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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. Pathology related to chronic arsenic exposure.

    PubMed Central

    Centeno, Jose A; Mullick, Florabel G; Martinez, Leonor; Page, Norbert P; Gibb, Herman; Longfellow, David; Thompson, Claudia; Ladich, Elena R

    2002-01-01

    Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water. PMID:12426152

  3. 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...

  4. 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...

  5. The Effect of Chronic Arsenic Exposure in Zebrafish

    PubMed Central

    Hallauer, Janell; Geng, Xiangrong; Yang, Hung-Chi; Shen, Jian; Tsai, Kan-Jen

    2016-01-01

    Abstract Arsenic is a prevalent environmental toxin and a Group one human carcinogenic agent. Chronic arsenic exposure has been associated with many human diseases. The aim of this study is to evaluate zebrafish as an animal model to assess arsenic toxicity in elevated long-term arsenic exposure. With prolonged exposure (6 months) to various concentrations of arsenic from 50 ppb to 300 ppb, effects of arsenic accumulation in zebrafish tissues, and phenotypes were investigated. Results showed that there are no significant changes of arsenic retention in zebrafish tissues, and zebrafish did not exhibit any visible tumor formation under arsenic exposure conditions. However, the zebrafish demonstrate a dysfunction in their neurological system, which is reflected by a reduction of locomotive activity. Moreover, elevated levels of the superoxide dismutase (SOD2) protein were detected in the eye and liver, suggesting increased oxidative stress. In addition, the progenies of arsenic-treated parents displayed a smaller biomass (four-fold reduction in body weight) compared with those from their parental controls. This result indicates that arsenic may induce genetic or epigenetic changes that are then passed on to the next generation. Overall, this study demonstrates that zebrafish is a convenient vertebrate model with advantages in the evaluation of arsenic-associated neurological disorders as well as its influences on the offspring. PMID:27140519

  6. 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 ...

  7. 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 ...

  8. Consequences of acute and chronic exposure to arsenic in children.

    PubMed

    Calderon, Rebecca L; Abernathy, Charles O; Thomas, David J

    2004-07-01

    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. For most people, the major exposure to arsenic comes from food (8 to 14 microg inorganic arsenic per day), but when the arsenic level in water is elevated, drinking water becomes the predominant source of exposure. Because it is very difficult to limit arsenic exposure from food, it would be wise to limit arsenic exposure from those more controllable sources. Pediatricians should ascertain the levels of arsenic in drinking water of patients with high arsenic levels, using the supplier or, in the case of private wells, a professional water-testing laboratory assay. The Safe Drinking Water Act does not cover private wells or those water systems with less than 15 hook-ups or those that serve less than 25 people. Pediatricians should instruct parents to use prepared baby formulas or prepare them using water with the arsenic removed and to curtail playing time for younger children in places that have sand containing large amounts of arsenic. Such procedures will limit arsenic exposure to a minimum.

  9. 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...

  10. 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...

  11. Cryptic exposure to arsenic.

    PubMed

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  12. Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

    PubMed

    Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

    2017-05-01

    The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Surveillance on chronic arsenic exposure in the Mekong River basin of Cambodia using different biomarkers.

    PubMed

    Phan, Kongkea; Sthiannopkao, Suthipong; Kim, Kyoung-Woong

    2011-12-01

    Thousands of Cambodia populations are currently at high risks of both toxic and carcinogenic effects through drinking arsenic-rich groundwater. In order to determine and assess the use of arsenic contents in different biological samples as biomarkers of chronic arsenic exposure from drinking arsenic-rich groundwater in Cambodia, individual scalp hair, fingernail and toenail were collected from three different provinces in the Mekong River basin of Cambodia. After washing and acid-digestion, digestate was analyzed for total arsenic by an inductively coupled plasma mass spectrometry. Chemical analysis of the acid-digested hair revealed that among 270 hair samples cut from Kandal, 78.1% had arsenic content in scalp hair (As(h)) greater than the typical As(h) (1.00 μg g(-1)), indicating possible arsenic toxicity. Concurrently, 1.2% and 0.6% were found elevated in Kratie (n=84) and Kampong Cham (n=173), respectively. Similarly, the upper end of the ranges for arsenic contents in fingernail (As(fn)) and toenail (As(tn)) clipped from Kandal (fingernail n=241; toenail n=187) were higher than the normal arsenic content in nail (0.43-1.08 μg g(-1)), however, none was observed elevated in both Kratie (fingernail n=76, toenail n=42) and Kampong Cham (fingernail n=83; toenail n=52). Significant positive intercorrelations between groundwater arsenic concentration (As(w)), average daily dose (ADD) of arsenic, As(h), As(fn) and As(tn) suggest that As(h), As(fn) and As(tn) can be used as biomarkers of chronic arsenic exposure from drinking arsenic-rich groundwater, in which As(h) is more favorable than As(fn) and As(tn) due to the ease of sample processing and analytical measurements, respectively.

  14. 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.

  15. Vascular Dysfunction in Patients with Chronic Arsenosis Can Be Reversed by Reduction of Arsenic Exposure

    PubMed Central

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P.; Kumagai, Yoshito

    2005-01-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3′,5′-monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean ± SEM: male, 37.0 ± 6.1; female, 37.2 ± 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 ± 5.6; female, 70.6 ± 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure. PMID:15743725

  16. Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure.

    PubMed

    Pi, Jingbo; Yamauchi, Hiroshi; Sun, Guifan; Yoshida, Takahiko; Aikawa, Hiroyuki; Fujimoto, Wataru; Iso, Hiroyasu; Cui, Renzhe; Waalkes, Michael P; Kumagai, Yoshito

    2005-03-01

    Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.

  17. A Review of the Effects of Chronic Arsenic Exposure on Adverse Pregnancy Outcomes

    PubMed Central

    Milton, Abul H.; Hussain, Sumaira; Akter, Shahnaz; Rahman, Mijanur; Mouly, Tafzila A.; Mitchell, Kane

    2017-01-01

    Exposure to arsenic has a number of known detrimental health effects but impact on pregnancy outcomes is not as widely recognized. This narrative review examines existing epidemiological evidence investigating the association between arsenic exposure via drinking water and adverse pregnancy outcomes. We reviewed published epidemiological studies from around the world on impact of chronic arsenic exposure on spontaneous abortion, stillbirth, neonatal death, post neonatal death, low birth weight and preterm baby. Plausible mechanisms of arsenic toxicity causing adverse pregnancy outcomes were also determined through literature review. There is convincing evidence to support the association between high inorganic arsenic exposure (>50 ppb) and spontaneous abortion, stillbirth and low birth weight. Limitations of certain studies include study design, small sample size, recall constraints and exposure assessment. There needs to be further research investigating the dose metered impact of arsenic exposure on pregnancy outcomes. Further research on impact of low–moderate arsenic concentration exposure on pregnancy outcomes will allow for appropriate public health policy recommendations. PMID:28545256

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

    PubMed Central

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

    2011-01-01

    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. PMID:21983427

  19. 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...

  20. 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...

  1. Chronic Arsenic Exposure in Nanomolar Concentrations Compromises Wound Response and Intercellular Signaling in Airway Epithelial Cells

    PubMed Central

    Boitano, Scott

    2013-01-01

    Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4–5 weeks and examined for wound repair efficiency and ATP-mediated Ca2+ signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca2+ signaling. We further show that arsenic compromises ATP-mediated Ca2+ signaling by altering both Ca2+ release from intracellular stores (via metabotropic P2Y receptors) and Ca2+ influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca2+ signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca2+ signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10–50 ppb) alters cellular mechanisms critical to airway innate immunity. PMID:23204110

  2. 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...

  3. 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...

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh.

    PubMed

    Hossain, Khaled; Suzuki, Takehiro; Hasibuzzaman, M M; Islam, Md Shofikul; Rahman, Atiqur; Paul, Sudip Kumar; Tanu, Tanzina; Hossain, Shakhawoat; Saud, Zahangir Alam; Rahman, Mashiur; Nikkon, Farjana; Miyataka, Hideki; Himeno, Seiichiro; Nohara, Keiko

    2017-03-07

    Chronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP). A total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects' arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects' LINE-1 methylation levels were determined by pyrosequencing. The average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation. Our findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.

  9. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    PubMed

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  10. 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

  11. Hypertension in chronic arsenic exposure: A case control study in West Bengal.

    PubMed

    Guha Mazumder, Debendra; Purkayastha, Ishanikar; Ghose, Aloke; Mistry, Goutom; Saha, Chandan; Nandy, Ashoke K; Das, Arabinda; Majumdar, Kunal K

    2012-01-01

    Various systemic manifestations are reported to be caused by chronic arsenic exposure in the population living in the Indo-Bangladesh subcontinent. This study from West Bengal assesses the likelihood of occurrence of hypertension (HTN) in individuals resident in an area of high groundwater contamination with arsenic (Nadia district) compared to those from a non-contaminated area (Hoogly district) in West Bengal, India. Two hundred and eight study participants (Group 1) were recruited from a cross-sectional study in six villages in the Nadia district and 100 controls (Group 2) from a village in the Hoogly district. The two groups were evenly matched in regard to age and sex. History taking and clinical examination including blood pressure measurement were undertaken in each participant. Water samples from current and previous drinking water sources and hair and urine samples from each participant were collected for estimation of arsenic. The present study shows evidence of increased association of HTN in individuals resident in arsenic endemic region compared to those from a non-endemic region in West Bengal. There were increased odds ratios for HTN [Adjusted Odds Ratio, OR, 2.87 (95 %CI = 1.26-4.83)] in Group- 1 participants compared to Group- 2 people. Within Group 1, there was no difference in prevalence of HTN between those with and without skin lesion. There was a dose-effect relationship seen with increasing cumulative arsenic exposure and arsenic level in hair and HTN in participants living in arsenic endemic region.The findings reported here support an association between arsenic exposure and HTN. More work is needed to characterize the link further.

  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.

  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. 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...

  15. SILAC-based quantitative proteomic analysis reveals widespread molecular alterations in human skin keratinocytes upon chronic arsenic exposure.

    PubMed

    Mir, Sartaj Ahmad; Pinto, Sneha M; Paul, Somnath; Raja, Remya; Nanjappa, Vishalakshi; Syed, Nazia; Advani, Jayshree; Renuse, Santosh; Sahasrabuddhe, Nandini A; Prasad, T S Keshava; Giri, Ashok K; Gowda, Harsha; Chatterjee, Aditi

    2017-03-01

    Chronic exposure to arsenic is associated with dermatological and nondermatological disorders. Consumption of arsenic-contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs, and gastrointestinal tract. Although arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues including skin. Epidemiological studies suggest the association of skin cancer upon arsenic exposure, however, the mechanism of arsenic-induced carcinogenesis is not completely understood. We developed a cell line based model to understand the molecular mechanisms involved in arsenic-mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT, was chronically exposed to 100 nM sodium arsenite over a period of 6 months. We observed an increase in basal ROS levels in arsenic-exposed cells. SILAC-based quantitative proteomics approach resulted in identification of 2111 proteins of which 42 proteins were found to be overexpressed and 54 downregulated (twofold) upon chronic arsenic exposure. Our analysis revealed arsenic-induced overexpression of aldo-keto reductase family 1 member C2 (AKR1C2), aldo-keto reductase family 1 member C3 (AKR1C3), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H dehydrogenase [quinone] 1 (NQO1) among others. We observed downregulation of several members of the plakin family including periplakin (PPL), envoplakin (EVPL), and involucrin (IVL) that are essential for terminal differentiation of keratinocytes. MRM and Western blot analysis confirmed differential expression of several candidate proteins. Our study provides insights into molecular alterations upon chronic arsenic exposure on skin.

  16. Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study.

    PubMed

    Das, Sushmita; Mandal, Rakesh; Rabidas, Vidya Nand; Verma, Neena; Pandey, Krishna; Ghosh, Ashok Kumar; Kesari, Sreekant; Kumar, Ashish; Purkait, Bidyut; Lal, Chandra Sekhar; Das, Pradeep

    2016-10-01

    Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients. In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient's house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development. Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1-200 μg/L and 200.1-432.0 μg/L were 1.85 (1.13-3.03) and 2.31 (1.39-3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02-2.7; p = 0.04). Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.

  17. Chronic Arsenic Exposure and Cardiac Repolarization Abnormalities with QT Interval Prolongation in a Population-based Study

    PubMed Central

    Mumford, Judy L.; Wu, Kegong; Xia, Yajuan; Kwok, Richard; Yang, Zhihui; Foster, James; Sanders, William E.

    2007-01-01

    Background Chronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias. Objective The objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic. Methods Residents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (≤ 21 μg/L), medium (100–300 μg/L), and high (430–690 μg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33–0.44 sec, and QTc ≥ 0.45 sec was considered to be prolonged. Results The prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males. Conclusions We found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity. PMID:17520054

  18. Chronic arsenic exposure and cardiac repolarization abnormalities with QT interval prolongation in a population-based study.

    PubMed

    Mumford, Judy L; Wu, Kegong; Xia, Yajuan; Kwok, Richard; Yang, Zhihui; Foster, James; Sanders, William E

    2007-05-01

    Chronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias. The objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic. Residents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (< or = 21 microg/L), medium (100-300 microg/L), and high (430-690 microg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33-0.44 sec, and QTc > or = 0.45 sec was considered to be prolonged. The prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males. We found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity.

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Metabolism of inorganic arsenic in children with chronic high arsenic exposure in northern Argentina.

    PubMed Central

    Concha, G; Nermell, B; Vahter, M V

    1998-01-01

    This study concerns the metabolism of inorganic arsenic (As) in children in three villages in northern Argentina: San Antonio de los Cobres and Taco Pozo, each with about 200 microg As/l in the drinking water, and Rosario de Lerma, with 0.65 microg As/l. Findings show that the concentrations of As in the blood and urine of the children in the two As-rich villages were on average 9 and 380 microg/l, respectively, the highest ever recorded for children. The concentrations were about 10 and 30 times higher for blood and urine, respectively, than in Rosario de Lerma. Total As in urine was only slightly higher than the sum of metabolites of inorganic As (U-Asmet), i.e., inorganic As, methylarsonic acid (MMA), and dimethylarsinic acid (DMA); this shows that inorganic As was the main form of As ingested. In contrast to previous studies on urinary metabolites of inorganic As in various population groups, the children and women in the present study excreted very little MMA. Thus, there seems to be a polymorphism for the enzymes (methyltransferases) involved in the methylation of As. Interestingly, the children had a significantly higher percentage of inorganic As in urine than the women, about 50% versus 32%. Also, the percentage of inorganic As in the children is considerably higher than in previous studies on children (about 13% in the two studies available) and adults (about 15-25%) in other population groups. This may indicate that children are more sensitive to As-induced toxicity than adults, as the methylated metabolites bind less to tissue constituents than inorganic As. In the children, the percentage inorganic arsenic in urine decreased, and the percentage of DMA increased with increasing U-Asmet, indicating an induction of As methylation with increasing exposure. Images Figure 1 Figure 2 Figure 3 PMID:9618352

  4. 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

  5. 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

  6. Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug-resistance mdr1a/1b(-/-) double knockout mice.

    PubMed

    Xie, Yaxiong; Liu, Jie; Liu, Yaping; Klaassen, Curtis D; Waalkes, Michael P

    2004-01-01

    Multidrug-resistance gene knockout mdr1a/1b(-/-) mice, which are deficient in P-glycoproteins, are more sensitive than wild-type (WT) mice to acute arsenic toxicity. This study assessed toxic manifestations of chronic oral arsenic in mdr1a/1b(-/-) mice, including oxidative stress and altered gene expression, and investigated altered toxicokinetics as a potential basis of enhanced arsenic toxicity. Thus, mdr1a/1b(-/-) and WT mice were exposed to sodium arsenite (0-80 ppm as arsenic) in the drinking water for 10 weeks at which time hepatic arsenic accumulation, lipid peroxidation (LPO), redox status and change in gene expression level were assessed. All mice survived the arsenic exposure, but body weight gain in the highest dose group was reduced in both mdr1a/1b(-/-) and WT mice. Arsenic induced pathological changes, elevated LPO levels and enhanced glutathione S-transferase (GST) activity, in the liver to a greater extent in mdr1a/1b(-/-) than in WT mice. Arsenic also decreased Cu/Zn superoxide dismutase activity in both mdr1a/1b(-/-) and WT mice. The expressions of certain genes, such as those encoding cell proliferation, GST, acute-phase proteins and metabolic enzymes, were modestly altered in arsenic-exposed mice. The expression of cyclin D1, a potential hepatic oncogene, was enhanced in arsenic-exposed mdr1a/1b(-/-) mice only. At the highest level of exposure, hepatic arsenic content was higher in mdr1a/1b(-/-) than in WT mice, suggesting that enhanced accumulation due to transport deficiency may, in part, account for the enhanced toxicity in these mice. In summary, this study shows that chronic arsenic toxicity, including liver pathology and oxidative stress, is enhanced in mdr1a/1b(-/-) mice, possibly due to enhanced accumulation of arsenic as a result of transport system deficiency.

  7. Assessment of arsenic levels in body samples and chronic exposure in people using water with a high concentration of arsenic: a field study in Kutahya.

    PubMed

    Arikan, Inci; Namdar, Nazli Dizen; Kahraman, Cuneyt; Dagci, Merve; Ece, Ezgi

    2015-01-01

    This study aimed to evaluate the prevalence of skin lesions, which is a health effect of chronic arsenic (As) exposure, and determine the hair/blood arsenic concentrations of people living in Kutahya villages who are using and drinking tap water with a high concentration of arsenic. A total of 303 people were included in the present cross-sectional study. A prepared questionnaire form was used to collect the participants' information and environmental history. Skin examination was performed on all participants. Hair, blood and water samples were analyzed using atomic absorption spectroscopy. The cumulative arsenic index (CAI) was calculated for all participants. Villages were divided into two groups according to the arsenic level (<20 μg/L, Group I; >20 μg/L, Group II) in their water. The prevalence of skin lesions, hair and blood arsenic level, and CAI were found to be higher in the Group II participants. There was a positive association between body arsenic levels and CAI in the participants of each group. The number of skin lesions and arsenic concentrations in body samples were found to increase with the water arsenic level and exposure time. We hope that sharing this study's results with local administrators will help accelerate the rehabilitation of water sources in Kutahya.

  8. Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

    PubMed

    Islam, Rafiqul; Khan, Ismail; Hassan, Sheikh Nazmul; McEvoy, Mark; D'Este, Catherine; Attia, John; Peel, Roseanne; Sultana, Munira; Akter, Shahnaz; Milton, Abul Hasnat

    2012-06-07

    Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

  9. Association between type 2 diabetes and chronic arsenic exposure in drinking water: A cross sectional study in Bangladesh

    PubMed Central

    2012-01-01

    Background Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. Methods This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. Results A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 μg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose–response pattern was also observed. Conclusions These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years. PMID:22676249

  10. Association between Hypertension and Chronic Arsenic Exposure in Drinking Water: A Cross-Sectional Study in Bangladesh

    PubMed Central

    Islam, Mohammad Rafiqul; Khan, Ismail; Attia, John; Hassan, Sheikh Mohammad Nazmul; McEvoy, Mark; D’Este, Catherine; Azim, Syed; Akhter, Ayesha; Akter, Shahnaz; Shahidullah, Sheikh Mohammad; Milton, Abul Hasnat

    2012-01-01

    Chronic arsenic exposure and its association with hypertension in adults are inconclusive and this cross-sectional study investigated the association. The study was conducted between January and July 2009 among 1,004 participants from 1,682 eligible women and men aged ≥30 years living in rural Bangladesh who had continuously consumed arsenic-contaminated drinking water for at least 6 months. Hypertension was defined as systolic blood pressure ≥140 mmHg (systolic hypertension) and diastolic blood pressure ≥90 mmHg (diastolic hypertension). Pulse pressure was calculated by deducting diastolic from systolic pressure and considered to be increased when the difference was ≥55 mmHg. The prevalence of hypertension was 6.6% (95% CI: 5.1–8.3%). After adjustment for other factors, no excess risk of hypertension was observed for arsenic exposure >50μg/L or to that of arsenic exposure as quartiles or as duration. Arsenic concentration as quartiles and >50 μg/L did show a strong relationship with increased pulse pressure (adjusted OR: 3.54, 95% CI: 1.46–8.57), as did arsenic exposure for ≥10 years (adjusted OR: 5.25, 95% CI: 1.41–19.51). Arsenic as quartiles showed a dose response relationship with increased pulse pressure. Our study suggests an association between higher drinking water arsenic or duration and pulse pressure, but not hypertension. PMID:23222207

  11. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    PubMed Central

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  12. Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds.

    PubMed

    Gentry, P Robinan; Covington, Tammie R; Lawrence, Greg; McDonald, Tracy; Snow, Elizabeth T; Germolec, Dori; Moser, Glenda; Yager, Janice W; Clewell, Harvey J

    2005-03-12

    Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 xCBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/U of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues.

  13. Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study

    PubMed Central

    Das, Sushmita; Mandal, Rakesh; Rabidas, Vidya Nand; Verma, Neena; Pandey, Krishna; Ghosh, Ashok Kumar; Kesari, Sreekant; Kumar, Ashish; Purkait, Bidyut; Lal, Chandra Sekhar; Das, Pradeep

    2016-01-01

    Background Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients. Methods In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development. Results Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04). Conclusion Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar. PMID:27776123

  14. 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).

  15. Neurosensory effects of chronic exposure to arsenic via drinking water in Inner Mongolia: II. Vibrotactile and visual function.

    PubMed

    Otto, David; He, Linlin; Xia, Yanhong; Li, Yajuan; Wu, Kegong; Ning, Zhixiong; Zhao, Baixiao; Hudnell, H Kenneth; Kwok, Richard; Mumford, Judy; Geller, Andrew; Wade, Timothy

    2006-03-01

    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 into three exposure groups- low (non-detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking water (AsW). Three visual tests were administered: acuity, contrast sensitivity and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration thresholds were measured with a vibrothesiometer. Vibration thresholds were significantly elevated in the high exposure group compared to other groups. Further analysis using a spline regression model suggested that the threshold for vibratory effects is between 150-170 microg/l AsW. These findings provide the first evidence that chronic exposure to arsenic in drinking water impairs vibrotactile thresholds. The results also indicate that arsenic affects neurological function well below the 1000 microg/I concentration reported by NRC (1999). No evidence of arsenic-related effects on visual function was found.

  16. 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

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

    PubMed

    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 6month 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.

  18. 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...

  19. 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...

  20. Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh.

    PubMed

    Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

    2013-08-01

    Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7-17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66-42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09-13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22-8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry.

  1. Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

    PubMed Central

    Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

    2013-01-01

    Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

  2. 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...

  3. 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...

  4. CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure.

    PubMed

    Huang, S; Guo, S; Guo, F; Yang, Q; Xiao, X; Murata, M; Ohnishi, S; Kawanishi, S; Ma, N

    2013-01-14

    Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure results in various types of human skin lesions, including squamous cell carcinoma (SCC). To investigate whether mutant stem cells participate in arsenic-associated carcinogenesis, we repeatedly exposed the HaCaT cells line to an environmentally relevant level of arsenic (0.05 ppm) in vitro for 18 weeks. Following sodium arsenic arsenite administration, cell cycle, colony-forming efficiency (CFE), cell tumorigenicity, and expression of CD44v6, NF-κB and p53, were analyzed at different time points (0, 5, 10, 15, 20, 25 and 30 passages). We found that a chronic exposure of HaCaT cells to a low level of arsenic induced a cancer stem- like phenotype. Furthermore, arsenic-treated HaCaT cells also became tumorigenic in nude mice, their growth cycle was predominantly in G2/M and S phases. Relative to nontreated cells, they exhibited a higher growth rate and a significant increase in CFE. Western blot analysis found that arsenic was capable of increasing cell proliferation and sprouting of cancer stem-like phenotype. Additionally, immunohistochemical analysis demonstrated that CD44v6 expression was up-regulated in HaCaT cells exposed to a low level of arsenic during early stages of induction. The expression of CD44v6 in arsenic-treated cells was positively correlated with their cloning efficiency in soft agar (r=0.949, P=0.01). Likewise, the expressions of activating transcription factor NF-κB and p53 genes in the arsenic-treated HaCaT cells were significantly higher than that in non-treated cells. Higher expressions of CD44v6, NF-κB and p53 were also observed in tumor tissues isolated from Balb/c nude mice. The present results suggest that CD44v6 may be a biomarker of arsenic-induced neoplastic transformation in human skin cells, and that arsenic promotes malignant transformation in human skin lesions through a NF-κB signaling pathway-stimulated expression of CD44v6.

  5. 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

  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. 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.

  8. 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.

  9. Chronic Arsenic poisoning.

    PubMed

    Ahsan, Tasnim; Zehra, Kaneez; Munshi, Alia; Ahsan, Samiah

    2009-02-01

    Chronic Arsenic Toxicity may have varied clinical presentations ranging from non-cancerous manifestations to malignancy of skin and different internal organs. Dermal lesions such as hyper pigmentation and hyperkeratosis, predominantly over palms and soles are diagnostic of Chronic Arsenicosis. We report two cases from a family living in Sukkur who presented with classical skin lesions described in Chronic Arsenicosis. The urine, nail and hair samples of these patients contained markedly elevated levels of arsenic. Also the water samples from their household and the neighbouring households were found to have alarming levels of inorganic Arsenic.

  10. 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

  11. Association between chronic arsenic exposure and nutritional status among the women of child bearing age: a case-control study in Bangladesh.

    PubMed

    Milton, Abul H; Shahidullah, S M; Smith, Wayne; Hossain, Kazi S; Hasan, Ziaul; Ahmed, Kazi T

    2010-07-01

    The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 microg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5) and 360 controls (BMI 18.5-24.99) were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant's age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 microg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1-3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20-45 years.

  12. Association between Chronic Arsenic Exposure and Nutritional Status among the Women of Child Bearing Age: A Case-Control Study in Bangladesh

    PubMed Central

    Milton, Abul H.; Shahidullah, S. M.; Smith, Wayne; Hossain, Kazi S.; Hasan, Ziaul; Ahmed, Kazi T.

    2010-01-01

    The role of nutritional factors in arsenic metabolism and toxicity is yet to be fully elucidated. A low protein diet results in decreased excretion of DMA and increased tissue retention of arsenic in experimental studies. Malnourished women carry a higher risk of adverse pregnancy outcomes. Chronic exposure to high arsenic (>50 μg/L) through drinking water also increases the risk of adverse pregnancy outcomes. The synergistic effects (if any) of malnutrition and chronic arsenic exposure may worsen the adverse pregnancy outcomes. This population based case control study reports the association between chronic arsenic exposure and nutritional status among the rural women in Bangladesh. 348 cases (BMI < 18.5) and 360 controls (BMI 18.5–24.99) were recruited from a baseline survey conducted among 2,341 women. An excess risk for malnutrition was observed among the participants chronically exposed to higher concentrations of arsenic in drinking water after adjusting for potential confounders such as participant’s age, religion, education, monthly household income and history of oral contraceptive pills. Women exposed to arsenic >50 μg/L were at 1.9 times (Odds Ratio = 1.9, 95% CI = 1.1–3.6) increased risk of malnutrition compared to unexposed. The findings of this study suggest that chronic arsenic exposure is likely to contribute to poor nutritional status among women of 20–45 years. PMID:20717540

  13. CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure

    PubMed Central

    Huang, S.; Guo, S.; Guo, F.; Yang, Q.; Xiao, X.; Murata, M.; Ohnishi, S.; Kawanishi, S.; Ma, N.

    2013-01-01

    Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure results in various types of human skin lesions, including squamous cell carcinoma (SCC). To investigate whether mutant stem cells participate in arsenic-associated carcinogenesis, we repeatedly exposed the human spontaneously immortalized skin keratinocytes (HaCaT) cell line to an environmentally relevant level of arsenic (0.05 ppm) in vitrofor 18 weeks. Following sodium arsenite administration, cell cycle, colony-forming efficiency (CFE), cell tumorigenicity, and expression of CD44v6, NF-κB and p53, were analyzed at different time points (0, 5, 10, 15, 20, 25 and 30 passages). We found that a chronic exposure of HaCaT cells to a low level of arsenic induced a cancer stem-like phenotype. Furthermore, arsenictreated HaCaT cells also became tumorigenic in nude mice, their growth cycle was predominantly in G2/M and S phases. Relative to nontreated cells, they exhibited a higher growth rate and a significant increase in CFE. Western blot analysis found that arsenic was capable of increasing cell proliferation and sprouting of cancer stem-like phenotype. Additionally, immunohistochemical analysis demonstrated that CD44v6 expression was upregulated in HaCaT cells exposed to a low level of arsenic during early stages of induction. The expression of CD44v6 in arsenic-treated cells was positively correlated with their cloning efficiency in soft agar (r=0.949, P=0.01). Likewise, the expressions of activating transcription factor NF-κB and p53 genes in the arsenic-treated HaCaT cells were significantly higher than that in non-treated cells. Higher expressions of CD44v6, NF-κB and p53 were also observed in tumor tissues isolated from Balb/c nude mice. The present results suggest that CD44v6 may be a biomarker of arsenicinduced neoplastic transformation in human skin cells, and that arsenic promotes malignant transformation in human skin lesions through a NF-κB signaling pathway

  14. 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

  15. Comparative oxidative stress, metallothionein induction and organ toxicity following chronic exposure to arsenic, lead and mercury in rats.

    PubMed

    Agrawal, S; Flora, G; Bhatnagar, P; Flora, S J S

    2014-06-22

    Globally, arsenic, mercury and lead constitutes as the three most hazardous environmental toxicants perturbing imbalance in pro—oxidant and antioxidant homeostasis. Individual toxicity of these environmental toxicants is well known but there is lack of comparative data on variables indicative of oxidative stress. We thus investigated the effects of chronic exposure to sodium arsenite, mercuric chloride and lead acetate on blood and tissue oxidative stress, metal concentration and metallothionein (MT) contents. Male rats were exposed to sodium arsenite, mercuric chloride and lead acetate (0.05 mg/kg each, orally, once daily) for 6 months. Arsenic, mercury and lead exposure led to a significant inhibition of blood δ—aminolevulinic acid dehydratase (ALAD) activity and glutathione level supported by increased thiobarbituric acid reactive substance (TBARS). The level of inhibition was more pronounced in case of lead followed by mercury and arsenic. These metals/ metalloid significantly increased reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and glutathione peroxidase (GPx) activity accompanied by a decreased superoxide dismutase (SOD), catalase and reduced and oxidized glutathione (GSH and GSSG) levels in blood and tissues. Mercury alone produced a significant induction of hepatic and renal MT concentrations. Serum transaminases, lactate dehydrogenase and alkaline phosphatase activities increased significantly on exposure to arsenic and mercury exposure suggesting liver injury which was less pronounced in case of lead exposure. These biochemical alterations were supported by increased arsenic, mercury and lead concentrations in blood and soft tissues. The present study suggests that exposure to sodium arsenite and mercuric chloride lead to more pronounced oxidative stress and hepatotoxicity while lead acetate caused significant alterations in haem synthesis pathway compared to two other thiol binding metal/metalloid.

  16. Arsenic pesticides and environmental pollution: exposure, poisoning, hazards and recommendations.

    PubMed

    El-Bahnasawy, Mamdouh M; Mohammad, Amina El-Hosini; Morsy, Tosson A

    2013-08-01

    Arsenic is a metalloid element. Acute high-dose exposure to arsenic can cause severe systemic toxicity and death. Lower dose chronic arsenic exposure can result in subacute toxicity that can include peripheral sensorimotor neuropathy, skin eruptions, and hepatotoxicity. Long-term effects of arsenic exposure include an in Due to the physiologic effects of the arsenic on all body systems, thus, chronic arsenic-poisoned patient is a major nursing challenge. The critical care nurse provides valuable assessment and interventions that prevent major multisystem complications from arsenic toxicity.

  17. A perspective of chronic low exposure of arsenic on non-working women: Risk of hypertension.

    PubMed

    Yu, Yanxin; Guo, Yunhe; Zhang, Jingxu; Xie, Jing; Zhu, Yibing; Yan, Jingjing; Wang, Bin; Li, Zhiwen

    2017-02-15

    The relationship between arsenic (As) exposure and hypertension risk are extensively studied. The As content in scalp hair has been used as a reliable indicator of population for long-time exposure from different sources. Therefore, we investigated the association between hair As concentration and hypertension risk, as well as the potential modifying effects of single nucleotide polymorphisms (SNPs) related to phase II metabolism enzyme genes. We recruited 398 non-working women in Shanxi Province, northern China, from Aug 2012 to May 2013, including 163 subjects with hypertension (cases) and 235 healthy controls. Scalp hair and blood samples were collected from each subject. We analyzed the As concentrations of ~24-cm-long strands of hair representing the two most recent years of growth and SNPs of three genes (epoxide hydrolase 1, N-acetyltransferase 2, and glutathione S-transferase P1) in each subject. The results revealed that the hair As concentration of this population was significantly lower than in populations living near high As polluted sources in China and other countries. The median As concentration (inter-quartile range) of hair in the cases (i.e. 0.211 [0.114-0.395] μg/g hair) was higher than in the controls (i.e. 0.101 [0.048-0.227] μg/g hair). Higher hair As concentrations were associated with an elevated hypertension risk, with an adjusted odds ratio of 2.55 [95% confidence interval: 1.55-4.20]. No interaction effects between hair As concentration and SNPs related to phase II metabolism enzymes on hypertension risk were observed. It was concluded that chronic low exposure level of As might be associated with hypertension risk among the study subjects.

  18. Chronic arsenic exposure and risk of carotid artery disease: The Strong Heart Study.

    PubMed

    Mateen, Farrah J; Grau-Perez, Maria; Pollak, Jonathan S; Moon, Katherine A; Howard, Barbara V; Umans, Jason G; Best, Lyle G; Francesconi, Kevin A; Goessler, Walter; Crainiceanu, Ciprian; Guallar, Eliseo; Devereux, Richard B; Roman, Mary J; Navas-Acien, Ana

    2017-08-01

    Inorganic arsenic exposure from naturally contaminated groundwater is related to vascular disease. No prospective studies have evaluated the association between arsenic and carotid atherosclerosis at low-moderate levels. We examined the association of long-term, low-moderate inorganic arsenic exposure with carotid arterial disease. American Indians, 45-74 years old, in Arizona, Oklahoma, and North and South Dakota had arsenic concentrations (sum of inorganic and methylated species, μg/g urine creatinine) measured from baseline urine samples (1989-1991). Carotid artery ultrasound was performed in 1998-1999. Vascular disease was assessed by the carotid intima media thickness (CIMT), the presence of atherosclerotic plaque in the carotid, and by the number of segments containing plaque (plaque score). 2402 participants (mean age 55.3 years, 63.1% female, mean body mass index 31.0kg/m(2), diabetes 45.7%, hypertension 34.2%) had a median (interquintile range) urine arsenic concentration of 9.2 (5.00, 17.06) µg/g creatinine. The mean CIMT was 0.75mm. 64.7% had carotid artery plaque (3% with >50% stenosis). In fully adjusted models comparing participants in the 80th vs. 20th percentile in arsenic concentrations, the mean difference in CIMT was 0.01 (95% confidence interval (95%CI): 0.00, 0.02) mm, the relative risk of plaque presence was 1.04 (95%CI: 0.99, 1.09), and the geometric mean ratio of plaque score was 1.05 (95%CI: 1.01, 1.09). Urine arsenic was positively associated with CIMT and increased plaque score later in life although the association was small. The relationship between urinary arsenic and the presence of plaque was not statistically significant when adjusted for other risk factors. Arsenic exposure may play a role in increasing the severity of carotid vascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study.

    PubMed

    Argos, Maria; Kalra, Tara; Rathouz, Paul J; Chen, Yu; Pierce, Brandon; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Slavkovich, Vesna; van Geen, Alexander; Graziano, Joseph; Ahsan, Habibul

    2010-07-24

    Millions of people worldwide are chronically exposed to arsenic through drinking water, including 35-77 million people in Bangladesh. The association between arsenic exposure and mortality rate has not been prospectively investigated by use of individual-level data. We therefore prospectively assessed whether chronic and recent changes in arsenic exposure are associated with all-cause and chronic-disease mortalities in a Bangladeshi population. In the prospective cohort Health Effects of Arsenic Longitudinal Study (HEALS), trained physicians unaware of arsenic exposure interviewed in person and clinically assessed 11 746 population-based participants (aged 18-75 years) from Araihazar, Bangladesh. Participants were recruited from October, 2000, to May, 2002, and followed-up biennially. Data for mortality rates were available throughout February, 2009. We used Cox proportional hazards model to estimate hazard ratios (HRs) of mortality, with adjustment for potential confounders, at different doses of arsenic exposure. 407 deaths were ascertained between October, 2000, and February, 2009. Multivariate adjusted HRs for all-cause mortality in a comparison of arsenic at concentrations of 10.1-50.0 microg/L, 50.1-150.0 microg/L, and 150.1-864.0 microg/L with at least 10.0 microg/L in well water were 1.34 (95% CI 0.99-1.82), 1.09 (0.81-1.47), and 1.68 (1.26-2.23), respectively. Results were similar with daily arsenic dose and total arsenic concentration in urine. Recent change in exposure, measurement of total arsenic concentrations in urine repeated biennially, did not have much effect on the mortality rate. Chronic arsenic exposure through drinking water was associated with an increase in the mortality rate. Follow-up data from this cohort will be used to assess the long-term effects of arsenic exposure and how they might be affected by changes in exposure. However, solutions and resources are urgently needed to mitigate the resulting health effects of arsenic exposure

  20. Arsenic exposure and cardiovascular disorders: an overview.

    PubMed

    Balakumar, Pitchai; Kaur, Jagdeep

    2009-12-01

    The incidence of arsenic toxicity has been observed in various countries including Taiwan, Bangladesh, India, Argentina, Australia, Chile, China, Hungary, Peru, Thailand, Mexico and United States of America. Arsenic is a ubiquitous element present in drinking water, and its exposure is associated with various cardiovascular disorders. Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atherosclerosis by increasing the platelet aggregation and reducing fibrinolysis. Moreover, arsenic exposure may cause arrhythmia by increasing the QT interval and accelerating the cellular calcium overload. The chronic exposure to arsenic upregulates the expression of tumor necrosis factor-alpha, interleukin-1, vascular cell adhesion molecule and vascular endothelial growth factor to induce cardiovascular pathogenesis. The present review critically discussed the detrimental role of arsenic in the cardiovascular system.

  1. 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. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. 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

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

    PubMed

    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; Stýblo, Miroslav

    2016-01-01

    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.

  4. Sub-chronic exposure to arsenic and dichlorvos on erythrocyte antioxidant defense systems and lipid peroxidation in rats.

    PubMed

    Dwivedi, Nidhi; Flora, S J S

    2015-03-01

    The effect of combined exposure to arsenic (25 ppm in drinking water) and dichlorvos (2.5 mg kg1, orally) for 56 days on biochemical variables, indicative of lipid peroxidation, antioxidant enzyme system and AChE activity in erythrocytes of rats, were examined. While arsenic caused a significant increase in AChE, DDVP produced marked depletion. Combined exposure to arsenic and DDVP produced no additional decrease in AChE activity, which was comparable to DDVP. Arsenic and DDVP also increased the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), suggesting free radical generation. Interestingly, glutathione linked enzymes (GSH, GPx, GST and GR) significantly increased on arsenic and DDVP exposure. SOD activity also increased significantly in the individually exposed groups, while catalase activity remained unchanged. Blood arsenic level increased significantly on coexposure to arsenic alone and with DDVP exposed group. However, arsenic content in co-exposed group depleted marginally as compared to arsenic alone group, indicating possible arsenic redistribution. It might be concluded from the study that the combined exposure to arsenic and DDVP may lead to synergistic effects on certain biochemical indicators of oxidative stress like ROS, GSH and SOD, suggesting a more pronounced induction of lipid peroxidation in erythrocytes.

  5. Effect of acute and chronic arsenic exposure on growth, structure and virulence of Aeromonas hydrophila isolated from fish.

    PubMed

    Goswami, Ramansu; Ghosh, Debabrata; Saha, Dhira Rani; Padhy, Pratap Kumar; Mazumder, Shibnath

    2011-02-01

    Aeromonas hydrophila being a ubiquitous bacterium is prone to arsenic exposure. The present study was designed to determine the role of arsenic on growth and virulence of A. hydrophila. Exposure to arsenic (1 mg L(-1) and 2 mg L(-1)) had no effect on growth but significantly inhibited the hemolytic and cytotoxic potential of exposed bacteria. Transmission electron microscopy revealed loss of membrane integrity and presence of condensed cytoplasm suggestive of acute stress in bacteria exposed to arsenic. Arsenic-adapted bacteria were developed by repeated sub-culturing in presence of arsenic. Arsenic-adaptation led to significant recovery in hemolytic and cytotoxic potential. The arsenic-adapted bacteria exhibited normal membrane integrity, decreased cytoplasmic condensation and possessed scattered polysome like structures in the cytoplasm. A positive correlation was observed between arsenic tolerance and resistance to several antimicrobials. Arsenic-adaptation failed to confer cross-protection to mercury and cadmium stress. SDS-PAGE analysis revealed the expression of two new proteins of approximately 85 kDa and 79 kDa respectively in arsenic-adapted A. hydrophila. Plasmid-curing and transformation studies clearly indicate plasmid has no role on arsenic resistance trait of the bacteria. Our study, for the first time, reports a structure and function relationship of xenobiotics on bacteria. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. 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

  7. Environmental source of arsenic exposure.

    PubMed

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

    2014-09-01

    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.

  8. Associations of arsenic metabolites, methylation capacity, and skin lesions caused by chronic exposure to high arsenic in tube well water.

    PubMed

    Yang, Linsheng; Chai, Yuanqing; Yu, Jiangping; Wei, Binggan; Xia, Yajuan; Wu, Kegong; Gao, Jianwei; Guo, Zhiwei; Cui, Na

    2017-01-01

    To investigate the interaction between skin lesion status and arsenic methylation profiles, the concentrations and proportions of arsenic metabolites in urine and arsenic methylation capacities of study subjects were determined. The results showed that the mean urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinic acid), and TAs (total arsenic) were 75.65, 68.78, 265.81, and 410.24 μg/L, respectively, in the skin lesions subjects. The highest values were observed in the multiple skin lesions subjects. Higher %iAs and %MMA, and lower %DMA, PMI (primary methylation index), and SMI (secondary methylation index) were found in skin lesions subjects. The multiple skin lesions subjects had highest %iAs and %MMA, and lowest %DMA, PMI, and SMI. The prevalence of skin lesions strongly, positively correlated with arsenic levels in drinking water. The elder persons also had higher frequency of skin lesions compared with younger persons. It can be concluded that arsenic levels in drinking water significantly affected the prevalence of skin lesions. Male subjects usually had higher proportions of skin lesions when compared with female subjects. Moreover, it may be concluded that MMA was significantly related to single skin lesion, whereas DMA and iAs were associated with multiple skin lesions. It seemed that MMA had greater toxicity to hyperkeratosis, whereas DMA and iAs had higher toxicity to depigmentation or pigmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 28-36, 2017. © 2015 Wiley Periodicals, Inc.

  9. Arsenic methylation and skin lesions in migrant and native adult women with chronic exposure to arsenic from drinking groundwater.

    PubMed

    Wei, Binggan; Yu, Jiangping; Yang, Linsheng; Li, Hairong; Chai, Yuanqing; Xia, Yajuan; Wu, Kegong; Gao, Jianwei; Guo, Zhiwei; Cui, Na

    2017-02-01

    In order to figure out the prevalence of skin lesions and methylation capacity for migrant and native adult women in an endemic area for arsenic poisoning in Inner Mongolia, China, 207 adult women were selected for study subjects. The results showed that the prevalence of skin lesions for the external group, provincial group and native group was 36.54, 26.15 and 35.56 %, respectively. The nail content of arsenic and urinary concentrations of dimethylarsenic (DMA), monomethylarsenic (MMA) and inorganic arsenic (iAs) were significantly higher in women with skin lesions than in those without skin lesions. The highest urinary concentrations of DMA, MMA and iAs were 213.93, 45.72 and 45.01 μg/L in the native group. The arsenic methylation capacity index revealed that the external group had the greatest capacity, while the native group had the lowest. The odds ratios of skin lesions in relation to arsenic metabolites and arsenic methylation capacity varied widely among the three groups. Urinary MMA and iAs concentrations were positively associated with risk of skin lesions in the three groups of adult women, while primary and secondary methylation capacities were negatively related to risk of skin lesions in native and provincial groups. The external group might be more susceptible to MMA and iAs, while the provincial and native groups were more tolerance to MMA and iAs. Lower primary and secondary arsenic methylation capacities increased the risk of skin lesions in native and provincial groups. Moreover, higher nail arsenic concentration increased the risk of skin lesions of adult women.

  10. Interplay between Cellular Methyl Metabolism and Adaptive Efflux during Oncogenic Transformation from Chronic Arsenic Exposure in Human Cells*S⃞

    PubMed Central

    Coppin, Jean-François; Qu, Wei; Waalkes, Michael P.

    2008-01-01

    After protracted low level arsenic exposure, the normal human prostate epithelial cell line RWPE-1 acquires a malignant phenotype with DNA hypomethylation, indicative of disrupted methyl metabolism, and shows arsenic adaptation involving glutathione overproduction and enhanced arsenic efflux. Thus, the interplay between methyl and glutathione metabolism during this progressive arsenic adaptation was studied. Arsenic-treated cells showed a time-dependent increase in LC50 and a marked increase in homocysteine (Hcy) levels. A marked suppression of S-adenosylmethionine (SAM) levels occurred with decreased methionine adenosyltransferase 2A (converts methionine to SAM) expression and increased negative regulator methionine adenosyltransferase B, suggesting reduced conversion of Hcy to SAM. Consistent with Hcy overproduction, activity and expression of S-adenosylhomocysteine hydrolase (converts S-adenosylhomocysteine to Hcy) were both increased. Expression of cystathionine β-synthase, a key gene in the transsulfuration pathway, and various glutathione production genes were increased, resulting in a 5-fold increase in glutathione. Arsenic efflux increased along with expression of ATP-binding cassette protein C1, which effluxes arsenic as a glutathione conjugate. Evidence of genomic DNA hypomethylation was observed during early arsenic exposure, indicating that the disruption in methyl metabolism had a potential impact related to oncogenesis. Thus, cellular arsenic adaptation is a dynamic, progressive process that involves decreased SAM recycling and concurrent accumulation of Hcy, which is channeled via transsulfuration to increase glutathione and enhance arsenic efflux but may also impact the carcinogenic process. PMID:18487201

  11. Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway

    PubMed Central

    He, Jun; Wang, Min; Jiang, Yue; Chen, Qiudan; Xu, Shaohua; Xu, Qing; Jiang, Bing-Hua

    2014-01-01

    Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood. Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth. Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis. Results: We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis. Conclusion: The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis. Citation: He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255–261; http://dx.doi.org/10.1289/ehp.1307545 PMID:24413338

  12. Nonmalignant Respiratory Effects of Chronic Arsenic Exposure from Drinking Water among Never-Smokers in Bangladesh

    PubMed Central

    Parvez, Faruque; Chen, Yu; Brandt-Rauf, Paul W.; Bernard, Alfred; Dumont, Xavier; Slavkovich, Vesna; Argos, Maria; D’Armiento, Jeanine; Foronjy, Robert; Hasan, M. Rashidul; Eunus, HEM Mahbubul; Graziano, Joseph H.; Ahsan, Habibul

    2008-01-01

    Background Arsenic from drinking water has been associated with malignant and nonmalignant respiratory illnesses. The association with nonmalignant respiratory illnesses has not been well established because the assessments of respiratory symptoms may be influenced by recall bias or interviewer bias because participants had visible skin lesions. Objectives We examined the relationship of the serum level of Clara cell protein CC16—a novel biomarker for respiratory illnesses—with well As, total urinary As, and urinary As methylation indices. Methods We conducted a cross-sectional study in nonsmoking individuals (n = 241) selected from a large cohort with a wide range of As exposure (0.1–761 μg/L) from drinking water in Bangladesh. Total urinary As, urinary As metabolites, and serum CC16 were measured in urine and serum samples collected at baseline of the parent cohort study. Results We observed an inverse association between urinary As and serum CC16 among persons with skin lesions (β = −0.13, p = 0.01). We also observed a positive association between secondary methylation index in urinary As and CC16 levels (β = 0.12, p = 0.05) in the overall study population; the association was stronger among people without skin lesions (β = 0.18, p = 0.04), indicating that increased methylation capability may be protective against As-induced respiratory damage. In a subsample of study participants undergoing spirometric measures (n = 31), we observed inverse associations between urinary As and predictive FEV1 (forced expiratory volume measured in 1 sec) (r = −0.37; FEV1/forced vital capacity ratio and primary methylation index (r = −0.42, p = 0.01). Conclusions The findings suggest that serum CC16 may be a useful biomarker of epithelial lung damage in individuals with arsenical skin lesions. Also, we observed the deleterious respiratory effects of As exposure at concentrations lower than reported in earlier studies. PMID:18288317

  13. 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...

  14. 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...

  15. 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 ...

  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. 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...

  18. 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...

  19. 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:...

  20. 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:...

  1. 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

  2. Chronic arsenic exposure and its adverse health effects in Taiwan: a paradigm for management of a global environmental problem.

    PubMed

    Lan, Cheng-Che; Yu, Hsin-Su; Ko, Ying-Chin

    2011-09-01

    It was estimated that, nearly 100 million people are at risk for drinking arsenic (As)-contaminated drinking water. Although the WHO guideline recommends that levels of As in drinking water should not exceed 10 μm/L, it was estimated that more than 30 million people drink As-containing water at levels more than 50 μm/L in Bangladesh and India alone. Therefore, the adverse health effects resulting from chronic As exposure pose a global threat. In Taiwan, studies focusing on the health effects resulting from chronic As exposure through contaminated drinking water have been ongoing for more than 50 years. During the past half century, it was recognized that the impact of high As exposure on human health is much more complicated than originally anticipated. Chronic As exposure resulted in infamous blackfoot disease, which is unique to As endemic areas in Taiwan, and various diseases including cancers and non-cancers. Although the potential-biological outcomes have been well-documented, the pathomechanisms leading from As exposure to occurrence and development of the diseases remain largely unclear. One of the major obstacles that hindered further understanding regarding the adverse health effect resulting from chronic As exposure is documentation of cumulative As exposure from the distant past, which remains difficult as the present technologies mostly document relatively recent As exposure. Furthermore, the susceptibility to As exposure appears to differ between different ethnic groups and individuals and is modified by lifestyle factors including smoking habits and nutrition status. No consensus data has yet been reached even after comparing the study results obtained from different parts of the world focusing on associations between human As toxicity and genetic polymorphisms in terms of cellular detoxification enzymes, tumor suppressor proteins, and DNA repair pathway. With the availability of the new powerful "OMIC" technologies, it may now be possible to gain

  3. Acute and chronic arsenic toxicity

    PubMed Central

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water. PMID:12897217

  4. Acute and chronic arsenic toxicity.

    PubMed

    Ratnaike, R N

    2003-07-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption occurs from skin contact and inhalation. Arsenic exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways and DNA synthesis and repair. Acute arsenic poisoning is associated initially with nausea, vomiting, abdominal pain, and severe diarrhoea. Encephalopathy and peripheral neuropathy are reported. Chronic arsenic toxicity results in multisystem disease. Arsenic is a well documented human carcinogen affecting numerous organs. There are no evidence based treatment regimens to treat chronic arsenic poisoning but antioxidants have been advocated, though benefit is not proven. The focus of management is to reduce arsenic ingestion from drinking water and there is increasing emphasis on using alternative supplies of water.

  5. 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...

  6. 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

  7. Breast-feeding protects against arsenic exposure in Bangladeshi infants.

    PubMed

    Fängström, Britta; Moore, Sophie; Nermell, Barbro; Kuenstl, Linda; Goessler, Walter; Grandér, Margaretha; Kabir, Iqbal; Palm, Brita; Arifeen, Shams El; Vahter, Marie

    2008-07-01

    Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. Arsenic concentrations in breast-milk samples were low (median, 1 microg/kg; range, 0.25-19 microg/kg), despite high arsenic exposures via drinking water (10-1,100 microg/L in urine and 2-40 microg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 microg/L; range, 0.3-29 microg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 microg/L (median 1.9 microg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic.

  8. Breast-feeding Protects against Arsenic Exposure in Bangladeshi Infants

    PubMed Central

    Fängström, Britta; Moore, Sophie; Nermell, Barbro; Kuenstl, Linda; Goessler, Walter; Grandér, Margaretha; Kabir, Iqbal; Palm, Brita; Arifeen, Shams El; Vahter, Marie

    2008-01-01

    Background Chronic arsenic exposure causes a wide range of health effects, but little is known about critical windows of exposure. Arsenic readily crosses the placenta, but the few available data on postnatal exposure to arsenic via breast milk are not conclusive. Aim Our goal was to assess the arsenic exposure through breast milk in Bangladeshi infants, living in an area with high prevalence of arsenic-rich tube-well water. Methods We analyzed metabolites of inorganic arsenic in breast milk and infant urine at 3 months of age and compared them with detailed information on breast-feeding practices and maternal arsenic exposure, as measured by concentrations in blood, urine, and saliva. Results Arsenic concentrations in breast-milk samples were low (median, 1 μg/kg; range, 0.25–19 μg/kg), despite high arsenic exposures via drinking water (10–1,100 μg/L in urine and 2–40 μg/L in red blood cells). Accordingly, the arsenic concentrations in urine of infants whose mothers reported exclusive breast-feeding were low (median, 1.1 μg/L; range, 0.3–29 μg/L), whereas concentrations for those whose mothers reported partial breast-feeding ranged from 0.4 to 1,520 μg/L (median 1.9 μg/L). The major part of arsenic in milk was inorganic. Still, the infants had a high fraction (median, 87%) of the dimethylated arsenic metabolite in urine. Arsenic in breast milk was associated with arsenic in maternal blood, urine, and saliva. Conclusion Very little arsenic is excreted in breast milk, even in women with high exposure from drinking water. Thus, exclusive breast-feeding protects the infant from exposure to arsenic. PMID:18629322

  9. 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.

  10. An Interesting Case of Basal Cell Carcinoma with Raynaud's Phenomenon Following Chronic Arsenic Exposure.

    PubMed

    Gulshan, S; Rahman, M J; Sarkar, R; Ghosh, S; Hazra, R

    2016-01-01

    Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma. On further enquiry, he was found to reside in an arsenic endemic zone and was investigated for blood arsenic level which was elevated. Punch biopsy from different lesions from body confirmed nodular basal cell carcinoma. Presently the patient has stopped drinking water from the local tubewell. On follow-up he shows improvement of Raynaud's phenomenon and skin lesions.

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

    PubMed

    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(2)O(2)) from the early stages of arsenic exposure, while superoxide (O(2)(*-)) and hydroxyl radical ((*)OH) 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. Copyright 2008 Elsevier Inc. All rights reserved.

  12. 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.

  13. Metabolomic analysis of the effects of chronic arsenic exposure in a mouse model of diet-induced fatty liver disease

    PubMed Central

    Shi, Xue; Wei, Xiaoli; Koo, Imhoi; Schmidt, Robin H.; Yin, Xinmin; Kim, Seong Ho; Vaughn, Andrew; McClain, Craig J.; Arteel, Gavin E.

    2014-01-01

    Arsenic is a widely-distributed environmental component that is associated with a variety of cancer and non-cancer adverse health effects. Additional lifestyle factors, such as diet, contribute to the manifestation of disease. Recently, arsenic was found to increase inflammation and liver injury in a dietary model of fatty liver disease. The purpose of the present study was to investigate potential mechanisms of this diet-environment interaction via a high throughput metabolomics approach. GC×GC-TOF MS was used to identify metabolites that were significantly increased or decreased in the livers of mice fed a Western diet (a diet high in fat and cholesterol) and co-exposed to arsenic-contaminated drinking water. The results showed that there are distinct hepatic metabolomic profiles associated with eating a high fat diet, drinking arsenic-contaminated water, and the combination of the two. Among the metabolites that were decreased when arsenic exposure was combined with a high fat diet were short-chain and medium-chain fatty acid metabolites and the anti-inflammatory amino acid, glycine. These results are consistent with the observed increase in inflammation and cell death in the livers of these mice, and they point to potentially novel mechanisms by which these metabolic pathways could be altered by arsenic in the context of diet-induced fatty liver disease. PMID:24328084

  14. Metabolomic analysis of the effects of chronic arsenic exposure in a mouse model of diet-induced Fatty liver disease.

    PubMed

    Shi, Xue; Wei, Xiaoli; Koo, Imhoi; Schmidt, Robin H; Yin, Xinmin; Kim, Seong Ho; Vaughn, Andrew; McClain, Craig J; Arteel, Gavin E; Zhang, Xiang; Watson, Walter H

    2014-02-07

    Arsenic is a widely distributed environmental component that is associated with a variety of cancer and non-cancer adverse health effects. Additional lifestyle factors, such as diet, contribute to the manifestation of disease. Recently, arsenic was found to increase inflammation and liver injury in a dietary model of fatty liver disease. The purpose of the present study was to investigate potential mechanisms of this diet-environment interaction via a high-throughput metabolomics approach. GC×GC-TOF MS was used to identify metabolites that were significantly increased or decreased in the livers of mice fed a Western diet (a diet high in fat and cholesterol) and co-exposed to arsenic-contaminated drinking water. The results showed that there are distinct hepatic metabolomic profiles associated with eating a high fat diet, drinking arsenic-contaminated water, and the combination of the two. Among the metabolites that were decreased when arsenic exposure was combined with a high fat diet were short-chain and medium-chain fatty acid metabolites and the anti-inflammatory amino acid, glycine. These results are consistent with the observed increase in inflammation and cell death in the livers of these mice and point to potentially novel mechanisms by which these metabolic pathways could be altered by arsenic in the context of diet-induced fatty liver disease.

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. Arsenic and Chronic Kidney Disease: A Systematic Review

    PubMed Central

    Zheng, Laura; Kuo, Chin-Chi; Fadrowski, Jeffrey; Agnew, Jackie; Weaver, Virginia M.; Navas-Acien, Ana

    2014-01-01

    In epidemiologic studies, high arsenic exposure has been associated with adverse kidney disease outcomes. We performed a systematic review of the epidemiologic evidence of the association between arsenic and various kidney disease outcomes. The search period was January 1966 through January 2014. Twenty-five papers (comprising 24 studies) meeting the search criteria were identified and included in this review. In most studies, arsenic exposure was assessed by measurement of urine concentrations or with an ecological indicator. There was a generally positive association between arsenic and albuminuria and proteinuria outcomes. There was mixed evidence of an association between arsenic exposure and chronic kidney disease (CKD), β-2 microglobulin (β2MG), and N-acetyl-β-D-glucosaminidase (NAG) outcomes. There was evidence of a positive association between arsenic exposure and kidney disease mortality. Assessment of a small number of studies with three or more categories showed a clear dose-response association between arsenic and prevalent albuminuria and proteinuria, but not with CKD outcomes. Eight studies lacked adjustment for possible confounders, and two had small study populations. The evaluation of the causality of the association between arsenic exposure and kidney disease outcomes is limited by the small number of studies, lack of study quality, and limited prospective evidence. Because of the high prevalence of arsenic exposure worldwide, there is a need for additional well-designed epidemiologic and mechanistic studies of arsenic and kidney disease outcomes. PMID:25221743

  20. 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.

  1. [Significance of field epidemiologic study to identification of chronic arsenic poisoning].

    PubMed

    Su, Li-Qin; Jin, Yin-Long

    2005-09-01

    Chronic arsenic poisoning has serious and extensive impact on human health, which attracts wide attention worldwide. Bases on vast public survey, this article introduces recent field studies on chronic arsenic poisoning from three aspects: exposure history, clinical symptoms and laboratory evidences, and also explains the meaning of each index to the determination of chronic arsenic poisoning, then bring forward some considerations on further epidemiological studies on chronic arsenic poisoning.

  2. Biomarkers of exposure: a case study with inorganic arsenic.

    PubMed

    Hughes, Michael F

    2006-11-01

    The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4-5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trivalent arsenicals are more potent toxicants than pentavalent forms. Several mechanisms of action have been proposed for arsenic-induced toxicity, but a scientific consensus has not been achieved. Biomarkers of exposure may be used to quantify exposure to iAs. The most common biomarker of exposure for iAs is the measurement of total urinary arsenic. However, consumption of seafood containing high concentrations of organic arsenic can confound estimation of iAs exposure. Because these organic species are thought to be relatively nontoxic, their presence in urine may not represent increased risk. Speciation of urinary arsenic into inorganic and organic forms, and even oxidation state, gives a more definitive indication of the exposure to iAs. Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs.

  3. 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.

  4. Chronic arsenicosis in goats with special reference to its exposure, excretion and deposition in an arsenic contaminated zone.

    PubMed

    Rana, Tanmoy; Bera, Asit Kumar; Bhattacharya, Debasis; Das, Subhashree; Pan, Diganta; Das, Subrata Kumar

    2012-03-01

    Thirty goats were selected randomly from a village of Nadia district, West Bengal according to the previous reports of human being suffering from chronic arsenicosis. Environmental samples viz. drinking water, rice plants and grass used for goat and biological samples viz. blood, urine, faeces, hair and meat were collected to evaluate the arsenic status. It was found that arsenic concentration in both environmental and biological samples was significantly (p<0.01) higher rather than respective samples on control zone. Bio-concentration factor (BCF) and bio-transfer factor (BTF) are indicated to evaluate the subclinical toxicity in goat as they do not exhibit clinical manifestation like human beings. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Low-level arsenic exposure in wood processing plants.

    PubMed

    Rosenberg, M J; Landrigan, P J; Crowley, S

    1980-01-01

    In October 1978, seven construction workers building a pier in Monterey, California, developed symptoms consistent with arsenic intoxication and had elevated urinary levels of arsenic. The wood used for the pier had been pressure-treated with an arsenic preservative. To evaluate the potential acute medical hazards of preserving wood with arsenic, we evaluated employees at three California plants where arsenic preservatives are mixed and applied to wood. Histories, physical examinations, and urine specimens for arsenic analysis were collected from 44 workers exposed to arsenic and from 37 controls in three woodworking plants where arsenic is not used. A comparison of the groups failed to show any significant differences in history or physical examination. Adjustment for age, length of employment, and smoking histories did not alter the pattern. Urinary arsenic concentration was found to increase with increased exposure. These results do not imply absence of chronic or delayed toxicity, nor do they preclude the presence of a more subtle toxicity such as nerve conduction deficits. The data indicate existence of an arsenic exposure hazard in wood processing.U

  6. Arsenic Exposure and Cardiovascular Disease: An Updated Systematic Review

    PubMed Central

    Moon, Katherine; Guallar, Eliseo; Navas–Acien, Ana

    2012-01-01

    In epidemiologic studies, high-chronic arsenic exposure has been associated with cardiovascular disease, despite methodological limitations. At low-moderate arsenic levels, the evidence was inconclusive. Here, we update a previous systematic review (Am J Epidemiol 2005;162: 1037–49) examining the association between arsenic exposure and cardiovascular disease. Eighteen studies published since 2005 were combined with 13 studies from the previous review. We calculated pooled relative risks by comparing the highest versus the lowest exposure category across studies. For high exposure (arsenic in drinking water > 50 μg/L), the pooled relative risks (95 % confidence interval) for cardiovascular disease, coronary heart disease, stroke, and peripheral arterial disease were 1.32 (95 % CI: 1.05–1.67), 1.89 (95 % CI: 1.33–2.69), 1.08 (95 % CI: 0.98–1.19), and 2.17 (95 % CI: 1.47–3.20), respectively. At low-moderate arsenic levels, the evidence was inconclusive. Our review strengthens the evidence for a causal association between high-chronic arsenic exposure and clinical cardiovascular endpoints. Additional high quality studies are needed at low-moderate arsenic levels. PMID:22968315

  7. 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

  8. Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

    PubMed

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

    2012-04-01

    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.

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Effect of chronic arsenic exposure under environmental conditions on bioaccumulation, oxidative stress, and antioxidant enzymatic defenses in wild trout Salmo trutta (Pisces, Teleostei).

    PubMed

    Greani, Samuel; Lourkisti, Radia; Berti, Liliane; Marchand, Bernard; Giannettini, Jean; Santini, Jérémie; Quilichini, Yann

    2017-06-16

    The present study evaluates the relation between chronic arsenic (As) exposure in the natural distribution area of wild brown trout (Salmo trutta), oxidative stress and antioxidant enzymatic defenses. Two rivers of the same watershed were evaluated to highlight the correlation between As accumulation and the resulting stress: (i) the Presa River, which has high chronic As levels (2281.66 µg/L) due to past mining activity, and (ii) the Bravona River (control river). This metalloid was measured in main fish tissues (gills, kidney, liver, muscle, gonads and fins) and water. As organotropism in S. trutta was kidney > liver > gill > fin > gonad > muscle. The HepatoSomatic Index (HSI) and somatic condition (CF) were used to compare fish population conditions from both sites. Arsenic can be absorbed by the gills and can induce oxidative stress and disturb antioxidant defenses. The aim of this study was to evaluate oxidative stress response by measuring malondialdehyde (MDA) content, as a marker of lipid peroxidation, and antioxidant enzymatic defenses (Superoxide dismutase (SOD), catalase CAT, glutathione peroxidase (GPx) and glutathione S-transferase (GST)), in the main tissues of control and exposed trout. The highest MDA content was found in the kidney and liver of exposed trout. SOD and CAT activities in exposed livers and kidneys were considerably increased while a significant rise of GPx activity was observed only in the liver. GST activity was found to be significantly induced in the liver of exposed trout. The results demonstrate that arsenic bioaccumulation can induce lipid peroxidation and substantial modifications in antioxidant enzymatic defenses in main wild trout tissues.

  16. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh.

    PubMed

    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; Ahsan, Habibul

    2015-01-01

    Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10(-7). Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10(-11)) and blood arsenic concentrations (p = 1.48 × 10(-11)). Three additional novel methylation loci-SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)--were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.

  17. 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...

  18. 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.

  19. Synchrotron microscopic X-ray fluorescence analysis of the effects of chronic arsenic exposure in rat brain

    NASA Astrophysics Data System (ADS)

    Rubio, Marcelo; Perez, Roberto D.; Perez, Carlos A.; Eynard, Aldo H.; Bongiovanni, Guillermina A.

    2008-01-01

    Synchrotron microscopic X-ray fluorescence (μ-SRXRF) scanning and conventional XRF analysis were applied for studying elemental concentrations in lyophilised brain rat slices. The animals received drinking water—100 ppm of sodium arsenite—ad libitum for 30 and 60 days. Accumulation of arsenic was corroborated and its dependence with arsenic dosage suggests the existence of a protection mechanism which limits the transport of inorganic arsenic to the brain. Chlorine, potassium and iron were reduced changing their spatial distributions while copper and zinc were redistributed.

  20. 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

    2013-12-03

    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.

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

    PubMed Central

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

    2013-01-01

    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

  2. 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. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. 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...

  4. 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...

  5. Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism

    PubMed Central

    Kundu, Manjari; Ghosh, Pritha; Mitra, Sanhita; Das, J.K.; Sau, T.J.; Banerjee, Saptarshi; States, J. Christopher; Giri, Ashok K.

    2012-01-01

    Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR= 0.45, 95% CI: 0.30 – 0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30–0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40–0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis. PMID:21035470

  6. Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study.

    PubMed

    Pesola, Gene R; Parvez, Faruque; Chen, Yu; Ahmed, Alauddin; Hasan, Rabiul; Ahsan, Habibul

    2012-05-01

    Bangladesh has high well water arsenic exposure. Chronic arsenic ingestion may result in diseases that manifest as dyspnoea, although information is sparse. Baseline values were obtained from an arsenic study. Trained physicians ascertained data on dyspnoea among 11,746 subjects. Data were collected on demographic factors, including smoking, blood pressure and arsenic exposure. Logistic regression models estimated odds ratios and confidence intervals for the association between arsenic exposure and dyspnoea. The adjusted odds of having dyspnoea was 1.32-fold (95% CI 1.15-1.52) greater in those exposed to high well water arsenic concentrations (≥ 50 μg · L(-1)) compared with low-arsenic-exposed nonsmokers (p<0.01). A significant dose-response relationship was found for arsenic (as well as smoking) in relation to dyspnoea. In nonsmokers, the adjusted odds of having dyspnoea were 1.36, 1.96, 2.34 and 1.80-fold greater for arsenic concentrations of 7-38, 39-90, 91-178 and 179-864 μg · L(-1), respectively, compared with the reference arsenic concentration of <7 μg · L(-1) (p<0.01; Chi-squared test for trend). Arsenic exposure through well water is associated with dyspnoea, independently of smoking status. This study suggests that mandated well water testing for arsenic with reduction in exposure may significantly reduce diseases that manifest as dyspnoea, usually cardiac or pulmonary.

  7. Arsenic exposure from drinking water and dyspnoea risk in Araihazar, Bangladesh: a population-based study

    PubMed Central

    Pesola, Gene R.; Parvez, Faruque; Chen, Yu; Ahmed, Alauddin; Hasan, Rabiul; Ahsan, Habibul

    2014-01-01

    Bangladesh has high well water arsenic exposure. Chronic arsenic ingestion may result in diseases that manifest as dyspnoea, although information is sparse. Baseline values were obtained from an arsenic study. Trained physicians ascertained data on dyspnoea among 11,746 subjects. Data were collected on demographic factors, including smoking, blood pressure and arsenic exposure. Logistic regression models estimated odds ratios and confidence intervals for the association between arsenic exposure and dyspnoea. The adjusted odds of having dyspnoea was 1.32-fold (95% CI 1.15–1.52) greater in those exposed to high well water arsenic concentrations (≥50 μg·L−1) compared with low-arsenic-exposed nonsmokers (p<0.01). A significant dose–response relationship was found for arsenic (as well as smoking) in relation to dyspnoea. In nonsmokers, the adjusted odds of having dyspnoea were 1.36, 1.96, 2.34 and 1.80-fold greater for arsenic concentrations of 7–38, 39–90, 91–178 and 179–864 μg·L−1, respectively, compared with the reference arsenic concentration of <7 μg·L−1 (p<0.01; Chi-squared test for trend). Arsenic exposure through well water is associated with dyspnoea, independently of smoking status. This study suggests that mandated well water testing for arsenic with reduction in exposure may significantly reduce diseases that manifest as dyspnoea, usually cardiac or pulmonary. PMID:22088973

  8. Characterization of the impaired glucose homeostasis produced in C57BL/6 mice by chronic exposure to arsenic and high-fat diet.

    PubMed

    Paul, David S; Walton, Felecia S; Saunders, R Jesse; Stýblo, Miroslav

    2011-08-01

    Type 2 diabetes is characterized by glucose intolerance and insulin resistance. Obesity is the leading cause of type 2 diabetes. Growing evidence suggests that chronic exposure to inorganic arsenic (iAs) also produces symptoms consistent with diabetes. Thus, iAs exposure may further increase the risk of diabetes in obese individuals. Our goal was to characterize diabetogenic effects of iAs exposure and high-fat diet (HFD) in weaned C57BL/6 mice. Mice were fed HFD or low-fat diet (LFD) while exposed to iAs in drinking water (25 or 50 ppm As) for 20 weeks; control HFD and LFD mice drank deionized water. Body mass and adiposity were monitored throughout the study. We measured glucose and insulin levels in fasting blood and in blood collected during oral glucose tolerance tests (OGTT) to evaluate the diabetogenic effects of the treatment. Control mice fed HFD accumulated more fat, had higher fasting blood glucose, and were more insulin resistant than were control LFD mice. However, these diabetes indicators decreased with iAs intake in a dose-dependent manner. OGTT showed impaired glucose tolerance for both control and iAs-treated HFD mice compared with respective LFD mice. Notably, glucose intolerance was more pronounced in HFD mice treated with iAs despite a significant decrease in adiposity, fasting blood glucose, and insulin resistance. Our data suggest that iAs exposure acts synergistically with HFD-induced obesity in producing glucose intolerance. However, mechanisms of the diabetogenic effects of iAs exposure may differ from the mechanisms associated with the obesity-induced type 2 diabetes.

  9. Chronic arsenic poisoning following ayurvedic medication.

    PubMed

    Pinto, Benzeeta; Goyal, Palvi; Flora, S J S; Gill, K D; Singh, Surjit

    2014-12-01

    Ayurveda, Indian traditional system of medicine, is practiced commonly in South East Asia and in many parts of the world. Many ayurvedic drugs contain heavy metals and may lead to metal toxicity. Of these, chronic lead poisoning is the most common. Chronic arsenic poisoning following the use of ayurvedic medication, though reported, is rare. We describe three patients who presented with features of chronic arsenic poisoning following prolonged ayurvedic medication use. The diagnosis of chronic arsenic poisoning was confirmed by high arsenic levels in the blood, urine, hair, and nails in all the three patients and in ayurvedic drug in two patients. The ayurvedic medication was discontinued and treatment with D-penicillamine started. At 6 months after treatment, blood arsenic levels returned to normal with clinical recovery in all of them. Arsenic poisoning following ayurvedic medication is much less common than lead poisoning, though mineral ayurvedic medicines may lead to it. We used D-penicillamine as chelator and all of them recovered. Whether withdrawal of medication alone or D-penicillamine also played a role in recovery is unclear and needs to be assessed.

  10. Arsenic Exposure and Hypertension: A Systematic Review

    PubMed Central

    Abhyankar, Lalita N.; Jones, Miranda R.; Guallar, Eliseo

    2011-01-01

    Background: Environmental exposure to arsenic has been linked to hypertension in persons living in arsenic-endemic areas. Objective: We summarized published epidemiologic studies concerning arsenic exposure and hypertension or blood pressure (BP) measurements to evaluate the potential relationship. Data sources and extraction: We searched PubMed, Embase, and TOXLINE and applied predetermined exclusion criteria. We identified 11 cross-sectional studies from which we abstracted or derived measures of association and calculated pooled odds ratios (ORs) using inverse-variance weighted random-effects models. Data synthesis: The pooled OR for hypertension comparing the highest and lowest arsenic exposure categories was 1.27 [95% confidence interval (CI): 1.09, 1.47; p-value for heterogeneity = 0.001; I2 = 70.2%]. In populations with moderate to high arsenic concentrations in drinking water, the pooled OR was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I2 = 76.6%) and 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I2 = 46.6%) before and after excluding an influential study, respectively. The corresponding pooled OR in populations with low arsenic concentrations in drinking water was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I2 = 24.6%). A dose–response assessment including six studies with available data showed an increasing trend in the odds of hypertension with increasing arsenic exposure. Few studies have evaluated changes in systolic and diastolic BP (SBP and DBP, respectively) measurements by arsenic exposure levels, and those studies reported inconclusive findings. Conclusion: In this systematic review we identified an association between arsenic and the prevalence of hypertension. Interpreting a causal effect of environmental arsenic on hypertension is limited by the small number of studies, the presence of influential studies, and the absence of prospective evidence. Additional evidence is needed to evaluate the

  11. 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

  12. Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damage in vivo

    PubMed Central

    Rao, Chinthalapally V.; Pal, Sanya; Mohammed, Altaf; Farooqui, Mudassir; Doescher, Mark P.; Asch, Adam S.; Yamada, Hiroshi Y.

    2017-01-01

    Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide “hot spots” where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis. High arsenic exposure is epidemiologically associated with skin, lung, bladder, liver, kidney and pancreatic cancer, and cardiovascular, neuronal, and other diseases. This review briefly summarizes the biological effects of arsenic exposure and epidemiological cancer studies worldwide, and provides an overview for emerging rodent-based studies of reagents that can ameliorate the effects of arsenic exposure in vivo. These reagents may be translated to human populations for disease prevention. We propose the importance of developing a biomarker-based precision prevention approach for the health issues associated with arsenic exposure that affects millions of people worldwide. PMID:28915699

  13. 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.

  14. Whole-house arsenic water treatment provided more effective arsenic exposure reduction than point-of-use water treatment at New Jersey homes with arsenic in well water

    PubMed Central

    Spayd, Steven E.; Robson, Mark G.; Buckley, Brian T.

    2014-01-01

    A comparison of the effectiveness of whole house (point-of-entry) and point-of-use arsenic water treatment systems in reducing arsenic exposure from well water was conducted. The non-randomized observational study recruited 49 subjects having elevated arsenic in their residential home well water in New Jersey. The subjects obtained either point-of-entry or point-of-use arsenic water treatment. Prior ingestion exposure to arsenic in well water was calculated by measuring arsenic concentrations in the well water and obtaining water-use histories for each subject, including years of residence with the current well and amount of water consumed from the well per day. A series of urine samples were collected from the subjects, some starting before water treatment was installed and continuing for at least nine months after treatment had begun. Urine samples were analyzed and speciated for inorganic-related arsenic concentrations. A two-phase clearance of inorganic-related arsenic from urine and the likelihood of a significant body burden from chronic exposure to arsenic in drinking water were identified. After nine months of water treatment the adjusted mean of the urinary inorganic-related arsenic concentrations were significantly lower (p < 0.0005) in the point-of-entry treatment group (2.5 μg/g creatinine) than in the point-of-use treatment group (7.2 μg/g creatinine). The results suggest that whole house arsenic water treatment systems provide a more effective reduction of arsenic exposure from well water than that obtained by point-of-use treatment. PMID:24975493

  15. Whole-house arsenic water treatment provided more effective arsenic exposure reduction than point-of-use water treatment at New Jersey homes with arsenic in well water.

    PubMed

    Spayd, Steven E; Robson, Mark G; Buckley, Brian T

    2015-02-01

    A comparison of the effectiveness of whole house (point-of-entry) and point-of-use arsenic water treatment systems in reducing arsenic exposure from well water was conducted. The non-randomized observational study recruited 49 subjects having elevated arsenic in their residential home well water in New Jersey. The subjects obtained either point-of-entry or point-of-use arsenic water treatment. Prior ingestion exposure to arsenic in well water was calculated by measuring arsenic concentrations in the well water and obtaining water-use histories for each subject, including years of residence with the current well and amount of water consumed from the well per day. A series of urine samples was collected from the subjects, some starting before water treatment was installed and continuing for at least nine months after treatment had begun. Urine samples were analyzed and speciated for inorganic-related arsenic concentrations. A two-phase clearance of inorganic-related arsenic from urine and the likelihood of a significant body burden from chronic exposure to arsenic in drinking water were identified. After nine months of water treatment the adjusted mean of the urinary inorganic-related arsenic concentrations was significantly lower (p<0.0005) in the point-of-entry treatment group (2.5 μg/g creatinine) than in the point-of-use treatment group (7.2 μg/g creatinine). The results suggest that whole house arsenic water treatment systems provide a more effective reduction of arsenic exposure from well water than that obtained by point-of-use treatment.

  16. ARE ALL ARSENIC EXPOSURES TOXIC? SUPPORTING REGIONAL RISK ASSESSMENTS THROUGH IMPROVED ARSENIC SPECIATION METHODOLOGY

    EPA Science Inventory

    Arsenic exposure assessments require the evaluation of the relative contribution of both media (water, food, etc.) and routes of exposure (ingestion, inhalation, dermal). For arsenic, the important media are predominately water and food and therefore, the route of concern for ...

  17. 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...

  18. 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...

  19. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism.

    PubMed

    Tyler, Christina R; Solomon, Benjamin R; Ulibarri, Adam L; Allan, Andrea M

    2014-09-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.

  20. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

    PubMed Central

    Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

    2014-01-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

  1. Does arsenic exposure increase the risk for prostate cancer?

    PubMed

    Yang, Chun-Yuh; Chang, Chih-Ching; Chiu, Hui-Fen

    2008-01-01

    Arsenic has been well documented as the major risk factor for blackfoot disease (BFD), a unique peripheral vascular disease that was endemic to the southwestern coast of Taiwan, where residents consumed artesian well water containing high levels of arsenic for more than 50 yr. Chronic arsenic exposure was also reported to be associated with mortality attributed to prostate cancer in a dose-response relationship. A tap-water supply system was implemented in the early 1960s in the BFD-endemic areas in Taiwan. Artesian well water was no longer used for drinking and cooking after the mid-1970s. The objective of this study was to determine whether prostate cancer mortality decreased after the improvement of drinking-water supply system through elimination of arsenic ingestion from artesian well water. Standardized mortality ratios (SMRs) for prostate cancer were calculated for the BFD-endemic area for the years 1971-2006. Results showed that mortality attributed to prostate cancer declined gradually after the improvement of drinking-water supply system. Based on the reversibility criterion, the association between arsenic exposure and development of prostate cancer is likely to be causal.

  2. 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...

  3. 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...

  4. Association Between Arsenic Exposure From Drinking Water and Plasma Levels of Cardiovascular Markers

    PubMed Central

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Wójcik, Oktawia; Parvez, Faruque; Rahaman, Ronald; Roy, Shantanu; Paul-Brutus, Rachelle; Segers, Stephanie; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; Mey, Jacob L.; van Geen, Alexander; Graziano, Joseph H.; Ahsan, Habibul; Chen, Yu

    2012-01-01

    The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007–2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease. PMID:22534204

  5. Association between arsenic exposure from drinking water and plasma levels of cardiovascular markers.

    PubMed

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Wójcik, Oktawia; Parvez, Faruque; Rahaman, Ronald; Roy, Shantanu; Paul-Brutus, Rachelle; Segers, Stephanie; Slavkovich, Vesna; Islam, Tariqul; Levy, Diane; Mey, Jacob L; van Geen, Alexander; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

    2012-06-15

    The authors conducted a cross-sectional study to assess the relation between arsenic exposure from drinking water and plasma levels of markers of systemic inflammation and endothelial dysfunction (matrix metalloproteinase-9, myeloperoxidase, plasminogen activator inhibitor-1, soluble E-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular adhesion molecule-1 (VCAM-1)) using baseline data from 668 participants (age, >30 years) in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2007-2008). Both well water arsenic and urinary arsenic were positively associated with plasma levels of soluble VCAM-1. For every 1-unit increase in log-transformed well water arsenic (ln μg/L) and urinary arsenic (ln μg/g creatinine), plasma soluble VCAM-1 was 1.02 (95% confidence interval: 1.01, 1.03) and 1.04 (95% confidence interval: 1.01, 1.07) times greater, respectively. There was a significant interaction between arsenic exposure and higher body mass index, such that the increased levels of plasminogen activator inhibitor-1 and soluble VCAM-1 associated with arsenic exposure were stronger among people with higher body mass index. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation and endothelial dysfunction that could be modified by body mass index and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.

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

    PubMed

    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: 8.68-45.71mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06mg-year), medium (1.37-3.55mg-year), and high (4.26-48.13mg-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.

  7. 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...

  8. 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...

  9. Exposure to Moderate Arsenic Concentrations Increases Atherosclerosis in ApoE−/− Mouse Model

    PubMed Central

    Lemaire, Maryse; Lemarié, Catherine A.; Flores Molina, Manuel; Schiffrin, Ernesto L.; Lehoux, Stéphanie; Mann, Koren K.

    2011-01-01

    Arsenic is a widespread environmental contaminant to which millions of people are exposed worldwide. Exposure to arsenic is epidemiologically linked to increased cardiovascular disease, such as atherosclerosis. However, the effects of moderate concentrations of arsenic on atherosclerosis formation are unknown. Therefore, we utilized an in vivo ApoE−/− mouse model to assess the effects of chronic moderate exposure to arsenic on plaque formation and composition in order to facilitate mechanistic investigations. Mice exposed to 200 ppb arsenic developed atherosclerotic lesions, a lower exposure than previously reported. In addition, arsenic modified the plaque content, rendering them potentially less stable and consequently, potentially more dangerous. Moreover, we observed that the lower exposure concentration was more atherogenic than the higher concentration. Arsenic-enhanced lesions correlated with several proatherogenic molecular changes, including decreased liver X receptor (LXR) target gene expression and increased proinflammatory cytokines. Significantly, our observations suggest that chronic moderate arsenic exposure may be a greater cardiovascular health risk than previously anticipated. PMID:21512104

  10. Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh.

    PubMed

    Raqib, Rubhana; Ahmed, Sultan; Sultana, Rokeya; Wagatsuma, Yukiko; Mondal, Dinesh; Hoque, A M Waheedul; Nermell, Barbro; Yunus, Mohammed; Roy, Shantonu; Persson, Lars Ake; Arifeen, Shams El; Moore, Sophie; Vahter, Marie

    2009-03-28

    Chronic exposure to arsenic, a potent carcinogen and toxicant, via drinking water is a worldwide public health problem. Because little is known about early-life effects of arsenic on immunity, we evaluated the impact of in utero exposure on infant immune parameters and morbidity in a pilot study. Pregnant women were enrolled at 6-10 weeks of gestation in Matlab, a rural area of Bangladesh, extensively affected by arsenic contamination of tubewell water. Women (n=140) delivering at local clinics were included in the study. Anthropometry and morbidity data of the pregnant women and their children, as well as infant thymic size by sonography were collected. Maternal urine and breast milk were collected for immune marker and arsenic assessment. Maternal urinary arsenic during pregnancy showed significant negative correlation with interleukin-7 (IL-7) and lactoferrin (Ltf) in breast milk and child thymic index (TI). Urinary arsenic was also positively associated with fever and diarrhea during pregnancy and acute respiratory infections (ARI) in the infants. The effect of arsenic exposure on ARI was only evident in male children. The findings suggest that in utero arsenic exposure impaired child thymic development and enhanced morbidity, probably via immunosuppression. The effect seemed to be partially gender dependent. Arsenic exposure also affected breast milk content of trophic factors and maternal morbidity.

  11. Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex.

    PubMed

    Ferrario, Daniele; Gribaldo, Laura; Hartung, Thomas

    2016-03-01

    Increasing evidence suggests that inorganic arsenic, a major environmental pollutant, exerts immunosuppressive effects in epidemiological, in vitro, and animal models. The mechanisms, however, remain unclear, and little is known about variation in susceptibilities due to age and sex. We performed a review of the experimental and epidemiologic evidence on the association of arsenic exposure and immune diseases. The majority of the studies described arsenic as a potent immunosuppressive compound, though others have reported an increase in allergy and autoimmune diseases, suggesting that arsenic may also act as an immune system stimulator, depending on the dose or timing of exposure. Limited information, due to either the high concentrations of arsenic used in in vitro studies or the use of non-human data for predicting human risks, is available from experimental studies. Moreover, although there is emerging evidence that health effects of arsenic manifest differently between men and women, we found limited information on sex differences on the immunotoxic effects of arsenic. In conclusion, preliminary data show that chronic early-life exposure to arsenic might impair immune responses, potentially leading to increased risk of infections and inflammatory-like diseases during childhood and in adulthood. Further investigation to evaluate effects of arsenic exposure on the developing immune system of both sexes, particularly in human cells and using concentrations relevant to human exposure, should be a research priority.

  12. Arsenic exposure from drinking-water and carotid artery intima-medial thickness in healthy young adults in Bangladesh.

    PubMed

    Chen, Yu; Hakim, Mohammad Enamul; Parvez, Faruque; Islam, Tariqul; Rahman, Atiar M; Ahsan, Habibul

    2006-06-01

    Epidemiological studies have linked high levels (>200 microg/L) of chronic exposure to arsenic in drinking-water with elevated risks of several vascular diseases. In this pilot study, the association between low-level arsenic exposure and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy, normotensive, relatively young individuals (mean age 35 years) participating in the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh. Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75 mm). Although the differences in average arsenic exposure between the two groups were not statistically significant, the findings suggest a possible association between low-level arsenic exposure from drinking-water and carotid atherosclerosis, warranting the need for larger studies.

  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. 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...

  15. Differential Methylation of the Arsenic (III) Methyltransferase Promoter According to Arsenic Exposure

    PubMed Central

    Gribble, Matthew O.; Tang, Wan-yee; Shang, Yan; Pollak, Jonathan; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K.; Guallar, Eliseo; Cole, Shelley A.; Fallin, M. Daniele; Navas-Acien, Ana

    2013-01-01

    Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase. Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for arsenic (III) methyltransferase, is differentially methylated as a function of arsenic exposure. In this study we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989–1991 and 1998–1999. For this study, all data are from the 1989–1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene. PMID:24154821

  16. 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

  17. Chronic arsenic intoxication diagnostic score (CAsIDS).

    PubMed

    Dani, Sergio Ulhoa; Walter, Gerhard Franz

    2017-08-31

    Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Association between arsenic exposure and soluble thrombomodulin: A cross sectional study in Bangladesh

    PubMed Central

    Islam, Md. Shofikul; Rahman, Atiqur; Anjum, Adiba; Hossain, Faruk; Mohanto, Nayan Chandra; Karim, Md. Rezaul; Hoque, Md. Mominul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2017-01-01

    Chronic exposure to arsenic is associated with increased morbidity and mortality from cardiovascular disease (CVD); however, plausible biomarker for early prediction and the underlying mechanism of arsenic-related CVD have not yet been clearly understood. Endothelial dysfunction plays a central role in the development of CVD. We hypothesized that endothelial damage or dysfunction is an important aspect and may be an early event of arsenic-related CVD. Soluble thrombomodulin (sTM) in serum is thought to be a specific and stable marker for endothelial damage or dysfunction. This study was designed to evaluate the association between chronic exposure to arsenic and sTM among human subjects in arsenic-endemic and non-endemic rural areas in Bangladesh. A total of 321 study subjects (217 from arsenic-endemic areas and 104 from a non-endemic area) were recruited. Subjects’ arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by Inductively Coupled Plasma Mass Spectroscopy. The subjects’ serum sTM levels were quantified by immunoassay kit. The average sTM levels of the subjects in arsenic-endemic and non-endemic areas were 4.58 ± 2.20 and 2.84 ± 1.29 (ng mL-1) respectively, and the difference was significant (p<0.001). Arsenic exposure levels showed a significant (water arsenic: rs = 0.339, p<0.001, hair arsenic: rs = 0.352, p<0.001 and nail arsenic: rs = 0.308, p<0.001) positive associations with sTM levels. Soluble TM levels were higher in the higher exposure gradients if we stratified the subjects into tertile groups (low, medium and high) based on the arsenic concentrations of the subjects’ drinking water, hair and nails. Finally, increased levels of sTM were negatively correlated with high density lipoprotein cholesterol (HDL-C), and positively correlated with intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Results of this study show that chronic exposure to arsenic has

  19. The prevalence of subjective symptoms after exposure to arsenic in drinking water in Inner Mongolia, China.

    PubMed

    Guo, Xiaojuan; Fujino, Yoshihisa; Chai, Jinshan; Wu, Kegong; Xia, Yajuan; Li, Yanhong; Lv, Jiangang; Sun, Zhiming; Yoshimura, Takesumi

    2003-07-01

    In Inner Mongolia, China, more than 300,000 people are chronically exposed to arsenic via their drinking water. We have previously reported that the prevalence of arsenical dermatosis was as high as 40% in the Hetao Plain area. However, the association between exposure to arsenic in drinking water and adverse health effects has not been fully examined. The purpose of this study was to examine the association between exposure to arsenic and prevalence of subjective symptoms. A cross-sectional study was carried out in 431 residents of an arsenic-affected village and 189 residents of an arsenic-free village in 1996. Health-related interviews and physical examinations were conducted. The odds ratio for each subjective symptom was estimated, comparing residents of arsenic-free and affected villages. An arsenic level of 50+ microg/L was found in 90.6% of wells in the arsenic-affected village. Adjusted odds ratios of subjective symptoms, including coughs (odds ratio [OR] = 12.8, 95% confidence interval [CI]: 6.4-25.6), stomachaches (OR = 5.8, 95% CI: 3.6-9.4), palpitations (OR = 3.6, 95% CI: 1.5-8.2), urination problems (OR = 14.7, 95% CI: 3.3-65.5) and spontaneous abortions (OR = 2.7, 95% CI: 0.8-8.4), were markedly higher amongst residents of the arsenic-affected village, including those without arsenic dermatosis. The present study shows a high prevalence of subjective symptoms amongst residents of an arsenic-affected village. Symptoms occurred in people with and without arsenic dermatosis. Our findings suggest that symptoms other than dermatosis should be considered when a clinical diagnosis of arsenic toxicosis is made.

  20. 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

  1. An investigation of the health effects caused by exposure to arsenic from drinking water and coal combustion: arsenic exposure and metabolism.

    PubMed

    Wei, Binggan; Yu, Jiangping; Kong, Chang; Li, Hairong; Yang, Linsheng; Guo, Zhiwei; Cui, Na; Xia, Yajuan; Wu, Kegong

    2017-09-23

    Few studies have been conducted to compare arsenic exposure, metabolism, and methylation in populations exposed to arsenic in drinking water and from coal combustion. Therefore, arsenic concentrations in the environment and arsenic speciation in the urine of subjects exposed to arsenic as a consequence of coal combustion in a rural area in Shaanxi province (CCA) and in drinking water in a rural area in Inner Mongolia (DWA) were investigated. The mean arsenic concentrations in drinking water, indoor air, and soil in CCA were 4.52 μg/L, 0.03 mg/m(3), and 14.93 mg/kg, respectively. The mean arsenic concentrations in drinking water and soil in DWA were 144.71 μg/L and 10.19 mg/kg, respectively, while the level in indoor air was lower than the limit of detection. The total daily intakes of arsenic in DWA and CCA were 4.47 and 3.13 μg/day·kg, respectively. The mean urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and total arsenic (TAs) for subjects with skin lesions in DWA were 50.41, 47.01, 202.66, and 300.08 μg/L. The concentrations for subjects without skin lesions were 49.76, 44.20, 195.60, and 289.56 μg/L, respectively. The %iAs, %MMA, and %DMA in the TAs in the urine of subjects from CCA were 12.24, 14.73, and 73.03%, while the corresponding values from DWA were 17.54, 15.57, and 66.89%, respectively. The subjects in DWA typically had a higher %iAs and %MMA, and a lower %DMA, and primary and secondary methylation index (PMI and SMI) than the subjects in CCA. It was concluded that the arsenic methylation efficiency of subjects in DWA and CCA was significantly influenced by chronic exposure to high levels of arsenic in the environment. The lower PMI and SMI values in DWA revealed lower arsenic methylation capacity due to ingestion of arsenic in drinking water. However, it remained unclear if the differences in arsenic metabolism between the two groups were due to differences in exposure levels

  2. Arsenic exposure disrupts the normal function of the FA/BRCA repair pathway.

    PubMed

    Peremartí, Jana; Ramos, Facundo; Marcos, Ricard; Hernández, Alba

    2014-11-01

    Chronic arsenic exposure is known to enhance the genotoxicity/carcinogenicity of other DNA-damaging agents by inhibiting DNA repair activities. Interference with nucleotide excision repair and base excision repair are well documented, but interactions with other DNA repair pathways are poorly explored so far. The Fanconi anemia FA/BRCA pathway is a DNA repair mechanism required for maintaining genomic stability and preventing cancer. Here, interactions between arsenic compounds and the FA/BRCA pathway were explored by using isogenic FANCD2(-/-) (FA/BRCA-deficient) and FANCD2(+/+) (FA/BRCA-corrected) human fibroblasts. To study whether arsenic disrupts the normal FA/BRCA function, FANCD2(+/+) cells were preexposed to subtoxic concentrations of the trivalent arsenic compounds methylarsonous acid (MMA(III)) and arsenic trioxide (ATO) for 2 weeks. The cellular response to mitomicin-C, hydroxyurea, or diepoxybutane, typical inducers of the studied pathway, was then evaluated and compared to that of FANCD2(-/-) cells. Our results show that preexposure to the trivalent arsenicals MMA(III) and ATO induces in corrected cells, a cellular FA/BRCA-deficient phenotype characterized by hypersensitivity, enhanced accumulation in the G2/M compartment and increased genomic instability--measured as micronuclei. Overall, our data demonstrate that environmentally relevant arsenic exposures disrupt the normal function of the FA/BRCA activity, supporting a novel source of arsenic co- and carcinogenic effects. This is the first study linking arsenic exposure with the FA/BRCA DNA repair pathway.

  3. 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.

  4. In Utero and Postnatal Exposure to Arsenic Alters Pulmonary Structure and Function

    PubMed Central

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

    2009-01-01

    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 μm 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. PMID:19095001

  5. 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

  6. Arsenic Exposure and Type 2 Diabetes: A Systematic Review of the Experimental and Epidemiologic Evidence

    PubMed Central

    Navas-Acien, Ana; Silbergeld, Ellen K.; Streeter, Robin A.; Clark, Jeanne M.; Burke, Thomas A.; Guallar, Eliseo

    2006-01-01

    Chronic arsenic exposure has been suggested to contribute to diabetes development. We performed a systematic review of the experimental and epidemiologic evidence on the association of arsenic and type 2 diabetes. We identified 19 in vitro studies of arsenic and glucose metabolism. Five studies reported that arsenic interfered with transcription factors involved in insulin-related gene expression: upstream factor 1 in pancreatic β-cells and peroxisome proliferative-activated receptor γ in preadipocytes. Other in vitro studies assessed the effect of arsenic on glucose uptake, typically using very high concentrations of arsenite or arsenate. These studies provide limited insight on potential mechanisms. We identified 10 in vivo studies in animals. These studies showed inconsistent effects of arsenic on glucose metabolism. Finally, we identified 19 epidemiologic studies (6 in high-arsenic areas in Taiwan and Bangladesh, 9 in occupational populations, and 4 in other populations). In studies from Taiwan and Bangladesh, the pooled relative risk estimate for diabetes comparing extreme arsenic exposure categories was 2.52 (95% confidence interval, 1.69–3.75), although methodologic problems limit the interpretation of the association. The evidence from occupational studies and from general populations other than Taiwan or Bangladesh was inconsistent. In summary, the current available evidence is inadequate to establish a causal role of arsenic in diabetes. Because arsenic exposure is widespread and diabetes prevalence is reaching epidemic proportions, experimental studies using arsenic concentrations relevant to human exposure and prospective epidemiologic studies measuring arsenic biomarkers and appropriately assessing diabetes should be a research priority. PMID:16675414

  7. Role of complex organic arsenicals in food in aggregate exposure to arsenic

    EPA Science Inventory

    For much of the world’s population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels has been linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is impo...

  8. Role of complex organic arsenicals in food in aggregate exposure to arsenic

    EPA Science Inventory

    For much of the world’s population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels has been linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is impo...

  9. 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

  10. A Systematic Review of Arsenic Exposure and Its Social and Mental Health Effects with Special Reference to Bangladesh

    PubMed Central

    Brinkel, Johanna; Khan, Mobarak H.; Kraemer, Alexander

    2009-01-01

    Underground water in many regions of the world is contaminated with high concentrations of arsenic and the resulting toxicity has created a major environmental and public health problem in the affected regions. Chronic arsenic exposure can cause many diseases, including various physical and psychological harms. Although the physical problems caused by arsenic toxicity are well reported in literature, unfortunately the consequences of arsenic exposure on mental health are not adequately studied. Therefore we conducted a review of the available literature focusing on the social consequences and detrimental effects of arsenic toxicity on mental health. Chronic arsenic exposures have serious implications for its victims (i.e. arsenicosis patients) and their families including social instability, social discrimination, refusal of victims by community and families, and marriage-related problems. Some studies conducted in arsenic affected areas revealed that arsenic exposures are associated with various neurologic problems. Chronic arsenic exposure can lead to mental retardation and developmental disabilities such as physical, cognitive, psychological, sensory and speech impairments. As health is defined by the World Health Organization as “a state of complete physical, mental and social wellbeing”, the social dimensions have a large impact on individual’s mental health. Furthermore studies in China und Bangladesh have shown that mental health problems (e.g. depression) are more common among the people affected by arsenic contamination. Our study indicates various neurological, mental and social consequences among arsenic affected victims. Further studies are recommended in arsenic-affected areas to understand the underlying mechanisms of poor mental health caused by arsenic exposure. PMID:19543409

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

    SciTech Connect

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

    2008-01-15

    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.

  12. 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.

  13. Potential Exposure to Arsenic from Infant Rice Cereal.

    PubMed

    Carignan, Courtney C; Punshon, Tracy; Karagas, Margaret R; Cottingham, Kathryn L

    2016-01-01

    Rice is known to be high in arsenic, including in infant rice cereal. Although arsenic in drinking water is currently regulated, there are currently no US regulations regarding arsenic concentrations in food. We used published values to estimate arsenic exposure via rice cereal relative to breast milk or formula for 6- to 12-month-old infants in the general US population. We found that arsenic exposure from 3 servings of rice cereal exceeded that of formula made with water containing arsenic at 10 μg/L, the US Environmental Protection Agency maximum contaminant level. Our findings suggest that rice cereal can markedly increase arsenic exposure among US infants relative to breast milk and formula. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. 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

    Islam, Khairul; Haque, Abedul; Karim, Rezaul; Fajol, Abul; Hossain, Ekhtear; Salam, Kazi Abdus; Ali, Nurshad; Saud, Zahangir Alam; Rahman, Matiar; Rahman, Mashiur; Karim, Rezaul; Sultana, Papia; Hossain, Mostaque; Akhand, Anwarul Azim; Mandal, Abul; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2011-07-08

    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. 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. 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. 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 novel exposure- and dose- response

  15. 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

  16. Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

    PubMed Central

    Truong, Lisa; Barton, Carrie L.; Chase, Tyler T.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

    2017-01-01

    Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa) were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes. PMID:28837703

  17. Arsenic in drinking water and peripheral nerve conduction velocity among residents of a chronically arsenic-affected area in Inner Mongolia.

    PubMed

    Fujino, Yoshihisa; Guo, Xiaojuan; Shirane, Kiyoyumi; Liu, Jun; Wu, Kegong; Miyatake, Munetoshi; Tanabe, Kimiko; Kusuda, Tetsuya; Yoshimura, Takesumi

    2006-09-01

    It remains unclear whether chronic ingestion of arsenic in drinking water affects the peripheral nervous system. We examined the effects of arsenic exposure on nerve conduction velocity using electromyography. A cross-sectional study was conducted of a population living in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 (93.7%) of 143 inhabitants took part in the study, and 36 (76.6%) of 47 inhabitants in a low-arsenic exposed village were recruited as a control group. Of the participants, 109 inhabitants in the arsenic-affected village and 32 in the low-arsenic exposed village aged > or =18 years were used for the analyses. An expert physician performed skin examinations, and median nerve conduction velocity was examined by electromyography. Arsenic levels in tube-well water and urine were measured. A mean level of arsenic in tube-well water in the arsenic-affected village was 158.3 microg/L, while that in the low-arsenic exposed village was 5.3 microg/L. No significant differences in the means of the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) were observed in relation to arsenic levels in tube wells, urine, and the duration of tube-well use. Further, no differences in mean MCV or SCV were found between the subjects with and without arsenic dermatosis, with mean SCV of 52.8 m/s (SD 6.3) in those without and 54.6 m/s (5.2) in subjects with arsenic dermatosis (p=0.206). These findings suggest that chronic arsenic poisoning from drinking water is unlikely to affect nerve conduction velocity, at least within the range of arsenic in drinking water examined in the present study.

  18. Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents.

    PubMed

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

    2015-02-01

    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. 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. 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. 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). Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.

  19. 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.

  20. 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.

  1. 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.

  2. Chronic arsenic toxicity: studies in West Bengal, India.

    PubMed

    Guha Mazumder, Debendranath; Dasgupta, U B

    2011-09-01

    Chronic arsenic toxicity (arsenicosis) as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 μg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been found to be

  3. Arsenic contents in rats' fur as an indicator of exposure to arsenic. Preliminary studies.

    PubMed

    Łoźna, Karolina; Styczyńska, Marzena; Bronkowska, Monika; Figurska-Ciura, Danuta; Biernat, Jadwiga

    2014-01-01

    Since arsenic compounds have an affinity to thiol groups their greatest amounts can then be found in the tissues containing sulphur-rich proteins, like beta-keratin in skin, hair and nails. Accumulation of arsenic also depends on the macronutrient content in daily food ration. The deficiency and excess of both the protein and fat may contribute to a higher content of arsenic in the organism, including hair in human or fur in animals. Hair and fur is a good indicator of population exposure to many toxic substances, including arsenic. The degree of arsenic accumulation may depend on the diet and nutritional status. The aim of this study was to determine the effect of protein and fat in diet on the accumulation of arsenic in rats' fur. A total number of 70 male Buffalo rats (body weight 200 - 220 g, age - 6 weeks) were divided into 10 groups. Rats were housed in plastic cages (4 per cage) in a 12h light/dark cycle for 6 weeks. The diets of different protein and fat contents ware administered to the animals. Five of ten groups of rats received throughout the whole period 10 ppm sodium arsenite dissolved in distilled drinking water (about 250 µg As/animal/day). The arsenic were determined with the method of atomic adsorption spectrometry in conjunction with a graphite-furnace atomize using a Varian AA240FS apparatus. The highest arsenic concentrations were found in fur of rats which were given low protein diet and water with arsenic. The lowest arsenic contents were found in fur of rats, which were given control diet and high protein diet with arsenic in water. Balanced control diet or high protein diet protected organism from arsenic accumulation, only small increase of arsenic content in rats' fur, compared to the control group, was observed. arsenic, rats' fur, protein and fat in diet, exposure to arsenic.

  4. [Tracing for arsenic exposure--a differentiation of arsenic compounds is essential for the health assessment].

    PubMed

    Weistenhöfer, Wobbeke; Ochsmann, Elke; Drexler, Hans; Göen, Thomas; Klotz, Katrin

    2016-01-01

    Arsenic is ubiquitous and harmful to health in occupation and environment. Arsenic exposure is measured through analysis of arsenic compounds in urine. The identification of several arsenic species is necessary to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. To estimate the extent of an occupational exposure to arsenic, arsenic species were evaluated for the first time by the working group "Setting of Threshold Limit Values in Biological Material" of the DFG Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area and Biologische Arbeitsstoffreferenzwerte (BAR) of 0.5 μg / L urine for arsenic (III), 0.5 μg / L urine for arsenic (V), 2 μg / L urine for monomethylarsonic acid (MMA) and 10 μg / L urine for dimethylarsinic acid (DMA) were set. If the reference value for total arsenic is exceeded, a further differentiation of arsenic species now enables to estimate the individual health risks taking into account special influences such as seafood consumption. © Georg Thieme Verlag KG Stuttgart · New York.

  5. 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.

  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.

    PubMed

    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 microg/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 microg/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 predominantly at low-to-moderate levels (0.1 to 864 microg/L, mean 99 microg/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. 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

    PubMed Central

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

    2012-01-01

    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 µg/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 µg/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 µg/L, mean 99 µg/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. PMID:19371619

  8. 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...

  9. 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...

  10. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  11. Dietary arsenic exposure with low level of arsenic in drinking water and biomarker: a study in West Bengal.

    PubMed

    Mazumder, Debendra Nath Guha; Deb, Debasree; Biswas, Anirban; Saha, Chandan; Nandy, Ashoke; Das, Arabinda; Ghose, Aloke; Bhattacharya, Kallol; Mazumdar, Kunal Kanti

    2014-01-01

    The authors investigated association of arsenic intake through water and diet and arsenic level in urine in people living in arsenic endemic region in West Bengal supplied with arsenic-safe water (<50 μg L(-1)). Out of 94 (Group-1A) study participants using water with arsenic level <50 μg L(-1), 72 participants (Group-1B) were taking water with arsenic level <10 μg L(-1). Multiple regressions analysis conducted on the Group-1A participants showed that daily arsenic dose from water and diet were found to be significantly positively associated with urinary arsenic level. However, daily arsenic dose from diet was found to be significantly positively associated with urinary arsenic level in Group-1B participants only, but no significant association was found with arsenic dose from water in this group. In a separate analysis, out of 68 participants with arsenic exposure through diet only, urinary arsenic concentration was found to correlate positively (r = 0.573) with dietary arsenic in 45 participants with skin lesion while this correlation was insignificant (r = 0.007) in 23 participants without skin lesion. Our study suggested that dietary arsenic intake was a potential pathway of arsenic exposure even where arsenic intake through water was reduced significantly in arsenic endemic region in West Bengal. Observation of variation in urinary arsenic excretion in arsenic-exposed subjects with and without skin lesion needed further study.

  12. Associations between prenatal arsenic exposure with adverse pregnancy outcome and child mortality.

    PubMed

    Shih, Yu-Hsuan; Islam, Tariqul; Hore, Samar Kumar; Sarwar, Golam; Shahriar, Mohammad Hasan; Yunus, Mohammad; Graziano, Joseph H; Harjes, Judith; Baron, John A; Parvez, Faruque; Ahsan, Habibul; Argos, Maria

    2017-10-01

    Chronic arsenic exposure is a public health concern in many parts of the world, with elevated concentrations in groundwater posing a threat to millions of people. Arsenic is associated with various cancers and an array of chronic diseases; however, the relationship with adverse pregnancy outcomes and child mortality is less established. We evaluated associations between individual-level prenatal arsenic exposure with adverse pregnancy outcomes and child mortality in a pregnancy study among 498 women nested in a larger population-based cohort in rural Bangladesh. Creatinine-adjusted urinary total arsenic concentration, a comprehensive measure of exposure from water, food, and air sources, reflective of the prenatal period was available for participants. Self-reported pregnancy outcomes (livebirth, stillbirth, spontaneous/elective abortion) were ascertained. Generalized estimating equations, accounting for multiple pregnancies of participants, were used to estimate odds ratios and 95% confidence intervals in relation to adverse pregnancy outcomes. Vital status of livebirths was subsequently ascertained through November 2015. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals in relation to child mortality. We observed a significant association between prenatal arsenic exposure and the risk of stillbirth (greater than median; adjusted OR = 2.50; 95% CI = 1.04, 6.01). We also observed elevated risk of child mortality (greater than median; adjusted HR = 1.92; 95% CI = 0.78, 4.68) in relation to prenatal arsenic exposure. Prospective studies should continue to evaluate prenatal and early life health effects of arsenic exposure and arsenic remediation strategies for women of child-bearing age. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Correlation of arsenic exposure through drinking groundwater and urinary arsenic excretion among adults in Pakistan.

    PubMed

    Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

    2014-01-01

    Long-term exposure to arsenic has been associated with manifestation of skin lesions (melanosis/keratosis) and increased risk of internal cancers (lung/bladder). The objective of the study described here was to determine the relationship between exposure of arsenic through drinking groundwater and urinary arsenic excretion among adults > or =15 years of age living in Khairpur district, Pakistan. Total arsenic was determined in drinking groundwater and in spot urine samples of 465 randomly selected individuals through hydride generation-atomic absorption spectrometry. Spearman's rank correlation coefficient was calculated between arsenic in drinking groundwater and arsenic excreted in urine. The median arsenic concentration in drinking water was 2.1 microg/L (range: 0.1-350), and in urine was 28.5 microg/L (range: 0.1-848). Positive correlation was found between total arsenic in drinking water and in urine (r = .52, p < .01). Urinary arsenic may be used as a biomarker of arsenic exposure through drinking water.

  14. Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

    PubMed

    Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

    2017-02-11

    Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO2) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

  15. The health effects of exposure to arsenic-contaminated drinking water: a review by global geographical distribution.

    PubMed

    Huang, Lei; Wu, Haiyun; van der Kuijp, Tsering Jan

    2015-01-01

    Chronic arsenic exposure through drinking water has been a vigorously studied and debated subject. However, the existing literature does not allow for a thorough examination of the potential regional discrepancies that may arise among arsenic-related health outcomes. The purpose of this article is to provide an updated review of the literature on arsenic exposure and commonly discussed health effects according to global geographical distribution. This geographically segmented approach helps uncover the discrepancies in the health effects of arsenic. For instance, women are more susceptible than men to a few types of cancer in Taiwan, but not in other countries. Although skin cancer and arsenic exposure correlations have been discovered in Chile, Argentina, the United States, and Taiwan, no evident association was found in mainland China. We then propose several globally applicable recommendations to prevent and treat the further spread of arsenic poisoning and suggestions of future study designs and decision-making.

  16. 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

  17. Environmental arsenic exposure and microbiota in induced sputum.

    PubMed

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

    2014-02-21

    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.

  18. Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

    PubMed

    James, Katherine A; Meliker, Jaymie R; Buttenfield, Barbara E; Byers, Tim; Zerbe, Gary O; Hokanson, John E; Marshall, Julie A

    2014-08-01

    Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

  19. 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.

  20. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

    PubMed Central

    Liu, Jie; Zheng, Baoshan; Aposhian, H Vasken; Zhou, Yunshu; Chen, Ming-Liang; Zhang, Aihua; Waalkes, Michael P

    2002-01-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area. PMID:11836136

  1. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China.

    PubMed

    Liu, Jie; Zheng, Baoshan; Aposhian, H Vasken; Zhou, Yunshu; Chen, Ming-Liang; Zhang, Aihua; Waalkes, Michael P

    2002-02-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  2. 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.

  3. Role of complex organic arsenicals in food in aggregate exposure to arsenic.

    PubMed

    Thomas, David J; Bradham, Karen

    2016-11-01

    For much of the world's population, food is the major source of exposure to arsenic. Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important in assessing risk and developing strategies that protect public health. Although most emphasis has been placed on inorganic arsenic as human carcinogen and toxicant, an array of arsenic-containing species are found in plants and animals used as foods. Here, we 2evaluate the contribution of complex organic arsenicals (arsenosugars, arsenolipids, and trimethylarsonium compounds) that are found in foods and consider their origins, metabolism, and potential toxicity. Commonalities in the metabolism of arsenosugars and arsenolipids lead to the production of di-methylated arsenicals which are known to exert many toxic effects. Evaluating foods as sources of exposure to these complex organic arsenicals and understanding the formation of reactive metabolites may be critical in assessing their contribution to aggregate exposure to arsenic. Copyright © 2016. Published by Elsevier B.V.

  4. 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...

  5. Exposure to inorganic arsenic in drinking water and total urinary arsenic concentration in a Chilean population.

    PubMed

    Caceres, Dante D; Pino, Paulina; Montesinos, Nestor; Atalah, Eduardo; Amigo, Hugo; Loomis, Dana

    2005-06-01

    The relationship of inorganic arsenic exposure through drinking water and total urinary arsenic excretion in a nonoccupationally exposed population was evaluated in a cross-sectional study in three mayor cities of Chile (Antofagasta, Santiago, and Temuco). A total of 756 individuals in three population strata (elderly, students, and workers) provided first morning void urine specimens the day after exposure and food surveys were administered. Arsenic intake from drinking water was estimated from analysis of tap water samples, plus 24-h dietary recall and food frequency questionnaires. Multilevel analysis was used to evaluate the effects of the age group and city factors adjusted by predictor variables. Arsenic levels in drinking water and urine were significantly higher in Antofagasta compared with the other cities. City-and individual-level factors, 12% and 88%, respectively, accounted for the variability in urinary arsenic concentration. The main predictors of urinary arsenic concentration were total arsenic consumption through water and age. These findings indicate that arsenic concentration in drinking water continues to be the principal contributing factor to exposure to inorganic arsenic in the Chilean population.

  6. 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.

  7. Arsenic exposure from drinking water, arsenic methylation capacity, and carotid intima-media thickness in Bangladesh.

    PubMed

    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

    2013-08-01

    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.

  8. 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

  9. Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes.

    PubMed

    Li, Xin; Li, Bing; Xi, Shuhua; Zheng, Quanmei; Lv, Xiuqiang; Sun, Guifan

    2013-11-01

    Prolonged exposure to inorganic arsenic has been a severe environmental public health issue worldwide in the recent decades. Increasing evidence has suggested a possible role of prolonged arsenic exposure through drinking water in the development of arsenic-induced chronic noncancer diseases, among which hypertension and type 2 diabetes (T2D) are the focus of concern. Although exposure to high levels of arsenic has been reported to be associated with excess risk of hypertension or T2D in a dose-dependent manner, the association has yet to be established, especially low-level exposure. This cross-sectional study was designed to evaluate the potential association between prolonged environmental arsenic exposure through drinking water and the prevalence of hypertension and T2D in Inner Mongolia, China, with emphasis on the assessment of low-level exposure. In this study (a total of 669 men and women), we found that the blood pressure levels were significantly correlated with cumulative arsenic exposure and that the systolic blood pressure of the subjects with arsenic exposure>50 μg/L was significantly higher than those of the subjects with <10 and 10-50 μg/L exposure. Significant prevalence of hypertension was found in the subjects of the >50 μg/L group both before and after adjustment for confounders. In addition, a significant negative relationship was found between urinary arsenic percentage of dimethylated arsenic (DMA%) and the prevalence of hypertension in the >50 μg/L group. However, low-level arsenic exposure (10-50 μg/L) was not statistically associated with hypertension. No significant difference of blood glucose was found among the groups with different arsenic exposure levels. No statistical association was found between arsenic exposure and T2D. Our findings suggested that prolonged arsenic exposure might play a role in the development of hypertension; however, only high-level arsenic was associated with the risk of hypertension. Our findings also

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. Arsenic Exposure through Drinking Water Is Associated with Longer Telomeres in Peripheral Blood

    PubMed Central

    2012-01-01

    Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred two women with a wide range in exposure to arsenic via drinking water (3.5–200 μg/L) were recruited. Concentrations of arsenic metabolites in urine [inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were measured. The relative telomere length in blood was measured by quantitative real-time polymerase chain reaction. Genotyping (N = 172) for eight SNPs in AS3MT and gene expression of telomere-related genes (in blood; N = 90) were performed. Urinary arsenic (sum of metabolites) was positively associated with telomere length (β = 0.65 × 10–4, 95% CI = 0.031 × 10–4–1.3 × 10–4, adjusted for age and BMI). Individuals with above median fractions of iAs and MMA showed significantly longer telomeres by increasing urinary arsenic (β = 1.0 × 10–4, 95% CI = 0.21 × 10–4–1.8 × 10–4 at high % iAs; β = 0.88 × 10–4 95% CI = 0.12 × 10–4–1.6 × 10–4 at high % MMA) than those below the median (p = 0.80 and 0.44, respectively). Similarly, carriers of the slow and more toxic metabolizing AS3MT haplotype showed stronger positive associations between arsenic exposure and telomere length, as compared to noncarriers (interaction urinary arsenic and haplotype p = 0.025). Urinary arsenic was positively correlated with the expression of telomerase reverse transcriptase (TERT, Spearman r = 0.22, p = 0.037), but no association was found between TERT expression and telomere length. Arsenic in drinking water influences the telomere length, and this may be a mechanism for its carcinogenicity. A faster and less toxic arsenic metabolism diminishes arsenic-related telomere elongation. PMID:22917110

  17. Arsenic exposure through drinking water is associated with longer telomeres in peripheral blood.

    PubMed

    Li, Huiqi; Engström, Karin; Vahter, Marie; Broberg, Karin

    2012-11-19

    Inorganic arsenic is a strong carcinogen, possibly by interaction with the telomere length. The aim of the study was to evaluate how chronic arsenic exposure from drinking water as well as the arsenic metabolism efficiency affect the individual telomere length and the expression of telomere-related genes. Two hundred two women with a wide range in exposure to arsenic via drinking water (3.5-200 μg/L) were recruited. Concentrations of arsenic metabolites in urine [inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA)] were measured. The relative telomere length in blood was measured by quantitative real-time polymerase chain reaction. Genotyping (N = 172) for eight SNPs in AS3MT and gene expression of telomere-related genes (in blood; N = 90) were performed. Urinary arsenic (sum of metabolites) was positively associated with telomere length (β = 0.65 × 10(-4), 95% CI = 0.031 × 10(-4)-1.3 × 10(-4), adjusted for age and BMI). Individuals with above median fractions of iAs and MMA showed significantly longer telomeres by increasing urinary arsenic (β = 1.0 × 10(-4), 95% CI = 0.21 × 10(-4)-1.8 × 10(-4) at high % iAs; β = 0.88 × 10(-4) 95% CI = 0.12 × 10(-4)-1.6 × 10(-4) at high % MMA) than those below the median (p = 0.80 and 0.44, respectively). Similarly, carriers of the slow and more toxic metabolizing AS3MT haplotype showed stronger positive associations between arsenic exposure and telomere length, as compared to noncarriers (interaction urinary arsenic and haplotype p = 0.025). Urinary arsenic was positively correlated with the expression of telomerase reverse transcriptase (TERT, Spearman r = 0.22, p = 0.037), but no association was found between TERT expression and telomere length. Arsenic in drinking water influences the telomere length, and this may be a mechanism for its carcinogenicity. A faster and less toxic arsenic metabolism diminishes arsenic-related telomere elongation.

  18. Rice consumption contributes to arsenic exposure in US women

    PubMed Central

    Gilbert-Diamond, Diane; Cottingham, Kathryn L.; Gruber, Joann F.; Punshon, Tracy; Sayarath, Vicki; Gandolfi, A. Jay; Baker, Emily R.; Jackson, Brian P.; Folt, Carol L.; Karagas, Margaret R.

    2011-01-01

    Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (μg/d) were significantly associated with natural log-transformed total urinary arsenic (, , both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 μg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of >2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States. PMID:22143778

  19. 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.

  20. Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population.

    PubMed

    Andrew, Angeline S; Jewell, David A; Mason, Rebecca A; Whitfield, Michael L; Moore, Jason H; Karagas, Margaret R

    2008-04-01

    Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 microg/L in the northeastern, western, and north central regions of the United States. We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999-2002) as part of a case-control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases.

  1. Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population

    PubMed Central

    Andrew, Angeline S.; Jewell, David A.; Mason, Rebecca A.; Whitfield, Michael L.; Moore, Jason H.; Karagas, Margaret R.

    2008-01-01

    Background Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States. Objectives We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. Methods We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) as part of a case–control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. Results The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. Conclusions These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases. PMID:18414638

  2. Measured versus modeled dietary arsenic and relation to urinary arsenic excretion and total exposure

    PubMed Central

    Kurzius-Spencer, Margaret; O’Rourke, Mary Kay; Hsu, Chiu-Hsieh; Hartz, Vern; Harris, Robin B.; Burgess, Jefferey L.

    2014-01-01

    Chronic exposure to arsenic (As) in food and water is a significant public health problem. Person-specific aggregate exposure is difficult to collect, and modeling based on limited food As residue databases is of uncertain reliability. Two, cross-sectional, population exposure studies—the National Human Exposure Assessment Survey (NHEXAS)-Arizona and the Arizona Border Survey (ABS)— had a total of 252 subjects with diet, water, and urinary As data. Total As was measured in 24-hour duplicate diet samples and modeled using 24-hour diet diaries in conjunction with several published food surveys of As. Two-stage regression was used to assess the effects of dietary As on urinary total As (uAs): 1) generalized linear mixed models of uAs above versus below the limit of detection (LOD); and 2) restricted models limited to those subjects with uAs > LOD, using bootstrap sampling and mixed models adjusted for age, sex, BMI, ethnicity, current smoking, and As intake from drinking and cooking water. In restricted models, measured and modeled estimates were significant predictors of uAs. Modeled dietary As based on Total Diet Study mean residues greatly underestimated dietary intake. In households with tap water As ≤ 10 ppb, over 93% of total As exposure was attributable to diet. PMID:23321855

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

    PubMed Central

    Stanton, Bruce A.

    2015-01-01

    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 U.S. Environmental Protection Agency (EPA) has set a limit of 10 micrograms per liter (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

  4. Exposure to inorganic arsenic metabolites during early human development.

    PubMed

    Concha, G; Vogler, G; Lezcano, D; Nermell, B; Vahter, M

    1998-08-01

    Because of the lack of data on the exposure to and toxic effects of inorganic arsenic during early human development, the transfer of arsenic to the fetus and suckling infant was studied in a native Andean population, living in the village San Antonio de los Cobres in the North west of Argentina, where the drinking water contains about 200 micrograms/liter. The concentration of arsenic in cord blood (median, 9 micrograms/liter) was almost as high as in maternal blood (median, 11 micrograms/liter), and there was a significant correlation between the two. Thus, at least in late gestation, arsenic is easily transferred to the fetus. The median concentration of arsenic in the placenta was 34 micrograms/kg, compared with 7 micrograms/kg previously reported for nonexposed women. Interestingly, essentially all arsenic in the blood plasma of both the newborns and their mothers was in the form of dimethylarsinic acid (DMA), the end product of inorganic arsenic metabolism. Similarly, about 90% of the arsenic in the urine of both the newborns and mothers in late gestation was present as DMA, compared with about 70% in nonpregnant women (p < 0.001). This may indicate that methylation of arsenic is increased during pregnancy and that DMA is the major form of arsenic transferred to the fetus. The increased methylation in late gestation was associated with lower arsenic concentrations in blood and higher concentrations in urine, compared with a few months postpartum. The arsenic concentrations in the urine of the infants decreased from about 80 micrograms/liter during the first 2 days of life to less than 30 micrograms/liter at 4.4 months (p = 0.025). This could be explained by the low concentrations of arsenic in the breast milk, about 3 micrograms/kg.

  5. Association between arsenic exposure from drinking water and plasma levels of soluble cell adhesion molecules.

    PubMed

    Chen, Yu; Santella, Regina M; Kibriya, Muhammad G; Wang, Qiao; Kappil, Maya; Verret, Wendy J; Graziano, Joseph H; Ahsan, Habibul

    2007-10-01

    Epidemiologic studies of cardiovascular disease risk factors and appropriate biomarkers in populations exposed to a wide range of arsenic levels are a public health research priority. We investigated the relationship between inorganic arsenic exposure from drinking water and plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), both markers of endothelial dysfunction and vascular inflammation, in an arsenic-exposed population in Araihazar, Bangladesh. The study participants included 115 individuals with arsenic-related skin lesions participating in a 2 x 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation. Arsenic exposure status and plasma levels of sICAM-1 and sVCAM-1 were assessed at baseline and after 6 months of follow-up. Baseline well arsenic, a long-term measure of arsenic exposure, was positively associated with baseline levels of both sICAM-1 and sVCAM-1 and with changes in the two markers over time. At baseline, for every 1-mug/L increase in well arsenic there was an increase of 0.10 ng/mL [95% confidence interval (CI), 0.00-0.20] and 0.33 ng/mL (95% CI, 0.15-0.51) in plasma sICAM-1 and sVCAM-1, respectively. Every 1-microg/L increase in well arsenic was associated with a rise of 0.11 ng/mL (95% CI, 0.01-0.22) and 0.17 ng/mL (95% CI, 0.00-0.35) in sICAM-1 and sVCAM-1 from baseline to follow-up, respectively, in spite of recent changes in urinary arsenic as well as vitamin E and selenium supplementation during the study period. The findings indicate an effect of chronic arsenic exposure from drinking water on vascular inflammation that persists over time and also suggest a potential mechanism underlying the association between arsenic exposure and cardiovascular disease.

  6. Association between Low to Moderate Arsenic Exposure and Incident Cardiovascular Disease. A Prospective Cohort Study

    PubMed Central

    Moon, Katherine A.; Guallar, Eliseo; Umans, Jason G.; Devereux, Richard B.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Pollak, Jonathan; Silbergeld, Ellen K.; Howard, Barbara V.; Navas-Acien, Ana

    2014-01-01

    Background Inorganic arsenic exposure in water and food is a global public health problem. Chronic exposure to high levels of arsenicis consistently associated with increased risk of cardiovascular disease, whereas prospective data on low to moderate chronic arsenic exposure (<100μg/L in drinking water) are lacking. Objective To evaluate the association between chronic low to moderate arsenic exposure and incident cardiovascular disease. Design Prospective cohort study. Setting The Strong Heart Study baseline visit in 1989-1991, with follow-up through 2008. Patients 3,575 American Indian men and women aged 45-74 years living in Arizona, Oklahoma, and North and South Dakota. Measurements The sum of inorganic and methylated arsenic species in urine at baseline was used as a biomarker of chronic arsenic exposure. Participants were followed for incident fatal and non-fatal cardiovascular disease, including coronary heart disease and stroke. Results 1,184 participants developed fatal and non-fatal cardiovascular disease and 439 participants developed fatal cardiovascular disease. Comparing the highest to lowest quartile arsenic concentrations (>15.7 vs. <5.8 μg/g creatinine), the hazard ratios (95% confidence interval) for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for socio-demographic factors, smoking, body mass index, and lipids were 1.65 (1.20, 2.27; p-trend<0.001), 1.71 (1.19, 2.44; p-trend<0.001) and 3.03 (1.08, 8.50; p-trend=0.061), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (1.09, 1.59; p-trend=0.002), 1.30 (1.04, 1.62; p-trend=0.006), and 1.47 (0.97, 2.21; p-trend=0.032), respectively. These associations varied by study region and were attenuated following further adjustment for diabetes, hypertension, and measures of kidney disease. Limitations Direct measurement of individual arsenic in drinking water was unavailable. Residual

  7. 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

  8. Association between multi-level inorganic arsenic exposure from drinking water and skin lesions in China.

    PubMed

    Guo, Xiaojuan; Fujino, Yoshihisa; Ye, Xiaolei; Liu, Jun; Yoshimura, Takesumi

    2006-09-01

    Arsenic is one of the most important toxicants in the environment. In Inner Mongolia of China, 300,000 residents are believed to be drinking water containing >50 microg/liter. Skin lesions have been known as the most common consequences resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic-induced skin lesions, it is important to assess the impact of this problem among the target population, and to make future planning. We evaluated the association between multi-levels inorganic arsenic exposure from drinking water and skin lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine and 32 subjects in high (>50 microg/liter) and low (<50 microg/liter) arsenic-affected villages were recruited and had the detailed physical examination with special emphasis on arsenic-related skin lesions. Arsenic exposure was measured for each participant with respect to iAs concentration of primary well and the duration using the well. Arsenic-induced skin lesions including keratosis, pigmentation, and/or depigmentation were diagnosed in 56 and 3 subjects in the two villages, respectively. Logistic regression was conducted to calculate odd ratios of skin lesions associated with arsenic exposure with adjustments for sex, age group, smoking and duration of exposure. A consistent dose-response relationship between arsenic exposure level and skin lesion risk was observed. Compared to those with iAs concentration <50 microg/liter, the adjusted odds ratios of skin lesions for the subjects with 51-99, 100-149 and >150 microg/liter were 33.3% (OR =15.50, 95% CI: 1.53-248.70), 46.7% (OR =16.10, 95% CI: 3.73-69.63) and 55.7% (OR= 25.70, 95% CI: 6.43-102.87), respectively. Duration of using well was not associated with increased risk of skin lesions in this population; (OR =1.68, 95% CI: 0.40-6.91 for 6-15 years, OR = 2.30, 95% CI: 0.58-9.14 for over 15 years) compared with the duration of less than 5 years.

  9. [Spina bifida occulta associated with environmental arsenic exposure in a prehispanic sample from northern Chile].

    PubMed

    Silva-Pinto, Verónica; Arriaza, Bernardo; Standen, Vivien

    2010-04-01

    The Camarones River Valley, located in the extreme north of Chile, is characterized by high environmental arsenic levels and an arid desert. It has been inhabited by humans for the past 7,000 years. Evidence exists for chronic arsenic poisoning in both prehispanic and present populations residing in the area. Chronic arsenic exposure causes multi-systemic problems and can induce congenital malformations, in particular neural tube development defects such as spina bifida. To study the prevalence of spina bifida among prehispanic mummies of the area. One hundred and twenty prehistoric adult individuals were analyzed for evidence of spina bifda occulta of the sacrum in skeletal samples from the sites of Camarones 8, Camarones 9, Azapa 140 and Lluta 54, held in repository at the Museo Universidad de Tarapacá de Arica- San Miguel de Azapa. A diagnosis was considered positive when at least S1, S2 or S3 were affected. As controls, mummies of individuals that resided in Lluta and Azapa valley, with a low arsenic exposure, were analyzed. The frequency of spina bifida occulta among samples from the Camarones coast and Lluta and Azapa Valley were 13.5 and 2.4% respectively. Considering these were contemporaneous samples, and are believed to have had no other differences in diet or other factors, the differential exposures to arsenic could have produced the observed differences in spina bifida frequencies.

  10. A Prospective Study of Arsenic Exposure From Drinking Water and Incidence of Skin Lesions in Bangladesh

    PubMed Central

    Argos, Maria; Kalra, Tara; Pierce, Brandon L.; Chen, Yu; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Hasan, Khaled; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Graziano, Joseph H.; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000–2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1–50.0, 50.1–100.0, 100.1–200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (Ptrend = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L). PMID:21576319

  11. A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.

    PubMed

    Argos, Maria; Kalra, Tara; Pierce, Brandon L; Chen, Yu; Parvez, Faruque; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Hasan, Khaled; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Graziano, Joseph H; Rathouz, Paul J; Ahsan, Habibul

    2011-07-15

    Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS). The analyses used data on 10,182 adults free of skin lesions at baseline through the third biennial follow-up of the cohort (2000-2009). Discrete-time hazard regression models were used to estimate hazard ratios and 95% confidence intervals for incident skin lesions. Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001). Results were similar for the other measures of arsenic exposure, and the increased risks remained unchanged with changes in exposure in recent years. Dose-dependent associations were more pronounced in females, but the incidence of skin lesions was greater in males and older individuals. Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).

  12. Prenatal arsenic exposure and drowning among children in Bangladesh.

    PubMed

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

    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.

  13. Assessment of human dietary exposure to arsenic through rice.

    PubMed

    Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

    2017-05-15

    Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health.

  14. 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 I 2 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

  15. 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

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

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

    PubMed

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

    1999-08-01

    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.

  2. 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

  3. 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

  4. 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

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

    PubMed

    Das, Nandana; Paul, Somnath; Chatterjee, Debmita; Banerjee, Nilanjana; Majumder, Niladri S; Sarma, Nilendu; Sau, Tanmoy J; Basu, Santanu; Banerjee, Saptarshi; Majumder, Papiya; Bandyopadhyay, Apurba K; States, J Christopher; Giri, Ashok K

    2012-08-10

    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. 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. 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. Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk.

  6. 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

  7. 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

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

    PubMed

    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 microg of As/L); Spot method (detection limit, 10 microg of As/L); and air assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic-concentrations ranged from below limit of detection to 1200 microg 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 microg of As/L (14,500 above 50 microg of As/L-the current China national standard in drinking water and 2198 above 300 microg 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.

  9. Nerve conduction studies in chronic arsenic poisoning patients.

    PubMed

    Supapong, Soontorn; Phanthumchinda, Kammant; Srirattanaban, Jiruth

    2004-09-01

    To assess the nerve conduction functions among female patients with arsenical dermatoses compared with the controls. Cross-sectional analytic study Thirty females with skin lesions consistent with arsenical dermatoses and 27 controls who met the inclusion criteria were investigated by nerve conduction functions. Case findings resulted from a house-to-house survey in village 12, Ronphibun subdistrict and village 5, Saothong subdistrict, Nakhon Si Thammarat Province, southern Thailand in 1995. Differences between the arsenic-exposed population and the reference group regarding nerve conduction velocities (NCVs), proximal and distal latencies and amplitudes of sensory and motor nerve action potentials were not found except for the absent response to the sural nerve stimulation in three subjects of the exposed group. The effects of arsenic toxicity on the peripheral nerves in the form of slow nerve conduction velocities were not found among female patients with arsenical dermatoses in Ronphibun. Some patients might have experienced arsenic neuropathy to some degree in the past (before 1987) but they had recovered to some degree at the time of the present investigation (1996) as most of the patients with chronic arsenic poisoning in the present study changed their sources of drinking water from arsenic-contaminated shallow-well water to other sources such as rainwater, tap water or commercial bottled water.

  10. Assessment of Prenatal Exposure to Arsenic in Tenerife Island

    PubMed Central

    Vall, Oriol; Gómez-Culebras, Mario; Garcia-Algar, Oscar; Joya, Xavier; Velez, Dinoraz; Rodríguez-Carrasco, Eva; Puig, Carme

    2012-01-01

    Introduction Increasing awareness of the potential chronic health effects of arsenic (As) at low exposure levels has motivated efforts to better understand impaired child development during pregnancy by biomarkers of exposure. The aims of this study were to evaluate the prenatal exposure to As by analysis of an alternative matrix (meconium), to examine its effects on neonatal outcomes and investigate the association with maternal lifestyle and dietary habits during pregnancy. Methods A transversal descriptive study was conducted in Tenerife (Spain). A total of 96 mother-child pairs participated in the study. A questionnaire on sociodemographic, lifestyle and dietary habits during pregnancy was administered the day after the delivery. Analysis of total As in meconium was performed by inductively coupled plasma-optical emission spectrometer. Results Total As was detected in 37 (38.5%) meconium samples. The univariate logistic regression model indicates that prenatal exposure to As was associated with a low intake of eggs per week (OR 0.56; CI (95%): 0.34–0.94) during pregnancy. Conversely, frequent intake of vegetables was associated with prenatal As exposure (OR: 1.19; CI (95%): 1.01–1.41) and frequent intake of processed meat (as bacon, Frankfurt’s sausage, and hamburger) shows a trend to As prenatal exposure (OR: 8.54; CI (95%): 0.80–90.89). The adjusted multivariate logistic regression model indicates that only frequent intake of vegetables maintains the association (OR: 1.31; CI (95%): 1.02–1.68). Conclusion The studied population presented a low As exposure and was not associated with neonatal effects. Maternal consumption of vegetables during pregnancy was associated with detectable meconium As levels; however the concentration detected in meconium was too low to be considered a major public health concern in this geographical area. PMID:23209747

  11. 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.

  12. Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

    PubMed

    Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

    2015-07-01

    After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

  13. Arsenic exposure and prevalence of diabetes mellitus in Korean adults.

    PubMed

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

    2013-06-01

    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.

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

    PubMed

    Ramsey, Kathryn A; Larcombe, Alexander N; Sly, Peter D; Zosky, Graeme R

    2013-02-18

    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. Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/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. 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. 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.

  15. 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

  16. Arsenic poisoning.

    PubMed

    Schoolmeester, W L; White, D R

    1980-02-01

    Arsenic poisoning continues to require awareness of its diverse clinical manifestations. Industry is the major source of arsenic exposure. Although epidemiologic studies strongly contend that arsenic is carcinogenic, there are little supportive research data. Arsenic poisoning, both acute and chronic, is often overlooked initially in the evaluation of the patient with multisystem disease, but once it is suspected, many accurate methods are available to quantitate the amount and duration of exposure. Treatment with dimercaprol remains the mainstay of therapy, and early treatment is necessary to prevent irreversible complications.

  17. Urinary Trivalent Methylated Arsenic Species in a Population Chronically Exposed to Inorganic Arsenic

    PubMed Central

    Valenzuela, Olga L.; Borja-Aburto, Victor H.; Garcia-Vargas, Gonzalo G.; Cruz-Gonzalez, Martha B.; Garcia-Montalvo, Eliud A.; Calderon-Aranda, Emma S.; Del Razo, Luz M.

    2005-01-01

    Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs–exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. PMID:15743710

  18. Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic.

    PubMed

    Valenzuela, Olga L; Borja-Aburto, Victor H; Garcia-Vargas, Gonzalo G; Cruz-Gonzalez, Martha B; Garcia-Montalvo, Eliud A; Calderon-Aranda, Emma S; Del Razo, Luz M

    2005-03-01

    Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

  19. Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: Evidence from the Strong Heart Study.

    PubMed

    Spratlen, Miranda Jones; Gamble, Mary V; Grau-Perez, Maria; Kuo, Chin-Chi; Best, Lyle G; Yracheta, Joseph; Francesconi, Kevin; Goessler, Walter; Mossavar-Rahmani, Yasmin; Hall, Meghan; Umans, Jason G; Fretts, Amanda; Navas-Acien, Ana

    2017-07-01

    B-vitamins involved in one-carbon metabolism (OCM) can affect arsenic metabolism efficiency in highly arsenic exposed, undernourished populations. We evaluated whether dietary intake of OCM nutrients (including vitamins B2, B6, folate (B9), and B12) was associated with arsenic metabolism in a more nourished population exposed to lower arsenic than previously studied. Dietary intake of OCM nutrients and urine arsenic was evaluated in 405 participants from the Strong Heart Study. Arsenic exposure was measured as the sum of iAs, monomethylarsonate (MMA) and dimethylarsenate (DMA) in urine. Arsenic metabolism was measured as the individual percentages of each metabolite over their sum (iAs%, MMA%, DMA%). In adjusted models, increasing intake of vitamins B2 and B6 was associated with modest but significant decreases in iAs% and MMA% and increases in DMA%. A significant interaction was found between high folate and B6 with enhanced arsenic metabolism efficiency. Our findings suggest OCM nutrients may influence arsenic metabolism in populations with moderate arsenic exposure. Stronger and independent associations were observed with B2 and B6, vitamins previously understudied in relation to arsenic. Research is needed to evaluate whether targeting B-vitamin intake can serve as a strategy for the prevention of arsenic-related health effects at low-moderate arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Chronic arsenic toxicity from Ayurvedic medicines.

    PubMed

    Khandpur, Sujay; Malhotra, Amit K; Bhatia, Vidhyut; Gupta, Subandhu; Sharma, Vinod K; Mishra, Rakesh; Arora, Narendra K

    2008-06-01

    Ayurvedic medicines are known to contain arsenic and concentrations up to toxic levels have been reported in certain formulations. However, clinical disease due to arsenic containing ayurvedic medicines has rarely been reported. We seek to highlight the existence of toxic levels of arsenic in certain ayurvedic preparations that can produce serious systemic manifestations. An 11-year-old girl developed manifestations of arsenical keratosis (punctuate palmoplantar keratoderma and leucomelanoderma) and non-cirrhotic portal hypertension, 6 months and 18 months respectively after intake of ayurvedic medications, prescribed for epilepsy. The eight ayurvedic preparations consumed by the patient and her serum levels were analyzed for arsenic content. Arsenic content of ayurvedic medicines ranged from 5 mg/L to 248 mg/L. The serum arsenic level was 202.20 microg/L (normal < 60 microg/L). Skin manifestations improved after the discontinuation of ayurvedic medications. Ayurvedic medications should be consumed under strict guidance and supervision of qualified practitioners to prevent such catastrophies.

  1. 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.

  2. Relations between exposure to arsenic, skin lesions, and glucosuria

    PubMed Central

    Rahman, M.; Tondel, M.; Chowdhury, I. A.; Axelson, O.

    1999-01-01

    OBJECTIVES: Exposure to arsenic causes keratosis, hyperpigmentation, and hypopigmentation and seemingly also diabetes mellitus, at least in subjects with skin lesions. Here we evaluate the relations of arsenical skin lesions and glucosuria as a proxy for diabetes mellitus. METHODS: Through existing measurements of arsenic in drinking water in Bangladesh, wells with and without arsenic contamination were identified. Based on a questionnaire, 1595 subjects > or = 30 years of age were interviewed; 1481 had a history of drinking water contaminated with arsenic whereas 114 had not. Time weighted mean arsenic concentrations and mg-years/l of exposure to arsenic were estimated based on the history of consumption of well water and current arsenic concentrations. Urine samples from the study subjects were tested by means of a glucometric strip. People with positive tests were considered to be cases of glucosuria. RESULTS: A total of 430 (29%) of the exposed people were found to have skin lesions. Corresponding to drinking water with < 0.5, 0.5-1.0, and > 1.0 mg/l of arsenic, and with the 114 unexposed subjects as the reference, the prevalence ratios for glucosuria, as adjusted for age and sex, were 0.8, 1.4, and 1.4 for those without skin lesions, and 1.1, 2.2, and 2.6 for those with skin lesions. Taking exposure as < 1.0, 1.0-5.0, > 5.0-10.0 and > 10.0 mg- years/l of exposure to arsenic the prevalence ratios, similarly adjusted, were 0.4, 0.9, 1.2, and 1.7 for those without and 0.8, 1.7, 2.1, and 2.9 for those with skin lesions. All series of risk estimates were significant for trend, (p < 0.01). CONCLUSIONS: The results suggest that skin lesions and diabetes mellitus, as here indicated by glucosuria, are largely independent effects of exposure to arsenic although glucosuria had some tendency to be associated with skin lesions. Importantly, however, glucosuria (diabetes mellitus) may occur independently of skin lesions.   PMID:10450246

  3. Arsenic exposure to killifish during embryogenesis alters muscle development.

    PubMed

    Gaworecki, Kristen M; Chapman, Robert W; Neely, Marion G; D'Amico, Angela R; Bain, Lisa J

    2012-02-01

    Epidemiological studies have correlated arsenic exposure in drinking water with adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, delays in the use of musculature, and altered locomotor activity. Killifish (Fundulus heteroclitus) were used as a model to help to determine the mechanisms by which arsenic could impact development. Killifish embryos were exposed to three different sodium arsenite concentrations and were collected at 32 h post-fertilization (hpf), 42 hpf, 168 hpf, or < 24 h post-hatch. A killifish oligo microarray was developed and used to examine gene expression changes between control and 25-ppm arsenic-exposed hatchlings. With artificial neural network analysis of the transcriptomic data, accurate prediction of each group (control vs. arsenic-exposed embryos) was obtained using a small subset of only 332 genes. The genes differentially expressed include those involved in cell cycle, development, ubiquitination, and the musculature. Several of the genes involved in cell cycle regulation and muscle formation, such as fetuin B, cyclin D-binding protein 1, and CapZ, were differentially expressed in the embryos in a time- and dose-dependent manner. Examining muscle structure in the hatchlings showed that arsenic exposure during embryogenesis significantly reduces the average muscle fiber size, which is coupled with a significant 2.1- and 1.6-fold upregulation of skeletal myosin light and heavy chains, respectively. These findings collectively indicate that arsenic exposure during embryogenesis can initiate molecular changes that appear to lead to aberrant muscle formation.

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

    PubMed

    Coronado-González, José Antonio; Del Razo, Luz María; García-Vargas, Gonzalo; Sanmiguel-Salazar, Francisca; Escobedo-de la Peña, Jorge

    2007-07-01

    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 > or = 126 mg/100 ml (> or = 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 microg/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.

  5. 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.

  6. Biological and behavioral factors modify biomarkers of arsenic exposure in a U.S. population.

    PubMed

    Calderon, Rebecca L; Hudgens, Edward E; Carty, Cara; He, Bin; Le, X Chris; Rogers, John; Thomas, David J

    2013-10-01

    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 insight into the effects of biological and behavioral factors on arsenic exposure, we determined arsenic concentrations in urine and toenails in a U.S. population that uses public or private water supplies containing inorganic arsenic. Study participants were 904 adult residents of Churchill County, Nevada, whose home tap water supplies contained <3 to about 1200 µg of arsenic per liter. Biomarkers of exposure for this study were summed urinary concentrations of inorganic arsenic and its methylated metabolites (speciated arsenical), of all urinary arsenicals (total arsenical), and of all toenail arsenicals (total arsenical). Increased tap water arsenic concentration and consumption were associated with significant upward trends for urinary speciated and total and toenail total arsenical concentrations. Significant gender differences in concentrations of speciated and total arsenicals in urine and toenails reflected male-female difference in water intake. Both recent and higher habitual seafood consumption significantly increased urinary total but not speciated arsenical concentration. In a stepwise general linear model, seafood consumption significantly predicted urinary total arsenical but not urinary speciated or toenail total arsenical concentrations. Smoking behavior significantly predicted urinary speciated or total arsenical concentration. Gender, tap water arsenic concentration, and primary drinking water source significantly predicted urinary speciated and total concentrations and toenail total arsenical concentrations. These findings confirm the primacy of home tap water as a determinant of arsenic concentration in urine and toenails. However, biological and behavioral factors can

  7. Arsenic and cardiovascular disease.

    PubMed

    States, J Christopher; Srivastava, Sanjay; Chen, Yu; Barchowsky, Aaron

    2009-02-01

    Chronic arsenic exposure is a worldwide health problem. Although arsenic-induced cancer has been widely studied, comparatively little attention has been paid to arsenic-induced vascular disease. Epidemiological studies have shown that chronic arsenic exposure is associated with increased morbidity and mortality from cardiovascular disease. In addition, studies suggest that susceptibility to arsenic-induced vascular disease may be modified by nutritional factors in addition to genetic factors. Recently, animal models for arsenic-induced atherosclerosis and liver sinusoidal endothelial cell dysfunction have been developed. Initial studies in these models show that arsenic exposure accelerates and exacerbates atherosclerosis in apolipoprotein E-knockout mice. Microarray studies of liver mRNA and micro-RNA abundance in mice exposed in utero suggest that a permanent state of stress is induced by the arsenic exposure. Furthermore, the livers of the arsenic-exposed mice have activated pathways involved in immune responses suggesting a pro-hyperinflammatory state. Arsenic exposure of mice after weaning shows a clear dose-response in the extent of disease exacerbation. In addition, increased inflammation in arterial wall is evident. In response to arsenic-stimulated oxidative signaling, liver sinusoidal endothelium differentiates into a continuous endothelium that limits nutrient exchange and waste elimination. Data suggest that nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide or its derivatives are essential second messengers in the signaling pathway for arsenic-stimulated vessel remodeling. The recent findings provide future directions for research into the cardiovascular effects of arsenic exposure.

  8. A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus.

    PubMed

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

    2013-05-01

    Consumption of drinking water with high levels of inorganic arsenic (over 500 μg/L) has been associated with type II diabetes mellitus (DM), but previous studies have been inconclusive about risks at lower levels (<100 μg/L). We present 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 DM. This case-cohort study included 141 cases of DM diagnosed between 1984 and 1998 as part of the prospective San Luis Valley Diabetes Study. A comparison sub-cohort of 488 participants was randomly sampled from 936 eligible participants who were disease free at baseline. Individual lifetime arsenic exposure estimates were determined using a methodology that incorporates the use of a structured interview to determine lifetime residence and employment history, geospatial modeling of arsenic concentrations in drinking water, and urine arsenic concentrations. A Cox proportional hazards model with known DM risk factors as time-dependent covariates was used to assess the association between lifetime exposure to inorganic arsenic in drinking water and incident DM. Our findings show a significant association between inorganic arsenic exposure and DM risk (hazard ratio [HR]=1.27, 95%=1.01, 1.59 per 15 μg/L) while adjusting for ethnicity and time varying covariates age, body mass index and physical activity level. Exposure to low-level inorganic arsenic in drinking water is associated with increased risk for type II DM in this population based on a comprehensive lifetime exposure assessment. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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

  10. 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 ...

  11. 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....

  12. 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....

  13. 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 ...

  14. Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population.

    PubMed

    Argos, Maria; Kibriya, Muhammad G; Parvez, Faruque; Jasmine, Farzana; Rakibuz-Zaman, Muhammad; Ahsan, Habibul

    2006-07-01

    Millions of individuals worldwide are chronically exposed to arsenic through their drinking water. In this study, the effect of arsenic exposure and arsenical skin lesion status on genome-wide gene expression patterns was evaluated using RNA from peripheral blood lymphocytes of individuals selected from the Health Effects of Arsenic Longitudinal Study. Affymetrix HG-U133A GeneChip (Affymetrix, Santa Clara, CA) arrays were used to measure the expression of approximately 22,000 transcripts. Our primary statistical analysis involved identifying differentially expressed genes between participants with and without arsenical skin lesions based on the significance analysis of microarrays statistic with an a priori defined 1% false discovery rate to minimize false positives. To better characterize differential expression, we also conducted Gene Ontology and pathway comparisons in addition to the gene-specific analyses. Four-hundred sixty-eight genes were differentially expressed between these two groups, from which 312 differentially expressed genes were identified by restricting the analysis to female never-smokers. We also explored possible differential gene expression by arsenic exposure levels among individuals without manifest arsenical skin lesions; however, no differentially expressed genes could be identified from this comparison. Our findings show that microarray-based gene expression analysis is a powerful method to characterize the molecular profile of arsenic exposure and arsenic-induced diseases. Genes identified from this analysis may provide insights into the underlying processes of arsenic-induced disease and represent potential targets for chemoprevention studies to reduce arsenic-induced skin cancer in this population.

  15. 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

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

    PubMed

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

    2016-01-16

    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.

  17. 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...

  18. 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...

  19. Low-level arsenic exposure and developmental neurotoxicity in children: A systematic review and risk assessment.

    PubMed

    Tsuji, Joyce S; Garry, Michael R; Perez, Vanessa; Chang, Ellen T

    2015-11-04

    chronic lifetime exposure, thus indicating protectiveness of the existing value for potential neurotoxicity in children. This reference dose is undergoing revision as EPA considers various health endpoints in the reassessment of inorganic arsenic health risks. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  20. [Nervous system disorders induced by occupational exposure to arsenic and its inorganic compounds: a literature review].

    PubMed

    Sińczuk-Walczak, Halina

    2009-01-01

    This paper presents a review of the effect of arsenic (As) and its inorganic compounds on the nervous system. In humans, inhalation exposure mostly occurs in occupational conditions. In the occupational environment, the most extensive exposure to this element is observed in the copper industry. Chronic As poisoning is manifested by skin and mucous membrane lesions, impairment of the nervous system in the form of disorders of psychic functions and polyneuropathies, retrobulbar neuritis, disorders of peripheral circulation and the risk for Raynaud's syndrome. Arsenic-induced polyneuropathy is usually a very serious and chronic disease. A complete recovery is observed in only 15-20% of patients. As-induced encephalopathy is an irreversible process.

  1. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats.

    PubMed

    Bhadauria, S; Flora, S J S

    2007-03-01

    Arsenic and its compounds cause adverse health effects in humans. Current treatment employs administration of thiol chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), which facilitate its excretion from the body. However, these chelating agents are compromised by number of limitations due to their lipophobic nature, particularly in case of chronic poisoning. Combination therapy is a new approach to ensure enhanced removal of metal from the body, reduced doses of potentially toxic chelators, and no redistribution of metal from one organ to another, following chronic metal exposure. The present study attempts to investigate dose-related effects of two thiol chelators, DMSA and one of its new analogues, monoisoamyl dimercaptosuccinic acid (MiADMSA), when administered in combination with the aim of achieving normalization of altered biochemical parameters suggestive of oxidative stress and depletion of inorganic arsenic following chronic arsenic exposure. Twenty-five adult male Wistar rats were given 25 ppm arsenic for 10 weeks followed by chelation therapy with the above chelating agents at a dose of 0.3 mmol/kg (orally) when administered individually or 0.15 mmol/kg and 0.3 mmol/kg (once daily for 5 consecutive days), respectively, when administered in combination. Arsenic exposure led to the inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity and depletion of glutathione (GSH) level. These changes were accompanied by significant depletion of hemoglobin, RBC and Hct as well as blood superoxide dismutase (SOD) acitivity. There was an increase in hepatic and renal levels of thiobarbituric acid-reactive substances, while GSH:GSSG ratio decreased significantly, accompanied by a significant increase in metallothionein (MT) in hepatocytes. DNA damage based on denaturing polyacrylamide gel electrophoresis revealed significant loss in the integrity of DNA extracted from the liver of arsenic

  2. 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.

  3. Human exposure asseessment to different arsenic species in tea.

    PubMed

    Mania, Monika; Szynal, Tomasz; Rebeniak, Małgorzata; Wojciechowska-Mazurek, Maria; Starska, Krystyna; Strzelecka, Agnieszka

    2014-01-01

    Inorganic forms of arsenic are much more highly toxic to humans than organic species. Their effects include being carcinogenic, genotoxic and neurotoxic, where in the latter case, above all, they affect nervous system development in the foetus, infants and children. The main foodstuffs contributing significantly to its total dietary intake are drinking water, rice (and its products), fish, seafood, cereals, seaweed, root vegetables, food supplements, mushrooms and tea. After water, tea is the second most popular beverage drunk in Poland with average consumption annually indicating that statistically every Polish inhabitant drinks at least one cup of tea daily. The aim of the study was to determine the total and inorganic content of arsenic in various black and green teas available on the market and thus to estimate consumer exposure to inorganic arsenic from this foodstuff. Analyses of total and inorganic arsenic were performed on 23 samples of black and green teas that consisted of tea leaves, teas in bags and granules, from various sources. The analytical method was hydride generation atomic absorption spectrometry (HGAAS), after dry ashing of samples and reduction of arsenic to arsenic hydride using sodium borohydride. In order to isolate only the inorganic forms of arsenic prior to mineralisation, samples were subjected to concentrated HCl hydrolysis, followed by reduction with hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of adults was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL05) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 μg/kg body weight (b.w.) per day). Green teas were found to be more highly contaminated with both total and inorganic arsenic than black teas. Contamination of black teas total and inorganic arsenic was mean: 0.058 mg/kg (median: 0.042 mg

  4. [Geographic information system based spatial analysis on chronic arsenic poisoning in a tin mining area, Thailand].

    PubMed

    Zhang, Jianjun; Wu, Liping; Lin, Kun

    2007-05-01

    To explore the spatial features of arsenic contamination and its association with chronic arsenic poisoning in a tin mining area of Thailand. Geographic information system(GIS) was built up with integration of arsenic concentration in varied environmental media and occurring location data of chronic arsenism patients. Then, the spatial interpolation (IDW), buffer zoning, query and rank correlation analysis were applied. Groundwater and surface farming land were classified according to local environmental arsenic standards; the relative risk areas were identified. The incidence of chronic arsenic poisoning was significantly correlated with arsenic level in groundwater and soil type (P < 0.05), and insignificantly related with water soluble arsenic in soil (P > 0.05). The arsenic content in drinking water could be critical to chronic arsenic poisoning. The soil type could be an important factor affecting such poisoning. Trend analysis in GIS could provide a valuable tool for understanding the pollution situation and disease surveillance.

  5. Children's intellectual function in relation to arsenic exposure.

    PubMed

    von Ehrenstein, Ondine S; Poddar, Shalini; Yuan, Yan; Mazumder, Debendra Guha; Eskenazi, Brenda; Basu, Arin; Hira-Smith, Meera; Ghosh, Nalima; Lahiri, Sabari; Haque, Reina; Ghosh, Alakendu; Kalman, Dave; Das, Subankar; Smith, Allan H

    2007-01-01

    Very little evidence exists concerning the possible impairment of children's intellectual function in relation to arsenic exposure in utero and during childhood. We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001-2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates. Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, -0.14, -0.28; P for trend = 0.02), the object assembly test (0, -0.16, -0.24; P for trend = 0.03), and the picture completion test (0, -0.15, -0.26; P for trend = 0.02). These findings correspond to relative declines of 12% (95% confidence interval =0.4% to 24%) in the vocabulary test, 21% (-0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood. Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in school-aged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function.

  6. 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...

  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. Health hazards and mitigation of chronic poisoning from arsenic in drinking water: Taiwan experiences.

    PubMed

    Chen, Chien-Jen

    2014-01-01

    There are two endemic areas of long-term exposure to arsenic from drinking water in Taiwan. Residents in the southwestern and northeastern endemic areas started using high-arsenic artesian well water in the early 1910s and late 1940s, respectively. Public water supply system using surface water was implemented in southwestern and northeastern endemic areas in the 1970s and 1990s, respectively. Systemic health hazards of long-term exposure to arsenic in drinking water have been intensively investigated since the 1960s, especially after 1985 in Taiwan. Several diseases have been well documented to be associated with chronic arsenic poisoning from drinking water showing a dose-response relation. They include characteristic skin lesions like hyperpigmentation or depigmentation, hyperkeratosis in palms and soles, and Bowen disease, peripheral vascular disease (specifically blackfoot disease), ischemic heart disease, cerebral infarction, microvascular diseases, abnormal peripheral microcirculation, carotid atherosclerosis, QT prolongation and increased dispersion in electrocardiography, hypertension, goiter, diabetes mellitus, cataract (specifically posterior subcapsular lens opacity), pterygium, slow neural conduction, retarded neurobehavioral development, erectile dysfunction, and cancers of the skin, lung, urinary bladder, kidney, and liver. The method of choice to mitigate arsenic poisoning through drinking water is to use safe drinking water from uncontaminated sources.

  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. Epidemiology of chronic disease related to arsenic in Argentina: A systematic review.

    PubMed

    Bardach, Ariel Esteban; Ciapponi, Agustin; Soto, Natalie; Chaparro, Martin R; Calderon, Maria; Briatore, Agustina; Cadoppi, Norma; Tassara, Roberto; Litter, Marta I

    2015-12-15

    Four million people in Argentina are exposed to arsenic contamination from drinking waters of several center-northern provinces. A systematic review to examine the geographical distribution of arsenic-related diseases in Argentina was conducted, searching electronic databases and gray literature up to November 2013. Key informants were also contacted. Of the 430 references identified, 47 (mostly cross-sectional and ecological designs) referred to arsenic concentration in water and its relationship with the incidence and mortality of cancer, dermatological diseases and genetic disorders. A high percentage of the water samples had arsenic concentrations above the WHO threshold value of 10μg/L, especially in the province of Buenos Aires. The median prevalence of arsenicosis was 2.6% in exposed areas. The proportion of skin cancer in patients with arsenicosis reached 88% in case-series from the Buenos Aires province. We found higher incidence rate ratios per 100μg/L increment in inorganic arsenic concentration for colorectal, lung, breast, prostate and skin cancer, for both genders. Liver and skin cancer mortality risk ratios were higher in regions with medium/high concentrations than in those with low concentrations. The relative risk of mortality by skin cancer associated to arsenic exposure in the province of Buenos Aires ranged from 2.5 to 5.2. In the north of this province, high levels of arsenic in drinking water were reported; however, removal interventions were scarcely documented. Arsenic contamination in Argentina is associated with an increased risk of serious chronic diseases, including cancer, showing the need for adequate and timely actions.

  11. Maternal Arsenic Exposure and Impaired Glucose Tolerance during Pregnancy

    PubMed Central

    Ettinger, Adrienne S.; Zota, Ami R.; Amarasiriwardena, Chitra J.; Hopkins, Marianne R.; Schwartz, Joel; Hu, Howard; Wright, Robert O.

    2009-01-01

    Background Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results Arsenic concentrations ranged from 0.2 to 24.1 μg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (> 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD. PMID:19654913

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

    PubMed Central

    Howard, Barbara V.; Umans, Jason G.; Gribble, Matthew O.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Lee, Elisa; Guallar, Eliseo; Navas-Acien, Ana

    2015-01-01

    OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. PMID:25583752

  13. 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.

  14. Neonatal Metabolomic Profiles Related to Prenatal Arsenic Exposure.

    PubMed

    Laine, Jessica E; Bailey, Kathryn A; Olshan, Andrew F; Smeester, Lisa; Drobná, Zuzana; Stýblo, Miroslav; Douillet, Christelle; García-Vargas, Gonzalo; Rubio-Andrade, Marisela; Pathmasiri, Wimal; McRitchie, Susan; Sumner, Susan J; Fry, Rebecca C

    2017-01-03

    Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in Gómez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure.

  15. Evaluation of biochemical changes in chronic arsenic poisoning among Bangladeshi patients.

    PubMed

    Nabi, A H M Nurun; Rahman, M Mahfuzur; Islam, Laila N

    2005-12-01

    An estimated 40 million people in Bangladesh have been suffering from arsenic toxicity-related diseases because of drinking water contamination with high levels of naturally occurring arsenic. To evaluate the biochemical changes in chronic arsenic exposure, a total of 115 exposed subjects diagnosed as arsenicosis patients were examined and interviewed, and 120 unexposed volunteers were enrolled in this study. Drinking water, urine and peripheral blood samples were collected from all participants and analyzed. The average levels of arsenic in the drinking water and spot urine samples of the arsenicosis patients were 218.1 microg/L and 234.6 microg/L, respectively, and duration of exposure was 7.6 +/- 5.2 yrs that ranged from 1-25 yrs. Prevalence of diabetes mellitus among chronic arsenic-exposed subjects was about 2.8 times higher than the unexposed subjects. The activities of alkaline phosphatase were significantly elevated in the patients, 197 U/L compared to 149 U/L in the controls, but alanine transaminase and aspartate transaminase were mostly normal. The patients had significantly lower levels of serum creatinine, 0.97 mg/dL compared to 1.15 mg/dL in the controls; but had significantly elevated levels of total protein, 84 g/L and 77 g/L respectively. The mean level of inorganic phosphate in the serum of arsenicosis patients was 6.4 mg/dL compared to 4.6 mg/dL in the unexposed subjects and the level was significantly higher, indicating substitution of the pentavalent arsenate for the phosphate ion causing underutilization of the latter. Evaluation of the lipid profiles showed while the levels of triacylglycerol were not much different, the patients had significantly lower levels of cholesterol, HDL-cholesterol and LDL-cholesterol compared to the unexposed subjects. These findings suggest significant changes in biochemical parameters in human arsenic toxicity.

  16. Acute arsenic exposure treated with oral D-penicillamine

    SciTech Connect

    Watson, W.A.; Veltri, J.C.; Metcalf, T.J.

    1981-06-01

    Arsenic trioxide (As2O3) is the arsenic compound most commonly implicated in acute toxic exposures. The toxicity of As2O3 is a function of the preparation's particle size and solubility. A 16-month-old female presented at a local emergency room with a history of acute ingestion of As2O3 obtained from a commonly available pesticide. Classic gastrointestinal symptoms of arsenic toxicity were exhibited shortly after ingestion; however, aggressive decontamination followed by early chelation therapy resulted in the cessation of toxic manifestations and an uneventful recovery. Oral chelation therapy with D-penicillamine has rarely been reported as an effective agent in the treatment of arsenic poisoning. The case reported herein is further documentation that D-penicillamine is effective in increasing the mobilization of arsenic. The authors also recommend that products containing arsenic compounds should not be used where children may come in contact with them until the Environmental Protection Agency's child resistant packaging regulations become effective.

  17. Males in rural Bangladeshi communities are more susceptible to chronic arsenic poisoning than females: analyses based on urinary arsenic.

    PubMed Central

    Watanabe, C; Inaoka, T; Kadono, T; Nagano, M; Nakamura, S; Ushijima, K; Murayama, N; Miyazaki, K; Ohtsuka, R

    2001-01-01

    Spot urine samples were collected from the inhabitants of two rural communities in northwestern Bangladesh. We compared arsenic levels in the urine samples ([As](u); n = 346) with those in water from tube wells ([As](tw); range < 1-535 microg/L; n = 86) on an individual basis. The small variation of [As](u) within subjects and highly positive correlation with [As](tw) indicate that [As](u) is a useful indicator of exposure. Analyses of [As](u) showed that creatinine correction was necessary, that [As](u) only reflected recent exposure, and that there were substantial interindividual differences for a given [As](tw) level. To evaluate the toxic effects of arsenic exposure, we constructed a system for rating skin manifestations, which revealed distinct sex-related differences. Comparison of males and females in the same households confirmed that skin manifestations were more severe in the males, and in the males of one community a dose-response relationship between [As](u) and the degree of skin manifestation was evident. The results of this study indicate that [As](u) in spot urine samples can be used as an exposure indicator for As. They suggest that there might be sex-related, and perhaps community-related, differences in the relationship between [As](u) and skin manifestations, although several confounding factors, including sunlight exposure and smoking habits, might contribute to the observed sex difference. The existence of such differences should be further confirmed and examined in other populations to identify the subpopulations sensitive to chronic arsenic toxicity. PMID:11748034

  18. Inorganic arsenic and respiratory health, from early life exposure to sex-specific effects: A systematic review.

    PubMed

    Sanchez, Tiffany R; Perzanowski, Matthew; Graziano, Joseph H

    2016-05-01

    This systematic review synthesizes the diverse body of epidemiologic research accrued on inorganic arsenic exposure and respiratory health effects. Twenty-nine articles were identified that examined the relationship between inorganic arsenic exposure and respiratory outcomes (i.e. lung function, symptoms, acute respiratory infections, chronic non-malignant lung diseases, and non-malignant lung disease mortality). There was strong evidence of a general association between arsenic and non-malignant respiratory illness, including consistent evidence on lung function impairment, acute respiratory tract infections, respiratory symptoms, and non-malignant lung disease mortality. Overall, early life exposure (i.e. in utero and/or early-childhood) had a marked effect throughout the lifespan. This review also identified some research gaps, including limited evidence at lower levels of exposure (water arsenic <100μg/L), mixed evidence of sex differences, and some uncertainty on arsenic and any single non-malignant respiratory disease or pathological process. Common limitations, including potential publication bias; non-comparability of outcome measures across included articles; incomplete exposure histories; and limited confounder control attenuated the cumulative strength of the evidence as it relates to US populations. This systematic review provides a comprehensive assessment of the epidemiologic evidence and should be used to guide future research on arsenic's detrimental effects on respiratory health.

  19. Arsenic Exposure and Type 2 Diabetes: MicroRNAs as Mechanistic Links?

    PubMed

    Beck, Rowan; Styblo, Miroslav; Sethupathy, Praveen

    2017-03-01

    The goal of this review is to delineate the following: (1) the primary means of inorganic arsenic (iAs) exposure for human populations, (2) the adverse public health outcomes associated with chronic iAs exposure, (3) the pathophysiological connection between arsenic and type 2 diabetes (T2D), and (4) the incipient evidence for microRNAs as candidate mechanistic links between iAs exposure and T2D. Exposure to iAs in animal models has been associated with the dysfunction of several different cell types and tissues, including liver and pancreatic islets. Many microRNAs that have been identified as responsive to iAs exposure under in vitro and/or in vivo conditions have also been shown in independent studies to regulate processes that underlie T2D etiology, such as glucose-stimulated insulin secretion from pancreatic beta cells. Defects in insulin secretion could be, in part, associated with aberrant microRNA expression and activity. Additional in vivo studies need to be performed with standardized concentrations and durations of arsenic exposure in order to evaluate rigorously microRNAs as molecular drivers of iAs-associated diabetes.

  20. 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

  1. 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...

  2. Cancer excess after arsenic exposure from contaminated milk powder.

    PubMed

    Yorifuji, Takashi; Tsuda, Toshihide; Doi, Hiroyuki; Grandjean, Philippe

    2011-05-01

    Long-term exposure to inorganic arsenic is related to increased risk of cancer in the lung, skin, bladder, and, possibly, other sites. However, little is known about the consequences of developmental exposures in regard to cancer risk. During early summer in 1955, mass arsenic poisoning of infants occurred in the western part of Japan because of contaminated milk powder. Okayama Prefecture was most severely affected. We examined whether the affected birth cohorts in this prefecture experienced increased cancer mortality. We targeted subjects who were born from September 1950 to August 1960 and died in Okayama Prefecture between January 1969 and March 2008 due to malignant neoplasm (N = 3,141). We then compared cancer mortality (total, liver, pancreatic, lung, bladder/kidney, and hematopoietic cancers) between cohorts born before the milk poisoning (exposed group) and cohorts born after the poisoning (nonexposed group). We estimated mortality ratios and 95% confidence intervals. Total and liver cancers were elevated in the cohort up to 1 year of age at time of the poisoning. In addition, pancreatic and hematopoietic cancers were elevated in the cohorts up to 5 years of age, and mortality ratios were approximately twice those of the nonexposed group. Increased risk of lung and bladder/kidney cancers was not apparent. Although dilution is present in these cohort-based data, our study highlights the notion that developmental arsenic exposure may lead to a different pattern of cancer, including increases in pancreatic and hematopoietic cancer, as compared with adult or lifetime exposures to inorganic arsenic.

  3. Environmental exposure to arsenic and chromium in an industrial area.

    PubMed

    Vimercati, Luigi; Gatti, Maria F; Gagliardi, Tommaso; Cuccaro, Francesco; De Maria, Luigi; Caputi, Antonio; Quarato, Marco; Baldassarre, Antonio

    2017-04-01

    Arsenic and chromium are widespread environmental contaminants that affect global health due to their toxicity and carcinogenicity. To date, few studies have investigated exposure to arsenic and chromium in a population residing in a high-risk environmental area. The aim of this study is to evaluate the exposure to arsenic and chromium in the general population with no occupational exposure to these metals, resident in the industrial area of Taranto, Southern Italy, through biological monitoring techniques. We measured the levels of chromium, inorganic arsenic, and methylated metabolites, in the urine samples of 279 subjects residing in Taranto and neighboring areas. Qualified health staff administered a standardized structured questionnaire investigating lifestyle habits and controlling for confounding factors. The biological monitoring data showed high urinary concentrations of both the heavy metals investigated, particularly Cr. On this basis, it will be necessary to carry out an organized environmental monitoring program, taking into consideration all exposure routes so as to correlate the environmental concentrations of these metals with the biomonitoring results.

  4. 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...

  5. Arsenic exposure alters hepatic arsenic species composition and stress-mediated gene expression in the common killifish (Fundulus heteroclitus).

    PubMed

    Bears, Heather; Richards, Jeff G; Schulte, Patricia M

    2006-05-10

    In the present paper, we examine how arsenic species accumulate in fish liver and explore the hypothesis that sublethal arsenic concentrations in fish hepatic tissue interfere with stress-mediated gene expression. We exposed killifish (Fundulus heteroclitus) to 787 or 0 microg/L arsenic in tank water for 2 weeks. Arsenic exposure elevated total liver arsenic from 3.4 microg/g wet weight (control fish) to 9.6 microg/g wet weight, and resulted in a higher relative proportion of toxic (e.g. monomethylarsenous acid, dimethylarsenous acid, arsenic V) versus benign (arsenobetaine) arsenic species in this tissue. Following the exposure period, arsenic-treated and control fish were then subjected to a stress protocol: confinement and mechanical chasing for 15 min every 3 h. Liver tissue and blood were sampled from fish not exposed to the stressor at time 0, and at 8, 12, 24 and 40 h following the first stressor. Concentrations of the stress hormone cortisol increased significantly, and glucocorticoid receptor mRNA levels increased and then decreased in both groups, but patterns were nearly identical between arsenic pre-treated and arsenic untreated fish. Prior arsenic exposure prevented the stress-induced increases in stress-responsive LDH-B mRNA levels and enzyme activity observed in fish that had not been exposed to arsenic. However, in another stress-responsive gene, PEPCK, arsenic did not interfere with the stress-induced increase in gene expression, suggesting that the effects of arsenic on stress-mediated gene expression are complex and may involve regulatory pathways that differ between these two genes.

  6. Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

    PubMed

    Rahman, M M; Chowdhury, U K; Mukherjee, S C; Mondal, B K; Paul, K; Lodh, D; Biswas, B K; Chanda, C R; Basu, G K; Saha, K C; Roy, S; Das, R; Palit, S K; Quamruzzaman, Q; Chakraborti, D

    2001-01-01

    Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. ARSENIC IN DRINKING WATER: EPIDEMIOOOGIC STUDIES OF LOW EXPOSURE IN THE UNITED STATES

    EPA Science Inventory

    Because there is no animal model fully adequate to study the mechanisms of arsenic toxicity and carcinogenicity; human epidemiological studies incorporating sensitive biomarkers for assessing exposure, cancer, noncancer effects and susceptibility of arsenic are needed to evalua...

  12. ARSENIC IN DRINKING WATER: EPIDEMIOOOGIC STUDIES OF LOW EXPOSURE IN THE UNITED STATES

    EPA Science Inventory

    Because there is no animal model fully adequate to study the mechanisms of arsenic toxicity and carcinogenicity; human epidemiological studies incorporating sensitive biomarkers for assessing exposure, cancer, noncancer effects and susceptibility of arsenic are needed to evalua...

  13. 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 ...

  14. 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 ...

  15. Treating chronic arsenic toxicity with high selenium lentil diets.

    PubMed

    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 (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. 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 14weeks 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.

  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

    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.

  17. 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

  18. 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

  19. Association between Arsenic Exposure and Diabetes Mellitus in Cambodia

    PubMed Central

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

    2014-01-01

    Whereas studies in Taiwan found associations between arsenic exposure from drinking water and diabetes mellitus (DM), studies in other countries yielded inconsistent results, and diet might be a confounder. We conducted a study in Cambodia, where people have non-Western style diet, to evaluate the association. We measured well water and urine samples and examined skin signs of arsenicosis to assess arsenic exposure and used questionnaires to collect data on potential risk factors. We performed a fingertip blood glucose test followed by measurement of hemoglobin A1c to assess DM. The 43-male and 99-female participants had an average age of 40.4 years. We found that participants with skin signs of arsenicosis had a higher level of arsenic in the drinking water (1101.1 versus 972.2 μg/L, P = 0.02). Drinking water with arsenic levels above the median (907.25 μg/L) was associated with a nearly twofold increase in the risk of DM (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 0.5–5.8), so was having skin sings of arsenicosis (OR = 1.7, 95% CI: 0.5–5.6). The ORs did not reach statistical significance most likely because of the small case number. Therefore, further studies with larger study populations are needed to confirm our findings. PMID:24949461

  20. Factors associated with arsenicosis and arsenic exposure status in Nepal: implications from community based study.

    PubMed

    Maden, Narendra; Singh, Anjana; Smith, Linda S; Maharjan, Makhan; Shrestha, Shreekrishna

    2011-02-01

    A significant public health problem due to exposure to arsenic via groundwater in communities of lowland Terai region of Nepal has issued forth need to assess the exposure status and factors associated with arsenicosis. We observed arsenical dermal manifestations and collected and assessed total arsenic content in tubewell water, urine, and hair samples of study subjects at arsenic affected communities in Nawalparasi district of Nepal. The explanatory variables associated with arsenicosis were elevated arsenic in tubewell, male gender and increased age (P < 0.05). 67% (73/109) and 66% (77/117) of subjects exceeded the normal urinary and hair arsenic levels respectively. Among them 52% (57/109) and 47% (55/117) exceeded normal urinary and hair arsenic levels having no arsenical dermal manifestations. Males and symptomatic cases had significantly higher hair arsenic levels (P < 0.05). We also observed significant positive correlation of both urine and hair arsenic levels to tubewell arsenic levels (r = 0.27, 0.37, P < 0.01) and negative correlation of urine arsenic levels with the age of the subjects (r = -0.18, P = 0.06). We conclude that elucidating factors associated with arsenicosis could be of prime importance in intervention and preventive measures. In arsenic affected communities of Nepal exposure to arsenic is still a major problem despite mitigation efforts and the potential for sub-clinical effects in exposed population is high.

  1. Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals.

    PubMed

    Li, Changzhao; Srivastava, Ritesh K; Athar, Mohammad

    2016-08-01

    Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. On the basis of these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the best-known agent that was synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies that describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology-based antidotes against these agents are also described.

  2. Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

    PubMed Central

    Li, Changzhao; Srivastava, Ritesh K.; Athar, Mohammad

    2016-01-01

    Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. Based on these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the most known agent synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, their stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, their access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies which describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology–based antidotes against these agents are also described. PMID:27636894

  3. 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

  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. Inorganic arsenic and respiratory health, from early life exposure to sex-specific effects: a systematic review

    PubMed Central

    Sanchez, Tiffany R.; Perzanowski, Matthew

    2016-01-01

    This systematic review synthesizes the diverse body of epidemiologic research accrued on inorganic arsenic exposure and respiratory health effects. Twenty-nine articles were identified that examined the relationship between inorganic arsenic exposure and respiratory outcomes (i.e. lung function, symptoms, acute respiratory infections, chronic non-malignant lung diseases, and non-malignant lung disease mortality). There was strong evidence of a general association between arsenic and non-malignant respiratory illness, including consistent evidence on lung function impairment, acute respiratory tract infections, respiratory symptoms, and non-malignant lung disease mortality. Overall, early life exposure (i.e. in utero and/or early-childhood) had a marked effect throughout the lifespan. This review also identified some research gaps, including limited evidence at lower levels of exposure (water arsenic <100 μg/L), mixed evidence of sex differences, and some uncertainty on arsenic and any single non-malignant respiratory disease or pathological process. Common limitations, including potential publication bias; non-comparability of outcome measures across included articles; incomplete exposure histories; and limited confounder control attenuated the cumulative strength of the evidence as it relates to US populations. This systematic review provides a comprehensive assessment of the epidemiologic evidence and should be used to guide future research on arsenic’s detrimental effects on respiratory health. PMID:26891939

  6. Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure

    PubMed Central

    Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

    2015-01-01

    Objectives Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. Methods A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940–2002), a revised cadmium (Cd) exposure matrix and improved work history information. Results Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure–response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m3 Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20–25 years. Conclusions These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m3 Cd. PMID:22271639

  7. 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...

  8. 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...

  9. Arsenic exposure, dermatological lesions, hypertension, and chromosomal abnormalities among people in a rural community of northwest Iran.

    PubMed

    Dastgiri, Saeed; Mosaferi, Mohammad; Fizi, Mohammad A H; Olfati, Nahid; Zolali, Shahin; Pouladi, Nasser; Azarfam, Parvin

    2010-02-01

    Chronic exposure to arsenic compounds is one of the major public-health problems in many developing and some developed countries. The aim of this study was to investigate the effects of chronic exposure to arsenic on dermatological lesions, hypertension, and chromosomal abnormalities among people in a community in the northwest of Iran. The occurrence of dermatological lesions, hypertension, and chromosomal abnormalities was investigated in two groups: Ghopuz village, including 101 subjects with chronic exposure to arsenic in drinking-water and Mayan village, including 107 subjects with no exposure. Daily/yearly absorbed amounts of arsenic were calculated for all subjects. Cumulative arsenic index for each individual was then estimated on the basis of age, water consumption, and location of residence. Arsenic concentration in drinking-water sources in Ghopuz and Mayan villages was 1031 +/- 1103 microg/L and non-detectable respectively. The mean systolic blood pressure in the exposure group [n=137, 95% confidence interval (CI 132-142)] was significantly higher than that in the control group (n=107, 95% CI 99.9-114). A similar significant difference was observed for diastolic blood pressure (exposed: n=82, 95% CI 79-85 vs non-exposed: n=71, 95% CI 66-75). The incidence of hyperkeratosis was 34 times higher among the exposure group compared to the control subjects [odds ratio (OR)=34, p<0.001)]. A significant difference was also observed in the occurrence of skin-pigmentation between the two groups (OR=2.4, p<0.007). Location and severity of the pigmentations were statistically different between the two groups. Twenty-five percent of the subjects in the exposure group showed chromosomal abnormalities (p=0.05). Arsenic exposure was a serious health problem in the region. More studies are needed to investigate the long-term effects and dose-response relationship of arsenic in the region and similar areas. Wide-ranging monitoring programmes for drinking-water sources

  10. Arsenic Exposure, Dermatological Lesions, Hypertension, and Chromosomal Abnormalities among People in a Rural Community of Northwest Iran

    PubMed Central

    Dastgiri, Saeed; Fizi, Mohammad A.H.; Olfati, Nahid; Zolali, Shahin; Pouladi, Nasser; Azarfam, Parvin

    2010-01-01

    Chronic exposure to arsenic compounds is one of the major public-health problems in many developing and some developed countries. The aim of this study was to investigate the effects of chronic exposure to arsenic on dermatological lesions, hypertension, and chromosomal abnormalities among people in a community in the northwest of Iran. The occurrence of dermatological lesions, hypertension, and chromosomal abnormalities was investigated in two groups: Ghopuz village, including 101 subjects with chronic exposure to arsenic in drinking-water and Mayan village, including 107 subjects with no exposure. Daily/yearly absorbed amounts of arsenic were calculated for all subjects. Cumulative arsenic index for each individual was then estimated on the basis of age, water consumption, and location of residence. Arsenic concentration in drinking-water sources in Ghopuz and Mayan villages was 1031±1103 μg/L and non-detectable respectively. The mean systolic blood pressure in the exposure group [n=137, 95% confidence interval (CI 132–142)] was significantly higher than that in the control group (n=107, 95% CI 99.9–114). A similar significant difference was observed for diastolic blood pressure (exposed: n=82, 95% CI 79–85 vs non-exposed: n=71, 95% CI 66–75). The incidence of hyperkeratosis was 34 times higher among the exposure group compared to the control subjects [odds ratio (OR)=34, p<0.001)]. A significant difference was also observed in the occurrence of skin-pigmentation between the two groups (OR=2.4, p<0.007). Location and severity of the pigmentations were statistically different between the two groups. Twenty-five percent of the subjects in the exposure group showed chromosomal abnormalities (p=0.05). Arsenic exposure was a serious health problem in the region. More studies are needed to investigate the long-term effects and dose-response relationship of arsenic in the region and similar areas. Wide-ranging monitoring programmes for drinking-water sources

  11. Evidence of antiapoptotic properties of Pleurotus florida lectin against chronic arsenic toxicity in renal cells of rats.

    PubMed

    Rana, Tanmoy; Bera, Asit Kumar; Bhattacharya, Debasis; Das, Subhashree; Pan, Diganta; Das, Subrata Kumar

    2012-01-01

    Chronic arsenic exposure results in toxicity in humans and causes many toxicologic manifestations. Apoptosis was measured by cell adhesion, morphologic alterations, cell proliferation, terminal deoxyuridine triphosphate nick-end labeling (TUNEL), and caspase-3/CPP32 fluorometric protease assay. Results of the present study suggested that arsenic administration in rats caused apoptosis by elevating morphologic alterations, TUNEL-positive nuclei, caspase-3 activity, and DNA damage and by reducing cell adhesion and cell proliferation in a time-dependent manner. The apoptosis in renal cells of arsenic-exposed rats reverted to normal values after coadministration of mushroom lectin. This study provided significant evidence that Pleurotus florida lectin has an antiapoptotic property by protecting from arsenic-induced toxicity. The beneficial effect of Pleurotus florida lectin was proportional to its duration of exposure. This finding might be of therapeutic benefit in people suffering from chronic exposure to arsenic from natural sources, a global problem that is especially relevant to millions of people on the Indian subcontinent.

  12. Human exposure to arsenic through foodstuffs cultivated using arsenic contaminated groundwater in areas of West Bengal, India.

    PubMed

    Samal, Alok C; Kar, Sandeep; Bhattacharya, Piyal; Santra, Subhas C

    2011-01-01

    The widespread incidence of chronic arsenicosis in the Bengal Delta has led to intensive research on arsenic (As) enrichment in groundwater as well as accumulation in foodstuffs, as there are potential health risks associated with exposure to As from both sources. This study deals with human As exposure through the drinking of groundwater, consumption of locally grown foodstuffs (e.g., crops and vegetables) and cooked food in Nadia district, West Bengal. Groundwater and foodstuffs were collected and analyzed with FI-HG-AAS to estimate the total As content. Urine samples collected from human subjects were analyzed to assess the As exposure. Two major crops, boro and aman rice, showed a considerable amount of As, with mean values of 194 and 156 μg kg(-1), respectively. Significant levels of As were also found in other common crops and vegetables cultivated in this area (for example, the mean As in Arum and radish was 780 and 674 μg kg(-1), respectively). Total intake of As from foodstuffs by adults (560 μg day(-1)) and children (393 μg day(-1)) in the area was found to be at alarming levels. Arsenic exposure was demonstrated by the presence of As in urine (ranging between 154 and 276 μg L(-1)), with overall As retention of 50-60 %. The results of this study further indicate the potential risk of As exposure to local inhabitants through the food chain which is associated with continuous consumption of As-contaminated foodstuffs. Therefore, more action needs to be taken to control the contamination pathways (such as the water-soil-crop system) to protect humans from continuous ingestion of As through foodstuffs.

  13. Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect.

    PubMed

    Andrade, V M; Mateus, M L; Batoréu, M C; Aschner, M; Marreilha dos Santos, A P

    2015-07-01

    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 three 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 may represent an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters, and effects on the hematopoietic system, we address putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture.

  14. 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

  15. 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

  16. Arsenic exposure and hepatitis E virus infection during pregnancy

    PubMed Central

    Heaney, Christopher D.; Kmush, Brittany; Navas-Acien, Ana; Francesconi, Kevin; Gössler, Walter; Schulze, Kerry; Fairweather, DeLisa; Mehra, Sucheta; Nelson, Kenrad E.; Klein, Sabra L.; Li, Wei; Ali, Hasmot; Shaikh, Saijuddin; Merrill, Rebecca D.; Wu, Lee; West, Keith P.; Christian, Parul; Labrique, Alain B.

    2015-01-01

    Background Arsenic has immunomodulatory properties and may have the potential to alter susceptibility to infection in humans. Objectives We aimed to assess the relation of arsenic exposure during pregnancy with immune function and hepatitis E virus (HEV) infection, defined as seroconversion during pregnancy and postpartum. Methods We assessed IgG seroconversion to HEV between 1st and 3rd trimester (TM) and 3 months postpartum (PP) among 1100 pregnancies in a multiple micronutrient supplementation trial in rural Bangladesh. Forty women seroconverted to HEV and were matched with 40 non-seroconverting women (controls) by age, parity and intervention. We assessed urinary inorganic arsenic plus methylated species (∑As) (µg/L) at 1st and 3rd TM and plasma cytokines (pg/mL) at 1st and 3rd TM and 3 months PP. Results HEV seroconverters’ urinary ∑As was elevated throughout pregnancy. Non-seroconverters’ urinary ∑As was similar to HEV seroconverters at 1st TM but declined at 3rd TM. The adjusted odds ratio (95% confidence interval) of HEV seroconversion was 2.17 (1.07, 4.39) per interquartile range (IQR) increase in average-pregnancy urinary ∑As. Increased urinary ∑As was associated with increased concentrations of IL-2 during the 1st and 3rd TM and 3 months PP among HEV seroconverters but not non-seroconverters. Conclusions The relation of urinary arsenic during pregnancy with incident HEV seroconversion and with IL-2 levels among HEV-seroconverting pregnant women suggests arsenic exposure during pregnancy may enhance susceptibility to HEV infection. PMID:26186135

  17. Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats.

    PubMed

    Zhu, Yu-Peng; Xi, Shu-Hua; Li, Ming-Yan; Ding, Ting-Ting; Liu, Nan; Cao, Fu-Yuan; Zeng, Yang; Liu, Xiao-Jing; Tong, Jun-Wang; Jiang, Shou-Fang

    2017-03-01

    Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data

  18. Lung function decrement with arsenic exposure to drinking groundwater along River Indus: a comparative cross-sectional study.

    PubMed

    Nafees, Asaad Ahmed; Kazi, Ambreen; Fatmi, Zafar; Irfan, Muhammad; Ali, Arif; Kayama, Fujio

    2011-04-01

    This study was designed to determine the association between chronic arsenic exposure through drinking groundwater and decrement in lung function, particularly among individuals who do not have signs of arsenic lesions, among an adult population. This was a comparative cross-sectional study conducted during the months of January to March 2009. One hundred participants ≥15 years of age in each group, i.e. exposed (≥100 μg/l) and unexposed (≤10 μg/l) to arsenic, determined by testing drinking water samples (using portable kits), were compared for effects on lung function using spirometry. A structured and validated questionnaire was administered. Examination for arsenic skin lesions was also done. There was a decline in the mean adjusted FEV1 of 154.3 ml (95% CI: -324.7, 16.0; p = 0.076), in mean adjusted FVC of 221.9 ml (95% CI: -419.5, -24.3; p = 0.028), and in FEV1/FVC ratio of 2.0 (95% CI: -25.3, 29.4; p = 0.884) among participants who were exposed to arsenic compared to those unexposed. A separate model comprising a total of 160 participants, 60 exposed to arsenic concentrations ≥250 μg/l and 100 unexposed at arsenic concentrations of ≤10 μg/l, showed a decrement in mean adjusted FEV1 of 226.4 ml (95% CI: -430.4, -22.4; p = 0.030), in mean adjusted FVC of 354.8 ml (95% CI: -583.6, -126.0; p = 0.003), and in FEV1/FVC ratio of 9.9 (95% CI: -21.8, 41.6; p = 0.539) among participants who were exposed to arsenic in drinking groundwater. This study demonstrated that decrement in lung function is associated with chronic exposure to arsenic in drinking groundwater, occurring independently, and even before any manifestation, of arsenic skin lesions or respiratory symptoms. The study also demonstrated a dose-response effect of arsenic exposure and lung function decrement.

  19. EXTRACTION TECHNIQUES FOR THE REMOVAL OF ARSENICALS FROM SEAFOOD EXPOSURE MATRICES WITH ICP-MS DETECTION

    EPA Science Inventory

    Most of the existing arsenic dietary databases were developed from the analysis of total arsenic in water and dietary samples. These databases have been used to estimate arsenic exposure and in turn human health risk. However, these dietary databases are becoming obsolete as the ...

  20. EXTRACTION TECHNIQUES FOR THE REMOVAL OF ARSENICALS FROM SEAFOOD EXPOSURE MATRICES WITH ICP-MS DETECTION

    EPA Science Inventory

    Most of the existing arsenic dietary databases were developed from the analysis of total arsenic in water and dietary samples. These databases have been used to estimate arsenic exposure and in turn human health risk. However, these dietary databases are becoming obsolete as the ...

  1. 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

  2. Human exposure to organic arsenic species from seafood.

    PubMed

    Taylor, Vivien; Goodale, Britton; Raab, Andrea; Schwerdtle, Tanja; Reimer, Ken; Conklin, Sean; Karagas, Margaret R; Francesconi, Kevin A

    2017-02-15

    Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be non-toxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.

  3. Arsenic exposure is associated with DNA hypermethylation of the tumor suppressor gene p16.

    PubMed

    Lu, Guangming; Xu, Huiwen; Chang, De; Wu, Zhenglai; Yao, Xiaoyuan; Zhang, Shiying; Li, Zhenlong; Bai, Jieben; Cai, Qing; Zhang, Wen

    2014-01-01

    Occupational and environmental exposure to inorganic arsenic leads to development of cancer and represents a significant health hazard in more than 70 countries. The underlying mechanism for arsenic-induced carcinogenesis remains unclear. Laboratory studies suggest that arsenic is a poor mutagen but may cause epigenetic silencing of key tumor suppressor genes such as p16 through DNA hypermethylation. However, the evidence for an association between human arsenic exposure and abnormal DNA methylation of tumor suppressor genes is lacking. Paired case-control studies were conducted involving 40 individuals with high arsenic exposure and arsenicosis, 40 individuals with similarly high exposure to arsenic but without arsenicosis, and 40 individuals with normal exposure to arsenic. DNA methylation status of p16 was determined using methylation-specific PCR. Conditional logistic regression analysis showed that DNA hypermethylation of p16 gene was significantly associated with high arsenic exposure (Odds Ratio = 10.0, P = 0.0019) independently of the development of arsenicosis (Odds Ratio = 2.0, P = 0.1343). High exposure of arsenic in human is positively linked to DNA hypermethylation of p16 gene, suggesting that epigenetic silencing of key tumor suppressor may be an important mechanism by which arsenic promotes cancer initiation.

  4. Increased Mortality Associated with Well-Water Arsenic Exposure in Inner Mongolia, China

    PubMed Central

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

    2009-01-01

    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

  5. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  6. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  7. 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. Copyright © 2015. Published by Elsevier B.V.

  8. [Study of relationship between arsenic methylation and skin lesion in a population with long-term high arsenic exposure].

    PubMed

    Su, Liqin; Cheng, Yibin; Lin, Shaobin; Wu, Chuanye

    2007-05-01

    To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion. 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method. Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively. The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

  9. Arsenic Exposure from Drinking Water and QT-Interval Prolongation: Results from the Health Effects of Arsenic Longitudinal Study

    PubMed Central

    Wu, Fen; Parvez, Faruque; Ahmed, Alauddin; Eunus, Mahbub; McClintock, Tyler R.; Patwary, Tazul Islam; Islam, Tariqul; Ghosal, Anajan Kumar; Islam, Shahidul; Hasan, Rabiul; Levy, Diane; Sarwar, Golam; Slavkovich, Vesna; van Geen, Alexander; Graziano, Joseph H.

    2013-01-01

    Background: Arsenic exposure from drinking water has been associated with heart disease; however, underlying mechanisms are uncertain. Objective: We evaluated the association between a history of arsenic exposure from drinking water and the prolongation of heart rate–corrected QT (QTc), PR, and QRS intervals. Method: We conducted a study of 1,715 participants enrolled at baseline from the Health Effects of Arsenic Longitudinal Study. We assessed the relationship of arsenic exposure in well water and urine samples at baseline with parameters of electrocardiogram (ECG) performed during 2005–2010, 5.9 years on average since baseline. Results: The adjusted odds ratio (OR) for QTc prolongation, defined as a QTc ≥ 450 msec in men and ≥ 460 msec in women, was 1.17 (95% CI: 1.01, 1.35) for a 1-SD increase in well-water arsenic (108.7 µg/L). The positive association appeared to be limited to women, with adjusted ORs of 1.24 (95% CI: 1.05, 1.47) and 1.24 (95% CI: 1.01, 1.53) for a 1-SD increase in baseline well-water and urinary arsenic, respectively, compared with 0.99 (95% CI: 0.73, 1.33) and 0.86 (95% CI: 0.49, 1.51) in men. There were no apparent associations of baseline well-water arsenic or urinary arsenic with PR or QRS prolongation in women or men. Conclusions: Long-term arsenic exposure from drinking water (average 95 µg/L; range, 0.1–790 µg/L) was associated with subsequent QT-interval prolongation in women. Future longitudinal studies with repeated ECG measurements would be valuable in assessing the influence of changes in exposure. PMID:23384555

  10. Arsenic exposure to dairy cows in Bangladesh.

    PubMed

    Ghosh, Amalendu; Majumder, Shankar; Awal, Md Abdul; Rao, D Ramkishan

    2013-01-01

    Food-chain contamination by arsenic (As) is a newly uncovered disaster. Effects of As-contaminated drinking water and paddy straw on the excretion of As through milk, urine, and dung of dairy cows (n = 240) were studied in As-prone areas of Bangladesh. Mean (±SEM) total As (inorganic plus organic) concentration in drinking water, paddy straw [dry weight dw)], cow's urine (specific gravity adjusted to 1.035), dung (dw), and milk (wet weight) were 89.6 ± 6.5 μg/l, 1,114.4 ± 57.3 μg/kg, 123.6 ± 7.6 μg/l, 1,693.0 ± 65.1 μg/kg, and 26.2 ± 2.8 μg/l, respectively. Significantly (p < 0.01) greater As was in Boro straw (1,386.9 ± 71.8 μg/kg) than Aus (702.4 ± 67.1 μg/kg) and Aman (431.7 ± 28.8 μg/kg) straw and in straw irrigated with shallow (1,697.3 ± 81.9 μg/kg) than deep well water (583.6 ± 62.7 μg/kg) and surface water (511.8 ± 30.0 μg/kg). Significant (p < 0.01) positive correlations were found between As contents of cow's urine and drinking water (r = 0.92) as well as cow dung and straw (r = 0.82). Concentrations of As in cow urine, dung, and milk were increased with the relative increment of As in drinking water and/or straw. These results provide evidence that dairy cows excrete ingested As mainly through urine and dung; thus, As biotransformation through milk remains low. This low concentration of As in milk may be of concern when humans are exposed to multiple sources of As simultaneously. Moreover, As in cow dung could be an environmental issue in Bangladesh.

  11. Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico.

    PubMed

    Meza, Maria Mercedes; Kopplin, Michael J; Burgess, Jefferey L; Gandolfi, A Jay

    2004-10-01

    The objective of this study was to determine arsenic exposure via drinking water and to characterize urinary arsenic excretion among adults in the Yaqui Valley, Sonora, Mexico. A cross-sectional study was conducted from July 2001 to May 2002. Study subjects were from the Yaqui Valley, Sonora, Mexico, residents of four towns with different arsenic concentrations in their drinking water. Arsenic exposure was estimated through water intake over 24 h. Arsenic excretion was assessed in the first morning void urine. Total arsenic concentrations and their species arsenate (As V), arsenite (As III), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) were determined by HPLC/ICP-MS. The town of Esperanza with the highest arsenic concentration in water had the highest daily mean intake of arsenic through drinking water, the mean value was 65.5 microg/day. Positive correlation between total arsenic intake by drinking water/day and the total arsenic concentration in urine (r = 0.50, P < 0.001) was found. Arsenic excreted in urine ranged from 18.9 to 93.8 microg/L. The people from Esperanza had the highest geometric mean value of arsenic in urine, 65.1 microg/L, and it was statistically significantly different from those of the other towns (P < 0.005). DMA was the major arsenic species in urine (47.7-67.1%), followed by inorganic arsenic (16.4-25.4%), and MMA (7.5-15%). In comparison with other reports the DMA and MMA distribution was low, 47.7-55.6% and 7.5-9.7%, respectively, in the urine from the Yaqui Valley population (except the town of Cocorit). The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations.

  12. 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

  13. 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

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

    PubMed

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

    2015-01-01

    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). 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. 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. 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. Results provide new evidence for risk assessment of low-medium concentrations of arsenic and contribute to the ongoing debate about the threshold-dose of effect, suggesting that

  15. Chronic toxicity of arsenic in goats: clinicobiochemical changes, pathomorphology and tissue residues.

    PubMed

    Biswas; Sarkar; Bhowmik; Samanta; Biswas

    2000-11-01

    Chronic inorganic arsenic toxicity was induced in goats by oral administration of one-fifth of the acute lethal dose 50 (ALD(50)) of sodium arsenite (25mgkg(-1) body weight) packed in gelatin capsules and given daily for 12 weeks. Clinical signs of toxicity developed from 3 week post-exposure, consisting of gastrointestinal disturbances and renal insufficiency with 100% mortality in all animals. There were significant (p<0.01) decreases in total serum protein and the albumin: globulin ratio, and increases in blood glucose and various enzymatic activities of treated animals. Toxicity also induced severe pathomorphological changes, indicative of haemorrhagic and degenerative and/or necrotic lesions in most organs. In addition, proliferative pneumonia in lungs, hyperplastic goitre in thyroid and chronic proliferative lesions in skin were observed. Liver contained the largest residues of arsenic, followed by intestine, kidneys, thyroid, abomasum, spleen, skin, lungs and lowest in brain. The intensity of pathomorphological changes was proportional to the accumulated amount of arsenic in tissues/organs.

  16. Arsenic exposure and adverse health effects: a review of recent findings from arsenic and health studies in Matlab, Bangladesh.

    PubMed

    Yunus, Mohammad; Sohel, Nazmul; Hore, Samar Kumar; Rahman, Mahfuzar

    2011-09-01

    The recent discovery of large-scale arsenic (As) contamination of groundwater has raised much concern in Bangladesh. Reliable estimates of the magnitude of As exposure and related health problems have not been comprehensively investigated in Bangladesh. A large population-based study on As and health consequences in Matlab (AsMat) was done in Matlab field site where International Centre for Diarrhoeal Disease Research, Bangladesh has maintained a health and demographic surveillance system registering prospectively all vital events. Taking advantage of the health and demographic surveillance system and collecting data on detailed individual level As exposure using water and urine samples, AsMat investigated the morbidity and mortality associated with As exposure. Reviews of findings to date suggest the adverse effects of As exposure on the risk of skin lesions, high blood pressure, diabetes mellitus, chronic disease, and all-cause infant and adult disease mortality. Future studies of clinical endpoints will enhance our knowledge gaps and will give directions for disease prevention and mitigations. Copyright © 2011. Published by Elsevier B.V.

  17. Site-specific data confirm arsenic exposure predicted by the U.S. Environmental Protection Agency.

    PubMed Central

    Walker, S; Griffin, S

    1998-01-01

    The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic absorption rates were used, measured and predicted urinary arsenic concentrations were in reasonable agreement. The central tendency exposure assessment model successfully described the measured urinary arsenic concentration for the majority of children at the site. The reasonable maximum exposure assessment model successfully identified the uppermost exposed population. While the agreement between measured and predicted urinary arsenic is good, it is not exact. The variables that were identified which influenced agreement included soil and dust sample collection methodology, daily urinary volume, soil ingestion rate, and the ability to define the exposure unit. The concentration of arsenic in food affected agreement between measured and predicted total urinary arsenic, but was not considered when comparing measured and predicted speciated urinary arsenic. Speciated urinary arsenic is the recommended biomarker for recent inorganic arsenic exposure. By using site-specific data in the exposure assessment model, predicted risks from exposure to arsenic were less than predicted risks would have been if the EPA's default values had been used in the exposure assessment model. This difference resulted in reduced magnitude and cost of remediation while still protecting human health. Images Figure 1 PMID:9452415

  18. RKIP expression of liver and kidney after arsenic exposure.

    PubMed

    Tsao, Der-An; Tseng, Wei-Chang; Chang, Huoy-Rou

    2017-03-01

    Arsenic is associated with cancers of kidney and liver. Raf kinase inhibitor protein (RKIP) has been identified as a member of a novel class of molecules that suppress the metastatic spread of tumors. In order to investigate the effect of arsenic to RKIP of liver and kidney, the expression of RKIP of liver and kidney with As (III) was explored in this study. Thirty male mice were chronically fed with 42.5 ppm, 85 ppm NaAsO2 and water for 180 days. The kidney and liver accumulation levels of As (III) in mice were determined by electro-thermal atomic absorption spectrometry. The method of RT-PCR, Western blotting analysis and immunohistochemistry were used to determine gene expression and protein expression of RKIP. The results showed that arsenic level was significantly increased in kidney and liver of As (III)-exposed mice as compared with control group. The gene expression and protein expression of RKIP was significantly decreased in kidney and liver of As (III)-exposed mice in comparison with these of control mice. These data suggested that RKIP decrease of liver and kidney with As (III) may be dangerous index in formation of cancer. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1079-1082, 2017. © 2016 Wiley Periodicals, Inc.

  19. Arsenic: bioaccessibility from seaweed and rice, dietary exposure calculations and risk assessment.

    PubMed

    Brandon, Esther F A; Janssen, Paul J C M; de Wit-Bos, Lianne

    2014-01-01

    Arsenic is a metalloid that occurs in food and the environment in different chemical forms. Inorganic arsenic is classified as a class I carcinogen. The inorganic arsenic intake from food and drinking water varies depending on the geographic arsenic background. Non-dietary exposure to arsenic is likely to be of minor importance for the general population within the European Union. In Europe, arsenic in drinking water is on average low, but food products (e.g. rice and seaweed) are imported from all over the world including from regions with naturally high arsenic levels. Therefore, specific populations living in Europe could also have a high exposure to inorganic arsenic due to their consumption pattern. Current risk assessment is based on exposure via drinking water. For a good estimation of the risks of arsenic in food, it is important to investigate if the bioavailability of inorganic arsenic from food is different from drinking water. The present study further explores the issue of European dietary exposure to inorganic arsenic via rice and seaweed and its associated health risks. The bioavailability of inorganic arsenic was measured in in vitro digestion experiments. The data indicate that the bioavailability of inorganic arsenic is similar for rice and seaweed compared with drinking water. The calculated dietary intake for specific European Union populations varied between 0.44 and 4.51 µg kg⁻¹ bw day⁻¹. The margins of exposure between the inorganic intake levels and the BMDL0.5 values as derived by JECFA are low. Decreasing the intake of inorganic arsenic via Hijiki seaweed could be achieved by setting legal limits similar to those set for rice by the Codex Alimentarius Commission in July 2014.

  20. Use of human metabolic studies and urinary arsenic speciation is assessing arsenic exposure

    SciTech Connect

    Johnson, L.R.; Farmer, J.G. Univ. of Edinburgh )

    1991-01-01

    The use of hair and nail analyses to assess human exposure to the trace metalloid arsenic (As) is hindered by the possibility of external contamination. Even though urine represents the major excretory route, its use as an indicator of exposure is limited when no distinction is made between the nontoxic organoarsenical (arsenobetaine) excreted following the consumption of seafood and the toxic inorganic forms of As and related metabolites. The development of analytical techniques capable of separating the different chemical species of As in urine have shown that the ingestion of inorganic As (AsV or AsIII) by animals and man triggers an in vivo reduction/methylation process resulting in excretion of the less toxic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA). This paper establishes the uptake, bio-transformation and elimination patterns reflected in urinary As following carefully controlled experimental exposure.

  1. 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 ...

  2. Low dose chronic treatment of human keratinocytes with inorganic arsenic causes hyperproliferation and altered protein phosphorylation

    SciTech Connect

    Steinberg, M.L.; Su, L.; Snow, E.T. |

    1997-10-01

    Chronic exposure to arsenate [As(V)] or arsenite [As(III)] causes hyperproliferation of normal and SV40-transformed human epidermal keratinocytes. Line 327 SV40-infected human keratinocytes were grown in the presence of either As(III) or As(V) (0.01 to 10 {mu}M) in complete medium for seven days prior to harvesting and counting. Both As(III) and As(V) were cytotoxic at micromolar concentrations, however submicromolar arsenic caused a significant increase in cell growth. Cell numbers in cultures exposed to As(V) were increased more than 186% relative to controls, and an even larger stimulation in cell growth was observed after treatment with 50 nM As(III). Normal non-SV40 T-antigen. Preliminary cell cycle analysis using unselected, log-phase cultures of arsenic-treated keratinocytes shows an increased proportion of cells in S- and G2/M-phase. Isoelectric focusing of phosphotyrosine-containing proteins from cells labeled with {sup 32}P-inorganic phosphate showed that the hyperproliferation of keratinocytes grown in low concentrations of arsenic is accompanied by altered tyrosine-specific protein phosphorylation. A number of phosphorylated proteins were observed in As-treated cells that were not observed in the controls; and minor bands at IEPs of 3.0, 4.2, 7.2, 7.5 and 8.2. These results, together with the lack of direct enzyme inhibition by arsenic shown by Su et al., this volume, suggest that arsenic-induced skin lesions and carcinogenesis may be the result of altered cell cycle control rather than DNA damage or reduced DNA repair.

  3. ARSENIC EXPOSURE INDUCES THE WARBURG EFFECT IN CULTURED HUMAN CELLS

    PubMed Central

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

    2013-01-01

    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-deoxyglucose. 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 1α. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. PMID:23648393

  4. 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

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

    PubMed

    Sun, Bao-Fei; Wang, Qing-Qing; 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.

  6. Relation of dietary inorganic arsenic exposure and urinary inorganic arsenic metabolites excretion in Japanese subjects.

    PubMed

    Oguri, Tomoko; Yoshinaga, Jun; Suzuki, Yayoi; Tao, Hiroaki; Nakazato, Tetsuya

    2017-06-03

    Inorganic arsenic (InAs) is a ubiquitous metalloid that has been shown to exert multiple adverse health outcomes. Urinary InAs and its metabolite concentration has been used as a biomarker of arsenic (As) exposure in some epidemiological studies, however, quantitative relationship between daily InAs exposure and urinary InAs metabolites concentration has not been well characterized. We collected a set of 24-h duplicated diet and spot urine sample of the next morning of diet sampling from 20 male and 19 female subjects in Japan from August 2011 to October 2012. Concentrations of As species in duplicated diet and urine samples were determined by using liquid chromatography-ICP mass spectrometry with a hydride generation system. Sum of the concentrations of urinary InAs and methylarsonic acid (MMA) was used as a measure of InAs exposure. Daily dietary InAs exposure was estimated to be 0.087 µg kg(-1) day(-1) (Geometric mean, GM), and GM of urinary InAs+MMA concentrations was 3.5 ng mL(-1). Analysis of covariance did not find gender-difference in regression coefficients as significant (P > 0.05). Regression equation Log 10 [urinary InAs+MMA concentration] = 0.570× Log 10 [dietary InAs exposure level per body weight] + 1.15 was obtained for whole data set. This equation would be valuable in converting urinary InAs concentration to daily InAs exposure, which will be important information in risk assessment.

  7. 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

  8. Multi-trace elements level in drinking water and the prevalence of multi-chronic arsenical poisoning in residents in the west area of Iran.

    PubMed

    Barati, A H; Maleki, A; Alasvand, M

    2010-03-01

    First, we determined the levels of 8 trace elements (As, Se, Hg, Cd, Ag, Mn, Cr and Pb) in 530 village drinking water sources by graphite furnace or flame atomic absorption spectroscopy method, in Kurdistan Province in the west of Iran. The results showed that the level of As, Cd and Se in 28 village drinking water sources exceeded WHO or National Standard limits. The levels of concentration of arsenic in drinking water ranged from 42 to 1500microg/L. Then in a cross-sectional survey, 587 people from 211 households were chosen for clinical examinations of multi-chronic arsenical poisoning including pigment disorders, keratosis of palms and soles, Mee's line in fingers and nails and the gangrene as a systemic manifestation. Of 587 participants, 180 (30.7%) participants were affected by representing the type of chronic arsenical poisoning. The prevalence of Mee's line, keratosis, and pigment disorders were 86.1%, 77.2% and 67.8% respectively. Therefore, the prevalence of Mee's line between inhabitants was higher than the other disorders. The results show a strong linear relationship between arsenic exposure and occurrence of multi-chronic arsenical poisoning (R(2)=0.76). The association between age for more than 40 years and gender for more than 60 years with chronic arsenical poisoning is significant (p<0.05). Also, there is a relationship between subjects who were affected with disorders and duration of living in the village. Except for gangrene disorder, the odds ratio of prevalence of other disorders with arsenic exposure level in drinking water show a highly significant relationship between arsenic content and the risk of chronic disorders (p<0.01). These results confirm the need to further study trace elements in drinking waters, food products and other samples in this area and the relationship to other chronic diseases arising out of arsenicosis.

  9. Arsenic

    MedlinePlus

    ... lesions and skin cancer are the most characteristic effects. Drinking-water and food The greatest threat to public health from arsenic originates from contaminated groundwater. Inorganic arsenic ...

  10. 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.

  11. Low molecular weight thiols in arsenic hyperaccumulator Pteris vittata upon exposure to arsenic and other trace elements.

    PubMed

    Cai, Yong; Su, Jinhui; Ma, Lena Q

    2004-05-01

    Low molecular weight thiol-containing compounds have been reported to play an important role in metal detoxification and accumulation in some higher plants. The formation of these low molecular weight thiols in the recently discovered arsenic hyperaccumulator, Chinese Brake fern (Pteris vittata) upon exposure to arsenic and other trace metals was investigated. In addition to cysteine and glutathione, an unidentified thiol was observed in the plants exposed to arsenic, which was not found in the control. The concentration of the unidentified thiol showed a very strong and positive correlation with arsenic concentration in the leaflets. The unidentified thiol was low in rachises and undetectable in the roots for As-treated plants. Total and acid-soluble thiols were also measured and the results indicated that arsenic mainly stimulated the synthesis of acid-soluble thiol in Chinese Brake. The investigations of other trace elements (Cd, Cu, Cr, Zn, Pb, Hg, and Se) showed that these elements were not accumulated in Chinese Brake to high levels and the synthesis of the unidentified thiol in the plant was not observed. Our study suggests that the unidentified thiol was induced specifically by arsenic and the distribution patterns of the unidentified thiol and arsenic in the plant were consistent, indicating that the synthesis of this compound was related to As exposure.

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. Arsenic Exposure and Epigenetic Alterations: Recent Findings Based on the Illumina 450K DNA Methylation Array.

    PubMed

    Argos, Maria

    2015-06-01

    Arsenic is a major public health concern worldwide. While it is an established carcinogen and associated with a number of other adverse health outcomes, the molecular mechanisms underlying arsenic toxicity are not completely clarified. There is mounting evidence from human studies suggesting that arsenic exposure is associated with epigenetic alterations, including DNA methylation. In this review, we summarize several recent human studies that have evaluated arsenic exposure using the Illumina HumanMethylation 450K BeadChip, which interrogates more than 485,000 methylation sites across the genome. Many of these studies have observed novel regions of the genome associated with arsenic exposure. However, few studies have evaluated the biological and functional relevance of these DNA methylation changes, which are still needed. We emphasize the need for future studies to replicate the identified DNA methylation signals as well as assess whether these markers are associated with risk of arsenic-related diseases.

  19. Association of low to moderate levels of arsenic exposure with risk of type 2 diabetes in Bangladesh.

    PubMed

    Pan, Wen-Chi; Seow, Wei Jie; Kile, Molly L; Hoffman, Elaine B; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Lu, Quan; Christiani, David C

    2013-11-15

    Chronic exposure to high levels of arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM), but the association between lower levels of arsenic and T2DM is more controversial. Therefore, this study evaluated the association between low to moderate arsenic exposure and T2DM. In 2009-2011, we conducted a study of 957 Bangladeshi adults who participated in a case-control study of skin lesions in 2001-2003. The odds ratio of T2DM was evaluated in relationship to arsenic exposure measured in drinking water and in subjects' toenails (in 2001-2003) prior to the diagnosis of T2DM (in 2009-2011). Compared with those exposed to the lowest quartile of arsenic in water (≤ 1.7 µg/L), the adjusted odds ratio for T2DM was 1.92 (95% confidence interval (CI): 0.82, 4.35) for those in the second quartile, 3.07 (95% CI: 1.38, 6.85) for those in the third quartile, and 4.51 (95% CI: 2.01, 10.09) for those in the fourth quartile. The relative excess risk of T2DM was 4.78 for individuals who smoked and 8.93 for people who had a body mass index (weight (kg)/height (m)(2)) greater than 25. These findings suggest that exposure to modest levels of arsenic in drinking water was associated with increased risk of T2DM in Bangladesh. Being overweight or smoking was also associated with increased risk of T2DM.

  20. Association of Low to Moderate Levels of Arsenic Exposure With Risk of Type 2 Diabetes in Bangladesh

    PubMed Central

    Pan, Wen-Chi; Seow, Wei Jie; Kile, Molly L.; Hoffman, Elaine B.; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Lu, Quan; Christiani, David C.

    2013-01-01

    Chronic exposure to high levels of arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM), but the association between lower levels of arsenic and T2DM is more controversial. Therefore, this study evaluated the association between low to moderate arsenic exposure and T2DM. In 2009–2011, we conducted a study of 957 Bangladeshi adults who participated in a case-control study of skin lesions in 2001–2003. The odds ratio of T2DM was evaluated in relationship to arsenic exposure measured in drinking water and in subjects’ toenails (in 2001–2003) prior to the diagnosis of T2DM (in 2009–2011). Compared with those exposed to the lowest quartile of arsenic in water (≤1.7 µg/L), the adjusted odds ratio for T2DM was 1.92 (95% confidence interval (CI): 0.82, 4.35) for those in the second quartile, 3.07 (95% CI: 1.38, 6.85) for those in the third quartile, and 4.51 (95% CI: 2.01, 10.09) for those in the fourth quartile. The relative excess risk of T2DM was 4.78 for individuals who smoked and 8.93 for people who had a body mass index (weight (kg)/height (m)2) greater than 25. These findings suggest that exposure to modest levels of arsenic in drinking water was associated with increased risk of T2DM in Bangladesh. Being overweight or smoking was also associated with increased risk of T2DM. PMID:24049161

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

    PubMed

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

    2015-11-01

    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. We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. 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. 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. Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and glucose intolerance/insulin resistance in

  2. 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...

  3. 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...

  4. Estimated exposure to arsenic in breastfed and formula-fed infants in a United States cohort.

    PubMed

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

    2015-05-01

    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. We estimated the relative contributions of breast milk and formula to arsenic exposure during early infancy in a U.S. 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. Urinary arsenic concentrations were generally low (median, 0.17 μg/L; maximum, 2.9 μg/L) [corrected] 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. 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.

  5. Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors.

    PubMed

    Suzuki, Takehiro; Yamashita, Satoshi; Ushijima, Toshikazu; Takumi, Shota; Sano, Tomoharu; Michikawa, Takehiro; Nohara, Keiko

    2013-12-01

    Inorganic arsenic is known to be a human carcinogen. Previous studies have reported that DNA methylation changes are involved in arsenic-induced carcinogenesis, therefore, DNA methylation changes that are specific to arsenic-induced tumors would be useful to distinguish tumors induced by arsenic from tumors caused by other factors and to dissect arsenic carcinogenesis. Previous studies have shown that gestational arsenic exposure of C3H mice, which tend to spontaneously develop liver tumors, increases the incidence of tumors in male offspring. In this study we used the same experimental protocol as in those previous studies and searched for DNA regions where methylation status was specifically altered in the liver tumors of arsenic-exposed offspring by using methylated DNA immunoprecipitation-CpG island microarrays. The methylation levels of the DNA regions selected were measured by quantitative methylation-specific PCR and bisulfite sequencing. The results of this study clarified a number of regions where DNA methylation status was altered in the liver tumors in the C3H mice compared to normal liver tissues. Among such regions, we showed that a gene body region of the oncogene Fosb underwent alteration in DNA methylation by gestational arsenic exposure. We also showed that Fosb expression significantly increased corresponding to the DNA methylation level of the gene body in the arsenic-exposed group. These findings suggest that the DNA methylation status can be used to identify tumors increased by gestational arsenic exposure. © 2013 Japanese Cancer Association.

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

    PubMed

    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

    2011-08-01

    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 10 μg/L) and Mn (above and below 500 μg/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>0.25). 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. 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

  8. Association between arsenic exposure from drinking water and proteinuria: results from the Health Effects of Arsenic Longitudinal Study

    PubMed Central

    Chen, Yu; Parvez, Faruque; Liu, Mengling; Pesola, Gene R; Gamble, Mary V; Slavkovich, Vesna; Islam, Tariqul; Ahmed, Alauddin; Hasan, Rabiul; Graziano, Joseph H; Ahsan, Habibul

    2011-01-01

    Background Proteinuria has been recognized as a marker for an increased risk of chronic renal disease. It is unclear whether arsenic (As) exposure from drinking water is associated with proteinuria. Methods We evaluated the association between As exposure from drinking water and proteinuria in 11 122 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Proteinuria was detected by urinary dipstick tests at baseline and at 2-year intervals. As exposure variables included baseline well As and changes in urinary As during follow-up modelled as time-dependent variables in the analyses. Results At baseline, well As was positively related to prevalence of proteinuria; prevalence odds ratios (PORs) for proteinuria in increasing quintiles of well As (≤7, 8–39, 40–91, 92–179 and 180–864 µg/l) were 1.00 (ref), POR 0.99 [95% confidence interval (CI) 0.77–1.27], POR 1.23 (95% CI 0.97–1.57), POR 1.50 (95% CI 1.18–1.89) and POR 1.59 (95% CI 1.26–2.00) (P for trend <0.01). Hazard ratios for incidence of proteinuria were POR 0.83 (95% CI 0.67–1.03) and POR 0.91 (95% CI 0.74–1.12) for participants with a decreasing level of >70 and 17–70 µg/l in urinary As over time, respectively, and were POR 1.17 (95% CI 0.97–1.42) and POR 1.42 (95% CI 1.16–1.73) for participants with an increasing level of 16–68 and >68 µg/l in urinary As over time, respectively, compared with the gr