Lead contamination in human milk affects infants' language trajectory: results from a prospective cohort study.

Infants growing up in low- and middle-income countries are at increased risk of suffering adverse childhood experiences, including exposure to environmental pollution and lack of cognitive stimulation. In this study, we aimed to examine the levels of metals in the human milk of women living in São Paulo City, Brazil, and determine the effects on infants' neurodevelopment. For such, a total of 185 human milk samples were analyzed for arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd) using inductively coupled plasma mass spectrometry (ICP-MS). We applied the Bayley scales of infant and toddler development Third Edition (Bayley-III) to assess developmental milestones. In our analysis, we found a mean (standard deviation) concentration of As in human milk equal to 2.76 (4.09) µg L-1, followed by Pb 2.09 (5.36) and Hg 1.96 (6.68). Cd was not detected. We observed that infants exposed to Pb presented language trajectories lower than non-exposed infants (ß = -0.413; 95% CI -0.653, -0.173) after adjustment for infant age, maternal education, socioeconomic status, infant sex, and sample weights. Our results report As, Pb, and Hg contamination in human milk, and that infant exposure to Pb decreased infants' language development. These results evidence maternal-child environmental exposure and its detrimental impact on infants' health.

Enduring Ethanol-Induced Behavioral Alterations in Caenorhabditis elegans After Developmental Lead Exposure.

The roundworm Caenorhabditis elegans (C. elegans) has become a powerful tool to evaluate the deleterious effects of early-life exposure to xenobiotics, including metals. The present chapter describes a detailed protocol for developmental lead (Pb)-exposure in C. elegans. Preliminary assays as well as the final procedure are described in detail. In addition, further protocols aimed to assess ethanol exposure at later stages of life demonstrate the impact of this drug on locomotor behavior, revealing the enduring effects that Pb can imprint on this organism when exposure occurs during development.

Adaptive changes in redox response and decreased platelet aggregation in lead-exposed workers.

Chronic lead exposure can generate pro-oxidative and pro-inflammatory conditions in the blood, related to high platelet activation and aggregation, altering cell functions. We studied ADP-stimulated aggregation and the oxidant/antioxidant system of platelets from chronically lead-exposed workers and non-exposed workers. Platelet aggregation was low in lead-exposed workers (62 vs. 97%), who had normal platelet counts and showed no clinical manifestations of hemostatic failure. ADP-activated platelets from lead-exposed workers failed to increase superoxide release (3.3 vs. 6.6 µmol/g protein), had low NADPH concentration (60 vs. 92 nmol/mg protein), high concentration of hydrogen peroxide (224 vs. 129 nmol/mg protein) and high plasma PGE2 concentration (287 vs. 79 pg/mL). Altogether, those conditions, on the one hand, could account for the low platelet aggregation and, on the other, indicate an adaptive mechanism for the oxidative status of platelets and anti-aggregating molecules to prevent thrombotic problems in the pro-oxidant and pro-inflammatory environment of chronic lead exposure.

Lead Exposure Can Affect Early Childhood Development and Could Be Aggravated by Stunted Growth: Perspectives from Mexico.

BACKGROUND: Lead can affect early childhood development (ECD) differentially due to nutritional deficiencies that lead to stunted growth, defined as being at least two standard deviations below the average height-for-age. These deficiencies are more frequent among children living in rural locations or with lower socioeconomic status (SES); however, studies at a population level are scarce worldwide. Early childhood development plays a crucial role in influencing a child's health and wellbeing throughout life. Therefore, the aim of this study was to analyze how stunted growth can modify the association between lead exposure and ECD in children from disadvantaged communities. METHODS: Data were analyzed from the 2018 National Health and Nutrition Survey in localities with fewer than 100,000 inhabitants in Mexico (ENSANUT-100K). Capillary blood lead (BPb) levels were measured using a LeadCare II device and dichotomized as detectable (cutoff point ≥ 3.3 µg/dL) and non-detectable. As a measure of ECD, language development was assessed in n = 1394 children, representing 2,415,000 children aged 12-59 months. To assess the association between lead exposure and language z-scores, a linear model was generated adjusted by age, sex, stunted growth, maternal education, socioeconomic status, area, region (north, center, south), and family care characteristics; afterwards, the model was stratified by stunted growth. RESULTS: Fifty percent of children had detectable BPb and 15.3% had stunted growth. BPb showed a marginal inverse association with language z-scores (ß: -0.08, 95% CI: -0.53, 0.36). Children with detectable BPb and stunted growth had significantly lower language z-scores (ß: -0.40, 95% CI: -0.71, -0.10) than those without stunted growth (ß: -0.15, 95% CI: -0.36, 0.06). CONCLUSIONS: Children with stunted growth are more vulnerable to the adverse effects of lead exposure. These results add to previous research calling for action to reduce lead exposure, particularly in children with chronic undernutrition.

The intertwining between lead and ethanol in the model organism Caenorhabditis elegans.

Caenorhabditis elegans (C. elegans) is a model organism widely used to evaluate the mechanistic aspects of toxicants with the potential to predict responses comparable to those of mammals. We report here the consequences of developmental lead (Pb) exposure on behavioral responses to ethanol (EtOH) in C. elegans. In addition, we present data on morphological alterations in the dopamine (DA) synapse and DA-dependent behaviors aimed to dissect the neurobiological mechanisms that underlie the relationship between these neurotoxicants. Finally, the escalation to superior animals that parallels the observed effects in both experimental models with references to EtOH metabolism and oxidative stress is also discussed. Overall, the literature revised here underpins the usefulness of C. elegans to evidence behavioral responses to a combination of neurotoxicants in mechanistic-orientated studies.

Risk of lead exposure from wild game consumption from cross-sectional studies in Madre de Dios, Peru.

Background: Studies have shown elevated blood lead levels (BLL) in residents of remote communities in the Amazon, yet sources of lead exposure are not fully understood, such as lead ammunition consumed in wild game. Methods: Data was collected during two cross-sectional studies that enrolled 307 individuals in 26 communities. Regression models with community random effects were used to evaluate risk factors for BLLs, including diet, water source, smoking, sex, age, and indigenous status. The All-Ages Lead Model (AALM) from the Environmental Protection Agency (EPA) was used to estimate background and dose from wild game consumption. Findings: Indigenous status and wild game consumption were associated with increased BLLs. Indigenous participants had 2.52 µg/dL (95% CI: 1.95-3.24) higher BLLs compared to non-indigenous. Eating wild game was associated with a 1.41 µg/dL (95% CI: 1.20-1.70) increase in BLLs. Two or more portions per serving were associated with increased BLLs of 1.66 µg/dL (95% CI: 1.10-2.57), compared to smaller servings. Using the AALM, we estimate background lead exposures to be 20 µg/day with consumption of wild game contributing 500 µg/meal. Lastly, we found a strong association between BLLs and mercury exposure. Interpretation: Consumption of wild game hunted with lead ammunition may pose a common source of lead exposure in the Amazon. Communities that rely on wild game and wild fish may face a dual burden of exposure to lead and mercury, respectively.

Early life exposure to lead and its association with parent-reported aggression and conduct problems during childhood and adolescence.

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

A review of studies on blood lead concentrations of traditional Mexican potters.

BACKGROUND: Traditional Mexican potters and their families have been occupationally exposed to lead for centuries; however, studies on blood lead levels (BLL) and their adverse health impact on this population are scarce. There is no safe BLL, even at 1 µg/dL there are associated health effects. OBJECTIVE: To systematize and characterize Mexican potters' historic lead exposure through their BLL and associated health outcomes. METHODS: Using PRISMA guidelines, we conducted a systematic review through January 2021 of published studies on BLL and associated health outcomes in Mexican potters. RESULTS: Fifteen studies containing data from 1980 to 2013 met the inclusion criteria and were published between 1980 and 2018. Study populations ranged from n = 5 to n = 457, and included adult potters (mean BLL 37.9 ± 16.2 µg/dL) and/or their children (mean BLL 22.5 ± 10.5 µg/dL). Studies reported on general lead poisoning symptoms, neurotoxic and nephrotoxic outcomes as well as correlated biomarkers. CONCLUSIONS: Our results confirm high occupational and para-occupational lead exposure. Despite governmental and non-governmental initiatives to promote lead-free glazes, lead continues to be used by traditional potters and their families.

Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead.

BACKGROUND: Some studies in animal models and humans suggest that exposure to lead is associated with hearing loss. Lead can reach the inner ear through the blood circulation; evidence suggests that lead could accumulate in the inner ear, causing inner ear damage. AIM: To evaluate prestin and otolin-1 protein levels and their relationship with an increased hearing threshold in participants exposed to lead. METHODS: We conducted a cross-sectional study with 315 participants from Tlaxcala, Mexico. Blood lead levels (BPb) were evaluated by graphite furnace atomic absorption spectrometry. Serum prestin and otolin-1 were quantified using ELISA. Auditory function at frequencies of 0.125 to 8 kHz was evaluated in a soundproof chamber. RESULTS: Participants were classified according to BPb: group I (<10 µg/dL) had a median BPb of 6 µg/dL and prestin levels of 11.06 ng/mL. While participants in group II (≥10 µg/dL) had a median of BPb 20.7 µg/dL (p < 0.05) and prestin levels of 0.15 ng/mL (p < 0.001). Participants in both groups showed a normal hearing. Otolin-1 levels were higher for participants with normal hearing and lower for participants with hearing loss in both groups, p > 0.05. Multiple linear regression models predict an average decrease of 0.17 to 0.26 ng/mL in prestin levels per decibel increase for the frequencies evaluated. CONCLUSIONS: Participants with high BPb showed an increase in hearing threshold, and prestin levels decreased proportionally to the hearing threshold increase. This is the first study to evaluate prestin as a potential biomarker for hearing damage, evaluated by audiometry, in participants with lead exposure.

Association between cumulative childhood blood lead exposure and hepatic steatosis in young Mexican adults.

BACKGROUND: Exposure to environmental toxicants may play a role in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD). Cumulative exposure to lead (Pb) has chronic and permanent effects on liver function. Pediatric populations are vulnerable to the toxic effects of Pb, even at low exposure levels. The purpose of the study was to estimate the association between cumulative Pb exposure during childhood and hepatic steatosis biomarkers in young Mexican adults. METHODS: A subsample of 93 participants from the ELEMENT cohort were included in this study. Childhood blood samples were collected annually from ages 1-4 years and were used to calculate the Cumulative Childhood Blood Lead Levels (CCBLL). Hepatic steatosis during adulthood was defined as an excessive accumulation of hepatic triglycerides (>5%) determined using Magnetic Resonance Imaging (MRI). Liver enzymes were also measured at this time, and elevated liver enzyme levels were defined as ALT (≥30 IU/L), AST (≥30 IU/L), and GGT (≥40 IU/L). Adjusted linear regression models were fit to examine the association between CCBLL (quartiles) and the hepatic steatosis in young adulthood. RESULTS: In adulthood, the mean age was 21.4 years, 55% were male. The overall prevalence of hepatic steatosis by MRI was 19%. Elevate levels of the enzymes ALT, AST, and GGT were present in 25%, 15%, and 17% of the sample, respectively. We found a positive association between the highest quartile of CCBLL with the steatosis biomarkers of hepatic triglycerides (Q4 vs. Q1: ß = 6.07, 95% CI: 1.91-10.21), elevated ALT (Q4 vs. Q1: ß = 14.5, 95% CI: 1.39-27.61) and elevated AST (Q4 vs. Q1: ß = 7.23, 95% CI: 0.64-13.82). No significant associations were found with GGT. CONCLUSIONS: Chronic Pb exposure during early childhood is associated with a higher levels of hepatic steatosis biomarkers and hepatocellular injury in young adulthood. More actions should be taken to eliminate sources of Pb during the first years of life.

Chronic Low-Level Lead Exposure Increases Mesenteric Vascular Reactivity: Role of Cyclooxygenase-2-Derived Prostanoids.

Lead (Pb) exposure causes hazardous effects as hypertension and other cardiovascular diseases. We evaluated whether chronic Pb exposure alters the peripheral vascular resistance measuring the vascular reactivity of mesenteric resistance arteries in rats to identify the underlying mechanisms that are associated to the development of Pb-induced hypertension. Mesenteric resistance arteries from lead-treated and untreated Wistar rats (1st dose: 10 µg/100 g; subsequent doses: 0.125 µg/100 g, intramuscular, 30 days) were used. Contractile responses to phenylephrine increased, while acetylcholine and sodium nitroprusside-induced relaxation was not affected by lead treatment. Endothelium removal and inhibition of NO synthase by L-NAME similarly enhanced the response to phenylephrine in untreated and lead-treated rats. The antioxidants apocynin and superoxide dismutase (SOD) did not affect vasoconstriction in either group. The vascular expression of cyclooxygenase-2 (COX-2) protein increased after lead exposure. The respective non-specific or specific COX-2 inhibitors indomethacin and NS398 reduced more strongly the response to phenylephrine in treated rats. Antagonists of EP1 (SC19220), TP (SQ29548), IP (CAY10441) and angiotensin II type 1 (losartan) receptors reduced vasoconstriction only in treated rats. These conclusions present further evidence that lead, even in small concentration, produces cardiovascular hazards being an environmental contaminant that account for lead-induced hypertension.

Systems Biology-Based Analysis Indicates Global Transcriptional Impairment in Lead-Treated Human Neural Progenitor Cells.

Lead poisoning effects are wide and include nervous system impairment, peculiarly during development, leading to neural damage. Lead interaction with calcium and zinc-containing metalloproteins broadly affects cellular metabolism since these proteins are related to intracellular ion balance, activation of signaling transduction cascades, and gene expression regulation. In spite of lead being recognized as a neurotoxin, there are gaps in knowledge about the global effect of lead in modulating the transcription of entire cellular systems in neural cells. In order to investigate the effects of lead poisoning in a systemic perspective, we applied the transcriptogram methodology in an RNA-seq dataset of human embryonic-derived neural progenitor cells (ES-NP cells) treated with 30 µM lead acetate for 26 days. We observed early downregulation of several cellular systems involved with cell differentiation, such as cytoskeleton organization, RNA, and protein biosynthesis. The downregulated cellular systems presented big and tightly connected networks. For long treatment times (12 to 26 days), it was possible to observe a massive impairment in cell transcription profile. Taking the enriched terms together, we observed interference in all layers of gene expression regulation, from chromatin remodeling to vesicle transport. Considering that ES-NP cells are progenitor cells that can originate other neural cell types, our results suggest that lead-induced gene expression disturbance might impair cells' ability to differentiate, therefore influencing ES-NP cells' fate.

Brain ethanol-metabolizing enzymes are differentially expressed in lead-exposed animals after voluntary ethanol consumption: Pharmacological approaches.

Developmentally-lead (Pb)-exposed rats showed an enhanced vulnerability to the stimulating and motivational effects of ethanol (EtOH). This is accompanied by differential activity of the brain EtOH-metabolizing enzymes catalase (CAT) and mitochondrial aldehyde dehydrogenase (ALDH2). Based on the theory that brain acetaldehyde accumulation is associated with the reinforcing properties of EtOH, this study sought to determine brain CAT and ALDH2 expression in limbic areas of control and Pb-exposed animals after voluntary EtOH intake. Thirty-five-day-old rats perinatally exposed to 220 ppm Pb were offered with water or increasing EtOH solutions (2-10% v/v) during 28 days until postnatal day (PND) 63. Once intake was stable, the animals were administered: 1) saline (SAL; test days 21-24 or 21-28, as corresponds), or 2) a CAT inhibitor: 3-amine 1, 2, 4-triazole (AT; 250 mg/kg intraperitoneally [i.p.], 5 h before the last eight EtOH intake sessions -test days 21-24 and 25-28), or 3) a CAT booster: 3-nitropropionic acid (3NPA; 20 mg/kg subcutaneously [s.c.], 45 min before the last four EtOH intake sessions -test days 25-28). Two additional groups were centrally-administered cyanamide (CY, an ALDH2 inhibitor, 0.3 mg i.c.v. immediately before the last four EtOH sessions, test days 25-28) or its corresponding vehicle (VEH). Lead exposure increased EtOH intake, an effect potentiated in both groups by 3NPA or CY pretreatments and reduced by AT, albeit selectivity in the Pb group. Catalase abundance in limbic areas parallels these observations in the Pb group, showing higher CAT expression in all areas after EtOH consumption respect to the controls, an effect prevented by AT administration. In contrast, ALDH2 expression was reduced in the Pb animals after EtOH intake, with CY potentiating this effect in all brain areas under study. Based on these results and on previous evidences, we suggest that Pb exposure promotes acetaldehyde accumulation in limbic regions, providing some insights into the mechanism of action that underlies the vulnerability to the excessive EtOH consumption reported in these animals.

Sources of lead exposure in various countries.

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.

The associations between lead exposure at multiple sensitive life periods and dental caries risks in permanent teeth.

BACKGROUND: Dental caries is an important public health problem in Mexico, a country also faced with high exposure to toxicants including lead (Pb). METHODS: Participants were 386 children living in Mexico City. Prenatal (trimester 1-3), early-childhood (12, 24, 36, and 48 months of age) and peri-pubertal (10-18 years of age) blood Pb levels were quantified using graphite-furnace atomic-absorption spectroscopy. Maternal patella and tibia bone Pb at 1 month postpartum were quantified with K X-ray fluorescence instrument. Dental caries presence was evaluated using decayed, missing, and filled teeth (DMFT) scores. Peri-pubertal sugar sweetened beverage (SSB) intake was estimated using a 116-item, interview-administered semi-quantitative food frequency questionnaire (FFQ). Total energy adjusted daily SSB intake was generated using the residual approach. Zero inflated negative binomial (ZINB) Poisson regression models were used to examine the associations between Pb with D1MFT and D4MFT at adolescence. RESULTS: Maternal second and third trimester and cumulative early childhood Pb exposure were positively associated with peri-pubertal D1MFT scores in unadjusted ZINB models (2nd trimester: RR = 1.17 (1.00, 1.37); 3rd trimester: RR = 1.20 (1.03, 1.40); early childhood: RR = 1.22 (1.02, 1.48)). These effect sizes were attenuated and no longer statistically significant after adjusting for covariates. When stratified by high/low SSB intake, a one unit increase of log-transformed 2nd trimester Pb exposure was associated with a 1.41 times (1.06, 1.86) higher D1MFT count, and 3rd trimester Pb exposure was associated with a 1.50 times (1.18, 1.90) higher D1MFT count among those with higher than median peri-pubertal SSB. Associations among those with lower SSB intake were roughly half those of the higher group and not statistically significant. CONCLUSIONS: Pb exposure during sensitive developmental periods was not statistically significantly associated with caries risk after accounting for confounders among our cohort. However, evidence from stratified analysis suggested a Pb-caries association among children with high SSB intake.

Altered cord blood mitochondrial DNA content and pregnancy lead exposure in the PROGRESS cohort.

INTRODUCTION: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. MATERIALS AND METHODS: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. RESULTS: Maternal blood Pb measured in the second (mean 3.79 µg/dL, SD 2.63; ß = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 µg/dL; SD 2.84; ß = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 µg/dL, SD 2.59; ß = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). CONCLUSION: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead.

Silencing brain catalase expression reduces ethanol intake in developmentally-lead-exposed rats.

Lead (Pb) is a developmental neurotoxicant. We have demonstrated that perinatally Pb-exposed rats consume more ethanol than their control counterparts, a response that seems to be mediated by catalase (CAT) and centrally-formed acetaldehyde, ethanol's first metabolite with attributed reinforcing effects in the brain. The present study sought to disrupt ethanol intake (2-10% ethanol v/v) in rats exposed to 220 ppm Pb or filtered water during gestation and lactation. Thus, to block brain CAT expression, a lentiviral vector coding for a shRNA against CAT (LV-antiCAT vector) was microinfused in the posterior ventral tegmental area (pVTA) either at the onset or towards the end of a chronic voluntary ethanol consumption test. At the end of the study, rats were euthanized and pVTA dissected to measure CAT expression by Western blot. The LV-antiCAT vector administration not only reversed, but also prevented the emergence of the elevated ethanol intake reported in the perinatally Pb-exposed animals, changes that were supported by a significant reduction in CAT expression in the pVTA. These results provide further evidence of the crucial role of this enzyme in the reinforcing properties of ethanol and in the impact of the perinatal Pb programming to challenging events later in life.

Association of Low Lead Levels with Behavioral Problems and Executive Function Deficits in Schoolers from Montevideo, Uruguay.

The negative effect of lead exposure on children's intelligence is well-documented. Less is known about the impact of lead on the use of executive functions to self-regulate behavior. We measured blood lead level (BLL) in a sample of first grade children from Montevideo, Uruguay (n = 206, age 6.7 ± 0.5 years, 59.7% boys). Behavior was assessed with teacher versions of the Conners Rating Scale (CRS) and the Behavior Rating Inventory of Executive Functions (BRIEF). Mean BLL was 4.2 ± 2.1 µg/dL; 10% had mild-to-severe ratings of Attentional Deficit with Hyperactivity Disorder (ADHD) (T score > 65). In negative binomial regression, BLL was not associated with CRS sub-scales, but was associated with a poorer ability to inhibit inappropriate behaviors, prevalence ratio (PR) [95% CI]: 1.01 [1.00, 1.03] as measured by the BRIEF. In covariate-adjusted models, the association with BLL was attenuated. When stratified by sex, the covariate-adjusted association between BLL, hyperactivity, poorer inhitibion, emotional control, and behavioral regulation was marginally significant for girls but not boys. In summary, among children with low lead-exposure, we found some, but nonetheless modest, evidence of a relationship between higher BLL and child behavior. If confirmed by larger studies and other objective measures of behavior, such links could have implications for learning and social interaction, particularly among girls.

Lead exposure from households and school settings: influence of diet on blood lead levels.

Lead is known as a potent toxicant to human health, particularly for children while their central nervous system is developing. The aim of this study was to investigate the associations between blood lead levels (BLLs) and lead exposure in the children's diet, home, and school environments. A cross-sectional study was conducted with 153 children aged 1-4 years, in four day care centers (DCCs), where a high prevalence of lead exposure was previously found. Lead determination by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64). Environmental screenings were conducted to evaluate lead concentrations in the tableware, buildings, and playground items in all DCCs and children's homes (n = 18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean was 2.71 µg dL-1. Means for 24-h lead concentrations in the diet were 1.61 and 2.24 µg kg-1 of body weight (BW) in two DCCs. Lead concentrations in the water supply were lower than 2 µg L-1. More than 11% of the DCCs' environmental analyses presented lead concentrations higher than or equal to 1 mg cm-2, as defined by the USEPA. The diet was not found to be a risk factor for lead exposure, but households and DCC settings raised concern. Children's exposure to lead in DCC environments, where they spend the most part of their weekdays, appeared to be relevant. Graphical abstract ᅟ.

A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in Aggressive Behavior Induced by Exposure to Lead.

The effects caused by exposure to lead (Pb) are still considered as a relevant health risk despite public policies aimed to restricting the use of this element. The toxicity limit in the blood (10 µg/dL, established by the Center for Disease Control and Prevention) has been insufficient to prevent adverse effects and even lower values have been related to neurobehavioral dysfunctions in children. Currently, there is not a safe limit of exposure to Pb. A large body of evidence points to environmental pollutant exposure as the cause of predisposition to violent behavior, among others. Considering the evidence by our group and others, we propose that Pb exposure induces alterations in the brain vasculature, specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic system and leading to heightened aggressive behavior in the exposed individuals. This review article describes the consequences of Pb exposure on the nitrergic and serotonergic systems as well as its relationship with aggressive behavior. In addition, it summarizes the available therapy to prevent damage in gestation and among infants.