Total Urinary Arsenic Research Articles

Trends in urinary arsenic among the U.S. population by drinking water source: Results from the National Health and Nutritional Examinations Survey 2003–2014

BackgroundIn 2001, the United States revised the arsenic maximum contaminant level for public drinking water systems from 50µg/L to 10µg/L. This study aimed to examine temporal trends in urinary arsenic concentrations in the U.S. population from 2003 to 2014 by drinking water source among individuals aged 12 years and older who had no detectable arsenobetaine - a biomarker of arsenic exposure from seafood intake. MethodsWe examined data from 6 consecutive cycles of the National Health and Nutrition Examination Survey (2003–2014; N=5848). Total urinary arsenic (TUA) was calculated by subtracting arsenobetaine’s limit of detection and detectable arsenocholine from total arsenic. Additional sensitivity analyses were conducted using a second total urinary arsenic index (TUA2, calculated by adding arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid). We classified drinking water source using 24-h dietary questionnaire data as community supply (n=3427), well or rain cistern (n=506), and did not drink tap water (n=1060). ResultsGeometric means (GM) of survey cycles were calculated from multivariate regression models adjusting for age, gender, race/ethnicity, BMI, income, creatinine, water source, type of water consumed, recent smoking, and consumption of seafood, rice, poultry, and juice. Compared to 2003–2004, adjusted TUA was 35.5% lower in 2013–2014 among the general U.S. population. Stratified analysis by smoking status indicated that the trend in lower TUA was only consistent among non-smokers. Compared to 2003–2004, lower adjusted TUA was observed in 2013–2014 among non-smoking participants who used community water supplies (1.98 vs 1.16µg/L, p<0.001), well or rain cistern users (1.54 vs 1.28µg/L, p<0.001) and who did not drink tap water (2.24 vs 1.53µg/L, p<0.001). Sensitivity analyses showed consistent results for participants who used a community water supplier and to a lesser extent those who did not drink tap water. However, the sensitivity analysis showed overall exposure stayed the same or was higher among well or rain cistern users. Finally, the greatest decrease in TUA was among participants within the highest exposure percentiles (e.g. 95th percentile had 34% lower TUA in 2013/2014 vs 2003/2004, p<0.001). ConclusionsOverall, urinary arsenic levels in the U.S. population declined over a 12-year period that encompassed the adoption of the revised Arsenic Rule. The most consistent trends in declining exposure were observed among non-smoking individuals using public community water systems. These results suggest regulation and prevention strategies to reduce arsenic exposures in the U.S. may be succeeding.

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.

Low-level arsenic exposure during pregnancy and its association with postpartum depression: A cohort study of women from Arica, Chile

BackgroundWhile the relationship between inorganic arsenic exposure and psychological impairment has been studied previously, the association between low-level arsenic exposure during pregnancy and postpartum depression has not yet been examined. The objective is to estimate the association between low-level arsenic exposure during pregnancy and the Edinburgh score. MethodsA sample of 223 women was collected from five public health services in Arica, Chile. Participation was voluntary and written consent was mandatory. Sociodemographic data related to arsenic exposure and urine samples for total inorganic arsenic assessments were collected during the second trimester. Postpartum depression symptoms were estimated by the Edinburgh Postpartum Depression scale. We examined descriptive statistics and ran multiple linear regressions. The modifying effect of age and depression history was evaluated separately. ResultsThe median for total urinary inorganic arsenic was 14.6μg/L (range: 2-69.2μg/L), the median for postpartum depression score was 8 points (range: 0-27 points) and 20.6% of women were considered as postpartum depressed. For women older than 25years old without depression history, the adjusted coefficient for the total urinary natural logarithm of inorganic arsenic in multiple linear regressions was −2.51 (95% CI: −4.54, −0.48; P-value=0.02). For women older than 25years old with a depression history, this value was 2.09 (95% CI: −0.90, 5.08; P-value=0.16). ConclusionsIn this cohort, the number of children, physical perception, depression history, stressful maternity, and age were associated with postpartum depression score. The Edinburgh score was associated with inorganic arsenic in women older than 25years without depression history.

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Associations between urinary total arsenic levels, fetal development, and neonatal birth outcomes: A cohort study in Taiwan

BackgroundArsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. ObjectivesTo assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. MethodsIn this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22–45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. ResultsWe observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (β=−1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (β=−0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (β=−173.26g, p<0.01), head circumference (β=−0.611cm, p<0.05), and chest circumference (β=−0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. ConclusionsWe identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.

Rice Consumption and Squamous Cell Carcinoma of the Skin in a United States Population.

Background:Rice contains arsenic, a known skin carcinogen. Rice intake has been associated with arsenic-related skin lesions in South Asia, but its association with skin cancers is as yet unknown.Objectives:We aimed to investigate whether rice intake contributes to urinary arsenic concentration and risk of squamous cell carcinoma (SCC) of the skin in a U.S. population.Methods:Rice consumption was assessed using a food frequency questionnaire administered as part of a population-based case–control study of 487 SCC cases and 462 age- and gender-matched controls. Arsenic concentration in household tap water and urine samples were measured using inductively coupled mass spectrometry (ICP-MS) and high-resolution ICP-MS, respectively. Odds ratios (OR) for SCC associated with the frequency of rice consumption were estimated using logistic regression, with adjustment for age, gender, and caloric intake.Results:Those who reported any rice consumption had higher urinary arsenic concentrations than those who did not consume rice, and the association was most pronounced among those with arsenic in their household water (19.2% increase in total urinary arsenic, 95% CI: 5.0, 35.3%). Any rice consumption was associated with a 1.5-fold (95% CI: 1.1, 2.0) higher odds of SCC compared with those who reported no rice consumption, and the relation appeared to be largely among those with water arsenic.Conclusion:Rice consumption may be related to the occurrence of SCC in the United States, especially among those with relatively low drinking water arsenic exposure. https://doi.org/10.1289/EHP1065

Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study

Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively. Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to2011. HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 104 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria. Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured. This study describes the temporal relationship between arsenic concentrations≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria.

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes.

Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality

BackgroundChronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. ObjectivesWe evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. MethodsCreatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. ResultsWe observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. ConclusionsProspective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age.

The polymorphism XRCC1 Arg194Trp and 8-hydroxydeoxyguanosine increased susceptibility to arsenic-related renal cell carcinoma

This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification. Genomic DNA was used to examine the genotype of XRCC1(Arg399Gln), XRCC1(Arg194Trp), XRCC3(Thr241Met) and XPD(Lys751Gln) by PCR-RFLP. Liquid chromatography with tandem mass spectrometry was used to determine urinary 8-OHdG levels. A HPLC-HG-AAS was used to determine the concentrations of urinary arsenic species. Participants with the genotype XRCC1(Arg194Trp) Arg/Trp+Trp/Trp had a significantly higher OR of RCC than those with the Arg/Arg genotype; the OR and 95% confidence interval was 0.66 (0.45–0.97) after multivariate adjustment. The OR of RCC for the combined effect of high urinary 8-OHdG levels and high urinary total arsenic concentration in individuals with a XRCC1(Arg194Trp) Arg/Trp+Trp/Trp genotype was higher than in patients with an Arg/Arg genotype, which was evident in a dose response manner. In conclusion, this is the first study to show that the XRCC1 Arg194 allele is a predicting factor for RCC. The more risk factors (high urinary 8-OHdG levels, high urinary total arsenic concentrations, and XRCC1 Arg194 allele) that were present, the higher the OR of RCC.

Association of arsenobetaine with beta-cell function assessed by homeostasis model assessment (HOMA) in nondiabetic Koreans: data from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009

BackgroundArsenic is known as an endocrine disruptor that people are exposed to through various sources such as drinking water and indigestion of marine products. Although some epidemiological and animal studies have reported a correlation between arsenic exposure and diabetes development, there are limited studies regarding the toxic effects of organic arsenic including arsenobetaine on the human body. Here, we analyzed the association between urine arsenobetaine and the homeostasis model assessment of β-cell function (HOMA-β), which is an index for predicting diabetes development and reflecting the function of pancreatic β-cells.MethodsIn the fourth Korea National Health and Nutrition Examination Survey (KNHANES), health and nutrition surveys and screening tests were performed. Of the total survey population, people with confirmed values for urine total arsenic and arsenobetaine were included, and known diabetic patients were excluded. A total 369 participants were finally included in the study. We collected surveys on health, height, body weight, body mass index, blood mercury level, fasting glucose level, and serum insulin level and calculated HOMA index. Owing to sexual discrepancy, we performed sexually stratified analysis.ResultsUrine total arsenic and total arsenic minus arsenobetaine was not associated with HOMA-IR and HOMA-β in univariate analysis or in sexually stratified analysis. However, urine arsenobetaine showed a statistically significant relationship with HOMA-β in univariate analysis, and only male participants showed a significant correlation in sexually stratified analysis. In the analysis adjusted for age, BMI, smoking, alcohol drinking, physical activity and blood mercury, the HOMA-β value in the group below the 25th percentile of arsenobetaine was significantly higher than the group between 50 and 75th percentile, while no difference was shown for HOMA-IR. In sexually stratified analysis, The value of HOMA-β was significantly higher in male participants with below the 25th percentile urine arsenobetaine than the group between 25 and 50th and between 50 and 75th, while no difference was shown for HOMA-IR. However, female participants did not demonstrate a relationship between HOMA–IR, HOMA-β and urine arsenobetaine.ConclusionThis study revealed the association between urine arsenobetaine and pancreatic β-cell function assessed by HOMA-β in the normal population (without diabetes), especially in males, despite adjusting for factors affecting pancreatic β-cell function and diabetes.

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04–0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06–2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC.

Total arsenic and speciation analysis of saliva and urine samples from individuals living in a chronic arsenicosis area in China

BackgroundIt is generally acknowledged that the determination of harmful chemical compounds excreted into saliva is useful for assessing their exposure levels. The aim of the present study was to compare the total arsenic and its species in saliva and urine samples collected from the people residing in an arsenic-contaminated area of China and to further verify the feasibility of using salivary arsenic as a new biomarker of arsenic exposure.MethodsTotal arsenic and speciation analyses in urine and saliva samples among 70 residents exposed to arsenic from drinking water in Shanxi, China were carried out by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP/MS).ResultsThe result showed that, total arsenic concentration in saliva was relatively lower than in urine samples, but it existed a strong positive correlation with total urinary arsenic, drinking water arsenic and different skin lesions. For arsenic metabolism analyses, AsIII, AsV, MMA, and DMA were detected in all of the urine samples with the dominating species of DMA (73.2%). Different with urinary arsenic species, most arsenic species in saliva were not methylated. The major species in saliva was iAs (AsIII + AsV, 76.18%), followed by DMA (13.08%) and MMA (9.13%). And the primary methylation index (PMI), second methylation index (SMI) and proportion of the four different species (AsIII, AsV, MMA, and DMA) in saliva showed no significant positive relationship with that of in urine.ConclusionsThese findings indicated saliva may be used as a useful tool for biological monitoring of total arsenic exposure in the crowd rather than an efficient tool for assessing arsenic metabolism in human body after exposed to arsenic.

Total arsenic concentrations in Chinese children's urine by different geographic locations, ages, and genders.

Little is known about the variation of Chinese children's exposure to arsenic by geography, age, gender, and other potential factors. The main objective of this study was to investigate the total arsenic concentration in Chinese children's urine by geographic locations, ages, and genders. In total, 259 24-h urine samples were collected from 210 2- to 12-year-old children in China and analyzed for total arsenic and creatinine concentrations. The results showed that the upper limit (upper limit of the 90% confidence interval for the 97.5 fractile) was 27.51µg/L or 55.88µg/g creatinine for Chinese children. The total urinary arsenic levels were significantly different for children in Guangdong, Hubei, and Gansu provinces (P<0.05), where the upper limits were 24.29, 58.70, and 44.29µg/g creatinine, respectively. In addition, the total urinary arsenic levels were higher for 2- to 7-year-old children than for 7- to 12-year-old children (P<0.05; the upper limits were 59.06 and 44.29µg/g creatinine, respectively) and higher for rural children than for urban children (P<0.05; the upper limits were 59.06 and 50.44µg/g creatinine, respectively). The total urinary arsenic levels for boys were not significantly different from those for girls (P>0.05), although the level for boys (the upper limit was 59.30µg/g) was slightly higher than that for girls (the upper limit was 58.64µg/g creatinine). Because the total urinary arsenic concentrations are significantly different for general populations of children in different locations and age groups, the reference level of total urinary arsenic might be dependent on the geographic site and the child's age.

Chronic early childhood exposure to arsenic is associated with a TNF-mediated proteomic signaling response

Exposure to inorganic arsenic (iAs) in drinking water is a global public health concern and is associated with a range of health outcomes, including immune dysfunction. Children are a particularly sensitive population to the effects of inorganic arsenic, yet the biological mechanisms underlying adverse health outcomes are understudied. Here we used a proteomic approach to examine the effects of iAs exposure on circulating serum protein levels in a cross-sectional children’s cohort in Mexico. To identify iAs-associated proteins, levels of total urinary arsenic (U-tAs) and its metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins that displayed decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the proportions of urinary arsenic metabolites in children, the most robust response was observed in relation to the monomethylated arsenicals. This study is among the first serum proteomics assessment in children exposed to iAs.

Iron and Zinc Supplementation Does Not Impact Urinary Arsenic Excretion in Mexican School Children

To examine the role of iron and zinc in arsenic excretion and metabolism in children. An analysis of urinary arsenic (UAs) concentrations from a double-blind randomized trial originally testing the efficacy of iron and zinc for lowering blood lead levels in children. A 2 × 2 factorial design was used, with children randomized individually, stratified by sex and classroom, to receive 30?mg ferrous fumarate (n?=?148), 30?mg zinc oxide (n?=?144), iron and zinc together (n?=?148), or placebo (n?=?151). Of the 602 children enrolled, 527 completed the 6-month treatment, and 485 had both baseline and final UAs values. The baseline total UAs concentration ranged from 3.2 to 215.9?µg/L. At baseline, children in the highest tertile of serum ferritin concentration had higher excretion of dimethylarsinic acid (DMA; 1.93?±?0.86%; P?<?.05), but lower excretion of monomethylarsonic acid (-0.91?±?0.39%; P?<?.05), compared with children in the lowest tertile. In an intention-to-treat analysis, iron had no effect on arsenic methylation or UAs excretion, but children receiving zinc had lower %DMA in urine (-1.7?±?0.8; P?<?.05). Iron and zinc status are not related to arsenic metabolism in children, and supplementation with these minerals has limited application in lowering arsenic concentrations. ClinicalTrials.gov: NCT02346188.

Application of ICP-MS and HPLC-ICP–MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic

ICP-MS and HPLC-ICP–MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP–MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070μg/L in whole blood and plasma, respectively, and 4540μg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206μg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126μg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists.

Poultry Consumption and Arsenic Exposure in the U.S. Population.

Background:Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown.Objectives:Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone.Methods:We evaluated 3,329 participants ≥ 6 years old from the 2003–2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake.Results:After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p-trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p-trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer.Conclusions:Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003–2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic exposure in the U.S. population.Citation:Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien A. 2017. Poultry consumption and arsenic exposure in the U.S. population. Environ Health Perspect 125:370–377; http://dx.doi.org/10.1289/EHP351

Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO2). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO2 groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What’s more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid.

Impact of exposure to tobacco smoke, arsenic, and phthalates on locally advanced cervical cancer treatment-preliminary results.

BackgroundCancer research is a national and international priority, with the efficiency and effectiveness of current anti-tumor therapies being one of the major challenges with which physicians are faced.ObjectiveTo assess the impact of exposure to tobacco smoke, arsenic, and phthalates on cervical cancer treatment.MethodsWe investigated 37 patients with locally advanced cervical carcinoma who underwent chemotherapy and radiotherapy. We determined cotinine and five phthalate metabolites in urine samples collected prior to cancer treatment, by gas chromatography coupled to mass spectrometry, and urinary total arsenic by atomic absorption spectrometry with hydride generation. We used linear regression to evaluate the effects of cotinine, arsenic, and phthalates on the change in tumor size after treatment, adjusted for confounding variables.ResultsWe detected no significant associations between urinary cotinine, arsenic, or phthalate monoesters on change in tumor size after treatment, adjusted for urine creatinine, age, baseline tumor size, and cotinine (for arsenic and phthalates). However, higher %mono-ethylhexyl phthalate (%MEHP), a putative indicator of phthalate diester metabolism, was associated with a larger change in tumor size (β = 0.015, 95% CI [0.003–0.03], P = 0.019).ConclusionWe found no statistically significant association between the urinary levels of arsenic, cotinine, and phthalates metabolites and the response to cervical cancer treatment as measured by the change in tumor size. Still, our results suggested that phthalates metabolism may be associated with response to treatment for locally advanced cervical cancer. However, these observations are preliminary and will require confirmation in a larger, more definitive investigation.