iAs In Urine Research Articles

The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (ƩAs) at baseline. The proportions of urine iAs, MMA and DMA over the ƩiAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in ƩAs (12.5μg/L, overall range 0.7-194.1μg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Water Dilutes and Alcohol Concentrates Urinary Arsenic Species When Food is the Dominant Source of Exposure

Exposure to certain arsenic (As) species has been associated with increased cancer risk and a wide range of other health concerns, even at low levels. Here we used urine as a biomarker of As internal dose in a well-characterized cohort to relate diet, demographics and geography to exposure. As speciation in spot urine samples was determined for 89 participants aged ≥ 50 years from the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA), stratified to cover the country. Principal component analysis showed that all As species clustered together, suggesting that arsenobetaine, inorganic As (iAs) and the methylated species monomethylarsonic acid and dimethylarsinic acid forms have a common source. Seafood and alcohol consumption were positively correlated with As species, while dairy products (i.e. milk) and tap water were negatively correlated. Multiple regression analysis showed that diet explained approximately 30% of the variability in urinary iAs concentrations. Geography was not found to be a predictor of As exposure. Dairy consumption was negatively correlated and the best predictor of iAs in urine, explaining 15.9% of the variability. The majority of the variation in As biomarkers was not explained, suggesting the contribution of other sources and other non-predicted variables on As metabolism and elimination.

The use of structural equation modeling to estimate the effect of low-level arsenic exposure on birth weight in Chilean newborns

Introduction: Prenatal arsenic exposure and pediatric outcomes have been previously explored. Although some studies have shown an inverse association between birth weight and arsenic exposure (iAs), the relationship remains unclear. The main objective is to use structural equation modeling to estimate the effect of low-level iAs exposure on birth weight while controlling for potential mediation effects and exogenous effects. Methods: This study is a cohort of pregnant women, recruited from 5 primary health care centers in Arica, Chile during 2013. Sociodemographic information and urine samples were collected during the 2nd trimester. iAs exposure during pregnancy was estimated by determining the sum of arsenical species. Birth weight was obtained from birth records in grams (g). Structural equation models were then used to estimate total iAs effects, indirect and direct effects, on birth weight. Results: The median of total urine iAs was 14 μg/L (IQR=12.3 μg/L). The median of birth weight was 3350 g (IQR=480 g). After adjusting for risk factors, iAs was no longer associated with birth weight (β=4.373, 95%CI: -2.02, 10.77). The Chi-square test model had a p-value of 0.063 and the root mean square error of approximation (RMSEA) had a p-value of 0.062. Moreover, total effects of iAs on birth weight had a borderline association (p-value: 0.051). The indirect effects were not mediated by gestational age or gestational diabetes. In this sample, gestational age (β=213.5, 95%CI: 163.6, 263.4), gestational diabetes (β=-112.8, 95%CI:-192.2, -53.4), maternal age (β=11.9, 95%CI: 0.91, 22.9) and newborn sex (β=264.3, 95%CI: 137.1, 391.5) were associated with newborn birth weight. Conclusion: In our study, iAs exposure was not directly associated with birth weight. However, iAs total effects did show a tendency towards having an effect. Gestational age, maternal age, and newborn sex were positively associated with birth weight, which is consistent with previous literature.

Is arsenic exposure during pregnancy associated with saliva cortisol in 2 years old children from Arica, Chile? Preliminary results.

Introduction: Exposure to inorganic arsenic (iAs) during pregnancy generates lower expression of glucocorticoid receptors in hypothalamus of offspring in murine models. This association has not been studied in children exposed in utero to low concentrations of iAs. The aim is to study the association between low-level iAs exposure during pregnancy and salivary cortisol in 2-years-old children belonging to Arica, Chile. Methods: In this prospective cohort study, a sample of pregnant women was recruited from 5 public health services in Arica. Participation was voluntary and written consent was mandatory. Urine samples to assess total iAs (μg/L) and sociodemographic data were collected from 242 mothers during 2nd trimester of pregnancy. Data related to acute stressful situations and salivary samples, both in children and mothers, were collected when children were around 2-years-old to assess salivary cortisol. Descriptive statistics and multiple linear regression models were fitted to study the association between iAs and salivary cortisol, adjusting by other variables. The modifying effect of PPD variable was evaluated. Results: For these preliminary results we included the analysis of forty-one mother-child pairs. The median of total urine iAs was 14.8μg/L (IQR: 9.2μg/L). The cortisol mean was 0.98μg/dL (SD: 0.19μg/dL). iAs distribution was positively biased and cortisol distribution was symmetric. iAs exposure was transformed in quartile to perform multiple linear regression. iAs was positively associated with salivary cortisol in children whose mothers had postpartum depression (PPD) and inversely associated when the mother did not have PPD. Child’s acute sickness and circadian rhythm were associated with salivary cortisol in children whose mothers had PPD. Conclusions: Preliminary results indicate that iAs was associated with salivary cortisol. However, the addition of a biomarker for acute stressful situations is needed to confirm our preliminary results.

Contribution of inorganic arsenic sources to population exposure risk on a regional scale.

Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27% (the daily iAs intake for 27% study subjects exceeded the WHO-recommended value, 2.1μgiAsday(-1)kg(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41%, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17%, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available.

Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study.

OBJECTIVELittle is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study.RESEARCH DESIGN AND METHODSA total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications.RESULTSOver 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations.CONCLUSIONSArsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.

A pilot study: The importance of inter-individual differences in inorganic arsenic metabolism for birth weight outcome

Inorganic arsenic (iAs) exposure is detrimental to birth outcome. We lack information regarding the potential for iAs metabolism to affect fetal growth. Our pilot study evaluated postpartum Romanian women with known birth weight outcome for differences in iAs metabolism. Subjects were chronically exposed to low-to-moderate drinking water iAs. We analyzed well water, arsenic metabolites in urine, and toenail arsenic. Urine iAs and metabolites, toenail iAs, and secondary methylation efficiency increased as an effect of exposure (p<0.001). Urine iAs and metabolites showed a significant interaction effect between exposure and birth weight. Moderately exposed women with low compared to normal birth weight outcome had greater metabolite excretion (p<0.03); 67% with low compared to 10% with normal birth weight outcome presented urine iAs >9μg/L (p=0.019). Metabolic partitioning of iAs toward excretion may impair fetal growth. Prospective studies on iAs excretion before and during pregnancy may provide a biomarker for poor fetal growth risk.

DETERMINANTS OF URINARY ARSENIC CONCENTRATION IN A MEXICAN POPULATION

Background and Ams. Millions of people worldwide are exposed to inorganic arsenic (iAs), a known carcinogen, in drinking water. This study examined potential predictors of urinary arsenic concentration in two areas in central Mexico with historically high iAs levels in village water supplies. Methods. Participants were adults and children age •5 years residing in the La Laguna and Zimapán regions in Durango-Coahuila and Hidalgo states, respectively. Information on residential history and water use was obtained by questionnaire and participants provided samples of drinking water and spot urine. Concentrations of iAs in water and As species in urine, iAs, MAs and DMAs, were determined by hydride-generation atomic absorption spectrometry. Potential predictors of iAs in water and urine were examined using linear regression and linear mixed models on log-transformed concentrations. Results. The concentration of iAs in water samples was significantly associated with the source of drinking water and place of residence, including the village as well as the region. Interactions of location and water source were significant. Total arsenic (tAs) in urine was significantly associated with iAs concentration in water, source of drinking water and region of residence, as well as with sex and urinary creatinine. Higher urinary tAs concentrations were observed among those drinking municipal tap water rather than bottled water or water from springs or dug wells. Other environmental and personal factors including source of cooking water, length of residence, duration of water use, recent absence from the area, age and obesity were not associated with urinary tAs. Trivalent and pentavalent species of iAs in urine were associated with tAs in urine but not with environmental or personal factors. Conclusions. The level of tAs is strongly related to the concentration of iAs in drinking water, but sex and factors specific to location also play a role.

ASSOCIATION OF DIABETES WITH ARSENIC EXPOSURE, ARSENIC METABOLITES AND AS3MT POLYMORPHISM

Background and Aims. Exposure to inorganic arsenic (iAs) is suspected of causing diabetes mellitus and other diseases. This study examined associations of diabetes with exposure to iAs in drinking water, metabolites of iAs in urine and AS3MT polymorphism. Methods. Participants were adults and children age •5 years living in Durango-Coahuila and Hidalgo states, Mexico. Information on water used and residential and medical history was obtained by questionnaire and participants provided samples of drinking water and spot urine. Prevalent diabetes was classified by fasting blood glucose (FBG) (≥125 mg/dl), oral glucose tolerance test (OGTT) (≥200 mg/dl) and self-report of diabetes diagnosis or treatment. iAs and its metabolites in urine were analyzed by hydride generation-atomic absorption spectroscopy. Associations between diabetes and iAs and urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. Urinary creatinine was evaluated as a covariate in analyses of urinary metabolites of iAs. Results. Odds ratios (ORs) for diabetes classified by FBG and OGTT were similar. The OR increased about 1% per ppb of As in water (95% CI 1.01-1.02). Diabetes was associated with current iAs exposure, but cumulative arsenic exposure, or with total urinary arsenic concentration or total tri- or pentavalent iAs in urine. However, the OR for urinary dimethyl-AsIII was 1.07 (95% CI 1.01-1.13) per ng As/ml after adjustment for creatinine (1.05 without adjustment). Neither methyl-AsIII nor pentavalent methylated arsenicals in urine were associated with diabetes. Met287Thr polymorphism was associated with FBG •126 mg/dl (OR = 2.36) and OGTT •200 mg/dl (OR = 2.86), although neither association was statistically significant. Conclusions. This study links diabetes with exposure to iAs and is the first to suggest that the dimethyl-MAsIII may be a marker of risk of developing diabetes.