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Sample records for chronic arsenic exposure

  1. Health Effects of Chronic Arsenic Exposure

    PubMed Central

    Hong, Young-Seoub; Song, Ki-Hoon; Chung, Jin-Yong

    2014-01-01

    Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments. PMID:25284195

  2. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    EPA Science Inventory

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  3. Biomarkers for assessing potential carcinogenic effects of chronic arsenic exposure in Inner Mongolia, CHINA

    EPA Science Inventory

    Arsenic is ubiquitous in the environment. Chronic arsenic exposure via drinking water has been associated. with carcinogenic, cardiovascular, neurological and diabetic effects in humans and has been of great public health concern worldwide. In 2001, U.S. Environmental Protection ...

  4. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: IV. DISTRIBUTION OF ARSENIC CONCENTRATIONS IN WELLS

    EPA Science Inventory

    HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA:
    IV. DISTRIBUTION OF ARSENIC CONCENTRATIONS IN WELLS

    Zhixiong Ning, B.S., Zhiyi Liu,B.S., Shiying Zhang, B.S., Chenglong Ma, B.S., Inner Mongolia Ba Men Anti-epidemic Station, Michael Ri...

  5. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    SciTech Connect

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-12-15

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.

  6. HEALTH RISKS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER: FINDINGS FROM THE CLINICAL INVESTIGATIONS DATA IN INNER MONGOLIA, CHINA

    EPA Science Inventory

    Prior studies have reported a large number of arsenicism cases in the Mongolia Autonomous Region of China due to drinking arsenic-contaminated water with concentrations up to 1.8 mg/L. However, the endemic health risks from chronic exposure to arsenic in this population have not...

  7. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: I. BIOMARKERS FOR ASSESSING EXPOSURE AND EFFECTS

    EPA Science Inventory

    Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: I. Biomarkers for Assessing Exposure and Effects

    Judy L. Mumford, Ph.D., Mike Schmitt, M.S.P.H., Richard K. Kwok, M.S.P.H., Rebecca Calderon, Ph.D., National Health and Environmental Effect...

  8. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: VI. DEVELOPMENTAL EFFECTS.

    EPA Science Inventory

    HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA:
    VI. DEVELOPMENTAL EFFECTS

    Richard K. Kwok, M.S.P.H., Judy L. Mumford, Ph.D., Pauline Mendola, Ph.D. Epidemiology and Biomarkers Branch, NHEERL, US Environmental Protection Agency; Yajua...

  9. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    PubMed

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  10. Considerations when using longitudinal cohort studies to assess dietary exposure to inorganic arsenic and chronic health outcomes.

    PubMed

    Scrafford, Carolyn G; Barraj, Leila M; Tsuji, Joyce S

    2016-07-01

    Dietary arsenic exposure and chronic health outcomes are of interest, due in part to increased awareness and data available on inorganic arsenic levels in some foods. Recent concerns regarding levels of inorganic arsenic, the primary form of arsenic of human health concern, in foods are based on extrapolation from adverse health effects observed at high levels of inorganic arsenic exposure; the potential for the occurrence of these health effects from lower levels of dietary inorganic arsenic exposure has not been established. In this review, longitudinal cohort studies are evaluated for their utility in estimating dietary inorganic arsenic exposure and quantifying statistically reliable associations with health outcomes. The primary limiting factor in longitudinal studies is incomplete data on inorganic arsenic levels in foods combined with the aggregation of consumption of foods with varying arsenic levels into a single category, resulting in exposure misclassification. Longitudinal cohort studies could provide some evidence to evaluate associations of dietary patterns related to inorganic arsenic exposure with risk of arsenic-related diseases. However, currently available data from longitudinal cohort studies limit causal analyses regarding the association between inorganic arsenic exposure and health outcomes. Any conclusions should therefore be viewed with knowledge of the analytical and methodological limitations. PMID:27155067

  11. Chronic arsenic exposure and risk of infant mortality in two areas of Chile.

    PubMed Central

    Hopenhayn-Rich, C; Browning, S R; Hertz-Picciotto, I; Ferreccio, C; Peralta, C; Gibb, H

    2000-01-01

    Chronic arsenic exposure has been associated with a range of neurologic, vascular, dermatologic, and carcinogenic effects. However, limited research has been directed at the association of arsenic exposure and human reproductive health outcomes. The principal aim of this study was to investigate the trends in infant mortality between two geographic locations in Chile: Antofagasta, which has a well-documented history of arsenic exposure from naturally contaminated water, and Valparaíso, a comparable low-exposure city. The arsenic concentration in Antofagasta's public drinking water supply rose substantially in 1958 with the introduction of a new water source, and remained elevated until 1970. We used a retrospective study design to examine time and location patterns in infant mortality between 1950 and 1996, using univariate statistics, graphical techniques, and Poisson regression analysis. Results of the study document the general declines in late fetal and infant mortality over the study period in both locations. The data also indicate an elevation of the late fetal, neonatal, and postneonatal mortality rates for Antofagasta, relative to Valparaíso, for specific time periods, which generally coincide with the period of highest arsenic concentration in the drinking water of Antofagasta. Poisson regression analysis yielded an elevated and significant association between arsenic exposure and late fetal mortality [rate ratio (RR) = 1.7; 95% confidence interval (CI), 1.5-1.9], neonatal mortality (RR = 1.53; CI, 1.4-1.7), and postneonatal mortality (RR = 1.26; CI, 1.2-1.3) after adjustment for location and calendar time. The findings from this investigation may support a role for arsenic exposure in increasing the risk of late fetal and infant mortality. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:10903622

  12. Oxidative DNA damage enhances the carcinogenic potential of in vitro chronic arsenic exposures.

    PubMed

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramanyam; Marcos, Ricard; Hernández, Alba

    2016-08-01

    Chronic exposure to arsenic is known to increase the incidence of cancer in humans. Our previous work demonstrated that environmentally relevant arsenic exposures generate an accelerated accumulation of pre-carcinogen 8-OH-dG DNA lesions under Ogg1-deficient backgrounds, but it remains unproved whether this observed arsenic-induced oxidative DNA damage (ODD) is certainly important in terms of cancer. Here, isogenic MEF Ogg1 (+/+) cells and MEF Ogg1 (-/-) cells-unable to properly eliminate 8-OH-dG from DNA-were exposed to 0.5, 1 and 2 µM of sodium arsenite for 40 weeks. The acquisition of an in vitro cancer-like phenotype was assessed throughout the exposure; matrix metalloproteinase (MMP) activities were measured by zymography, colony formation and promotion were evaluated by soft agar assay, and cellular invasiveness was measured by the transwell assay. Alterations in cellular morphology, growth and differentiation status were also included as complementary measures of transformation. MEF Ogg1 (-/-) cells showed a cancer-associated phenotype after 30 weeks of exposure, as indicated by morphological changes, increased proliferation, deregulated differentiation status, increased MMPs secretion, anchorage-independent cell growth and enhancement of tumor growth and invasiveness. Conversely, MEF Ogg1 (+/+) cells did not present changes in morphology or proliferation, exhibited a milder degree of gene deregulation and needed 10 weeks of additional exposure to the highest arsenite doses to show tumor enhancing effects. Thus, Ogg1 genetic background and arsenic-induced 8-OH-dG proved relevant for arsenic-mediated carcinogenic effects. To our knowledge, this is the first study directly linking ODD with arsenic carcinogenesis. PMID:26438402

  13. CONSEQUENCES OF ACUTE AND CHRONIC EXPOSURE TO ARSENIC

    EPA Science Inventory

    Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. Fo...

  14. Diffuse parenchymal lung disease in a case of chronic arsenic exposure.

    PubMed

    Bhattacharya, Somnath; Dey, Atin; Saha, Sayantan; Kar, Saurav

    2016-01-01

    A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD). Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date. PMID:27625453

  15. Diffuse parenchymal lung disease in a case of chronic arsenic exposure

    PubMed Central

    Bhattacharya, Somnath; Dey, Atin; Saha, Sayantan; Kar, Saurav

    2016-01-01

    A 42-year-old housewife, the resident of rural part of West Bengal, presented with gradually progressive exertional dyspnea associated with a dry cough for last 3 years clinical features were suggestive of diffuse parenchymal lung disease (DPLD). Her chest X-ray posteroanterior view and high resolution computed tomography scan of the thorax showed bilateral patchy ground glass opacities and reticulonodular pattern. Search for the etiology revealed classical skin findings of chronic arsenic exposure in the form of generalized darkening and thickening of skin and keratotic lesions over the palms and soles and classical raindrop pigmentation over leg which was present for last 7 years subsequently her bronchoalveolar lavage fluid, hair, nail, and drinking water showed significant amount of arsenic contamination. By exclusion of all known causes of DPLD, we concluded that it was a case of DPLD due to chronic arsenic exposure. To the best of our knowledge, only few case report of DPLD in chronic arsenicosis has been reported till date. PMID:27625453

  16. Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity.

    PubMed

    Wang, Xiaoxue; Mu, Xiaoli; Zhang, Jie; Huang, Qingyu; Alamdar, Ambreen; Tian, Meiping; Liu, Liangpo; Shen, Heqing

    2015-03-01

    Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses. Eighteen differential metabolites were identified, and most of them showed dose-dependent responses to arsenic exposure. Metabolic abnormalities mainly involved lipid metabolism and amino acid metabolism. The metabolic alterations were further confirmed by hepatic gene expression. Expressions of cpt2, lcat, cact, crot and mtr were significantly elevated in high dose groups. This study provides novel evidence to support the association between arsenic exposure and metabolic disruption, and it contributes to understanding the mechanism of chronic arsenic toxicity. PMID:25697676

  17. Total arsenic concentrations in toenails quantified by two techniques provide a useful biomarker of chronic arsenic exposure in drinking water

    SciTech Connect

    Adair, Blakely M. . E-mail: adair.blakely@epa.gov; Hudgens, Edward E.; Schmitt, Michael T.; Calderon, Rebecca L.; Thomas, David J.

    2006-06-15

    Accurate quantitation of any contaminant of interest is critical for exposure assessment and metabolism studies that support risk assessment. A preliminary step in an arsenic exposure assessment study in Nevada quantified total arsenic (TAs) concentrations in tissues as biomarkers of exposure. Participants in this study (n=95) were at least 45 years old, had lived in the area for more than 20 years, and were exposed to a wide range of arsenic concentrations in drinking water (3-2100ppb). Concentrations of TAs in blood, urine, and toenails determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) ranged from below detection to 0.03, 0.76, and 12ppm, respectively; TAs in blood rarely exceeded the limit of detection. For comparison, TAs in toenails determined by neutron activation analysis (NAA) ranged from below detection to 16ppm. Significant (P<0.0001) positive regressions were seen between the TAs concentration in toenails and in drinking water (adjusted r{sup 2}=0.3557 HG-AFS, adjusted r{sup 2}=0.3922 NAA); TAs concentrations in urine were not described by drinking water As (adjusted r{sup 2}=0.0170, P=0.1369). Analyses of TAs in toenails by HGAFS and NAA yielded highly concordant estimates (r=0.7977, P<0.0001). These results suggest that toenails are a better biomarker of chronic As exposure than urine in the current study, because the sequestration of As in toenails provides an integration of exposure over time that does not occur in urine.

  18. The Broad Scope of Health Effects from Chronic Arsenic Exposure: Update on a Worldwide Public Health Problem

    PubMed Central

    Anderson, Beth; Ahsan, Habibul; Aposhian, H. Vasken; Graziano, Joseph H.; Thompson, Claudia; Suk, William A.

    2013-01-01

    Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure. PMID:23458756

  19. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    SciTech Connect

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J.

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  20. Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water.

    PubMed Central

    Pi, Jingbo; Yamauchi, Hiroshi; Kumagai, Yoshito; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Hopenhayn-Rich, Claudia; Shimojo, Nobuhiro

    2002-01-01

    Exposure of experimental animals or cultured cells to arsenic induces oxidative stress, but, to date, no examination of this phenomenon in humans has been reported. In this study we conducted a cross-sectional study in Wuyuan, Inner Mongolia, China, to explore the relationship between chronic arsenic exposure from drinking water and oxidative stress in humans. Thirty-three inhabitants who had been drinking tube-well water with high concentrations of inorganic arsenic (mean value = 0.41 mg/L) for about 18 years constituted the high-exposure group, and 10 residents who lived nearby but were exposed to much lower concentrations of arsenic in their drinking water (mean value = 0.02 mg/L) were selected as the low-exposure comparison group. Results of the present study indicated that although the activity for superoxide dismutase (SOD) in blood did not differ significantly between the two groups, the mean serum level of lipid peroxides (LPO) was significantly higher among the high-exposed compared with the low-exposed group. Elevated serum LPO concentrations were correlated with blood levels of inorganic arsenic and its methylated metabolites. In addition, they showed an inverse correlation with nonprotein sulfhydryl (NPSH) levels in whole blood. The subjects in the high-arsenic-exposure group had mean blood NPSH levels 57.6% lower than those in the low-exposure group. Blood NPSH levels were inversely correlated with the concentrations of inorganic arsenic and its methylated metabolites in blood and with the ratio of monomethylarsenic to inorganic arsenic. These results provide evidence that chronic exposure to arsenic from drinking water in humans results in induction of oxidative stress, as indicated by the reduction in NPSH and the increase in LPO. Some possible mechanisms for the arsenic-induced oxidative stress are discussed. PMID:11940449

  1. Neurosensory effects of chronic human exposure to arsenic associated with body burden and environmental measures.

    PubMed

    Otto, D; Xia, Y; Li, Y; Wu, K; He, L; Telech, J; Hundell, H; Prah, J; Mumford, J; Wade, T

    2007-03-01

    Exposure to arsenic in drinking water is known to produce a variety of health problems, including peripheral neuropathy. Auditory, visual and somatosensory impairment have been reported in Mongolian farmers living in the Yellow River Valley, where drinking water is contaminated by arsenic. In the present study, sensory tests, including pinprick and vibration thresholds, were administered to 320 residents with well-water arsenic levels, ranging from non-detectable to 690 microg/L. Vibration thresholds in the second and fifth fingers of both hands were measured using a vibrothesiometer. Drinking water, urine and toenail samples were obtained to assess arsenic exposure and body burden. Regression analyses indicated significant associations of pinprick scores and vibration thresholds with all arsenic measures. Vibration thresholds were more strongly associated with urinary than water or nail arsenic measures, but odds ratios for decreased pinprick sensitivity were highest for the water arsenic measure. Results of the current study indicate neurosensory effects of arsenic exposure at concentrations well below the 1000 microg/L drinking water level specified by NRC, and suggest that non-carcinogenic end-points, such as vibration thresholds, are useful in the risk assessment of exposure to arsenic in drinking water. PMID:17439919

  2. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: V. BIOMARKER STUDIES - A PILOT STUDY

    EPA Science Inventory

    Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: V. Biomarker Studies - a Pilot Study

    Michael T. Schmitt, M.S.P.H., Judy S. Mumford, Ph.D., National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agenc...

  3. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    PubMed Central

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. PMID:22521957

  4. Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

    SciTech Connect

    Pei, Qiuling; Ma, Ning; Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping; Mu, Jinjun; Li, Yuanfei; Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen

    2013-01-01

    There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs).

  5. NEUROSENSORY EFFECTS OF CHRONIC HUMAN EXPOSURE TO ARSENIC ASSOCIATED WITH BODY BURDEN AND ENVIRONMENTAL MEASURES

    EPA Science Inventory

    Exposure to arsenic in drinking water is known to produce a variety of health problems including peripheral neuropathy. Auditory, visual and somatosensory impairments have been reported in Mongolian farmers living in the Yellow River Valley where drinking water is contami...

  6. Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

    PubMed Central

    Hall, Megan N.; Niedzwiecki, Megan; Liu, Xinhua; Harper, Kristin N.; Alam, Shafiul; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; Siddique, Abu B.; Parvez, Faruque; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph

    2013-01-01

    D, Siddique AB, Parvez F, Mey JL, van Geen A, Graziano J, Gamble MV. 2013. Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in Bangladeshi adults. Environ Health Perspect 121:1068–1074; http://dx.doi.org/10.1289/ehp.1205727 PMID:23792557

  7. Ameliorative effect of polydatin on oxidative stress-mediated testicular damage by chronic arsenic exposure in rats.

    PubMed

    Ince, S; Avdatek, F; Demirel, H H; Arslan-Acaroz, D; Goksel, E; Kucukkurt, I

    2016-06-01

    Arsenic causes lipid peroxidation leading to alterations in antioxidant status in organisms. In this study, the reproductive effects of chronic exposure to arsenic and the protective effects of polydatin (PD) were evaluated in 35 Wistar male rats, which were divided equally into five groups. The control group received a normal diet and tap water, arsenic (100 mg l(-1) , approximately 1/50 of oral LD50 ) was given via drinking water to experimental groups except control group, and PD was orally given to the other groups at dose of 50, 100 and 200 mg kg(-1) for 60 days. Arsenic administration decreased sperm motility, glutathione level, superoxide dismutase and catalase activities in testicular tissue of rats. In contrast, malondialdehyde level and DNA damage were found to be high levels in arsenic-treated group. Histopathologically, it was observed that decreased sperm concentration and degeneration of Sertoli cells in testicular tissue. PD administration, partially 200 mg kg(-1) , reversed arsenic-induced lipid peroxidation, DNA damage, antioxidant enzyme activity and cell integrity in testis of rats. These results demonstrate that PD decreases arsenic-induced lipid peroxidation, enhances the antioxidant defence mechanism and regenerates tissue damage in testis of rats. PMID:26302725

  8. Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

    SciTech Connect

    Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.; Contreras-Ruiz, Jose; Garcia-Vargas, Gonzalo G.; Razo, Luz M. del

    2007-08-01

    Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-{alpha}) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs{sup III}, MAs{sup V}, DMAs{sup III}, DMAs{sup V}). This study examines the relationship between TGF-{alpha} concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-{alpha} in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-{alpha} concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-{alpha} levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-{alpha} concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-{alpha} than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-{alpha} in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas.

  9. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    SciTech Connect

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  10. Arsenic Exposure and Toxicology: A Historical Perspective

    PubMed Central

    Hughes, Michael F.; Beck, Barbara D.; Chen, Yu; Lewis, Ari S.; Thomas, David J.

    2011-01-01

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve. PMID:21750349

  11. Chronic Exposure to Low-Dose Arsenic Modulates Lipogenic Gene Expression in Mice

    PubMed Central

    Adebayo, Adeola O.; Zandbergen, Fokko; Kozul-Horvath, Courtney D.; Gruppuso, Philip A.; Hamilton, Joshua W.

    2016-01-01

    Arsenic, a ubiquitous environmental toxicant, can affect lipid metabolism through mechanisms that are not well understood. We studied the effect of arsenic on serum lipids, lipid-regulating genes, and transcriptional regulator sterol regulatory element binding protein 1c (SREBP-1c). C57BL/6 mice were administered 0 or 100 ppb sodium arsenite in drinking water for 5 weeks. Arsenic exposure was associated with decreased liver weight but no change in body weight. Serum triglycerides level fell in arsenic-exposed animals, but not in fed animals, after short-term fasting. Hepatic expression of SREBP-1c was reduced in arsenic-exposed fed animals, with a 16-fold change in reduction. Similar effects were seen for SREBP-1c in white adipose tissue. However, fasting resulted in dissociation of the expression of SREBP-1c and its targets, and SREBP-1c protein content could not be shown to correlate with its mRNA expression. We conclude that arsenic modulates hepatic expression of genes involved in lipid regulation through mechanisms that are independent of SREBP-1c expression. PMID:25155036

  12. Chronic low level arsenic exposure evokes inflammatory responses and DNA damage.

    PubMed

    Dutta, Kaustav; Prasad, Priyanka; Sinha, Dona

    2015-08-01

    The cross-sectional study investigated the impact of chronic low level arsenic (As) exposure (11-50μg/L) on CD14 expression and other inflammatory responses in rural women of West Bengal enrolled from control (As level <10μg/L; N, 131) and exposed area (As level 11-50μg/L, N, 142). Atomic absorption spectroscopy revealed that As level in groundwater was higher in endemic areas (22.93±10. 1 vs. 1.61±0.15, P<0.0001) and showed a positive correlation [Pearsons r, 0.9281; 95% confidence interval, 0.8192-0.9724] with As content in nails of the exposed women. Flow cytometric analysis showed that CD 14 expression on monocytes was significantly higher (P<0.001) in exposed women and positively correlated with groundwater As [Pearsons r, 0.9191; 95% confidence interval, 0.7584-0.9745]. Leucocytes and airway cells of As exposed women exhibited up regulation of an inflammatory mediator, tumor necrosis factor-α (TNF-α) and transcription factor, nuclear factor-κB (NF-κB) (P<0.0001). Plasma pro inflammatory cytokines like - TNF-α, interleukins (ILs) - IL-6, IL-8, IL-12 were elevated whereas anti-inflammatory cytokine IL-10 was depleted in the exposed women. Sputa of the exposed women had elevated activity of inflammatory markers - MMP-2 and MMP-9 whereas sera were observed with only increased activity of MMP-9. Airway cells of the exposed women had exacerbated DNA damage than control. Level of oxidative DNA adducts like 8-hydroxy-2'-deoxyguanosine (8OHdG) were also enhanced in plasma of exposed women. Therefore it might be indicated that low level As exposure elicited a pro-inflammatory profile which might have been contributed in part by CD14 expressing monocytes and prolong persistence of pulmonary and systemic inflammation might have promoted oxidative DNA damage in the rural women. PMID:26118750

  13. Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico

    PubMed Central

    Mendez, Michelle A.; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A. Baeza; Ishida, María C.; Gutiérrez-Torres, Daniela S.; Saunders, R. Jesse; Drobná, Zuzana; Fry, Rebecca C.; Buse, John B.; Loomis, Dana; García-Vargas, Gonzalo G.; Del Razo, Luz M.

    2015-01-01

    , Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742 PMID:26068977

  14. Environmental Source of Arsenic Exposure

    PubMed Central

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  15. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA. III. NEUROLOGICAL SYMPTOMS AND PIN-PRICK MEASURES

    EPA Science Inventory

    Health Effects of Chronic Exposure to Arsenic via Drinking Water in Inner Mongolia: III. Neurological Symptoms and Pin-prick Measures

    Yanhong Li, M.D.,Yajuan.Xia, M.D., Kegong Wu, M.D., Inner Mongolia Center For Endemic Disease Control and Research, Ling Ling He, B.S., Zhi...

  16. HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: II. VIBROTACTILE AND VISUAL MEASURES FINAL DOCUMENT TITLE.

    EPA Science Inventory

    HEALTH EFFECTS OF CHRONIC EXPOSURE TO ARSENIC IN DRINKING WATER IN INNER MONGOLIA: II. VIBROTACTILE AND VISUAL MEASURES.

    David Otto, Ph.D., Judy Mumford, Ph.D., Richard Kwok, M.S.P.H., Ken Hudnell, Ph.D.,
    U.S. Environmental Protection Agency; Yanhong Li, M.D., Yajuan ...

  17. NEUROSENSORY EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: II. VIBROTACTILE AND VISUAL FUNCTION

    EPA Science Inventory

    This study was designed to assess the effects of exposure to arsenic in drinking water on visual and vibrotactile function in residents of the BaMen region of Inner Mongolia, China. Arsenic was measured by hydride generation atomic fluorescence. 321 participants were divided in...

  18. Elevated Human telomerase reverse transcriptase gene expression in blood cells associated with chronic and arsenic exposure in Inner Mongolia, China

    EPA Science Inventory

    BACKGROUND: Arsenic exposure is associated with human cancer. Telomerase containing the catalytic subunit, human telomerase reverse transcriptase (hTERT), can extend telomeres of chromosomes, delay senescence and promoting cell proliferation leading to tumorigenesis. OBJECTIVE:...

  19. Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

    PubMed Central

    Argos, Maria; Chen, Lin; Jasmine, Farzana; Tong, Lin; Pierce, Brandon L.; Roy, Shantanu; Paul-Brutus, Rachelle; Gamble, Mary V.; Harper, Kristin N.; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Slavkovich, Vesna; Baron, John A.; Graziano, Joseph H.; Kibriya, Muhammad G.

    2014-01-01

    , Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884 PMID:25325195

  20. COMPARISON OF TWO ARSENIC EXPOSURE ASSESSMENT PROTOCOLS IN A CHRONICALLY EXPOSED POPULATION

    EPA Science Inventory

    Consistent with the US EPA 1997 Arsenic Research Plan's emphasis on studies in US populations to obtain data to support a revised Maximum Contaminant Level (MCL) for arsenic, two studies were conducted in Millard County, Utah; the first in 1997 and a second in 1999. This locat...

  1. HEALTH EFFECTS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA

    EPA Science Inventory

    Arsenite and arsenate are widely present in natural waters. The inorganic forms , especially arsenite, are believed to be the most toxic species. Methylation is often considered to be the primary detoxification pathway for the metaboliism of inorganic arsenic. Recently studi...

  2. Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic☆

    PubMed Central

    Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Víctor H.; Contreras-Ruiz, José; García-Vargas, Gonzalo G.; Del Razo, Luz M.

    2009-01-01

    Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAsIII, MAsV, DMAsIII, DMAsV). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p<0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p=0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas. PMID:17267001

  3. Acute arsenic intoxication from environmental arsenic exposure

    SciTech Connect

    Franzblau, A.; Lilis, R. )

    1989-11-01

    Reports of acute arsenic poisoning arising from environmental exposure are rare. Two cases of acute arsenic intoxication resulting from ingestion of contaminated well water are described. These patients experienced a variety of problems: acute gastrointestinal symptoms, central and peripheral neurotoxicity, bone marrow suppression, hepatic toxicity, and mild mucous membrane and cutaneous changes. Although located adjacent to an abandoned mine, the well water had been tested for microorganisms only and was found to be safe. Regulations for testing of water from private wells for fitness to drink are frequently nonexistent, or only mandate biologic tests for microorganisms. Well water, particularly in areas near mining activity, should be tested for metals.

  4. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure.

    PubMed

    Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang, Luoping

    2009-12-15

    Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As(III)). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As(III) through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As(III) and to its more toxic metabolite monomethylarsonous acid (MMA(III)) at doses relevant to high environmental human exposures. In addition, both As(III) and MMA(III) treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic. PMID:19732783

  5. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

    SciTech Connect

    Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang Luoping

    2009-12-15

    Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As{sup III}). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As{sup III} through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As{sup III} and to its more toxic metabolite monomethylarsonous acid (MMA{sup III}) at doses relevant to high environmental human exposures. In addition, both As{sup III} and MMA{sup III} treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

  6. Reduced cellular redox status induces 4-hydroxynonenal-mediated caspase 3 activation leading to erythrocyte death during chronic arsenic exposure in rats

    SciTech Connect

    Biswas, Debabrata; Sen, Gargi; Biswas, Tuli

    2010-05-01

    Chronic exposure to arsenic in rats led to gradual accumulation of the toxicant in erythrocytes causing oxidative stress in these cells. 4-Hydroxynonenal (4-HNE), a major aldehyde product of lipid peroxidation, contributed significantly to the cytopathological events observed during oxidative stress in the erythrocytes of exposed rats. 4-HNE triggered death signal cascade that was initiated with the formation of HNE-protein adducts in cytosol. HNE-protein adduct formation resulted in depletion of cytosolic antioxidants followed by increased generation of ROS. Results showed accumulation of hydrogen peroxide (H{sub 2}O{sub 2}) from the early stages of arsenic exposure, while superoxide (O{sub 2}{sup c}entre dot{sup -}) and hydroxyl radical ({sup c}entre dotOH) also contributed to the oxidative stress during longer period of exposure. Suppression of antioxidant system coupled with increased generation of ROS eventually led to activation of caspase 3 during arsenic exposure. Attenuation of HNE-mediated activation of caspase 3 in presence of N-acetylcysteine (NAC) indicated the involvement of GSH in the process. Prevention of HNE-mediated degradation of membrane proteins in presence of Z-DEVD-FMK identified caspase 3 as the principal mediator of HNE-induced cellular damage during arsenic exposure. Degradation of band 3 followed by its aggregation on the red cell surface promoted immunologic recognition of redistributed band 3 by autologous IgG with subsequent attachment of C3b. Finally, the formation of C3b-IgG-band 3 immune complex accelerated the elimination of affected cells from circulation and led to the decline of erythrocyte life span during chronic arsenic toxicity.

  7. NEUROTOXIC EFFECTS OF CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA: I. SYMPTOMS AND PINPRICK TESTING

    EPA Science Inventory


    This study was designed to assess the effects of exposure to arsenic in drinking water on neurosensory function. A symptom questionnaire and brief neurological exam consisting of pinprick testing of the arms and legs and knee-jerk test were administered to 321 residents of...

  8. Atorvastatin acts synergistically with N-acetyl cysteine to provide therapeutic advantage against Fas-activated erythrocyte apoptosis during chronic arsenic exposure in rats

    SciTech Connect

    Biswas, Debabrata; Sen, Gargi; Sarkar, Avik; Biswas, Tuli

    2011-01-01

    Arsenic is an environmental toxicant that reduces the lifespan of circulating erythrocytes during chronic exposure. Our previous studies had indicated involvement of hypercholesterolemia and reactive oxygen species (ROS) in arsenic-induced apoptotic death of erythrocytes. In this study, we have shown an effective recovery from arsenic-induced death signaling in erythrocytes in response to treatment with atorvastatin (ATV) and N-acetyl cysteine (NAC) in rats. Our results emphasized on the importance of cholesterol in the promotion of ROS-mediated Fas signaling in red cells. Arsenic-induced activation of caspase 3 was associated with phosphatidylserine exposure on the cell surface and microvesiculation of erythrocyte membrane. Administration of NAC in combination with ATV, proved to be more effective than either of the drugs alone towards the rectification of arsenic-mediated disorganization of membrane structural integrity, and this could be linked with decreased ROS accumulation through reduced glutathione (GSH) repletion along with cholesterol depletion. Moreover, activation of caspase 3 was capable of promoting aggregation of band 3 with subsequent binding of autologous IgG and opsonization by C3b that led to phagocytosis of the exposed cells by the macrophages. NAC-ATV treatment successfully amended these events and restored lifespan of erythrocytes from the exposed animals almost to the control level. This work helped us to identify intracellular membrane cholesterol enrichment and GSH depletion as the key regulatory points in arsenic-mediated erythrocyte destruction and suggested a therapeutic strategy against Fas-activated cell death related to enhanced cholesterol and accumulation of ROS.

  9. Arsenic Exposure and the Induction of Human Cancers

    PubMed Central

    Martinez, Victor D.; Vucic, Emily A.; Becker-Santos, Daiana D.; Gil, Lionel; Lam, Wan L.

    2011-01-01

    Arsenic is a metalloid, that is, considered to be a human carcinogen. Millions of individuals worldwide are chronically exposed through drinking water, with consequences ranging from acute toxicities to development of malignancies, such as skin and lung cancer. Despite well-known arsenic-related health effects, the molecular mechanisms involved are not fully understood; however, the arsenic biotransformation process, which includes methylation changes, is thought to play a key role. This paper explores the relationship of arsenic exposure with cancer development and summarizes current knowledge of the potential mechanisms that may contribute to the neoplastic processes observed in arsenic exposed human populations. PMID:22174709

  10. Human exposure to arsenic from drinking water in Vietnam.

    PubMed

    Agusa, Tetsuro; Trang, Pham Thi Kim; Lan, Vi Mai; Anh, Duong Hong; Tanabe, Shinsuke; Viet, Pham Hung; Berg, Michael

    2014-08-01

    Vietnam is an agricultural country with a population of about 88 million, with some 18 million inhabitants living in the Red River Delta in Northern Vietnam. The present study reports the chemical analyses of 68 water and 213 biological (human hair and urine) samples conducted to investigate arsenic contamination in tube well water and human arsenic exposure in four districts (Tu Liem, Dan Phuong, Ly Nhan, and Hoai Duc) in the Red River Delta. Arsenic concentrations in groundwater in these areas were in the range of <1 to 632 μg/L, with severe contamination found in the communities Ly Nhan, Hoai Duc, and Dan Phuong. Arsenic concentrations were markedly lowered in water treated with sand filters, except for groundwater from Hoai Duc. Human hair samples had arsenic levels in the range of 0.07-7.51 μg/g, and among residents exposed to arsenic levels ≥50 μg/L, 64% of them had hair arsenic concentrations higher than 1 μg/g, which is a level that can cause skin lesions. Urinary arsenic concentrations were 4-435 μg/g creatinine. Concentrations of arsenic in hair and urine increased significantly with increasing arsenic content in drinking water, indicating that drinking water is a significant source of arsenic exposure for these residents. The percentage of inorganic arsenic (IA) in urine decreased with age, whereas the opposite trend was observed for monomethylarsonic acid (MMA) in urine. Significant co-interactions of age and arsenic exposure status were also detected for concentrations of arsenic in hair and the sum of IA, MMA, and dimethylarsinic acid (DMA) in urine and %MMA. In summary, this study demonstrates that a considerable proportion of the Vietnamese population is exposed to arsenic levels of chronic toxicity, even if sand filters reduce exposure in many households. Health problems caused by arsenic ingestion through drinking water are increasingly reported in Vietnam. PMID:24262873

  11. Airborne arsenic exposure and excretion of methylated arsenic compounds.

    PubMed Central

    Smith, T J; Crecelius, E A; Reading, J C

    1977-01-01

    First void urine samples were collected from copper smelter workers exposed to inorganic arsenic and from unexposed controls. Arsenic compounds (As (III), As (V), methylarsonic acid and dimethylarsinic acid) in these samples were analyzed by selective volatilization as arsines with determination of arsenic by plasma excitation emission spectrometry. On the day preceding the urine sample collection a breathing zone measurement was made of respirable arsenic particulates for each subject. It was found that all of the subjects, including the controls excreted arsenic primarily as methylated species. Approximately 50% of the total arsenic was excreted as dimethylarsinic acid and 20% as methylarsonic acid. Slight differences in the proportion of various arsenic compounds were observed with varying levels of inorganic arsenic exposure. Amounts of arsenic species were all closely correlated with each other and with exposure. Irrespirable particulate exposures were measured on a subset of high exposure workers. Irrespirable arsenic was found to be more closely correlated with excretion of arsenic compounds than was respirable arsenic. PMID:908318

  12. Human health risk assessment from arsenic exposures in Bangladesh.

    PubMed

    Joseph, Tijo; Dubey, Brajesh; McBean, Edward A

    2015-09-15

    High arsenic exposures, prevalent through dietary and non-dietary sources in Bangladesh, present a major health risk to the public. A quantitative human health risk assessment is described as a result of arsenic exposure through food and water intake, tea intake, accidental soil ingestion, and chewing of betel quid, while people meet their desirable dietary intake requirements throughout their lifetime. In evaluating the contribution of each intake pathway to average daily arsenic intake, the results show that food and water intake combined, makes up approximately 98% of the daily arsenic intake with the balance contributed to by intake pathways such as tea consumption, soil ingestion, and quid consumption. Under an exposure scenario where arsenic concentration in water is at the WHO guideline (0.01 mg/L), food intake is the major arsenic intake pathway ranging from 67% to 80% of the average daily arsenic intake. However, the contribution from food drops to a range of 29% to 45% for an exposure scenario where arsenic in water is at the Bangladesh standard (0.05 mg/L). The lifetime excess risk of cancer occurrence from chronic arsenic exposure, considering a population of 160 million people, based on an exposure scenario with 85 million people at the WHO guideline value and 75 million people at the Bangladesh standard, and assuming that 35 million people are associated with a heavy activity level, is estimated as 1.15 million cases. PMID:26006052

  13. ARSENIC EXPOSURE STUDY, WASHINGTON STATE

    EPA Science Inventory

    The Port Gamble SKlallam tribe has requested that the US Environmental Protection Agency assist them in understanding their exposures to arsenic from both food and water. A previous study has suggested that locally harvested shellfish which are a component of their diet contain ...

  14. Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.

    PubMed

    Rodríguez, Verónica Mireya; Limón-Pacheco, Jorge Humberto; Carrizales, Leticia; Mendoza-Trejo, María Soledad; Giordano, Magda

    2010-01-01

    Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D₂ mRNA levels in the nucleus accumbens. DAR-D₁ and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D₁ mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L. PMID:20699118

  15. Arsenic exposure and its impact on health in Chile.

    PubMed

    Ferreccio, Catterina; Sancha, Ana María

    2006-06-01

    The problem of arsenic in Chile was reviewed. In Chile, the population is exposed to arsenic naturally via drinking-water and by air pollution resulted from mining activities. The sources of arsenic were identified to estimate the exposure of population to arsenic through air, water, and food. Health effects, particularly early effects, observed in children and adults, such as vascular diseases (premature cardiac infarct), respiratory illnesses (bronchiectasis), and skin lesions have been described. Chronic effects, such as lung and bladder cancers, were reported 20 years after peak exposure and persisted 27 years after mitigation measures for removing arsenic from drinking surface water were initiated. Although the effects of arsenic are similar in different ethnic and cultural groups (e.g. Japanese, Chinese, Indian, Bangladeshi, American, and Taiwanese), variations could be explained by age at exposure, the dose received, smoking, and nutrition. Since health effects were observed at arsenic levels of 50 microg/L in drinking-water, it is advised that Chile follows the World Health Organization's recommendation of 10 microg/L. The Chilean experience in removal of arsenic suggests that it is feasible to reach this level using the conventional coagulation process. PMID:17195557

  16. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    PubMed Central

    Roberge, Jason; O’Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L.; Harris, Robin B.

    2012-01-01

    The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated. PMID:22690182

  17. PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES

    EPA Science Inventory

    Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

  18. PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES

    EPA Science Inventory

    Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

  19. PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES (SOT 2008)

    EPA Science Inventory

    Chronic exposure to arsenic has been associated with human cancers of the bladder, kidney, lung, liver, and skin. Inorganic arsenic is biotransformed in a stepwise manner via both a reduction and then an oxidative methylation step in which arsenic cycles between +5 and +3 oxidati...

  20. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice.

    PubMed

    Bardullas, U; Limón-Pacheco, J H; Giordano, M; Carrizales, L; Mendoza-Trejo, M S; Rodríguez, V M

    2009-09-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain. PMID:19121333

  1. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice

    SciTech Connect

    Bardullas, U.; Limon-Pacheco, J.H.; Giordano, M.; Carrizales, L.; Mendoza-Trejo, M.S.; Rodriguez, V.M.

    2009-09-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.

  2. EXCRETION OF ARSENIC IN URINE AS A FUNCTION OF EXPOSURE TO ARSENIC IN DRINKING WATER

    EPA Science Inventory

    Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first mornin...

  3. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    PubMed

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-01

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is. PMID:24167266

  4. Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

    PubMed

    Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

    2012-11-30

    Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. PMID:23085348

  5. AS 2008: Arsenic exposure a nd health effects in Inner Mongolia: studies on cardiac, diabetes and cancer-related effects

    EPA Science Inventory

    Chronic arsenic exposure via drinking water has been of great public health concern world wide. Arsenic exposure has been associated with human cancers, diabetes and cardiovascular diseases. The objectives of this study were to investigate health effects of arsenic and to asses...

  6. Global Gene Expression Profiling of Hyperkeratotic Skin Lesions from Inner Mongolians Chronically Exposed to Arsenic

    EPA Science Inventory

    The skin is an organ that is highly sensitive to chronic arsenic exposure. Skin lesions such as hyperkeratoses (HKs), which are characterized by hyperproliferation and aberrations in terminal epidermal differentiation, are common early manifestations of arsenicosis in humans. H...

  7. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

    SciTech Connect

    Wang, C.-H.; Hsiao, C.K.; Chen, C.-L.; Hsu, L.-I; Chiou, H.-Y.; Chen, S.-Y.; Hsueh, Y.-M.; Wu, M.-M.; Chen, C.-J.

    2007-08-01

    Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality.

  8. Arsenic exposure, telomere length, and expression of telomere-related genes among Bangladeshi individuals

    PubMed Central

    Gao, Jianjun; Roy, Shantanu; Tong, Lin; Argos, Maria; Jasmine, Farzana; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Hore, Samar K; Sarwar, Golam; Slavkovich, Vesna; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A.; Graziano, Joseph H.; Ahsan, Habibul; Pierce, Brandon L.

    2014-01-01

    Background Inorganic arsenic is a carcinogen whose mode of action may involve telomere dysfunction. Recent epidemiological studies suggest that chronic arsenic exposure is associated with longer telomeres and altered expression of telomere-related genes in peripheral blood. In this study, we evaluated the association of urinary arsenic concentration with expression of telomere-related genes and telomere length in Bangladeshi individuals with a wide range of arsenic exposure through naturally contaminated drinking water. Methods We used linear regression models to estimate associations between urinary arsenic and array-based expression measures for 69 telomere related genes using mononuclear cell RNA samples from 1,799 individuals. Association between arsenic exposure and a qPCR-based telomere length was assessed among 167 individuals. Results Urinary arsenic was possitively associated with expression of WRN, and negatively associated with TERF2, DKC1, TERF2IP and OBFC1 (all P < 0.00035, Bonferroni correction threshold). We detected interaction between urinary arsenic and arsenic metabolism efficiency in relation to expression of WRN (P for interaction = 0.00008). In addition, we observed that very high arsenic exposure was associated with longer telomeres compared to very low exposure (P=0.02). Discussion Our findings suggest that arsenic’s carcinogenic mode of action may involve alteration of telomere maintenance and/or telomere damage. This study extends our knowledge regarding the effect of arsenic on telomere length and expression of telomere-related genes. PMID:25460668

  9. Arsenic Toxicity to Juvenile Fish: Effects of Exposure Route, Arsenic Speciation, and Fish Species

    EPA Science Inventory

    Arsenic toxicity to juvenile rainbow trout and fathead minnows was evaluated in 28-day tests using both dietborne and waterborne exposures, both inorganic and organic arsenic species, and both a live diet and an arsenic-spiked pellet diet. Effects of inorganic arsenic on rainbow...

  10. Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

    EPA Science Inventory

    Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

  11. Treating chronic arsenic toxicity with high selenium lentil diets

    SciTech Connect

    Sah, Shweta; Vandenberg, Albert; Smits, Judit

    2013-10-01

    Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0 ppm As) or As (40 ppm As) water while consuming SK lentils (0.3 ppm Se) or northwestern USA lentils (< 0.01 ppm Se) diets for 14 weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14 weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. - Highlights: • We reduce chronic arsenic toxicity in rats with a whole food solution. • High selenium lentils decrease liver damage and increase blood glutathione levels. • High selenium lentil diets increase urinary and fecal arsenic excretion. • High selenium lentil diets decrease arsenic levels in kidney, the storage organ. • High selenium lentil diets reverse arsenic suppression of the B cell

  12. LUNG, ARSENIC EXPOSURE, AND TISSUE REMODELING

    EPA Science Inventory

    In Specific Aim 1, we will develop a lung model of in utero arsenic exposure. We will assess the best graft conditions, including size, site and initial stage to ensure optimal graft survival and maturation. In addition, we will study the pharmacokinetic relationship between a...

  13. Population Based Exposure Assessment of Bioaccessible Arsenic in Carrots

    EPA Science Inventory

    The two predominant arsenic exposure routes are food and water. Estimating the risk from dietary exposures is complicated, owing to the chemical form dependent toxicity of arsenic and the diversity of arsenicals present in dietary matrices. Two aspects of assessing dietary expo...

  14. Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water

    SciTech Connect

    Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Feng, Hongqi; Wang, Cheng; Wei, Wei; Ding, Yunpeng; Sun, Dianjun

    2012-02-15

    It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68–45.71 mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00–1.06 mg-year), medium (1.37–3.55 mg-year), and high (4.26–48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. -- Highlights: ► Three regions are selected as the areas affected by endemic arsenicosis of China. ► We first examine changes in serum TRX1 among individuals exposed to arsenic. ► A positive correlation was seen between serum TRX1 and total water arsenic intake. ► The same relationship

  15. Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh

    PubMed Central

    2010-01-01

    Background Arsenic is a potent pollutant that has caused an environmental catastrophe in certain parts of the world including Bangladesh where millions of people are presently at risk due to drinking water contaminated by arsenic. Chronic arsenic exposure has been scientifically shown as a cause for liver damage, cancers, neurological disorders and several other ailments. The relationship between plasma cholinesterase (PChE) activity and arsenic exposure has not yet been clearly documented. However, decreased PChE activity has been found in patients suffering liver dysfunction, heart attack, cancer metastasis and neurotoxicity. Therefore, in this study, we evaluated the PChE activity in individuals exposed to arsenic via drinking water in Bangladesh. Methods A total of 141 Bangladeshi residents living in arsenic endemic areas with the mean arsenic exposure of 14.10 ± 3.27 years were selected as study subjects and split into tertile groups based on three water arsenic concentrations: low (< 129 μg/L), medium (130-264 μg/L) and high (> 265 μg/L). Study subjects were further sub-divided into two groups (≤50 μg/L and > 50 μg/L) based on the recommended upper limit of water arsenic concentration (50 μg/L) in Bangladesh. Blood samples were collected from the study subjects by venipuncture and arsenic concentrations in drinking water, hair and nail samples were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PChE activity was assayed by spectrophotometer. Results Arsenic concentrations in hair and nails were positively correlated with the arsenic levels in drinking water. Significant decreases in PChE activity were observed with increasing concentrations of arsenic in water, hair and nails. The average levels of PChE activity in low, medium and high arsenic exposure groups were also significantly different between each group. Lower levels of PChE activity were also observed in the > 50 μg/L group compared to the ≤50 μg/L group. Moreover

  16. In utero and postnatal exposure to arsenic alters pulmonary structure and function

    SciTech Connect

    Lantz, R. Clark Chau, Binh; Sarihan, Priyanka; Witten, Mark L.; Pivniouk, Vadim I.; Chen, Guan Jie

    2009-02-15

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.

  17. Environmental arsenic exposure and serum matrix metalloproteinase-9

    PubMed Central

    Burgess, Jefferey L.; Kurzius-Spencer, Margaret; O’Rourke, Mary Kay; Littau, Sally R.; Roberge, Jason; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Harris, Robin B.

    2014-01-01

    The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake estimated. Urine was speciated for arsenic and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike’s Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9, than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure was positively associated with MMP-9 using all three exposure metrics evaluated. PMID:23232971

  18. Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage

    SciTech Connect

    Banerjee, Mayukh; Banerjee, Nilanjana; Ghosh, Pritha; Das, Jayanta K.; Basu, Santanu; Sarkar, Ajoy K.; States, J. Christopher; Giri, Ashok K.

    2010-11-15

    Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.

  19. Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou Province, China

    SciTech Connect

    Ng, J.C.; Wang, J.P.; Zheng, B.S.; Zhai, C.; Maddalena, R.; Liu, F.; Moore, M.R.

    2005-08-07

    Coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-borne arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those in the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age ({lt} 20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation.

  20. Subhepatotoxic exposure to arsenic enhances lipopolysaccharide-induced liver injury in mice

    PubMed Central

    Arteel, Gavin E.; Guo, Luping; Schlierf, Thomas; Beier, Juliane I; Kaiser, J. Phillip; Chen, Theresa S; Liu, Marsha; Conklin, Daniel P.; Miller, Heather L.; von Montfort, Claudia; States, J. Christopher

    2008-01-01

    Exposure to arsenic via drinking water is a serious health concern in the US. Whereas studies have identified arsenic alone as an independent risk factor for liver disease, concentrations of arsenic required to damage this organ are generally higher than found in the US water supply. The purpose of the current study was to test the hypothesis that arsenic (at subhepatotoxic doses) may also sensitize the liver to a second hepatotoxin. To test this hypothesis, the effect of chronic exposure to arsenic on liver damage caused by acute lipopolysaccharide (LPS) was determined in mice. Male C57Bl/6J mice (4-6 weeks) were exposed to arsenic (49 ppm as sodium arsenite in drinking water). After 7 months of exposure, animals were injected with LPS (10 mg/kg i.p.) and sacrificed 24 h later. Arsenic alone caused no overt hepatotoxicity, as determined by plasma enzymes and histology. In contrast, arsenic exposure dramatically enhanced liver damage caused by LPS, increasing the number and size of necroinflammatory foci. This effect of arsenic was coupled with increases in indices of oxidative stress (4-HNE adducts, depletion of GSH and methionine pools). The number of apoptotic (TUNEL) hepatocytes was similar in the LPS and arsenic/LPS groups. In contrast, arsenic pre-exposure blunted the increase in proliferating (PCNA) hepatocytes caused by LPS; this change in the balance between cell death and proliferation was coupled with a robust loss of liver weight in the arsenic/LPS compared to the LPS alone group. The impairment of proliferation after LPS caused by arsenic was also coupled with alterations in the expression of key mediators of cell cycle progression (p27, p21, CDK6 and Cyclin D1). Taken together, these results suggest that arsenic, at doses that are not overtly hepatotoxic per se, significantly enhances LPS-induced liver injury. These results further suggest that arsenic levels in the drinking water may be a risk modifier for the development of chronic liver diseases

  1. Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh

    PubMed Central

    2011-01-01

    Background Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. Methods A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. Results Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. Conclusions The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a

  2. Arsenic exposure induces the Warburg effect in cultured human cells

    SciTech Connect

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  3. Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

    SciTech Connect

    Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. )

    1989-11-01

    In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

  4. Elevated ERCC-1 Gene Expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia

    EPA Science Inventory

    Background: Chronic arsenic exposure has been associated with human cancers. The objective of this study was to investigate arsenic effects on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. Material and Methods: Water and toe nail samples were coll...

  5. DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC

    EPA Science Inventory

    DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMAsIII and DMAsIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC.
    L. M. Del Razo1, M. Styblo2, W. R. Cullen3, and D.J. Thomas4.
    1Toxicology Section, Cinvestav-IPN, Mexico, D.F., 2Univ. North Carolina, Chapel Hill, NC; 3Uni...

  6. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    SciTech Connect

    Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2009-09-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 {mu}g/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 {mu}g/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 {mu}g/L, mean 99 {mu}g/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  7. Environmental Arsenic Exposure and Microbiota in Induced Sputum

    PubMed Central

    White, Allison G.; Watts, George S.; Lu, Zhenqiang; Meza-Montenegro, Maria M.; Lutz, Eric A.; Harber, Philip; Burgess, Jefferey L.

    2014-01-01

    Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb) and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb). To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%), Proteobacteria (17%) and Bacteriodetes (12%) were the main phyla in all samples, with Neisseriaceae (15%), Prevotellaceae (12%) and Veillonellacea (7%) being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota. PMID:24566055

  8. Evaluation of Exposure to Arsenic in Residential Soil

    PubMed Central

    Tsuji, Joyce S.; Van Kerkhove, Maria D.; Kaetzel, Rhonda S.; Scrafford, Carolyn G.; Mink, Pamela J.; Barraj, Leila M.; Crecelius, Eric A.; Goodman, Michael

    2005-01-01

    In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89–17.7 μg/L, respectively) and older participants (3.8, 1.9, 0.91–19.9 μg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background. PMID:16330356

  9. Evaluation of Exposure to Arsenic in Residential Soil

    SciTech Connect

    Tsuji, Joyce S.; Van Kerkhove, Maria D.; Kaetzel, Rhonda; Scrafford, Carolyn; Mink, Pamela; Barraj, Leila M.; Crecelius, Eric A.; Goodman, Michael

    2005-12-01

    In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89?17.7 ?g/L, respectively) and older participants (3.8, 1.9, 0.91?19.9 ?g/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background.

  10. Arsenic Exposure and Oral Cavity Lesions in Bangladesh

    PubMed Central

    Syed, Emdadul H.; Melkonian, Stephanie; Poudel, Krishna C.; Yasuoka, Junko; Otsuka, Keiko; Ahmed, Alauddin; Islam, Tariqul; Parvez, Faruque; Slavkovich, Vesna; Graziano, Joseph H.; Ahsan, Habibul; Jimba, Masamine

    2012-01-01

    Objective To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh. Methods We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study (HEALS). HEALS is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions. Results Participants with high urinary arsenic levels (286.1–5000.0μg/g) were more likely to develop arsenical lesions of the gums [multinomial odds ratio (M-OR 2.90; 95% CI= 1.11–7.54)], and tongue (M-OR 2.79; 95% CI= 1.51– 5.15), compared with those of urinary arsenic levels of 7.0–134.0μg/g. Conclusions Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue. PMID:23201591

  11. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth.

    PubMed

    Winterbottom, Emily F; Fei, Dennis L; Koestler, Devin C; Giambelli, Camilla; Wika, Eric; Capobianco, Anthony J; Lee, Ethan; Marsit, Carmen J; Karagas, Margaret R; Robbins, David J

    2015-06-01

    Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health. PMID:26288817

  12. Chronic toxicity of arsenic to the Great Salt Lake brine shrimp, Artemia franciscana.

    PubMed

    Brix, Kevin V; Cardwell, Rick D; Adams, William J

    2003-02-01

    We determined the chronic toxicity of arsenic (sodium arsenate) to the Great Salt Lake brine shrimp, Artemia franciscana. Chronic toxicity was determined by measuring the adverse effects of arsenic on brine shrimp growth, survival, and reproduction under intermittent flow-through conditions. The study commenced with <24-h-old nauplii, continued through reproduction of the parental generation, and ended after 28 days of exposure. The concentrations tested were 4, 8, 15, 31, and 56mg/L dissolved arsenic. The test was conducted using water from the Great Salt Lake, Utah as the dilution water. Adult survival was the most sensitive biological endpoint, with growth and reproduction somewhat less sensitive than survival. The no observed effect concentration (NOEC) for survival was 8mg/L, and the lowest observed effect concentration (LOEC) was 15mg/L dissolved arsenic. The LOEC for growth and reproduction was greater than the highest concentration tested, 56mg/L. Based on survival, the final chronic value (geometric mean of the NOEC and LOEC) was 11mg/L dissolved arsenic. The F(1) generation appeared to acclimate to the prior arsenic exposure of the parental generation and was significantly less sensitive than the parental generation. For example, survival for the F(1) generation through day 12 was 100% in 56mg/L dissolved arsenic, compared to 26% for the parental generation. Growth of the F(1) generation was significantly less than that of the parental generation across all concentrations including the control, indicating a generational difference in brine shrimp growth rather than an arsenic effect. This study represents one of the few full life cycle toxicity tests conducted with brine shrimp. PMID:12550094

  13. A critical review of arsenic exposures for Bangladeshi adults.

    PubMed

    Joseph, Tijo; Dubey, Brajesh; McBean, Edward A

    2015-09-15

    Groundwater, the most important source of water for drinking, cooking, and irrigation in Bangladesh, is a significant contributor to the daily human intake of arsenic. Other arsenic intake pathways, established as relevant for Bangladeshi adults through this review, include consumption of contaminated edible plant parts and animal-origin food, inhalation of contaminated air, soil ingestion, betel quid chewing, and tobacco smoking. This review qualifies and quantifies these arsenic intake pathways through analysis of the range of arsenic levels observed in different food types, water, soil, and air in Bangladesh, and highlights the contributions of dietary intake variation and cooking method in influencing arsenic exposures. This study also highlights the potential of desirable dietary patterns and intakes in increasing arsenic exposure which is relevant to Bangladesh where nutritional deficiencies and lower-than-desirable dietary intakes continue to be a major concern. PMID:26004539

  14. Arsenic Exposure From Drinking Water, Arsenic Methylation Capacity, and Carotid Intima-Media Thickness in Bangladesh

    PubMed Central

    Chen, Yu; Wu, Fen; Graziano, Joseph H.; Parvez, Faruque; Liu, Mengling; Paul, Rina Rani; Shaheen, Ishrat; Sarwar, Golam; Ahmed, Alauddin; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T.; Desvarieux, Moise; Ahsan, Habibul

    2013-01-01

    We conducted a cross-sectional study to evaluate the interrelationships between past arsenic exposure, biomarkers specific for susceptibility to arsenic exposure, and carotid intima-media thickness (cIMT) in 959 subjects from the Health Effects of Arsenic Longitudinal Study in Bangladesh. We measured cIMT levels on average 7.2 years after baseline during 2010–2011. Arsenic exposure was measured in well water at baseline and in urine samples collected at baseline and during follow-up. Every 1-standard-deviation increase in urinary arsenic (357.9 µg/g creatinine) and well-water arsenic (102.0 µg/L) concentration was related to a 11.7-µm (95% confidence interval (CI): 1.8, 21.6) and 5.1-µm (95% CI: −0.2, 10.3) increase in cIMT, respectively. For every 10% increase in monomethylarsonic acid (MMA) percentage, there was an increase of 12.1 µm (95% CI: 0.4, 23.8) in cIMT. Among participants with a higher urinary MMA percentage, a higher ratio of urinary MMA to inorganic arsenic, and a lower ratio of dimethylarsinic acid to MMA, the association between well-water arsenic and cIMT was stronger. The findings indicate an effect of past long-term arsenic exposure on cIMT, which may be potentiated by suboptimal or incomplete arsenic methylation capacity. Future prospective studies are needed to confirm the association between arsenic methylation capacity and atherosclerosis-related outcomes. PMID:23788675

  15. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

    PubMed

    Stanton, Bruce A; Caldwell, Kathleen; Congdon, Clare Bates; Disney, Jane; Donahue, Maria; Ferguson, Elizabeth; Flemings, Elsie; Golden, Meredith; Guerinot, Mary Lou; Highman, Jay; James, Karen; Kim, Carol; Lantz, R Clark; Marvinney, Robert G; Mayer, Greg; Miller, David; Navas-Acien, Ana; Nordstrom, D Kirk; Postema, Sonia; Rardin, Laurie; Rosen, Barry; SenGupta, Arup; Shaw, Joseph; Stanton, Elizabeth; Susca, Paul

    2015-09-01

    This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 μg/L in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies. PMID:26231509

  16. Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide

    PubMed Central

    Udensi, Udensi K.; Cohly, Hari H.P.; Graham-Evans, Barbara E.; Ndebele, Kenneth; Garcia-Reyero, Natàlia; Nanduri, Bindu; Tchounwou, Paul B.; Isokpehi, Raphael D.

    2011-01-01

    Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes. PMID:21461292

  17. Arsenic Exposure and Toxicology: A Historical Perspective

    EPA Science Inventory

    The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, in various forms, has also been used as a pesticide and a ch...

  18. SPECIATION OF ARSENIC IN EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

    The speciaton of arsenic in water, food and urine are analytical capabilities which are an essential part in arsenic risk assessment. The cancer risk associated with arsenic has been the driving force in generating the analytical research in each of these matrices. This presentat...

  19. CHURCHILL COUNTY, NEVADA ARSENIC STUDY: WATER CONSUMPTION AND EXPOSURE BIOMARKERS

    EPA Science Inventory

    The US Environmental Protection Agency is required to reevaluate the Maximum Contaminant Level (MCL) for arsenic in 2006. To provide data for reducing uncertainties in assessing health risks associated with exposure to low levels (<200 g/l) of arsenic, a large scale biomarker st...

  20. Arsenic exposure in children living near a former copper smelter

    SciTech Connect

    Binder, S.; Forney, D.; Kaye, W.; Paschal, D.

    1987-07-01

    About 10,000 people live in communities surrounding the former copper smelter at Anaconda, Montana. Most of these people live in the town of Anaconda, which is generally upwind of the smelter. The smelter ceased operations in 1980, after almost a century of ore processing. Soil and dust on the smelter site and in the vicinity remain contaminated with arsenic, although at this time air and drinking water arsenic levels are not elevated. Results of soil and dust sampling for arsenic in the communities around the smelter are reported. In the town of Anaconda, surface soil arsenic levels from residential sites have averaged around 100 ppm or greater. Young children are generally believed to be the population with the most nonoccupational exposure to soil. Several models of exposure to environmental arsenic in the Anaconda area have predicted that children living in all communities surrounding the smelter would be having significant and measurable exposure to arsenic. Two exposures surveys, conducted while the smelter was operative, demonstrated that excess exposure to arsenic was occurring in young children. Until the present surveys, no exposure data had been collected since the smelter was closed.

  1. Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure

    SciTech Connect

    Pu, Y.-S.; Yang, S.-M.; Huang, Y.-K.; Chung, C.-J.; Huang, Steven K.; Chiu, Allen Wen-Hsiang; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M. . E-mail: ymhsueh@tmu.edu.tw

    2007-01-15

    Arsenic exposure is associated with an increased risk of urothelial carcinoma (UC). To explore the association between individual risk and urinary arsenic profile in subjects without evident exposure, 177 UC cases and 313 age-matched controls were recruited between September 2002 and May 2004 for a case-control study. Urinary arsenic species including the following three categories, inorganic arsenic (As{sup III} + As{sup V}), monomethylarsonic acid (MMA{sup V}) and dimethylarsinic acid (DMA{sup V}), were determined with high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Arsenic methylation profile was assessed by percentages of various arsenic species in the sum of the three categories measured. The primary methylation index (PMI) was defined as the ratio between MMA{sup V} and inorganic arsenic. Secondary methylation index (SMI) was determined as the ratio between DMA{sup V} and MMA{sup V}. Smoking is associated with a significant risk of UC in a dose-dependent manner. After multivariate adjustment, UC cases had a significantly higher sum of all the urinary species measured, higher percent MMA{sup V}, lower percent DMA{sup V}, higher PMI and lower SMI values compared with controls. Smoking interacts with the urinary arsenic profile in modifying the UC risk. Differential carcinogenic effects of the urinary arsenic profile, however, were seen more prominently in non-smokers than in smokers, suggesting that smoking is not the only major environmental source of arsenic contamination since the UC risk differs in non-smokers. Subjects who have an unfavorable urinary arsenic profile have an increased UC risk even at low exposure levels.

  2. The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease: Evidence from the Strong Heart Study

    PubMed Central

    Zheng, Laura Y.; Umans, Jason G.; Yeh, Fawn; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K; Bandeen-Roche, Karen; Guallar, Eliseo; Howard, Barbara V.; Weaver, Virginia M.; Navas-Acien, Ana

    2016-01-01

    Background Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults. Methods We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study (SHS) in 3,851 adults aged 45–74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as eGFR≤60 mL/min/1.73m2, kidney transplant or dialysis. Results CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted OR (95% CI) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR 0.4 (0.3, 0.4)). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR 3.8 and 1.8). The adjusted HR of incident CKD for an IQR in ΣAs was 1.2 (1.03, 1.41). The corresponding HR for inorganic arsenic, monomethylarsonate and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3) and 1.2 (1.0, 1.4). Conclusions The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relationship between arsenic and kidney disease development. PMID:25929811

  3. Responses of Daphnia magna to pulsed exposures of arsenic.

    PubMed

    Hoang, Tham C; Gallagher, Jeffrey S; Klaine, Stephen J

    2007-06-01

    Research on the toxicity of arsenic has focused on sublethal effects that do not provide sufficient information for risk estimation. While most studies have focused on organism response to constant arsenic exposures, organisms in nature are exposed to fluctuating As concentrations. Consequently, results obtained from standardized bioassays with constant exposures may not adequately characterize risk to indigenous biota. This research was designed to characterize the response of Daphnia magna to fluctuating arsenic exposures during 21-day experiments. At concentrations > or =3000 microg/L As, 21-day pulsed exposure mortality increased as a function of exposure concentration and duration. In addition, 21-day pulsed exposure mortality increased with increasing recovery time. Pulsed As exposure did not affect the growth of D. magna over 21 days. Twenty-one day accumulative reproduction of D. magna was only affected by pulsed exposures of high As concentration and long durations. PMID:17497644

  4. Multiple risk factors associated with arsenic-induced skin cancer: effects of chronic liver disease and malnutritional status.

    PubMed Central

    Hsueh, Y. M.; Cheng, G. S.; Wu, M. M.; Yu, H. S.; Kuo, T. L.; Chen, C. J.

    1995-01-01

    In order to evaluate the prevalence and multiple risk factors of arsenic-induced skin cancer among residents in Taiwanese villages in which chronic arseniasis is hyperendemic, a total of 1571 subjects aged 30 or more years were recruited between September 1988 and March 1989. All of them were interviewed personally by a public health nurse using a structured questionnaire, and 1081 interviewed study subjects, including 468 men and 613 women, participated in physical examination, giving a participation rate of 68.8%. The overall prevalence of skin cancer was as high as 6.1%, showing an increase with age in both men and women. There was a significant dose-response relation between skin cancer prevalence and chronic arsenic exposure as indexed by duration of residence in the endemic area, duration of consumption of high-arsenic artesian well water, average arsenic exposure in parts per million (p.p.m.) and cumulative arsenic exposure in p.p.m.-years. Chronic carriers of hepatitis B surface antigen with liver dysfunction had an increased prevalence of skin cancer. Undernourishment, indexed by a high consumption of dried sweet potato as a staple food, was also significantly associated with an increased prevalence of arsenic-induced skin cancer. All these risk factors remained statistically significant in the multiple logistic regression analysis. Consistent with animal experiments, the findings imply that liver function and nutritional status may affect the metabolism of inorganic arsenic and the development of subsequent skin cancers. PMID:7819025

  5. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    SciTech Connect

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  6. Excretion of arsenic in urine as a function of exposure to arsenic in drinking water.

    PubMed Central

    Calderon, R L; Hudgens, E; Le, X C; Schreinemachers, D; Thomas, D J

    1999-01-01

    Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first morning urine voids for up to 5 consecutive days. The study population was 56% male, and 44% was younger than 18 years of age. On one day of the study period, all voided urines were collected over a 24-hr period. Arsenic intake from drinking water was estimated from daily food diaries. Comparison between the concentration of As in individual urine voids with that in the 24-hr urine collection indicated that the concentration of As in urine was stable throughout the day. Comparison of the concentration of As in each first morning urine void over the 5-day study period indicated that there was little day-to-day variation in the concentration of As in urine. The concentration of As in drinking water was a better predictor of the concentration of As in urine than was the estimated intake of As from drinking water. The concentration of As in urine did not vary by gender. An age-dependent difference in the concentration of As in urine may be attributed to the higher As dosage rate per unit body weight in children than in adults. These findings suggest that the analysis of a small number of urine samples may be adequate to estimate an individual's exposure to InAs from drinking water and that the determination of the concentration of InAs in a drinking water supply may be a useful surrogate for estimating exposure to this metalloid. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10417365

  7. Prenatal arsenic exposure and drowning among children in Bangladesh

    PubMed Central

    Rahman, Mahfuzar; Sohel, Nazmul; Kumar Hore, Samar; Yunus, Mohammad; Bhuiya, Abbas; Kim Streatfield, Peter

    2015-01-01

    There is increasing concern regarding adverse effects of prenatal arsenic exposure on the neurodevelopment of children. We analyzed mortality data for children, who were born to 11,414 pregnant women between 2002 and 2004, with an average age of 5 years of follow-up. Individual drinking-water arsenic exposure during pregnancy was calculated using tubewell water arsenic concentration between last menstrual period and date of birth. There were 84 drowning deaths registered, with cause of death ascertained using verbal autopsy (International Classification of Diseases, 10th revision, codes X65–X70). The prenatal water arsenic exposure distribution was tertiled, and the risk of drowning mortality was estimated by Cox proportional hazard models, adjusted for potential confounders. We observed a significant association between prenatal arsenic exposure and drowning in children aged 1–5 years in the highest exposure tertile (HR=1.74, 95% CI: 1.03–2.94). This study showed that in utero arsenic exposure might be associated with excess mortality among children aged 1–5 years due to drowning. PMID:26511679

  8. Association between Arsenic Exposure and Diabetes: A Meta-Analysis

    PubMed Central

    Sung, Tzu-Ching; Huang, Jhih-Wei; Guo, How-Ran

    2015-01-01

    Studies on the association between arsenic exposure and diabetes mellitus (DM) yielded inconsistent results. Epidemiologic data on the associations between arsenic exposures via inhalation and DM are limited. Therefore, we conducted a meta-analysis to evaluate the risk of DM associated with arsenic exposure. We searched the related literature through a systematic approach and analyzed the data according to the exposure route (inhalation and ingestion). We used random-effect models to estimate the summary relative risks (RRs) for DM associated with arsenic exposure and used I2 statistics to assess the heterogeneity of studies. We identified 38 relevant studies, of which the 32 on the ingestion route showed a significant association between arsenic exposure and DM (RR = 1.57; 95% CI 1.27–1.93). Focusing on the 24 studies in which the diagnosis of DM was confirmed using laboratory tests or medical records, we found that the summary RR was 1.71 (95% CI 1.32–2.23), very close to the overall estimates. We concluded that ingested arsenic is associated with the development of DM, but the heterogeneity among the studies may affect the results. PMID:26000288

  9. Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India

    PubMed Central

    2012-01-01

    Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk. PMID:22883023

  10. Arsenic

    MedlinePlus

    ... mainly found in its less toxic organic form. Industrial processes Arsenic is used industrially as an alloying ... are also required to reduce occupational exposure from industrial processes. Education and community engagement are key factors ...

  11. Evaluation of urinary speciated arsenic in NHANES: Issues in interpretation in the context of potential inorganic arsenic exposure

    EPA Science Inventory

    Urinary dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA) are among the commonly used biomarkers for inorganic arsenic (iAs) exposure, but may also arise from seafood consumption and organoarsenical pesticide applications. We examined speciated urinary arsenic data from...

  12. Association between Lifetime Exposure to Inorganic Arsenic in Drinking Water and Coronary Heart Disease in Colorado Residents

    PubMed Central

    Byers, Tim; Hokanson, John E.; Meliker, Jaymie R.; Zerbe, Gary O.; Marshall, Julie A.

    2014-01-01

    Background: Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure. Objectives: We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. Methods: This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. Results: We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20–30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30–45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45–88 μg/L). Conclusions: Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population. Citation: James KA, Byers T, Hokanson JE, Meliker JR, Zerbe GO, Marshall JA. 2015. Association between lifetime exposure to

  13. Evaluation of arsenic speciation in rainbow trout and fathead minnows from dietary exposure

    EPA Science Inventory

    The concentration of total arsenic and various arsenic species were measured in food and fish tissue samples from two dietary arsenic exposures to juvenile fish. For arsenic speciation, samples were extracted with 10% MeOH and analyzed by HPLC/ICPMS. Total arsenic concentration...

  14. Chronic arsenic poisoning in drinking water in Inner Mongolia and its associated health effects.

    PubMed

    Guo, Juan X; Hu, Lin; Yand, Peng Z; Tanabe, Kimiko; Miyatalre, Munetoshi; Chen, Yao

    2007-10-01

    Since 1990, a large number of people have been experiencing various health problems from drinking arsenic contaminated water (50-1860 microg/L) in 13 counties of Inner Mongolia, China, most of which are located in the Hetao Plain area. It is calculated that 411,243 people are currently at risk from arsenic poisoning. Clinical and epidemiological investigations were carried out on 13,021 people to ascertain the nature and degree of morbidity that occurred due to chronic arsenic toxicity. In all of the studied patients, 22% had typical hyperkeratosis on the palms or soles and some had raindrop-like hyperpigmentation and depigmentation on the trunk. Other data recorded included subjective and objective symptoms, such as chronic cough (35.0%) and insomnia (37.5%). During physical checkups of 680 villagers in arsenic affected areas, liver function tests showed elevated globulin levels in 6.8% (P value=0.006) of the subjects. Neurotoxicity manifesting as loss of hearing 5.88 (P value=0.005), loss of taste 5.44% (P value=0.001), blurred vision 17.35% (P value=0.000), tingling and numbness of the limbs 33.53% (P value=0.000) and hypertension 8.09% (P value=0.000) were significantly higher in the arsenic affected villages and arsenic pollution also seemed to affect patients' social life and mental health. To solve the problem of arsenic exposure, the quality of drinking water needs to be improved by reducing the arsenic content. We also plan to carry out a survey to detect the incidence and types of cancer among this population. PMID:17952786

  15. A Dose-Response Study of Arsenic Exposure and Markers of Oxidative Damage in Bangladesh

    PubMed Central

    Harper, Kristin N.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Oka, Julie; Calancie, Larissa; Slavkovich, Vesna; Levy, Diane; Siddique, Abu; Alam, Shafiul; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph H.; Gamble, Mary V.

    2014-01-01

    Objective To evaluate the dose-response relationship between arsenic exposure and markers of oxidative damage in Bangladeshi adults. Methods We recruited 378 participants drinking from wells assigned to five water arsenic exposure categories; the distribution of subjects was as follows: 1) <10 μg/L (n=76); 2) 10–100 μg/L (n=104); 3) 101–200 μg/L (n=86); 4) 201–300 μg/L (n=67); and 5) > 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8-oxo-2’-deoxyguanosine (8-oxo-dG) and plasma protein carbonyls were measured to assess oxidative damage. Results None of our measures of arsenic exposure were significantly associated with protein carbonyl or 8-oxo-dG levels. Conclusions We found no evidence to support a significant relationship between chronic exposure to arsenic-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults. PMID:24854259

  16. Arsenic exposure and DNA methylation among elderly men

    PubMed Central

    Lambrou, Angeliki; Baccarelli, Andrea; Wright, Robert O.; Weisskopf, Marc; Bollati, Valentina; Amarasiriwardena, Chitra; Vokonas, Pantel; Schwartz, Joel

    2012-01-01

    BACKGROUND Arsenic exposure has been linked to epigenetic modifications such as DNA methylation in in vitro and animal studies. This association has also been explored in highly exposed human populations, but studies among populations environmentally exposed to low arsenic levels are lacking. METHODS We evaluated the association between exposure to arsenic, measured in toenails, and blood DNA methylation in Alu and Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements in elderly men environmentally exposed to low levels of arsenic. We also explored potential effect modification by plasma folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6). The study population was 581 participants from the Normative Aging Study in Boston, of whom 434, 140, and 7 had 1, 2, and 3 visits, respectively, between 1999-2002 and 2006-2007. We used mixed-effects models and included interaction terms to assess potential effect modification by nutritional factors. RESULTS There was a trend of increasing Alu and decreasing LINE-1 DNA methylation as arsenic exposure increased. In subjects with plasma folate below the median (< 14.1 ng/ml), arsenic was positively associated with Alu DNA methylation (β=0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06μg/g] increase in arsenic) while a negative association was observed in subjects with plasma folate above the median (β=-0.08 [-0.17 to 0.01]). CONCLUSIONS We found an association between arsenic exposure and DNA methylation in Alu repetitive elements that varied by folate level. This suggests a potential role for nutritional factors in arsenic toxicity. PMID:22833016

  17. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    SciTech Connect

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Gonzalez-De Alba, Cesar; Froines, John R.; Espinosa-Fematt, Jorge A.

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  18. Arsenic occurrence in Brazil and human exposure.

    PubMed

    de Figueiredo, Bernardino Ribeiro; Borba, Ricardo Perobelli; Angélica, Rômulo Simões

    2007-04-01

    Environmental exposure to arsenic (As) in terms of public health is receiving increasing attention worldwide following cases of mass contamination in different parts of the world. However, there is a scarcity of data available on As geochemistry in Brazilian territory, despite the known occurrence of As in some of the more severely polluted areas of Brazil. The purpose of this paper is to discuss existing data on As distribution in Brazil based on recent investigations in three contaminated areas as well as results from the literature. To date, integrated studies on environmental and anthropogenic sources of As contamination have been carried out only in three areas in Brazil: (1) the Southeastern region, known as the Iron Quadrangle, where As was released into the drainage systems, soils and atmosphere as a result of gold mining; (2) the Ribeira Valley, where As occurs in Pb-Zn mine wastes and naturally in As-rich rocks and soils; (3) the Amazon region, including the Santana area, where As is associated with manganese ores mined over the last 50 years. Toxicological studies revealed that the populations were not exposed to elevated levels of As, with the As concentrations in surface water in these areas rarely exceeding 10 microg/L. Deep weathering of bedrocks along with formation of Fe/Al-enriched soils and sediments function as a chemical barrier that prevents the release of As into the water. In addition, the tropical climate results in high rates of precipitation in the northern and southeastern regions and, hence, the As contents of drinking water is diluted. Severe cases of human As exposure related to non-point pollution sources have not been reported in Brazil. However, increasing awareness of the adverse health effects of As will eventually lead to a more complete picture of the distribution of As in Brazil. PMID:17351814

  19. Purification and characterization of thiols in an arsenic hyperaccumulator under arsenic exposure.

    PubMed

    Zhang, Weihua; Cai, Yong

    2003-12-15

    Pteris vittata (Chinese brake fern) is the first reported arsenic hyperaccumulator. To investigate the arsenic tolerance mechanism in this plant, reversed-phase HPLC with postcolumn derivatization was used to analyze the thiols induced under arsenic exposure. A major thiol in the plant leaflets was found to be responsive to arsenic exposure. The arsenic-induced compound was purified on a large scale by combining covalent chromatography and preparative reversed-phase HPLC. About 2 mg of this compound was isolated from 1 kg of fresh leaflets. The purified arsenic-induced compound was characterized using electrospray ionization mass spectrometry. A molecular ion (M + 1) of 540 and fragments were obtained, which indicated that the arsenic-induced thiol was a phytochelatin with two subunits (PC(2)). Compared to the classical methods for purification of phytochelatins, this new method is more specific, simple, and rapid and is suitable for purification of PCs in a large scale as well as sample preparation for mass spectrometry analysis. PMID:14670068

  20. In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

    PubMed Central

    2013-01-01

    Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

  1. Arsenic Exposure and Prevalence of Diabetes Mellitus in Korean Adults

    PubMed Central

    Rhee, Sang Youl; Hwang, You-Cheol; Chin, Sang Ouk; Chon, Suk; Kim, Young Seol

    2013-01-01

    It has been suggested that there is an association between environmental, low-level arsenic exposure and the risk of diabetes mellitus (DM), but little research has been conducted. Here, the glucose tolerance status and urinary creatinine adjusted total arsenic concentrations were analyzed in 3,602 subjects ≥ 20 yr of age who were registered for the Korea National Health and Nutrition Examination Survey, 2008-2009. Various demographic parameters were associated with urinary arsenic concentrations. After adjusting for these variables, urinary arsenic concentrations in subjects with DM were significantly higher than those in subjects with normal glucose tolerance and those with impaired fasting glucose (P < 0.001). Compared with the lowest quartile ( < 70.7 µg/g creatinine), the odds ratios and 95% confidence intervals for DM were 1.11 (0.73-1.68), 1.42 (0.94-2.13), and 1.56 (1.03-2.36) for urinary arsenic concentrations of 70.7 to < 117.7, 117.7 to < 193.4, and ≥ 193.4 µg/g creatinine, respectively, following multivariate adjustment. Furthermore, the urinary total arsenic concentration was inversely associated with the insulin secretion index, HOMA2 %B (β = -0.033, P = 0.032). These findings suggest that arsenic exposure, possibly involving beta cell dysfunction, is associated with an increased risk of DM in the Korean population. PMID:23772150

  2. Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico

    SciTech Connect

    Coronado-Gonzalez, Jose Antonio; Razo, Luz Maria del; Garcia-Vargas, Gonzalo; Sanmiguel-Salazar, Francisca; Escobedo-de la Pena, Jorge . E-mail: jorgeep@servidor.unam.mx

    2007-07-15

    Inorganic arsenic exposure in drinking water has been recently related to diabetes mellitus. To evaluate this relationship the authors conducted in 2003, a case-control study in an arseniasis-endemic region from Coahuila, a northern state of Mexico with a high incidence of diabetes. The present analysis includes 200 cases and 200 controls. Cases were obtained from a previous cross-sectional study conducted in that region. Diagnosis of diabetes was established following the American Diabetes Association criteria, with two fasting glucose values {>=}126 mg/100 ml ({>=}7.0 mmol/l) or a history of diabetes treated with insulin or oral hypoglycemic agents. The next subject studied, subsequent to the identification of a case in the cross-sectional study was taken as control. Inorganic arsenic exposure was measured through total arsenic concentrations in urine, measured by hydride-generation atomic absorption spectrophotometry. Subjects with intermediate total arsenic concentration in urine (63.5-104 {mu}g/g creatinine) had two-fold higher risk of having diabetes (odds ratio=2.16; 95% confidence interval: 1.23, 3.79), but the risk was almost three times greater in subjects with higher concentrations of total arsenic in urine (odds ratio=2.84; 95% confidence interval: 1.64, 4.92). This data provides additional evidence that inorganic arsenic exposure may be diabetogenic.

  3. Chronic Arsenic Poisoning Probably Caused by Arsenic-Based Pesticides: Findings from an Investigation Study of a Household

    PubMed Central

    Li, Yongfang; Ye, Feng; Wang, Anwei; Wang, Da; Yang, Boyi; Zheng, Quanmei; Sun, Guifan; Gao, Xinghua

    2016-01-01

    In addition to naturally occurring arsenic, man-made arsenic-based compounds are other sources of arsenic exposure. In 2013, our group identified 12 suspected arsenicosis patients in a household (32 living members). Of them, eight members were diagnosed with skin cancer. Interestingly, all of these patients had lived in the household prior to 1989. An investigation revealed that approximately 2 tons of arsenic-based pesticides had been previously placed near a well that had supplied drinking water to the family from 1973 to 1989. The current arsenic level in the well water was 620 μg/L. No other high arsenic wells were found near the family’s residence. Based on these findings, it is possible to infer that the skin lesions exhibited by these family members were caused by long-term exposure to well water contaminated with arsenic-based pesticides. Additionally, biochemical analysis showed that the individuals exposed to arsenic had higher levels of aspartate aminotransferase and γ-glutamyl transpeptidase than those who were not exposed. These findings might indicate the presence of liver dysfunction in the arsenic-exposed individuals. This report elucidates the effects of arsenical compounds on the occurrence of high levels of arsenic in the environment and emphasizes the severe human health impact of arsenic exposure. PMID:26784217

  4. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: Assessment by real-time PCR array

    EPA Science Inventory

    Arsenic contamination in drinking water has become a great public health concern worldwide. Chronic arsenic exposure results in higher risk of skin, lung and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects o...

  5. Maternal drinking water arsenic exposure and perinatal outcomes in Inner Mongolia, China

    EPA Science Inventory

    Exposure to high levels of arsenic has been reported to increase adverse birth outcomes including spontaneous abortion, preterm birth, and low birthweight. This study evaluated the relationship between maternal arsenic exposure and perinatal endpoints (term birthweight, preterm ...

  6. A Case control study of cardiovascular disease and arsenic exposure in Inner Mongolia, China

    EPA Science Inventory

    Background: Millions of people are at risk from the adverse effects of waterborne arsenic. Although the cardiovascular effects of high exposures to arsenic have been well documented, few individual level prospective studies have assessed cardiovascular risk at moderate exposures....

  7. ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE INORGANIC ARSENIC METHYLATION PHENOTYPE

    EPA Science Inventory

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidence suggest that some of the adverse health effects associated with chronic exposure to in...

  8. Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population.

    PubMed

    Borghini, Andrea; Faita, Francesca; Mercuri, Antonella; Minichilli, Fabrizio; Bustaffa, Elisa; Bianchi, Fabrizio; Andreassi, Maria Grazia

    2016-09-01

    Arsenic-induced health effects may be associated with critically shortened telomeres. However, few data are available on the effects of arsenic exposure on telomere length. The aim of this study was to investigate the effects of chronic arsenic exposure on leukocyte telomere length (LTL) as well as the contribution of common polymorphisms in genes implicated in arsenic metabolism (GSTT1 and GSTM1) and DNA repair (hOGG1 and XRCC1). A group of 241 healthy subjects was enrolled from four areas of Italy known to be affected by natural or anthropogenic arsenic pollution. Urine samples were tested for inorganic As (iAs), monomethylarsinic (MMA) and dimethylarsinic acid (DMA). LTL was evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Genotyping was carried out by PCR-RFLP on leukocyte DNA. In multiple linear regression analysis, LTL was significantly and inversely correlated with age (β = -0.231, P = 0.006) and showed a certain trend toward significance with iAs urinary concentration (log10 iAs, β = -0.106, P = 0.08). The genotype distribution showed significant associations between GSTT1 and the As concentration (log10 iAs, P = 0.01) and metabolite patterns (log10 DMA, P = 0.05) in the urine. However, GST genes did not interact with arsenic exposure in the modulation of LTL. Conversely, the combined presence of a higher level of iAs + MMA + DMA ≥ 19.3 μg/l (F = 6.0, P interaction = 0.01), Asi ≥ 3.86 (F = 3.9, P interaction = 0.04) μg/l, iAs + MMA + DMA ≥ 15 μg/l (F = 4.2, P interaction = 0.04) and hOGG1 Cys allele was associated with a significantly lower LTL. An interaction between XRCC1 Arg399Gln and arsenic exposure was also observed (all P interaction = 0.04). These findings suggest that telomere shortening may represent a mechanism that contributes to arsenic-related disease. The interaction of hOGG1 and XRCC1 DNA repair polymorphisms and exposure enhances telomeric DNA damage. Future studies are warranted to understand

  9. Arsenic exposures in Mississippi: A review of cases

    SciTech Connect

    Park, M.J.; Currier, M. )

    1991-04-01

    Arsenic poisonings occur in Mississippi despite public education campaigns to prevent poisonings in the home. We reviewed 44 Mississippi cases of arsenic exposures occurring from January 1986 to May 1990. We compared the epidemiologic differences between unintentional and intentional poisonings. Cases were found and characterized through the two toxicology laboratories and hospital records. Arsenic-based rodenticides were the arsenic source in 23 of the 44 exposures. Other sources were monosodium methylarsenate (4 cases), dodecyl ammonium methane arsonate (5 cases), and other compounds (12 cases). Of the 44 exposures, 27 were unintentional, 7 were suicide attempts, 6 were homicide attempts, and 4 were of unknown intent. Of the 27 unintentionally exposed patients, 19 were black and 14 were male; their median age was 3 years. Of the 13 intentionally poisoned persons, 9 were male and 10 were black, with a median age of 28 years. Six of the seven patients who attempted suicide were white; four of the six victims of attempted homicide were black. We recommend removal of remaining bottles of arsenic-based rodenticides from store shelves, and we urge practicing physicians to warn patients of the dangers of using such rodenticides.

  10. Residential exposure to drinking water arsenic in Inner Mongolia, China

    SciTech Connect

    Ning Zhixiong; Lobdell, Danelle T.; Kwok, Richard K. Liu Zhiyi; Zhang Shiying; Ma Chenglong; Riediker, Michael; Mumford, Judy L.

    2007-08-01

    In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic arsenism has been reported in earlier studies. A survey of the arsenic contamination among wells from groundwater was conducted to better understand the occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all wells in the region) were analyzed for their arsenic-content. Methods used to detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5 {mu}g of As/L); Spot method (detection limit, 10 {mu}g of As/L); and air assisted Colorimetry method (detection limit, 20 {mu}g of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 {mu}g of As/L. Elevated concentrations were related to well depth (10 to 29 m), the date the well was built (peaks from 1980-1990), and geographic location (near mountain range). Over 25,900 individuals utilized wells with drinking water arsenic concentrations above 20 {mu}g of As/L (14,500 above 50 {mu}g of As/L-the current China national standard in drinking water and 2198 above 300 {mu}g of As/L). The presented database of arsenic in wells of the Ba Men region provides a useful tool for planning future water explorations when combined with geological information as well as support for designing upcoming epidemiological studies on the effects of arsenic in drinking water for this region.

  11. RESIDENTIAL EXPOSURE TO DRINKING WATER ARSENIC IN INNER MONGOLIA, CHINA

    EPA Science Inventory

    Residential exposure to drinking water arsenic in Inner Mongolia, China
    Zhixiong Ning1, Richard K. Kwok2, Zhiyi Liu1, Shiying Zhang1, Chenglong Ma1, Danelle T. Lobdell2, Michael Riediker3 and Judy L. Mumford2
    1) Institute of Endemic Disease for Prevention and Treatment in I...

  12. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    PubMed Central

    Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

    2016-01-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

  13. Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

    EPA Science Inventory

    Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

  14. Well Water Arsenic Exposure, Arsenic Induced Skin-Lesions and Self-Reported Morbidity in Inner Mongolia

    PubMed Central

    Xia, Yajuan; Wade, Timothy J.; Wu, Kegong; Li, Yanhong; Ning, Zhixiong; Le, X Chris; He, Xingzhou; Chen, Binfei; Feng, Yong; Mumford, Judy L.

    2009-01-01

    Residents of the Bayingnormen region of Inner Mongolia have been exposed to arsenic-contaminated well water for over 20 years, but relatively few studies have investigated health effects in this region. We surveyed one village to document exposure to arsenic and assess the prevalence of arsenic-associated skin lesions and self-reported morbidity. Five-percent (632) of the 12,334 residents surveyed had skin lesions characteristics of arsenic exposure. Skin lesions were strongly associated with well water arsenic and there was an elevated prevalence among residents with water arsenic exposures as low as 5 μg/L-10 μg/L. The presence of skin lesions was also associated with self-reported cardiovascular disease. PMID:19440430

  15. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice.

    PubMed

    Moreno Ávila, Claudia Leticia; Limón-Pacheco, Jorge H; Giordano, Magda; Rodríguez, Verónica M

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID:27375740

  16. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice

    PubMed Central

    Moreno Ávila, Claudia Leticia

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID:27375740

  17. Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic.

    PubMed

    Recio-Vega, Rogelio; González-Cortes, Tania; Olivas-Calderón, Edgar; Clark Lantz, R; Jay Gandolfi, A; Michel-Ramirez, Gladis

    2016-08-01

    Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism-related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6-12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT-Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT-Met287Thr polymorphism with %MMA and between the GSTO1-Glu155del and As(v) was found; whereas, a negative relationship was identified between AS3MT-Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1-Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516-525, 2016. © 2016 Wiley Periodicals, Inc. PMID:27327299

  18. Low-level environmental arsenic exposure correlates with unexplained male infertility risk.

    PubMed

    Wang, Xiaofei; Zhang, Jie; Xu, Weipan; Huang, Qingyu; Liu, Liangpo; Tian, Meiping; Xia, Yankai; Zhang, Weibing; Shen, Heqing

    2016-11-15

    Humans are exposed to arsenic via drinking water, dietary intake and inhaled particulates. Endemic chronic arsenic exposure related reproductive toxicity is well documented, but the effect of low-level general environmental arsenic exposure on unexplained male infertility (UMI) remains unclear. In this case-control study, we aimed to investigate the relationship between non-geogenic environmental arsenic exposure and UMI risk. One hundred and one infertile men with normal semen as cases and sixty one fertile men as controls were recruited. Five urinary arsenic species: pentavalent arsenate (Asi(V)), trivalent arsenite (Asi(III)), methylated to monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), arsenobetaine (AsB) were quantitatively measured by liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). To assess the semen quality, semen volume, sperm concentration, total motility, and progressive motility were measured. The nonparametric Mann-Whitney U test was used to compare the differences of arsenic species and index between the case and the control group; we observed that concentrations of Asi(V), AsB, MMA(V), DMA(V), total inorganic As and total As were significantly higher in the cases than the controls. The urine Asi(V) level increased more than twenty folds in case group. Moreover, higher redox index (Asi(V)/Asi(III)) and lower primary arsenic methylation index (PMI=MMA(V)/Asi) were observed for case group. Furthermore, through the logistic regression analysis, we observed that the urine Asi(V) level and PMI were most significantly associated with UMI risk among the observations. Specifically, in comparison to the first quartile, the subjects with higher Asi(V) levels were more likely to exhibit UMI with increasing adjusted odds ratios (AORs) (adjusted by age, body mass index, drinking status and smoking status) of 8.39 [95% confidence interval (CI), 2.59-27.17], 13.12 (95% CI, 3.44-50.12) and 36.51 (95% CI, 8

  19. Biological and Behavorial Factors Modify Biomarkers of Arsenic Exposure in a U.S. Population**

    EPA Science Inventory

    Although consumption of drinking water contaminated with inorganic arsenic is usually considered the primary exposure route, aggregate exposure to arsenic depends on direct consumption of water, use of water in food preparation, and the presence in arsenicals in foods. To gain in...

  20. Maternal drinking water arsenic exposure and perinatal outcomes in Inner Mongolia, China, Journal

    EPA Science Inventory

    BACKGROUND: Bayingnormen is a region located in western Inner Mongolia China with a population that is exposed to a wide range of drinking water Arsenic concentrations. This study evaluated the relationship between maternal drinking water arsenic exposure and perinatal endpoints ...

  1. On the interaction between occupational arsenic exposure and smoking and its relationship to lung cancer.

    PubMed

    Pershagen, G; Wall, S; Taube, A; Linnman, L

    1981-12-01

    The interaction between occupational arsenic exposure and tobacco smoking and its relationship to lung cancer mortality among 228 deceased Swedish copper smelter workers was studied with the case-referent technique. Arsenic exposure was assessed via detailed company records, and information on smoking habits was gathered from the next of kin. The age standardized rate ratio for death from lung cancer was 3.0 for arsenic-exposed nonsmokers and 4.9 for smokers without occupational arsenic exposure in relation to nonarsenic-exposed nonsmokers. For arsenic-exposed smokers the rate ratio was 14.6, indicating a multiplicative effect of the two exposures. Eighty-five percent of all deaths from long cancer among the smelter workers could be "explained" by arsenic exposure and/or smoking. The interaction between arsenic and smoking suggests that a strong preventive effect on lung cancer incidence could be obtained by decreasing either one of the exposures or by disaggregating them. PMID:7347915

  2. Altered Gene Expression by Low-Dose Arsenic Exposure in Humans and Cultured Cardiomyocytes: Assessment by Real-Time PCR Arrays

    PubMed Central

    Mo, Jinyao; Xia, Yajuan; Wade, Timothy J.; DeMarini, David M.; Davidson, Mercy; Mumford, Judy

    2011-01-01

    Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-μM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes. PMID:21776218

  3. Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: assessment by real-time PCR arrays.

    PubMed

    Mo, Jinyao; Xia, Yajuan; Wade, Timothy J; DeMarini, David M; Davidson, Mercy; Mumford, Judy

    2011-06-01

    Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-μM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes. PMID:21776218

  4. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    SciTech Connect

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  5. Lead, arsenic and manganese metal mixture exposures: focus on biomarkers of effect

    PubMed Central

    Andrade, VL; Mateus, ML; Batoréu, MC; Aschner, M; Marreilha dos Santos, AP

    2015-01-01

    Summary The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As) and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These 3 metals are commonly detected in different environmental, occupational and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals represents an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters and effects on hematopoietic system, we address putative biomarkers, which may be assist in assessing onset of neurological diseases associated with exposure to this metal mixture. PMID:25693681

  6. Well water arsenic exposure, arsenic induced skin-lesions and self-reported morbidity in Inner Mongolia

    EPA Science Inventory

    Arsenic exposure from contaminated well water is a cause of skin and bladder cancer and linked to numerous other adverse health effects. Residents of the Bayingnormen region of Inner Mongolia, China, have been exposed to arsenic-contaminated well water for over 20 years but few s...

  7. Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

    PubMed Central

    Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

    2014-01-01

    Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10

  8. Exposure of Soil Microbial Communities to Chromium and Arsenic Alters Their Diversity and Structure

    PubMed Central

    Rizvi, Fariha Z.; Rehman, Yasir; Faisal, Muhammad; Hasnain, Shahida; McInerney, Michael J.; Krumholz, Lee R.

    2012-01-01

    Extensive use of chromium (Cr) and arsenic (As) based preservatives from the leather tanning industry in Pakistan has had a deleterious effect on the soils surrounding production facilities. Bacteria have been shown to be an active component in the geochemical cycling of both Cr and As, but it is unknown how these compounds affect microbial community composition or the prevalence and form of metal resistance. Therefore, we sought to understand the effects that long-term exposure to As and Cr had on the diversity and structure of soil microbial communities. Soils from three spatially isolated tanning facilities in the Punjab province of Pakistan were analyzed. The structure, diversity and abundance of microbial 16S rRNA genes were highly influenced by the concentration and presence of hexavalent chromium (Cr (VI)) and arsenic. When compared to control soils, contaminated soils were dominated by Proteobacteria while Actinobacteria and Acidobacteria (which are generally abundant in pristine soils) were minor components of the bacterial community. Shifts in community composition were significant and revealed that Cr (VI)-containing soils were more similar to each other than to As contaminated soils lacking Cr (VI). Diversity of the arsenic resistance genes, arsB and ACR3 were also determined. Results showed that ACR3 becomes less diverse as arsenic concentrations increase with a single OTU dominating at the highest concentration. Chronic exposure to either Cr or As not only alters the composition of the soil bacterial community in general, but affects the arsenic resistant individuals in different ways. PMID:22768219

  9. Exposure of soil microbial communities to chromium and arsenic alters their diversity and structure.

    PubMed

    Sheik, Cody S; Mitchell, Tyler W; Rizvi, Fariha Z; Rehman, Yasir; Faisal, Muhammad; Hasnain, Shahida; McInerney, Michael J; Krumholz, Lee R

    2012-01-01

    Extensive use of chromium (Cr) and arsenic (As) based preservatives from the leather tanning industry in Pakistan has had a deleterious effect on the soils surrounding production facilities. Bacteria have been shown to be an active component in the geochemical cycling of both Cr and As, but it is unknown how these compounds affect microbial community composition or the prevalence and form of metal resistance. Therefore, we sought to understand the effects that long-term exposure to As and Cr had on the diversity and structure of soil microbial communities. Soils from three spatially isolated tanning facilities in the Punjab province of Pakistan were analyzed. The structure, diversity and abundance of microbial 16S rRNA genes were highly influenced by the concentration and presence of hexavalent chromium (Cr (VI)) and arsenic. When compared to control soils, contaminated soils were dominated by Proteobacteria while Actinobacteria and Acidobacteria (which are generally abundant in pristine soils) were minor components of the bacterial community. Shifts in community composition were significant and revealed that Cr (VI)-containing soils were more similar to each other than to As contaminated soils lacking Cr (VI). Diversity of the arsenic resistance genes, arsB and ACR3 were also determined. Results showed that ACR3 becomes less diverse as arsenic concentrations increase with a single OTU dominating at the highest concentration. Chronic exposure to either Cr or As not only alters the composition of the soil bacterial community in general, but affects the arsenic resistant individuals in different ways. PMID:22768219

  10. Arsenic in Drinking Water and Mortality for Cancer and Chronic Diseases in Central Italy, 1990-2010

    PubMed Central

    D’Ippoliti, Daniela; Santelli, Enrica; De Sario, Manuela; Scortichini, Matteo; Davoli, Marina; Michelozzi, Paola

    2015-01-01

    Background In several volcanic areas of Italy, arsenic levels exceed European regulatory limits (10 μg/L in drinking water). There is still uncertainty about health risks from arsenic at low-medium doses (<100 μg/L). Objectives A large population-based study using an administrative cohort of residents in the Viterbo province (Central Italy), chronically exposed to low-medium arsenic levels via drinking water, was investigated to evaluate the effects of a lifetime exposure to arsenic on mortality from cancers and chronic diseases. Methods The study population consisted of 165,609 residents of 17 municipalities, followed from 1990 until 2010. Average individual arsenic exposure at the first residence (AsI) was estimated through a space-time modeling approach using residential history and arsenic concentrations from water supply. A time-dependent Cumulative Arsenic dose Indicator (CAI) was calculated, accounting for daily water intake and exposure duration. Mortality Hazard Ratios (HR) were estimated by gender for different diseases using Cox proportional models, adjusting for individual and area-level confounders. A flexible non-parametric approach was used to investigate dose-response relationships. Results Mean AsI exposure was 19.3 μg/L, and average exposure duration was 39.5 years. Associations of AsI and CAI indicators with several diseases were found, with greatest risks found for lung cancer in both sexes (HR = 2.61 males; HR = 2.09 females), myocardial infarction, peripheral arterial disease and COPD in males (HR = 2.94; HR = 2.44; HR = 2.54 respectively) and diabetes in females (HR = 2.56). For lung cancer and cardiovascular diseases dose-response relationship is modelled by piecewise linear functions revealing effects even for doses lower than 10 μg/L, and no threshold dose value was identified as safe for health. Conclusions Results provide new evidence for risk assessment of low-medium concentrations of arsenic and contribute to the ongoing debate

  11. Relation of arsenic exposure to lung cancer among tin miners in Yunnan Province, China.

    PubMed Central

    Taylor, P R; Qiao, Y L; Schatzkin, A; Yao, S X; Lubin, J; Mao, B L; Rao, J Y; McAdams, M; Xuan, X Z; Li, J Y

    1989-01-01

    The relation of mining and smelting exposure to arsenic and lung cancer was studied among tin miners in Yunnan Province in the People's Republic of China. Interviews were conducted in 1985 with 107 living tin miners who had lung cancer and an equal number of age matched controls from among tin miners without lung cancer to obtain information on risk factors for lung cancer including detailed history of employment and tobacco use. Occupational history was combined with industrial hygiene data to estimate cumulative arsenic exposure. Similar methods were also used to estimate radon exposure for simultaneous evaluation in this analysis. The results indicate that subjects in the highest quarter of cumulative arsenic exposure have a relative risk of 22.6 compared with subjects without exposure after adjusting for tobacco and radon exposure, and a positive dose response relation was observed. Simultaneous evaluation of arsenic and tobacco exposure indicates a greater risk for arsenic, whereas simultaneous assessment of arsenic and radon exposure suggests radon to be the greater risk. There is no evidence of synergism between arsenic and tobacco exposure. Among arsenic exposed individuals, cases of lung cancer have longer duration but lower average intensity of arsenic exposure than controls, indicating that duration of exposure to arsenic may be more important than intensity in the aetiology of lung cancer. Finally, risk of lung cancer among workers exposed to arsenic only in mining is only slightly less than for miners whose exposure to arsenic was limited to smelting, although risks are highest when workers were exposed to both mining and smelting. PMID:2611163

  12. An assessment of health risks associated with arsenic exposure via consumption of homegrown vegetables near contaminated glassworks sites.

    PubMed

    Uddh-Söderberg, Terese E; Gunnarsson, Sara J; Hogmalm, K Johan; Lindegård, M I Boel G; Augustsson, Anna L M

    2015-12-01

    The health risk posed by arsenic in vegetables grown in private gardens near 22 contaminated glassworks sites was investigated in this study. Firstly, vegetable (lettuce and potato) and soil samples were collected and arsenic concentrations measured to characterize the arsenic uptake in the selected crops. Secondly, a probabilistic exposure assessment was conducted to estimate the average daily intake (ADIveg), which was then evaluated against toxicological reference values by the calculation of hazard quotients (HQs) and cancer risks (CRs). The results show that elevated arsenic concentrations in residential garden soils are mirrored by elevated concentrations in vegetables, and that consumption of these vegetables alone may result in an unacceptable cancer risk; the calculated reasonable maximum exposure, for example, corresponded to a cancer incidence 20 times higher than the stated tolerance limit. However, the characterization of risk depends to a great extent on which toxicological reference value is used for comparison, as well as how the exposure is determined. Based on the assumptions made in the present study, the threshold levels for chronic non-carcinogenic or acute effects were not exceeded, but the cancer risks indicated highlight the need for further exposure studies, as dietary intake involves more than just homegrown vegetables and total exposure is a function of more than just one exposure pathway. In addition, glassworks sites--and contaminated sites in general--contain multiple contaminants, affecting the final and total risk. PMID:26204055

  13. Arsenicals in maternal and fetal mouse tissues after gestational exposure to arsenite

    PubMed Central

    Devesa, Vicenta; Adair, Blakely M.; Liu, Jie; Waalkes, Michael P.; Diwan, Bhalchandra A.; Styblo, Miroslav; Thomas, David J.

    2008-01-01

    Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of these exposure regimens. Tissues were collected from three females and from associated fetuses exposed to each dosage level. Concentrations of total speciated arsenic (sum of inorganic, methyl, and dimethyl arsenic) were higher in maternal tissues than in placenta and fetal tissues; total speciated arsenic concentration in placenta exceeded those in fetal tissues. Significant dosage-dependent (42.5 ppm versus 85 ppm of arsenite in drinking water) differences were found in total speciated arsenic concentrations in maternal lung (p < 0.01) and liver (p < 0.001). Total speciated arsenic concentrations did not differ significantly between dosage levels for maternal blood or for fetal lung, liver, and blood, or for placenta. Percentages of inorganic, methyl, or dimethyl arsenic in maternal or fetal tissues were not dosage-dependent. Over the range of total speciated arsenic concentrations in most maternal and fetal tissues, dimethyl arsenic was the most abundant arsenical. However, in maternal liver at the highest total speciated arsenic concentration, inorganic arsenic was the most abundant arsenical, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ. Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus. PMID:16753250

  14. Increased mortality associated with well-water arsenic exposure in Inner Mongolia, China.

    PubMed

    Wade, Timothy J; Xia, Yajuan; Wu, Kegong; Li, Yanhong; Ning, Zhixiong; Le, X Chris; Lu, Xiufen; Feng, Yong; He, Xingzhou; Mumford, Judy L

    2009-03-01

    We conducted a retrospective mortality study in an Inner Mongolian village exposed to well water contaminated by arsenic since the 1980s. Deaths occurring between January 1, 1997 and December 1, 2004 were classified according to underlying cause and water samples from household wells were tested for total arsenic. Heart disease mortality was associated with arsenic exposure, and the association strengthened with time exposed to the water source. Cancer mortality and all-cause mortality were associated with well-water arsenic exposure among those exposed 10-20 years. This is the first study to document increased arsenic-associated mortality in the Bayingnormen region of Inner Mongolia. PMID:19440436

  15. DEVELOPMENT OF ARSENIC SPECIATION METHODOLOGY FOR DETERMINING BACKGROUND EXPOSURE LEVELS OF INORGANIC ARSENIC IN DIETARY SAMPLES AND APPLICATION TO IN VITRO BIOACCESSIBILITY STUDIES

    EPA Science Inventory

    Ingestion of arsenic is the primary route of exposure for most people, with dietary intake and drinking water as the primary sources of that exposure. Traditionally, measurements of arsenic dietary intake are based on food consumption data coupled with total arsenic data from a ...

  16. Association of oxidative stress with arsenic methylation in chronic arsenic-exposed children and adults

    SciTech Connect

    Xu Yuanyuan; Wang Yi; Zheng Quanmei; Li Xin; Li Bing; Jin Yaping; Sun Xiance; Sun Guifan

    2008-10-01

    Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress.

  17. Postnatal arsenic exposure and attention impairment in school children.

    PubMed

    Rodríguez-Barranco, Miguel; Gil, Fernando; Hernández, Antonio F; Alguacil, Juan; Lorca, Andres; Mendoza, Ramón; Gómez, Inmaculada; Molina-Villalba, Isabel; González-Alzaga, Beatriz; Aguilar-Garduño, Clemente; Rohlman, Diane S; Lacasaña, Marina

    2016-01-01

    Over the last few decades there has been an increased concern about the health risks from exposure to metallic trace elements, including arsenic, because of their potential neurotoxic effects on the developing brain. This study assessed whether urinary arsenic (UA) levels are associated with attention performance and Attention-Deficit/Hyperactivity Disorder (ADHD) in children living in an area with high industrial and mining activities in Southwestern Spain. A cross-sectional study was conducted on 261 children aged 6-9 years. Arsenic levels were determined in urine samples. Attention was measured by using 4 independent tools: a) tests from the Behavioral Assessment and Research System (BARS) designed to measure attention function: Simple Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT); b) AULA Test, a virtual reality (VR)-based test that evaluates children's response to several stimuli in an environment simulating a classroom; c) Child Behavior Checklist (CBCL), administered to parents; and d) Teacher's Report Form (TRF), administered to teachers. Multivariate linear and logistic regression models, adjusted for potential confounders, were used to estimate the magnitude of the association between UA levels and attention performance scores. Higher UA levels were associated with an increased latency of response in RTT (β = 12.3; 95% confidence interval (CI): 3.5-21.1) and SAT (β = 3.6; 95% CI: .4-6.8) as well as with worse performance on selective and focalized attention in the AULA test (β for impulsivity = .6; 95% CI: .1-1.1; β for inattention = .5; 95% CI: .03-1.0). A dose-response relationship was observed between UA levels and inattention and impulsivity scores. In contrast, results from the CBCL and TRF tests failed to show a significant association with UA levels. In conclusion, UA levels were associated with impaired attention/cognitive function, even at levels considered safe. These results provide

  18. Behavioural and physical effects of arsenic exposure in fish are aggravated by aquatic algae.

    PubMed

    Magellan, Kit; Barral-Fraga, Laura; Rovira, Marona; Srean, Pao; Urrea, Gemma; García-Berthou, Emili; Guasch, Helena

    2014-11-01

    Arsenic contamination has global impacts and freshwaters are major arsenic repositories. Arsenic toxicity depends on numerous interacting factors which makes effects difficult to estimate. The use of aquatic algae is often advocated for bioremediation of arsenic contaminated waters as they absorb arsenate and transform it into arsenite and methylated chemical species. Fish are another key constituent of aquatic ecosystems. Contamination in natural systems is often too low to cause mortality but sufficient to interfere with normal functioning. Alteration of complex, naturally occurring fish behaviours such as foraging and aggression are ecologically relevant indicators of toxicity and ideal for assessing sublethal impacts. We examined the effects of arsenic exposure in the invasive mosquitofish, Gambusia holbrooki, in a laboratory experiment incorporating some of the complexity of natural systems by including the interacting effects of aquatic algae. Our aims were to quantify the effects of arsenic on some complex behaviours and physical parameters in mosquitofish, and to assess whether the detoxifying mechanisms of algae would ameliorate any effects of arsenic exposure. Aggression increased significantly with arsenic whereas operculum movement decreased non-significantly and neither food capture efficiency nor consumption were notably affected. Bioaccumulation increased with arsenic and unexpectedly so did fish biomass. Possibly increased aggression facilitated food resource defence allowing fish to gain weight. The presence of algae aggravated the effects of arsenic exposure. For increase in fish biomass, algae acted antagonistically with arsenic, resulting in a disadvantageous reduction in weight gained. For bioaccumulation the effects were even more severe, as algae operated additively with arsenic to increase arsenic uptake and/or assimilation. Aggression was also highest in the presence of both algae and arsenic. Bioremediation of arsenic contaminated waters

  19. Mortality in Young Adults following in Utero and Childhood Exposure to Arsenic in Drinking Water

    PubMed Central

    Marshall, Guillermo; Liaw, Jane; Yuan, Yan; Ferreccio, Catterina; Steinmaus, Craig

    2012-01-01

    Background: Beginning in 1958, the city of Antofagasta in northern Chile was exposed to high arsenic concentrations (870 µg/L) when it switched water sources. The exposure abruptly stopped in 1970 when an arsenic-removal plant commenced operations. A unique exposure scenario like this—with an abrupt start, clear end, and large population (125,000 in 1970), all with essentially the same exposure—is rare in environmental epidemiology. Evidence of increased mortality from lung cancer, bronchiectasis, myocardial infarction, and kidney cancer has been reported among young adults who were in utero or children during the high-exposure period. Objective: We investigated other causes of mortality in Antofagasta among 30- to 49-year-old adults who were in utero or ≤ 18 years of age during the high-exposure period. Methods: We compared mortality data between Antofagasta and the rest of Chile for people 30–49 years of age during 1989–2000. We estimated expected deaths from mortality rates in all of Chile, excluding Region II where Antofagasta is located, and calculated standardized mortality ratios (SMRs). Results: We found evidence of increased mortality from bladder cancer [SMR = 18.1; 95% confidence interval (CI): 11.3, 27.4], laryngeal cancer (SMR = 8.1; 95% CI: 3.5, 16.0), liver cancer (SMR = 2.5; 95% CI: 1.6, 3.7), and chronic renal disease (SMR = 2.0; 95% CI: 1.5, 2.8). Conclusions: Taking together our findings in the present study and previous evidence of increased mortality from other causes of death, we conclude that arsenic in Antofagasta drinking water has resulted in the greatest increases in mortality in adults < 50 years of age ever associated with early-life environmental exposure. PMID:22949133

  20. Prolonged exposure to arsenic in UK private water supplies: toenail, hair and drinking water concentrations.

    PubMed

    Middleton, D R S; Watts, M J; Hamilton, E M; Fletcher, T; Leonardi, G S; Close, R M; Exley, K S; Crabbe, H; Polya, D A

    2016-05-18

    Chronic exposure to arsenic (As) in drinking water is an established cause of cancer and other adverse health effects. Arsenic concentrations >10 μg L(-1) were previously measured in 5% of private water supplies (PWS) in Cornwall, UK. The present study investigated prolongued exposure to As by measuring biomarkers in hair and toenail samples from 212 volunteers and repeated measurements of As in drinking water from 127 households served by PWS. Strong positive Pearson correlations (rp = 0.95) indicated stability of water As concentrations over the time period investigated (up to 31 months). Drinking water As concentrations were positively correlated with toenail (rp = 0.53) and hair (rp = 0.38) As concentrations - indicative of prolonged exposure. Analysis of washing procedure solutions provided strong evidence of the effective removal of exogenous As from toenail samples. Significantly higher As concentrations were measured in hair samples from males and smokers and As concentrations in toenails were negatively associated with age. A positive association between seafood consumption and toenail As and a negative association between home-grown vegetable consumption and hair As was observed for volunteers exposed to <1 As μg L(-1) in drinking water. These findings have important implications regarding the interpretation of toenail and hair biomarkers. Substantial variation in biomarker As concentrations remained unaccounted for, with soil and dust exposure as possible explanations. PMID:27120003

  1. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB

    PubMed Central

    Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan; Tian, Guang

    2015-01-01

    High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training) was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cAMP-response element binding protein (pCREB) in the CA1 and dentate gyrus areas (DG) of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus. PMID:26368803

  2. Carcinogenic Effects of “Whole-Life” Exposure to Inorganic Arsenic in CD1 Mice

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Ward, Jerrold M.; Delker, Don A.; Waalkes, Michael P.

    2011-01-01

    In a previously developed mouse model, arsenic exposure in utero induces tumors at multiple sites in the offspring as adults, often duplicating human targets. However, human environmental inorganic arsenic exposure occurs during the entire life span, not just part of gestation. Thus, “whole-life” inorganic arsenic carcinogenesis in mice was studied. CD1 mice were exposed to 0, 6, 12, or 24 ppm arsenic in the drinking water 2 weeks prior to breeding, during pregnancy, lactation, and after weaning through adulthood. Tumors were assessed in offspring until 2 years of age. Arsenic induced dose-related increases in lung adenocarcinoma (both sexes), hepatocellular carcinoma (both sexes), gallbladder tumors (males), and uterine carcinomas. Arsenic induced dose-related increases in ovarian tumors (including carcinomas) starting with the lowest dose. Adrenal tumors increased at all doses (both sexes). Arsenic-induced lung and liver cancers were highly enriched for cancer stem cells, consistent with prior work with skin cancers stimulated by prenatal arsenic. Reproductive tract tumors overexpressed cyclooxygenase-2 and estrogen receptor-α. Arsenic target sites were remarkably similar to prior transplacental studies, although tumors from whole-life exposure were generally more aggressive and frequent. This may indicate that arsenic-induced events in utero dictate target site in some tissues, whereas other exposure periods of arsenic enhance incidence or progression, though other factors could be at play, like cumulative dose. Whole-life arsenic exposure induced tumors at dramatically lower external doses than in utero arsenic only while more realistically duplicating human exposure. PMID:20937726

  3. Arsenic

    MedlinePlus

    Arsenic is a natural element found in soil and minerals. Arsenic compounds are used to preserve wood, as pesticides, and in some industries. Arsenic can get into air, water, and the ground from wind- ...

  4. Arsenic

    MedlinePlus

    ... and minerals. Arsenic compounds are used to preserve wood, as pesticides, and in some industries. Arsenic can ... Breathing sawdust or burning smoke from arsenic-treated wood Living in an area with high levels of ...

  5. DNA repair genotype interacts with arsenic exposure to increase bladder cancer risk

    PubMed Central

    Andrew, Angeline S.; Mason, Rebecca A.; Kelsey, Karl T.; Schned, Alan R.; Marsit, Carmen J.; Nelson, Heather H.; Karagas, Margaret R.

    2009-01-01

    Drinking water arsenic exposure has been associated with increased bladder cancer susceptibility. Epidemiologic and experimental data suggest a co-carcinogenic effect of arsenic with exposure to DNA damaging agents, such as cigarette smoke. Recent evidence further supports the hypothesis that genetic variation in DNA repair genes can modify the arsenic – cancer relationship, possibly because arsenic impairs DNA repair capacity. We tested this hypothesis in a population-based study of bladder cancer with XRCC3, ERCC2 genotype/haplotype and arsenic exposure data on 549 controls and 342 cases. Individual exposure to arsenic was determined in toenail samples by neutron activation. Gene-environment interaction with arsenic exposure was observed in relation to bladder cancer risk for a variant allele of the double-strand break repair gene XRCC3 T241M (adjusted OR 2.8 (1.1–7.3) comparing to homozygous wild type among those in the top arsenic exposure decile (interaction p-value 0.01). Haplotype analysis confirmed the association of the XRCC3 241. Thus, double-strand break repair genotype may enhance arsenic associated bladder cancer susceptibility in the U.S. population. PMID:19429237

  6. The effect of arsenic exposure on the biochemical and mineral contents of Labeo rohita bones: An FT-IR study

    NASA Astrophysics Data System (ADS)

    Palaniappan, PL. RM.; Vijayasundaram, V.

    2009-01-01

    Arsenic compounds are ubiquitous and widespread in the environment as a result of natural or anthropogenic occurrence. Fish are the major source of protein for human consumption. They are also a source of contamination, because of the amounts of heavy elements they can contain, some of which are highly toxic. Fish bones are high in calcium, which is an essential mineral for normal body function. It consists of water, organic material, and mineral matter. Chelating agents have been used clinically as antidotes for acute and chronic metal intoxications. In the present study, an attempt is made to investigate the bio-accumulation of arsenic and its effect on the biochemical and mineral contents of Labeo rohita bones using, Fourier transform infrared (FT-IR) spectroscopy. The results of the present study indicate that arsenic exposure induces significant reduction on the biochemical and mineral contents of the L. rohita bones. Further, the DMSA treatment significantly improves these levels. This shows that DMSA is an effective chelator for arsenic toxicity. Quantitative curve-fitting analyses of amide I band have proved useful in studying the nature and the extent of protein conformational changes. A decrease in α-helical and random coil structures and an increase in β-sheet structures have been observed due to arsenic exposure. In conclusion, the present study shows that the FT-IR spectroscopy coupled with second derivative and curve-fitting analysis gives useful information about the biochemical and mineral contents of the L. rohita bones.

  7. CHRONIC EXPOSURE TO ARSENITE IN DRINKING WATER IMPAIRS GLUCOSE TOLERANCE IN C57BL/6 MICE

    EPA Science Inventory

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased prevalence of type 2 diabetes mellitus. This study examines in vivo diabetogenic effects of iAs in an animal model. Here, weanling male C57BL/6 mice received deionized water containing iAs(III) (25 ...

  8. Probabilistic Modeling of Dietary Arsenic Exposure and Dose and Evaluation with 2003-2004 NHANES Data

    EPA Science Inventory

    Dietary exposure from food to toxic inorganic arsenic (iAs) in the general U.S. population has not been well studied. The goal of this research was to quantify dietary arsenic As exposure and analyze the major contributors to total As (tAs) and iAs. Another objective was to com...

  9. Cardiovascular disease and arsenic exposure in Inner Mongolia, China: a case control study

    EPA Science Inventory

    BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in...

  10. GENE EXPRESSION PROFILING OF HYPERKERATOTIC SKIN FROM INNER MONGOLIANS CHRONICALLY EXPOSED TO ARSENIC

    EPA Science Inventory

    Millions of people worldwide have been chronically exposed to arsenic levels in drinking water that greatly exceed the current World Health Organization¿s recommended limit of 10 µg/ml. The skin is a major target of arsenic toxicity, and some of the first clinical signs of chroni...

  11. ASSESSING MULTIMEDIA/MULTIPATHWAY EXPOSURE TO ARSENIC USING A MECHANISTIC SOURCE-TO-DOSE MODELING FRAMEWORK

    EPA Science Inventory

    A series of case studies is presented focusing on multimedia/multipathway population exposures to arsenic, employing the Population Based Modeling approach of the MENTOR (Modeling Environment for Total Risks) framework. This framework considers currently five exposure routes: i...

  12. Arsenic and manganese exposure and children's intellectual function

    PubMed Central

    Wasserman, Gail A.; Liu, Xinhua; Parvez, Faruque; Factor-Litvak, Pam; Ahsan, Habibul; Levy, Diane; Kline, Jennie; van Geen, Alexander; Mey, Jacob; Slavkovich, Vesna; Siddique, Abu B.; Islam, Tariqul; Graziano, Joseph H.

    2014-01-01

    Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10μg/L) and Mn (above and below 500μg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's > .25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels. PMID:21453724

  13. Assessment of Arsenic Exposure by Measurement of Urinary Speciated Inorganic Arsenic Metabolites in Workers in a Semiconductor Manufacturing Plant

    PubMed Central

    2013-01-01

    Objectives The purpose of this study was to evaluate the exposure to arsenic in preventive maintenance (PM) engineers in a semiconductor industry by detecting speciated inorganic arsenic metabolites in the urine. Methods The exposed group included 8 PM engineers from the clean process area and 13 PM engineers from the ion implantation process area; the non-exposed group consisted of 14 office workers from another company who were not occupationally exposed to arsenic. A spot urine specimen was collected from each participant for the detection and measurement of speciated inorganic arsenic metabolites. Metabolites were separated by high performance liquid chromatography-inductively coupled plasma spectrometry-mass spectrometry. Results Urinary arsenic metabolite concentrations were 1.73 g/L, 0.76 g/L, 3.45 g/L, 43.65 g/L, and 51.32 g/L for trivalent arsenic (As3+), pentavalent arsenic (As5+), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total inorganic arsenic metabolites (As3+ + As5+ + MMA + DMA), respectively, in clean process PM engineers. In ion implantation process PM engineers, the concentrations were 1.74 g/L, 0.39 g/L, 3.08 g/L, 23.17 g/L, 28.92 g/L for As3+, As5+, MMA, DMA, and total inorganic arsenic metabolites, respectively. Levels of urinary As3+, As5+, MMA, and total inorganic arsenic metabolites in clean process PM engineers were significantly higher than that in the non-exposed group. Urinary As3+ and As5+ levels in ion implantation process PM engineers were significantly higher than that in non-exposed group. Conclusion Levels of urinary arsenic metabolites in PM engineers from the clean process and ion implantation process areas were higher than that in office workers. For a complete assessment of arsenic exposure in the semiconductor industry, further studies are needed. PMID:24472712

  14. Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

    PubMed Central

    Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

    2016-01-01

    Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users. PMID:27156998

  15. Urinary arsenic profiles reveal exposures to inorganic arsenic from private drinking water supplies in Cornwall, UK

    NASA Astrophysics Data System (ADS)

    Middleton, D. R. S.; Watts, M. J.; Hamilton, E. M.; Ander, E. L.; Close, R. M.; Exley, K. S.; Crabbe, H.; Leonardi, G. S.; Fletcher, T.; Polya, D. A.

    2016-05-01

    Private water supplies (PWS) in Cornwall, South West England exceeded the current WHO guidance value and UK prescribed concentration or value (PCV) for arsenic of 10 μg/L in 5% of properties surveyed (n = 497). In this follow-up study, the first of its kind in the UK, volunteers (n = 207) from 127 households who used their PWS for drinking, provided urine and drinking water samples for total As determination by inductively coupled plasma mass spectrometry (ICP-MS) and urinary As speciation by high performance liquid chromatography ICP-MS (HPLC-ICP-MS). Arsenic concentrations exceeding 10 μg/L were found in the PWS of 10% of the volunteers. Unadjusted total urinary As concentrations were poorly correlated (Spearman’s ρ = 0.36 (P < 0.001)) with PWS As largely due to the use of spot urine samples and the dominance of arsenobetaine (AB) from seafood sources. However, the osmolality adjusted sum, U-AsIMM, of urinary inorganic As species, arsenite (AsIII) and arsenate (AsV), and their metabolites, methylarsonate (MA) and dimethylarsinate (DMA), was found to strongly correlate (Spearman’s ρ: 0.62 (P < 0.001)) with PWS As, indicating private water supplies as the dominant source of inorganic As exposure in the study population of PWS users.

  16. Arsenic Exposure within the Korean Community (United States) Based on Dietary Behavior and Arsenic Levels in Hair, Urine, Air, and Water

    PubMed Central

    Cleland, Bill; Tsuchiya, Ami; Kalman, David A.; Dills, Russell; Burbacher, Thomas M.; White, Jim W.; Faustman, Elaine M.; Mariën, Koenraad

    2009-01-01

    Background Determining arsenic exposure in groups based on geographic location, dietary behaviors, or lifestyles is important, as even moderate exposures may lead to health concerns. Objectives/Methods The Korean community in Washington State, represents a group warranting investigation, as they consume foods (e.g., shellfish, rice, finfish, and seaweed) known to contain arsenic. As part of the Arsenic Mercury Intake Biometric Study, we examined the arsenic levels in hair and urine along with the diets of 108 women of childbearing age from within this community. Arsenic levels in indoor air and drinking water were also investigated, and shellfish commonly consumed were collected and analyzed for total and speciated arsenic. Results The six shellfish species analyzed (n = 667) contain total arsenic (range, 1–5 μg/g) but are a small source of inorganic arsenic (range, 0.01–0.12 μg/g). Six percent of the individuals may have elevated urinary inorganic arsenic levels (> 10 μg/L) due to diet. Seaweed, rice, shellfish, and finfish are principal sources for total arsenic intake/excretion based on mass balance estimates. Rice consumption (163 g/person/day) may be a significant source of inorganic arsenic. Air and water are not significant sources of exposure. Hair is a poor biometric for examining arsenic levels at low to moderate exposures. Conclusions We conclude that a portion of this community may have dietary inorganic arsenic exposure resulting in urine levels exceeding 10 μg/L. Although their exposure is below that associated with populations exposed to high levels of arsenic from drinking water (> 100 μg/L), their exposure may be among the highest in the United States. PMID:19440504

  17. Arsenic Toxicity in Male Reproduction and Development

    PubMed Central

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-01-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children’s health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity. PMID:26973968

  18. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

    Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity. PMID:26973968

  19. Variation in arsenic speciation and concentration in paddy rice related to dietary exposure.

    PubMed

    Williams, P N; Price, A H; Raab, A; Hossain, S A; Feldmann, J; Meharg, A A

    2005-08-01

    Ingestion of drinking water is not the only elevated source of arsenic to the diet in the Bengal Delta. Even at background levels, the arsenic in rice contributes considerably to arsenic ingestion in subsistence rice diets. We set out to survey As speciation in different rice varieties from different parts of the globe to understand the contribution of rice to arsenic exposure. Pot experiments were utilized to ascertain whether growing rice on As contaminated soil affected speciation and whether genetic variation accounted for uptake and speciation. USA long grain rice had the highest mean arsenic level in the grain at 0.26 microg As g(-1) (n = 7), and the highest grain arsenic value of the survey at 0.40 microg As g(-1). The mean arsenic level of Bangladeshi rice was 0.13 microg As g(-1) (n = 15). The main As species detected in the rice extract were AsIII, DMAV, and AsV. In European, Bangladeshi, and Indian rice 64 +/- 1% (n = 7), 80 +/- 3% (n = 11), and 81 +/- 4% (n = 15), respectively, of the recovered arsenic was found to be inorganic. In contrast, DMAV was the predominant species in rice from the USA, with only 42 +/- 5% (n = 12) of the arsenic being inorganic. Pot experiments show that the proportions of DMAV in the grain are significantly dependent on rice cultivar (p = 0.026) and that plant nutrient status is effected by arsenic exposure. PMID:16124284

  20. Intervention trial to assess arsenic exposure from food crops in Bangladesh.

    PubMed

    Ranmuthugala, Geetha; Milton, Abul H; Smith, Wayne T; Ng, Jack C; Sim, Malcolm; Dear, Keith; Caldwell, Bruce K

    2004-04-01

    The authors assessed the contribution of food irrigated with arsenic-contaminated water to human exposure to arsenic in Bangladesh. An intervention trial was conducted in a village in the Jessore District of Bangladesh, where irrigation water had been field-tested in March 2000 and was found to contain arsenic with concentrations ranging from 100 to 500 microg/l. In May 2000, a random sample of 63 households was selected from the village, and 1 eligible person from each household was recruited to the study and randomized to an intervention or control group. The intervention group received food purchased from a village where irrigation water was found to contain < 10 microg/l arsenic. The control group received food purchased from markets in the study village, where irrigation water was found to contain > 100 microg/l arsenic. Pre- and postintervention urine samples were collected for urinary arsenic speciation assays. Preintervention, the mean urinary total arsenic concentrations were 139.25 microg/l and 129.15 microg/l for the intervention and control groups, respectively. These concentrations did not change significantly following intervention. Arsenic concentrations in samples of selected raw and cooked foods from the low-contamination area did not contain less arsenic than samples from the high-contamination area. Further studies to investigate the arsenic content of food grown in areas with high and low arsenic contamination of irrigation water are recommended. PMID:16189994

  1. Characterizing arsenic in preserved hair for assessing exposure potential and discriminating poisoning

    SciTech Connect

    Kempson, Ivan M.; Henry, Dermot; Francis, James

    2009-05-21

    Advanced analytical techniques have been used to characterize arsenic in taxidermy specimens. Arsenic was examined to aid in discriminating its use as a preservative from that incorporated by ingestion and hence indicate poisoning (in the case of historical figures). The results are relevant to museum curators, occupational and environmental exposure concerns, toxicological and anthropological investigations. Hair samples were obtained from six taxidermy specimens preserved with arsenic in the late 1800s and early 1900s to investigate the arsenic incorporation. The presence of arsenic poses a potential hazard in museum and private collections. For one sample, arsenic was confirmed to be present on the hair with time-of-flight secondary ion mass spectrometry and then measured with neutron activation analysis to comprise 176 {mu}g g{sup -1}. The hair cross section was analysed with synchrotron micro-X-ray fluorescence to investigate the transverse distribution of topically applied arsenic. It was found that the arsenic had significantly penetrated all hair samples. Association with melanin clusters and the medulla was observed. Lead and mercury were also identified in one sample. X-ray absorption near-edge spectroscopy of the As K-edge indicated that an arsenate species predominantly existed in all samples; however, analysis was hindered by very rapid photoreduction of the arsenic. It would be difficult to discriminate arsenic consumption from topically applied arsenic based on the physical transverse distribution. Longitudinal distributions and chemical speciation may still allow differentiation.

  2. Arsenic exposure, smoking, and lung cancer in smelter workers--a case-control study

    SciTech Connect

    Jaerup, L.P.; Pershagen, G. )

    1991-09-15

    A cohort of 3,916 Swedish copper smelter workers employed for at least 3 months between 1928 and 1967 was followed up through 1981. Arsenic exposure was estimated for different time periods at each workplace within the smelter. Detailed job records were linked to the exposure matrix, thus forming individual cumulative arsenic exposure measures for each smelter worker. Smoking history was collected for 107 lung cancer cases and 214 controls from the cohort. Lung cancer risks were positively related to cumulative arsenic exposure with smoking standardized relative risks ranging from 0.7 to 8.7 in different exposure groups. A negative confounding by smoking was suggested in the higher exposure categories. The interaction between arsenic and smoking for the risk of developing lung cancer was intermediate between additive and multiplicative and appeared less pronounced among heavy smokers.

  3. Association of hypothyroidism with low-level arsenic exposure in rural West Texas

    SciTech Connect

    Gong, Gordon; Basom, Janet; Mattevada, Sravan; Onger, Frederick

    2015-04-15

    It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2–22 µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8 µg/L in 36% of the subjects' wells while iodine concentration was <1 µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8 µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8 µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas. - Highlights: • We determined if arsenic exposure is associated with hypothyroidism in rural Texas. • Groundwater arsenic level is associated with hypothyroidism among Hispanics only. • The rate of hypothyroidism in rural Texas was higher than the US general population.

  4. COMPARISON OF THE URINARY METABOLITES OF RATS, MICE, AND HUMANS AFTER ORAL ARSENIC EXPOSURE FOCUSING ON THIOARSENICALS

    EPA Science Inventory

    Urinary metabolites of arsenic are useful as biomarkers of exposure because ingested arsenic is excreted primarily in urine1. Complete urinary arsenic speciation can provide insight into possible metabolic pathways as well as potential exposure sources. The pattern of excreted me...

  5. Effects of freshwater exposure to arsenic trioxide on the parr-smolt transformation of coho salmon (Oncorhynchus kisutch)

    USGS Publications Warehouse

    Nichols, J.W.; Wedemeyer, G.A.; Mayer, F.L.; Dickhoff, Walton W.; Gregory, S.V.; Yasutake, W.T.; Smith, S.D.

    1984-01-01

    The effects of chronic (6 months) exposure to arsenic trioxide in fresh water on the Parr-smolt transformation of coho salmon (Oncorhynchus kisutch) were evaluated. Exposure to 300 μg As/L (as As2O3) appeared to delay the onset of the normal increase in plasma thyroxine concentration and cause a transient reduction of gill Na+,K+-ATPase activity. Fish exposed to 300 μg As/L also migrated to the sea less successfully than did nonexposed smolts, but there were no effects on the survival and growth of smolts held in 28‰ salt water for 6 months.

  6. ARSENICALS IN MATERNAL AND FETAL MOUSE TISSUES AFTER GESTATIONAL EXPOSURE TO ARSENITE

    EPA Science Inventory

    Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 to 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methy...

  7. EFFECTS OF ARSENIC TRIOXIDE INHALATION EXPOSURE ON PULMONARY ANTIBACTERIAL DEFENSES IN MICE

    EPA Science Inventory

    The effects of single and multiple (5 and 20) 3 hr inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0.4 microme...

  8. CARDIOVASCULAR AND OTHER HEALTH EFFECTS ASSOCIATED WITH ARSENIC EXPOSURE IN INNER MONGOLIA

    EPA Science Inventory

    Arsenic exposure is associated with cardiovascular and other health effects. The study objectives were to investigate the mode of action and to assess dose-response relationships of arsenic on cardiovascular, diabetic and carcinogenic effects in Ba Men, Inner Mongolia. Ba Men res...

  9. Assessing arsenic exposure in households using bottled water or point-of-use treatment systems to mitigate well water contamination.

    PubMed

    Smith, Andrew E; Lincoln, Rebecca A; Paulu, Chris; Simones, Thomas L; Caldwell, Kathleen L; Jones, Robert L; Backer, Lorraine C

    2016-02-15

    There is little published literature on the efficacy of strategies to reduce exposure to residential well water arsenic. The objectives of our study were to: 1) determine if water arsenic remained a significant exposure source in households using bottled water or point-of-use treatment systems; and 2) evaluate the major sources and routes of any remaining arsenic exposure. We conducted a cross-sectional study of 167 households in Maine using one of these two strategies to prevent exposure to arsenic. Most households included one adult and at least one child. Untreated well water arsenic concentrations ranged from <10 μg/L to 640 μg/L. Urine samples, water samples, daily diet and bathing diaries, and household dietary and water use habit surveys were collected. Generalized estimating equations were used to model the relationship between urinary arsenic and untreated well water arsenic concentration, while accounting for documented consumption of untreated water and dietary sources. If mitigation strategies were fully effective, there should be no relationship between urinary arsenic and well water arsenic. To the contrary, we found that untreated arsenic water concentration remained a significant (p ≤ 0.001) predictor of urinary arsenic levels. When untreated water arsenic concentrations were <40 μg/L, untreated water arsenic was no longer a significant predictor of urinary arsenic. Time spent bathing (alone or in combination with water arsenic concentration) was not associated with urinary arsenic. A predictive analysis of the average study participant suggested that when untreated water arsenic ranged from 100 to 500 μg/L, elimination of any untreated water use would result in an 8%-32% reduction in urinary arsenic for young children, and a 14%-59% reduction for adults. These results demonstrate the importance of complying with a point-of-use or bottled water exposure reduction strategy. However, there remained unexplained, water-related routes of exposure

  10. Effects of low arsenic concentration exposure on freshwater fish in the presence of fluvial biofilms.

    PubMed

    Tuulaikhuu, Baigal-Amar; Bonet, Berta; Guasch, Helena

    2016-02-15

    Arsenic (As) is a highly toxic element and its carcinogenic effect on living organisms is well known. However, predicting real effects in the environment requires an ecological approach since toxicity is influenced by many environmental and biological factors. The purpose of this paper was to evaluate if environmentally-realistic arsenic exposure causes toxicity to fish. An experiment with four different treatments (control (C), biofilm (B), arsenic (+As) and biofilm with arsenic (B+As)) was conducted and each one included sediment to enhance environmental realism, allowing the testing of the interactive effects of biofilm and arsenic on the toxicity to fish. Average arsenic exposure to Eastern mosquitofish (Gambusia holbrooki) was 40.5 ± 7.5 μg/L for +As treatment and 34.4 ± 1.4 μg/L for B+As treatment for 56 days. Fish were affected directly and indirectly by this low arsenic concentration since exposure did not only affect fish but also the function of periphytic biofilms. Arsenic effects on the superoxide dismutase (SOD) and glutathione reductase (GR) activities in the liver of mosquitofish were ameliorated in the presence of biofilms at the beginning of exposure (day 9). Moreover, fish weight gaining was only affected in the treatment without biofilm. After longer exposure (56 days), effects of exposure were clearly seen. Fish showed a marked increase in the catalase (CAT) activity in the liver but the interactive influence of biofilms was not further observed since the arsenic-affected biofilm had lost its role in water purification. Our results highlight the interest and application of incorporating some of the complexity of natural systems in ecotoxicology and support the use of criterion continuous concentration (CCC) for arsenic lower than 150 μg/L and closer to the water quality criteria to protect aquatic life recommended by the Canadian government which is 5 μg As/L. PMID:26657392

  11. Arsenic exposure triggers a shift in microRNA expression.

    PubMed

    Sturchio, Elena; Colombo, Teresa; Boccia, Priscilla; Carucci, Nicoletta; Meconi, Claudia; Minoia, Claudio; Macino, Giuseppe

    2014-02-15

    Exposure to inorganic Arsenic (iAs) through drinking water is a major public health problem affecting most countries. iAs has been classified by the International Agency for Research on Cancer as Group 1: "Carcinogenic to humans". Although numerous studies have shown the related adverse effects of iAs, sensitive appropriate biomarkers for studies of environmental epidemiology are still required. The present work aims at investigate the role of microRNAs (miRNAs), powerful negative regulators of gene expression, playing a key role in many physiological and pathological cellular processes, in iAs exposure. To this end, we analyzed miRNA changes in expression profile triggered by iAs exposure in Jurkat cell line. We used microarray technology to profile the expression of miRNAs following 2 μmol/L sodium arsenite treatment at different time points. Moreover, we performed phenotypic analysis of iAs treated cells. Real Time Polymerase Chain Reaction (RT-PCR) was used to validate miRNA microarray data and to assay expression modulation of selected relevant mRNAs. Finally, bioinformatics techniques were applied to reconstruct iAs-relevant molecular pathways and miRNA regulatory networks from the expression data. We report miRNAs modulated after iAs treatment in Jurkat cells. In particular, we highlight 36 miRNAs exhibiting consistent dysregulation and particularly a panel of 8 miRNAs which we also validated by RT-PCR analysis. Computational analysis of lists of putative target genes for these 8 miRNAs points to an involvement in arsenic-response pathways, for a subset of them, that were analyzed by RT-PCR. Furthermore, iAs exposure reveals induction of cell cycle progression and the failure of apoptosis, supporting the idea of iAs carcinogenic activity. Our study provides a list of miRNAs whose expression levels are affected by iAs treatment, corroborating the importance of proceeding with the hunt for specific subset of miRNAs, which can serve as potential biomarkers of

  12. High exposure to inorganic arsenic by food: the need for risk reduction.

    PubMed

    Gundert-Remy, Ursula; Damm, Georg; Foth, Heidi; Freyberger, Alexius; Gebel, Thomas; Golka, Klaus; Röhl, Claudia; Schupp, Thomas; Wollin, Klaus-Michael; Hengstler, Jan Georg

    2015-12-01

    Arsenic is a human carcinogen that occurs ubiquitously in soil and water. Based on epidemiological studies, a benchmark dose (lower/higher bound estimate) between 0.3 and 8 μg/kg bw/day was estimated to cause a 1 % increased risk of lung, skin and bladder cancer. A recently published study by EFSA on dietary exposure to inorganic arsenic in the European population reported 95th percentiles (lower bound min to upper bound max) for different age groups in the same range as the benchmark dose. For toddlers, a highly exposed group, the highest values ranged between 0.61 and 2.09 µg arsenic/kg bw/day. For all other age classes, the margin of exposure is also small. This scenario calls for regulatory action to reduce arsenic exposure. One priority measure should be to reduce arsenic in food categories that contribute most to exposure. In the EFSA study the food categories 'milk and dairy products,' 'drinking water' and 'food for infants' represent major sources of inorganic arsenic for infants and also rice is an important source. Long-term strategies are required to reduce inorganic arsenic in these food groups. The reduced consumption of rice and rice products which has been recommended may be helpful for a minority of individuals consuming unusually high amounts of rice. However, it is only of limited value for the general European population, because the food categories 'grain-based processed products (non rice-based)' or 'milk and dairy products' contribute more to the exposure with inorganic arsenic than the food category 'rice.' A balanced regulatory activity focusing on the most relevant food categories is required. In conclusion, exposure to inorganic arsenic represents a risk to the health of the European population, particularly to young children. Regulatory measures to reduce exposure are urgently required. PMID:26586021

  13. Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

    PubMed

    Farmer, J G; Johnson, L R

    1990-05-01

    An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases. PMID:2357455

  14. Assessment of occupational exposure to inorganic arsenic based on urinary concentrations and speciation of arsenic.

    PubMed Central

    Farmer, J G; Johnson, L R

    1990-01-01

    An analytical speciation method, capable of separating inorganic arsenic (As (V), As (III] and its methylated metabolites (MMAA, DMAA) from common, inert, dietary organoarsenicals, was applied to the determination of arsenic in urine from a variety of workers occupationally exposed to inorganic arsenic compounds. Mean urinary arsenic (As (V) + As (III) + MMAA + DMAA) concentrations ranged from 4.4 micrograms/g creatinine for controls to less than 10 micrograms/g for those in the electronics industry, 47.9 micrograms/g for timber treatment workers applying arsenical wood preservatives, 79.4 micrograms/g for a group of glassworkers using arsenic trioxide, and 245 micrograms/g for chemical workers engaged in manufacturing and handling inorganic arsenicals. The maximum recorded concentration was 956 micrograms/g. For the most exposed groups, the ranges in the average urinary arsenic speciation pattern were 1-6% As (V), 11-14% As (III), 14-18% MMAA, and 63-70% DMAA. The highly raised urinary arsenic concentrations for the chemical workers, in particular, and some glassworkers are shown to correspond to possible atmospheric concentrations in the workplace and intakes in excess of, or close to, recommended and statutory limits and those associated with inorganic arsenic related diseases. PMID:2357455

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

    PubMed

    Chou, Wei-Chun; Chen, Jein-Wen; Liao, Chung-Min

    2016-07-01

    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, 2.1 μg iAs day(-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. PMID:27048329

  16. Estimated Exposure to Arsenic in Breastfed and Formula-Fed Infants in a United States Cohort

    PubMed Central

    Carignan, Courtney C.; Jackson, Brian P.; Farzan, Shohreh F.; Gandolfi, A. Jay; Punshon, Tracy; Folt, Carol L.; Karagas, Margaret R.

    2015-01-01

    Background: Previous studies indicate that concentrations of arsenic in breast milk are relatively low even in areas with high drinking-water arsenic. However, it is uncertain whether breastfeeding leads to reduced infant exposure to arsenic in regions with lower arsenic concentrations. Objective: We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. population. Methods: We measured arsenic in home tap water (n = 874), urine from 6-week-old infants (n = 72), and breast milk from mothers (n = 9) enrolled in the New Hampshire Birth Cohort Study (NHBCS) using inductively coupled plasma mass spectrometry. Using data from a 3-day food diary, we compared urinary arsenic across infant feeding types and developed predictive exposure models to estimate daily arsenic intake from breast milk and formula. Results: Urinary arsenic concentrations were generally low (median, 0.17 μg/L; maximum, 2.9 μg/L) but 7.5 times higher for infants fed exclusively with formula than for infants fed exclusively with breast milk (β = 2.02; 95% CI: 1.21, 2.83; p < 0.0001, adjusted for specific gravity). Similarly, the median estimated daily arsenic intake by NHBCS infants was 5.5 times higher for formula-fed infants (0.22 μg/kg/day) than for breastfed infants (0.04 μg/kg/day). Given median arsenic concentrations measured in NHBCS tap water and previously published for formula powder, formula powder was estimated to account for ~ 70% of median exposure among formula-fed NHBCS infants. Conclusions: Our findings suggest that breastfed infants have lower arsenic exposure than formula-fed infants, and that both formula powder and drinking water can be sources of exposure for U.S. infants. Citation: Carignan CC, Cottingham KL, Jackson BP, Farzan SF, Gandolfi AJ, Punshon T, Folt CL, Karagas MR. 2015. Estimated exposure to arsenic in breastfed and formula-fed infants in a United States cohort. Environ Health Perspect 123:500–506;

  17. Modeling the probability of arsenic in groundwater in New England as a tool for exposure assessment

    USGS Publications Warehouse

    Ayotte, J.D.; Nolan, B.T.; Nuckols, J.R.; Cantor, K.P.; Robinson, G.R., Jr.; Baris, D.; Hayes, L.; Karagas, M.; Bress, W.; Silverman, D.T.; Lubin, J.H.

    2006-01-01

    We developed a process-based model to predict the probability of arsenic exceeding 5 ??g/L in drinking water wells in New England bedrock aquifers. The model is being used for exposure assessment in an epidemiologic study of bladder cancer. One important study hypothesis that may explain increased bladder cancer risk is elevated concentrations of inorganic arsenic in drinking water. In eastern New England, 20-30% of private wells exceed the arsenic drinking water standard of 10 micrograms per liter. Our predictive model significantly improves the understanding of factors associated with arsenic contamination in New England. Specific rock types, high arsenic concentrations in stream sediments, geochemical factors related to areas of Pleistocene marine inundation and proximity to intrusive granitic plutons, and hydrologic and landscape variables relating to groundwater residence time increase the probability of arsenic occurrence in groundwater. Previous studies suggest that arsenic in bedrock groundwater may be partly from past arsenical pesticide use. Variables representing historic agricultural inputs do not improve the model, indicating that this source does not significantly contribute to current arsenic concentrations. Due to the complexity of the fractured bedrock aquifers in the region, well depth and related variables also are not significant predictors. ?? 2006 American Chemical Society.

  18. Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood

    PubMed Central

    Kile, Molly L; Houseman, E Andres; Baccarelli, Andrea A; Quamruzzaman, Quazi; Rahman, Mahmuder; Mostofa, Golam; Cardenas, Andres; Wright, Robert O; Christiani, David C

    2014-01-01

    Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic’s ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range < 1- 510 µg/L). Log10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects. PMID:24525453

  19. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    EPA Science Inventory

    Exposure to inorganic arsenic remains a serious public health problem at many locations worldwide. If has often been noted that prevalences of signs and symptoms of chronic arsenic poisoning differ among various populations. For example, skin lesions or peripheral vascular dis...

  20. Spatial and Temporal Variations in Arsenic Exposure via Drinking-water in Northern Argentina

    PubMed Central

    Concha, Gabriela; Nermell, Barbro

    2006-01-01

    This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from <1 to about 200 μg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 μg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3–900 μg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20–1,500 μg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair. PMID:17366773

  1. Characterization of glutathione reductase and catalase in the fronds of two Pteris ferns upon arsenic exposure.

    PubMed

    Kertulis-Tartar, Gina M; Rathinasabapathi, Bala; Ma, Lena Q

    2009-10-01

    To better understand the mechanisms of plant tolerance to high concentration of arsenic, we characterized two antioxidant enzymes, glutathione reductase (GR) and catalase (CAT), in the fronds of Pteris vittata, an arsenic-hyperaccumulating fern, and Pteris ensiformis, an arsenic-sensitive fern. The induction, activation and apparent kinetics of GR and CAT in the plants upon arsenic exposure were investigated. Under arsenic exposure (sodium arsenate), CAT activity in P. vittata was increased by 1.5-fold, but GR activity was unchanged. Further, GR was not inhibited or activated by the arsenic in assays. No significant differences in K(m) and V(max) values of GR or CAT were observed between the two ferns. However, CAT activity in P. vittata was activated by 200 microM arsenate up to 300% compared to the control. Similar but much smaller increases were observed for P. ensiformis and purified bovine liver catalase (133% and 120%, respectively). This research reports, for the first time, the activation of CAT by arsenic in P. vittata. The increased CAT activities may allow P. vittata to more efficiently mediate arsenic-induced stress by preparing the fern for the impeding production of reactive oxygen species resulting from arsenate reduction to arsenite in the fronds. PMID:19574057

  2. Biologically based modeling of multimedia, multipathway, multiroute population exposures to arsenic

    PubMed Central

    Georgopoulos, Panos G.; Wang, Sheng-Wei; Yang, Yu-Ching; Xue, Jianping; Zartarian, Valerie G.; Mccurdy, Thomas; Özkaynak, Halûk

    2011-01-01

    This article presents an integrated, biologically based, source-to-dose assessment framework for modeling multimedia/multipathway/multiroute exposures to arsenic. Case studies demonstrating this framework are presented for three US counties (Hunderton County, NJ; Pima County, AZ; and Franklin County, OH), representing substantially different conditions of exposure. The approach taken utilizes the Modeling ENvironment for TOtal Risk studies (MENTOR) in an implementation that incorporates and extends the approach pioneered by Stochastic Human Exposure and Dose Simulation (SHEDS), in conjunction with a number of available databases, including NATA, NHEXAS, CSFII, and CHAD, and extends modeling techniques that have been developed in recent years. Model results indicate that, in most cases, the food intake pathway is the dominant contributor to total exposure and dose to arsenic. Model predictions are evaluated qualitatively by comparing distributions of predicted total arsenic amounts in urine with those derived using biomarker measurements from the NHEXAS — Region V study: the population distributions of urinary total arsenic levels calculated through MENTOR and from the NHEXAS measurements are in general qualitative agreement. Observed differences are due to various factors, such as interindividual variation in arsenic metabolism in humans, that are not fully accounted for in the current model implementation but can be incorporated in the future, in the open framework of MENTOR. The present study demonstrates that integrated source-to-dose modeling for arsenic can not only provide estimates of the relative contributions of multipathway exposure routes to the total exposure estimates, but can also estimate internal target tissue doses for speciated organic and inorganic arsenic, which can eventually be used to improve evaluation of health risks associated with exposures to arsenic from multiple sources, routes, and pathways. PMID:18073786

  3. Low-level arsenic exposure: Nutritional and dietary predictors in first-grade Uruguayan children.

    PubMed

    Kordas, Katarzyna; Queirolo, Elena I; Mañay, Nelly; Peregalli, Fabiana; Hsiao, Pao Ying; Lu, Ying; Vahter, Marie

    2016-05-01

    Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9µg/L) and household water (water As: median 0.45µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. PMID:26828624

  4. Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study

    PubMed Central

    Graziano, Joseph H; Parvez, Faruque; Liu, Mengling; Slavkovich, Vesna; Kalra, Tara; Argos, Maria; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; van Geen, Alexander

    2011-01-01

    Objective To evaluate the association between arsenic exposure and mortality from cardiovascular disease and to assess whether cigarette smoking influences the association. Design Prospective cohort study with arsenic exposure measured in drinking water from wells and urine. Setting General population in Araihazar, Bangladesh. Participants 11 746 men and women who provided urine samples in 2000 and were followed up for an average of 6.6 years. Main outcome measure Death from cardiovascular disease. Results 198 people died from diseases of circulatory system, accounting for 43% of total mortality in the population. The mortality rate for cardiovascular disease was 214.3 per 100 000 person years in people drinking water containing <12.0 µg/L arsenic, compared with 271.1 per 100 000 person years in people drinking water with ≥12.0 µg/L arsenic. There was a dose-response relation between exposure to arsenic in well water assessed at baseline and mortality from ischaemic heart disease and other heart disease; the hazard ratios in increasing quarters of arsenic concentration in well water (0.1-12.0, 12.1-62.0, 62.1-148.0, and 148.1-864.0 µg/L) were 1.00 (reference), 1.22 (0.65 to 2.32), 1.35 (0.71 to 2.57), and 1.92 (1.07 to 3.43) (P=0.0019 for trend), respectively, after adjustment for potential confounders including age, sex, smoking status, educational attainment, body mass index (BMI), and changes in urinary arsenic concentration since baseline. Similar associations were observed when baseline total urinary arsenic was used as the exposure variable and for mortality from ischaemic heart disease specifically. The data indicate a significant synergistic interaction between arsenic exposure and cigarette smoking in mortality from ischaemic heart disease and other heart disease. In particular, the hazard ratio for the joint effect of a moderate level of arsenic exposure (middle third of well arsenic concentration 25.3-114.0 µg/L, mean 63.5 µg/L) and

  5. Evaluation of an Elementary School–based Educational Intervention for Reducing Arsenic Exposure in Bangladesh

    PubMed Central

    Khan, Khalid; Ahmed, Ershad; Factor-Litvak, Pam; Liu, Xinhua; Siddique, Abu B.; Wasserman, Gail A.; Slavkovich, Vesna; Levy, Diane; Mey, Jacob L.; van Geen, Alexander

    2015-01-01

    Background Chronic exposure to well water arsenic (As) remains a major rural health challenge in Bangladesh and some other developing countries. Many mitigation programs have been implemented to reduce As exposure, although evaluation studies for these efforts are rare in the literature. Objectives In this study we estimated associations between a school-based intervention and various outcome measures of As mitigation. Methods We recruited 840 children from 14 elementary schools in Araihazar, Bangladesh. Teachers from 7 schools were trained on an As education curriculum, whereas the remaining 7 schools without any training formed the control group. Surveys, knowledge tests, and well-water testing were conducted on 773 children both at baseline and postintervention follow-up. Urine samples were collected from 210 children from 4 intervention schools and the same number of children from 4 control schools. One low-As (< 10 μg/L) community well in each study village was ensured during an 18-month intervention period. Results After adjustment for the availability of low-As wells and other sociodemographic confounders, children receiving the intervention were five times more likely to switch from high- to low-As wells (p < 0.001). We also observed a significant decline of urinary arsenic (UAs) (p = < 0.001) (estimated β = –214.9; 95% CI: –301.1, –128.7 μg/g creatinine) among the children who were initially drinking from high-As wells (> Bangladesh standard of 50 μg/L) and significantly improved As knowledge attributable to the intervention after controlling for potential confounders. Conclusions These findings offer strong evidence that school-based intervention can effectively reduce As exposure in Bangladesh by motivating teachers, children, and parents. Citation Khan K, Ahmed E, Factor-Litvak P, Liu X, Siddique AB, Wasserman GA, Slavkovich V, Levy D, Mey JL, van Geen A, Graziano JH. 2015. Evaluation of an elementary school–based educational intervention

  6. Paraoxonase 1 activity in subchronic low-level inorganic arsenic exposure through drinking water.

    PubMed

    Afolabi, Olusegun K; Wusu, Adedoja D; Ogunrinola, Olufunmilayo O; Abam, Esther O; Babayemi, David O; Dosumu, Oluwatosin A; Onunkwor, Okechukwu B; Balogun, Elizabeth A; Odukoya, Olusegun O; Ademuyiwa, Oladipo

    2016-02-01

    Epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. While the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic, epidemiological studies indicate a role for paraoxonase 1 (PON1) in cardiovascular diseases. To investigate the association between inorganic arsenic exposure and cardiovascular diseases, rats were exposed to sodium arsenite (trivalent; 50, 100, and 150 ppm As) and sodium arsenate (pentavalent; 100, 150, and 200 ppm As) in their drinking water for 12 weeks. PON1 activity towards paraoxon (PONase) and phenylacetate (AREase) in plasma, lipoproteins, hepatic, and brain microsomal fractions were determined. Inhibition of PONase and AREase in plasma and HDL characterized the effects of the two arsenicals. While the trivalent arsenite inhibited PONase by 33% (plasma) and 46% (HDL), respectively, the pentavalent arsenate inhibited the enzyme by 41 and 34%, respectively. AREase activity was inhibited by 52 and 48% by arsenite, whereas the inhibition amounted to 72 and 67%, respectively by arsenate. The pattern of inhibition in plasma and HDL indicates that arsenite induced a dose-dependent inhibition of PONase whereas arsenate induced a dose-dependent inhibition of AREase. In the VLDL + LDL, arsenate inhibited PONase and AREase while arsenite inhibited PONase. In the hepatic and brain microsomal fractions, only the PONase enzyme was inhibited by the two arsenicals. The inhibition was more pronounced in the hepatic microsomes where a 70% inhibition was observed at the highest dose of pentavalent arsenic. Microsomal cholesterol was increased by the two arsenicals resulting in increased cholesterol/phospholipid ratios. Our findings indicate that decreased PON1 activity observed in arsenic exposure may be an incipient biochemical event in the cardiovascular effects of arsenic. Modulation of PON1 activity by arsenic may also be

  7. Arsenic Exposure and Motor Function among Children in Bangladesh

    PubMed Central

    Parvez, Faruque; Wasserman, Gail A.; Factor-Litvak, Pam; Liu, Xinhua; Slavkovich, Vesna; Siddique, Abu B.; Sultana, Rebeka; Sultana, Ruksana; Islam, Tariqul; Levy, Diane; Mey, Jacob L.; van Geen, Alexander; Khan, Khalid; Kline, Jennie; Ahsan, Habibul

    2011-01-01

    Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children’s intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function. Methods: We investigated the associations of WAs and WMn with motor function in 304 children in Bangladesh, 8–11 years of age. We measured As and Mn concentrations in drinking water, blood, urine, and toenails. We assessed motor function with the Bruininks-Oseretsky test, version 2, in four subscales—fine manual control (FMC), manual coordination (MC), body coordination (BC), and strength and agility—which can be summarized with a total motor composite score (TMC). Results: Log-transformed blood As was associated with decreases in TMC [β = –3.63; 95% confidence interval (CI): –6.72, –0.54; p < 0.01], FMC (β = –1.68; 95% CI: –3.19, –0.18; p < 0.05), and BC (β = –1.61; 95% CI: –2.72, –0.51; p < 0.01), with adjustment for sex, school attendance, head circumference, mother’s intelligence, plasma ferritin, and blood Mn, lead, and selenium. Other measures of As exposure (WAs, urinary As, and toenail As) also were inversely associated with motor function scores, particularly TMC and BC. Square-transformed blood selenium was positively associated with TMC (β = 3.54; 95% CI: 1.10, 6.0; p < 0.01), FMC (β = 1.55; 95% CI: 0.40, 2.70; p < 0.005), and MC (β = 1.57; 95% CI: 0.60, 2.75; p < 0.005) in the unadjusted models. Mn exposure was not significantly associated with motor function. Conclusion: Our research demonstrates an adverse association of As exposure and a protective association of Se on motor function in children. PMID:21742576

  8. GENE EXPRESSION CHANGES IN MOUSE BLADDER TISSUE IN RESPONSE TO INORGANIC ARSENIC

    EPA Science Inventory

    Chronic human exposures to high arsenic concentrations are associated with lung, skin, and bladder cancer. Considerable controversy exists concerning arsenic mode of action and low dose extrapolation. This investigation was designed to identify dose-response changes in gene expre...

  9. Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

    PubMed Central

    Huang, Chun-Fa; Yang, Ching-Yao; Chan, Ding-Cheng; Wang, Ching-Chia; Huang, Kuo-How; Wu, Chin-Ching; Tsai, Keh-Sung; Yang, Rong-Sen

    2015-01-01

    Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic

  10. ASSESSING ARSENIC EXPOSURE AND SKIN HYPERKERATOSIS IN INNER MONGOLIA, CHINA

    EPA Science Inventory

    Arsenic is a known human carcinogen. The inorganic forms, especially arsenite (As+3), are believed to be the most toxic species. Methylation is often considered to be the
    detoxification pathway for the metabolism of inorganic arsenic. The ground water in Ba
    Men, Inner Mo...

  11. Human biomonitoring of arsenic and antimony in case of an elevated geogenic exposure.

    PubMed Central

    Gebel, T W; Suchenwirth, R H; Bolten, C; Dunkelberg, H H

    1998-01-01

    Part of the northern Palatinate region in Germany is characterized by elevated levels of arsenic and antimony in the soil due to the presence of ore sources and former mining activities. In a biomonitoring study, 218 residents were investigated for a putative increased intake of these elements. Seventy-six nonexposed subjects in a rural region in south lower Saxony were chosen as the reference group. Urine and scalp hair samples were obtained as surrogates to determine the internal exposures to arsenic and antimony. The analyses were performed using graphite furnace atomic absorption spectrometry except for arsenic in urine, which was determined by the hydride technique. This method does not detect organoarsenicals from seafood, which are not toxicologically relevant. In the northern Palatinate subjects, slightly elevated arsenic contents in urine and scalp hair (presumably not hazardous) could be correlated with an increased arsenic content in the soil. On the other hand, the results did not show a correlation between the antimony contents in the soil of the housing area and those in urine and hair. Except for antimony in scalp hair, age tended to be associated with internal exposures to arsenic and antimony in both study groups. Consumption of seafood had a slight impact on the level of urinary arsenic, which is indicative of the presence of low quantities of inorganic arsenicals and dimethylarsinic acid in seafood. The arsenic and antimony contents in scalp hair were positively correlated with the 24-hr arsenic excretion in urine. However, antimony in scalp hair was not correlated with seafood consumption as was arsenic in scalp hair and in urine. This indicated the existence of unidentified common pathways of exposure contributing to the alimentary body burden. Short time peaks in the 24-hr excretion of arsenic in urine, which could not be assigned to a high consumption of seafood, were detected for six study participants. This suggests that additional factors

  12. Effects of arsenic exposure on DNA methylation and epigenetic gene regulation

    PubMed Central

    Reichard, John F; Puga, Alvaro

    2010-01-01

    Arsenic is a nonmutagenic human carcinogen that induces tumors through unknown mechanisms. A growing body of evidence suggests that its carcinogenicity results from epigenetic changes, particularly in DNA methylation. Changes in gene methylation status, mediated by arsenic, have been proposed activate oncogene expression or silence tumor suppressor genes, leading to long-term changes in activity of genes controlling cell transformation. Mostly descriptive, and often contradictory, studies have demonstrated that arsenic exposure is associated with both hypo- and hyper-methylation at various genetic loci in vivo or in vitro. This ambiguity has made it difficult to assess whether the changes induced by arsenic are causally involved in the transformation process or are simply a reflection of the altered physiology of rapidly dividing cancer cells. Here, we discuss the evidence supporting changes in DNA methylation as a cause of arsenic carcinogenesis and highlight the strengths and limitations of these studies, as well areas where consistencies and inconsistencies exist. PMID:20514360

  13. Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

    SciTech Connect

    McClintock, Tyler R.; Chen, Yu; Parvez, Faruque; Makarov, Danil V.; Ge, Wenzhen; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; Bjurlin, Marc A.; Graziano, Joseph H.; and others

    2014-04-01

    Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As. - Highlights: • Hematuria is the most common symptom of urinary tract disease. • Arsenic exposure is associated with renal dysfunction and urologic malignancy. • Water arsenic was positively associated with prevalence and incidence of hematuria. • Reduction in exposure lowered hematuria risk especially in low-to-moderate exposed

  14. Association of hypothyroidism with low-level arsenic exposure in rural West Texas.

    PubMed

    Gong, Gordon; Basom, Janet; Mattevada, Sravan; Onger, Frederick

    2015-04-01

    It has been reported recently that a higher airborne arsenic level was correlated with higher urinary arsenic concentration and lower serum thyroxin level among urban policemen and rural highway workmen in Italy. The current study was to determine whether exposure to low-level arsenic groundwater (2-22µg/L) is associated with hypothyroidism among 723 participants (118 male and 267 female Hispanics; 108 male and 230 female non-Hispanic whites, NHW) living in rural West Texas counties. Arsenic and iodine levels in their groundwater used for drinking and or cooking were estimated by the inverse distance weighted (IDW) interpolation technique. Groundwater arsenic was ≥8µg/L in 36% of the subjects' wells while iodine concentration was <1µg/L in 91% of their wells. Logistic regression analysis showed that arsenic in groundwater ≥8µg/L and cumulative arsenic exposure (groundwater arsenic concentration multiplied by the number of years living in the current address) but not groundwater iodine concentration were significant predictors for hypothyroidism among Hispanics (p<0.05) but not NHW after adjusting for covariates such as age, gender, annual household income and health insurance coverage. The ethnic difference may be due to a marginally higher percentage of Hispanics (p=0.0622) who lived in areas with groundwater arsenic ≥8µg/L compared with NHW. The prevalence of hypothyroidism was significantly higher in Hispanics or NHW of this rural cohort than the national prevalence. Measures should be taken to reduce arsenic in drinking water in order to prevent hypothyroidism in rural areas. PMID:25721242

  15. The Role of Arsenic Speciation in Dietary Exposure Assessment and the Need to Include Bioaccessibility and Biotransformation

    EPA Science Inventory

    Chemical form specific exposure assessment for arsenic has long been identified as a source of uncertainty in estimating the risk associated with the aggregate exposure for a population. Some speciation based assessments document occurrence within an exposure route; however, the...

  16. Transcriptomic Responses During Early Development Following Arsenic Exposure in Western Clawed Frogs, Silurana tropicalis.

    PubMed

    Zhang, Jing; Koch, Iris; Gibson, Laura A; Loughery, Jennifer R; Martyniuk, Christopher J; Button, Mark; Caumette, Guilhem; Reimer, Kenneth J; Cullen, William R; Langlois, Valerie S

    2015-12-01

    Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development. PMID:26427749

  17. Pathways of human exposure to arsenic in a community surrounding a copper smelter

    SciTech Connect

    Polissar, L.; Lowry-Coble, K.; Kalman, D.A.; Hughes, J.P.; van Belle, G.; Covert, D.S.; Burbacher, T.M.; Bolgiano, D.; Mottet, N.K. )

    1990-10-01

    Several studies have found elevated levels of urinary arsenic among residents living near a copper smelter in Tacoma, Washington. To assess pathways of exposure to arsenic from the smelter, biological and environmental samples were collected longitudinally from 121 households up to 8 miles from the smelter. The concentration of inorganic and methylated arsenic compounds in spot urine samples was used as the primary measure of exposure to environmental arsenic. Urinary concentration of arsenic dropped off to a constant background level within one-half mile of the smelter in contrast to environmental concentrations, which decreased more steadily with increasing distance. Among all age-sex-specific groups in all areas, only children ages 0-6 living within one-half mile of the smelter had elevated levels of arsenic in urine. A separate analysis of data for these children suggests that hand-to-mouth activity was the primary source of exposure. Inhalation of ambient air and resuspension of contaminated soil were not important sources of exposure for children or adults.

  18. In utero and early life arsenic exposure in relation to long-term health and disease

    SciTech Connect

    Farzan, Shohreh F.; Karagas, Margaret R.; Chen, Yu

    2013-10-15

    Background: There is a growing body of evidence that prenatal and early childhood exposure to arsenic from drinking water can have serious long-term health implications. Objectives: Our goal was to understand the potential long-term health and disease risks associated with in utero and early life exposure to arsenic, as well as to examine parallels between findings from epidemiological studies with those from experimental animal models. Methods: We examined the current literature and identified relevant studies through PubMed by using combinations of the search terms “arsenic”, “in utero”, “transplacental”, “prenatal” and “fetal”. Discussion: Ecological studies have indicated associations between in utero and/or early life exposure to arsenic at high levels and increases in mortality from cancer, cardiovascular disease and respiratory disease. Additional data from epidemiologic studies suggest intermediate effects in early life that are related to risk of these and other outcomes in adulthood. Experimental animal studies largely support studies in humans, with strong evidence of transplacental carcinogenesis, atherosclerosis and respiratory disease, as well as insight into potential underlying mechanisms of arsenic's health effects. Conclusions: As millions worldwide are exposed to arsenic and evidence continues to support a role for in utero arsenic exposure in the development of a range of later life diseases, there is a need for more prospective studies examining arsenic's relation to early indicators of disease and at lower exposure levels. - Highlights: • We review in utero and early-life As exposure impacts on lifelong disease risks. • Evidence indicates that early-life As increases risks of lung disease, cancer and CVD. • Animal work largely parallels human studies and may lead to new research directions. • Prospective studies and individual exposure assessments with biomarkers are needed. • Assessing intermediary endpoints may

  19. Estimating Effects of Arsenic Exposure During Pregnancy on Perinatal Outcomes in a Bangladeshi Cohort

    PubMed Central

    Cardenas, Andres; Rodrigues, Ema; Mazumdar, Maitreyi; Dobson, Christine; Golam, Mostofa; Quamruzzaman, Quazi; Rahman, Mahmudar; Christiani, David C.

    2016-01-01

    Background: The relationship between arsenic and birth weight is not well understood. The objective was to evaluate the causal relationship between prenatal arsenic exposure and birth weight considering the potential mediation effects of gestational age and maternal weight gain during pregnancy using structural equation models. Methods: A prospectively enrolled cohort of pregnant women was recruited in Bangladesh from 2008 to 2011. Arsenic was measured in personal drinking water at the time of enrollment (gestational age <16 weeks, N = 1,140) and in toenails collected ≤1 month postpartum (N = 624) using inductively coupled plasma mass spectrometry. Structural equation models estimated the direct and indirect effects of arsenic on birth weight with gestational age and maternal weight gain considered as mediating variables. Results: Every unit increase in natural log water arsenic was indirectly associated with decreased birth weight (β = −19.17 g, 95% confidence interval [CI]: −24.64, −13.69) after adjusting for other risk factors. This association was mediated entirely through gestational age (β = −17.37 g, 95% CI: −22.77, −11.98) and maternal weight gain during pregnancy (β = −1.80 g, 95% CI: −3.72, 0.13). When exposure was modeled using toenail arsenic concentrations, similar results were observed. Every increase in natural log toenail arsenic was indirectly associated with decreased birth weight (β = −15.72 g, 95% CI: −24.52, −6.91) which was mediated through gestational age (β = −13.59 g, 95% CI: −22.10, −5.07) and maternal weight gain during pregnancy (β = −2.13 g, 95% CI: −5.24, 0.96). Conclusion: Arsenic exposure during pregnancy was associated with lower birth weight. The effect of arsenic on birth weight appears to be mediated mainly through decreasing gestational age and to a lesser extent by lower maternal weight gain during pregnancy. PMID:26583609

  20. Arsenic Exposure, Dietary Patterns, and Skin Lesion Risk in Bangladesh: A Prospective Study

    PubMed Central

    Pierce, Brandon L.; Argos, Maria; Chen, Yu; Melkonian, Stephanie; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Dietary factors are believed to modulate arsenic toxicity, potentially influencing risk of arsenical skin lesions. The authors evaluated associations among dietary patterns, arsenic exposure, and skin lesion risk using baseline food frequency questionnaire data collected in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000–2009). They identified dietary patterns and estimated dietary pattern scores using factor analysis. Scores were tested for association with incident skin lesion risk and interaction with water arsenic exposure by using ∼6 years of follow-up data (814 events among 9,677 individuals) and discrete time hazards models (adjusting for key covariates). The authors identified 3 clear dietary patterns: the “gourd and root,” “vegetable,” and “animal protein” patterns. The gourd and root pattern score was inversely associated with skin lesion risk (Ptrend = 0.001), with hazard ratios of 0.86, 0.73, and 0.69 for the second, third, and fourth highest quartiles. Furthermore, the association between water arsenic and skin lesion incidence was stronger among participants with low gourd and root scores (multiplicative Pinteraction < 0.001; additive Pinteraction = 0.05). The vegetable pattern and animal protein pattern showed similar but weaker associations and interactions. Eating a diet rich in gourds and root vegetables and increasing dietary diversity may reduce arsenical skin lesion risk in Bangladesh. PMID:21178101

  1. Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort

    PubMed Central

    Punshon, Tracy; Davis, Matthew A.; Marsit, Carmen J.; Theiler, Shaleen K.; Baker, Emily R.; Jackson Brian, P.; Conway, David C.; Karagas, Margaret R.

    2015-01-01

    Arsenic crosses the placenta and may have adverse consequences in utero and later in life. At present, little is known about arsenic concentrations in placenta and their relation to maternal and infant exposures particularly at common levels of exposure. We measured placenta arsenic in a US cohort potentially exposed via drinking water from private wells, and evaluated the relationships between placenta and maternal and infant biomarker arsenic concentrations. We measured total arsenic concentrations in placental samples from women enrolled in the New Hampshire Birth Cohort Study (N=766). We compared these data to maternal urinary arsenic (total arsenic and individual species) collected at approximately 24–28 week gestation, along with maternal post-partum toenails and infant toenails using non-parametric multivariate analysis of log10-transformed data. We also examined the association between placental arsenic and household drinking water arsenic. Placenta arsenic concentrations were related to arsenic concentrations in maternal urine (β 0.55, P value <0.0001), maternal (β 0.30, P value 0.0196) and infant toenails (β 0.40, P value 0.0293) and household drinking water (β 0.09, P value <0.0001). Thus, our data suggest that placenta arsenic concentrations reflect both maternal and infant exposures. PMID:25805251

  2. Placental arsenic concentrations in relation to both maternal and infant biomarkers of exposure in a US cohort.

    PubMed

    Punshon, Tracy; Davis, Matthew A; Marsit, Carmen J; Theiler, Shaleen K; Baker, Emily R; Jackson, Brian P; Conway, David C; Karagas, Margaret R

    2015-01-01

    Arsenic crosses the placenta and may have adverse consequences in utero and later in life. At present, little is known about arsenic concentrations in placenta and their relation to maternal and infant exposures particularly at common levels of exposure. We measured placenta arsenic in a US cohort potentially exposed via drinking water from private wells, and evaluated the relationships between placenta and maternal and infant biomarker arsenic concentrations. We measured total arsenic concentrations in placental samples from women enrolled in the New Hampshire Birth Cohort Study (N=766). We compared these data to maternal urinary arsenic (total arsenic and individual species) collected at approximately 24-28 week gestation, along with maternal post-partum toenails and infant toenails using non-parametric multivariate analysis of log10-transformed data. We also examined the association between placental arsenic and household drinking water arsenic. Placenta arsenic concentrations were related to arsenic concentrations in maternal urine (β 0.55, P value <0.0001), maternal (β 0.30, P value 0.0196) and infant toenails (β 0.40, P value 0.0293) and household drinking water (β 0.09, P value <0.0001). Thus, our data suggest that placenta arsenic concentrations reflect both maternal and infant exposures. PMID:25805251

  3. SPECIATION OF ARSENIC IN DIETARY AND DIETARY COMPOSITE SAMPLES TO PROVIDE A MORE COMPLETE ASSESSMENT OF ARSENIC EXPOSURE FROM DIETARY SOURCES

    EPA Science Inventory

    The FDA's market basket study reports total arsenic concentrations from composite diet samples. The use of composite diets, based on market basket sampling, is the most cost effective means of obtaining a generic arsenic exposure estimate for a population. For example, the tota...

  4. Contribution of breast milk and formula to arsenic exposure during the first year of life in a US prospective cohort.

    PubMed

    Carignan, Courtney C; Karagas, Margaret R; Punshon, Tracy; Gilbert-Diamond, Diane; Cottingham, Kathryn L

    2016-09-01

    Arsenic is a carcinogen that can also affect the cardiac, respiratory, neurological and immune systems. Children have higher dietary arsenic exposure than adults owing to their more restricted diets and greater intake per unit body mass. We evaluated the potential contributions of breast milk and formula to arsenic exposure throughout the first year of life for 356 infants in the prospective New Hampshire Birth Cohort Study (NHBCS) using infant diets reported by telephone at 4, 8 and 12 months of age; measured household water arsenic concentrations; and literature data. Based on our central-tendency models, population-wide geometric mean (GM) estimated arsenic exposures in the NHBCS were relatively low, decreasing from 0.1 μg/kg/day at 4 months of age to 0.07 μg/kg/day at 12 months of age. At all three time points, exclusively formula-fed infants had GM arsenic exposures ~8 times higher than exclusively breastfed infants owing to arsenic in both tap water and formula powder. Estimated maximum exposures reached 9 μg/kg/day among exclusively formula-fed infants in households with high tap water arsenic (80 μg/l). Overall, modeled arsenic exposures via breast milk and formula were low throughout the first year of life, unless formula was prepared with arsenic-contaminated tap water. PMID:26531802

  5. Why Does Exposure to Arsenic from Drinking Groundwater in Asian Megadeltas Continue to be High?

    NASA Astrophysics Data System (ADS)

    van Geen, A.; Ahmed, K. M.; Ahmed, E. B.; Choudhury, I.; Mozumder, M. R. H.; Bostick, B. C.; Mailloux, B. J.; Knappett, P. S.; Schlosser, P.

    2014-12-01

    Concentrations of arsenic in groundwater pumped from a significant fraction of the millions of shallow tubewells installed, mostly privately, across S/SE Asia exceed the WHO guideline value of 10 ug/L by a factor of 10 to 100. The resulting exposure has been linked to cancers and cardio-vascular disease in adults and inhibited intellectual function in children. In Bangladesh, the most affected country, the impact of early mitigation efforts relying on water treatment has been limited by the cost and logistics of maintenance. A simpler approach based on switching human consumption to low-arsenic wells has proved to be more resilient although it remains far from sufficiently adopted. A decade ago, there was concern that low-arsenic wells might become contaminated upon use. Observations and modeling have since shown that groundwater arsenic concentrations are likely to rise only in certain hydrogeologically vulnerable areas and then only gradually. Our recently completed blanket-testing campaign of 50,000 wells in 300 villages of Bangladesh has shown that, instead, a leading cause of current exposure is that households have continued to install wells and typically have nowhere to turn for a reliable arsenic test. The same campaign has shown that another reason for continued exposure is that deeper wells that are low in arsenic and whose installation has been subsidized by the Bangladesh government are not located to maximize public access. The geographic clustering of these deep wells suggests that, all too often, their location is decided on the basis of political allegiance rather than need. Such obstacles to lowering arsenic exposure might be overcome with more widespread testing and the public posting of maps of test results also showing where deep wells have been installed. We will show that obtaining and sharing such information has been greatly facilitated by a reliable field-kit for arsenic and the increasing use of smartphones in Bangladesh.

  6. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    SciTech Connect

    Qu, Wei Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  7. Effect of chronic intake of arsenic-contaminated water on liver

    SciTech Connect

    Guha Mazumder, D.N. . E-mail: dngm@apexmail.com

    2005-08-07

    The hepatotoxic effect of arsenic when used in therapeutic dose has long been recognized. We described the nature and degree of liver involvement and its pathogenesis due to prolonged drinking of arsenic-contaminated water in West Bengal, India. From hospital-based studies on 248 cases of arsenicosis, hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The portal fibrosis was characterized by expansion of portal zones with streaky fibrosis, a few of which contained leash of vessels. However, portal hypertension was found in smaller number of cases. A cross-sectional epidemiological study was carried out on 7683 people residing in arsenic-affected districts of West Bengal. Out of these, 3467 and 4216 people consumed water-containing arsenic below and above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001). The incidence of hepatomegaly was found to have a linear relationship proportionate to increasing exposure of arsenic in drinking water in both sexes (P < 0.001). In an experimental study, BALB/C mice were given water contaminated with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at 3-month intervals. We observed progressive reduction of hepatic glutathione and enzymes of anti-oxidative defense system associated with lipid peroxidation. Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15 months. Our studies show that prolong drinking of arsenic-contaminated water is associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to be caused by arsenic induced oxystress.

  8. Arsenic Exposure in Latin America: Biomarkers, Risk Assessments and Related Health Effects

    PubMed Central

    McClintock, Tyler R.; Chen, Yu; Bundschuh, Jochen; Oliver, John T.; Navoni, Julio; Olmos, Valentina; Lepori, Edda Villaamil; Ahsan, Habibul; Parvez, Faruque

    2013-01-01

    In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries. It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (>50µg/L), some to as high as 2000 µg/L - 200 times higher than the World Health Organization (WHO) provisional standard for drinking water. We conducted a systematic review of 82 peer reviewed papers and reports to fully explore the current understanding of As exposure and its health effects, as well as the influence of genetic factors that modulate those effects in the populations of Latin America. Despite some methodological limitations, these studies suggested important links between high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America - including internal and external cancers, reproductive outcomes, and childhood cognitive function. Several studies demonstrated genetic polymorphisms that influence susceptibility to these and other disease states through their modulation of As metabolism, with As methyltransferase (AS3MT), glutathione S-transferase (GST), and genes of one-carbon metabolism being specifically implicated. While the full extent and nature of the health burden are yet to be known in Latin America, these studies have significantly enriched knowledge of As toxicity and led to subsequent research. Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts. PMID:22119448

  9. In utero and early childhood exposure to arsenic decreases lung function in children

    PubMed Central

    Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

    2016-01-01

    Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

  10. Implications of oxidative stress and hepatic cytokine (TNF-{alpha} and IL-6) response in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity

    SciTech Connect

    Das, Subhankar; Santra, Amal; Lahiri, Sarbari; Guha Mazumder, D.N. . E-mail: dngm@apexmail.com

    2005-04-01

    Introduction: Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor {alpha} (TNF-{alpha}) and interleukin 6 (IL-6) are suspected to play a role in hepatic collagenesis. The present study has been carried out to find out whether increased oxystress and cytokine response are associated with increased accumulation of collagen in the liver due to prolonged arsenic exposure and these follow a dose-response relationship. Methods: Male BALB/c mice were given orally 200 {mu}l of water containing arsenic in a dose of 50, 100, and 150 {mu}g/mouse/day for 6 days a week (experimental group) or arsenic-free water (<0.01 {mu}g/l, control group) for 3, 6, 9 and 12 months. Hepatic glutathione (GSH), protein sulfhydryl (PSH), glutathione peroxidase (GPx), Catalase, lipid peroxidation (LPx), protein carbonyl (PC), interleukin (IL-6), tumor necrosis factor (TNF-{alpha}), arsenic and collagen content in the liver were estimated from sacrificed animals. Results: Significant increase of lipid peroxidation and protein oxidation in the liver associated with depletion of hepatic thiols (GSH, PSH), and antioxidant enzymes (GPx, Catalase) occurred in mice due to prolonged arsenic exposure in a dose-dependent manner. Significant elevation of hepatic collagen occurred at 9 and 12 months in all the groups associated with significant elevation of TNF-{alpha} and IL-6. However, arsenic level in the liver increased progressively from 3 months onwards. There was a positive correlation between the hepatic arsenic level and collagen content (r = 0.8007), LPx (r = 0.779) and IL-6 (r = 0.7801). Further, there was a significant negative correlation between GSH and TNF-{alpha} (r = -0.5336)) and LPx (r = -0.644). Conclusion: Increasing dose and duration of arsenic exposure in

  11. Concentrations of Inorganic Arsenic in Milled Rice from China and Associated Dietary Exposure Assessment.

    PubMed

    Huang, Yatao; Wang, Min; Mao, Xuefei; Qian, Yongzhong; Chen, Tianjin; Zhang, Ying

    2015-12-23

    Total arsenic (As) and inorganic As (Asi) in milled rice (n = 1653) collected from China were studied to evaluate the contamination level, distribution, and health risks. The mean concentrations of the total As and Asi were 116.5 and 90.9 μg/kg, respectively. There were significant differences (P < 0.01) between the 11 provinces, and 1.1% of samples exceeded the maximum contaminant level established by Chinese legislation. According to the exposure assessment method of probabilistic simulation, all values of the target hazard quotients (THQs) for chronic noncarcinogenic risks (skin lesions as the point of departure) were below 1, suggesting that the Chinese population will not encounter a significant noncarcinogenic risk. However, the mean values of margin of exposure (MOE) for lung cancer risks ranging from 3.86 to 8.54 were under 100 for all age groups and genders of the Chinese population; moreover, MOE values for some major rice-producing and -consuming countries, such as Japan, Thailand, Bangladesh, and the United States, were all also below 100. More attention should be paid to carcinogenic risks from rice Asi intake, and some control measures to reduce rice Asi intake should be taken. PMID:26641731

  12. Arsenic Exposure Is Associated with Decreased DNA Repair in Vitro and in Individuals Exposed to Drinking Water Arsenic

    PubMed Central

    Andrew, Angeline S.; Burgess, Jefferey L.; Meza, Maria M.; Demidenko, Eugene; Waugh, Mary G.; Hamilton, Joshua W.; Karagas, Margaret R.

    2006-01-01

    The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action. PMID:16882524

  13. Sex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome.

    PubMed

    Chi, Liang; Bian, Xiaoming; Gao, Bei; Ru, Hongyu; Tu, Pengcheng; Lu, Kun

    2016-06-20

    The gut microbiome is deeply involved in numerous aspects of human health; however, it can be readily perturbed by environmental toxicants, such as arsenic. Meanwhile, the interaction among host, gut microbiome, and xenobiotics is a very complex dynamic process. Previously, we have demonstrated that gut microbiome phenotypes driven by host genetics and bacterial infection affect the responses to arsenic exposure. The role of host sex in shaping the gut microbiome raises the question whether sex plays a role in exposure-induced microbiome responses. To examine this, we used 16S rRNA sequencing and metagenomics sequencing to analyze the changes of the gut microbiome and its associated functional metagenome in both female and male C57/BL6 mice. Our results clearly demonstrated that arsenic exposure perturbed the trajectory and function of the gut microbiome in a sex-specific manner. PMID:27268458

  14. In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort

    PubMed Central

    Nadeau, Kari C.; Li, Zhigang; Farzan, Shohreh; Koestler, Devin; Robbins, David; Fei, Dennis Liang; Malipatlolla, Meena; Maecker, Holden; Enelow, Richard; Korrick, Susan; Karagas, Margaret R.

    2014-01-01

    Arsenic has wide-ranging effects on human health and there is evidence that it alters the immune response by influencing CD4+/CD8+ T cell ratios, IL-2 cytokine levels, and the expression of immune-response genes. We investigated the impact of in utero environmental arsenic exposure on immune development and function in newborns participating in a pregnancy cohort in New Hampshire, U.S., where arsenic levels have exceeded the current EPA maximum contaminant level of 10 μg/L. Our results showed that maternal urinary arsenic concentrations were inversely related to absolute total CD45RA+ CD4+ cord blood CD69+ T cell counts (N=116, p=0.04) and positively associated with CD45RA+ CD69− CD294+ cell counts (p=0.01). In placental samples (N=70), higher in utero urinary arsenic concentrations were positively associated with expression of IL1β (p=0.03). These data provide evidence that relatively low-level arsenic exposure in utero may alter the fetal immune system and lead to immune dysregulation. PMID:25229165

  15. Synergistic effect of polymorphisms of paraoxonase gene cluster and arsenic exposure on electrocardiogram abnormality

    SciTech Connect

    Liao, Y.-T.; Li, W.-F.; Chen, C.-J.; Prineas, Ronald J.; Chen, Wei J.; Zhang Zhuming; Sun, C.-W.; Wang, S.-L.

    2009-09-01

    Arsenic has been linked to increased prevalence of cancer and cardiovascular disease (CVD), but the long-term impact of arsenic exposure remains unclear. Human paraoxonase (PON1) is a high-density lipoprotein-associated antioxidant enzyme which hydrolyzes oxidized lipids and is thought to be protective against atherosclerosis, but evidence remains limited to case-control studies. Only recently have genes encoding enzymes responsible for arsenic metabolism, such as AS3MT and GSTO, been cloned and characterized. This study was designed to evaluate the synergistic interaction of genetic factors and arsenic exposure on electrocardiogram abnormality. A total of 216 residents from three tap water implemented villages of previous arseniasis-hyperendemic regions in Taiwan were prospectively followed for an average of 8 years. For each resident, a 12-lead conventional electrocardiogram (ECG) was recorded and coded by Minnesota Code standard criteria. Eight functional polymorphisms of PON1, PON2, AS3MT, GSTO1, and GSTO2 were examined for genetic susceptibility to ECG abnormality. Among 42 incident cases with ECG deterioration identified among 121 baseline-normal subjects, arsenic exposure was significantly correlated with incidence of ECG abnormality. In addition, polymorphisms in two paraoxonase genes were also found associated with the incidence of ECG abnormality. A haplotype R-C-S constituted by polymorphisms of PON1 Q192R, -108C/T and PON2 C311S was linked to the increased risk. Subjects exposed to high levels of As (cumulative As exposure > 14.7 ppm-year or drinking artesian well water > 21 years) and carrying the R-C-S haplotype had significantly increased risks for ECG abnormality over those with only one risk factor. Results of this study showed a long-term arsenic effect on ECG abnormality and significant gene-gene and gene-environment interactions linked to the incidence of CVD. This finding might have important implications for a novel and potentially useful

  16. Effect of Arsenic Exposure during Pregnancy on Infant Development at 7 Months in Rural Matlab, Bangladesh

    PubMed Central

    Tofail, Fahmida; Vahter, Marie; Hamadani, Jena D.; Nermell, Barbro; Huda, Syed N.; Yunus, Mohammad; Rahman, Mahfuzar; Grantham-McGregor, Sally M.

    2009-01-01

    Background Exposure to arsenic-contaminated drinking water during pregnancy is associated with low birth weight and fetal loss, and there is concern that the infants’ development may be affected. Objective We assessed the effects of in utero arsenic exposure during pregnancy on infants’ problem-solving ability and motor development. Methods We conducted a large population-based study of nutritional supplementation with 4,436 pregnant women in Matlab, Bangladesh, an area of high-arsenic–contaminated tube wells. We measured arsenic concentration in spot urine specimens at 8 and 30 weeks of pregnancy. We assessed a subsample of 1,799 infants, born to these mothers, at 7 months of age on two problem-solving tests (PSTs), the motor scale of the Bayley Scales of Infant Development–II, and behavior ratings. Result Arsenic concentrations in maternal urine were high, with a median (interquartile range) of 81 μg/L (37–207 μg/L) at 8 weeks of gestation and of 84 μg/L (42–230 μg/L) at 30 weeks. Arsenic exposure was related to many poor socioeconomic conditions that also correlated with child development measures. Multiple regressions of children’s motor and PST scores and behavior ratings, controlling for socioeconomic background variables, age, and sex, showed no significant effect of urinary arsenic concentration on any developmental outcome. Conclusion We detected no significant effect of arsenic exposure during pregnancy on infant development. However, it is possible that other effects are as yet unmeasured or that effects will become apparent at a later age. PMID:19270801

  17. Multimedia exposures to arsenic and lead for children near an inactive mine tailings and smelter site.

    PubMed

    Loh, Miranda M; Sugeng, Anastasia; Lothrop, Nathan; Klimecki, Walter; Cox, Melissa; Wilkinson, Sarah T; Lu, Zhenqiang; Beamer, Paloma I

    2016-04-01

    Children living near contaminated mining waste areas may have high exposures to metals from the environment. This study investigates whether exposure to arsenic and lead is higher in children in a community near a legacy mine and smelter site in Arizona compared to children in other parts of the United States and the relationship of that exposure to the site. Arsenic and lead were measured in residential soil, house dust, tap water, urine, and toenail samples from 70 children in 34 households up to 7 miles from the site. Soil and house dust were sieved, digested, and analyzed via ICP-MS. Tap water and urine were analyzed without digestion, while toenails were washed, digested and analyzed. Blood lead was analyzed by an independent, certified laboratory. Spearman correlation coefficients were calculated between each environmental media and urine and toenails for arsenic and lead. Geometric mean arsenic (standard deviation) concentrations for each matrix were: 22.1 (2.59) ppm and 12.4 (2.27)ppm for soil and house dust (<63μm), 5.71 (6.55)ppb for tap water, 14.0 (2.01)μg/L for specific gravity-corrected total urinary arsenic, 0.543 (3.22)ppm for toenails. Soil and vacuumed dust lead concentrations were 16.9 (2.03)ppm and 21.6 (1.90) ppm. The majority of blood lead levels were below the limit of quantification. Arsenic and lead concentrations in soil and house dust decreased with distance from the site. Concentrations in soil, house dust, tap water, along with floor dust loading were significantly associated with toenail and urinary arsenic but not lead. Mixed models showed that soil and tap water best predicted urinary arsenic. In our study, despite being present in mine tailings at similar levels, internal lead exposure was not high, but arsenic exposure was of concern, particularly from soil and tap water. Naturally occurring sources may be an additional important contributor to exposures in certain legacy mining areas. PMID:26803211

  18. Chronic respiratory effects of indoor formaldehyde exposure

    SciTech Connect

    Krzyzanowski, M.; Quackenboss, J.J.; Lebowitz, M.D.

    1990-01-01

    The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers two one-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR linearly decreased with HCHO exposure, with estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children.

  19. DNA DAMAGE IN BUCCAL EPITHELIAL CELLS FROM INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA, CHINA

    EPA Science Inventory

    The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 ? 23.7 g/L (mean ? SEM) and ...

  20. Arsenic Exposure Increases Monocyte Adhesion to the Vascular Endothelium, a Pro-Atherogenic Mechanism.

    PubMed

    Lemaire, Maryse; Negro Silva, Luis Fernando; Lemarié, Catherine A; Bolt, Alicia M; Flores Molina, Manuel; Krohn, Regina M; Smits, Judit E; Lehoux, Stéphanie; Mann, Koren K

    2015-01-01

    Epidemiological studies have shown that arsenic exposure increases atherosclerosis, but the mechanisms underlying this relationship are unknown. Monocytes, macrophages and platelets play an important role in the initiation of atherosclerosis. Circulating monocytes and macrophages bind to the activated vascular endothelium and migrate into the sub-endothelium, where they become lipid-laden foam cells. This process can be facilitated by platelets, which favour monocyte recruitment to the lesion. Thus, we assessed the effects of low-to-moderate arsenic exposure on monocyte adhesion to endothelial cells, platelet activation and platelet-monocyte interactions. We observed that arsenic induces human monocyte adhesion to endothelial cells in vitro. These findings were confirmed ex vivo using a murine organ culture system at concentrations as low as 10 ppb. We found that both cell types need to be exposed to arsenic to maximize monocyte adhesion to the endothelium. This adhesion process is specific to monocyte/endothelium interactions. Hence, no effect of arsenic on platelet activation or platelet/leukocyte interaction was observed. We found that arsenic increases adhesion of mononuclear cells via increased CD29 binding to VCAM-1, an adhesion molecule found on activated endothelial cells. Similar results were observed in vivo, where arsenic-exposed mice exhibit increased VCAM-1 expression on endothelial cells and increased CD29 on circulating monocytes. Interestingly, expression of adhesion molecules and increased binding can be inhibited by antioxidants in vitro and in vivo. Together, these data suggest that arsenic might enhance atherosclerosis by increasing monocyte adhesion to endothelial cells, a process that is inhibited by antioxidants. PMID:26332580

  1. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    SciTech Connect

    Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  2. Effects of arsenic trioxide inhalation exposure on pulmonary antibacterial defenses in mice

    SciTech Connect

    Aranyi, C.; Bradof, J.N.; O'Shea, W.J.; Graham, J.A.; Miller, F.J.

    1985-01-01

    The effects of single and multiple (5 and 20) 3-h inhalation exposures to aerosols of arsenic trioxide on the pulmonary defense system of mice were investigated. Arsenic trioxide mist was generated from an aqueous solution and dried to produce particulate aerosols of 0. 4 micron mass median aerodynamic diameter. Aerosol mass concentration ranged from 125 to 1000 micrograms As/m3. Effects of the exposures were evaluated by determination of changes in susceptibility to experimentally induced streptococcal aerosol infection and in pulmonary bactericidal activity to /sup 35/S-labeled Klebsiella pneumoniae. Significant increases in mortality due to the infectious challenge and decreases in bactericidal activity were seen after single 3-h exposures to 270, 500, and 940 micrograms As/m3. Similarly, 5 or 20 multiple 3-h exposures to 500 micrograms As/m3 produced consistently significant increases in mortality and decreases in pulmonary bactericidal activity. At 125 or 250 micrograms As/m3, a decrease in bactericidal activity was seen only after 20 exposures to 250 micrograms/m3. Results from earlier studies with an arsenic-containing copper smelter dust were compared to these data. The possibility of the development of adaptation during multiple exposures to arsenic trioxide is also considered.

  3. GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

    EPA Science Inventory

    Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

  4. Chronic effects of arsenic on American red crayfish, Procambarus clarkii, exposed to monosodium methanearsonate (MSMA) herbicide

    SciTech Connect

    Naqvi, S.M. ); Flagge, C.T. )

    1990-07-01

    Bioaccumulative and biomagnifying effects of arsenic on crayfish have been reported. However, no work has been done on the chronic effects of this heavy metal on crayfish populations. There is a great concern for MSMA (Monosodium Methanearsonate) herbicide in the vicinity of natural waters due to its high water solubility and bioaccumulative potential. American red crayfish (Procambarus clarkii) account for 98% of the annual crayfish harvest in North America. Those pesticides which have greater water solubility (i.e. MSMA) than other less soluble compounds may cause higher mortalities of aquatic organisms, or cause adverse chronic effects if the non-target animals are sublethally exposed. This work was conducted in the laboratory to assess the possible chronic effects of arsenic on crayfish.

  5. DRINKING WATER ARSENIC EXPOSURE AND BLOOD PRESSURE IN HEALTHY WOMEN OF REPRODUCTIVE AGE IN INNER MONGOLIA, CHINA

    EPA Science Inventory

    The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on ...

  6. The Relative Importance of Waterborne and Dietborne Arsenic Exposure on Survival and Growth of Juvenile Rainbow Trout

    EPA Science Inventory

    Previous work in our laboratory demonstrated toxicity to rainbow trout fed oligochaetes contaminated with arsenic via waterborne exposure. While this demonstrated the potential hazard of dietborne exposure, it did not address the relative and combined potency of waterborne and d...

  7. Sequence of exposure to cadmium and arsenic determines the extent of toxic effects in male Fischer rats.

    PubMed

    Hochadel, J F; Waalkes, M P

    1997-01-15

    Arsenic and cadmium are both priority hazardous substances and human carcinogens. Although there is the potential for simultaneous exposure to both metals, the interactions of cadmium and arsenic are not well defined. We examined the toxicity of these metals when given alone or in alternating sequence to adult male Fischer rats. In the first study, a non-toxic dose of arsenic (22.5 micromol NaAsO2/kg, s.c.) was given 24 h before cadmium (10, 20, or 30 micromol CdCl2/kg, s.c.) and toxicity was assessed 24 h later. Arsenic pretreatment markedly reduced mortality in rats given the high dose of cadmium (9 survivors/10 treated) compared to rats given cadmium alone (2/10). Arsenic pretreatment also reduced cadmium-induced hepatotoxicity, as indicated by serum glutamic oxalacetic transaminase (SGOT) activity, and markedly reduced cadmium-induced testicular hemorrhagic necrosis. Arsenic pretreatment produced an 8-fold increase in hepatic levels of metallothionein (MT), a metal-binding protein often associated with cadmium tolerance. In the second study, a non-toxic dose of cadmium (3 micromol CdCl2/kg, s.c.) was given 24 h before arsenic (68, 79, 84, or 90 micro/mol NaAsO2/kg. s.c.) and toxicity was assessed 24 h later. Cadmium pretreatment did not alter the lethality of the high dose of arsenic and had no effect on arsenic-induced hepatotoxicity. Although cadmium pretreatment had no effect on arsenic toxicity, it produced large increases in hepatic MT (26-fold) before the arsenic challenge and greatly enhanced MT induction after the challenge. Thus, even though both arsenic and cadmium induce MT synthesis, only arsenic pretreatment protects against cadmium intoxication, and cadmium pretreatment does not effect arsenic toxicity. Thus, toxic interactions of arsenic and cadmium appear to depend on the sequence of exposure. PMID:9020510

  8. Inorganic arsenic exposure affects pain behavior and inflammatory response in rat

    SciTech Connect

    Aguirre-Banuelos, Patricia; Escudero-Lourdes, Claudia; Sanchez-Pena, Luz Carmen; Del Razo, Luz Maria; Perez-Urizar, Jose

    2008-06-15

    Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem associated with an increased risk for the development of various types of cancer and noncancerous damage. In vitro studies have suggested that iAs can modulate the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX-2) and resulting in an increase in prostaglandin E{sub 2} (PGE{sub 2}) concentrations in endothelial cells. These effects may lead to an in vivo enhancement of inflammatory and pain responses. Our aim was to determine the effect of a single dose of arsenic or subchronic exposure to arsenic on pain behavior and tissue inflammation in rats. Rats were given a single dose of sodium arsenite (0.1, 1 and 10 mg/kg i.p.) or submitted to subchronic exposure to arsenic added to the drinking water for 4 weeks (0.1, 1, 10 and 100 ppm). Inflammatory pain was assessed by using the formalin and tail-flick tests, while inflammation was evaluated with the carrageenan model. Arsenite did not induce pain or significant inflammation by itself. In contrast, arsenite in both single dose administration and subchronic exposure increased not only the inflammatory process and the underlying hyperalgesic pain, but also induced a decrease in the pain threshold. Alterations in pain processing were dependent on the arsenic dose and the length of exposure, and the underlying mechanism involved an increased release of local PGE{sub 2}. These results suggest that inorganic arsenic exposure enhances pain perception and exacerbates the pathological state of inflammatory diseases.

  9. APPLICATION OF PROTEOMIC METHODS TO ARSENIC EXPOSURE RESEARCH

    EPA Science Inventory

    Arsenic, an environmental contaminant, is introduced to drinking water through the leaching of soil and the result of anthropogenic sources such as industrial effluents and combustion of fossil fuels. It also occurs naturally in ground water sources in some geographic areas. Chro...

  10. Association between In Utero arsenic exposure, placental gene expression, and infant birth weight: a US birth cohort study

    PubMed Central

    2013-01-01

    Background Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels. Methods Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from enrollees were homogenized and profiled for gene expression across a panel of candidate genes, including known arsenic regulated targets and genes involved in arsenic transport, metabolism, or disease susceptibility. Multivariable adjusted linear regression models were used to examine the relationship of candidate gene expression with arsenic exposure or with birth weight of the baby. Results Placental expression of the arsenic transporter AQP9 was positively associated with maternal urinary arsenic levels during pregnancy (coefficient estimate: 0.25; 95% confidence interval: 0.05 – 0.45). Placental expression of AQP9 related to expression of the phospholipase ENPP2 which was positively associated with infant birth weight (coefficient estimate: 0.28; 95% CI: 0.09 – 0.47). A structural equation model indicated that these genes may mediate arsenic’s effect on infant birth weight (coefficient estimate: -0.009; 95% confidence interval: -0.032 – -0.001; 10,000 replications for bootstrapping). Conclusions We identified the expression of AQP9 as a potential fetal biomarker for arsenic exposure. Further, we identified a positive association between the placental expression of phospholipase ENPP2 and infant birth weight. These findings suggest a path by which arsenic may affect