Background: Arsenic methylation relies on folate-dependent one-carbon metabolism and facilitates ... more Background: Arsenic methylation relies on folate-dependent one-carbon metabolism and facilitates urinary As elimination. Clinical manifestations of As toxicity vary considerably among individuals and populations, and poor methylation capacity is thought to confer greater susceptibility. oBjective: After determining that folate deficiency, hyperhomocysteinemia, and low urinary creatinine are associated with reduced As methylation, and that As exposure is associated with increased genomic methylation of leukocyte DNA, we asked whether these factors are associated with As-induced skin lesion risk among Bangladeshi adults. Methods: We conducted a nested case-control study of 274 cases who developed lesions 2 years after recruitment, and 274 controls matched to cases for sex, age, and water As. results: The odds ratios and 95% confidence intervals (CIs) for development of skin lesions for participants who had low folate (< 9 nmol/L), hyperhomocysteinemia (men, > 11.4 µmol/L; women, > 10.4 µmol/L), or hypomethylated leukocyte DNA at recruitment (< median) were 1.8 (95% CI, 1.1-2.9), 1.7 (95% CI, 1.1-2.6), and 1.8 (95% CI, 1.2-2.8), respectively. Compared with the subjects in the first quartile, those in the third and fourth quartiles for urinary creatinine had a 0.4-fold decrease in the odds of skin lesions (p < 0.01). conclusions: These results suggest that folate deficiency, hyperhomocysteinemia, and low urinary creatinine, each associated with decreased As methylation, are risk factors for As-induced skin lesions. The increased DNA methylation associated with As exposure previously observed, and confirmed among controls in this study, may be an adaptive change because hypomethylation of leukocyte DNA is associated with increased risk for skin lesions.
The American Journal of Clinical Nutrition, Oct 1, 2007
Background: Studies in cell culture and animal models indicate that arsenic exposure induces modi... more Background: Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water. Objective: The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenicinduced alterations in DNA methylation may be influenced by folate nutritional status. Design: PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [ 3 H]-methyl incorporation assay. Results: Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P ҃ 0.009, 0.03, and 0.03, respectively). Stratification of participants by folate nutritional status [9 nmol/L (n ҃ 190) or ͧ9 nmol/L (n ҃ 104)] showed that the associations between arsenic exposure and methylation of PBL DNA were restricted to persons with folate concentrations ͧ 9 nmol/L. Conclusions: Contrary to our a priori hypothesis, arsenic exposure was positively associated with genomic PBL DNA methylation in a dose-dependent manner. This effect is modified by folate, which suggests that arsenic-induced increases in DNA methylation cannot occur in the absence of adequate folate. The underlying mechanisms and physiologic implications of increased genomic DNA methylation are unclear, and they warrant further study.
To evaluate the potential effects of betel quid chewing on mortality. (A quid consists of betel n... more To evaluate the potential effects of betel quid chewing on mortality. (A quid consists of betel nut, wrapped in betel leaves; tobacco is added to the quid by some users). Prospective data were available on 20 033 individuals aged 18-75 years, living in Araihazar, Bangladesh. Demographic and exposure data were collected at baseline using a standardized questionnaire. Cause of death was defined by verbal autopsy questionnaires administered to next of kin. We estimated hazard ratios (HR) and their 95% confidence intervals (CI) for associations between betel use and mortality from all causes and from specific causes, using Cox proportional hazards models. We adjusted for age, sex, body mass index, educational attainment and tobacco smoking history. There were 1072 deaths during an average of 10 years of follow-up. Participants who had ever used betel were significantly more likely to die from all causes (HR: 1.26; 95% CI: 1.09-1.44) and cancer (HR: 1.55; 95% CI: 1.09-2.22); but not cardiovascular disease (HR: 1.16; 95% CI: 0.93-1.43). These findings were robust to adjustment for potential confounders. There was a dose-response relationship between mortality from all causes and both the duration and the intensity of betel use. The population attributable fraction for betel use was 14.1% for deaths from all causes and 24.2% for cancer. Betel quid use was associated with mortality from all causes and from cancer in this cohort.
Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly ... more Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk- is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hydroxymethylcytosine (5-hmC) has not been widely studied. We evaluated associations of As in drinking water (wAs), urine (uAs), and blood (bAs) with global %5-mC and %5-hmC in two studies of Bangladeshi adults: i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity (NIAT) study (n=196; 49% male, 19-66 years); and ii) peripheral blood mononuclear cell (PBMC) DNA in the Folate and Oxidative Stress (FOX) study (n=375; 49% male, 30-63 years). Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (p for interaction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (p for interaction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.10). In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys. Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.
In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations ex... more In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations exceeding the WHO standard of 10 μg/L, even though arsenic safe water is often available within a short walking distance. Arsenic mitigation typically involves a person coming into a village to test the well water for arsenic. This person often leaves the village without providing the resources to address health concerns or advice on mitigation options. We developed an arsenic education training program for local staff and conducted a longitudinal intervention study of 20 villages to investigate the impact of having local resident staff conduct water arsenic testing and to provide arsenic awareness education as well as mitigation options on arsenic exposure. A pre- and post-intervention questionnaire was administered to the person in each randomly selected household responsible for primary drinking water collection. The results of this study, conducted in 20 villages in Singair, Bangladesh...
Chronic exposure to well water arsenic (As) remains a major rural health challenge in Bangladesh ... more 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. This study estimates associations between a school-based intervention and various outcome measures of As mitigation. 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 seven schools without any training formed the control group. Surveys, knowledge tests and well-water testing were conducted on 773 children both at baseline and post-intervention follow-up. Urine samples were collected from 210 children from four intervention schools and the same number of children from four control schools. One low As (<10 μg/L) community well in each study village was ensured during an 18-month intervention p...
Studies in cell culture and animal models indicate that arsenic exposure induces modifications in... more Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water. The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenic-induced alterations in DNA methylation may be influenced by folate nutritional status. PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [(3)H]-methyl incorporation assay. Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P = 0.0...
Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of inge... more Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of ingested inorganic arsenic (InAs) to monomethylarsonic (MMAs) and dimethylarsinic (DMAs) acids relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic elimination. We hypothesized that folic acid supplementation to arsenic-exposed Bangladeshi adults would increase arsenic methylation and thereby lower total blood arsenic. In this randomized, double-blind, placebo-controlled trial, we evaluated blood concentrations of total arsenic, InAs, MMAs, and DMAs in 130 participants with low plasma folate (<9 nmol/L) before and after 12 wk of supplementation with folic acid (400 microg/d) or placebo. MMAs in blood was reduced by a mean +/- SE of 22.24 +/- 2.86% in the folic acid supplementation group and by 1.24 +/- 3.59% in the placebe group (P < 0.0001). There was no change in DMAs in blood; DMAs is rapidly excreted in urine as evidenced by an increase in urinary DMAs (...
Observational studies and clinical trials have shown associations of diet and high blood pressure... more Observational studies and clinical trials have shown associations of diet and high blood pressure (BP). However, prospective studies on the association between dietary patterns and longitudinal BP change are lacking, especially in low-income populations. We evaluated the association of dietary patterns and food groups with longitudinal change of BP in 10 389 participants in the Health Effects of Arsenic Longitudinal Study, with a median of 6.7 years of follow-up. Dietary information was obtained through a previously validated food-frequency questionnaire. BP was measured at baseline and at each biennial follow-up using the same method. Each standard deviation (SD) increase for the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;gourd vegetable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; dietary pattern score was related to a slower annual change of 0.08, 0.04, and 0.05 mmHg in SBP, DBP, or pulse pressure, respectively. Each SD increase in the…
Background: An emerging body of evidence indicates that early-life arsenic (As) exposure may infl... more Background: An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown.
Background: Arsenic can naturally occur in the groundwater without an anthropogenic source of con... more Background: Arsenic can naturally occur in the groundwater without an anthropogenic source of contamination. In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations exceeding the World Health Organization's guideline of 10 μg/L. Selenium and arsenic have been shown to facilitate the excretion of each other in bile. Recent evidence suggests that selenium may play a role in arsenic elimination by forming a selenium-arsenic conjugate in the liver before excretion into the bile. Methods: A cross-sectional study of 1601 adults and 287 children was conducted to assess the relationship between blood selenium and urinary and blood arsenic in a study population residing in a moderately arsenic-contaminated rural area in Bangladesh. Results: The results of this study indicate a statistically significant inverse relationship between blood selenium and urinary arsenic concentrations in both adult and pediatric populations in rural Bangladesh after adjustment for age, sex, Body Mass Index, plasma folate and B12 (in children), and ever smoking and current betel nut use (in adults). In addition, there appears to be a statistically significant inverse relationship between blood selenium and blood arsenic in children. Conclusions: Our results suggest that selenium is inversely associated with biomarkers of arsenic burden in both adults and children. These findings support the hypothesis that Se facilitates the biliary elimination of As, possibly via the putative formation of a Se-As conjugate using a glutathione complex. However, laboratory based studies are needed to provide further evidence to elucidate the presence of Se-As conjugate and its role in arsenic elimination in humans.
Background: Populations in South and East Asia and many other regions of the world are chronicall... more Background: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic- contaminated drinking water. To various degrees, ingested inor- ganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one- carbon metabolism; impaired methylation is associated with ad- verse health outcomes. Consequently, folate nutritional status may influence
Journal of Occupational and Environmental Medicine, 2014
To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative... more To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative damage in Bangladeshi adults. We recruited 378 participants drinking water from wells assigned to five water As exposure categories; the distribution of subjects was as follows: (1) less than 10 μg/L (n=76); (2) 10 to 100 μg/L (n=104); (3) 101 to 200 μg/L (n=86); (4) 201 to 300 μg/L (n=67); and (5) more than 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyguanosine and plasma protein carbonyls were measured to assess oxidative damage. None of our measures of As exposure were significantly associated with protein carbonyl or 8-oxo-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyguanosine levels. We found no evidence to support a significant relationship between long-term exposure to As-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults.
Environmental health : a global access science source, 2012
To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to ... more To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to perform water arsenic (WAs) testing and provide As education compared to sending representatives from outside communities to conduct these tasks. We conducted a cluster based randomized controlled trial of 20 villages in Singair, Bangladesh. Fifty eligible respondents were randomly selected in each village. In 10 villages, a community member provided As education and WAs testing. In a second set of 10 villages an outside representative performed these tasks. Overall, 53% of respondents using As contaminated wells, relative to the Bangladesh As standard of 50 μg/L, at baseline switched after receiving the intervention. Further, when there was less than 60% arsenic contaminated wells in a village, the classification used by the Bangladeshi and UNICEF, 74% of study households in the community tester villages, and 72% of households in the outside tester villages reported switching to an As s...
Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of... more Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Cons...
Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure f... more Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = −5.1 μm, 95% CI = −31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = −3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.
Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase... more Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 μg/L) and Mn (above and below 500 μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels.
Drinking water manganese (WMn) is a potential threat to children's health due to its associations... more Drinking water manganese (WMn) is a potential threat to children's health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available.. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8-11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400 μg/L was associated with 6.4 percentage score loss (95% CI=0.5, 12.3) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water.
Background: Arsenic methylation relies on folate-dependent one-carbon metabolism and facilitates ... more Background: Arsenic methylation relies on folate-dependent one-carbon metabolism and facilitates urinary As elimination. Clinical manifestations of As toxicity vary considerably among individuals and populations, and poor methylation capacity is thought to confer greater susceptibility. oBjective: After determining that folate deficiency, hyperhomocysteinemia, and low urinary creatinine are associated with reduced As methylation, and that As exposure is associated with increased genomic methylation of leukocyte DNA, we asked whether these factors are associated with As-induced skin lesion risk among Bangladeshi adults. Methods: We conducted a nested case-control study of 274 cases who developed lesions 2 years after recruitment, and 274 controls matched to cases for sex, age, and water As. results: The odds ratios and 95% confidence intervals (CIs) for development of skin lesions for participants who had low folate (< 9 nmol/L), hyperhomocysteinemia (men, > 11.4 µmol/L; women, > 10.4 µmol/L), or hypomethylated leukocyte DNA at recruitment (< median) were 1.8 (95% CI, 1.1-2.9), 1.7 (95% CI, 1.1-2.6), and 1.8 (95% CI, 1.2-2.8), respectively. Compared with the subjects in the first quartile, those in the third and fourth quartiles for urinary creatinine had a 0.4-fold decrease in the odds of skin lesions (p < 0.01). conclusions: These results suggest that folate deficiency, hyperhomocysteinemia, and low urinary creatinine, each associated with decreased As methylation, are risk factors for As-induced skin lesions. The increased DNA methylation associated with As exposure previously observed, and confirmed among controls in this study, may be an adaptive change because hypomethylation of leukocyte DNA is associated with increased risk for skin lesions.
The American Journal of Clinical Nutrition, Oct 1, 2007
Background: Studies in cell culture and animal models indicate that arsenic exposure induces modi... more Background: Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water. Objective: The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenicinduced alterations in DNA methylation may be influenced by folate nutritional status. Design: PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [ 3 H]-methyl incorporation assay. Results: Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P ҃ 0.009, 0.03, and 0.03, respectively). Stratification of participants by folate nutritional status [9 nmol/L (n ҃ 190) or ͧ9 nmol/L (n ҃ 104)] showed that the associations between arsenic exposure and methylation of PBL DNA were restricted to persons with folate concentrations ͧ 9 nmol/L. Conclusions: Contrary to our a priori hypothesis, arsenic exposure was positively associated with genomic PBL DNA methylation in a dose-dependent manner. This effect is modified by folate, which suggests that arsenic-induced increases in DNA methylation cannot occur in the absence of adequate folate. The underlying mechanisms and physiologic implications of increased genomic DNA methylation are unclear, and they warrant further study.
To evaluate the potential effects of betel quid chewing on mortality. (A quid consists of betel n... more To evaluate the potential effects of betel quid chewing on mortality. (A quid consists of betel nut, wrapped in betel leaves; tobacco is added to the quid by some users). Prospective data were available on 20 033 individuals aged 18-75 years, living in Araihazar, Bangladesh. Demographic and exposure data were collected at baseline using a standardized questionnaire. Cause of death was defined by verbal autopsy questionnaires administered to next of kin. We estimated hazard ratios (HR) and their 95% confidence intervals (CI) for associations between betel use and mortality from all causes and from specific causes, using Cox proportional hazards models. We adjusted for age, sex, body mass index, educational attainment and tobacco smoking history. There were 1072 deaths during an average of 10 years of follow-up. Participants who had ever used betel were significantly more likely to die from all causes (HR: 1.26; 95% CI: 1.09-1.44) and cancer (HR: 1.55; 95% CI: 1.09-2.22); but not cardiovascular disease (HR: 1.16; 95% CI: 0.93-1.43). These findings were robust to adjustment for potential confounders. There was a dose-response relationship between mortality from all causes and both the duration and the intensity of betel use. The population attributable fraction for betel use was 14.1% for deaths from all causes and 24.2% for cancer. Betel quid use was associated with mortality from all causes and from cancer in this cohort.
Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly ... more Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk- is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hydroxymethylcytosine (5-hmC) has not been widely studied. We evaluated associations of As in drinking water (wAs), urine (uAs), and blood (bAs) with global %5-mC and %5-hmC in two studies of Bangladeshi adults: i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity (NIAT) study (n=196; 49% male, 19-66 years); and ii) peripheral blood mononuclear cell (PBMC) DNA in the Folate and Oxidative Stress (FOX) study (n=375; 49% male, 30-63 years). Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (p for interaction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Analyses examining interactions by elevated plasma total homocysteine (tHcys), an indicator of B-vitamin deficiency, found that tHcys also modified the association between As and global %5-hmC (p for interaction &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.10). In two samples, we observed associations between As exposure and global %5-hmC in blood DNA that were modified by sex and tHcys. Our findings suggest that As induces sex-specific changes in 5-hmC, an epigenetic mark that has been associated with cancer. Future research should explore whether altered %5-hmC is a mechanism underlying the sex-specific influences of As on skin lesion and cancer outcomes.
In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations ex... more In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations exceeding the WHO standard of 10 μg/L, even though arsenic safe water is often available within a short walking distance. Arsenic mitigation typically involves a person coming into a village to test the well water for arsenic. This person often leaves the village without providing the resources to address health concerns or advice on mitigation options. We developed an arsenic education training program for local staff and conducted a longitudinal intervention study of 20 villages to investigate the impact of having local resident staff conduct water arsenic testing and to provide arsenic awareness education as well as mitigation options on arsenic exposure. A pre- and post-intervention questionnaire was administered to the person in each randomly selected household responsible for primary drinking water collection. The results of this study, conducted in 20 villages in Singair, Bangladesh...
Chronic exposure to well water arsenic (As) remains a major rural health challenge in Bangladesh ... more 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. This study estimates associations between a school-based intervention and various outcome measures of As mitigation. 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 seven schools without any training formed the control group. Surveys, knowledge tests and well-water testing were conducted on 773 children both at baseline and post-intervention follow-up. Urine samples were collected from 210 children from four intervention schools and the same number of children from four control schools. One low As (<10 μg/L) community well in each study village was ensured during an 18-month intervention p...
Studies in cell culture and animal models indicate that arsenic exposure induces modifications in... more Studies in cell culture and animal models indicate that arsenic exposure induces modifications in DNA methylation, including genome-wide DNA hypomethylation. It is not known whether arsenic exposure influences genomic DNA methylation in human populations chronically exposed to arsenic-contaminated drinking water. The objective of this study was to determine whether arsenic is associated with genomic hypomethylation of peripheral blood leukocyte (PBL) DNA in Bangladeshi adults who are chronically exposed to arsenic. We also investigated whether arsenic-induced alterations in DNA methylation may be influenced by folate nutritional status. PBL DNA methylation and concentrations of plasma folate, plasma arsenic, and urinary arsenic were assessed in 294 adults in Araihazar, Bangladesh. Genomic PBL DNA methylation was measured by using a [(3)H]-methyl incorporation assay. Urinary arsenic, plasma arsenic, and plasma folate were positively associated with the methylation of PBL DNA (P = 0.0...
Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of inge... more Chronic arsenic exposure currently affects >100 million persons worldwide. Methylation of ingested inorganic arsenic (InAs) to monomethylarsonic (MMAs) and dimethylarsinic (DMAs) acids relies on folate-dependent one-carbon metabolism and facilitates urinary arsenic elimination. We hypothesized that folic acid supplementation to arsenic-exposed Bangladeshi adults would increase arsenic methylation and thereby lower total blood arsenic. In this randomized, double-blind, placebo-controlled trial, we evaluated blood concentrations of total arsenic, InAs, MMAs, and DMAs in 130 participants with low plasma folate (<9 nmol/L) before and after 12 wk of supplementation with folic acid (400 microg/d) or placebo. MMAs in blood was reduced by a mean +/- SE of 22.24 +/- 2.86% in the folic acid supplementation group and by 1.24 +/- 3.59% in the placebe group (P < 0.0001). There was no change in DMAs in blood; DMAs is rapidly excreted in urine as evidenced by an increase in urinary DMAs (...
Observational studies and clinical trials have shown associations of diet and high blood pressure... more Observational studies and clinical trials have shown associations of diet and high blood pressure (BP). However, prospective studies on the association between dietary patterns and longitudinal BP change are lacking, especially in low-income populations. We evaluated the association of dietary patterns and food groups with longitudinal change of BP in 10 389 participants in the Health Effects of Arsenic Longitudinal Study, with a median of 6.7 years of follow-up. Dietary information was obtained through a previously validated food-frequency questionnaire. BP was measured at baseline and at each biennial follow-up using the same method. Each standard deviation (SD) increase for the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;gourd vegetable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; dietary pattern score was related to a slower annual change of 0.08, 0.04, and 0.05 mmHg in SBP, DBP, or pulse pressure, respectively. Each SD increase in the…
Background: An emerging body of evidence indicates that early-life arsenic (As) exposure may infl... more Background: An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown.
Background: Arsenic can naturally occur in the groundwater without an anthropogenic source of con... more Background: Arsenic can naturally occur in the groundwater without an anthropogenic source of contamination. In Bangladesh over 50 million people are exposed to naturally occurring arsenic concentrations exceeding the World Health Organization's guideline of 10 μg/L. Selenium and arsenic have been shown to facilitate the excretion of each other in bile. Recent evidence suggests that selenium may play a role in arsenic elimination by forming a selenium-arsenic conjugate in the liver before excretion into the bile. Methods: A cross-sectional study of 1601 adults and 287 children was conducted to assess the relationship between blood selenium and urinary and blood arsenic in a study population residing in a moderately arsenic-contaminated rural area in Bangladesh. Results: The results of this study indicate a statistically significant inverse relationship between blood selenium and urinary arsenic concentrations in both adult and pediatric populations in rural Bangladesh after adjustment for age, sex, Body Mass Index, plasma folate and B12 (in children), and ever smoking and current betel nut use (in adults). In addition, there appears to be a statistically significant inverse relationship between blood selenium and blood arsenic in children. Conclusions: Our results suggest that selenium is inversely associated with biomarkers of arsenic burden in both adults and children. These findings support the hypothesis that Se facilitates the biliary elimination of As, possibly via the putative formation of a Se-As conjugate using a glutathione complex. However, laboratory based studies are needed to provide further evidence to elucidate the presence of Se-As conjugate and its role in arsenic elimination in humans.
Background: Populations in South and East Asia and many other regions of the world are chronicall... more Background: Populations in South and East Asia and many other regions of the world are chronically exposed to arsenic- contaminated drinking water. To various degrees, ingested inor- ganic arsenic (InAs) is methylated to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) via folate-dependent one- carbon metabolism; impaired methylation is associated with ad- verse health outcomes. Consequently, folate nutritional status may influence
Journal of Occupational and Environmental Medicine, 2014
To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative... more To evaluate the dose-response relationship between arsenic (As) exposure and markers of oxidative damage in Bangladeshi adults. We recruited 378 participants drinking water from wells assigned to five water As exposure categories; the distribution of subjects was as follows: (1) less than 10 μg/L (n=76); (2) 10 to 100 μg/L (n=104); (3) 101 to 200 μg/L (n=86); (4) 201 to 300 μg/L (n=67); and (5) more than 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyguanosine and plasma protein carbonyls were measured to assess oxidative damage. None of our measures of As exposure were significantly associated with protein carbonyl or 8-oxo-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyguanosine levels. We found no evidence to support a significant relationship between long-term exposure to As-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults.
Environmental health : a global access science source, 2012
To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to ... more To reduce arsenic (As) exposure, we evaluated the effectiveness of training community members to perform water arsenic (WAs) testing and provide As education compared to sending representatives from outside communities to conduct these tasks. We conducted a cluster based randomized controlled trial of 20 villages in Singair, Bangladesh. Fifty eligible respondents were randomly selected in each village. In 10 villages, a community member provided As education and WAs testing. In a second set of 10 villages an outside representative performed these tasks. Overall, 53% of respondents using As contaminated wells, relative to the Bangladesh As standard of 50 μg/L, at baseline switched after receiving the intervention. Further, when there was less than 60% arsenic contaminated wells in a village, the classification used by the Bangladeshi and UNICEF, 74% of study households in the community tester villages, and 72% of households in the outside tester villages reported switching to an As s...
Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of... more Kidney disease is emerging as an arsenic (As)-linked disease outcome, however further evidence of this association is warranted. Our first objective for this paper was to examine the potential renal toxicity of As exposure in Bangladesh. Our second objective relates to examining whether the previously reported positive association between urinary creatinine (uCrn) and As methylation may be explained by renal function. We had hypothesized that these associations relate to supply and demand for s-adenosylmethionine, the methyl donor for both creatine synthesis and As methylation. Alternatively, renal function could influence both As and creatinine excretion, or the As metabolites may influence renal function, which in turn influences uCrn. We conducted a cross-sectional study (N = 478) of adults, composed of a sample recruited in 2001 and a sample recruited in 2003. We assessed renal function using plasma cystatin C, and calculated the estimated glomerular filtration rate (eGFR). Cons...
Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure f... more Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = −5.1 μm, 95% CI = −31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = −3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.
Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase... more Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 μg/L) and Mn (above and below 500 μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels.
Drinking water manganese (WMn) is a potential threat to children's health due to its associations... more Drinking water manganese (WMn) is a potential threat to children's health due to its associations with a wide range of outcomes including cognitive, behavioral and neuropsychological effects. Although adverse effects of Mn on cognitive function of the children indicate possible impact on their academic achievement little evidence on this issue is available.. Moreover, little is known regarding potential interactions between exposure to Mn and other metals, especially water arsenic (WAs). In Araihazar, a rural area of Bangladesh, we conducted a cross-sectional study of 840 children to investigate associations between WMn and WAs and academic achievement in mathematics and languages among elementary school-children, aged 8-11 years. Data on As and Mn exposure were collected from the participants at the baseline of an ongoing longitudinal study of school-based educational intervention. Annual scores of the study children in languages (Bangla and English) and mathematics were obtained from the academic achievement records of the elementary schools. WMn above the WHO standard of 400 μg/L was associated with 6.4 percentage score loss (95% CI=0.5, 12.3) in mathematics achievement test scores, adjusted for WAs and other sociodemographic variables. We did not find any significant associations between WMn and academic achievement in either language. Neither WAs nor urinary As was significantly related to any of the three academic achievement scores. Our finding suggests that a large number of children in rural Bangladesh may experience deficits in mathematics due to high concentrations of Mn exposure in drinking water.
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Papers by Diane Levy