Maternal Arsenic Exposure and Impaired Glucose Tolerance during Pregnancy

Background

Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD).

Objectives

We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy.

Methods

Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell.

Results

Arsenic concentrations ranged from 0.2 to 24.1 μg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (> 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008).

Conclusions

Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD.     

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

Background

Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy.

Objectives

We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population.

Methods

The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy.

Results

Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy.

Conclusions

In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk.

Citation

Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472     

Evaluation of an Elementary School–based Educational Intervention for Reducing Arsenic Exposure in Bangladesh

Background

Chronic exposure to well water arsenic (As) remains a major rural health challenge in Bangladesh and some other developing countries. Many mitigation programs have been implemented to reduce As exposure, although evaluation studies for these efforts are rare in the literature.

Objectives

In this study we estimated associations between a school-based intervention and various outcome measures of As mitigation.

Methods

We recruited 840 children from 14 elementary schools in Araihazar, Bangladesh. Teachers from 7 schools were trained on an As education curriculum, whereas the remaining 7 schools without any training formed the control group. Surveys, knowledge tests, and well-water testing were conducted on 773 children both at baseline and postintervention follow-up. Urine samples were collected from 210 children from 4 intervention schools and the same number of children from 4 control schools. One low-As (< 10 μg/L) community well in each study village was ensured during an 18-month intervention period.

Results

After adjustment for the availability of low-As wells and other sociodemographic confounders, children receiving the intervention were five times more likely to switch from high- to low-As wells (p < 0.001). We also observed a significant decline of urinary arsenic (UAs) (p = < 0.001) (estimated β = –214.9; 95% CI: –301.1, –128.7 μg/g creatinine) among the children who were initially drinking from high-As wells (> Bangladesh standard of 50 μg/L) and significantly improved As knowledge attributable to the intervention after controlling for potential confounders.

Conclusions

These findings offer strong evidence that school-based intervention can effectively reduce As exposure in Bangladesh by motivating teachers, children, and parents.

Citation

Khan K, Ahmed E, Factor-Litvak P, Liu X, Siddique AB, Wasserman GA, Slavkovich V, Levy D, Mey JL, van Geen A, Graziano JH. 2015. Evaluation of an elementary school–based educational intervention for reducing arsenic exposure in Bangladesh. Environ Health Perspect 123:1331–1336; http://dx.doi.org/10.1289/ehp.1409462     

Blood Pressure,Left Ventricular Geometry,and Systolic Function in Children Exposed to Inorganic Arsenic

Background:

Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure–related cardiovascular disease in children.

Objective:

In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children.

Methods:

A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation–cryotrapping–atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography.

Results:

U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: –7.14, –0.20) and 3.41% (95% CI: –6.44, –0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL.

Conclusion:

Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children.

Citation:

Osorio-Yáñez C, Ayllon-Vergara JC, Arreola-Mendoza L, Aguilar-Madrid G, Hernández-Castellanos E, Sánchez-Peña LC, Del Razo LM. 2015. Blood pressure, left ventricular geometry, and systolic function in children exposed to inorganic arsenic. Environ Health Perspect 123:629–635; http://dx.doi.org/10.1289/ehp.1307327     

No Association between Arsenic Exposure from Drinking Water and Diabetes Mellitus: A Cross-Sectional Study in Bangladesh

Background

The long-term effects of arsenic exposure from drinking water at levels < 300 μg/L and the risk of diabetes mellitus remains a controversial topic.

Method

We conducted a population-based cross-sectional study using baseline data from 11,319 participants in the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, to evaluate the associations of well water arsenic and total urinary arsenic concentration and the prevalence of diabetes mellitus and glucosuria. We also assessed the concentrations of well water arsenic, total urinary arsenic, and urinary arsenic metabolites in relation to blood glycosylated hemoglobin (HbA1c) levels in subsets of the study population.

Results

More than 90% of the cohort members were exposed to drinking water with arsenic concentration < 300 μg/L. We found no association between arsenic exposure and the prevalence of diabetes. The adjusted odds ratios for diabetes were 1.00 (referent), 1.35 [95% confidence interval (CI), 0.90–2.02], 1.24 (0.82–1.87), 0.96 (0.62–1.49), and 1.11 (0.73–1.69) in relation to quintiles of time-weighted water arsenic concentrations of 0.1–8, 8–41, 41–91, 92–176, and ≥ 177 μg/L, respectively, and 1.00 (referent), 1.29 (0.87–1.91), 1.05 (0.69–1.59), 0.94 (0.61–1.44), and 0.93 (0.59–1.45) in relation to quintiles of urinary arsenic concentrations of 1–36, 37–66, 67–114, 115–204, and ≥ 205 μg/L, respectively. We observed no association between arsenic exposure and prevalence of glucosuria and no evidence of an association between well water arsenic, total urinary arsenic, or the composition of urinary arsenic metabolites and HbA1c level.

Conclusions

Our findings do not support an association of arsenic exposure from drinking water and a significantly increased risk of diabetes mellitus in the range of levels observed. Further prospective studies would be valuable in confirming the findings.     

Association of Prenatal Exposure to Persistent Organic Pollutants with Obesity and Cardiometabolic Traits in Early Childhood: The Rhea Mother–Child Cohort (Crete,Greece)

Background

Prenatal exposure to endocrine-disrupting chemicals such as persistent organic pollutants (POPs) may increase risk of obesity later in life.

Objective

We examined the relation of in utero POPs exposure to offspring obesity and cardiometabolic risk factors at 4 years of age in the Rhea mother–child cohort in Crete, Greece (n = 689).

Methods

We determined concentrations of polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) in first-trimester maternal serum. We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP), blood levels of lipids, C-reactive protein, and adipokines at 4 years of age. Childhood obesity was defined using age- and sex-specific cut points for body mass index (BMI) as recommended by the International Obesity Task Force.

Results

On multivariable regression analyses, a 10-fold increase in HCB was associated with a higher BMI z-score (adjusted β = 0.49; 95% CI: 0.12, 0.86), obesity [relative risk (RR) = 8.14; 95% CI: 1.85, 35.81], abdominal obesity (RR = 3.49; 95% CI: 1.08, 11.28), greater sum of skinfold thickness (β = 7.71 mm; 95% CI: 2.04, 13.39), and higher systolic BP (β = 4.34 mmHg; 95% CI: 0.63, 8.05) at 4 years of age. Prenatal DDE exposure was associated with higher BMI z-score (β = 0.27; 95% CI: 0.04, 0.5), abdominal obesity (RR = 3.76; 95% CI: 1.70, 8.30), and higher diastolic BP (β = 1.79 mmHg; 95% CI: 0.13, 3.46). PCBs were not significantly associated with offspring obesity or cardiometabolic risk factors.

Conclusions

Prenatal exposure to DDE and HCB was associated with excess adiposity and higher blood pressure levels in early childhood.

Citation

Vafeiadi M, Georgiou V, Chalkiadaki G, Rantakokko P, Kiviranta H, Karachaliou M, Fthenou E, Venihaki M, Sarri K, Vassilaki M, Kyrtopoulos SA, Oken E, Kogevinas M, Chatzi L. 2015. Association of prenatal exposure to persistent organic pollutants with obesity and cardiometabolic traits in early childhood: the Rhea mother–child cohort (Crete, Greece). Environ Health Perspect 123:1015–1021; http://dx.doi.org/10.1289/ehp.1409062     

Arsenic Exposure within the Korean Community (United States) Based on Dietary Behavior and Arsenic Levels in Hair,Urine, Air,and Water

Background

Determining arsenic exposure in groups based on geographic location, dietary behaviors, or lifestyles is important, as even moderate exposures may lead to health concerns.

Objectives/Methods

The Korean community in Washington State, represents a group warranting investigation, as they consume foods (e.g., shellfish, rice, finfish, and seaweed) known to contain arsenic. As part of the Arsenic Mercury Intake Biometric Study, we examined the arsenic levels in hair and urine along with the diets of 108 women of childbearing age from within this community. Arsenic levels in indoor air and drinking water were also investigated, and shellfish commonly consumed were collected and analyzed for total and speciated arsenic.

Results

The six shellfish species analyzed (n = 667) contain total arsenic (range, 1–5 μg/g) but are a small source of inorganic arsenic (range, 0.01–0.12 μg/g). Six percent of the individuals may have elevated urinary inorganic arsenic levels (> 10 μg/L) due to diet. Seaweed, rice, shellfish, and finfish are principal sources for total arsenic intake/excretion based on mass balance estimates. Rice consumption (163 g/person/day) may be a significant source of inorganic arsenic. Air and water are not significant sources of exposure. Hair is a poor biometric for examining arsenic levels at low to moderate exposures.

Conclusions

We conclude that a portion of this community may have dietary inorganic arsenic exposure resulting in urine levels exceeding 10 μg/L. Although their exposure is below that associated with populations exposed to high levels of arsenic from drinking water (> 100 μg/L), their exposure may be among the highest in the United States.     

Lung Cancer in a U.S. Population with Low to Moderate Arsenic Exposure

Background

Little is known about the carcinogenic potential of arsenic in areas with low to moderate concentrations of arsenic (< 100 μg/L) in drinking water.

Objectives

We examined associations between arsenic and lung cancer.

Methods

A population-based case–control study of primary incident lung cancer was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The study included 223 lung cancer cases and 238 controls, each of whom provided toenail clippings for arsenic exposure measurement by inductively coupled–plasma mass spectrometry. We estimated odds ratios (ORs) of the association between arsenic exposure and lung cancer using unconditional logistic regression with adjustment for potential confounders (age, sex, race/ethnicity, smoking pack-years, education, body mass index, fish servings per week, and toenail selenium level).

Results

Arsenic exposure was associated with small-cell and squamous-cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00–7.57] for toenail arsenic concentration ≥ 0.114 μg/g, versus < 0.05 μg/g. A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39–5.91). We also observed an elevated risk of lung cancer among participants with a history of lung disease and toenail arsenic ≥ 0.05 μg/g (OR = 4.78; 95% CI, 1.87–12.2) than among individuals with low toenail arsenic and no history of lung disease.

Conclusion

Although this study supports the possibility of an increased risk of specific lung cancer histologic types at lower levels of arsenic exposure, we recommend large-scale population-based studies.     

Arsenic Exposure and Prevalence of the Varicella Zoster Virus in the United States: NHANES (2003–2004 and 2009–2010)

Background

Arsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide.

Objective

We evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S. population.

Methods

We analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2009–2010 pooled survey cycles. Participants were eligible if they were 6–49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine.

Results

The overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively.

Conclusions

In this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S. population. This finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms.

Citation

Cardenas A, Smit E, Houseman EA, Kerkvliet NI, Bethel JW, Kile ML. 2015. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003–2004 and 2009–2010). Environ Health Perspect 123:590–596; http://dx.doi.org/10.1289/ehp.1408731     

Effect of Organic Diet Intervention on Pesticide Exposures in Young Children Living in Low-Income Urban and Agricultural Communities

Background

Recent organic diet intervention studies suggest that diet is a significant source of pesticide exposure in young children. These studies have focused on children living in suburban communities.

Objectives

We aimed to determine whether consuming an organic diet reduced urinary pesticide metabolite concentrations in 40 Mexican-American children, 3–6 years of age, living in California urban and agricultural communities.

Methods

In 2006, we collected urine samples over 16 consecutive days from children who consumed conventionally grown food for 4 days, organic food for 7 days, and then conventionally grown food for 5 days. We measured 23 metabolites, reflecting potential exposure to organophosphorous (OP), pyrethroid, and other pesticides used in homes and agriculture. We used linear mixed-effects models to evaluate the effects of diet on urinary metabolite concentrations.

Results

For six metabolites with detection frequencies > 50%, adjusted geometric mean concentrations during the organic phase were generally lower for all children, and were significant for total dialkylphosphates (DAPs) and dimethyl DAPs (DMs; metabolites of OP insecticides) and 2,4-D (2,4-dichlorophenoxyacetic acid, a herbicide), with reductions of 40%, 49%, and 25%, respectively (p < 0.01). Chemical-specific metabolite concentrations for several OP pesticides, pyrethroids, and herbicides were either infrequently detected and/or not significantly affected by diet. Concentrations for most of the frequently detected metabolites were generally higher in Salinas compared with Oakland children, with DMs and metolachlor at or near significance (p = 0.06 and 0.03, respectively).

Conclusion

An organic diet was significantly associated with reduced urinary concentrations of nonspecific dimethyl OP insecticide metabolites and the herbicide 2,4-D in children. Additional research is needed to clarify the relative importance of dietary and non-dietary sources of pesticide exposures to young children.

Citation

Bradman A, Quirós-Alcalá L, Castorina R, Aguilar Schall R, Camacho J, Holland NT, Barr DB, Eskenazi B. 2015. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environ Health Perspect 123:1086–1093; http://dx.doi.org/10.1289/ehp.1408660     

Respiratory Cancer and Inhaled Inorganic Arsenic in Copper Smelters Workers: A Linear Relationship with Cumulative Exposure that Increases with Concentration

Background

Inhalation of high levels of airborne inorganic arsenic is a recognized cause of respiratory cancer. Although multiple epidemiologic studies have demonstrated this association, there have been few analyses of the mathematical relationship between cumulative arsenic exposure and risk of respiratory cancer, and no assessment as to whether and how arsenic concentration may modify this association.

Objectives

The objective is an evaluation of the shape of the relationship between respiratory cancer mortality and cumulative inhaled arsenic exposure among copper smelter workers, and the modification of that relationship by arsenic concentration.

Methods

We used Poisson regression methods to analyze data from a cohort of arsenic-exposed copper smelter workers under a linear-exponential model for the excess relative risk.

Results

Within categories of arsenic concentration, the association between respiratory cancer and cumulative arsenic exposure was consistent with linearity. The slope of the linear relationship with cumulative exposure increased with increasing arsenic concentration category.

Conclusions

Our results suggested a direct concentration effect from inhaled inorganic arsenic, whereby the excess relative risk for a fixed cumulative exposure was greater when delivered at a higher concentration and shorter duration than when delivered at a lower concentration and longer duration.     

Confusion about Cadmium Risks: The Unrecognized Limitations of an Extrapolated Paradigm

Background

Cadmium (Cd) risk assessment presently relies on tubular proteinuria as a critical effect and urinary Cd (U-Cd) as an index of the Cd body burden. Based on this paradigm, regulatory bodies have reached contradictory conclusions regarding the safety of Cd in food. Adding to the confusion, epidemiological studies implicate environmental Cd as a risk factor for bone, cardiovascular, and other degenerative diseases at exposure levels that are much lower than points of departure used for setting food standards.

Objective

The objective was to examine whether the present confusion over Cd risks is not related to conceptual or methodological problems.

Discussion

The cornerstone of Cd risk assessment is the assumption that U-Cd reflects the lifetime accumulation of the metal in the body. The validity of this assumption as applied to the general population has been questioned by recent studies revealing that low-level U-Cd varies widely within and between individuals depending on urinary flow, urine collection protocol, and recent exposure. There is also evidence that low-level U-Cd increases with proteinuria and essential element deficiencies, two potential confounders that might explain the multiple associations of U-Cd with common degenerative diseases. In essence, the present Cd confusion might arise from the fact that this heavy metal follows the same transport pathways as plasma proteins for its urinary excretion and the same transport pathways as essential elements for its intestinal absorption.

Conclusions

The Cd risk assessment paradigm needs to be rethought taking into consideration that low-level U-Cd is strongly influenced by renal physiology, recent exposure, and factors linked to studied outcomes.

Citation

Bernard A. 2016. Confusion about cadmium risks: the unrecognized limitations of an extrapolated paradigm. Environ Health Perspect 124:1–5; http://dx.doi.org/10.1289/ehp.1509691     

Exposure to Endocrine-Disrupting Chemicals during Pregnancy and Weight at 7 Years of Age: A Multi-pollutant Approach

Background

Prenatal exposure to endocrine-disrupting chemicals (EDCs) may induce weight gain and obesity in children, but the obesogenic effects of mixtures have not been studied.

Objective

We evaluated the associations between pre- and perinatal biomarker concentrations of 27 EDCs and child weight status at 7 years of age.

Methods

In pregnant women enrolled in a Spanish birth cohort study between 2004 and 2006, we measured the concentrations of 10 phthalate metabolites, bisphenol A, cadmium, arsenic, and lead in two maternal pregnancy urine samples; 6 organochlorine compounds in maternal pregnancy serum; mercury in cord blood; and 6 polybrominated diphenyl ether congeners in colostrum. Among 470 children at 7 years, body mass index (BMI) z-scores were calculated, and overweight was defined as BMI > 85th percentile. We estimated associations with EDCs in single-pollutant models and applied principal-component analysis (PCA) on the 27 pollutant concentrations.

Results

In single-pollutant models, HCB (hexachlorobenzene), βHCH (β-hexachlorocyclohexane), and polychlorinated biphenyl (PCB) congeners 138 and 180 were associated with increased child BMI z-scores; and HCB, βHCH, PCB-138, and DDE (dichlorodiphenyldichloroethylene) with overweight risk. PCA generated four factors that accounted for 43.4% of the total variance. The organochlorine factor was positively associated with BMI z-scores and with overweight (adjusted RR, tertile 3 vs. 1: 2.59; 95% CI: 1.19, 5.63), and these associations were robust to adjustment for other EDCs. Exposure in the second tertile of the phthalate factor was inversely associated with overweight.

Conclusions

Prenatal exposure to organochlorines was positively associated with overweight at age 7 years in our study population. Other EDCs exposures did not confound this association.

Citation

Agay-Shay K, Martinez D, Valvi D, Garcia-Esteban R, Basagaña X, Robinson O, Casas M, Sunyer J, Vrijheid M. 2015. Exposure to endocrine-disrupting chemicals during pregnancy and weight at 7 years of age: a multi-pollutant approach. Environ Health Perspect 123:1030–1037; http://dx.doi.org/10.1289/ehp.1409049     

Perturbation of Defense Pathways by Low-Dose Arsenic Exposure in Zebrafish Embryos

Background

Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown.

Objectives

The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action.

Methods

We exposed zebrafish embryos at 0.25–1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development.

Results

We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10⁻⁴¹). Arsenic-mediated expression changes were validated by QPCR.

Conclusions

In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development.     

The Genetic Architecture of Arsenic Metabolism Efficiency:A SNP-Based Heritability Study of Bangladeshi Adults

Background

Consumption of arsenic-contaminated drinking water adversely affects health. There is interindividual variation in arsenic metabolism efficiency, partially due to genetic variation in the arsenic methyltransferase (AS3MT) gene region.

Objectives

The goal of this study was to assess the overall contribution of genetic factors to variation in arsenic metabolism efficiency, as measured by the relative concentration of dimethylarsinic acid (DMA%) in urine.

Methods

Using data on genome-wide single nucleotide polymorphisms (SNPs) and urinary DMA% for 2,053 arsenic-exposed Bangladeshi individuals, we employed various SNP-based approaches for heritability estimation and polygenic modeling.

Results

Using data on all participants, the percent variance explained (PVE) for DMA% by all measured and imputed SNPs was 16% (p = 0.08), which was reduced to 5% (p = 0.34) after adjusting for AS3MT SNPs. Using information on close relatives only, the PVE was 63% (p = 0.0002), but decreased to 41% (p = 0.01) after adjusting for AS3MT SNPs. Regional heritability analysis confirmed 10q24.32 (AS3MT) as a major arsenic metabolism locus (PVE = 7%, p = 4.4 × 10^–10), but revealed no additional regions. We observed a moderate association between a polygenic score reflecting elevated DMA% (composed of thousands of non-AS3MT SNPs) and reduced skin lesion risk in an independent sample (p < 0.05). We observed no associations for SNPs reported in prior candidate gene studies of arsenic metabolism.

Conclusions

Our results suggest that there are common variants outside of the AS3MT region that influence arsenic metabolism in Bangladeshi individuals, but the effects of these variants are very weak compared with variants near AS3MT. The high heritability estimates observed using family-based heritability approaches suggest substantial effects for rare variants and/or unmeasured environmental factors.

Citation

Gao J, Tong L, Argos M, Scannell Bryan M, Ahmed A, Rakibuz-Zaman M, Kibriya MG, Jasmine F, Slavkovich V, Graziano JH, Ahsan H, Pierce BL. 2015. The genetic architecture of arsenic metabolism efficiency: a SNP-based heritability study of Bangladeshi adults. Environ Health Perspect 123:985–992; http://dx.doi.org/10.1289/ehp.1408909     

Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

Background

Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear.

Objectives

We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood.

Methods

Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood.

Results

Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance.

Conclusion

Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice.

Citation

Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic parameters in female CD-1 mice. Environ Health Perspect 124:336–343; http://dx.doi.org/10.1289/ehp.1509703     

High Ambient Temperatures and Risk of Motor Vehicle Crashes in Catalonia,Spain (2000–2011): A Time-Series Analysis

Background

Experimental studies have shown a decrease in driving performance at high temperatures. The epidemiological evidence for the relationship between heat and motor vehicle crashes is not consistent.

Objectives

We estimated the impact of high ambient temperatures on the daily number of motor vehicle crashes and, in particular, on crashes involving driver performance factors (namely distractions, driver error, fatigue, or sleepiness).

Methods

We performed a time-series analysis linking daily counts of motor vehicle crashes and daily temperature or occurrence of heat waves while controlling for temporal trends. All motor vehicle crashes with victims that occurred during the warm period of the years 2000–2011 in Catalonia (Spain) were included. Temperature data were obtained from 66 weather stations covering the region. Poisson regression models adjusted for precipitation, day of the week, month, year, and holiday periods were fitted to quantify the associations.

Results

The study included 118,489 motor vehicle crashes (an average of 64.1 per day). The estimated risk of crashes significantly increased by 2.9% [95% confidence interval (CI): 0.7%, 5.1%] during heat wave days, and this association was stronger (7.7%, 95% CI: 1.2%, 14.6%) when restricted to crashes with driver performance–associated factors. The estimated risk of crashes with driver performance factors significantly increased by 1.1% (95% CI: 0.1%, 2.1%) for each 1°C increase in maximum temperature.

Conclusions

Motor vehicle crashes involving driver performance–associated factors were increased in association with heat waves and increasing temperature. These findings are relevant for designing preventive plans in a context of global warming.

Citation

Basagaña X, Escalera-Antezana JP, Dadvand P, Llatje Ò, Barrera-Gómez J, Cunillera J, Medina-Ramón M, Pérez K. 2015. High ambient temperatures and risk of motor vehicle crashes in Catalonia, Spain (2000–2011): a time-series analysis. Environ Health Perspect 123:1309–1316; http://dx.doi.org/10.1289/ehp.1409223     

Exposure to Free and Conjugated Forms of Bisphenol A and Triclosan among Pregnant Women in the MIREC Cohort

Background:

Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols.

Objectives:

The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women.

Methods:

Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatograpy–tandem mass spectrometry using isotope dilution.

Results:

The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education.

Conclusions:

The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.

Citation:

Arbuckle TE, Marro L, Davis K, Fisher M, Ayotte P, Bélanger P, Dumas P, LeBlanc A, Bérubé R, Gaudreau É, Provencher G, Faustman EM, Vigoren E, Ettinger AS, Dellarco M, MacPherson S, Fraser WD. 2015. Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort. Environ Health Perspect 123:277–284; http://dx.doi.org/10.1289/ehp.1408187     

Road Traffic and Railway Noise Exposures and Adiposity in Adults: A Cross-Sectional Analysis of the Danish Diet,Cancer, and Health Cohort

Background

Traffic noise has been associated with cardiovascular and metabolic disorders. Potential modes of action are through stress and sleep disturbance, which may lead to endocrine dysregulation and overweight.

Objectives

We aimed to investigate the relationship between residential traffic and railway noise and adiposity.

Methods

In this cross-sectional study of 57,053 middle-aged people, height, weight, waist circumference, and bioelectrical impedance were measured at enrollment (1993–1997). Body mass index (BMI), body fat mass index (BFMI), and lean body mass index (LBMI) were calculated. Residential exposure to road and railway traffic noise exposure was calculated using the Nordic prediction method. Associations between traffic noise and anthropometric measures at enrollment were analyzed using general linear models and logistic regression adjusted for demographic and lifestyle factors.

Results

Linear regression models adjusted for age, sex, and socioeconomic factors showed that 5-year mean road traffic noise exposure preceding enrollment was associated with a 0.35-cm wider waist circumference (95% CI: 0.21, 0.50) and a 0.18-point higher BMI (95% CI: 0.12, 0.23) per 10 dB. Small, significant increases were also found for BFMI and LBMI. All associations followed linear exposure–response relationships. Exposure to railway noise was not linearly associated with adiposity measures. However, exposure > 60 dB was associated with a 0.71-cm wider waist circumference (95% CI: 0.23, 1.19) and a 0.19-point higher BMI (95% CI: 0.0072, 0.37) compared with unexposed participants (0–20 dB).

Conclusions

The present study finds positive associations between residential exposure to road traffic and railway noise and adiposity.

Citation

Christensen JS, Raaschou-Nielsen O, Tjønneland A, Overvad K, Nordsborg RB, Ketzel M, Sørensen TI, Sørensen M. 2016. Road traffic and railway noise exposures and adiposity in adults: a cross-sectional analysis of the Danish Diet, Cancer, and Health cohort. Environ Health Perspect 124:329–335; http://dx.doi.org/10.1289/ehp.1409052