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Background: Lifelong health is dependent on prenatal growth and development, influenced by the placental intrauterine environment. Charged with dual functions--exchange of oxygen and nutrients as well as a barrier against toxins--the placenta itself is susceptible to environmental exposure to heavy metals., Objective: To examine the use of placenta weight as a biomarker for heavy metal exposure using a large Japanese cohort of pregnant women., Methods: The placenta weight, as a biomarker of exposure to heavy metals (cadmium, lead, and mercury), was investigated using data from the Japan Environment and Children's Study (2011-2014). Selenium and manganese were included as factors directly affecting fetal growth or heavy metal toxicity. Maternal blood samples collected in the second or third trimester were used to measure heavy metal concentrations. The association between maternal blood metal concentrations and placenta weight was explored by applying Z scores and multivariable logistic regression analysis and classifying participants into quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations., Results: This study included a total of 73,005 singleton pregnant women who delivered via live births and met the inclusion criteria. The median heavy metal concentrations in the maternal whole blood were 0.662 ng/g cadmium, 5.85 ng/g lead, 3.61 ng/g mercury, 168 ng/g selenium, and 15.3 ng/g manganese. Regression analysis revealed a significant correlation between placenta weight Z scores and maternal blood metal concentrations: cadmium, 0.0660 (standard error = 0.0074, p < 0.001); selenium, -0.3137 (standard error = 0.0276, p < 0.001); and manganese, 0.1483 (standard error = 0.0110, p < 0.001)., Conclusion: This study provides a robust examination of the association between heavy metal exposure and placenta weight. Cadmium and manganese showed a positive correlation with significant differences, whereas selenium showed a negative correlation. Essential elements notably affect placenta weight differently. No significant association was noted between lead or mercury and placenta weight., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Associations between plasma elements and chronic kidney disease (CKD) among the elderly are poorly understood. In this cross-sectional study, we explored the associations between exposure to four plasma elements and CKD in elderly people aged ≥90 years in longevity areas in China. We measured plasma selenium, manganese, iron, and zinc levels and used logistic regression models to investigate associations between CKD and these four plasma elements after adjusting for confounding factors among 461 participants aged ≥90 years in the fifth wave of the Chinese Longitudinal Healthy Longevity Study (CLHLS) conducted in 2009. The median plasma selenium, manganese, iron, and zinc levels were 120.51 μg/L, 26.64 μg/L, 2880.52 μg/L, and 1882.42 μg/L in the CKD group and 108.76 μg/L, 31.55 μg/L, 4512.00 μg/L, and 2294.24 μg/L in the non-CKD group, respectively. Single- and multiple-element multivariable models showed that plasma manganese, iron, and zinc were negatively associated with CKD. In the multiple-element multivariable models, the adjusted odds ratios for CKD were 0.48 (95% confidence interval [CI]: 0.27-0.86) for the second highest quartile of manganese, 0.37 (95% CI: 0.21-0.68) and 0.36 (95% CI: 0.19-0.65) for the third highest and highest quartiles of iron, respectively, and 0.53 (95% CI: 0.29-0.94) for the highest quartile of zinc, compared with the lowest quartiles of these three elements. Plasma manganese, iron, and zinc levels protect against CKD in elderly people aged ≥90 years in longevity areas., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

It has been suggested that manganese (Mn) plays a fundamental role in the reproductive system through interference with the regulation of the secretion of hormones related to puberty. The objective of this study was to evaluate the environmental exposure to Mn and its effects on the endocrine regulation of hormones related to puberty in school-aged children living near a ferro-manganese alloy plant. Toenails, occipital hair, and blood samples were collected from 225 children, between 7 and 12 years of age, in four elementary schools in Simões Filho, Bahia, Brazil, who were exposed to different Mn levels owing to different Mn dust deposition rates. The Mn content was determined in the toenails (MnTn), hair (MnH), and blood (MnB), in addition to blood lead levels (PbB), by using graphite furnace atomic absorption spectrometry. Luteinizing hormone (LH), prolactin (PRL), estradiol (E 2 ), testosterone (T), and thyroid stimulating hormone (TSH) levels were determined by using a chemiluminescence method. Of the total participants, 50.2% were boys, with an average age of 9 years. PRL values were higher in children attending the school with a higher Mn deposition rate (p < 0.004). We observed that MnTn was positively correlated with PRL levels and exhibited a non-linear association with LH levels. None of the tested Mn biomarkers were associated with E 2 , T, or TSH levels. To date, despite several animal studies that have focused on the correlation between Mn exposure and the endocrine regulation of hormones and pubertal development, very few studies have reported a similar relationship between environmental Mn effects and the human endocrine system. Our findings support the hypothesis that elevated exposure to Mn in children may be associated with hormonal imbalances that might trigger the early onset of puberty., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV)., Materials and Methods: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers., Results: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (β = 0.04-0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (β high  = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and β low  = -0.06; 95% CI = 0.03, -0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN., Conclusions: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Epidemiological studies have hypothesized that both insufficient and excess blood manganese (Mn) levels during pregnancy are associated with reduced fetal growth. This literature is characterized by inconsistent results and a limited focus on women with exposures representative of the general North American population. We examined the relationship between maternal and cord blood Mn levels and fetal growth among women enrolled in the Maternal-Infant Research on Environmental Chemicals Study (MIREC). Mothers with singleton, term infants and complete maternal first and third trimester blood Mn data were eligible for inclusion in the present study (n = 1519). Mean birth weight and odds ratios of small for gestational age (SGA) births according to maternal and cord blood Mn levels (low (<10), referent (10-<90), high (≥90) percentiles) were estimated. We also evaluated the association between the ratio of cord and maternal blood Mn and birth weight. Women with low (<0.82 μg/dL) maternal blood third trimester Mn levels had infants that weighed an average of 64.7 g (95% CI: -142.3,12.8) less than infants born to women in the referent exposure group. This association was strengthened and became statistically significant when adjusted for toxic metals (lead, mercury, arsenic, and cadmium) [-83.3 g (95% CI: -162.4, -4.1)]. No statistically significant associations were observed in models of maternal first trimester or cord blood Mn. A one unit increase in the cord/maternal blood Mn ratio was associated with a 29.4 g (95% CI: -50.2, -8.7), when adjusted for maternal and neonatal characteristics. Our findings motivate additional research regarding the relation between Mn exposure and fetal growth. Further inquiry is necessary to determine whether an exposure threshold exists, how growth related effects of maternal and fetal Mn may differ, and how concurrent exposure to other toxic metals may impact the association between Mn and growth., (Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The deficit in the visuospatial skills, thinking, learning and memory is termed as cognitive impairment. Human exposure to heavy metals is a potential risk factor for developing cognitive impairment. This study aimed to investigate the possible association between the concentration of heavy metals and the extent of cognitive impairment. Blood samples were subjected to microwave assisted acid digestion and evaluated for metals levels using atomic absorption spectrophotometry. We measured the levels of Cu, Pb, Al, Zn, Cd and Mn in 183 patients diagnosed with cognitive impairment; mild (n = 72), moderate (n = 86) and severe (n = 25) and compared them to age-matched healthy controls (n = 90). Results showed that all the aforementioned elements were significantly higher in cognitively impaired patients and increasing concentration was strongly correlated with increase in severity of the disease. The correlation study has shown that among the studied metals, Al and Cu are strongly associated with the cognitive impairment. This suggests the need for decrease in metal exposure to humans from environment, food and industries., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Environmental manganese exposure has been associated with adverse neurodevelopmental outcomes among school-aged children; yet, few studies have evaluated prenatal exposure., Objectives: Our study examines associations between prenatal manganese concentrations and placental transfer of manganese with neurodevelopment in 224 2-y-old children residing near the Tar Creek Superfund Site., Methods: We collected maternal and cord blood at delivery, measured manganese using inductively coupled plasma mass spectrometry, and assessed neurodevelopment using the Bayley Scales of Infant Development-II. Associations between manganese and mental (MDI) and psychomotor (PDI) development indices were estimated in multivariable models. Placental transfer, approximated by cord/maternal manganese ratio, cord/total manganese ratio (total=maternal+cord), and by joint classification according to high or low (above or below median) maternal and cord manganese, was evaluated as a predictor of neurodevelopment., Results: Median levels [interquartile ranges (IQR)] of manganese in maternal and cord blood, respectively, were 24.0 (19.5-29.7) and 43.1 (33.5-52.1) μg/L. Adjusting for lead, arsenic, and other potential confounders, an IQR increase in maternal manganese was associated with -3.0 (95% CI: -5.3, -0.7) points on MDI and -2.3 (95% CI: -4.1, -0.4) points on PDI. Cord manganese concentrations were not associated with neurodevelopment scores. Cord/maternal and cord/total manganese ratios were positively associated with MDI [cord/maternal: β=2.6 (95% Cl: −0.04, 5.3); cord/total: β=22.0 (95% Cl: 3.2, 40.7)] and PDI (cord/maternal: β=1.7 (95% Cl: −0.5, 3.9); cord/total: β=15.6 (95% Cl: 0.3, 20.9)). Compared to mother-child pairs with low maternal and cord manganese, associations with neurodevelopment scores were negative for pairs with either high maternal, high cord, or high maternal and cord manganese., Conclusions: Maternal blood manganese concentrations were negatively associated with early childhood neurodevelopment scores in our study. Findings highlight the importance of understanding maternal exposures during pregnancy and factors influencing placental transfer. https://doi.org/10.1289/EHP925.

Manganese (Mn) is an essential dietary nutrient for human health serving as a cofactor for many enzymes; however, exposure to excessive quantities of Mn may lead to toxicity with symptoms analogous to Parkinson's disease (PD). Population-based biomonitoring is an effective tool for characterizing the body burden of environmental or occupational pollutants, including Mn. The objective of this cross-sectional study was to (1) estimate reference values (RV) for blood Mn in an adult population and (2) assess the variables that were associated with higher blood metal levels. A total of 947 adults, aged 40 years or older, were randomly selected in a city in Southern Brazil. Information on socioeconomic, dietary, lifestyle, and occupational background was collected by trained interviewers. Blood Mn levels (μg/L) were analyzed by inductively coupled plasma-mass spectrometer (ICP-MS). The RV for blood Mn concentrations were obtained from the upper limits of the 95% confidence intervals (CI) of the 95th percentile distributions. Cluster analysis was performed to identify variables associated with high or low blood Mn concentrations. The RV for blood Mn levels in this study were 18.54 and 20.15 μg/L for men and women, respectively. Mn blood concentrations decreased with age and were higher in females compared to males. No marked association was noted between blood Mn and smoking or drinking habits, education levels and socioeconomic status. Diastolic blood pressure was higher in a group of women approximately 54 years of age associated with elevated blood Mn levels. Important reference data stratified by demographic and lifestyle factors that may prove useful for future surveillance of environmental exposure to Mn and health risks associated with this metal are presented.

Background: Children's exposure to manganese (Mn) is a public health concern and consistent policy guidelines for safe levels of Mn exposure is lacking. The complexity of establishing exposure thresholds for Mn partially relates to its dual role as an essential micronutrient with low levels required for good health, but also as a neurotoxin at high levels. Questions exist about the age-related susceptibility to excess Mn, particularly for children, and how best to measure chronic exposures. To address this concern we conducted a systematic review of studies examining children's exposure to Mn and neurodevelopmental outcomes focused on selection of biomarker-based and environmental measurements of Mn exposure to identify the scientific advances and research gaps., Methods: PubMed and EMBASE databases were searched through March 2016 for studies that were published in English, used a biomarker-based or environmental measurement of Mn exposure, and measured at least one neurological outcome for children aged 0-18 years. Ultimately, thirty-six papers from 13 countries were selected. Study designs were cross-sectional (24), prospective cohorts (9), and case control (3). Neurodevelopmental outcomes were first assessed for Mn exposure in infants (6 papers), toddlers or preschoolers (3 papers) and school-age children (27 papers)., Results: Studies of school-aged children most frequently measured Intelligence Quotient (IQ) scores using Mn biomarkers of hair or blood. Higher hair concentrations of Mn were consistently associated with lower IQ scores while studies of blood biomarkers and IQ scores had inconsistent findings. Studies of infants and toddlers most frequently measured mental and psychomotor development; findings were inconsistent across biomarkers of Mn (hair, cord blood, tooth enamel, maternal or child blood and dentin). Although few studies measured environmental sources of Mn, hair biomarkers were associated with Mn in drinking water and infant formula. Only one paper quantified the associations between environmental sources of Mn and blood concentrations., Conclusion: Hair-Mn was the more consistent and valid biomarker of Mn exposure in school-aged children. Accurate measurement of children's exposure to Mn is crucial for addressing these knowledge gaps in future studies. However, research on biomarkers feasible for fetuses and infants is urgently needed given their unique vulnerability to excessive Mn.

Human beings working or living near an industrial site where toxic chemicals such as As, Hg, Cd, Cu, Mn, Pb, Zn and or their compounds are used or indiscriminately discharged into the environment, are constantly exposed to such chemicals via ingestion (drinking or eating), dermal contact or inhalation (breathing). However, in developing countries such as Ghana, limited data on levels of the aforementioned chemicals in whole blood and serum of human beings as a result of exposure to the aforementioned chemicals from mining communities and non-mining communities is preventing effective policy formulation to protect human health. Hence, this study was undertaken to measure the levels of the aforementioned toxic chemicals in whole blood and serum of 300 resident adults from mining (Tarkwa Nsuaem Municipality Assembly (TNMA) and Prestea Huni Valley District (PHVD)) and non-mining (Cape Coast Metropolis) communities in Ghana, using neutron activation analysis (NAA). Blood samples were taken from 200 resident adults (105 males and 95 females) from mining and 100 resident adults (60 males and 40 males) from non-mining communities in the study area following the completion of an informed consent and the issuance of ethical clearance by the Ghana Health Service Ethical Committee. The mean concentrations for As, Hg, Cd, Cu, Mn, Pb and Zn in whole blood of residents from mining communities were as follows: 38 ± 320 μg/L, 63 ± 0.23 μg/L, 303 ± 117 μg/L, 3300 ± 953, 195 ± 90 μg/L, 28 ± 14 μg/L and 1405 ± 458 μg/L, respectively; while the levels of measured toxic chemicals in the serum of resident adults from mining communities were as follows: 65 ± 14 μg/L, 358 ± 22 μg/l, 134 ± 12 μg/L, 3590 ± 254 μg/L, 401 ± 113 μg/L, 58 ± 5.8 μg/L and 49 ± 31 μg/L, respectively, for As, Hg, Cd, Cu, Mn, Pb and Zn and were found to have exceeded the permissible WHO guideline values.

Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6-12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions - inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), δ-aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl2 (ALA-RE/ZnCl2), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-β-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children (p<0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (β=0.649; p<0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions - inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers (p<0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks (p<0.05). The findings of this study suggest an important association between environmental exposure to Mn and toxic effects on neuropsychological function, oxidative damage and kidney function in children., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Manganese (Mn) plays a vital role in brain growth and development, yet excessive exposure can result in neurotoxicity. Marietta, Ohio, is home to the nation's longest-operating ferromanganese refinery, and community concern about exposure led to the development of the research study., Objectives: Our overall goal was to address the community's primary research question: "Does Mn affect cognitive development of children?" We evaluated the relationships between Mn exposure as measured by blood and hair Mn, along with other neurotoxicants including blood lead (Pb) and serum cotinine, and child cognition., Methods: Children 7-9 years of age were enrolled (n = 404) in the Communities Actively Researching Exposure Study (CARES) from Marietta and Cambridge, Ohio, and their surrounding communities from October 2008 through March 2013. Blood and hair were analyzed for Mn and Pb, and serum was analyzed for cotinine. We used penalized splines to assess potential nonlinear associations between biological measures and IQ subscale scores, followed by multivariable regression models with categorical variables based on quartiles of the distribution for biological measures with nonlinear associations and continuous variables for biological measures with linear associations., Results: Geometric mean blood (n = 327) and hair Mn (n = 370) concentrations were 9.67 ± 1.27 μg/L and 416.51 ± 2.44 ng/g, respectively. After adjusting for potential confounders, both low and high blood and hair Mn concentrations were associated with lower Full Scale IQ and subscale scores, with significant negative associations between the highest quartile and middle two quartiles of blood Mn (β -3.51; 95% CI: -6.64, -0.38) and hair Mn (β -3.66; 95% CI: -6.9, -0.43%) and Full Scale IQ., Conclusions: Both low and high Mn concentrations in blood and hair were negatively associated with child IQ scores. Serum cotinine was negatively associated with child cognitive function.

Prenatal exposure and the health effects of that exposure have been intensively studied for a variety of environmental pollutants and trace elements. However, few studies have compared susceptibilities among the three trimesters of gestation. Manganese (Mn) is a naturally occurring and abundant trace element in the environment. Although the effects of Mn on animals are well documented, knowledge of the effects of Mn exposure on pregnant women and fetuses remains limited. A longitudinal study was conducted by collecting blood samples during all three trimesters, and Mn exposure was completely characterized during gestation. The aims of this study were to examine the effects of maternal Mn exposure on neonatal birth outcomes and to explore the critical stage of these effects. In total, 38, 76 and 76 samples were obtained from singleton pregnant women in their first, second and third trimesters, respectively. The cohort of pregnant women was selected at a medical center in northern Taiwan. Erythrocyte samples were collected during the first, second and third trimesters of gestation. Erythrocyte Mn concentrations were measured by inductively coupled plasma mass spectrometry. Neonatal birth outcomes were evaluated immediately after delivery. A multivariate regression model was used to determine the associations between maternal Mn levels in erythrocytes in each trimester and neonatal birth outcomes. The geometric mean concentrations of Mn were 2.93 μg/dL, 3.96 μg/dL and 4.41 μg/dL in the first, second and third trimesters, respectively. After adjusting for potential confounders, a consistently negative association was found between maternal Mn levels throughout the three trimesters and birth outcomes. Log-transformed Mn levels in maternal erythrocytes in the second trimester were significantly associated with neonatal birth weight, head and chest circumferences, respectively (β=-556.98 g, p=0.038; β=-1.87 cm, p=0.045; β=-2.74 cm, p=0.024). Despite the limited sample size in the first trimester, negative effects of maternal Mn levels on birth weight (β=-1108.95 g, p<0.01) and chest circumference (β=-4.40 cm, p=0.019) were also observed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Manganese is an essential element for human health and development. Previous studies have shown neurotoxic effects in children exposed to higher levels of manganese. Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that impairs social interaction and communication. Several studies have hypothesized that ASD is caused through environmental exposures during crucial stages in brain development. We investigated the possible association between blood manganese concentrations (BMC) and ASD. We also identified factors associated with BMC in typically developing (TD) Jamaican children., Methods: We used data from 109 ASD cases with their 1:1 age- and sex-matched TD controls to compare mean BMC in Jamaican children (2-8 years of age) with and without ASD. We administered a pre-tested questionnaire to assess demographic and socioeconomic information, medical history, and potential exposure to manganese. Finally, we collected 2 mL of whole blood from each child for analysis of manganese levels. Using General Linear Models (GLM), we assessed the association between BMC and ASD status. Furthermore, we used two independent sample t-tests to identify factors associated with BMC in TD children., Results: In univariable GLM analysis, we found no significant association between BMC and ASD, (10.9 μg/L for cases vs. 10.5 μg/L for controls; P = 0.29). In a multivariable GLM adjusting for paternal age, parental education, place of child's birth (Kingston parish), consumption of root vegetables, cabbage, saltwater fish, and cakes/buns, there was still no significant association between BMC and ASD status, (11.5 μg/L for cases vs. 11.9 μg/L for controls; P = 0.48). Our findings also indicated TD children who ate fresh water fish had a higher BMC than children who did not (11.0 μg/L vs. 9.9 μg/L; P = 0.03) as younger TD children (i.e., 2 ≤ age ≤4), (12.0 μg/L vs. 10.2 μg/L; P = 0.01)., Conclusions: While these results cannot be used to assess early exposure at potentially more susceptible time period, our findings suggest that there is no significant association between manganese exposures and ASD case status in Jamaica. Our findings also indicate that BMC in Jamaican children resemble those of children in the developed world and are much lower than those in the developing countries.

We monitored 108 children ≤5 years on a 6-month basis for up to 5 years in a major urban setting. Samples (n ∼ 7000) included blood, urine, handwipes (interior, and after exterior playing), 6-day duplicate diet, drinking water, interior house and day care dust-fall accumulation using petri dishes, exterior dust-fall accumulation, exterior dust sweepings, paint, soil and urban air. The geometric mean blood Pb (PbB) was 2.1 μg/dL and blood Mn (MnB) was 10.0 μg/L. Following a path modelling approach, mixed model analyses for a fully adjusted model showed the strongest associations for PbB were with interior house dust and soil; for MnB there were no significant associations with any predictors. Predictor variables only explained 9% of the variance for Pb and 0.7% for Mn. Relationships between environmental measures and PbB in children are not straightforward; soil and dust sweepings contribute only about 1/5th of the amounts to PbB found in other studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Manganese (Mn) is an essential mineral nutrient in mammals. The physiological role of Mn in animal models is well documented, but little is known about the adverse effects of Mn deficiency or overexposure in humans, including pregnancy outcomes such as birth weight. We examined the relationship of the maternal and cord blood Mn levels with birth weight in a cohort of 172 mother-infant pairs born in Shanghai, China. Non-linear spline and quadratic regression models were used to test the hypothesis of an inverted U-shaped association between the Mn levels and birth weight. The median (range) levels of Mn in the maternal and cord blood were 5.38 (2.34-30.37) μg/dL and 7.66 (2.57-34.23) μg/dL, respectively. An inverted U-shaped relationship was observed between maternal Mn and birth weight after adjusting for potential confounders. The birth weight increased with Mn levels up to 4.18 μg/dL, and a slight reduction in weight was observed at higher levels. The cord blood Mn levels were not found to be associated with birth weight. Both lower and higher Mn exposures are associated with lower birth weight, which may influence important developmental parameters; the association of higher Mn levels with lower weight was weak and imprecise.

Background: Manganese (Mn) is an essential trace element for humans and animals, but excess intake of Mn can lead to adverse developmental outcome. Few studies have investigated the effects of deficiency or excess of Mn on the human foetus. In this study, we assessed the quantitative relationship between maternal blood Mn and birth weight of a newborn., Methods: We performed analysis on 331 full-term, live birth singleton mother-infant pairs enrolled from July 2007 to December 2009 in the Mother and Children's Environmental Health (MOCEH) study in Korea. A questionnaire on general characteristics, a review of medical records, and maternal whole blood Mn analysis were performed at full-term pregnancy. We evaluated the relationship between maternal blood level of Mn and the birth outcome using logistic regression and generalised additive model., Results: The mean Mn concentration in whole maternal blood was 22.5 μg/L. We found a curvilinear relationship between maternal blood Mn and birth weight after adjusting for potential confounders. Birth weight peaked at the maternal blood Mn level of 30 and 35 μg/L. An increased probability of birth weight below 3000 g was observed at both below 16.9 μg/L (odds ratio = 2.77, 95% CI: 0.89-8.65) and above 26.9 μg/L of maternal blood Mn level (odds ratio = 2.66, 95% CI: 0.84-8.08)., Conclusions: Our study found that both extreme level of maternal Mn level was associated with lower birth weight outcome in a nonlinear fashion.

The informal processing of electronic waste or e-waste contributes to the release of high concentrations of transition metals into the ambient air. The damage caused by chromium, nickel and manganese exposure on lung function in school children from an e-waste recycling area and the role of oxidative stress in this process were evaluated. We recruited school children (n=144, 8-13 years) from an e-waste recycling area in China compared with the control. Spirometry was performed to assess lung function status. The blood levels of chromium, nickel and manganese, antioxidant enzyme activities and lipid peroxidation of the subjects were examined. The concentrations of blood manganese (bMn) and serum nickel (sNi) in the exposed group were significantly higher than those in controls for all three age groups. The forced vital capacity value of boys aged 8-9 years was significantly lower than that of the control. Malondialdehyde levels and superoxide dismutase activities increased significantly in children aged 8-9 years from e-waste environment, but catalase activities declined. School children from an e-waste recycling area were exposed to high levels of the three transition metals. The accumulation of bMn and sNi may be risk factors for oxidative damage and decreased pulmonary function.

This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The extent of children's exposure to multiple toxic metals is not well described in many developing countries. We examined metal exposures in young children (6-37 months) from Montevideo, Uruguay and their mothers (15-47 years) participating in a community-based study. Hair samples collected from 180 children and their mothers were analyzed for: lead (Pb), cadmium (Cd), manganese (Mn), and arsenic (As) concentration using inductively coupled plasma-mass spectrometry (ICP-MS). Median metal levels (microg/g) were: Pb 13.69, Mn 1.45, Cd 0.17, and As 0.09 for children and Pb 4.27, Mn 1.42, Cd 0.08, and As 0.02 for mothers. Of the child and maternal samples, 1.7% and 2.9% were below the limit of detection (LOD) for Cd, and 21.3% and 38.5% were below the LOD for As, respectively. Correlations between maternal and child levels ranged 0.38-0.55 (p<0.01). Maternal hair metal levels were the strongest predictors of metal concentrations in children's hair. Girls had significantly lower As levels than boys (p<0.01) but did not differ on other metals. In addition, in bivariate logistic regressions predicting the likelihood that the child would be exposed to multiple metals, hemoglobin <10.5 g/dL (OR=2.12, p<0.05), blood lead (OR=1.17, p<0.01), and the mother being exposed to two or more metals (OR=3.34, p<0.01) were identified as significant predictors of increased likelihood of multiple metal exposure. Older child age (OR=0.96, p<0.05), higher maternal education (OR=0.35, p<0.01), and higher number of household possessions (OR=0.83, p<0.01) were significantly associated with decreased likelihood of multiple metal exposure. Preschool children in Uruguay are exposed to multiple metals at levels that in other studies have been associated with cognitive and behavioral deficits. Sources of exposure, as well as cognitive and behavioral consequences of multiple metal exposure, should be investigated in this population., (Copyright 2010 Elsevier B.V. All rights reserved.)

Copper, manganese and selenium are elements involved in protecting the body against oxidative stress. Determining their plasma level may contribute to assessing the health and nutritional status of populations. The aim of this study was to assess factors influencing copper, manganese and selenium plasma levels in an adult Mediterranean population and to identify groups at risk of deficiency. A cross-sectional survey was carried out in Andalusia, a region in southern Spain. Blood samples were obtained in a random subsample of 340 subjects. Food consumption was assessed by 48-h recall. Height, weight, skinfolds, waist and hip circumferences were measured. Copper, manganese and selenium were measured in plasma. Information about physical exercise, educational level, alcohol and smoking habits was obtained with a structured questionnaire. Plasma copper was found to be higher in women than among men. Hypocupraemia was found in 4.4% of the population, while 9.7% presented hypomanganesemia. Moreover, 86.5% presented plasma selenium values below 125microg/L (cutoff for optimal glutathione peroxidase activity). No association was found between plasma elements, anthropometric indices and lifestyle factors; there were tendencies, no more. Copper tended to decrease in obese and increase in sedentary, while selenium tended to decrease among smokers. Plasma Cu was positively correlated with the consumption of monounsaturated and polyunsaturated fats. Plasma Mn was directly correlated with the consumption of dairy products. Levels of Se were positively correlated with age, the consumption of fruit, vegetables, energy obtained from carbohydrates, and the consumption of fibre, and inversely correlated with the consumption of meat and sweets. Our results provide an estimate of the copper, manganese and selenium status in the adult population of southern Spain. The correlations found for Se suggest that there is a tendency for Se levels to be better maintained among the population that shows a stronger preference for the traditional diet., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Exposure to environmental levels of lead (Pb) and manganese (Mn) has been associated with detrimental effects to neurodevelopment. However, little is known about the potential association between environmental levels of Pb and Mn on intelligence of children. The aims of the study were to investigate the association of community level of Pb and Mn with the intelligence of school-aged children, and to explore the implications of joint exposure to these two heavy metals., Methods: A cross-sectional examination of blood Pb and Mn concentrations was performed, and the intelligence quotient (IQ) was determined for 261 Korean children aged 8-11 years., Results: The mean blood concentrations of Pb and Mn were 1.73 microg/dL (SD=0.8; median=1.55; range=0.42-4.91) and 14.3 microg/L (SD=3.8; median=14.0; range=5.30-29.02), respectively. Both Pb and Mn showed significant linear relationship with full-scale IQ (Pb, beta=-0.174, p=0.005; Mn, beta=-0.123, p=0.042) and verbal IQ (Pb, beta=-0.187, p=0.003; Mn, beta=-0.127, p=0.036). Blood Pb (DeltaR(2)=0.03) and Mn (DeltaR(2)=0.01) explained 4% of the variances of the full-scale IQ and 5% of the variances of the verbal IQ. When Pb and Mn levels were entered as predictive variables, additive increase in the explained variances was observed. Finally, full-scale IQ and verbal IQ of the children with blood Mn>14 microg/L showed significant association with Pb, whereas group with Mn<14 microg/L did not, suggesting effect modification between Pb and Mn., Conclusions: The present study suggests the presence of additive interaction and effect modification between Pb and Mn on the intelligence of school-aged children, suggesting more attention should be paid to preventing the exposure of disadvantaged children to various combinations of toxic materials.

Manganese (Mn) is considered an essential metal; nevertheless, excessive Mn exposure in humans is known to affect central nervous system. Mn access to its toxic target, the brain, is a complex phenomenon subject to physiological and physiopathological processes; in which, among others, the route of exposure plays an important role. Mn airborne exposure has gained interest both in occupational and environmental studies in order to understand the effects of low-level, long-term exposure. The objective of the present study was to describe the relationship between blood Mn and prolactin as marker of effect exposure, as well as other variables from subjects dwelling in a mining district in central Mexico environmentally exposed to the metal. This study was conducted on 230 volunteers; blood samples were obtained from cubital vein and hemoglobin, prolactin, lead (Pb), and Mn levels were measured. Non-parametrical Spearman's correlation showed statistical associations between blood and Mn levels and prolactin (rho=0.197), hemoglobin (rho= -0.213), age (rho= -0.186), and blood lead (rho= -0.167). Multiple regression analysis showed that blood Mn levels as an important factor to determine serum prolactin levels (beta=0.111, p=0.029) in a model corrected by gender and age. Results suggest that assessment of Mn exposure by biomarkers on general population is complex due to the variability and characteristics of the metal; however, specific subpopulations such as iron-deficient individuals are suspected to accumulate Mn in blood and thus they may be susceptible to the neurotoxic effects of Mn.

This study assessed the possibility of relationship between manganese and lead levels in blood in schoolchildren residing in different geographical regions of South Africa. A cross-sectional survey was carried out in schools of three cities: Cape Town (11 schools), Johannesburg (10 schools), Kimberley (six schools) and in the Northern Cape in three rural sites (four schools). A total of 1282 venous blood samples were collected from grade one children. The relationships between blood manganese and blood lead levels (treating each in turn as the response variable in order to adjust for the effect of confounding variables) were investigated by fitting mixed models. Mixed models were fitted with natural log (manganese concentration) as the response variable, and blood lead level as the principal explanatory factor. The model also included terms for centre and a centre by lead interaction and examined potential confounders. The important confounders were found to be gender, race and whether there was paint peeling from the outside walls. There was a significant centre by lead interaction (P<0.0001) with the effect of lead on ln(Mn) being different in the various centres. Mixed models fitted with blood lead level as the response variable and blood manganese as the principal explanatory factor, with terms for centre, a centre by manganese interaction and potential confounders, again found overwhelming evidence (P<0.0001) of a centre by manganese interaction. The study found great variability in both blood lead and manganese levels, both within and between sites, and there was not a consistent relationship between the two metals in the four sites.

Overexposure to manganese (Mn) causes neurotoxicity (a Parkinson-like syndrome) or psychiatric damage ("manganese madness"). Several studies have shown alterations to motor and neural behavior associated with exposure to Mn in the workplace. However, there are few studies on the effects of environmental exposure of whole populations. We studied the risk of motor alterations in people living in a mining district in Mexico. We studied 288 individual people (168 women and 120 men) from eight communities at various distances from manganese extraction or processing facilities in the district of Molango. We measured manganese concentrations in airborne particles, water, soil and crops and evaluated the possible routes of Mn exposure. We also took samples of people's blood and determined their concentrations of Mn and lead (Pb). We used "Esquema de Diagnóstico Neuropsicológico" Ardila and Ostrosky-Solís's neuropsychological battery to evaluate motor functions. Concentrations of Mn in drinking water and maize grain were less than detection limits at most sampling sites. Manganese extractable by DTPA in soils ranged between 6 and 280 mg kg(-1) and means were largest close to Mn extraction or processing facilities. Air Mn concentration ranged between 0.003 and 5.86 microg/m(3); the mean value was 0.42 microg/m(3) and median was 0.10 microg/m(3), the average value (geometric mean) resulted to be 0.13 microg/m(3). Mean blood manganese concentration was 10.16 microg/l, and geometric mean 9.44 microg/l, ranged between 5.0 and 31.0 mcrog/l. We found no association between concentrations of Mn in blood and motor tests. There was a statistically significant association between Mn concentrations in air and motor tests that assessed the coordination of two movements (OR 3.69; 95% CI 0.9, 15.13) and position changes in hand movements (OR 3.09; CI 95% 1.07, 8.92). An association with tests evaluating conflictive reactions (task that explores verbal regulations of movements) was also found (OR 2.30; CI 95% 1.00, 5.28). It seems from our results that people living close to the manganese mines and processing plants suffer from an incipient motor deficit, as a result of their inhaling manganese-rich dust.

Unlabelled: Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se., Population and Methods: 248 mother-newborn pairs were recruited at Robert Debré University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed., Results: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model., Conclusion: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns.

As lead is phased out of gasoline, other additives with anti-knock properties, particularly organic manganese compounds, are being substituted. Unavoidably, such compounds go through the combustion process, are eliminated in exhaust gases, and become part of the city environment. To obtain some indication of the extent of this new pollution street soils from various locations in a heavily trafficked city (Newark, NJ) were analyzed for manganese and lead by atomic absorption. Highly signigicant inverse relationships were found between the concentrations of both contaminants and distances from major traffic arteries. Strong circumstantial evidence is thus provided that: 1) manganese pollution is occurring, along with lead, in the city environment; 2) this new pollution is related to traffic density; and 3) the most likely sources are automobile exhausts. This suspicion is further strengthened by the significant correlations observed between manganese and lead contents in children's blood, suggesting a common source for both. Substantiation of the safety of this practice of adding manganese to gasoline is needed.