Urinary Arsenic Concentrations Research Articles

The effect of toxic metals in drinking water on the human microbiome

S15: Interaction between environmental chemicals and toxicants and the human microbiome, Room 217, Floor 2, August 28, 2019, 10:30 AM - 12:00 PM In utero and early life exposure to inorganic arsenic occurs primarily through drinking water and food and is associated with altered immune response, including infant’s risk of infections. In animal studies, and in our own cohort study of infants, greater exposure to arsenic during infancy associated with differences in the gut microbiome composition and the relative abundance of individual microbial taxa. However, the functional significance of these changes is not well understood but is critical for determining the direct impacts of microbial gene products on host immunity and metabolism. Therefore, in addition to taxonomic profiling and metagenomic analyses, we analyzed infant stool samples using 1H NMR on a Bruker Avance III 700 MHz NMR Spectrometer and concentration-fit 36 known microbial metabolites using Chenomix. We examined the relation between these metabolites and both in utero and 6-week log 2 urinary arsenic concentrations in linear regression models, adjusted for infant sex, age, type of delivery (vaginal vs. C-section), feeding mode (breast milk vs. any formula) and specific gravity. In our preliminary analyses, higher 6-week urinary arsenic concentrations were associated with increases in butyrate, propionate, asparagine, malonate, leucine, cholate, and tryptophan (p<0.05). Metabolomic analyses of infant stool samples provide further support to our initial findings that suggests that the infant gut microbiome is sensitive to arsenic exposure and may influence early immune system development.

Assessment of Heavy Metal Exposure to Residents around Abandoned Metal Mines

TPS 621: Exposure to metals, Johan Friso Foyer, Floor 1, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim: Abandoned metal mines are areas of great concern for the health effects of residents due to hazardous substances such as heavy metals. The purpose of this study was to compare the exposure of heavy metals to residents of the abandoned metal mines and general population through National Health Survey. Methods: We examined 4,499 residents of the abandoned mines of 2nd phase health effects survey of abandoned metal mines (AMS, ‘13~’17). We used data from the Korea national health and nutrition examination survey (KNHANES, ‘12, ‘13, ‘16) and the Korean national environmental health survey (KNEHS ‘09~’15). Based on the gender and age distribution of AMS, KNHANES (n=980) and KNEHS (n=1,412) were randomly sampled for the same distribution. The geometric mean concentrations (95% confidence interval) of blood lead, blood cadmium, urinary cadmium, and urinary arsenic concentration were presented, the excess proportion was given by reference to the 95th percentile concentration of the general population. Results: The geometric mean concentration of lead in blood was significantly higher in AMS than those of the general population (AMS: 2.27(2.24-2.30)a μg/dL; KNHANES: 2.11(2.06-2.17)b μg/dL; KNEHS: 2.23(2.18-2.29)b μg/dL; p<0.001). The geometric mean concentration of blood cadmium in AMS was also higher than those of the general population (AMS: 1.42(1.40-1.44) μg/L; KNHANES: 1.24(1.20-1.28) μg/L; p<0.001), and cadmium in urine was remarkably different and statistically significant (AMS: 1.47(1.42-1.53) μg/L; KNEHS: 0.47(0.45-0.49) μg/L; p<0.001). Conclusions: The concentration of heavy metals in residents of the abandoned metal mines was higher than those of the general population. We considered the routes of exposure of crops ingestion, groundwater intake, soil contact, and inhalation of scattered dust in contaminated environment. Therefore, continuous individual and national management are needed to evaluate the health risks of residents in the abandoned metal mine areas.

Urinary Metals and Metal Mixtures in Midlife Women

TPS 621: Exposure to metals, Johan Friso Foyer, Floor 1, August 26, 2019, 3:00 PM - 4:30 PM Background: Little is known about the extent of exposure to multiple metals among midlife women. Objectives: We assessed exposure to multiple metals in the Study of Women’s Health Across the Nation (SWAN), a multi-site, multi-ethnic cohort of women at midlife. Methods: We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) using high-resolution inductively coupled plasma-mass spectrometry among 1,335 white, black, Chinese and Japanese women aged 45-56 years at the third SWAN annual visit (1999-2000). Least squared geometric mean concentrations were compared across race/ethnicity, education, financial hardship, smoking, secondhand smoking, sea food intake and rice intake groups. Overall exposure patterns of multiple metals were derived using k-means clustering method. Results: The percentage of women with detectable concentrations of metals ranged from 100% for arsenic, cesium, molybdenum and zinc, to less than 5% for platinum; 15 metals had detection rates of 70% or more. Asian populations, including both Chinese and Japanese women, had higher urinary concentrations of arsenic, cadmium, copper, mercury, molybdenum, lead, thallium, compared with other racial/ethnic groups, independent of sociodemographic, lifestyle, dietary, and geographic characteristics. Seafood and rice intakes were important contributors to arsenic, cesium, mercury, molybdenum and lead uptake. Two distinct overall exposure patterns- “high” vs. “low” -- were identified. Women in the “high” overall exposure pattern were more likely to be Asians, current smokers, and those with high consumption of seafood and rice, while they were less likely to be black. Conclusions: Exposures of midlife women to metals differs by racial/ethnic, sociodemographic, lifestyle, dietary, and geographic characteristics. Asian women may be experiencing the highest exposures to multiple metals compared with other racial/ethnic groups in the United States.

In utero and peripubertal metals exposure in relation to reproductive hormones and sexual maturation and progression among girls in Mexico City

There is increasing evidence that several metals are endocrine disrupting chemicals (EDCs). In utero development and adolescence are critical windows of susceptibility to EDC exposure. With the exception of a few heavy metals, few human studies have evaluated the impact of metal exposure on pubertal development. Our aim was to investigate measures of in utero and peripubertal metal exposure in relation to reproductive hormone levels and sexual maturation and progression among girls from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohorts. We measured urinary concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), nickel (Ni), antimony (Sb), selenium (Se), and zinc (Zn) in samples collected from women during their third trimester of pregnancy and from their female children at 8–13 years (n = 132). We measured serum testosterone, estradiol, dehydroepiandrosterone sulfate (DHEA-S), inhibin B, and sex hormone-binding globulin (SHBG) at age 8–13, and assessed Tanner stages for sexual maturation (breast, pubic hair development, and menarche status), at two time points (8–13, 14–18 years). We used linear regression to independently examine in utero and peripubertal metal concentrations as predictors of peripubertal hormones. In a longitudinal analysis using generalized estimation equations, we evaluated Tanner stage and menarche progression in relation to individual in utero and peripubertal metal concentrations. We found that higher in utero Zn was associated with increased inhibin B. Several metals at 8–13 years were associated with higher DHEA-S and estradiol, while Ni was positively but Cu was negatively associated with testosterone. In utero Ni, Al, and Cd were associated with slower progression of breast development after adjustment for child age and BMI z-score. For example, an IQR increase in in utero Al exposure was associated with 0.82 times lower odds of progressing to a higher Tanner stage for breast development per year (95% CI: 0.68, 0.99). Peripubertal concentrations of Ba and Al were also associated with being at a higher pubic hair Tanner stage and menarche at 8–13, but lower odds of progressing to the next stage at 14–18 years. We used Bayesian kernel machine regression (BKMR) to model the joint effect of multiple metals while accounting for correlated exposures, as well as potential non-linear relationships between metals and outcomes of interest, which yielded results similar to individual analyses. These findings suggest that female reproductive development may be vulnerable to the effects of metal exposure, and using both Tanner stages and hormone levels may provide clues about underlying mechanisms in two sensitive periods of development.

Dietary determinants of inorganic arsenic exposure in the Strong Heart Family Study

BackgroundChronic exposure to inorganic arsenic (iAs) in the US occurs mainly through drinking water and diet. Although American Indian (AI) populations have elevated urinary arsenic concentrations compared to the general US population, dietary sources of arsenic exposure in AI populations are not well characterized. MethodsWe evaluated food frequency questionnaires to determine the major dietary sources of urinary arsenic concentrations (measured as the sum of arsenite, arsenate, monomethylarsonate, and dimethylarsinate, ΣAs) for 1727 AI participants in the Strong Heart Family Study (SHFS). We compared geometric mean ratios (GMRs) of urinary ΣAs for an interquartile range (IQR) increase in reported food group consumption. Exploratory analyses were stratified by gender and study center. ResultsIn fully adjusted generalized estimating equation models, the percent increase (95% confidence interval) of urinary ΣAs per increase in reported food consumption corresponding to the IQR was 13% (5%, 21%) for organ meat, 8% (4%, 13%) for rice, 7% (2%, 13%) for processed meat, and 4% (1%, 7%) for non-alcoholic drinks. In analyses stratified by study center, the association with organ meat was only observed in North/South Dakota. Consumption of red meat [percent increase −7% (−11%, −3%)] and fries and chips [-6% (−10%, −2%)] was inversely associated with urinary ΣAs. ConclusionsOrgan meat, processed meat, rice, and non-alcoholic drinks contribute to ΣAs exposure in the SHFS population. Organ meat is a unique source of ΣAs exposure for North and South Dakota participants and may reflect local food consumption. Further studies should comprehensively evaluate drinking water arsenic in SHFS communities and determine the relative contribution of diet and drinking water to total arsenic exposure.

Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model.

Arsenic is one of the naturally occurring heavy metal that has been reported to cause damaging effects on different body organs. This study was aimed to determine the arsenic level in different water sources and investigate the effect of arsenic exposure on risk factors of diabetes mellitus (DM) in human participants and experimental animals. We recruited 150 participants to investigate the arsenic exposure in their urine and from drinking water. We found that males contained significantly higher (P < 0.001) concentrations of urinary arsenic as compared with that of their female counterparts. Similarly, urinary arsenic concentration was high and showed significant association in the age of ≥ 60 years (P < 0.05), illiterate (P < 0.001), smokers (P < 0.0001), and diabetic (P < 0.0001) participants. Moreover, urinary arsenic exposure was also associated with higher levels of fasting (P < 0.001) and random blood glucose (P < 0.001), HbA1c (P < 0.001), AST, ALT, MDA, IL-6, CRP, blood urea nitrogen, and creatinine in arsenic-exposed diabetics as compared with that of unexposed diabetics. Further, we also exposed the white albino rats with arsenic in drinking water for 30 days and their blood glucose was measured at 15th and 30th days of treatment that was significantly higher (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. Similarly, arsenic-exposed animals failed to tolerate exogenously administered glucose (P < 0.001) as compared with that of unexposed animals. Likewise, insulin and glutathione concentrations were also significantly decreased (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. The alterations in normal values of glucose, insulin, and glutathione exhibited the damaging effects of arsenic exposure in experimental rats. This study showed that arsenic exposed to human beings and animals through drinking water resulted in the disruption of pancreatic β-cell functioning that provoked the risk factor for development of DM. This study also suggested that long-term arsenic exposure induces hyperglycemia, inflammation, and oxidative stress that may lead to the onset of development of DM.

A Study of urinary total arsenic concentration and its effect on health in industrial areas

A Study of urinary total arsenic concentration and its effect on health in industrial areas

Urinary metal/metalloid levels in relation to hypertension among occupationally exposed workers

Occupational exposure to metals can have an adverse effect on the cardiovascular system. However, epidemiological studies of the associations of metals expose with hypertension among occupationally exposed workers were limited. The aim of this study was to investigate the potential association between urinary metal levels and the risk of hypertension among molybdenum miners and iron and steel foundry workers. The cross-sectional study had 395 participants. Urinary metal levels were determined by inductively coupled plasma mass spectrometry. Log-binomial regression model and two-piece-wise regression model were applied to assess the dose-response relationship between metal exposure and hypertension. We observed that increased prevalence ratios for hypertension among the quartile of urinary concentrations of molybdenum, arsenic and lead were positive (all P for trend <0.05). Compared with the lowest quartiles, participants in the highest quartiles of molybdenum, arsenic and lead had a 2.58-fold, 4.30-fold and 4.85-fold increased probability of having hypertension, respectively. In the threshold effect analyses, we found the relationship was nonlinear between urinary molybdenum, cobalt, cadmium, arsenic and lead concentrations and the prevalence of hypertension. In addition, Pb, Mo, As and Co may have joint effect, and a strong positive correlation with the prevalence of hypertension. Conversely, the association between the joint effect of Cd, Pb and Mo versus the prevalence of hypertension is not significant. We provide reference levels of molybdenum, cobalt, cadmium, arsenic and lead that can be used to assess the effects of occupational metal exposure on hypertension.

Association of prenatal exposure to arsenic with newborn telomere length: Results from a birth cohort study

ObjectivesThe telomere length at birth has important implications for telomere dynamics over the lifespan; however, few studies have explored the relationship between prenatal arsenic exposure and newborn telomere length (TL). We investigated whether newborn TL is related to prenatal arsenic exposure. MethodsWe used data from a birth cohort study of 762 mother-newborn pairs conducted between November 2013 and March 2015 in Wuhan, China. We measured relative cord blood TL using quantitative real-time polymerase chain reaction. Arsenic concentrations were measured in spot urine samples collected during three trimesters using inductively coupled plasma mass spectrometry. We applied multiple informant models to explore the relationships between prenatal urinary arsenic concentrations and cord blood TL. ResultsThe geometric means of urinary arsenic concentrations were 21.7 μg/g creatinine, 27.3 μg/g creatinine, and 27.1 μg/g creatinine in the first, second, and third trimesters, respectively. After adjustment for potential confounders, a doubling of maternal urinary arsenic concentration during the third trimester was related to a 5.75% (95% CI: 1.70%, 9.95%) increase in cord blood TL, particularly in female infants. Similarly, mothers in the highest quartile of urinary arsenic during the third trimester had an 11.45% (95% CI: 1.91%, 21.88%) longer cord blood TL than those in the lowest quartile. However, no significant association was found between maternal urinary arsenic concentration and cord blood TL during the first and second trimesters. ConclusionOur findings suggested that maternal arsenic exposure during the third trimester was positively associated with newborn TL. The elongation of newborn telomeres due to prenatal arsenic exposure may offer new insights into the mechanisms underlying arsenic-related disorders.

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.

Urinary metals and metal mixtures in midlife women: The Study of Women's Health Across the Nation (SWAN).

Little is known about the extent of exposure to metals and metal mixtures among midlife women. We assessed exposure to multiple metals in the Study of Women's Health Across the Nation (SWAN), a multi-site, multi-racial/ethnic cohort of women at midlife. We measured urinary concentrations of 21 metals (arsenic, barium, beryllium, cadmium, cobalt, chromium, cesium, copper, mercury, manganese, molybdenum, nickel, lead, platinum, antimony, tin, thallium, uranium, vanadium, tungsten and zinc) using high-resolution inductively coupled plasma-mass spectrometry among 1335 white, black, Chinese and Japanese women aged 45-56 years at the third SWAN annual visit (1999-2000). Least squared geometric mean concentrations were compared across race/ethnicity, education, financial hardship, smoking, secondhand smoking, seafood intake and rice intake groups. Overall exposure patterns of multiple metals were derived using k-means clustering method. The percentage of women with detectable concentrations of metals ranged from 100% for arsenic, cesium, molybdenum and zinc, to less than 5% for platinum; 15 metals had detection rates of 70% or more. Asian women, both Chinese and Japanese, had higher urinary concentrations of arsenic, cadmium, copper, mercury, molybdenum, lead and thallium, compared with other race/ethnic groups, independent of sociodemographic, lifestyle, dietary, and geographic characteristics. Seafood and rice intake were important determinants of urinary arsenic, cesium, mercury, molybdenum and lead levels. Two distinct overall exposure patterns- "high" vs. "low" -- were identified. Women in the "high" overall exposure pattern were more likely to be Asians, current smokers, and to report high consumption of seafood and rice. Black women were less likely to have the high exposure pattern. Metal exposure of midlife women differs by racial/ethnic, sociodemographic, lifestyle, dietary, and geographic characteristics. Asian women may be experiencing the highest exposures to multiple metals compared with other racial/ethnic groups in the United States.

Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population.

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.

Exposure assessment for the abandoned metal mine area contaminated by arsenic

Among the results of community health impact assessments completed in 2014, residents of the Indae abandoned metal mine area showed high average urinary concentrations of harmful arsenic (As), at 148.9 µg/L. The concentration of harmful As was derived as the sum of As(V), As(III), MMA, and DMA concentrations known to be toxic. In this area, mining hazard prevention work was not carried out and the pollution source was neglected, and the health effect of the residents due to arsenic exposure was concerned. We re-assessed As exposure levels and tried to identify exposure factors for residents of this area. Analysis of the soil, sediment, and river water to assess the association between the soil of the Indae abandoned metal mine area and the soil in residential areas confirmed a correlation between Pb and As concentrations in the soil. Since Pb and As behave similarly, the use of the stable Pb isotope ratio for assessment of the pollution source tracking was validated. In the 3-isotope plot (207/206Pb vs. 208/206Pb) of soil samples in this area, a stable Pb isotope ratio was located on the same trend line, which confirmed that the soil in the residential area was within the area of influence of the Indae abandoned metal mine. Therefore, we judged that the pollution source of As was the Indae abandoned metal mine. The results by As species were As (III) 1.45 μg/L, As (V) 0.74 μg/L, monomethylarsonic acid (MMA) 2.43 μg/L, dimethylarsinic acid (DMA) 27.63 μg/L, and arsenobetaine 88.62 μg/L. The urinary harmful As was 31.92 μg/L, much lower than the 148.9 μg/L reported in a 2014 survey, due to the implementation of a multi-regional water supply in November 2014 that restricted As exposure through drinking river water. However, concerns remain over chronic exposure to As because As in river water used for farming and in agricultural soil still exceeds environmental standards; thus, ongoing work to address hazards from former mining areas and continued environmental monitoring is necessary.

Arsenic exposure through drinking Water and oxidative stress Status: A cross-sectional study in the Ayeyarwady region, Myanmar

Arsenic is a well-known toxic heavy metal that is naturally dispersed in groundwater. Whereas arsenic is widely accepted to be involved in oxidative stress damage, little is known about arsenic-induced oxidative damage in relationship to contaminated drinking water as a source. The aim of this study was to determine the association between arsenic exposure through drinking water and oxidative stress status by measuring levels of urinary 8-hydroxydeoxyguanosine (8−OHdG) as a biomarker of oxidative stress damage in a Myanmar population. A questionnaire-based survey and drinking water and urine sampling (n = 198) were performed to assess the association between arsenic exposure and urinary 8−OHdG concentration in the Ayeyarwady Region, Myanmar. Urinary arsenic concentrations were significantly correlated with drinking water arsenic concentrations (Spearman’s rho = 0.32, p < 0.001). Multivariate linear regression analysis showed that higher urinary arsenic concentrations were significantly associated with higher 8−OHdG concentrations (coefficient = 0.09, 95% confidence interval, 0.03 – 0.15; p = 0.002). The present study identified that exposure to arsenic through drinking water could induce an increase in the urinary 8−OHdG concentration, reflecting increased oxidative DNA damage. These findings provide evidence that may explain the role of arsenic-induced oxidative stress in the pathophysiology of arsenic-induced diseases including cancers.

Relative miRNA and mRNA expression involved in arsenic methylation.

Three arsenic species in urine are measured using an atomic absorption spectrophotometer. RT-PCR is performed to detect the expression levels of AS3MT, 3 miRNAs, and 17 relative mRNAs in 43 workers producing arsenic trioxide, 36 workers who stopped exposure to arsenic for 85 days, and 24 individuals as the control group. The concentrations of urinary arsenic are very high in workers. A negative correlation between AS3MT and MiR-548c-3p is found. There exist significant changes for most selected miRNAs and mRNAs in workers. There are no significant differences between workers who stopped exposure to arsenic and the control group for most miRNAs and mRNAs, but the MiR-548c-3p levels show significant changes. Similar positive correlations between the expression of AS3MT and all selected mRNAs are found. Negative correlations between the expression of MiR-548c-3p and many relative mRNAs are found as well. AS3MT and MiR-548c-3p may regulate arsenic methylation jointly, which when involved in a group of relative mRNAs may play roles in arsenic metabolism and epigenetic changes caused by this metabolism.

Association between maternal urinary speciated arsenic concentrations and gestational diabetes in a cohort of Canadian women

BackgroundEpidemiological and toxicological evidence suggests that maternal total arsenic (As) levels are associated with an elevated risk of gestational diabetes (GDM). Uncertainty remains regarding the metabolic toxicity of specific arsenic species, comprised of both organic and inorganic sources of arsenic exposure. ObjectivesWe assessed associations between speciated As and GDM using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. MethodsConcentrations of speciated As [(inorganic (trivalent, pentavalent)), methylated arsenic species metabolites (monomethylarsonic acid (MMA), dimethylarsinic acid (DMA)), and organic (arsenobetaine)] were measured in first trimester maternal urine samples. GDM cases were identified in accordance with Canadian guidelines. Multivariable regression models were used to estimate associations between speciated As and GDM, evaluate potential interaction between speciated As exposures, and assess fetal sex-specific findings. ResultsAmong 1243 women who had a live, singleton birth and no previous history of diabetes, 4% met the diagnostic criteria for GDM. Our analyses focused on DMA and arsenobetaine as these were the subtypes with detectable concentrations in at least 40% of samples. Compared to women in the lowest tertile of DMA (<1.49 μg As/L), women with concentrations exceeding 3.52 μg As/L (3rd tertile) experienced an increased risk of GDM (aOR = 3.86; 95% CI: 1.18, 12.57) (p-value for trend across tertiles = 0.04). When restricted to women carrying male infants, the magnitude of this association increased (aOR 3rd tertile = 4.71; 95% CI: 1.05, 21.10). ConclusionsThese results suggest a positive relation between DMA and GDM; potential differences in risk by fetal sex requires further investigation.

Preliminary study of urinary arsenic concentration and arsenic methylation capacity effects on neurodevelopment in very low birth weight preterm children under 24 months of corrected age.

The neurological prognoses of very low birth weight preterm (VLBWP) children during the first 2 years of life will influence their neurodevelopment during subsequent childhood years and adolescence. The objective of this study was to systemic investigate relationships of urinary arsenic (As) concentrations, the As methylation capability, and toenail As concentrations on cognitive, language, and motor development in VLBWP children under 24 months of corrected age.Participants (n = 60) in our study were recruited from October 2010 to April 2013. Urine and toenail samples were collected for evaluation to assess As exposure. The Bayley scales of infant development III were used to evaluate neurodevelopment at 2 years of corrected age. Concentrations of As species in urine and the As concentration in toenails were, respectively, analyzed using HPLC-HG-AAS and ICP-MS.The mean concentration of total As was 28.6 μg/g creatinine, and inorganic As was 1.01 μg/L in urine. The urine contained an average of 3% inorganic As, 2% monomethylarsonic acid, and 95% dimethylarsinic acid (DMA). The mean concentration of As in toenails was 225 ng/g. Children with a longer gestational age (≥28 weeks) and higher DMA % levels appeared to have the highest unadjusted cognitive and fine motor scores.Our study results suggest that gestational age is associated with neurodevelopment in VLBWP children. We recommend that further study simultaneously analyze multiple environmental contaminants that may have adverse effects on neurodevelopment, use biomarkers for the mother–child pair, and determine whether prenatal or postnatal As exposure has a greater influence on the neurological development of VLBWP children.

A new potential biomarker in early diagnosis of firefighter lung function impairment: dynamic thiol/disulphide homeostasis.

The aim of this study was to investigate the associations between urinary arsenic, oxidative stress, assessed by thiol/disulphide homeostasis, and lung diseases in firefighters. The study conducted among the municipality-based male firefighters (n = 100) who were admitted to occupational diseases clinic for periodic medical examination. The control group consisted of non-exposed male office workers (n = 50). Urinary arsenic levels, thiol/disulphide homeostasis parameters of participants were determined. Also, lung diseases were assessed by chest X-ray and pulmonary function tests. The mean age and work year did not differ in the study and control group. The median urinary arsenic concentration of firefighters was significantly higher than in the control group: 15.65 (2.5-246) μg/L and 3 (0.10-6) μg/L, respectively (p < 0.001). The parameters of pulmonary function tests (PFT) FVC (%), FEV1 (%), FEV1/FVC ratio and FEF 25-75 (%) were all significantly lower in firefighters compared to controls. A significant increase in mean serum disulphide concentration (17.10 ± 8.31 μmol/L vs. 7.48 ± 5.91) (Fig. 1) and disulphide/native thiol % ratio: 3.63 (0.53-11.43) vs. 1.51 (0.03-7.65) (p < 0.001) were found between exposed group and controls. The Spearman's correlation analysis revealed a positive correlation between urinary arsenic and disulphide (r = 0.422, p < 0.001), disulphide/native thiol % ratio (r = 0.409, p < 0.001). Nevertheless, urinary arsenic correlated negatively with all PFT parameters including FVC (%), FEV1 (%), FEV1/FVC and FEF 25-75 (%) (p < 0.001). We showed the arsenic-induced oxidative stress in firefighters with impairments of several lung functions determined by thiol/disulphide homeostasis using a novel method.

Urinary Inorganic Arsenic Concentration and Type 2 Diabetes Mellitus and Hypertension Development: A Population-Based Analysis in Arica, Chile

Introduction: Studies that evaluated the association between type 2 diabetes mellitus and hypertension has been consistent in population exposed to high levels of arsenic. However, the evidence is no clear regarding low levels of exposure. The aim of this study was to explore the association between the concentration of inorganic arsenic in urine and the development of type 2 diabetes mellitus and hypertension. Methods: Data analysis of 10.340 individuals over the age of 14, of the population register of people exposed to polymetals, evaluated between 2009 and 2015. Outcome variable: Self-report of diagnosis of type 2 diabetes mellitus (T2DM) and hypertension (HBP). Exposure variable: Concentration of inorganic arsenic in urine. To evaluate association, we used multiple logistic regression models adjusted for creatinine, age, and body mass index. Results: Average age 40 years. The prevalence of diabetes was 8% (CI95% 0.073-0.085) and hypertension 15% (CI95% 0.143-0.159), (31% lost data). The median of inorganic arsenic was 18 &amp;#956;g/L (p25-p75 11-27 &amp;#956;g/L). The adjusted model showed a modest association between inorganic arsenic and T2DM (OR: 1.008, 95% CI 1.003-1.013). Regarding the relationship with HBP, the association was not significant (OR: 0.99, IC95% 0.993-1.004). Conclusion: The results support the hypothesis that low levels of arsenic exposure could be associated with T2DM; however, should be considered with caution due limitations as the way of measuring the outcome variable, the % of lost data and the lack of information from other confounding.