Urinary Monomethylarsonic Acid Research Articles

Associations of Urinary Total Arsenic and Arsenic Species and Periodontitis

AimsArsenic exposure is a significant global public health concern and has been implicated in endocrine disruption and increased oxidative stress, both of which are crucial pathogenic mechanisms of periodontitis. This study aimed to investigate the association of urinary total arsenic and arsenic species with periodontitis and to further explore the potential mediating roles of sex hormones and oxidative stress indicators. MethodsData used in this study were derived from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) in the US population. In all, 1063 participants with complete data were included in this study. Weighted logistic regression analyses were used to evaluate the relationship between urinary arsenic and periodontitis. Mediation analyses were used to explore the effects of potential mediators on these associations. ResultsHigh concentrations of urinary dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), 2 types of toxic urinary arsenic (TUA2), and 4 types of toxic urinary arsenic (TUA4) were positively related to periodontitis (P < .05). After adjusting for potential confounders, the positive association remained significant (odds ratio, 1.32; 95% confidence interval, 1.01–1.71). Testosterone may partially mediate the relationship between MMA and periodontitis, with mediating effects of 21.78% and 39.73% of the total effect. No significant mediation effect of oxidative stress indicators was found for this relationship. ConclusionsThis study reports a positive association between urinary MMA and periodontitis, and testosterone may mediate this relationship. Our findings serve as a call for action to avoid the deployment of arsenic-containing therapeutic agents as treatment modalities for oral afflictions.

Arsenic metabolism, N6AMT1 and AS3MT single nucleotide polymorphisms, and their interaction on gestational diabetes mellitus in Chinese pregnant women

BackgroundSingle nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM). ObjectiveThis study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM. MethodsA cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism. ResultsPregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, −0.13) and MMA% (B: 0.21; 95% CI: 0.39, −0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%. ConclusionsGenetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.

Prevalence of type 2 diabetes mellitus in relation to arsenic exposure and metabolism in Mexican women.

BackgroundExperimental studies have shown the diabetogenic potential of inorganic arsenic (iAs); however, the epidemiological evidence is still inconclusive. This could be explained by differences in exposure, metabolism efficiency, nutritional and genetic factors. ObjectiveTo evaluate the association between type 2 diabetes mellitus (T2DM) prevalence with arsenic exposure and metabolism, considering one-carbon metabolism nutrient intake and arsenite methyltransferase (AS3MT) polymorphisms. MethodsFrom healthy controls of a case control study for female breast cancer in northern Mexico, 227 self-reported diabetic women were age-matched with 454 non-diabetics. Participants were interviewed about dietary, sociodemographic and clinical characteristics. Urinary iAs metabolites were determined by HPLC-ICP-MS, methylation efficiency parameters were calculated, and AS3MT c.860 T > C and c.529-56G > C genotypes were determined. Unconditional logistic regression models were used to evaluate associations. ResultsTotal arsenic in urine (TAs) ranged from 0.73 to 248.12 μg/L with a median of 10.48 μg/L. In unadjusted analysis, TAs (μg/g) was significantly higher in cases than controls, but not when expressed as TAs (μg/L). Cases had significantly lower urinary monomethylarsonic acid percentage (%MMA), first methylation ratio (FMR), creatinine, and choline and selenium intakes. In multi-adjusted models and in women without HTA history T2DM showed significant positive associations with %iAs and FMR, respectively, and a significant negative association with %DMA. In participants with HTA history there was a marginal positive association (p = 0.08) between T2DM and TAs concentrations (μg/g) without other significant associations. ConclusionsOur results support an association between T2DM prevalence and iAs metabolism but not with urinary arsenic levels. However, elucidation of the interplay among iAs metabolism, T2DM and HTA merit further studies.

Association of albumin to creatinine ratio with urinary arsenic and metal exposure: evidence from NHANES 2015-2016.

Urinary metals can be used to identify metal exposure in humans from various sources in the environment. Decreased renal function and cardiovascular dysfunction may occur due to low levels of metal exposure in the general population. The purpose of this study is to assess the association between urinary arsenic and metals and a higher albumin to creatinine ratio (ACR) among adults in the general US population. We conducted a cross sectional analyses using the 2015-2016 National Health and Nutrition Examination Survey (NHANES) dataset. Multiple linear logistic models were used to examine the association between 21 urinary arsenic and metal concentrations (arsenous acid, arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid, monomethylarsonic acid, total arsenic, mercury, barium, cadmium, cobalt, cesium, molybdenum, manganese, lead, antinomy, tin, strontium, thallium, tungsten, uranium) and increased ACR (≥ 30mg/g). The sample included 4122 adults, of whom approximately 9.4% of males and 10.7% females had increased ACRs. The exposure included urinary arsenic compounds (7) and urinary metal compounds (14) at or above the limit of detection. Urinary dimethylarsinic acid [OR 38.9, 95% CI 3.6-414.6], urinary monomethylarsonic acid [OR 18.6, 95% CI 1.1-308.2], urinary cadmium [OR 11.9, 95% CI 1.2-122.0], urinary cesium [OR 17.0, 95% CI 2.7-105.8], and urinary antimony [OR 10.7, 95% CI 2.2-51.3] were associated with an increased ACR. No other urinary metals were significantly associated with increased ACR. Increased ACR was positively associated with urinary dimethylarsinic acid, monomethylarsonic acid, cadmium, cesium, and antimony.

Arsenic Exposure, Arsenic Metabolism, and Glycemia: Results from a Clinical Population in New York City.

Little information is available regarding the glycemic effects of inorganic arsenic (iAs) exposure in urban populations. We evaluated the association of total arsenic and the relative proportions of arsenic metabolites in urine with glycemia as measured by glycated blood hemoglobin (HbA1c) among 45 participants with prediabetes (HbA1c ≥ 5.7–6.4%), 65 with diabetes (HbA1c ≥ 6.5%), and 36 controls (HbA1c < 5.7%) recruited from an academic medical center in New York City. Each 10% increase in the proportion of urinary dimethylarsinic acid (DMA%) was associated with an odds ratio (OR) of 0.59 (95% confidence interval (CI): 0.28–1.26) for prediabetes, 0.46 (0.22–0.94) for diabetes, and 0.51 (0.26–0.99) for prediabetes and diabetes combined. Each 10% increase in the proportion of urinary monomethylarsonic acid (MMA%) was associated with a 1.13% (0.39, 1.88) increase in HbA1c. In contrast, each 10% increase in DMA% was associated with a 0.76% (0.24, 1.29) decrease in HbA1c. There was no evidence of an association of total urinary arsenic with prediabetes, diabetes, or HbA1c. These data suggest that a lower arsenic methylation capacity indicated by higher MMA% and lower DMA% in urine is associated with worse glycemic control and diabetes. Prospective, longitudinal studies are needed to evaluate the glycemic effects of low-level iAs exposure in urban populations.

Executive Functions in School Children from Montevideo, Uruguay and their Associations with Concurrent Low-level Arsenic Exposure

Background: Arsenic is a known childhood neurotoxicant, but its neurotoxicity at low exposure levels is still not well established. Our cross-sectional study aimed to test the association between low-level arsenic exposure and executive functions (EF) among children in Montevideo. We also assessed effect modification by arsenic methylation capacity, a susceptibility factor for the health effects of arsenic, and by B-vitamin intake, which impacts arsenic methylation. Methods: Arsenic exposure was assessed as the specific gravity-adjusted sum of urinary arsenic metabolites (U-As) among 255 ~7 year-old children, and methylation capacity as the proportion of urinary monomethylarsonic acid (%MMA). B-vitamin intake was calculated from the average of two 24-hour dietary recalls. EF was measured using three tests from the Cambridge Neuropsychological Test Automated Battery - Stockings of Cambridge (SOC), Intra-dimensional/extra-dimensional shift task (IED), and Spatial Span (SSP). Generalized linear models assessed associations between U-As and EF measures, adjusting for age, sex, maternal education, possessions score, Home Observation for Measurement of the Environment Inventory score, season, and school clusters. A “B-vitamin index” was calculated using principalcomponent analysis. Effect modification by the index and urinary %MMA was assessed in strata split at the respective medians of these variables. Results: The median (range) U-As and water arsenic levels were 9.9 µg/L (2.2, 47.7) and 0.45 µg/L (0.1, 18.9) respectively. U-As was inversely associated with the number of stages completed (β = -0.02; 95% CI: -0.03, -0.002) and pre-executive shift errors (β = -0.08; 95% CI: -0.14, -0.02) of the IED task, and span length of the SSP task (β = -0.01; 95% CI: -0.02, -0.004). There was no clear pattern of effect modification by B-vitamin intake or urinary %MMA. Conclusion: Low-level arsenic exposure may adversely affect executive function among children but additional, including longitudinal, studies are necessary to confirm these findings.

Executive functions in school children from Montevideo, Uruguay and their associations with concurrent low-level arsenic exposure

ObjectiveArsenic is a known childhood neurotoxicant, but its neurotoxicity at low exposure levels is still not well established. The aim of our cross-sectional study was to test the association between low-level arsenic exposure and executive functions (EF) among children in Montevideo. We also assessed effect modification by arsenic methylation capacity, a susceptibility factor for the health effects of arsenic, and by B-vitamin intake, which impacts arsenic methylation. MethodsArsenic exposure was assessed as the specific gravity-adjusted sum of urinary arsenic metabolites (U-As) among 255 ~ 7 year-old children, and methylation capacity as the proportion of urinary monomethylarsonic acid (%MMA). Arsenic concentrations from kitchen water samples at participants’ homes were assessed. B-vitamin intake was calculated from the average of two 24-hour dietary recalls. EF was measured using three tests from the Cambridge Neuropsychological Test Automated Battery– Stockings of Cambridge (SOC), Intra-dimensional/extra-dimensional shift task (IED), and Spatial Span (SSP). Generalized linear models assessed the association between U-As and EF measures; models were adjusted for age, sex, maternal education, possessions score, Home Observation for Measurement of the Environment Inventory score, season, and school clusters. Additional analyses were conducted to address issues of residual confounding and sample size. A “B-vitamin index” was calculated using principal component analysis. Effect modification by the index and urinary %MMA was assessed in strata split at the respective medians of these variables. ResultsThe median (range) U-As and water arsenic levels were 9.9 µg/L (2.2, 47.7) and 0.45 µg/L (0.1, 18.9) respectively, indicating that exposure originated mainly from other sources. U-As was inversely associated with the number of stages completed (β = −0.02; 95% CI: −0.03, −0.002) and pre-executive shift errors (β = −0.08; 95% CI: −0.14, −0.02) of the IED task, and span length of the SSP task (β = −0.01; 95% CI: −0.02, −0.004). There was no clear pattern of effect modification by B-vitamin intake or urinary %MMA. ConclusionLow-level arsenic exposure may adversely affect executive function among children but additional, including longitudinal, studies are necessary to confirm these findings.

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic

Evidence suggests that the relationship between arsenic metabolism and diseases, including metabolic syndrome, is complex. The aim of this study was to evaluate the different types of arsenic methylation and its association with metabolic syndrome in an arsenic endemic area. A cross-sectional study was conducted on 132 subjects from Shahid-Abad Village, Qazvin province, Iran (arsenic endemic area). Demographic characteristics, metabolic syndrome, and urinary arsenic species, including iAs (inorganic arsenic), MMA (monomethylarsonic acid), and DMA (dimethylarsinic acid) were measured for all patients and their relationship was analyzed by appropriate statistical methods. In this study, 34.5% of the participants had metabolic syndrome. The decrease in %MMA, increase in %DMA and increase in secondary methylation index (DMA/MMA) were associated with increased risk of metabolic syndrome (p<0.05). We did not find any association between the incidence of metabolic syndrome with primary methylation index (MMA/iAs) and %iAs (p>0.05). This study showed that the prevalence of metabolic syndrome was significantly higher in people with metabolic syndrome than in the general population. A closer examination revealed that the secondary methylation index is related to the metabolic syndrome and its components. Given the higher prevalence of cardiovascular disease and diabetes in patients with metabolic syndrome, it is necessary to change the pathogenesis of the disease using comprehensive management methods for decreasing patient complications.

Evaluation of different types of arsenic methylation and its relationship with metabolic syndrome in an area chronically exposed to arsenic.

Evidence suggests that the relationship between arsenic metabolism and diseases, including metabolic syndrome, is complex. The aim of this study was to evaluate the different types of arsenic methylation and its association with metabolic syndrome in an arsenic endemic area. A cross-sectional study was conducted on 132 subjects from Shahid-Abad Village, Qazvin province, Iran (arsenic endemic area). Demographic characteristics, metabolic syndrome, and urinary arsenic species, including iAs (inorganic arsenic), MMA (monomethylarsonic acid), and DMA (dimethylarsinic acid) were measured for all patients and their relationship was analyzed by appropriate statistical methods. In this study, 34.5% of the participants had metabolic syndrome. The decrease in %MMA, increase in %DMA and increase in secondary methylation index (DMA/MMA) were associated with increased risk of metabolic syndrome (p<0.05). We did not find any association between the incidence of metabolic syndrome with primary methylation index (MMA/iAs) and %iAs (p>0.05). This study showed that the prevalence of metabolic syndrome was significantly higher in people with metabolic syndrome than in the general population. A closer examination revealed that the secondary methylation index is related to the metabolic syndrome and its components. Given the higher prevalence of cardiovascular disease and diabetes in patients with metabolic syndrome, it is necessary to change the pathogenesis of the disease using comprehensive management methods for decreasing patient complications.

Vitamin B-6 Intake Is Modestly Associated with Arsenic Methylation in Uruguayan Children with Low-Level Arsenic Exposure

Background:Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. Objectives:Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (<50 µg/L in water; urinary arsenic 5–50 µg/L). Methods:We conducted a cross-sectional study in 290 ~7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. Results:Median (range) arsenic concentrations in urine and water were 9.9 (2.2–48.7) and 0.45 (0.1–18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0–33.8), 9.7% (2.6–24.8), and 79.1% (58.5–95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19–2.56), 1.0 (0.30–2.24), 8.6 (3.5–23.3), and 0.67 (0.25–1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75–466) and 1.7 (0.34–8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (β = –1.60; 95% CI: –3.07, –0.15). No other statistically significant associations were observed. Conclusions:Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.

Arsenic Exposure and Association with Hepatitis E IgG Antibodies

Arsenic is a known toxic chemical, has immuno-modulatory properties, and can change the susceptibility of infection in humans. Acute hepatitis E is an infectious disease; it can be self-limiting, but in severe cases, can cause acute-on-chronic liver failure. The presence of IgG anti-HEV (hepatitis E IgG antibody) in blood represents a past hepatitis E infection in an individual. Very few studies have investigated the association between arsenic levels and hepatitis E seroconversion in humans. The primary objective of this study was to assess the relationship between total urinary arsenic and speciated urinary arsenic (urinary arsenous acid, urinary arsenic acid, urinary arsenobetaine, urinary arsenocholine, urinary dimethylarsinic acid, urinary monomethylarsonic acid) and the presence of IgG anti-HEV. The 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey (NHANES) III data sets were analyzed, with participants aged 20 years and older (n = 7061). We used weighted logistic regression to determine the association between total and speciated urinary arsenic concentrations and IgG anti-HEV. For each analyte considered, a separate weighted logistic regression model was fitted. Each of these models regressed log-transformed analyte levels on the log-odds of the presence of IgG Anti-HEV. To evaluate the relationships between the urinary arsenic measurements, pairwise Pearson correlation coefficients were determined for each of the urinary arsenic measurements. Of the human subjects included, 6628 (93.9%) were negative for IgG Anti-HEV while 433 (6.1%) were positive for IgG anti-HEV. Total urinary arsenic was associated with 1.161 times greater odds of IgG anti-HEV (95% CI: [1.035, 1.303]) for each unit increase in concentration on a log-scale. For speciated urinary arsenic measurements, the odds ratios and 95% CI’s were: arsenobetanine 1.168 [1.075, 1.270], arsenocholine 1.201 [0.944, 1.529], dimethylarsinic acid 1.183 [1.009, 1.386], monomethylacrsonic acid 1.095 [0.915, 1.310], aresnous acid 0.907 [0.762, 1.079], and arsenic acid 1.951 [0.905, 4.209]. Our analysis indicates that total urinary arsenic, arsenobetanine, and dimethylarsinic acid are significantly associated with the odds of the presence of IgG anti-HEV. Future prospective studies are required to evaluate the association between hepatitis E infection and arsenic exposures.

Low level arsenic exposure, B-vitamins, and achievement among Uruguayan school children.

Millions of children globally, including the U.S., are exposed to low levels of arsenic from water and food. Arsenic is a known neurotoxicant at high levels but its effects at lower exposure levels are understudied. Arsenic methylation capacity, influenced by B-vitamin intake and status, potentially influences arsenic toxicity. In a cross-secitonal study of 5-8 year-old children from Montevideo, we assessed the relationship between urinary arsenic (U-As) and academic achievement, and tested for effect modification by B-vitamin intake, status, and arsenic methylation capacity. Broad math and reading scores were calculated based on six subtests (calculation, math facts fluency, applied problems, sentence reading fluency, letter word identification, passage comprehension) from the Woodcock-Muñoz Achievement Battery. B-vitamin intake was assessed from two non-consecutive 24-h dietary recalls, serum folate and vitamin B-12 levels were measured in a subset of participants. Arsenic methylation capacity was measured as the proportion of urinary monomethylarsonic acid (%MMA). Multiple imputation using chained equations was conducted to account for missing covariate and exposure data. Ordinal regressions assessed associations between U-As and achievement score tertiles in the complete case and imputed samples. A "B-vitamin index" was calculated using principal component analysis. Interactions by urinary %MMA and the B-vitamin index were assessed. Median specific gravity adjusted U-As was 11.7 μg/L (range: 2.6, 50.1). We found no association between U-As and broad math and reading scores, nor effect modification by %MMA or B-vitamins. At low-levels of exposure, U-As does not appear to affect children's academic achievement.

Metal Biomonitoring and Comparative Assessment in Urine of Workers in Lead-Zinc and Steel-Iron Mining and Smelting.

The exposure of heavy metals (lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), and metalloid arsenicals) and their effects on workers' health from a lead-zinc mine (145 workers) and a steel smelting plant (162 workers) was investigated. Information on subject characteristics was obtained through a questionnaire. We determined the urinary levels of Pb, Cd, Cu, Ni, and arsenicals (including inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), as were 8-hydroxydeoxyguanosine (8-OHdG) and cystatin C. Lead-zinc mine foundry workers had significantly higher concentrations of urinary Pb, Cd, Cu, Ni, iAs, and MMA than did steel smelting plant workers. Individuals who had consumed seafood in the previous 3days had higher concentrations of urinary Ni than did individuals who had not consumed seafood. The urinary Cd concentrations in the two groups of factory workers may have been affected by daily smoking. There was no significant difference in urinary 8-OHdG between workers from the lead-zinc mine foundry and the steel smelting plant. Urinary Pb and Cd had significant positive linear dose-dependent effects on 8-OHdG. Urinary cystatin C, a sensitive biological indicator reflecting early renal damage, was found at higher levels in lead-zinc mine workers than in steel smelting plant workers. Binary logistic regression analysis showed that age and urinary Cd were significantly associated with urinary cystatin C. These results indicated that workers from lead-zinc mines may be exposed to higher levels of heavy metals which could lead to greater risk of kidney damage.

Inorganic arsenic exposure increased expression of Fas and Bax gene in vivo and vitro

Accumulating evidences have shown that apoptosis plays an important role in mediating the therapeutic effects and toxicity of arsenic. Fas and Bax genes are critical regulatory genes for apoptosis. In this study, we investigated the association between levels of Fas and Bax expression and the three arsenic species (inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in vivo and vitro. Three arsenic species in urine were measured and levels of Fas and Bax expression were examined by the quantitative real-time PCR (qPCR) for all subjects. We found that Fas and Bax mRNA expression in the exposed group were significantly higher than that in the control group. The levels of gene expression were positively correlated with the concentrations of urinary iAs, MMA and DMA in all subjects. Sodium arsenite induced Fas and Bax mRNA expression, then MMA and DMA did not induce mRNA expression in MDA-MB-231 and XWLC-05 cells. The findings of the present study indicated that iAs, MMA, and DMA had different effects on expression of Bax and Fas gene.

Serum folate levels and urinary arsenic methylation profiles in the US population: NHANES, 2003-2012.

Arsenic is a prevalent environmental contaminant, and its folate-dependent methylation is important for detoxification in the body. In this study, we investigated the association between serum folate levels and methylation using data from the US National Health and Nutrition Examination Survey (NHANES) (2003-2012) (N = 11,016). Multivariate linear regression and penalized spline regression models were used to examine the association and possible upper limit of folate level regarding its impact on methylation in children (≤18 years) and adults (>18 years), respectively. Serum folate levels, methylation metabolites including urinary monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and demographic variables were extracted from NHANES. Results showed that urinary percentage of DMA(V) (%DMA(V)) was positively associated with log(serum folate levels) after adjustment in children (β = 1.93, p < 0.01); urinary percentage of MMA(V) (%MMA(V)) was positively associated with log (serum folate levels) after adjustment in adults (β = 0.40, p < 0.01). No upper limit of folate level regarding its impact on arsenic methylation was identified. More than 50% of Non-Hispanic black and smokers with high total urinary arsenic levels had low serum folate levels. Our results indicate that folate promotes arsenic methylation, but the patterns are different in children versus in adults. Future interventions may be needed for the population exposed to high level of arsenic but with low serum folate to protect against the potential adverse health effects of arsenic.

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

The effect of association between inefficient arsenic methylation capacity and demographic characteristics on the risk of skin lesions

This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090μgL−1. The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10μgL−1 with a daily arsenic intake of 3.23±3.75mgday−1 from household ground water sources for an exposure duration of 10–20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48μgg−1Cr), MMA (106.38±135.04 vs. 35.43±39.97μgg−1Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09–12.27), lower DMA% (OR 0.64, 95% CI: 0.33–1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28–1.12) and SMI (OR 0.43, 95% CI: 0.21–0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations.

Levels of infants' urinary arsenic metabolites related to formula feeding and weaning with rice products exceeding the EU inorganic arsenic standard.

Early childhood inorganic arsenic (i-As) exposure is of particular concern since it may adversely impact on lifetime health outcomes. Infants’ urinary arsenic (As) metabolites were analysed in 79 infants by inductively coupled plasma—mass spectrometric detection (IC-ICP-MS) to evaluate i-As exposure pre- and post-weaning. Levels of i-As in rice-based weaning and infants’ foods were also determined to relate to urinary As levels. Higher As levels, especially of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were found in urine from formula fed infants compared to those breastfed. Urine from infants post-weaning consuming rice-products resulted in higher urinary MMA and DMA compared to the paired pre-weaning urine samples. The European Union (EU) has regulated i-As in rice since 1st January 2016. Comparing infants’ rice-based foods before and after this date, little change was found. Nearly ¾ of the rice-based products specifically marketed for infants and young children contained i-As over the 0.1 mg/kg EU limit. Efforts should be made to provide low i-As rice and rice-based products consumed by infants and young children that do not exceed the maximum i-As level to protect this vulnerable subpopulation.

Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007–2012

ABSTRACTLead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007–2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011–2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.

Association of XRCC1 polymorphisms with arsenic methylation.

The associations of four single nucleotide polymorphisms (p.Arg194Trp, p.Arg280His, p.Pro206Pro, and p.Arg399Gln) in X-ray repair cross-complementing group 1 with urinary arsenic metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated in a Vietnamese population (n = 100). Individuals with genotype AA in p.Pro206Pro showed significantly higher urinary monomethylarsonic acid (MMA(V)) and lower dimethylarsinic acid (DMA(V))/MMA(V) ratio than genotype AG. As for p.Arg399Gln, both Arg/Arg homozygous subjects and Arg/Gln heterozygous individuals showed a significantly higher urinary inorganic As percentage and lower 8-OHdG concentrations than Gln/Gln homozygous. Our results suggested that Arg399Gln is a functional SNP that may be related to DNA repair activity.