Search tips
Search criteria

Results 1-20 (20)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Maternal and Neonatal Levels of Perfluoroalkyl Substances in Relation to Gestational Weight Gain 
Perfluoroalkyl substances (PFASs) are ubiquitous, persistent pollutants widely used in the production of common household and consumer goods. There is a limited body of literature suggesting that these chemicals may alter metabolic pathways and growth trajectories. The relationship between prenatal exposures to these chemicals and gestational weight gain (GWG) has received limited attention. One objective was to analyze the associations among maternal plasma levels of three common perfluoroalkyl substances (perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS)) and GWG. Additionally, we explored whether GWG was associated with cord blood PFAS levels. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analysis quantified associations between (1) maternal PFAS concentrations and GWG and (2) GWG and cord blood PFAS concentrations. Maternal PFOS concentrations were positively associated with GWG (β = 0.39 95% CI: 0.02, 0.75). Interquartile increases in GWG were significantly associated with elevated cord blood PFOA (OR = 1.33; 95% CI: 1.13 to 1.56) and PFOS (OR = 1.20; 95% CI: 1.03 to 1.40) concentrations. No statistically significant associations were observed between GWG and either measure of PFHxS. These findings warrant elucidation of the potential underlying mechanisms.
PMCID: PMC4730537  PMID: 26805861
perfluoroalkyl substances; gestational weight gain; environmental contaminants; birth cohort
2.  Respiratory manganese particle size, time-course and neurobehavioral outcomes in workers at a manganese alloy production plant 
Neurotoxicology  2014;45:276-284.
The progression of manganism with chronic exposure to airborne manganese (Mn) is not well understood. Here, we further investigate the findings on exposure and neurobehavioral outcomes of workers from a silico- and ferromanganese production plant and non-exposed workers from the same community in 1990 and 2004, using a variety of exposure metrics that distinguish particle size and origin within the range of respirable airborne exposures. Mn exposure matrices for large respirable particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based on process origins, were used together with detailed work histories since 1973 (plant opening), to construct exposure metrics including burdens and cumulative burdens with various clearance half-lives. For three out of eight 1990 neurobehavioral tests analyzed with linear regression models, duration of Mn exposure was the best predictor: Luria-Nebraska Neuropsychological Battery – Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale had the strongest association (t ~ 5.0, p < 10−6). For outcomes on three other tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A, Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word Recall was best predicted by Mn-SRP (based on square root or truncated air-concentrations). The Word score on the Stroop Color-Word Test was the only outcome for which Mn-LRP was the leading predictor (t = −2.92, p = 0.003), while performance on the WAIS-R Digit Span Test was not significantly predicted by any metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear regression model was used to examine estimates of within-individual trends. Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor Scale, as well as with other outcomes that appeared to have both reversible and progressive features, including Trail Making A and B, Cancellation H and Delayed Word Recall. With the mixed-effect model, Digit Span exhibited a significant irreversible association with exposure duration (t = −2.34, p = 0.021) and Mn-SRP (square root; t =−2.38, p = 0.019) metrics. The strong prediction using duration of exposure is consistent with effective homeostatic regulation of tissue-level Mn in the observed exposure range of respirable Mn (<0.2 mg/m3).
PMCID: PMC4552041  PMID: 24721790
Manganese; Burden; Fume; Half-life; Homeostasis
3.  Airborne manganese as dust vs. fume determining blood levels in workers at a manganese alloy production plant 
Neurotoxicology  2014;45:267-275.
The appropriate exposure metrics for characterizing manganese (Mn) exposure associated with neurobehavioral effects have not been established. Blood levels of Mn (B-Mn) provide a potentially important intermediate marker of Mn airborne exposures. Using data from a study of a population of silicon- and ferro-manganese alloy production workers employed between 1973 and 1991, B-Mn levels were modeled in relation to prior Mn exposure using detailed work histories and estimated respirable Mn concentrations from air-sampling records. Despite wide variation in exposure levels estimated for individual jobs, duration of employment (exposure) was itself a strong predictor of B-Mn levels and strongest when an 80-day half-life was applied to contributions over time (t = 6.95, 7.44, respectively; p < 10 −5). Partitioning exposure concentrations based on process origin into two categories: (1) “large” respirable particulate (Mn-LRP) derived mainly from mechanically generated dust, and (2) “small” respirable particulate (Mn-SRP) primarily electric furnace condensation fume, revealed that B-Mn levels largely track the small, fume exposures. With a half-life of 65 days applied in a model with cumulative exposure terms for both Mn-LRP (t = −0.16, p = 0.87) and Mn-SRP (t = 6.45, p < 10 −5), the contribution of the large-size fraction contribution was negligible. Constructing metrics based on the square root of SRP exposure concentrations produced a better model fit (t = 7.87 vs. 7.44, R2 = 0.2333 vs. 0.2157). In a model containing both duration (t = 0.79, p = 0.43) and (square root) fume (t = 2.47, p = 0.01) metrics, the duration term was a weak contributor. Furnace-derived, small respirable Mn particulate appears to be the primary contributor to B-Mn levels, with a dose-rate dependence in a population chronically exposed to Mn, with air-concentrations declining in recent years. These observations may reflect the presence of homeostatic control of Mn levels in the blood and other body tissues and be useful in assessing Mn exposures for evaluating neurotoxic effects.
PMCID: PMC4552042  PMID: 24726792
Manganese; Respiratory particle size; Half-life; Blood manganese; Manganese alloy production
4.  Neurobehavioral Function in School-Age Children Exposed to Manganese in Drinking Water 
Environmental Health Perspectives  2014;122(12):1343-1350.
Background: Manganese neurotoxicity is well documented in individuals occupationally exposed to airborne particulates, but few data are available on risks from drinking-water exposure.
Objective: We examined associations of exposure from concentrations of manganese in water and hair with memory, attention, motor function, and parent- and teacher-reported hyperactive behaviors.
Methods: We recruited 375 children and measured manganese in home tap water (MnW) and hair (MnH). We estimated manganese intake from water ingestion. Using structural equation modeling, we estimated associations between neurobehavioral functions and MnH, MnW, and manganese intake from water. We evaluated exposure–response relationships using generalized additive models.
Results: After adjusting for potential confounders, a 1-SD increase in log10 MnH was associated with a significant difference of –24% (95% CI: –36, –12%) SD in memory and –25% (95% CI: –41, –9%) SD in attention. The relations between log10 MnH and poorer memory and attention were linear. A 1-SD increase in log10 MnW was associated with a significant difference of –14% (95% CI: –24, –4%) SD in memory, and this relation was nonlinear, with a steeper decline in performance at MnW > 100 μg/L. A 1-SD increase in log10 manganese intake from water was associated with a significant difference of –11% (95% CI: –21, –0.4%) SD in motor function. The relation between log10 manganese intake and poorer motor function was linear. There was no significant association between manganese exposure and hyperactivity.
Conclusion: Exposure to manganese in water was associated with poorer neurobehavioral performances in children, even at low levels commonly encountered in North America.
Citation: Oulhote Y, Mergler D, Barbeau B, Bellinger DC, Bouffard T, Brodeur ME, Saint-Amour D, Legrand M, Sauvé S, Bouchard MF. 2014. Neurobehavioral function in school-age children exposed to manganese in drinking water. Environ Health Perspect 122:1343–1350;
PMCID: PMC4256698  PMID: 25260096
5.  The Orthopaedic Trauma Patient Experience: A Qualitative Case Study of Orthopaedic Trauma Patients in Uganda 
PLoS ONE  2014;9(10):e110940.
The disability adjusted life years (DALYs) associated with injuries have increased by 34% from 1990 to 2010, making it the 10th leading cause of disability worldwide, with most of the burden affecting low-income countries. Although disability from injuries is often preventable, limited access to essential surgical services contributes to these increasing DALY rates. Similar to many other low- and middle-income countries (LMIC), Uganda is plagued by a growing volume of traumatic injuries. The aim of this study is to explore the orthopaedic trauma patient's experience in accessing medical care in Uganda and what affects the injury might have on the socioeconomic status for the patient and their dependents. We also evaluate the factors that impact an individual's ability to access an appropriate treatment facility for their traumatic injury. Semi-structured interviews were conducted with patients 18 year of age or older admitted with a fractured tibia or femur at Mulago National Referral Hospital in Kampala, Uganda. As limited literature exists on the socioeconomic impacts of disability from trauma, we designed a descriptive qualitative case study, using thematic analysis, to extract unique information for which little has been previously been documented. This methodology is subject to less bias than other qualitative methods as it imposes fewer preconceptions. Data analysis of the patient interviews (n = 35) produced over one hundred codes, nine sub-themes and three overarching themes. The three overarching categories revealed by the data were: 1) the importance of social supports; 2) the impact of and on economic resources; and 3) navigating the healthcare system. Limited resources to fund the treatment of orthopaedic trauma patients in Uganda leads to reliance of patients on their friends, family, and hospital connections, and a tremendous economic burden that falls on the patient and their dependents.
PMCID: PMC4215992  PMID: 25360815
6.  Sex- and age-differences in blood manganese levels in the U.S. general population: national health and nutrition examination survey 2011–2012 
Environmental Health  2014;13:87.
Manganese is an essential element, but excessive manganese exposure has neurotoxic effects.
To examine blood manganese levels in the general population with respect to sex, age, race/ethnicity, pregnancy and menauposal status, as well as levels of trace elements in blood.
We used data from the National Health and Nutrition Examination Survey, a national survey of U.S. residents (n = 7720 participants, ages 1 to 80 years). General linear models and generalized additive models were used to examine the association between blood manganese concentration and participants’ characterisics, accounting for the complex survey design.
Blood manganese levels ranged from 1.6 to 62.5 μg/L, with arithmetic means of 10.6 and 9.2 μg/L for women and men, respectively. The following characteristics were significantly associated with higher blood manganese levels: female sex, younger age, Asian origin, and being pregnant. In addition, there were non-linear relationships between blood manganese levels and cadmium, iron, lead, and mercury levels.
The higher blood manganese levels observed among females suggest sex-related metabolic differences in the regulation of manganese, and elevated levels among pregnant women suggest an important role of manganese in reproduction. The present study supports the need to take into consideration age- and sex-related differences in blood manganese levels, as well as pregnancy status when examining manganese essentiality or toxicity.
PMCID: PMC4271487  PMID: 25342305
Blood manganese; Sex; Age; Population survey; NHANES
7.  A birth cohort study to investigate the association between prenatal phthalate and bisphenol A exposures and fetal markers of metabolic dysfunction 
Environmental Health  2014;13:84.
Obesity and type-2 diabetes are on the rise and in utero exposure to environmental contaminants is a suspected contributing factor. Our objective was to examine associations between prenatal exposure to potential endocrine disrupting chemicals and markers of fetal metabolic dysfunction.
The Maternal-Infant Research on Environmental Chemicals Study (MIREC) recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. First trimester maternal urine was measured for 11 phthalate metabolites and bisphenol A (BPA). Leptin and adioponectin measured in 1,363 available umbilical cord blood samples served as markers of metabolic function. Restricted cubic spline curves were used to assess the relationship between continuous measures of phthalate and BPA levels and cord blood adipokines. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between phthalates and BPA and both high (≥90th percentile) and low (≤10th percentile) fetal adiponectin and leptin, adjusting for confounding factors. Analyses were conducted for all subjects, overall, and separately by fetal sex.
Leptin was significantly higher in female than male infants. We observed an inverse, non-linear relationship between BPA and adiponectin among males in the restricted cubic spline and linear regression analysis. Mono-(3-carboxypropyl) (MCPP) was associated with increased odds of high leptin among males in the polytomous logistic regression models (4th quartile OR = 3.5 95% CI: 1.1-11.6).
Our findings contribute to the growing body of evidence examining the influence of early life exposure on metabolic regulation and function. Associations between maternal exposure to chemicals and markers of metabolic function appear to be potentially sex specific. However, further investigation is required to determine whether in utero and childhood exposure to BPA and phthalates are associated with metabolic dysfunctions later in life.
PMCID: PMC4271497  PMID: 25336252
Phthalates; Bisphenol A; Leptin; Adiponectin; Pregnancy; Cohort study; Canada
8.  Polychlorinated Biphenyl Exposures and Cognition in Older U.S. Adults: NHANES (1999–2002) 
Background: Polychlorinated biphenyls (PCBs) are ubiquitously present in humans because of their resistance to degradation and accumulation in fatty tissues. Data on neurotoxic effects in older adults are limited.
Objective: We examined the cross-sectional association between serum PCB concentrations and cognitive function in older adults from the general U.S. population.
Methods: We analyzed data from 708 respondents, 60–84 years of age, participating in the National Health and Nutrition Examination Survey (1999–2002). We used the summed concentrations of 12 lipid-standardized PCB congeners as the measure of exposure and assessed cognitive function with the Digit-Symbol Coding test. We adjusted analyses for age, education, race/ethnicity, and poverty/income ratio.
Results: The median concentration of lipid-standardized PCBs in serum was 271 ng/g (interquartile range, 193–399 ng/g). We found a significant interaction between dioxin-like PCB concentration and age in association with cognitive score (p = 0.04). Among older individuals (70–84 years of age), a 100-ng/g increase in serum concentrations of dioxin-like PCBs was associated with a significantly lower cognitive score (–2.7 points; 95% CI: –5.1, –0.2; p = 0.04); however, in younger individuals (60–69 years of age), there was a nonsignificant positive association (2.9 points; 95% CI: –1.8, 7.7; p = 0.32). Among the older participants, the negative association was more pronounced in women than in men.
Conclusion: Our findings support the hypothesis that PCB exposure has adverse cognitive effects even at levels generally considered to pose low or no risk, perhaps affecting mainly those of advanced age.
Citation: Bouchard MF, Oulhote Y, Sagiv SK, Saint-Amour D, Weuve J. 2014. Polychlorinated biphenyl exposures and cognition in older U.S. adults: NHANES (1999–2002). Environ Health Perspect 122:73–78;
PMCID: PMC3888566  PMID: 24275543
9.  Urinary Metabolites of Organophosphate and Pyrethroid Pesticides and Behavioral Problems in Canadian Children 
Environmental Health Perspectives  2013;121(11-12):1378-1384.
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.
Citation: Oulhote Y, Bouchard MF. 2013. Urinary metabolites of organophosphate and pyrethroid pesticides and behavioral problems in Canadian children. Environ Health Perspect 121:1378–1384;
PMCID: PMC3855516  PMID: 24149046
10.  Neurobehavioural and neurodevelopmental effects of pesticide exposures 
Neurotoxicology  2012;33(4):887-896.
The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective and neurodevelopmental outcomes amongst occupational (both adolescent and adult workers) and non-occupational populations (children). The symposium discussion highlighted many challenges for researchers concerned with the prevention of neurotoxic illness due to pesticides and generated a number of directions for further research and policy interventions for the protection of human health, highlighting the importance of examining potential long-term effects across the lifespan arising from early adolescent, childhood or pre-natal exposure.
PMCID: PMC3371394  PMID: 22269431
pesticides; neurobehavioural; neurodevelopmental; toxicity; acute poisoning; long-term exposures; injury; affective disorders
Pediatrics  2010;125(6):e1270-e1277.
Exposure to organophosphate (OP) pesticides is common, and although these compounds have known neurotoxic properties, few studies examined risks for children in the general population.
To examine the association between the concentrations of urinary dialkyl phosphate (DAP) metabolites of OPs and attention deficit/hyperactivity disorder (ADHD) in children age 8 to 15 years.
Participants and Methods
Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1,139 children representative of the general U.S. population. A structured interview with a parent was used to ascertain ADHD diagnostic status, based on slightly modified criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV.
One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher concentrations of urinary DAPs, especially dimethyl alkylphosphates (DMAP), were more likely to be diagnosed with ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio (OR) of 1.55 (95% confidence intervals [CI], 1.14–2.10), after adjusting for sex, age, race/ethnicity, poverty-income ratio, fasting duration, and urinary creatinine concentration. For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had double the odds of ADHD (adjusted OR, 1.93 [95% CI, 1.23–3.02]) compared with those with non-detectable levels.
These findings support the hypothesis that OP exposure, at levels common in U.S. children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.
PMCID: PMC3706632  PMID: 20478945
attention deficit/hyperactivity disorder; ADHD; pesticides; organophosphates; OP; National Health and Nutrition Examination Survey; NHANES; Center for Health Statistics; NCHS; Centers for Disease Control and Prevention; CDC
12.  Corruption in the health care sector: A barrier to access of orthopaedic care and medical devices in Uganda 
Globally, injuries cause approximately as many deaths per year as HIV/AIDS, tuberculosis and malaria combined, and 90% of injury deaths occur in low- and middle- income countries. Given not all injuries kill, the disability burden, particularly from orthopaedic injuries, is much higher but is poorly measured at present. The orthopaedic services and orthopaedic medical devices needed to manage the injury burden are frequently unavailable in these countries. Corruption is known to be a major barrier to access of health care, but its effects on access to orthopaedic services is still unknown.
A qualitative case study of 45 open-ended interviews was conducted to investigate the access to orthopaedic health services and orthopaedic medical devices in Uganda. Participants included orthopaedic surgeons, related healthcare professionals, industry and government representatives, and patients. Participants’ experiences in accessing orthopaedic medical devices were explored. Thematic analysis was used to analyze and code the transcripts.
Analysis of the interview data identified poor leadership in government and corruption as major barriers to access of orthopaedic care and orthopaedic medical devices. Corruption was perceived to occur at the worker, hospital and government levels in the forms of misappropriation of funds, theft of equipment, resale of drugs and medical devices, fraud and absenteeism. Other barriers elicited included insufficient health infrastructure and human resources, and high costs of orthopaedic equipment and poverty.
This study identified perceived corruption as a significant barrier to access of orthopaedic care and orthopaedic medical devices in Uganda. As the burden of injury continues to grow, the need to combat corruption and ensure access to orthopaedic services is imperative. Anti-corruption strategies such as transparency and accountability measures, codes of conduct, whistleblower protection, and higher wages and benefits for workers could be important and initial steps in improving access orthopaedic care and OMDs, and managing the global injury burden.
PMCID: PMC3492067  PMID: 22554349
13.  Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year-Old Children 
Environmental Health Perspectives  2011;119(8):1189-1195.
Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development.
Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.
Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.
Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.
Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.
PMCID: PMC3237357  PMID: 21507776
agriculture; children; cognitive development; farmworker; insecticides; intelligence quotient; neurodevelopment; organophosphate; pesticides
14.  Maternal Blood Manganese Levels and Infant Birth Weight 
Epidemiology (Cambridge, Mass.)  2009;20(3):367-373.
Manganese is both an essential element and a known neurotoxicant to children. High manganese exposures have been associated with negative reproductive outcomes in animals, but few epidemiologic studies have examined the effects of human fetal manganese exposure.
We studied the association between maternal and umbilical cord blood manganese levels and birth weight in a cohort of 470 mother-infant pairs born at term (≥37 weeks gestation) in Ottawa County, Oklahoma. Nonlinear spline and quadratic regression models were used to test the hypothesis of an inverted U-shaped relationship between manganese levels and birth weight.
Mean (standard deviation) concentration of manganese was 2.4 (0.95) μg/dL in the maternal blood and 4.2 (1.6) μg/dL in the cord blood. Umbilical cord manganese was not associated with birth weight. A nonlinear relationship was observed between maternal manganese and birth weight after adjusting for potential confounders. Birth weight increased with manganese levels up to 3.1 μg/L, and then a slight reduction in weight was observed at higher levels. Compared with the 3.1-μg/L point of inflection, birth weight estimates at the 5th (1.3 μg/L) and 95th (4.0 μg/L) percentiles of exposure were −160 g (95% confidence interval = −286 to −33) and −46 g (−38 to 131), respectively.
Maternal blood manganese levels during pregnancy are associated with birth weight in a nonlinear pattern in full-term infants. These findings suggest that manganese may affect fetal growth. Possible detrimental effects of elevated manganese levels on the fetus should be further examined in more highly exposed populations.
PMCID: PMC3113478  PMID: 19289966
16.  Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water 
Environmental Health Perspectives  2010;119(1):138-143.
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.
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.
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.
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.
The findings of this cross-sectional study suggest that exposure to manganese at levels common in groundwater is associated with intellectual impairment in children.
PMCID: PMC3018493  PMID: 20855239
children; intellectual quotient; manganese; neurotoxicity; water
17.  Blood lead levels and major depressive disorder, panic disorder, and generalized anxiety disorder in U.S. young adults 
Archives of general psychiatry  2009;66(12):1313-1319.
Lead is a ubiquitous neurotoxicant, and adverse cognitive and behavioral effects are well documented in children and occupationally exposed adults but not in adults with low environmental exposure.
To investigate the association of current blood lead levels with three common psychiatric disorders, major depression, panic, and generalized anxiety, among young adults.
Cross-sectional epidemiologic survey.
Representative sample of non-institutionalized United States adults.
A total of 1,987 respondents of age 20–39 years to the National Health and Nutrition Examination Survey conducted from 1999 to 2004.
Main Outcome Measures
Twelve-month DSM-IV criteria-based diagnoses of major depressive disorder, panic disorder, and generalized anxiety disorder assessed by the Composite International Diagnostic Interview.
Mean blood lead level was 1.61 μg/dL (SD 1.72, range 0.3–37.3 μg/dL). Increasing blood lead level was associated with higher odds of major depression (p for trend 0.05) and panic disorder (p for trend 0.02), but not generalized anxiety disorder (p for trend 0.75), after adjustment for sex, age, race/ethnicity, education, and poverty-income ratio. Persons with blood lead level in the highest quintile had 2.3 times the odds of major depressive disorder (95% CI 1.13 – 4.75) and 4.9 times the odds of panic disorder (95% CI 1.32 – 18.48) as those in the lowest quintile. Cigarette smoking was associated with higher blood lead level and the outcomes, but models excluding current smokers also resulted in significantly increased odds for major depression (p for trend 0.03) and panic disorder (p for trend 0.01) with higher blood lead quintile.
In this sample of young adults with low levels of lead exposure, higher blood lead was associated with increased odds of major depression and panic disorder. Exposure to lead at levels generally considered safe could result in adverse mental health outcomes.
PMCID: PMC2917196  PMID: 19996036
18.  Dose–effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders 
Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore‐processing and ferroalloy production, the risks among welders with lower exposures are less well understood.
Confined space welding in construction of a new span of the San Francisco–Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose–effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn‐air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education.
The mean time weighted average of Mn‐air ranged from 0.11–0.46 mg/m3 (55% >0.20 mg/m3). MnB >10 µg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV1/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose–effect relationships with CEI and/or MnB were found for IQ (p⩽0.05), executive function (p⩽0.03), sustaining concentration and sequencing (p⩽0.04), verbal learning (p⩽0.01), working (p⩽0.04) and immediate memory (p⩽0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose–effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant.
Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.
PMCID: PMC2092523  PMID: 17018581
19.  Lead Exposure and Behavior among Young Children in Chennai, India 
Environmental Health Perspectives  2009;117(10):1607-1611.
Lead exposure has long been associated with deficits in IQ among children. However, few studies have assessed the impact of lead on specific domains of behavior and cognition.
We evaluated the associations between lead and different domains of neurobehavior and their relative sensitivity to lead.
We determined blood lead levels using a LeadCare instrument in 756 children 3–7 years of age attending pre- and elementary schools in Chennai, India. Anxiety, social problems, inattention, hyperactivity, and attention deficit hyperactivity disorder (ADHD), as well as executive function were assessed in children by their schoolteachers using Conners’ Teacher Rating Scales-39, Conners’ ADHD/Diagnostic and Statistical Manual for Mental Disorders, 4th Edition Scales (CADS), and the Behavior Rating Inventory of Executive Function questionnaires, with higher scores denoting worse behavior. Analyses were carried out using multivariate generalized estimating equations with comparisons of outcome Z-scores to assess the relative strengths of the associations between log-blood lead and the different domains of behavior.
Mean blood lead level was 11.4 ± 5.3 μg/dL. Blood lead was associated with higher anxiety (β = 0.27, p = 0.01), social problems (β = 0.20, p = 0.02), and higher scores in the ADHD index (β = 0.17; p = 0.05). The effect estimate was highest for global executive function (β = 0.42; p< 0.001).
Higher blood lead levels in this population of young children is associated with increased risk of neurobehavioral deficits and ADHD, with executive function and attention being particularly vulnerable domains to the effects of lead.
PMCID: PMC2790517  PMID: 20019913
ADHD; anxiety; blood lead; children; executive function; India; sociability
20.  Hair Manganese and Hyperactive Behaviors: Pilot Study of School-Age Children Exposed through Tap Water 
Environmental Health Perspectives  2006;115(1):122-127.
Neurotoxic effects are known to occur with inhalation of manganese particulates, but very few data are available on exposure to Mn in water. We undertook a pilot study in a community in Québec (Canada) where naturally occurring high Mn levels were present in the public water system. Our objective was to test the hypothesis that greater exposure to Mn via drinking water would be reflected in higher Mn content in hair which, in turn, would be associated with increased level of hyperactive behaviors.
Forty-six children participated in the study, 24 boys and 22 girls, 6–15 years of age (median, 11 years). Their homes received water from one of two wells (W) with different Mn concentrations: W1: mean 610 μg/L; W2: mean 160 μg/L. The Revised Conners’ Rating Scale for parents (CPRS-R) and for teachers (CTRS-R) were administered, providing T-scores on the following subscales: Oppositional, Hyperactivity, Cognitive Problems/Inattention, and ADHD Index.
Children whose houses were supplied by W1 had higher hair Mn (MnH) than those supplied by W2 (mean 6.2 ± 4.7 μg/g vs. 3.3 ± 3.0 μg/g, p = 0.025). MnH was significantly associated with T-scores on the CTRS-R Oppositional (p = 0.020) and Hyperactivity (p = 0.002) subscales, after adjustment for age, sex, and income. All children with Oppositional and Hyperactivity T-scores ≥ 65 had MnH > 3.0 μg/g.
The findings of this pilot study are sufficiently compelling to warrant more extensive investigations into the risks of Mn exposure in drinking water.
PMCID: PMC1797845  PMID: 17366831
children; CPRS-R; CTRS-R; hair; hyperactive behaviors; manganese; well water

Results 1-20 (20)