Environmental inequality and disparities in school readiness: The role of neurotoxic lead.

Developmental science has increasingly scrutinized how environmental hazards influence child outcomes, but few studies examine how contaminants affect disparities in early skill formation. Linking research on environmental inequality and early childhood development, this study assessed whether differences in exposure to neurotoxic lead explain sociodemographic gaps in school readiness. Using panel data tracking a representative sample of 1266 Chicago children (50% female, 16% White, 30% Black, 49% Hispanic, µage = 5.2 months at baseline, collected 1994-2002), analyses quantified the contribution of lead contamination to class and racial disparities in vocabulary skills and attention problems at ages 4 and 5. Results suggested that lead contamination explains 15%-25% and 33%-66% of the disparities in each outcome, respectively, although imprecise estimates preclude drawing firm inferences about attention problems.

Amyotrophic lateral sclerosis and lead: A systematic update.

Heavy metals are considered to be among the leading environmental factors that trigger amyotrophic lateral sclerosis (ALS). However, no convincing biopathological mechanism and therapeutic clinical implication of such metals in ALS pathogenesis have been established. This is partly attributable to the technical and scientific difficulties in demonstrating a direct and causative role of heavy metals in the onset of ALS in patients. However, a body of epidemiological, clinical and experimental evidences suggest that lead (Pb), more than other metals, could actually play a major role in the onset and progression of ALS. Here, to clarify the nature of the association and the causative role of Pb in ALS, we comprehensively reviewed the scientific literature of the last decade with objective database searches and the methods typically adopted in systematic reviews, critically analysing and summarising the various scientifically sound evidence on the relationship between ALS and Pb. From these tasks, we noted a number of multidisciplinary associations between ALS and Pb, and specifically the importance of occupational exposure to Pb in ALS development and/or progression. We also report the possible involvement of TAR DNA binding protein (TDP-43)-based molecular mechanism in Pb-mediated ALS, although these data rely on a single study, which included both in vitro experiments and an animal model, and are therefore still preliminary. Finally, we briefly examined whether this knowledge could inspire new targeted therapies and policies in the fight against ALS.

Developmental Neurotoxicity of Lead.

Lead exposure is a major concern for the developing nervous system. Environmental exposures to lead, predominantly from contaminated water or lead paint chips, account for the majority of exposures to children. In utero and early life exposures to lead have been associated with lower IQ, antisocial and delinquent behaviors, and attention-deficit hyperactivity disorder. In this review, we will discuss sources of developmental lead exposure and mechanisms of lead neurotoxicity. We will highlight both human epidemiological studies showing associations between lead exposure and behavioral abnormalities as well as experimental data from animal studies. Finally, we will discuss the effects of lead on neurological endpoint past childhood, namely, development of Alzheimer's disease in old age.

Patrón geográfico de la mortalidad por enfermedad de Parkinson en España y su asociación con los niveles de plomo en el aire / Geographical distribution of mortality by Parkinson’s disease and its association with air lead levels in Spain

Fundamentos y objetivo: La enfermedad de Parkinson (EP) es la segunda dolencia neurodegenerativa más frecuente y su etiología en las formas esporádicas es desconocida. El presente estudio analiza las variaciones temporales y geográficas en la mortalidad por EP en España a lo largo de los últimos 14 años, y la relación entre la mortalidad por EP y los niveles de plomo en las partículas del aire. Método: Se ha realizado un estudio ecológico en el que se han analizado las muertes por EP por grupos de edad, en las 50 provincias españolas entre 2000 y 2013. La tendencia anual de la mortalidad por EP se calculó mediante el test no paramétrico Rho de Spearman. Finalmente, se analizó la asociación entre los niveles de plomo y la mortalidad por EP. Resultados: Entre 2000 y 2013 fallecieron en España 36.180 pacientes con EP. Existe una tendencia ascendente en la mortalidad por EP a lo largo del período estudiado (p < 0,0001). La Rioja, Asturias, el País Vasco y el valle del Bajo Ebro acumulan la mayor incidencia de mortalidad por EP. En las regiones con más plomo, la tasa de mortalidad por EP en mayores de 64 años es superior (p = 0,02). Conclusiones: En la última década la mortalidad por EP ha aumentado en España, siendo la mitad norte del país la que registra una mayor incidencia. La mortalidad en varones fue mayor que en mujeres. Además, se encuentra una asociación entre los niveles de plomo en el aire y la tasa de mortalidad por EP (AU)

Background and objective: Parkinson’s disease (PD) is the second most common neurodegenerative disease, and the etiology of its sporadic form is unknown. The present study analyzes the temporal and spatial variations of mortality by PD in Spain over a period of 14 years and its relationship with lead concentration levels in the atmosphere. Method: An ecological study was performed, in which deaths by PD and age group in 50 Spanish provinces between 2000 and 2013 were analyzed. The annual trend of PD mortality was assessed using the nonparametric Spearman’s Rho test. Finally, the relationship between lead concentration levels in the air and mortality by PD was evaluated. Results: Between 2000 and 2013, 36,180 patients with PD died in Spain. There is an increasing trend in mortality through PD over the study period (P < 0,0001). La Rioja, Asturias, Basque Country and the Lower Ebro valley were the regions with the highest values of PD mortality. Those regions with the highest lead concentrations also showed higher mortality by this disease in people over 64 (P = .02). Conclusions: Over our period of study, there has been an increase in mortality through PD in Spain, with the northernmost half of the country registering the highest values. Mortality in men was higher than mortality in women. Moreover, a direct correlation was found between lead levels in the air and mortality through PD (AU)

Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms.

Our objective was to examine whether functional polymorphisms in hemochromatosis (HFE; H63D and C282Y), transferrin (TfC2), and glutathione-s-transferase Pi1 (GSTP1; Ile105Val) genes modify any lead-ALS association. We measured blood lead using atomic absorption spectroscopy and bone lead - a biomarker of cumulative lead exposure - using K-shell-X-ray fluorescence in 100 neurologist-confirmed ALS cases and 194 controls, the latter recruited as part of two separate studies; all subjects lived in New England. Participants were considered variant carriers or wild-type for each polymorphism. To assess effect modification, we included cross-product terms between lead biomarkers and each polymorphism in separate adjusted polytomous logistic regression models. Compared with wild-type, the odds ratio (OR) per 15.6 µg/g patella lead (interquartile range; IQR) was 8.24 (95% CI 0.94-72.19) times greater among C282Y variant carriers, and 0.34 (95% CI 0.15-0.78) times smaller among H63D variant carriers. Results were weaker for tibia lead. Compared with wild-type the OR per 2 µg/dl blood lead (IQR) was 0.36 (95% CI 0.19-0.68) times smaller among H63D variant carriers, and 1.96 (95% CI 0.98-3.92) times greater among GSTP1 variant carriers. In conclusion, we found that HFE and GSTP1 genotypes modified the association between lead biomarkers and ALS. Contrasting modification by the HFE polymorphisms H63D and C282Y may suggest that the modification is not simply the result of increased iron.

Occupational and environmental lead exposure to adolescent workers in battery recycling workshops.

Lead (Pb), as other environmental neurotoxicant substances, has the capability to interfere with many biochemical events present in cells throughout the body. In the present study, the environmental and occupational exposure to Pb has been assessed by analyzing the scalp hair samples of male adolescents aged 12-15 years, who have worked for the last 12-36 months in Pb battery recycling workshops (BRWs). For comparative purposes, gender and age-matched subjects living in the vicinity of recycling workshops as well as in areas without industrial activity were used as controls. The scalp hair samples were oxidized by acid in a microwave oven prior to determination of Pb by electrothermal atomic absorption spectrometry. The results indicated that both workers and nonworking exposed subjects had higher levels of Pb than nonexposed controls. The contents of Pb in scalp hair of adolescent workers in the present study were compared with those reported in other studies.

Estudio de la evolución de la exposición a plomo en la población infantil española en los últimos 20 años. ¿ Un ejemplo no reconocido de «salud en todas las políticas»? / Trend in lead exposure in the Spanish child population in the last 20 years. An unrecognized example of health in all policies?

Objetivo: Describir la evolución temporal de las concentraciones de plomo en el aire en España, desde antes de su prohibición como aditivo de la gasolina hasta la actualidad, así como estudiar la evolución de la carga corporal de plomo en la población infantil española. Métodos: Se obtuvieron las concentraciones medias anuales de plomo en el aire en diversas ciudades españolas, desde la década de 1980 hasta la actualidad. Se realizó una búsqueda bibliográfica con el fin de identificar estudios publicados sobre concentraciones de plomo en la población infantil española. Resultados: En general se observó una disminución de las concentraciones de plomo, de mayor magnitud entre 1991 y 1999. Esta evolución decreciente se asocia con una disminución de las concentraciones de plomo en la población infantil española, desde 1989 (año en que se publica el primer estudio sobre exposición infantil al plomo) hasta hoy. La disminución, tanto en el aire como en la población infantil, es muy probable que sea consecuencia de las medidas legislativas que han regulado la cantidad máxima de plomo en la gasolina, desde 1987 hasta su prohibición total en agosto de 2001. Conclusiones: Desde el punto de vista de la salud pública, la prohibición del uso de gasolina con plomo fue una acción que aumentó la protección de la salud de la población española (AU)

Objective: To describe the time trend in atmospheric lead concentrations in Spain, from before lead was banned as a gasoline additive to the present, and to determine the trend in lead body burden in the Spanish child population. Methods: We obtained the annual average for atmospheric lead levels in several Spanish cities from the 1980s to the present. A literature search was conducted to identify published studies on lead concentrations in populations of Spanish children. Results: Overall, atmospheric lead levels decreased, particularly between 1991 and 1999. This downward trend was related to a decrease in lead concentrations in Spanish children from 1989, the year in which the first study of childhood lead exposure was published, until the present. The decreased concentrations in both air and in children was most probably a result of legislative measures regulating the maximum amount of lead in gasoline in 1987 until a complete ban in August 2001. Conclusions: From a public health point of view, the banning of leaded gasoline has significantly increased health protection in the Spanish population (AU)

Effects of occupational lead exposure on renal and nervous system of workers of traditional tile factories in Mashhad (northeast of Iran).

Occupational lead poisoning is a health problem in Iran. Renal and neuropsychiatric complications of occupational lead poisoning are the main concerns for the workers and their employers. It was thus aimed to investigate the renal and neurotoxic effects of lead poisoning in the workers of two traditional-tile-factories. Researchers visited the workers in the factories and collected data by taking direct history and physical examinations in summer of 2005. Data were recorded in previously designed forms. Blood and urine lead concentrations were measured by an atomic absorption technique. A neurologist examined all workers and electrophysiological investigations were undertaken as clinically indicated. Data were analyzed by SPSS software and chi-square, student t test and Pearson correlation tests were used accordingly. The numerical data were expressed as mean ± standard deviation and p < 0.05 was considered as the significant level. Overall, 108 male subjects aged 37 ± 7.8 years were studied. Duration of lead exposure was 9.8 ± 6 years. Lead concentration in 2005 was 361.5 ± 176.9 µg/L. The main objective clinical findings were lead line (64.8%), peripheral neuropathy of upper limb (37%), suppression of deep tendon reflexes (DTR) in upper limbs (25.7%), tremor (23.3%), peripheral neuropathy of lower limbs (17%) and abdominal tenderness (15.1%). The subjective findings were mainly on the central nervous system, such as loss of memory (57%), moodiness (56.1%), agitation (47.7%), drowsiness (36.4%), and headache (29.9%). There was no significant correlation between blood lead concentration and glomerular filtration rate (GFR). But there were significant correlations between the blood lead concentrations and urine lead concentration (p < 0.001). This study showed that lead had toxic effects on the teeth (bone), central and peripheral nervous system, more than renal function. Prophylactic and treatment measures were performed.

Surface dental enamel lead levels and antisocial behavior in Brazilian adolescents.

Lead poisoning has been reportedly linked to a high risk of learning disabilities, aggression and criminal offenses. To study the association between lead exposure and antisocial/delinquent behavior, a cross-sectional study was conducted with 173 Brazilian youths aged 14-18 and their parents (n=93), living in impoverished neighborhoods of Bauru-SP, with high criminality indices. Self-Reported Delinquency (SRD) and Child Behavior Checklist (CBCL) questionnaires were used to evaluate delinquent/antisocial behavior. Body lead burdens were evaluated in surface dental enamel acid microbiopsies. The dental enamel lead levels (DELL) were quantified by graphite furnace atomic absorption spectrometry (GFAAS) and phosphorus content was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Logistic regression was used to identify associations between DELL and each scale defined by CBCL and SRD scores. Odd ratios adjusted for familial and social covariates, considering a group of youths exposed to high lead levels (>or=75 percentile), indicated that high DELL is associated with increased risk of exceeding the clinical score for somatic complaints, social problems, rule-breaking behavior and externalizing problems (CI 95%). High DELL was not found to be associated with elevated SRD scores. In conclusion, our data support the hypothesis that high-level lead exposure can trigger antisocial behavior, which calls for public policies to prevent lead poisoning.

Neurotoxic effects and biomarkers of lead exposure: a review.

Lead, a systemic toxicant affecting virtually every organ system, primarily affects the central nervous system, particularly the developing brain. Consequently, children are at a greater risk than adults of suffering from the neurotoxic effects of lead. To date, no safe lead-exposure threshold has been identified. The ability of lead to pass through the blood-brain barrier is due in large part to its ability to substitute for calcium ions. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurologic disorders. At the molecular level, lead interferes with the regulatory action of calcium on cell functions and disrupts many intracellular biological activities. Experimental studies have also shown that lead exposure may have genotoxic effects, especially in the brain, bone marrow, liver, and lung cells. Knowledge of the neurotoxicology of lead has advanced in recent decades due to new information on its toxic mechanisms and cellular specificity. This paper presents an overview, updated to January 2009, of the neurotoxic effects of lead with regard to children, adults, and experimental animals at both cellular and molecular levels, and discusses the biomarkers of lead exposure that are useful for risk assessment in the field of environmental health.

Lead encephalopathy due to traditional medicines.

Traditional medicine use is common in developing countries and increasingly popular in the western world. Despite the popularity of traditional medicines, scientific research on safety and efficacy is limited. However documented fatalities and severe illness due to lead poisoning are increasingly recognized to be associated with traditional medicine use. As society becomes more globalized, it is imperative for pharmacists and health care providers to learn about the safety of traditional medical practices. The information presented educates and alerts pharmacists and health care providers about the potential of traditional medicines to cause lead encephalopathy. Case reports were located through systematic literature searches using MEDLINE, CINAHL, AMED, CISCOM, EMBASE and The Cochrane library from 1966 to the February 2007. Reference lists of identified articles and the authors' own files were also searched. Inclusion criteria were cases of human lead encephalopathy associated with traditional medical practices. There were no restrictions regarding the language of publication. Data were subsequently extracted and summarized in narrative and tabular form. We found 76 cases of lead encephalopathy potentially associated with traditional medicine. Ayurvedic medicines were associated with 5 cases (7%), Middle eastern traditional medicines with 66 cases (87%) and 5 cases (7%) with other traditional medicines. Of the 76 cases, 5% were in adults and 95% were in infants and young children. Of the 4 adult cases, at least one was left with residual neurological impairment. In infants and young children, among 72 cases 8 (11%) were fatal, and at least 15 (21%) had residual neurological deficits. Traditional medicine users should be screened for lead exposure and strongly encouraged to discontinue metal-containing remedies. Therefore, the United States Food and Drug Administration and corresponding agencies in other countries should require and enforce heavy metal testing for all imported traditional medicines and "dietary supplements".

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p

Avaliação dos efeitos tóxicos sobre o sistema nervoso periférico, decorrentes da exposição ocupacional ao chumbo / Evaluation of toxic effects on the peripheral nervous system, as a consequence of the occupational exposure to lead

Após descrever a interação do homem com meio ambiente, em particular nas atividades laborativas, se destaca a extração e o processamento dos minérios de chumbo como importante fonte de exposição ocupacional a este metal, que gerou no passado grandes casuísticas de intoxicação. Em seguida é feito um relato de como ocorreu a exposição ocupacional ao chumbo em Santo Amaro da Purificação na Bahia, e uma revisão da toxicologia deste metal, identificando-se a necessidade de se trabalhar com indicadores, parâmetros, que melhor reflitam os efeitos cumulativos, como os que ocorrem no sistema nervoso periférico. Analisar e discutir as alterações do sistema nervoso periférico pós exposição ocupacional, em um grupo de ex-empregados de uma metalurgia primária de chumbo; e identificar marcadores que melhor reflitam os efeitos da bioacumulação deste metal. A partir de dados secundários, foi construída uma serie de casos, na qual se analisou o passado clínico e toxicológico, e a relação com os achados neurofisiológicos. Os dados analisados, demonstraram a ocorrência, de um leque de neuropatias periféricas em todo o grupo, mas as alterações da condução motora em membros superiores, que tem sido melhor relacionadas aos efeitos tóxicos do chumbo, não foram tão consistentes. Ficou comprovado ser a media acumulada do chumbo no sangue um marcador biológico mais fidedigno, para avaliações de efeitos de longo prazo como as alterações sobre o sistema nervoso periférico.

Environmental factors associated with a spectrum of neurodevelopmental deficits.

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent.

Maternal bone lead as an independent risk factor for fetal neurotoxicity: a prospective study.

OBJECTIVE: A number of prospective studies have examined lead levels in umbilical cord blood at birth as predictors of infant mental development. Although several have found significant inverse associations, others have not. Measurement of lead levels in maternal bone, now recognized as the source of much fetal exposure, has the potential to serve as a better or complementary predictor of lead's effect on the fetus. Our objective was to compare lead levels in umbilical cord blood and maternal bone as independent predictors of infant mental development using a prospective design. METHODS: We recruited women who were giving birth at 3 maternity hospitals in Mexico City that serve a homogeneous middle-class community. Umbilical cord blood lead levels were measured by graphite furnace atomic absorption spectroscopy, and maternal lead levels in cortical (tibial) and trabecular (patellar) bone were measured within 4 weeks of giving birth using a 109-Cd K-x-ray fluorescence instrument. At 24 months of age, each infant was assessed using the Bayley Scales of Infant Development-II (Spanish Version). RESULTS: A total of 197 mother-infant pairs completed this portion of the study and had data on all variables of interest. After adjustment for other well-known determinants of infant neurodevelopment, including maternal age, IQ, and education; paternal education; marital status; breastfeeding duration; infant gender; and infant illness, lead levels in umbilical cord blood and trabecular bone were significantly, independently, and inversely associated with the Mental Development Index (MDI) scores of the Bayley Scale. In relation to the lowest quartile of trabecular bone lead, the second, third, and fourth quartiles were associated with 5.4-, 7.2-, and 6.5-point decrements in adjusted MDI scores. A 2-fold increase in cord blood lead level (eg, from 5 to 10 micro g/dL) was associated with a 3.1-point decrement in MDI score, which is comparable to the magnitude of effect seen in previous studies. CONCLUSION: Higher maternal trabecular bone lead levels constitute an independent risk factor for impaired mental development in infants at 24 months of age. This effect is probably attributable to mobilization of maternal bone lead stores, a phenomenon that may constitute a significant public health problem in view of the long residence time of lead in bone.