Intellectual Impairment in School-Age Children Exposed to Manganese from Drinking Water

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.     

Lithium in drinking water and thyroid function

Background

High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function.

Objectives

We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function.

Methods

Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T₄) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods.

Results

The median urinary lithium concentration was 3,910 μg/L (5th, 95th percentiles, 270 μg/L, 10,400 μg/L). Median plasma concentrations (5th, 95th percentiles) of T₄ and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T₄ [β for a 1,000-μg/L increase = −0.19; 95% confidence interval (CI), −0.31 to −0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T₄, β = −0.17; 95% CI, −0.32 to −0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T₄ (adjusted T₄ for a 1 μg/L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006).

Conclusions

Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources.     

Hemoglobin, lead exposure, and intelligence quotient: effect modification by the DRD2 Taq IA polymorphism

Background

Anemia and lead exposure remain significant public health issues in many parts of the world, often occurring together. Animal studies suggest that the dopamine D2 receptor (DRD2) mediates the effects of both lead and iron on cognition and behavior.

Objective

We tested the hypothesis that the DRD2 Taq IA polymorphism modifies the effects of lead and hemoglobin on intelligence quotient (IQ) among children.

Methods

Blood lead and hemoglobin were assessed in 717 children 3–7 years of age attending 12 schools in Chennai, India. IQ was determined using the Binet-Kamat scales of intelligence. Genotyping for the DRD2 polymorphism was carried out using a MassARRAY iPLEX platform. Stratified analyses and interaction models, using generalized estimating equations (GEEs), were used to explore interactions between lead and hemoglobin, and DRD2 Taq IA categories [homozygous variant (A1) vs. presence of wild-type allele (A2)].

Results

After we controlled for potential confounders, a one-unit increase in log blood lead was associated with a decrease of 9 IQ points [95% confidence interval (CI), −18.08 to −0.16] in the homozygous-variant children (n = 73) compared with a decrease of 4 IQ points (95% CI, −7.21 to −0.69) among those with the wild-type allele (n = 644). Higher hemoglobin levels were associated with higher IQ in the children who carried the wild-type allele DRD2, but in children homozygous for the variant allele, an increase of 1 g/dL hemoglobin was associated with a decrease in 1.82 points of IQ (95% CI, −5.28 to 1.64; interaction term p-value = 0.02).

Conclusion

The results of this study suggest that the DRD2 Taq IA polymorphism disrupts the protective effect of hemoglobin on cognition and may increase the susceptibility to the deficits in IQ due to lead exposure.     

Case-control study of blood lead levels and attention deficit hyperactivity disorder in Chinese children

Background

Attention deficit/hyperactivity disorder (ADHD) and lead exposure are high-prevalence conditions among children.

Objective

Our goal was to investigate the association between ADHD and blood lead levels (BLLs) in Chinese children, adjusting for known ADHD risk factors and potential confounding variables.

Methods

We conducted a pair-matching case–control study with 630 ADHD cases and 630 non-ADHD controls 4–12 years of age, matched on the same age, sex, and socioeconomic status. The case and control children were systematically evaluated via structured diagnostic interviews, including caregiver interviews, based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., revised criteria (DSM-IV-R). We evaluated the association between BLLs and ADHD using the Pearson chi-square test for categorical variables and the Student t-test for continuous data. We then performed conditional multiple variables logistic regression analyses with backward stepwise selection to predict risk factors for ADHD.

Results

There was a significant difference in BLLs between ADHD cases and controls. ADHD cases were more likely to have been exposed to lead during childhood than the non-ADHD control subjects, with adjustment for other known risk factors [children with BLLs ≥ 10 μg/dL vs. ≤ 5 μg/dL; OR = 6.0; 95% confidence interval (CI) = 4.10–8.77, p < 0.01; 5–10 μg/dL vs.≤ 5 μg/dL, OR = 4.9; 95% CI = 3.47–6.98, p < 0.01]. These results were not modified by age and sex variables.

Conclusions

This was the largest sample size case–control study to date to study the association between BLLs and ADHD in Chinese children. ADHD may be an additional deleterious outcome of lead exposure during childhood, even when BLLs are < 10 μg/dL.     

Differences in heart rate variability associated with long-term exposure to NO2

Background

Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV.

Objective

Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).

Methods

We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants ≥ 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO₂ at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO₂ and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects.

Results

For women, but not for men, each 10-μg/m³ increment in 1-year averaged NO₂ level was associated with a decrement of 3% (95% CI, −4 to −1) for the standard deviation of all normal-to-normal RR intervals (SDNN), −6% (95% CI, −11 to −1) for nighttime low frequency (LF), and −5% (95% CI, −9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, −8 to −1) per 10-μg/m³ increase in NO₂.

Conclusions

There is some evidence that long-term exposure to NO₂ is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease.     

Biomarkers of chlorpyrifos exposure and effect in Egyptian cotton field workers

Background

Chlorpyrifos (CPF), a widely used organophosphorus pesticide (OP), is metabolized to CPF-oxon, a potent cholinesterase (ChE) inhibitor, and trichloro-2-pyridinol (TCPy). Urinary TCPy is often used as a biomarker for CPF exposure, whereas blood ChE activity is considered an indicator of CPF toxicity. However, whether these biomarkers are dose related has not been studied extensively in populations with repeated daily OP exposures.

Objective

We sought to determine the relationship between blood ChE and urinary TCPy during repeated occupational exposures to CPF.

Methods

Daily urine samples and weekly blood samples were collected from pesticide workers (n = 38) in Menoufia Governorate, Egypt, before, during, and after 9–17 consecutive days of CPF application to cotton fields. We compared blood butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) activities with the respective urinary TCPy concentrations in each worker.

Results

Average TCPy levels during the middle of a 1- to 2-week CPF application period were significantly higher in pesticide applicators (6,437 μg/g creatinine) than in technicians (184 μg/g) and engineers (157 μg/g), both of whom are involved in supervising the application process. We observed a statistically significant inverse correlation between urinary TCPy and blood BuChE and AChE activities. The no-effect level (or inflection point) of the exposure–effect relationships has an average urinary TCPy level of 114 μg/g creatinine for BuChE and 3,161 μg/g creatinine for AChE.

Conclusions

Our findings demonstrate a dose–effect relationship between urinary TCPy and both plasma BuChE and red blood cell AChE in humans exposed occupationally to CPF. These findings will contribute to future risk assessment efforts for CPF exposure.     

Ambient air pollution and birth weight in full-term infants in Atlanta, 1994-2004

Background

An emerging body of evidence suggests that ambient levels of air pollution during pregnancy are associated with fetal growth.

Objectives

We examined relationships between birth weight and temporal variation in ambient levels of carbon monoxide, nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone, particulate matter ≤ 10 μm in diameter (PM₁₀), ≤ 2.5 μm (PM_2.5), 2.5 to 10 μm (PM_2.5–10), and PM_2.5 chemical component measurements for 406,627 full-term births occurring between 1994 and 2004 in five central counties of metropolitan Atlanta.

Methods

We assessed relationships between birth weight and pollutant concentrations during each infant’s first month of gestation and third trimester, as well as in each month of pregnancy using distributed lag models. We also conducted capture-area analyses limited to mothers residing within 4 miles (6.4 km) of each air quality monitoring station.

Results

In the five-county analysis, ambient levels of NO₂, SO₂, PM_2.5 elemental carbon, and PM_2.5 water-soluble metals during the third trimester were significantly associated with small reductions in birth weight (−4 to −16 g per interquartile range increase in pollutant concentrations). Third-trimester estimates were generally higher in Hispanic and non-Hispanic black infants relative to non-Hispanic white infants. Distributed lag models were also suggestive of associations between air pollutant concentrations in late pregnancy and reduced birth weight. The capture-area analyses provided little support for the associations observed in the five-county analysis.

Conclusions

Results provide some support for an effect of ambient air pollution in late pregnancy on birth weight in full-term infants.     

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

Background

Concern over phthalates has emerged because of their potential toxicity to humans.

Objective

We investigated the relationship between the urinary concentrations of phthalate metabolites and children’s intellectual functioning.

Methods

This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuropsychological tests were obtained from both the children and their mothers.

Results

We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl)phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 μg/L [geometric SD (GSD) = 2.2 μg/L; range, 0.5–445.4], 18.0 μg/L (GSD = 2.4; range, 0.07–291.1), and 48.9 μg/L (GSD = 2.2; range, 2.1–1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children’s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables.

Conclusion

Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.     

Urinary cadmium and osteoporosis in U.S. Women >or= 50 years of age: NHANES 1988-1994 and 1999-2004

Background

Urinary cadmium (U-Cd) has been associated with decreased peripheral bone mineral density (BMD) and osteoporosis. This association, however, has not been confirmed using femoral BMD, the international standard for diagnosing osteoporosis, at levels < 1.0 μg Cd/g creatinine.

Objectives

Our goal was to investigate the statistical association between U-Cd, at levels ≤ 1 μg/g creatinine, and osteoporosis, as indicated by hip BMD and self-report in a population-based sample of U.S. women ≥ 50 years of age.

Methods

We drew data from the National Health and Nutrition Examination Surveys for 1988–1994 (n = 3,207) and 1999–2004 (n = 1,051). Osteoporosis was indicated by hip BMD cutoffs based on the international standard and self-report of physician diagnosis. We analyzed U-Cd levels for association with osteoporosis using multiple logistic regression.

Results

Women ≥ 50 years of age with U-Cd levels between 0.50 and 1.00 μg/g creatinine were at 43% greater risk for hip-BMD–defined osteoporosis, relative to those with levels ≤ 0.50 μg/g (odds ratio = 1.43; 95% confidence interval, 1.02–2.00; p = 0.04). We observed similar effect estimates using self-report of physician-diagnosed osteoporosis. Smokers did not show a statistically increased risk.

Conclusions

Results suggest that U.S. women are at risk for osteoporosis at U-Cd levels below the U.S. Occupational Safety and Health Administration’s 3-μg/g safety standard. Given null findings among smokers, dietary Cd, rather than tobacco, is the likely source of Cd-related osteoporosis risk for the U.S. female population ≥ 50 years of age.     

Population-based inorganic mercury biomonitoring and the identification of skin care products as a source of exposure in New York City

Background

Mercury is a toxic metal that has been used for centuries as a constituent of medicines and other items.

Objective

We assessed exposure to inorganic mercury in the adult population of New York City (NYC).

Methods

We measured mercury concentrations in spot urine specimens from a representative sample of 1,840 adult New Yorkers in the 2004 NYC Health and Nutrition Examination Survey. Cases with urine concentrations ≥ 20 μg/L were followed up with a telephone or in-person interview that asked about potential sources of exposure, including ritualistic/cultural practices, skin care products, mercury spills, herbal medicine products, and fish.

Results

Geometric mean urine mercury concentration in NYC was higher for Caribbean-born blacks [1.39 μg/L; 95% confidence interval (CI), 1.14–1.70] and Dominicans (1.04 μg/L; 95% CI, 0.82–1.33) than for non-Hispanic whites (0.67 μg/L; 95% CI, 0.60–0.75) or other racial/ethnic groups. It was also higher among those who reported at least 20 fish meals in the past 30 days (1.02 μg/L; 95% CI, 0.83–1.25) than among those who reported no fish meals (0.50 μg/L; 95% CI, 0.41–0.61). We observed the highest 95th percentile of exposure (21.18 μg/L; 95% CI, 7.25–51.29) among Dominican women. Mercury-containing skin-lightening creams were a source of exposure among those most highly exposed, and we subsequently identified 12 imported products containing illegal levels of mercury in NYC stores.

Conclusion

Population-based biomonitoring identified a previously unrecognized source of exposure to inorganic mercury among NYC residents. In response, the NYC Health Department embargoed products and notified store owners and the public that skin-lightening creams and other skin care products that contain mercury are dangerous and illegal. Although exposure to inorganic mercury is not a widespread problem in NYC, users of these products may be at risk of health effects from exposure.     

Associations of plasma selenium with arsenic and genomic methylation of leukocyte DNA in Bangladesh

Background

Global hypomethylation of DNA is thought to constitute an early event in some cancers and occurs in response to arsenic (As) exposure and/or selenium (Se) deficiency in both in vitro and animal models. In addition, antagonism between As and Se, whereby each reduces toxicity of the other, has been well documented in animal models. Se status may therefore modify the health effects of As in As-exposed populations.

Objective

The primary objectives of our study were to test the hypothesis that Se deficiency is associated with genomic hypomethylation of lymphocyte DNA and to determine whether Se levels are associated with blood As (bAs) and urinary As (uAs) concentrations in adults exposed to As-contaminated groundwater in Bangladesh. A secondary objective was to explore the relationships between plasma Se and As metabolites.

Design

We assessed plasma Se concentrations, As metabolite profiles in blood and urine, and genomic methylation of leukocyte DNA in a cross-sectional study of 287 adults.

Results

After adjustment for potential confounders, we observed an inverse association between Se (micrograms per liter) and genomic DNA methylation (disintegrations per minute per 1-μg/L increase in Se): β = 345.6; 95% confidence interval (CI), 59–632. Se concentrations were inversely associated with total As concentrations (micrograms per liter) in blood (β = −0.04; 95% CI, −0.08 to −0.01) and urine (β = −20.1; 95% CI, −29.3 to −10.9). Se levels were negatively associated with the percentage of monomethylarsinic acid (β = −0.59; 95% CI, −1.04 to −0.13) and positively associated with the percentage of dimethylarsinic acid (β = 0.53; 95% CI, 0.04 to 1.01) in blood.

Conclusions

Our results suggest that Se is inversely associated with genomic DNA methylation. The underlying mechanisms and implications of this observation are unclear and warrant further investigation. In addition, Se may influence bAs and uAs concentrations, as well as relative proportions of As metabolites in blood.     

Low-level lead exposure and elevations in blood pressure during pregnancy

Background

Lead exposure is associated with elevated blood pressure during pregnancy; however, the magnitude of this relationship at low exposure levels is unclear.

Objectives

Our goal was to determine the association between low-level lead exposure and blood pressure during late pregnancy.

Methods

We collected admission and maximum (based on systolic) blood pressures during labor and delivery among 285 women in Baltimore, Maryland. We measured umbilical cord blood lead using inductively coupled plasma mass spectrometry. Multivariable models were adjusted for age, race, median household income, parity, smoking during pregnancy, prepregnancy body mass index, and anemia. These models were used to calculate benchmark dose values.

Results

Geometric mean cord blood lead was 0.66 μg/dL (95% confidence interval, 0.61–0.70). Comparing blood pressure measurements between those in the highest and those in the lowest quartile of lead exposure, we observed a 6.87-mmHg (1.51–12.21 mmHg) increase in admission systolic blood pressure and a 4.40-mmHg (0.21–8.59 mmHg) increase in admission diastolic blood pressure after adjustment for confounders. Corresponding values for maximum blood pressure increase were 7.72 (1.83–13.60) and 8.33 (1.14–15.53) mmHg. Benchmark dose lower limit values for a 1-SD increase in blood pressure were < 2 μg/dL blood lead for all blood pressure end points.

Conclusions

A significant association between low-level lead exposures and elevations in maternal blood pressure during labor and delivery can be observed at umbilical blood lead levels < 2 μg/dL.     

Variability and predictors of urinary bisphenol A concentrations during pregnancy

Background

Prenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy.

Objective

Our goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy.

Methods

We measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log₁₀-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models.

Results

Geometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 μg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 μg/g) compared with those consuming no canned vegetables (GM = 1.6 μg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations.

Conclusions

These results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.     

Private drinking water wells as a source of exposure to perfluorooctanoic acid (PFOA) in communities surrounding a fluoropolymer production facility

Background

The C8 Health Project was established in 2005 to collect data on perfluorooctanoic acid (PFOA, or C8) and human health in Ohio and West Virginia communities contaminated by a fluoropolymer production facility.

Objective

We assessed PFOA exposure via contaminated drinking water in a subset of C8 Health Project participants who drank water from private wells.

Methods

Participants provided demographic information and residential, occupational, and medical histories. Laboratory analyses were conducted to determine serum-PFOA concentrations. PFOA data were collected from 2001 through 2005 from 62 private drinking water wells. We examined the relationship between drinking water and PFOA levels in serum using robust regression methods. As a comparison with regression models, we used a first-order, single-compartment pharmacokinetic model to estimate the serum:drinking-water concentration ratio at steady state.

Results

The median serum PFOA concentration in 108 study participants who used private wells was 75.7 μg/L, approximately 20 times greater than the levels in the U.S. general population but similar to those of local residents who drank public water. Each 1 μg/L increase in PFOA levels in drinking water was associated with an increase in serum concentrations of 141.5 μg/L (95% confidence interval, 134.9–148.1). The serum:drinking-water concentration ratio for the steady-state pharmacokinetic model was 114.

Conclusions

PFOA-contaminated drinking water is a significant contributor to PFOA levels in serum in the study population. Regression methods and pharmacokinetic modeling produced similar estimates of the relationship.     

Manganese Exposure and Neurocognitive Outcomes in Rural School-Age Children: The Communities Actively Researching Exposure Study (Ohio,USA)

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.

Citation

Haynes EN, Sucharew H, Kuhnell P, Alden J, Barnas M, Wright RO, Parsons PJ, Aldous KM, Praamsma ML, Beidler C, Dietrich KN. 2015. Manganese exposure and neurocognitive outcomes in rural school-age children: the Communities Actively Researching Exposure Study (Ohio, USA). Environ Health Perspect 123:1066–1071; http://dx.doi.org/10.1289/ehp.1408993     

Mitochondrial oxidative stress significantly influences atherogenic risk and cytokine-induced oxidant production

Background

Oxidative stress associated with cardiovascular disease (CVD) risk factors contributes to disease development. However, less is known whether specific subcellular components play a role in disease susceptibility. In this regard, it has been previously reported that vascular mitochondrial damage and dysfunction are associated with atherosclerosis. However, no studies have determined whether altered mitochondrial oxidant production directly influences atherogenic susceptibility and response in primary cells to atherogenic factors such as tumor necrosis factor-α (TNF-α).

Objectives

We undertook this study to determine whether increased mitochondrial oxidant production affects atherosclerotic lesion development associated with CVD risk factor exposure and endothelial cell response to TNF-α.

Methods

We assessed atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage in male apolipoprotein E (apoE)-null mice with normal and decreased levels of mitochondrial superoxide dismutase-2 (SOD2; apoE^{−/ −} and apoE^{−/ −}, SOD2^+/−, respectively) exposed to environmental tobacco smoke or filtered air.

Results

Atherogenesis, oxidative stress, and mitochondrial damage were significantly higher in apoE^{−/ −}, SOD2^+/− mice than in apoE^{−/ −} controls. Furthermore, experiments with small interfering RNA in endothelial cells revealed that decreased SOD2 activity increased TNF-α–mediated cellular oxidant levels compared with controls.

Conclusions

Endogenous mitochondrial oxidative stress is an important CVD risk factor that can modulate atherogenesis and cytokine-induced endothelial cell oxidant generation. Consequently, CVD risk factors that induce mitochondrial damage alter cellular response to endogenous atherogenic factors, increasing disease susceptibility.     

Association between traffic-related black carbon exposure and lung function among urban women

Background

Although a number of studies have documented the relationship between lung function and traffic-related pollution among children, few have focused on adult lung function or examined community-based populations.

Objective

We examined the relationship between black carbon (BC), a surrogate of traffic-related particles, and lung function among women in the Maternal–Infant Smoking Study of East Boston, an urban cohort in Boston, Massachusetts.

Methods

We estimated local BC levels using a validated spatiotemporal land-use regression model, derived using ambient and indoor monitor data. We examined associations between percent predicted pulmonary function and predicted BC using linear regression, adjusting for sociodemographics (individual and neighborhood levels), smoking status, occupational exposure, type of cooking fuel, and a diagnosis of asthma or chronic bronchitis.

Results

The sample of 272 women 18–42 years of age included 57% who self-identified as Hispanic versus 43% white, and 18% who were current smokers. Mean ± SD predicted annual BC exposure level was 0.62 ± 0.2 μg/m³. In adjusted analysis, BC (per interquartile range increase) was associated with a 1.1% decrease [95% confidence interval (CI), −2.5% to 0.3%] in forced expiratory volume in 1 sec, a 0.6% decrease (95% CI, −1.9% to 0.6%) in forced vital capacity, and a 3.0% decrease (95% CI, −5.8% to −0.2%) in forced mid-expiratory flow rate. We noted differential effects by smoking status in that former smokers were most affected by BC exposure, whereas current smokers were not affected.

Conclusion

In this cohort, exposure to traffic-related BC, a component of particulate matter, independently predicted decreased lung function in urban women, when adjusting for tobacco smoke, asthma diagnosis, and socioeconomic status.     

Association between Lead and Cadmium and Reproductive Hormones in Peripubertal U.S. Girls

Background

Lead (Pb) and cadmium (Cd) are known reproductive toxicants thought to disrupt hormone production throughout sensitive developmental windows, although this has not been previously examined in nationally representative peripubertal children.

Objectives

We examined the association between blood Pb and urinary Cd concentrations and the reproductive hormones inhibin B and luteinizing hormone (LH) in girls 6–11 years of age who participated in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III) (1988–1994).

Methods

Pb (micrograms per deciliter) was measured in whole blood, and Cd was measured in urine (nanograms per milliliter). Inhibin B (picograms per milliliter) and LH (milli–International units per milliliter) were measured in residual sera for 705 girls. Survey logistic regression was used to estimate associations with pubertal onset based on inhibin B concentration > 35 pg/mL or LH concentration > 0.4 mIU/mL, and multinomial logistic regression was used to estimate the association between Pb and increasing categories of hormone concentrations.

Results

High Pb (≥ 5 μg/dL) was inversely associated with inhibin B > 35 pg/mL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.11–0.60; compared with Pb < 1 μg/dL]. At 10 and 11 years of age, girls with low Pb (< 1 μg/dL) had significantly higher inhibin B than did girls with moderate (1–4.99 μg/dL) or high Pb (≥ 5 μg/dL). In the subsample of 260 girls with levels of inhibin B above the level of detection and using survey regression modeling, inhibin B levels were lower among girls with both high Pb and high Cd (β = −0.52; 95% CI, −0.09 to −1.04) than among girls with high Pb alone (β = −0.35; 95% CI, −0.13 to −0.57), relative to girls with low Pb and low Cd.

Conclusions

Higher Pb was inversely associated with inhibin B, a marker of follicular development, and estimated effects suggestive of pubertal delays appeared to be stronger in the context of higher Cd concentrations. These data underscore the importance of Pb and Cd as reproductive toxicants for young girls.     

The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children

Background

Several epidemiologic studies have demonstrated relationships between prenatal exposure to polychlorinated biphenyls (PCBs) and modest cognitive impairments in infancy and early childhood. However, few studies have followed cohorts of exposed children long enough to examine the possible impact of prenatal PCB exposure on psychometric intelligence in later childhood. Of the few studies that have done so, one in the Great Lakes region of the United States reported impaired IQ in children prenatally exposed to PCBs, whereas another found no association.

Objectives

This study was designed to determine whether environmental exposure to PCBs predicts lower IQ in school-age children in the Great Lakes region of the northeastern United States.

Methods

We measured prenatal exposure to PCBs and IQ at 9 years of age in 156 subjects from Oswego, New York. We also measured > 50 potential predictors of intelligence in children, including repeated measures of the home environment [Home Observation for Measurement of the Environment (HOME)], socioeconomic status (SES), parental IQ, alcohol/cigarette use, neonatal risk factors, and nutrition.

Results

For each 1-ng/g (wet weight) increase in PCBs in placental tissue, Full Scale IQ dropped by three points (p = 0.02), and Verbal IQ dropped by four points (p = 0.003). The median PCB level was 1.50 ng/g, with a lower quartile of 1.00 ng/g and an upper quartile of 2.06 ng/g. Moreover, this association was significant after controlling for many potential confounders, including prenatal exposure to methylmercury, dichlorodiphenyldichloroethylene, hexachlorobenzene, and lead.

Conclusions

These results, in combination with similar results obtained from a similar study in the Great Lakes conducted 10 years earlier, indicate that prenatal PCB exposure in the Great Lakes region is associated with lower IQ in children.     

Windblown Lead Carbonate as the Main Source of Lead in Blood of Children from a Seaside Community: An Example of Local Birds as “Canaries in the Mine”

Background

In late 2006, the seaside community in Esperance, Western Australia, was alerted to thousands of native bird species dying. The source of the lead was thought to derive from the handling of Pb carbonate concentrate from the Magellan mine through the port of Esperance, begun in July 2005. Concern was expressed for the impact of this process on the community.

Objective

This study was designed to evaluate the source of Pb in blood of a random sample of the community using Pb isotope ratios.

Methods

The cohort comprised 49 children (48 < 5 years of age) along with 18 adults (> 20 years of age) with a bias toward higher blood lead (PbB) values to facilitate source identification.

Results

Mean PbB level of the children was 7.5 μg/dL (range, 1.5–25.7 μg/dL; n = 49; geometric mean, 6.6 μg/dL), with four children whose PbB was > 12 μg/dL. The isotopic data for blood samples lay around two distinct arrays. The blood of all children analyzed for Pb isotopes contained a contribution of Pb from the Magellan mine, which for young children ranged from 27% up to 93% (mean, 64%; median, 71%). Subtraction of the ore component gave a mean background PbB of 2.3 μg/dL. Several children whose PbB was > 9 μg/dL and most of the older subjects have complex sources of Pb.

Conclusions

The death of the birds acted as a sentinel event; otherwise, the exposure of the community, arising from such a toxic form of Pb, could have been tragic. Isotopic data and mineralogic and particle size analyses indicate that, apart from the recognized pathway of Pb exposure by hand-to-mouth activity in children, the inhalation pathway could have been a significant contributor to PbB for some of the very young children and in some parents.