Association between urinary arsenic species and vitamin D deficiency: a cross-sectional study in Chinese pregnant women.

Background: An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women. Objectives: This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence. Methods: We measured urinary arsenite (As3+), arsenate (As5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D2, 25(OH)D3, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD. Results: Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As3+, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As3+ was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As3+, MMA and VDD. However, negative correlations were found between As5+, DMA and VDD. Conclusion: According to our study, there were positive correlations between iAs, especially As3+, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.

Associations of arsenic exposure and arsenic metabolism with the risk of non-alcoholic fatty liver disease.

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 µg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 µg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

Gut Microbiota Control the Bioavailability and Metabolism of Organoarsenicals of Seaweeds in Mice after Oral Ingestion.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Biomonitoring California Protocol for Following up on Elevated Levels of Urinary Arsenic.

OBJECTIVES: to develop and implement a follow-up protocol for Biomonitoring California study participants with elevated levels of urinary arsenic, particularly inorganic forms. METHODS: We selected 20 µg/L as the level of concern for urinary inorganic arsenic; samples with total arsenic ≥20 µg/L were speciated. Participants with elevated inorganic arsenic were notified of their level and invited to participate in a telephone survey to help determine possible exposure sources. We illustrate the protocol in four Biomonitoring California studies, which collected samples from 2010-2013 in locations across the state. RESULTS: 48 participants in the four studies had elevated urinary inorganic arsenic levels. Consumption of rice and rice-based products was the most commonly identified potential source of inorganic arsenic exposure. CONCLUSIONS: Of 48 participants with elevated inorganic arsenic, 27 would have been missed if we had used the previously published threshold of 50 µg/L total arsenic to identify urine samples for speciation. This protocol fills a gap in the clinical literature by providing a more health-protective approach to identify individuals with elevated urinary inorganic arsenic and help determine potentially significant exposure sources.

Prenatal arsenic exposure, arsenic metabolism and neurocognitive development of 2-year-old children in low-arsenic areas.

BACKGROUND: There is limited evidence on the effects of arsenic species and metabolic capacity on child neurodevelopment, particularly at low levels. Further, little is known about the critical window of exposure. OBJECTIVE: To estimate the associations of arsenic exposure and arsenic metabolism in different pregnancy periods with neurodevelopment of two-year-old children. METHODS: Concentrations of arsenobetaine (AsB), arsenite, arsenate, monomethyl arsenic acid (MMA), and dimethyl arsenic acid (DMA) in urine samples collected in three trimesters from 1006 mothers were measured using HPLC - ICPMS. Inorganic arsenic (iAs) was calculated as the sum of arsenite and arsenate. Total arsenic (tAs) was calculated as the sum of iAs, MMA and DMA. Child neurodevelopment was assessed with the Bayley Scales of Infant Development. RESULTS: The geometric mean (GM) of SG-adjusted tAs in the first, second, third trimester was 16.37, 12.94, 13.04 µg/L, respectively. The mental development index (MDI) score was inversely associated with iAs and tAs. Compared to the 1st quartile, the MDI score decreased 0.43 (95%CI: -4.22, 3.36) for the 2nd, 6.50 (95%CI: -11.73, -1.27) for the 3rd, 5.42 (95%CI: -10.74, -0.10) for the 4th quartiles of iAs, and decreased 4.03 (95%CI: -7.90, -0.15) in the 4th quartile of tAs. In trimester-specific models, negative associations of DMA [-1.94 (95%CI: -3.18, -0.71)] and tAs [-1.61 (95%CI: -3.02, -0.20)] with the psychomotor development index (PDI) were only observed in 1st trimester. CONCLUSIONS: Our study found inverse associations between prenatal arsenic exposure, especially in early pregnancy, and neurodevelopment of children at two years old, even at low exposure levels.

Human urinary arsenic species, associated exposure determinants and potential health risks assessed in the HBM4EU Aligned Studies.

The European Joint Programme HBM4EU coordinated and advanced human biomonitoring (HBM) in Europe in order to provide science-based evidence for chemical policy development and improve chemical management. Arsenic (As) was selected as a priority substance under the HBM4EU initiative for which open, policy relevant questions like the status of exposure had to be answered. Internal exposure to inorganic arsenic (iAs), measured as Toxic Relevant Arsenic (TRA) (the sum of As(III), As(V), MMA, DMA) in urine samples of teenagers differed among the sampling sites (BEA (Spain) > Riksmaten adolescents (Sweden), ESTEBAN (France) > FLEHS IV (Belgium), SLO CRP (Slovenia)) with geometric means between 3.84 and 8.47 µg/L. The ratio TRA to TRA + arsenobetaine or the ratio TRA to total arsenic varied between 0.22 and 0.49. Main exposure determinants for TRA were the consumption of rice and seafood. When all studies were combined, Pearson correlation analysis showed significant associations between all considered As species. Higher concentrations of DMA, quantitatively a major constituent of TRA, were found with increasing arsenobetaine concentrations, a marker for organic As intake, e.g. through seafood, indicating that other sources of DMA than metabolism of inorganic As exist, e.g. direct intake of DMA or via the intake of arsenosugars or -lipids. Given the lower toxicity of DMA(V) versus iAs, estimating the amount of DMA not originating from iAs, or normalizing TRA for arsenobetaine intake could be useful for estimating iAs exposure and risk. Comparing urinary TRA concentrations with formerly derived biomonitoring equivalent (BE) for non-carcinogenic effects (6.4 µg/L) clearly shows that all 95th percentile exposure values in the different studies exceeded this BE. This together with the fact that cancer risk may not be excluded even at lower iAs levels, suggests a possible health concern for the general population of Europe.

Environment-Wide Association Study of CKD.

BACKGROUND AND OBJECTIVES: Exposure to environmental chemicals has been recognized as one of the possible contributors to CKD. We aimed to identify environmental chemicals that are associated with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed the data obtained from a total of 46,748 adults who participated in the National Health and Nutrition Examination Survey (1999-2016). Associations of chemicals measured in urine or blood (n=262) with albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g), reduced eGFR (<60 ml/min per 1.73 m2), and a composite of albuminuria or reduced eGFR were tested and validated using the environment-wide association study approach. RESULTS: Among 262 environmental chemicals, seven (3%) chemicals showed significant associations with increased risk of albuminuria, reduced eGFR, or the composite outcome. These chemicals included metals and other chemicals that have not previously been associated with CKD. Serum and urine cotinines, blood 2,5-dimethylfuran (a volatile organic compound), and blood cadmium were associated with albuminuria. Blood lead and cadmium were associated with reduced eGFR. Blood cadmium and lead and three volatile compounds (blood 2,5-dimethylfuran, blood furan, and urinary phenylglyoxylic acid) were associated with the composite outcome. A total of 23 chemicals, including serum perfluorooctanoic acid, seven urinary metals, three urinary arsenics, urinary nitrate and thiocyanate, three urinary polycyclic aromatic hydrocarbons, and seven volatile organic compounds, were associated with lower risks of one or more manifestations of CKD. CONCLUSIONS: A number of chemicals were identified as potential risk factors for CKD among the general population.

Association of dietary intake and urinary excretion of inorganic arsenic in the Japanese subjects.

Quantitative relationship between intake of inorganic arsenic (iAs) and urinary excretion of iAs and its metabolite, methylarsonic acid (MMA), was investigated for 150 adult Japanese subjects. Duplicate diet was used for the determination of intake and first void of urine on the next day of duplicate diet sampling was used for urinary iAs + MMA determination. Speciation analysis of arsenic in diet and urine was carried out with liquid chromatography-inductively coupled plasma mass spectrometry. Geometric mean iAs intake of the subjects was 0.349 µg/kg/day and that of urinary iAs + MMA concentration was 5.20 ng As/mL (specific gravity (SG) corrected) or 4.05 ng As/mg creatinine (Cre). There was a significant positive correlation between iAs intake and urinary iAs + MMA concentration: the correlation coefficient between intake and Cre-corrected urinary concentration (r = 0.544) was greater than that between intake and SG-corrected concentration (r = 0.458). The regression equation of intake-excretion was: log10[dailyintake]=0.451×log10[creatininecorrectedurinaryiAs+MMA]+0.814. This equation has a practical value for converting urinary As levels, measured as a biomarker of exposure in epidemiologic study, to dietary intake levels in the future risk assessment.

As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater.

The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (µg/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697, GSTP1-rs1695, As3MT-rs3740400, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 µg/L and the median of LADD for the high exposure dose was 0.33 µg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variants As3MT*GSTM1 and GSTO2*GSTP1 could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.

Arsenic exposure in northern Mexican women.

OBJECTIVE: To describe interindividual metabolism variations and sociodemographic characteristics associated to urinary arsenic, and to estimate the arsenic contamination in water from urinary total arsenic (TAs). MATERIALS AND METHODS: Women (n=1 028) from northern Mexico were interviewed about their sociodemographic characteristics and their urinary concentrations of arsenic species were measured by liquid chromatography. Inorganic arsenic (iAs) in water was estimated from urinary TAs. RESULTS: Women were 20-88 years old. TAs in urine ranged from p10=3.41 to p90=56.93 µg/L; 74% of women had levels >6.4 µg/L. iAs in water varied from p10=3.04 to p90=202.12 µg/L; 65% of women had concentrations >10 µg/L, and 41%, concentrations >25 µg/L. Large variations in iAs metabolism were observed. TAs was significantly negatively associated with age and schooling, and positively with the state of residence. CONCLUSIONS: Exposure to iAs is an environmental problem in Mexico. Individual variations in metabolism are a challenge to design prevention and control programs.

OBJETIVO: Describir las variaciones interindividuales del metabolismo y las características sociodemográficas asociadas con el arsénico urinario, así como estimar su contaminación en el agua. MATERIAL Y MÉTODOS: Se entrevistó a 1 028 mujeres del norte de México; por cromatografía de líquidos se midieron los metabolitos urinarios de arsénico y, a partir de ellos, se estimó la concentración en agua. RESULTADOS: Las mujeres tuvieron 20-88 años. El arsénico urinario varió de p10=3.41 a p90=56.93 µg/L; 74% de las mujeres tuvieron niveles >6.4 µg/L. El arsénico en agua varió de p10=3.04 a p90=202.12 µg/L; 65% de las mujeres tenían concentraciones >10 µg/L, y 41%, >25 µg/L. Se observaron amplias variaciones en el metabolismo del arsénico. El arsénico urinario se asoció negativamente con la edad y escolaridad, y positivamente con el estado de residencia. CONCLUSIONES: La exposición a arsénico es un problema ambiental en México. Las variaciones individuales en su metabolismo son un desafío para diseñar programas de prevención y control.

Arsenic exposure in northern Mexican women / Exposición a arsénico en mujeres del norte de México

Abstract: Objective: To describe interindividual metabolism variations and sociodemographic characteristics associated to urinary arsenic, and to estimate the arsenic contamination in water from urinary total arsenic (TAs). Materials and methods: Women (n=1 028) from northern Mexico were interviewed about their sociodemographic characteristics and their urinary concentrations of arsenic species were measured by liquid chromatography. Inorganic arsenic (iAs) in water was estimated from urinary TAs. Results: Women were 20-88 years old. TAs in urine ranged from p10=3.41 to p90=56.93 μg/L; 74% of women had levels >6.4 μg/L. iAs in water varied from p10=3.04 to p90=202.12 μg/L; 65% of women had concentrations >10 μg/L, and 41%, concentrations >25 μg/L. Large variations in iAs metabolism were observed. TAs was significantly negatively associated with age and schooling, and positively with the state of residence. Conclusion: Exposure to iAs is an environmental problem in Mexico. Individual variations in metabolism are a challenge to design prevention and control programs.

Resumen: Objetivo: Describir las variaciones interindividuales del metabolismo y las características sociodemográficas asociadas con el arsénico urinario, así como estimar su contaminación en el agua. Material y métodos. Se entrevistó a 1 028 mujeres del norte de México; por cromatografía de líquidos se midieron los metabolitos urinarios de arsénico y, a partir de ellos, se estimó la concentración en agua. Resultados: Las mujeres tuvieron 20-88 años. El arsénico urinario varió de p10=3.41 a p90=56.93 μg/L; 74% de las mujeres tuvieron niveles >6.4 μg/L. El arsénico en agua varió de p10=3.04 a p90=202.12 μg/L; 65% de las mujeres tenían concentraciones >10 μg/L, y 41%, >25 μg/L. Se observaron amplias variaciones en el metabolismo del arsénico. El arsénico urinario se asoció negativamente con la edad y escolaridad, y positivamente con el estado de residencia. Conclusión: La exposición a arsénico es un problema ambiental en México. Las variaciones individuales en su metabolismo son un desafío para diseñar programas de prevención y control.

Changes in urinary arsenic species and methylation capacity in original arsenic exposure cohort after water quality improvement.

Water quality improvement is the most efficient way to prevent arsenic exposure. After the cessation of arsenic ingestion, arsenic methylation capacity of the exposed population can change significantly. The factors associated with these changes remain poorly understood. Therefore, arsenic methylation capacity in a study cohort was estimated before and after water quality improvement in the present study. Results indicated that urinary content of the arsenic species in the study cohort significantly decreased after water quality improvement. In addition, the proportions of inorganic arsenic (%iAs) and monomethyl arsenic acid (%MMA) were significantly decreased, while proportions of dimethyl arsenic (%DMA) increased. The primary methylation index (PMI) and secondary methylation index (SMI) increased from 0.85 to 0.92 and 0.82 to 0.84, respectively. Arsenic species urinary content and arsenic methylation index varied slightly between the study cohort after water quality improvement and the control cohort. The rate of increase in PMI was higher than that in SMI. The study group aged 31-50 years had the highest increase in PMI. Logistic regression revealed that %DMA before water quality improvement was negatively associated with the increase in PMI, while %iAs were positively related, and %MMA were positively associated with the increase in SMI. It is concluded that urinary arsenic species content and arsenic methylation capacity increased to the levels of the control cohort after water quality improvement. An increase in primary arsenic methylation capacity may be a burden on the secondary arsenic methylation capacity. The main role of arsenic methylation capacity recovery may be the cessation of arsenic exposure.

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

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

Assessment of YAP gene polymorphisms and arsenic interaction in Mexican women with breast cancer.

The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.

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

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

Speciation analysis of arsenic in samples containing high concentrations of chloride by LC-HG-AFS.

Chloride widely exists in the environment and will cause serious interference for arsenic speciation analysis. The determination of four arsenic species including arsenite (As(III)), arsenate (As(V)), monomethylarsenate (MMA), and dimethylarsonate (DMA) in samples containing high concentrations of Cl- was carried out in this work by coupling of liquid chromatography (LC) with hydride generation atomic fluorescence spectrometry (HG-AFS). The interference of Cl- was successfully eliminated by coupling two anion-exchange chromatographic columns in series and eluting with 35.0 mmol L-1 (NH4)2HPO4 (pH = 6.00). A novel pre-treatment system was subsequently developed to realize on-line column switch and pre-reduction of As(V). The analysis time was shortened by an isocratic elution but programmed flow rate method, and the sensitivity of As(V) was also enhanced by the introduction of pre-reduction using the developed system. The proposed method can resist at least 10 g L-1 Cl- without any pre-treatment operations. Since LC-HG-AFS is low-cost and can be afforded or self-assembled by most labs, the developed method can be adopted as a routine analysis method for arsenic species in chloride-bearing samples, such as urine and seawater. Graphical abstract.

Association of plasma folate, vitamin B12 levels, and arsenic methylation capacity with developmental delay in preschool children in Taiwan.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

Availability of arsenic in rice grains by in vitro and in vivo (humans) assays.

BACKGROUND: Rice grains are consumed by approximately half of the world's population. This cereal has higher arsenic (As) concentrations in grains than wheat or barley. Arsenic determination in food and/or in vitro studies are important for risk assessment; however, it is not enough to assess the real human exposure. METHOD: In vitro bioaccessibility was carried out in husked-rice using gastric and intestinal solutions similar to humans. Also, As naturally found in husked-rice was evaluated by in vivo bioavailability in humans. For this purpose, diets from the 1st and 2nd days were free of foods known to be high in As; 3rd and 4th days the diets were composed by rice and water and; 5th and 6th the diet was similar the 1st and 2nd days. During all experimentation, a representative aliquot of each meal, blood and urine were collected for total As (t-As) determination. Arsenic species were determined in the urine. RESULTS: t-As in husked rice varied from 157.3 ±â€¯30.6 to 240.2 ±â€¯85.2 µg kg-1. The in vitrobioaccessible fractions ranged from 91 to 94%. Inorganic As (i-As) ranged from 99.7 ±â€¯11.2 to 159.5 ±â€¯29.4 µg kg-1. For the in vivo assay, t-As concentrations in the woman and man blood were about 3 µg mL-1 from the 1st to 6th day. Arsenic from the rice ingested was excreted by urine about 72 h after ingestion. The t-As and dimethyl As (DMA) in urine ranged from 3.59 to 47.17 and 1.02 to 2.55 µg g-1 creatinine for the volunteers, indicating a two-fold DMA-increase in urine after ingestion of husked-rice. CONCLUSION: After rice ingestion, As was quickly metabolized. The higher As concentrations were found in urine 72 h after rice ingestion. The main As-specie found in urine was DMA, indicating that methylation of As from rice followed by urine excretion is the main biological pathway for As excretion.

A urinary metabolomics study of a Polish subpopulation environmentally exposed to arsenic.

BACKGROUND: Almost every organ in the human body can be affected by arsenic (As) exposure associated with various industrial processes, as well as with contaminated food, drinking water and polluted air. Much is known about high exposure to inorganic As but there is little data on the metabolic changes connected to a low exposure e.g. in people living in smelter areas. OBJECTIVES: The objectives of the study were: (1) characterise urinary concentration of total arsenic (AsT) in Polish inhabitants of the vicinity of a copper smelter area, (2) speciation analysis of various forms of arsenic in girls (GL), boys (BL), women (WL) and men (ML) with a slightly elevated AsT concentration and age/sex matched groups with a substantially higher AsT concentration, (GH, BH, WH and MH - respectively), (3) comparison of metabolomics profiles of urine between the age/sex matched people with low and high AsT concentrations. METHODS: Urine samples were analysed for total arsenic and its chemical forms (AsIII; AsV, methylarsonic acid, dimethylarsinic acid, arsenobetaine) using HPLC-ICP-MS. Untargeted metabolomics analysis of the urine samples was performed using UPLC system connected to Q-TOF-MS equipped with an electrospray source. The XCMS Online program was applied for feature detection, retention time correction, alignment, statistics, annotation and identification. Potentially identified compounds were fragmented and resulting spectra were compared to the spectra in the Human Metabolome Database. RESULTS: Urine concentration of AsT was, as follows: GL 16.40 ± 0.83; GH 115.23 ± 50.52; BL 16.48 ± 0.83; BH 95.00 ± 50.03; WL 16.93 ± 1.21; WH 170.13 ± 96.47; ML 16.91 ± 1.20; MH 151.71 ± 84.31 µg/l and percentage of arsenobetaine in AsT was, as follows: GL 65.5 ± 13.8%, GH 87.2 ± 4.7%, BL 59.8 ± 12.5%, BH 90.5 ± 2.4%, WL 50.8 ± 14.1%, WH 90.4 ± 3.5%, ML 53.3 ± 10.0%, MH 74.6 ± 20.2%. In the people with low and high AsT concentrations there were significant differences in the intensity of signal (is.) from numerous compounds being metabolites of neurotransmitters, nicotine and hormones transformation (serotonin in the girls and women; catecholamines in the girls, boys and women; mineralocorticoids and glucocorticoids in the boys, androgens in the women and men and nicotine in the boys, women and men). These changes might have been associated with higher is. from metabolites of leucine, tryptophan, purine degradation (in the GH, WH), urea cycle (in the WH and MH), glycolysis (in the WH) and with lower is. from metabolites of tricarboxylic acid cycle (in the BH) in comparison with low AsT matched groups. In the MH vs. ML higher is. from metabolite of lipid peroxidation (4-hydroxy-2-nonenal) was observed. Additionally, the presence of significant differences was reported in is. from food components metabolites, which might have modulated the negative effects of As (vitamin C in the girls, boys and men, vitamin B6 in the girls, boys and women as well as phenolic compounds in the boys and girls). We hypothesize that the observed higher is. from metabolites of sulphate (in MH) and glucoronate degradation (in BH, WH and MH) than in the matched low AsT groups may be related to the impaired glucuronidation and sulfonation and higher is. from catecholamines, nicotine and hormones. CONCLUSION: Our results indicated that even a low exposure to As is associated with metabolic changes and that urine metabolomics studies could be a good tool to reflect their wide spectrum connected to specific environmental exposure to As, e.g. in smelter areas.