Dimethylarsinic Acid Research Articles

Arsenic accumulation, speciation and bioavailability in rice cultivated in arsanilic acid exposed soil

The present study used various amounts of P-arsanilic acid (AsA) in pot experiments to evaluate the effects of AsA on arsenic (As) accumulation, speciation and meanwhile using the in vitro digestion/Caco-2 cell model to evaluate the bioavailability of As in rice. The results indicated a linear relationship between As in rice and As in soil, and at 75 mg AsA/kg of soil, As content in rice exceeded the statutory permissible limit of 0.2 mg As/kg dry weight in China. Speciation studies indicated that inorganic As (Asi), dimethylarsinic acid (DMA), and monomethylarsonic acid (MMA) were the main As species in rice. Bioavailability of As experiment indicated that As uptake and transport amount by Caco-2 cells increased with increasing As accumulation in rice. In general, the content of AsA in soil reached or exceeded 75 mg/kg, which is not suitable for growing rice.

Powder X-ray diffraction data for dimethylarsinic acid, (CH3)2AsO(OH)

Synchrotron powder diffraction data is presented for the monoclinic polymorph of dimethylarsinic acid, (CH3)2AsO(OH) (DMAV). Rietveld refinement with GSASII yielded lattice parameters of a = 15.9264(15) Å, b = 6.53999(8) Å, c = 11.3401(9) Å, and β = 125.8546(17)° (Z = 8, space group C2/c). The Rietveld-refined structure was compared with both a density functional theory (DFT)-optimized structure and the published, low-temperature single-crystal structure, and all three structures exhibited excellent agreement. The triclinic polymorph of DMAV was also DFT optimized with CRYSTAL17 to determine the positions of the hydrogen atoms. Monoclinic DMAV forms zigzag chains parallel to the b-axis with adjacent DMAV molecules connected by an O–H⋯O bond, whereas triclinic DMAV forms dimers connected by two O–H⋯O bonds.

Exposure to Arsenic in the Air and 15-F2t-Isoprostane in Urine in a Sub-population of Inhabitants of a Copper Smelter Region

Most studies on arsenic toxicity have been conducted among populations exposed to arsenic contained in drinking water. Relatively little research concerns effects of airborne arsenic. The aim of this study was to determine whether there is an association between urinary 15-F2t-isoprostane (u15-F2t-IsoP) levels in relation to renal function (urinary creatinine and N-acetyl-β-d-glucosaminidase––uNAG) and urinary arsenic (uAs) in inhabitants from copper smelter impact zone. The secondary purpose of the analysis was to assess utility of a potential association between uAs and u15-F2t-IsoP as a biomarker of systemic oxidative stress. Urinary 15-F2t-IsoP, NAG, and creatinine were measured in 967 urine samples collected from 649 adult women (51.9 ± 13.2 years old) and 318 adult men (53.8 ± 14.9 years old). Total uAs concentration was measured in 918 samples using HPLC-ICP-MS. Arsenic species, such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid, and arsenobetaine, were measured in urine collected from 255 participants with uAs exceeding the upper norm. Data were analyzed using multivariate linear regression and logistic regression models. In the studied population urinary creatinine was positively associated with uAs. A positive linear correlation (p < 0.0000) between lg(uAs) and u15-F2t-IsoP was found both for normal and elevated uAs. A positive linear correlation was observed also between lg(ΣuAs) and u15-F2t-IsoP (p < 0.0000). In the logistic regression model, after adjustment for confounders, elevated uAs was the only predictor of increased u15-F2t-IsoP (OR = 1.31, 95% CI 1.08–1.59, p < 0.01). Cigarette smoking was associated with renal proximal tubular dysfunction only in people with uNAG concentration above 75th quartile. In the studied population chronically exposed to airborne arsenic, increase in urinary arsenic is associated with renal dysfunction and systemic oxidative stress. Urinary 15-F2t-isoprostane may be useful in the monitoring of health status in populations exposed to airborne arsenic.

Monomethylated arsenic was the Major methylated arsenic in Red blood cells of acute promyelocytic leukemia patients treated with arsenic trioxide

BackgroundArsenic trioxide (ATO) has been successfully applied in the treatment of acute promyelocytic leukemia (APL). Arsenic metabolites including inorganic arsenic and methylated arsenic could lead to different toxicity and curative effect. This study aims to establish a method to determine arsenic species in red blood cells (RBCs), clarify the distribution characteristics of arsenic species in RBCs. MethodsSteady state blood samples were collected from 97 APL patients. H2O2 and HClO4 were used to release the hemoglobin bounding arsenic and precipitate protein. Arsenite (iAsIII), arsenate (iAsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in plasma and RBCs were detected by HPLC-HG-AFS. Free and bound arsenic species in RBCs were separated by 30 kDa molecular mass cutoff filters and determined to evaluate hemoglobin binding capacity of different arsenic species. ResultsThe method was validated with accuracy ranged from 84.75% to 104.13%. Arsenic species in RBCs followed the trend iAs > MMA > DMA (p < 0.01), while the concentration of DMA was significantly higher than iAs and MMA in plasma (p < 0.01). The correlation between iAs concentration in plasma and corresponding RBCs arsenic level was weak. And the concentrations of DMA and MMA in plasma were moderately positive correlated with those in RBCs. Hemoglobin-binding ratios of iAs, MMA and DMA were all over 70 %. ConclusionsIn this study, we provided a reliable method to determine arsenic species in RBCs of APL patients treated with ATO by HPLC-HG-AFS. It was confirmed that the concentration of DMA is the highest in plasma, while MMA is the most predominant methylated arsenic in RBCs. High affinity of MMA with human Hb was responsible for the accumulation of arsenic in RBCs of APL patients.

Multi-elemental risk assessment of various baby rice cereals: some cause for concern?

This study used batch and online methods to accurately determine how much arsenic (As), chromium (Cr), selenium (Se), cadmium (Cd), lead (Pb), copper (Cu), iron (Fe), and zinc (Zn) can be leached from baby rice cereals into a baby’s body. Speciation analysis of the saliva and gastric juice leachates was conducted to further assess the risk associated with the continued consumption of baby rice cereal for infants. A simple 15 min chromatographic analysis successfully separated eight species consisting of As(III), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), As(V), Se(IV), Se(VI), Cr(III), and Cr(VI). Given that 95%–100% As, 29%–100% Cr, 62%–100% Pb, 70%–100% Se, 63%–100% Cd, 36%–100% Cu, 67%–100% Fe, and 70%–100% Zn were bio-accessible and the speciation analysis results showed all bio-accessible As and Se to be in the forms of As(V) and Se(VI) and 70%–100% of Cr to be in the Cr(III) form, a variety of foods should be fed to infants rather than just baby rice cereal to ensure a well-balanced diet and less exposure to As at such a young age.

On-line speciation analysis of arsenic compounds in commercial edible seaweed by HPLC–UV-thermo-oxidation-HG-AFS

Arsenic speciation analysis in dried seaweeds was carried out using an on-line HPLC–UV-thermo-oxidation-HG-AFS system. Species separated and quantified were: arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and different arsenosugars. Extraction efficiency ranged between 38 and 83%. Chromatographic separation was achieved in gradient elution mode using (NH4)2CO3 as mobile phase in the pH range 9–10.3. Total As concentration was quantified by ICP-MS after microwave digestion. Limits of detection were in the range 3.0 to 6.0 ng g−1 for the species under study based on peak height and the relative standard deviation was <8% at 10 µg L−1 As. The accuracy of the procedure was verified by analyzing the CRM BCR-279 Ulva lactuca. Results for total As were in agreement with the certified values. The HPLC-(UV)-HG-AFS system resulted suitable for quantification of eight As compounds. Results showed that arsenosugars are the most abundant compounds in the investigated seaweeds.

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.

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

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

Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects.

The toxic metalloid inorganic arsenic (iAs) is widely distributed in the environment. Chronic exposure to iAs from environmental sources has been linked to a variety of human diseases. Methylation of iAs is the primary pathway for metabolism of iAs. In humans, methylation of iAs is catalyzed by arsenic (+ 3 oxidation state) methyltransferase (AS3MT). Conversion of iAs to mono- and di-methylated species (MAs and DMAs) detoxifies iAs by increasing the rate of whole body clearance of arsenic. Interindividual differences in iAs metabolism play key roles in pathogenesis of and susceptibility to a range of disease outcomes associated with iAs exposure. These adverse health effects are in part associated with the production of methylated trivalent arsenic species, methylarsonous acid (MAsIII) and dimethylarsinous acid (DMAsIII), during AS3MT-catalyzed methylation of iAs. The formation of these metabolites activates iAs to unique forms that cause disease initiation and progression. Taken together, the current evidence suggests that methylation of iAs is a pathway for detoxification and for activation of the metalloid. Beyond this general understanding of the consequences of iAs methylation, many questions remain unanswered. Our knowledge of metabolic targets for MAsIII and DMAsIII in human cells and mechanisms for interactions between these arsenicals and targets is incomplete. Development of novel analytical methods for quantitation of MAsIII and DMAsIII in biological samples promises to address some of these gaps. Here, we summarize current knowledge of the enzymatic basis of MAsIII and DMAsIII formation, the toxic actions of these metabolites, and methods available for their detection and quantification in biomatrices. Major knowledge gaps and future research directions are also discussed.

Arsenic speciation in rice samples for trace level determination by high performance liquid chromatography-inductively coupled plasma-mass spectrometry

Six arsenic species, namely arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenobetaine (AsB) and arsenocholine (AsC) were speciated using a combination of high-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC–ICP-MS). Under optimum chromatographic conditions, six arsenic species were well separated, and the performance of the combined system (HPLC–ICP-MS) for the species was determined. The limits of detection were calculated in the range of 0.14–0.29 ng/mL, and the corresponding quantification limits ranged between 0.45 and 0.97 ng mL−1 for the species. Spike recovery experiments performed on rice samples were used to validate the method’s applicability to complex matrices. The recovery results calculated ranged between 93 and 109%, validating the method’s applicability. Triplicate measurements for all spiked samples recorded percent relative standard deviation values below 10%.

Opposite Effects of Potassium Ions on the Thermal Stability of i-Motif DNA in Different Buffer Systems.

i-motifs are noncanonical DNA structures formed via the stack of intercalating hemi-protonated C+: C base pairs in C-rich DNA strands and play essential roles in the regulation of gene expression. Here, we systematically investigated the impacts of K+ on i-motif DNA folding using different buffer systems. We found that i-motif structures display very different Tm values at the same pH and ion strength in different buffer systems. More importantly, K+ disrupts the i-motif formed in the MES and Bis-Tris buffer; however, K+ stabilizes the i-motif in phosphate, citrate, and sodium cacodylate buffers. Next, we selected phosphate buffer and confirmed by single-molecule fluorescence resonance energy transfer that K+ indeed has the stabilizing effect on the folding of i-motif DNA from pH 5.8 to 8.0. Nonetheless, circular dichroism spectra further indicate that the structures formed by i-motif sequences at high K+ concentrations at neutral and alkaline pH are not i-motif but other types of higher-order structures and most likely C-hairpins. We finally proposed the mechanisms of how K+ plays the opposite roles in different buffer systems. The present study may provide new insights into our understanding of the formation and stability of i-motif DNA.

Characteristics of arsenic species in cerebrospinal fluid (CSF) of acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide plus mannitol.

Arsenic speciation in cerebrospinal fluid (CSF) is critical for treatment/prevention of central nervous system (CNS) relapse in acute promyelocytic leukaemia (APL) patients treated with arsenic trioxide (ATO). Previous study showed low total arsenic level in CSF of APL patients. Mannitol infusion was applied to improve blood-brain barrier (BBB) permeability for arsenic. Arsenite (AsIII ), monomethylarsonic acid (MMAV ), dimethylarsinic acid (DMAV ), and arsenate (AsV ) in CSF and plasma were analysed by high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS). The profile and concentration of arsenic species in CSF from APL patients administered ATO alone and in combination with mannitol were compared. The overall distribution trend of arsenic species in CSF was AsIII , DMAV > MMAV > AsV . Arsenicals accumulated in CSF with administration frequency. The permeability of BBB for AsIII was higher than that for MMAV and DMAV . Arsenic concentration in CSF was much lower than that in plasma. There were significantly higher arsenic species concentrations in CSF of APL patients treated with mannitol than that without mannitol. Mannitol infusion significantly increased AsIII penetration into CSF, which was beneficial to optimize efficacy in APL patients with CNS relapse.

Simultaneous quantitative speciation of selected toxic elements in water using high performance liquid chromatography coupled to inductively coupled plasma-mass spectrometry (HPLC-ICP-MS)

The aim of this study was to conduct multi-elemental speciation of As(III), dimethylarsinic acid (DMA), monomethylarsenic acid (MMA), As(V) and Cr(VI) in water samples using high performance liquid chromatography coupled to inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) in a single analytical run. Chromatographic parameters, spectral interference identification, and elimination and the performance characteristics of the method were successfully optimized for quantification of As(III), DMA, MMA, As(V), Cr(VI) and Cr(III) in water samples. The percentage errors of 6.93–43.2% for identified potential interferences were eliminated by applying the inter-element mathematical correction method. The limit of detection (LOD) and limit of quantification (LOQ) of As species and Cr(VI) were varied from 0.040-0.298 μg L−1 and 0.133–2.98 μg L−1, respectively. The LOD and LOQ of total As, Cr and Pb determined using ICP-MS were ranged from 0.013-0.203 μg L−1 and 0.045–0.675 μg L−1, respectively. The accuracy of the method was confirmed by achieving the percentage recovery of 83.4% for As species, 90.2% for Cr(VI) and 110–118% for total concentrations of As, Cr and Pb using standard reference material for trace elements in water (SRM 1643f). Furthermore, the accuracy of the speciation analysis method was checked using the spiking and recovery studies and yielded percentage recoveries in the range of 78.3–95.4% for the analyte species. The quantities of species determined in water samples were in the range of 0.314–0.402 μg L−1 for As(III), 0.168–0.533 μg L−1 for DMA, 0.226–0.312 μg L−1 for MMA, 0.191–0.459 μg L−1 for As(V), 0.500–3.28 μg L−1 for Cr(VI) and 0.390–12.6 μg L−1 for Cr(III) in high-flow seasonal state of the river. In the low-flow seasonal state, concentrations varied from 0.314-0.391 μg L−1 for As(III), <0.094 μg L−1 for DMA, 0.315–26.7 μg L−1 for MMA, 0.290–0.744 μg L−1 for As(V), 0.426–5.42 μg L−1 for Cr(VI) and 0.424–96.8 μg L−1 Cr(III). Total concentrations of As, Cr and Pb in water samples of high-flow seasonal state ranged from 0.949-1.88 μg L−1, 1.08–14.9 μg L−1 and 0.190–33.8 μg L−1, respectively. In low-flow seasonal state, the total concentrations of As, Cr and Pb in water samples varied from 1.13-26.5 μg L−1, 3.28–97.5 μg L−1 and 0.455–0.610 μg L−1, respectively. The variations between analytes species and total As, Cr and Pb in seasonal states of the river were statistically insignificant (p > 0.05) at a 95% confidence level except for DMA. The nonpoint sources pollution such as atmospheric deposition of dust released from coal mining, power stations, sewage effluents discharge and agricultural activities are presumably the sources of potentially toxic elements in the Mokolo River.

Effects of sodium arsenite and dimethyl arsenic acid on Liaoning cashmere goat skin fibroblasts.

The morphology and oxidation state of arsenic in its compounds affects the skin cell toxicity. Accordingly, the present study was conducted to explore the effects of two different arsenic compounds on the proliferation and survival of Liaoning cashmere goat skin fibroblasts. Based on MTT assay results, at 24h, the proliferation concentration, critical concentration, and half inhibitory concentration (IC50) of sodium arsenite were 0.50, 5.00, and 45.66μmol/L, respectively. The corresponding values for dimethyl arsenic acid were 0.85, 1.00, and 38.68mmol/L. Immunofluorescence, transmission electron microscopy, and mitochondria membrane potential (MMP) assays showed that sodium arsenite promotes microtubule polymerization and increases MMP, while cells treated with dimethyl arsenic acid exhibited cytoskeletal collapse and decreased MMP. In the IC50 groups for both arsenic agents, the cytoskeletons collapsed, microtubules were gathered into bundles, and MMP was significantly decreased. Dimethyl arsenic acid had a stronger effect on MMP than sodium arsenite. Flow cytometry revealed a slightly lower occurrence of apoptosis in the sodium arsenite proliferation group, while it was slightly increased in the dimethyl arsenic acid proliferation group. Apoptosis was increased more significantly in the sodium arsenite IC50 group than in the dimethyl arsenic acid IC50 group. These results indicate that the differences in cell proliferation and cytotoxicity induced by inorganic and organic arsenic are related to their effects on cellular structures.

Accumulation, transformation and subcellular distribution of arsenite associated with five carbon nanomaterials in freshwater zebrafish specific-tissues

Although carbon nanomaterials (CNMs) commonly exist throughout the aquatic environment, their effect on arsenic (As) distribution and toxicity is unclear. In this study, arsenite accumulation, transformation, subcellular distribution, and enzyme activity were assessed in adult zebrafish (Danio rerio) intestines, heads and muscles, following co-exposure to arsenite and CNMs with different structures (single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), fullerene (C60), graphene oxide (GO), and graphene (GN)). Results show that GN and GO promoted As toxicity in D. rerio, as carriers increasing total As accumulation in the intestine, resulting in arsenite adsorbed by GO and GN being released and transformed mainly into moderately-toxic monomethylarsonic acid (MMA), which was mostly distributed in organelles and metallothionein-like proteins (MTLPs). Moreover, GO and GN influenced As species distribution in D. rerio due to the excellent electron transfer ability. However, the effect was marginal for SWCNT, MWCNT and C60, because of the different structure and suspension stability in fish-culture water. In addition, in the muscle and head tissues, As was mainly distributed in cellular debris in the forms of dimethylarsinic acid (DMA) and arsenobetaine (AsB). These findings help better understand the influence of CNMs on the mechanism of As toxicity in natural aquatic environments.

Carryover effects of silicon‐rich amendments in rice paddies

AbstractRice (Oryza sativa L.) readily accumulates the nutrient silicon (Si) and the toxin arsenic (As), elements that can interact antagonistically both in the plant and in the soil. Thus, many studies have been performed where Si‐rich materials are incorporated into soils to increase plant‐available Si and thereby decrease plant As. However, studies have not examined the dissolution kinetics of Si from Si‐rich materials over multiple seasons and the resulting effects on rice systems. Here, we analyzed the porewater chemistry, CH4 emissions, and rice elemental concentrations from rice paddies in Year 2 that had been amended with Si‐rich materials (silicate fertilizer, rice husk, and charred rice husk) in Year 1. After two crop cycles, plant‐available Si and plant Si concentrations remained elevated in Si‐amended paddies. Silicon‐rich amendments also decreased plant As concentrations, although this effect was only observed in the vegetative tissues. Husk treatment resulted in the lowest porewater redox, highest CH4 emissions, and highest porewater inorganic As. Porewater concentrations and dynamics of inorganic As, dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO) differed for each amendment, but Si‐rich amendments exhibited elevated inorganic and organic As early in the growing season. These Si‐rich amendments can continue to provide Si and impact rice systems two growing seasons after application.

Dietary intake and urinary excretion of methylated arsenicals of Japanese adults consuming marine foods and rice

ABSTRACT Dietary intake and urinary excretion of monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine (AsB) were measured in 150 adult Japanese subjects. Duplicate diet (DD) samples and first void of urine on the next morning of DD sampling day were collected and analysed for arsenic species with liquid chromatography-ICP mass spectrometry. Median (min-max) intakes of MMA, DMA and AsB were <2.3 (<2.3-<2.3), 4.57 (<2.3–24.3), and 13.6 (<2.4–231) μg As/day, respectively, and median urinary concentrations were 1.90 (<0.37–26.), 21.9 (<0.27–141) and 19.6 (<0.37–1063) ng As/mg creatinine, respectively. Interrelationships between intake levels and urinary concentrations were mostly significant with positive coefficients indicating mutual association due to co-exposure, metabolism and/or dietary habit. Urinary concentrations and intake levels of AsB were also positively correlated confirming the applicability of urine analysis as biomarker of exposure. The present descriptive results provide with essential piece of information in assessing health risk of methylated arsenicals for population who consume marine products and rice.

Solid-state and solution-state self-association of dimethylarsinic acid: IR, NMR and theoretical study

The structure of dimethylarsinic acid (Me2AsOOH, DMA) in crystal and in solution in aprotic medium was studied by X-ray, spectroscopic (IR, NMR and Raman) and quantum chemical calculation (DFT) methods. Two polymorphs of DMA – hydrogen-bonded cyclic dimers or infinite chains – were obtained by growing crystals from protic and aprotic solvents. By comparison of the experimental data with the results of quantum-chemical calculations performed with periodic boundary conditions we propose ways how to distinguish two polymorphs using IR marker bands. The self-association of DMA in polar aprotic solution was studied by low-temperature NMR (T = 100 K, solvent CDF3/CDF2Cl mixture). By using H/D isotope effects on 1H NMR chemical shifts (appearing after a partial deuteration of DMA in the mobile proton sites) we were able to prove that in solution DMA forms cyclic dimers with two equivalent strong hydrogen bonds (in contrast, for example, to Me2POOH acid, which forms predominantly cyclic trimers). Based on the available IR spectra, the type of complexation does not change when the aprotic solvent is varied.

Antibiotic exposure decreases soil arsenic oral bioavailability in mice by disrupting ileal microbiota and metabolic profile

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg−1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg−1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81–3.81-fold less As in kidneys, excreted 1.02–1.35-fold less As in urine, and showed lower As-RBA (25.7–29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.

Urinary arsenic species and methylation efficiency during pregnancy: Concentrations and associated factors in Spanish pregnant women

BackgroundArsenic (As) is considered to be toxic for humans, the main routes of exposure being through drinking water and the diet. Once ingested, inorganic arsenic can be methylated sequentially to monomethyl and dimethyl arsenicals. Several factors can affect both As exposure and methylation efficiency. ObjectivesTo describe the urinary concentrations of the different As species and evaluate the methylation efficiency during pregnancy, as well as their associated factors in a birth cohort of pregnant Spanish women. MethodsParticipants in this cross-sectional study were 1017 pregnant women from two areas of Spain who had taken part in the INMA (Environment and Childhood) project (2003–2008). Total As (organic and inorganic compounds) and its main metabolites (monomethylarsonic acid, [MMA], dimethylarsinic acid, [DMA], inorganic As [iAs]) and arsenobetaine [AB]) were measured in urine samples collected during the first trimester. Sociodemographic and dietary information was collected through questionnaires. Multivariate linear regression models were used to explore the association between As species concentrations and covariates. Arsenic methylation efficiency was determined through the percentages of the metabolites and using As methylation phenotypes, obtained from principal component analysis. ResultsMedian urine concentrations were 33.0, 21.6, 6.5, 0.35 and 0.33 μg/g creatinine for total As, AB, DMA, MMA and iAs, respectively. Daily consumption of rice and seafood during the first trimester of pregnancy were positively associated with the concentration of As species (i.e., β [CI95%] = 0.36 [0.09, 0.64] for rice and iAs, and 1.06 [0.68, 1.44] for seafood and AB). TAs, AB and iAs concentrations, and DMA and MMA concentrations were associated with legume and vegetable consumption, respectively. The medians of the percentage of As metabolites were 89.7 for %DMA, 5.1 for %MMA and 4.7 for %iAs. Non-smoker women and those with higher body mass index presented a higher methylation efficiency (denoted by a higher %DMA and lower %MMA). DiscussionCertain dietary, lifestyle, and environmental factors were observed to have an influence on both As species concentrations and methylation efficiency in our population. Further birth cohort studies in low exposure areas are necessary to improve knowledge about arsenic exposure, especially to inorganic forms, and its potential health impact during childhood.