Levels Of Arsenic Exposure Research Articles

Induction of oxidative stress upon low level exposure of arsenic using lipid peroxidation assay in freshwater fish Channa punctatus

Elevated level of arsenic exposure through drinking water induces noticeable change in the level of oxidative stress parameter such as lipid peroxidation. However, there is paucity of available information at low level exposure of arsenic for inducing oxidative damage. Present work was undertaken to investigate the oxidative stress inducing potential of arsenic at its low level exposure in fresh water fish Channa puntatus using lipid peroxidation, an established biomarker of oxidative stress. Fish specimen were exposed to 10, 50 (low level exposure) and 500μgL-1(high level exposure) of arsenic using sodium arsenite as a test substance. Samples of gill, liver, kidney and brain tissues were collected after 14 days of exposure and the lipid peroxidation assay was performed through the quantification of malondialdehyde (MDA) by TBARS assay for determination of oxidative damage in different tissues of fish. Significant increased levels of LPO were observed in all the organs. The present study showed that gills were the most sensitive organ, therefore, showed maximum peroxidative damage at 500 μgL-1 of arsenic exposure.

The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (ƩAs) at baseline. The proportions of urine iAs, MMA and DMA over the ƩiAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in ƩAs (12.5μg/L, overall range 0.7-194.1μg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Variation in Arsenic metabolism in schistosomiasis associated bladder pathology in a rural community, Eggua, Ogun State, Nigeria

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T>C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P> 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology.

Long-term Lung Cancer Risk Associated with Sputum Atypia: A 27-Year Follow-up Study of an Occupational Lung Screening Cohort in Yunnan, China.

Sputum cytologic atypia is associated with increased lung cancer risk. However, little is known about the long-term magnitude and temporal trend of this risk. An extended follow-up was conducted in a prospective screening cohort among occupational tin miners in Yunnan, China. Sputum samples were collected prospectively at baseline and 7 annual screenings since enrollment. The associations between sputum cytologic results from baseline screening, the first 4 consecutive rounds of sputum screening, and lung cancer risk were analyzed by time-varying covariate Cox regression model. A moderate or worse cytologic result was associated with a significantly increased lung cancer risk. This relative hazard significantly decreased over time. Compared with negative screening results, the adjusted hazard ratios of baseline-moderate or worse atypia, at least one moderate or worse atypia in the first 4 consecutive screening rounds during the first 10 years of follow-up were 3.11 [95% confidence interval (CI): 2.37-4.07], 3.25 (95% CI: 2.33-4.54) respectively. This association was stronger for persistent atypia (adjusted hazard ratio = 17.55, 95% CI: 8.32-37.03); atypia identified in the recent screening rounds (adjusted HR = 4.14, 95% CI: 2.70-6.35), and those were old in age, had higher level of smoking, occupational radon, and arsenic exposure. In terms of histology, this increased risk was significant for squamous cell carcinoma and small cell lung cancer. Although decreasing over time, an increased lung cancer risk concerning moderate or worse sputum atypia can continue at least for 10 years. Sputum atypia might be helpful for identifying high-risk individuals for screening, surveillance, or chemoprevention of lung cancer.

A cohort study of the association between prenatal arsenic exposure and age at menarche in a rural area, Bangladesh

BackgroundMillions of individuals worldwide, particularly in Bangladesh, are exposed to arsenic, mainly through drinking water from tube wells. Arsenic is a reproductive toxicant, but there is limited knowledge of whether it influences pubertal development. ObjectivesWe evaluated the association between prenatal arsenic exposure and age at menarche. MethodsThis prospective study was based on data from two studies conducted in Matlab, Bangladesh—the Maternal and Infant Nutrition Interventions in Matlab (MINIMat) trial and the Health Consequences of Arsenic in Matlab (AsMat) study. We included 809 MINIMat girls who participated in assessing age at menarche from July 2016 to June 2017 and had prenatal arsenic exposure data through the AsMat study via measurements in tube well water used by the mothers during pregnancy. The exposure was categorized into <10, 10–49, 50–99, 100–199, and ≥200 µg/L. We used Kaplan-Meier and Cox proportional hazards analyses with adjustment for potential confounders to evaluate the association between arsenic exposure and age at menarche. The results were presented by adjusted hazards ratio (aHR) with a 95% confidence interval (CI). ResultsThe median arsenic concentration in tube well water consumed by pregnant women was 80 µg/L (interquartile range 2–262 µg/L), and 55% drank water with concentrations above Bangladesh’s acceptable value of 50 µg/L. The median age at menarche was 13.0 years. The unadjusted analysis revealed 3.2 months delay in menarche for girls exposed to arsenic concentrations ≥200 µg/L compared with the girl exposed to arsenic concentrations <10 µg/L. Girls exposed to the same higher arsenic concentrations were 23% (aHR 0.77, 95% CI: 0.63–0.95) less likely to have reached menarche than girls exposed to low arsenic concentrations. ConclusionsIncreased levels of prenatal arsenic exposure were associated with older age at menarche. This delay may indicate endocrine disruptions that could potentially result in adverse health consequences in later life. This finding, along with other severe adverse health reinforces the need for arsenic mitigation at the population level.

T helper 2-driven immune dysfunction in chronic arsenic-exposed individuals and its link to the features of allergic asthma

Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators— interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators— interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As.

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study.

Background:Common genetic variation in the arsenic methyltransferase (AS3MT) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine. Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated.Objectives:We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants.Methods:We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, ), Strong Heart Study (SHS, ), and New Hampshire Skin Cancer Study (NHSCS, ). We assessed the collective effects of rare (allele frequency ), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32 region, age, sex, and population structure).Results:We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants. DMA% was 6–10% lower in carriers compared with noncarriers in HEALS [ (95% CI: , )], SHS [ (95% CI: , )], and NHSCS [ (95% CI: , )]. In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [ (95% CI: , )].Discussion:Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME. Although a small percentage of the population (0.5–0.7%) carry these variants, they are associated with a 6–10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds. https://doi.org/10.1289/EHP8152

A review of low-dose arsenic risks and human cancers

The linear no-threshold (LNT) model has historically been the default assumption in assessing carcinogenic risk from arsenic ingestion based on epidemiological studies. This contrasts with the threshold model used in assessing carcinogenic risk from arsenic ingestion derived from toxicological investigations of experimental animals. We present here a review of our epidemiological work that has examined models that may better explain the human cancer risk from the ingestion of arsenic, particularly from low level exposures, than does the LNT model. While previous epidemiology studies have demonstrated increased risks of bladder, lung, and skin cancers at arsenic exposures of 200 ug/L or greater, we seek here to examine the dose-response patterns at lower exposure levels. These include ecological, case/control, and cohort designs. Methodologic issues include choice of continuous or stratified analysis of exposure data, search for sources of non-conformity or variability, and distinctions in water sources and geography. Multiple studies have yielded useful data-based models, including threshold models, hockey-stick models, and “J-shaped” linear-quadratic models. These models have found that increased cancer risk may only begin at specific arsenic exposure levels greater than zero. These results provide guidance in seeking toxicological explanations and public health reference levels.

Association between arsenic exposure, DNA damage, and urological cancers incidence: A long-term follow-up study of residents in an arseniasis endemic area of northeastern Taiwan

Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43–14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer.

Aortic Strain -Threshold Analysis of Non-Cancer Outcome from Arsenic Exposure

Background: While arsenic has been shown in many studies to behave as a threshold carcinogen, analyses of non-cancer outcomes (e.g., cardiovascular) have generally been presented only using linear models. Alternative models have received little consideration. We choose here to examine aortic strain data, a known risk factor for hypertension and cardiovascular disease, on arsenic-exposed workers with alternative analytic modeling.Method: A previously published study (Karakulak et al., 2016) of aortic strain measurements in arsenic-exposed workers had demonstrated that aortic strain was markedly reduced among workers with high levels of arsenic exposure (urinary arsenic in ug/L). The original analysis was limited to a linear model without model validation. We have analyzed the data using alternative models.Results: Examination of the linear analysis and its residuals demonstrated significant heteroscedascity with unequal variances, particularly at urinary levels of &gt; 160 ug arsenic per liter (ug/L). The test of equal variances from samples with &gt;160 and samples &lt;= 160 demonstrated inequality (p &lt; 0.0001). The better alternative model was a step-function with a mean aortic strain of 11.3% for those with urinary arsenic &lt;= 160 ug/L and with a mean aortic strain of 5.3% for those with urinary arsenic &gt; 160 ug/L. A further stratified analysis with bins of 40 ug/L showed no effect on aortic strain for the urinary arsenic range of &lt;= 160 ug/L and, separately, no effect for the urinary arsenic range of &gt; 160 ug/L.Conclusion: Aortic elasticity parameters show an adverse effect from arsenic exposure only at urinary exposure levels of &gt; 160 ug/L and not below, indicating a step-function rather than a linear function. Restriction of analyses to a linear no-threshold model may have blinded the finding of a more useful demonstration of a dose-response pattern that may offer different toxicological interpretations.

Low levels of arsenic exposure during pregnancy and maternal and neonatal thyroid hormone parameters: The determinants for these associations

BackgroundThe potential maternal and neonatal thyrotoxicity associated with exposure to arsenic during pregnancy is very limited and unclear. ObjectivesThis study aimed to examine the associations between arsenic exposure levels in maternal and cord serum and maternal and neonatal thyroid hormone parameters in a prospective birth cohort study. MethodsThe study including 2089 mother-neonate pairs was based upon Ma’an Shan birth cohort study in China. The exposure variables including maternal serum arsenic levels in the first, second and third trimester and average arsenic exposure level during pregnancy and cord serum arsenic level. Maternal serum TSH and FT4 levels in the first, second and third trimester and cord serum TSH and FT4 levels were determined using the electrochemiluminescence immunoassay with Cobas Elecsys 411. Linear mixed models were used to examine associations between arsenic exposure variables during pregnancy and maternal thyroid hormone parameters, and multiple linear regression analyses were used to examine associations between arsenic exposure during pregnancy and neonatal thyroid hormone parameters. Bayesian kernal machine regression (BKMR) analyses based on a kernel function were also used to examine the effects of exposure to metal mixtures (arsenic, mercury, cadmium and selenium). ResultsThe geometric means of arsenic exposure levels across 3 trimesters were 1.74 μg/L, 1.81 μg/L and 1.99 μg/L, respectively, and 1.90 μg/L in cord serum; the geometric means of maternal FT4 levels across 3 trimesters were 16.91 pmol/L, 11.91 pmol/L and 13.16 pmol/L, respectively, and 16.10 pmol/L in cord serum; the geometric means of maternal TSH levels across 3 trimesters were 1.27 μIU/mL, 2.32 μIU/mL and 2.08 μIU/mL, respectively, and 8.47 μIU/mL in cord serum. Maternal serum arsenic levels in the first, seond, third trimester and average arsenic exposure level during pregnancy were all not associated with maternal thyroid hormone parameters after adjustment for all the covariates, the adjusted β (95% CI) were −0.002 (−0.10 to 0.09), 0.05 (−0.05 to 0.16), −0.09 (−0.17 to 0.003) and −0.05 (−0.22 to 0.11) for maternal FT4, respectively; and −0.005 (−0.04 to 0.03), −0.003 (−0.04 to 0.03), −0.004 (−0.03 to 0.02) and −0.01 (−0.06 to 0.04) for maternal lnTSH, respectively. Maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy were all inversely associated with neonatal FT4 level after adjustment for all the confounders, the adjusted β (95% CI) were −0.19 (−0.31 to −0.07), −0.14 (−0.26 to −0.01), −0.22 (−0.42 to −0.02), respectively; and cord serum arsenic level was positively related with neonatal TSH level, the adjusted β (95% CI) were 0.04 (0.001 to 0.08). The adverse joint toxic effect of the four metals in maternal serum in the first trimester and in cord serum on neonatal thyroid hormone parameters were also found. ConclusionsIn this study, exposure to low levels of arsenic during pregnancy could directly affect neonatal thyroid hormone parameters without being mediated by maternal effect of exposure, and maternal serum arsenic levels in the first, second trimester and average arsenic exposure level during pregnancy and cord serum arsenic level may be risk factors affecting neonatal thyroid hormones. These findings indicate that neonates are more sensitive to the thyrotoxicity of arsenic exposure even at low levels. In addition, the adverse joint toxic effect of metal mixtures is also worthy of attention.

Low- and moderate- levels of arsenic exposure in young adulthood and incidence of chronic kidney disease: Findings from the CARDIA Trace Element Study

BackgroundIt is unclear whether arsenic exerts adverse health effects on the kidney at low- and moderate- levels of exposure. We prospectively examined toenail arsenic concentrations measured during young adulthood in relation to incidence of chronic kidney disease (CKD) in midlife. MethodsA total of 3768 participants (53 % female and 48 % blacks) in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Arsenic concentration in toenail clippings was assessed by using inductively coupled plasma mass spectrometry at CARDIA exam year 2. Incident CKD was identified if having estimated glomerular filtration rate <60 mL/min per 1.73 m² or albuminuria >30 mg/g. The association between toenail arsenic levels and CKD incidence over a mean of 24 years of follow-up was examined using multivariable-adjusted Cox proportional hazards models. ResultsAfter controlling for potential confounders, including demographics, socioeconomics, lifestyle factors, clinical measurements of blood pressure, lipids, and glucose, and medical history, arsenic exposure measured in toenails was not associated with CKD incidence (quintile 5 versus quintile 1: hazard ratio = 1.04, 95 % confidence interval = 0.78–1.40, P for trend = 0.38). ConclusionThis longitudinal study does not support the hypothesis that low- and moderate- levels of arsenic exposure are associated with elevated incidence of CKD in the US general population. Further studies are need to investigate species of arsenic biomarkers in relation to nephrotoxicity.

Use of study-specific MOE-like estimates to prioritize health effects from chemical exposure for analysis in human health assessments

There are unique challenges in estimating dose-response with chemicals that are associated with multiple health outcomes and numerous studies. Some studies are more suitable than others for quantitative dose-response analyses. For such chemicals, an efficient method of screening studies and endpoints to identify suitable studies and potentially important health effects for dose-response modeling is valuable. Using inorganic arsenic as a test case, we developed a tiered approach that involves estimating study-specific margin of exposure (MOE)-like unitless ratios for two hypothetical scenarios. These study-specific unitless ratios are derived by dividing the exposure estimated to result in a 20% increase in relative risk over the background exposure (RRE20) by the background exposure, as estimated in two different ways. In our case study illustration, separate study-specific ratios are derived using estimates of United States population background exposure (RRB-US) and the mean study population reference group background exposure (RRB-SP). Systematic review methods were used to identify and evaluate epidemiologic studies, which were categorized based on study design (case-control, cohort, cross-sectional), various study quality criteria specific to dose-response analysis (number of dose groups, exposure ascertainment, exposure uncertainty), and availability of necessary dose-response data. Both case-control and cohort studies were included in the RRB analysis. The RRE20 estimates were derived by modeling effective counts of cases and controls estimated from study-reported adjusted odds ratios and relative risks. Using a broad (but not necessarily comprehensive) set of epidemiologic studies of multiple health outcomes selected for the purposes of illustrating the RRB approach, this test case analysis would suggest that diseases of the circulatory system, bladder cancer, and lung cancer may be arsenic health outcomes that warrant further analysis. This is suggested by the number of datasets from adequate dose-response studies demonstrating an effect with RRBs close to 1 (i.e., RRE20 values close to estimated background arsenic exposure levels).

Health risk assessment of inorganic arsenic exposure through fish consumption in Yellowknife, Northwest Territories, Canada

Yellowknife, Northwest Territories, Canada, is located near two closed gold mines. Elevated arsenic concentrations reported in fish are a public health concern. We collected 180 samples of three species of commonly consumed fish in 2013–2018 and analyzed arsenic species, including inorganic arsenic (As(III) and As(V)), monomethylarsonate (MMA), dimethylarsinic acid (DMA), and arsenobetaine. The average total arsenic concentration in fish muscle tissue was 2.30 ± 1.72 µg/g dry weight, and that in burbot liver tissue was 3.16 ± 2.49 µg/g dry weight. Nontoxic arsenobetaine was the main arsenic species in fish muscle (mean = 58.6 ± 34.5%), whereas DMA was the predominant species in burbot liver (mean = 76.6 ± 21.6%). On average, inorganic arsenic species accounted for less than 20% of the arsenic detected in fish. Data on the consumption of locally caught fish were collected from 1611 residents in Yellowknife in 2017 and 2018, including 1417 general residents and 194 members of the Yellowknives Dene First Nation. We evaluated the health risks from inorganic arsenic exposure using Monte Carlo simulations. Our results indicated that there were negligible non-cancer health risks, and the cancer risk was below the baseline cancer risk level of arsenic exposure among the Canadian general population.

Arsenic exposure-related hyperglycemia is linked to insulin resistance with concomitant reduction of skeletal muscle mass

BackgroundAlargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified. ObjectiveWe explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia. MethodsA total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects’ arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-β were used to calculate insulin resistance and β-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators. ResultsWater, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-β in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females’ HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia. ConclusionArsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.

Urinary Arsenic Species are Detectable in Urban Underserved Hispanic/Latino Populations: A Pilot Study from the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS).

Background: Hispanics/Latinos represent >15% of the United States (US) population and experience a high burden of cardiovascular disease (CVD) and diabetes. Dietary exposure, particularly to arsenic (As), may be associated with CVD and diabetes in Hispanics/Latinos. Rural populations in the US exposed to As in drinking water have increased risk of diabetes and CVD; however, little is known about the risk among urban populations with low As in water who are mostly exposed to As through food. Methods: To explore the levels of inorganic arsenic exposure (the sum of inorganic and methylated arsenic species in urine, ∑As, corrected by a residual-based method) in persons of Hispanic/Latino origin, we conducted a pilot study quantifying urinary arsenic levels among 45 participants in the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS). Results: The median (interquartile range) of the urinary arsenic species (µg/L) were as follows: inorganic As 0.6 (0.4, 1.0), monomethylarsonic acid 1.2 (0.7, 1.9), dimethylarsinic acid 7.2 (4.3, 15.3), and ∑As 6.0 (4.3, 10.5). Conclusions: This study adds to the existing evidence that harmful forms of arsenic are present in this group of Hispanics/Latinos.

Association between prenatal arsenic exposure, birth outcomes, and pregnancy complications: An observational study within the National Children's Study cohort

BackgroundChronic arsenic exposure has been associated with pregnancy complications and reduced fetal growth in populations where total arsenic exposure exceeds 50 μg/L. However, the potential effect on pregnancy outcomes remains unclear at lower levels of arsenic exposure, such as those most commonly observed in the United States. ObjectivesWe evaluated the associations between arsenic exposure during pregnancy with fetal growth and risk of pregnancy complications using data from mother-infant pairs participating in the National Children's Study. MethodsPrenatal arsenic exposure was measured using maternal urine collected during the third trimester. Information about pregnancy complications was abstracted from medical records. Fetal growth, including gestational age, birth weight, birth length, head circumference, and ponderal index, was ascertained through physical measurement at birth and extracted from medical records. ResultsMedians [interquartile range (IQR)] of maternal urinary total arsenic and dimethylarsinic acid (DMA) were 7.77 μg/L (7.98) and 3.44 μg/L (3.13), respectively. Each increase in IQR of prenatal total arsenic level was associated with greater birth length (+0.28 cm; 95% CI: 0.14, 0.42), greater head circumference (+0.12 cm; 95% CI: 0.04, 0.21), and lower ponderal index (−0.37 kg/m3; 95% CI: −0.58, −0.17). Similar results were obtained for levels of prenatal DMA. Tests for multiplicative interaction indicate that prenatal urinary DMA was negatively associated with gestational age among female infants (−0.44 week decrease in gestational age estimated for each IQR increase in DMA; 95% CI: −0.84, −0.05), while no association was observed among male infants (pinteraction = 0.02). No significant associations were detected between arsenic and birth weight or pregnancy complications. ConclusionsHigher prenatal arsenic exposure was associated with longer birth length, greater head circumference, and lower ponderal index. Associations between arsenic and gestational age may be modified by infant sex.

Determinants of arsenic methylation efficiency and urinary arsenic level in pregnant women in Bangladesh

BackgroundPrenatal inorganic arsenic (iAs) exposure is associated with pregnancy outcomes. Maternal capabilities of arsenic biotransformation and elimination may influence the susceptibility of arsenic toxicity. Therefore, we examined the determinants of arsenic metabolism of pregnant women in Bangladesh who are exposed to high levels of arsenic.MethodsIn a prospective birth cohort, we followed 1613 pregnant women in Bangladesh and collected urine samples at two prenatal visits: one at 4–16 weeks, and the second at 21–37 weeks of pregnancy. We measured major arsenic species in urine, including iAs (iAs%) and methylated forms. The proportions of each species over the sum of all arsenic species were used as biomarkers of arsenic methylation efficiency. We examined the difference in arsenic methylation using a paired t-test between first and second visits. Using linear regression, we examined determinants of arsenic metabolism, including age, BMI at enrollment, education, financial provider income, arsenic exposure level, and dietary folate and protein intake, adjusted for daily energy intake.ResultsComparing visit 2 to visit 1, iAs% decreased 1.1% (p < 0.01), and creatinine-adjusted urinary arsenic level (U-As) increased 21% (95% CI: 15, 26%; p < 0.01). Drinking water arsenic concentration was positively associated with iAs% at both visits. When restricted to participants with higher adjusted urinary arsenic levels (adjusted U-As > 50 μg/g-creatinine) gestational age at measurement was strongly associated with DMA% (β = 0.38, p < 0.01) only at visit 1. Additionally, DMA% was negatively associated with daily protein intake (β = − 0.02, p < 0.01) at visit 1, adjusting for total energy intake and other covariates.ConclusionsOur findings indicate that arsenic metabolism and adjusted U-As level increase during pregnancy. We have identified determinants of arsenic methylation efficiency at visit 1.

MicroRNAs play an important role in contributing to arsenic susceptibility in the chronically exposed individuals of West Bengal, India

Arsenic exposure by groundwater contamination is a menace which threatens more than 26 million individuals of West Bengal. Interestingly, with similar levels of arsenic exposure, only 15-20% of the population show arsenic-induced skin lesions, the hallmarks of chronic arsenic toxicity, but the rest do not. In this study, our aim was to identify whether microRNAs (miRNA) have any role to play in causing such arsenic susceptibility. Global plasma miRNA profiling was done in 12 arsenic-exposed individuals with skin lesions and 12 exposed individuals without skin lesions. Two hundred two miRNAs were found to be differentially regulated between the two study groups. Results were validated by quantitative real-time PCR in 30 exposed subjects from each of the groups, which showed that among others miR-21, miR-23a, miR-27a, miR-122, miR-124, miR-126, miR-619, and miR-3613 were significantly upregulated and miR-1282 and miR-4530 were downregulated in the skin lesion group compared with the no skin lesion group. Bioinformatic analyses predicted that these altered miRNAs have targets in 7 different biochemical pathways, including glycerophospholipid metabolism, colorectal cancer, glycosphingolipid biosynthesis, T cell receptor signaling, and neurotrophin signaling pathways; glycerophospholipid metabolism pathway being the most enriched pathway. Association study show that these microRNAs contribute significantly to the increased prevalence of other non-dermatological health effects like conjunctival irritations of the eyes and respiratory distress in the study subjects. To our knowledge, this is the first study of its kind involving miRNA expressions contributing to arsenic susceptibility in the exposed population of West Bengal.

Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor

BackgroundArsenic poisoning is a public health problem worldwide. A few studies have reported the effects of arsenic exposure on adult cognitive function, but with limitations in the subject selection and exposure markers. Moreover, information regarding the association between arsenic exposure and biomarker of cognitive impairment is scarce. ObjectivesWe examined the associations between arsenic exposure and adult cognitive impairment using the Mini-Mental State Examination (MMSE) and the serum levels of brain-derived neurotrophic factor (BDNF), a potential biomarker of cognitive health status. MethodsWe designed a cross-sectional study that recruited 693 adult (18–60 years old) subjects from the areas of low- and high‑arsenic exposure in rural Bangladesh. The subjects' arsenic exposure levels (drinking water, hair, and nail arsenic concentrations) were measured by inductively coupled plasma-mass spectroscopy. The Bangla version of the MMSE was used as a cognitive assessment tool. Serum BDNF (sBDNF) levels were assessed by immunoassay. ResultsIn this study, we found that average MMSE score and sBDNF level of the subjects in arsenic-endemic areas were significantly (p < 0.001 for both) lower than those of the subjects in non-endemic area. Our analyses revealed that both MMSE scores and sBDNF levels were decreased with the increasing concentrations of arsenic in drinking water, hair, and nails in a dose-dependent fashion. In regression analyses, significant associations of arsenic exposure metrics with MMSE scores and sBDNF levels were observed even after adjustment for several variables. Intriguingly, MMSE scores showed a significantly positive correlation with sBDNF levels. ConclusionOur findings demonstrate that chronic exposure to arsenic dose-dependently decreases cognitive function in adults, with a concomitant reduction of sBDNF levels. A decreased BDNF level may be part of the biochemical basis of chronic arsenic exposure-related cognitive impairment.