Search

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 μg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Manganese (Mn) is an essential nutrient; however, overexposure can be neurotoxic. Recent evidence suggests that exposure to Mn from drinking water could be neurotoxic; however, research is hampered by the lack of consensus on a reliable biomarker of Mn exposure. Naturally high concentrations of Mn can occur in groundwater, particularly for private, unregulated water systems. This study aimed to investigate the association between exposure to Mn from drinking water with a relatively low Mn content (median of 2.9 μg/L; range, undetectable-8,340 μg/L) and Mn in toenails from women collected at two time points: during and after pregnancy. Mn concentrations in the paired toenail samples gathered during the second to third trimester of pregnancy and 2 weeks postpartum were correlated (r = 0.47, p < 0.001, n = 596). Among women consuming drinking water Mn in the highest tertile (i.e., > 9.8 μg/L) significant positive correlations were found between water Mn and toenails Mn (r = 0.31 and r = 0.38, for toenail samples collected during pregnancy and postpartum, respectively), whereas little to no correlation was observed at lower water concentrations. Overall, our data suggest that maternal toenail samples are a reliable environmental Mn exposure biomarker and reflect exposure from drinking water.

Background: Manganese is an essential nutrient, but in excess, can be a potent neurotoxicant. We previously reported findings from two cross-sectional studies on children, showing that higher concentrations of manganese in drinking water were associated with deficits in IQ scores. Despite the common occurrence of this neurotoxic metal, its concentration in drinking water is rarely regulated., Objective: We aimed to apply a benchmark concentration analysis to estimate water manganese levels associated with pre-defined levels of cognitive impairment in children, i.e. drop of 1%, 2% and 5% in Performance IQ scores., Methods: Data from two studies conducted in Canada were pooled resulting in a sample of 630 children (ages 5.9-13.7 years) with data on tap water manganese concentration and cognition, as well as confounders. We used the Bayesian Benchmark Dose Analysis System to compute weight-averaged median estimates for the benchmark concentration (BMC) of manganese in water and the lower bound of the credible interval (BMCL), based on seven different exposure-response models., Results: The BMC for manganese in drinking water associated with a decrease of 1% Performance IQ score was 133 μg/L (BMCL, 78 μg/L); for a decrease of 2%, this concentration was 266 μg/L (BMCL, 156 μg/L) and for a decrease of 5% it was 676 μg/L (BMCL, 406 μg/L). In sex-stratified analyses, the manganese concentrations associated with a decrease of 1%, 2% and 5% Performance IQ in boys were 185, 375 and 935 μg/L (BMCLs, 75, 153 and 386 μg/L) and 78, 95, 192 μg/L (BMCLs, 9, 21 and 74 μg/L) for girls., Conclusion: Studies suggest that a maximum acceptable concentration for manganese in drinking water should be set to protect children, the most vulnerable population, from manganese neurotoxicity. The present risk analysis can guide decision-makers responsible for developing these standards., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Manganese (Mn) is an element found in the environment and certain geographic areas have elevated concentrations in soil and water du to natural conditions or anthropic activities. A growing body of data suggests that exposure to manganese in drinking water could be neurotoxic., Objective: Firstly, we aimed to examine the association between exposure to manganese from drinking water and cognition in children consuming well water. Secondly, we also aimed to examine the relation between cognition and manganese concentrations in children's hair, nail, and saliva., Methods: A total 259 children from 189 households consuming well water were included in the present study (ages 5.9 to 13.7 years). We assessed children's cognition with the WISC-IV, and we used five indicators of manganese exposure: concentration in tap water, intake from the consumption of water divided by child's weight, manganese concentration in children's hair, toe nail, and saliva. We used General Estimating Equation analysis to assess the relation between manganese exposure indicators and IQ scores, adjusting for potential confounders, and taking into account family clusters., Results: Drinking water manganese concentrations were generally low, with 48% of children consuming water <5μg/L, 25% >50μg/L, and 4% >400μg/L. Results differed by sex. In girls, higher manganese concentration in water, hair, and toe nail were associated with poorer Performance IQ scores but this was significant only for toe nail (for a 10-fold increase in manganese, β: -5.65, 95% CIs: -10.97, -0.32). Opposite associations were observed in boys, i.e., better Performance IQ scores with higher manganese concentration hair, toe nail, and water, the latter being significant (β: 2.66, 95% CIs: 0.44, 4.89). Verbal IQ scores did not seem to be associated with manganese exposure indicators., Conclusions: Drinking water manganese levels were considerably lower than in previous studies reporting neurotoxic effects. There was no clear indication of an association between exposure to manganese and cognitive development in this sample of school-age children although the data suggest there might be sex-specific associations. Given the low levels of exposure and sex-specific associations, a larger sample size would have been required to increase the statistical power and better characterize the relations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Manganese is commonly found in water but potential neurotoxic effects from exposure through drinking water are poorly understood. We previously reported a cross-sectional study showing that drinking water Mn concentration was associated with lower IQ in children aged 6 to 13 years., Objective: For this follow-up study, we aimed to re-assess the relation between exposure to Mn from drinking water and IQ at adolescence. In addition, we aimed to examine whether changes in drinking water Mn concentration was associated with changes in IQ scores., Methods: From the 380 children enrolled in the baseline study, 287 participated to this follow-up study conducted in average 4.4 years after. Mn concentration was measured in home tap water and children's hair. The relationships between these Mn exposure indicators and IQ scores (Weschsler Abbreviated Scale of Intelligence) at follow-up were assessed with linear regression analysis, adjusting for potential confounders. Intra-individual differences in IQ scores between the two examinations were compared for children whose Mn concentration in water remained stable between examinations, increased or decreased., Results: The mean age at follow-up was 13.7 years (range, 10.5 to 18.0 years). Geometric mean of Mn concentration in water at follow-up was 14.5μg/L. Higher Mn concentration in water measured at follow-up was associated with lower Performance IQ in girls (β for a 10-fold increase=-2.8, 95% confidence intervals [CI] -4.8 to -0.8) and higher Performance IQ in boys (β=3.9, 95% CI 1.4 to 6.4). IQ scores were not significantly associated with Mn concentration in hair, although similar trends as for concentration in water were observed. For children whose Mn concentration in water increased between baseline and follow-up, Performance IQ scores decreased significantly (intra-individual difference, -2.4 points)., Conclusion: Higher levels of Mn in drinking water were associated with lower Performance IQ in girls, whereas the opposite was observed in boys. These findings suggest long-term exposure to Mn through drinking water is associated differently with cognition in boys and girls., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We evaluated hair, toenails, and saliva (whole and supernatant) as biomarkers of exposure to manganese (Mn) in 274 school age children (6-13 years) consuming well water in southeastern New Brunswick, Canada. Mn concentrations in tap water ranged from <0.03 to 1046μgL -1 (geometric mean 5.96μgL -1 ). The geometric mean of Mn intake resulting from the consumption of water was 0.25 (0-34.95) μg kg -1 day -1 . Both Mn concentration in water and Mn intake were significantly correlated with Mn in hair (r=0.60 and r=0.53, respectively), Mn in toenail (r=0.29 and r=0.37 respectively) and to a lesser extent with Mn in saliva supernatant (r=0.14 and r=0.18, respectively). Mn in whole saliva did not correlate with Mn in water or Mn intake. Both Mn in hair and Mn in toenail allowed to discriminate the most exposed group from the least exposed group, based on Mn in water and Mn intake from water. In this group of children with low level Mn exposure, Mn concentrations in hair, and toenails reflected reasonably well Mn exposure from drinking water, whereas Mn content in saliva correlated less strongly., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Previous research suggests that exposure to pesticides might be associated with human myopia, although data were obtained only from highly exposed individuals. The present study aimed to assess whether exposure to organophosphates and pyrethroids in the United States general population was associated with the prevalence of myopia., Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES, years 1999-2008). One-spot urine samples were used to estimate the concentration of several pesticide metabolites. Exposure data and equivalent spherical refraction errors were available for 5147 and 2911 individuals for organophosphates and pyrethroids, respectively. Multiple logistic regression models were used to assess the relation between log10-transformed urinary levels of pesticide metabolites and the risk of moderate (≤-1 and >-5 diopters [D]) and high myopia (≤-5 D) in adolescents (12- to 19-years old) and young adults (20- to 40-years old). Models were adjusted for sex, age, ethnicity, diabetes, creatinine, cadmium and lead concentrations, and income in both age groups, but also for education level and cigarette and alcohol consumption in the adult group., Results: No association between organophosphates or pyrethroid metabolites and myopia was observed. However, after adjusting for education level and cigarette and alcohol consumption, a statistically significant decreased risk of high myopia in those with a 10-fold increase of dialkyl phosphate metabolites was found in adults but only in men (P < 0.05)., Conclusions: Our results suggest that exposure to organophosphates or pyrethroids do not increase the risk of myopia in the United States general population.

Background: Prenatal bisphenol A (BPA) exposure has been associated with adverse neurodevelopment in epidemiological studies. However, prior studies had limited statistical power to examine sex-specific effects, and few examined child cognition., Objectives: We estimated the association between prenatal BPA exposure and child neurobehavior at 3 y of age in a prospective cohort of 812 mothers and their children., Methods: We measured BPA concentration in urine samples collected at ∼12 wk gestation among women enrolled in a 10-city Canadian cohort study. At approximately 3 y of age, we assessed children’s cognitive abilities with the Wechsler Primary and Preschool Scale of Intelligence TM –III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function–Preschool (BRIEF-P). Parents reported children’s behavior using the Behavior Assessment System for Children–2 (BASC-2) and the Social Responsiveness Scale TM –2 (SRS-2). We estimated covariate-adjusted differences in neurobehavioral outcomes with a doubling in BPA concentration and sex-specific associations., Results: BPA was not associated with WPPSI-III scores; child sex did not modify these associations. The association between BPA and BRIEF-P scores was modified by child sex (BPA×sex  p -values≤0.03). For example, a doubling of BPA concentration was associated with 1-point (95% CI: 0.3, 1.7) poorer working memory in boys and 0.5-point (95% CI: −1.1, 0.1) better scores in girls. BPA was not associated with most BASC-2 scales; however, it was associated with more internalizing and somatizing behaviors in boys, but not in girls (BPA×sex p& -values≤0.08). A doubling of BPA concentration was associated with poorer SRS-2 scores [β=0.3 ( 95% CI: 0, 0.7)]; this association was not modified by sex., Conclusion: Prenatal urinary BPA concentration was associated with some aspects of child behavior in this cohort, and some associations were stronger among boys. https://doi.org/10.1289/EHP984.

Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children., Competing Interests: The authors declare no competing financial interests.

Context: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a wide range of products, resulting in widespread human exposure. Epidemiological studies in some populations reported exposure to PBDEs and thyroid hormone levels but little epidemiological data are available among women from the general population., Objective: The objective of the study was to examine the association of PBDEs with hypothyroidism., Design and Setting: This was a cross-sectional analysis of the 2007-2009 Canadian Health Measures Survey., Participants: A total of 745 women representative of Canadian women aged 30-79 years participated in the study. Main Outcome and Methods: We estimated the prevalence ratios (PRs) for hypothyroidism in relation to plasma concentrations of BDE-47, -99, -100, and -153 and their sum (ΣPBDEs). Women were identified as cases if they reported a doctor-diagnosed thyroid condition and underwent thyroid hormone replacement therapy (n = 90)., Results: Higher plasma levels of brominated diphenyl ether (BDE)-47 and -100 and ΣPBDEs were associated with an increased prevalence of hypothyroidism. The PR for a 10-fold increase in ΣPBDEs was 1.7 (95% confidence interval [CI] 1.0, 3.0). Associations were consistently higher among women aged 30-50 years than among those 51-79 years for ΣPBDEs and the other PBDE congeners, although the interaction was significant only for BDE-100. For instance, in the younger age group, women with detectable levels of BDE-100 had a PR of 3.8 (95% CI 1.2, 12.3) compared with women with undetectable levels; the corresponding PR in the older age group was 1.2 (95% CI 0.6, 2.3). No association was observed for BDE-99 and -153., Conclusion: Plasma PBDE levels were associated with an increased prevalence of hypothyroidism in Canadian women aged 30-50 years. Although the cross-sectional design of the study limits inferences of causality, these findings have important implications, given the key role of thyroid hormones in several biological mechanisms during reproductive age.

Background: Exposure to organophosphate pesticides has been associated with neurobehavioral deficits in children, although data on low levels of exposure experienced by the general population are sparse. Pyrethroids are insecticides rapidly gaining popularity, and epidemiological evidence on their potential effects is lacking., Objective: We examined the association between exposure to organophosphate and pyrethroid pesticides, indicated by urinary metabolites, and parentally reported behavioral problems in children., Methods: We used data on children 6-11 years of age from the Canadian Health Measures Survey (2007-2009). We used logistic regressions to estimate odds ratios (ORs) for high scores on the Strengths and Difficulties Questionnaire (SDQ), which may indicate behavioral problems, in association with concentrations of pyrethroid and organophosphate metabolites in the urine of 779 children, adjusting for covariates (sex, age, race/ethnicity, income, parental education, blood lead levels, maternal smoking during pregnancy, and others)., Results: At least one urinary metabolite for organophosphates was detected in 91% of children, and for pyrethroids in 97% of children. Organophosphate metabolites were not significantly associated with high SDQ scores. The pyrethroid metabolite cis-DCCA [3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid] was significantly associated with high scores for total difficulties on the SDQ (OR for a 10-fold increase = 2.0; 95% CI: 1.1, 3.6), and there was a nonsignificant association with trans-DCCA (OR = 1.6; 95% CI: 0.9, 3.0)., Conclusion: In contrast with previous studies, we did not observe an association between exposure to organophosphate pesticides and behavioral scores in children. However, some pyrethroid urinary metabolites were associated with a high level of parent-reported behavioral problems. Longitudinal studies should be conducted on the potential risks of pyrethroids.

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.)

Background: Manganese is an essential nutrient, but in excess it can be a potent neurotoxicant. Despite the common occurrence of manganese in groundwater, the risks associated with this source of exposure are largely unknown., Objectives: Our first aim was to assess the relations between exposure to manganese from drinking water and children's intelligence quotient (IQ). Second, we examined the relations between manganese exposures from water consumption and from the diet with children's hair manganese concentration., Methods: This cross-sectional study included 362 children 6-13 years of age living in communities supplied by groundwater. Manganese concentration was measured in home tap water (MnW) and children's hair (MnH). We estimated manganese intake from water ingestion and the diet using a food frequency questionnaire and assessed IQ with the Wechsler Abbreviated Scale of Intelligence., Results: The median MnW in children's home tap water was 34 µg/L (range, 1-2,700 µg/L). MnH increased with manganese intake from water consumption, but not with dietary manganese intake. Higher MnW and MnH were significantly associated with lower IQ scores. A 10-fold increase in MnW was associated with a decrease of 2.4 IQ points (95% confidence interval: -3.9 to -0.9; p < 0.01), adjusting for maternal intelligence, family income, and other potential confounders. There was a 6.2-point difference in IQ between children in the lowest and highest MnW quintiles. MnW was more strongly associated with Performance IQ than Verbal IQ., Conclusions: The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children.