead and Pregnancy Outcomes

We examined the relationship between the concentrations of blood lead and pregnancy outcomes in a subset of 349 African American women who enrolled in the program project, "Nutrition, Other Factors, and the Outcome of Pregnancy." Vitamin-mineral supplement users had significantly higher serum levels of ascorbic acid and vitamin E. Also, in supplement users, there were significantly lower mean concentrations of maternal blood lead. Inverse correlations were found between maternal levels of lead and the antioxidant vitamins, vitamin E and ascorbic acid. In addition, significant Pearson's correlations were observed between maternal blood lead levels and the following variables: positive correlations with calcium, phosphorus, mean corpuscular volume; inverse correlations with gestational age, Ponderal Index, infant orientation, and hematologic values. In the total subset, the three trimester sample means for maternal blood lead concentrations were not significantly different for mothers of infants who weighed less than 2500 g (low birth weight) and those who were delivered infants who weighed 2500 g or more. Clinically, nutrition may play a role in the reduction of potentially adverse effects from lead during pregnancy, i.e. protection of the fetus against lead toxicity and/or free radical damage through the antioxidant actions of vitamin E and ascorbic acid. Even when maternal blood lead levels are within the so-called "safe" range, maternal/use of a vitamin supplement supplying vitamin E and ascorbic acid during pregnancy may offer protection.

Assessment and Prevention of Lead Poisoning in Refugee Populations.

Lead is a neurotoxin, and there are no safe blood lead levels identified for children. Even low levels of lead in blood have been shown to permanently harm the brain, affecting a child's development, intelligence, and academic achievement. In the U.S., refugee children are at an increased risk for lead poisoning. Preventing lead exposure can reduce damage to children's health. It is imperative that clinicians conduct an exposure assessment and offer anticipatory guidance to prevent exposure to lead, especially with sources such as cosmetics, ceramics, herbs, and toys.

Cognitive and functional outcomes at age 21 after prenatal cocaine/polydrug exposure and foster/adoptive care

ObjectivePrenatal cocaine exposure (PCE) has been linked to specific cognitive deficits and behavioral outcomes through early adolescence but there is little information on adult outcomes nor on the relationship of environmental interventions, such as foster/adoptive care, to outcomes. MethodsAt 21 years, data were available on 325 young adults, [163 PCE and 162 non-exposed (NCE)], primarily African-American, with low SES, who were followed from birth in a prospective longitudinal cohort study. Participants were administered the Wechsler Abbreviated Scale of Intelligence (WASI-II) and surveyed regarding high school completion, problematic substance use, and incarceration/probation history. In the PCE group, 32 remained in non-kinship foster/adoptive care (PCE/FA) from early in life (< 4 years) to 17 years. Group differences were examined through t-tests, MANOVA/ MANCOVA with post-hoc analyses, comparing outcomes and environmental correlates of young adults with PCE vs. NCE, as well as outcomes of PCE young adults in non-kinship foster/adoptive care (PCE/ FA) vs. PCE in birth/kinship care and NCE young adults. ResultsAt 21 years, young adults with PCE had lower mean Full Scale (83.7 ± 10.4 vs. 87.3 ± 12.5, p < .01) and Perceptual Reasoning IQs (87.3 ± 11.5 vs. 91.4 ± 13.9, (p < .02), lower high school completion rates (75% vs. 86%, p < .02), and were marginally more likely to have been on probation than NCE young adults, but did not differ in Verbal IQ, self-report of problematic substance use or incarceration. Young adults with PCE in F/A had similar lower IQ scores but had better verbal skills and high school graduation rates that did not differ from NCE young adults (80.6 vs 86.2%, p > .05). They had higher drug exposure at birth and more experiences of maltreatment (p's < 0.05) but their home environment quality was better and lead levels lower (p's < 0.05) than those of young adults with PCE in birth/kinship care. ConclusionsYoung adults with PCE had lower Perceptual Reasoning and Full-Scale IQ scores, independent of caregiving placement, compared to non-exposed young adults. Young adults with PCE placed in non-kinship foster/adoptive care had lower lead levels, more stimulating home environments, better vocabulary skills and were more likely to graduate from high school than those in birth/kinship care,but were not different in their self-report of problematic substance use, or experiences of incarceration or probation. Our data suggest that some cognitive deficits observed in young adults with PCE may be biologically based, but that some functional outcomes can be modified through environmental interventions. Our data also reflect the complexity of disentangling the effects of teratologic exposures on long term outcomes across a variety of domains and the need for studies of children in the foster care system.

Comparison of Blood Lead Levels in Children and Adolescents with and without Functional Abdominal Pain.

Functional abdominal pain is a health concern with chronic abdominal discomfort without clear etiology. Several etiologic factors are raised in this regard, one related to environmental factors. This study aimed to compare blood lead levels between children and adolescents with and without functional abdominal pain. This case-control study was performed in 2019-2020 in Isfahan, Iran. The sample size was calculated as 70 cases and an equal number of controls. Cases were children and adolescents with functional gastrointestinal disorder (FGID), and controls were grouped age- and sex-matched. Controls were randomly selected from those referred for routine health screening. Both groups obtained blood lead, iron, and calcium levels. All participants completed the FFQ Food Consumption and Environmental Pollutants Questionnaire. Participants were 139 children (68 cases and 71 controls). The mean (SD) age was 9.40 (3.91) years in the FGID group and 8.79 (3.46) years in the controls (P = 0.330). The mean (SD) blood lead level was not significantly different between the FGID group and the controls (3.98 ± 2.56 vs 3.81 ± 1.96 μg/dl, respectively, P = 0.670). We found that 55.3% of children with high lead levels had FGID, while 44.4% of children with lower lead levels had FGID, but the difference was not statistically significant (P = 0.33). We found that the lead level was higher in patients with FGID than in the controls; however, this difference was not significantly different. This might be because of elevated lead levels in both groups. Future ecological studies with a large sample size are necessary in this regard.

Early-life low-level lead exposure alters anxiety-like behavior, voluntary alcohol consumption and AC5 protein content in adult male and female C57BL/6 J mice

Despite efforts to eradicate sources of environmental lead (Pb), children, predominately in lower socioeconomic areas, are still frequently exposed to unsafe levels of Pb from soils, dust, and water. Human studies suggest that Pb exposure is associated with altered drug consumption in adults; however, there is limited research at comparable exposure levels (blood Pb levels <10 μg/dL). To model how early-life, low-level Pb exposure affects alcohol consumption in adulthood, we exposed postnatal day (PND) 21 C57Bl/6 J mice to either 30 ppm or 0 ppm Lead (IV) Acetate in distilled water until PND 42, and testing began in adulthood. We predicted that mice with early-life Pb exposure would exhibit greater anxiety-like behavior and consume more alcohol in a three-week Drinking-in-the-Dark procedure (20% v/v) and a 24-h two-bottle choice procedure (10% v/v). We also predicted that Pb exposure would decrease whole-brain content of Adenylate Cyclase-5 (AC5), a protein linked to anxiety-like behaviors and alcohol drinking. There was no difference in limited-access binge-like consumption between exposure groups; however, Pb-exposed mice displayed higher two-bottle choice alcohol intake and preference. Furthermore, Pb-exposed mice exhibited greater anxiety-like behaviors in experiments conducted before an alcohol drinking history but not after. Finally, Pb-exposed mice exhibited an upregulation of whole-brain AC5 protein content. However, this difference was not found in the nucleus accumbens, dorsomedial or dorsolateral striatum. These findings conclude that early-life Pb exposure alters voluntary alcohol consumption and whole-brain AC5 protein content in adulthood. Future studies are necessary to further understand the mechanism behind how Pb exposure alters alcohol intake.

Exploring the endocrine disrupting potential of lead through benchmark modelling – Study in humans

Exposure to low levels of a toxic metal lead (Pb) affects human health, and its effect as an endocrine disruptor has been reported. However, the precise role of Pb in endocrine health is still unclear because no dose-response relationship has been established for such an effect. The present study aimed to examine blood Pb levels (BLLs) in relation to serum levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and insulin in 435 nonoccupationally exposed Serbian subjects (218 women, 217 men, 18–94 years of age, mean age 48). In addition, benchmark dose (BMD) values were calculated for these endocrine endpoints using the PROAST 70.1 software. An explicit dose-response dependency between BLL and TSH, fT3, fT4, testosterone, and insulin serum levels was evident from BMD modelling. The results support the positive association between BLLs and serum insulin levels, with observed dose-response and calculated BMD values of 1.49 and 0.74 μg Pb/dL in males and females, respectively. Collectively, our findings reported potential endocrine-disrupting effects of Pb at the environmental exposure levels experienced by current Serbian population. They also strengthen the notion that the blood Pb threshold level for an endocrine effect is low.

The association between metals, vitamin D and preterm birth in the MIREC Cohort Study

BACKGROUND Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have explored this association at the low levels currently found in the Canadian population. Conversely, studies suggest that vitamin D may have antioxidant activity and protect against PTB. In this study, we sought to investigate associations between toxic metals (lead, mercury, cadmium and arsenic) and PTB, and to determine if maternal plasma vitamin D concentrations modify these associations. METHODS We investigated whether metals in whole blood measured in early and late pregnancy were associated with PTB (&amp;#x3c;37 weeks) and spontaneous PTB (a subset of PTBs with spontaneous labour) in 1,851 pregnancies resulting in live births from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) using discrete time survival analysis. In addition, we investigated whether the risk of PTB was modified by plasma 25OHD concentration measured in the 1st trimester. RESULTS Six percent (n=117) of live births in the MIREC study were PTBs; 4% (n=89) were spontaneous PTBs. A 1 &amp;#x3bc;g/dL increase in blood lead concentrations during pregnancy was associated with increased risk of PTB (OR=1.5, 95% CI: 1.0, 2.3) and spontaneous PTB (OR=1.7, 95% CI: 1.1, 2.8). In stratified analysis, the risk of PTB (OR=2.7, 95% CI: 1.0, 7.2) and spontaneous PTB (OR=3.4, 95% CI: 1.1, 10.8) was higher in women with insufficient vitamin D concentrations (25OHD &amp;#x3c;50 nmol/L). However, a statistical interaction was not seen. Arsenic was associated with a higher risk of PTB (OR=1.1, 95% CI: 1.0, 1.2) and spontaneous PTB (OR=1.1, 95% CI: 1.0, 1.2) per µg/L, but these associations were not modified by vitamin D. CONCLUSIONS Low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; the association with lead was stronger in participants with insufficient plasma vitamin D. Replication of these findings is warranted.