Dimethylarsonic Acid Research Articles

Trans-Global Biogeochemistry of Soil to Grain Transport of Arsenic and Cadmium

Previous studies have shown that arsenic and cadmium can accumulate in rice grain to levels that cause health concerns. Furthermore, geographical survey has shown that there is considerable variation (~ 100-fold) in accumulation of these carcinogens in rice grain. This variance must be due to heterogeneity in soil biogeochemistry and contrasting rice management regimens. Here we present the first systematic global study to investigate the impact of soil biogeochemistry on accumulation of these elements in rice grain. Matched grain, shoot, root and soil samples were collected across a latitudinal gradient from East Africa to Europe and soil, shoot, grain chemistry and soil microbial community (prokaryotes and fungi) assessed within the context of arsenic and cadmium biogeochemistry. European and Vietnamese grain sum of arsenic species (inorganic arsenic plus dimethylarsonic acid) concentration medians, ~ 0.1 mg/kg, were found to be around ten-fold higher compared to those in East Africa and Sri Lanka. Arsenic concentrations were linked to higher levels of soil arsenic, and to higher abundance of soil sulphur-oxidising and sulphate reducing bacteria and methanogenic archaea. For cadmium, Sri Lanka showed highest (median 0.0156 mg/kg) and Europe lowest (median of 0.001 mg/kg) levels in grain, with the other regions showing intermediate values. Interestingly, grain cadmium was unrelated to soil cadmium concentrations, with Europe having the highest levels of cadmium in soil. Instead, grain cadmium correlated with higher oxidation/reduction potential, lower -log[hydrogen ion], lower soil calcium, and to a higher abundance of aerobic bacteria and fungi (lowest abundance of these organisms in European soils).

Preparation of magnetic composites and their dimethyl arsonic acid adsorption performances.

Dimethyl arsonic acid, the most common organic arsenic pollutant, is widely present in the environment and seriously threatens the safety of drinking water. Syntheses of magnetite, magnetic bentonite, and magnetic ferrihydrite via hydrothermal methods, and the magnetic composites were examined using XRD, BET, VSM, and SEM. SEM images revealed that many monodispersible pellets were attached to the surface of magnetic bentonite. The magnetic ferrihydrite contained abundant pores and had a rich pore structure, which expanded the specific surface area of the original magnetite. The specific surface areas of the magnetic bentonite and magnetic ferrihydrite were 65.17 and 220.30 m2·g-1, respectively. The adsorption kinetics and adsorption isotherms of dimethyl arsonic acid on magnetic composites were studied. The adsorption of dimethyl arsonic acid on the magnetic composites conformed to the pseudo-second-order model and Freundlich isothermal adsorption model. By comparing the isotherms of the adsorption of dimethyl arsonic acid by the magnetic composites at pH values of 3, 7, and 11, respectively, it was found that the adsorption of dimethyl arsonic acid was the greatest at neutral pH of 7. The adsorption mechanism was analyzed via zeta potential determination, Fourier transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS). The zeta potential results revealed that magnetic bentonite electrostatic activity occurred with dimethyl arsonic acid, and the magnetic ferrihydrite indicated a coordination complex with dimethyl arsonic acid. The XPS results revealed that the Fe-O bonds on the surfaces of the magnetic ferrihydrite had coordination complexation effects on the As-O of the dimethyl arsonic acid.

Recycled Household Ash in Rice Paddies of Bangladesh for Sustainable Production of Rice Without Altering Grain Arsenic and Cadmium

In Bangladesh most agronomic biomass (straw, husk, dried dung) is burnt for domestic cooking use. Consequently, the soil is continuously stripped of mineral nutrients and carbon (C) substrate. Here we investigate if recycling of household ash (ash) as fertilizer can sustainably improve soil fertility as well as minimise accumulation of toxic elements (As, Cd) in rice grain. Large scale field trials across two geographic regions (Barind, Madhupur) and two seasons (wet, dry) and with application of 3 fertiliser treatments (NPKS, ash, NPKS + ash) were conducted. At the end of each season, the impact of region*season*treatment on soil microbial comunities, rice yield, and grain quality (As, Cd, nutrient elements) was assessed. When compared to conventional field application rates of NPKS (control), application of ash boosted rice yield by circa. 20% in both regions during wet and dry season, with no effect on rice grain carcinogenic inorganic arsenic (iAs), dimethylarsonic acid (DMA) or cadmium (Cd), but with potential to increase zinc (Zn). For soil microbial communities, a significant region and season effect as well as correlation with elements in rice grain was observed, amongst these Cd, Zn, iAs and DMA. This study illustrates that application of ash can reduce the requirement for expensive chemical fertiliser, whilst at the same time increasing rice yield and maintaining grain quality, making farming in Bangladesh more sustainable and productive. The study also implies that the combined impact of region, season, and soil microbes determines accumulation of elements in rice grain.

Effects of exogenous salicylic acid on alleviation of arsenic-induced oxidative damages in rice

Salicylic acid (SA) is a phenolic phytohormone that plays a vital role in plant development and mediates plant responses to plenty of adversity including arsenic (As) stress. The effects of exogenous addition of SA on As tolerance and As accumulation were assessed in two cultivars of rice (Oryza sativa L.) Nipponbare and Zhongzao 39, hydroponically grown with Kimura B nutrient solution under arsenite [As (III)] and dimethylarsonic acid (DMA) exposure. In the second ex-periment, the influence of soaking seed with SA on As uptake and As damages was investigated in rice (cv. Nipponbare) exposed to As (III) and DMA. The results showed that exogenous addition of SA significantly decreased the concentrations of hydrogen peroxide (H2O2) and malondialdehyde (MDA) in both As (III)- and DMA-stressed rice, indicating that SA alleviates As-induced oxidative damages in rice. SA increased the activity of antioxidant enzymes and, moreover, increased the relative amount of glutathione (GSH) and ascorbate (ASA) by accelerating the GSH-ASA circle system. Exogenous addition of SA significantly decreased the As concentration in both roots and shoots of rice under As(III) stress by influencing the expression of genes encoding As transporters, viz. OsLsi1, OsLsi2. The addition of SA significantly decreased the As content in shoots under DMA stress, which may be related to the expression of OsPTR7 involved in shoot xylem unloading. This finding may foster a novel perspective for reducing As accumulation in rice grains.

Development of an interpretable machine learning model associated with heavy metals’ exposure to identify coronary heart disease among US adults via SHAP: Findings of the US NHANES from 2003 to 2018

Limited information is available on the links between heavy metals' exposure and coronary heart disease (CHD). We aim to establish an efficient and explainable machine learning (ML) model that associates heavy metals' exposure with CHD identification. Our datasets for investigating the associations between heavy metals and CHD were sourced from the US National Health and Nutrition Examination Survey (US NHANES, 2003–2018). Five ML models were established to identify CHD by heavy metals' exposure. Further, 11 discrimination characteristics were used to test the strength of the models. The optimally performing model was selected for identification. Finally, the SHapley Additive exPlanations (SHAP) tool was used for interpreting the features to visualize the selected model's decision-making capacity. In total, 12,554 participants were eligible for this study. The best performing random forest classifier (RF) based on 13 heavy metals to identify CHD was chosen (AUC: 0.827; 95%CI: 0.777–0.877; accuracy: 95.9%). SHAP values indicated that cesium (1.62), thallium (1.17), antimony (1.63), dimethylarsonic acid (0.91), barium (0.76), arsenous acid (0.79), total arsenic (0.01) in urine, and lead (3.58) and cadmium (4.66) in blood positively contributed to the model, while cobalt (−0.15), cadmium (−2.93), and uranium (−0.13) in urine negatively contributed to the model. The RF model was efficient, accurate, and robust in identifying an association between heavy metals' exposure and CHD among US NHANES 2003–2018 participants. Cesium, thallium, antimony, dimethylarsonic acid, barium, arsenous acid, and total arsenic in urine, and lead and cadmium in blood show positive relationships with CHD, while cobalt, cadmium, and uranium in urine show negative relationships with CHD.

Global Geographical Variation in Elemental and Arsenic Species Concentration in Paddy Rice Grain Identifies a Close Association of Essential Elements Copper, Selenium and Molybdenum with Cadmium

Despite the centrality of staple grains for human well-being, both as a source of nutrients and of toxic ions, there is little understanding of where and how elements vary, and if there are particular elements that correlate. Here, for shop bought polished (white) rice, we comprehensively characterized trace (arsenic species, cadmium, copper, iron, manganese, molybdenum, rubidium and zinc) and macro-nutrients (calcium, chlorine, potassium, phosphorus and sulphur) for grain purchased in 18 countries, across four continents, a total of 1045 samples. This was to investigate if there were any major differences between geographic location and elemental content, and to observe if there were any patterns in elemental distribution. Greatest variation in the median was observed for the non-essential rubidium (15-fold) and arsenic species (fivefold). Rubidium was the highest in the Americas, lowest in Europe, while inorganic arsenic (iAs) and dimethylarsonic acid (DMA) were low for Africa and high in the South American and European continents. The highest concentrations of cadmium were found in Asian samples, and lowest in South America, with variation within these regions. At the extremes of individual counties, China had fivefold higher concentrations than the global median, while Tanzania was fourfold lower than this value. Calcium, potassium, molybdenum and phosphorus were the highest in European and lowest in African grain, though the fold-differences were relatively low, ~ 0.2, while iron was the highest in African grain and lowest in European, Asian and South American grain, with a ~ twofold difference. Selenium was also higher in Africa versus other regions, and copper, manganese and zinc were the highest in American grain. Factor analysis showed that copper, cadmium, molybdenum, rubidium and selenium were strongly associated together, and these element’s factor loadings were diametrically opposed to less tightly associated calcium, chlorine, manganese, potassium, phosphorus and sulphur. Stepwise additions linear region analysis was performed on log-transformed concentrations to investigate cadmium associations in more detail. Selenium was the greatest predictor of cadmium concentration, followed by molybdenum, accounting for over 50% of the contribution to the adjusted R2. Arsenic species were only weakly correlated with other elements. The implications for these findings with respect to dietary nutrition are discussed. Vietnamese rice was notable in being deficient in macro- and micro-nutrients while also being elevated in cadmium at a median of 0.02 mg/kg, with China though still having a median that is ~ 2.5-fold this concentration. These Chinese concentrations are of particular concern as the 75th percentile for China is 0.1 mg/kg, a value that triggers regulatory action for rice products.

Arsenic Speciation and Metallomics Profiling of Human Toenails as a Biomarker to Assess Prostate Cancer Cases: Atlantic PATH Cohort Study.

Chronic exposure to inorganic arsenic and trace metals has been linked to prostate cancer, and altered arsenic methylation capacity may have an important role in arsenic carcinogenesis. Biomarkers may be able to elucidate this role. Our objectives were to characterize profiles of arsenic species and metallome in toenails and urine samples, compare profiles between prostate cancer cases and controls, and determine the discriminant ability of toenail and urine biomarkers. Toenail samples (n = 576), urine samples (n = 152), and questionnaire data were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. Healthy controls were matched to prostate cancer cases (3:1 ratio) on sex, age, smoking status, and the province of residence. Metallome profiles and proportions of arsenic species were measured in toenail and urine samples. Analysis of covariance (ANCOVA) was used to compare the mean percent monomethylarsonic acid (%MMA), dimethylarsonic acid (%DMA), inorganic arsenic (%iAs), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). Multivariate analysis of covariance (MANCOVA) was used to compare selected metal concentrations. Mean %MMA was significantly lower and SMI was significantly higher in toenails from prostate cancer cases compared to controls in unadjusted and adjusted models. Proportions of arsenic species were correlated with total arsenic in toenails. Arsenic speciation in urine was not different between cases and controls, nor were metallome profiles in toenails and urine. Our results indicate that toenails are a viable biomarker for altered arsenic speciation in prostate cancer cases and may have greater utility than urine in this context.

Simple and reliable determination of total arsenic and its species in seafood by ICP-MS and HPLC-ICP-MS

Quantitative, rapid, selective and sensitive methods for the determination of total arsenic (tAs) and six arsenic compounds (arsenite (As(III)), arsenate (As(V)), arsenobetaine (AsB), arsenocholine (AsC), monomethylarsonic acid (MMA), dimethylarsonic acid (DMA)) in seafood were developed. The measurement of the tAs concentration was performed using quadrupole inductively-coupled plasma mass spectrometry (ICP-MS). Microwave-assisted extraction was used for the isolation of arsenic species. The separation and quantification of analysed compounds were performed by ion-exchange chromatography coupled with ICP-MS in one chromatographic run using ammonium carbonate-based buffers, which has little effect on ICP-MS sensitivity compared to commonly used phosphate buffers. The results of validation and proficiency tests confirmed the reliability, robustness, and applicability of the developed procedures to various types of matrices. The proposed methods are relatively simple, time- and cost-efficient, therefore could be used to routinely analyse tAs content and arsenic species in different types of seafood at trace and ultra-trace levels.

Association between urinary arsenic, blood cadmium, blood lead, and blood mercury levels and serum prostate-specific antigen in a population-based cohort of men in the United States.

Exposures to heavy metals have been linked to prostate cancer risk. The relationship of these exposures with serum prostate-specific antigen (PSA), a marker used for prostate cancer screening, is unknown. We examined whether total urinary arsenic, urinary dimethylarsonic acid, blood cadmium, blood lead, and total blood mercury levels are associated with elevated PSA among presumably healthy U.S. men. Prostate cancer-free men, aged ≥40 years, were identified from the 2003–2010 National Health and Nutrition Examination Survey. Logistic regression analyses with survey sample weights were used to examine the association between heavy metal levels and elevated PSA for the total population and stratified by black and white race, after adjusting for confounders. There were 5,477 men included. Approximately 7% had elevated PSA. Men with an elevated PSA had statistically significantly higher levels of blood cadmium and blood lead compared to men with a normal PSA (p-values ≤ 0.02), with black men having higher levels. After adjusting for age, race/ethnicity, body mass index, smoking, and education, there was no association found between any of the heavy metal levels and elevated PSA for the total population. In addition, there was no association found when stratified by black and white race. Further investigation is warranted in a larger cohort of men who persistently are exposed to these heavy metals.

Risks associated with the consumption of inorganic and organic arsenic

It is known that the chronic intake of arsenic (As) leads to the development of multisystem pathologies. In the case of high levels of As consumption, the risks of negative effects of exposure to inorganic and methylated forms persist for decades. The International Agency for Research on Cancer (IARC) has established that all inorganic forms of As are absolute carcinogens (group 1). Methylated forms of As are classified as substances possibly carcinogenic to humans (group 2b). Not metabolized in the human body forms of organic As are not carcinogenic to humans (group 3). The aim - assessment of health risks of various forms of As contained in food, including seafood. Material and methods. The scientific data regarding the risks associated with As contamination of food obtained by using PubMed, Web of Science, Google Scholar databases, legislative and regulatory acts of the Eurasian Economic Union, the Russian Federation, the Codex Alimentarius Commission, the European Union and other coun tries have been analyzed. Results. The analysis of the available data showed that the degree of As toxicity decreased in the following order: glutathione of dimethylarsonic acid (DMAIIIGl) > methylarsic acid (MMAIII) > dimethylarsic acid (DMAIII) > arsenic hydrocarbons (AsHC) > arsenite (AsIII) > arsenate (AsV) > trimethylarsine (TMAIII) > methylarsonic acid (MMAV) > dimethylarsonic acid (DMAV) > DMAIII-sugar glyceride > DMAV-sugar glyceride > thio compounds of DMAV > arsenosugarsIII > arsenosugarsV > tetramethylarsonium chloride (TETPA) > trimethylarsine oxide (TMAO), arsenocholine (AsC) > arsenobetaine (AB). Consequently, the toxicity of some methylated and organic forms of As (for example, DMAIIIGl, AsHC) may be higher than that of its inorganic forms. It is known that As is found in foods mainly in organic forms. When ingested with food, As organic forms are metabolized and, thus, could cause a number of negative effects in the organism. Conclusion. High levels of organic and inorganic forms of As in food, including seafood, could have a negative impact on the health of the population, which makes it necessary to conduct additional assessments of the health risks of various forms of As entering the body. The insufficient amount of data on the toxicity of organic forms of As indicates the impossibility of separate setting of safety maximum levels for organic and inorganic forms of As in foods.

S1065 Arsenic Exposure and Risk of Liver Injury Among U.S. Adults: An Association Modified by Gender

INTRODUCTION: Arsenic has toxic effects on multiple organ systems; however, arsenic toxicity on the liver has not been well explored. Therefore, we examined the association between arsenic exposure and serum ALT, a marker for liver injury and effect modification by gender. METHODS: Individuals >19 years of age from 7 cycles of the National Nutrition and Health Examination Survey (NHANES 2003–16) were included. Associations between serum ALT and creatinine-standardized urinary concentrations of total and 7 arsenic forms were examined. Data were summarized with mean (standard deviation) or frequencies. Urinary arsenic and serum ALT were log-transformed due to right-skewed distributions. We used survey-weighted linear regression without and with adjustments for gender, age, diabetes, hypertension, race, smoking, alcohol use, estimated GFR, and body mass index(BMI). Effect-modification by gender was examined by with an interaction term between gender and arsenic forms. RESULTS: Of the 12,439 participants, 52% were females, 33% hypertensives, 9% were diabetics, 54% were non-smokers, and 68% were whites. The mean age was 48 years. BMI 29 Kg/m2, ALT 26 U/L, and total urinary arsenic 18.4 ug/L. As compared to females, males had significantly higher ALT (30.3 vs 21.9; P < 0.001) and total urinary arsenic levels (19.7 vs 17.3 P = 0.02). In adjusted models, each 10% increase in urinary total arsenic, dimethylarsonic acid, trimethylarsine oxide was associated with 0.1%, 0.4%, and 0.2% increase in serum ALT respectively (all P-values< 0.01); ALT increase with other urinary arsenic forms was not significant. Females had larger increases in ALT than males for 5 arsenic forms; for each 10% increase in arsenous acid, arsenic acid, arsenocholine, monomethylarsonic acid, and dimethylarsenic acid were associated with 0.3%, 0.6%, 0.4%, 0.6%, and 0.4% larger increase in ALT than males (all P < 0.05) (Figure). CONCLUSION: Urinary arsenic levels within an acceptable range (total urinary arsenic< 100ug/L) are associated with a small but significant risk of liver injury as measured by elevation in serum ALT. Females are particularly at a higher risk of liver injury than males. The clinical significance of this liver injury needs examination in longitudinal studies.Figure 1

Urinary arsenic concentration, airway inflammation, and lung function in the U.S. adult population

BackgroundInorganic arsenic (iAs) is ubiquitous in the environment and has been linked to lung cancer and a number of non-malignant lung disease in both adults and children. However, most studies were conducted in populations with higher arsenic exposure levels in drinking water and relatively little epidemiologic research evaluated the impacts of low levels iAs exposure on non-malignant lung disease among populations that are not primarily exposed to arsenic through drinking water. ObjectivesWe assessed the associations of arsenic exposure with airway inflammation and lung function among U.S. adults aged 20–79 years using data from the National Health and Nutrition Examination Survey 2007–2012 cycles. MethodsTwo measures of arsenic exposure, urinary total arsenic and dimethylarsonic acid (DMA), were used. We calibrated these two exposure measures by regressing their concentrations by arsenobetaine and extracting the residuals to calculate estimated total arsenic and estimated DMA. Arsenic exposures were modeled as log-transformed continuous variables as well as quartile categories. Fractional exhaled nitric oxide (FENO), an indicator of respiratory inflammation, was available for participants. For lung function, the best forced expiratory volume in the first one second (FEV1), forced vital capacity (FVC), forced expiratory flow rate (FEF) 25–75%, their percent estimated values, ratios of FEV1 to FVC, and FEF 25–75% to FVC were used (i.e. FEV1/FVC and FEF/FVC). Weighted multivariable linear regression models, adjusted for potential confounders, were used to evaluate the association of arsenic exposure with airway inflammation and lung function overall, and among males and females. ResultsSignificant associations between arsenic exposure and increased airway inflammation were found. A two-fold increase in urinary total arsenic and DMA was associated with 23.87% (95% CI: 2.66, 49.46) and 14.05% (95% CI: 1.77, 27.81) higher levels of FENO, respectively. In addition, participants in the highest quartile of urinary total arsenic had FENO levels 8.49% (95% CI: 1.13, 16.39) higher than those in the lowest quartile. These associations were similar between males and females. Limited evidence was found for the association with respect to lung function and potential modification effect of sex. ConclusionsArsenic exposure was related to increased risk of airway inflammation but there is limited evidence of an association in relation to lung function. Future research conducted in populations with relatively lower exposure levels that are not primarily exposed to arsenic through drinking water is needed to confirm our findings.

A combined analytical method for biological monitoring of arsenic, benzene and polycyclic aromatic hydrocarbons in human urine by liquid chromatography tandem mass spectrometry

An analytical method for the biomonitoring of arsenic, benzene and polycyclic aromatic hydrocarbons (PAHs) in human urine was developed using liquid chromatography tandem mass spectrometry (LC-MS/MS). The urinary metabolites of monomethylarsonic acid (MMAA), dimethylarsonic acid (DMAA), s-phenylmercapturic acid (S-PMA), and 1-hydroxypyrene (1-OHP) were selected as the corresponding marker compounds. After enzymatic deconjugation, 4 mL urine sample was extracted by 2 steps of solvent extractions. The 1-OHP was first extracted with n-hexane with 10% ethyl acetate, and MMAA, DMMA, and S-PMA were then extracted in a 2nd extraction/back-extraction using chloroform/ammonium bicarbonate aqueous solution. The two extracts were mixed and analyzed by LC-MS/MS. The method was validated with spiked urine samples. The obtained linear ranges (r2 > 0.99) of the urinary markers were 2–64 ng/mL MMAA, 1–64 ng/mL DMAA, 0.78–100 ng/mL S-PMA and 0.05–6.4 ng/mL 1-OHP. The measured accuracy (% Error) and precision (CV%) were -16.67 to 29.17% and 2.03–30.99% (3 spiked levels, 6 replicates), respectively. The method was applied to 10 real urine samples, and the presence of MMAA, DMAA, S-PMA and 1-OHP were clearly detected. The detected concentrations were BQL-8.38 ng/mL of MMAA, BQL-10.71 ng/mL of DMAA, BQL-2.55 ng/mL of SPMA, and BQL-0.17 ng/mL of 1-OHP, which were all consistent with the reported background levels.

Associations of renal function with urinary excretion of metals: Evidence from NHANES 2003–2012

BackgroundUrinary metals are considered measures of long-term exposures of metals, such as cadmium (Cd). Some studies indicate reduced renal function may affect the urinary excretion of several metals in general population making assessments difficult. ObjectivesTo examine whether reduced renal function is associated with reduced urinary excretion of 12 metals or their metabolites and, in turn, an underestimated measure of Cd in general population. MethodsWe conducted analyses using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2012. Multiple linear regression models were used to examine the associations between urinary metal levels and estimated glomerular filtration rate (eGFR). Restricted cubic spline regression models were used to evaluate the nonlinearity. ResultsUrinary metal levels significantly increased (p < 0.001) with increasing eGFR, except for antimony (p = 0.172). Urinary levels of arsenic, dimethylarsonic acid, cobalt, molybdenum and tungsten increased linearly with eGFR, while Cd, lead, mercury, barium, cesium and thallium increased nonlinearly (p < 0.001) with eGFR. Based on a restricted cubic spline regression model, we found, corresponding to a fixed blood Cd adverse cutpoint of 5 μg/L, predicted urinary Cd cutpoints substantially varied from 0.78–1.21 μg/g for urinary Cd between those aged <40 years and who had chronic kidney disease and those aged 60 years or over with normal renal function, respectively. ConclusionReduced renal function is associated with reduced urinary metals; and associations are also observed across the eGFR range not just in the reduced range. Urinary abnormal cutpoints of metals are likely dependent on eGFR and age. The associations between urinary exposure of metals and disease risk are likely underestimated without considering the modifying effect of renal function.

Arsenic species in herbal tea leaves and infusions determination by HPLC-ICP-MS

A simple method for arsenic species As (III), As (V), monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA) were investigated in 18 herbal tea leaves and their infusion by high performance liquid chromatography hyphenated with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The proposed method presented absence of interconversion between the arsenic species and high sensitivity, being limits of detection and quantification 11 and 38 μg L−1 for herbal tea leaves and 0.20 and 0.66 μg L−1 for their infusions, respectively. About 28% samples present total arsenic levels above Brazilian and MERCOSUR maximum limits (0.6 mg kg−1). The estimative of exposure to inorganic arsenic was made taking into account the benchmark dose lower limit (BMDL05) considering the daily ingestion of one cup of herbal tea (200 mL) for adults (70 kg) and children (20 kg). Although this estimative demonstrates low exposure for adults (2.9% of BMDL05), for children, however, the daily consumption of a single cup of herbal tea can reach 10.3% of BMDL05 for inorganic arsenic.

Arsenic speciation in tree moss by mass spectrometry based hyphenated techniques

A method based on ion-pair reversed phase high performance liquid chromatography (HPLC) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) was developed for arsenic speciation in extract of tree moss. Under the optimal conditions, the limit of detection of eight arsenic species including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsonic acid (DMA), trimethylarsinoxide (TMAO), tetramethylarsonium (Tetra), arsenocholine (AsC) and arsenobetaine (AsB) is between 0.04 and 0.07 ng/mL, with a linear range of 0.2 − 500 ng/mL. Three unknown arsenic species (Unk1, Unk2 and Unk3) and six specific arsenic species (AsIII, AsV, DMA, TMAO, Tetra and AsB) were detected in the extract of tree moss. Unk3 was identified as a kind of arsenosugars (2,3-dihydroxypropyl-5-deoxy-5(dimethylarsenoso)furanoside, arsenosugar X) by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-qTOF-MS).

Construction of Environmental Risk Score beyond Standard Linear Models: Application to Metal Mixtures, Oxidative Stress and Cardiovascular Disease in NHANES

Background/Aim: There is growing concern of potential health effects of exposure to pollutant mixtures. We initially proposed an Environmental Risk Score (ERS) as a summary measure to examine the risk of exposure to multiple pollutants in epidemiologic research considering only pollutant main effects (Park et al., 2014). We expand the ERS by consideration of pollutant-pollutant interactions using modern machine learning methods. We illustrate the multi-pollutant approaches to predicting a marker of oxidative stress (gamma-glutamyl transferase (GGT)), a common disease pathway linking environmental exposure and numerous health endpoints. Methods: We examined 20 metal biomarkers measured in urine or whole blood from 6 cycles of the National Health and Nutrition Examination Survey (NHANES 2003-2004 to 2013-2014, n=9664). We randomly split the full data evenly into training and testing sets and constructed ERS’s of metal mixtures for GGT using adaptive elastic-net with main effects and pairwise interactions (AENET-I), Bayesian additive regression tree (BART), Bayesian kernel machine regression, and SuperLearner in the training set and evaluated their performances in the testing set. We evaluated the concordance of various ERS and the associations between ERS and cardiovascular endpoints. Results: ERS based on AENET-I performed better than other approaches in terms of prediction errors in the testing set. Important metals identified in relation to GGT include lead, cadmium, dimethylarsonic acid, mercury, cobalt, tungsten, and barium. All ERS’s showed significant associations with systolic and diastolic blood pressure and hypertension. For hypertension, one standard deviation increase in each ERS from AENET-I, BART and SuperLearner were associated with odds ratios of 1.50 (95% CI, 1.15, 1.94), 1.38 (1.09, 1.76), and 1.31 (1.02, 1.66), respectively. ERS’s showed non-significant positive associations with mortality outcomes. Conclusions: ERS is a useful tool for characterizing cumulative risk from pollutant mixtures, with accounting for statistical challenges such as high degrees of correlations and pollutant-pollutant interactions.

Construction of environmental risk score beyond standard linear models using machine learning methods: application to metal mixtures, oxidative stress and cardiovascular disease in NHANES

BackgroundThere is growing concern of health effects of exposure to pollutant mixtures. We initially proposed an Environmental Risk Score (ERS) as a summary measure to examine the risk of exposure to multi-pollutants in epidemiologic research considering only pollutant main effects. We expand the ERS by consideration of pollutant-pollutant interactions using modern machine learning methods. We illustrate the multi-pollutant approaches to predicting a marker of oxidative stress (gamma-glutamyl transferase (GGT)), a common disease pathway linking environmental exposure and numerous health endpoints.MethodsWe examined 20 metal biomarkers measured in urine or whole blood from 6 cycles of the National Health and Nutrition Examination Survey (NHANES 2003–2004 to 2013–2014, n = 9664). We randomly split the data evenly into training and testing sets and constructed ERS’s of metal mixtures for GGT using adaptive elastic-net with main effects and pairwise interactions (AENET-I), Bayesian additive regression tree (BART), Bayesian kernel machine regression (BKMR), and Super Learner in the training set and evaluated their performances in the testing set. We also evaluated the associations between GGT-ERS and cardiovascular endpoints.ResultsERS based on AENET-I performed better than other approaches in terms of prediction errors in the testing set. Important metals identified in relation to GGT include cadmium (urine), dimethylarsonic acid, monomethylarsonic acid, cobalt, and barium. All ERS’s showed significant associations with systolic and diastolic blood pressure and hypertension. For hypertension, one SD increase in each ERS from AENET-I, BART and SuperLearner were associated with odds ratios of 1.26 (95% CI, 1.15, 1.38), 1.17 (1.09, 1.25), and 1.30 (1.20, 1.40), respectively. ERS’s showed non-significant positive associations with mortality outcomes.ConclusionsERS is a useful tool for characterizing cumulative risk from pollutant mixtures, with accounting for statistical challenges such as high degrees of correlations and pollutant-pollutant interactions. ERS constructed for an intermediate marker like GGT is predictive of related disease endpoints.

Case-control study of chronic low-level exposure of inorganic arsenic species and non-melanoma skin cancer.

A significant relationship between arsenic exposure and non-melanoma skin cancer (NMSC) is well known. The toxicity of arsenics which develop NMSC is dependent on their species. Accordingly, total arsenic levels are unreliable for risk assessment of NMSC. However, there are few studies on quantitative exposure assessment of arsenic species in NMSC patients. To validate the contribution of each arsenic species to NMSC, we compared the creatinine-adjusted urinary concentration of arsenic species in NMSC patients and community controls. A total of 124 biopsy-proven NMSC cases and 125 age- and sex-matched community controls, drinking tap water with low-level arsenic concentration (<5 μg/L), were included in the study. High-performance liquid chromatography and inductively coupled plasma mass spectrometry were used for the measurement. The NMSC group was found to have significantly higher levels of total inorganic arsenic, trivalent and pentavalent arsenic and monomethylarsonic acid than the control group. Total arsenic, organic arsenic and dimethylarsonic acid levels were lower in the NMSC group. We suggest that inorganic arsenic species, trivalent arsenic and pentavalent arsenic may influence the prevalence of NMSC, in spite of these levels being lower than the Agency for Toxic Substances and Disease Registry-recommended standard or the levels reported by other highly contaminated areas and neighboring countries in East Asia. Furthermore, it also suggests that total arsenic level cannot represent the risk of NMSC.

Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population.

Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc.