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Sample records for arsenic exposure transforms

  1. Arsenic Exposure Transforms Human Epithelial Stem/Progenitor Cells into a Cancer Stem-like Phenotype

    PubMed Central

    Tokar, Erik J.; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2010-01-01

    Background Inorganic arsenic is a ubiquitous environmental carcinogen affecting millions of people worldwide. Evolving theory predicts that normal stem cells (NSCs) are transformed into cancer stem cells (CSCs) that then drive oncogenesis. In humans, arsenic is carcinogenic in the urogenital system (UGS), including the bladder and potentially the prostate, whereas in mice arsenic induces multiorgan UGS cancers, indicating that UGS NSCs may represent targets for carcinogenic initiation. However, proof of emergence of CSCs induced by arsenic in a stem cell population is not available. Methods We continuously exposed the human prostate epithelial stem/progenitor cell line WPE-stem to an environmentally relevant level of arsenic (5 μM) in vitro and determined the acquired cancer phenotype. Results WPE-stem cells rapidly acquired a malignant CSC-like phenotype by 18 weeks of exposure, becoming highly invasive, losing contact inhibition, and hypersecreting matrix metalloproteinase-9. When hetero-transplanted, these cells (designated As-CSC) formed highly pleomorphic, aggressive tumors with immature epithelial- and mesenchymal-like cells, suggesting a highly pluripotent cell of origin. Consistent with tumor-derived CSCs, As-CSCs formed abundant free-floating spheres enriched in CSC-like cells, as confirmed by molecular analysis and the fact that only these floating cells formed xenograft tumors. An early loss of NSC self-renewal gene expression (p63, ABCG2, BMI-1, SHH, OCT-4, NOTCH-1) during arsenite exposure was subsequently reversed as the tumor suppressor gene PTEN was progressively suppressed and the CSC-like phenotype acquired. Conclusions Arsenite transforms prostate epithelial stem/progenitor cells into CSC-like cells, indicating that it can produce CSCs from a model NSC population. PMID:20056578

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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...

  14. Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression

    PubMed Central

    Zhao, Christopher Q.; Young, Matthew R.; Diwan, Bhalchandra A.; Coogan, Timothy P.; Waalkes, Michael P.

    1997-01-01

    Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis. PMID:9380733

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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...

  20. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    SciTech Connect

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  1. 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

  2. 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

  3. 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...

  4. 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.

  5. 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.

  6. p38α MAPK is required for arsenic-induced cell transformation.

    PubMed

    Kim, Hong-Gyum; Shi, Chengcheng; Bode, Ann M; Dong, Zigang

    2016-05-01

    Arsenic exposure has been reported to cause neoplastic transformation through the activation of PcG proteins. In the present study, we show that activation of p38α mitogen-activated protein kinase (MAPK) is required for arsenic-induced neoplastic transformation. Exposure of cells to 0.5 μM arsenic increased CRE and c-Fos promoter activities that were accompanied by increases in p38α MAPK and CREB phosphorylation and expression levels concurrently with AP-1 activation. Introduction of short hairpin (sh) RNA-p38α into BALB/c 3T3 cells markedly suppressed arsenic-induced colony formation compared with wildtype cells. CREB phosphorylation and AP-1 activation were decreased in p38α knockdown cells after arsenic treatment. Arsenic-induced AP-1 activation, measured as c-Fos and CRE promoter activities, and CREB phosphorylation were attenuated by p38 inhibition in BALB/c 3T3 cells. Thus, p38α MAPK activation is required for arsenic-induced neoplastic transformation mediated through CREB phosphorylation and AP-1 activation.

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

    PubMed

    Reichard, John F; Puga, Alvaro

    2010-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Epithelial to mesenchymal transition in arsenic-transformed cells promotes angiogenesis through activating β-catenin–vascular endothelial growth factor pathway

    SciTech Connect

    Wang, Zhishan; Humphries, Brock; Xiao, Hua; Jiang, Yiguo; Yang, Chengfeng

    2013-08-15

    Arsenic exposure represents a major health concern increasing cancer risks, yet the mechanism of arsenic carcinogenesis has not been elucidated. We and others recently reported that cell malignant transformation by arsenic is accompanied by epithelial to mesenchymal transition (EMT). However, the role of EMT in arsenic carcinogenesis is not well understood. Although previous studies showed that short term exposure of endothelial cells to arsenic stimulated angiogenesis, it remains to be determined whether cells that were malignantly transformed by long term arsenic exposure have a pro-angiogenic effect. The objective of this study was to investigate the effect of arsenic-transformed human bronchial epithelial cells that underwent EMT on angiogenesis and the underlying mechanism. It was found that the conditioned medium from arsenic-transformed cells strongly stimulated tube formation by human umbilical vein endothelial cells (HUVECs). Moreover, enhanced angiogenesis was detected in mouse xenograft tumor tissues resulting from inoculation of arsenic-transformed cells. Mechanistic studies revealed that β-catenin was activated in arsenic-transformed cells up-regulating its target gene expression including angiogenic-stimulating vascular endothelial growth factor (VEGF). Stably expressing microRNA-200b in arsenic-transformed cells that reversed EMT inhibited β-catenin activation, decreased VEGF expression and reduced tube formation by HUVECs. SiRNA knockdown β-catenin decreased VEGF expression. Adding a VEGF neutralizing antibody into the conditioned medium from arsenic-transformed cells impaired tube formation by HUVECs. Reverse transcriptase-PCR analysis revealed that the mRNA levels of canonical Wnt ligands were not increased in arsenic-transformed cells. These findings suggest that EMT in arsenic-transformed cells promotes angiogenesis through activating β-catenin–VEGF pathway. - Highlights: • Arsenic-transformed cells that underwent EMT displayed a pro

  18. SPECIATION OF ARSENIC IN EXPOSURE ASSESSMENT MATRICES

    EPA Science Inventory

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

  19. 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...

  20. 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...

  1. Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/{beta}-catenin pathway in human colorectal adenocarcinoma DLD1 cells

    SciTech Connect

    Zhang Zhuo; Wang Xin; Cheng Senping; Sun Lijuan; Son, Young-Ok; Yao Hua; Li Wenqi; Budhraja, Amit; Li Li; Shelton, Brent J.; Tucker, Thomas; Arnold, Susanne M.; Shi Xianglin

    2011-10-15

    Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, {beta}-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47{sup phox} and p67{sup phox}, two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased {beta}-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced {beta}-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/{beta}-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells. - Highlights: > Arsenic activates NADPH oxidase and increases reactive oxygen species generation in DLD1 cells. > Arsenic increases {beta}-catenin expression. > Inhibition of ROS induced by arsenic reduce {beta}-catenin expression. > Arsenic increases cell transformation in DLD1 cells and tumorigenesis in nude mice. > Blockage of ROS decrease cell transformation and tumorigenesis induced by arsenic.

  2. 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.

  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. 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

  5. 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

  6. 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.

  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. 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...

  9. 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...

  10. 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

  11. 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

  12. Microbial transformation of elements: the case of arsenic and selenium

    USGS Publications Warehouse

    Stolz, J.; Basu, P.; Oremland, R.

    2002-01-01

    Microbial activity is responsible for the transformation of at least one third of the elements in the periodic table. These transformations are the result of assimilatory, dissimilatory, or detoxification processes and form the cornerstones of many biogeochemical cycles. Arsenic and selenium are two elements whose roles in microbial ecology have only recently been recognized. Known as "essential toxins", they are required in trace amounts for growth and metabolism but are toxic at elevated concentrations. Arsenic is used as an osmolite in some marine organisms while selenium is required as selenocysteine (i.e. the twenty-first amino acid) or as a ligand to metal in some enzymes (e.g. FeNiSe hydrogenase). Arsenic resistance involves a small-molecular-weight arsenate reductase (ArsC). The use of arsenic and selenium oxyanions for energy is widespread in prokaryotes with representative organisms from the Crenarchaeota, thermophilic bacteria, low and high G+C gram-positive bacteria, and Proteobacteria. Recent studies have shown that both elements are actively cycled and play a significant role in carbon mineralization in certain environments. The occurrence of multiple mechanisms involving different enzymes for arsenic and selenium transformation indicates several different evolutionary pathways (e.g. convergence and lateral gene transfer) and underscores the environmental significance and selective impact in microbial evolution of these two elements.

  13. Microbial transformation of elements: the case of arsenic and selenium.

    PubMed

    Stolz, J F; Basu, P; Oremland, R S

    2002-12-01

    Microbial activity is responsible for the transformation of at least one third of the elements in the periodic table. These transformations are the result of assimilatory, dissimilatory, or detoxification processes and form the cornerstones of many biogeochemical cycles. Arsenic and selenium are two elements whose roles in microbial ecology have only recently been recognized. Known as "essential toxins", they are required in trace amounts for growth and metabolism but are toxic at elevated concentrations. Arsenic is used as an osmolite in some marine organisms while selenium is required as selenocysteine (i.e. the twenty-first amino acid) or as a ligand to metal in some enzymes (e.g. FeNiSe hydrogenase). Arsenic resistance involves a small-molecular-weight arsenate reductase (ArsC). The use of arsenic and selenium oxyanions for energy is widespread in prokaryotes with representative organisms from the Crenarchaeota, thermophilic bacteria, low and high G+C gram-positive bacteria, and Proteobacteria. Recent studies have shown that both elements are actively cycled and play a significant role in carbon mineralization in certain environments. The occurrence of multiple mechanisms involving different enzymes for arsenic and selenium transformation indicates several different evolutionary pathways (e.g. convergence and lateral gene transfer) and underscores the environmental significance and selective impact in microbial evolution of these two elements.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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 ...

  19. 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....

  20. 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.

  1. 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.

  2. Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

    SciTech Connect

    Sun Yang; Kojima, Chikara; Chignell, Colin; Mason, Ronald; Waalkes, Michael P.

    2011-09-15

    Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm{sup 2}) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: > Arsenic transformation adapted to UV-induced apoptosis. > Arsenic transformation diminished oxidant response. > Arsenic transformation enhanced UV-induced DNA damage.

  3. 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.

  4. Overabundance of Putative Cancer Stem Cells in Human Skin Keratinocyte Cells Malignantly Transformed by Arsenic

    PubMed Central

    Sun, Yang; Tokar, Erik J.; Waalkes, Michael P.

    2012-01-01

    Arsenic is a human skin carcinogen. Cancer is probably a disease driven by stem cells (SCs), and SCs are likely a key target during arsenic oncogenesis. In utero arsenic exposure predisposes mice to skin cancers that overproduce cancer SCs (CSCs) and have distorted CSC signaling and population dynamics. Therefore, we hypothesized CSC accumulation may occur during arsenic-induced malignant transformation in vitro of human skin keratinocytes. Thus, the HaCaT cell line, malignantly transformed by arsenite (100nM, 30 weeks; termed As-TM cells) in prior work, was further studied for the quantity and nature of SCs after this transformation. SCs were isolated from passage-matched control and As-TM cells by a magnetic bead system that enriches for CD34-positive cells. There were 2.5 times more SCs isolated from As-TM cells than control. Holoclone production from As-TM putative CSCs was 2.5-fold higher by 1 week and 3.5-fold higher by 2 weeks than control SCs. Potential malignant phenotype was assessed in isolated SC/CSCs. Transcript level of SC/CSC markers were elevated in both isolated As-TM CSCs and control SCs compared with parental cells, but compared with control SCs, As-TM putative CSCs had elevated CD34, K5, K14, K15, and K19 transcripts and dramatically stronger staining for p63, Rac1, K5, Notch1, and K19. As-TM putative CSCs also showed markedly elevated MMP-9 secretion and colony formation, indicators of cancer phenotype, even compared with total population of As-TM cells. Thus, malignant phenotype is particularly pronounced in CSCs after arsenic-induced transformation of human skin cells and occurs concurrently with a potential overproduction of these cells. PMID:22011395

  5. 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...

  6. Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation

    SciTech Connect

    Jensen, Taylor J.; Wozniak, Ryan J.; Eblin, Kylee E.; Wnek, Sean M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-02-15

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation.

  7. Epigenetic Mediated Transcriptional Activation of WNT5A Participates in Arsenical-Associated Malignant Transformation

    PubMed Central

    Jensen, Taylor J.; Wozniak, Ryan J.; Eblin, Kylee E.; Wnek, Sean M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2015-01-01

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggests that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicate that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation. PMID:19061910

  8. Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation.

    PubMed

    Jensen, Taylor J; Wozniak, Ryan J; Eblin, Kylee E; Wnek, Sean M; Gandolfi, A Jay; Futscher, Bernard W

    2009-02-15

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation.

  9. 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...

  10. 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 ...

  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. 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 ...

  13. Arsenic transport and transformation associated with MSMA application on a golf course green.

    PubMed

    Feng, Min; Schrlau, Jill E; Snyder, Raymond; Snyder, George H; Chen, Ming; Cisar, John L; Cai, Yong

    2005-05-04

    The impact of extensively used arsenic-containing herbicides on groundwater beneath golf courses has become a topic of interest. Although currently used organoarsenicals are less toxic, their application into the environment may produce the more toxic inorganic arsenicals. The objective of this work was to understand the behavior of arsenic species in percolate water from monosodium methanearsonate (MSMA) applied golf course greens, as well as to determine the influences of root-zone media for United State Golf Association (USGA) putting green construction on arsenic retention and species conversion. The field test was established at the Fort Lauderdale Research and Education Center (FLREC), University of Florida. Percolate water was collected after MSMA application for speciation and total arsenic analyses. The results showed that the substrate composition significantly influenced arsenic mobility and arsenic species transformation in the percolate water. In comparison to uncoated sands (S) and uncoated sands and peat (S + P), naturally coated sands and peat (NS + P) showed a higher capacity of preventing arsenic from leaching into percolate water, implying that the coatings of sands with clay reduce arsenic leaching. Arsenic species transformation occurred in soil, resulting in co-occurrence of four arsenic species, arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in percolate water. The results indicated that substrate composition can significantly affect both arsenic retention in soil and arsenic speciation in percolate water. The clay coatings on the soil particles and the addition of peat in the soil changed the arsenic bioavailability, which in turn controlled the microorganism-mediated arsenic transformation. To better explain and understand arsenic transformation and transport after applying MSMA in golf green, a conceptual model was proposed.

  14. Arsenic Transport and Transformation Associated with MSMA Application on a Golf Course Green

    PubMed Central

    Feng, Min; Schrlau, Jill E.; Snyder, Raymond; Snyder, George H.; Chen, Ming; Cisar, John L.; Cai, Yong

    2008-01-01

    The impact of extensively used arsenic-containing herbicides on groundwater beneath golf courses has become a topic of interest. Although currently used organoarsenicals are less toxic, their application into the environment may produce the more toxic inorganic arsenicals. The objective of this work was to understand the behavior of arsenic species in percolate water from monosodium methanearsonate (MSMA) applied golf course greens, as well as to determine the influences of root-zone media for United State Golf Association (USGA) putting green construction on arsenic retention and species conversion. The field test was established at the Fort Lauderdale Research and Education Center (FLREC), University of Florida. Percolate water was collected after MSMA application for speciation and total arsenic analyses. The results showed that the substrate composition significantly influenced arsenic mobility and arsenic species transformation in the percolate water. In comparison to uncoated sands (S) and uncoated sands and peat (S + P), naturally coated sands and peat (NS + P) showed a higher capacity of preventing arsenic from leaching into percolate water, implying that the coatings of sands with clay reduce arsenic leaching. Arsenic species transformation occurred in soil, resulting in co-occurrence of four arsenic species, arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in percolate water. The results indicated that substrate composition can significantly affect both arsenic retention in soil and arsenic speciation in percolate water. The clay coatings on the soil particles and the addition of peat in the soil changed the arsenic bioavailability, which in turn controlled the microorganism-mediated arsenic transformation. To better explain and understand arsenic transformation and transport after applying MSMA in golf green, a conceptual model was proposed. PMID:15853401

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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 ...

  7. 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...

  8. 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...

  9. 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...

  10. Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism

    PubMed Central

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Wang, Lei; Zhang, Zhuo; Shi, Xianglin

    2016-01-01

    Arsenic is a well-documented human carcinogen. The present study explored the role of the onco-miR, miR-21 and its target protein, programmed cell death 4 (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our results showed that treatment of human bronchial epithelial (BEAS-2B) cells with arsenic induces ROS through p47phox, one of the NOX subunits that is the key source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21 expression associated with inhibition of PDCD4, and caused malignant cell transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3 transcriptional activation by IL-6 is crucial for the arsenic induced miR-21 increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4 or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream protein E-cadherin expression and induced β-catenin/TCF-dependent transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21-PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis. PMID:27876813

  11. 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...

  12. 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

  13. 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.

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

    PubMed

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

    2016-01-01

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

  15. 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.

  16. Synthesis and phase transformations involving scorodite, ferric arsenate and arsenical ferrihydrite: Implications for arsenic mobility

    NASA Astrophysics Data System (ADS)

    Paktunc, Dogan; Dutrizac, John; Gertsman, Valery

    2008-06-01

    Scorodite, ferric arsenate and arsenical ferrihydrite are important arsenic carriers occurring in a wide range of environments and are also common precipitates used by metallurgical industries to control arsenic in effluents. Solubility and stability of these compounds are controversial because of the complexities in their identification and characterization in heterogeneous media. To provide insights into the formation of scorodite, ferric arsenate and ferrihydrite, series of synthesis experiments were carried out at 70 °C and pH 1, 2, 3 and 4.5 from 0.2 M Fe(SO 4) 1.5 solutions also containing 0.02-0.2 M Na 2HAsO 4. The precipitates were characterized by transmission electron microscopy, X-ray diffraction and X-ray absorption fine structure techniques. Ferric arsenate, characterized by two broad diffuse peaks on the XRD pattern and having the structural formula of FeAsO 4·4-7H 2O, is a precursor to scorodite formation. As defined by As XAFS and Fe XAFS, the local structure of ferric arsenate is profoundly different than that of scorodite. It is postulated that the ferric arsenate structure is made of single chains of corner-sharing Fe(O,OH) 6 octahedra with bridging arsenate tetrahedra alternating along the chains. Scorodite was precipitated from solutions with Fe/As molar ratios of 1 over the pH range of 1-4.5. The pH strongly controls the kinetics of scorodite formation and its transformation from ferric arsenate. The scorodite crystallite size increased from 7 to 33 nm by ripening and aggregation. Precipitates, resulting from continuous synthesis at pH 4.5 from solutions having Fe/As molar ratios ranging from 1 to 4 and resembling the compounds referred to as ferric arsenate, arsenical ferrihydrite and As-rich hydrous ferric oxide in the literature, represent variable mixtures of ferric arsenate and ferrihydrite. When the Fe/As ratio increases, the proportion of ferrihydrite increases at the expense of ferric arsenate. Arsenate adsorption appears to retard

  17. 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.

  18. 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

    2017-03-08

    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.

  19. 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.

  20. 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

  1. Isolation and identification of indigenous prokaryotic bacteria from arsenic-contaminated water resources and their impact on arsenic transformation.

    PubMed

    Jebelli, Mohammad Ahmadi; Maleki, Afshin; Amoozegar, Mohammad Ali; Kalantar, Enayatollah; Shahmoradi, Behzad; Gharibi, Fardin

    2017-06-01

    Arsenic is a known human carcinogen. Arsenite [As(III), H3AsO3] and arsenate [As(V), H2AsO4(-) and HAsO4(2-)] are the two predominant compounds of As found in surface water and groundwater. The aim of this study was to explore a bioremediation strategy for biotransformation of arsenite to arsenate by microorganisms. In this study, Babagorgor Spring, located west of Iran, was selected as the arsenic-contaminated source and its physicochemical characteristics and in situ microbiological composition were analyzed. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) analysis indicated that the arsenic level was 614μg/l. Fourteen arsenic tolerant indigenous bacteria were isolated from arsenic-contaminated water using chemically defined medium (CDM), supplemented with 260-3900mg/l arsenite and 1560-21800mg/l arsenate. Among the isolates, a strain As-11 exhibited high ability of arsenic transformation. Biochemical tests were used for bacterial identification and confirmation was conducted by 16S rRNA sequence analysis. Results confirmed that As-11 was related to the genus Pseudomonas. This bacterium showed maximum tolerable concentration to arsenite up to 3250mg/l and arsenate up to 20280mg/l. Under heterotrophic conditions, the bacterium exhibited 48% of As(III) and 78% of As(V) transformation from the medium amended with 130 and 312mg/l of sodium arsenite and sodium arsenate, respectively. Moreover, under chemolithotrophic conditions, bacterium was able to transform 41% of 130mg/l of As(III) from the medium amended with nitrate as the terminal electron acceptor. Pseudomonas strain As-11 was reported as an arsenic transformer, for the first time.

  2. 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...

  3. 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...

  4. Arsenic

    MedlinePlus

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

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. Sulfidogenesis Controls on Ferrihydrite Transformation and Repartitioning of Sorbed Arsenic

    NASA Astrophysics Data System (ADS)

    Kocar, B. D.; Fendorf, S.

    2007-12-01

    Iron (hydr)oxides are ubiquitous sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here, we examine diverging pathways of solid phase iron (Fe) transformation during sulfate reduction in the presence of varying As loadings. Columns initially containing As(V)- ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Additionally, abiotic batch reaction experiments were conducted to examine Fe secondary products rapidly formed during sulfidization of As-loaded ferrihydrite. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed within column solids possessing low As(V) surface coverage (10% of the adsorption maximum). Column experiments illustrated that at high As(V) surface coverage (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. The dominant Fe solid-phase transformation products at low As coverage include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II)aq concentrations exceed 1 mM. Arsenic(V) is reduced to As(III) and displaced from the zone of sulfidogenesis and Fe(III)s depletion. At higher As coverage, green rust carbonate, as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Abiotic batch reactor experiments illustrate that As is readily released from ferrihydrite during sulfidization, and that low As loadings yield initial Fe secondary products of lepidocrocite and FeS, while high loadings inhibit rapid secondary Fe mineral formation. Our observations illustrate that

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure.

    PubMed

    Huang, Madelyn C; Douillet, Christelle; Su, Mingming; Zhou, Kejun; Wu, Tao; Chen, Wenlian; Galanko, Joseph A; Drobná, Zuzana; Saunders, R Jesse; Martin, Elizabeth; Fry, Rebecca C; Jia, Wei; Stýblo, Miroslav

    2017-01-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL/6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation.

  17. Prevalence of arsenic exposure in population of Ballia district from drinking water and its correlation with blood arsenic level.

    PubMed

    Katiyar, Shashwat; Singh, Dharam

    2014-05-01

    An investigation was carried out to ascertain the effect of arsenic in the blocks of Ballia district in Uttar Pradesh in the upper and middle Ganga plain, India. Analysis of 100 drinking water samples revealed that arsenic concentration was below 10 μg l⁻¹ in 60% samples, 10-50 μg l⁻¹ in 6%, 100 μg l⁻¹ in 24% and 200 μg l⁻¹ in 10% samples, respectively. The arsenic concentration in drinking water ranged from 12.8 to 132.2 μg l⁻¹. The depth of source of drinking water (10-60 m) was also found with a mean of 36.12 ± 13.61 μg l⁻¹ arsenic concentration. Observations revealed that at depth ranging from 10 to 20 m, the mean level of arsenic concentration was 17.398 ± 21.796 μg l⁻¹, while at 21 to 40 m depth As level was 39.685 ± 40.832 μg l⁻¹ and at 41 to 60 m As level was 46.89 ± 52.80 μg l⁻¹, respectively. These observations revealed a significant positive correlation (r = 0.716, t = 4.215, P < 0.05) between depth and arsenic concentration in drinking water. The age of water sources were ranged from zero to 30 years. The study indicates that the older sources of drinking water showed higher chance of contamination. Results showed that group 21-30 years having maximum arsenic concentration with mean value of 52.57 ± 53.79 μg l⁻¹. Correlation analysis also showed a significant positive correlation (r = 0.801, t = 5.66, P < 0.05) between age of drinking water sources and their respective arsenic concentration (μg l⁻¹). Arsenic concentration in blood with mean value 0.226 ± 0.177 μg dl⁻¹ significantly increased as compared to control. The blood arsenic content correlated significantly (r = 0.6823, t = 3.93, P < 0.05) with drinking water arsenic level and exposure time (r = 0.545, t = 3.101 & *P < 0.05) for populations residing in Ballia districts. Observations and correlation analysis revealed that individuals having depth of drinking water sources 20-30 m were less affected with arsenic exposure.

  18. Poultry Consumption and Arsenic Exposure in the U.S. Population

    PubMed Central

    Nigra, Anne E.; Nachman, Keeve E.; Love, David C.; Grau-Perez, Maria; Navas-Acien, Ana

    2016-01-01

    Background: Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown. Objectives: Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone. Methods: We evaluated 3,329 participants ≥ 6 years old from the 2003–2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake. Results: After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p-trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p-trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer. Conclusions: Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003–2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic

  19. Arsenic repartitioning during biogenic sulfidization and transformation of ferrihydrite

    NASA Astrophysics Data System (ADS)

    Kocar, Benjamin D.; Borch, Thomas; Fendorf, Scott

    2010-02-01

    Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II) (aq) concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III) (s) depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.

  20. Arsenic Repartitioning during Biogenic Sulfidization and Transformation of Ferrihydrite

    SciTech Connect

    Kocar, B.; Borch, T; Fendorf, S

    2010-01-01

    Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II){sub (aq)} concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III){sub (s)} depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.

  1. Arsenic repartitioning during biogenic sulfidization and transformation of ferrihydrite

    SciTech Connect

    Kocar, Benjamin D.; Borch, Thomas; Fendorf, Scott

    2012-04-30

    Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II)(aq) concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III)(s) depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  4. Distribution and speciation of arsenic by transplacental and early life exposure to inorganic arsenic in offspring rats.

    PubMed

    Xi, Shuhua; Jin, Yaping; Lv, Xiuqiang; Sun, Guifan

    2010-04-01

    The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO(2) from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood-brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.

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

    SciTech Connect

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

    2009-05-21

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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Arsenic exposure in US public and domestic drinking water supplies: a comparative risk assessment.

    PubMed

    Kumar, Arun; Adak, Probas; Gurian, Patrick L; Lockwood, John R

    2010-05-01

    Although approximately 35 million people in the US obtain drinking water from domestic wells, few studies have investigated the risk of arsenic exposure from this source. In this paper arsenic concentrations were modeled for public and domestic wells using a dataset from the US Geological Survey (USGS). Excess lifetime and annual risks for lung and bladder cancer were calculated based on the carcinogenic potency and average arsenic concentrations in public and domestic water supplies. Monte Carlo uncertainty analysis was used to estimate the degree of confidence in these estimations. Results indicated that domestic well users accounted for 12% of the US population, but 23% of overall arsenic exposure from drinking water. Assuming that the new and more restrictive arsenic maximum contaminant limit (MCL) is implemented for public water supplies, it is anticipated that the proportion of people experiencing excess annual fatalities from drinking water from domestic wells will increase to 29% unless corresponding efforts are made to reduce exposures among domestic well users. Differences between public and domestic wells were not consistent across the nation. Public wells tend to tap deeper aquifers than domestic wells, and as a result local arsenic-depth trends can contribute to differences between public and domestic wells. Domestic wells and public wells in the western US have the highest arsenic levels with excess fatality risks estimated to be in the range of 1 per 9300 to 1 per 6600 in these regions. Uncertainty distributions of excess fatalities were developed and resultant uncertainties were propagated in arsenic exposure and potency factor. Uncertainty in the carcinogenic potency of arsenic was the dominant source of uncertainty in most regions, but for domestic wells in the New England and Southeast regions uncertainty in arsenic exposure was dominant, indicating that additional data on arsenic concentrations in these areas would substantially improve regional

  11. Exposure to Inorganic Arsenic Is Associated with Increased Mitochondrial DNA Copy Number and Longer Telomere Length in Peripheral Blood

    PubMed Central

    Ameer, Syeda S.; Xu, YiYi; Engström, Karin; Li, Huiqi; Tallving, Pia; Nermell, Barbro; Boemo, Analia; Parada, Luis A.; Peñaloza, Lidia G.; Concha, Gabriela; Harari, Florencia; Vahter, Marie; Broberg, Karin

    2016-01-01

    Background: Exposure to inorganic arsenic (iAs) through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn) and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity. Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N = 264, 89% females) and one in Chaco (N = 169, 75% females). We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA), dimethylarsinic acid (DMA)] in urine (U-As) using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR. Results: Median U-As was 196 (5–95 percentile: 21–537) μg/L in Andes and 80 (5–95 percentile: 15–1637) μg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity) in Chaco (β = 0.027 per 100 μg/L, p = 0.0085; adjusted for age and sex), but not in Andes (β = 0.025, p = 0.24). U-As was also associated with longer telomere length in Chaco (β = 0.016, p = 0.0066) and Andes (β = 0.0075, p = 0.029). In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs. Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer. PMID:27597942

  12. 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.

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

    EPA Science Inventory

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

  14. 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...

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

    SciTech Connect

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

    2015-04-15

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

  16. A comparison of elementary schoolchildren's exposure to arsenic and lead.

    PubMed

    Chiang, Wan-Fu; Yang, Hao-Jan; Lung, Shih-Chun Candice; Huang, Shuai; Chiu, Chih-Yuan; Liu, I-Ling; Tsai, Ching-Ling; Kuo, Chung-Yih

    2008-01-01

    One hundred fifty seven fifth-grade students (aged 10-12 years) from three elementary schools in three different towns in Taichung County, Taiwan were chosen as study subjects for the present arsenic and lead exposure study. The three towns--Longgang, Shalach, and Shuntain--are known to be highly, moderately, and lightly (control) polluted by As and Pb, respectively. Spot morning urine samples of students were collected and analyzed for arsenic and lead. The levels of As in the urine of Longgang schoolchildren showed the highest value among the three schools, while those of the control group (Shuntain) had the lowest values. In addition, the levels of Pb in the urine of the schoolchildren in Shuntain were significantly lower than those in Longgang and Shalach, while the levels of Pb in the urine of the schoolchildren in Longgang and Shalach showed no significant difference. Results of daily intake of metals from the different exposure pathways (i.e., ingestion from drinking water, household dust and food, and inhalation from airborne particles) showed that the Longgang area had the highest daily intake of As and Pb among the three areas, while the lowest daily intake of As and Pb occurred in the control area (Shuntain). A significant correlation between the doses of daily intake and urinary concentrations of As (p = 0.002) and Pb (p = 0.020) was observed. This correlation suggests that the increase of unit dose of the daily intake for As resulted in an increase of 0.953 microg g(-1) creatinine of As, whereas the increase of unit dose of the daily intake for Pb led to an increase of 0.053 microg g(-1) creatinine of Pb. These data indicate that the level of As in urine increased about 18 times higher than that of Pb for the same amount of increase in daily intake.

  17. Arsenic exposure to drinking water in the Mekong Delta.

    PubMed

    Merola, R B; Hien, T T; Quyen, D T T; Vengosh, A

    2015-04-01

    Arsenic (As) contamination of groundwater drinking sources was investigated in the Mekong Delta, Vietnam in order to assess the occurrence of As in the groundwater, and the magnitude of As exposure of local residents through measurements of As in toenails of residents consuming groundwater as their major drinking water source. Groundwater (n=68) and toenail (n=62) samples were collected in Dong Thap Province, adjacent to the Mekong River, in southern Vietnam. Fifty-three percent (n=36) of the wells tested had As content above the World Health Organization's (WHO) recommended limit of 10 ppb. Samples were divided into Northern (mean As=4.0 ppb) and Southern (329.0 ppb) groups; wells from the Southern group were located closer to the Mekong River. Elevated As contents were associated with depth (<200 m), salinity (low salinity), and redox state (reducing conditions) of the study groundwater. In 79% of the wells, As was primarily composed of the reduced As(III) species. Arsenic content in nails collected from local residents was significantly correlated to As in drinking water (r=0.49, p<0.001), and the relationship improved for pairs in which As in drinking water was higher than 1 ppb (r=0.56, p<0.001). Survey data show that the ratio of As in nail to As in water varied among residents, reflecting differential As bioaccumulation in specific exposed sub-populations. The data show that water filtration and diet, particularly increased consumption of animal protein and dairy, and reduced consumption of seafood, were associated with lower ratios of As in nail to As in water and thus could play important roles in mitigating As exposure in areas where As-rich groundwater is the primary drinking water source.

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  20. Biological monitoring of occupational exposure to inorganic arsenic

    PubMed Central

    Apostoli, P.; Bartoli, D.; Alessio, L.; Buchet, J. P.

    1999-01-01

    OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide

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

    PubMed

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

    2016-02-15

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

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

    PubMed

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

    2016-02-15

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

  3. Arsenic transformation and mobilization from minerals by the arsenite oxidizing strain WAO.

    PubMed

    Rhine, E Danielle; Onesios, Katheryn M; Serfes, Michael E; Reinfelder, John R; Young, L Y

    2008-03-01

    Analysis of arsenic concentrations in New Jersey well water from the Newark Basin showed up to 15% of the wells exceed 10 microg L(-1), with a maximum of 215 microg L(-1). In some geologic settings in the basin, this mobile arsenic could be from the weathering of pyrite (FeS2) found in black shale that contains up to 4% arsenic by weight. We hypothesized that under oxic conditions at circumneutral pH, the microbially mediated oxidation of sulfide in the pyrite lattice would lead to the release of pyrite-bound arsenic. Moreover, the oxidation of aqueous As(III) to As(V) by aerobic microorganisms could further enhance arsenic mobilization from the solid phase. Enrichment cultures under aerobic, As(III)-oxidizing conditions were established under circumneutral pH with weathered black shale from the Newark Basin as the inoculum source. Strain WAO, an autotrophic inorganic-sulfur and As(III)-oxidizer, was isolated and phylogenetically and physiologically characterized. Arsenic mobilization studies from arsenopyrite (FeAsS) mineral, conducted with strain WAO at circumneutral pH, showed microbially enhanced mobilization of arsenic and complete oxidation of released arsenic and sulfur to stoichiometric amounts of arsenate and sulfate. In addition, WAO preferentially colonized pyrite on the surface of arsenic-bearing, black shale thick sections. These findings support the hypothesis that microorganisms can directly mobilize and transform arsenic bound in mineral form at circumneutral pH and suggest that the microbial mobilization of arsenic into groundwater may be important in other arsenic-impacted aquifers.

  4. Arsenic transformation and mobilization from minerals by the arsenite oxidizing strain WAO

    USGS Publications Warehouse

    Rhine, E.D.; Onesios, K.M.; Serfes, M.E.; Reinfelder, J.R.; Young, L.Y.

    2008-01-01

    Analysis of arsenic concentrations in New Jersey well water from the Newark Basin showed up to 15% of the wells exceed 10 ??g L-1, with a maximum of 215 ??g L-1. In some geologic settings in the basin, this mobile arsenic could be from the weathering of pyrite (FeS2) found in black shale that contains up to 4% arsenic by weight. We hypothesized that under oxic conditions at circumneutral pH, the microbially mediated oxidation of sulfide in the pyrite lattice would lead to the release of pyrite-bound arsenic. Moreover, the oxidation of aqueous As(III) to As(V) by aerobic microorganisms could further enhance arsenic mobilization from the solid phase. Enrichment cultures under aerobic, As(III)-oxidizing conditions were established under circumneutral pH with weathered black shale from the Newark Basin as the inoculum source. Strain WAO, an autotrophic inorganic-sulfur and As(III)-oxidizer, was isolated and phylogenetically and physiologically characterized. Arsenic mobilization studies from arsenopyrite (FeAsS) mineral, conducted with strain WAO at circumneutral pH, showed microbially enhanced mobilization of arsenic and complete oxidation of released arsenic and sulfur to stoichiometric amounts of arsenate and sulfate. In addition, WAO preferentially colonized pyrite on the surface of arsenic-bearing, black shale thick sections. These findings support the hypothesis that microorganisms can directly mobilize and transform arsenic bound in mineral form at circumneutral pH and suggest that the microbial mobilization of arsenic into groundwater may be important in other arsenic-impacted aquifers. ?? 2008 American Chemical Society.

  5. 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.

  6. 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.

  7. Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats.

    PubMed

    Waghe, Prashantkumar; Sarkar, Souvendra Nath; Sarath, Thengumpallil Sasindran; Kandasamy, Kannan; Choudhury, Soumen; Gupta, Priyanka; Harikumar, Sankarankutty; Mishra, Santosh Kumar

    2017-04-01

    Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.

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

    PubMed

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

    2014-05-01

    Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic's ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range<1- 510 µg/L). Log 10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log 10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects.

  9. 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

  10. 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

  11. Arsenic accumulation in rice (Oryza sativa L.): human exposure through food chain.

    PubMed

    Azizur Rahman, M; Hasegawa, H; Mahfuzur Rahman, M; Mazid Miah, M A; Tasmin, A

    2008-02-01

    Although human exposure to arsenic is thought to be caused mainly through arsenic-contaminated underground drinking water, the use of this water for irrigation enhances the possibility of arsenic uptake into crop plants. Rice is the staple food grain in Bangladesh. Arsenic content in straw, grain and husk of rice is especially important since paddy fields are extensively irrigated with underground water having high level of arsenic concentration. However, straw and husk are widely used as cattle feed. Arsenic concentration in rice grain was 0.5+/-0.02 mg kg(-1) with the highest concentrations being in grains grown on soil treated with 40 mg As kg(-1) soil. With the average rice consumption between 400 and 650 g/day by typical adults in the arsenic-affected areas of Bangladesh, the intake of arsenic through rice stood at 0.20-0.35 mg/day. With a daily consumption of 4 L drinking water, arsenic intake through drinking water stands at 0.2mg/day. Moreover, when the rice plant was grown in 60 mg of As kg(-1) soil, arsenic concentrations in rice straw were 20.6+/-0.52 at panicle initiation stage and 23.7+/-0.44 at maturity stage, whereas it was 1.6+/-0.20 mg kg(-1) in husk. Cattle drink a considerable amount of water. So alike human beings, arsenic gets deposited into cattle body through rice straw and husk as well as from drinking water which in turn finds a route into the human body. Arsenic intake in human body from rice and cattle could be potentially important and it exists in addition to that from drinking water. Therefore, a hypothesis has been put forward elucidating the possible food chain pathways through which arsenic may enter into human body.

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

    PubMed Central

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

    2015-01-01

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

  13. 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...

  14. Environmental Arsenic Exposure and Urinary 8-OHdG in Arizona and Sonora.

    PubMed

    Burgess, Jefferey L; Meza, María M; Josyula, Arun B; Poplin, Gerald S; Kopplin, Michael J; McClellen, Hannah E; Stürup, Stefan; Lantz, R Clark

    2007-01-01

    Although at high levels arsenic exposure is associated with increased cancer incidence, information on the health effects of lower exposure levels is limited. The objective of this study was to determine whether arsenic at concentrations below 40 microg/L in drinking water is associated with increased urinary 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage and repair. Urine samples were collected from 73 nonsmoking adults residing in two communities in Arizona (mean tap water arsenic (microg/L) 4.0 +/- 2.3 and 20.3 +/- 3.7), and 51 subjects in four communities in Sonora, Mexico (mean tap water arsenic (microg/L) ranging from 4.8 +/- 0.1 to 33.3 +/- 0.6). Although urinary arsenic concentration increased with higher exposure in tap water, urinary 8-OHdG concentration did not differ by community within Arizona or Sonora, and was not associated with urinary arsenic concentration. At the exposure levels evaluated in this study, drinking water arsenic was not associated with increased DNA oxidation as measured by urinary 8-OHdG.

  15. 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

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

    PubMed Central

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

    2014-01-01

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

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

    USGS Publications Warehouse

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

    2006-01-01

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

  18. Redox transformations of arsenic oxyanions in periphyton communities

    USGS Publications Warehouse

    Kulp, T.R.; Hoeft, S.E.; Oremland, R.S.

    2004-01-01

    Periphyton (Cladophora sp.) samples from a suburban stream lacking detectable dissolved As were able to reduce added As(V) to As(III) when incubated under anoxic conditions and, conversely, oxidized added As(III) to As(V) with aerobic incubation. Both types of activity were abolished in autoclaved controls, thereby demonstrating its biological nature. The reduction of As(V) was inhibited by chloramphenicol, indicating that it required the synthesis of new protein. Nitrate also inhibited As(V) reduction, primarily because it served as a preferred electron acceptor to which the periphyton community was already adapted. However, part of the inhibition was also caused by microbial reoxidation of As(III) linked to nitrate. Addition of [ 14C]glucose to anoxic samples resulted in the production of 14CO2, suggesting that the observed As(V) reduction was a respiratory process coupled to the oxidation of organic matter. The population density of As(V)-reducing bacteria within the periphyton increased with time and with the amount of As(V) added, reaching values as high as ???106 cells ml-1 at the end of the incubation. This indicated that dissimilatory As(V) reduction in these populations was linked to growth. However, As(V)-respiring bacteria were found to be present, albeit at lower numbers (???102 ml-1), in freshly sampled periphyton. These results demonstrate the presence of a bacterial population within the periphyton communities that is capable of two key arsenic redox transformations that were previously studied in As-contaminated environments, which suggests that these processes are widely distributed in nature. This assumption was reinforced by experiments with estuarine samples of Cladophora sericea in which we detected a similar capacity for anaerobic As(V) reduction and aerobic As(III) oxidation.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

    Georgopoulos, Panos G; Wang, Sheng-Wei; Yang, Yu-Ching; Xue, Jianping; Zartarian, Valerie G; McCurdy, Thomas; Ozkaynak, Halûk

    2008-09-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Concha, Gabriela; Nermell, Barbro

    2006-01-01

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

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

    PubMed

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

    2016-02-01

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

  4. Embryonic arsenic exposure reduces the number of muscle fibers in killifish (Fundulus heteroclitus).

    PubMed

    D'Amico, Angela R; Gibson, Alec W; Bain, Lisa J

    2014-01-01

    Arsenic is a contaminant of drinking water and has been correlated with adverse developmental outcomes such as low birth weight, reduced weight gain, and altered locomotor activity. Previous research has shown that killifish (Fundulus heteroclitus) exposed to high arsenic levels during embryogenesis had smaller muscle fiber diameters. The current study was designed to determine whether changes in muscle fibers persisted, were exacerbated, or resolved over time. Killifish embryos were exposed to 0-5 ppm arsenite and, upon hatching, were transferred into either clean water or continued receiving the same exposure to arsenic for up to 16 weeks. Arsenic significantly decreased the weight of both embryonic-only exposed juveniles and continuously exposed juveniles between 4 and 16 weeks of development at concentrations as low as 0.8 ppm. Although arsenite exposure increased the percentage of small diameter fibers during the early weeks, fiber diameters returned to control levels in the embryonic-only exposed fish. However, muscle fiber density was still reduced to 85.7%, 80.3%, and 73.8% of control for the 0.8, 2, and 5 ppm embryonic-only exposure groups, respectively, even after 16 weeks of development. These results indicate that while continuous exposure to arsenic may alter the size of muscle fibers, embryonic-only exposure to arsenic has lasting effects on the number of muscle fibers formed.

  5. Association of arsenic exposure with smoking, alcohol, and caffeine consumption: data from NHANES 2005-2010.

    PubMed

    Jain, Ram B

    2015-03-01

    Association of arsenic exposure with smoking, alcohol, and caffeine consumption was investigated. Data from National Health and Nutrition Examination Survey for the years 2005-2010 were used for this investigation. Urinary levels of total arsenic (UAS) and dimethylarsonic acid (UDMA) were evaluated for children aged 6-12 years and adolescents and adults aged ≥ 12 years. Urinary levels of arsenobetaine (UAB) were evaluated for adolescents and adults only. Regression models were fitted for log transformed values of UAB, UAS, and UDMA. For the models for children, however, gender, race/ethnicity, SES, and fish/shell fish consumption during the last 30 days were the only independent variables that were included in the models. Nonsmokers were found to have higher levels of UAS and UDMA than smokers. Elevated levels of UAB, UAS, and UDMA were associated with higher amounts of daily alcohol consumption. The associations were in the opposite direction for daily caffeine consumption. Females were found to have statistically significantly lower adjusted levels of UDMA than males for those aged ≥ 12 years. Irrespective of age, those with unclassified race/ethnicity had the highest levels of UAB, UAS, and UDMA and non-Hispanic whites had the lowest levels. Adolescents had the higher levels of UAB, UAS, and UDMA than adults. Higher SES was associated with higher levels of UAB, UAS, and UDMA among adolescents and adults. Irrespective of age, fish consumption was associated with higher levels of UAB, UAS, and UDMA.

  6. Arsenic drinking water regulations in developing countries with extensive exposure.

    PubMed

    Smith, Allan H; Smith, Meera M Hira

    2004-05-20

    The United States Public Health Service set an interim standard of 50 microg/l in 1942, but as early as 1962 the US Public Health Service had identified 10 microg/l as a goal which later became the World Health Organization Guideline for drinking water in 1992. Epidemiological studies have shown that about one in 10 people drinking water containing 500 microg/l of arsenic over many years may die from internal cancers attributable to arsenic, with lung cancer being the surprising main contributor. A prudent public health response is to reduce the permissible drinking water arsenic concentrations. However, the appropriate regulatory response in those developing countries with large populations with much higher concentrations of arsenic in drinking water, often exceeding 100 microg/l, is more complex. Malnutrition may increase risks from arsenic. There is mounting evidence that smoking and arsenic act synergistically in causing lung cancer, and smoking raises issues of public health priorities in developing countries that face massive mortality from this product. Also, setting stringent drinking water standards will impede short term solutions such as shallow dugwells. Developing countries with large populations exposed to arsenic in water might reasonably be advised to keep their arsenic drinking water standards at 50 microg/l.

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

    EPA Science Inventory

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

  8. Toxicological responses in Laeonereis acuta (annelida, polychaeta) after arsenic exposure.

    PubMed

    Ventura-Lima, Juliane; Sandrini, Juliana Z; Cravo, Marlize Ferreira; Piedras, Fernanda R; Moraes, Tarsila B; Fattorini, Daniele; Notti, Alessandra; Regoli, Francesco; Geracitano, Laura A; Marins, Luis F F; Monserrat, José M

    2007-05-01

    Several environmental pollutants, including metals, can induce oxidative stress. So, the objective of this study was to evaluate the effects of arsenic (As(III), as As(2)O(3)) on the antioxidant responses in the polychaete Laeonereis acuta. Worms were exposed to two environmentally relevant concentrations of As, including the highest previously allowed by Brazilian legislation (50 microg As/l). A control group was kept in saline water (10 per thousand) without added metal. It was observed that: (1) a peak concentration of lipid peroxide was registered after 2 days of exposure to 50 microg As/l (61+/-3.2 nmol CHP/g wet weight) compared to the control group (43+/-4.5 nmol CHP/g wet weight), together with a lowering of the activity of the antioxidant enzyme catalase (-47 and -48%, at 50 or 500 microg As/l respectively) and a higher superoxide dismutase activity (+305% at 50 microg As/l with respect to the control group); (2) a lower conjugation capacity through glutathione-S-transferase activity was observed after 7 days of exposure to 50 microg As/l (-48% compared to the control group); (3) a significant increase in As concentration was verified after 1 week of exposure to both As concentrations (50 and 500 microg/l); (4) worms exposed to As showed a limited accumulation of related methylated As species and the levels of non-toxic As species like arsenobetaine (AsB) and arsenocholine (AsC) remained unchanged during the exposure period when compared with the controls. Overall, it can be concluded that As interfered in the antioxidant defense system of L. acuta, even at low concentrations (50 microg/l) that Brazilian legislation previously considered safe. The fact that worms exposed to As showed high levels of methylated As species indicates the methylation capability of L. acuta, although the high levels of inorganic As suggest that not all the administered As(III) (as As(2)O(3)) is completely removed or biotransformed after 7 days of exposure.

  9. 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...

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

    PubMed Central

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

    1998-01-01

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

  11. A prospective study of the synergistic effects of arsenic exposure and smoking, sun exposure, fertilizer use, and pesticide use on risk of premalignant skin lesions in Bangladeshi men.

    PubMed

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J; Ahsan, Habibul

    2011-01-15

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond.

  12. A Prospective Study of the Synergistic Effects of Arsenic Exposure and Smoking, Sun Exposure, Fertilizer Use, and Pesticide Use on Risk of Premalignant Skin Lesions in Bangladeshi Men

    PubMed Central

    Melkonian, Stephanie; Argos, Maria; Pierce, Brandon L.; Chen, Yu; Islam, Tariqul; Ahmed, Alauddin; Syed, Emdadul H.; Parvez, Faruque; Graziano, Joseph; Rathouz, Paul J.; Ahsan, Habibul

    2011-01-01

    Skin lesions are classic clinical signs of toxicity due to long-term exposure to arsenic, and they are considered precursors to arsenic-related skin cancer. The authors prospectively evaluated synergisms between effects of arsenic exposure and those of tobacco use, sun exposure, and pesticide and fertilizer use on incident skin lesions using risk factor data from 5,042 men from the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh, which recruited participants from October 2000 to May 2002. Discrete time hazard models were used to estimate measures of synergistic interactions on the additive scale. The authors observed significant synergistic effects between various measures of arsenic exposure and smoking and fertilizer use. The relative excess risks for the interactions between smoking status and arsenic exposure were 0.12 (95% confidence interval: 0.06, 0.19) for water arsenic and 0.11 (95% confidence interval: 0.05, 0.15) for urinary arsenic measures, respectively. Significant synergistic effects were also observed between fertilizer use and water arsenic (relative excess risk for the interaction = 0.06, 95% confidence interval: 0.01, 0.12). This is the first prospective study based on individual-level data that supports a role for smoking and certain occupational risk factors in modification of the effect of long-term arsenic exposure on skin lesions. Understanding differential arsenic susceptibility allows researchers to develop interventions to prevent the health consequences of this massive problem in the Bangladeshi population and beyond. PMID:21098630

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

    SciTech Connect

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

    2014-04-01

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2015-04-01

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

  16. 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.

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

    SciTech Connect

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

    2013-10-15

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

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

    PubMed Central

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

    2016-01-01

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

  19. 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...

  20. Environmental exposure to arsenic, AS3MT polymorphism and prevalence of diabetes in Mexico.

    PubMed

    Drobná, Zuzana; Del Razo, Luz M; García-Vargas, Gonzalo G; Sánchez-Peña, Luz C; Barrera-Hernández, Angel; Stýblo, Miroslav; Loomis, Dana

    2013-03-01

    Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAs(III)), a toxic product of arsenic methylation by arsenic (+3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes. Fasting blood glucose, oral glucose tolerance and self-reported diagnoses were used to identify diabetic individuals. Inorganic arsenic and its metabolites were measured in urine. Genotyping analysis focused on six polymorphic sites of AS3MT. Individuals with M287T and G4965C polymorphisms had higher levels of urinary DMAs(III) and were more frequently diabetic than the respective wild-type carriers, although the excess was not statistically significant. Odds ratios were 11.4 (95% confidence interval (CI) 2.2-58.8) and 8.8 (95% CI 1.6-47.3) for the combined effects of arsenic exposure >75th percentile and 287T and 4965C genotypes, respectively. Carriers of 287T and 4965C may produce more DMAs(III) and be more likely to develop diabetes when exposed to arsenic.

  1. Arsenic exposure, dietary patterns, and skin lesion risk in bangladesh: a prospective study.

    PubMed

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

    2011-02-01

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

  2. Arsenic

    MedlinePlus

    ... basis for regulation and standard setting worldwide. The current recommended limit of arsenic in drinking-water is 10 μg/litre, although this guideline value is designated as provisional because of measurement difficulties and the practical difficulties in removing arsenic ...

  3. A biological indicator of inorganic arsenic exposure using the sum of urinary inorganic arsenic and monomethylarsonic acid concentrations

    PubMed Central

    Hata, Akihisa; Kurosawa, Hidetoshi; Endo, Yoko; Yamanaka, Kenzo; Fujitani, Noboru; Endo, Ginji

    2016-01-01

    Objectives: The sum of urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations is used for the biological monitoring of occupational iAs exposure. Although DMA is a major metabolite of iAs, it is an inadequate index because high DMA levels are present in urine after seafood consumption. We estimated the urinary iAs+MMA concentration corresponding to iAs exposure. Methods: We used data from two arsenic speciation analyses of urine samples from 330 Bangladeshi with oral iAs exposure and 172 Japanese workers without occupational iAs exposure using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Results: iAs, MMA, and DMA, but not arsenobetaine (AsBe), were detected in the urine of the Bangladeshi subjects. The correlation between iAs+MMA+DMA and iAs+MMA was obtained as log (iAs+MMA) = 1.038 log (iAs+MMA+DMA) -0.658. Using the regression formula, the iAs+MMA value was calculated as 2.15 and 7.5 μg As/l, corresponding to 3 and 10 μg As/m3 of exposures, respectively. In the urine of the Japanese workers, arsenic was mostly excreted as AsBe. We used the 95th percentile of iAs+MMA (12.6 μg As/l) as the background value. The sum of the calculated and background values can be used as a biological indicator of iAs exposure. Conclusion: We propose 14.8 and 20.1 μg As/l of urinary iAs+MMA as the biological indicators of 3 and 10 μg As/m3 iAs exposure, respectively. PMID:27010090

  4. Prey-specific determination of arsenic bioaccumulation and transformation in a marine benthic fish.

    PubMed

    Zhang, Wei; Zhang, Li; Wang, Wen-Xiong

    2017-02-06

    The sediments from Chinese coastal waters contain relatively high concentrations of arsenic (As), mainly arsenate As(V), which may be transferred along the marine benthic food chain. The prey-specific determination of As bioaccumulation and transformation in marine benthic fish remains little known. In this study, we focused on a typical marine benthic food chain comprising of sediments, deposit-feeding invertebrates (polychaete Nereis succinea and clam Gafrarium tumidum) and goby fish Mugilogobius chulae. Graded exposed experiments using different As exposure durations and concentrations were conducted to examine their transformation rate and efficiency. Radiotracer techniques were used to determine the rates of As uptake (as arsenate) from seawater, assimilation from two prey and its subsequent efflux in the goby fish. We demonstrated that the two prey (polychates and clams) displayed different As biotransformation in the goby fish. Biotransformation rate was higher in the goby fish fed on the clams than on the polychaetes, and biotransformation efficiency was lower with increasing inorganic As concentration in the prey. The As overall bioaccumulation in the goby fish was very low, mainly because of the low dissolved uptake and dietary assimilation and high efflux. Combining the biotransformation and biokinetics measurements, our findings highlighted that different prey containing different As concentrations and As species resulted in the comparable As bioaccumulation in the goby fish.

  5. Prenatal Arsenic Exposure and DNA Methylation in Maternal and Umbilical Cord Blood Leukocytes

    PubMed Central

    Baccarelli, Andrea; Hoffman, Elaine; Tarantini, Letizia; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Mostofa, Golam; Hsueh, Yu-Mei; Wright, Robert O.; Christiani, David C.

    2012-01-01

    Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming. Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes. Methods: Drinking-water and urine samples were collected when women were at ≤ 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure. Results: Mean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 μg/L (range: < 1–230 μg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation. Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects. PMID:22466225

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  7. 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).

  8. 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

  9. Role of Soil-derived Dissolved Substances in Arsenic Transport and Transformation in Laboratory Experiments

    PubMed Central

    Chen, Zhangrong; Cai, Yong; Liu, Guangliang; Solo-Gabriele, Helena; Snyder, George H.; Cisar, John L.

    2011-01-01

    Dissolved substances derived from soil may interact with both soil surfaces and with arsenic and subsequently influence arsenic mobility and species transformation. The purpose of this study was to investigate arsenic transport and transformation in porous media with a specific focus on the impact of soil-derived dissolved substances, mainly consisting of inorganic colloids and dissolved organic matter (DOM), on these processes. Arsenic transport and transformation through columns, which were packed with uncoated sand (UC) or naturally coated sand (NC) and fed with arsenate (AsV) or monomethylarsonic acid (MMA) spiked influents, were investigated in the presence or absence of soil-derived dissolved substances. The presence of soil-derived inorganic colloids and/or DOM clearly enhanced As transport through the column, with the fraction of As leached out of column (referring to the total amount added) being increased from 23 to 46% (UC) and 21 to 50% (NC) in AsV experiments while 46 to 64% (UC) and 28 to 63% (NC) in MMA experiments. The association of arsenic with DOM and the competitive adsorption between arsenic and DOM could account for, at least partly, the enhanced As movement. Distinct species transformation of As during transport through soil columns was observed. When AsV was the initial species spiked in the influent solutions, only arsenite (AsIII) was detected in the effluents for UC columns; while both AsIII (dominant) and AsV were present for NC columns, with AsIII being the dominant species. When MMA was initially spiked in the influent solutions, all method detectable As species, AsIII, AsV, MMA, and dimethylarsenic acid (DMA) were present in the effluents for both soil columns. These results indicate that risk assessment associated with As contamination, particularly due to previous organoarsenical pesticide applications, should take into account the role of soil-derived dissolved substances in promoting As transport and As species transformation

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

    SciTech Connect

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

    2007-08-01

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

  11. Enrichment of arsenic transforming and resistant heterotrophic bacteria from sediments of two salt lakes in Northern Chile.

    PubMed

    Lara, José; Escudero González, Lorena; Ferrero, Marcela; Chong Díaz, Guillermo; Pedrós-Alió, Carlos; Demergasso, Cecilia

    2012-05-01

    Microbial populations are involved in the arsenic biogeochemical cycle in catalyzing arsenic transformations and playing indirect roles. To investigate which ecotypes among the diverse microbial communities could have a role in cycling arsenic in salt lakes in Northern Chile and to obtain clues to facilitate their isolation in pure culture, sediment samples from Salar de Ascotán and Salar de Atacama were cultured in diluted LB medium amended with NaCl and arsenic, at different incubation conditions. The samples and the cultures were analyzed by nucleic acid extraction, fingerprinting analysis, and sequencing. Microbial reduction of As was evidenced in all the enrichments carried out in anaerobiosis. The results revealed that the incubation factors were more important for determining the microbial community structure than arsenic species and concentrations. The predominant microorganisms in enrichments from both sediments belonged to the Firmicutes and Proteobacteria phyla, but most of the bacterial ecotypes were confined to only one system. The occurrence of an active arsenic biogeochemical cycle was suggested in the system with the highest arsenic content that included populations compatible with microorganisms able to transform arsenic for energy conservation, accumulate arsenic, produce H(2), H(2)S and acetic acid (potential sources of electrons for arsenic reduction) and tolerate high arsenic levels.

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

    SciTech Connect

    Qu, Wei Waalkes, Michael P.

    2015-02-01

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

  13. Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water

    PubMed Central

    2013-01-01

    Background Limited data exist on the contribution of dietary sources of arsenic to an individual’s total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest. Methods Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 μg/L versus ≥1 μg/L. Results As expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (≥1 μg/L). Conclusions This study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential

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

    PubMed Central

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

    2016-01-01

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

  15. Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.

    PubMed

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

    2006-08-01

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

  16. 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.

  17. Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kutty, Harikumar Sankaran; Kandasamy, Kannan; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-12-01

    We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health.

  18. Arsenic Exposure and Cancer Mortality in a US-based Prospective Cohort: the Strong Heart Study

    PubMed Central

    García-Esquinas, Esther; Pollán, Marina; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Guallar, Eliseo; Howard, Barbara; Farley, John; Yeh, Jeunliang; Best, Lyle G.; Navas-Acien, Ana

    2013-01-01

    Background Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. Prospective studies on carcinogenic effects at low-moderate arsenic levels are lacking. Methods We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians 45–74 years from Arizona, Oklahoma and North/South Dakota who participated in the Strong Heart Study in 1989–1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, 40 lymphatic/hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate and kidney cancer. Results Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8–15.6) μg/g creatinine. The adjusted hazard ratios (95% CI) comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92–1.41) for overall cancer, 1.56 (1.02–2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28–8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09–5.58) for pancreatic cancer, and 0.46 (0.22–0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. Conclusions Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate and pancreas. Impact These findings support the role of low-moderate arsenic exposure in lung, prostate and pancreas cancer development and can inform arsenic risk assessment. PMID:23800676

  19. Microbial transformations of arsenic: Mobilization from glauconitic sediments to water

    USGS Publications Warehouse

    Mumford, Adam C.; Barringer, Julia L.; Benzel, William M.; Reilly, Pamela A.; Young, L.Y.

    2012-01-01

    In the Inner Coastal Plain of New Jersey, arsenic (As) is released from glauconitic sediment to carbon- and nutrient-rich shallow groundwater. This As-rich groundwater discharges to a major area stream. We hypothesize that microbes play an active role in the mobilization of As from glauconitic subsurface sediments into groundwater in the Inner Coastal Plain of New Jersey. We have examined the potential impact of microbial activity on the mobilization of arsenic from subsurface sediments into the groundwater at a site on Crosswicks Creek in southern New Jersey. The As contents of sediments 33–90 cm below the streambed were found to range from 15 to 26.4 mg/kg, with siderite forming at depth. Groundwater beneath the streambed contains As at concentrations up to 89 μg/L. Microcosms developed from site sediments released 23 μg/L of As, and active microbial reduction of As(V) was observed in microcosms developed from site groundwater. DNA extracted from site sediments was amplified with primers for the 16S rRNA gene and the arsenate respiratory reductase gene, arrA, and indicated the presence of a diverse anaerobic microbial community, as well as the presence of potential arsenic-reducing bacteria. In addition, high iron (Fe) concentrations in groundwater and the presence of iron-reducing microbial genera suggests that Fe reduction in minerals may provide an additional mechanism for release of associated As, while arsenic-reducing microorganisms may serve to enhance the mobility of As in groundwater at this site.

  20. Transformation and Mobilization of Arsenic in the Historic Cobalt Mining Camp, Ontario, Canada.

    SciTech Connect

    Kwong,J.; Beauchemin, S.; Hossain, F.; Gould, D.

    2007-01-01

    More than eight decades of silver mining in the Cobalt mining camp of northern Ontario, Canada, have left large volumes of As-bearing mine wastes widely distributed in and along watercourses in the Cobalt area. Metal leaching from these mine wastes has led to the contamination of the area drainage with dissolved As concentrations at least an order of magnitude higher than the Canadian drinking water criterion of 0.025 mg l{sup -1}. To clarify the transformation and mobilization of arsenic in the historic mining camp, a portion of an extensive wetland located in northeast Cobalt and partially filled with historic tailings has been sampled for detailed characterization, chemical analysis and extraction tests. Field deployment of anionic exchange membranes, As sorption isotherm and desorption analyses in conjunction with chemical and mineralogical analyses indicate that: (1) the submerged tailings are likely a source instead of a sink of arsenic to the local streams; and (2) Al-minerals are the main sorbents for As with significant P competing for the available sorbing sites. Subjecting selected samples to a laboratory redox experiment complemented with X-ray absorption spectroscopic analyses confirms that changes in arsenic speciation readily occur with changes in redox conditions in the surface sediments, resulting in rapid mobilization of arsenic. Preliminary enumeration of iron- and sulfur-reducing bacteria at selected sites coupled with scanning electron microscopic analyses show that microbial sulfate reduction occurs locally in the wetland, possibly leading to co-precipitation of arsenic as a sulfide in associated with framboidal pyrite. Further detailed study of the bacteria responsible for the arsenic transformation in conjunction with arsenic speciation analysis is recommended.

  1. 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

  2. Biological monitoring of exposures to aluminium, gallium, indium, arsenic, and antimony in optoelectronic industry workers.

    PubMed

    Liao, Y-H; Yu, H-S; Ho, C-K; Wu, M-T; Yang, C-Y; Chen, J-R; Chang, C-C

    2004-09-01

    The main objective of this study was to investigate aluminum, gallium, indium, arsenic, and antimony exposures on blood and urine levels in the optoelectronic workers. One hundred seventy subjects were enrolled in this cohort study. Whole blood and urine levels were determined by inductively coupled plasma-mass spectrometry. Blood indium and urine gallium and arsenic levels in the 103 workers were significantly higher than that in 67 controls during the follow-up period. In regression models, the significant risk factors of exposure were job title, preventive equipment, Quetelet's index, sex, and education level. The findings of this study suggest that gallium, indium, and arsenic exposure levels may affect their respective levels in blood and urine. The use of clean, preventive equipment is recommended when prioritizing the administration of safety and hygiene in optoelectronics industries.

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

    SciTech Connect

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

    2009-09-01

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

  4. Influence of cooking method on arsenic retention in cooked rice related to dietary exposure.

    PubMed

    Rahman, M Azizur; Hasegawa, H; Rahman, M Arifur; Rahman, M Mahfuzur; Miah, M A Majid

    2006-10-15

    Arsenic concentration in raw rice is not only the determinant in actual dietary exposure. Though there have been many reports on arsenic content in raw rice and different tissues of rice plant, little is known about arsenic content retained in cooked rice after being cooked following the traditional cooking methods employed by the people of arsenic epidemic areas. A field level experiment was conducted in Bangladesh to investigate the influence of cooking methods on arsenic retention in cooked rice. Rice samples were collected directly from a severely arsenic affected area and also from an unaffected area, to compare the results. Rice was cooked according to the traditional methods employed by the population of subjected areas. Arsenic concentrations were 0.40+/-0.03 and 0.58+/-0.12 mg/kg in parboiled rice of arsenic affected area, cooked with excess water and 1.35+/-0.04 and 1.59+/-0.07 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. In non-parboiled rice, arsenic concentrations were 0.39+/-0.04 and 0.44+/-0.03 mg/kg in rice cooked with excess water and 1.62+/-0.07 and 1.74+/-0.05 mg/kg in gruel for BRRI dhan28 and BRRI hybrid dhan1, respectively. Total arsenic content in rice, cooked with limited water (therefore gruel was absorbed completely by rice) were 0.89+/-0.07 and 1.08+/-0.06 mg/kg (parboiled) and 0.75+/-0.04 and 1.09+/-0.06 mg/kg (non-parboiled) for BRRI dhan28 and BRRI hybrid dhan1, respectively. Water used for cooking rice contained 0.13 and 0.01 mg of As/l for contaminated and non-contaminated areas, respectively. Arsenic concentrations in cooked parboiled and non-parboiled rice and gruel of non-contaminated area were significantly lower (p<0.01) than that of contaminated area. The results imply that cooking of arsenic contaminated rice with arsenic contaminated water increases its concentration in cooked rice.

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

    PubMed

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

    2016-04-01

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

  6. Multimedia Exposures to Arsenic and Lead for Children Near an Inactive Mine Tailings and Smelter Site

    PubMed Central

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

    2016-01-01

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

  7. Arsenic Exposure and Incidence of Type 2 Diabetes in Southwestern American Indians

    PubMed Central

    Kim, Nan Hee; Mason, Clinton C.; Nelson, Robert G.; Afton, Scott E.; Essader, Amal S.; Medlin, James E.; Levine, Keith E.; Hoppin, Jane A.; Lin, Cynthia; Knowler, William C.; Sandler, Dale P.

    2013-01-01

    Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2–4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation. PMID:23504692

  8. Arsenic exposure and incidence of type 2 diabetes in Southwestern American Indians.

    PubMed

    Kim, Nan Hee; Mason, Clinton C; Nelson, Robert G; Afton, Scott E; Essader, Amal S; Medlin, James E; Levine, Keith E; Hoppin, Jane A; Lin, Cynthia; Knowler, William C; Sandler, Dale P

    2013-05-01

    Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2-4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation.

  9. 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.

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

    SciTech Connect

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

    1985-01-01

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

  11. 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

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

    SciTech Connect

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

    2014-11-15

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

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

    EPA Science Inventory

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

  14. Controlling the healthy worker survivor effect: an example of arsenic exposure and respiratory cancer.

    PubMed Central

    Arrighi, H M; Hertz-Picciotto, I

    1996-01-01

    OBJECTIVE--This investigation sought to examine whether methods proposed to control the healthy worker survivor effect would influence the shape or magnitude of the dose-response curve for respiratory cancer induced by arsenic. METHODS--Results from an unadjusted analysis are compared with results obtained by applying four different methods for control of the healthy worker survivor effect to data on arsenic exposure and respiratory cancer. The four methods are: exposure lag, adjustment for work status, cohort restriction, and the G null test. RESULTS--Cohort restriction gave erratic results depending upon the minimum years of follow up used. Exposure lag substantially increased the rate ratios and a non-linear shape (decreasing slope) compared with an unlagged analysis. Adjusting for work status (currently employed upsilon retired or otherwise not employed) yielded slightly higher rate ratios than an unadjusted analysis, with an overall shape similar to the baseline analysis. Results from the G null test procedure of Robins (1986), although not directly comparable with the baseline analysis, did show an adverse effect of exposure that seemed to reach a maximum when exposure was lagged between 10 and 20 years. CONCLUSIONS--All results confirm an adverse effect of arsenic exposure on respiratory cancer. In these data, it seems that the healthy worker survivor effect was not strong enough to mask the strong effect of arsenic exposure on respiratory cancer. Nevertheless, several methods show a stronger association between arsenic exposure and respiratory cancer after adjustment for the healthy worker survivor effect, suggesting that for weaker causal associations, studies not controlling for this source of bias will have low power to detect results. Although the G methods are theoretically the most unbiased, further work elucidating the validity of the assumptions underlying lagging, adjustment for work status, and the G methods are needed before clear recommendations

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

    SciTech Connect

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

    2008-06-15

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

  16. Environmental Fate and Exposure Assessment for Arsenic in Groundwater

    DTIC Science & Technology

    2008-08-01

    arsenic associated with pyrite , which was presumed to be detrital. Selective extractions of the Tyndall source area soil and Devens sediment...to be associated with detrital pyrite , only As(V) was detected in the solid phase. The absence of a signal for sorbed As(III) might indicate

  17. 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...

  18. APPLICATION OF PROTEOMIC METHODS TO ARSENIC EXPOSURE RESEARCH

    EPA Science Inventory

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

  19. Dose-Responsive Gene Expression Changes in Juvenile and Adult Mummichogs (Fundulus heteroclitus) After Arsenic Exposure

    PubMed Central

    Gonzalez, Horacio O.; Hu, Jianjun; Gaworecki, Kristen M.; Roling, Jonathan A.; Baldwin, William S.; Gardea-Torresdey, Jorge L.; Bain, Lisa J.

    2010-01-01

    The present study investigated arsenic's effects on mummichogs (Fundulus heteroclitus), while also examining what role that gender or exposure age might play. Adult male and female mummichogs were exposed to 172ppb, 575ppb, or 1,720ppb arsenic as sodium arsenite for 10 days immediately prior to spawning. No differences were noted in the number or viability of eggs between the groups, but there was a significant increase in deformities in 1,720ppb arsenic exposure group. Total RNA from adult livers or 6-week old juveniles was used to probe custom macroarrays for changes in gene expression. In females, 3% of the genes were commonly differentially expressed in the 172 and 575ppb exposure groups compared to controls. In the males, between 1.1-3% of the differentially expressed genes were in common between the exposure groups. Several genes, including apolipoprotein and serum amyloid precursor were commonly expressed in either a dose-responsive manner or were dose-specific, but consistent across genders. These patterns of regulation were confirmed by QPCR. These findings will provide us with a better understanding of the effects of dose, gender, and exposure age on the response to arsenic. PMID:20451245

  20. Arsenic exposure affects embryo development of sea urchin, Paracentrotus lividus (Lamarck, 1816).

    PubMed

    Gaion, Andrea; Scuderi, Alice; Pellegrini, David; Sartori, Davide

    2013-11-01

    Toxicity tests were performed with embryos of Paracentrotus lividus to investigate the toxicological effect of two arsenic species: arsenate (As(V)), expected to be more toxic, and dimethyl-arsinate (DMA) expected to be less toxic. Exposures to toxicants were performed at different developmental stages in order to identify the most sensitive phase of embryological development. Statistical analysis revealed a high significance of each factor (Molecule, Concentration and Time of exposure) and their interaction for the dependent variable "Percentage of normal-shaped plutei". In particular, the 8 cell stage was the most sensitive to arsenic; at a concentration of 50 μg L(-1) DMA proved to be more toxic than As(V), resulting in nearly 50 % of normal-shaped plutei against the 74 % recorded for As(V). Starting the administration of arsenic at the morula stage, arsenate proved to be significantly more toxic when compared to DMA.

  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. Maternal exposure to arsenic and cadmium and the risk of congenital heart defects in offspring.

    PubMed

    Jin, Xi; Tian, Xiaoxian; Liu, Zhen; Hu, Hui; Li, Xiaohong; Deng, Ying; Li, Nana; Zhu, Jun

    2016-01-01

    Hair arsenic and cadmium from 339 women with congenital heart defect (CHD)-affected pregnancies (case women) and 333 women with normal live births (control women) in China were estimated using inductively coupled plasma mass spectrometry. The median levels of hair arsenic and cadmium in the case women were 98.30 (74.30-136.30)ng/g and 14.60 (8.30-32.50)ng/g, respectively, which were significantly higher than the levels in the control group (P<0.05). Arsenic concentrations ≥62.03ng/g were associated with increased risk for almost every CHD subtype, with a dose-response relationship. However, only the group with the highest cadmium levels (≥25.85ng/g) displayed an increased risk of CHDs (AOR 1.96; 95% CI 1.24-3.09), with a 2.81-fold increase found for the occurrence of conotruncal defects in their offspring. Furthermore, an interaction between arsenic and cadmium was observed. Our findings suggest that maternal exposure to arsenic and cadmium may be a significant risk factor for CHDs in offspring. Cadmium may have an enhancing effect on the association between arsenic and the risk of CHDs in offspring.

  3. Subacute arsenic exposure through drinking water reduces the pharmacodynamic effects of ketoprofen in male rats.

    PubMed

    Ahmad, Wasif; Prawez, Shahid; Chanderashekara, H H; Tandan, Surendra Kumar; Sankar, Palanisamy; Sarkar, Souvendra Nath

    2012-03-01

    We evaluated the modulatory role of the groundwater contaminant arsenic on the pharmacodynamic responses of the nonsteroidal analgesic-antipyretic drug ketoprofen and the major pro-inflammatory mediators linked to the mechanism of ketoprofen's therapeutic effects. Rats were pre-exposed to sodium arsenite (0.4, 4 and 40 ppm) through drinking water for 28 days. The pharmacological effects of orally administered ketoprofen (5 mg/kg) were evaluated the following day. Pain, inflammation and pyretic responses were, respectively, assessed through formalin-induced nociception, carrageenan-induced inflammation and lipopolysaccharide-induced pyrexia. Arsenic inhibited ketoprofen's analgesic, anti-inflammatory and antipyretic effects. Further, arsenic enhanced cyclooxygenase-1 and cyclooxygenase-2 activities and tumor necrosis factor-α, interleukin-1β and prostaglandin-E(2) production in hind paw muscle. These results suggest a functional antagonism of ketoprofen by arsenic. This may relate to arsenic-mediated local release of tumor necrosis factor-α and interleukin-1β, which causes cyclooxygenase induction and consequent prostaglandin-E(2) release. In conclusion, subacute exposure to environmentally relevant concentrations of arsenic through drinking water may aggravate pain, inflammation and pyrexia and thereby, may reduce the therapeutic efficacy of ketoprofen.

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

    PubMed

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

    2014-04-01

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

  5. Health burden of skin lesions at low arsenic exposure through groundwater in Pakistan. Is river the source?

    SciTech Connect

    Fatmi, Zafar; Azam, Iqbal; Ahmed, Faiza; Kazi, Ambreen; Gill, Albert Bruce; Kadir, Muhmmad Masood; Ahmed, Mubashir; Ara, Naseem; Janjua, Naveed Zafar

    2009-07-15

    A significant proportion of groundwater in south Asia is contaminated with arsenic. Pakistan has low levels of arsenic in groundwater compared with China, Bangladesh and India. A representative multi-stage cluster survey conducted among 3874 persons {>=}15 years of age to determine the prevalence of arsenic skin lesions, its relation with arsenic levels and cumulative arsenic dose in drinking water in a rural district (population: 1.82 million) in Pakistan. Spot-urine arsenic levels were compared among individuals with and without arsenic skin lesions. In addition, the relation of age, body mass index, smoking status with arsenic skin lesions was determined. The geographical distribution of the skin lesions and arsenic-contaminated wells in the district were ascertained using global positioning system. The total arsenic, inorganic and organic forms, in water and spot-urine samples were determined by atomic absorption spectrophotometry. The prevalence of skin lesions of arsenic was estimated for complex survey design, using surveyfreq and surveylogistic options of SAS 9.1 software.The prevalence of definitive cases i.e. hyperkeratosis of both palms and soles, was 3.4 per 1000 and suspected cases i.e. any sign of arsenic skin lesions (melanosis and/or keratosis), were 13.0 per 1000 among {>=}15-year-old persons in the district. Cumulative arsenic exposure (dose) was calculated from levels of arsenic in water and duration of use of current drinking water source. Prevalence of skin lesions increases with cumulative arsenic exposure (dose) in drinking water and arsenic levels in urine. Skin lesions were 2.5-fold among individuals with BMI <18.5 kg/m{sup 2}. Geographically, more arsenic-contaminated wells and skin lesions were alongside Indus River, suggests a strong link between arsenic contamination of groundwater with proximity to river.This is the first reported epidemiological and clinical evidence of arsenic skin lesions due to groundwater in Pakistan. Further

  6. Urinary 8-hydroxydeoxyguanosine and urothelial carcinoma risk in low arsenic exposure area

    SciTech Connect

    Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

    2008-01-01

    Arsenic is a well-documented human carcinogen and is known to cause oxidative stress in cultured cells and animals. A hospital-based case-control study was conducted to evaluate the relationship among the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), the arsenic profile, and urothelial carcinoma (UC). Urinary 8-OHdG was measured by using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The urinary species of inorganic arsenic and their metabolites were analyzed by high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). This study showed that the mean urinary concentration of total arsenics was significantly higher, at 37.67 {+-} 2.98 {mu}g/g creatinine, for UC patients than for healthy controls of 21.10 {+-} 0.79 {mu}g/g creatinine (p < 0.01). Urinary 8-OHdG levels correlated with urinary total arsenic concentrations (r = 0.19, p < 0.01). There were significantly higher 8-OHdG levels, of 7.48 {+-} 0.97 ng/mg creatinine in UC patients, compared to healthy controls of 5.95 {+-} 0.21 ng/mg creatinine. Furthermore, female UC patients had higher 8-OHdG levels of 9.22 {+-} 0.75 than those of males at 5.76 {+-} 0.25 ng/mg creatinine (p < 0.01). Multiple linear regression analyses revealed that high urinary 8-OHdG levels were associated with increased total arsenic concentrations, inorganic arsenite, monomethylarsonic acid (MMA), and dimethylarsenate (DMA) as well as the primary methylation index (PMI) even after adjusting for age, gender, and UC status. The results suggest that oxidative DNA damage was associated with arsenic exposure, even at low urinary level of arsenic.

  7. Genetic identification of arsenate reductase and arsenite oxidase in redox transformations carried out by arsenic metabolising prokaryotes - A comprehensive review.

    PubMed

    Kumari, Nisha; Jagadevan, Sheeja

    2016-11-01

    Arsenic (As) contamination in water is a cause of major concern to human population worldwide, especially in Bangladesh and West Bengal, India. Arsenite (As(III)) and arsenate (As(V)) are the two common forms in which arsenic exists in soil and groundwater, the former being more mobile and toxic. A large number of arsenic metabolising microorganisms play a crucial role in microbial transformation of arsenic between its different states, thus playing a key role in remediation of arsenic contaminated water. This review focuses on advances in biochemical, molecular and genomic developments in the field of arsenic metabolising bacteria - covering recent developments in the understanding of structure of arsenate reductase and arsenite oxidase enzymes, their gene and operon structures and their mechanism of action. The genetic and molecular studies of these microbes and their proteins may lead to evolution of successful strategies for effective implementation of bioremediation programs.

  8. Maternal exposure to arsenic, cadmium, lead, and mercury and neural tube defects in offspring

    SciTech Connect

    Brender, Jean D. . E-mail: jdbrender@aol.com; Suarez, Lucina; Felkner, Marilyn; Gilani, Zunera; Stinchcomb, David; Moody, Karen; Henry, Judy; Hendricks, Katherine

    2006-05-15

    Arsenic, cadmium, lead, and mercury are neurotoxins, and some studies suggest that these elements might also be teratogens. Using a case-control study design, we investigated the relation between exposure to these heavy metals and neural tube defects (NTDs) in offspring of Mexican-American women living in 1 of the 14 Texas counties bordering Mexico. A total of 184 case-women with NTD-affected pregnancies and 225 control-women with normal live births were interviewed about their environmental and occupational exposures during the periconceptional period. Biologic samples for blood lead and urinary arsenic, cadmium, and mercury were also obtained for a subset of these women. Overall, the median levels of these biomarkers for heavy metal exposure did not differ significantly (P>0.05) between case- and control-women. However, among women in the highest income group, case-women were nine times more likely (95% confidence interval (CI) 1.4-57) than control-women to have a urinary mercury >=5.62{mu}g/L. Case-women were 4.2 times more likely (95% CI 1.1-16) to report burning treated wood during the periconceptional period than control-women. Elevated odds ratios (ORs) were observed for maternal and paternal occupational exposures to arsenic and mercury, but the 95% CIs were consistent with unity. The 95% CIs of the ORs were also consistent with unity for higher levels of arsenic, cadmium, lead, and mercury in drinking water and among women who lived within 2 miles at the time of conception to industrial facilities with reported emissions of any of these heavy metals. Our findings suggest that maternal exposures to arsenic, cadmium, or lead are probably not significant risk factors for NTDs in offspring. However, the elevated urinary mercury levels found in this population and exposures to the combustion of treated wood may warrant further investigation.

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

    PubMed

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

    2012-01-01

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

  10. LACK OF DNA SINGLE STRAND BREAKS IN A LUNG EPITHELIAL CELL LINE AFTER EXPOSURE TO ARSENIC

    EPA Science Inventory

    Arsenic (As) is a carcinogen whose most important target organs include the skin and lungs. Exposure can occur via water ingestion, or inhalation, as As is a by-product of fossil fuel combustion and other industrial activities. The carcinogenic mechanism of action for As remains ...

  11. 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...

  12. SPATIAL DISTRIBUTIONS OF ARSENIC EXPOSURE AND MINING COMMUNITIES FROM NHEXAS ARIZONA

    EPA Science Inventory

    Within the context of the National Human Exposure Assessment Survey (NHEXAS), metals were evaluated in the air, soil, dust, water, food, beverages, and urine of a single respondent. Potential doses were calculated for five metals including arsenic. In this paper, we seek to val...

  13. ESTIMATING RESIDENTIAL EXPOSURE TO DRINKING WATER ARSENIC IN INNER MONGOLIA, CHINA FOR EPIDEMIOLOGIC STUDIES

    EPA Science Inventory

    ESTIMATING RESIDENTIAL EXPOSURE TO DRINKING WATER ARSENIC IN INNER MONGOLIA, CHINA FOR EPIDEMIOLOGIC STUDIES

    Richard Kwok1, Pauline Mendola1 Zhixiong Ning2, Zhiyi Liu2 and Judy Mumford1

    1) Epidemiology and Biomarkers Branch, Human Studies Division, NHEERL, US EPA, R...

  14. PREGNANCY AND PERINATAL OUTCOMES IN RELATION TO DRINKING WATER ARSENIC EXPOSURE IN BAMEN, INNER MONGOLIA, CHINA

    EPA Science Inventory

    Pregnancy and Perinatal Outcomes in Relation to Drinking Water Arsenic Exposure in BaMen, Inner Mongolia, China
    Danelle T. Lobdell, Zhixiong Ning, Richard K. Kwok, Judy Mumford, Zhi Yi Liu, Pauline Mendola

    Introduction: Close to 40 million people worldwide are exposed t...

  15. Soil-Root Processes Responsible for Arsenic Uptake in Rice: A Route of Human Exposure

    NASA Astrophysics Data System (ADS)

    Seyfferth, A.; Fendorf, S.

    2010-12-01

    Arsenic contamination of groundwater is causing the largest mass poisoning in history, but we are only beginning to understand the extent of human exposure through contaminated food. Although second to drinking water in terms of human exposure, the consumption of As-laden food, such as rice, can be a significant portion of daily As exposure especially for populations already exposed through drinking water. Arsenic contamination of soils and groundwater is widespread In South and Southeast Asia, which is also one of the largest rice-growing regions of the world. As the demand for food has increased, so too has the use of irrigation practices to meet food demand, and much of this is via water contaminated with arsenic. In order to accurately predict human exposure to arsenic through rice consumption, we must first understand the processes that affect As dynamics in the rhizosphere and thus uptake by rice. Here, we examine As cycling in the rhizosphere, As distribution on and uptake by rice roots, the influence of Fe dynamics on As uptake, and mitigation strategies to reduce concentrations of As in rice grains.

  16. 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.

  17. 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.

  18. 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.

  19. Transformation of arsenic in the presence of cow dung and arsenic sludge disposal and management strategy in Bangladesh

    NASA Astrophysics Data System (ADS)

    Rahman, Mohammad Azizur; Jalil, Md. Abdul; Ali, M. Ashraf

    2014-10-01

    With increasing use of arsenic (As) removal units for treatment of As-contaminated groundwater in rural Bangladesh, concerns have been raised regarding safe disposal of the As-rich wastes from such units and possible contamination of the environment. In the absence of any clear guideline for safe disposal of wastes generated from As removal units, the wastes are usually disposed of in the open environment, often on cow dung beds in the backyard. Short term (up to 6 weeks) batch experiments performed in this study suggest that bio-chemical (e.g., bio-methylation) processes in the presence of only fresh cow dung may lead to a significant removal of As, both from aqueous solution and As-rich treatment wastes. Arsenic removal appears to increase with decreasing As to cow dung weight ratio. This study also suggests that arsenate transforms to arsenite before removal from aqueous As solution in the presence of cow dung. In most cases majority of As removal takes place during first few days. Removal of As under cap-open (to facilitate aerobic condition) and cap-closed conditions (to facilitate aerobic condition) were found to be similar. No significant variation was observed in the removal As from aqueous solution and from treatment wastes (As bound to iron solids). This study concludes that disposal of As-rich treatment wastes to cow dung pits could be an effective option of As sludge disposal and management in rural areas of Bangladesh.

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

    PubMed Central

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

    2002-01-01

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

  1. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

    PubMed

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.

  2. Arsenic and ultraviolet radiation exposure: melanoma in a New Mexico non-Hispanic white population.

    PubMed

    Yager, Janice W; Erdei, Esther; Myers, Orrin; Siegel, Malcolm; Berwick, Marianne

    2016-06-01

    Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 μg/L (±3.67) vs. 3.47 μg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (μg/L).

  3. Further studies on aberrant gene expression associated with arsenic-induced malignant transformation in rat liver TRL1215 cells

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Benbrahim-Tallaa, Lamia; Qian Xun; Yu, Limei; Xie Yaxiong; Boos, Jennifer; Qu Wei; Waalkes, Michael P.

    2006-11-01

    Chronic arsenic exposure of rat liver epithelial TRL1215 cells induced malignant transformation in a concentration-dependent manner. To further define the molecular events of these arsenic-transformed cells (termed CAsE cells), gene expressions associated with arsenic carcinogenesis or influenced by methylation were examined. Real-time RT-PCR showed that at carcinogenic concentrations (500 nM, and to a less extent 250 nM of arsenite), the expressions of {alpha}-fetoprotein (AFP), Wilm's tumor protein-1 (WT-1), c-jun, c-myc, H-ras, c-met and hepatocyte growth factor, heme oxygenase-1, superoxide dismutase-1, glutathione-S-transferase-{pi} and metallothionein-1 (MT) were increased between 3 to 12-fold, while expressions of insulin-like growth factor II (IGF-II) and fibroblast growth factor receptor (FGFR1) were essentially abolished. These changes were not significant at the non-carcinogenic concentration (125 nM), except for IGF-II. The positive cell-cycle regulators cyclin D1 and PCNA were overexpressed in CAsE cells, while the negative regulators p21 and p16 were suppressed. Western-blot confirmed increases in AFP, WT-1, cyclin D1 and decreases in p16 and p21 protein in CAsE cells. The CAsE cells over-expressed MT but the demethylating agent 5-aza-deoxycytidine (5-aza-dC, 2.5 {mu}M, 72 h) stimulated further MT expression. 5-Aza-deoxycytidine restored the loss of expression of p21 in CAsE cells to control levels, but did not restore the expression of p16, IGF-II, or FGFR1, indicating the loss of expression of these genes is due to factors other than DNA methylation changes. Overall, an intricate variety of gene expression changes occur in arsenic-induced malignant transformation of liver cells including oncogene activation and alterations in expression of genes critical to growth regulation.

  4. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development.

    PubMed

    Caldwell, Katharine E; Labrecque, Matthew T; Solomon, Benjamin R; Ali, Abdulmehdi; Allan, Andrea M

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

  5. Prenatal arsenic exposure alters the programming of the glucocorticoid signaling system during embryonic development

    PubMed Central

    Caldwell, Katharine E.; Labrecque, Matthew T.; Solomon, Benjamin R.; Ali, Abdulmehdi; Allan, Andrea M.

    2015-01-01

    The glucocorticoid system, which plays a critical role in a host of cellular functions including mood disorders and learning and memory, has been reported to be disrupted by arsenic. In previous work we have developed and characterized a prenatal moderate arsenic exposure (50 ppb) model and identified several deficits in learning and memory and mood disorders, as well as alterations within the glucocorticoid receptor signaling system in the adolescent mouse. In these present studies we assessed the effects of arsenic on the glucocorticoid receptor (GR) pathway in both the placenta and the fetal brain in response at two critical periods, embryonic days 14 and 18. The focus of these studies was on the 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2) which play a key role in glucorticoid synthesis, as well as the expression and set point of the GR negative feedback regulation. Negative feedback regulation is established early in development. At E14 we found arsenic exposure significantly decreased expression of both protein and message in brain of GR and the 11β-HSD1, while 11β-HSD2 enzyme protein levels were increased but mRNA levels were decreased in the brain. These changes in brain protein continued into the E18 time point, but mRNA levels were no longer significantly altered. Placental HSD11B2 mRNA was not altered by arsenic treatment but protein levels were elevated at E14. GR placental protein levels were decreased at E18 in the arsenic exposed condition. This suggests that arsenic exposure may alter GR expression levels as a consequence of a prolonged developmental imbalance between 11β-HSD1 and 11β-HSD2 protein expression despite decreased 11HSDB2 mRNA. The suppression of GR and the failure to turn down 11β-HSD2 protein expression during fetal development may lead to an altered set point for GR signaling throughout adulthood. To our knowledge, these studies are the first to demonstrate that gestational exposure to moderate levels of

  6. 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

  7. Speciated arsenic concentrations, exposure, and associated health risks for rice and bulgur.

    PubMed

    Sofuoglu, Sait C; Güzelkaya, Hilal; Akgül, Özlem; Kavcar, Pınar; Kurucaovalı, Filiz; Sofuoglu, Aysun

    2014-02-01

    Arsenic species were determined in rice and bulgur samples that were collected from 50 participants who also supplied exposure related information through a questionnaire survey. Speciation analysis was conducted using an HPLC-ICP-MS system. Ingestion exposure to arsenic and associated health risks were assessed by combining the concentration and questionnaire data both for individual participants and the subject population. Inorganic arsenic dominated both in rice and bulgur but concentrations were about an order of magnitude higher in rice (160±38 ng/g) than in bulgur. Because participants also consumed more rice than bulgur, exposures were significantly higher for rice resulting in carcinogenic risks above acceptable level for 53% and 93% of the participants when the in-effect and the proposed potencies were used, respectively, compared to 0% and 5% for bulgur. An inorganic arsenic standard for rice would be useful to lower the risks while public awareness about the relation between excessive rice consumption and health risks is built, and bulgur consumption is promoted.

  8. 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...

  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. 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. Exposure to non‐arsenic pesticides is associated with lymphoma among farmers in Spain

    PubMed Central

    van Balen, E; Font, R; Cavallé, N; Font, L; Garcia‐Villanueva, M; Benavente, Y; Brennan, P; de Sanjose, S

    2006-01-01

    Objectives To estimate the risk of lymphoma among farmers in Spain. Methods This is a multicentre case control study conducted in Spain. Cases were subjects diagnosed with lymphoma according to the World Health Organization (WHO) classification in four hospitals between 1998–2002. Hospital controls were frequency matched to the cases by sex, age, and centre. All subjects were interviewed about jobs ever held in lifetime for at least one year and the exposures in those jobs were recorded. The risk of lymphomas among subjects ever having had a job as a farmer was compared with all other occupations. Farmers were analysed according to the type of farming job performed: crop farming, animal farming, and general farming. Occupational exposure was summarised into 15 main categories: organic dust, radiation, contact with animals, PAH, non‐arsenic pesticides (carbamates, organophosphates, chlorinated hydrocarbons, triazines and triazoles, phenoxy herbicides, chlorophenols, dibenzodioxin, and dibenzofuran), arsenic pesticides, contact with meat, contact with children, solvents, asbestos, soldering fumes, organic colourants, polychlorinated biphenyls, ethylene oxide, and hair dyes. Results Although farmers were not at an increased risk of lymphoma as compared with all other occupations, farmers exposed to non‐arsenic pesticides were found to be at increased risk of lymphoma (OR = 1.8, 95% CI 1.1 to 2). This increased risk was observed among farmers working exclusively either as crop farmers or as animal farmers (OR = 2.8, 95% CI 1.3 to 5.8). Risk was highest for exposure to non‐arsenic pesticides for over nine years (OR = 2.4, 95% CI 1.2 to 2.8). Conclusions Long term exposure to non‐arsenic pesticides may induce lymphomagenesis among farmers. PMID:16757510

  12. Arsenic Exposure and Cell-Mediated Immunity in Pre-School Children in Rural Bangladesh

    PubMed Central

    Ahmed, Sultan; Moore, Sophie E.; Kippler, Maria; Gardner, Renee; Hawlader, M. D. H.; Wagatsuma, Yukiko; Raqib, Rubhana; Vahter, Marie

    2014-01-01

    Prenatal arsenic exposure has been associated with reduced thymic index and increased morbidity in infants, indicating arsenic-related impaired immune function. We aimed at elucidating potential effects of pre- and postnatal arsenic exposure on cell-mediated immune function in pre-school aged children. Children born in a prospective mother-child cohort in rural Bangladesh were followed up at 4.5 years of age (n = 577). Arsenic exposure was assessed by concentrations of arsenic metabolites (U-As) in child urine and maternal urine during pregnancy, using high-performance liquid chromatography online with inductively coupled plasma mass spectrometry. For assessment of delayed type hypersensitivity response, an intradermal injection of purified protein derivative (PPD) was given to Bacillus Calmette-Guerin vaccinated children. The diameter (mm) of induration was measured after 48–72 h. Plasma concentrations of 27 cytokines were analyzed by a multiplex cytokine assay. Children's concurrent, but not prenatal, arsenic exposure was associated with a weaker response to the injected PPD. The risk ratio (RR) of not responding to PPD (induration <5 mm) was 1.37 (95% confidence interval (CI): 1.07, 1.74) in children in the highest quartile of U-As (range 126–1228 μg/l), compared with the lowest (range 12–34 μg/l). The p for trend across the quartiles was 0.003. The association was stronger in undernourished children. Children's U-As in tertiles was inversely associated with two out of 27 cytokines only, i.e., IL-2 and TNF-α, both Th1 cytokines (in the highest tertile, regression coefficients (95% CI): −1.57 (−2.56, −0.57) and −4.53 (−8.62, −0.42), respectively), but not with Th2 cytokines. These associations were particularly strong in children with recent infections. In conclusion, elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines. PMID:24924402

  13. Environmental Fate and Exposure Assessment for Arsenic in Groundwater (Addendum)

    DTIC Science & Technology

    2010-06-01

    orpiment (As2S3) and amorphous and crystalline iron sulfide phases (mackinawite (FeS), greigite (Fe3S4), and pyrite (FeS2)). Iron, arsenic, and sulfur...Fig. 1). At pH 3 and room temperature, greigite with a small fraction of pyrite was precipitated from Fe2+ + S2- solutions when the molar ratio...amorphous solid with emergent XRD reflections of pyrite (FeS2) after 7 d of aging at pH 4 (exp. 2.3) In synthesis experiments with Fe3++ S2- at pH 3

  14. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh.

    PubMed

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T; Desvarieux, Moise; Ahsan, Habibul; Chen, Yu

    2014-05-01

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.

  15. 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...

  16. Dietary exposure of the Italian population to inorganic arsenic: The 2012-2014 Total Diet Study.

    PubMed

    Cubadda, Francesco; D'Amato, Marilena; Aureli, Federica; Raggi, Andrea; Mantovani, Alberto

    2016-12-01

    Dietary exposure of the Italian population to inorganic arsenic has been assessed in the national Total Diet Study (TDS) carried out in 2012-2014. Within the TDS, food samples (>3000) were collected to be representative of the whole diet of the population, prepared as consumed, and pooled into 51 food groups, thus modelling the Italian diet. Inorganic arsenic was determined by HPLC-ICP-MS after chemical extraction and quantified in all samples. Occurrence data were combined with national individual consumption data to estimate mean and high level dietary exposure of the general population and of population subgroups according to age and gender, both at the national level and for each of the four main geographical areas of Italy. The intakes assessed are in the lower range of iAs exposure estimates in other European countries carried out without the support of the TDS approach. However, taking the lower limit of the BMDL01 range established by the EFSA as reference point, the margins of exposure are <2 for the mean intake in infants and toddlers and <1 for the 95th percentile intakes in all younger age groups. Our results indicate the goal to check and further reduce the dietary exposure to inorganic arsenic.

  17. Association of soil arsenic and nickel exposure with cancer mortality rates, a town-scale ecological study in Suzhou, China.

    PubMed

    Chen, Kai; Liao, Qi Lin; Ma, Zong Wei; Jin, Yang; Hua, Ming; Bi, Jun; Huang, Lei

    2015-04-01

    Heavy metals and arsenic are well-known carcinogens. However, few studies have examined whether soil heavy metals and arsenic concentrations associate with cancer in the general population. In this ecological study, we aimed to evaluate the association of heavy metals and arsenic in soil with cancer mortality rates during 2005-2010 in Suzhou, China, after controlling for education and smoking prevalence. In 2005, a total of 1683 soil samples with a sampling density of one sample every 4 km(2) were analyzed. Generalized linear model with a quasi-Poisson regression was applied to evaluate the association between town-scale cancer mortality rates and soil heavy metal concentrations. Results showed that soil arsenic exposure had a significant relationship with colon, gastric, kidney, lung, and nasopharyngeal cancer mortality rates and soil nickel exposure was significantly associated with liver and lung cancer. The associations of soil arsenic and nickel exposure with colon, gastric, kidney, and liver cancer in male were higher than those in female. The observed associations of soil arsenic and nickel with cancer mortality rates were less sensitive to alternative exposure metrics. Our findings would contribute to the understanding of the carcinogenic effect of soil arsenic and nickel exposure in general population.

  18. Arsenic Exposure and Prevalence of the Varicella Zoster Virus in the United States: NHANES (2003–2004 and 2009–2010)

    PubMed Central

    Cardenas, Andres; Smit, Ellen; Houseman, E. Andres; Kerkvliet, Nancy I.; Bethel, Jeffrey W.

    2015-01-01

    Background Arsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide. Objective We evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S. population. Methods We analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2009–2010 pooled survey cycles. Participants were eligible if they were 6–49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine. Results The overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively. Conclusions In this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S. population. This finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms. Citation Cardenas A, Smit E, Houseman EA, Kerkvliet NI, Bethel JW, Kile ML. 2015. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003–2004 and 2009–2010). Environ Health Perspect 123:590–596;

  19. Persistent Exposure to Arsenic via Drinking Water in Rural Bangladesh Despite Major Mitigation Efforts

    PubMed Central

    Gardner, Renee; Hamadani, Jena; Grandér, Margaretha; Tofail, Fahmida; Nermell, Barbro; Palm, Brita; Kippler, Maria

    2011-01-01

    Objectives. Elevated arsenic levels in tube-well water in Bangladesh have prompted extensive mitigation projects. We evaluated the effectiveness of long-term mitigation efforts by longitudinally measuring arsenic exposure in pregnant women and their children, the most susceptible population groups. Methods. The study was nested in a population-based nutrition intervention in Matlab, Bangladesh. Mother–child pairs (n = 1951) were followed from 2001 to 2003, beginning in early gestation and continuing to 5 years postpartum. We measured arsenic concentrations in urine (U-As) of the 5-year-old children by using high-performance liquid chromatography online with hydride generation and inductively coupled plasma mass spectrometry and compared them with earlier childhood U-As and maternal U-As during pregnancy. Results. Children had elevated U-As at 5 years old (median = 51 μg/L, 5th–95th percentiles = 16–355 μg/L), and U-As distribution was similar to that observed in the mothers during gestation. Children's U-As at 5 years old significantly correlated with their U-As at 1.5 years old and to maternal U-As during early and late gestation. Conclusions. Despite major mitigation efforts, arsenic exposure remains highly elevated in rural Bangladesh. Further mitigation strategies are required and must be rigorously evaluated for long-term efficacy. PMID:21778503

  20. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    SciTech Connect

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek; Binukumar, B.K.; Gill, Kiran Dip; Flora, Swaran J.S.

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  1. 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.

  2. Maternal/fetal metabolomes appear to mediate the impact of arsenic exposure on birth weight: A pilot study.

    PubMed

    Wei, Yongyue; Shi, Qianwen; Wang, Zhaoxi; Zhang, Ruyang; Su, Li; Quamruzzaman, Quazi; Rahman, Mahmuder; Chen, Feng; Christiani, David C

    2016-12-14

    Arsenic exposure has been associated with low birth weight. However, the underlying mechanisms are not well understood. Alterations to metabolites may act as causal mediators of the effect of arsenic exposure on low birth weight. This pilot study aimed to explore the role of metabolites in mediating the association of arsenic exposure on infant birth weight. Study samples were selected from a well-established prospectively enrolled cohort in Bangladesh comprising 35 newborns and a subset of 20 matched mothers. Metabolomics profiling was performed on 35 cord blood samples and 20 maternal peripheral blood samples collected during the second trimester of pregnancy. Inorganic arsenic (iAs) exposure was evaluated via cord blood samples and maternal toenail samples collected during the first trimester. Multiple linear regression and mediation analyses were used to explore the relationship between iAs exposure, metabolite alterations, and low birth weight. Cord blood arsenic level was correlated with elevated levels of 17-methylstearate, laurate (12:0) and 4-vinylphenol sulfate along with lower birth weight. Prenatal maternal toenail iAs level was associated with two peripheral blood metabolites (butyrylqlycine and tartarate), which likely contributed to higher cord blood iAs levels both independently and interactively. Findings of this pilot study indicate that both intrauterine and maternal peripheral blood metabolites appear to influence the toxic effect of inorganic arsenic exposure on low birth weight.Journal of Exposure Science and Environmental Epidemiology advance online publication, 14 December 2016; doi:10.1038/jes.2016.74.

  3. 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

  4. DEVELOPING A TECHNICAL BASIS FOR REDUCING RISK FROM ARSENIC EXPOSURE IN WATER RESOURCES ACROSS THE UNITED STATES

    EPA Science Inventory

    Successful prevention of public exposure to arsenic in ground-water resources impacted by natural sources or contaminated sites is dependent on scientifically-based strategies for site remediation and water resource management. Research within the National Risk Management Resear...

  5. 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:...

  6. 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.

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

    PubMed Central

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

    2014-01-01

    Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7,843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (−10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by >47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and >41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by short-term changes in drinking water As. PMID:24486435

  8. 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.

  9. 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).

  10. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

    SciTech Connect

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Islam, Tariqul; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T.; Desvarieux, Moise; and others

    2014-05-01

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT

  11. Bacillus flexus strain As-12, a new arsenic transformer bacterium isolated from contaminated water resources.

    PubMed

    Jebeli, Mohammad Ahmadi; Maleki, Afshin; Amoozegar, Mohammad Ali; Kalantar, Enayatollah; Izanloo, Hassan; Gharibi, Fardin

    2017-02-01

    A total of 14 arsenic-resistant bacteria were isolated from an arsenic-contaminated travertine spring water in the central district of Qorveh county, Kurdistan Province, Iran. One of strains designated As-12 was selected for further investigation because of its ability to transform arsenic. The strain was identified by cultural, morphological and biochemical tests, and 16S rRNA gene sequencing. Finally, the growth characteristics of the isolate were investigated in a chemically defined medium which included varied ranges of environmental factors such as pH, temperature and salinity. Moreover, the resistance of this strain to some heavy metals was evaluated. The bacterium was a Gram-positive, endospore-forming with all other characteristics of the genus Bacillus. It revealed maximum similarity at the 16S rRNA gene level with Bacillus flexus. The optimum growth of the strain was observed at 38 °C, pH 9 and 2% salinity. This strain was resistant to heavy metals such as zinc, chromium, lead, nickel, copper, mercuric and cadmium at concentrations of 15 mM, 15.5 mM, 11.5 mM, 12 mM, 11 mM, 5.5 mM, and 1 mM, respectively. The isolated bacterium was able to reduce As (V) to As (III) (about 28%) and oxidize As (III) to As (V) (about 45%) after 48 h of incubation at 37 °C. In conclusion, Bacillus flexus strain As-12, was identified as an arsenic transformer, for the first time.

  12. Bhas 42 cell transformation activity of cigarette smoke condensate is modulated by selenium and arsenic.

    PubMed

    Han, Sung Gu; Pant, Kamala; Bruce, Shannon W; Gairola, C Gary

    2016-04-01

    Cigarette smoking remains a major health risk worldwide. Development of newer tobacco products requires the use of quantitative toxicological assays. Recently, v-Ha-ras transfected BALB/c3T3 (Bhas 42) cell transformation assay was established that simulates the two-stage animal tumorigenesis model and measures tumor initiating and promoting activities of chemicals. The present study was performed to assess the feasibility of using this Bhas 42 cell transformation assay to determine the initiation and promotion activities of cigarette smoke condensate (CSC) and its water soluble fraction. Further, the modulating effects of selenium and arsenic on cigarette smoke-induced cell transformation were investigated. Dimethyl sulfoxide (DMSO) and water extracts of CSC (CSC-D and CSC-W, respectively) were tested at concentrations of 2.5-40 µg mL(-1) in the initiation or promotion assay formats. Initiation protocol of the Bhas 42 assay showed a 3.5-fold increase in transformed foci at 40 µg mL(-1) of CSC-D but not CSC-W. The promotion phase of the assay yielded a robust dose response with CSC-D (2.5-40 µg mL(-1)) and CSC-W (20-40 µg mL(-1)). Preincubation of cells with selenium (100 nM) significantly reduced CSC-induced increase in cell transformation in initiation assay. Co-treatment of cells with a sub-toxic dose of arsenic significantly enhanced cell transformation activity of CSC-D in promotion assay. The results suggest a presence of both water soluble and insoluble tumor promoters in CSC, a role of oxidative stress in CSC-induced cell transformation, and usefulness of Bhas 42 cell transformation assay in comparing tobacco product toxicities and in studying the mechanisms of tobacco carcinogenesis.

  13. 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

  14. Current status of arsenic exposure and social implication in the Mekong River basin of Cambodia.

    PubMed

    Phan, Kongkea; Kim, Kyoung-Woong; Huoy, Laingshun; Phan, Samrach; Se, Soknim; Capon, Anthony Guy; Hashim, Jamal Hisham

    2016-06-01

    To evaluate the current status of arsenic exposure in the Mekong River basin of Cambodia, field interview along with urine sample collection was conducted in the arsenic-affected area of Kandal Province, Cambodia. Urine samples were analyzed for total arsenic concentrations by inductively coupled plasma mass spectrometry. As a result, arsenicosis patients (n = 127) had As in urine (UAs) ranging from 3.76 to 373 µg L(-1) (mean = 78.7 ± 69.8 µg L(-1); median = 60.2 µg L(-1)). Asymptomatic villagers (n = 108) had UAs ranging from 5.93 to 312 µg L(-1) (mean = 73.0 ± 52.2 µg L(-1); median = 60.5 µg L(-1)). About 24.7 % of all participants had UAs greater than 100 µg L(-1) which indicated a recent arsenic exposure. A survey found that females and adults were more likely to be diagnosed with skin sign of arsenicosis than males and children, respectively. Education level, age, gender, groundwater drinking period, residence time in the village and amount of water drunk per day may influence the incidence of skin signs of arsenicosis. This study suggests that residents in Kandal study area are currently at risk of arsenic although some mitigation has been implemented. More commitment should be made to address this public health concern in rural Cambodia.

  15. Prenatal Arsenic Exposure and Birth Outcomes among a Population Residing near a Mining-Related Superfund Site

    PubMed Central

    Henn, Birgit Claus; Ettinger, Adrienne S.; Hopkins, Marianne R.; Jim, Rebecca; Amarasiriwardena, Chitra; Christiani, David C.; Coull, Brent A.; Bellinger, David C.; Wright, Robert O.

    2016-01-01

    Background: Limited epidemiologic data exist on prenatal arsenic exposure and fetal growth, particularly in the context of co-exposure to other toxic metals. Objective: We examined whether prenatal arsenic exposure predicts birth outcomes among a rural U.S. population, while adjusting for exposure to lead and manganese. Methods: We collected maternal and umbilical cord blood samples at delivery from 622 mother–infant pairs residing near a mining-related Superfund site in Northeast Oklahoma. Whole blood arsenic, lead, and manganese were measured using inductively coupled plasma mass spectrometry. We modeled associations between arsenic concentrations and birth weight, gestational age, head circumference, and birth weight for gestational age. Results: Median (25th–75th percentile) maternal and umbilical cord blood metal concentrations, respectively, were as follows: arsenic, 1.4 (1.0–2.3) and 2.4 (1.8–3.3) μg/L; lead, 0.6 (0.4–0.9) and 0.4 (0.3–0.6) μg/dL; manganese, 22.7 (18.8–29.3) and 41.7 (32.2–50.4) μg/L. We estimated negative associations between maternal blood arsenic concentrations and birth outcomes. In multivariable regression models adjusted for lead and manganese, an interquartile range increase in maternal blood arsenic was associated with –77.5 g (95% CI: –127.8, –27.3) birth weight, –0.13 weeks (95% CI: –0.27, 0.01) gestation, –0.22 cm (95% CI: –0.42, –0.03) head circumference, and –0.14 (95% CI: –0.24, –0.04) birth weight for gestational age z-score units. Interactions between arsenic concentrations and lead or manganese were not statistically significant. Conclusions: In a population with environmental exposure levels similar to the U.S. general population, maternal blood arsenic was negatively associated with fetal growth. Given the potential for relatively common fetal and early childhood arsenic exposures, our finding that prenatal arsenic can adversely affect birth outcomes is of considerable public health

  16. Vascular leakage induced by exposure to arsenic via increased production of NO, hydroxyl radical and peroxynitrite.

    PubMed

    Chen, Shih-Chieh; Chen, Wei-Chi

    2008-04-01

    Previous studies have shown that in situ exposure to arsenic induced increased vascular leakage. However, the underlying mechanism remains unclear. Reactive nitrogen and oxygen species such as nitric oxide (NO) and hydroxyl radical (OH(-)) are known to affect vascular permeability. Therefore, the goal of our present studies is to investigate the functional impact of the generation of NO or OH(-) on arsenic-induced vascular leakage. Vascular permeability changes were evaluated by means of Evans blue (EB) assay. Rats were anesthetized and intravenously injected with EB. Permeability changes were induced in back skin by intradermal injections of sodium arsenite mixed with NOS inhibitor: N(omega)-Nitro-L-arginine methyl ester (L-NAME) or aminoguanidine (AG) and OH(-) scavenger: 1,3 Dimethyl-2 thiourea (DMTU). Experiments were also performed to determine whether DMTU mixed with L-NAME would further inhibit arsenic-induced vascular leakage as compared with attenuation effects by either DMTU or L-NAME. One hour after administration, EB accumulated in the skin was extracted and quantified. Both L-NAME (0.02, 0.1 and 0.5 micromol/site) and DMTU (0.05, 0.2 and 1.2 micromol/site) inhibited the increase in vascular leakage induced by arsenite. However, only high dose (1 micromol/site) of AG significantly attenuated arsenite-induced vascular leakage. In contrast, neither D-NAME (0.02, 0.1 and 0.5 micromol/site) nor AG (0.04 and 0.2 micromol/site) attenuated increased vascular leakage by arsenic. DMTU mixed with L-NAME caused no further inhibition of arsenic-induced vascular leakage by either DMTU or L-NAME. The techniques of India ink and immunostaining were used to demonstrate both vascular labeling and nitrotyrosine staining in tissue treated with arsenic. L-NAME apparently reduced the density of leaky vessels and the levels of peroxynitrite staining induced by arsenite. These results suggest that NO, OH(-) and peroxynitrite play a role in increased vascular permeability

  17. Arsenic-contaminated cold-spring water in mountainous areas of Hui County, Northwest China: a new source of arsenic exposure.

    PubMed

    Zhang, Qiang; Zheng, Quanmei; Sun, Guifan

    2011-11-15

    Although pump-well is the primary drinking water source in rural areas of China, there are still 8.4% of villages reliant on cold-spring. In this study, a survey of arsenic concentration in cold-springs and pump-wells was carried out in Hui County, Northwest China. A total of 352 drinking water samples, including 177 cold-springs and 175 pump-wells, were collected. The maximum arsenic concentrations in cold-springs and pump-wells were 0.482 mg/L and 0.067 mg/L, respectively. We found that 15.8% (28) of total cold-springs and 1.1% (2) of total pump-wells had arsenic concentrations exceeding the maximum allowable concentration of arsenic in drinking water of rural China (0.05 mg/L). Our findings show that 5 cold spring-contaminated villages are located in the mountainous areas of Hui County and 2224 inhabitants may be at risk of high arsenic exposure. This paper indicates that arsenic contamination of cold-springs may be more serious than expected in mountainous areas of Northwest China and extensive surveys and epidemiological studies should be carried out to investigate the potential contaminated areas and affected population.

  18. Nitarsone, Inorganic Arsenic, and Other Arsenic Species in Turkey Meat: Exposure and Risk Assessment Based on a 2014 U.S. Market Basket Sample

    PubMed Central

    Nachman, Keeve E.; Love, David C.; Baron, Patrick A.; Nigra, Anne E.; Murko, Manuela; Raber, Georg; Francesconi, Kevin A.; Navas-Acien, Ana

    2016-01-01

    Background: Use of nitarsone, an arsenic-based poultry drug, may result in dietary exposures to inorganic arsenic (iAs) and other arsenic species. Nitarsone was withdrawn from the U.S. market in 2015, but its use in other countries may continue. Objectives: We characterized the impact of nitarsone use on arsenic species in turkey meat and arsenic exposures among turkey consumers, and we estimated cancer risk increases from consuming turkey treated with nitarsone before its 2015 U.S. withdrawal. Methods: Turkey from three cities was analyzed for total arsenic, iAs, methylarsonate (MA), dimethylarsinate, and nitarsone, which were compared across label type and month of purchase. Turkey consumption was estimated from NHANES data to estimate daily arsenic exposures for adults and children 4–30 months of age and cancer risks among adult consumers. Results: Turkey meat from conventional producers not prohibiting nitarsone use showed increased mean levels of iAs (0.64 μg/kg) and MA (5.27 μg/kg) compared with antibiotic-free and organic meat (0.39 μg/kg and 1.54 μg/kg, respectively) and meat from conventional producers prohibiting nitarsone use (0.33 μg/kg and 0.28 μg/kg, respectively). Samples with measurable nitarsone had the highest mean iAs and MA (0.92 μg/kg and 10.96 μg/kg, respectively). Nitarsone was higher in October samples than in March samples, possibly resulting from increased summer use. Based on mean iAs concentrations in samples from conventional producers with no known policy versus policies prohibiting nitarsone, estimated lifetime daily consumption by an 80-kg adult, and a recently proposed cancer slope factor, we estimated that use of nitarsone by all turkey producers would result in 3.1 additional cases of bladder or lung cancer per 1,000,000 consumers. Conclusions: Nitarsone use can expose turkey consumers to iAs and MA. The results of our study support the U.S. Food and Drug Administration’s removal of nitarsone from the U.S. market and

  19. 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.

  20. Influence of co-contaminant exposure on the absorption of arsenic, cadmium and lead.

    PubMed

    Ollson, Cameron J; Smith, Euan; Herde, Paul; Juhasz, Albert L

    2017-02-01

    Incidental ingestion of contaminated soil and dust is a major pathway for human exposure to many inorganic contaminants. To date, exposure research has focused on arsenic (As), cadmium (Cd) and lead (Pb), however, these studies have typically assessed metal(loid) bioavailability individually, even when multiple elements are present in the same matrix. As a consequence, it is unclear whether interactions between these elements occur within the gastro-intestinal tract, which may impact absorption and accumulation. In this study, the influence of contaminant co-exposure was assessed using a mouse bioassay and soluble forms of As, Cd and Pb supplied in mouse chow as individual, binary and tertiary elemental combinations. Arsenic urinary excretion and Pb-liver accumulation were unaffected by As-Pb co-exposure (1-10 mg As kg(-1) and 3-30 mg Pb kg(-1)) while Cd-kidney accumulation was unaffected by the presence of As and/or Pb. However, Cd co-exposure decreased As urinary excretion and increased Pb-liver accumulation. It was hypothesized that Cd influenced arsenate absorption as a consequence of the impairment of phosphate transporters. Although the reason for increasing Pb-liver accumulation following Cd co-exposure is unclear, enhanced Pb accumulation may occur as a result of transport protein overexpression or changes in divalent metal compartmentalization.

  1. The risk of arsenic induced skin lesions in Bangladeshi men and women is affected by arsenic metabolism and the age at first exposure

    SciTech Connect

    Lindberg, Anna-Lena; Rahman, Mahfuzar; Persson, Lars-Ake; Vahter, Marie

    2008-07-01

    It is known that a high fraction of methylarsonate (MA) in urine is a risk modifying factor for several arsenic induced health effects, including skin lesions, and that men are more susceptible for developing skin lesions than women. Thus, we aimed at elucidating the interaction between gender and arsenic metabolism for the risk of developing skin lesions. This study is part of a population-based case-referent study concerning the risk for skin lesions in relation to arsenic exposure via drinking water carried out in Matlab, a rural area 53km south-east of Dhaka, Bangladesh. We randomly selected 526 from 1579 referents and all 504 cases for analysis of arsenic metabolites in urine using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). The present study confirm previous studies, with the risk for skin lesions being almost three times higher in the highest tertile of %MA (adjusted OR 2.8, 95% CI: 1.9-4.2, p < 0.001) compared to the lowest tertile. The present study is the first to show that the well documented higher risk for men to develop arsenic-related skin lesions compared to women is mainly explained by the less efficient methylation of arsenic, as defined by a higher fraction of MA and lower fraction of DMA in the urine, among men. Our previously documented lower risk for skin lesions in individuals exposed since infancy, or before, was found to be independent of the observed arsenic methylation efficiency. Thus, it can be speculated that this is due to a programming effect of arsenic in utero.

  2. 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.

  3. 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.

  4. 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

  5. Microbial transformations of arsenic in the environment: From soda lakes to aquifers

    USGS Publications Warehouse

    Lloyd, J.R.; Oremland, R.S.

    2006-01-01

    Arsenic is a highly toxic element that supports a surprising range of biogeochemical transformations. The biochemical basis of these microbial interactions is described, with an emphasis on energy-yielding redox biotransformations that cycle between the As5+ and As3+ oxidation states. The subsequent impact of As3+-oxidising and As 5+-reducing prokaryotes on the chemistry of selected environments is also described, focusing on soda lakes with naturally high concentrations of the metalloid and on Southeast Asian aquifer sediments, where the microbial reduction of sorbed As5+ and subsequent mobilisation of As 3+ into water abstracted for drinking and irrigation threaten the lives of millions.

  6. Relation between in Utero Arsenic Exposure and Birth Outcomes in a Cohort of Mothers and Their Newborns from New Hampshire

    PubMed Central

    Gilbert-Diamond, Diane; Emond, Jennifer A.; Baker, Emily R.; Korrick, Susan A.; Karagas, Margaret R.

    2016-01-01

    Background: Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. Objective: We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Methods: Among 706 mother–infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Results: Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7–6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: –0.19, –0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: –0.82, –0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: –111.6, –14.2) in birth weight, though the association was null in the other strata. Conclusions: Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Citation: Gilbert

  7. Arsenic and sulfur transformations in hydrothermal spring waters and microbial mats of Yellowstone National Park

    NASA Astrophysics Data System (ADS)

    Druschel, G. K.; Lorenson, G. W.; Oduro, H.; McDermott, T.

    2006-12-01

    Many Yellowstone National Park hydrothermal waters contain high concentrations of arsenic and sulfur species which support various communities of chemotrophic microorganisms. In order to delineate the spatial and temporal variability of these organisms, which is critical in defining their ecological niche and role in element cycling, both temporal and spatial resolution of arsenic and sulfur speciation is needed. We present results from 2 years of field data and experiments showing the utility of Au-amalgam voltammetric microelectrodes in describing specific arsenic and sulfur speciation in hydrothermal systems. New insights on sulfur cycling in several hydrothermal pools, particularly facilitated by the in situ observation of polysulfides in these waters, are becoming evident and may help to resolve key issues surrounding the activity of organisms in these systems. The additional observation and description of voltammetric signals for dissolved and surfactant-stabilized colloidal forms of elemental sulfur with polysulfides in these systems suggests that sulfur cycling in many springs is largely dependent on the formation and oxidation of polysulfides derived from the interaction of dissolved hydrogen sulfide and elemental sulfur. We will present laboratory and field evidence for these reactions and discuss their importance in sulfur cycling and the potential role of microorganisms in these transformations. Arsenic (As(III)) and sulfide (H2S) oxidation in biofilms of Dragon spring in the Norris Geyser basin have now been described with high spatial resolution (as fine as 25 micron step sizes for vertical profiles). Small-scale coring with immediate freeze preservation and cryomicrotoming of those materials was attempted to develop techniques which will facilitate the description of coupled geochemical and microbiological changes on the micron scale in these systems. We will additionally describe the initial limited success of these microbial sampling techniques and

  8. Arsenicals Produce Stable Progressive Changes in DNA Methylation Patterns that are Linked to Malignant Transformation of Immortalized Urothelial Cells

    PubMed Central

    Jensen, Taylor J.; Novak, Petr; Wnek, Shawn M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-01-01

    Aberrant DNA methylation participates in carcinogenesis and is a molecular hallmark of a tumor cell. Tumor cells generally exhibit a redistribution of DNA methylation resulting in global hypomethylation with regional hypermethylation; however, the speed in which these changes emerge has not been fully elucidated and may depend on the temporal location of the cell in the path from normal, finite lifespan to malignant transformation. We used a model of arsenical-induced malignant transformation of immortalized human urothelial cells and DNA methylation microarrays to examine the extent and temporal nature of changes in DNA methylation that occur during the transition from immortal to malignantly transformed. Our data presented herein suggest that during arsenical-induced malignant transformation, aberrant DNA methylation occurs non-randomly, progresses gradually at hundreds of gene promoters, alters expression of the associated gene, and these changes are coincident with the acquisition of malignant properties, such as anchorage independent growth and tumor formation in immunocompromised mice. The DNA methylation changes appear stable, since malignantly transformed cells removed from the transforming arsenical exhibited no reversion in DNA methylation levels, associated gene expression, or malignant phenotype. These data suggest that arsenicals act as epimutagens and directly link their ability to induce malignant transformation to their actions on the epigenome. PMID:19716837

  9. Biomarkers of renal toxicity caused by exposure to arsenic in drinking water.

    PubMed

    Feng, Hongqi; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Li, Yuanyuan; Wei, Wei; Wu, Yu; Sun, Dianjun

    2013-05-01

    This study is intended to explore effective and sensitive biomarkers for kidney damage after low level arsenic (As) exposure and to provide scientific evidence on cut-off values of arsenic concentrations in drinking water. The levels of α1-MG detected in urine samples were found to have statistically significant differences between high As group (As>0.05 mg/L) and a combination of low and medium As exposure groups (As<0.05 mg/L, p=0.018), as well as between the patient and high As groups (As in two group were both higher than 0.05 mg/L, p<0.001). After the logistic regression analysis the AUC values of α1-MG between two comparisons were 0.613 and 0.701, and p value was less than 0.05. The present data demonstrate the potential value of α1-MG excretion as a biomarker of renal toxicity, which could contribute to the enforcement of the maximum limit of 0.05 mg/L arsenic in drinking water for non-central water supply in rural areas.

  10. 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

  11. 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

  12. Arsenic Exposure and Predicted 10-Year Atherosclerotic Cardiovascular Risk Using the Pooled Cohort Equations in U.S. Hypertensive Adults

    PubMed Central

    Nong, Qingjiao; Zhang, Yiyi; Guallar, Eliseo; Zhong, Qiuan

    2016-01-01

    This study was to evaluate the association of urine arsenic with predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk in U.S. adults with hypertension. Cross-sectional analysis was conducted in 1570 hypertensive adults aged 40–79 years in the 2003–2012 National Health and Nutrition Examination Survey (NHANES) with determinations of urine arsenic. Predicted 10-year ASCVD risk was estimated by the Pooled Cohort Equations, developed by the American College of Cardiology/American Heart Association in 2013. For men, after adjustment for sociodemographic factors, urine dilution, ASCVD risk factors and organic arsenic intake from seafood, participants in the highest quartiles of urine arsenic had higher 10-year predicted ASCVD risk than in the lowest quartiles; the increases were 24% (95% confidence interval (CI): 2%, 53%) for total arsenic, 13% (95% CI: 2%, 25%) for dimethylarsinate and 22% (95% CI: 5%, 40%) for total arsenic minus arsenobetaine separately. For women, the corresponding increases were 5% (95% CI: −15%, 29%), 10% (95% CI: −8%, 30%) and 0% (95% CI: −15%, 19%), respectively. Arsenic exposure, even at low levels, may contribute to increased ASCVD risk in men with hypertension. Furthermore, our findings suggest that particular circumstances need urgently to be considered while elucidating cardiovascular effects of low inorganic arsenic levels. PMID:27828001

  13. Arsenic

    MedlinePlus

    ... although the levels can vary widely.) In drinking water Drinking water is an important and potentially controllable ... have not been as convincing. Exposure from drinking water Studies of people in parts of Southeast Asia ...

  14. Contribution of breast milk and formula to arsenic exposure during the first year of life in a U.S. prospective cohort

    PubMed Central

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

    2016-01-01

    Arsenic is a carcinogen that can also affect the cardiac, respiratory, neurological and immune systems. Children have higher dietary arsenic exposure than adults due to their more restricted diets and greater intake per unit body mass. We evaluated the potential contributions of breast milk and formula to arsenic exposure throughout the first year of life for 356 infants in the prospective New Hampshire Birth Cohort Study (NHBCS) using infant diets reported by telephone at 4, 8 and 12 months of age; measured household water arsenic concentrations; and literature data. Based on our central-tendency models, population-wide geometric mean (GM) estimated arsenic exposures in the NHBCS were relatively low, decreasing from 0.1 μg kg−1 d−1 at 4 months of age to 0.07 μg kg−1 d−1 at 12 months of age. At all three time points, exclusively formula-fed infants had GM arsenic exposures ~8 times higher than exclusively breastfed infants due to arsenic in both tap water and formula powder. Estimated maximum exposures reached 9 μg kg−1 d−1 among exclusively formula-fed infants in households with high tap water arsenic (80 μg/L). Overall, modeled arsenic exposures via breast milk and formula were low throughout the first year of life, unless formula was prepared with arsenic-contaminated tap water. PMID:26531802

  15. Arsenic surveillance program

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Background information about arsenic is presented including forms, common sources, and clinical symptoms of arsenic exposure. The purpose of the Arsenic Surveillance Program and LeRC is outlined, and the specifics of the Medical Surveillance Program for Arsenic Exposure at LeRC are discussed.

  16. 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.

  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. Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.

    PubMed

    Michailidi, Christina; Hayashi, Masamichi; Datta, Sayantan; Sen, Tanusree; Zenner, Kaitlyn; Oladeru, Oluwadamilola; Brait, Mariana; Izumchenko, Evgeny; Baras, Alexander; VandenBussche, Christopher; Argos, Maria; Bivalacqua, Trinity J; Ahsan, Habibul; Hahn, Noah M; Netto, George J; Sidransky, David; Hoque, Mohammad Obaidul

    2015-03-01

    Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection.

  19. 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

  20. Toenails as a biomarker of inorganic arsenic intake from drinking water and foods.

    PubMed

    Slotnick, Melissa J; Meliker, Jaymie R; AvRuskin, Gillian A; Ghosh, Debashis; Nriagu, Jerome O

    2007-01-15

    Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure.

  1. Exposure and bioavailability of arsenic in contaminated soils from the La Parrilla mine, Spain

    NASA Astrophysics Data System (ADS)

    Anawar, H. M.; Garcia-Sanchez, A.; Murciego, A.; Buyolo, T.

    2006-05-01

    Arsenic derived from mining activity may contaminate water, soil and plant ecosystems resulting in human health and ecotoxicological risks. In this study, exposure assessment of arsenic (As) in soil, spoil, pondwater and plants collected from the areas contaminated by mine tailings and spoils in and around the La Parrilla mine, Caceres province, Spain, was carried out using AAS method. Water solubility, bioavailability and soil-plant transfer coefficients of As and phytoremediation potential of plants were determined. Arsenic concentrations varied from 148 to 2,540 mg/kg in soils of site 1 and from 610 to 1,285 mg/kg in site 2 exceeding the guideline limit for agricultural soil (50 mg/kg). Arsenic concentrations in pond waters varied from 8.8 to 101.4 μg/l. High concentrations of water-soluble As in the soils that ranged from 0.10 to 4.71 mg/kg in site 1 and from 0.46 to 4.75 mg/kg in site 2 exceeded the maximum permitted level of water-soluble As (0.04 mg/kg) in agricultural soils. Arsenic concentrations varied from 0.8 to 149.5 mg/kg dry wt in the plants of site 1 and from 2.0 to 10.0 mg/kg in the plants of site 2. Arsenic concentrations in plants increased in the approximate order: Retama sphaerocarpa < Pteridium aquilinum < Erica australis < Juncus effusus < Phalaris caerulescens < Spergula arvensis in site 1. The soil-plant transfer coefficients for As ranged from 0.001 to 0.21 in site 1 and from 0.004 to 0.016 in site 2. The bioconcentration factor based on water-soluble As of soil varied from 3.2 to 593.9 in the plants of site 1 whereas it varied from 2.1 to 20.7 in the plants of site 2. To our knowledge, this is the first study in Europe to report that the fern species P. aquilinum accumulates extremely low contents of As in its fronds despite high As levels in the soils. Therefore, the S. arvensis, P. caerulescens and J. effusus plant species grown in this area might be used to partly remove the bioavailable toxic As for the purpose of minimization of

  2. 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.

  3. Arsenic Exposure and Outcomes of Antimonial Treatment in Visceral Leishmaniasis Patients in Bihar, India: A Retrospective Cohort Study

    PubMed Central

    Perry, Meghan R.; Prajapati, Vijay K.; Menten, Joris; Raab, Andrea; Feldmann, Joerg; Chakraborti, Dipankar; Sundar, Shyam; Fairlamb, Alan H.; Boelaert, Marleen; Picado, Albert

    2015-01-01

    Background In the late twentieth century, emergence of high rates of treatment failure with antimonial compounds (SSG) for visceral leishmaniasis (VL) caused a public health crisis in Bihar, India. We hypothesize that exposure to arsenic through drinking contaminated groundwater may be associated with SSG treatment failure due to the development of antimony-resistant parasites. Methods A retrospective cohort design was employed, as antimony treatment is no longer in routine use. The study was performed on patients treated with SSG between 2006 and 2010. Outcomes of treatment were assessed through a field questionnaire and treatment failure used as a proxy for parasite resistance. Arsenic exposure was quantified through analysis of 5 water samples from within and surrounding the patient’s home. A logistic regression model was used to evaluate the association between arsenic exposure and treatment failure. In a secondary analysis survival curves and Cox regression models were applied to assess the risk of mortality in VL patients exposed to arsenic. Results One hundred and ten VL patients treated with SSG were analysed. The failure rate with SSG was 59%. Patients with high mean local arsenic level had a non-statistically significant higher risk of treatment failure (OR = 1.78, 95% CI: 0.7–4.6, p = 0.23) than patients using wells with arsenic concentration <10 μg/L. Twenty one patients died in our cohort, 16 directly as a result of VL. Arsenic levels ≥ 10 μg/L increased the risk of all-cause (HR 3.27; 95% CI: 1.4–8.1) and VL related (HR 2.65; 95% CI: 0.96–7.65) deaths. This was time dependent: 3 months post VL symptom development, elevated risks of all-cause mortality (HR 8.56; 95% CI: 2.5–29.1) and of VL related mortality (HR 9.27; 95% CI: 1.8–49.0) were detected. Discussion/Conclusion This study indicates a trend towards increased treatment failure in arsenic exposed patients. The limitations of the retrospective study design may have masked a strong

  4. A Concurrent Exposure to Arsenic and Fluoride from Drinking Water in Chihuahua, Mexico

    PubMed Central

    González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C.; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L.; Saunders, R. Jesse; Drobná, Zuzana; Mendez, Michelle A.; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M.

    2015-01-01

    Inorganic arsenic (iAs) and fluoride (F−) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F− in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F− concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F−/L. Urinary arsenic (U-tAs) and urinary F− (U-F−) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F−/mL. A strong positive correlation was found between iAs and F− concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F− concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F−, raising questions about possible contribution of F− exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F− exposures and its related health risks deserves immediate attention. PMID:25918912

  5. A concurrent exposure to arsenic and fluoride from drinking water in Chihuahua, Mexico.

    PubMed

    González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Sánchez-Ramírez, Blanca; Ishida, María C; Barrera-Hernández, Angel; Gutiérrez-Torres, Daniela; Zacarias, Olga L; Saunders, R Jesse; Drobná, Zuzana; Mendez, Michelle A; García-Vargas, Gonzalo; Loomis, Dana; Stýblo, Miroslav; Del Razo, Luz M

    2015-04-24

    Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.

  6. Exposure, metabolism, and health effects of arsenic in residents from arsenic-contaminated groundwater areas of Vietnam and Cambodia: a review.

    PubMed

    Agusa, Tetsuro; Kunito, Takashi; Kubota, Reiji; Inoue, Suguru; Fujihara, Junko; Minh, Tu Binh; Ha, Nguyen Ngoc; Tu, Nguyen Phuc Cam; Trang, Pham Thi Kim; Chamnan, Chhoun; Takeshita, Haruo; Iwata, Hisato; Tuyen, Bui Cach; Viet, Pham Hung; Tana, Touch Seang; Tanabe, Shinsuke

    2010-01-01

    In this review, we summarize the current knowledge on exposure, metabolism, and health effects of arsenic (As) in residents from As-contaminated groundwater areas of Vietnam and Cambodia based on our findings from 2000 and other studies. The health effects of As in humans include severe gastrointestinal disorders, hepatic and renal failure, cardiovascular disturbances, skin pigmentation, hyperkeratosis, and cancers in the lung, bladder, liver, kidney, and skin. Arsenic contamination in groundwater is widely present at Vietnam and Cambodia and the highest As levels are frequently found in groundwater from Cambodia. Sand filter system can reduce As concentration in raw groundwater. The results of hair and urine analyses indicate that residents from these As-contaminated areas are exposed to As. In general, sex, age, body mass index, and As exposure level are significantly associated with As metabolism. Genetic polymorphisms in arsenic (+III) methyltransferase and glutathione-S-transferase isoforms may be influenced As metabolism and accumulation in a Vietnamese population. It is suggested oxidative DNA damage is caused by exposure to As in groundwater from residents in Cambodia. An epidemiologic study on an association of As exposure with human health effects is required in these areas.

  7. Impact of early developmental arsenic exposure on promotor CpG-island methylation of genes involved in neuronal plasticity.

    PubMed

    Martínez, Liborio; Jiménez, Verónica; García-Sepúlveda, Christian; Ceballos, Fátima; Delgado, Juan Manuel; Niño-Moreno, Perla; Doniz, Lesly; Saavedra-Alanís, Víctor; Castillo, Claudia G; Santoyo, Martha E; González-Amaro, Roberto; Jiménez-Capdeville, María E

    2011-04-01

    Epigenetic mechanisms are crucial to regulate the expression of different genes required for neuronal plasticity. Neurotoxic substances such as arsenic, which induces cognitive deficits in exposed children before any other manifestation of toxicity, could interfere with the epigenetic modulation of neuronal gene expression required for learning and memory. This study assessed in Wistar rats the effects that developmental arsenic exposure had on DNA methylation patterns in hippocampus and frontal cortex. Animals were exposed to arsenic in drinking water (3 and 36ppm) from gestation until 4 months of age, and DNA methylation in brain cells was determined by flow cytometry, immunohistochemistry and methylation-specific polymerase chain reaction (PCR) of the promoter regions of reelin (RELN) and protein phosphatase 1 (PP1) at 1, 2, 3 and 4 months of age. Immunoreactivity to 5 methyl-cytosine was significantly higher in the cortex and hippocampus of exposed animals compared to controls at 1 month, and DNA hypomethylation was observed the following months in the cortex at high arsenic exposure. Furthermore, we observed a significant increase in the non-methylated form of PP1 gene promoter at 2 and 3 months of age, either in cortex or hippocampus. In order to determine whether this exposure level is associated with memory deficits, a behavioral test was performed at the same age points, revealing progressive and dose-dependent deficits of fear memory. Our results demonstrate alterations of the methylation pattern of genes involved in neuronal plasticity in an animal model of memory deficit associated with arsenic exposure.

  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.

  9. Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

    SciTech Connect

    Huang, Chao-Yuan; Su, Chien-Tien; Chung, Chi-Jung; Pu, Yeong-Shiau; Chu, Jan-Show; Yang, Hsiu-Yuan; Wu, Chia-Chang; Hsueh, Yu-Mei

    2012-08-01

    8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.

  10. Arsenic in private well water part 3 of 3: Socioeconomic vulnerability to exposure in Maine and New Jersey.

    PubMed

    Flanagan, Sara V; Spayd, Steven E; Procopio, Nicholas A; Marvinney, Robert G; Smith, Andrew E; Chillrud, Steven N; Braman, Stuart; Zheng, Yan

    2016-08-15

    Arsenic is a naturally occurring toxic element often concentrated in groundwater at levels unsafe for human consumption. Private well water in the United States is mostly unregulated by federal and state drinking water standards. It is the responsibility of the over 13 million U.S. households regularly depending on private wells for their water to ensure it is safe for drinking. There is a consistent graded association with health outcomes at all levels of socioeconomic status (SES) in the U.S. Differential exposure to environmental risk may be contributing to this persistent SES-health gradient. Environmental justice advocates cite overwhelming evidence that income and other SES measures are consistently inversely correlated with exposure to suboptimal environmental conditions including pollutants, toxins, and their impacts. Here we use private well household surveys from two states to investigate the association between SES and risks for arsenic exposure, examining the potentially cumulative effects of residential location, testing and treatment behavior, and psychological factors influencing behavior. We find that the distribution of natural arsenic hazard in the environment is socioeconomically random. There is no evidence that higher SES households are avoiding areas with arsenic or that lower SES groups are disproportionately residing in areas with arsenic. Instead, disparities in exposure arise from differing rates of protective action, primarily testing well water for arsenic, and secondly treating or avoiding contaminated water. We observe these SES disparities in behavior as well as in the psychological factors that are most favorable to these behaviors. Assessment of risk should not be limited to the spatial occurrence of arsenic alone. It is important that social vulnerability factors are incorporated into risk modeling and identifying priority areas for intervention, which should include strategies that specifically target socioeconomically vulnerable

  11. Evaluation of gene expression changes in human primary lung epithelial cells following 24-hr exposures to inorganic arsenic and its methylated metabolites and to arsenic trioxide.

    PubMed

    Efremenko, Alina Y; Seagrave, JeanClare; Clewell, Harvey J; Van Landingham, Cynthia; Gentry, P Robinan; Yager, Janice W

    2015-06-01

    The concentration response for altered gene expression in primary lung epithelial cells was determined following two treatments with arsenicals: (1) a mixture of trivalent arsenic compounds representative of urinary arsenic concentrations in exposed human populations, and (2) arsenite (As2 O3 ) a common form of inhaled arsenic dust that is frequently used in both in vivo and in vitro experimental exposures. Biochemical assays did not detect any evidence of cytotoxicity at the concentrations used, apart from a concentration-related increase in cellular heme oxygenase that was also indicated by the genomic analysis. Cell signal pathway enrichment analysis indicated similar responses to both treatments, with concentration-related responses in pathways related to cell adhesion, cytoskeleton remodeling, development (morphogenesis), cell cycle control, and to a lesser extent inflammatory responses. These cellular responses to arsenic were consistent with those observed in a previous study with primary uroepithelial cells. Benchmark dose analysis also demonstrated similar potency of the two treatments as well as comparable sensitivity of the two cell types. A number of genes showing similar concentration-dependent expression across individuals in both bladder and lung cells were identified, including heme oxygenase 1, thioredoxin reductase, DNA damage binding protein 2, and thrombomodulin. The data on human primary lung cells from this study, together with the data from human primary uroepithelial cells, support a conclusion that biological responses to arsenic by human cells under study conditions are unlikely to occur at concentrations below 0.1 µM. Environ. Mol. Mutagen. 56:477-490, 2015. © 2015 Wiley Periodicals, Inc.

  12. Dose-Response Relationship between Inorganic Arsenic Exposure and Lung Cancer among Arseniasis Residents with Low Methylation Capacity.

    PubMed

    Hsu, Kuang-Hung; Tsui, Ke-Hung; Hsu, Ling-I; Chiou, Hung-Yi; Chen, Chien-Jen

    2016-12-22

    Background Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence. Methods We followed 1300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazard model was performed. Results The results demonstrated that participants with either the primary methylation index (monomethylarsonic acid [MMA]/InAs) or the secondary methylation index (dimethylarsinic acid[DMA]/MMA) lower than their respective median values were at a higher risk of lung cancer (hazard ratios from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100000 (year-1) to 467.4/100000 (year-1) for residents with low methylation capacity and from 0 to 158.5/100000 (year-1) for residents with high methylation capacity when the arsenic exposure dose increased from 2-10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < .05 and P < .05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylaters was not statistically significant. Conclusions Hypomethylation responses to InAs exposure may dose-dependently increase lung cancer occurrence. Impact The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis.

  13. Arsenic levels in wipe samples collected from play structures constructed with CCA-treated wood: impact on exposure estimates.

    PubMed

    Barraj, Leila M; Scrafford, Carolyn G; Eaton, W Cary; Rogers, Robert E; Jeng, Chwen-Jyh

    2009-04-01

    Lumber treated with chromated copper arsenate (CCA) has been used in residential outdoor wood structures and playgrounds. The U.S. EPA has conducted a probabilistic assessment of children's exposure to arsenic from CCA-treated structures using the Stochastic Human Exposure and Dose Simulation model for the wood preservative scenario (SHEDS-Wood). The EPA assessment relied on data from an experimental study using adult volunteers and designed to measure arsenic in maximum hand and wipe loadings. Analyses using arsenic handloading data from a study of children playing on CCA-treated play structures in Edmonton, Canada, indicate that the maximum handloading values significantly overestimate the exposure that occurs during actual play. The objective of our paper is to assess whether the dislodgeable arsenic residues from structures in the Edmonton study are comparable to those observed in other studies and whether they support the conclusion that the values derived by EPA using modeled maximum loading values overestimate hand exposures. We compared dislodgeable arsenic residue data from structures in the playgrounds in the Edmonton study to levels observed in studies used in EPA's assessment. Our analysis showed that the dislodgeable arsenic levels in the Edmonton playground structures are similar to those in the studies used by EPA. Hence, the exposure estimates derived using the handloading data from children playing on CCA-treated structures are more representative of children's actual exposures than the overestimates derived by EPA using modeled maximum values. Handloading data from children playing on CCA-treated structures should be used to reduce the uncertainty of modeled estimates derived using the SHEDS-Wood model.

  14. 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.

  15. [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological studies on population exposed to low-to-moderate arsenic concentration in drinking water].

    PubMed

    Bustaffa, Elisa; Bianchi, Fabrizio

    2014-01-01

    Arsenic and its inorganic compounds are classified as human carcinogens. Several epidemiological studies conducted in areas of the world characterized by high arsenic concentration in drinking water, even up to 3,000 μg/l, report associations between arsenic exposure and skin, bladder, lung, liver and kidney cancer as well as cardiovascular diseases, diabetes and reproductive and developmental effects. Since general population is not exposed to these high arsenic concentrations in the last years attention focused on adverse health effects that low-to-moderate arsenic concentrations (0-150 μg/l) in drinking water could induce. The World Health Organization recommends a maximum limit of 10 μg/l for arsenic in drinking water. Almost all epidemiological studies conducted on populations exposed to low-to-moderate arsenic concentrations in drinking water are limited due to problems arising from both individual exposure assessment and low subjects number. The aim of the present review is to collect literature-based evidences regarding adverse health effects associated with exposure to low-to-moderate arsenic concentrations in drinking water (10-150 μg/l) in order to obtain a comprehensive picture of the health outcomes that such exposure can have on general population.

  16. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression.

    PubMed

    Chang, Chia-Yu; Guo, How-Ran; Tsai, Wan-Chen; Yang, Kai-Lin; Lin, Li-Chuan; Cheng, Tain-Junn; Chuu, Jiunn-Jye

    2015-01-01

    Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  17. Studies on the accumulation and transformation of arsenic in ecosystem in Guandu Wetland, Taiwan

    NASA Astrophysics Data System (ADS)

    Chen, Y. Y.; Liu, C. W.; Kao, Y. H.

    2012-04-01

    High arsenic (As) is naturally occurred in geothermal areas, it may result in pollution of downstream wetland and estuary ecosystem. Arsenic concentration is up to 4.32 mg/L in geothermal spring water and overly exceeded the drinking water guideline of WHO (0.01 mg/L) that may result in wetland ecosystem damage. The influence of aqueous, solid and plant phase on As mobility in Guandu wetland, Taiwan, is not properly distinguished yet. The mangroves are particularly growing in study area and Kandelia obovata is one of the most dominant plant species. The purpose of this study is to discriminate that integration of aqueous, solid and plant phase is affected by As redox cycling. The chemical compounds (As, Fe, Mn, TOC, SO42-, FeS2) and isotopic compositions (δ34S ) in surface water and soil samples were analyzed, to characterize of As distribution. The sequential extraction of As and total As in plant samples were analyzed, to estimate the bioconcentration factor (BCF) and transfer factor (TF), and understand the accumulation and transformation of As for Kandelia obovata in aqueous and solid phase. The As concentration in plants (23.69 mg/kg) are higher than the surrounding water (0.0028 mg/L) and soils (16.33 mg/kg). Arsenic concentration in various plant tissues at maturity follow the order: roots (19.74 mg/kg) > stems (1.76 mg/kg) > leaves (1.71 mg/kg) > seedlings (0.48 mg/kg), and they are mostly accumulated in the roots. However, the result of As sequential extraction in the sediments indicate uptake of chemical compound in plant from sediments is difficult, depending on low bioavailability in plants. Besides, low transfer factor (TFstems/roots=0.088, TFleaves/roots=0.088 and TFseedlings/roots=0.024) indicate that the transformation of As in various plant tissues is very low. The results show that Kandelia obovata content low As bioavailability and low TF, cause of easy adaption to grow on As contaminated wetland ecosystem. BCFplants/porewater (10742.68) is

  18. TRANSFORMATION AND MOBILIZATION OF ARSENIC ADSORBED ON GRANULAR FERRIC HYDROXIDE UNDER BIO-REDUCTIVE CONDITIONS

    EPA Science Inventory

    Biotic and abiotic reduction of arsenic (V) and iron (III) influences the partioning of arsenic (As) between the solid and aqueous phases in soils, sediments and wastes. In this study, laboratory experiments on arsenic adsorbed on granular ferric hydroxide (GFH) was performed to ...

  19. Association between occupational exposure to arsenic and neurological, respiratory and renal effects

    SciTech Connect

    Halatek, Tadeusz Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

    2009-09-01

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and {beta}{sub 2}-microglobulin ({beta}{sub 2}M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m{sup 3}). The contents of lead did not exceed the TLV (0.05 mg/m{sup 3}). Low CC16 levels in serum (12.1 {mu}g/l) of workers with SNS and VEP symptoms and highest level As-U (x{sub a} 39.0 {mu}g/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum {beta}{sub 2}M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

  20. Low-level arsenic exposure in drinking water and bladder cancer: a review and meta-analysis.

    PubMed

    Mink, Pamela J; Alexander, Dominik D; Barraj, Leila M; Kelsh, Michael A; Tsuji, Joyce S

    2008-12-01

    Although exposure to high levels of arsenic in drinking water is associated with excess cancer risk (e.g., skin, bladder, and lung), lower exposures (e.g., <100-200 microg/L) generally are not. Lack of significant associations at lower exposures may be attributed to methodologic issues (e.g., inadequate statistical power, exposure misclassification), or to differences in the dose-response relationship at high versus low exposures. The objectives of this review and meta-analysis were to evaluate associations, examine heterogeneity across studies, address study design and sample size issues, and improve the precision of estimates. Eight studies of bladder cancer and low-level arsenic exposure met our inclusion criteria. Meta-analyses of never smokers produced summary relative risk estimates (SRREs) below 1.0 (highest versus lowest exposure). The SRRE for never and ever smokers combined was elevated slightly, but not significantly (1.11; 95% CI: 0.95-1.30). The SRRE was somewhat elevated among ever smokers (1.24; 95% CI: 0.99-1.56), and statistical significance was observed in some subgroup analyses; however, heterogeneity across studies was commonly present. Although uncertainties remain, low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer. More studies with detailed smoking history will help resolve whether smoking is an effect modifier.

  1. 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

  2. National Human Exposure Assessment Survey: analysis of exposure pathways and routes for arsenic and lead in EPA Region 5.

    PubMed

    Clayton, C A; Pellizzari, E D; Quackenboss, J J

    2002-01-01

    The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 (Great Lakes Area) provides extensive exposure data on a representative sample of approximately 250 residents of the region. Associated environmental media and biomarker (blood, urine) concentration data were also obtained for the study participants to aid in understanding of the relationships of exposures to both contaminant pathways and doses. Besides fulfilling the primary NHEXAS objectives, the NHEXAS data provided an opportunity to explore secondary usages, such as examining pathway to route of exposure relationships. A generic type of structural equation model was used to define the anticipated relationships among the various data types for both arsenic (As) and lead (Pb). Since, by design, only a few participants provided data for all sample types, implementing this model required that some media concentrations (outdoor air and soil) be imputed for subjects with missing information by using measurements collected in the same geographic area and time period. The model, and associated pairwise correlations, generally revealed significant but weak associations among the concentrations, exposures, and doses; the strongest associations occurred for the various air measurements (indoor versus outdoor and personal). The generally weak associations were thought to be partly due to the absence of complete coverage of nonresidential environmental media and to nonsynchronization of relevant measurement times and integration periods of collection across the various sample types. In general, relationships between the NHEXAS questionnaire data and the various concentration, exposure, and body-burden measures were also weak. The model results and the modeling exercise suggest several ways for optimizing the design of future exposure assessment studies that are aimed at supporting structural modeling activities.

  3. 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.

  4. 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

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

    PubMed

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

    2016-07-01

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

  6. Elucidating the selenium and arsenic metabolic pathways following exposure to the non-hyperaccumulating Chlorophytum comosum, spider plant.

    PubMed

    Afton, Scott E; Catron, Brittany; Caruso, Joseph A

    2009-01-01

    Although many studies have investigated the metabolism of selenium and arsenic in hyperaccumulating plants for phytoremediation purposes, few have explored non-hyperaccumulating plants as a model for general contaminant exposure to plants. In addition, the result of simultaneous supplementation with selenium and arsenic has not been investigated in plants. In this study, Chlorophytum comosum, commonly known as the spider plant, was used to investigate the metabolism of selenium and arsenic after single and simultaneous supplementation. Size exclusion and ion-pairing reversed phase liquid chromatography were coupled to an inductively coupled plasma mass spectrometer to obtain putative metabolic information of the selenium and arsenic species in C. comosum after a mild aqueous extraction. The chromatographic results depict that selenium and arsenic species were sequestered in the roots and generally conserved upon translocation to the leaves. The data suggest that selenium was directly absorbed by C. comosum roots when supplemented with Se(VI), but a combination of passive and direct absorption occurred when supplemented with Se(IV) due to the partial oxidation of Se(IV) to Se(VI) in the rhizosphere. Higher molecular weight selenium species were more prevalent in the roots of plants supplemented with Se(IV), but in the leaves of plants supplemented with Se(VI) due to an increased translocation rate. When supplemented as As(III), arsenic is proposed to be passively absorbed as As(III) and partially oxidized to As(V) in the plant root. Although total elemental analysis demonstrates a selenium and arsenic antagonism, a compound containing selenium and arsenic was not present in the general aqueous extract of the plant.

  7. Elucidating the selenium and arsenic metabolic pathways following exposure to the non-hyperaccumulating Chlorophytum comosum, spider plant

    PubMed Central

    Afton, Scott E.; Catron, Brittany; Caruso, Joseph A.

    2009-01-01

    Although many studies have investigated the metabolism of selenium and arsenic in hyperaccumulating plants for phytoremediation purposes, few have explored non-hyperaccumulating plants as a model for general contaminant exposure to plants. In addition, the result of simultaneous supplementation with selenium and arsenic has not been investigated in plants. In this study, Chlorophytum comosum, commonly known as the spider plant, was used to investigate the metabolism of selenium and arsenic after single and simultaneous supplementation. Size exclusion and ion-pairing reversed phase liquid chromatography were coupled to an inductively coupled plasma mass spectrometer to obtain putative metabolic information of the selenium and arsenic species in C. comosum after a mild aqueous extraction. The chromatographic results depict that selenium and arsenic species were sequestered in the roots and generally conserved upon translocation to the leaves. The data suggest that selenium was directly absorbed by C. comosum roots when supplemented with SeVI, but a combination of passive and direct absorption occurred when supplemented with SeIV due to the partial oxidation of SeIV to SeVI in the rhizosphere. Higher molecular weight selenium species were more prevalent in the roots of plants supplemented with SeIV, but in the leaves of plants supplemented with SeVI due to an increased translocation rate. When supplemented as AsIII, arsenic is proposed to be passively absorbed as AsIII and partially oxidized to AsV in the plant root. Although total elemental analysis demonstrates a selenium and arsenic antagonism, a compound containing selenium and arsenic was not present in the general aqueous extract of the plant. PMID:19273464

  8. Response to Comments on Probabilistic Modeling Dietary Arsenic Exposure and Dose and Evaluation with 2003-2004 NHANES Data

    EPA Science Inventory

    In our article (Xue et al. (2010), we cited Boyce et al. (2008) based on their major conclusion, stated at the end of their abstract that. "typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity." We agr...

  9. SPECIES SPECIFIC DIETARY ARSENIC EXPOSURE ASSESSMENT: THE NEED TO ESTIMATE BIOACCESSIBILITY AND ASSESSING THE IMPLIED PRESYSTEMIC METABOLISM IMPLICATIONS

    EPA Science Inventory

    The chemical form specific toxicity of arsenic dictates the need for species specific quantification in order to accurately assess the risk from an exposure. The literature has begun to produce preliminary species specific databases for certain dietary sources, but a quantitativ...

  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. 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...

  12. 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...

  13. Arsenic exposure levels in relation to different working departments in a copper mining and smelting plant

    NASA Astrophysics Data System (ADS)

    Sun, Qingshan; Song, Yingli; Liu, Shengnan; Wang, Fei; Zhang, Lin; Xi, Shuhua; Sun, Guifan

    2015-10-01

    The investigation was carried out to evaluate arsenic exposure and the urine metabolite profiles of workers with different working departments, including administration (Group1), copper ore mining (Group2), copper ore grinding (Group3), electrolytic procession (Group4) and copper smelting (Group5) in a Copper mining and processing plant in China. Information about characteristics of each subject was obtained by questionnaire and inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The highest urinary levels of iAs, MMA and DMA all were found in the Group 5. Group 4 workers had a higher iAs% and a lower PMI compared to Group 3. The urinary total As (TAs) levels of 54.7% subjects exceeded 50 μg/g Cr, and the highest percentage (93.3%) was found in Group 5, smelters. The results of the present study indicate that workers in copper production plant indeed exposed to As, especially for smelters and workers of electrolytic process.

  14. Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

    PubMed

    Kim, Yong-Dae; Eom, Sang-Yong; Yim, Dong-Hyuk; Kim, In-Soo; Won, Hee-Kwan; Park, Choong-Hee; Kim, Guen-Bae; Yu, Seung-Do; Choi, Byung-Sun; Park, Jung-Duck; Kim, Heon

    2016-04-01

    Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

  15. Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea

    PubMed Central

    2016-01-01

    Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure. PMID:27051230

  16. Assessment of children's exposure to arsenic from CCA-wood staircases at apartment complexes in Florida.

    PubMed

    Gress, Julia Ky; Lessl, Jason T; Dong, Xiaoling; Ma, Lena Q

    2014-04-01

    Arsenic exposure from wood treated with chromated copper arsenate (CCA) remains a concern due to its presence around homes. This study evaluated children's exposure to As from CCA-treated staircases through determination of bioaccessible soil As and measurements of dislodgeable As on hand railings, steps and surfaces of household objects impacted by CCA-wood leachate. Total As concentrations in 84 soil samples from 4 apartment complexes were elevated at 1.2-66.6 mg/kg with bioaccessible As at 17-84%. Deterministic risk equations were used to estimate daily doses of As in children with estimates ranging from 0.41-54.9 μg/day from ingestion of dislodgeable As. Lifetime average daily doses from ingestion of dislodgeable As and soil ranged from 8.1×10(-6) to 3.0×10(-5) mg/kg/day, with estimated cancer risks being 1.2-4.5×10(-5). Collectively, these results highlight potential health risks in children who have near-daily exposure to As from CCA-wood and are consistent with estimates generated by USEPA's SHEDS-Wood probabilistic exposure model.

  17. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

    PubMed Central

    Aung, Kyaw H.; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  18. In utero arsenic exposure and epigenome-wide associations in placenta, umbilical artery, and human umbilical vein endothelial cells.

    PubMed

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

    2015-01-01

    Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and 4 CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F P < 0.001), placenta (Max F P < 0.001), and HUVEC (Max F P = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F P = 0.02), placenta (Max F P = 0.02), and HUVEC (Max F P = 0.02). Our results show that prenatal arsenic exposure can alter DNA methylation in artery and placenta but not in HUVEC. Further studies are needed to determine if these alterations in DNA methylation mediate the effect of prenatal arsenic exposure and health outcomes later in life.

  19. In utero arsenic exposure and epigenome-wide associations in placenta, umbilical artery, and human umbilical vein endothelial cells

    PubMed Central

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

    2015-01-01

    Exposure to arsenic early in life has been associated with increased risk of several chronic diseases and is believed to alter epigenetic programming in utero. In the present study, we evaluate the epigenome-wide association of arsenic exposure in utero and DNA methylation in placenta (n = 37), umbilical artery (n = 45) and human umbilical vein endothelial cells (HUVEC) (n = 52) in a birth cohort using the Infinium HumanMethylation450 BeadChip array. Unadjusted and cell mixture adjusted associations for each tissue were examined along with enrichment analyses relative to CpG island location and omnibus permutation tests of association among biological pathways. One CpG in artery (cg26587014) and 4 CpGs in placenta (cg12825509; cg20554753; cg23439277; cg21055948) reached a Bonferroni adjusted level of significance. Several CpGs were differentially methylated in artery and placenta when controlling the false discovery rate (q-value<0.05), but none in HUVEC. Enrichment of hypomethylated CpG islands was observed for artery while hypermethylation of open sea regions were present in placenta relative to prenatal arsenic exposure. The melanogenesis pathway was differentially methylated in artery (Max F P < 0.001), placenta (Max F P < 0.001), and HUVEC (Max F P = 0.02). Similarly, the insulin-signaling pathway was differentially methylated in artery (Max F P = 0.02), placenta (Max F P = 0.02), and HUVEC (Max F P = 0.02). Our results show that prenatal arsenic exposure can alter DNA methylation in artery and placenta but not in HUVEC. Further studies are needed to determine if these alterations in DNA methylation mediate the effect of prenatal arsenic exposure and health outcomes later in life. PMID:26646901

  20. Significance of exposure assessment to analysis of cancer risk from inorganic arsenic in drinking water in Taiwan

    SciTech Connect

    Brown, K.G.; Chen, C.J.

    1995-08-01

    The primary source of evidence that inorganic arsenic in drinking water is associated with increased mortality from cancer at internal sites (bladder, liver, lung, and other organs) is a large ecologic study conducted in regions of Southwest Taiwan endemic to Blackfoot disease. The dose-response patterns for lung, liver, and bladder cancers display a nonlinear dose-response relationship with arsenic exposure. The data do not appear suitable, however, for the more refined task of dose-response assessment, particularly for inference of risk at the low arsenic concentrations found in some U.S. water supplies. The problem lies in variable arsenic concentrations between the wells within a village, largely due to a mix of shallow wells and deep artesian wells, and in having only one well test for 24 (40%) of the 60 villages. The current analysis identifies 14 villages where the exposure appears most questionable, based on criteria described in the test. The exposure values were then changed for seven of the villages, from the median well test being used as a default to some other point in the village`s range of well tests that would contribute to smoothing the appearance of a dose-response curve. The remaining seven villages, six of which had only one well test, were deleted as outliers. The resultant dose-response patterns showed no evidence of excess risk below arsenic concentrations of 0.1 mg/l. Of course, that outcome is dependent on manipulation of the data, as described. Inclusion of the seven deleted villages would make estimates of risk much higher at low doses. In those seven villages the cancer mortality rates are significantly high for their exposure levels, suggesting that their exposure values may be too low or that other etiological factors need to be taken into account. 10 refs., 4 figs., 5 tabs.

  1. Significance of exposure assessment to analysis of cancer risk from inorganic arsenic in drinking water in Taiwan.

    PubMed

    Brown, K G; Chen, C J

    1995-08-01

    The primary source of evidence that inorganic arsenic in drinking water is associated with increased mortality from cancer at internal sites (bladder, liver, lung, and other organs) is a large ecologic study conducted in regions of Southwest Taiwan endemic to Blackfoot disease. The dose-response patterns for lung, liver, and bladder cancers display a nonlinear dose-response relationship with arsenic exposure. The data do not appear suitable, however, for the more refined task of dose-response assessment, particularly for inference of risk at the low arsenic concentrations found in some U.S. water supplies. The problem lies in variable arsenic concentrations between the wells within a village, largely due to a mix of shallow wells and deep artesian wells, and in having only one well test for 24 (40%) of the 60 villages. The current analysis identifies 14 villages where the exposure appears most questionable, based on criteria described in the text. The exposure values were then changed for seven of the villages, from the median well test being used as a default to some other point in the village's range of well tests that would contribute to smoothing the appearance of a dose-response curve. The remaining seven villages, six of which had only one well test, were deleted as outliers. The resultant dose-response patterns showed no evidence of excess risk below arsenic concentrations of 0.1 mg/l. Of course, that outcome is dependent on manipulation of the data, as described. Inclusion of the seven deleted villages would make estimates of risk much higher at low doses. In those seven villages, the cancer mortality rates are significantly high for their exposure levels, suggesting that their exposure values may be too low or that other etiological factors need to be taken into account.

  2. Molecular features in arsenic-induced lung tumors

    PubMed Central

    2013-01-01

    Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. Lungs are one of the main target organs for arsenic-related carcinogenesis. These tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. Arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. Based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. In this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer. PMID:23510327

  3. Human Arsenic exposure via dust across the different ecological zones of Pakistan.

    PubMed

    Alamdar, Ambreen; Eqani, Syed Ali Musstjab Akber Shah; Ali, Saeed Waqar; Sohail, Mohammad; Bhowmik, Avit Kumar; Cincinelli, Alessandra; Subhani, Marghoob; Ghaffar, Bushra; Ullah, Rizwan; Huang, Qingyu; Shen, Heqing

    2016-04-01

    The present study aims to assess the arsenic (As) levels into dust samples and its implications for human health, of four ecological zones of Pakistan, which included northern frozen mountains (FMZ), lower Himalyian wet mountains (WMZ), alluvial riverine plains (ARZ), and low lying agricultural areas (LLZ). Human nail samples (N=180) of general population were also collected from the similar areas and all the samples were analysed by using ICP-MS. In general the higher levels (p<0.05) in paired dust and human nail samples were observed from ARZ and LLZ than those of other mountainous areas (i.e., WMZ and FMZ), respectively. Current results suggested that elevated As concentrations were associated to both natural, (e.g. geogenic influences) and anthropogenic sources. Linear regression model values indicated that As levels into dust samples were associated with altitude (r(2)=0.23), soil carbonate carbon density (SCC; r(2)=0.33), and population density (PD; r(2)=0.25). The relationship of paired dust and nail samples was also investigated and associations were found for As-nail and soil organic carbon density (SOC; r(2)=0.49) and SCC (r(2)=0.19) in each studied zone, evidencing the dust exposure as an important source of arsenic contamination in Pakistan. Risk estimation reflected higher hazard index (HI) values of non-carcinogenic risk (HI>1) for children populations in all areas (except FMZ), and for adults in LLZ (0.74) and ARZ (0.55), suggesting that caution should be paid about the dust exposure. Similarly, carcinogenic risk assessment also highlighted potential threats to the residents of LLZ and ARZ, as in few cases (5-10%) the values exceeded the range of US-EPA threshold limits (10(-6)-10(-4)).

  4. 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.

  5. 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...

  6. Spontaneous pregnancy loss in humans and exposure to arsenic in drinking water.

    PubMed

    Bloom, Michael S; Fitzgerald, Edward F; Kim, Keewan; Neamtiu, Iulia; Gurzau, Eugen S

    2010-11-01

    Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss.

  7. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia

    SciTech Connect

    Vibol, Sao; Hashim, Jamal Hisham; Sarmani, Sukiman

    2015-02-15

    The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300–500 μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50–300 μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samples were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93 μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22 μg/g, and the control site (n=214) had a median hair As level of 0.08 μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57–4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93 µg/g among those from the highly

  8. Effects of individual and combined exposure to sodium arsenite and sodium fluoride on tissue oxidative stress, arsenic and fluoride levels in male mice.

    PubMed

    Mittal, Megha; Flora, S J S

    2006-08-25

    Arsenic and fluoride are potent toxicants, widely distributed through drinking water and food and often result in adverse health effects. The present study examined the effects of sodium meta-arsenite (100 mg/l in drinking water) and sodium fluoride (5 mg/kg, oral, once daily), administered either alone or in combination for 8 weeks, on various biochemical variables indicative of tissue oxidative stress and cell injury in Swiss albino male mice. A separate group was first exposed to arsenic for 4 weeks followed by 4 weeks of fluoride exposure. Exposure to arsenic or fluoride led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity and glutathione (GSH) level. These changes were accompanied by increased level of blood and tissues reactive oxygen species (ROS) level. An increase in the level of liver and kidney thiobarbituric acid reactive substance (TBARS) along with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) and reduced GSH content were observed in both arsenic and fluoride administered mice. The changes were significantly more pronounced in arsenic exposed animals than in fluoride. It was interesting to observe that during combined exposure the toxic effects were less pronounced compared to the effects of arsenic or fluoride alone. In some cases antagonistic effects were noted following co-exposure to arsenic and fluoride. Arsenic and fluoride concentration increased significantly on exposure. Interestingly, their concentration decreased significantly on concomitant exposure for 8 weeks. However, the group which was administered arsenic for 4 weeks followed by 4 weeks of fluoride administration showed no such protection suggesting that the antagonistic effect of fluoride on arsenic or vice versa is possible only during interaction at the gastro intestinal sites. These results are new and interesting and require further exploration.

  9. Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

    PubMed

    Rivera-Núñez, Zorimar; Meliker, Jaymie R; Meeker, John D; Slotnick, Melissa J; Nriagu, Jerome O

    2012-01-01

    The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1 μg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

  10. 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

  11. Indoor transformer stations and ELF magnetic field exposure: use of transformer structural characteristics to improve exposure assessment.

    PubMed

    Okokon, Enembe Oku; Roivainen, Päivi; Kheifets, Leeka; Mezei, Gabor; Juutilainen, Jukka

    2014-01-01

    Previous studies have shown that populations of multiapartment buildings with indoor transformer stations may serve as a basis for improved epidemiological studies on the relationship between childhood leukaemia and extremely-low-frequency (ELF) magnetic fields (MFs). This study investigated whether classification based on structural characteristics of the transformer stations would improve ELF MF exposure assessment. The data included MF measurements in apartments directly above transformer stations ("exposed" apartments) in 30 buildings in Finland, and reference apartments in the same buildings. Transformer structural characteristics (type and location of low-voltage conductors) were used to classify exposed apartments into high-exposure (HE) and intermediate-exposure (IE) categories. An exposure gradient was observed: both the time-average MF and time above a threshold (0.4 μT) were highest in the HE apartments and lowest in the reference apartments, showing a statistically significant trend. The differences between HE and IE apartments, however, were not statistically significant. A simulation exercise showed that the three-category classification did not perform better than a two-category classification (exposed and reference apartments) in detecting the existence of an increased risk. However, data on the structural characteristics of transformers is potentially useful for evaluating exposure-response relationship.

  12. Radiofrequency exposure and mammalian cell toxicity, genotoxicity, and transformation.

    PubMed

    Meltz, Martin L

    2003-01-01

    The published in vitro literature relevant to the issue of the possible induction of toxicity, genotoxicity, and transformation of mammalian cells due to radiofrequency field (RF) exposure is examined. In some instances, information about related in vivo studies is presented. The review is from the perspective of technical merit and also biological consistency, especially with regard to those publications reporting a positive effect. The weight of evidence available indicates that, for a variety of frequencies and modulations with both short and long exposure times, at exposure levels that do not (or in some instances do) heat the biological sample such that there is a measurable increase in temperature, RF exposure does not induce (a). DNA strand breaks, (b). chromosome aberrations, (c). sister chromatid exchanges (SCEs), (d). DNA repair synthesis, (e). phenotypic mutation, or (f). transformation (cancer-like changes). While there is limited experimental evidence that RF exposure induces micronuclei formation, there is abundant evidence that it does not. There is some evidence that RF exposure does not induce DNA excision repair, suggesting the absence of base damage. There is also evidence that RF exposure does not inhibit excision repair after the induction of thymine dimers by UV exposure, as well as evidence that indicates that RF is not a co-carcinogen or a tumor promoter. The article is in part a tutorial, so that the reader can consider similarities and discrepancies between reports of RF-induced effects relative to one another.

  13. Comparison of drinking water, raw rice and cooking of rice as arsenic exposure routes in three contrasting areas of West Bengal, India.

    PubMed

    Mondal, Debapriya; Banerjee, Mayukh; Kundu, Manjari; Banerjee, Nilanjana; Bhattacharya, Udayan; Giri, Ashok K; Ganguli, Bhaswati; Sen Roy, Sugata; Polya, David A

    2010-12-01

    Remediation aimed at reducing human exposure to groundwater arsenic in West Bengal, one of the regions most impacted by this environmental hazard, are currently largely focussed on reducing arsenic in drinking water. Rice and cooking of rice, however, have also been identified as important or potentially important exposure routes. Quantifying the relative importance of these exposure routes is critically required to inform the prioritisation and selection of remediation strategies. The aim of our study, therefore, was to determine the relative contributions of drinking water, rice and cooking of rice to human exposure in three contrasting areas of West Bengal with different overall levels of exposure to arsenic, viz. high (Bhawangola-I Block, Murshidibad District), moderate (Chakdha Block, Nadia District) and low (Khejuri-I Block, Midnapur District). Arsenic exposure from water was highly variable, median exposures being 0.02 μg/kg/d (Midnapur), 0.77 μg/kg/d (Nadia) and 2.03 μg/kg/d (Murshidabad). In contrast arsenic exposure from cooked rice was relatively uniform, with median exposures being 0.30 μg/kg/d (Midnapur), 0.50 μg/kg/d (Nadia) and 0.84 μg/kg/d (Murshidabad). Cooking rice typically resulted in arsenic exposures of lower magnitude, indeed in Midnapur, median exposure from cooking was slightly negative. Water was the dominant route of exposure in Murshidabad, both water and rice were major exposure routes in Nadia, whereas rice was the dominant exposure route in Midnapur. Notwithstanding the differences in balance of exposure routes, median excess lifetime cancer risk for all the blocks were found to exceed the USEPA regulatory threshold target cancer risk level of 10(-4)-10(-6). The difference in balance of exposure routes indicate a difference in balance of remediation approaches in the three districts.

  14. Drinking water arsenic exposure and blood pressure in healthy women of reproductive age in Inner Mongolia, China

    SciTech Connect

    Kwok, Richard K. Mendola, Pauline; Liu Zhiyi; Savitz, David A.; Heiss, Gerardo; Ling Heling; Xia Yajuan; Lobdell, Danelle; Zeng Donglin; Thorp, John M.; Creason, John P.; Mumford, Judy L.

    2007-08-01

    The extremely high exposure levels evaluated in prior investigations relating elevated levels of drinking water arsenic and hypertension prevalence make extrapolation to potential vascular effects at lower exposure levels very difficult. A cross-sectional study was conducted on 8790 women who had recently been pregnant in an area of Inner Mongolia, China known to have a gradient of drinking water arsenic exposure. This study observed increased systolic blood pressure levels with increasing drinking water arsenic, at lower exposure levels than previously reported in the literature. As compared to the referent category (below limit of detection to 20 {mu}g of As/L), the overall population mean systolic blood pressure rose 1.29 mm Hg (95% CI 0.82, 1.75), 1.28 mm Hg (95% CI 0.49, 2.07), and 2.22 mm Hg (95% CI 1.46, 2.97) as drinking water arsenic concentration increased from 21 to 50, 51 to 100, and > 100 {mu}g of As/L, respectively. Controlling for age and body weight (n = 3260), the population mean systolic blood pressure rose 1.88 mm Hg (95% CI 1.03, 2.73), 3.90 mm Hg (95% CI 2.52, 5.29), and 6.83 mm Hg (95% CI 5.39, 8.27) as drinking water arsenic concentration increased, respectively. For diastolic blood pressure effect, while statistically significant, was not as pronounced as systolic blood pressure. Mean diastolic blood pressure rose 0.78 mm Hg (95% CI 0.39, 1.16), 1.57 mm Hg (95% CI 0.91, 2.22) and 1.32 mm Hg (95% CI 0.70, 1.95), respectively, for the overall population and rose 2.11 mm Hg (95% CI 1.38, 2.84), 2.74 mm Hg (95% CI 1.55, 3.93), and 3.08 mm Hg (95% CI 1.84, 4.31), respectively, for the adjusted population (n = 3260) at drinking water arsenic concentrations of 21 to 50, 51 to 100, and > 100 {mu}g of As/L. If our study results are confirmed in other populations, the potential burden of cardiovascular disease attributable to drinking water arsenic is significant.

  15. The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area

    SciTech Connect

    Huang, Chao-Yuan; Su, Chien-Tien; Chu, Jan-Show; Huang, Shu-Pin; Pu, Yeong-Shiau; Yang, Hsiu-Yuan; Chung, Chi-Jung; Wu, Chia-Chang; Hsueh, Yu-Mei

    2011-12-15

    Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, and MDM2, which plays a role in gene stability, and the arsenic-related RCC risk. Here, we found that p53 Pro/Pro genotype and MDM2 SNP309 GG genotype significantly increased RCC risk compared to the p53 Arg/Arg genotype and MDM2 SNP309 TT genotype. RCC patients with the p53Arg/Arg genotype had a signicantly low percentage of inorganic arsenic, a low percentage of monomethylarsonic acid (MMA), and a high percentage of dimethylarsinic acid (DMA), which indicates efcient arsenic methylation capacity. Subjects with the p53 Arg/Pro + Pro/Pro genotype or MDM2 SNP309 TG + GG genotype, in conjunction with high urinary total arsenic ({>=} 14.02 {mu}g/L), had a signicantly higher RCC risk than those with the p53 Arg/Arg or MDM2 SNP309 TT genotypes and low urinary total arsenic. Taken together, this is the first study to show that a variant genotype of p53 Arg{sup 72}Pro or MDM2 SNP309 may modify the arsenic-related RCC risk even in a non-obvious arsenic exposure area. -- Highlights: Black-Right-Pointing-Pointer Subjects with p53 Pro/Pro or MDM2 GG genotype significantly increased RCC risk. Black-Right-Pointing-Pointer A significant multiplicative joint effect of p53 and p21 on RCC risk. Black-Right-Pointing-Pointer RCC patients with p53 Arg/Arg genotype had efficient arsenic methylation capacity. Black-Right-Pointing-Pointer Joint effect of p53 or MDM2 genotype and high urinary total arsenic on RCC risk.

  16. Sustained Early Disruption of Mitochondrial Function Contributes to Arsenic-Induced Prostate Tumorigenesis.

    PubMed

    Singh, B; Kulawiec, M; Owens, K M; Singh, A; Singh, K K

    2016-10-01

    Arsenic is a well-known human carcinogen that affects millions of people worldwide, but the underlying mechanisms of carcinogenesis are unclear. Several epidemiological studies have suggested increased prostate cancer incidence and mortality due to exposure to arsenic. Due to lack of an animal model of arsenic-induced carcinogenesis, we used a prostate epithelial cell culture model to identify a role for mitochondria in arsenic-induced prostate cancer. Mitochondrial morphology and membrane potential was impacted within a few hours of arsenic exposure of non-neoplastic prostate epithelial cells. Chronic arsenic treatment induced mutations in mitochondrial genes and altered mitochondrial functions. Human non-neoplastic prostate epithelial cells continuously cultured for seven months in the presence of 5 µM arsenite showed tumorigenic properties in vitro and induced tumors in SCID mice, which indicated transformation of these cells. Protein and mRNA expression of subunits of mtOXPHOS complex I were decreased in arsenic-transformed cells. Alterations in complex I, a main site for reactive oxygen species (ROS) production as well as increased expression of ROS-producing NOX4 in arsenic-transformed cells suggested a role of oxidative stress in tumorigenic transformation of prostate epithelial cells. Whole genome cGH array analyses of arsenic-transformed prostate cells identified extensive genomic instability. Our study revealed mitochondrial dysfunction induced oxidative stress and decreased expression of p53 in arsenic-transformed cells as an underlying mechanism of the mitochondrial and nuclear genomic instability. These studies suggest that early changes in mitochondrial functions are sustained during prolong arsenic exposure. Overall, our study provides evidence that arsenic disruption of mitochondrial function is an early and key step in tumorigenic transformation of prostate epithelial cells.

  17. Inorganic Arsenic and Human Prostate Cancer

    PubMed Central

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

    Objective We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. PMID:18288312

  18. Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

    PubMed

    Tsuji, Joyce S; Alexander, Dominik D; Perez, Vanessa; Mink, Pamela J

    2014-03-20

    While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.

  19. Arsenic Exposure Induces Unscheduled Mitotic S Phase Entry Coupled with Cell Death in Mouse Cortical Astrocytes

    PubMed Central

    Htike, Nang T. T.; Maekawa, Fumihiko; Soutome, Haruka; Sano, Kazuhiro; Maejima, Sho; Aung, Kyaw H.; Tokuda, Masaaki; Tsukahara, Shinji

    2016-01-01

    There is serious concern about arsenic in the natural environment, which exhibits neurotoxicity and increases the risk of neurodevelopmental disorders. Adverse effects of arsenic have been demonstrated in neurons, but it is not fully understood how arsenic affects other cell types in the brain. In the current study, we examined whether sodium arsenite (NaAsO2) affects the cell cycle, viability, and apoptosis of in vitro-cultured astrocytes isolated from the cerebral cortex of mice. Cultured astrocytes from transgenic mice expressing fluorescent ubiquitination-based cell cycle indicator (Fucci) were subjected to live imaging analysis to assess the effects of NaAsO2 (0, 1, 2, and 4 μM) on the cell cycle and number of cells. Fucci was designed to express monomeric Kusabira Orange2 (mKO2) fused with the ubiquitylation domain of hCdt1, a marker of G1 phase, and monomeric Azami Green (mAG) fused with the ubiquitylation domain of hGem, a marker of S, G2, and M phases. NaAsO2 concentration-dependently decreased the peak levels of the mAG/mKO2 emission ratio when the ratio had reached a peak in astrocytes without NaAsO2 exposure, which was due to attenuating the increase in the mAG-expressing cell number. In contrast, the mAG/mKO2 emission ratio and number of mAG-expressing cells were concentration-dependently increased by NaAsO2 before their peak levels, indicating unscheduled S phase entry. We further examined the fate of cells forced to enter S phase by NaAsO2. We found that most of these cells died up to the end of live imaging. In addition, quantification of the copy number of the glial fibrillary acidic protein gene expressed specifically in astrocytes revealed a concentration-dependent decrease caused by NaAsO2. However, NaAsO2 did not increase the amount of nucleosomes generated from DNA fragmentation and failed to alter the gene expression of molecules relevant to unscheduled S phase entry-coupled apoptosis (p21, p53, E2F1, E2F4, and Gm36566). These findings

  20. Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation

    NASA Astrophysics Data System (ADS)

    Rea, Matthew; Eckstein, Meredith; Eleazer, Rebekah; Smith, Caroline; Fondufe-Mittendorf, Yvonne N.

    2017-02-01

    Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated during iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how CTCF binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin.

  1. Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation

    PubMed Central

    Rea, Matthew; Eckstein, Meredith; Eleazer, Rebekah; Smith, Caroline; Fondufe-Mittendorf , Yvonne N.

    2017-01-01

    Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated during iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how CTCF binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin. PMID:28150704

  2. Low-level arsenic exposure is associated with bladder cancer risk and cigarette smoking: a case-control study among men in Tunisia.

    PubMed

    Feki-Tounsi, Molka; Olmedo, Pablo; Gil, Fernando; Khlifi, Rim; Mhiri, Mohamed-Nabil; Rebai, Ahmed; Hamza-Chaffai, Amel

    2013-06-01

    Although exposure to high levels of arsenic is associated with excess bladder cancer risk, lower exposures generally are not. This study represents the first biomonitoring of arsenic exposure in Tunisia and focuses on a possible association with bladder cancer risk. In this context, 124 male bladder cancer cases and 220 controls were recruited and blood samples were analyzed to determine the concentration of As. The study subjects were stratified into median groups based on concentrations of arsenic in their blood. Blood arsenic (B-As) was significantly two to threefold higher in bladder cancer cases than in controls (p<0.05). The arsenic concentrations were significantly higher among both smokers and workers in construction. However, neither drinking water nor seafood was found to be incriminated as exposure sources. The adjusted risk ratios for B-As concentration categories 0.1-0.67 and ≥ 0.67 μg/L were 0.18 (95% CI=0.014-2.95) and 2.44 (95% CI=1.11-5.35), respectively. Arsenic levels were not found to be associated with tumor grade or stage. The considerable risk in the category of highest cumulative exposure argues for an association between bladder cancer risk and low-level arsenic exposure. Future investigations with larger samples and using techniques that allow the distinction of the different arsenic species should better elucidate this association. Furthermore, the modulation of arsenic level according to the histological grade may be of potential to be used as a diagnostic marker of the disease process and its possible relationship etiologically.

  3. IMMUNOTOXICITY AND BIODISTRIBUTION ANALYSIS OF ARSENIC TRIOXIDE IN C57Bl/6 MICE FOLLOWING A TWO-WEEK INHALATION EXPOSURE

    PubMed Central

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun, Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu, Ke Jian

    2010-01-01

    In these studies the immunotoxicity of arsenic trioxide (ATO, As2O3) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 hrs per day) at concentrations of 50 μg/m3 and 1 mg/m3. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 μg/mg tissue following the 1 mg/m3 exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 μg/m3 and 1 mg/m3 exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents. PMID:19800901

  4. Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

    SciTech Connect

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

    2009-12-15

    In these studies the immunotoxicity of arsenic trioxide (ATO, As{sub 2}O{sub 3}) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 mug/m{sup 3} and 1 mg/m{sup 3}. A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 mug/g tissue following the 1 mg/m{sup 3} exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 mug/m{sup 3} and 1 mg/m{sup 3} exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

  5. Transformation and characterization of an arsenic gene operon from urease-positive thermophilic Campylobacter (UPTC) in Escherichia coli.

    PubMed

    Matsuda, M; Kuribayashi, T; Yamamoto, S; Millar, B C; Moore, J E

    2016-01-01

    An arsenate susceptibility test was performed with transformed and cultured Escherichia coli DH5α cells, which carried recombinant DNA of full-length arsenic (ars) operon, namely a putative membrane permease, ArsP; a transcriptional repressor, ArsR; an arsenate reductase, ArsC; and an arsenical-resistance membrane transporter, Acr3, from the Japanese urease-positive thermophilic Campylobacter lari (UPTC) CF89-12. The E. coli DH5α transformant showed reduced susceptibility to arsenate (~1536 μg/mL), compared to the control. Thus, these ars four-genes from the UPTC CF89-12 strain cells could confer a reduced susceptibility to arsenate in the transformed and E. coli DH5α cells. E. coli transformants with truncated ars operons, acr3 (acr3) and arsC-acr3 (∆arsC-acr3), of the ars operon, showed an MIC value of 384 μg/mL (~384 μg/mL), similar to the E. coli cells which carried the pGEM-T vector (control). Reverse transcription PCR confirmed in vivo transcription of recombinant full-length ars operon and deletion variants (∆acr3 and ∆arsC-acr3) in the transformed E. coli cells.

  6. Risk assessment from exposure to arsenic, antimony, and selenium in urban gardens (Madrid, Spain).

    PubMed

    De Miguel, Eduardo; Izquierdo, Miguel; Gómez, Amaia; Mingot, Juan; Barrio-Parra, Fernando

    2017-02-01

    The authors discuss the geochemical behavior of arsenic (As), antimony (Sb), and selenium (Se) in urban gardens and the human health implications associated with urban agriculture. A total of 42 samples from 7 urban gardens in Madrid, Spain, were collected from the top 20 cm of soil. Concentrations of As, Sb, and Se and the main soil properties (i.e., total iron, pH, texture, calcium carbonate, and organic matter) were determined. A significant correlation was found between As and Sb and calcium carbonate, indicating the possibility of surface adsorption or ligand exchange with the carbonate group. Also, Sb seemed to form stable chelates with soil organic matter. On the other hand, Se showed a significant association with clay and iron content. The concentration of Sb in soil exceeded the recommended value for agricultural use in 70% of the urban gardens. A human health risk assessment resulted in acceptable levels of both noncarcinogenic and carcinogenic risks (although with elevated values of the latter), with As as the main risk driver and soil and food ingestion as the main exposure pathways. The numerical results of the risk assessment should be interpreted with caution given the considerable uncertainties in some exposure variables and the lack of quantitative values for the suspected carcinogenicity of Sb and Se. Environ Toxicol Chem 2017;36:544-550. © 2016 SETAC.

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

    PubMed

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

    2015-12-23

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

  8. Arsenic redox transformation by Pseudomonas sp. HN-2 isolated from arsenic-contaminated soil in Hunan, China.

    PubMed

    Zhang, Zhennan; Yin, Naiyi; Cai, Xiaolin; Wang, Zhenzhou; Cui, Yanshan

    2016-09-01

    A mesophilic, Gram-negative, arsenite[As(III)]-oxidizing and arsenate[As(V)]-reducing bacterial strain, Pseudomonas sp. HN-2, was isolated from an As-contaminated soil. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that the strain was closely related to Pseudomonas stutzeri. Under aerobic conditions, this strain oxidized 92.0% (61.4μmol/L) of arsenite to arsenate within 3hr of incubation. Reduction of As(V) to As(III) occurred in anoxic conditions. Pseudomonas sp. HN-2 is among the first soil bacteria shown to be capable of both aerobic As(III) oxidation and anoxic As(V) reduction. The strain, as an efficient As(III) oxidizer and As(V) reducer in Pseudomonas, has the potential to impact arsenic mobility in both anoxic and aerobic environments, and has potential application in As remediation processes.

  9. Effect of Vitamin E Supplementation on Hematological and Plasma Biochemical Parameters during Long Term Exposure of Arsenic in Goats

    PubMed Central

    Das, Tapan Kumar; Mani, Veena; Kaur, Harjit; Kewalramani, Neelam; Agarwal, Anjali

    2012-01-01

    The present investigation was designed to determine whether supplementation of different level of vitamin E for 12 months to arsenic exposed goats (50 ppm as sodium arsenite) affords protection against the blood hemato-biochemical parameters caused by the metalloid. A total of 24 crossbred (Alpine×Beetal) lactating goats were assigned randomly into 4 equal groups (control, T1, T2 and T3) of 6 in each, on the basis of average body weight (36.10±0.11 kg) and milk yield (1.61±0.04 kg/d). The animals in T1, T2 and T3 were given 50 ppm arsenic, while in T2 and T3, additionally; vitamin E at the rate of 100 IU and 150 IU/kg dry matter (DM) respectively was additionally supplemented for the period of 12 months. Hemoglobin (Hb), total leukocyte (TLC) and blood lymphocyte % were decreased (p<0.05) in arsenic fed groups and vitamin E supplementation in the experimental group showed a protective potential. Significant increases (p<0.05) in aspertate transaminase (AST) and alanine transaminase (ALT) activities among arsenic supplemented groups were recorded, however vitamin E supplementation at higher doses showed a protective effect (p<0.05) against AST but in the case of ALT no ameliorating effect was found in either of the doses. Plasma total protein was decreased (p>0.05) but creatinine level was periodically increased in all As supplemented groups and vitamin E supplementation did not produce any protective effect. It can be concluded that arsenic exposure resulted in varying degree of changes in hemato-biochemical parameters and activities of antioxidant enzymes in goats but concomitant treatment with Vitamin E is partially helpful in reducing the burden of arsenic induced effect. PMID:25049689

  10. Impact of exposure to tobacco smoke, arsenic, and phthalates on locally advanced cervical cancer treatment—preliminary results

    PubMed Central

    Bloom, Michael S.; Dumitrascu, Irina; Roba, Carmen A.; Pop, Cristian; Ordeanu, Claudia; Balacescu, Ovidiu; Gurzau, Eugen S.

    2016-01-01

    Background Cancer research is a national and international priority, with the efficiency and effectiveness of current anti-tumor therapies being one of the major challenges with which physicians are faced. Objective To assess the impact of exposure to tobacco smoke, arsenic, and phthalates on cervical cancer treatment. Methods We investigated 37 patients with locally advanced cervical carcinoma who underwent chemotherapy and radiotherapy. We determined cotinine and five phthalate metabolites in urine samples collected prior to cancer treatment, by gas chromatography coupled to mass spectrometry, and urinary total arsenic by atomic absorption spectrometry with hydride generation. We used linear regression to evaluate the effects of cotinine, arsenic, and phthalates on the change in tumor size after treatment, adjusted for confounding variables. Results We detected no significant associations between urinary cotinine, arsenic, or phthalate monoesters on change in tumor size after treatment, adjusted for urine creatinine, age, baseline tumor size, and cotinine (for arsenic and phthalates). However, higher %mono-ethylhexyl phthalate (%MEHP), a putative indicator of phthalate diester metabolism, was associated with a larger change in tumor size (β = 0.015, 95% CI [0.003–0.03], P = 0.019). Conclusion We found no statistically significant association between the urinary levels of arsenic, cotinine, and phthalates metabolites and the response to cervical cancer treatment as measured by the change in tumor size. Still, our results suggested that phthalates metabolism may be associated with response to treatment for locally advanced cervical cancer. However, these observations are preliminary and will require confirmation in a larger, more definitive investigation. PMID:27652000

  11. Impact of silica on the reductive transformation of schwertmannite and the mobilization of arsenic

    NASA Astrophysics Data System (ADS)

    Burton, Edward D.; Johnston, Scott G.

    2012-11-01

    proceed prior to the formation of surface-passivating Si species. The Fe2+ catalyzed transformation of As(V)-coprecipitated schwertmannite to goethite caused a major increase in PO43--extractable As, but had little effect on aqueous As concentrations. The reduction of Fe(III) and the subsequent onset of dissimilatory SO42- reduction led to formation of siderite (FeCO3) and mackinawite (FeS), respectively. The reduction of As(V) to As(III) was associated with the Si-dependent mobilization of As into the aqueous-phase. There was a concurrent decrease over time in the concentrations of PO43--extractable As, which occurred independent of Si concentrations and appeared to be related to formation of siderite and mackinawite. The findings from this study provide new insights into the evolution of iron mineralogy and associated arsenic mobility following the establishment of reducing conditions in schwertmannite- and Si-rich environments.

  12. Trivalent methylated arsenical-induced phosphatidylserine exposure and apoptosis in platelets may lead to increased thrombus formation

    SciTech Connect

    Bae, Ok-Nam; Lim, Kyung-Min; Chung, Jin-Ho

    2009-09-01

    Trivalent methylated metabolites of arsenic, monomethylarsonous acid (MMA{sup III}) and dimethylarsinous acid (DMA{sup III}), have been found highly reactive and toxic in various cells and in vivo animal models, suggesting their roles in the arsenic-associated toxicity. However, their effects on cardiovascular system including blood cells, one of the most important targets for arsenic toxicity, remain poorly understood. Here we found that MMA{sup III} and DMA{sup III} could induce procoagulant activity and apoptosis in platelets, which play key roles in the development of various cardiovascular diseases (CVDs) through excessive thrombus formation. In freshly isolated human platelets, treatment of MMA{sup III} resulted in phosphatidylserine (PS) exposure, a hallmark of procoagulant activation, accompanied by distinctive apoptotic features including mitochondrial membrane potential disruption, cytochrome c release, and caspase-3 activation. These procoagulant activation and apoptotic features were found to be mediated by the depletion of protein thiol and intracellular ATP, and flippase inhibition by MMA{sup III}, while the intracellular calcium increase or reactive oxygen species generation was not involved. Importantly, increased platelet procoagulant activity by MMA{sup III} resulted in enhanced blood coagulation and excessive thrombus formation in a rat in vivo venous thrombosis model. DMA{sup III} also induced PS-exposure with apoptotic features mediated by protein thiol depletion, which resulted in enhanced thrombin generation. In summary, we believe that this study provides an important evidence for the role of trivalent methylated arsenic metabolites in arsenic-associated CVDs, giving a novel insight into the role of platelet apoptosis in toxicant-induced cardiovascular toxicity.

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

    PubMed Central

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

    2015-01-01

    Background Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. Objective This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. Methods We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. Results After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Conclusions Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Citation Mendez MA, González-Horta C, Sánchez-Ramírez B

  14. Monitoring the arsenic and iodine exposure of seaweed-eating North Ronaldsay sheep from the gestational and suckling periods to adulthood by using horns as a dietary archive.

    PubMed

    Caumette, Guilhem; Ouypornkochagorn, Sairoong; Scrimgeour, Charlie M; Raab, Andrea; Feldmann, Jörg

    2007-04-15

    Trace elements often accumulate in keratin-rich tissues. Hair, nails, and horns grow steadily but once formed are metabolically inactive and provide an archive of trace element exposure when analyzed in segments. Here we demonstrate the use of laser ablation ICP-MS for the high-resolution monitoring of trace elements in the horns of seaweed-eating sheep from North Ronaldsay, which live on grass only during lambing time. Due to this peculiar husbandry/dietary pattern and the fact that seaweed is rich in arsenic and iodine, we hoped to use iodine and arsenic as markers for seaweed ingestion. Cross sections and scans along the growing axis (representing the first 8-10 months of the sheep's life) revealed that these elements were not homogeneously distributed in the horn, with arsenic representing the amount of seaweed intake. The scans show the periods in which the lambs were fed on milk and grass and the change to seaweed ingestion with the successive replacement of milk with seaweed; this was supported by the carbon and nitrogen isotope signatures (delta13C and delta15N) of the horn and the arsenic speciation in the horn. The period of low arsenic accumulation in the horn had terrestrial isotope signatures and accumulated arsenic of mainly inorganic origin. The period of high arsenic accumulation was characterized by isotope signatures of marine origin, and the majority of accumulated arsenic in the horn was the main arsenosugar metabolite dimethylarsinic acid. Although we have investigated only four different horns of individual sheep, this study shows that arsenic is not significantly transported with milk. However, the high concentration of arsenic in the oldest part of the horn, which was formed in utero, points to a relatively high placental transport of arsenic while the ewe was eating seaweed. In contrast to arsenic, iodine is transported not only through milk ingestion but also through the placenta in large quantities.

  15. Arsenic exposure, inflammation, and renal function in Bangladeshi adults: effect modification by plasma glutathione redox potential

    PubMed Central

    Peters, Brandilyn A.; Liu, Xinhua; Hall, Megan N.; Ilievski, Vesna; Slavkovich, Vesna; Siddique, Abu B.; Alam, Shafiul; Islam, Tariqul; Graziano, Joseph H.; Gamble, Mary V.

    2015-01-01

    Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (EhGSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having EhGSH > median (uAs pWald = 0.03; bAs pWald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by EhGSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma EhGSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma EhGSH and reduces risk for As-induced diseases. PMID:25916185

  16. Maternal-infant biomarkers of prenatal exposure to arsenic and manganese.

    PubMed

    Rodrigues, Ema G; Kile, Molly; Dobson, Christine; Amarasiriwardena, Chitra; Quamruzzaman, Quazi; Rahman, Mahmuder; Golam, Mostofa; Christiani, David C

    2015-01-01

    Because arsenic (As) and manganese (Mn) are able to pass the placenta, infants among exposed populations may be exposed to considerable levels in utero. The main objective of this paper is to evaluate infant toenails, hair, and cord blood as biomarkers of prenatal exposure to As and Mn and determine the relationship between maternal and infant As and Mn concentrations in these biomarkers. Of the 1196 pregnant women in Bangladesh who were monitored throughout pregnancy until 1 month post-partum and completed all study visits, we included 711 mother-infant pairs who had at least one maternal and one infant biomarker of exposure available for analysis. Toenail and hair samples were collected from the women during the first trimester and 1 month post-partum and from the infants at the age of 1 month. Cord blood was collected at the time of delivery. Maternal toenail concentrations were correlated with infant toenail concentrations for As and Mn (n=258, r=0.52, 95% CI: 0.43-0.60, P<0.0001 and r=0.39, 95% CI: 0.28-0.49, P<0.0001), respectively. Similarly, maternal hair concentrations were correlated with infant hair As (n=685, r=0.61, 95% CI: 0.56-0.65, P<0.0001) and infant hair Mn (n=686, r=0.21, 95% CI: 0.14-0.28, P<0.0001). Cord blood As was correlated with infant toenail and hair As, although cord blood Mn was only correlated with infant toenail. Toenails and cord blood appear to be valid biomarkers of maternal-fetal transfer of As and Mn, whereas hair may not be a suitable biomarker for in utero exposure to Mn.

  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. Biotransformation of inorganic arsenic in a marine herbivorous fish Siganus fuscescens after dietborne exposure.

    PubMed

    Zhang, Wei; Chen, Lizhao; Zhou, Yanyan; Wu, Yun; Zhang, Li

    2016-03-01

    Arsenic (As) is well known to be biodiminished along marine food chains. The marine herbivorous fish at a lower trophic level are expected to accumulate more As. However, little is known about how marine herbivorous fish biotransform the potential high As bioaccumulation. Therefore, the present study quantified the biotransformation of two inorganic As species (As(III) and As(V)) in a marine herbivorous fish Siganus fuscescens following dietborne exposure. The fish were fed on As contaminated artificial diets at nominal concentrations of 400 and 1500 μg As(III) or As(V) g(-1) (dry weight) for 21 d and 42 d. After exposure, As concentrations in intestine, liver, and muscle tissues of rabbitfish increased significantly and were proportional to the inorganic As exposure concentrations. The present study demonstrated that both inorganic As(III) and As(V) in the dietborne phases were able to be biotransformed to the less toxic arsenobetaine (AsB) (63.3-91.3% in liver; 79.0%-95.2% in muscle). The processes of As biotransformation in rabbitfish could include oxidation of As(III) to As(V), reduction of As(V) to As(III), methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to AsB. These results also demonstrated that AsB synthesis processes were diverse facing different inorganic As species in different tissues. In summary, the present study elucidated that marine herbivorous fish had high ability to biotransform inorganic As to the organic forms (mainly AsB), resulting in high As bioaccumulation. Therefore, marine herbivorous fish could detoxify inorganic As in the natural environment.

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

    PubMed Central

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

    2013-01-01

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

  20. Arsenic-induced health crisis in peri-urban Moyna and Ardebok villages, West Bengal, India: an exposure assessment study.

    PubMed

    Maity, Jyoti Prakash; Nath, Bibhash; Kar, Sandeep; Chen, Chien-Yen; Banerjee, Satabdi; Jean, Jiin-Shuh; Liu, Ming-Yie; Centeno, José A; Bhattacharya, Prosun; Chang, Christina L; Santra, Subhas Chandra

    2012-10-01

    Drinking of arsenic (As)-contaminated groundwater has adverse effects on health of millions of people worldwide. This study aimed to determine the degree of severity of As exposure from drinking water in peri-urban Moyna and Ardebok villages, West Bengal, India. Arsenic concentrations in hair, nail and urine samp les of the individuals were determined. Arsenical dermatosis, keratosis and melanosis were investigated through medical evaluation. We have evaluated the association between As exposure from drinking water, and keratosis and melanosis outcomes. The results showed that 82.7 % of the sampled tube wells contain As concentrations above 10 μg/L, while 57.7 % contain As concentrations above 50 μg/L. The hair, nail and urine As concentrations were positively correlated with As concentrations in drinking water. In our study population, we observed a strong association between As concentrations ranging 51-99 μg/L and keratosis and melanosis outcomes, although the probability decreases at higher concentration ranges perhaps due to switching away from the use of As-contaminated tube wells for drinking and cooking purposes. High As concentrations in hair, nail and urine were observed to be associated with the age of the study population. The level of As concentrations in hair, nail and urine samples of the study population indicated the degree of severity of As exposure in the study region.

  1. DIETARY ARSENIC EXPOSURE ASSESSMENT USING ENZYMATIC BASED EXTRACTION CONDITIONS AND DETECTION OF URINARY THIO-ARSENICALS AS METABOLITES OF EXPOSURE - MCEARD2

    EPA Science Inventory

    Inorganic arsenic is classified as a carcinogen and has been linked to lung and bladder cancer as well as other non-cancerous health effects. Because of these health effects the U.S. EPA has set a Maximum Contaminant Level (MCL) at 10ppb based on a linear extrapolation of risk an...

  2. Design of a rural water provision system to decrease arsenic exposure in Bangladesh

    SciTech Connect

    Mathieu, Johanna

    2009-01-09

    Researchers at the Lawrence Berkeley National Laboratory have invented ARUBA (Arsenic Removal Using Bottom Ash) a material that effectively and affordably removes high concentrations of arsenic from contaminated groundwater. The technology is cost-effective because the substrate-bottom ash from coal fired power plants-is a waste material readily available in South Asia. During fieldwork in four sub-districts of Bangladesh, ARUBA reduced groundwater arsenic concentrations as high as 680 ppb to below the Bangladesh standard of 50 ppb. Key results from three trips in Bangladesh and one trip to Cambodia include (1) ARUBA removes more than half of the arsenic from contaminated water within the first five minutes of contact, and continues removing arsenic for 2-3 days; (2) ARUBA's arsenic removal efficiency can be improved through fractionated dosing (adding a given amount of ARUBA in fractions versus all at once); (3) allowing water to first stand for two to three days followed by treatment with ARUBA produced final arsenic concentrations ten times lower than treating water directly out of the well; and (4) the amount of arsenic removed per gram of ARUBA is linearly related to the initial arsenic concentration of the water. Through analysis of existing studies, observations, and informal interviews in Bangladesh, eight design strategies have been developed and used in the design of a low-cost, community-scale water treatment system that uses ARUBA to remove arsenic from drinking water. We have constructed, tested, and analyzed a scale version of the system. Experiments have shown that the system is capable of reducing high levels of arsenic (nearly 600 ppb) to below 50 ppb, while remaining affordable to people living on less than $2 per day. The system could be sustainably implemented as a public-private partnership in rural Bangladesh.

  3. Arsenic in the groundwater of Majuli - The largest river island of the Brahmaputra: Magnitude of occurrence and human exposure

    NASA Astrophysics Data System (ADS)

    Goswami, Ritusmita; Rahman, Mohammad Mahmudur; Murrill, Matthew; Sarma, Kali Prasad; Thakur, Ritu; Chakraborti, Dipankar

    2014-10-01

    Arsenic (As) concentrations in tube-well water, sediment, and biological samples, including hair, nail and urine were measured to determine the degree of contamination in groundwater and its impact on local inhabitants in the largest populated riverine island Majuli, Assam, India. Arsenic in the groundwater (n = 380) ranged from <3 to 468 μg/L with 37.6% and 16% of the samples having As above 10 μg/L and 50 μg/L, respectively. Arsenic concentration in the groundwater gradually decreased beyond 25 m depth of tube-wells. Nearly 90% of urine, 100% of hair and 97% of nail samples had As above the normal ranges, but mean As concentrations in hair, nail and urine of Majuli residents were lower than those in other contaminated areas of the Ganga-Meghna-Brahmaputra Plain. Significant positive correlations were observed between As in drinking water and As concentrations in hair, nail and urine samples (r = 0.71-0.78). The range of As concentration in bore-hole sediment was 0.29-1.44 mg/kg. The correlation between As and iron in sediment was found to be very poor. Hydrogeological studies are required to understand the source and mobilization process of As in groundwater of Majuli. Early mitigation measures are urgently needed to save the inhabitants of Majuli from arsenic exposure and possible health effects.

  4. Relationship between long-term exposure to low-level arsenic in drinking water and the prevalence of abnormal blood pressure.

    PubMed

    Zhang, Chuanwu; Mao, Guangyun; He, Suxia; Yang, Zuopeng; Yang, Wei; Zhang, Xiaojing; Qiu, Wenting; Ta, Na; Cao, Li; Yang, Hui; Guo, Xiaojuan

    2013-11-15

    Arsenic increases the risk and incidence of cardiovascular disease. To explore the impact of long-term exposure to low-level arsenic in drinking water on blood pressure including pulse pressure (PP) and mean arterial blood pressure (MAP), a cross-sectional study was conducted in 2010 in which the blood pressure of 405 villagers was measured, who had been drinking water with an inorganic arsenic content <50 μg/L. A multivariate logistic regression model was used to estimate odds ratios and 95% confidence intervals. After adjusting for age, gender, Body Mass Index (BMI), alcohol consumption and smoking, the odds ratios showed a 1.45-fold (95%CI: 0.63-3.35) increase in the group with >30-50 years of arsenic exposure and a 2.95-fold (95%CI: 1.31-6.67) increase in the group with >50 years exposure. Furthermore, the odds ratio for prevalence of abnormal PP and MAP were 1.06 (95%CI: 0.24-4.66) and 0.87 (95%CI: 0.36-2.14) in the group with >30-50 years of exposure, and were 2.46 (95%CI: 0.87-6.97) and 3.75 (95%CI: 1.61-8.71) for the group with >50 years exposure, compared to the group with arsenic exposure ≤ 30 years respectively. Significant trends for Hypertension (p<0.0001), PP (p<0.0001) and MAP (p=0.0016) were found. The prevalence of hypertension and abnormal PP as well as MAP is marked among a low-level arsenic exposure population, and significantly increases with the duration of arsenic exposure.

  5. Inequitable allocation of deep community wells for reducing arsenic exposure in Bangladesh

    PubMed Central

    van Geen, A.; Ahmed, K. M.; Ahmed, E. B.; Choudhury, I.; Mozumder, M. R.; Bostick, B. C.; Mailloux, B. J.

    2015-01-01

    Community wells that extend deeper than most private wells are crucial for reducing exposure to groundwater arsenic (As) in rural Bangladesh. This study evaluates the impact on access to safe drinking water of 915 such intermediate (90–150 m) and deep (>150 m) wells across a 180 km2 area where a total of 48,790 tubewells were tested with field kits in 2012–13. Half the shallow private wells meet the Bangladesh standard of 50 µg/L for As in drinking water, whereas 92% of the intermediate and deep wells meet the more restrictive World Health Organization guideline for As in drinking water of 10 µg/L. As a proxy for water access, distance calculations show that 29% of shallow wells with >50 µg/L As are located within walking distance (100 m) of at least one of the 915 intermediate or deep wells. Similar calculations for a hypothetical more even distribution of deep wells show that 74% of shallow wells with >50 µg/L As could have been located within 100 m of the same number deep wells. These observations and well-usage data suggest that community wells in Araihazar, and probably elsewhere in Bangladesh, were not optimally allocated by the government because of elite capture. PMID:27087915

  6. Inequitable allocation of deep community wells for reducing arsenic exposure in Bangladesh.

    PubMed

    van Geen, A; Ahmed, K M; Ahmed, E B; Choudhury, I; Mozumder, M R; Bostick, B C; Mailloux, B J

    2016-03-01

    Community wells that extend deeper than most private wells are crucial for reducing exposure to groundwater arsenic (As) in rural Bangladesh. This study evaluates the impact on access to safe drinking water of 915 such intermediate (90-150 m) and deep (>150 m) wells across a 180 km(2) area where a total of 48,790 tubewells were tested with field kits in 2012-13. Half the shallow private wells meet the Bangladesh standard of 50 µg/L for As in drinking water, whereas 92% of the intermediate and deep wells meet the more restrictive World Health Organization guideline for As in drinking water of 10 µg/L. As a proxy for water access, distance calculations show that 29% of shallow wells with >50 µg/L As are located within walking distance (100 m) of at least one of the 915 intermediate or deep wells. Similar calculations for a hypothetical more even distribution of deep wells show that 74% of shallow wells with >50 µg/L As could have been located within 100 m of the same number deep wells. These observations and well-usage data suggest that community wells in Araihazar, and probably elsewhere in Bangladesh, were not optimally allocated by the government because of elite capture.

  7. Modulation of antioxidant defense system after long term arsenic exposure in Zantedeschia aethiopica and Anemopsis californica.

    PubMed

    Del-Toro-Sánchez, Carmen Lizette; Zurita, Florentina; Gutiérrez-Lomelí, Melesio; Solis-Sánchez, Brenda; Wence-Chávez, Laura; Rodríguez-Sahagún, Araceli; Castellanos-Hernández, Osvaldo A; Vázquez-Armenta, Gabriela; Siller-López, Fernando

    2013-08-01

    Zantedeschia aethiopica (calla lily) and Anemopsis californica (yerba mansa) are plant species capable of accumulating arsenic (As) and therefore proposed as phytoremediation for removal of As from drinking water. The effects of a continuous 6 month As exposure (34±11 μg/L) from local contaminated groundwater on the antioxidant response of Z. aethiopica and A. californica were evaluated in leaves and stems of the plants bimonthly in a subsurface flow constructed wetland. As increased the activities of the antioxidant enzymes ascorbate peroxidase, glutathione reductase and catalase where higher levels were observed in Z. aethiopica than A. californica. No significant differences were detected on lipid peroxidation levels or antioxidant capacity evaluated by ORAC and DPPH assays or total phenol contents in any part of the plant, although in general the leaves of both plants showed the best antioxidant defense against the metal. In conclusion, Z. aethiopica and A. californica were able to cope to As through induction of a more sensitive enzymatic antioxidant response mechanism.

  8. Adverse health effects due to arsenic exposure: Modification by dietary supplementation of jaggery in mice

    SciTech Connect

    Singh, Nrashant; Kumar, D.; Lal, Kewal; Raisuddin, S.; Sahu, Anand P.

    2010-02-01

    Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.

  9. Role and mechanism of miR-222 in arsenic-transformed cells for inducing tumor growth.

    PubMed

    Wang, Min; Ge, Xin; Zheng, Jitai; Li, Dongmei; Liu, Xue; Wang, Lin; Jiang, Chengfei; Shi, Zhumei; Qin, Lianju; Liu, Jiayin; Yang, Hushan; Liu, Ling-Zhi; He, Jun; Zhen, Linlin; Jiang, Bing-Hua

    2016-04-05

    High levels of arsenic in drinking water, soil, and air are associated with the higher incidences of several kinds of cancers worldwide, but the mechanism is yet to be fully discovered. Recently, a number of evidences show that dysregulation of microRNAs (miRNAs) induces carcinogenesis. In this study, we found miR-222 was upregulated in arsenic-transformed human lung epithelial BEAS-2B cells (As-T cells). Anti-miR-222 inhibitor treatment decreased cell proliferation, migration, tube formation, and induced apoptosis. In addition, anti-miR-222 inhibitor expression decreased tumor growth in vivo. We also found that inhibition of miR-222 induced the expression of its direct targets ARID1A and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and activated apoptosis of As-T cells in part through ARID1A downregulation. These results indicate that miR-222 plays an important role in arsenic-induced tumor growth.

  10. Role and mechanism of miR-222 in arsenic-transformed cells for inducing tumor growth

    PubMed Central

    Wang, Min; Li, Dongmei; Liu, Xue; Wang, Lin; Jiang, Chengfei; Shi, Zhumei; Qin, Lianju; Liu, Jiayin; Yang, Hushan; Liu, Ling-Zhi; He, Jun; Zhen, Linlin; Jiang, Bing-Hua

    2016-01-01

    High levels of arsenic in drinking water, soil, and air are associated with the higher incidences of several kinds of cancers worldwide, but the mechanism is yet to be fully discovered. Recently, a number of evidences show that dysregulation of microRNAs (miRNAs) induces carcinogenesis. In this study, we found miR-222 was upregulated in arsenic-transformed human lung epithelial BEAS-2B cells (As-T cells). Anti-miR-222 inhibitor treatment decreased cell proliferation, migration, tube formation, and induced apoptosis. In addition, anti-miR-222 inhibitor expression decreased tumor growth in vivo. We also found that inhibition of miR-222 induced the expression of its direct targets ARID1A and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and activated apoptosis of As-T cells in part through ARID1A downregulation. These results indicate that miR-222 plays an important role in arsenic-induced tumor growth. PMID:26909602

  11. Potential arsenic exposures in 25 species of zoo animals living in CCA-wood enclosures.

    PubMed

    Gress, J; da Silva, E B; de Oliveira, L M; Zhao, Di; Anderson, G; Heard, D; Stuchal, L D; Ma, L Q

    2016-05-01

    Animal enclosures are often constructed from wood treated with the pesticide chromated copper arsenate (CCA), which leaches arsenic (As) into adjacent soil during normal weathering. This study evaluated potential pathways of As exposure in 25 species of zoo animals living in CCA-wood enclosures. We analyzed As speciation in complete animal foods, dislodgeable As from CCA-wood, and As levels in enclosure soils, as well as As levels in biomarkers of 9 species of crocodilians (eggs), 4 species of birds (feathers), 1 primate species (hair), and 1 porcupine species (quills). Elevated soil As in samples from 17 enclosures was observed at 1.0-110mg/kg, and enclosures housing threatened and endangered species had As levels higher than USEPA's risk-based Eco-SSL for birds and mammals of 43 and 46mg/kg. Wipe samples of CCA-wood on which primates sit had dislodgeable As residues of 4.6-111μg/100cm(2), typical of unsealed CCA-wood. Inorganic As doses from animal foods were estimated at 0.22-7.8μg/kg bw/d. Some As levels in bird feathers and crocodilian eggs were higher than prior studies on wild species. However, hair from marmosets had 6.37mg/kg As, 30-fold greater than the reference value, possibly due to their inability to methylate inorganic As. Our data suggested that elevated As in soils and dislodgeable As from CCA-wood could be important sources of As exposure for zoo animals.

  12. Transplacental arsenic plus postnatal 12-O-teradecanoyl phorbol-13-acetate exposures associated with hepatocarcinogenesis induce similar aberrant gene expression patterns in male and female mouse liver

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Xie Yaxiong; Merrick, B. Alex; Shen Jun; Ducharme, Danica M.K.; Collins, Jennifer; Diwan, Bhalchandra A.; Logsdon, Daniel; Waalkes, Michael P.

    2006-06-15

    Our prior work shows that in utero arsenic exposure alone is a complete transplacental carcinogen, producing hepatocellular carcinoma in adult male offspring but not in females. In a follow-up study to potentially promote arsenic-initiated tumors, mice were exposed to arsenic (85 ppm) from gestation day 8 to 18 and then exposed to 12-O-teradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter after weaning. The dermal application of TPA (2 {mu}g/0.1 ml acetone, twice/week for 21 weeks) after transplacental arsenic did not further increase arsenic-induced liver tumor formation in adult males but significantly increased liver tumor formation in adult females. Thus, for comparison, liver tumors and normal liver samples taken from adult male and female mice at necropsy were analyzed for aberrant gene/protein expression by microarray, real-time RT-PCR and Western blot analysis. Arsenic/TPA treatment resulted in increased expression of {alpha}-fetoprotein, k-ras, c-myc, estrogen receptor-{alpha}, cyclin D1, cdk2na, plasminogen activator inhibitor-1, cytokeratin-8, cytokeratin-18, glutathione S-transferases and insulin-like growth factor binding proteins in liver and liver tumors from both male and female mice. Arsenic/TPA also decreased the expression of BRCA1, betaine-homocysteine methyltransferase, CYP7B1, CYP2F2 and insulin-like growth factor-1 in normal and cancerous livers. Alterations in these gene products were associated with arsenic/TPA-induced liver tumors, regardless of sex. Thus, transplacental arsenic plus postnatal TPA exposure induced similar aberrant gene expression patterns in male and female mouse liver, which are persistent and potentially important to the mechanism of arsenic initiation of hepatocarcinogenesis.

  13. Neurobehavioral effects of arsenic exposure among secondary school children in the Kandal Province, Cambodia.

    PubMed

    Vibol, Sao; Hashim, Jamal Hisham; Sarmani, Sukiman

    2015-02-01

    The research was carried out at 3 study sites with varying groundwater arsenic (As) levels in the Kandal Province of Cambodia. Kampong Kong Commune was chosen as a highly contaminated site (300-500μg/L), Svay Romiet Commune was chosen as a moderately contaminated site (50-300μg/L) and Anlong Romiet Commune was chosen as a control site. Neurobehavioral tests on the 3 exposure groups were conducted using a modified WHO neurobehavioral core test battery. Seven neurobehavioral tests including digit symbol, digit span, Santa Ana manual dexterity, Benton visual retention, pursuit aiming, trail making and simple reaction time were applied. Children's hair samples were also collected to investigate the influence of hair As levels on the neurobehavioral test scores. The results from the inductively coupled plasma-mass spectrometry (ICP-MS) analyses of hair samples showed that hair As levels at the 3 study sites were significantly different (p<0.001), whereby hair samples from the highly contaminated site (n=157) had a median hair As level of 0.93μg/g, while the moderately contaminated site (n=151) had a median hair As level of 0.22μg/g, and the control site (n=214) had a median hair As level of 0.08μg/g. There were significant differences among the 3 study sites for all the neurobehavioral tests scores, except for digit span (backward) test. Multiple linear regression clearly shows a positive significant influence of hair As levels on all the neurobehavioral test scores, except for digit span (backward) test, after controlling for hair lead (Pb), manganese (Mn) and cadmium (Cd). Children with high hair As levels experienced 1.57-4.67 times greater risk of having lower neurobehavioral test scores compared to those with low hair As levels, after adjusting for hair Pb, Mn and Cd levels and BMI status. In conclusion, arsenic-exposed school children from the Kandal Province of Cambodia with a median hair As level of 0.93µg/g among those from the highly contaminated study

  14. Arsenic exposure and the seroprevalence of total hepatitis A antibodies in the US population: NHANES, 2003-2012.

    PubMed

    Cardenas, A; Smit, E; Bethel, J W; Houseman, E A; Kile, M L

    2016-06-01

    We evaluated the association between urinary arsenic and the seroprevalence of total hepatitis A antibodies (total anti-HAV: IgG and IgM) in 11 092 participants aged ⩾6 years using information collected in the US National Health and Nutrition Examination Survey (2003-2012). Multivariate logistic regression models evaluated associations between total anti-HAV and total urinary arsenic defined as the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate (TUA1). Effect modification by self-reported HAV immunization status was evaluated. Total anti-HAV seroprevalence was 35·1% [95% confidence interval (CI) 33·3-36·9]. Seropositive status was associated with higher arsenic levels and this association was modified by immunization status (P = 0·03). For participants that received ⩾2 vaccine doses or did not know if they had received any doses, a positive dose-response association was observed between increasing TUA1 and odds of total anti-HAV [odds ratio (OR) 1·42, 95% CI 1·11-1·81; and OR 1·75, 95% CI 1·22-2·52], respectively. A positive but not statistically significant association was observed in those who received <2 doses (OR 1·46, 95% CI 0·83-2·59) or no dose (OR 1·12, 95% CI 0·98-1·30). Our analysis indicates that prevalent arsenic exposure was associated with positive total anti-HAV seroprevalence. Further studies are needed to determine if arsenic increases the risk for incident hepatitis A infection or HAV seroconversion.

  15. What Do We Know of Childhood Exposures to Metals (Arsenic, Cadmium, Lead, and Mercury) in Emerging Market Countries?

    PubMed Central

    Horton, Lindsey M.; Mortensen, Mary E.; Iossifova, Yulia; Wald, Marlena M.; Burgess, Paula

    2013-01-01

    Arsenic, cadmium, lead, and mercury present potential health risks to children who are exposed through inhalation or ingestion. Emerging Market countries experience rapid industrial development that may coincide with the increased release of these metals into the environment. A literature review was conducted for English language articles from the 21st century on pediatric exposures to arsenic, cadmium, lead, and mercury in the International Monetary Fund's (IMF) top 10 Emerging Market countries: Brazil, China, India, Indonesia, Mexico, Poland, Russia, South Korea, Taiwan, and Turkey. Seventy-six peer-reviewed, published studies on pediatric exposure to metals met the inclusion criteria. The reported concentrations of metals in blood and urine from these studies were generally higher than US reference values, and many studies identified adverse health effects associated with metals exposure. Evidence of exposure to metals in the pediatric population of these Emerging Market countries demonstrates a need for interventions to reduce exposure and efforts to establish country-specific reference values through surveillance or biomonitoring. The findings from review of these 10 countries also suggest the need for country-specific public health policies and clinician education in Emerging Markets. PMID:23365584

  16. What do we know of childhood exposures to metals (arsenic, cadmium, lead, and mercury) in emerging market countries?

    PubMed

    Horton, Lindsey M; Mortensen, Mary E; Iossifova, Yulia; Wald, Marlena M; Burgess, Paula

    2013-01-01

    Arsenic, cadmium, lead, and mercury present potential health risks to children who are exposed through inhalation or ingestion. Emerging Market countries experience rapid industrial development that may coincide with the increased release of these metals into the environment. A literature review was conducted for English language articles from the 21st century on pediatric exposures to arsenic, cadmium, lead, and mercury in the International Monetary Fund's (IMF) top 10 Emerging Market countries: Brazil, China, India, Indonesia, Mexico, Poland, Russia, South Korea, Taiwan, and Turkey. Seventy-six peer-reviewed, published studies on pediatric exposure to metals met the inclusion criteria. The reported concentrations of metals in blood and urine from these studies were generally higher than US reference values, and many studies identified adverse health effects associated with metals exposure. Evidence of exposure to metals in the pediatric population of these Emerging Market countries demonstrates a need for interventions to reduce exposure and efforts to establish country-specific reference values through surveillance or biomonitoring. The findings from review of these 10 countries also suggest the need for country-specific public health policies and clinician education in Emerging Markets.

  17. Association of Rice and Rice-Product Consumption With Arsenic Exposure Early in Life

    PubMed Central

    Karagas, Margaret R.; Punshon, Tracy; Sayarath, Vicki; Jackson, Brian P.; Folt, Carol L.; Cottingham, Kathryn L.

    2016-01-01

    IMPORTANCE Rice—a typical first food and major ingredient in various infant foods—contains inorganic arsenic (As), but the extent of As exposure from these foods has not been well characterized in early childhood. OBJECTIVE To determine the types and frequency of rice and rice-containing products consumed by infants in the first year of life and the association with As biomarker concentrations. DESIGN, SETTING, AND PARTICIPANTS Included were infants from singleton births of pregnant women enrolled in the New Hampshire Birth Cohort Study from 2011 to 2014 whose parents were interviewed during their first year of life. Enrolled women from selected clinics were aged 18 to 45 years, living in the same residence since their last menstrual period, in households served by a private water system, and had no plans to move during pregnancy. Data on infants’ intake of rice and rice products were collected from interviews with their parents at 4, 8, and 12 months’ follow-up and from a 3-day food diary at 12 months from March 2013 to August 2014. EXPOSURES Infants’ intake of rice and rice products. MAIN OUTCOMES AND MEASURES Total urinary As and the sum of As species measured using inductively coupled mass spectrometry and high-performance liquid chromatography with inductively coupled mass spectrometry. Commonly reported infant rice snacks were tested for As. RESULTS We obtained dietary data on 759 of 951 infants (79.8% participation rate). Of these, 391 infants (51.7%) were male, and the mean (SD) gestational age was 39.4 (1.7) weeks. An estimated 80% were introduced to rice cereal during their first year. At 12 months, 32.6% of infants (42 of 129) were fed rice snacks. Among infants aged 12 months who did not eat fish or seafood, the geometric mean total urinary As concentrations were higher among those who ate infant rice cereal (9.53 μg/L) or rice snacks (4.97 μg/L) compared with those who did not eat rice or rice products (2.85 μg/L; all P < .01). Infant rice

  18. Case studies--arsenic.

    PubMed

    Chou, C H Selene J; De Rosa, Christopher T

    2003-08-01

    Arsenic is found naturally in the environment. People may be exposed to arsenic by eating food, drinking water, breathing air, or by skin contact with soil or water that contains arsenic. In the U.S., the diet is a predominant source of exposure for the general population with smaller amounts coming from drinking water and air. Children may also be exposed to arsenic because of hand to mouth contact or eating dirt. In addition to the normal levels of arsenic in air, water, soil, and food, people could by exposed to higher levels in several ways such as in areas containing unusually high natural levels of arsenic in rocks which can lead to unusually high levels of arsenic in soil or water. People living in an area like this could take in elevated amounts of arsenic in drinking water. Workers in an occupation that involves arsenic production or use (for example, copper or lead smelting, wood treatment, pesticide application) could be exposed to elevated levels of arsenic at work. People who saw or sand arsenic-treated wood could inhale/ingest some of the sawdust which contains high levels of arsenic. Similarly, when pressure-treated wood is burned, high levels of arsenic could be released in the smoke. In agricultural areas where arsenic pesticides were used on crops the soil could contain high levels of arsenic. Some hazardous waste sites contain large quantities of arsenic. Arsenic ranks #1 on the ATSDR/EPA priority list of hazardous substances. Arsenic has been found in at least 1,014 current or former NPL sites. At the hazardous waster sites evaluated by ATSDR, exposure to arsenic in soil predominated over exposure to water, and no exposure to air had been recorded. However, there is no information on morbidity or mortality from exposure to arsenic in soil at hazardous waste sites. Exposure assessment, community and tribal involvement, and evaluation and surveillance of health effects are among the ATSDR future Superfund research program priority focus areas

  19. European bee-eater (Merops apiaster) populations under arsenic and metal stress: evaluation of exposure at a mining site.

    PubMed

    Lopes, I; Sedlmayr, A; Moreira-Santos, M; Moreno-Garrido, I; Blasco, J; Ribeiro, R

    2010-02-01

    Two populations of the European bee-eater were studied, one living at a reference site and the other at a metal mining site. The concentration of arsenic and 11 metals (Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) was measured in feathers and regurgitated pellets collected at both sites. Cadmium, chromium, mercury, nickel, and lead were at least twofold higher in feathers of birds from the contaminated site than in the reference site, suggesting that this population was exposed to higher metal levels. Similarly, levels of aluminum, arsenic, cadmium, cobalt, chromium, iron, and lead were also at least twofold higher in pellets from the contaminated area. The obtained results suggested that the impacted population of Merops apiaster is at risk due to the exposure to some metals.

  20. Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: a comparative study in three cell types.