Environmental Co-Exposure to Lead and Manganese and Intellectual Deficit in School-Aged Children

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Abstract

Studies have demonstrated that, for urban children, dust represents the main exposure to sources of metals like lead (Pb) and manganese (Mn). We aimed to investigate the exposure to these metals and their association with intellectual deficit in children living in an industrial region. This cross-sectional study recruited volunteers from four elementary schools in the town of Simões Filho, Brazil. We evaluated 225 school-aged children (7–12 years) for blood lead (PbB) and manganese hair (MnH) and toenails (MnTn) by graphite furnace atomic absorption spectrometry. Child and maternal IQs were estimated using the Wechsler Abbreviated Scale for Intelligence (WASI). Median and range PbB were 1.2 (0.3–15.6) μg/dL. MnH and MnTn medians (ranges) were 0.74 (0.16–8.79) μg/g and 0.85 (0.15–13.30) μg/g, respectively. After adjusting for maternal IQ, age and Mn exposure, child IQ drops by 8.6 points for a 10-fold increase in PbB levels. Moreover, an effect modification of Mn co-exposure was observed. In children with low MnTn, association between Pb and child IQ was not significant (β = −6.780, p = 0.172). However, in those with high MnTn, the association was increased by 27.9% (β = −8.70, p = 0.036). Low Pb exposure is associated with intellectual deficit in children, especially in those with high MnTn.

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Low-Level Environmental Lead Exposure and Children’s Intellectual Function: An International Pooled Analysis

Bruce Lanphear, Richard Hornung, Jane Khoury … (2005)

Lead is a confirmed neurotoxin, but questions remain about lead-associated intellectual deficits at blood lead levels < 10 μg/dL and whether lower exposures are, for a given change in exposure, associated with greater deficits. The objective of this study was to examine the association of intelligence test scores and blood lead concentration, especially for children who had maximal measured blood lead levels < 10 μg/dL. We examined data collected from 1,333 children who participated in seven international population-based longitudinal cohort studies, followed from birth or infancy until 5–10 years of age. The full-scale IQ score was the primary outcome measure. The geometric mean blood lead concentration of the children peaked at 17.8 μg/dL and declined to 9.4 μg/dL by 5–7 years of age; 244 (18%) children had a maximal blood lead concentration < 10 μg/dL, and 103 (8%) had a maximal blood lead concentration < 7.5 μg/dL. After adjustment for covariates, we found an inverse relationship between blood lead concentration and IQ score. Using a log-linear model, we found a 6.9 IQ point decrement [95% confidence interval (CI), 4.2–9.4] associated with an increase in concurrent blood lead levels from 2.4 to 30 μg/dL. The estimated IQ point decrements associated with an increase in blood lead from 2.4 to 10 μg/dL, 10 to 20 μg/dL, and 20 to 30 μg/dL were 3.9 (95% CI, 2.4–5.3), 1.9 (95% CI, 1.2–2.6), and 1.1 (95% CI, 0.7–1.5), respectively. For a given increase in blood lead, the lead-associated intellectual decrement for children with a maximal blood lead level < 7.5 μg/dL was significantly greater than that observed for those with a maximal blood lead level ≥7.5 μg/dL (p = 0.015). We conclude that environmental lead exposure in children who have maximal blood lead levels < 7.5 μg/dL is associated with intellectual deficits.

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The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20–40 Months of Age: Evidence from Rural Bangladesh

Linda Valeri, Maitreyi M. Mazumdar, Jennifer F. Bobb … (2017)

Background: Exposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects. Objectives: We aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children’s neurodevelopment. Methods: We employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother–child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry. Results: Analyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18 μ g / dl ], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile ( As ≥ 0.7 μ g / dl , Mn ≥ 6.6 μ g / dl , Pb ≥ 4.2 μ g / dl ) compared to the median ( As = 0.5 μ g / dl , Mn = 5.8 μ g / dl , Pb = 3.1 μ g / dl ). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of − 0.3 ( − 0.5 , − 0.1 ) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity. Conclusions: Employing a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614

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Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

Venkatanaidu Karri, Marta Schuhmacher, Vikas Kumar (2016)

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na(+) - K(+) ATP-ase pump (Cd, MeHg), biological Ca(+2) (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Environ Res Public Health

Journal ID (iso-abbrev): Int J Environ Res Public Health

Journal ID (publisher-id): ijerph

Title: International Journal of Environmental Research and Public Health

Publisher: MDPI

ISSN (Print): 1661-7827

ISSN (Electronic): 1660-4601

Publication date (Electronic): 31 October 2018

Publication date (Print): November 2018

Volume: 15

Issue: 11

Electronic Location Identifier: 2418

Affiliations

[1 ]Laboratory of Toxicology, School of Pharmacy, Federal University of Bahia, Salvador 40170-115, Brazil; julgrodrigues3@ 123456gmail.com (J.L.G.R.); nathalias@ 123456ufba.br (N.R.d.S.); matheus.jesus@ 123456ufba.br (M.J.B.); anjos.ana@ 123456ufba.br (A.L.S.A.); ferreol40@ 123456hotmail.com (H.A.F.B.)

[2 ]Institute of Psychology, Federal University of Bahia, Salvador 40170-115, Brazil; chrissie.carvalho@ 123456pro.ucsal.br (C.F.C.); cassio.lima@ 123456ufba.br (C.S.L.); lsmbrenoa@ 123456gmail.com (B.L.d.S.M.); neander.abreu@ 123456ufba.br (N.A.)

[3 ]Environmental and Public Health Program, National School of Public Health, Oswald Cruz Foundation, Rio de Janeiro 21041-210, Brazil; cecilia.araujo@ 123456posgrad.ensp.fiocruz.br

[4 ]Centre de Recherche Interdisciplinaire sur la Biologie, la Santé, la Société et l’Environnement (CINBIOSE), Université du Québec a Montreal, Montreal, QC H3C 3P8, Canada; philibert.aline@ 123456uqam.ca (A.P.); mergler.donna@ 123456uqam.ca (D.M.)

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[* ]Correspondence: antomen@ 123456ufba.br ; Tel.: +55-71-991-447-719

Author information

José A. Menezes-Filho https://orcid.org/0000-0002-3191-4484

Chrissie F. Carvalho https://orcid.org/0000-0002-1369-6188

Article

Publisher ID: ijerph-15-02418

DOI: 10.3390/ijerph15112418

PMC ID: 6266231

PubMed ID: 30384464

SO-VID: 896cb749-abba-4828-a58b-7c55609378cf

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Environmental Co-Exposure to Lead and Manganese and Intellectual Deficit in School-Aged Children

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Chinese Journal of School Health

Most cited references 36

Low-Level Environmental Lead Exposure and Children’s Intellectual Function: An International Pooled Analysis

The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20–40 Months of Age: Evidence from Rural Bangladesh

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

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