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Sample records for low-dose inorganic arsenic

  1. Arsenic, inorganic

    Integrated Risk Information System (IRIS)

    Arsenic , inorganic ; CASRN 7440 - 38 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  2. Arsenic, mode of action at biologically plausible low doses: What are the implications for low dose cancer risk?

    SciTech Connect

    Snow, Elizabeth T. . E-mail: esnow@deakin.edu.au; Sykora, Peter; Durham, Troy R.; Klein, Catherine B.

    2005-09-01

    Arsenic is an established human carcinogen. However, there has been much controversy about the shape of the arsenic response curve, particularly at low doses. This controversy has been exacerbated by the fact that the mechanism(s) of arsenic carcinogenesis are still unclear and because there are few satisfactory animal models for arsenic-induced carcinogenesis. Recent epidemiological studies have shown that the relative risk for cancer among populations exposed to {<=}60 ppb As in their drinking water is often lower than the risk for the unexposed control population. We have found that treatment of human keratinocyte and fibroblast cells with 0.1 to 1 {mu}M arsenite (As{sup III}) also produces a low dose protective effect against oxidative stress and DNA damage. This response includes increased transcription, protein levels and enzyme activity of several base excision repair genes, including DNA polymerase {beta} and DNA ligase I. At higher concentrations (> 10 {mu}M), As induces down-regulation of DNA repair, oxidative DNA damage and apoptosis. This low dose adaptive (protective) response by a toxic agent is known as hormesis and is characteristic of many agents that induce oxidative stress. A mechanistic model for arsenic carcinogenesis based on these data would predict that the low dose risk for carcinogenesis should be sub-linear. The threshold dose where toxicity outweighs protection is hard to predict based on in vitro dose response data, but might be estimated if one could determine the form (metabolite) and concentration of arsenic responsible for changes in gene regulation in the target tissues.

  3. PATHWAY OF INORGANIC ARSENIC METABOLISM

    EPA Science Inventory

    A remarkable aspect of the metabolism of inorganic arsenic in humans is its conversion to methylated metabolites. These metabolites account for most of the arsenic found in urine after exposure to inorganic arsenic. At least some of the adverse health effects attributed to inor...

  4. Arsenic toxicity at low doses: epidemiological and mode of action considerations.

    PubMed

    Schoen, Ari; Beck, Barbara; Sharma, Raj; Dubé, Eric

    2004-08-01

    Current approaches to risk assessment typically assume a linear dose-response for mutagenic compounds that directly interact with DNA or when the carcinogenic mechanism is unknown. Because the mode of action of arsenic-induced carcinogenesis is not well established, recent dose-response assessments for arsenic have assumed linearity at low doses despite evidence that arsenic is not a direct-acting mutagen. Several modes of action, including generation of oxidative stress, perturbation of DNA methylation patterns, inhibition of DNA repair, and modulation of signal transduction pathways, have been proposed to characterize arsenic's toxicity. It is probable that these mechanisms do not act in isolation, but overlap, and contribute to the complex nature of arsenic-induced carcinogenesis. All of the proposed mechanisms are likely to be nonlinear at low does. Furthermore, studies of populations outside the US exposed to arsenic in drinking water show increases in cancer only at relatively high concentrations, that is, concentrations in drinking water of several hundred micrograms per liter (microg/l). Studies in the US of populations exposed to average concentrations in drinking water up to about 190 microg/l do not provide evidence of increased cancer. Consideration of arsenic's plausible mechanisms and evidence from epidemiological studies support the use of nonlinear methods, either via biologically based modeling or use of a margin-of-exposure analysis, to characterize arsenic risks.

  5. Low-dose risk assessment for arsenic: a meta-analysis approach.

    PubMed

    Begum, Munni; Horowitz, John; Hossain, Md Irfan

    2015-03-01

    We conducted a meta-analysis to explore dose-response relationships for bladder and lung cancers when people are chronically exposed to low doses of arsenic. We searched electronic databases for articles published through 2010. Ten studies on bladder cancer and ingested arsenic exposure and five studies on lung cancer and ingested arsenic exposure fit our selection criteria. We also investigate the sensitivity of the absolute risk of lung and bladder cancer under different underlying prevalence measures. Males have a higher risk of bladder cancer than do females at all maximum contamination levels. The absolute risk of bladder cancer and lung cancer from ingested arsenic correlates highly with smoking rates. For a maximum contamination level of 10 µg/L, we estimate that there are about 2.91 additional bladder cancer cases per 100,000 people and, considering studies since 2000, we estimate that there are about 4.51 additional lung cancer cases per 100,000 people.

  6. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 8 2011-07-01 2011-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  7. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 8 2012-07-01 2012-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  8. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 8 2014-07-01 2014-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  9. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 8 2013-07-01 2013-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  10. 29 CFR 1926.1118 - Inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Inorganic arsenic. 1926.1118 Section 1926.1118 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inorganic arsenic. Note: The requirements applicable to construction work under this section are...

  11. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  12. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  13. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  14. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  15. 29 CFR 1915.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Inorganic arsenic. 1915.1018 Section 1915.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... § 1915.1018 Inorganic arsenic. Note: The requirements applicable to shipyard employment under...

  16. Inorganic arsenic toxicosis in cattle.

    PubMed

    Riviere, J E; Boosinger, T R; Everson, R J

    1981-03-01

    In 4 occurrences of arsenic poisoning in cattle, the principal clinical sign was acute hemorrhagic diarrhea attributable to hemorrhagic gastroenteritis. Arsenic concentrations in the liver, kidney and rumen contents varied. In one occurrence, arsenic in the hair of affected survivors was assayed at 0.8-3.40 ppm, vs 0.09-0.10 ppm in randomly selected control samples of hair. Sudden death was the only clinical sign in another occurrence in which gastric contents contained arsenic at 671 ppm. In another occurrence, arsenic poisoning caused lesions similar to those of salmonellosis.

  17. Effects of Low-Dose Drinking Water Arsenic on Mouse Fetal and Postnatal Growth and Development

    PubMed Central

    Kozul-Horvath, Courtney D.; Zandbergen, Fokko; Jackson, Brian P.; Enelow, Richard I.; Hamilton, Joshua W.

    2012-01-01

    Background Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level). Methodology and Findings C57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age. Conclusions/Significance Exposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations. PMID:22693606

  18. Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus.

    PubMed

    Via, Charles S; Nguyen, Phuong; Niculescu, Florin; Papadimitriou, John; Hoover, Dennis; Silbergeld, Ellen K

    2003-08-01

    Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.

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

    PubMed Central

    2013-01-01

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

  20. Perturbation of Defense Pathways by Low-Dose Arsenic Exposure in Zebrafish Embryos

    PubMed Central

    Mattingly, Carolyn J.; Hampton, Thomas H.; Brothers, Kimberly M.; Griffin, Nina E.; Planchart, Antonio

    2009-01-01

    Background Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown. Objectives The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action. Methods We exposed zebrafish embryos at 0.25–1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development. Results We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10−41). Arsenic-mediated expression changes were validated by QPCR. Conclusions In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development. PMID:19590694

  1. Exposure to inorganic arsenic in soil increases urinary inorganic arsenic concentrations of residents living in old mining areas.

    PubMed

    Hinwood, Andrea L; Sim, Malcolm R; Jolley, Damien; de Klerk, Nick; Bastone, Elisa B; Gerostamoulos, Jim; Drummer, Olaf H

    2004-03-01

    The short term human exposure studies conducted on populations exposed to high concentrations of inorganic arsenic in soil have been inconsistent in demonstrating a relationship between environmental concentrations and exposure measures. In Australia there are many areas with very high arsenic concentrations in residential soil most typically associated with gold mining activities in rural areas. This study aimed to investigate the relationship between environmental arsenic and urinary inorganic arsenic concentrations in a population living in a gold mining area (soil arsenic concentrations between 9 and 9900 mg kg(-1)), and a control population with low arsenic levels in soil (between 1 and 80 mg kg(-1)). Risk factors for increased urinary arsenic concentrations were also explored. There was a weak but significant relationship between soil arsenic concentrations and inorganic urinary arsenic concentration with a Spearman correlation coefficient of 0.39. When participants with greater than 100 mg kg(-1) arsenic in residential soil were selected, the coefficient increased to 0.64. The geometric mean urinary inorganic arsenic concentration for the exposed group was 1.64 microg L(-1) (inorganic arsenic concentration of 2.46 microg L(-1). In a random effects linear regression model, soil arsenic concentration was the significant predictor of increased urinary arsenic concentrations. Season was shown to have a significant influence on urinary inorganic arsenic concentrations. Other factors such as age, gender and hours of contact with soil may also be important risk factors. These results show that high concentrations of arsenic in soil can make a contribution to urinary inorganic arsenic concentrations.

  2. Inorganic arsenic: a need and an opportunity to improve risk assessment.

    PubMed

    Chappell, W R; Beck, B D; Brown, K G; Chaney, R; Cothern, R; Cothern, C R; Irgolic, K J; North, D W; Thornton, I; Tsongas, T A

    1997-10-01

    This paper presents views on the current status of (inorganic) arsenic risk assessment in the United States and recommends research needed to set standards for drinking water. The opinions are those of the Arsenic Task Force of the Society for Environmental Geochemistry and Health, which has met periodically since 1991 to study issues related to arsenic risk assessment and has held workshops and international conferences on arsenic. The topic of this paper is made timely by current scientific interest in exposure to and adverse health effects of arsenic in the United States and passage of the Safe Drinking Water Act Amendment of 1996, which has provisions for a research program on arsenic and a schedule mandating the EPA to revise the maximum contaminant level of arsenic in drinking water by the year 2001. Our central premise and recommendations are straightforward: the risk of adverse health effects associated with arsenic in drinking water is unknown for low arsenic concentrations found in the United States, such as at the current interim maximum contaminant level of 50 microg/l and below. Arsenic-related research should be directed at answering that question. New epidemiological studies are needed to provide data for reliable dose-response assessments of arsenic and for skin cancer, bladder cancer, or other endpoints to be used by the EPA for regulation. Further toxicological research, along with the observational data from epidemiology, is needed to determine if the dose-response relationship at low levels is more consistent with the current assumption of low-dose linearity or the existence of a practical threshold. Other recommendations include adding foodborne arsenic to the calculation of total arsenic intake, calculation of total arsenic intake, and encouraging cooperative research within the United States and between the United States and affected countries. PMID:9349827

  3. Inorganic arsenic: a need and an opportunity to improve risk assessment.

    PubMed Central

    Chappell, W R; Beck, B D; Brown, K G; Chaney, R; Cothern, R; Cothern, C R; Irgolic, K J; North, D W; Thornton, I; Tsongas, T A

    1997-01-01

    This paper presents views on the current status of (inorganic) arsenic risk assessment in the United States and recommends research needed to set standards for drinking water. The opinions are those of the Arsenic Task Force of the Society for Environmental Geochemistry and Health, which has met periodically since 1991 to study issues related to arsenic risk assessment and has held workshops and international conferences on arsenic.The topic of this paper is made timely by current scientific interest in exposure to and adverse health effects of arsenic in the United States and passage of the Safe Drinking Water Act Amendment of 1996, which has provisions for a research program on arsenic and a schedule mandating the EPA to revise the maximum contaminant level of arsenic in drinking water by the year 2001. Our central premise and recommendations are straightforward: the risk of adverse health effects associated with arsenic in drinking water is unknown for low arsenic concentrations found in the United States, such as at the current interim maximum contaminant level of 50 microg/l and below. Arsenic-related research should be directed at answering that question. New epidemiological studies are needed to provide data for reliable dose-response assessments of arsenic and for skin cancer, bladder cancer, or other endpoints to be used by the EPA for regulation. Further toxicological research, along with the observational data from epidemiology, is needed to determine if the dose-response relationship at low levels is more consistent with the current assumption of low-dose linearity or the existence of a practical threshold. Other recommendations include adding foodborne arsenic to the calculation of total arsenic intake, calculation of total arsenic intake, and encouraging cooperative research within the United States and between the United States and affected countries. Images p1060-a Figure 1. PMID:9349827

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

    EPA Science Inventory

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

  5. Inorganic arsenic in cooked rice and vegetables from Bangladeshi households.

    PubMed

    Smith, Nicole M; Lee, Robin; Heitkemper, Douglas T; DeNicola Cafferky, Katie; Haque, Abidul; Henderson, Alden K

    2006-11-01

    Many Bangladeshi suffer from arsenic-related health concerns. Most mitigation activities focus on identifying contaminated wells and reducing the amount of arsenic ingested from well water. Food as a source of arsenic exposure has been recently documented. The objectives of this study were to measure the main types of arsenic in commonly consumed foods in Bangladesh and estimate the average daily intake (ADI) of arsenic from food and water. Total, organic and inorganic, arsenic were measured in drinking water and in cooked rice and vegetables from Bangladeshi households. The mean total arsenic level in 46 rice samples was 358 microg/kg (range: 46 to 1,110 microg/kg dry weight) and 333 microg/kg (range: 19 to 2,334 microg/kg dry weight) in 39 vegetable samples. Inorganic arsenic calculated as arsenite and arsenate made up 87% of the total arsenic measured in rice, and 96% of the total arsenic in vegetables. Total arsenic in water ranged from 200 to 500 microg/L. Using individual, self-reported data on daily consumption of rice and drinking water the total arsenic ADI was 1,176 microg (range: 419 to 2,053 microg), 14% attributable to inorganic arsenic in cooked rice. The ADI is a conservative estimate; vegetable arsenic was not included due to limitations in self-reported daily consumption amounts. Given the arsenic levels measured in food and water and consumption of these items, cooked rice and vegetables are a substantial exposure pathway for inorganic arsenic. Intervention strategies must consider all sources of dietary arsenic intake. PMID:16875714

  6. Mutagenicity of dimethylated metabolites of inorganic arsenics.

    PubMed

    Yamanaka, K; Ohba, H; Hasegawa, A; Sawamura, R; Okada, S

    1989-10-01

    The genotoxic effects of dimethylarsinic acid (DMAA), one of the main metabolites of inorganic arsenics in mammals, and its further metabolites were investigated using Escherichia coli B tester strains. When H/r30R (wild-type; Exc+Rec+) and Hs30R (uvrA-; Exc-Rec+) cells were incubated with DMAA for 3 h in liquid NB medium, many more revertants appeared in sealed tubes than in the control, but this was not the case in unsealed tubes, suggesting that volatile metabolites of DMAA caused the mutagenesis. By gas chromatography-mass spectrometry (GC-MS), dimethylarsine and trimethylarsine, known to be volatile metabolites in microorganisms, were detected in the gas phase of DMAA-added tester strain cell suspensions in sealed tubes. Among these arsines, dimethylarsine was mutagenic in WP2 (wild-type; Exc+Rec+) and WP2uvrA (uvrA-; Exc-Rec+), while trimethylarsine was not. The mutagenesis induced by dimethylarsine required oxygen gas in the assay system; the number of revertants markedly increased in an oxygen-replaced system and diminished in a nitrogen-replaced one. These results suggest that the reaction product(s) between dimethylarsine and molecular oxygen is responsible for the mutagenesis. The significance of this mutagenesis in the genetoxic action of inorganic arsenics is discussed.

  7. Electrochemical determination of inorganic mercury and arsenic--A review.

    PubMed

    Zaib, Maria; Athar, Muhammad Makshoof; Saeed, Asma; Farooq, Umar

    2015-12-15

    Inorganic mercury and arsenic encompasses a term which includes As(III), As(V) and Hg(II) species. These metal ions have been extensively studied due to their toxicity related issues. Different analytical methods are used to monitor inorganic mercury and arsenic in a variety of samples at trace level. The present study reviews various analytical techniques available for detection of inorganic mercury and arsenic with particular emphasis on electrochemical methods especially stripping voltammetry. A detailed critical evaluation of methods, advantages of electrochemical methods over other analytical methods, and various electrode materials available for mercury and arsenic analysis is presented in this review study. Modified carbon paste electrode provides better determination due to better deposition with linear and improved response under studied set of conditions. Biological materials may be the potent and economical alternative as compared to macro-electrodes and chemically modified carbon paste electrodes in stripping analysis of inorganic mercury and arsenic.

  8. Is ingested inorganic arsenic a "threshold" carcinogen?

    PubMed

    Abernathy, C O; Chappell, W R; Meek, M E; Gibb, H; Guo, H R

    1996-02-01

    Ingested inorganic arsenic (As) is known to be a human carcinogen. An intriguing question is whether there is a threshold for the carcinogenic effects of As, i.e., is there a level below which it does not induce the development of cancer(s)? This Roundtable will discuss the United States Environmental Protection Agency's As risk assessment using the Taiwan data from different viewpoints. It will also consider the hypothesis that there is a threshold for As and data for or against this hypothesis. For example, some scientists believe that epidemiological data cannot answer this question, while others feel that different study designs and larger sampling will provide adequate data. Reasons for each position are given. This Roundtable discussion demonstrates the controversy surrounding the use of the Taiwan data for risk assessment.

  9. Use of arsenic-73 in research supports USEPA's regulatory decisions on inorganic arsenic in drinking water*

    EPA Science Inventory

    Inorganic arsenic is a natural contaminant of drinking water in the United States and throughout the world. Long term exposure to inorganic arsenic in drinking water at elevated levels (>100 ug/L) is associated with development of cancer in several organs, cardiovascular disease,...

  10. [Health effects of exposure of humans to inorganic arsenic compounds].

    PubMed

    Szymańska, J A; Chmielnicka, J

    1991-01-01

    This paper is a review of references concerning health effects of environmental and occupational exposure to inorganic arsenic compounds. Special attention is paid to epidemiological studies indicating a relationship between time and amount of arsenic absorbed via the gastrointestinal tract (drinking water, contaminated food, drugs) and an increase in skin cancer rate. Occupational and environmental exposure of humans to arsenic dust induces a higher risk of lung cancer.

  11. Total and inorganic arsenic in fish samples from Norwegian waters.

    PubMed

    Julshamn, Kaare; Nilsen, Bente M; Frantzen, Sylvia; Valdersnes, Stig; Maage, Amund; Nedreaas, Kjell; Sloth, Jens J

    2012-01-01

    The contents of total arsenic and inorganic arsenic were determined in fillet samples of Northeast Artic cod, herring, mackerel, Greenland halibut, tusk, saithe and Atlantic halibut. In total, 923 individual fish samples were analysed. The fish were mostly caught in the open sea off the coast of Norway, from 40 positions. The determination of total arsenic was carried out by inductively coupled plasma mass spectrometry following microwave-assisted wet digestion. The determination of inorganic arsenic was carried out by high-performance liquid chromatography-ICP-MS following microwave-assisted dissolution of the samples. The concentrations found for total arsenic varied greatly between fish species, and ranged from 0.3 to 110 mg kg(-1) wet weight. For inorganic arsenic, the concentrations found were very low (<0.006 mg kg(-1)) in all cases. The obtained results question the assumptions made by the European Food Safety Authority (EFSA) on the inorganic arsenic level in fish used in the recent EFSA opinion on arsenic in food.

  12. Luminescence Studies of Residual Damage in Low-Dose Arsenic Implanted Silicon after High-Temperature Annealing

    NASA Astrophysics Data System (ADS)

    Sagara, Akihiko; Hiraiwa, Miori; Shibata, Satoshi; Sugie, Ryuichi; Yamada, Keiichi

    2011-01-01

    In order to prevent the degradation of device performance, it is necessary to detect and reduce residual damage remaining after ion implantation and annealing. In this study, we focused on the high-temperature annealing process after low-dose arsenic (As) implantation in silicon (Si) and evaluated the correlation of annealing conditions and damage by cathodoluminescence (CL) compared to Secondary Ion Mass Spectrometry (SIMS) and Junction Photo-Voltage (JPV) results. Increasing the annealing temperature with the high-heat-up rate, As profile and the sheet resistance didn't change. However, the intensity of the band-to-band transition increased with temperature. This implies the some kind of residual damage remains after low-temperature annealing and it is removed with increasing annealing temperature. On the other hand, with increasing the annealing time at 1200 °C, more As was piled-up at the SiO2/Si interface and the luminescence intensity decreased. We guess this piled-up As is inactive and it may create some kind of damage combined with the defects around the interface, and these damage types cause the suppression of the luminescence intensity. We concluded that the luminescence intensity reflects the various kinds of damage and optical characterization methods have a potential to evaluate defect evolution in annealing process.

  13. Evaluation of the carcinogenicity of inorganic arsenic.

    PubMed

    Cohen, Samuel M; Arnold, Lora L; Beck, Barbara D; Lewis, Ari S; Eldan, Michal

    2013-10-01

    Inorganic arsenic (iAs) at high exposures is a human carcinogen, affecting mainly the urinary bladder, lung and skin. We present an assessment of the mode of action (MOA) of iAs's carcinogenicity based on the United States Environmental Protection Agency/International Programme on Chemical Safety (USEPA/IPCS) framework, focusing primarily on bladder cancer. Evidence is presented for a MOA involving formation of reactive trivalent metabolites interacting with critical cellular sulfhydryl groups, leading to cytotoxicity and regenerative cell proliferation. Metabolism, kinetics, cell transport, and reaction with specific proteins play a critical role in producing the effects at the cellular level, regardless of cell type, whether urothelium, lung epithelium or epidermis. The cytotoxicity induced by iAs results in non-cancer toxicities, and the regenerative cell proliferation enhances development of epithelial cancers. In other tissues, such as vascular endothelium, different toxicities develop, not cancer. Evidence supporting this MOA comes from in vitro investigations on animal and human cells, from animal models, and from epidemiological studies. This MOA implies a non-linear, threshold dose-response relationship for both non-cancer and cancer end points. The no effect levels in animal models (approximately 1 ppm of water or diet) and in vitro (>0.1 µM trivalent arsenicals) are strikingly consistent. Cancer effects of iAs in humans generally are not observed below exposures of 100-150 ppb in drinking water: below these exposures, human urine concentrations of trivalent metabolites are generally below 0.1 µM, a concentration not associated with bladder cell cytotoxicity in in vitro or animal models. Environmental exposures to iAs in most of the United States do not approach this threshold.

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

    EPA Science Inventory

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

  15. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  16. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  17. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  18. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  19. 40 CFR 61.184 - Ambient air monitoring for inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... arsenic. 61.184 Section 61.184 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.184 Ambient air monitoring for inorganic arsenic. (a) The owner or operator of each source to...

  20. Determination of total arsenic, inorganic and organic arsenic species in wine.

    PubMed

    Herce-Pagliai, C; Moreno, I; González, G; Repetto, M; Cameán, A M

    2002-06-01

    Forty-five wine samples from the south of Spain of different alcoholic strength were analysed for total arsenic and its inorganic [As(III), As(V)] and organic (monomethylarsonic acid [MMAA], dimethylarsinic acid [DMAA]) species. The As levels of the wine samples ranged from 2.1 to 14.6 microg l(-1). The possible effect of the alcoholic fermentation process on the levels of the total arsenic and arsenical species was studied. The average total arsenic levels for the different samples were very similar, without significant differences between all types of wines. In table wines and sherry, the percentages of total inorganic arsenic were 18.6 and 15.6%, with DMAA or MMAA being the predominant species, respectively. In most samples, DMAA was the most abundant species, but the total inorganic aresenic fraction was considerable, representing 25.4% of the total concentration of the element. The estimated daily intakes of total arsenic and total inorganic arsenic for average Spanish consumers were 0.78 and 0.15 microg/person day(-1), respectively. The results suggest that the consumption of these types of wines makes no significant contribution to the total and inorganic arsenic intake for normal drinkers. However, wine consumption contributes a higher arsenic intake than through consumption of beers and sherry brandies.

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

    PubMed Central

    Farmer, J G; Johnson, L R

    1990-01-01

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

  2. Arsenic speciation in Chinese Herbal Medicines and human health implication for inorganic arsenic.

    PubMed

    Liu, Xiao-Juan; Zhao, Quan-Li; Sun, Guo-Xin; Williams, Paul; Lu, Xiu-Jun; Cai, Jing-Zhu; Liu, Wen-Ju

    2013-01-01

    Rice and drinking water are recognized as the dominant sources of arsenic (As) for human intake, while little is known about As accumulation and speciation in Chinese Herbal Medicines (CHMs), which have been available for many hundreds of years for the treatment of diseases in both eastern and western cultures. Inorganic arsenic was the predominant species in all of CHMs samples. The levels of inorganic arsenic in CHMs from fields and markets or pharmacies ranged from 63 to 550 ng/g with a mean of 208 ng/g and 94 to 8683 ng/g with a mean of 1092 ng/g, respectively. The highest concentration was found in the Chrysanthemum from pharmacies. It indicates that the risk of inorganic As in CHMs to human health is higher in medicines from markets or pharmacies than that collected directly from fields. Some CHMs may make a considerable contribution to the human intake of inorganic arsenic.

  3. METHYLATED ASIII COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC

    EPA Science Inventory

    METHYLATED Asm COMPOUNDS AS POTENTIAL PROXIMATE/ULTIMATE GENOTOXIC METABOLITES OF INORGANIC ARSENIC.

    The methylation of inorganic arsenic has typically been viewed as a detoxification process. Genotoxicity tests have generally shown that arsenite has greater mutagenic p...

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

    PubMed

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

    2007-07-01

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

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

    SciTech Connect

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

    2007-07-15

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

  6. Biosensors for Inorganic and Organic Arsenicals

    PubMed Central

    Chen, Jian; Rosen, Barry P.

    2014-01-01

    Arsenic is a natural environmental contaminant to which humans are routinely exposed and is strongly associated with human health problems, including cancer, cardiovascular and neurological diseases. To date, a number of biosensors for the detection of arsenic involving the coupling of biological engineering and electrochemical techniques has been developed. The properties of whole-cell bacterial or cell-free biosensors are summarized in the present review with emphasis on their sensitivity and selectivity. Their limitations and future challenges are highlighted. PMID:25587436

  7. 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...

  8. IRIS Toxicological Review of Inorganic Arsenic (Preliminary Assessment Materials)

    EPA Science Inventory

    In April 2014, EPA released the draft literature searches and associated search strategies, evidence tables, and exposure response arrays for inorganic arsenic (iAs) to obtain input from stakeholders and the public prior to developing the draft IRIS assessment. Specifically, EPA ...

  9. Inorganic arsenic toxicosis in a beef herd.

    PubMed

    Faires, Meredith C

    2004-04-01

    Over a 44-day period, 4 of 5 affected calves in a 170-head herd of beef cattle died after exhibiting clinical signs of lethargy, ataxia, anorexia, and diarrhea. Histopathological examination of tissues and toxicological analysis of a suspicious powder discovered in the pasture confirmed arsenic trioxide toxicosis.

  10. Fractionation of inorganic arsenic by adjusting hydrogen ion concentration.

    PubMed

    Oliveira, Andrea; Gonzalez, Mario Henrique; Queiroz, Helena Müller; Cadore, Solange

    2016-12-15

    The inorganic fraction of arsenic species, iAs=∑[As(III)+As(V)] present in fish samples can be quantified in the presence of other arsenic species also found in fishes, such as: monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine (AsB). The toxic arsenic fraction was selected taking into account the dissociation constants of these arsenic species in different hydrogen ions concentration leading to the arsine formation from iAs compounds detected as As(III) by HG AAS. For thus, a microwave assisted extraction was carried out using HCl 1molL(-1) in order to maintain the integrity of the arsenic species in this mild extraction media. Recovery experiments were done for iAs fraction, in the presence of other arsenic species. The recovery values obtained for iAs fraction added were quantitative about 87-107% (for N=3, RSD⩽3%). The limit of detection (LOD), and the limit of quantification (LOQ), were 5μgkg(-1) and 16μgkg(-1) respectively. PMID:27451157

  11. High levels of inorganic arsenic in rice in areas where arsenic-contaminated water is used for irrigation and cooking.

    PubMed

    Rahman, M Azizur; Hasegawa, H

    2011-10-15

    Rice is the staple food for the people of arsenic endemic South (S) and South-East (SE) Asian countries. In this region, arsenic contaminated groundwater has been used not only for drinking and cooking purposes but also for rice cultivation during dry season. Irrigation of arsenic-contaminated groundwater for rice cultivation has resulted high deposition of arsenic in topsoil and uptake in rice grain posing a serious threat to the sustainable agriculture in this region. In addition, cooking rice with arsenic-contaminated water also increases arsenic burden in cooked rice. Inorganic arsenic is the main species of S and SE Asian rice (80 to 91% of the total arsenic), and the concentration of this toxic species is increased in cooked rice from inorganic arsenic-rich cooking water. The people of Bangladesh and West Bengal (India), the arsenic hot spots in the world, eat an average of 450g rice a day. Therefore, in addition to drinking water, dietary intake of arsenic from rice is supposed to be another potential source of exposure, and to be a new disaster for the population of S and SE Asian countries. Arsenic speciation in raw and cooked rice, its bioavailability and the possible health hazard of inorganic arsenic in rice for the population of S and SE Asia have been discussed in this review.

  12. Arsenic speciation in rice and risk assessment of inorganic arsenic in Taiwan population.

    PubMed

    Chen, Hsiu-Ling; Lee, Ching-Chang; Huang, Winn-Jung; Huang, Han-Ting; Wu, Yi-Chen; Hsu, Ya-Chen; Kao, Yi-Ting

    2016-03-01

    This study assessed the total arsenic content and arsenic speciation in rice to determine the health risks associated with rice consumption in various age-gender subgroups in Taiwan. The average total arsenic levels in white rice and brown rice were 116.6 ± 39.2 and 215.5 ± 63.5 ng/g weight (n = 51 and 13), respectively. The cumulative cancer risk among males was 10.4/100,000. The highest fraction of inorganic/total arsenic content in white rice ranged from 76.9 to 88.2 % and from 81.0 to 96.5 % in brown rice. The current study found different arsenic speciation of rice in southern Taiwan, where the famous blackfoot disease has been reported compared with arsenic speciation from other Taiwan areas. Therefore, rice and other grains should be further monitored in southern Taiwan to evaluate whether arsenic contamination is well controlled in this area. PMID:26511258

  13. Arsenic speciation in rice and risk assessment of inorganic arsenic in Taiwan population.

    PubMed

    Chen, Hsiu-Ling; Lee, Ching-Chang; Huang, Winn-Jung; Huang, Han-Ting; Wu, Yi-Chen; Hsu, Ya-Chen; Kao, Yi-Ting

    2016-03-01

    This study assessed the total arsenic content and arsenic speciation in rice to determine the health risks associated with rice consumption in various age-gender subgroups in Taiwan. The average total arsenic levels in white rice and brown rice were 116.6 ± 39.2 and 215.5 ± 63.5 ng/g weight (n = 51 and 13), respectively. The cumulative cancer risk among males was 10.4/100,000. The highest fraction of inorganic/total arsenic content in white rice ranged from 76.9 to 88.2 % and from 81.0 to 96.5 % in brown rice. The current study found different arsenic speciation of rice in southern Taiwan, where the famous blackfoot disease has been reported compared with arsenic speciation from other Taiwan areas. Therefore, rice and other grains should be further monitored in southern Taiwan to evaluate whether arsenic contamination is well controlled in this area.

  14. 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.

  15. Total and inorganic arsenic in natural and aquacultural freshwater fish in Thailand: a comparative study.

    PubMed

    Ruangwises, Nongluck; Saipan, Piyawat; Ruangwises, Suthep

    2012-12-01

    Total and inorganic arsenic were determined in 108 samples of four freshwater fish species collected from natural water sources and aquaculture systems in the central region of Thailand between March and May 2010. Concentrations of total and inorganic arsenic (dry wt) and percentages of inorganic arsenic in four aquacultural fish species were not significantly different from those found in natural fish. Inorganic arsenic levels found in the four fish species from both sources in this study were much lower than the Thai regulatory standard of 2 μg/g, and hence are considered safe for human consumption.

  16. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    SciTech Connect

    Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  17. Total and inorganic arsenic in freshwater fish and prawn in Thailand.

    PubMed

    Saipan, Piyawat; Ruangwises, Suthep; Tengjaroenkul, Bundit; Ruangwises, Nongluck

    2012-10-01

    Total and inorganic arsenic levels were determined in 120 samples of eight freshwater animal species collected from five distribution centers in the central region of Thailand between January and March 2011. Eight species with the highest annual catch, consisting of seven fish species and one prawn species, were analyzed. Concentrations of inorganic arsenic (on a wet weight basis) ranged from 0.010 μg/g in giant prawn (Macrobrachium rosenbergii) to 0.230 μg/g in striped snakehead (Channa striata). Climbing perch (Anabas testudineus) exhibited the highest mean concentrations of total arsenic (0.459 ± 0.137 μg/g), inorganic arsenic (0.121 ± 0.044 μg/g), and percentage of inorganic arsenic (26.2%). Inorganic arsenic levels found in freshwater animals in this study were much lower than the Thai regulatory standard of 2 μg/g. PMID:23043844

  18. Total and inorganic arsenic in freshwater fish and prawn in Thailand.

    PubMed

    Saipan, Piyawat; Ruangwises, Suthep; Tengjaroenkul, Bundit; Ruangwises, Nongluck

    2012-10-01

    Total and inorganic arsenic levels were determined in 120 samples of eight freshwater animal species collected from five distribution centers in the central region of Thailand between January and March 2011. Eight species with the highest annual catch, consisting of seven fish species and one prawn species, were analyzed. Concentrations of inorganic arsenic (on a wet weight basis) ranged from 0.010 μg/g in giant prawn (Macrobrachium rosenbergii) to 0.230 μg/g in striped snakehead (Channa striata). Climbing perch (Anabas testudineus) exhibited the highest mean concentrations of total arsenic (0.459 ± 0.137 μg/g), inorganic arsenic (0.121 ± 0.044 μg/g), and percentage of inorganic arsenic (26.2%). Inorganic arsenic levels found in freshwater animals in this study were much lower than the Thai regulatory standard of 2 μg/g.

  19. The predominance of inorganic arsenic species in plants from Yellowknife, Northwest Territories, Canada

    SciTech Connect

    Koch, I.; Wang, L.; Ollson, C.A.; Cullen, W.R.; Reimer, K.J.

    2000-01-01

    Elevated levels of arsenic in Yellowknife, NWT, Canada, from historic and recent gold mine operations, are of increasing concern to Yellowknife residents. The study of arsenic in Yellowknife plants is a part of ongoing bioavailability and food chain research. A variety of plants from Yellowknife were analyzed for total arsenic and water soluble arsenic species. The plants included vascular plants and bryophytes (mosses). Total amounts of arsenic were greatest in mosses and varied greatly within specimens of the same plant species from different locations. Mostly inorganic arsenic species were extracted from plants using methanol/water (1:1). This result is very important from a toxicological point of view, since inorganic species are relatively toxic arsenic species. Small amounts of methylated arsenic species, as well as arsenosugars, were present in some plants. On average, greater than 50% of arsenic in these plants was not extracted; the chemical and toxicological characteristics of this fraction remain a topic for further study.

  20. 75 FR 7477 - Draft Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

    ... AGENCY Draft Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the... document titled, ``Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the... (ORD). The Toxicological Review of Inorganic Arsenic was submitted to the EPA's Science Advisory...

  1. Total and inorganic arsenic in dietary supplements based on herbs, other botanicals and algae--a possible contributor to inorganic arsenic exposure.

    PubMed

    Hedegaard, Rikke V; Rokkjær, Inge; Sloth, Jens J

    2013-05-01

    The content of total and inorganic arsenic was determined in 16 dietary supplements based on herbs, other botanicals and algae purchased on the Danish market. The dietary supplements originated from various regions, including Asia, Europe and USA. The contents of total and inorganic arsenic was determined by inductively coupled plasma mass spectrometry (ICP-MS) and anion exchange HPLC-ICP-MS, respectively, were in the range of 0.58 to 5.0 mgkg(-1) and 0.03 to 3.2 mg kg(-1), respectively, with a ratio between inorganic arsenic and total arsenic ranging between 5 and 100%. Consumption of the recommended dose of the individual dietary supplement would lead to an exposure to inorganic arsenic within the range of 0.07 to 13 μg day(-1). Such exposure from dietary supplements would in worst case constitute 62.4% of the range of benchmark dose lower confidence limit values (BMDL01 at 0.3 to 8 μg kg bw(-1) kg(-1) day(-1)) put down by European Food Safety Authority (EFSA) in 2009, for cancers of the lung, skin and bladder, as well as skin lesions. Hence, the results demonstrate that consumption of certain dietary supplements could contribute significantly to the dietary exposure to inorganic arsenic at levels close to the toxicological limits established by EFSA.

  2. Total and inorganic arsenic in dietary supplements based on herbs, other botanicals and algae--a possible contributor to inorganic arsenic exposure.

    PubMed

    Hedegaard, Rikke V; Rokkjær, Inge; Sloth, Jens J

    2013-05-01

    The content of total and inorganic arsenic was determined in 16 dietary supplements based on herbs, other botanicals and algae purchased on the Danish market. The dietary supplements originated from various regions, including Asia, Europe and USA. The contents of total and inorganic arsenic was determined by inductively coupled plasma mass spectrometry (ICP-MS) and anion exchange HPLC-ICP-MS, respectively, were in the range of 0.58 to 5.0 mgkg(-1) and 0.03 to 3.2 mg kg(-1), respectively, with a ratio between inorganic arsenic and total arsenic ranging between 5 and 100%. Consumption of the recommended dose of the individual dietary supplement would lead to an exposure to inorganic arsenic within the range of 0.07 to 13 μg day(-1). Such exposure from dietary supplements would in worst case constitute 62.4% of the range of benchmark dose lower confidence limit values (BMDL01 at 0.3 to 8 μg kg bw(-1) kg(-1) day(-1)) put down by European Food Safety Authority (EFSA) in 2009, for cancers of the lung, skin and bladder, as well as skin lesions. Hence, the results demonstrate that consumption of certain dietary supplements could contribute significantly to the dietary exposure to inorganic arsenic at levels close to the toxicological limits established by EFSA. PMID:23436171

  3. The addition of arsenic trioxide to low-dose Ara-C in older patients with AML does not improve outcome.

    PubMed

    Burnett, A K; Hills, R K; Hunter, A; Milligan, D; Kell, J; Wheatley, K; Yin, J; McMullin, M-F; Cahalin, P; Craig, J; Bowen, D; Russell, N

    2011-07-01

    Most patients with acute myeloid leukaemia (AML) are older, with many unsuitable for conventional chemotherapy. Low-dose Ara-C (LDAC) is superior to best supportive care but is still inadequate. The combination of arsenic trioxide (ATO) and LDAC showed promise in an unrandomised study. We report a randomised trial of LDAC versus LDAC+ATO. Patients with AML according to WHO criteria or myelodysplastic syndrome with >10% blasts, considered as unfit for conventional chemotherapy, were randomised between subcutaneous Ara-C (20 mg b.d. for 10 days) and the same LDAC schedule with ATO (0.25 mg/kg) on days 1-5, 9 and 11, for at least four courses every 4 to 6 weeks. Overall 166 patients were entered; the trial was terminated on the advice of the DMC, as the projected benefit was not observed. Overall 14% of patients achieved complete remission (CR) and 7% CRi. Median survival was 5.5 months and 19 months for responders (CR: not reached; CRi: 14 months; non-responders: 4 months). There were no differences in response or survival between the arms. Grade 3/4 cardiac and liver toxicity, and supportive care requirements were greater in the ATO arm. This randomised comparison demonstrates that adding ATO to LDAC provides no benefit for older patients with AML.

  4. Dietary intake of total and inorganic arsenic by adults in arsenic-contaminated area of Ron Phibun district, Thailand.

    PubMed

    Ruangwises, Suthep; Saipan, Piyawat

    2010-03-01

    Ron Phibun District, approximately 800 km south of Bangkok, is the site of tin mines operated almost 100 years ago. As a result of mining activities, arsenic contaminated the soil and groundwater of the district. The specific aim of this study was to estimate the dietary intakes of total and inorganic arsenic in 20 adults (10 males and 10 females) residing in Ron Phibun District by a duplicate food approach for 7-consecutive days. The weekly intake rates of inorganic arsenic ranged from 5.54 to 13.3 microg/kg BW for males and 6.11-12.1 microg/kg BW for females.

  5. Individual Variations in Inorganic Arsenic Metabolism Associated with AS3MT Genetic Polymorphisms

    PubMed Central

    Agusa, Tetsuro; Fujihara, Junko; Takeshita, Haruo; Iwata, Hisato

    2011-01-01

    Individual variations in inorganic arsenic metabolism may influence the toxic effects. Arsenic (+3 oxidation state) methyltransferase (AS3MT) that can catalyze the transfer of a methyl group from S-adenosyl-l-methionine (AdoMet) to trivalent arsenical, may play a role in arsenic metabolism in humans. Since the genetic polymorphisms of AS3MT gene may be associated with the susceptibility to inorganic arsenic toxicity, relationships of several single nucleotide polymorphisms (SNPs) in AS3MT with inorganic arsenic metabolism have been investigated. Here, we summarize our recent findings and other previous studies on the inorganic arsenic metabolism and AS3MT genetic polymorphisms in humans. Results of genotype dependent differences in arsenic metabolism for most of SNPs in AS3MT were Inconsistent throughout the studies. Nevertheless, two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis. Thus, these SNPs may be useful indicators to predict the arsenic metabolism via methylation pathways. PMID:21731446

  6. Geographical variation in total and inorganic arsenic content of polished (white) rice.

    PubMed

    Meharg, Andrew A; Williams, Paul N; Adomako, Eureka; Lawgali, Youssef Y; Deacon, Claire; Villada, Antia; Cambell, Robert C J; Sun, Guoxin; Zhu, Yong-Guan; Feldmann, Joerg; Raab, Andrea; Zhao, Fang-Jie; Islam, Rafiqul; Hossain, Shahid; Yanai, Junta

    2009-03-01

    An extensive data set of total arsenic analysis for 901 polished (white) grain samples, originating from 10 countries from 4 continents, was compiled. The samples represented the baseline (i.e., notspecifically collected from arsenic contaminated areas), and all were for market sale in major conurbations. Median total arsenic contents of rice varied 7-fold, with Egypt (0.04 mg/kg) and India (0.07 mg/kg) having the lowest arsenic content while the U.S. (0.25 mg/kg) and France (0.28 mg/kg) had the highest content. Global distribution of total arsenic in rice was modeled by weighting each country's arsenic distribution by that country's contribution to global production. A subset of 63 samples from Bangladesh, China, India, Italy, and the U.S. was analyzed for arsenic species. The relationship between inorganic arsenic contentversus total arsenic contentsignificantly differed among countries, with Bangladesh and India having the steepest slope in linear regression, and the U.S. having the shallowest slope. Using country-specific rice consumption data, daily intake of inorganic arsenic was estimated and the associated internal cancer risk was calculated using the U.S. Environmental Protection Agency (EPA) cancer slope. Median excess internal cancer risks posed by inorganic arsenic ranged 30-fold for the 5 countries examined, being 0.7 per 10,000 for Italians to 22 per 10,000 for Bangladeshis, when a 60 kg person was considered.

  7. In vitro methylation of inorganic arsenic in mouse intestinal cecum.

    PubMed

    Hall, L L; George, S E; Kohan, M J; Styblo, M; Thomas, D J

    1997-11-01

    The capacity of mouse intestinal cecal microflora to methylate inorganic arsenicals (iAs) was examined in vitro under conditions of restricted bacterial growth. Cecal contents incubated under anaerobic conditions at 37 degrees C for 21 hr methylated up to 40% of either 0.1 microM arsenite (iAsIII) or 0.1 microM arsenate (iAsV). Methylarsenic (MAs) was the predominant metabolite; however, about 3% of either substrate was converted to dimethylarsenic (DMAs). Over the first 6 hr, the rate of methylation was several times greater for iAsIII than for iAsV. There was a 3-hr delay in the production of methylated metabolites from iAsV, suggesting that reduction of iAsV to iAsIII before methylation could be rate limiting. Over the concentration range of 0.1 to 10 microM of iAsIII or iAsV, there was an approximately linear increase in the production of MAs and DMAs. There was evidence of saturation or inhibition of methylation at 100 microM of either substrate. Substrate concentration had little effect on MAs/DMAs ratio. Incubation of cecal contents at 0 degrees C abolished methylation of either arsenical. Under aerobic or anaerobic conditions, cecal tissue homogenates produced little MAs or DMAs from either arsenical. Addition of potential methyl group donors, L-methionine and methylcobalamin, into cecal contents significantly increased the rate of methylation, especially for iAsV. Addition of glutathione, but not L-cysteine, had a similar effect. Selenite, a recognized inhibitor of iAs methylation in mammalian tissues, inhibited methylation of either substrate by cecal contents. These data suggest that cecal microflora are a high capacity methylation system that might contribute significantly to methylation of iAs in intact animals.

  8. Inorganic arsenic in Chinese food and its cancer risk.

    PubMed

    Li, Gang; Sun, Guo-Xin; Williams, Paul N; Nunes, Luis; Zhu, Yong-Guan

    2011-10-01

    Even moderate arsenic exposure may lead to health problems, and thus quantifying inorganic arsenic (iAs) exposure from food for different population groups in China is essential. By analyzing the data from the China National Nutrition and Health Survey (CNNHS) and collecting reported values of iAs in major food groups, we developed a framework of calculating average iAs daily intake for different regions of China. Based on this framework, cancer risks from iAs in food was deterministically and probabilistically quantified. The article presents estimates for health risk due to the ingestion of food products contaminated with arsenic. Both per individual and for total population estimates were obtained. For the total population, daily iAs intake is around 42 μg day(-1), and rice is the largest contributor of total iAs intake accounting for about 60%. Incremental lifetime cancer risk from food iAs intake is 106 per 100,000 for adult individuals and the median population cancer risk is 177 per 100,000 varying between regions. Population in the Southern region has a higher cancer risk than that in the Northern region and the total population. Sensitive analysis indicated that cancer slope factor, ingestion rates of rice, aquatic products and iAs concentration in rice were the most relevant variables in the model, as indicated by their higher contribution to variance of the incremental lifetime cancer risk. We conclude that rice may be the largest contributor of iAs through food route for the Chinese people. The population from the South has greater cancer risk than that from the North and the whole population.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. METABOLISM AS A DETERMINING FACTOR IN ACUTE AND CHRONIC TOXICITY OF INORGANIC ARSENIC

    EPA Science Inventory

    The metabolism of inorganic arsenic (iAs) in humans involves reduction of As(V)-species to trivalency and oxidative methylation of As(III)-species. In this pathway, iAs is converted to methylarsenic (MAs) and dimethyl arsenic (DMAs) metabolites that contain As(III) or As(V). Rec...

  15. ORGANIC AND INORGANIC ARSENICALS SENSITIZE HUMAN BRONCHIAL EPITHELIAL CELLS TO HYDROGEN PEROXIDE-INDUCED DNA DAMAGE

    EPA Science Inventory

    The lungs are a target organ for arsenic carcinogenesis, however, its mechanism of action remains unclear. Furthermore, it has been suggested that inorganic arsenic (iAs) can potentiate DNA damage induced by other agents. Once inside the human body iAs generally undergoes two ...

  16. Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects.

    PubMed

    Schuhmacher-Wolz, Ulrike; Dieter, Hermann H; Klein, Dominik; Schneider, Klaus

    2009-01-01

    Inorganic arsenic, which is extensively metabolised in humans into even more toxic methylated arsenicals, is a potent carcinogen, causing tumours of the skin, lung, urinary bladder, and other organs. It also induces a number of non-cancer effects. Consumption of drinking water highly contaminated by arsenic causes serious health problems in some countries in southeastern Asia, and arsenic poses problems for drinking-water safety world-wide. Existing risk assessments are based on epidemiological studies from regions with high exposure concentrations (in the mg/L range). It is a matter of debate whether these findings are useful at predicting arsenic-induced effects at low concentrations. In recent years numerous epidemiological studies on cancer and non-cancer effects of inorganic arsenic have been published. This work aims at reviewing recent toxicological and epidemiological data on inorganic arsenic with emphasis on effects at low exposure concentrations. Information obtained from epidemiological studies is supplemented with mechanistic data from in vitro and in vivo studies. Various modes of action for arsenic carcinogenicity are discussed. The information gathered was used to evaluate the reliability of existing cancer-risk assessments and to improve current assessments of non-cancer health effects. A tolerable daily dose, based on epidemiological studies on arsenic-induced skin disorders, is presented.

  17. Total arsenic in selected food samples from Argentina: Estimation of their contribution to inorganic arsenic dietary intake.

    PubMed

    Sigrist, Mirna; Hilbe, Nandi; Brusa, Lucila; Campagnoli, Darío; Beldoménico, Horacio

    2016-11-01

    An optimized flow injection hydride generation atomic absorption spectroscopy (FI-HGAAS) method was used to determine total arsenic in selected food samples (beef, chicken, fish, milk, cheese, egg, rice, rice-based products, wheat flour, corn flour, oats, breakfast cereals, legumes and potatoes) and to estimate their contributions to inorganic arsenic dietary intake. The limit of detection (LOD) and limit of quantification (LOQ) values obtained were 6μgkg(-)(1) and 18μgkg(-)(1), respectively. The mean recovery range obtained for all food at a fortification level of 200μgkg(-)(1) was 85-110%. Accuracy was evaluated using dogfish liver certified reference material (DOLT-3 NRC) for trace metals. The highest total arsenic concentrations (in μgkg(-)(1)) were found in fish (152-439), rice (87-316) and rice-based products (52-201). The contribution to inorganic arsenic (i-As) intake was calculated from the mean i-As content of each food (calculated by applying conversion factors to total arsenic data) and the mean consumption per day. The primary contributors to inorganic arsenic intake were wheat flour, including its proportion in wheat flour-based products (breads, pasta and cookies), followed by rice; both foods account for close to 53% and 17% of the intake, respectively. The i-As dietary intake, estimated as 10.7μgday(-)(1), was significantly lower than that from drinking water in vast regions of Argentina.

  18. Total arsenic in selected food samples from Argentina: Estimation of their contribution to inorganic arsenic dietary intake.

    PubMed

    Sigrist, Mirna; Hilbe, Nandi; Brusa, Lucila; Campagnoli, Darío; Beldoménico, Horacio

    2016-11-01

    An optimized flow injection hydride generation atomic absorption spectroscopy (FI-HGAAS) method was used to determine total arsenic in selected food samples (beef, chicken, fish, milk, cheese, egg, rice, rice-based products, wheat flour, corn flour, oats, breakfast cereals, legumes and potatoes) and to estimate their contributions to inorganic arsenic dietary intake. The limit of detection (LOD) and limit of quantification (LOQ) values obtained were 6μgkg(-)(1) and 18μgkg(-)(1), respectively. The mean recovery range obtained for all food at a fortification level of 200μgkg(-)(1) was 85-110%. Accuracy was evaluated using dogfish liver certified reference material (DOLT-3 NRC) for trace metals. The highest total arsenic concentrations (in μgkg(-)(1)) were found in fish (152-439), rice (87-316) and rice-based products (52-201). The contribution to inorganic arsenic (i-As) intake was calculated from the mean i-As content of each food (calculated by applying conversion factors to total arsenic data) and the mean consumption per day. The primary contributors to inorganic arsenic intake were wheat flour, including its proportion in wheat flour-based products (breads, pasta and cookies), followed by rice; both foods account for close to 53% and 17% of the intake, respectively. The i-As dietary intake, estimated as 10.7μgday(-)(1), was significantly lower than that from drinking water in vast regions of Argentina. PMID:27211625

  19. Distribution and fate of inorganic and organic arsenic species in landfill leachates and biogases.

    PubMed

    Pinel-Raffaitin, P; Le Hecho, I; Amouroux, D; Potin-Gautier, M

    2007-07-01

    The arsenic release from landfills requires special attention both due to its potential toxicity and due to the increasing global municipal solid waste production. The determination of arsenic species in both leachates and biogases has been performed in this work to determine the fate of arsenic in landfills. Both inorganic and methylated arsenic species occur in leachates with concentrations varying from 0.1 to 80 microg As L(-1). These species are representative of the leachate arsenic composition, as the mean recovery obtained for the speciation analyses is 67% of the total arsenic determined in elementary analyses. In biogases, both methylated and ethylated volatile arsenic species have been identified and semiquantified (0-15 microg As m(-3)). The landfill monitoring has emphasized close relationships between the concentrations of mono-, di-, and tri-methylated arsenic compounds in leachates. A biomethylation pathway has thus been proposed as a source of these methylated compounds in the leachates from waste arsenic, which is supposed to be in major part under inorganic forms. In addition, peralkylation mechanisms of both biomethylation and bioethylation have been suggested to explain the occurrence of the identified volatile species. This combined speciation approach provides a qualitative and quantitative characterization of the potential emissions of arsenic from domestic waste disposal in landfills. This work highlights the possible formation of less harmful organoarsenic species in both leachates and biogases during the waste degradation process.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

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

  2. Bioavailability of inorganic arsenic from bog ore-containing soil in the dog.

    PubMed Central

    Groen, K; Vaessen, H A; Kliest, J J; de Boer, J L; van Ooik, T; Timmerman, A; Vlug, R F

    1994-01-01

    In some parts of The Netherlands, bog ore-containing soils predominate, which have natural arsenic levels that exceed, by a factor of 10, existing standards for maximum allowable levels of inorganic arsenic in soil. These standards are based on the assumption that in humans the bioavailability of arsenic from ingested soil is equal to that from an aqueous solution. In view of the regulatory problem that the arsenic levels of these soils present, we questioned the validity of this assumption. To obtain a more realistic estimate, the bioavailability of inorganic arsenic from soil in a suitable animal model was studied. In this report, a study performed in six dogs in a two-way cross-over design is presented. The dogs received orally, in random order, arsenic both as an intravenous solution and as arsenic-containing soil. During a 120-hr period after administration urine was collected in 24-hr fractions. Levels of arsenic were determined using a method of wet digestion, isolation and complexation of arsine, followed by molecule absorption spectrometry. Within 120 hr after intravenous administration, 88 +/- 16% of the dose was excreted renally. After oral administration of arsenic-containing soil, only 7.0 +/- 1.5% was excreted renally. From the urinary excretion data for these two routes of administration, the calculated bioavailability of inorganic arsenic from soil was 8.3 +/- 2.0%. The results from this study demonstrate the need to reconsider the present risk assessment for arsenic in soil. Images Figure 1. Figure 2. PMID:8033848

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

    PubMed Central

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

    2011-01-01

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

  4. Total and inorganic arsenic in rice and rice bran purchased in Thailand.

    PubMed

    Ruangwises, Suthep; Saipan, Piyawat; Tengjaroenkul, Bundit; Ruangwises, Nongluck

    2012-04-01

    Concentrations of total and inorganic arsenic were determined in 180 samples of polished and brown rice of three rice types, namely white, jasmine, and sticky, and 44 samples of rice bran from these three rice types purchased in Thailand. Concentrations (expressed in nanograms per gram) of inorganic arsenic in polished white, jasmine, and sticky rice were 68.3 ± 17.6 (with a range of 45.0 to 106), 68.4 ± 15.6 (41.7 to 101), and 75.9 ± 24.8 (43.5 to 156), respectively, while those in the three brown rice samples were 124 ± 34.4 (74.5 to 193), 120 ± 31.6 (73.1 to 174), and 131 ± 35.6 (78.0 to 188), respectively. Inorganic arsenic concentrations (expressed in nanograms per gram) in rice bran produced from the three rice types were 633 ± 182 (375 to 919), 599 ± 112 (447 to 824), and 673 ± 195 (436 to 1,071), respectively. Rice bran contained concentrations of total and inorganic arsenic approximately seven and nine times higher, respectively, than those found in the corresponding polished rice. The levels of inorganic arsenic in the three rice types of both polished and brown rice were within the only published regulatory limit of 200 ng/g.

  5. Total and inorganic arsenic in rice and rice bran purchased in Thailand.

    PubMed

    Ruangwises, Suthep; Saipan, Piyawat; Tengjaroenkul, Bundit; Ruangwises, Nongluck

    2012-04-01

    Concentrations of total and inorganic arsenic were determined in 180 samples of polished and brown rice of three rice types, namely white, jasmine, and sticky, and 44 samples of rice bran from these three rice types purchased in Thailand. Concentrations (expressed in nanograms per gram) of inorganic arsenic in polished white, jasmine, and sticky rice were 68.3 ± 17.6 (with a range of 45.0 to 106), 68.4 ± 15.6 (41.7 to 101), and 75.9 ± 24.8 (43.5 to 156), respectively, while those in the three brown rice samples were 124 ± 34.4 (74.5 to 193), 120 ± 31.6 (73.1 to 174), and 131 ± 35.6 (78.0 to 188), respectively. Inorganic arsenic concentrations (expressed in nanograms per gram) in rice bran produced from the three rice types were 633 ± 182 (375 to 919), 599 ± 112 (447 to 824), and 673 ± 195 (436 to 1,071), respectively. Rice bran contained concentrations of total and inorganic arsenic approximately seven and nine times higher, respectively, than those found in the corresponding polished rice. The levels of inorganic arsenic in the three rice types of both polished and brown rice were within the only published regulatory limit of 200 ng/g. PMID:22488070

  6. Evaluation of potential effects of soil available phosphorus on soil arsenic availability and paddy rice inorganic arsenic content.

    PubMed

    Jiang, Wei; Hou, Qingye; Yang, Zhongfang; Zhong, Cong; Zheng, Guodong; Yang, Zhiqiang; Li, Jie

    2014-05-01

    The transfer of arsenic from paddy field to rice is a major exposure route of the highly toxic element to humans. The aim of our study is to explore the effects of soil available phosphorus on As uptake by rice, and identify the effects of soil properties on arsenic transfer from soil to rice under actual field conditions. 56 pairs of topsoil and rice samples were collected. The relevant parameters in soil and the inorganic arsenic in rice grains were analyzed, and then all the results were treated by statistical methods. Results show that the main factors influencing the uptake by rice grain include soil pH and available phosphorus. The eventual impact of phosphorus is identified as the suppression of As uptake by rice grains. The competition for transporters from soil to roots between arsenic and phosphorus in rhizosphere soil has been a dominant feature. PMID:24598788

  7. 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...

  8. Toxicity of so-called edible hijiki seaweed (Sargassum fusiforme) containing inorganic arsenic.

    PubMed

    Yokoi, Katsuhiko; Konomi, Aki

    2012-07-01

    The UK Food Standards Agency and its counterparts in other countries have warned consumers not to eat hijiki (Sargassum fusiforme; synonym Hizikia fusiformis), a Sargasso seaweed, because it contains large amounts of inorganic arsenic. We investigated dietary exposure of hijiki in weaning male F344/N rats fed an AIN-93G diet supplemented with 3% (w/w) hijiki powder for 7 weeks, compared with those fed only an AIN-93G diet. Body weight, body temperature, blood and tissue arsenic concentrations, plasma biochemistry and hematological parameters were measured. We found that feeding rats a 3% hijiki diet led to a marked accumulation of arsenic in blood and tissues, and evoked a high body temperature and abnormal blood biochemistry including elevated plasma alkaline phosphatase activity and inorganic phosphorus, consistent with arsenic poisoning. These findings should prompt further investigations to identify the health hazards related to consumption of hijiki and related Sargassum species in humans.

  9. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    PubMed

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

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

    PubMed

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

    2005-03-01

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

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

    PubMed Central

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

    2005-01-01

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

  12. 76 FR 65217 - Inorganic Arsenic Standard; Extension of the Office of Management and Budget's (OMB) Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-20

    ... 1995 (44 U.S.C. 3506 et seq.) and Secretary of Labor's Order No. 4-2010 (75 FR 55355). Signed at... Occupational Safety and Health Administration Inorganic Arsenic Standard; Extension of the Office of Management...) approval of the information collection requirements specified in the Inorganic Arsenic Standard (29...

  13. Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

    PubMed Central

    Smith, Allan H.; Marshall, Guillermo; Yuan, Yan; Steinmaus, Craig; Liaw, Jane; Smith, Martyn T.; Wood, Lily; Heirich, Marissa; Fritzemeier, Rebecca M.; Pegram, Mark D.; Ferreccio, Catterina

    2014-01-01

    Background Arsenic trioxide is effective in treating promyelocytic leukemia, and laboratory studies demonstrate that arsenic trioxide causes apoptosis of human breast cancer cells. Region II in northern Chile experienced very high concentrations of inorganic arsenic in drinking water, especially in the main city Antofagasta from 1958 until an arsenic removal plant was installed in 1970. Methods We investigated breast cancer mortality from 1950 to 2010 among women in Region II compared to Region V, which had low arsenic water concentrations. We conducted studies on human breast cancer cell lines and compared arsenic exposure in Antofagasta with concentrations inducing apoptosis in laboratory studies. Findings Before 1958, breast cancer mortality rates were similar, but in 1958–1970 the rates in Region II were half those in Region V (rate ratio RR = 0.51, 95% CI 0.40–0.66; p < 0.0001). Women under the age of 60 experienced a 70% reduction in breast cancer mortality during 1965–1970 (RR = 0.30, 0.17–0.54; p < 0.0001). Breast cancer cell culture studies showed apoptosis at arsenic concentrations close to those estimated to have occurred in people in Region II. Interpretation We found biologically plausible major reductions in breast cancer mortality during high exposure to inorganic arsenic in drinking water which could not be attributed to bias or confounding. We recommend clinical trial assessment of inorganic arsenic in the treatment of advanced breast cancer. PMID:25580451

  14. 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

  15. 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

  16. Stress-related gene expression in mice treated with inorganic arsenicals.

    PubMed

    Liu, J; Kadiiska, M B; Liu, Y; Lu, T; Qu, W; Waalkes, M P

    2001-06-01

    Arsenic (As) is an environmental chemical of high concern for human health. Acute toxicity of arsenic is dependent on its chemical forms and proximity to high local arsenic concentrations is one of the mechanisms for cell death. This study was designed to define acute arsenic-induced stress-related gene expression in vivo. Mice were injected sc with either sodium arsenite [As(III), 100 micromol/kg], sodium arsenate [As(V), 300 micromol/kg], or saline. To examine stress-related gene expression, livers were removed 3 h after arsenic injection for RNA and protein extraction. The Atlas Mouse Stress/Toxicology array revealed that the expression of genes related to stress, DNA damage, and metabolism was altered by acute arsenic treatments. Expression of heme oxygenase 1 (HO-1), a hallmark for arsenic-induced stress, was increased 10-fold, along with increases in heat shock protein-60 (HSP60), DNA damage inducible protein GADD45, and the DNA excision repair protein ERCC1. Downregulation of certain cytochrome P450 enzymes occurred with arsenic treatment. Multiprobe RNase protection assay revealed the activation of the c-Jun/AP-1 transcription complex after arsenic treatments. Western blot analysis further confirmed the enhanced production of arsenic-induced stress proteins such as HO-1, HSP70, HSP90, metallothionein, the metal-responsive transcription factor MTF-1, nuclear factor kappa B and c-Jun/AP-1. Increases in caspase-1 and cytokines such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 were also evident. In summary, this study profiled the gene expression pattern in mice treated with inorganic arsenicals, which adds to our understanding of acute arsenic poisoning and toxicity.

  17. Nrf2-dependent repression of interleukin-12 expression in human dendritic cells exposed to inorganic arsenic.

    PubMed

    Macoch, Mélinda; Morzadec, Claudie; Génard, Romain; Pallardy, Marc; Kerdine-Römer, Saadia; Fardel, Olivier; Vernhet, Laurent

    2015-11-01

    Inorganic arsenic, a well-known Nrf2 inducer, exerts immunosuppressive properties. In this context, we recently reported that the differentiation of human blood monocytes into immature dendritic cells (DCs), in the presence of low and noncytotoxic concentrations of arsenic, represses the ability of DCs to release key cytokines in response to different stimulating agents. Particularly, arsenic inhibits the expression of human interleukin-12 (IL-12, also named IL-12p70), a major proinflammatory cytokine that controls the differentiation of Th1 lymphocytes. In the present study, we determined if Nrf2 could contribute to these arsenic immunotoxic effects. To this goal, human monocyte-derived DCs were first differentiated in the absence of metalloid and then pretreated with arsenic just before DC stimulation with lipopolysaccharide (LPS). Under these experimental conditions, arsenic rapidly and stably activates Nrf2 and increases the expression of Nrf2 target genes. It also significantly inhibits IL-12 expression in activated DCs, at both mRNA and protein levels. Particularly, arsenic reduces mRNA levels of IL12A and IL12B genes which encodes the p35 and p40 subunits of IL-12p70, respectively. tert-Butylhydroquinone (tBHQ), a reference Nrf2 inducer, mimics arsenic effects and potently inhibits IL-12 expression. Genetic inhibition of Nrf2 expression markedly prevents the repression of both IL12 mRNA and IL-12 protein levels triggered by arsenic and tBHQ in human LPS-stimulated DCs. In addition, arsenic significantly reduces IL-12 mRNA levels in LPS-activated bone marrow-derived DCs from Nrf2+/+ mice but not in DCs from Nrf2-/- mice. Finally, we show that, besides IL-12, arsenic significantly reduces the expression of IL-23, another heterodimer containing the p40 subunit. In conclusion, our study demonstrated that arsenic represses IL-12 expression in human-activated DCs by specifically stimulating Nrf2 activity.

  18. Implications of inorganic/organic interconversion on fluxes of arsenic in marine food webs.

    PubMed Central

    Penrose, W R; Conacher, H B; Black, R; Méranger, J C; Miles, W; Cunningham, H M; Squires, W R

    1977-01-01

    An organic form of arsenic is commonly encountered in marine organisms; in greysole and shrimp, it accounted for all arsenic found in muscle tissue. It has been isolated from flounder tissue by two independent procedures; it was hydrophilic, cationic, and was not decomposed to inorganic arsenic by hot nitric and sulfuric acids. NMR spectroscopy indicated all nonexchangeable protons to be equivalent; they behaved more like N-methyl protons than As-methyl protons. High-resolution mass spectroscopy from a heated probe yielded a spectrum corresponding to tetramethylarsonium (AsMe4+); the authentic ion, however, had TLC and ion-exchange behavior different from that of the natural product. Infrared spectrometry likewise produced conflicting or uninterpretable data. Decomposition of the compound for analytical purposes was accomplished by dry ashing under oxidizing conditions. Sea urchins, like trout, converted arsenic to an organic form, but to a more limited degree. Arsenic found naturally in sea urchins and in a species of macroalga was also organic. In individual containers, sea urchins were fed on the alga for 7 weeks. During this time they consumed 0.203 +/- 0.075 mg total As and excreted only 0.036 +/- 0.015 mg as feces. Measurement of inorganic As in the seawater did not account for the discrepancy, but measurements of total As did (0.202 +/- 0.095 mg). Sea urchins, like humans, appear to be able to rapidly excrete these organic forms of arsenic. PMID:908313

  19. IRIS Toxicological Review of Inorganic Arsenic (Cancer) (2010 External Review Draft)

    EPA Science Inventory

    EPA's Science Advisory Board (SAB) conducted a review of the scientific basis supporting the human health cancer hazard and dose-response assessment of inorganic arsenic that will appear on the Integrated Risk Information System (IRIS) database. EPA revised the assessment and is...

  20. IRIS Toxicological Review for Inorganic Arsenic (Scoping and Problem Formulation Materials)

    EPA Science Inventory

    In November 2012, EPA released scoping and problem formulation materials for the IRIS assessment of inorganic arsenic for public comment and discussion. The scoping information was based on input from EPA's program and regional offices and was provided for informational purposes....

  1. IRIS Toxicological Review of Inorganic Arsenic (Cancer) (Interagency Science Consultation Draft)

    EPA Science Inventory

    On February 19, 2010, the draft IRIS Toxicological Review of Inorganic Arsenic (Cancer) external review draft document and the charge to external peer reviewers were released for public review and comment. The draft document and the charge to external peer reviewers were reviewed...

  2. APPARENT SEXUAL DIFFERENCES IN METABOLISM OF INORGANIC ARSENIC IN HUMAN HEPATOCYTES

    EPA Science Inventory

    APPARENT SEXUAL DIFFERENCES IN METABOLISM OF INORGANIC ARSENIC IN HUMAN HEPATOCYTES. M Styblo1, G A Hamilton1, E L LeCluyse1 and D J Thomas2. 1University of North Carolina, Chapel Hill, NC, USA; 2US EPA, ORD, NHEERL, Research Triangle Park, NC, USA.
    The liver is considered a m...

  3. SPE speciation of inorganic arsenic in rice followed by hydride-generation atomic fluorescence spectrometric quantification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due to high toxicity, inorganic arsenics (iAs) are the focus of monitoring effort worldwide. In this work, extraction was performed by microwave-assisted digestion in HCl-H2O2, during which AsIII was oxidized to AsV. AsV was separated from organoarsenic species using silica-based SAX cartridge and r...

  4. DIFFERENTIAL ACTIVATION OF AP-1 IN HUMAN BLADDER EPITHELIAL CELLS BY INORGANIC AND METHYLATED ARSENICALS

    EPA Science Inventory

    Differential Activation of AP-1 in Human Bladder Epithelial Cells by Inorganic and Methylated Arsenicals

    Zuzana Drobna, Ilona Jaspers, David J. Thomas, and Miroslav Styblo

    ABSTRACT

    Epidemiological studies have linked chronic ingestion of drinking water contai...

  5. SPECIATION AND PRESERVATION OF INORGANIC ARSENIC IN DRINKING WATER SUPPLIES WITH IC-ICP-MS

    EPA Science Inventory

    The speciation of inorganic arsenic in drinking water supplies is an essential part of devising an appropriate treatment process. Arsenate, because of its anion characteristics at drinking water pHs, is effectively removed by anion exchange treatment while arsenite remains in the...

  6. [Relationship between Arsenic (+3 Oxidation State) Methyltransferase Genetic Polymorphisms and Methylation Capacity of Inorganic Arsenic].

    PubMed

    Agusa, Tetsuro; Kunito, Takashi; Minh Tue, Nguyen; Thi Mai Lan, Vi; Binh Minh, Tu; Thi Kim Trang, Pham; Fujihara, Junko; Takeshita, Haruo; Takahashi, Shin; Hung Viet, Pham; Tanabe, Shinsuke; Iwata, Hisato

    2015-01-01

    Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step.

  7. [Relationship between Arsenic (+3 Oxidation State) Methyltransferase Genetic Polymorphisms and Methylation Capacity of Inorganic Arsenic].

    PubMed

    Agusa, Tetsuro; Kunito, Takashi; Minh Tue, Nguyen; Thi Mai Lan, Vi; Binh Minh, Tu; Thi Kim Trang, Pham; Fujihara, Junko; Takeshita, Haruo; Takahashi, Shin; Hung Viet, Pham; Tanabe, Shinsuke; Iwata, Hisato

    2015-01-01

    Arsenic metabolism affects the susceptibility of humans to arsenic toxicity; therefore, clarification of the factors associated with individual variations in arsenic metabolism is an important task. Genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in arsenic (+3 oxidation state) methyltransferase (AS3MT), which can methylate arsenic compounds using S-adenosyl-l-methionine (AdoMet), have been reported to modify arsenic methylation. In this review, we summarize studies conducted by us in Vietnam and by others on the association of AS3MT genetic polymorphisms with arsenic metabolism as well as human health effects. Most of the SNPs in AS3MT showed inconsistent results in terms of genotype-dependent differences in arsenic metabolism among the studies. However, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the study population: AS3MT 12390 (rs3740393) affected the second step of methylation of arsenic, whereas 14458 (rs11191439) affected the first methylation step. PMID:26411936

  8. Total and Inorganic Arsenic Contents in Some Edible Zingiberaceous Rhizomes in Thailand

    PubMed Central

    Ubonnuch, Chomkamon; Ruangwises, Suthep; Gritsanapan, Wandee; Ruangwises, Nongluck

    2013-01-01

    The arsenic accumulation in rhizomes of Zingiberaceous plants was determined by atomic absorption spectrometry interfaced with hydride generation system (HG-AAS). The raw herbal materials, rhizomes, were collected from different regions of Thailand between December 2011 and January 2012. Six well-known Zingiberaceous plants, 16 samples from each and a total of 96 samples, were analyzed Alpinia galanga (Khaa), Boesenbergia rotunda (Kra-chaai), Curcuma longa (Khamin-chan), Curcuma zedoaria (Khamin-oi), Zingiber cassumunar (Plai) and Zingiber officinale (Ginger). Concentrations of total arsenic based on dry weight were 92.4 ± 9.2, 103.5 ± 20.8, 61.7 ± 12.5, 89.8 ± 17.5, 106.7 ± 19.5 and 69.3 ± 11.8 ng/g, respectively and inorganic arsenic were 48.8 ± 7.0, 66.3 ± 12.7, 25.5 ± 5.0, 38.7 ± 4.7, 71.2 ± 11.6, and 38.5 ± 5.5 ng/g, respectively. Among these, Plai and Kra-chaai exhibited the highest levels of total arsenic and inorganic arsenic accumulation that remind consumers to be aware of excess consuming of these rhizomes. On the contrary, the lowest value found in Khamin-chan indicating natural dietary supplements and herbal medicines comprising Kamin-chan are safe from arsenic poison. All investigated amounts of total and inorganic arsenic were much lower than limits recommended by Thai Food and Drug Administration. PMID:23690845

  9. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats.

    PubMed

    Xi, Shuhua; Sun, Wenjuan; Wang, Fengzhi; Jin, Yaping; Sun, Guifan

    2009-06-01

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p < 0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p < 0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex.

  10. Low-dose synergistic immunosuppression of T-dependent antibody responses by polycyclic aromatic hydrocarbons and arsenic in C57BL/6J murine spleen cells

    SciTech Connect

    Li Qian; Lauer, Fredine T.; Liu Kejian; Hudson, Laurie G.; Burchiel, Scott W.

    2010-06-15

    Polycyclic aromatic hydrocarbons (PAHs) and arsenic are both environmental agents that are known to have significant immunotoxicity. Previous studies have shown that PAH exposure of spleen cells in vitro produces significant immune suppression of humoral immunity, especially when P450 activation products are examined. Exposure to arsenic, particularly sodium arsenite, has also been found to be suppressive to antibody responses in vitro and in vivo. The purpose of the present studies was to examine the immunotoxicity of PAHs and arsenite following coexposures with the theory being that the agents may exert synergistic actions, which might be based on their different mechanisms of action. Spleen cells were isolated from male C57BL/6J wild-type mice and treated with PAHs and/or arsenic (arsenite or arsenate). Immunotoxicity assays were used to assess the T-dependent antibody response (TDAR) to sheep red blood cells (SRBCs), measured by a direct plaque-forming cell (PFC) assay. Cell viability was measured by trypan blue staining. Spleen cell viability was not altered following 4 days of PAH and/or arsenic treatment. However, the TDAR demonstrated suppression by both PAHs and arsenic in a concentration-dependent manner. p53 was also induced by NaAsO{sub 2} (As{sup 3+}) and PAHs alone or in combination. The PAHs and their metabolites investigated included benzo[a]pyrene (BaP), BaP-7,8-diol, BaP-7,8-diol-9,10-epoxide (BPDE), 7,12-dimethylbenz[a]anthracene (DMBA), DMBA-3,4-diol, dibenzo[a,l]pyrene (DB[a,l]P). PAH metabolites were found to be more potent than parent compounds in producing immunosuppression and inducing p53 expression. Interestingly, DB[a,l]P, a potent carcinogenic PAH not previously characterized for immunotoxicity, was also found to be strongly immunosuppressive. Arsenite (NaAsO{sub 2}, As{sup 3+}) was found to produce immunosuppression at concentrations as low as 0.5 {mu}M and was immunosuppressive at a 10-fold lower concentration than sodium arsenate (Na

  11. Dietary intake of total and inorganic arsenic by adults in arsenic-contaminated Dan Chang district, Thailand, using duplicate food approach.

    PubMed

    Ruangwises, Suthep; Ruangwises, Nongluck; Saipan, Piyawat

    2011-02-01

    Dan Chang district, approximately 100 km west of Bangkok, was a site of tin mines operated almost 40 years ago. Mining operations caused arsenic contamination in soil, surface water, and groundwater within the district. The specific aim of this study was to estimate the dietary intakes of total and inorganic arsenic in 60 adults (30 males and 30 females) residing in Dan Chang district, using a duplicate food approach. The daily intake rates of inorganic arsenic ranged from 0.496 to 1.817 μg/kg BW for males and 0.342 to 1.778 μg/kg BW for females.

  12. Geographical variation in inorganic arsenic in paddy field samples and commercial rice from the Iberian Peninsula.

    PubMed

    Signes-Pastor, Antonio J; Carey, Manus; Carbonell-Barrachina, Angel A; Moreno-Jiménez, Eduardo; Green, Andy J; Meharg, Andrew A

    2016-07-01

    This study investigated total arsenic and arsenic speciation in rice using ion chromatography with mass spectrometric detection (IC-ICP-MS), covering the main rice-growing regions of the Iberian Peninsula in Europe. The main arsenic species found were inorganic and dimethylarsinic acid. Samples surveyed were soil, shoots and field-collected rice grain. From this information soil to plant arsenic transfer was investigated plus the distribution of arsenic in rice across the geographical regions of Spain and Portugal. Commercial polished rice was also obtained from each region and tested for arsenic speciation, showing a positive correlation with field-obtained rice grain. Commercial polished rice had the lowest i-As content in Andalucia, Murcia and Valencia while Extremadura had the highest concentrations. About 26% of commercial rice samples exceeded the permissible concentration for infant food production as governed by the European Commission. Some cadmium data is also presented, available with ICP-MS analyses, and show low concentration in rice samples. PMID:26920305

  13. Slow recovery from severe inorganic arsenic poisoning despite treatment with DMSA (2.3-dimercaptosuccinic acid).

    PubMed

    Stenehjem, Aud-E; Vahter, Marie; Nermell, Barbro; Aasen, Jorulf; Lierhagen, Syverin; Mørland, Jørg; Jacobsen, Dag

    2007-05-01

    A 39-year-old woman was hospitalized for nausea, diarrhea, vomiting, and weakness of unknown etiology. Her condition progressively deteriorated and she developed multiple organ failure and tetraplegia. The diagnosis of inorganic arsenic poisoning was established by measurements of arsenic in urine and serum, showing 2,000 microg/L (normal < 10 microg/L) and 290 mug/Kg (normal < 2 microg/Kg), respectively. Hair arsenic was 57 mg/kg (normal < 0.2 mg/kg). Chelating therapy with 2.3-dimercaptosuccinic acid (DMSA) 600 mg three times daily was given for a period of 45 days with three abruption periods during a total of 13 days. The clinical manifestations of arsenic toxicosis disappeared very slowly and five years after the hospitalization she still suffers from peripheral neuropathy. Although the use of DMSA was associated with increased urinary elimination of arsenic and a decrease in blood arsenic concentrations, DMSA treatment probably had no significant effect on the total body clearance in our patient. The source of the poisoning was never detected, nor the motivation behind it. Criminal intent was suspected, but no verdict was given.

  14. Geographical variation in inorganic arsenic in paddy field samples and commercial rice from the Iberian Peninsula.

    PubMed

    Signes-Pastor, Antonio J; Carey, Manus; Carbonell-Barrachina, Angel A; Moreno-Jiménez, Eduardo; Green, Andy J; Meharg, Andrew A

    2016-07-01

    This study investigated total arsenic and arsenic speciation in rice using ion chromatography with mass spectrometric detection (IC-ICP-MS), covering the main rice-growing regions of the Iberian Peninsula in Europe. The main arsenic species found were inorganic and dimethylarsinic acid. Samples surveyed were soil, shoots and field-collected rice grain. From this information soil to plant arsenic transfer was investigated plus the distribution of arsenic in rice across the geographical regions of Spain and Portugal. Commercial polished rice was also obtained from each region and tested for arsenic speciation, showing a positive correlation with field-obtained rice grain. Commercial polished rice had the lowest i-As content in Andalucia, Murcia and Valencia while Extremadura had the highest concentrations. About 26% of commercial rice samples exceeded the permissible concentration for infant food production as governed by the European Commission. Some cadmium data is also presented, available with ICP-MS analyses, and show low concentration in rice samples.

  15. Total and inorganic arsenic levels in some marine organisms from Izmir Bay (Eastern Aegean Sea): a risk assessment.

    PubMed

    Kucuksezgin, Filiz; Gonul, Lutfi Tolga; Tasel, Didem

    2014-10-01

    The arsenic compounds in marine biota were evaluated from Izmir Bay (Eastern Aegean) and found that inorganic arsenic occurred as a minor fraction. No information is available on the annual variations of arsenic in important edible biota species from Izmir Bay. Fish and mussel samples were taken from different regions of Izmir Bay between 2009 and 2011 (n=854 individual specimens). The average percentages of inorganic arsenic to total arsenic for all biota samples were 3.43±3.38% with a range of 0.11-11.8%. The importance of speciation analysis for arsenic is supported by our work, because arsenic is ubiquitous in the ecosystem, and flexible toxicity of arsenic is based on chemical form. The average total As levels in Mullus barbatus were 6 times higher than Diplodus annularis and Mytilus galloprovincialis. This study also revealed that spatial variation influenced the arsenic levels in the fish samples and the highest concentrations of arsenic were found in Gediz site. Our study showed that estimated daily intakes of arsenic via consumption of flesh fish and shell fish were below the BMDL0.5 values established by FAO/WHO. PMID:25048921

  16. 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.

  17. RESEARCH TOWARD THE DEVELOPMENT OF A BIOLOGICALLY BASED DOSE RESPONSE ASSESSMENT FOR INORGANIC ARSENIC CARCINOGENICITY: A PROGRESS REPORT

    EPA Science Inventory

    Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose-response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an ad...

  18. 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.

  19. Optimization of a GFAAS method for determination of total inorganic arsenic in drinking water.

    PubMed

    Michon, Jérôme; Deluchat, Véronique; Al Shukry, Raad; Dagot, Christophe; Bollinger, Jean-Claude

    2007-01-15

    The new 10mugl(-1) arsenic standard in drinking water has been a spur to the search for reliable routine analytical methods with a limit of detection at the mugl(-1) level. These methods also need to be easy to handle due to the routine analyses that are required in drinking water monitoring. Graphite furnace atomic absorption spectrometry (GFAAS) meets these requirements, but the limit of detection is generally too high except for methods using a pre-concentration or separation step. The use of a high-intensity boosted discharge hollow-cathode lamp decreases the baseline noise level and therefore allows a lower limit of detection. The temperature program, chemical matrix modifier and thermal stabilizer additives were optimized for total inorganic arsenic determination with GFAAS, without preliminary treatment. The optimal furnace program was validated with a proprietary software. The limit of detection was 0.26mugAsl(-1) for a sample volume of 16mul corresponding to 4.2pgAs. This attractive technique is rapid as 20 samples can be analysed per hour. This method was validated with arsenic reference solutions. Its applicability was verified with artificial and natural groundwaters. Recoveries from 91 to 105% with relative standard deviation <5% can be easily achieved. The effect of interfering anions and cations commonly found in groundwater was studied. Only phosphates and silicates (respectively at 4 and 20mgl(-1)) lead to significant interferences in the determination of total inorganic arsenic at 4mugl(-1).

  20. Preserving the distribution of inorganic arsenic species in groundwater and acid mine drainage samples

    USGS Publications Warehouse

    Bednar, A.J.; Garbarino, J.R.; Ranville, J.F.; Wildeman, T.R.

    2002-01-01

    The distribution of inorganic arsenic species must be preserved in the field to eliminate changes caused by metal oxyhydroxide precipitation, photochemical oxidation, and redox reactions. Arsenic species sorb to iron and manganese oxyhydroxide precipitates, and arsenite can be oxidized to arsenate by photolytically produced free radicals in many sample matrices. Several preservatives were evaluated to minimize metal oxyhydroxide precipitation, such as inorganic acids and ethylenediaminetetraacetic acid (EDTA). EDTA was found to work best for all sample matrices tested. Storing samples in opaque polyethylene bottles eliminated the effects of photochemical reactions. The preservation technique was tested on 71 groundwater and six acid mine drainage samples. Concentrations in groundwater samples reached 720 ??g-As/L for arsenite and 1080 ??g-As/L for arsenate, and acid mine drainage samples reached 13 000 ??g-As/L for arsenite and 3700 ??g-As/L for arsenate. The arsenic species distribution in the samples ranged from 0 to 90% arsenite. The stability of the preservation technique was established by comparing laboratory arsenic speciation results for samples preserved in the field to results for subsamples speciated onsite. Statistical analyses indicated that the difference between arsenite and arsenate concentrations for samples preserved with EDTA in opaque bottles and field speciation results were analytically insignificant. The percentage change in arsenite:arsenate ratios for a preserved acid mine drainage sample and groundwater sample during a 3-month period was -5 and +3%, respectively.

  1. Association between Multi-level Inorganic Arsenic Exposure from Drinking Water and Skin Lesions in China

    PubMed Central

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

    2006-01-01

    Arsenic is one of the most important toxicants in the environment. In Inner Mongolia of China, 300,000 residents are believed to be drinking water containing >50μg/liter. Skin lesions have been known as the most common consequences resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic-induced skin lesions, it is important to assess the impact of this problem among the target population, and to make future planning. We evaluated the association between multi-levels inorganic arsenic exposure from drinking water and skin lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine and 32 subjects in high (>50μg/liter) and low (<50μg/liter) arsenic-affected villages were recruited and had the detailed physical examination with special emphasis on arsenic-related skin lesions. Arsenic exposure was measured for each participant with respect to iAs concentration of primary well and the duration using the well. Arsenic-induced skin lesions including keratosis, pigmentation, and/or depigmentation were diagnosed in 56 and 3 subjects in the two villages, respectively. Logistic regression was conducted to calculate odd ratios of skin lesions associated with arsenic exposure with adjustments for sex, age group, smoking and duration of exposure. A consistent dose-response relationship between arsenic exposure level and skin lesion risk was observed. Compared to those with iAs concentration <50μg/liter, the adjusted odds ratios of skin lesions for the subjects with 51–99, 100–149 and >150μg/liter were 33.3% (OR =15.50, 95% CI: 1.53–248.70), 46.7% (OR =16.10, 95% CI: 3.73–69.63) and 55.7% (OR= 25.70, 95% CI: 6.43–102.87), respectively. Duration of using well was not associated with increased risk of skin lesions in this population; (OR =1.68, 95% CI: 0.40–6.91 for 6–15 years, OR = 2.30, 95% CI: 0.58–9.14 for over 15 years) compared with the duration of less than 5 years. PMID:16968972

  2. Geographical and temporal differences in the urinary excretion of inorganic arsenic: a Belgian population study.

    PubMed Central

    Buchet, J P; Staessen, J; Roels, H; Lauwerys, R; Fagard, R

    1996-01-01

    OBJECTIVE: This Belgian study assessed the geographical and temporal differences in the exposure of the population to inorganic arsenic, a known carcinogen. METHODS: In the CadmiBel study (1985-9) the 24 h urinary arsenic excretion was measured, as an index of recent exposure, in industrialised cities (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397), and in rural districts in which the population had possibly been exposed through the drinking water or the emissions of nonferrous smelters (Wezel: n = 93, Lommel: n = 111, and Pelt: n = 133). In the PheeCad study, in 1991-5, the rural areas (n = 609) were re-examined together with an urban control area (Leuven: n = 152). RESULTS: The CadmiBel results showed that after adjustment for sex, age, and body mass index, the 24 h arsenic excretion was on average low in Liège (91 nmol), Charleroi (155 nmol), Hechtel-Eksel (144 nmol), and Wezel (158 nmol), whereas the highest excretions were found in Lommel (570 nmol) and Pelt (373 nmol). During the PheeCad study, the mean 24 h arsenic excretion in the rural areas ranged from 81 to 111 nmol. This was lower than six years earlier and similar to the excretion in the control town (108 nmol). Longitudinal studies in 529 people living in the rural areas confirmed that their 24 h arsenic excretion had decreased (P < 0.001) from 222 to 100 nmol. As well as the drinking water, industry was likely to be a source of the increased exposure in Lommel and Pelt in 1985-9, because at that time the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, because the fall in the arsenic excretion over time coincided with the implementation by industry of stricter environmental regulations, because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter, and because an increased arsenic excretion was only found downwind from the main

  3. Speciation of inorganic arsenic and selenium in leachates from landfills in relation to water quality assessment.

    PubMed

    Yusof, A M; Salleh, S; Wood, A K

    1999-01-01

    Speciation of arsenic and selenium was carried out on water samples taken from rivers used as water intake points in the vicinity of landfill areas used for land-based waste disposal system. Leachates from these landfill areas may contaminate the river water through underground seepage or overflowing, especially after a heavy downpour. Preconcentration of the chemical species was done using a mixture of ammonium pyrrolidinethiocarbamate-chloroform (APDTC-CHCl3). Because only the reduced forms of both arsenic and selenium species could be extracted by the preconcentrating mixture, suitable reducing agents such as 25% sodium thiosulfate for As(III) and 6M HCl for Se(IV) were used throughout the studies. Care was taken to exclude the interfering elements such as the alkali and alkali earth metals from the inorganic arsenic and selenium species by introducing 12% EDTA solution as the masking agent. The extracted mixture was irradiated in a thermal neutron flux of 4 x 10(12)/cm/s from a TRIGA Mk.II reactor at the Malaysia Institute of Nuclear Technology Research (MINT). Gamma rays of 559 keV and 297 keV from 76As and 75Se, respectively, were used in the quantitative determination of the inorganic species. Mixed standards of As(III) and Se(IV) used in the percentage efficiency procedure were prepared from salts of Analar grade. The water quality evaluation was viewed from the ratio of the inorganic species present. PMID:10676488

  4. 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

  5. Characterization of arsenic compounds formed by Daphnia magna and Tetraselmis chuii from inorganic arsenate.

    PubMed Central

    Irgolic, K J; Woolson, E A; Stockton, R A; Newman, R D; Bottino, N R; Zingaro, R A; Kearney, P C; Pyles, R A; Maeda, S; McShane, W J; Cox, E R

    1977-01-01

    Experiments to grow Tetraselmis chuii (a marine alga) and Daphnia magna in the presence of inorganic arsenate are described. The algae incorporate arsenic rather efficiently and form a lipid-soluble organic arsenic compound. T. chuii has been successfully mass cultured in a medium containing 10 ppm arsenic as arsenate. Daphnia magna was cultured in a medium containing 74As-labeled H3AsO4 and 1 ppm Na2HAsO4 expressed as arsenic. The arsenic metabolites were extracted with a chloroform-methanol solution and isolated by using column and thin-layer chromatography. TLC analysis of the metabolites revealed the presence of a 74As-containing product which migrated with phosphatidylethanolamine. This product was hydrolyzed with the phospholipases A, C, and D. The experimental results are not inconsistent with the presence of an arsenocholine moiety in the lipids. Arsenocholine, arsenobetaine, and acetylarsenocholine have been synthesized and will serve as reference substances in the chromatography experiments. The preparation of arsenocholine-containing lipids is in progress. PMID:908314

  6. Neurological Toxicity of Individual and Mixtures of Low Dose Arsenic, Mono and Di (n-butyl) Phthalates on Sub-Chronic Exposure to Mice.

    PubMed

    Mao, Guanghua; Zhou, Zhaoxiang; Chen, Yao; Wang, Wei; Wu, Xueshan; Feng, Weiwei; Cobbina, Samuel Jerry; Huang, Jing; Zhang, Zhen; Xu, Hai; Yang, Liuqing; Wu, Xiangyang

    2016-03-01

    The objective of this study was to evaluate the toxicity of individual and mixtures of di(n-butyl) phthalates (DBP) and their active metabolite monobutyl phthalate (MBP) and arsenic (As) on spatial cognition associated with hippocampal apoptosis in mice. Mice were exposed, individually or in combination, to DBP (50 mg/kg body weight, intragastrically), MBP (50 mg/kg body weight, intragastrically), and As (10 mg/L, per os) for 8 weeks. The Morris water maze test showed that mice exposed to DBP/MBP combined with As exhibited longer escape latencies and the lower average number of crossing the platform. The As content in the hippocampus after As exposure increased as compared to those without As exposure. In mice exposed to DBP/MBP combined with As, pathological alterations and oxidative damage to the hippocampus were found. Expression of apoptosis-related protein: Bax and caspase-3 were significantly increased in the hippocampus, while there was no significant change in expression of Bcl-2. The results suggested that DBP and MBP combined with As can induce spatial cognitive deficits through altering the expression of apoptosis-related protein and As played a critical role in cognition impairments. And the joint exposure has antagonistic effect.

  7. Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

    PubMed Central

    Osorio-Yáñez, Citlalli; Ayllon-Vergara, Julio C.; Aguilar-Madrid, Guadalupe; Arreola-Mendoza, Laura; Hernández-Castellanos, Erika; Barrera-Hernández, Angel; De Vizcaya-Ruiz, Andrea

    2013-01-01

    Background: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk. Objectives: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs). Methods: We conducted a cross-sectional study in 199 children 3–14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry. Results: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-μmol/L increase in ADMA per 1-mm increase in cIMT). Conclusions: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water. Citation: Osorio-Yáñez C, Ayllon-Vergara JC, Aguilar-Madrid G, Arreola-Mendoza L, Hernández-Castellanos E, Barrera

  8. Inorganic arsenic in rice bran and its products are an order of magnitude higher than in bulk grain.

    PubMed

    Sun, Guo-Xin; Williams, Paul N; Carey, Anne-Marie; Zhu, Yong-Guan; Deacon, Claire; Raab, Andrea; Feldmann, Joerg; Islam, Rafiqul M; Meharg, Andrew A

    2008-10-01

    Rice is more elevated in arsenic than all other grain crops tested to date, with whole grain (brown) rice having higher arsenic levels than polished (white). It is reported here that rice bran, both commercially purchased and specifically milled for this study, have levels of inorganic arsenic, a nonthreshold, class 1 carcinogen, reaching concentrations of approximately 1 mg/kg dry weight, around 10-20 fold higher than concentrations found in bulk grain. Although pure rice bran is used as a health food supplement, perhaps of more concern is rice bran solubles, which are marketed as a superfood and as a supplement to malnourished children in international aid programs. Five rice bran solubles products were tested, sourced from the United States and Japan, and were found to have 0.61-1.9 mg/kg inorganic arsenic. Manufactures recommend approximately 20 g servings of the rice bran solubles per day, which equates to a 0.012-0.038 mg intake of inorganic arsenic. There are no maximum concentration levels (MCLs) set for arsenic or its species in food stuffs. EU and U.S. water regulations, set at 0.01 mg/L total or inorganic arsenic, respectively, are based on the assumption that 1 L of water per day is consumed, i.e., 0.01 mg of arsenic/ day. At the manufacturers recommended rice bran solubles consumption rate, inorganic arsenic intake exceeds 0.01 mg/ day, remembering that rice bran solubles are targeted at malnourished children and that actual risk is based on mg kg(-1) day(-1) intake.

  9. Considerations in deriving quantitative cancer criteria for inorganic arsenic exposure via inhalation.

    PubMed

    Lewis, Ari S; Beyer, Leslie A; Zu, Ke

    2015-01-01

    The inhalation unit risk (IUR) that currently exists in the United States Environmental Protection Agency's (US EPA's) Integrated Risk Information System was developed in 1984 based on studies examining the relationship between respiratory cancer and arsenic exposure in copper smelters from two US locations: the copper smelter in Anaconda, Montana, and the American Smelting And Refining COmpany (ASARCO) smelter in Tacoma, Washington. Since US EPA last conducted its assessment, additional data have become available from epidemiology and mechanistic studies. In addition, the California Air Resources Board, Texas Commission of Environmental Quality, and Dutch Expert Committee on Occupational Safety have all conducted new risk assessments. All three analyses, which calculated IURs based on respiratory/lung cancer mortality, generated IURs that are lower (i.e., less restrictive) than the current US EPA value of 4.3×10(-3) (μg/m(3))(-1). The IURs developed by these agencies, which vary more than 20-fold, are based on somewhat different studies and use different methodologies to address uncertainties in the underlying datasets. Despite these differences, all were developed based on a cumulative exposure metric assuming a low-dose linear dose-response relationship. In this paper, we contrast and compare the analyses conducted by these agencies and critically evaluate strengths and limitations inherent in the data and methodologies used to develop quantitative risk estimates. In addition, we consider how these data could be best used to assess risk at much lower levels of arsenic in air, such as those experienced by the general public. Given that the mode of action for arsenic supports a threshold effect, and epidemiological evidence suggests that the arsenic concentration in air is a reliable predictor of lung/respiratory cancer risk, we developed a quantitative cancer risk analysis using a nonlinear threshold model. Applying a nonlinear model to occupational data, we

  10. Assessing the risks on human health associated with inorganic arsenic intake from groundwater-cultured milkfish in southwestern Taiwan.

    PubMed

    Lin, M C; Liao, C M

    2008-02-01

    The risk of consuming groundwater-cultured milkfish (Chanos chanos) was assessed. Samples of water and milkfish from groundwater-cultured ponds in southwestern Taiwan were analyzed. One third of the 12 sampled ponds had arsenic concentrations in the water higher than 50 microg/L, which is the maximum allowed concentration for arsenic in aquacultural water in Taiwan. Of the total amount of arsenic in water, the percentage of inorganic arsenic was 67.5+/-8.8%. The inorganic arsenic level in milkfish was 44.1+/-10.2%. The bioconcentration factors (BCFs) of milkfish for total arsenic and inorganic arsenic were 11.55+/-4.42 and 6.8+/-2.64, respectively. The target cancer risk (TR) for intake of the milkfish from those ponds was higher than the safe standard 1 x 10(-6), while in 8 of the ponds the TR values were higher than 1 x 10(-4). Among the 12 ponds, 7 of those had the target hazard quotient (THQ) for intake of the milkfish higher than the safe standard 1. The actual consumption (IRF) of milkfish from most of those ponds were higher than the calculated acceptable consumption (RBIRF), based on TR = 1 x 10(-6)-1 x 10(-4). Only three sampled ponds (Putai 2, Peimen 2 and Peimen 3) did not show differences between the IRF and the RBIRF. Based on the standard TR = 1 x 10(-6), both the risk-based concentration for inorganic arsenic in milkfish (RBC(f)) and the risk-based concentration for inorganic arsenic in pond water (RBC(w)) were lower than the levels of inorganic arsenic in reared milkfish (C(b)) and the concentration of inorganic arsenic in pond water (C(w)), respectively. When the calculation was based on TR = 1 x 10(-4), only one sampled pond (Putai 3) had a RBC(f) value higher than C(b). The inhabitants might be exposed to arsenic pollution with carcinogenic and non-carcinogenic risks.

  11. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  12. Detection of Inorganic Arsenic in Rice Using a Field Test Kit: A Screening Method.

    PubMed

    Bralatei, Edi; Lacan, Severine; Krupp, Eva M; Feldmann, Jörg

    2015-11-17

    Rice is a staple food eaten by more than 50% of the world's population and is a daily dietary constituent in most South East Asian countries where 70% of the rice export comes from and where there is a high level of arsenic contamination in groundwater used for irrigation. Research shows that rice can take up and store inorganic arsenic during cultivation, and rice is considered to be one of the major routes of exposure to inorganic arsenic, a class I carcinogen for humans. Here, we report the use of a screening method based on the Gutzeit methodology to detect inorganic arsenic (iAs) in rice within 1 h. After optimization, 30 rice commodities from the United Kingdom market were tested with the field method and were compared to the reference method (high-performance liquid chromatography-inductively coupled plasma-mass spectrometry, HPLC-ICP-MS). In all but three rice samples, iAs compound can be determined. The results show no bias for iAs using the field method. Results obtained show quantification limits of about 50 μg kg(-1), a good reproducibility for a field method of ±12%, and only a few false positives and negatives (<10%) could only be recorded at the 2015 European Commission (EC) guideline for baby rice of 100 μg kg(-1), while none were recorded at the maximum level suggested by the World Health Organization (WHO) and implemented by the EC for polished and white rice of 200 μg kg(-1). The method is reliable, fast, and inexpensive; hence, it is suggested to be used as a screening method in the field for preselection of rice which violates legislative guidelines.

  13. Inorganic arsenic in drinking water accelerates N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder tissue damage in mice

    SciTech Connect

    Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin; Chen, Sin-Syu; Liu, Yi-Wen

    2012-02-15

    Epidemiological studies have revealed that exposure to an arsenic-contaminated environment correlates with the incidence of bladder cancer. Bladder cancer is highly recurrent after intravesical therapy, and most of the deaths from this disease are due to invasive metastasis. In our present study, the role of inorganic arsenic in bladder carcinogenesis is characterized in a mouse model. This work provides the first evidence that inorganic arsenic in drinking water promotes N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tissue damage, including the urothelium and submucosal layer. This damage to the bladder epithelium induced by BBN includes thickening of the submucosal layer, the loss of the glycosaminoglycan layer and an increase in both the deoxyguanosine oxidation and cytosine methylation levels in the DNA. Further, when 10 ppm inorganic arsenic is combined with BBN, the number of bladder submucosal capillaries is increased. In addition, inorganic arsenic also increases the deoxyguanosine oxidation level, alters the cytosine methylation state, decreases the activities of glutathione reductase and glucose-6-phosphate dehydrogenase, decreases the protein expression of NAD(P)H quinone oxidoreductase-1 (NQO-1) and increases the protein expression of specific protein 1 (Sp1) in bladder tissues. In summary, our data reveal that inorganic arsenic in drinking water promotes the BBN-induced pre-neoplastic damage of bladder tissue in mice, and that the 8-hydroxy-2′-deoxyguanosine, 5-methylcytosine, NQO-1 protein and Sp1 protein levels may be pre-neoplastic markers of bladder tumors. -- Highlights: ► The role of inorganic arsenic in bladder carcinogenesis is characterized in mice. ► We examine the changes in the histology and biochemistry of bladder tissues. ► Inorganic arsenic enhances BBN-induced DNA oxidation while decreases BBN-induced DNA methylation in the mouse bladder. ► Inorganic arsenic alters the activities of the anti-oxidant enzymes in

  14. The intake of inorganic arsenic from long grain rice and rice-based baby food in Finland - low safety margin warrants follow up.

    PubMed

    Rintala, Eeva-Maria; Ekholm, Päivi; Koivisto, Pertti; Peltonen, Kimmo; Venäläinen, Eija-Riitta

    2014-05-01

    We evaluated total and inorganic arsenic levels in long grain rice and rice based baby foods on Finnish market. Inorganic arsenic was analysed with an HPLC-ICP-MS system. The total arsenic concentration was determined with an ICP-MS method. In this study, the inorganic arsenic levels in long grain rice varied from 0.09 to 0.28mg/kg (n=8) and the total arsenic levels from 0.11 to 0.65mg/kg. There was a good correlation between the total and inorganic arsenic levels in long grain rice at a confidence level of 95%. The total arsenic levels of rice-based baby foods were in the range 0.02 - 0.29mg/kg (n=10), however, the level of inorganic arsenic could only be quantitated in four samples, on average they were 0.11mg/kg. Our estimation of inorganic arsenic intake from long grain rice and rice-based baby food in Finland indicate that in every age group the intake is close to the lowest BMDL0.1 value 0.3μg/kg bw/day set by EFSA. According to our data, the intake of inorganic arsenic should be more extensively evaluated.

  15. Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice.

    PubMed

    Waalkes, Michael P; Ward, Jerrold M; Liu, Jie; Diwan, Bhalchandra A

    2003-01-01

    Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic. Groups (n = 10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO(2)) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Dams were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (n = 25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose- related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm). In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring, dose-related increases occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26%; 85 ppm, 38%) and lung carcinoma incidence (control, 0%; 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common

  16. Estimation of Total and Inorganic Arsenic Intake from the Diet in Korean Adults.

    PubMed

    Seo, Mi-Na; Lee, Seul-Gi; Eom, Sang-Yong; Kim, Jeongseon; Oh, Se-Young; Kwon, Ho-Jang; Kim, Heon; Choi, Byung-Sun; Yu, Il-Je; Park, Jung-Duck

    2016-05-01

    Arsenic (As) is a major environmental pollutant and a known human carcinogen that is widely distributed in the air, soil, and water. General population is mainly exposed to As through drinking water and food from the contaminated water and soil. Arsenic in drinking water is generally well controlled now. This study was performed to estimate total and inorganic As intake and to determine the major contributing source in the Korean adult diet. The study subjects were 2117 healthy adults (922 males and 1195 females) who had not been occupationally exposed to As. Total dietary intake was studied using the 24-h recall method, which included 138 specific food items. The estimates of total As and inorganic As intake were based on total and inorganic As contents in each food item consumed during the last 24 h. Daily dietary intake was estimated to be 1373.6 g. Total As intake was estimated to be 145.4 µg As/day. Total dietary As intake was correlated with consumption of fish/shellfish, seaweeds, and grains. Approximately 87% of total dietary As intake was attributed to seafood, such as 105.5 µg As/day from fish/shellfish and 20.5 µg As/day from seaweeds. Inorganic As intake was estimated to be 10.4 µg As per day. Inorganic As intake was mainly provided by grains (6.4 µg As/day), followed by seaweeds and fish/shellfish. Our results indicate that seafood and grains are the main As dietary sources in Korean adults and that dietary As exposure may be associated with individual dietary habits and environmental As contamination among countries. PMID:26706926

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

    PubMed

    Sińczuk-Walczak, Halina

    2009-01-01

    This paper presents a review of the effect of arsenic (As) and its inorganic compounds on the nervous system. In humans, inhalation exposure mostly occurs in occupational conditions. In the occupational environment, the most extensive exposure to this element is observed in the copper industry. Chronic As poisoning is manifested by skin and mucous membrane lesions, impairment of the nervous system in the form of disorders of psychic functions and polyneuropathies, retrobulbar neuritis, disorders of peripheral circulation and the risk for Raynaud's syndrome. Arsenic-induced polyneuropathy is usually a very serious and chronic disease. A complete recovery is observed in only 15-20% of patients. As-induced encephalopathy is an irreversible process. PMID:20187500

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

    PubMed

    Sińczuk-Walczak, Halina

    2009-01-01

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

  19. Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: arsenic, manganese, fluoride, iron, and uranium.

    PubMed

    Bacquart, Thomas; Frisbie, Seth; Mitchell, Erika; Grigg, Laurie; Cole, Christopher; Small, Colleen; Sarkar, Bibudhendra

    2015-06-01

    In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic

  20. Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: arsenic, manganese, fluoride, iron, and uranium.

    PubMed

    Bacquart, Thomas; Frisbie, Seth; Mitchell, Erika; Grigg, Laurie; Cole, Christopher; Small, Colleen; Sarkar, Bibudhendra

    2015-06-01

    In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic

  1. Activation of the Nrf2 pathway by inorganic arsenic in human hepatocytes and the role of transcriptional repressor Bach1.

    PubMed

    Liu, Dan; Duan, Xiaoxu; Dong, Dandan; Bai, Caijun; Li, Xin; Sun, Guifan; Li, Bing

    2013-01-01

    Previous studies have proved that the environmental toxicant, inorganic arsenic, activates nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in many different cell types. This study tried to explore the hepatic Nrf2 pathway upon arsenic treatment comprehensively, since liver is one of the major target organs of arsenical toxicity. Our results showed that inorganic arsenic significantly induced Nrf2 protein and mRNA expression in Chang human hepatocytes. We also observed a dose-dependent increase of antioxidant response element- (ARE-) luciferase activity. Both the mRNA and protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were all upregulated dramatically. On the other hand, entry and accumulation of Nrf2 protein in the nucleus, while exportting the transcriptional repressor BTB and CNC homology 1 (Bach1) from nucleus to cytoplasm, were also confirmed by western blot and immunofluorescence assay. Our results therefore confirmed the arsenic-induced Nrf2 pathway activation in hepatocytes and also suggested that the translocation of Bach1 was associated with the regulation of Nrf2 pathway by arsenic. Hepatic Nrf2 pathway plays indispensable roles for cellular defenses against arsenic hepatotoxicity, and the interplay of Bach1 and Nrf2 may be helpful to understand the self-defensive responses and the diverse biological effects of arsenicals.

  2. Activation of the Nrf2 pathway by inorganic arsenic in human hepatocytes and the role of transcriptional repressor Bach1.

    PubMed

    Liu, Dan; Duan, Xiaoxu; Dong, Dandan; Bai, Caijun; Li, Xin; Sun, Guifan; Li, Bing

    2013-01-01

    Previous studies have proved that the environmental toxicant, inorganic arsenic, activates nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in many different cell types. This study tried to explore the hepatic Nrf2 pathway upon arsenic treatment comprehensively, since liver is one of the major target organs of arsenical toxicity. Our results showed that inorganic arsenic significantly induced Nrf2 protein and mRNA expression in Chang human hepatocytes. We also observed a dose-dependent increase of antioxidant response element- (ARE-) luciferase activity. Both the mRNA and protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were all upregulated dramatically. On the other hand, entry and accumulation of Nrf2 protein in the nucleus, while exportting the transcriptional repressor BTB and CNC homology 1 (Bach1) from nucleus to cytoplasm, were also confirmed by western blot and immunofluorescence assay. Our results therefore confirmed the arsenic-induced Nrf2 pathway activation in hepatocytes and also suggested that the translocation of Bach1 was associated with the regulation of Nrf2 pathway by arsenic. Hepatic Nrf2 pathway plays indispensable roles for cellular defenses against arsenic hepatotoxicity, and the interplay of Bach1 and Nrf2 may be helpful to understand the self-defensive responses and the diverse biological effects of arsenicals. PMID:23738048

  3. Activation of the Nrf2 Pathway by Inorganic Arsenic in Human Hepatocytes and the Role of Transcriptional Repressor Bach1

    PubMed Central

    Liu, Dan; Duan, Xiaoxu; Dong, Dandan; Bai, Caijun; Li, Xin; Sun, Guifan; Li, Bing

    2013-01-01

    Previous studies have proved that the environmental toxicant, inorganic arsenic, activates nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in many different cell types. This study tried to explore the hepatic Nrf2 pathway upon arsenic treatment comprehensively, since liver is one of the major target organs of arsenical toxicity. Our results showed that inorganic arsenic significantly induced Nrf2 protein and mRNA expression in Chang human hepatocytes. We also observed a dose-dependent increase of antioxidant response element- (ARE-) luciferase activity. Both the mRNA and protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were all upregulated dramatically. On the other hand, entry and accumulation of Nrf2 protein in the nucleus, while exportting the transcriptional repressor BTB and CNC homology 1 (Bach1) from nucleus to cytoplasm, were also confirmed by western blot and immunofluorescence assay. Our results therefore confirmed the arsenic-induced Nrf2 pathway activation in hepatocytes and also suggested that the translocation of Bach1 was associated with the regulation of Nrf2 pathway by arsenic. Hepatic Nrf2 pathway plays indispensable roles for cellular defenses against arsenic hepatotoxicity, and the interplay of Bach1 and Nrf2 may be helpful to understand the self-defensive responses and the diverse biological effects of arsenicals. PMID:23738048

  4. Comparison of Bioavailability and Biotransformation of Inorganic and Organic Arsenic to Two Marine Fish.

    PubMed

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

    2016-03-01

    Dietary uptake could be the primary route of arsenic (As) bioaccumulation in marine fish, but the bioavailability of inorganic and organic As remains elusive. In this study, we investigated the trophic transfer and bioavailability of As in herbivorous rabbitfish Siganus fuscescens and carnivorous seabass Lateolabrax japonicus. Rabbitfish were fed with one artificial diet or three macroalgae, whereas seabass were fed with one artificial diet, one polychaete, or two bivalves for 28 days. The six spiked fresh prey diets contained different proportions of inorganic As [As(III) and As(V)] and organic As compounds [methylarsenate (MMA), dimethylarsenate (DMA), and arsenobetaine (AsB)], and the spiked artificial diet mainly contained As(III) or As(V). We demonstrated that the trophic transfer factors (TTF) of As in both fish were negatively correlated with the concentrations of inorganic As in the diets, while there was no relationship between TTF and the AsB concentrations in the diets. Positive correlation was observed between the accumulated As concentrations and the AsB concentrations in both fish, suggesting that organic As compounds (AsB) were more trophically available than inorganic As. Furthermore, the biotransformation ability of seabass was higher than that in rabbitfish, which resulted in higher As accumulation in seabass than in rabbitfish. Our study demonstrated that different prey with different inorganic/organic As proportions resulted in diverse bioaccumulation of total As in different marine fish.

  5. Genotoxicity of inorganic arsenic exposure: Micronuclei frequencies in exfoliated human oral mucosa cells

    SciTech Connect

    Gonsebatt, M.E.; Guzman, P.; Salazar, A.M.

    1995-11-01

    Micronuclei (MN) can be formed by acentric chromosome fragments or whole lagging chromosomes. When used in vivo, this assay can potentially detect the clastogenic effect of an exposure. MN are easier to score than chromosome aberrations although both biomarkers of effect are useful tools in risk estimation. We investigated the frequency of MN in exfoliated cells from the oral mucosa in 25-30 volunteers lifetime exposed to approximately 400 {mu}g/L of arsenic in their drinking water. A group of individuals with similar composition with respect to sex, age, and socioeconomic status, but with As levels in the drinking water between 29-32 {mu}g/L, was used as controls. Exposure was assessed by questionnaires and by determining the levels of arsenic in urine and water samples. Oral mucosa cells were collected scraping the mucosa with a premoistened wooden spatula and smeared on microscope slides. Feulgen stained samples were scored blind on slides. The frequency of MN in oral mucosa cells was 0.05% in controls and 0.25% in exposed individuals. Exposed males showed higher frequencies of MN than exposed females. Smoking habits did not account for the observed differences. These results demonstrate that buccal mucosa cells are a target tissue in inorganic arsenic exposure via drinking water. Several studies have also reported elevated frequencies of MN in oral mucosa cells from individuals exposed to substances or factors associated with increased cancer risk, which makes this non-invasive technique appropriate and sensitive to monitor human exposure to carcinogens such as inorganic arsenic.

  6. Biological effects of inorganic arsenic on primary cultures of rat astrocytes.

    PubMed

    Catanzaro, Irene; Schiera, Gabriella; Sciandrello, Giulia; Barbata, Giusi; Caradonna, Fabio; Proia, Patrizia; Di Liegro, Italia

    2010-10-01

    It is well established that inorganic arsenic induces neurotoxic effects and neurological defects in humans and laboratory animals. The cellular and molecular mechanisms of its actions, however, remain elusive. Herein we report the effects of arsenite (NaAsO2) on primary cultures of rat astrocytes. Cells underwent induction of heat shock protein 70 only at the highest doses of inorganic arsenic (30 and 60 microM), suggesting a high threshold to respond to stress. We also investigated arsenic genotoxicity with the comet assay. Interestingly, although cells treated with 10 microM arsenite for 24 h maintained >70% viability, with respect to untreated cells, high DNA damage was already observed. Since arsenic is not known to be a direct-acting genotoxic agent, we investigated the possibility that its effects are due, in astrocytes as well, to ROS formation, as already described for other cell types. However, FACS analysis after CM-H2DCFDA staining did not evidence any significant increase of ROS production while, on the contrary, at the highest arsenite concentrations used, ROS production decreased. Concordantly, we found that, if most cells in the culture are still alive (i.e. up to 10 microM arsenite), they show a treatment-dependent increase in the concentration of SOD1. On the other hand, SOD2 concentration did not change. Finally, we found that astrocytes also synthesize PIPPin, an RNA-binding protein, the concentration of which was recently reported to change in response to stress induced by cadmium. Here we also report that, in cells exposed to high doses of arsenite, an anti-PIPPin antibody-positive faster migrating protein appears. PMID:20818482

  7. Contribution of water and cooked rice to an estimation of the dietary intake of inorganic arsenic in a rural village of West Bengal, India.

    PubMed

    Signes, A; Mitra, K; Burló, F; Carbonell-Barrachina, A A

    2008-01-01

    Arsenic contamination of rice plants by arsenic-polluted irrigation groundwater could result in high arsenic concentrations in cooked rice. The main objective of the study was to estimate the total and inorganic arsenic intakes in a rural population of West Bengal, India, through both drinking water and cooked rice. Simulated cooking of rice with different levels of arsenic species in the cooking water was carried out. The presence of arsenic in the cooking water was provided by four arsenic species (arsenite, arsenate, methylarsonate or dimethylarsinate) and at three total arsenic concentrations (50, 250 or 500 microg l(-1)). The results show that the arsenic concentration in cooked rice is always higher than that in raw rice and range from 227 to 1642 microg kg(-1). The cooking process did not change the arsenic speciation in rice. Cooked rice contributed a mean of 41% to the daily intake of inorganic arsenic. The daily inorganic arsenic intakes for water plus rice were 229, 1024 and 2000 microg day(-1) for initial arsenic concentrations in the cooking water of 50, 250 and 500 microg arsenic l(-1), respectively, compared with the tolerable daily intake which is 150 microg day(-1).

  8. Total and Inorganic Arsenic in Mid-Atlantic Marine Fish and Shellfish and Implications for Fish Advisories

    SciTech Connect

    Greene, Richard; Crecelius, Eric A.

    2006-02-06

    Up to 33.3 metric tons of arsenic trioxide were spilled off the Middle Atlantic coast of the United States in January of 1992 during a shipping accident. Historical fish tissue data for samples collected in the Delaware Inland Bays before and after the spill reveal a prominent spike in total arsenic in summer flounder following the spill and a gradual decline ever since. In 2002, a small study was conducted to determine whether summer flounder migrating into the Delaware Inland Bays from the Continental Shelf in the spring contain higher body burdens of arsenic than summer flounder migrating out of the Inland Bays in the fall. Total arsenic was significantly higher in the incoming fish. Considering that summer flounder overwinter at the spill site, that arsenic trioxide is a dense powder of limited solubility that would tend to incorporate into the sediments, and that summer flounder are demersal fish, we conclude that summer flounder accumulate arsenic offshore and that the likely source of their extra body burden is the spilled arsenic. Speciation of arsenic in the summer flounder, as well as in Atlantic croaker, striped bass, and hard clam reveal low concentrations (0.5 ? 20 ug/kg ww) of toxic inorganic arsenic. DMA was more than an order of magnitude greater in hard clam meats than in the other species tested, a finding attributed to arsenic uptake by phytoplankton and subsequent dietary uptake by the clam. Risk assessment using the inorganic arsenic concentrations was used to conclude that a fish advisory is not warranted.

  9. Methylarsonous acid causes oxidative DNA damage in cells independent of the ability to biomethylate inorganic arsenic

    PubMed Central

    Tokar, Erik J.; Kojima, Chikara; Waalkes, Michael P.

    2013-01-01

    Inorganic arsenic (iAs) and its toxic methylated metabolite, methylarsonous acid (MMAIII), both have carcinogenic potential. Prior study shows iAs induced malignant transformation in both arsenic methylation-proficient (liver) and methylation-deficient (prostate) cells, but only methylation-proficient cells show oxidative DNA damage (ODD) during this transformation. To further define if arsenic methylation is necessary for transformation or ODD induction, here we chronically exposed these same liver or prostate cell lines to MMAIII (0.25–1.0 μM) and tested for acquired malignant phenotype. Various metrics of oncogenic transformation were periodically assessed along with ODD during chronic MMAIII exposure. Methylation-deficient and methylation-proficient cells both acquired a cancer phenotype with MMAIII exposure at about 20 weeks, based on increased matrix metalloproteinase secretion, colony formation and invasion. In contrast, prior work showed iAs-induced transformation took longer in biomethylation-deficient cells (~30 weeks) than in biomethylation-proficient cells (~18 weeks). In the present study, MMAIII caused similar peak ODD levels at similar concentrations and at similar exposure times (18–22 weeks) in both cell types. At the approximate peak of ODD production both cell types showed similar alterations in arsenic and oxidative stress adaptation factors (i.e. ABCC1, ABCC2, GST-π, SOD-1). Thus, MMAIII causes oncogenic transformation associated with ODD in methylation-deficient cells, indicating further methylation is not required to induce ODD. Together, these results show that, MMAIII and iAs cause an acquired malignant phenotype in methylation-deficient cells, yet iAs does not induce ODD. This indicates iAs likely has both genotoxic and non-genotoxic mechanisms dictated by the target cell’s ability to methylate arsenic. PMID:24091636

  10. Methylarsonous acid causes oxidative DNA damage in cells independent of the ability to biomethylate inorganic arsenic.

    PubMed

    Tokar, Erik J; Kojima, Chikara; Waalkes, Michael P

    2014-02-01

    Inorganic arsenic (iAs) and its toxic methylated metabolite, methylarsonous acid (MMA(III)), both have carcinogenic potential. Prior study shows iAs-induced malignant transformation in both arsenic methylation-proficient (liver) and methylation-deficient (prostate) cells, but only methylation-proficient cells show oxidative DNA damage (ODD) during this transformation. To further define whether arsenic methylation is necessary for transformation or ODD induction, here we chronically exposed these same liver or prostate cell lines to MMA(III) (0.25-1.0 μM) and tested for acquired malignant phenotype. Various metrics of oncogenic transformation were periodically assessed along with ODD during chronic MMA(III) exposure. Methylation-deficient and methylation-proficient cells both acquired a cancer phenotype with MMA(III) exposure at about 20 weeks, based on increased matrix metalloproteinase secretion, colony formation, and invasion. In contrast, prior work showed iAs-induced transformation took longer in biomethylation-deficient cells (~30 weeks) than in biomethylation-proficient cells (~18 weeks). In the present study, MMA(III) caused similar peak ODD levels at similar concentrations and at similar exposure times (18-22 weeks) in both cell types. At the approximate peak of ODD production, both cell types showed similar alterations in arsenic and oxidative stress adaptation factors (i.e., ABCC1, ABCC2, GST-π, SOD-1). Thus, MMA(III) causes oncogenic transformation associated with ODD in methylation-deficient cells, indicating that further methylation is not required to induce ODD. Together, these results show that MMA(III) and iAs cause an acquired malignant phenotype in methylation-deficient cells, yet iAs does not induce ODD. This indicates iAs likely has both genotoxic and non-genotoxic mechanisms dictated by the target cell's ability to methylate arsenic. PMID:24091636

  11. Methylarsonous acid causes oxidative DNA damage in cells independent of the ability to biomethylate inorganic arsenic.

    PubMed

    Tokar, Erik J; Kojima, Chikara; Waalkes, Michael P

    2014-02-01

    Inorganic arsenic (iAs) and its toxic methylated metabolite, methylarsonous acid (MMA(III)), both have carcinogenic potential. Prior study shows iAs-induced malignant transformation in both arsenic methylation-proficient (liver) and methylation-deficient (prostate) cells, but only methylation-proficient cells show oxidative DNA damage (ODD) during this transformation. To further define whether arsenic methylation is necessary for transformation or ODD induction, here we chronically exposed these same liver or prostate cell lines to MMA(III) (0.25-1.0 μM) and tested for acquired malignant phenotype. Various metrics of oncogenic transformation were periodically assessed along with ODD during chronic MMA(III) exposure. Methylation-deficient and methylation-proficient cells both acquired a cancer phenotype with MMA(III) exposure at about 20 weeks, based on increased matrix metalloproteinase secretion, colony formation, and invasion. In contrast, prior work showed iAs-induced transformation took longer in biomethylation-deficient cells (~30 weeks) than in biomethylation-proficient cells (~18 weeks). In the present study, MMA(III) caused similar peak ODD levels at similar concentrations and at similar exposure times (18-22 weeks) in both cell types. At the approximate peak of ODD production, both cell types showed similar alterations in arsenic and oxidative stress adaptation factors (i.e., ABCC1, ABCC2, GST-π, SOD-1). Thus, MMA(III) causes oncogenic transformation associated with ODD in methylation-deficient cells, indicating that further methylation is not required to induce ODD. Together, these results show that MMA(III) and iAs cause an acquired malignant phenotype in methylation-deficient cells, yet iAs does not induce ODD. This indicates iAs likely has both genotoxic and non-genotoxic mechanisms dictated by the target cell's ability to methylate arsenic.

  12. Soil Incorporation of Silica-Rich Rice Husk Decreases Inorganic Arsenic in Rice Grain.

    PubMed

    Seyfferth, Angelia L; Morris, Andrew H; Gill, Rattandeep; Kearns, Kelli A; Mann, Jessica N; Paukett, Michelle; Leskanic, Corey

    2016-05-18

    Arsenic decreases rice yield, and inorganic grain As threatens human health; thus, strategies to decrease rice As are critically needed. Increased plant-available silica (Si) can decrease rice As, yet the source of Si matters. Rice husk, an underutilized and Si-rich byproduct of rice production that contains less labile C and an order of magnitude less As than rice straw, may be an economically viable Si resource to decrease rice As, yet the impact of rice husk incorporation on As in the rice-soil nexus has not been reported. This proof-of-concept study shows that rice husk incorporation to soil (1% w/w) decreases inorganic grain As by 25-50% without negatively affecting grain Cd, yield, or dissolved CH4 levels. Rice husk is a critical yet perhaps overlooked resource to improve soil quality through enhanced nutrient availability and attenuate human health risks through consumption of As-laden grain. PMID:27109244

  13. Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic.

    PubMed

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

    2016-09-01

    Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity.

  14. Relation of dietary inorganic arsenic to serum matrix metalloproteinase-9 (MMP-9) at different threshold concentrations of tap water arsenic

    PubMed Central

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

    2015-01-01

    Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As ≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As ≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity. PMID:25605447

  15. 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

  16. 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. PMID:26766368

  17. 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.

  18. Inorganic arsenic speciation in soil and groundwater near in-service chromated copper arsenate-treated wood poles.

    PubMed

    Zagury, Gérald J; Dobran, Simona; Estrela, Sandra; Deschênes, Louise

    2008-04-01

    The environmental impact of chromated copper arsenate (CCA)-treated utility poles is linked to the possible soil and groundwater contamination with arsenic. The objective of the present study was to determine the arsenic speciation in soil and groundwater near in-service CCA-treated poles. Arsenite (As[III]) and arsenate (As[V]) concentrations were determined in 29 surface and subsurface soil samples collected near eight CCA-treated wood poles. Temporal variability of total arsenic concentrations and inorganic arsenic speciation was also assessed in groundwater at two sites through four sampling events over a 19-month period. Arsenic speciation was carried out by a solvent extraction method using ammonium pyrrolidine dithiocarbamate-methyl isobutyl ketone, and total arsenic was quantified by inductively coupled plasma/atomic emission spectrometry/hydride generation. Average arsenic concentrations in surface soils immediately adjacent to utility poles ranged from 153+/-49 to 410+/-150 mg/kg but approached background levels (below 5 mg/kg) within 0.50 m from the poles. A positive correlation was found between surface soil As concentration and total Fe content. In subsurface samples (0.50 m), arsenic levels were generally high in sandy soils (up to 223+/-32 mg/kg), moderate in clayey soils (up to 126+/-26 mg/kg), and relatively lower in organic soils (up to 56+/-24 mg/ kg). Arsenic(V) was the predominant arsenic species in surface (>78%) and subsurface soils (>66%). Total arsenic concentrations in groundwater below the clayey site were high and varied widely over time (79-390 microg/L), with 30 to 68% as As(III). Below the utility pole located on the organic site with a high Fe content, lower total arsenic levels (12-33 microg/L) were found, with As(III) ranging from 0 to 100%.

  19. Photocatalytical removal of inorganic and organic arsenic species from aqueous solution using zinc oxide semiconductor.

    PubMed

    Rivera-Reyna, Nidia; Hinojosa-Reyes, Laura; Guzmán-Mar, Jorge Luis; Cai, Yong; O'Shea, Kevin; Hernández-Ramírez, Aracely

    2013-04-01

    The photocatalytic removal of arsenite [As(III)] and monomethylarsonic acid [MMA(V)] was investigated in the presence of UV light (350 nm) and aqueous suspensions of ZnO synthesized by the sol-gel technique. Photocatalytic removal of these potent arsenic compounds results in the effective and rapid mineralization to less toxic inorganic arsenate [As(V)]. The effect of ZnO loading and solution pH on the treatment efficiency of the UV/ZnO photocatalytic process was evaluated. The optimal conditions for the removal of 5 mg L(-1) [As(III)] and [MMA(V)] aqueous solutions were observed at catalyst loadings of 0.25 and 0.50 g L(-1) with solution pH values of 7 and 8, respectively. Under these conditions, the activity of photocatalyst sol-gel ZnO was compared with TiO2 Degussa P25 and commercial ZnO catalyst. The results demonstrate that the high adsorption capacity of ZnO synthesized by sol-gel gives enhanced removal of arsenic species from water samples, indicating that this catalyst is a promising material for treatment of arsenic contaminated groundwater. PMID:23064294

  20. Photocatalytical removal of inorganic and organic arsenic species from aqueous solution using zinc oxide semiconductor.

    PubMed

    Rivera-Reyna, Nidia; Hinojosa-Reyes, Laura; Guzmán-Mar, Jorge Luis; Cai, Yong; O'Shea, Kevin; Hernández-Ramírez, Aracely

    2013-04-01

    The photocatalytic removal of arsenite [As(III)] and monomethylarsonic acid [MMA(V)] was investigated in the presence of UV light (350 nm) and aqueous suspensions of ZnO synthesized by the sol-gel technique. Photocatalytic removal of these potent arsenic compounds results in the effective and rapid mineralization to less toxic inorganic arsenate [As(V)]. The effect of ZnO loading and solution pH on the treatment efficiency of the UV/ZnO photocatalytic process was evaluated. The optimal conditions for the removal of 5 mg L(-1) [As(III)] and [MMA(V)] aqueous solutions were observed at catalyst loadings of 0.25 and 0.50 g L(-1) with solution pH values of 7 and 8, respectively. Under these conditions, the activity of photocatalyst sol-gel ZnO was compared with TiO2 Degussa P25 and commercial ZnO catalyst. The results demonstrate that the high adsorption capacity of ZnO synthesized by sol-gel gives enhanced removal of arsenic species from water samples, indicating that this catalyst is a promising material for treatment of arsenic contaminated groundwater.

  1. Photocatalytical removal of inorganic and organic arsenic species from aqueous solution using zinc oxide semiconductor†

    PubMed Central

    Rivera-Reyna, Nidia; Hinojosa-Reyes, Laura; Guzmán-Mar, Jorge Luis; Cai, Yong; O'Shea, Kevin; Hernández-Ramírez, Aracely

    2012-01-01

    The photocatalytic removal of arsenite [As(III)] and monomethylarsonic acid [MMA(V)] was investigated in the presence of UV light (350 nm) and aqueous suspensions of ZnO synthesized by the sol–gel technique. Photocatalytic removal of these potent arsenic compounds results in the effective and rapid mineralization to less toxic inorganic arsenate [As(V)]. The effect of ZnO loading and solution pH on the treatment efficiency of the UV/ZnO photocatalytic process was evaluated. The optimal conditions for the removal of 5 mg L−1 [As(III)] and [MMA(V)] aqueous solutions were observed at catalyst loadings of 0.25 and 0.50 g L−1 with solution pH values of 7 and 8, respectively. Under these conditions, the activity of photocatalyst sol–gel ZnO was compared with TiO2 Degussa P25 and commercial ZnO catalyst. The results demonstrate that the high adsorption capacity of ZnO synthesized by sol–gel gives enhanced removal of arsenic species from water samples, indicating that this catalyst is a promising material for treatment of arsenic contaminated groundwater. PMID:23064294

  2. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    PubMed

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid. PMID:27165637

  3. Optimization of microwave-assisted extraction for six inorganic and organic arsenic species in chicken tissues using response surface methodology.

    PubMed

    Zhang, Wenfeng; Hu, Yuanan; Cheng, Hefa

    2015-09-01

    Response surface methodology was applied to optimize the parameters for microwave-assisted extraction of six major inorganic and organic arsenic species (As(III), As(V), dimethyl arsenic acid, monomethyl arsenic acid, p-arsanilic acid, and roxarsone) from chicken tissues, followed by detection using a high-performance liquid chromatography with inductively coupled mass spectrometry detection method, which allows the simultaneous analysis of both inorganic and organic arsenic species in the extract in a single run. Effects of extraction medium, solution pH, liquid-to-solid ratio, and the temperature and time of microwave-assisted extraction on the extraction of the targeted arsenic species were studied. The optimum microwave-assisted extraction conditions were: 100 mg of chicken tissue, extracted by 5 mL of 22% v/v methanol, 90 mmol/L (NH4 )2 HPO4 , and 0.07% v/v trifluoroacetic acid (with pH adjusted to 10.0 by ammonium hydroxide solution), ramping for 10 min to 71°C, and holding for 11 min. The method has good extraction performance for total arsenic in the spiked and nonspiked chicken tissues (104.0 ± 13.8% and 91.6 ± 7.8%, respectively), except for the ones with arsenic contents close to the quantitation limits. Limits of quantitation (S/N = 10) for As(III), As(V), dimethyl arsenic acid, monomethyl arsenic acid, p-arsanilic acid, and roxarsone in chicken tissues using this method were 0.012, 0.058, 0.039, 0.061, 0.102, and 0.240 mg/kg (dry weight), respectively.

  4. Biotransformation and detoxification of inorganic arsenic in Bombay oyster Saccostrea cucullata.

    PubMed

    Zhang, Wei; Guo, Zhiqiang; Zhou, Yanyan; Liu, Huaxue; Zhang, Li

    2015-01-01

    Arsenic (As) exists as the toxic inorganic forms in marine water and sediment, while marine oysters usually accumulate high As contents mostly as the less toxic organic forms. It has not yet been clear that how As is biotransformed in marine oysters. This study therefore investigated the biotransformation and detoxification of two inorganic As forms (As(III) and As(V)) in Bombay oyster Saccostrea cucullata after waterborne exposures for 30 days. Seven treatments of dissolved As exposure (clean seawater, 1, 5, 20 mg/L As(III), and 1, 5, 20 mg/L As(V)) were performed. Body As concentration increased significantly after all As exposure treatments except 1mg/L As(V). Total As, As(III), and As(V) concentration were positive correlated with glutathione-S-transferases (GST) activities, suggesting GST might play an important role in the As biotransformation and detoxification process. Organic As species were predominant in control and the low As exposed oysters, whereas a large fraction of As was remained as the inorganic forms in the high As exposed oysters, suggesting As could be biotransformed efficiently in the oysters in clean or light contaminated environment. The results of As speciation demonstrated the As biotransformation in the oysters included As(V) reduction, methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to arsenobetaine (AsB). More As was distributed in the subcellular metallothionein-like proteins fraction (MTLP) functioning sequestration and detoxification in the inorganic As exposed oysters, suggesting it was also a strategy for oysters against As stress. In summary, this study elucidated that marine oysters had high ability to accumulate, biotransform, and detoxify inorganic As.

  5. Biotransformation and detoxification of inorganic arsenic in Bombay oyster Saccostrea cucullata.

    PubMed

    Zhang, Wei; Guo, Zhiqiang; Zhou, Yanyan; Liu, Huaxue; Zhang, Li

    2015-01-01

    Arsenic (As) exists as the toxic inorganic forms in marine water and sediment, while marine oysters usually accumulate high As contents mostly as the less toxic organic forms. It has not yet been clear that how As is biotransformed in marine oysters. This study therefore investigated the biotransformation and detoxification of two inorganic As forms (As(III) and As(V)) in Bombay oyster Saccostrea cucullata after waterborne exposures for 30 days. Seven treatments of dissolved As exposure (clean seawater, 1, 5, 20 mg/L As(III), and 1, 5, 20 mg/L As(V)) were performed. Body As concentration increased significantly after all As exposure treatments except 1mg/L As(V). Total As, As(III), and As(V) concentration were positive correlated with glutathione-S-transferases (GST) activities, suggesting GST might play an important role in the As biotransformation and detoxification process. Organic As species were predominant in control and the low As exposed oysters, whereas a large fraction of As was remained as the inorganic forms in the high As exposed oysters, suggesting As could be biotransformed efficiently in the oysters in clean or light contaminated environment. The results of As speciation demonstrated the As biotransformation in the oysters included As(V) reduction, methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and subsequent conversion to arsenobetaine (AsB). More As was distributed in the subcellular metallothionein-like proteins fraction (MTLP) functioning sequestration and detoxification in the inorganic As exposed oysters, suggesting it was also a strategy for oysters against As stress. In summary, this study elucidated that marine oysters had high ability to accumulate, biotransform, and detoxify inorganic As. PMID:25461743

  6. Speciation of inorganic arsenic species and total inorganic arsenic in rice using microwave-assisted dispersive liquid-liquid micro-extraction and electrothermal atomic absorption spectrometry.

    PubMed

    Ahmadi-Jouibari, Toraj; Fattahi, Nazir

    2015-01-01

    Human exposure to inorganic arsenic (iAs) via rice consumption is of increasing concern. In the present study, microwave-assisted dispersive liquid-liquid micro-extraction (MADLLME) and electrothermal atomic absorption spectrometry (ETAAS) were developed for the speciation of iAs in rice samples. After microwave-assisted digestion, the As(III) ion reacted with diethyldithiophosphoric acid (DDTP) to form an As-DDTP complex and was extracted at the same time. Some parameters affecting digestion, complex formation, and extraction were studied and optimised. Under the optimised conditions, a detection limit of 0.2 µg kg(-1) with a correlation coefficient of 0.9901 were obtained with a calibration curve in the range of 0.5-200 µg kg(-1). Total iAs was determined after reduction of As(V) to As(III) with sodium thiosulfate and potassium iodide, and As(V) was calculated by difference. The proposed extraction procedure was successfully applied for the determination of iAs ions in certified reference materials (NIST CRM 1568a and NMIJ CRM 7503a) and 10 rice samples produced in Iran and other Asian countries.

  7. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: influence of ethnicity and genetic polymorphisms.

    PubMed

    Fu, Songbo; Wu, Jie; Li, Yuanyuan; Liu, Yan; Gao, Yanhui; Yao, Feifei; Qiu, Chuanying; Song, Li; Wu, Yu; Liao, Yongjian; Sun, Dianjun

    2014-01-01

    To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969μg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too.

  8. 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.

  9. Systematic review of differential inorganic arsenic exposure in minority, low-income, and indigenous populations in the United States

    EPA Science Inventory

    Inorganic arsenic (iAs) is carcinogenic in humans and also associated with cardiovascular, respiratory, and skin diseases. Natural and anthropogenic sources contribute to low concentrations of iAs in water, food, soil, and air. Minority and low income populations are often at hig...

  10. Inorganic arsenic in starchy roots, tubers, and plantain and assessment of cancer risk of sub-Saharan African populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Starchy roots, tubers, and plantain (RTP) are the staple food in sub-Saharan Africa, and also important energy sources in Asia, Europe, and America. In this work, inorganic arsenic (iAs) in these crops was quantified by hydride generation-atomic fluorescence spectrometry (HG-AFS) after solid phase e...

  11. TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

    EPA Science Inventory

    TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.

    The relationship o...

  12. Arbuscular mycorrhizal fungi reduced the ratios of inorganic/organic arsenic in rice grains.

    PubMed

    Li, H; Chen, X W; Wong, M H

    2016-02-01

    Arbuscular mycorrhizal fungi (AMF) - Rhizophagus intraradices was inoculated to rice to investigate its effects on arsenic (As) uptake, grain As speciation, and rhizospheric As concentration of six rice cultivars grown in As-amended soil (60 mg As kg(-1) soil). The AMF inoculation induced either positive, neutral or negative responses in rice grown in As contaminated soil, suggesting that functional diversity may exist in AMF symbiosis when As is taken up and transferred. The ratios of inorganic/organic As concentrations in rice grains of all cultivars were significantly reduced by AMF, that involved the transformation of inorganic As into less toxic organic form dimethylarsinic acid (DMA) in rice. AMF decreased significantly total As and inorganic As concentrations in rice grains of Handao 3. Positive correlations (R(2) = 0.30-0.56, P < 0.05) between As in the rhizospheric soil solution and As in rice grain at different periods were observed. This inferred that the As survey of soil solution can be an effective measure for evaluating As in grains.

  13. Arbuscular mycorrhizal fungi reduced the ratios of inorganic/organic arsenic in rice grains.

    PubMed

    Li, H; Chen, X W; Wong, M H

    2016-02-01

    Arbuscular mycorrhizal fungi (AMF) - Rhizophagus intraradices was inoculated to rice to investigate its effects on arsenic (As) uptake, grain As speciation, and rhizospheric As concentration of six rice cultivars grown in As-amended soil (60 mg As kg(-1) soil). The AMF inoculation induced either positive, neutral or negative responses in rice grown in As contaminated soil, suggesting that functional diversity may exist in AMF symbiosis when As is taken up and transferred. The ratios of inorganic/organic As concentrations in rice grains of all cultivars were significantly reduced by AMF, that involved the transformation of inorganic As into less toxic organic form dimethylarsinic acid (DMA) in rice. AMF decreased significantly total As and inorganic As concentrations in rice grains of Handao 3. Positive correlations (R(2) = 0.30-0.56, P < 0.05) between As in the rhizospheric soil solution and As in rice grain at different periods were observed. This inferred that the As survey of soil solution can be an effective measure for evaluating As in grains. PMID:26688259

  14. Identification of low inorganic and total grain arsenic rice cultivars from Bangladesh.

    PubMed

    Norton, Gareth J; Islam, M Rafiqul; Deacon, Claire M; Zhao, Fang-Jie; Stroud, Jacqueline L; McGrath, Steve P; Islam, Shofiqul; Jahiruddin, M; Feldmann, Joerg; Price, Adam H; Meharg, Andrew A

    2009-08-01

    For the world's population, rice consumption is a major source of inorganic arsenic (As), a nonthreshold class 1 carcinogen. Reducing the amount of total and inorganic As within the rice grain would reduce the exposure risk. In this study, grain As was measured in 76 cultivars consisting of Bangladeshi landraces, improved Bangladesh Rice Research Institute (BRRI) cultivars, and parents of permanent mapping populations grown in two field sites in Bangladesh, Faridpur and Sonargaon, irrigated with As-contaminated tubewell water. Grain As ranged from 0.16 to 0.74 mg kg(-1) at Faridpur and from 0.07 to 0.28 mg kg(-1) at Sonargaon. Highly significant cultivar differences were detected and a significant correlation (r = 0.802) in the grain As between the two field sites was observed, indicating stable genetic differences in As accumulation. The cultivars with the highest concentration of grain As were the Bangladeshi landraces. Landraces with red bran had significantly more grain As than the cultivars with brown bran. The percent of inorganic As decreased linearly with increasing total As, but genetic variation within this trend was identified. A number of local cultivars with low grain As were identified. Some tropical japonica cultivars with low grain As have the potential to be used in breeding programs and genetic studies aiming to identify genes which decrease grain As. PMID:19731720

  15. Determination of inorganic arsenic species by flow injection hydride generation atomic absorption spectrometry with variable sodium tetrahydroborate concentrations*1

    NASA Astrophysics Data System (ADS)

    Sigrist, Mirna E.; Beldoménico, Horacio R.

    2004-07-01

    This work describes a study on the determination of inorganic arsenic species in ground water and synthetic experimental matrices, using a flow injection system with on-line hydride generation device coupled to an atomic absorption spectrometer with flame-heated quartz atomizer (FI HG AAS). Specific trivalent arsenic determination is based on the slow kinetics of As(V) on the hydride generation reaction using sufficiently low concentrations of sodium tetrahydroborate (NaBH 4) as reductant in highly acidic conditions (pH<0). Under these conditions, the efficiency of hydride generation from As(V) is much lower than that from As(III). The pentavalent form is determined by the difference between total inorganic arsenic and As(III). As(V) interferences were studied using As(III) solutions ranging from 0% to 50% of total inorganic As. The optimized NaBH 4 concentration was 0.035% (w/v). The detection limit was 1.4 μg l -1 As(III). As(V) interferences were 6% in the case of water samples with 6 μg l -1 As(III) in the presence of 54 μg l -1 As(V) (i.e. 10% As(III)). Interferences of methylated arsenic species (MMA and DMA) were evaluated. Speciation method was satisfactorily applied to 20 field arsenical water samples from Santa Fe, Argentina, with values ranging from 30 to 308 μg l -1 total As. We found from 0% to 36% As(III) in the 20 field samples. The developed methodology constitutes an economic, simple and reliable way to evaluate inorganic arsenic distribution in underground waters or similar systems with negligible or no content of organoarsenicals.

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

    PubMed

    Person, Rachel J; Ngalame, Ntube N Olive; 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.

  17. Electrochemical measurement and speciation of inorganic arsenic in groundwater of Bangladesh.

    PubMed

    Rasul, S B; Munir, A K M; Hossain, Z A; Khan, A H; Alauddin, M; Hussam, A

    2002-08-16

    The presence of arsenic in groundwater above the maximum permissible limit of 50 mug l(-1) has threatened the health of more than 50 million people in Bangladesh and neighboring India. We report here the development of an inexpensive anodic stripping voltammetric (ASV) technique for routine measurement and speciation of arsenic in groundwater. The measurements are validated by more expensive atomic absorption, atomic emission and other techniques. To understand the present situation in Bangladesh, we measured As(III) in 960 water samples collected from 18 districts. A random distribution of 238 samples was used to measure both As(III) and As(V). The results from the present study indicate that most toxic form of inorganic arsenic, As(III), has the broad range of 30-98%. It shows 60% of the samples have 10 mug l(-1) and 44% of the samples have 50 mug l(-1) or more As(III). The fractional distribution pattern shows significant skew towards high percent occurrence which may indicate a progressive reduction process with a single source or a single mechanism for the formation of As(III). For direct consumption, this is possibly one of the most toxic groundwater known today. Speciation distribution at groundwater pH value shows H(3)AsO(3) is the predominant species including H(2)AsO(4)(-) and H(2)AsO(4)(2-) whose distribution is significantly pH dependent. This is also supported by E(h)-pH measurements. The depth distribution for Kushtia shows most of the As(III) is located within 100-200 ft deep aquifers. Similar fractional distribution of As(III) is found in deeper aquifers and may indicate contamination by leakage from upper aquifer. This study clearly demonstrates the aquifer environment is reductive and conducive to the formation of As(III) species.

  18. A comprehensive evaluation of inorganic arsenic in food and considerations for dietary intake analyses.

    PubMed

    Lynch, Heather N; Greenberg, Grace I; Pollock, Margaret C; Lewis, Ari S

    2014-10-15

    Arsenic (As) can exist in the environment in several different forms, each having unique chemical characteristics that influence its toxicity and potential for human and ecological exposure. Within the last decade or so, the focus on speciated As (both the inorganic and organic forms) and its potential toxicity has led to an increased availability of data on speciated As in different food types. To gain an understanding of these developments and the current science, we evaluated the state of knowledge regarding As speciation in food and calculated the average levels of several species of As measured in food. Because inorganic arsenic (inAs) is considered the most toxicologically important form of As, we focused our analysis on papers presenting information on total inAs and speciated inAs (inAs(3+) or inAs(5+)). We also evaluated speciated As forms (e.g., monomethylarsonic and dimethylarsinic acid) when presented with inAs information. Publications were drawn from the peer-reviewed literature and reports by authoritative health agencies. While a great deal of speciation data were identified, including over 6500 unique inAs data points, unclear study methodology and inconsistencies between studies introduced uncertainty into the analysis of these data. Despite these limitations, our analysis demonstrates that inAs in foods can vary widely by type and even by sample, with mean inAs concentrations ranging from undetectable (in milk) to 11,000 μg/kg (in seaweed/algae). We found a high percentage of non-measurable As in many food types, suggesting that the limits of detection of speciated As must be considered to accurately estimate dietary As exposure. The applicability of our analysis is limited by the inconsistencies and uncertainties in the available data; calculations of inAs dietary intake should be tailored to the study population of interest and should consider study quality.

  19. In vitro study of transporters involved in intestinal absorption of inorganic arsenic.

    PubMed

    Calatayud, Marta; Barrios, Julio A; Vélez, Dinoraz; Devesa, Vicenta

    2012-02-20

    Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs.

  20. Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood.

    PubMed

    Ullah, Naseem; Khan, Muhammad Farid; Jan, Syed Umer; Mukhtiar, Muhammad; Khan, Haroon; Rehman, Asim-ur

    2015-03-01

    Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity.

  1. Study of the effect of inorganic and organic complexes of arsenic metal on the status of GSH in T. cells and B. cells of blood.

    PubMed

    Ullah, Naseem; Khan, Muhammad Farid; Jan, Syed Umer; Mukhtiar, Muhammad; Khan, Haroon; Rehman, Asim-ur

    2015-03-01

    Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione (GSH), a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide (ATO) and organic arsenic in the form of nitro benzene arsenic acid (NBA). Lymphocytes (T.cells and B.cells) were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct (As-(SG)3) formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity. PMID:25730780

  2. Blood Pressure, Left Ventricular Geometry, and Systolic Function in Children Exposed to Inorganic Arsenic

    PubMed Central

    Osorio-Yáñez, Citlalli; Ayllon-Vergara, Julio C.; Arreola-Mendoza, Laura; Aguilar-Madrid, Guadalupe; Hernández-Castellanos, Erika; Sánchez-Peña, Luz C.

    2015-01-01

    Background: Inorganic arsenic (iAs) is a ubiquitous element present in the groundwater worldwide. Cardiovascular effects related to iAs exposure have been studied extensively in adult populations. Few epidemiological studies have been focused on iAs exposure–related cardiovascular disease in children. Objective: In this study we investigated the association between iAs exposure, blood pressure (BP), and functional and anatomical echocardiographic parameters in children. Methods: A cross-sectional study of 161 children between 3 and 8 years was conducted in Central Mexico. The total concentration of arsenic (As) species in urine (U-tAs) was determined by hydride generation–cryotrapping–atomic absorption spectrometry and lifetime iAs exposure was estimated by multiplying As concentrations measured in drinking water by the duration of water consumption in years (LAsE). BP was measured by standard protocols, and M-mode echocardiographic parameters were determined by ultrasonography. Results: U-tAs concentration and LAsE were significantly associated with diastolic (DBP) and systolic blood pressure (SBP) in multivariable linear regression models: DBP and SBP were 0.013 (95% CI: 0.002, 0.024) and 0.021 (95% CI: 0.004, 0.037) mmHg higher in association with each 1-ng/mL increase in U-tAs (p < 0.025), respectively. Left ventricular mass (LVM) was significantly associated with LAsE [5.5 g higher (95% CI: 0.65, 10.26) in children with LAsE > 620 compared with < 382 μg/L-year; p = 0.03] in an adjusted multivariable model. The systolic function parameters left ventricular ejection fraction (EF) and shortening fraction were 3.67% (95% CI: –7.14, –0.20) and 3.41% (95% CI: –6.44, –0.37) lower, respectively, in children with U-tAs > 70 ng/mL compared with < 35 ng/mL. Conclusion: Early-life exposure to iAs was significantly associated with higher BP and LVM and with lower EF in our study population of Mexican children. Citation: Osorio-Yáñez C, Ayllon-Vergara JC

  3. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    SciTech Connect

    Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie; Fardel, Olivier; Vernhet, Laurent

    2012-08-01

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

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

    PubMed Central

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

    2009-01-01

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

  5. Inorganic arsenic causes cell apoptosis in mouse cerebrum through an oxidative stress-regulated signaling pathway.

    PubMed

    Yen, Cheng Chien; Ho, Tsung Jung; Wu, Chin Ching; Chang, Chun Fang; Su, Chin Chuan; Chen, Ya Wen; Jinn, Tzyy Rong; Lu, Tien Hui; Cheng, Po Wen; Su, Yi Chang; Liu, Shing Hwa; Huang, Chun Fa

    2011-06-01

    Arsenic pollution is a major public health problem worldwide. Inorganic arsenic (iAs) is usually more harmful than organic ones. iAs pollution increases the risk of human diseases such as peripheral vascular disease and cancer. However, the toxicological effects of iAs in the brain are mostly unclear. Here, we investigated the toxic effects and possible mechanisms of iAs in the cerebrum of mice after exposure to iAs (0.5 and 5 ppm (mg/l) As(2)O(3), via the drinking water), which was the possible human exposed dose via the ingestion in iAs-contaminated areas, for 6 consecutive weeks. iAs dose-dependently caused an increase of LPO production in the plasma and cerebral cortex. iAs also decreased the reduced glutathione levels and the expressions of NQO1 and GPx mRNA in the cerebral cortex. These impairments in the cerebral cortex caused by iAs exposure were significantly correlated with the accumulation of As. Moreover, iAs induced the production of apoptotic cells and activation of caspase-3, up-regulation of Bax and Bak, and down-regulation of Mcl-1 in the cerebral cortex. Exposure to iAs also triggered the expression of ER stress-related genes, including GRP78, GRP94, and CHOP. Meanwhile, an increase of p38 activation and dephosphorylation of ERK1/2 were shown in the cerebral cortex as a result of iAs-exposed mice. These iAs-induced damages and apoptosis-related signals could be significantly reversed by NAC. Taken together, these results suggest that iAs-induced oxidative stress causes cellular apoptosis in the cerebrum, signaling of p38 and ERK1/2, and ER stress may be involved in iAs-induced cerebral toxicity.

  6. [Distribution, seasonal variation and influence factors of dissolved inorganic arsenic in the Sanggou Bay].

    PubMed

    Li, Lei; Ren, Jing-Ling; Liu, Su-Mei; Jiang, Zeng-Jie; Du, Jin-Zhou; Fang, Jian-Guang

    2014-07-01

    The biogeochemical behavior of arsenic in the aquatic environment has already captured the attentions of scientists due to its complex forms and toxicity. Four cruises were carried out in April, August, October 2011 and January 2012 in the Sanggou Bay. The concentrations of total dissolved inorganic arsenic (TDIAs, TDIAs = [ As(5+] + [As(3+)]) and arsenite (As(3+)) were measured by Hydride Generation-Atomic Fluorescence Spectrometry (HG-AFS). The concentrations of TDIAs ranged from 3.4-12.4 nmol x L(-1) in April, 8.9-16.9 nmol x L(-1) in August, 14.7-21.3 nmol x L(-1) in October and 13.8-21.9 nmol x L(-1) in January. The concentrations of arsenite ranged from 0.3-2.1 nmol x L(-1), 0.4-3.8 nmol x L(-1), 1.8-4.0 nmol x L(-1) and 0.3-2.9 nmol x L(-1) during four cruises, respectively. The concentrations of TDIAs in spring and summer were lower than those in autumn and winter, and high values of TDIAs appeared in the bay-mouth and the coastal estuary. The concentrations of arsenite in spring and winter were lower than those in summer and autumn. The maximum As(3+)/TDIAs ratios appeared in summer. The mean value of TDIAs in the Sanggou Bay was (13.9 +/- 4.7) nmol x L(-1), which was lower than the national primary drinking in water Standards from USEPA and met the first grade water quality based on the environmental quality standards for surface water of China. It indicates that there is no obvious anthropogenic pollution. The concentrations of TDIAs in the Sanggou Bay were lower than those in the Ailian Bay and the Lidao Bay in spring and summer due to the different hydrological environments and terrestrial inputs. Riverine input, incursion of Yellow Sea and biological activities were the three main factors impacting the distribution of TDIAs in the Sanggou Bay, and the influence of aquaculture activities was particularly significant. The enrichment of arsenic by aquaculture may lead to potential ecological crisis and food safety problems, and need to be paid more

  7. [Distribution, seasonal variation and influence factors of dissolved inorganic arsenic in the Sanggou Bay].

    PubMed

    Li, Lei; Ren, Jing-Ling; Liu, Su-Mei; Jiang, Zeng-Jie; Du, Jin-Zhou; Fang, Jian-Guang

    2014-07-01

    The biogeochemical behavior of arsenic in the aquatic environment has already captured the attentions of scientists due to its complex forms and toxicity. Four cruises were carried out in April, August, October 2011 and January 2012 in the Sanggou Bay. The concentrations of total dissolved inorganic arsenic (TDIAs, TDIAs = [ As(5+] + [As(3+)]) and arsenite (As(3+)) were measured by Hydride Generation-Atomic Fluorescence Spectrometry (HG-AFS). The concentrations of TDIAs ranged from 3.4-12.4 nmol x L(-1) in April, 8.9-16.9 nmol x L(-1) in August, 14.7-21.3 nmol x L(-1) in October and 13.8-21.9 nmol x L(-1) in January. The concentrations of arsenite ranged from 0.3-2.1 nmol x L(-1), 0.4-3.8 nmol x L(-1), 1.8-4.0 nmol x L(-1) and 0.3-2.9 nmol x L(-1) during four cruises, respectively. The concentrations of TDIAs in spring and summer were lower than those in autumn and winter, and high values of TDIAs appeared in the bay-mouth and the coastal estuary. The concentrations of arsenite in spring and winter were lower than those in summer and autumn. The maximum As(3+)/TDIAs ratios appeared in summer. The mean value of TDIAs in the Sanggou Bay was (13.9 +/- 4.7) nmol x L(-1), which was lower than the national primary drinking in water Standards from USEPA and met the first grade water quality based on the environmental quality standards for surface water of China. It indicates that there is no obvious anthropogenic pollution. The concentrations of TDIAs in the Sanggou Bay were lower than those in the Ailian Bay and the Lidao Bay in spring and summer due to the different hydrological environments and terrestrial inputs. Riverine input, incursion of Yellow Sea and biological activities were the three main factors impacting the distribution of TDIAs in the Sanggou Bay, and the influence of aquaculture activities was particularly significant. The enrichment of arsenic by aquaculture may lead to potential ecological crisis and food safety problems, and need to be paid more

  8. Urinary arsenic metabolism in a Western Chinese population exposed to high-dose inorganic arsenic in drinking water: Influence of ethnicity and genetic polymorphisms

    SciTech Connect

    Fu, Songbo; Wu, Jie; Li, Yuanyuan; Liu, Yan; Gao, Yanhui; Yao, Feifei; Qiu, Chuanying; Song, Li; Wu, Yu; Liao, Yongjian; Sun, Dianjun

    2014-01-01

    To investigate the differences in urinary arsenic metabolism patterns of individuals exposed to a high concentration of inorganic arsenic (iAs) in drinking water, an epidemiological investigation was conducted with 155 individuals living in a village where the arsenic concentration in the drinking water was 969 μg/L. Blood and urine samples were collected from 66 individuals including 51 cases with skin lesions and 15 controls without skin lesions. The results showed that monomethylated arsenic (MMA), the percentage of MMA (%MMA) and the ratio of MMA to iAs (MMA/iAs) were significantly increased in patients with skin lesions as compared to controls, while dimethylated arsenic (DMA), the percentage of DMA (%DMA) and the ratio of DMA to MMA (DMA/MMA) were significantly reduced. The percent DMA of individuals with the Ala/Asp genotype of glutathione S-transferase omega 1 (GSTO1) was significantly lower than those with Ala/Ala. The percent MMA of individuals with the A2B/A2B genotype of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) was significantly lower than those with AB/A2B. The iAs and total arsenic (tAs) content in the urine of a Tibetan population were significantly higher than that of Han and Hui ethnicities, whereas MMA/iAs was significantly lower than that of Han and Hui ethnicities. Our results showed that when exposed to the same arsenic environment, different individuals exhibited different urinary arsenic metabolism patterns. Gender and ethnicity affect these differences and above polymorphisms may be effectors too. - Highlights: • We first survey a village with high iAs content in the drinking water (969 μg/L). • 90 villagers suffered typical skin lesions with a morbidity rate of 58%. • Cases exhibited higher %MMA and MMA/iAs, and lower %DMA and DMA/MMA than controls. • Gender and ethnicity affect the differences of iAs methylation metabolism levels. • GSTO1 and AS3MT gene polymorphisms may be factors too.

  9. 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 ...

  10. Blood pressure hyperreactivity: an early cardiovascular risk in normotensive men exposed to low-to-moderate inorganic arsenic in drinking water

    PubMed Central

    Kunrath, Julie; Gurzau, Eugen; Gurzau, Anca; Goessler, Walter; Gelmann, Elyssa R.; Thach, Thu-Trang; Mccarty, Kathleen M.; Yeckel, Catherine W.

    2012-01-01

    Essential hypertension is associated with chronic exposure to high levels of inorganic arsenic in drinking water. However, early signs of risk for developing hypertension remain unclear in people exposed to chronic low-to-moderate inorganic arsenic. Objective We evaluated cardiovascular stress reactivity and recovery in healthy, normotensive, middle-aged men living in an arsenic-endemic region of Romania. Methods Unexposed (n=16) and exposed (n=19) participants were sampled from communities based on WHO limits for inorganic arsenic in drinking water (<10 μg/l). Water sources and urine samples were collected and analyzed for inorganic arsenic and its metabolites. Functional evaluation of blood pressure included clinical, anticipatory, cold pressor test, and recovery measurements. Results Blood pressure hyperreactivity was defined as a combined stress-induced change in SBP (>20 mmHg) and DBP (>15 mmHg). Drinking water inorganic arsenic averaged 40.2±30.4 and 1.0±0.2 μg/l for the exposed and unexposed groups, respectively (P<0.001). Compared to the unexposed group, the exposed group expressed a greater probability of blood pressure hyperreactivity to both anticipatory stress (47.4 vs. 12.5%; P=0.035) and cold stress (73.7 vs. 37.5%; P=0.044). Moreover, the exposed group exhibited attenuated blood pressure recovery from stress and a greater probability of persistent hypertensive responses (47.4 vs. 12.5%; P=0.035). Conclusions Inorganic arsenic exposure increased stress-induced blood pressure hyperreactivity and poor blood pressure recovery, including persistent hypertensive responses in otherwise healthy, clinically normotensive men. Drinking water containing even low-to-moderate inorganic arsenic may act as a sympathetic nervous system trigger for hypertension risk. PMID:23203141

  11. Controlling the fate of roxarsone and inorganic arsenic in poultry litter.

    PubMed

    Makris, Konstantinos C; Salazar, Jason; Quazi, Shahida; Andra, Syam S; Sarkar, Dibyendu; Bach, Stephan B H; Datta, Rupali

    2008-01-01

    A growing body of literature reports 3-nitro-4-hydroxyphenylarsonic acid (roxarsone) degradation in poultry litter (PL) to the more toxic inorganic arsenic (As). Aluminum-based drinking-water treatment residuals (WTR) present a low-cost amendment technology to reduce As availability in PL, similar to the use of alum to reduce phosphorus availability. Batch experiments investigated the effectiveness of WTR in removing roxarsone and inorganic As species from PL aqueous suspensions. Incubation experiments with WTR-amended PL evaluated the effects of WTR application rates (2.5-15% by weight) and incubation time (up to 32 d) at two incubation temperatures (23 and 35 degrees C) on As availability in PL. Batch PL aqueous experiments showed the high affinity of As(V), As(III), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), and roxarsone for the WTR. The 10% WTR amendment rate decreased As availability in PL by half of that of the unamended (no WTR) PL-incubated samples. The reduction in dissolved As concentrations during incubation of WTR-amended PL samples was kinetically limited, being complete within 13 d. Parallel reductions in roxarsone, As(V), and DMA concentrations were observed with liquid chromatography-inductively coupled plasma mass spectrometry, whereas As(III) and MMA concentrations were always <5% of dissolved As. Incubation temperature did not significantly (p > 0.05) influence dissolved As concentrations in the WTR-amended PL. Potential formation of a copper-containing roxarsone metabolite was considered in PL aqueous suspensions with the aid of electrospray mass spectrometry. Further experiments in the field are necessary to ensure that sorbed As is stable in WTR-amended PL.

  12. A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water.

    PubMed

    Lamm, Steven H; Ferdosi, Hamid; Dissen, Elisabeth K; Li, Ji; Ahn, Jaeil

    2015-12-07

    High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100-150 µg/L arsenic.

  13. A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water

    PubMed Central

    Lamm, Steven H.; Ferdosi, Hamid; Dissen, Elisabeth K.; Li, Ji; Ahn, Jaeil

    2015-01-01

    High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1–1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100–150 µg/L arsenic. PMID:26690190

  14. Simultaneously removal of inorganic arsenic species from stored rainwater in arsenic endemic area by leaves of Tecomella undulata: a multivariate study.

    PubMed

    Brahman, Kapil Dev; Kazi, Tasneem Gul; Afridi, Hassan Imran; Baig, Jameel Ahmed; Abro, Muhammad Ishaque; Arain, Sadaf Sadia; Ali, Jamshed; Khan, Sumaira

    2016-08-01

    In the present study, an indigenous biosorbent (leaves of Tecomella undulata) was used for the simultaneous removal of inorganic arsenic species (As(III) and As(V)) from the stored rainwater in Tharparkar, Pakistan. The Plackett-Burman experimental design was used as a multivariate strategy for the evaluation of the effects of six factors/variables on the biosorption of inorganic arsenic species, simultaneously. Central composite design (CCD) was used to found the optimum values of significant factors for the removal of As(III) and As(V). Initial concentrations of both inorganic As species, pH, biosorbent dose, and contact time were selected as independent factors in CCD, while the adsorption capacity (q e) was considered as a response function. The separation of inorganic As species in water samples before and after biosorption was carried out by cloud point and solid-phase extraction methods. Theoretical values of pH, concentration of analytes, biosorbent dose, and contact time were calculated by quadratic equation for 100 % biosorption of both inorganic As species in aqueous media. Experimental data were modeled by Langmuir and Freundlich isotherms. Thermodynamic and kinetic study indicated that the biosorption of As(III) and As(V) was followed by pseudo second order. It was concluded that the indigenous biosorbent material efficiently and simultaneously removed both As species in the range of 70.8 to 98.5 % of total contents in studied ground water samples. Graphical abstract Optimizing the significant varable by central 2(3) + star orthogonal composite design. PMID:27094273

  15. A luminescent-water soluble inorganic co-crystal for a selective pico-molar range arsenic(III) sensor in water medium.

    PubMed

    Dey, Biswajit; Saha, Rajat; Mukherjee, Priyanka

    2013-08-14

    The water solution of an intriguing luminescent 'Inorganic Co-crystal' of Cu(II) monomeric and dimeric units shows extremely selective sensing ability towards inorganic arsenic(III) in water medium in the pico-molar concentration range even in the presence of other cations.

  16. Urinary inorganic arsenic concentrations and semen quality of male partners of subfertile couples in Tokyo.

    PubMed

    Oguri, Tomoko; Yoshinaga, Jun; Toshima, Hiroki; Mizumoto, Yoshifumi; Hatakeyama, Shota; Tokuoka, Susumu

    2016-01-01

    Inorganic arsenic (iAs) has been known as a testicular toxicant in experimental rodents. Possible association between iAs exposure and semen quality (semen volume, sperm concentration, and sperm motility) was explored in male partners of couples (n = 42) who visited a gynecology clinic in Tokyo for infertility consultation. Semen parameters were measured according to WHO guideline at the clinic, and urinary iAs and methylarsonic acid (MMA), and dimethylarsinic acid concentrations were determined by liquid chromatography-hydride generation-ICP mass spectrometry. Biological attributes, dietary habits, and exposure levels to other chemicals with known effects on semen parameters were taken into consideration as covariates. Multiple regression analyses and logistic regression analyses did not find iAs exposure as significant contributor to semen parameters. Lower exposure level of subjects (estimated to be 0.5 μg kg(-1) day(-1)) was considered a reason of the absence of adverse effects on semen parameters, which were seen in rodents dosed with 4-7.5 mg kg(-1). PMID:26865228

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

    PubMed

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

    2015-12-23

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

  18. Fluxes of inorganic and organic arsenic species in a Norway spruce forest floor.

    PubMed

    Huang, Jen-How; Matzner, Egbert

    2007-09-01

    To identify the role of the forest floor in arsenic (As) biogeochemistry, concentrations and fluxes of inorganic and organic As in throughfall, litterfall and forest floor percolates at different layers were investigated. Nearly 40% of total As(total) input (5.3g Asha(-1)yr(-1)) was retained in Oi layer, whereas As(total) fluxes from Oe and Oa layers exceeded the input by far (10.8 and 20g Asha(-1)yr(-1), respectively). Except dimethylarsinic acid (DMA), fluxes of organic As decreased with depth of forest floor so that <10% of total deposition (all <0.3g Asha(-1)yr(-1)) reached the mineral soil. All forest floor layers are sinks for most organic As. Conversely, Oe and Oa layers are sources of As(total), arsenite, arsenate and DMA. Significant correlations (r>/=0.43) between fluxes of As(total), arsenite, arsenate or DMA and water indicate hydrological conditions and adsorption-desorption as factors influencing their release from the forest floor. The higher net release of arsenite from Oe and Oa and of DMA from Oa layer in the growing than dormant season also suggests microbial influences on the release of arsenite and DMA.

  19. 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.

  20. The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review.

    PubMed

    Carter, Dean E; Aposhian, H Vasken; Gandolfi, A Jay

    2003-12-15

    The aim of this review is to compare the metabolism, chemistry, and biological effects to determine if either of the industrial arsenicals (arsine and gallium arsenide) act like the environmental arsenic oxides (arsenite and arsenate). The metabolism of the arsenic oxides has been extensively investigated in the past 4 years and the differences between the arsenic metabolites in the oxidation states +III versus +V and with one or two methyl groups added have shown increased importance. The arsenic oxide metabolism has been compared with arsine (oxidation state -III) and arsenide (oxidation state between 0 to -III). The different metabolites appear to have different strengths of reaction for binding arsenic (III) to thiol groups, their oxidation-reduction reactions and their forming an arsenic-carbon bond. It is unclear if the differences in parameters such as the presence or absence of methyl metabolites, the rates of AsV reduction compared to the rates of AsIII oxidation, or the competition of phosphate and arsenate for cellular uptake are large enough to change biological effects. The arsine rate of decomposition, products of metabolism, target organ of toxic action, and protein binding appeared to support an oxidized arsenic metabolite. This arsine metabolite was very different from anything made by the arsenic oxides. The gallium arsenide had a lower solubility than any other arsenic compound and it had a disproportionate intensity of lung damage to suggest that the GaAs had a site of contact interaction and that oxidation reactions were important in its toxicity. The urinary metabolites after GaAs exposure were the same as excreted by arsenic oxides but the chemical compounds responsible for the toxic effects of GaAs are different from the arsenic oxides. The review concludes that there is insufficient evidence to equate the different arsenic compounds. There are several differences in the toxicity of the arsenic compounds that will require substantial

  1. The metabolism of inorganic arsenic oxides, gallium arsenide, and arsine: a toxicochemical review.

    PubMed

    Carter, Dean E; Aposhian, H Vasken; Gandolfi, A Jay

    2003-12-15

    The aim of this review is to compare the metabolism, chemistry, and biological effects to determine if either of the industrial arsenicals (arsine and gallium arsenide) act like the environmental arsenic oxides (arsenite and arsenate). The metabolism of the arsenic oxides has been extensively investigated in the past 4 years and the differences between the arsenic metabolites in the oxidation states +III versus +V and with one or two methyl groups added have shown increased importance. The arsenic oxide metabolism has been compared with arsine (oxidation state -III) and arsenide (oxidation state between 0 to -III). The different metabolites appear to have different strengths of reaction for binding arsenic (III) to thiol groups, their oxidation-reduction reactions and their forming an arsenic-carbon bond. It is unclear if the differences in parameters such as the presence or absence of methyl metabolites, the rates of AsV reduction compared to the rates of AsIII oxidation, or the competition of phosphate and arsenate for cellular uptake are large enough to change biological effects. The arsine rate of decomposition, products of metabolism, target organ of toxic action, and protein binding appeared to support an oxidized arsenic metabolite. This arsine metabolite was very different from anything made by the arsenic oxides. The gallium arsenide had a lower solubility than any other arsenic compound and it had a disproportionate intensity of lung damage to suggest that the GaAs had a site of contact interaction and that oxidation reactions were important in its toxicity. The urinary metabolites after GaAs exposure were the same as excreted by arsenic oxides but the chemical compounds responsible for the toxic effects of GaAs are different from the arsenic oxides. The review concludes that there is insufficient evidence to equate the different arsenic compounds. There are several differences in the toxicity of the arsenic compounds that will require substantial

  2. 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.

  3. 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

  4. A green sorbent of esterified egg-shell membrane for highly selective uptake of arsenate and speciation of inorganic arsenic.

    PubMed

    Chen, Ming-Li; Gu, Cui-Bo; Yang, Ting; Sun, Yan; Wang, Jian-Hua

    2013-11-15

    Egg-shell membrane (ESM) is a promising adsorbent for heavy metal uptake. However, carboxylic groups on ESM surface barrier arsenic adsorption. Herein, ESM is modified by esterification and the methyl esterified egg-shell membrane (MESM) possesses positive charge within pH 1-9. As a novel green sorbent material, MESM exhibits 200-fold improvement on sorption capacity of arsenate with respect to bare ESM. It presents an ultra-high selectivity of 256:1 toward arsenate against arsenite. At pH 6, 100% sorption efficiency is achieved for 2 μg L(-1) As(V) by 10 mg MESM, while virtually no adsorption of As(III) is observed. This provides great potential for selective sorption of arsenate in the presence of arsenite. By loading 4.0 mL sample within 0.05-5.00 μg L(-1) As(V) followed by elution with 300 μL HCl (1.5 mol L(-1)), a detection limit of 15 ng L(-1) is obtained along with a RSD of 3.5% at 0.5 μg L(-1). Total inorganic arsenic is achieved by converting As(III) to As(V) and following the same sorption process. This procedure is applied for arsenate determination and inorganic arsenic speciation in Hijiki and water samples. The results are confirmed by graphite furnace atomic absorption spectrometry and spiking recovery.

  5. Dynamics of organic and inorganic arsenic in the solution phase of an acidic fen in Germany

    NASA Astrophysics Data System (ADS)

    Huang, J.-H.; Matzner, E.

    2006-04-01

    Wetland soils play a key role for the transformation of heavy metals in forested watersheds, influencing their mobility, and ecotoxicity. Our goal was to investigate the mechanisms of release from solid to solution phase, the mobility, and the transformation of arsenic species in a fen soil. In methanol-water extracts, monomethylarsonic acid, dimethylarsinic acid, trimethylarsine oxide, arsenobetaine, and two unknown organic arsenic species were found with concentrations up to 14 ng As g -1 at the surface horizon. Arsenate is the dominant species at the 0-30 cm depth, whereas arsenite predominated at the 30-70 cm depth. Only up to 2.2% of total arsenic in fen was extractable with methanol-water. In porewaters, depth gradient spatial variation of arsenic species, pH, redox potentials, and the other chemical parameters along the profile was observed in June together with high proportion of organic arsenic species (up to 1.2 μg As L -1, 70% of total arsenic). Tetramethylarsonium ion and an unknown organic arsenic species were additionally detected in porewaters at deeper horizons. In comparison, the arsenic speciation in porewaters in April was homogeneous with depth and no organic arsenic species were found. Thus, the occurrence of microbial methylation of arsenic in fen was demonstrated for the first time. The 10 times elevated total arsenic concentrations in porewaters in June compared to April were accompanied by elevated concentrations of total iron, lower concentrations of sulfate and the presence of ammonium and phosphate. The low proportion of methanol-water extractable total arsenic suggests a generally low mobility of arsenic in fen soils. The release of arsenic from solid to solution phases in fen is dominantly controlled by dissolution of iron oxides, redox transformation, and methylation of arsenic, driven by microbial activity in the growing season. As a result, increased concentrations of total arsenic and potentially toxic arsenic species in fen

  6. Monomethylarsonous acid, but not inorganic arsenic, is a mitochondria-specific toxicant in vascular smooth muscle cells.

    PubMed

    Pace, Clare; Banerjee, Tania Das; Welch, Barrett; Khalili, Roxana; Dagda, Ruben K; Angermann, Jeff

    2016-09-01

    Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III). Exposure of VSMCs to MMA(III), but not iAs(III), significantly decreased basal and maximal oxygen consumption rates and concomitantly increased compensatory extracellular acidification rates, a proxy for glycolysis. Treatment with MMA(III) significantly increased hydrogen peroxide and superoxide levels compared to iAs(III). Exposure to MMA(III) resulted in significant decreases in mitochondrial ATP, aberrant perinuclear clustering of mitochondria, and decreased mitochondrial content. Mechanistically, we observed that mitochondrial superoxide and hydrogen peroxide contribute to mitochondrial toxicity, as treatment of cells with MnTBAP (a mitochondrial superoxide dismutase mimetic) and catalase significantly reduced mitochondrial respiration deficits and cell death induced by both arsenic compounds. Overall, our data demonstrates that MMA(III) is a mitochondria-specific toxicant that elevates mitochondrial and non-mitochondrial sources of ROS.

  7. Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan.

    PubMed

    Chiou, H Y; Hsueh, Y M; Liaw, K F; Horng, S F; Chiang, M H; Pu, Y S; Lin, J S; Huang, C H; Chen, C J

    1995-03-15

    In order to elucidate the dose-response relationship between ingested inorganic arsenic and internal cancers, a total of 263 patients with blackfoot disease and 2293 healthy residents in the endemic area of arseniasis were recruited and followed up for 7 years. The information on consumption of high-arsenic artesian well water, sociodemographic characteristics, life-style and dietary habits, and personal and family history of cancers was obtained through standardized interviews. The occurrence of internal cancers among study subjects was determined through annual health examinations, home visit personal interviews, household registration data checks, and national death certification and cancer registry profile linkages. A dose-response relationship was observed between the long-term arsenic exposure from drinking artesian well water and the incidence of lung cancer, bladder cancer, and cancers of all sites combined after adjustment for age, sex, and cigarette smoking through Cox's proportional hazards regression analysis. Blackfoot disease patients had a significantly increased cancer incidence after adjustment for cumulative arsenic exposure.

  8. ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE METHYLATION OF ARSENICALS

    EPA Science Inventory

    Metabolic conversion of inorganic arsenic into methylated products is a multistep process that yields mono, di, and trimethylated arsenicals. In recent years, it has become apparent that formation of methylated metabolites of inorganic arsenic is not necessarily a detoxification...

  9. Rethinking Rice Preparation for Highly Efficient Removal of Inorganic Arsenic Using Percolating Cooking Water.

    PubMed

    Carey, Manus; Jiujin, Xiao; Gomes Farias, Júlia; Meharg, Andrew A

    2015-01-01

    A novel way of cooking rice to maximize the removal of the carcinogen inorganic arsenic (Asi) is presented here. In conventional rice cooking water and grain are in continuous contact, and it is known that the larger the water:rice cooking ratio, the more Asi removed by cooking, suggesting that the Asi in the grain is mobile in water. Experiments were designed where rice is cooked in a continual stream of percolating near boiling water, either low in Asi, or Asi free. This has the advantage of not only exposing grain to large volumes of cooking water, but also physically removes any Asi leached from the grain into the water receiving vessel. The relationship between cooking water volume and Asi removal in conventional rice cooking was demonstrated for the rice types under study. At a water-to-rice cooking ratio of 12:1, 57±5% of Asi could be removed, average of 6 wholegrain and 6 polished rice samples. Two types of percolating technology were tested, one where the cooking water was recycled through condensing boiling water steam and passing the freshly distilled hot water through the grain in a laboratory setting, and one where tap water was used to cook the rice held in an off-the-shelf coffee percolator in a domestic setting. Both approaches proved highly effective in removing Asi from the cooking rice, with up to 85% of Asi removed from individual rice types. For the recycled water experiment 59±8% and 69±10% of Asi was removed, on average, compared to uncooked rice for polished (n=27) and wholegrain (n=13) rice, respectively. For coffee percolation there was no difference between wholegrain and polished rice, and the effectiveness of Asi removal was 49±7% across 6 wholegrain and 6 polished rice samples. The manuscript explores the potential applications and further optimization of this percolating cooking water, high Asi removal, discovery. PMID:26200355

  10. Rethinking Rice Preparation for Highly Efficient Removal of Inorganic Arsenic Using Percolating Cooking Water

    PubMed Central

    Carey, Manus; Jiujin, Xiao; Gomes Farias, Júlia; Meharg, Andrew A.

    2015-01-01

    A novel way of cooking rice to maximize the removal of the carcinogen inorganic arsenic (Asi) is presented here. In conventional rice cooking water and grain are in continuous contact, and it is known that the larger the water:rice cooking ratio, the more Asi removed by cooking, suggesting that the Asi in the grain is mobile in water. Experiments were designed where rice is cooked in a continual stream of percolating near boiling water, either low in Asi, or Asi free. This has the advantage of not only exposing grain to large volumes of cooking water, but also physically removes any Asi leached from the grain into the water receiving vessel. The relationship between cooking water volume and Asi removal in conventional rice cooking was demonstrated for the rice types under study. At a water-to-rice cooking ratio of 12:1, 57±5% of Asi could be removed, average of 6 wholegrain and 6 polished rice samples. Two types of percolating technology were tested, one where the cooking water was recycled through condensing boiling water steam and passing the freshly distilled hot water through the grain in a laboratory setting, and one where tap water was used to cook the rice held in an off-the-shelf coffee percolator in a domestic setting. Both approaches proved highly effective in removing Asi from the cooking rice, with up to 85% of Asi removed from individual rice types. For the recycled water experiment 59±8% and 69±10% of Asi was removed, on average, compared to uncooked rice for polished (n=27) and wholegrain (n=13) rice, respectively. For coffee percolation there was no difference between wholegrain and polished rice, and the effectiveness of Asi removal was 49±7% across 6 wholegrain and 6 polished rice samples. The manuscript explores the potential applications and further optimization of this percolating cooking water, high Asi removal, discovery. PMID:26200355

  11. Biotransformation and detoxification of inorganic arsenic in a marine juvenile fish Terapon jarbua after waterborne and dietborne exposure.

    PubMed

    Zhang, Wei; Huang, Liangmin; Wang, Wen-Xiong

    2012-06-30

    Arsenic (As) is a major hazardous metalloid in many aquatic environments. This study quantified the biotransformation of two inorganic As species [As(III) and As(V)] in a marine juvenile grunt Terapon jarbua following waterborne and dietborne exposures for 10d. The fish were fed As contaminated artificial diets at nominal concentrations of 50, 150, and 500μg As(III) and As(V)/g (dry weight), and their transformation and growth responses were compared to those exposed to 100μg/L waterborne As(III) and As(V). Within the 10d exposure period, waterborne and dietborne inorganic As exposure had no significant effect on the fish growth performance. The bioaccumulation of As was very low and not proportional to the inorganic As exposure concentration. We demonstrated that both inorganic As(III) and As(V) in the dietborne and waterborne phases were rapidly biotransformed to the less toxic arsenobetaine (AsB, 89-97%). After exposure to inorganic As, T. jarbua developed correspondingly detoxified strategies, such as the reduction of As(V) to As(III) followed by methylation to less toxic organic forms, as well as the synthesis of metal-binding proteins such as metallothionein-like proteins. This study elucidated that As(III) and As(V) had little potential toxicity on marine fish.

  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. THE CELLUAR METABOLISM OF ARSENIC

    EPA Science Inventory

    Because the methylation of arsenic produces intermediates and terminal products that exceed inorganic arsenic in potency as enzyme inhibitors, cytotoxins, and genotoxins, the methylation of arsenic is properly regarded as an activation process. The methylation of arsenic is an e...

  14. Evaluation of a novel hybrid inorganic/organic polymer type material in the arsenic removal process from drinking water.

    PubMed

    Iesan, Carmen M; Capat, Constantin; Ruta, Florin; Udrea, Ion

    2008-10-01

    The objective of this paper is the evaluation of a hybrid inorganic/organic polymer type material based on hydrated ferric oxide (HFO), in the adsorption process of arsenic oxyanions from contaminated waters used as drinking water. The study includes rapid small-scale column tests conducted in continuous flow operation in order to assess the arsenic removal capacity in various conditions. Thus it was evaluated the influence of some competing ions like silicate and phosphate on As(V) adsorption and the influence of feed water pH in the removal process of As(V) and As(III) species. Based on the As/pH variation in time at different feed water pH (5, 7 and 9), a possible sorption mechanism that fits the experimental data was suggested. The regeneration and re-use of the hybrid adsorbent was studied in the presence and in the absence of the contaminant ions. The novel hybrid material is very selective towards arsenic oxyanions even though the presence of silica and phosphate reduces the adsorption capacity.

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

    PubMed

    Gelmann, Elyssa R; Gurzau, Eugen; Gurzau, Anca; Goessler, Walter; Kunrath, Julie; Yeckel, Catherine W; McCarty, Kathleen M

    2013-11-01

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

  16. Speciation of inorganic arsenic in coastal seawater from Ionian and Tyrrhenian seas (Sicily, Italy) using derivative anodic stripping chronopotentiometry.

    PubMed

    La Pera, Lara; Di Bella, Giuseppa; Rando, Rossana; Vincenzo, Lo Turco; Dugo, Giacomo

    2008-10-01

    The purpose of this paper was to use derivative anodic stripping chronopotentiometry (dASCP) as a sensitive and accurate technique, to determine the concentrations of dissolved As (III) and As (V) in coastal seawater samples from the Straits of Messina, the Ionian and the Tyrrhenian seas, and to investigate the relationship between the anthropogenic activities on the coastal areas and the concentration of dissolved inorganic arsenic in seawaters. The obtained data indicated that As (V) was the most abundant species, with concentration ranging from 26.7 to 307 nM, whereas As (III) levels were lower than 48 nM in all the samples. In particular, As (III) and As (V) levels significantly decreased from high to low anthropogenic activities zones (p < 0.00001, ANOVA), with the reference samples, from a wildlife reserve, showing the lowest values. Furthermore it was observed that human activities influenced inorganic arsenic speciation, since the zones that received high human input presented the highest As(V)/As (III) ratio.

  17. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    The biotransformation of inorganic arsenic (iAs) involves methylation by an arsenic (+3 oxidation state) methyltransferase (AS3MT), yielding methyl arsenic (MA), dimethyl arsenic (DMA), and trimethylarsenic (TMA). To identify molecular mechanisms that coordinate arsenic biotra...

  18. Multiple transformation pathways of p-arsanilic acid to inorganic arsenic species in water during UV disinfection.

    PubMed

    Li, Suqi; Xu, Jing; Chen, Wei; Yu, Yingtan; Liu, Zizheng; Li, Jinjun; Wu, Feng

    2016-09-01

    p-Arsanilic acid (p-ASA) is widely used in China as livestock and poultry feed additive for promoting animal growth. The use of organoarsenics poses a potential threat to the environment because it is mostly excreted by animals in its original form and can be transformed by UV-Vis light excitation. This work examined the initial rate and efficiency of p-ASA phototransformation under UV-C disinfection lamp. Several factors influencing p-ASA phototransformation, namely, pH, initial concentration, temperature, as well as the presence of NaCl, NH4(+), and humic acid, were investigated. Quenching experiments and LC-MS were performed to investigate the mechanism of p-ASA phototransformation. Results show that p-ASA was decomposed to inorganic arsenic (including As(III) and As(V)) and aromatic products by UV-C light through direct photolysis and indirect oxidation. The oxidation efficency of p-ASA by direct photosis was about 32%, and those by HO and (1)O2 were 19% and 49%, respectively. Cleavage of the arsenic-benzene bond through direct photolysis, HO oxidation or (1)O2 oxidation results in simultaneous formation of inorganic As(III), As(IV), and As(V). Inorganic As(III) is oxidized to As(IV) and then to As(V) by (1)O2 or HO. As(IV) can undergo dismutation or simply react with oxygen to produce As(V) as well. Reactions of the organic moieties of p-ASA produce aniline, aminophenol and azobenzene derivatives as main products. The photoconvertible property of p-ASA implies that UV disinfection of wastewaters from poultry and swine farms containing p-ASA poses a potential threat to the ecosystem, especially agricultural environments.

  19. Size-fractionation of groundwater arsenic in alluvial aquifers of West Bengal, India: the role of organic and inorganic colloids.

    PubMed

    Majumder, Santanu; Nath, Bibhash; Sarkar, Simita; Chatterjee, Debashis; Roman-Ross, Gabriela; Hidalgo, Manuela

    2014-01-15

    Dissolved organic carbon (DOC) and Fe mineral phases are known to influence the mobility of arsenic (As) in groundwater. Arsenic can be associated with colloidal particles containing organic matter and Fe. Currently, no data is available on the dissolved phase/colloidal association of As in groundwater of alluvial aquifers in West Bengal, India. This study investigated the fractional distribution of As (and other metals/metalloids) among the particulate, colloidal and dissolved phases in groundwater to decipher controlling behavior of organic and inorganic colloids on As mobility. The result shows that 83-94% of As remained in the 'truly dissolved' phases (i.e., <0.05 μm size). Strong positive correlation between Fe and As (r(2) between 0.65 and 0.94) is mainly observed in the larger (i.e., >0.05 μm size) colloidal particles, which indicates the close association of As with larger Fe-rich inorganic colloids. In smaller (i.e., <0.05 μm size) colloidal particles strong positive correlation is observed between As and DOC (r(2)=0.85), which highlights the close association of As with smaller organic colloids. As(III) is mainly associated with larger inorganic colloids, whereas, As(V) is associated with smaller organic/organometallic colloids. Scanning Electron Microscopy and Energy Dispersive X-ray spectroscopy confirm the association of As with DOC and Fe mineral phases suggesting the formation of dissolved organo-Fe complexes and colloidal organo-Fe oxide phases. Attenuated total reflectance-Fourier transform infrared spectroscopy further confirms the formation of As-Fe-NOM organometallic colloids, however, a detailed study of these types of colloids in natural waters is necessary to underpin their controlling behavior.

  20. Multiple transformation pathways of p-arsanilic acid to inorganic arsenic species in water during UV disinfection.

    PubMed

    Li, Suqi; Xu, Jing; Chen, Wei; Yu, Yingtan; Liu, Zizheng; Li, Jinjun; Wu, Feng

    2016-09-01

    p-Arsanilic acid (p-ASA) is widely used in China as livestock and poultry feed additive for promoting animal growth. The use of organoarsenics poses a potential threat to the environment because it is mostly excreted by animals in its original form and can be transformed by UV-Vis light excitation. This work examined the initial rate and efficiency of p-ASA phototransformation under UV-C disinfection lamp. Several factors influencing p-ASA phototransformation, namely, pH, initial concentration, temperature, as well as the presence of NaCl, NH4(+), and humic acid, were investigated. Quenching experiments and LC-MS were performed to investigate the mechanism of p-ASA phototransformation. Results show that p-ASA was decomposed to inorganic arsenic (including As(III) and As(V)) and aromatic products by UV-C light through direct photolysis and indirect oxidation. The oxidation efficency of p-ASA by direct photosis was about 32%, and those by HO and (1)O2 were 19% and 49%, respectively. Cleavage of the arsenic-benzene bond through direct photolysis, HO oxidation or (1)O2 oxidation results in simultaneous formation of inorganic As(III), As(IV), and As(V). Inorganic As(III) is oxidized to As(IV) and then to As(V) by (1)O2 or HO. As(IV) can undergo dismutation or simply react with oxygen to produce As(V) as well. Reactions of the organic moieties of p-ASA produce aniline, aminophenol and azobenzene derivatives as main products. The photoconvertible property of p-ASA implies that UV disinfection of wastewaters from poultry and swine farms containing p-ASA poses a potential threat to the ecosystem, especially agricultural environments. PMID:27593271

  1. Meeting Materials for the 4th NRC Meeting on the Guidance for and the Review of EPA's Toxicological Assessment of Inorganic Arsenic

    EPA Science Inventory

    On December 2-3, 2015, the National Research Council (NRC) hosted the 4th meeting of the committee formed to peer review the draft IRIS assessment of inorganic arsenic. EPA presented background and overview materials during the public session on December 2nd. This information co...

  2. COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (IAS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV) AND ARSENITE (ASIII)

    EPA Science Inventory

    COMPARATIVE TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV) AND ARSENITE (AsIII). E M Kenyon, L M Del Razo and M F Hughes. U.S. EPA, ORD, NHEERL, ETD, PKB, RTP, NC, USA; ...

  3. Biogeochemistry of organic and inorganic arsenic species in a forested catchment in Germany.

    PubMed

    Huang, Jen-How; Matzner, Egbert

    2007-03-01

    Little is known about the fate and behavior of diffuse inputs of arsenic (As) species in forested catchments which often are the sources of drinking water. The objective of this study was to investigate the mobility and transformation of different As species in forest ecosystems to assess the environmental risk related to the diffuse pollution of As. We determined concentrations and fluxes in precipitation, litterfall, soil solutions (Oa horizon and 20- and 90-cm depth), and runoff of organic and inorganic As species and Astotal in a forest ecosystem in NE-Bavaria, Germany. The concentrations of Astotal were mostly <1 microg As L(-1) in aqueous samples and were highest in forestfloor percolates (7.6 microg As L(-1)). In litterfall, the concentrations of As species never exceeded 0.1 microg As g(-1). Arsenate and arsenite were the prevalent As species in all samples. Organic As species, comprising monomethylarsonic acid, dimethylarsinic acid, trimethylarsine oxide, arsenobetaine, and three unidentified organic As species, were mostly found in throughfall reaching up to 45% of Astotal. The total deposition of Astotal (calculated as throughfall + litterfall) was 5.6 g As ha(-1) yr(-1) with 16% contribution of litterfall. The annual Astotal fluxes were 30 g As ha(-1) yr(-1) for forest floor percolates, 8.0 g As ha(-1) yr(-1) at 20-cm soil depth, and 1.4 g As ha(-1) yr(-1) at 90-cm soil depth. The annual runoff of Astotal from the catchment amounted to 3.8 g As ha(-1) yr(-1). The annual fluxes of total organic As species was highest in total deposition (1.1 g As ha(-1) yr(-1)) and decreased largely with depth in the soil profile. The annual runoff of total organic As species was only 0.08 g As ha(-1) yr(-1). Significant correlations in soil solutions and runoff were found between Astotal and dissolved organic C and Fe. Correlations between Astotal concentrations in runoff and water fluxes were seasonally dependent and with a steeper slope in the growing season than in

  4. Merkel cell carcinoma and multiple Bowen's disease: incidental association or possible relationship to inorganic arsenic exposure?

    PubMed

    Ohnishi, Y; Murakami, S; Ohtsuka, H; Miyauchi, S; Shinmori, H; Hashimoto, K

    1997-05-01

    An 81-year-old Japanese male was referred to our clinic in 1991 with multiple Bowen's disease. The associated hyperpigmentation of the trunk and extremities and palmoplantar keratotic nodules indicated that he had suffered from chronic arsenic poisoning. Interestingly, he was a native of Namikata in Ehime, Japan, where many residents have suffered from multiple Bowen's disease with internal malignancy. Arsenic exposure was strongly suspected. Two years later, Merkel cell carcinoma developed on the dorsum of his right hand, where Bowen's disease lesions were absent. Metastasis of this Merkel cell carcinoma led to his eventual death one year later. To our knowledge, this is the first report of Merkel cell carcinoma associated with multiple Bowen's disease. Chronic arsenic poisoning may be responsible for the association of these two rare skin neoplasms.

  5. Significance of urinary arsenic speciation in assessment of seafood ingestion as the main source of organic and inorganic arsenic in a population resident near a coastal area.

    PubMed

    Soleo, Leonardo; Lovreglio, Piero; Iavicoli, Sergio; Antelmi, Annarita; Drago, Ignazio; Basso, Antonella; Di Lorenzo, Luigi; Gilberti, Maria Enrica; De Palma, Giuseppe; Apostoli, Pietro

    2008-09-01

    In order to characterize the different sources of exposure to arsenic (As), urinary excretion of total As, the sum of inorganic As+MMA+DMA determined by the hydride generation-atomic absorption spectrophotometry technique, and the species As3, As5, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine were determined in 49 workers at a steel foundry, with presumed occupational exposure to As, and 50 subjects from the general population, all males. No evidence of occupational exposure to As resulted from environmental monitoring performed in the foundry, although the analysis of minerals used as raw materials showed the presence of As, particularly in fossils and fine ores. The urinary concentrations of As3, MMA, DMA, the sum of inorganic As+MMA+DMA and total As were not different in the two groups, while arsenobetaine appeared significantly higher in the controls than in the workers. The different species of urinary As were all significantly correlated. Urinary excretion of As3 was associated with the consumption of mineral water and with residence in an industrial zone, while MMA, DMA, arsenobetaine, the sum of inorganic As+MMA+DMA and total As urinary excretion were associated with the consumption of crustaceans and/or shellfish 3 days or less before urine collection. Multiple regression analysis confirmed these results. In conclusion, in populations with a high consumption of seafood, living in areas characterized by coastal/marine As pollution, only speciation of As can identify a prevalent role of environmental sources, like the consumption of seafood contaminated by As, in determining urinary As excretion, and exclude an occupational origin of the exposure.

  6. IRIS Toxicological Review of Ingested Inorganic Arsenic (2005 Sab External Review Draft)

    EPA Science Inventory

    EPA's Office of Research and Development (ORD), Office of Pesticide Programs (OPP), and Office of Water (OW) requested the SAB to provide advice to the Agency on several issues about the mode of carcinogenic action of various arsenic species and the implications of these issues f...

  7. Systematic review of differential inorganic arsenic exposure in minority, low-income, and indigenous populations in the United States.

    PubMed

    Joca, Lauren; Sacks, Jason D; Moore, Danielle; Lee, Janice S; Sams, Reeder; Cowden, John

    2016-01-01

    Inorganic arsenic (iAs) is a human carcinogen and associated with cardiovascular, respiratory, and skin diseases. Natural and anthropogenic sources contribute to low concentrations of iAs in water, food, soil, and air. Differential exposure to environmental hazards in minority, indigenous, and low income populations is considered an environmental justice (EJ) concern, yet it is unclear if higher iAs exposure occurs in these populations. A systematic review was conducted to evaluate evidence for differential iAs exposure in the United States (US). The peer-reviewed literature was searched for studies that (1) estimated iAs exposure based on environmental concentrations of iAs in water, food, soil, or iAs biomarkers and (2) examined iAs exposure in minority, indigenous, and low income US populations. Five studies were identified that estimated exposures and provided demographic information about EJ populations. These studies reported arsenic concentrations in water, soil, or food to estimate exposure, with varied evidence of differential exposure. Additionally, six studies were identified that suggested potential arsenic exposure from environmental sources including soil, rice, private well-water, and fish, but did not report data stratified by demographic information. Evidence across these 11 studies was qualitatively integrated to draw conclusions about differential iAs exposure. The total body of evidence is limited by lack of individual exposure measures, lack of iAs concentration data, and insufficient comparative demographic data. Based upon these data gaps, there is inadequate evidence to conclude whether differential exposure to iAs is an EJ concern in the US. PMID:26896853

  8. Systematic review of differential inorganic arsenic exposure in minority, low-income, and indigenous populations in the United States.

    PubMed

    Joca, Lauren; Sacks, Jason D; Moore, Danielle; Lee, Janice S; Sams, Reeder; Cowden, John

    2016-01-01

    Inorganic arsenic (iAs) is a human carcinogen and associated with cardiovascular, respiratory, and skin diseases. Natural and anthropogenic sources contribute to low concentrations of iAs in water, food, soil, and air. Differential exposure to environmental hazards in minority, indigenous, and low income populations is considered an environmental justice (EJ) concern, yet it is unclear if higher iAs exposure occurs in these populations. A systematic review was conducted to evaluate evidence for differential iAs exposure in the United States (US). The peer-reviewed literature was searched for studies that (1) estimated iAs exposure based on environmental concentrations of iAs in water, food, soil, or iAs biomarkers and (2) examined iAs exposure in minority, indigenous, and low income US populations. Five studies were identified that estimated exposures and provided demographic information about EJ populations. These studies reported arsenic concentrations in water, soil, or food to estimate exposure, with varied evidence of differential exposure. Additionally, six studies were identified that suggested potential arsenic exposure from environmental sources including soil, rice, private well-water, and fish, but did not report data stratified by demographic information. Evidence across these 11 studies was qualitatively integrated to draw conclusions about differential iAs exposure. The total body of evidence is limited by lack of individual exposure measures, lack of iAs concentration data, and insufficient comparative demographic data. Based upon these data gaps, there is inadequate evidence to conclude whether differential exposure to iAs is an EJ concern in the US.

  9. Health risk assessment of inorganic arsenic intake of Cambodia residents through groundwater drinking pathway.

    PubMed

    Phan, Kongkea; Sthiannopkao, Suthipong; Kim, Kyoung-Woong; Wong, Ming Hung; Sao, Vibol; Hashim, Jamal Hisham; Mohamed Yasin, Mohamed Salleh; Aljunid, Syed Mohamed

    2010-11-01

    In order to compare the magnitudes and health impacts of arsenic and other toxic trace elements in well water, groundwater and hair samples were collected from three areas with different arsenic exposure scenarios in the Mekong River basin of Cambodia. Ampil commune in Kampong Cham province was selected as an uncontaminated area, Khsarch Andaet commune in Kratie province was selected as a moderately contaminated area, and Kampong Kong commune in Kandal Province was selected as an extremely contaminated area. Results of ICP-MS analyses of the groundwater samples revealed that As, Mn, Fe and Ba concentrations were significantly different among the three study areas (Kruskal-Wallis test, p < 0.0001). Out of 46 observed wells in the Kandal province study area, 100% detected As > 50 μg L(-1) and Fe > 300 μg L(-1); 52.17% had Mn > 400 μg L(-1) and 73.91% found Ba > 700 μg L(-1). In the Kratie province study area (n = 12), 25% of wells showed elevated arsenic levels above 10 μg L(-1) and 25% had Mn > 400 μg L(-1), whereas samples from Kampong Cham province study area (n = 18) were relatively clean, with As < 10 μg L(-1). A health risk assessment model derived from the USEPA was applied to calculate individual risks resulting from drinking groundwater. Computational results indicated that residents from Kandal Province study area (n = 297) confronted significantly higher non-carcinogenic and carcinogenic risks than those in Kratie (n = 89) and Kampong Cham (n = 184) province study areas (Kruskal-Wallis test, p < 0.0001). 98.65% of respondents from the Kandal province study area were at risk for the potential non-cancer effect and an average cancer risk index was found to be 5 in 1000 exposure. The calculations also indicated that, in the Kratie province study area, 13.48% of respondents were affected by non-cancer health risks and 33.71% were threatened by cancer, whereas none of respondents in the Kampong Cham province study area appeared to have non

  10. Quantification of inorganic arsenic exposure and cancer risk via consumption of vegetables in southern selected districts of Pakistan.

    PubMed

    Rehman, Zahir Ur; Khan, Sardar; Qin, Kun; Brusseau, Mark L; Shah, Mohammad Tahir; Din, Islamud

    2016-04-15

    Human exposures to arsenic (As) through different pathways (dietary and non-dietary) are considered to be one of the primary worldwide environmental health risks to humans. This study was conducted to investigate the presence of As in soil and vegetable samples collected from agricultural lands located in selected southern districts of Khyber Pakhtunkhwa (KPK) Province, Pakistan. We examined the concentrations of total arsenic (TAs), organic species of As such as monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA), and inorganic species including arsenite (AsIII) and arsenate (AsV) in both soil and vegetables. The data were used to determine several parameters to evaluate human health risk, including bioconcentration factor (BCF) from soil to plant, average daily intake (ADI), health risk index (HRI), incremental lifetime cancer risk (ILTCR), and hazard quotient (HQ). The total As concentration in soil samples of the five districts ranged from 3.0-3.9mgkg(-1), exhibiting minimal variations from site to site. The mean As concentration in edible portions of vegetable samples ranged from 0.03-1.38mgkg(-1). It was observed that As concentrations in 75% of the vegetable samples exceeded the safe maximum allowable limit (0.1mgkg(-1)) set by WHO/FAO. The highest value of ADI for As was measured for Momordica charantia, while the lowest was for Allium chinense. The results of this study revealed minimal health risk (HI<1) associated with consumption of vegetables for the local inhabitants. The ILTCR values for inorganic As indicated a minimal potential cancer risk through ingestion of vegetables. In addition, the HQ values for total As were <1, indicating minimal non-cancer risk.

  11. Quantification of inorganic arsenic exposure and cancer risk via consumption of vegetables in southern selected districts of Pakistan.

    PubMed

    Rehman, Zahir Ur; Khan, Sardar; Qin, Kun; Brusseau, Mark L; Shah, Mohammad Tahir; Din, Islamud

    2016-04-15

    Human exposures to arsenic (As) through different pathways (dietary and non-dietary) are considered to be one of the primary worldwide environmental health risks to humans. This study was conducted to investigate the presence of As in soil and vegetable samples collected from agricultural lands located in selected southern districts of Khyber Pakhtunkhwa (KPK) Province, Pakistan. We examined the concentrations of total arsenic (TAs), organic species of As such as monomethylarsonic acid (MMA) and dimethylarsonic acid (DMA), and inorganic species including arsenite (AsIII) and arsenate (AsV) in both soil and vegetables. The data were used to determine several parameters to evaluate human health risk, including bioconcentration factor (BCF) from soil to plant, average daily intake (ADI), health risk index (HRI), incremental lifetime cancer risk (ILTCR), and hazard quotient (HQ). The total As concentration in soil samples of the five districts ranged from 3.0-3.9mgkg(-1), exhibiting minimal variations from site to site. The mean As concentration in edible portions of vegetable samples ranged from 0.03-1.38mgkg(-1). It was observed that As concentrations in 75% of the vegetable samples exceeded the safe maximum allowable limit (0.1mgkg(-1)) set by WHO/FAO. The highest value of ADI for As was measured for Momordica charantia, while the lowest was for Allium chinense. The results of this study revealed minimal health risk (HI<1) associated with consumption of vegetables for the local inhabitants. The ILTCR values for inorganic As indicated a minimal potential cancer risk through ingestion of vegetables. In addition, the HQ values for total As were <1, indicating minimal non-cancer risk. PMID:26820935

  12. Zerovalent iron encapsulated chitosan nanospheres - a novel adsorbent for the removal of total inorganic arsenic from aqueous systems.

    PubMed

    Gupta, Anjali; Yunus, M; Sankararamakrishnan, Nalini

    2012-01-01

    Evaluation of Chitosan zerovalent Iron Nanoparticle (CIN) towards arsenic removal is presented. Addition of chitosan enhances the stability of Fe(0) nano particle. Prepared adsorbent was characterized by FT-IR, SEM EDX, BET and XRD. It was found that, with an initial dose rate of 0.5 g L(-1), concentrations of As (III) and As (V) were reduced from 2 mg L(-1) to <5 μg L(-1) in less than 180 min and the adsorbent was found to be applicable in wide range of pH. Langmuir monolayer adsorption capacity was found to be 94±1.5 mg g(-1) and 119±2.6 mg g(-1) at pH 7 for As (III) and As (V) respectively. Major anions including sulfate, phosphate and silicate did not cause significant interference in the adsorption behavior of both arsenite and arsenate. The adsorbent was successfully recycled five times and applied to the removal of total inorganic arsenic from real life groundwater samples.

  13. Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.

    PubMed

    Xu, Xiaofan; Drobná, Zuzana; Voruganti, V Saroja; Barron, Keri; 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; Crandell, Jamie; Fry, Rebecca C; Loomis, Dana; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav; Mendez, Michelle A

    2016-09-01

    Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level. PMID:27370415

  14. Arsenic

    MedlinePlus

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

  15. Synthesis and properties of arsenic(III)-reactive coumarin-appended benzothiazolines: a new approach for inorganic arsenic detection.

    PubMed

    Ezeh, Vivian C; Harrop, Todd C

    2013-03-01

    The EPA has established a maximum contaminant level (MCL) of 10 ppb for arsenic (As) in drinking water requiring sensitive and selective detection methodologies. To tackle this challenge, we have been active in constructing small molecules that react specifically with As(3+) to furnish a new fluorescent species (termed a chemodosimeter). We report in this contribution, the synthesis and spectroscopy of two small-molecule fluorescent probes that we term ArsenoFluors (or AFs) as As-specific chemodosimeters. The AFs (AF1 and AF2) incorporate a coumarin fluorescent reporter coupled with an As-reactive benzothiazoline functional group. AFs react with As(3+) to yield the highly fluorescent coumarin-6 dye (C6) resulting in a 20-25-fold fluorescence enhancement at λem ∼ 500 nm with detection limits of 0.14-0.23 ppb in tetrahydrofuran (THF) at 298 K. The AFs also react with common environmental As(3+) sources such as sodium arsenite in a THF/CHES (N-cyclohexyl-2-aminoethanesulfonic acid) (1:1, pH 9, 298 K) mixture resulting in a modest fluorescence turn-ON (1.5- to 3-fold) due to the quenched nature of coumarin-6 derivatives in high polarity solvents. Bulk analysis of the reaction of the AFs with As(3+) revealed that the C6 derivatives and the Schiff-base disulfide of the AFs (SB1 and SB2) are the ultimate end-products of this chemistry with the formation of C6 being the principle photoproduct responsible for the As(3+)-specific turn-ON. It appears that a likely species that is traversed in the reaction path is an As-hydride-ligand complex that is a putative intermediate in the proposed reaction path.

  16. Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water

    SciTech Connect

    Kenyon, E.M. Hughes, M.F.; Adair, B.M.; Highfill, J.H.; Crecelius, E.A.; Clewell, H.J.; Yager, J.W.

    2008-11-01

    The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for As{sup V} because its trivalent metabolites have unique toxicities and relatively greater potency compared to their pentavalent counterparts for many endpoints. In this study, dose-dependency in tissue distribution and urinary excretion for inorganic arsenic and its methylated metabolites was assessed in female C57Bl/6 mice exposed to 0, 0.5, 2, 10 or 50 ppm arsenic (as arsenate, As{sup V}) in their drinking water for 12 weeks. No adverse effects were observed and body weight gain did not differ significantly among groups. Urinary excretion of arsenite monomethylarsonous acid (MMA{sup III}), dimethylarsinous acid (DMA{sup III}), dimethylarsinic acid (DMA{sup V}), and trimethylarsine oxide (TMAO) increased linearly with dose, whereas As{sup V} and monomethylarsonic acid (MMA{sup V}) excretion was non-linear with respect to dose. Total tissue arsenic accumulation was greatest in kidney > lung > urinary bladder >>> skin > blood > liver. Monomethyl arsenic (MMA, i.e. MMA{sup III} + MMA{sup V}) was the predominant metabolite in kidney, whereas dimethylarsenic (DMA, i.e., DMA{sup III} + DMA{sup V}) was the predominant metabolite in lung. Urinary bladder tissue had roughly equivalent levels of inorganic arsenic and dimethylarsenic, as did skin. These data indicate that pharmacokinetic models for arsenic metabolism and disposition need to include mechanisms for organ-specific accumulation of some arsenicals and that urinary metabolite profiles are not necessarily reflective of target tissue dosimetry.

  17. Toxicity of arsenic species to three freshwater organisms and biotransformation of inorganic arsenic by freshwater phytoplankton (Chlorella sp. CE-35).

    PubMed

    Rahman, M Azizur; Hogan, Ben; Duncan, Elliott; Doyle, Christopher; Krassoi, Rick; Rahman, Mohammad Mahmudur; Naidu, Ravi; Lim, Richard P; Maher, William; Hassler, Christel

    2014-08-01

    In the environment, arsenic (As) exists in a number of chemical species, and arsenite (As(III)) and arsenate (As(V)) dominate in freshwater systems. Toxicity of As species to aquatic organisms is complicated by their interaction with chemicals in water such as phosphate that can influence the bioavailability and uptake of As(V). In the present study, the toxicities of As(III), As(V) and dimethylarsinic acid (DMA) to three freshwater organisms representing three phylogenetic groups: a phytoplankton (Chlorella sp. strain CE-35), a floating macrophyte (Lemna disperma) and a cladoceran grazer (Ceriodaphnia cf. dubia), were determined using acute and growth inhibition bioassays (EC₅₀) at a range of total phosphate (TP) concentrations in OECD medium. The EC₅₀ values of As(III), As(V) and DMA were 27 ± 10, 1.15 ± 0.04 and 19 ± 3 mg L(-1) for Chlorella sp. CE-35; 0.57 ± 0.16, 2.3 ± 0.2 and 56 ± 15 mg L(-1) for L. disperma, and 1.58 ± 0.05, 1.72 ± 0.01 and 5.9 ± 0.1 mg L(-1) for C. cf. dubia, respectively. The results showed that As(III) was more toxic than As(V) to L. disperma; however, As(V) was more toxic than As(III) to Chlorella sp. CE-35. The toxicities of As(III) and As(V) to C. cf. dubia were statistically similar (p>0.05). DMA was less toxic than iAs species to L. disperma and C. cf. dubia, but more toxic than As(III) to Chlorella sp. CE-35. The toxicity of As(V) to Chlorella sp. CE-35 and L. disperma decreased with increasing TP concentrations in the growth medium. Phosphate concentrations did not influence the toxicity of As(III) to either organism. Chlorella sp. CE-35 showed the ability to reduce As(V) to As(III), indicating a substantial influence of phytoplankton on As biogeochemistry in freshwater aquatic systems.

  18. Biosorptive removal of inorganic arsenic species and fluoride from aqueous medium by the stem of Tecomella undulate.

    PubMed

    Brahman, Kapil Dev; Kazi, Tasneem Gul; Baig, Jameel Ahmed; Afridi, Hassan Imran; Arain, Sadaf Sadia; Saraj, Saima; Arain, Muhammad B; Arain, Salma Aslam

    2016-05-01

    Simultaneous removal of fluoride (F(-)), inorganic arsenic species, As(III) and As(V), from aqueous samples has been performed using an economic indigenous biosorbent (Stem of Tecomella undulata). The inorganic As species in water samples before and after biosorption were determined by cloud point and solid phase extraction methods, while F(-) was determined by ion chromatography. Batch experiments were carried out to evaluate the equilibrium adsorption isotherm studies for As(III), As(V) and F(-) in aqueous solutions. Several parameters of biosorption were optimized such as pH, biomass dosage, analytes concentration, time and temperature. The surface of biosorbent was characterized by SEM and FTIR. The FTIR study indicated the presence of carbonyl and amine functional groups which may have important role in the sorption/removal of these ions. Thermodynamic and kinetic study indicated that the biosorption of As(III), As(V) and F(-) were spontaneous, exothermic and followed by pseudo-second-order. Meanwhile, the interference study revealed that there was no significant effect of co-existing ions for the removal of inorganic As species and F(-) from aqueous samples (p > 0.05). It was observed that the indigenous biosorbent material simultaneously adsorbed As(III) (108 μg g(-1)), As(V) (159 μg g(-1)) and F(-) (6.16 mg g(-1)) from water at optimized conditions. The proposed biosorbent was effectively regenerated and efficiently used for several experiments, to remove the As(III), As(V) and F(-) from real water sample collected from endemic area of Pakistan. PMID:26921585

  19. Determination of total cadmium, lead, arsenic, mercury and inorganic arsenic in mushrooms: outcome of IMEP-116 and IMEP-39

    PubMed Central

    Cordeiro, F.; Llorente-Mirandes, T.; López-Sánchez, J.F.; Rubio, R.; Sánchez Agullo, A.; Raber, G.; Scharf, H.; Vélez, D.; Devesa, V.; Fiamegos, Y.; Emteborg, H.; Seghers, J.; Robouch, P.; de la Calle, M.B.

    2015-01-01

    The Institute for Reference Materials and Measurements (IRMM) of the Joint Research Centre (JRC), a Directorate General of the European Commission, operates the International Measurement Evaluation Program (IMEP). IMEP organises inter-laboratory comparisons in support of European Union policies. This paper presents the results of two proficiency tests (PTs): IMEP-116 and IMEP-39, organised for the determination of total Cd, Pb, As, Hg and inorganic As (iAs) in mushrooms. Participation in IMEP-116 was restricted to National Reference Laboratories (NRLs) officially appointed by national authorities in European Union member states. IMEP-39 was open to all other laboratories wishing to participate. Thirty-seven participants from 25 countries reported results in IMEP-116, and 62 laboratories from 36 countries reported for the IMEP-39 study. Both PTs were organised in support to Regulation (EC) No. 1881/2006, which sets the maximum levels for certain contaminants in food. The test item used in both PTs was a blend of mushrooms of the variety shiitake (Lentinula edodes). Five laboratories, with demonstrated measurement capability in the field, provided results to establish the assigned values (X ref). The standard uncertainties associated to the assigned values (u ref) were calculated by combining the uncertainty of the characterisation (u char) with a contribution for homogeneity (u bb) and for stability (u st), whilst u char was calculated following ISO 13528. Laboratory results were rated with z- and zeta (ζ)-scores in accordance with ISO 13528. The standard deviation for proficiency assessment, σ p, ranged from 10% to 20% depending on the analyte. The percentage of satisfactory z-scores ranged from 81% (iAs) to 97% (total Cd) in IMEP-116 and from 64% (iAs) to 84% (total Hg) in IMEP-39. PMID:25365736

  20. Low Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James

    2002-09-14

    The overall research objective was to establish new levels of information about how people, groups, and communities respond to low dose radiation exposure. This is basic research into the social psychology of individual, group, and community responses to radiation exposures. The results of this research are directed to improving risk communication and public participation in management of environmental problems resulting from low dose radiation.

  1. Inorganic Arsenic and Basal Cell Carcinoma in Areas of Hungary, Romania, and Slovakia: A Case–Control Study

    PubMed Central

    Leonardi, Giovanni; Vahter, Marie; Clemens, Felicity; Goessler, Walter; Gurzau, Eugen; Hemminki, Kari; Hough, Rupert; Koppova, Kvetoslava; Kumar, Rajiv; Rudnai, Peter; Surdu, Simona

    2012-01-01

    Background: Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water. Objectives: We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism. Methods: The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case–control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression. Results: A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA. Conclusion: We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L. PMID:22436128

  2. Remediation of inorganic arsenic in groundwater for safe water supply: a critical assessment of technological solutions.

    PubMed

    Mondal, Priyanka; Bhowmick, Subhamoy; Chatterjee, Debashis; Figoli, Alberto; Van der Bruggen, Bart

    2013-06-01

    Arsenic contaminations of groundwater in several parts of the world are the results of natural and/or anthropogenic sources, and have a large impact on human health. Millions of people from different countries rely on groundwater containing As for drinking purposes. This paper reviews removal technologies (oxidation, coagulation flocculation, adsorption, ion exchange and membrane processes) with attention for the drawbacks and limitations of these applied technologies. The technologies suggested and applied for treatment of As rich water have various problems, including the need for further treatment of As containing secondary waste generated from these water treatment processes. More efficient technologies, with a lower tendency to generate waste include the removal of As by membrane distillation or forward osmosis, instead of using pressure driven membrane processes and subsequently reducing soluble As to commercially valuable metallic As are surveyed. An integrated approach of two or more techniques is suggested to be more beneficial than a single process. Advanced technologies such as membrane distillation, forward osmosis as well as some hybrid integrated techniques and their potentials are also discussed in this review. Membrane processes combined with other process (especially iron based technologies) are thought to be most sustainable for the removal of arsenic and further research allowing scale up of these technologies is suggested.

  3. Remediation of inorganic arsenic in groundwater for safe water supply: a critical assessment of technological solutions.

    PubMed

    Mondal, Priyanka; Bhowmick, Subhamoy; Chatterjee, Debashis; Figoli, Alberto; Van der Bruggen, Bart

    2013-06-01

    Arsenic contaminations of groundwater in several parts of the world are the results of natural and/or anthropogenic sources, and have a large impact on human health. Millions of people from different countries rely on groundwater containing As for drinking purposes. This paper reviews removal technologies (oxidation, coagulation flocculation, adsorption, ion exchange and membrane processes) with attention for the drawbacks and limitations of these applied technologies. The technologies suggested and applied for treatment of As rich water have various problems, including the need for further treatment of As containing secondary waste generated from these water treatment processes. More efficient technologies, with a lower tendency to generate waste include the removal of As by membrane distillation or forward osmosis, instead of using pressure driven membrane processes and subsequently reducing soluble As to commercially valuable metallic As are surveyed. An integrated approach of two or more techniques is suggested to be more beneficial than a single process. Advanced technologies such as membrane distillation, forward osmosis as well as some hybrid integrated techniques and their potentials are also discussed in this review. Membrane processes combined with other process (especially iron based technologies) are thought to be most sustainable for the removal of arsenic and further research allowing scale up of these technologies is suggested. PMID:23466274

  4. Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

    SciTech Connect

    Liu Jie . E-mail: Liu6@niehs.nih.gov; Xie Yaxiong; Cooper, Ryan; Ducharme, Danica M.K.; Tennant, Raymond; Diwan, Bhalchandra A.; Waalkes, Michael P.

    2007-05-01

    Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17{beta}-hydroxysteroid dehydrogenase-7 (HSD17{beta}7; involved in estradiol production) and decreased expression of HSD17{beta}5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood.

  5. Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis

    EPA Science Inventory

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt), yielding mono- , di- , and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation,...

  6. Evaluation of coexposure to inorganic arsenic and titanium dioxide nanoparticles in the marine shrimp Litopenaeus vannamei.

    PubMed

    Cordeiro, Lucas; Müller, Larissa; Gelesky, Marcos A; Wasielesky, Wilson; Fattorini, Daniele; Regoli, Francesco; Monserrat, José Marìa; Ventura-Lima, Juliane

    2016-01-01

    The acute toxicity of titanium dioxide nanoparticles (nTiO2) that occur concomitantly in the aquatic environment with other contaminants such as arsenic (As) is little known in crustaceans. The objective of the present study is to evaluate whether coexposure to nTiO2 can influence the accumulation, metabolism, and oxidative stress parameters induced by arsenic exposure in the gills and hepatopancreas of the shrimp Litopenaeus vannamei. Organisms were exposed by dissolving chemicals in seawater (salinity = 30) at nominal concentrations of 10 μg/L nTiO2 or As(III), dosed alone and in combination. Results showed that there was not a significant accumulation of As in either tissue type, but the coexposure altered the pattern of the metabolism. In the hepatopancreas, no changes were observed in the biochemical response, while in the gills, an increase in the glutamate-cysteine-ligase (GCL) activity was observed upon exposure to As or nTiO2 alone, an increase in the reduced glutathione (GSH) levels was observed upon exposure to As alone, and an increase in the total antioxidant capacity was observed upon exposure to nTiO2 or nTiO2 + As. However, these modulations were not sufficient enough to prevent the lipid damage induced by nTiO2 exposure. Our results suggest that coexposure to nTiO2 and As does not alter the toxicity of this metalloid in the gills and hepatopancreas of L. vannamei but does alter its metabolism, favoring its accumulation of organic As species considered moderately toxic.

  7. Inorganic arsenic speciation at river basin scales: the Tinto and Odiel rivers in the Iberian Pyrite Belt, SW Spain.

    PubMed

    Sarmiento, A M; Nieto, J M; Casiot, C; Elbaz-Poulichet, F; Egal, M

    2009-04-01

    The Tinto and Odiel rivers are heavily affected by acid mine drainage from mining areas in the Iberian Pyrite Belt. In this work we have conducted a study along these rivers where surface water samples have been collected. Field measurements, total dissolved metals and Fe and inorganic As speciation analysis were performed. The average total concentration of As in the Tinto river (1975 microg L(-1)) is larger than in the Odiel river (441 microg L(-1)); however, the mean concentration of As(III) is almost four times higher in the Odiel. In wet seasons the mean pH levels of both rivers (2.4 and 3.2 for the Tinto and Odiel, respectively) increase slightly and the amount of dissolved total arsenic tend to decrease, while the As(III)/(V) ratio strongly increase. Besides, the concentration of the reduced As species increase along the water course. As a result, As(III)/(V) ratio can be up to 100 times higher in the lower part of the basins. An estimation of the As(III) load transported by both rivers into the Atlantic Ocean has been performed, resulting in about 60 kg yr(-1) and 2.7t yr(-1) by the Tinto and Odiel rivers, respectively.

  8. Cloud point extraction for trace inorganic arsenic speciation analysis in water samples by hydride generation atomic fluorescence spectrometry

    NASA Astrophysics Data System (ADS)

    Li, Shan; Wang, Mei; Zhong, Yizhou; Zhang, Zehua; Yang, Bingyi

    2015-09-01

    A new cloud point extraction technique was established and used for the determination of trace inorganic arsenic species in water samples combined with hydride generation atomic fluorescence spectrometry (HGAFS). As(III) and As(V) were complexed with ammonium pyrrolidinedithiocarbamate and molybdate, respectively. The complexes were quantitatively extracted with the non-ionic surfactant (Triton X-114) by centrifugation. After addition of antifoam, the surfactant-rich phase containing As(III) was diluted with 5% HCl for HGAFS determination. For As(V) determination, 50% HCl was added to the surfactant-rich phase, and the mixture was placed in an ultrasonic bath at 70 °C for 30 min. As(V) was reduced to As(III) with thiourea-ascorbic acid solution, followed by HGAFS. Under the optimum conditions, limits of detection of 0.009 and 0.012 μg/L were obtained for As(III) and As(V), respectively. Concentration factors of 9.3 and 7.9, respectively, were obtained for a 50 mL sample. The precisions were 2.1% for As(III) and 2.3% for As(V). The proposed method was successfully used for the determination of trace As(III) and As(V) in water samples, with satisfactory recoveries.

  9. Inorganic arsenic speciation at river basin scales: the Tinto and Odiel rivers in the Iberian Pyrite Belt, SW Spain.

    PubMed

    Sarmiento, A M; Nieto, J M; Casiot, C; Elbaz-Poulichet, F; Egal, M

    2009-04-01

    The Tinto and Odiel rivers are heavily affected by acid mine drainage from mining areas in the Iberian Pyrite Belt. In this work we have conducted a study along these rivers where surface water samples have been collected. Field measurements, total dissolved metals and Fe and inorganic As speciation analysis were performed. The average total concentration of As in the Tinto river (1975 microg L(-1)) is larger than in the Odiel river (441 microg L(-1)); however, the mean concentration of As(III) is almost four times higher in the Odiel. In wet seasons the mean pH levels of both rivers (2.4 and 3.2 for the Tinto and Odiel, respectively) increase slightly and the amount of dissolved total arsenic tend to decrease, while the As(III)/(V) ratio strongly increase. Besides, the concentration of the reduced As species increase along the water course. As a result, As(III)/(V) ratio can be up to 100 times higher in the lower part of the basins. An estimation of the As(III) load transported by both rivers into the Atlantic Ocean has been performed, resulting in about 60 kg yr(-1) and 2.7t yr(-1) by the Tinto and Odiel rivers, respectively. PMID:19135765

  10. ELUCIDATING THE PATHWAY FOR ARSENIC METHYLATION

    EPA Science Inventory

    Enzymatically-catalyzed methylation of arsenic is part of a metabolic pathway that converts inorganic arsenic into methylated products. Hence, in humans chronically exposed to inorganic arsenic, methyl and dimethyl arsenic account for most of the arsenic that is excreted in the ...

  11. Efflux of glutathione and glutathione complexes from human erythrocytes in response to inorganic arsenic exposure.

    PubMed

    Yildiz, Deniz; Cakir, Yeliz

    2012-12-01

    The objective of the present study was to investigate if arsenic exposure results in glutathione efflux from human erythrocytes. Arsenite significantly depleted intracellular nonprotein thiol level in a time- and concentration-dependent manner. The intracellular nonprotein thiol level was decreased to 0.767 ± 0.0017 μmol/ml erythrocyte following exposure to 10 mM of arsenite for 4 h. Extracellular nonprotein thiol level was increased concomitantly with the intracellular decrease and reached to 0.481 ± 0.0005 μmol/ml erythrocyte in 4 h. In parallel with the change in extracellular nonprotein thiol levels, significant increases in extracellular glutathione levels were detected. Extracellular glutathione levels reached to 0.122 ± 0.0013, 0.226 ± 0.003, and 0.274 ± 0.004 μmol/ml erythrocyte with 1, 5, and 10 mM of arsenite, respectively. Dimercaptosuccinic acid treatment of supernatants significantly increased the glutathione levels measured in the extracellular media. Utilization of MK571 and verapamil, multidrug resistance-associated protein 1 and Pgp inhibitors, decreased the rate of glutathione efflux from erythrocytes suggesting a role for these membrane transporters in the process. The results of the present study indicate that human erythrocytes efflux glutathione in reduced free form and in conjugated form or forms that can be recovered with dimercaptosuccinic acid when exposed to arsenite. PMID:22890881

  12. Accuracy of a method based on atomic absorption spectrometry to determine inorganic arsenic in food: Outcome of the collaborative trial IMEP-41.

    PubMed

    Fiamegkos, I; Cordeiro, F; Robouch, P; Vélez, D; Devesa, V; Raber, G; Sloth, J J; Rasmussen, R R; Llorente-Mirandes, T; Lopez-Sanchez, J F; Rubio, R; Cubadda, F; D'Amato, M; Feldmann, J; Raab, A; Emteborg, H; de la Calle, M B

    2016-12-15

    A collaborative trial was conducted to determine the performance characteristics of an analytical method for the quantification of inorganic arsenic (iAs) in food. The method is based on (i) solubilisation of the protein matrix with concentrated hydrochloric acid to denature proteins and allow the release of all arsenic species into solution, and (ii) subsequent extraction of the inorganic arsenic present in the acid medium using chloroform followed by back-extraction to acidic medium. The final detection and quantification is done by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). The seven test items used in this exercise were reference materials covering a broad range of matrices: mussels, cabbage, seaweed (hijiki), fish protein, rice, wheat, mushrooms, with concentrations ranging from 0.074 to 7.55mgkg(-1). The relative standard deviation for repeatability (RSDr) ranged from 4.1 to 10.3%, while the relative standard deviation for reproducibility (RSDR) ranged from 6.1 to 22.8%.

  13. Accuracy of a method based on atomic absorption spectrometry to determine inorganic arsenic in food: Outcome of the collaborative trial IMEP-41.

    PubMed

    Fiamegkos, I; Cordeiro, F; Robouch, P; Vélez, D; Devesa, V; Raber, G; Sloth, J J; Rasmussen, R R; Llorente-Mirandes, T; Lopez-Sanchez, J F; Rubio, R; Cubadda, F; D'Amato, M; Feldmann, J; Raab, A; Emteborg, H; de la Calle, M B

    2016-12-15

    A collaborative trial was conducted to determine the performance characteristics of an analytical method for the quantification of inorganic arsenic (iAs) in food. The method is based on (i) solubilisation of the protein matrix with concentrated hydrochloric acid to denature proteins and allow the release of all arsenic species into solution, and (ii) subsequent extraction of the inorganic arsenic present in the acid medium using chloroform followed by back-extraction to acidic medium. The final detection and quantification is done by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). The seven test items used in this exercise were reference materials covering a broad range of matrices: mussels, cabbage, seaweed (hijiki), fish protein, rice, wheat, mushrooms, with concentrations ranging from 0.074 to 7.55mgkg(-1). The relative standard deviation for repeatability (RSDr) ranged from 4.1 to 10.3%, while the relative standard deviation for reproducibility (RSDR) ranged from 6.1 to 22.8%. PMID:27451169

  14. Inorganic arsenic contents in rice-based infant foods from Spain, UK, China and USA.

    PubMed

    Carbonell-Barrachina, Angel A; Wu, Xiangchun; Ramírez-Gandolfo, Amanda; Norton, Gareth J; Burló, Francisco; Deacon, Claire; Meharg, Andrew A

    2012-04-01

    Spanish gluten-free rice, cereals with gluten, and pureed baby foods were analysed for total (t-As) and inorganic As (i-As) using ICP-MS and HPLC-ICP-MS, respectively. Besides, pure infant rice from China, USA, UK and Spain were also analysed. The i-As contents were significantly higher in gluten-free rice than in cereals mixtures with gluten, placing infants with celiac disease at high risk. All rice-based products displayed a high i-As content, with values being above 60% of the t-As content and the remainder being dimethylarsinic acid (DMA). Approximately 77% of the pure infant rice samples showed contents below 150 μg kg(-1) (Chinese limit). When daily intake of i-As by infants (4-12 months) was estimated and expressed on a bodyweight basis (μg d(-1) kg(-1)), it was higher in all infants aged 8-12 months than drinking water maximum exposures predicted for adults (assuming 1 L consumption per day for a 10 μg L(-1) standard). PMID:22325434

  15. Inorganic arsenic contents in rice-based infant foods from Spain, UK, China and USA.

    PubMed

    Carbonell-Barrachina, Angel A; Wu, Xiangchun; Ramírez-Gandolfo, Amanda; Norton, Gareth J; Burló, Francisco; Deacon, Claire; Meharg, Andrew A

    2012-04-01

    Spanish gluten-free rice, cereals with gluten, and pureed baby foods were analysed for total (t-As) and inorganic As (i-As) using ICP-MS and HPLC-ICP-MS, respectively. Besides, pure infant rice from China, USA, UK and Spain were also analysed. The i-As contents were significantly higher in gluten-free rice than in cereals mixtures with gluten, placing infants with celiac disease at high risk. All rice-based products displayed a high i-As content, with values being above 60% of the t-As content and the remainder being dimethylarsinic acid (DMA). Approximately 77% of the pure infant rice samples showed contents below 150 μg kg(-1) (Chinese limit). When daily intake of i-As by infants (4-12 months) was estimated and expressed on a bodyweight basis (μg d(-1) kg(-1)), it was higher in all infants aged 8-12 months than drinking water maximum exposures predicted for adults (assuming 1 L consumption per day for a 10 μg L(-1) standard).

  16. Radiation Leukemogenesis at Low Dose Rates

    SciTech Connect

    Weil, Michael; Ullrich, Robert

    2013-09-25

    The major goals of this program were to study the efficacy of low dose rate radiation exposures for the induction of acute myeloid leukemia (AML) and to characterize the leukemias that are caused by radiation exposures at low dose rate. An irradiator facility was designed and constructed that allows large numbers of mice to be irradiated at low dose rates for protracted periods (up to their life span). To the best of our knowledge this facility is unique in the US and it was subsequently used to study radioprotectors being developed for radiological defense (PLoS One. 7(3), e33044, 2012) and is currently being used to study the role of genetic background in susceptibility to radiation-induced lung cancer. One result of the irradiation was expected; low dose rate exposures are ineffective in inducing AML. However, another result was completely unexpected; the irradiated mice had a very high incidence of hepatocellular carcinoma (HCC), approximately 50%. It was unexpected because acute exposures are ineffective in increasing HCC incidence above background. This is a potential important finding for setting exposure limits because it supports the concept of an 'inverse dose rate effect' for some tumor types. That is, for the development of some tumor types low dose rate exposures carry greater risks than acute exposures.

  17. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium

    SciTech Connect

    Pelch, Katherine E.; Tokar, Erik J.; Merrick, B. Alex; Waalkes, Michael P.

    2015-08-01

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10 μM Cd for 11 weeks (CTPE) or 5 μM iAs for 29 weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (> 25-fold) and S100P (> 40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (> 15-fold) and NTM (> 1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. - Highlights: • Cd and iAs are known human carcinogens, yet neither appears directly mutagenic. • Prior data suggest epigenetic modification plays a role in Cd or iAs induced cancer. • Altered methylation of four misregulated genes was found in Cd or iAs transformants. • The resulting altered gene expression may be relevant to cellular

  18. Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment

    PubMed Central

    Ramos-Chávez, Lucio A.; Rendón-López, Christian R. R.; Zepeda, Angélica; Silva-Adaya, Daniela; Del Razo, Luz M.; Gonsebatt, María E.

    2015-01-01

    Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system (CNS). In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females. PMID:25709567

  19. Tardive dyskinesia with low dose amisulpride.

    PubMed

    Tharoor, Hema; Padmavati, R

    2013-01-01

    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.

  20. Impact of carbon nanotubes on the toxicity of inorganic arsenic [AS(III) and AS(V)] to Daphnia magna: The role of certain arsenic species.

    PubMed

    Wang, Xinghao; Qu, Ruijuan; Allam, Ahmed A; Ajarem, Jamaan; Wei, Zhongbo; Wang, Zuoyao

    2016-07-01

    As a type of emerging nanomaterial, hydroxylated multiwalled carbon nanotubes (OH-MWCNTs) may interact with other pollutants in the aquatic environments and further influence their toxicity, transport, and fate. Thus, evaluation of toxicity to arsenic in the presence of CNTs needs to receive much more attention. The present study was conducted to explore the underlying mechanisms of OH-MWCNT-induced arsenic (As[III] and As[V]) toxicity changes in the aquatic organism Daphnia magna at different pH levels. The most toxic species for As(III) and As(V) to D. magna were found to be H2 AsO3 (-) and H2 AsO4 (-) . It appeared that the pH values were of greatest importance when the biological toxicity of As(III) and As(V) was compared. Furthermore, the effects of OH-MWCNTs on arsenic toxicity to D. magna indicated that the presence of OH-MWCNTs could enhance the toxicity of arsenic. The interactions of arsenic with OH-MWCNTs were further investigated by conducting adsorption experiments. The adsorption capacity of As(V) by OH-MWCNTs was found to be higher than that of As(III). To conclude, adsorption of certain arsenic species onto OH-MWCNTs is crucial for a reliable interpretation of enhanced toxicity. Environ Toxicol Chem 2016;35:1852-1859. © 2016 SETAC.

  1. Uptake of inorganic and organic derivatives of arsenic associated with induced cytotoxic and genotoxic effects in Chinese hamster ovary (CHO) cells.

    PubMed

    Dopp, E; Hartmann, L M; Florea, A-M; von Recklinghausen, U; Pieper, R; Shokouhi, B; Rettenmeier, A W; Hirner, A V; Obe, G

    2004-12-01

    Humans are exposed to arsenic and their organic derivatives, which are widely distributed in the environment, via food, water, and to a lesser extent, via air. Following uptake, inorganic arsenic undergoes biotransformation to mono- and dimethylated metabolites. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In the present study, the genotoxic effects and the cellular uptake of inorganic arsenic [arsenate, As(i)(V); arsenite, As(i)(III)] and the methylated arsenic species monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], dimethylarsinous acid [DMA(III)], trimethylarsenic oxide [TMAO(V)] were investigated in Chinese hamster ovary (CHO-9) cells. The chemicals were applied at different concentrations (0.1 microM to 10 mM) for 30 min and 1 h, respectively. Cytotoxic effects were investigated by the trypan blue extrusion test and genotoxic effects by the assessment of micronucleus (MN) induction, chromosome aberrations (CA), and sister chromatid exchanges (SCE). Intracellular arsenic concentrations were determined by ICP-MS techniques. Our results show that MMA(III) and DMA(III) induce cytotoxic and genotoxic effects to a greater extent than MMA(V) or DMA(V). Viability was significantly decreased after incubation (1 h) of the cells with > or = 1 microM As(i)(III), > or = 1 microM As(i)(V), > or = 500 microM MMA(III), > or = 100 microM MMA(V), and 500 microM DMA(V) and > or = 0.1 microM DMA(III). TMAO(V) was not cytotoxic at concentrations up to 10 mM. A significant increase of the number of MN, CA and SCE was found for DMA(III) and MMA(III). As(i)(III + V) induced CA and SCE but no MN. TMAO(V), MMA(V) and DMA(V) were not genotoxic in the concentration range tested (up to 5 mM). The nuclear division index (NDI) was not affected by any of the tested arsenic compounds after a recovery period of 14 to 35 h. When the uptake of the chemicals was measured by

  2. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

    A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer. PMID:7023936

  3. Low Dose Effects: Benefit or Harm?

    PubMed

    Woloschak, Gayle E

    2016-03-01

    This forum article discusses issues related to the effects of low dose radiation, an area that is under intense study but difficult to assess. Experiments with large-scale animal studies are included in this paper; these studies point to the need for international consortia to examine and balance the results of these large-scale studies and databases. PMID:26808889

  4. Anticancer Activity of Small Molecule and Nanoparticulate Arsenic(III) Complexes

    PubMed Central

    Swindell, Elden P.; Hankins, Patrick L.; Chen, Haimei; Miodragović, Ðenana U.; O'Halloran, Thomas V.

    2014-01-01

    Starting in ancient China and Greece, arsenic-containing compounds have been used in the treatment of disease for over 3000 years. They were used for a variety of diseases in the 20th century, including parasitic and sexually transmitted illnesses. A resurgence of interest in the therapeutic application of arsenicals has been driven by the discovery that low doses of a 1% aqueous solution of arsenic trioxide (i.e. arsenous acid) leads to complete remission of certain types of leukemia. Since FDA approval of arsenic trioxide (As2O3) for treatment of acute promyelocytic leukemia (APL) in 2000, it has become a front line therapy in this indication. There are currently over 100 active clinical trials involving inorganic arsenic or organoarsenic compounds registered with the FDA for the treatment of cancers. New generations of inorganic and organometallic arsenic compounds with enhanced activity or targeted cytotoxicity are being developed to overcome some of the shortcomings of arsenic therapeutics, namely short plasma half-lives and narrow therapeutic window. PMID:24147771

  5. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated ars...

  6. Assessing and managing the health risk due to ingestion of inorganic arsenic from fish and shellfish farmed in blackfoot disease areas for general Taiwanese.

    PubMed

    Liang, Ching-Ping; Liu, Chen-Wuing; Jang, Cheng-Shin; Wang, Sheng-Wei; Lee, Jin-Jing

    2011-02-15

    This paper assesses health risks due to the ingestion of inorganic arsenic from fish and shellfish farmed in blackfoot disease areas by general public in Taiwan. The provisional tolerable weekly intake of arsenic set by FAO/WHO and the target cancer risk assessment model proposed by USEPA were integrated to evaluate the acceptable consumption rate. Five aquacultural species, tilapia (Oreochromis mossambicus), milkfish (Chanos chanos), mullet (Mugil cephalus), clam (Meretrix lusoria) and oyster (Crassostrea gigas) were included. Monte Carlo analysis was used to propagate the parameter uncertainty and to probabilistically assess the health risk associated with the daily intake of inorganic As from farmed fish and shellfish. The integrated risk-based analysis indicates that the associated 50th and 95th percentile health risk are 2.06×10(-5) and 8.77×10(-5), respectively. Moreover, the acceptable intakes of inorganic As are defined and illustrated by a two dimensional graphical model. According to the relationship between C(inorg) and IR(f) derived from this study, two risk-based curves are constructed. An acceptable risk zone is determined (risk ranging from 1×10(-5) to 6.07×10(-5)) which is recommended for acceptable consumption rates of fish and shellfish. To manage the health risk due to the ingestion of inorganic As from fish and shellfish in BFD areas, a risk-based management scheme is derived which provide a convenient way for general public to self-determine the acceptable seafood consumption rate.

  7. GLUTATHIONE MODULATES RECOMBINANT RAT ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE-CATALYZED FORMATION OF TRIMETHYLARSINE OXIDE AND TRIMETHYLARSINE

    EPA Science Inventory


    Humans and other species enzymatically convert inorganic arsenic into methylated metabolites. Although the major metabolites are mono- and dimethylated arsenicals, trimethylated arsenicals have been detected in urine following exposure to inorganic arsenic. The AS3MT gene e...

  8. Assessing multimedia/multipathway exposures to inorganic arsenic at population and individual level using MERLIN-Expo.

    PubMed

    Van Holderbeke, Mirja; Fierens, Tine; Standaert, Arnout; Cornelis, Christa; Brochot, Céline; Ciffroy, Philippe; Johansson, Erik; Bierkens, Johan

    2016-10-15

    In this study, we report on model simulations performed using the newly developed exposure tool, MERLIN-Expo, in order to assess inorganic arsenic (iAs) exposure to adults resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed to estimate external iAs exposure as well as the toxicologically relevant As (tAs, i.e., iAs, MMA and DMA) body burden in adults living in the vicinity of the former industrial sites as compared to adults living in adjacent areas and a reference area. Two scenarios are discussed: a first scenario studying exposure to iAs at the aggregated population level and a second scenario studying exposure at the individual level for a random sub-sample of subjects in each of the three different study areas. These two scenarios only differ in the type of human related input data (i.e., time-activity data, ingestion rates and consumption patterns) that were used, namely averages (incl. probability density functions, PDFs) in the simulation at population level and subject-specific values in the simulation at individual level. The model predictions are shown to be lower than the corresponding biomonitoring data from the monitoring campaign. Urinary tAs levels in adults, irrespective of the area they lived in, were under-predicted by MERLIN-Expo by 40% on average. The model predictions for individual adults, by contrast, under-predict the biomonitoring data by 7% on average, but with more important under-predictions for subjects at the upper end of exposure. Still, average predicted urinary tAs levels from the simulations at population level and at individual level overlap, and, at least for the current case, lead to similar conclusions. These results constitute a first and partial verification of the model performance of MERLIN-Expo when dealing with iAs in a complex site-specific exposure scenario, and demonstrate the robustness of the modelling tool for these situations.

  9. Inorganic arsenic in drinking water and bladder cancer: a meta-analysis for dose-response assessment.

    PubMed

    Chu, Huei-An; Crawford-Brown, Douglas J

    2006-12-01

    Most arsenic cancer risk assessments have been based solely on epidemiological studies to characterize the dose-response relationship for arsenic-associated cancer and to perform risk calculations. However, current epidemiological evidence is too inconsistent and fraught with uncertainty regarding arsenic exposure to provide reliable estimates. This makes it hard to draw a firm conclusion about the shape and slope of the dose-response relationship from individual studies. Meta-analysis is a statistical approach to combining results across studies and offers expanded opportunities for obtaining an improved dose-response relationship. In this study, a meta-analysis of arsenic studies was conducted by combining seven epidemiological studies from different regions to get an overall dose-response relationship between the amount of arsenic intake and the excess probability of bladder cancer. Both the fixed-effect and random-effect models were used to calculate the averaged coefficient of the linear-logistic regression model. A homogeneity test was also conducted. The final product of this research is an aggregated dose-response model in the range of empirical observation of arsenic. Considering the most recent arsenic MCL (maximum contaminant level, i.e. 10microg/L), the associated bladder cancer risk (lifetime excess probability) at this MCL is 2.29 x 10-5.

  10. Oxidation state-differentiated measurement of aqueous inorganic arsenic by continuous flow electrochemical arsine generation coupled to gas-phase chemiluminescence detection.

    PubMed

    Sengupta, Mrinal K; Dasgupta, Purnendu K

    2011-12-15

    The electrochemical reduction of inorganic As on a graphite cathode depends on the current density. We observed that while only inorganic As(III) is reduced to AsH(3) at low current densities, at high current densities both forms of inorganic As are reduced. We describe a unique electrochemical reactor in which the cylindrical anode compartment is isolated from the outer concentric cathode compartment by a Nafion tube in which a hole is deliberately made and the entire anode compartment is inside the cylindrical cavity of a small volume (∼115 μL) cathode chamber. The evolved arsine is then quantitated by gas-phase chemiluminescence (GPCL) reaction with ozone; the latter is generated from oxygen formed during electrolysis. For the dimensions used, inorganic As(III) can be selectively determined at a current of 0.1 A while total inorganic As (both As(III) and As(V)) respond equally at an applied electrolysis current at 0.85 A, without any sample treatment. For a 1-mL sample, the system provides a limit of detection (LOD, S/N = 3) of 0.09 μg/L for total As (i = 0.85 A) and an LOD of 0.76 μg/L for As(III) (i = 0.10 A); As(V) is obtained by difference. Comparison of ICP-MS results for total As in groundwater samples that span a large range of concentration and total inorganic As determined by the present method showed a high correlation (r(2) = 0.9975) and a near unity slope. The basic electrochemical arsine generation technique and current-differentiated oxidation state speciation should be applicable as the front end to many other arsenic measurements techniques, including atomic spectrometry. PMID:22035322

  11. Bioaccumulation of arsenic by freshwater algae and the application to the removal of inorganic arsenic from an aqueous phase. Part II. By Chlorella vulgaris isolated from arsenic-polluted environment

    SciTech Connect

    Maeda, S.; Nakashima, S.; Takeshita, T.; Higashi, S.

    1985-01-01

    Green algae, Chlorella vulgaris Beijerinck var. vulgaris, isolated from an arsenic-polluted environment, was examined for the effects of arsenic levels, arsenic valence, temperature illumination intensity, phosphate levels, metabolism inhibitors, heat treatment on the growth, and arsenic bioaccumulation. The following conclusions were reached from the experimental results: (a) The growth of the cell increased with an increase of arsenic(V) levels of the medium up to 1000 ppm, and the cell survived even at 10,000 ppm; (b) The arsenic bioaccumulation increased with an increase of the arsenic level. The maximum accumulation of arsenic was about 50,000 ..mu..g As/g dry cell; (c) The growth decreased with an increase of the arsenic(III) level and the cell was cytolyzed at levels higher than 40 ppm; (d) No arsenic(V) was bioaccumulated by a cell which had been pretreated with dinitrophenol (respiratory inhibitor) or with heat. Little effect of NaN/sub 3/ (photosynthesis inhibitor) on the bioaccumulation was observed. 8 references, 2 figures, 6 tables.

  12. Lipid oxidative damage and distribution of inorganic arsenic and its metabolites in the rat nervous system after arsenite exposure: influence of alpha tocopherol supplementation.

    PubMed

    García-Chávez, Erika; Jiménez, Ismael; Segura, Bertha; Del Razo, Luz M

    2006-12-01

    Inorganic arsenic (iAs) exposure causes peripheral neuropathy. Oxidative effects caused by iAs exposure in peripheral nerves have been incompletely characterized. This study analyzed arsenic and lipid oxidative damage in the brain, spinal cord, and sciatic and sensory sural nerves following arsenite exposure. This study also explored whether alpha tocopherol (alpha-TOC) administration mitigates arsenite-induced oxidative damage. Thiobarbituric acid-reactive substance (TBARS) levels and distributions of iAs and its metabolites were evaluated in male Wistar rats following 30d of sodium arsenite exposure (10mg/kg bodyweight (bw)/d, by gavage). A second group also received alpha-TOC (125mg/kg bw/d, by gavage) during the final 20d of arsenite administration. Arsenite exposure caused increased TBARS levels within each region of the nervous system; oxidative stress was most pronounced in the sural and sciatic nerves. In addition there was a positive quadratic relationship between TBARS levels and the concentration of arsenicals found in the nervous system (r(2)=0.878, p<0.001). Dimethylarsenic was the predominant metabolite of iAs found. Animals alpha-TOC-treated had a 1.7-5.2-fold reduction in TBARS levels when compared with rats that received iAs alone. These results suggest that oxidative damage may be the main mechanism of toxicity induced by exposure of the peripheral nervous system to arsenite and that such damage could be attenuated by alpha-TOC-supplementation.

  13. Simultaneous separation of 17 inorganic and organic arsenic compounds in marine biota by means of high-performance liquid chromatography/inductively coupled plasma mass spectrometry.

    PubMed

    Kohlmeyer, Ute; Kuballa, Jürgen; Jantzen, Eckard

    2002-01-01

    A method using high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) has been developed to determine inorganic arsenic (arsenite, arsenate) along with organic arsenic compounds (monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, arsenocholine, trimethylarsine oxide, tetramethylarsonium ion and several arsenosugars) in fish, mussel, oyster and marine algae samples. The species were extracted by means of a methanol/water mixture and a dispersion unit in 2 min, with extraction efficiencies ranging from 83 to 107% in the different organisms. Up to 17 different species were determined within 15 min on an anion-exchange column, using a nitric acid gradient and an ion-pairing reagent. As all species are shown in one chromatogram, a clear overview of arsenic distribution patterns in different marine organisms is given. Arsenobetaine is the major compound in marine animals whereas arsenosugars and arsenate are dominant in marine algae. The method was validated with CRM DORM-2 (dogfish muscle). Concentrations were within the certified limits and low detection limits of 8 ng g(-1) (arsenite) to 50 ng g(-1) (arsenate) were obtained. PMID:11968129

  14. Epigenomic Adaptation to Low Dose Radiation

    SciTech Connect

    Gould, Michael N.

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  15. Genomic Instability Induced by Low Dose Irradiation

    SciTech Connect

    Evans, Helen H. Sedwick, David W. Veigl, Martina L.

    2006-07-15

    The goal of this project was to determine if genomic instability could be initiated by poorly repaired DNA damage induced by low doses of ionizing radiation leading to a mutator phenotype. Human cells were irradiated, then transfected with an unirradiated reporter gene at various times AFTER exposure. The vector carried an inactive GFP gene that fluoresced when the gene was activated by a delayed mutation. Fluorescent cells were measured in the interval of 50 hours to four days after transfection. The results showed that delayed mutations occurred in these cells after exposure to relatively low doses (0.3-1.0 Gy) of low or high ionizing radiation, as well as after treatment with hyrodgen peroxide (30-100 micromolar). The occurrence was both dose and time dependent, often decreasing at higher doses and later times. No marked difference was observed between the response of mis-match repair-proficient and -deficient cell lines. Although the results were quite reproducible within single experiments, difficulties were observed from experiment to experiment. Different reagents and assays were tested, but no improvement resulted. We concluded that this method is not sufficiently robust or consisent to be useful in the assay of the induction of genomic instability by low doses of radiation, at least in these cell lines under our conditions.

  16. Arsenic in Food

    MedlinePlus

    ... inorganic forms. The FDA has been measuring total arsenic concentrations in foods, including rice and juices, through its Total Diet Study program ... readily take up much arsenic from the ground, rice is different because it takes ... has high levels of less toxic organic arsenic. Do organic foods ...

  17. Cryptic exposure to arsenic.

    PubMed

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

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity. PMID:16394429

  18. Cryptic exposure to arsenic.

    PubMed

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

    2005-01-01

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

  19. *Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate ciona intestinalis

    EPA Science Inventory

    Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+3 oxidation state) methyltransferase (As3mt) , yielding mono-, di-, and trimethylated arsenicals. A comparative genomic approach focused on Ciona intestinaJis, an invertebrate chordate, was u...

  20. [Low dose naltrexone for treatment of pain].

    PubMed

    Plesner, Karin Bruun; Vægter, Henrik Bjarke; Handberg, Gitte

    2015-10-01

    Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy. PMID:26509454

  1. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance

    PubMed Central

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc- (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

  2. Hijacking microglial glutathione by inorganic arsenic impels bystander death of immature neurons through extracellular cystine/glutamate imbalance.

    PubMed

    Singh, Vikas; Gera, Ruchi; Kushwaha, Rajesh; Sharma, Anuj Kumar; Patnaik, Satyakam; Ghosh, Debabrata

    2016-01-01

    Arsenic-induced altered microglial activity leads to neuronal death, but the causative mechanism remains unclear. The present study showed, arsenic-exposed (10 μM) microglial (N9) culture supernatant induced bystander death of neuro-2a (N2a), which was further validated with primary microglia and immature neuronal cultures. Results indicated that arsenic-induced GSH synthesis by N9 unfavorably modified the extracellular milieu for N2a by lowering cystine and increasing glutamate concentration. Similar result was observed in N9-N2a co-culture. Co-exposure of arsenic and 250 μM glutamate, less than the level (265 μM) detected in arsenic-exposed N9 culture supernatant, compromised N2a viability which was rescued by cystine supplementation. Therefore, microglia executes bystander N2a death by competitive inhibition of system Xc(-) (xCT) through extracellular cystine/glutamate imbalance. We confirmed the role of xCT in mediating bystander N2a death by siRNA inhibition studies. Ex-vivo primary microglia culture supernatant from gestationally exposed mice measured to contain lower cystine and higher glutamate compared to control and N-acetyl cysteine co-treated group. Immunofluorescence staining of brain cryosections from treated group showed more dead immature neurons with no such effect on microglia. Collectively, we showed, in presence of arsenic microglia alters cystine/glutamate balance through xCT in extracellular milieu leading to bystander death of immature neurons. PMID:27477106

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

    EPA Science Inventory

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

  4. Low-dose radiation exposure and carcinogenesis.

    PubMed

    Suzuki, Keiji; Yamashita, Shunichi

    2012-07-01

    Absorption of energy from ionizing radiation by the genetic material in the cell leads to damage to DNA, which in turn leads to cell death, chromosome aberrations and gene mutations. While early or deterministic effects result from organ and tissue damage caused by cell killing, latter two are considered to be involved in the initial events that lead to the development of cancer. Epidemiological studies have demonstrated the dose-response relationships for cancer induction and quantitative evaluations of cancer risk following exposure to moderate to high doses of low-linear energy transfer radiation. A linear, no-threshold model has been applied to assessment of the risks resulting from exposure to moderate and high doses of ionizing radiation; however, a statistically significant increase has hardly been described for radiation doses below 100 mSv. This review summarizes our current knowledge of the physical and biological features of low-dose radiation and discusses the possibilities of induction of cancer by low-dose radiation. PMID:22641644

  5. Effects of compost amended lead-arsenate contaminated soils on total and inorganic arsenic concentration in rice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice (Oryza sativa L.), a staple crop for over fifty percent of the world’s population, is also a source of dietary arsenic because of its efficiency at accumulating As. Pesticides containing As were once widely used in agriculture, and some soils in which these pesticides were used are now being u...

  6. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    PubMed

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning.

  7. Protective effect of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic toxicity in rats induced by inorganic arsenic.

    PubMed

    Jiang, Yanhua; Wang, Lianzhu; Yao, Lin; Liu, Zhantao; Gao, Hua

    2013-09-01

    Arsenic, a potent environmental toxic agent, causes various hazardous effects on human health. This study was performed to evaluate the protective effects of edible marine algae, Laminaria japonica and Porphyra haitanensis, on subchronic stress of rats induced by arsenic trioxide (As2O3). The co-treatment of marine algae could slightly increase the growth rates of body weights compared to the As2O3-treated group. The marine algae application restored liver and renal function by preventing the increment in the activities of alanine transaminase and alkaline phosphatase, and the levels of total protein, blood urea nitrogen, and creatinine. The increase in the contents of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and decrease in the contents of high density lipoprotein cholesterol were observed in algae co-treated groups which indicated that marine algae could reverse the abnormal lipid metabolisms induced by arsenic. Moreover, these algae could protect the rats from lipid peroxidation by restoring the depletion of superoxide dismutase and glutathione peroxidase activities and sulfhydryl group contents, and lowering the enhanced malondialdehyde contents. Therefore, evidences indicate that L. japonica and P. haitanensis can serve as an effective regimen for treating arsenic poisoning. PMID:23842700

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

    PubMed

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

    2010-01-01

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

  9. Nitric acid-based partial-digestion method for selective determination of inorganic arsenic in hijiki and application to soaked hijiki.

    PubMed

    Hamano-Nagaoka, Megumi; Hanaoka, Ken'ichi; Usui, Masakatsu; Nishimura, Tsutomu; Maitani, Tamio

    2008-04-01

    Because there is a great difference between the toxicity of inorganic arsenic (As) and organic As in food, the JECFA has set a PTWI value for inorganic As (iAs) rather than for total As. The difference in As toxicity makes it necessary to extract iAs completely from food samples for toxicological analysis, but complete extraction of As from most foods including seaweed has not been achieved to date. We developed a partial-digestion method that uses nitric acid as a solvent in order to extract almost all arsenicals from the solid matrix of hijiki (Hizikia fusiforme, a brown alga) samples. In this method, organic As species were not converted into iAs. HPLC/ICP-MS was then used to determine the concentration of iAs. Total As was measured by hydride generation-atomic absorption spectrometry. The adopted conditions for 0.1 g of ground fine powder sample were: 2 mL of 0.3 mol/L nitric acid; heating, 80 degrees C for 1 hr. Intra-laboratory validation of the method showed good precision and accuracy. The repeatability and intermediate precision for iAs were 1.5% and 1.5%, respectively. The LOD and LOQ for iAs were 0.14 and 0.46 mg/kg dry weight, respectively. Recovery studies performed by spiking 0.5 mg/kg dry weight as the LOQ level and by spiking 3 mg/kg dry weight as the iAs concentration of an un-spiked hijiki sample showed good accuracy. The method was applied to hijiki samples after a water soaking process and a water soaking and simmering process. The results suggested that the As concentration in hijiki after both processes was lower than that before the treatments and that the water soaking and simmering process reduced the iAs concentration much more effectively than the water soaking process. PMID:18503244

  10. Atrazine is primarily responsible for the toxicity of long-term exposure to a combination of atrazine and inorganic arsenic in the nigrostriatal system of the albino rat.

    PubMed

    Bardullas, Ulises; Giordano, Magda; Rodríguez, Verónica Mireya

    2013-01-01

    Chronic and simultaneous exposure to a variety of chemicals present in the environment is an unavoidable fact. However, given the complexity of studying chemical mixtures, most toxicological studies have focused on the effects of short-term exposure to single substances. The aim of this study was to evaluate the effects on the nigrostriatal system of the chronic, simultaneous exposure to two widely distributed substances that have been identified as potential dopaminergic system toxicants, inorganic arsenic (iAs) and atrazine (ATR). Six groups of rats were treated daily for one year with atrazine (10mg ATR/kg), inorganic arsenic (0.5 or 50mgiAs/L of drinking water), or a combination of ATR+0.5mgiAs/L or ATR+50mgiAs/L. The 50mgiAs/L group showed locomotor hypoactivity, while all treatments decreased motor coordination in contrast no effects of treatment were found on the place and response learning tasks. Regarding markers for liver and muscle damage, there were no differences between groups in creatine kinase (CK) or aspartate transaminase (AST) activities, while decreases in lactate dehydrogenase (LDH) levels were found in some exposed groups. The striatal DA content was significantly reduced in ATR, 0.5mgiAs/L, ATR+0.5mgiAs/L, and ATR+50mgiAs/L groups, in comparison to the control group. The number of mesencephalic tyrosine hydroxylase positive cells decreased in the ATR and ATR+0.5mgiAs/L groups compared to the control. In contrast, immunoreactivity to cytochrome oxidase was reduced compared to the control in all treated groups, except for the group treated with 0.5iAsmg alone. Our results indicate that ATR has deleterious effects on dopaminergic neurons and that the combination of ATR and iAs does not exacerbate these effects.

  11. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

    Pesticides applied in agriculture can affect the structure and function of nontarget populations at lower doses and for longer timespans than predicted by the current risk assessment frameworks. We identified a mechanism for this observation. The populations of an aquatic invertebrate (Culex pipiens) exposed over several generations to repeated pulses of low concentrations of the neonicotinoid insecticide (thiacloprid) continuously declined and did not recover in the presence of a less sensitive competing species (Daphnia magna). By contrast, in the absence of a competitor, insecticide effects on the more sensitive species were only observed at concentrations 1 order of magnitude higher, and the species recovered more rapidly after a contamination event. The underlying processes are experimentally identified and reconstructed using a simulation model. We conclude that repeated toxicant pulse of populations that are challenged with interspecific competition may result in a multigenerational culmination of low-dose effects. PMID:23859631

  12. Low-Dose Radiotherapy in Indolent Lymphoma

    SciTech Connect

    Rossier, Christine; Schick, Ulrike; Miralbell, Raymond; Mirimanoff, Rene O.; Weber, Damien C.; Ozsahin, Mahmut

    2011-11-01

    Purpose: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). Methods and Materials: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 x 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). Results: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. Conclusions: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.

  13. Low dose neutron late effects: Cataractogenesis

    SciTech Connect

    Worgul, B.V.

    1991-12-01

    The work is formulated to resolve the uncertainty regarding the relative biological effectiveness (RBE) of low dose neutron radiation. The study exploits the fact that cataractogenesis is sensitive to the inverse dose-rate effect as has been observed with heavy ions and was an endpoint considered in the follow-up of the A-bomb survivors. The neutron radiations were initiated at the Radiological Research Accelerator facility (RARAF) of the Nevis Laboratory of Columbia University. Four week old ({plus minus} 1 day) rats were divided into eight dose groups each receiving single or fractionated total doses of 0.2, 1.0, 5.0 and 25.0 cGy of monoenergetic 435 KeV neutrons. Special restraining jigs insured that the eye, at the midpoint of the lens, received the appropriate energy and dose with a relative error of {plus minus}5%. The fractionation regimen consisted of four exposures, each administered at three hour ({plus minus}) intervals. The neutron irradiated groups are being compared to rats irradiated with 250kVp X-rays in doses ranging from 0.5 to 7 Gy. The animals are being examined on a biweekly basis utilizing conventional slit-lamp biomicroscopy and the Scheimpflug Slit Lamp Imaging System (Zeiss). The follows-ups, entering their second year, will continue throughout the life-span of the animals. This is essential inasmuch as given the extremely low doses which are being utilized clinically detectable opacities were not anticipated until a significant fraction of the life span has lapsed. Current data support this contention. At this juncture cataracts in the irradiated groups are beginning to exceed control levels.

  14. Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al; Buchner, Stephen; LaBel, Kenneth

    2011-01-01

    We have presented results of ultra-low dose rate irradiations (< or = 10 mrad(Si)/s) for a variety of radiation hardened and commercial linear bipolar devices. We observed low dose rate enhancement factors exceeding 1.5 in several parts. The worst case of dose rate enhancement resulted in functional failures, which occurred after 10 and 60 krad(Si), for devices irradiated at 0.5 and 10 mrad(Si)/s, respectively. Devices fabricated with radiation hardened processes and designs also displayed dose rate enhancement at below 10 mrad(Si)/s. Furthermore, the data indicated that these devices have not reached the damage saturation point. Therefore the degradation will likely continue to increase with increasing total dose, and the low dose rate enhancement will further magnify. The cases presented here, in addition to previous examples, illustrate the significance and pervasiveness of low dose rate enhancement at dose rates lower than 10 mrad(Si). These results present further challenges for radiation hardness assurance of bipolar linear circuits, and raise the question of whether the current standard test dose rate is conservative enough to bound degradations due to ELDRS.

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

    PubMed Central

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

    2012-01-01

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

  16. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    SciTech Connect

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  17. Role of Metabolism in Arsenic-Induced Toxicity: Identification and Quantification of Arsenic Metabolites in Tissues and Excreta

    EPA Science Inventory

    Arsenic is a known toxicant and carcinogen. Methylation of inorganic arsenic was once thought to be a detoxification mechanism because of the rapid excretion and relatively lower toxicity of the pentavalent organic arsenical metabolites. Advances in analytical chemistry have al...

  18. Arsenic Metabolism and Distribution in Developing Organisms

    EPA Science Inventory

    A growing body of evidence suggests that exposure to inorganic arsenic during early life has long term adverse effects. The extent of exposure to inorganic arsenic and its methylated metabolites in utero is determined not only by the rates of formation and transfer of arsenicals...

  19. Measurements of Arsenic in the Urine and Nails of Individuals Exposed to Low Concentrations of Arsenic in Drinking Water From Private Wells in a Rural Region of Québec, Canada.

    PubMed

    Gagnon, Fabien; Lampron-Goulet, Eric; Normandin, Louise; Langlois, Marie-France

    2016-01-01

    Chronic exposure to inorganic arsenic leads to an increased risk of cancer. A biological measurement was conducted in 153 private well owners and their families consuming water contaminated by inorganic arsenic at concentrations that straddle 10 μg/L. The relationship between the external dose indicators (concentration of inorganic arsenic in wells and daily well water inorganic arsenic intake) and the internal doses (urinary arsenic--sum of As(III), DMA, and MMA, adjusted for creatinine--and total arsenic in toenails) was evaluated using multiple linear regressions, controlling for age, gender, dietary sources of arsenic, and number of cigarettes smoked. It showed that urinary arsenic was associated with concentration of inorganic arsenic in wells (p < .001) and daily well water inorganic arsenic intake (p < .001) in adults, and with daily well water inorganic arsenic intake (p = .017) and rice consumption (p = .022) in children (n = 43). The authors' study reinforces the drinking-water quality guidelines for inorganic arsenic.

  20. Advancing Dose-Response Assessment Methods for Environmental Regulatory Impact Analysis: A Bayesian Belief Network Approach Applied to Inorganic Arsenic

    PubMed Central

    Zabinski, Joseph W.; Garcia-Vargas, Gonzalo; Rubio-Andrade, Marisela; Fry, Rebecca C.; Gibson, Jacqueline MacDonald

    2016-01-01

    Dose-response functions used in regulatory risk assessment are based on studies of whole organisms and fail to incorporate genetic and metabolomic data. Bayesian belief networks (BBNs) could provide a powerful framework for incorporating such data, but no prior research has examined this possibility. To address this gap, we develop a BBN-based model predicting birthweight at gestational age from arsenic exposure via drinking water and maternal metabolic indicators using a cohort of 200 pregnant women from an arsenic-endemic region of Mexico. We compare BBN predictions to those of prevailing slope-factor and reference-dose approaches. The BBN outperforms prevailing approaches in balancing false-positive and false-negative rates. Whereas the slope-factor approach had 2% sensitivity and 99% specificity and the reference-dose approach had 100% sensitivity and 0% specificity, the BBN's sensitivity and specificity were 71% and 30%, respectively. BBNs offer a promising opportunity to advance health risk assessment by incorporating modern genetic and metabolomic data.

  1. Emissions of inorganic and organic arsenic compounds via the leachate pathway from pretreated municipal waste materials: a landfill reactor study.

    PubMed

    Huang, J H; Ilgen, G; Vogel, D; Michalzik, B; Hantsch, S; Tennhardt, L; Bilitewski, B

    2009-09-15

    The emission of arsenic (As) with leachate from mechanically biologically pretreated municipal solid waste (MBP-MSW) was quantified over one year using landfill simulation reactors. Arsenic mobilization and transformation processes were studied by simulating different environmental conditions (anoxic conditions with underlying soil or oxic/anoxic conditions). Amounts of mono-, di-, and trimethylated As in MBP-MSW prior to simulation were < 48 microg As kg(-1) and were magnified to 300-390 microg As kg(-1) under anoxic conditions, whereas methylated As was undetectable in the oxic setup. The highest leachate concentrations (up to 84 microg L(-1)) occurred during the first four weeks of manipulation. The annual Astotal release with leachates averaged 19.6, 7.6, and 4.5 microg kg(-1) under an anoxic environment with underlying soil, oxic conditions, and anoxic conditions, respectively, with 15-50% occurring as organic As. The annually released As represented 0.2-0.8% of the Astotal pool, suggesting that As mobilization from waste is a slow process. The anoxia diminished As release rates, whereas anoxic conditions with underlying soil material elevated the As mobilization, probably due to reductive dissolution of soil-derived Fe and Mn (hydr)oxides. The mass balance of methylated As in MBP-MSW and leachates before and after the treatments highlights As methylation under anoxic conditions and demethylation under oxic landfill conditions.

  2. PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC

    EPA Science Inventory

    PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC.

    Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. In contrast,
    there is no accepted experimental animal model of inorganic arsenic carcinogenesis.
    Proposed mechanisms/modes of action for a...

  3. Inorganic phosphate-triggered release of anti-cancer arsenic trioxide from a self-delivery system: an in vitro and in vivo study

    NASA Astrophysics Data System (ADS)

    Chen, Fei-Yan; Yi, Jing-Wei; Gu, Zhe-Jia; Tang, Bin-Bing; Li, Jian-Qi; Li, Li; Kulkarni, Padmakar; Liu, Li; Mason, Ralph P.; Tang, Qun

    2016-03-01

    On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced toxicity compared to the free drug. These results suggest a new drug delivery strategy which might be applied for ATO therapy on solid tumors.On-demand drug delivery is becoming feasible via the design of either exogenous or endogenous stimulus-responsive drug delivery systems. Herein we report the development of gadolinium arsenite nanoparticles as a self-delivery platform to store, deliver and release arsenic trioxide (ATO, Trisenox), a clinical anti-cancer drug. Specifically, unloading of the small molecule drug is triggered by an endogenous stimulus: inorganic phosphate (Pi) in the blood, fluid, and soft or hard tissue. Kinetics in vitro demonstrated that ATO is released with high ON/OFF specificity and no leakage was observed in the silent state. The nanoparticles induced tumor cell apoptosis, and reduced cancer cell migration and invasion. Plasma pharmacokinetics verified extended retention time, but no obvious disturbance of phosphate balance. Therapeutic efficacy on a liver cancer xenograft mouse model was dramatically potentiated with reduced

  4. Low-dose effects of hormones and endocrine disruptors.

    PubMed

    Vandenberg, Laura N

    2014-01-01

    Endogenous hormones have effects on tissue morphology, cell physiology, and behaviors at low doses. In fact, hormones are known to circulate in the part-per-trillion and part-per-billion concentrations, making them highly effective and potent signaling molecules. Many endocrine-disrupting chemicals (EDCs) mimic hormones, yet there is strong debate over whether these chemicals can also have effects at low doses. In the 1990s, scientists proposed the "low-dose hypothesis," which postulated that EDCs affect humans and animals at environmentally relevant doses. This chapter focuses on data that support and refute the low-dose hypothesis. A case study examining the highly controversial example of bisphenol A and its low-dose effects on the prostate is examined through the lens of endocrinology. Finally, the chapter concludes with a discussion of factors that can influence the ability of a study to detect and interpret low-dose effects appropriately.

  5. Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite

    SciTech Connect

    Sykora, Peter; Snow, Elizabeth T.

    2008-05-01

    Base excision repair (BER) is crucial for development and for the repair of endogenous DNA damage. However, unlike nucleotide excision repair, the regulation of BER is not well understood. Arsenic, a well-established human carcinogen, is known to produce oxidative DNA damage, which is repaired primarily by BER, whilst high doses of arsenic can also inhibit DNA repair. However, the mechanism of repair inhibition by arsenic and the steps inhibited are not well defined. To address this question we have investigated the regulation of DNA polymerase {beta} (Pol {beta}) and AP endonuclease (APE1), in response to low, physiologically relevant doses of arsenic. GM847 lung fibroblasts and HaCaT keratinocytes were exposed to sodium arsenite, As(III), and mRNA, protein levels and BER activity were assessed. Both Pol {beta} and APE1 mRNA exhibited significant dose-dependant down regulation at doses of As(III) above 1 {mu}M. However, at lower doses Pol {beta} mRNA and protein levels, and consequently, BER activity were significantly increased. In contrast, APE1 protein levels were only marginally increased by low doses of As(III) and there was no correlation between APE1 and overall BER activity. Enzyme supplementation of nuclear extracts confirmed that Pol {beta} was rate limiting. These changes in BER correlated with overall protection against sunlight UV-induced toxicity at low doses of As(III) and produced synergistic toxicity at high doses. The results provide evidence that changes in BER due to low doses of arsenic could contribute to a non-linear, threshold dose response for arsenic carcinogenesis.

  6. Improved diffusive gradients in thin films (DGT) measurement of total dissolved inorganic arsenic in waters and soils using a hydrous zirconium oxide binding layer.

    PubMed

    Sun, Qin; Chen, Jing; Zhang, Hao; Ding, Shiming; Li, Zhu; Williams, Paul N; Cheng, Hao; Han, Chao; Wu, Longhua; Zhang, Chaosheng

    2014-03-18

    A high-capacity diffusive gradients in thin films (DGT) technique has been developed for measurement of total dissolved inorganic arsenic (As) using a long shelf life binding gel layer containing hydrous zirconium oxide (Zr-oxide). Both As(III) and As(V) were rapidly accumulated in the Zr-oxide gel and could be quantitatively recovered by elution using 1.0 M NaOH for freshwater or a mixture of 1.0 M NaOH and 1.0 M H2O2 for seawater. DGT uptake of As(III) and As(V) increased linearly with deployment time and was independent of pH (2.0-9.1), ionic strength (0.01-750 mM), the coexistence of phosphate (0.25-10 mg P L(-1)), and the aging of the Zr-oxide gel up to 24 months after production. The capacities of the Zr-oxide DGT were 159 μg As(III) and 434 μg As(V) per device for freshwater and 94 μg As(III) and 152 μg As(V) per device for seawater. These values were 5-29 times and 3-19 times more than those reported for the commonly used ferrihydrite and Metsorb DGTs, respectively. Deployments of the Zr-oxide DGT in As-spiked synthetic seawater provided accurate measurements of total dissolved inorganic As over the 96 h deployment, whereas ferrihydrite and Metsorb DGTs only measured the concentrations accurately up to 24 and 48 h, respectively. Deployments in soils showed that the Zr-oxide DGT was a reliable and robust tool, even for soil samples heavily polluted with As. In contrast, As in these soils was underestimated by ferrihydrite and Metsorb DGTs due to insufficient effective capacities, which were likely suppressed by the competing effects of phosphate.

  7. Acute arsenic ingestion.

    PubMed

    Levin-Scherz, J K; Patrick, J D; Weber, F H; Garabedian, C

    1987-06-01

    A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide. He died within 37 hours despite intensive treatment that included intramuscular dimercaprol and hemodialysis. Hemodynamic and laboratory data are presented illustrating the multisystem toxicities of inorganic arsenic. Hemodialysis, previously described as an effective therapeutic adjunct, was shown to be ineffective in this case.

  8. Speciation of inorganic arsenic in drinking water by wavelength-dispersive X-ray fluorescence spectrometry after in situ preconcentration with miniature solid-phase extraction disks.

    PubMed

    Hagiwara, Kenta; Inui, Tetsuo; Koike, Yuya; Aizawa, Mamoru; Nakamura, Toshihiro

    2015-03-01

    A rapid and simple method using wavelength-dispersive X-ray fluorescence (WDXRF) spectrometry after in situ solid-phase extraction (SPE) was developed for the speciation and evaluation of the concentration of inorganic arsenic (As) in drinking water. The method involves the simultaneous collection of As(III) and As(V) using 13 mm ϕ SPE miniature disks. The removal of Pb(2+) from the sample water was first conducted to avoid the overlapping PbLα and AsKα spectra on the XRF spectrum. To this end, a 50 mL aqueous sample (pH 5-9) was passed through an iminodiacetate chelating disk. The filtrate was adjusted to pH 2-3 with HCl, and then ammonium pyrrolidine dithiocarbamate solution was added. The solution was passed through a hydrophilic polytetrafluoroethylene filter placed on a Zr and Ca loaded cation-exchange disk at a flow rate of 12.5 mL min(-1) to separate As(III)-pyrrolidine dithiocarbamate complex and As(V). Each SPE disk was affixed to an acrylic plate using adhesive cellophane tape, and then examined by WDXRF spectrometry. The detection limits of As(III) and As(V) were 0.8 and 0.6 μg L(-1), respectively. The proposed method was successfully applied to screening for As speciation and concentration evaluation in spring water and well water.

  9. [Indications for low-dose CT in the emergency setting].

    PubMed

    Poletti, Pierre-Alexandre; Andereggen, Elisabeth; Rutschmann, Olivier; de Perrot, Thomas; Caviezel, Alessandro; Platon, Alexandra

    2009-08-19

    CT delivers a large dose of radiation, especially in abdominal imaging. Recently, a low-dose abdominal CT protocol (low-dose CT) has been set-up in our institution. "Low-dose CT" is almost equivalent to a single standard abdominal radiograph in term of dose of radiation (about one sixth of those delivered by a standard CT). "Low-dose CT" is now used routinely in our emergency service in two main indications: patients with a suspicion of renal colic and those with right lower quadrant pain. It is obtained without intravenous contrast media. Oral contrast is given to patients with suspicion of appendicitis. "Low-dose CT" is used in the frame of well defined clinical algorithms, and does only replace standard CT when it can reach a comparable diagnostic quality.

  10. Measurement of inorganic arsenic species in rice after nitric acid extraction by HPLC-ICPMS: verification using XANES.

    PubMed

    Maher, W; Foster, S; Krikowa, F; Donner, E; Lombi, E

    2013-06-01

    The measurement of As species in rice is normally accomplished by extraction followed by HPLC-ICPMS analysis. This method, however, has not been comprehensively validated by comparing these speciation results with XANES, which does not require sample extraction, due to the challenge of conducting XANES analysis at very low As concentrations. In this study As speciation data using nitric acid extraction/HPLC-ICPMS and XANES are compared to verify the efficacy of using 2% v/v nitric acid extraction and HPLC-ICPMS to measure inorganic As, DMA, and MA in reference rice materials and common rice varieties obtainable in Australia. Total As and As species (As(III), As(V), DMA, and MA) concentrations measured in 8 reference materials were in agreement with published values. XANES analysis was performed on 5 samples having total As concentrations ranging from 0.198 to 0.335 μg g(-1). XANES results gave similar proportions of total As(III), As(V), and DMA to HPLC-ICPMS. XANES was able to distinguish two forms of As(III): As(III) and As(III)GSH. Total As concentrations in rice samples varied from 0.006 to 0.45 μg g(-1) As (n = 47) with a mean ± std of 0.127 ± 0.112 μg g(-1) As with most As present as inorganic species (63 ± 26%). DMA was found in nearly all the rice samples with the majority of samples containing concentrations below 0.05 μg g(-1) As while MA concentrations were negligible (<0.003 μg g(-1) As). Six rice varieties produced in Australia, China, and Spain all had elevated DMA concentrations (0.170-0.399 μg g(-1) As) that were correlated with total As concentrations (r(2) = 0.7518). In conclusion, comparison of As speciation by HPLC-ICPMS and XANES showed that similar As species were detected indicating the appropriateness of using 2% v/v nitric acid for extraction of rice prior to speciation. Common rice varieties obtainable in Australia generally have low As concentrations with most As present as inorganic As. PMID:23621828

  11. Measurement of inorganic arsenic species in rice after nitric acid extraction by HPLC-ICPMS: verification using XANES.

    PubMed

    Maher, W; Foster, S; Krikowa, F; Donner, E; Lombi, E

    2013-06-01

    The measurement of As species in rice is normally accomplished by extraction followed by HPLC-ICPMS analysis. This method, however, has not been comprehensively validated by comparing these speciation results with XANES, which does not require sample extraction, due to the challenge of conducting XANES analysis at very low As concentrations. In this study As speciation data using nitric acid extraction/HPLC-ICPMS and XANES are compared to verify the efficacy of using 2% v/v nitric acid extraction and HPLC-ICPMS to measure inorganic As, DMA, and MA in reference rice materials and common rice varieties obtainable in Australia. Total As and As species (As(III), As(V), DMA, and MA) concentrations measured in 8 reference materials were in agreement with published values. XANES analysis was performed on 5 samples having total As concentrations ranging from 0.198 to 0.335 μg g(-1). XANES results gave similar proportions of total As(III), As(V), and DMA to HPLC-ICPMS. XANES was able to distinguish two forms of As(III): As(III) and As(III)GSH. Total As concentrations in rice samples varied from 0.006 to 0.45 μg g(-1) As (n = 47) with a mean ± std of 0.127 ± 0.112 μg g(-1) As with most As present as inorganic species (63 ± 26%). DMA was found in nearly all the rice samples with the majority of samples containing concentrations below 0.05 μg g(-1) As while MA concentrations were negligible (<0.003 μg g(-1) As). Six rice varieties produced in Australia, China, and Spain all had elevated DMA concentrations (0.170-0.399 μg g(-1) As) that were correlated with total As concentrations (r(2) = 0.7518). In conclusion, comparison of As speciation by HPLC-ICPMS and XANES showed that similar As species were detected indicating the appropriateness of using 2% v/v nitric acid for extraction of rice prior to speciation. Common rice varieties obtainable in Australia generally have low As concentrations with most As present as inorganic As.

  12. Response surface methodology based on central composite design as a chemometric tool for optimization of dispersive-solidification liquid-liquid microextraction for speciation of inorganic arsenic in environmental water samples.

    PubMed

    Asadollahzadeh, Mehdi; Tavakoli, Hamed; Torab-Mostaedi, Meisam; Hosseini, Ghaffar; Hemmati, Alireza

    2014-06-01

    Dispersive-solidification liquid-liquid microextraction (DSLLME) coupled with electrothermal atomic absorption spectrometry (ETAAS) was developed for preconcentration and determination of inorganic arsenic (III, V) in water samples. At pH=1, As(III) formed complex with ammonium pyrrolidine dithiocarbamate (APDC) and extracted into the fine droplets of 1-dodecanol (extraction solvent) which were dispersed with ethanol (disperser solvent) into the water sample solution. After extraction, the organic phase was separated by centrifugation, and was solidified by transferring into an ice bath. The solidified solvent was transferred to a conical vial and melted quickly at room temperature. As(III) was determined in the melted organic phase while As(V) remained in the aqueous layer. Total inorganic As was determined after the reduction of the pentavalent forms of arsenic with sodium thiosulphate and potassium iodide. As(V) was calculated by difference between the concentration of total inorganic As and As(III). The variable of interest in the DSLLME method, such as the volume of extraction solvent and disperser solvent, pH, concentration of APDC (chelating agent), extraction time and salt effect, was optimized with the aid of chemometric approaches. First, in screening experiments, fractional factorial design (FFD) was used for selecting the variables which significantly affected the extraction procedure. Afterwards, the significant variables were optimized using response surface methodology (RSM) based on central composite design (CCD). In the optimum conditions, the proposed method has been successfully applied to the determination of inorganic arsenic in different environmental water samples and certified reference material (NIST RSM 1643e). PMID:24725860

  13. Response surface methodology based on central composite design as a chemometric tool for optimization of dispersive-solidification liquid-liquid microextraction for speciation of inorganic arsenic in environmental water samples.

    PubMed

    Asadollahzadeh, Mehdi; Tavakoli, Hamed; Torab-Mostaedi, Meisam; Hosseini, Ghaffar; Hemmati, Alireza

    2014-06-01

    Dispersive-solidification liquid-liquid microextraction (DSLLME) coupled with electrothermal atomic absorption spectrometry (ETAAS) was developed for preconcentration and determination of inorganic arsenic (III, V) in water samples. At pH=1, As(III) formed complex with ammonium pyrrolidine dithiocarbamate (APDC) and extracted into the fine droplets of 1-dodecanol (extraction solvent) which were dispersed with ethanol (disperser solvent) into the water sample solution. After extraction, the organic phase was separated by centrifugation, and was solidified by transferring into an ice bath. The solidified solvent was transferred to a conical vial and melted quickly at room temperature. As(III) was determined in the melted organic phase while As(V) remained in the aqueous layer. Total inorganic As was determined after the reduction of the pentavalent forms of arsenic with sodium thiosulphate and potassium iodide. As(V) was calculated by difference between the concentration of total inorganic As and As(III). The variable of interest in the DSLLME method, such as the volume of extraction solvent and disperser solvent, pH, concentration of APDC (chelating agent), extraction time and salt effect, was optimized with the aid of chemometric approaches. First, in screening experiments, fractional factorial design (FFD) was used for selecting the variables which significantly affected the extraction procedure. Afterwards, the significant variables were optimized using response surface methodology (RSM) based on central composite design (CCD). In the optimum conditions, the proposed method has been successfully applied to the determination of inorganic arsenic in different environmental water samples and certified reference material (NIST RSM 1643e).

  14. Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals.

    PubMed

    Liu, J; Liu, Y; Goyer, R A; Achanzar, W; Waalkes, M P

    2000-06-01

    Metallothionein (MT) is a low-molecular-weight, sulfhydryl-rich, metal-binding protein that can protect against the toxicity of cadmium, mercury, and copper. However, the role of MT in arsenic (As)-induced toxicity is less certain. To better define the ability of MT to modify As toxicity, MT-I/II knockout (MT-null) mice and the corresponding wild-type mice (WT) were exposed to arsenite [As(III)] or arsenate [As(V)] either through the drinking water for 48 weeks, or through repeated sc injections (5 days/week) for 15 weeks. Chronic As exposure increased tissue MT concentrations (2-5-fold) in the WT but not in MT-null mice. Arsenic by both routes produced damage to the liver (fatty infiltration, inflammation, and focal necrosis) and kidney (tubular cell vacuolization, inflammatory cell infiltration, and interstitial fibrosis) in both MT-null and WT mice. However, in MT-null mice, the pathological lesions were more frequent and severe when compared to WT mice. This was confirmed biochemically, in that, at the higher oral doses of As, blood urea nitrogen (BUN) levels were increased more in MT-null mice (60%) than in WT mice (30%). Chronic As exposures produced 2-10 fold elevation of serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha levels, with greater increases seen by repeated injections than by oral exposure, and again, MT-null mice had higher serum cytokines than WT mice after As exposure. Repeated As injections also decreased hepatic glutathione (GSH) by 35%, but GSH-peroxidase and GSH-reductase were minimally affected. MT-null mice were more sensitive than WT mice to the effect of GSH depletion by As(V). Hepatic caspase-3 activity was increased (2-3-fold) in both WT and MT-null mice, indicative of apoptotic cell death. In summary, chronic inorganic As exposure produced injuries to multiple organs, and MT-null mice are generally more susceptible than WT mice to As-induced toxicity regardless of route of exposure, suggesting that MT could be a

  15. Quantification of Adaptive Protection Following Low-dose Irradiation.

    PubMed

    Feinendegen, Ludwig E

    2016-03-01

    The question whether low doses and low dose-rates of ionizing radiation pose a health risk to people is of public, scientific and regulatory concern. It is a subject of intense debate and causes much fear. The controversy is to what extent low-dose effects, if any, cause or protect against damage such as cancer. Even if immediate molecular damage in exposed biological systems rises linearly with the number of energy deposition events (i.e., with absorbed dose), the response of the whole biological system to that damage is not linear. To understand how initial molecular damage affects a complex living system is the current challenge. PMID:26808882

  16. Occurrence and stability of inorganic and organic arsenic species in wines, rice wines and beers from Central European market.

    PubMed

    Huang, J-H; Hu, K-N; Ilgen, J; Ilgen, G

    2012-01-01

    We investigated in total 80 wine samples of different types and seven grape juice and 23 beer samples purchased from markets in Central Europe in order to understand the arsenic (As) speciation and help assess the potential As toxicity via intake of alcoholic beverages. Generally, total As concentrations in most samples investigated were below the drinking water limit 10 µg l(-1) published by the World Health Organization (WHO); ranging from 0.46 to 21.0 µg l(-1) As in red and white wines and from 0.75 to 13.4 µg l(-1) As in beers. In addition, concentrations of total As in rice wine and in rice beer were 0.63-6.07 and 3.69-8.23 µg l(-1) As, respectively. The total As concentrations in ice wine ranged from 7.94 to 18.8 µg l(-1) As, significantly higher than in white and red wine. Arsenite predominated as the As species in most of the wine samples, whereas arsenate was the dominant species in rice wine, beer and rice beer. Methyl As components were usually minor components in all wine and beer samples. Monomethylarsonic acid, dimethylarsinic acid and two additional unknown As species were frequently found in grape juice, late harvest and ice wine with higher sweetness. After air exposure, arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid were stable at 4°C for months, probably due to the acidic conditions of wine and beer samples. The presence of sulfite had little influence on As speciation in wine. Despite the predominance of more toxic arsenite and arsenate in wine and beer, the estimated weekly exposure to As (via consumption of beer, wine and rice wine) is low. The As intake per capita is 6.81 µg from beer, <1.93 µg from wine and 0.88 µg from rice wine, estimated using the median of total As concentration multiplied by the average consumption per capita of the corresponding beverage.

  17. Three-dimensional honeycomb-like structured zero-valent iron/chitosan composite foams for effective removal of inorganic arsenic in water.

    PubMed

    Su, Fengchao; Zhou, Hongjian; Zhang, Yunxia; Wang, Guozhong

    2016-09-15

    A facile freeze-drying method was presented to fabricate three dimensional (3D) honeycomb-like structured nanoscale zero-valent iron/chitosan composite foams (ICCFs) for effective removal of inorganic arsenic in water. It was found that freezing temperature has important influence on the formation of 3D network structure of ICCFs. The ICCFs obtained at freeze temperature of -80°C exhibits oriented porous structure with good mechanical property than that at -20°C, thus improved excellent removal capability of As(III) and As(V) up to 114.9mgg(-1) and 86.87mgg(-1), respectively. Further, the adsorption kinetics of ICCFs on As(III) and As(V) can be described by pseudo-second order model and their adsorption isotherms follow Langmuir adsorption model. The superior removal performance of ICCFs on As(III) and As(V) can be ascribed to its oriented porous structure with abundant adsorption active sites resulted from nZVI and O, N-containing functional groups in ICCFs. Importantly, it was found that the O, N-containing functional groups of chitosan in ICCFs can adequately bind with the dissolved Fe(3+) ions from oxidation of nZVI to form Fe(3+)-Chitosan complex during removal of As(III) and As(V), thus effectively avoiding the dissolved Fe(3+) ions into solution to produce secondary pollution. A possible adsorption-coupled reduction mechanism of ICCFs on As(III) and As(V) was also proposed based on the experimental results. We believe that this work would be helpful to develop low-cost and abundant chitosan-based materials as high performance adsorbents for environmental remediation applications. PMID:27362398

  18. Risk of cancer subsequent to low-dose radiation

    SciTech Connect

    Warren, S.

    1980-01-01

    The author puts low dose irradiation risks in perspective using average background radiation doses for standards. He assailed irresponsible media coverage during the height of public interest in the Three-Mile Island Reactor incident. (PCS)

  19. Low-Dose Hyper-Radiosensitivity: Past, Present, and Future

    SciTech Connect

    Marples, Brian Collis, Spencer J.

    2008-04-01

    This review article discusses the biology of low-dose hyper-radiosensitivity (HRS) with reference to the molecular regulation of DNA repair and cell cycle control processes. Particular attention is paid to the significance of G2-phase cell cycle checkpoints in overcoming low-dose hyper-radiosensitivity and the impact of HRS on low-dose rate radiobiology. The history of HRS from the original in vivo discovery to the most recent in vitro and clinical data are examined to present a unifying hypothesis concerning the molecular control and regulation of this important low dose radiation response. Finally, preclinical and clinical data are discussed, from a molecular viewpoint, to provide theoretical approaches to exploit HRS biology for clinical gain.

  20. Response of Biological Systems to Low Doses of Ionizing Radiation.

    PubMed

    Hei, Tom K

    2016-03-01

    Radiation is ubiquitous in the environment. Biological effects of exposure to low doses of ionizing radiation are subjected to several modulating factors. Two of these, bystander response and adaptive protections, are discussed briefly. PMID:26808883

  1. Simultaneous speciation analysis of inorganic arsenic, chromium and selenium in environmental waters by 3-(2-aminoethylamino) propyltrimethoxysilane modified multi-wall carbon nanotubes packed microcolumn solid phase extraction and ICP-MS.

    PubMed

    Peng, Hanyong; Zhang, Nan; He, Man; Chen, Beibei; Hu, Bin

    2015-01-01

    Speciation analysis of inorganic arsenic, chromium and selenium in environmental waters is of great significance for the monitoring of environmental pollution. In this work, 3-(2-aminoethylamino) propyltrimethoxysilane (AAPTS) functionalized multi-wall carbon nanotubes (MWCNTs) were synthesized and employed as the adsorbent for simultaneous speciation analysis of inorganic arsenic, chromium and selenium in environmental waters by microcolumn solid-phase extraction (SPE)-inductively coupled plasma mass spectrometry (ICP-MS). It was found that As(V), Cr(VI) and Se(VI) could be selectively adsorbed on the microcolumn packed with AAPTS-MWCNTs adsorbent at pH around 2.2, while As(III), Cr(III) and Se(IV) could not be retained at this pH and passed through the microcolumn directly. Total inorganic arsenic, chromium and selenium was determined after the oxidation of As(III), Cr(III) and Se(IV) to As(V), Cr(VI) and Se(VI) with 10.0 μmol L(-1) KMnO4. The assay of As(III), Cr(III) and Se(IV) was based on subtracting As(V), Cr(VI) and Se(VI) from the total As, Cr and Se, respectively. Under the optimized conditions, the detection limits of 15, 38 and 16 ng L(-1) with the relative standard deviations (RSDs) of 7.4, 2.4 and 6.2% (c=1 µg L(-1), n=7) were obtained for As(V), Cr(VI) and Se(VI), respectively. The developed method was validated by analyzing four Certified Reference Materials, rainwater, Yangtze River and East Lake waters. PMID:25281102

  2. Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

    SciTech Connect

    Waalkes, Michael P. . E-mail: waalkes@niehs.nih.gov; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

    2006-09-15

    Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 {mu}g/pup/day) or tamoxifen (TAM; 10 {mu}g/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-{alpha}, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES.

  3. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

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

  4. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

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

  5. Can folate intake reduce arsenic toxicity?

    PubMed

    Kile, Molly L; Ronnenberg, Alayne G

    2008-06-01

    Arsenic-contaminated groundwater is a global environmental health concern. Inorganic arsenic is a known carcinogen, and epidemiologic studies suggest that persons with impaired arsenic metabolism are at increased risk for certain cancers, including skin and bladder carcinoma. Arsenic metabolism involves methylation to monomethylarsonic acid and dimethylarsinic acid (DMA) by a folate-dependent process. Persons possessing polymorphisms in certain genes involved in folate metabolism excrete a lower proportion of urinary arsenic as DMA, which may influence susceptibility to arsenic toxicity. A double-blind placebo-controlled trial in a population with low plasma folate observed that after 12 weeks of folic acid supplementation, the proportion of total urinary arsenic excreted as DMA increased and blood arsenic concentration decreased, suggesting an improvement in arsenic metabolism. Although no studies have directly shown that high folate intake reduces the risk of arsenic toxicity, these findings provide evidence to support an interaction between folate and arsenic metabolism.

  6. Low Dose Suppression of Neoplastic Transformation in Vitro

    SciTech Connect

    John Leslie Redpath

    2012-05-01

    This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

  7. An Investigation of Bioaccessibility of Arsenic in Rice using IC-ICP-MS

    EPA Science Inventory

    Arsenic exposure occurs mainly through drinking water and food; therefore, both aspects should be incorporated into any aggregate exposure assessment. Drinking water exposures are predominately inorganic arsenic while dietary exposures are made up of a diverse set of arsenicals w...

  8. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    PubMed Central

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  9. 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

  10. Arsenic speciation and fucoxanthin analysis from seaweed dietary supplements using LC-MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inorganic species are considered more toxic to humans than organic arsenic and total arsenic. Analysis of total arsenic in metallic form, organic and inorganic arsenic species from seaweeds and dietary supplements using LC-ICP-MS was developed. Solvent extraction with sonication and microwave extr...

  11. Low-Dose Risk, Decisions, and Risk Communication

    SciTech Connect

    Flynn, James; Slovic, Paul

    2001-06-01

    To conduct basic research on how people receive, evaluate, and form positions on scientific information and its relationship to low-dose radiation exposure. There are three major areas of study in our research program. First is the development of theories, frameworks and concepts essential to guiding data collection and analysis. The second area is a program of experimental studies on risk perception, evaluation of science information, and the structure of individual positions regarding low dose exposures. This involves the study of existing knowledge and the evaluation of science information presented within a variety of formats, as educational information, news media stories, and alternative communication methods (personal contact, small group interaction, email & internet, etc.). Third is the community-level studies to examine and record how the social conditions, under which science communications take place, influence the development of attitudes and opinions about: low- dose exposures, the available management options, control of radiation risks, and preferences for program and policy goals.

  12. Development of a simple, sensitive and inexpensive ion-pairing cloud point extraction approach for the determination of trace inorganic arsenic species in spring water, beverage and rice samples by UV-Vis spectrophotometry.

    PubMed

    Gürkan, Ramazan; Kır, Ufuk; Altunay, Nail

    2015-08-01

    The determination of inorganic arsenic species in water, beverages and foods become crucial in recent years, because arsenic species are considered carcinogenic and found at high concentrations in the samples. This communication describes a new cloud-point extraction (CPE) method for the determination of low quantity of arsenic species in the samples, purchased from the local market by UV-Visible Spectrophotometer (UV-Vis). The method is based on selective ternary complex of As(V) with acridine orange (AOH(+)) being a versatile fluorescence cationic dye in presence of tartaric acid and polyethylene glycol tert-octylphenyl ether (Triton X-114) at pH 5.0. Under the optimized conditions, a preconcentration factor of 65 and detection limit (3S blank/m) of 1.14 μg L(-1) was obtained from the calibration curve constructed in the range of 4-450 μg L(-1) with a correlation coefficient of 0.9932 for As(V). The method is validated by the analysis of certified reference materials (CRMs).

  13. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes.

  14. Low-dose radiation epidemiology studies: status and issues.

    PubMed

    Shore, Roy E

    2009-11-01

    Although the Japanese atomic bomb study and radiotherapy studies have clearly documented cancer risks from high-dose radiation exposures, radiation risk assessment groups have long recognized that protracted or low exposures to low-linear energy transfer radiations are key radiation protection concerns because these are far more common than high-exposure scenarios. Epidemiologic studies of human populations with low-dose or low dose-rate exposures are one approach to addressing those concerns. A number of large studies of radiation workers (Chernobyl clean-up workers, U.S. and Chinese radiological technologists, and the 15-country worker study) or of persons exposed to environmental radiation at moderate to low levels (residents near Techa River, Semipalatinsk, Chernobyl, or nuclear facilities) have been conducted. A variety of studies of medical radiation exposures (multiple-fluoroscopy, diagnostic (131)I, scatter radiation doses from radiotherapy, etc.) also are of interest. Key results from these studies are summarized and compared with risk estimates from the Japanese atomic bomb study. Ideally, one would like the low-dose and low dose-rate studies to guide radiation risk estimation regarding the shape of the dose-response curve, DDREF (dose and dose-rate effectiveness factor), and risk at low doses. However, the degree to which low-dose studies can do so is subject to various limitations, especially those pertaining to dosimetric uncertainties and limited statistical power. The identification of individuals who are particularly susceptible to radiation cancer induction also is of high interest in terms of occupational and medical radiation protection. Several examples of studies of radiation-related cancer susceptibility are discussed, but none thus far have clearly identified radiation-susceptible genotypes. PMID:19820457

  15. High-resolution low-dose scanning transmission electron microscopy

    PubMed Central

    Buban, James P.; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D.; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM. PMID:19915208

  16. High-resolution low-dose scanning transmission electron microscopy.

    PubMed

    Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

    2010-01-01

    During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

  17. Engineering the Soil Bacterium Pseudomonas putida for Arsenic Methylation

    PubMed Central

    Chen, Jian; Qin, Jie; Zhu, Yong-Guan; de Lorenzo, Víctor

    2013-01-01

    Accumulation of arsenic has potential health risks through consumption of food. Here, we inserted the arsenite [As(III)] S-adenosylmethionine methyltransferase (ArsM) gene into the chromosome of Pseudomonas putida KT2440. Recombinant bacteria methylate inorganic arsenic into less toxic organoarsenicals. This has the potential for bioremediation of environmental arsenic and reducing arsenic contamination in food. PMID:23645194

  18. ARSENIC - SUSCEPTIBILITY & IN UTERO EFFECTS

    EPA Science Inventory

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

  19. Chronic Arsenic poisoning.

    PubMed

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

    2009-02-01

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

  20. Low-dose high-resolution CT of lung parenchyma

    SciTech Connect

    Zwirewich, C.V.; Mayo, J.R.; Mueller, N.L. )

    1991-08-01

    To evaluate the efficacy of low-dose high-resolution computed tomography (HRCT) in the assessment of lung parenchyma, three observers reviewed the scans of 31 patients. The 1.5-mm-collimation, 2-second, 120-kVp scans were obtained at 20 and 200 mA at selected identical levels in the chest. The observers evaluated the visualization of normal pulmonary anatomy, various parenchymal abnormalities and their distribution, and artifacts. The low-dose and conventional scans were equivalent in the evaluation of vessels, lobar and segmental bronchi, and anatomy of secondary pulmonary lobules, and in characterizing the extent and distribution of reticulation, honeycomb cysts, and thickened interlobular septa. The low-dose technique failed to demonstrate ground-glass opacity in two of 10 cases (20%) and emphysema in one of nine cases (11%), in which they were evident but subtle on the high-dose scans. These differences were not statistically significant. Linear streak artifact was more prominent on images acquired with the low-dose technique, but the two techniques were judged equally diagnostic in 97% of cases. The authors conclude that HRCT images acquired at 20 mA yield anatomic information equivalent to that obtained with 200-mA scans in the majority of patients, without significant loss of spatial resolution or image degradation due to linear streak artifact.

  1. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    EPA Science Inventory

    Carcinogenic Effects of Low Doses of Ionizing Radiation

    R Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    The form of the dose-response curve for radiation-induced cancers, particu...

  2. Malignant melanoma of the tongue following low-dose radiation

    SciTech Connect

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-03-01

    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  3. Systemic response to low-dose endotoxin infusion in cats.

    PubMed

    DeClue, Amy E; Williams, Kurt J; Sharp, Claire; Haak, Carol; Lechner, Elizabeth; Reinero, Carol R

    2009-12-15

    Sepsis is a common problem in feline patients and is associated with substantial morbidity and mortality. There has been little research investigating the physiologic response to bacterial infection in cats, in part because appropriate models have not been developed. The objective of this study was to characterize the response to low-dose LPS infusion in conscious, healthy cats. Measures of systemic inflammation, hemodynamic stability, coagulation, metabolic function, and organ damage were compared between placebo and low-dose LPS infusion (2mcg/kg/hx4h, IV) in cats, with each cat serving as its own control. Markers of systemic inflammation including temperature, plasma TNF activity, IL-6, CXCL-8 and IL-10 concentrations were significantly increased and white blood cell counts were significantly decreased after LPS infusion. A biphasic hypotensive response was observed after initiation of LPS infusion without concurrent tachycardia. Additionally, LPS administration significantly increased blood glucose, lactate and creatinine concentrations. Patchy alveolar congestion, multifocal acute alveolar epithelial necrosis, and mild pulmonary edema were noted in the lungs along with acute centrilobular hepatocellular necrosis, and mild lymphocyte apoptosis in the spleen and/or intestinal Peyer's patches. No biologically significant alterations in coagulation parameters developed after LPS infusion. Low-dose LPS infusion in cats induced systemic inflammation, hemodynamic derangement, metabolic alterations and mild organ damage. Low-dose endotoxin infusion is a viable pre-clinical model to study naturally developing sepsis in cats.

  4. Mechanisms of Low Dose Radio-Suppression of Genomic Instability

    SciTech Connect

    Engelward, Bevin P

    2009-09-16

    The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

  5. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications.

  6. Mechanical Solitaire Thrombectomy with Low-Dose Booster Tirofiban Injection

    PubMed Central

    Goh, Duck-Ho; Jeong, Hae Woong; Ha, Sam Yeol

    2016-01-01

    Purpose Mechanical thrombectomy using a Solitaire stent has been associated with a high recanalization rate and favorable clinical outcome in intra-arterial thrombolysis. To achieve a higher recanalization rate for mechanical Solitaire thrombectomy, we used an intra-arterial low-dose booster tirofiban injection into the occluded segment after stent deployment. We report the safety and recanalization rates for mechanical Solitaire thrombectomy with a low-dose booster tirofiban injection. Materials and Methods Between February and March 2013, 13 consecutive patients underwent mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. The occlusion sites included the proximal middle cerebral artery (5 patients), the internal carotid artery (5 patients), the top of the basilar artery (2 patients) and the distal middle cerebral artery (M2 segment, 1 patient). Six patients underwent bridge treatment, including intravenous tissue plasminogen activator. Tirofiban of 250 µg was used in all patients except one (500 µg). All occluded vessels were recanalized after 3 attempts at stent retrieval (1 time, n=9; 2 times, n=2; 3 times, n=2). Results Successful recanalization was achieved in all patients (TICI 3, n=8; TICI 2b, n=5). Procedural complications developed in 3 patients (subarachnoid hemorrhage, n=2; hemorrhagic transformation, n=1). Mortality occurred in one patient with a basilar artery occlusion due to reperfusion brain swelling after mechanical Solitaire thrombectomy with low-dose booster tirofiban injection. Favorable clinical outcome (mRS≤2) was observed in 8 patients (61.5%). Conclusion Our modified mechanical Solitaire thrombectomy method using a low-dose booster tirofiban injection might enhance the recanalization rate with no additive hemorrhagic complications. PMID:27621948

  7. Arsenic and the Epigenome: Linked by Methylation(SOT)

    EPA Science Inventory

    Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide, and chronically-exposed individuals are susceptible to arsenic poisoning, or arsenicosis. In some exposed populations arsenicosis susceptibility is dependent in part on the abil...

  8. REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF ARSENIC IN RODENTS: A REVIEW

    EPA Science Inventory

    Arsenic is a recognized reproductive toxicant in humans and induces malformations, especially neural tube defects, in laboratory animals. Early studies showed that murine malformations occurred only when a high dose of inorganic arsenic was given by intravenous or intraperitoneal...

  9. Prenatal and developmental toxicology of arsenicals.

    PubMed

    Willhite, C C; Ferm, V H

    1984-01-01

    A variety of species, including the human, have been shown to be susceptible to the embryotoxic effects of inorganic arsenic. Malformations of the axial skeleton, neurocranium, viscerocranium, eyes, and genitourinary systems as well as prenatal death followed a bolus dose of trivalent or pentavalent inorganic arsenic. Trivalent arsenic was more teratogenic than pentavalent arsenic; in contrast, the methylated metabolites of arsenic possessed only limited teratogenic activity. Administration of inorganic arsenic to mammals results in concentration of arsenic within the placenta and small amounts are deposited within the embryo. Studies concerning the pathogenesis of arsenic-induced axial skeletal lesions revealed early failure of neural fold elevation and a subsequent, persistent failure of closure of the neural tube. Physical factors, drugs and heavy metals may modify the response to a teratogenic dose of inorganic arsenic. Medical problems associated with industrial or agricultural arsenicalism are most often typified by chronic exposure; future studies should emphasize those routes of administration and types of exposure that are characteristic of arsenic intoxication.

  10. Acute arsenic poisoning in two siblings.

    PubMed

    Lai, Melisa W; Boyer, Edward W; Kleinman, Monica E; Rodig, Nancy M; Ewald, Michele Burns

    2005-07-01

    We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy.

  11. Selective Toxicity at Low Doses: Experiments with Three Plant Species and Toxicants

    PubMed Central

    Sinkkonen, Aki; Myyrä, Mervi; Penttinen, Olli-Pekka; Rantalainen, Anna-Lea

    2010-01-01

    During the last decade, the paradigm that low toxicant doses often have stimulatory effects on plants has become widely accepted. At the same time, low toxicant doses of metal salts have been observed to inhibit the growth of the most vigorous seedlings of a population in vitro, although mean plant size has remained unaffected. We hypothesized that this kind of selective low-dose toxicity is not restricted to inorganic contaminants. We exposed annual plants (baby’s breath Gypsophila elegans, purslane Portulaca oleracea, and duckweed Lemna minor) to 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran (HHCB) and 4-tert-octylphenol and lead acetate. As compared to unexposed G. elegans roots, 4-tert-octylphenol did not affect the mean root size of all seedlings, but it reduced the average length of roots longer than the 98th percentile. A comparable response was found in case of G. elegans roots treated with lead acetate beyond the 90th percentile. The average size of roots beyond the 90th percentile was decreased also when L. minor was exposed to lead acetate though the means of all roots were constant. P. oleracea seemed to be insensitive to selective toxicity. We conclude that selective toxicity at low doses should be considered in parallel with hormesis. PMID:21431082

  12. Arsenic and diabetes: current perspectives.

    PubMed

    Huang, Chun Fa; Chen, Ya Wen; Yang, Ching Yao; Tsai, Keh Sung; Yang, Rong Sen; Liu, Shing Hwa

    2011-09-01

    Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose-response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM) in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM). These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with respect to human exposure

  13. Sheet Resistance Low Dose Monitoring Using The Double Implant Technique

    NASA Astrophysics Data System (ADS)

    Smith, A. K.; Johnson, W. H.; Keenan, W. A.

    1986-06-01

    Sheet resistance has become an industry standard for monitoring high and medium dose ion implants. For low dose there are two sheet resistance techniques available, the direct implant technique and the double implant technique. Careful processing has extended the range of direct sheet resistance measurements down to doses of 2E11 ions/cm2. The double implant technique requires an initial implant to create an easily measured sheet resistance layer that serves as the test vehicle for the second implant. The dose of the second implant is measured by monitoring the change in the sheet resistance due to the implant damage created by the second implant into the first. This double implant technique is not limited to low dose nor to species that are electrically active in the substrate.

  14. Patient release criteria for low dose rate brachytherapy implants.

    PubMed

    Boyce, Dale E; Sheetz, Michael A

    2013-04-01

    A lack of consensus regarding a model governing the release of patients following sealed source brachytherapy has led to a set of patient release policies that vary from institution to institution. The U.S. Nuclear Regulatory Commission has issued regulatory guidance on patient release in NUREG 1556, Volume 9, Rev. 2, Appendix U, which allows calculation of release limits following implant brachytherapy. While the formalism presented in NUREG is meaningful for the calculation of release limits in the context of relatively high energy gamma emitters, it does not estimate accurately the effective dose equivalent for the common low dose rate brachytherapy sources Cs, I, and Pd. NUREG 1556 states that patient release may be based on patient-specific calculations as long as the calculation is documented. This work is intended to provide a format for patient-specific calculations to be used for the consideration of patients' release following the implantation of certain low dose rate brachytherapy isotopes. PMID:23439145

  15. Etched track detectors and the low dose problem.

    PubMed

    Pálfalvi, J; Dám, A M; Bogdándi, E N; Polonyi, I; Szabó, J; Balásházy, I; Farkas, A

    2003-01-01

    The risk to human health of exposure to low-level radiation is not precisely known yet. One way of studying this is to carry out in vitro biological experiments with cell cultures and to extend the conclusions to biological models. To relate the macroscopically deteminable 'low dose' to the damage of cells caused by a certain type of ionising particle is nearly impossible. therefore the number of hits and the imparted energy are the significant quantities. They can be estimated by particle transport calculations and by direct measurements. The effect of low dose was investigated in radio-adaptation experiments when mono-layers of different unsynchronised cell cultures were irradiated by neutrons produced in the filtered beam of the Budapest Research Reactor (BRR). The energy deposition was investigated by replacing the mono-layers with etched track detectors of the CR-39 type. PMID:12678384

  16. Rapid low dose electron tomography using a direct electron detection camera

    PubMed Central

    Migunov, Vadim; Ryll, Henning; Zhuge, Xiaodong; Simson, Martin; Strüder, Lothar; Batenburg, K. Joost; Houben, Lothar; Dunin-Borkowski, Rafal E.

    2015-01-01

    We demonstrate the ability to record a tomographic tilt series containing 3487 images in only 3.5 s by using a direct electron detector in a transmission electron microscope. The electron dose is lower by at least one order of magnitude when compared with that used to record a conventional tilt series of fewer than 100 images in 15–60 minutes and the overall signal-to-noise ratio is greater than 4. Our results, which are illustrated for an inorganic nanotube, are important for ultra-low-dose electron tomography of electron-beam-sensitive specimens and real-time dynamic electron tomography of nanoscale objects with sub-ms temporal resolution. PMID:26434767

  17. Rapid low dose electron tomography using a direct electron detection camera.

    PubMed

    Migunov, Vadim; Ryll, Henning; Zhuge, Xiaodong; Simson, Martin; Strüder, Lothar; Batenburg, K Joost; Houben, Lothar; Dunin-Borkowski, Rafal E

    2015-01-01

    We demonstrate the ability to record a tomographic tilt series containing 3487 images in only 3.5 s by using a direct electron detector in a transmission electron microscope. The electron dose is lower by at least one order of magnitude when compared with that used to record a conventional tilt series of fewer than 100 images in 15-60 minutes and the overall signal-to-noise ratio is greater than 4. Our results, which are illustrated for an inorganic nanotube, are important for ultra-low-dose electron tomography of electron-beam-sensitive specimens and real-time dynamic electron tomography of nanoscale objects with sub-ms temporal resolution. PMID:26434767

  18. Rapid low dose electron tomography using a direct electron detection camera

    NASA Astrophysics Data System (ADS)

    Migunov, Vadim; Ryll, Henning; Zhuge, Xiaodong; Simson, Martin; Strüder, Lothar; Batenburg, K. Joost; Houben, Lothar; Dunin-Borkowski, Rafal E.

    2015-10-01

    We demonstrate the ability to record a tomographic tilt series containing 3487 images in only 3.5 s by using a direct electron detector in a transmission electron microscope. The electron dose is lower by at least one order of magnitude when compared with that used to record a conventional tilt series of fewer than 100 images in 15-60 minutes and the overall signal-to-noise ratio is greater than 4. Our results, which are illustrated for an inorganic nanotube, are important for ultra-low-dose electron tomography of electron-beam-sensitive specimens and real-time dynamic electron tomography of nanoscale objects with sub-ms temporal resolution.

  19. Role of animal studies in low-dose extrapolation

    SciTech Connect

    Fry, R.J.M.

    1981-01-01

    Current data indicate that in the case of low-LET radiation linear, extrapolation from data obtained at high doses appears to overestimate the risk at low doses to a varying degree. In the case of high-LET radiation, extrapolation from data obtained at doses as low as 40 rad (0.4 Gy) is inappropriate and likely to result in an underestimate of the risk.

  20. Responses of astrocytes in culture after low dose laser irradiation

    SciTech Connect

    Yew, D.T.; Zheng, D.R.; Au, C.; Li, W.W. )

    1990-03-01

    The effect of Helium-Neon low dose laser on astrocytes was investigated in cultures of isolated astrocytes from albino neonatal rats. The laser appeared to inhibit the growth of astrocytes as exemplified by the smaller sizes of the cells and the decreased leucine uptake in each cell after treatment. Temporary decrease in the number of mitoses was also observed, but this trend was reversed soon after. Electron microscopic studies revealed an increase in buddings from cell bodies and processes (branches) after irradiation.

  1. Screening for lung cancer using low dose computed tomography.

    PubMed

    Tammemagi, Martin C; Lam, Stephen

    2014-01-01

    Screening for lung cancer with low dose computed tomography can reduce mortality from the disease by 20% in high risk smokers. This review covers the state of the art knowledge on several aspects of implementing a screening program. The most important are to identify people who are at high enough risk to warrant screening and the appropriate management of lung nodules found at screening. An accurate risk prediction model is more efficient than age and pack years of smoking alone at identifying those who will develop lung cancer and die from the disease. Algorithms are available for assessing people who screen positive to determine who needs additional imaging or invasive investigations. Concerns about low dose computed tomography screening include false positive results, overdiagnosis, radiation exposure, and costs. Further work is needed to define the frequency and duration of screening and to refine risk prediction models so that they can be used to assess the risk of lung cancer in special populations. Another important area is the use of computer vision software tools to facilitate high throughput interpretation of low dose computed tomography images so that costs can be reduced and the consistency of scan interpretation can be improved. Sufficient data are available to support the implementation of screening programs at the population level in stages that can be expanded when found to perform well to improve the outcome of patients with lung cancer. PMID:24865600

  2. Low dose monitors — the movements and causes

    NASA Astrophysics Data System (ADS)

    Cherekdjian, S.

    1993-04-01

    A previous paper [Nucl. Instr. and Meth. B55 (1991) 178] has demonstrated that the correct equipment specification and process procedures enable the reliable direct probing of low dose sheet resistance monitors. Utilizing this, we are able to characterize the instability of low dose monitors to process and ambient conditions. Several experiments are conducted to determine the origin of the movements. These movements were found to be either "short term", or "long term". The former is a result of the interaction of the wafer and its processing prior to measurement. While the latter is a slow change after processing. The correct specification of the wafers, wafer processing, and the condition of the four point probe tips enable the low dose measurement to be performed. The value of the initial result, "short term movement", is shown to be directly the consequence of wet chemistry and the ambient anneal condition. While the stability of the wafer after measurement, "long term movement", is found to be the electrical degradation of the surface of the silicon. A key factor in this stability problem is the exposure of the wafer to air, especially to moisture in the atmosphere. X-ray photo spectroscopy (XPS), and time of flight secondary ion mass Spectrometry (TOP SIMS) results give an insight to the complexity of the surface condition. These range from oxide growth, surface chemistry, and hydrogen injection.

  3. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis. PMID:25355191

  4. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma

    SciTech Connect

    Schoenfeld, Gordon O.; Amdur, Robert J. . E-mail: amdurrj@ufl.edu; Schmalfuss, Ilona M.; Morris, Christopher G.; Keole, Sameer R.; Mendenhall, William M.; Marcus, Robert B.

    2006-06-01

    Purpose: To report outcomes of patients with localized intracranial germinoma treated with low-dose craniospinal irradiation (CSI) followed by a boost to the ventricular system and primary site. Methods and Materials: Thirty-one patients had pathologically confirmed intracranial germinoma and no spine metastases. Low-dose CSI was administered in 29 patients: usually 21 Gy of CSI, 9.0 Gy of ventricular boost, and a 19.5-Gy tumor boost, all at 1.5 Gy per fraction. Our neuroradiologist recorded three-dimensional tumor size on magnetic resonance images before, during, and after radiotherapy. Results: With a median follow-up of 7.0 years, 29 of 31 patients (94%) are disease free. One failure had nongerminomatous histology; the initial diagnosis was a sampling error. Of 3 patients who did not receive CSI, 1 died. No patient developed myelopathy, visual deficits, dementia, or skeletal growth problems. In locally controlled patients, tumor response according to magnetic resonance scan was nearly complete within 6 months after radiotherapy. Conclusions: Radiotherapy alone with low-dose prophylactic CSI cures almost all patients with localized intracranial germinoma. Complications are rare when the daily dose of radiotherapy is limited to 1.5 Gy and the total CSI dose to 21 Gy. Patients without a near-complete response to radiotherapy should undergo resection to rule out a nongerminomatous element.

  5. Exercise and sport performance with low doses of caffeine.

    PubMed

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (<3 mg/kg body mass, ~200 mg) are also ergogenic in some exercise and sport situations, although this has been less well studied. Lower caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  6. Environmental biochemistry of arsenic

    SciTech Connect

    Tamaki, S.; Frankenberger, W.T. Jr. )

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  7. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    PubMed

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  8. DEVELOPMENT OF A HUMAN PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR INORGANIC ARSENIC AND ITS MONO- AND DI-METHYLATED METABOLITES

    EPA Science Inventory

    A physiologically-based pharmacokinetic (PBPK) model was developed to estimate levels of arsenic and its metabolites in human tissues and urine after oral exposure to either arsenate (AsV) or arsnite (AsIII). The model consists of interconnected individual ...

  9. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  10. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no

  11. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  12. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  13. c-Jun/AP-1 pathway-mediated cyclin D1 expression participates in low dose arsenite-induced transformation in mouse epidermal JB6 Cl41 cells

    SciTech Connect

    Zhang Dongyun; Li Jingxia; Gao Jimin; Huang Chuanshu

    2009-02-15

    Arsenic is a well-documented human carcinogen associated with skin carcinogenesis. Our previous work reveals that arsenite exposure is able to induce cell transformation in mouse epidermal cell JB6 Cl41 through the activation of ERK, rather than JNK pathway. Our current studies further evaluate downstream pathway in low dose arsenite-induced cell transformation in JB6 Cl41 cells. Our results showed that treatment of cells with low dose arsenite induced activation of c-Jun/AP-1 pathway, and ectopic expression of dominant negative mutant of c-Jun (TAM67) blocked arsenite-induced transformation. Furthermore, our data indicated that cyclin D1 was an important downstream molecule involved in c-Jun/AP-1-mediated cell transformation upon low dose arsenite exposure, because inhibition of cyclin D1 expression by its specific siRNA in the JB6 Cl41 cells resulted in impairment of anchorage-independent growth of cells induced by low dose arsenite. Collectively, our results demonstrate that c-Jun/AP-1-mediated cyclin D1 expression is at least one of the key events implicated in cell transformation upon low dose arsenite exposure.

  14. High or low dose radioiodine ablation of thyroid remnants?

    PubMed

    Creutzig, H

    1987-01-01

    The need for high dose radioiodine for ablation of remnants in patients with thyroid cancer is still in question. We compared the effectiveness of high and low dose 131I for ablation in patients in a prospective randomized study after surgical thyroidectomy. Twenty patients with differentiated pT2-3NoMo thyroid cancer were studied. The uptake was 5%-10% at 24 h. Ten patients received 100 mCi, the others 30 mCi 131I. Three months later all patients received a therapeutic dose of 150 mCi 131I. Another twenty patients with known distant metastases (pulmonary and/or bone) of differentiated thyroid cancer were studied. The remnant uptake was between 4%-10%. Ten patients received 300 mCi and ten 30 mCi 131I as ablation dose. Three months later all received 300 mCi 131I. The uptake at day seven was calculated for the same metastases from a whole body scan after both treatments. If effective ablation was defined as 24 h uptake in the remnant of less than 1%, then the ablation was effective in eight out of ten of the high dose and in seven out of ten of the low dose group. In pT2-3, N X M1 patients the ablation was effective in seven out of ten cases in both groups. If "effective" ablation was defined as an uptake of less than 0.5%, then the ablation was effective both in NoMo and in N X M1 patients in five out of ten with low dose and in six out of ten with high dose ablation treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3569338

  15. Evaluation of in vivo low-dose mouse irradiation system

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Kim, H. J.; Kim, H.; Kye, Y.-U.; Kim, J. K.; Son, T. G.; Lee, M. W.; Jeong, D. H.; Yang, K. M.; Nam, S.-H.; Kang, Y.-R.

    2016-03-01

    This study aims to develop a facility that can irradiate subjects with a desired low dose, which can be used to assess the biological effects of low-dose radiation. We develop a single-occupancy mouse-cage and shelf system with adjustable geometric parameters, such as the distances and angles of the cages relative to the collimator. We assess the irradiation-level accuracy using two measurement methods. First, we calculate the angle and distance of each mouse cage relative to the irradiator. We employ a Monte Carlo n-particle simulation for all of the cages at a given distance from the radiation source to calculate the air kerma and the relative absorbed dose in the in-house designed shelving system; these are found to be approximately 0.108 and 0.109 Gy, respectively. Second, we measure the relative absorbed dose using glass dosimeters inserted directly into the heads and bodies of the mice. For a conventional irradiation system, the irradiation measurements show a maximum discrepancy of 42% between the absorbed and desired doses, whereas a discrepancy of only 6% from the desired dose is found for the designed mouse apartment system. In addition, multi-mouse cages are shown to yield to significantly greater differences in the mouse head and body relative absorbed doses, compared to the discrepancies found for single-occupancy cages in the conventional irradiation system. Our findings suggest that the in-house shelving system has greater reliability for the biological analysis of the effects of low-dose radiation.

  16. Extrapyramidal side effects with low doses of amisulpride.

    PubMed

    Mandal, Nikhiles; Singh, Om P; Sen, Subrata

    2014-04-01

    Amisulpride, the newly introduced antipsychotic in India, is claimed to be effective in both positive and negative symptom schizophrenia and related disorders, though it has little or no action on serotonergic receptors. Limbic selectivity and lower striatal dopaminergic receptor binding capacity causes very low incidence of EPS. But, in clinical practice, we are getting EPS with this drug even at lower doses. We have reported three cases of akathisia, acute dystonia, and drug-induced Parkinsonism with low doses of amisulpride. So, we should keep this side effect in mind when using amisulpride. In fact, more studies are required in our country to find out the incidence of EPS and other associated mechanism.

  17. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  18. Harderian Gland Tumorigenesis: Low-Dose and LET Response.

    PubMed

    Chang, Polly Y; Cucinotta, Francis A; Bjornstad, Kathleen A; Bakke, James; Rosen, Chris J; Du, Nicholas; Fairchild, David G; Cacao, Eliedonna; Blakely, Eleanor A

    2016-05-01

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ∼70 keV/μm) and 1,000 MeV/u titanium (LET ∼100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  19. Low Dose IR Creates an Oncogenic Microenvironment by Inducing Premature

    SciTech Connect

    Yuan, Zhi-Min

    2013-04-28

    Introduction Much of the work addressing ionizing radiation-induced cellular response has been carried out mainly with the traditional cell culture technique involving only one cell type, how cellular response to IR is influenced by the tissue microenvironment remains elusive. By use of a three-dimensional (3D) co-culture system to model critical interactions of different cell types with their neighbors and with their environment, we recently showed that low-dose IR-induced extracellular signaling via the tissue environment affects profoundly cellular responses. This proposal aims at determining the response of mammary epithelial cells in a tissue-like setting.

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

    SciTech Connect

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

    2008-10-01

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

  1. Determination of inorganic arsenic in marine food samples by hydrochloric acid distillation and flow-injection hydride-generation atomic absorption spectrometry.

    PubMed

    Oygard, J K; Lundebye, A K; Julshamn, K

    1999-01-01

    A simple, rapid, and reliable method was developed for determination of inorganic As in biological samples such as fish fillet. Inorganic AS was distilled from the sample as AsCl3 with HCl. The separated inorganic AS was determined by flow-injection hydride-generation atomic absorption spectrometry after prereduction with KI and HCl. The influences of various concentrations of KI, ascorbic acid, and HCl in the prereduction stage; NaBH4 as the reductant; and HCl as the carrier solution on analytical results were studied. Digestion was performed in a Kjeldahl digestion system for 75 min with 4 mL nitric acid and 1 mL sulfuric acid at 380 degrees C. The concentrations of inorganic As in samples were less than 0.1 mg/kg dry weight for fish fillet and somewhat higher for crustaceans and bivalve molluscs. The total and inorganic As contents of various marine biological samples and certified reference materials were determined.

  2. Segmentation of individual ribs from low-dose chest CT

    NASA Astrophysics Data System (ADS)

    Lee, Jaesung; Reeves, Anthony P.

    2010-03-01

    Segmentation of individual ribs and other bone structures in chest CT images is important for anatomical analysis, as the segmented ribs may be used as a baseline reference for locating organs within a chest as well as for identification and measurement of any geometric abnormalities in the bone. In this paper we present a fully automated algorithm to segment the individual ribs from low-dose chest CT scans. The proposed algorithm consists of four main stages. First, all the high-intensity bone structure present in the scan is segmented. Second, the centerline of the spinal canal is identified using a distance transform of the bone segmentation. Then, the seed region for every rib is detected based on the identified centerline, and each rib is grown from the seed region and separated from the corresponding vertebra. This algorithm was evaluated using 115 low-dose chest CT scans from public databases with various slice thicknesses. The algorithm parameters were determined using 5 scans, and remaining 110 scans were used to evaluate the performance of the segmentation algorithm. The outcome of the algorithm was inspected by an author for the correctness of the segmentation. The results indicate that over 98% of the individual ribs were correctly segmented with the proposed algorithm.

  3. Low dose scatter correction for digital chest tomosynthesis

    NASA Astrophysics Data System (ADS)

    Inscoe, Christina R.; Wu, Gongting; Shan, Jing; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping

    2015-03-01

    Digital chest tomosynthesis (DCT) provides superior image quality and depth information for thoracic imaging at relatively low dose, though the presence of strong photon scatter degrades the image quality. In most chest radiography, anti-scatter grids are used. However, the grid also blocks a large fraction of the primary beam photons requiring a significantly higher imaging dose for patients. Previously, we have proposed an efficient low dose scatter correction technique using a primary beam sampling apparatus. We implemented the technique in stationary digital breast tomosynthesis, and found the method to be efficient in correcting patient-specific scatter with only 3% increase in dose. In this paper we reported the feasibility study of applying the same technique to chest tomosynthesis. This investigation was performed utilizing phantom and cadaver subjects. The method involves an initial tomosynthesis scan of the object. A lead plate with an array of holes, or primary sampling apparatus (PSA), was placed above the object. A second tomosynthesis scan was performed to measure the primary (scatter-free) transmission. This PSA data was used with the full-field projections to compute the scatter, which was then interpolated to full-field scatter maps unique to each projection angle. Full-field projection images were scatter corrected prior to reconstruction. Projections and reconstruction slices were evaluated and the correction method was found to be effective at improving image quality and practical for clinical implementation.

  4. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy.

  5. The Effects of ELDRS at Ultra-Low Dose Rates

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi; Holcombe, Bruce; Little, Bradley; Salzman, James; Chaumont, Geraldine; Duperray, Herve; Ouellet, Al

    2011-01-01

    We present results on the effects on ELDRS at dose rates of 10, 5, 1, and 0.5 mrad(Si)/s for a variety of radiation hardened and commercial devices. We observed low dose rate enhancement below 10 mrad(Si)/s in several different parts. The magnitudes of the dose rate effects vary. The TL750L, a commercial voltage regulator, showed dose rate dependence in the functional failures, with initial failures occurring after 10 krad(Si) for the parts irradiated at 0.5 mrad(Si)/s. The RH1021 showed an increase in low dose rate enhancement by 2x at 5 mrad(Si)/s relative to 8 mrad(Si)/s and high dose rate, and parametric failure after 100 krad(Si). Additionally the ELDRS-free devices, such as the LM158 and LM117, showed evidence of dose rate sensitivity in parametric degradations. Several other parts also displayed dose rate enhancement, with relatively lower degradations up to approx.15 to 20 krad(Si). The magnitudes of the dose rate enhancement will likely increase in significance at higher total dose levels.

  6. Porous hydroxyapatite tablets as carriers for low-dosed drugs.

    PubMed

    Cosijns, A; Vervaet, C; Luyten, J; Mullens, S; Siepmann, F; Van Hoorebeke, L; Masschaele, B; Cnudde, V; Remon, J P

    2007-09-01

    The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250 degrees C) revealed tablets with an acceptable friability (<1%). Using 50% (w/w) Avicel PH 200 as pore forming agent resulted in tablets combining the highest porosity (50%) and the highest median pore diameter (5 microm). Aqueous drug solutions (metoprolol tartrate, riboflavin sodium phosphate) were spiked on the tablet surface. The maximum volume of drug solution absorbed was limited (2x100 microl), revealing that these porous carriers were ideal for low dosed formulations. Drug release from the tablets was slow, independent of the drug. To accelerate drug release, tablets were manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80 microm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.

  7. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M. ); Panozzo, J.; Libertin, C.R. )

    1993-01-01

    Studies were designed to identify genes induced following low-dose neutron but not following [gamma]-ray exposure in fibroblasts. Our past work had shown differences in the expression of [beta]-protein kinase C and c-fos genes, both being induced following [gamma]-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not [gamma]-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to [gamma] rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  8. Low doses of neutrons induce changes in gene expression

    SciTech Connect

    Woloschak, G.E.; Chang-Liu, C.M.; Panozzo, J.; Libertin, C.R.

    1993-06-01

    Studies were designed to identify genes induced following low-dose neutron but not following {gamma}-ray exposure in fibroblasts. Our past work had shown differences in the expression of {beta}-protein kinase C and c-fos genes, both being induced following {gamma}-ray but not neutron exposure. We have identified two genes that are induced following neutron, but not {gamma}-ray, exposure: Rp-8 (a gene induced by apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency (HIV). Rp-8 mRNA induction was demonstrated in Syrian hamster embryo fibroblasts and was found to be induced in cells exposed to neutrons administered at low (0.5 cGy/min) and at high dose rate (12 cGy/min). The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measures of CAT activity and CAT transcripts following irradiation demonstrated an unresponsiveness to {gamma} rays over a broad range of doses. Twofold induction of the HIV-LTR was detected following neutron exposure (48 cGy) administered at low (0.5 cGy/min) but not high (12 cGy/min) dose rates. Ultraviolet-mediated HIV-LTR induction was inhibited by low-dose-rate neutron exposure.

  9. Non linear processes modulated by low doses of radiation exposure

    NASA Astrophysics Data System (ADS)

    Mariotti, Luca; Ottolenghi, Andrea; Alloni, Daniele; Babini, Gabriele; Morini, Jacopo; Baiocco, Giorgio

    The perturbation induced by radiation impinging on biological targets can stimulate the activation of several different pathways, spanning from the DNA damage processing to intra/extra -cellular signalling. In the mechanistic investigation of radiobiological damage this complex “system” response (e.g. omics, signalling networks, micro-environmental modifications, etc.) has to be taken into account, shifting from a focus on the DNA molecule solely to a systemic/collective view. An additional complication comes from the finding that the individual response of each of the involved processes is often not linear as a function of the dose. In this context, a systems biology approach to investigate the effects of low dose irradiations on intra/extra-cellular signalling will be presented, where low doses of radiation act as a mild perturbation of a robustly interconnected network. Results obtained through a multi-level investigation of both DNA damage repair processes (e.g. gamma-H2AX response) and of the activation kinetics for intra/extra cellular signalling pathways (e.g. NFkB activation) show that the overall cell response is dominated by non-linear processes - such as negative feedbacks - leading to possible non equilibrium steady states and to a poor signal-to-noise ratio. Together with experimental data of radiation perturbed pathways, different modelling approaches will be also discussed.

  10. Effect of low dose rate radiation on cell growth kinetics.

    PubMed Central

    Gregg, E C; Yau, T M; Kim, S C

    1979-01-01

    Experimental determinations were made of cell number as a function of time for two strains of L5178Y mammalian cells maintained continuously in various environments of radiation. One strain possessed a shoulder in its dose response curve whereas the other did not. Neither strain showed any significant difference in growth rate for interdivision doses on the order of the median lethal dose or less delivered continuously at a low dose rate or pulsed every 4 h at a high instantaneous dose rate. It was also shown that large numbers of dead cells have little effect on growth rate and that these dead cells last as discrete entities for many days. A simple theory of growth rate in the presence of radiation is presented, and the agreement with the observations implies that there is no effect of any sublethal low dose rate radiation received in one generation on the growth rate or radiation sensitivity of the succeeding generation. Further analysis of the data also showed that for the no-shoulder cells at 37 degrees C, tritiated water had a relative biological effect close to unity for cell sterilization. PMID:262446

  11. A New Era of Low-Dose Radiation Epidemiology.

    PubMed

    Kitahara, Cari M; Linet, Martha S; Rajaraman, Preetha; Ntowe, Estelle; Berrington de González, Amy

    2015-09-01

    The last decade has introduced a new era of epidemiologic studies of low-dose radiation facilitated by electronic record linkage and pooling of cohorts that allow for more direct and powerful assessments of cancer and other stochastic effects at doses below 100 mGy. Such studies have provided additional evidence regarding the risks of cancer, particularly leukemia, associated with lower-dose radiation exposures from medical, environmental, and occupational radiation sources, and have questioned the previous findings with regard to possible thresholds for cardiovascular disease and cataracts. Integrated analysis of next generation genomic and epigenetic sequencing of germline and somatic tissues could soon propel our understanding further regarding disease risk thresholds, radiosensitivity of population subgroups and individuals, and the mechanisms of radiation carcinogenesis. These advances in low-dose radiation epidemiology are critical to our understanding of chronic disease risks from the burgeoning use of newer and emerging medical imaging technologies, and the continued potential threat of nuclear power plant accidents or other radiological emergencies. PMID:26231501

  12. Adaptively Tuned Iterative Low Dose CT Image Denoising.

    PubMed

    Hashemi, SayedMasoud; Paul, Narinder S; Beheshti, Soosan; Cobbold, Richard S C

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

  13. Thermoluminescent dosimeters for low dose X-ray measurements.

    PubMed

    Fernández, S Del Sol; García-Salcedo, R; Sánchez-Guzmán, D; Ramírez-Rodríguez, G; Gaona, E; de León-Alfaro, M A; Rivera-Montalvo, T

    2016-01-01

    The response of TLD-100, CaSO4:Dy and LiF:Mg,Cu,P for a range of X-ray low dose was measured. For calibration, the TLDs were arranged at the center of the X-ray field. The dose output of the X-ray machine was determined using an ACCU-Gold. All dosimeters were exposed at the available air kerma values of 14.69 mGy within a field 10×10 cm(2) at 80 cm of SSD. Results of LiF:Mg,Cu,P X-ray irradiated showed 4.8 times higher sensitivity than TLD-100. Meanwhile, TL response of CaSO4:Dy exposed at the same dose was 5.6 time higher than TLD-100. Experimental results show for low dose X-ray measurements a better linearity for LiF:Mg,Cu,P compared with that of TLD-100. CaSO4:Dy showed a linearity from 0.1 to 60 mGy. PMID:26609683

  14. Adaptively Tuned Iterative Low Dose CT Image Denoising

    PubMed Central

    Hashemi, SayedMasoud; Paul, Narinder S.; Beheshti, Soosan; Cobbold, Richard S. C.

    2015-01-01

    Improving image quality is a critical objective in low dose computed tomography (CT) imaging and is the primary focus of CT image denoising. State-of-the-art CT denoising algorithms are mainly based on iterative minimization of an objective function, in which the performance is controlled by regularization parameters. To achieve the best results, these should be chosen carefully. However, the parameter selection is typically performed in an ad hoc manner, which can cause the algorithms to converge slowly or become trapped in a local minimum. To overcome these issues a noise confidence region evaluation (NCRE) method is used, which evaluates the denoising residuals iteratively and compares their statistics with those produced by additive noise. It then updates the parameters at the end of each iteration to achieve a better match to the noise statistics. By combining NCRE with the fundamentals of block matching and 3D filtering (BM3D) approach, a new iterative CT image denoising method is proposed. It is shown that this new denoising method improves the BM3D performance in terms of both the mean square error and a structural similarity index. Moreover, simulations and patient results show that this method preserves the clinically important details of low dose CT images together with a substantial noise reduction. PMID:26089972

  15. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    USGS Publications Warehouse

    Wang, M.; Song, D.; Zheng, B.; Finkelman, R.B.; ,

    2008-01-01

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong. ?? 2008 New York Academy of Sciences.

  16. The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents

    SciTech Connect

    Mingshi Wang; Dangyu Song; Baoshan Zheng; R.B. Finkelman

    2008-10-15

    To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong.

  17. Arsenic behavior in newly drilled wells

    USGS Publications Warehouse

    Kim, M.-J.; Nriagu, J.; Haack, S.

    2003-01-01

    In the present paper, inorganic arsenic species and chemical parameters in groundwater were determined to investigate the factors related to the distribution of arsenic species and their dissolution from rock into groundwater. For the study, groundwater and core samples were taken at different depths of two newly drilled wells in Huron and Lapeer Counties, Michigan. Results show that total arsenic concentrations in the core samples varied, ranging from 0.8 to 70.7 mg/kg. Iron concentration in rock was about 1800 times higher than that of arsenic, and there was no correlation between arsenic and iron occurrences in the rock samples. Arsenic concentrations in groundwater ranged from <1 to 171 ??g/l. The arsenic concentration in groundwater depended on the amount of arsenic in aquifer rocks, and as well decreased with increasing depth. Over 90% of arsenic existed in the form of As(III), implying that the groundwater systems were in the reduced condition. The results such as high ferrous ion, low redox potential and low dissolved oxygen supported the observed arsenic species distribution. There was no noticeable difference in the total arsenic concentration and arsenic species ratio between unfiltered and filtered (0.45 ??m) waters, indicating that the particulate form of arsenic was negligible in the groundwater samples. There were correlations between water sampling depth and chemical parameters, and between arsenic concentration and chemical parameters, however, the trends were not always consistent in both wells. ?? 2003 Elsevier Science Ltd. All rights reserved.

  18. Arsenic Content in American Wine.

    PubMed

    Wilson, Denise

    2015-10-01

    Recent studies that have investigated arsenic content in juice, rice, milk, broth (beef and chicken), and other foods have stimulated an interest in understanding how prevalent arsenic contamination is in the U.S. food and beverage supply. The study described here focused on quantifying arsenic levels in wine. A total of 65 representative wines from the top four wine-producing states in the U.S. were analyzed for arsenic content. All samples contained arsenic levels that exceeded the U.S. Environmental Protection Agency (U.S. EPA) exposure limit for drinking water of 10 parts per billion (ppb) and all samples contained inorganic arsenic. The average arsenic detected among all samples studied was 23.3 ppb. Lead, a common co-contaminant to arsenic, was detected in 58% of samples tested, but only 5% exceeded the U.S. EPA exposure limit for drinking water of 15 ppb. Arsenic levels in American wines exceeded those found in other studies involving water, bottled water, apple juice, apple juice blend, milk, rice syrup, and other beverages. When taken in the context of consumption patterns in the U.S., the pervasive presence of arsenic in wine can pose a potential health risk to regular adult wine drinkers. PMID:26591333

  19. Ana insect model for assessing arsenic toxicity: Arsenic elevated glutathione content in the musca domestica and trichoplusia ni

    SciTech Connect

    Zaman, K.; Pardini, R.S.

    1995-12-01

    Throughout history, arsenic has acquired an unparalled reputation as a poison. Arsenic was used as a poison as early as 2000 B.C. The toxicity of arsenic (As) extends to mammals, fish, insects, plants and fungi. According to epidemiological evidence, inorganic arsenic compounds have been strongly suggested as human carcinogens. Human exposure to arsenic through various means is correlated with an increased incidence of skin, lung, and possibly liver cancers. Inorganic trivalent arsenic is systematically more poisonous than the pentavalent form and it is possible that pentavalent arsenic is reduced to the trivalent form before exerting any toxic effects. This study focuses on the potential to use two insect species, the housefly, Musca domestica and the cabbage looper moth, Trichoplusia ni, and a model for the study of arsenic toxicity. After 48 hours of exposure to Arsenic, a significant induction of Glutathione level and subsequent decrease in the level of GSSG in both species were observed. 21 refs., 2 figs., 1 tab.

  20. Gene Expression of Normal Human Epidermal Keratinocytes Modulated by Trivalent Arsenicals

    EPA Science Inventory

    Chronic exposure to inorganic arsenic (iAs) is associated with the development of benign and malignant human skin lesions including nonmelanoma skin cancers. The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (...

  1. Monitored Attenuation of Inorganic Contaminants in Ground Water Volume 2 – Assessment for Non-Radionuclides Including Arsenic, Cadmium, Chromium, Copper, Lead, Nickel, Nitrate, Perchlorate, and Selenium

    EPA Science Inventory

    This document represents the second volume of a set of three volumes that address the technical basis and requirements for assessing the potential applicability of MNA as part of a ground-water remedy for plumes with non-radionuclide and/or radionuclide inorganic contaminants. V...

  2. Low-dose aripiprazole for refractory burning mouth syndrome.

    PubMed

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  3. Quantifying exploratory low dose compounds in humans with AMS

    PubMed Central

    Dueker, Stephen R.; Vuong, Le T.; Lohstroh, Peter N.; Giacomo, Jason A.; Vogel, John S.

    2010-01-01

    Accelerator Mass Spectrometry is an established technology whose essentiality extends beyond simply a better detector for radiolabeled molecules. Attomole sensitivity reduces radioisotope exposures in clinical subjects to the point that no population need be excluded from clinical study. Insights in human physiochemistry are enabled by the quantitative recovery of simplified AMS processes that provide biological concentrations of all labeled metabolites and total compound related material at non-saturating levels. In this paper, we review some of the exploratory applications of AMS 14C in toxicological, nutritional, and pharmacological research. This body of research addresses the human physiochemistry of important compounds in their own right, but also serves as examples of the analytical methods and clinical practices that are available for studying low dose physiochemistry of candidate therapeutic compounds, helping to broaden the knowledge base of AMS application in pharmaceutical research. PMID:21047543

  4. Optical fiber sensor for low dose gamma irradiation monitoring

    NASA Astrophysics Data System (ADS)

    de Andrés, Ana I.; Esteban, Ã.`scar; Embid, Miguel

    2016-05-01

    An optical fiber gamma ray detector is presented in this work. It is based on a Terbium doped Gadolinium Oxysulfide (Gd2O2S:Tb) scintillating powder which cover a chemically etched polymer fiber tip. This etching improves the fluorescence gathering by the optical fiber. The final diameter has been selected to fulfill the trade-off between light gathering and mechanical strength. Powder has been encapsulated inside a microtube where the fiber tip is immersed. The sensor has been irradiated with different air Kerma doses up to 2 Gy/h with a 137Cs source, and the spectral distribution of the fluorescence intensity has been recorded in a commercial grade CCD spectrometer. The obtained signal-to-noise ratio is good enough even for low doses, which has allowed to reduce the integration time in the spectrometer. The presented results show the feasibility for using low cost equipment to detect/measure ionizing radiation as gamma rays are.

  5. Low-dose aripiprazole for refractory burning mouth syndrome

    PubMed Central

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  6. The spectrum of mutation produced by low dose radiation

    SciTech Connect

    Morley,Alexander,A; Turner, David,R

    2004-10-31

    Inherited mutations are the basis of evolution and acquired mutations in humans are important in ageing, cancer and possibly various forms of tissue degeneration. Mutations are responsible for many of the long-term effects of radiation. However, sensitive direct detection of mutations in humans has been difficult. The aims of the project were to develop methods for the sensitive enumeration of mutations in DNA, to measure mutation frequencies in a wide variety of tissue types and to quantify the mutational effect of direct oxidative damage produced by radiation, at both high and low doses. The project was successful in developing a sensitive method which could detect mutations directly in the genetic material, DNA at a sensitivity of 1 mutated molecule in 1000000000 unmutated molecules. However a number of methodological problems had to be overcome and lack of ongoing funding made it impossible to fulfill all of the aims of the project

  7. Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions

    SciTech Connect

    Davison, R.; Kaplan, K.; Bines, A.; Spies, S.; Reed, M.T.; Lesch, M.

    1986-12-01

    Thallium 201 (/sup 201/Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial /sup 201/Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

  8. Low-dose radiation: a cause of breast cancer

    SciTech Connect

    Land, C.E.

    1980-08-15

    It is likely that the breast is the organ most sensitive to radiation carcinogenesis in postpubertal women. Studies of different exposed populations have yielded remarkably consistent results, in spite of wide differences in underlying breast cancer rates and conditions of exposure. Excess risk is approximately proportional to dose, and is relatively independent of ionization density and fractionization of dose. This implies that the risk associated with low-dose exposures to ionizing radiation can be estimated with some confidence from higher-dose data. Excess risk is heavily dependent on age at exposure but relatively independent of population differences in normal risk. The temporal patterns after exposure of both radiation-induced and naturally occurring breast cancer are similar, suggesting a strong influence of factors other than radiation on radiation-induced breast cancer. Uncertainties remain about risks from exposures before puberty and after menopause.

  9. Radiobiological evaluation of low dose-rate prostate brachytherapy implants

    NASA Astrophysics Data System (ADS)

    Knaup, Courtney James

    Low dose-rate brachytherapy is a radiation therapy treatment for men with prostate cancer. While this treatment is common, the use of isotopes with varying dosimetric characteristics means that the prescription level and normal organ tolerances vary. Additionally, factors such as prostate edema, seed loss and seed migration may alter the dose distribution within the prostate. The goal of this work is to develop a radiobiological response tool based on spatial dose information which may be used to aid in treatment planning, post-implant evaluation and determination of the effects of prostate edema and seed migration. Aim 1: Evaluation of post-implant prostate edema and its dosimetric and biological effects. Aim 2: Incorporation of biological response to simplify post-implant evaluation. Aim 3: Incorporation of biological response to simplify treatment plan comparison. Aim 4: Radiobiologically based comparison of single and dual-isotope implants. Aim 5: Determine the dosimetric and radiobiological effects of seed disappearance and migration.

  10. Arsenic speciation in edible mushrooms.

    PubMed

    Nearing, Michelle M; Koch, Iris; Reimer, Kenneth J

    2014-12-16

    The fruiting bodies, or mushrooms, of terrestrial fungi have been found to contain a high proportion of the nontoxic arsenic compound arsenobetaine (AB), but data gaps include a limited phylogenetic diversity of the fungi for which arsenic speciation is available, a focus on mushrooms with higher total arsenic concentrations, and the unknown formation and role of AB in mushrooms. To address these, the mushrooms of 46 different fungus species (73 samples) over a diverse range of phylogenetic groups were collected from Canadian grocery stores and background and arsenic-contaminated areas. Total arsenic was determined using ICP-MS, and arsenic speciation was determined using HPLC-ICP-MS and complementary X-ray absorption spectroscopy (XAS). The major arsenic compounds in mushrooms were found to be similar among phylogenetic groups, and AB was found to be the major compound in the Lycoperdaceae and Agaricaceae families but generally absent in log-growing mushrooms, suggesting the microbial community may influence arsenic speciation in mushrooms. The high proportion of AB in mushrooms with puffball or gilled morphologies may suggest that AB acts as an osmolyte in certain mushrooms to help maintain fruiting body structure. The presence of an As(III)-sulfur compound, for the first time in mushrooms, was identified in the XAS analysis. Except for Agaricus sp. (with predominantly AB), inorganic arsenic predominated in most of the store-bought mushrooms (albeit with low total arsenic concentrations). Should inorganic arsenic predominate in these mushrooms from contaminated areas, the risk to consumers under these circumstances should be considered.

  11. Ultra Low Dose CT Pulmonary Angiography with Iterative Reconstruction

    PubMed Central

    Koehler, Thomas; Fingerle, Alexander A.; Brendel, Bernhard; Richter, Vivien; Rasper, Michael; Rummeny, Ernst J.; Noël, Peter B.; Münzel, Daniela

    2016-01-01

    Objective Evaluation of a new iterative reconstruction algorithm (IMR) for detection/rule-out of pulmonary embolism (PE) in ultra-low dose computed tomography pulmonary angiography (CTPA). Methods Lower dose CT data sets were simulated based on CTPA examinations of 16 patients with pulmonary embolism (PE) with dose levels (DL) of 50%, 25%, 12.5%, 6.3% or 3.1% of the original tube current setting. Original CT data sets and simulated low-dose data sets were reconstructed with three reconstruction algorithms: the standard reconstruction algorithm “filtered back projection” (FBP), the first generation iterative reconstruction algorithm iDose and the next generation iterative reconstruction algorithm “Iterative Model Reconstruction” (IMR). In total, 288 CTPA data sets (16 patients, 6 tube current levels, 3 different algorithms) were evaluated by two blinded radiologists regarding image quality, diagnostic confidence, detectability of PE and contrast-to-noise ratio (CNR). Results iDose and IMR showed better detectability of PE than FBP. With IMR, sensitivity for detection of PE was 100% down to a dose level of 12.5%. iDose and IMR showed superiority to FBP regarding all characteristics of subjective (diagnostic confidence in detection of PE, image quality, image noise, artefacts) and objective image quality. The minimum DL providing acceptable diagnostic performance was 12.5% (= 0.45 mSv) for IMR, 25% (= 0.89 mSv) for iDose and 100% (= 3.57 mSv) for FBP. CNR was significantly (p < 0.001) improved by IMR compared to FBP and iDose at all dose levels. Conclusion By using IMR for detection of PE, dose reduction for CTPA of up to 75% is possible while maintaining full diagnostic confidence. This would result in a mean effective dose of approximately 0.9 mSv for CTPA. PMID:27611830

  12. Low dose mTHPC photodynamic therapy for cholangiocarcinoma

    NASA Astrophysics Data System (ADS)

    Stepp, Herbert; Kniebühler, Gesa; Pongratz, Thomas; Betz, Christian S.; Göke, Burkhard; Sroka, Ronald; Schirra, Jörg

    2013-06-01

    Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion: Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

  13. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    SciTech Connect

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  14. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGES

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; et al

    2014-10-22

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initiallymore » improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Finally, understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.« less

  15. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    PubMed Central

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; Lee, JuYong; Yang, Yongyao; Mehrzad, Raman; Onufrak, Jillian; Song, Jin; Enderling, Heiko; Agarwal, Akhil; Rahimi, Layla; Morgan, James; Wilson, Paul F.; Carrozza, Joseph; Walsh, Kenneth; Kishore, Raj; Goukassian, David A.

    2014-01-01

    Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy. PMID:25337914

  16. Low-dose metronomic chemotherapy: a systematic literature analysis.

    PubMed

    Lien, K; Georgsdottir, S; Sivanathan, L; Chan, K; Emmenegger, U

    2013-11-01

    Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low doses of conventional chemotherapeutics, is an emerging alternative to conventional chemotherapy. While promising tumour control rates and excellent safety profiles have been observed, there are no definitive phase III trial results. Furthermore, the selection of patients, drug dosages and dosing intervals is empirical. To systematically review the current state of knowledge regarding LDM chemotherapy, we searched the MEDLINE, EMBASE, CENTRAL and PubMed databases for fully published LDM chemotherapy trials. We calculated the relative dose-intensity (RDI, mg/m(2)/week) of each LDM regimen as compared to conventional maximum tolerated dose (MTD) dosages and the 'dosing-density' (DD, % of days with chemotherapy administration per cycle). Meta-regression was performed to examine factors associated with disease control rate (DCR; complete response (CR)+partial response (PR)+stable disease (SD)). Eighty studies involving mainly pretreated patients with advanced/metastatic breast (26.25%) and prostate (11.25%) cancers were retrieved. The most commonly used drug was cyclophosphamide (43%). LDM chemotherapy was frequently combined with other therapies (64.5%). Response rate (RR) and progression-free survival (PFS) were the most frequent primary end-points (24% and 19%). Mean RR was 26.03% (95% confidence interval (CI): 21.4-30.7), median PFS was 4.6months (interquartile range (IQR): 2.9-7.0) and mean DCR was 56.3% (95% CI: 50.9-61.6). RDI, DD and metronomic drug used were not associated with DCR. Grade 3/4 adverse events were rare (anaemia 7.78%, fatigue 13.4%). Thus, LDM therapy appears to be clinically beneficial and safe in a broad range of tumors. However, meta-regression analysis did not identify predictive factors of response.

  17. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    SciTech Connect

    Kleiman, Norman Jay

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  18. IDENTIFYING CRITICAL CYSTEINE RESIDUES IN ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes methylation of inorganic arsenic to mono, di, and trimethylated arsenicals. Orthologous AS3MT genes in genomes ranging from simple echinoderm to human predict a protein with five conserved cysteine (C) residues. In ...

  19. Natural Antioxidants Against Arsenic-Induced Genotoxicity.

    PubMed

    Kumar, Munesh; Lalit, Minakshi; Thakur, Rajesh

    2016-03-01

    Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.

  20. 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...

  1. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    SciTech Connect

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  2. Simulated Microgravity and Low-Dose/Low-Dose-Rate Radiation Induces Oxidative Damage in the Mouse Brain.

    PubMed

    Mao, Xiao Wen; Nishiyama, Nina C; Pecaut, Michael J; Campbell-Beachler, Mary; Gifford, Peter; Haynes, Kristine E; Becronis, Caroline; Gridley, Daila S

    2016-06-01

    Microgravity and radiation are stressors unique to the spaceflight environment that can have an impact on the central nervous system (CNS). These stressors could potentially lead to significant health risks to astronauts, both acutely during the course of a mission or chronically, leading to long-term, post-mission decrements in quality of life. The CNS is sensitive to oxidative injury due to high concentrations of oxidizable, unsaturated lipids and low levels of antioxidant defenses. The purpose of this study was to evaluate oxidative damage in the brain cortex and hippocampus in a ground-based model for spaceflight, which includes prolonged unloading and low-dose radiation. Whole-body low-dose/low-dose-rate (LDR) gamma radiation using (57)Co plates (0.04 Gy at 0.01 cGy/h) was delivered to 6 months old, mature, female C57BL/6 mice (n = 4-6/group) to simulate the radiation component. Anti-orthostatic tail suspension was used to model the unloading, fluid shift and physiological stress aspects of the microgravity component. Mice were hindlimb suspended and/or irradiated for 21 days. Brains were isolated 7 days or 9 months after irradiation and hindlimb unloading (HLU) for characterization of oxidative stress markers and microvessel changes. The level of 4-hydroxynonenal (4-HNE) protein, an oxidative specific marker for lipid peroxidation, was significantly elevated in the cortex and hippocampus after LDR + HLU compared to controls (P < 0.05). The combination group also had the highest level of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression compared to controls (P < 0.05). There was a significant decrease in superoxide dismutase (SOD) expression in the animals that received HLU only or combined LDR + HLU compared to control (P < 0.05). In addition, 9 months after LDR and HLU exposure, microvessel densities were the lowest in the combination group, compared to age-matched controls in the cortex (P < 0.05). Our data provide the first evidence

  3. PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTLY WITH DNA

    EPA Science Inventory


    PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTL Y WITH DNA.

    Abstract:

    Although inorganic arsenic (iAs), arsenite or arsenate, is genotoxic, there has been no demonstration that iAs or a methylated metabolite...

  4. Comparative Distribution and Retention of Arsenic in Arsenic (+3 Oxidation State) Methyltransferase Knockout and Wild Type Mice

    EPA Science Inventory

    The mouse arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a ~ 43 kDa protein that catalyzes conversion of inorganic arsenic into methylated products. Heterologous expression of AS3MT or its silencing by RNA interference controls arsenic methylation phenotypes...

  5. ARSENIC (III) METHYLATED SPECIES REACT WITH DNA DIRECTLY AND COULD BE PROXIMATED/ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory


    ARSENIC(III) METHYLATED SPECIES REACT WITH DNA DIRECTL Y AND COULD BE PROXIMATE/ULTIMATE GENOTOXIC FORMS OF ARSENIC


    Arsenite and arsenate (iAs, inorganic arsenic) have been thought to act as genotoxicants without reacting directly with DNA; neither iAs nor As(V) m...

  6. Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

    EPA Science Inventory

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in whi...

  7. One step derivatization with British Anti-Lewsite in combination with gas chromatography coupled to triple-quadrupole tandem mass spectrometry for the fast and selective analysis of inorganic arsenic in rice.

    PubMed

    Kang, Ju Hui; Jung, Hyun Jeong; Jung, Mun Yhung

    2016-08-31

    We developed a new fast and selective analytical method for the determination of inorganic arsenic (iAs) in rice by a gas chromatography - tandem mass spectrometry (GC-MS/MS) in combination with one step derivatization of inorganic arsenic (iAs) with British Anti-Lewsite (BAL). Two step derivatization of iAs with BAL has been previously performed for the GC-MS analysis. In this paper, the quantitative one step derivatization condition was successfully established. The GC-MS/MS was carried out with a short nonpolar capillary column (0.25 mm × 10 m) under the conditions of fast oven temperature ramp rate (4 °C/s) and high linear velocity (108.8 cm/s) of the carrier gas. The established GC-MS/MS method showed an excellent linearity (r(2) > 0.999) in a tested range (0.2-100.0 μg L(-1)), ultra-low limit of detection (LOD, 0.08 pg), and high precision and accuracy. The GC-MS/MS technique showed far greater selectivity (22.5 fold higher signal to noise ratio in rice sample) on iAs than GC-MS method. The gas chromatographic running time was only 2.5 min with the iAs retention time of 1.98 min. The established method was successfully applied to quantify the iAs contents in polished rice. The mean iAs content in the Korean polished rice (n = 27) was 66.1 μg kg(-1) with the range of 37.5-125.0 μg kg(-1). This represents the first report on the GC-tandem mass spectrometry in combination with the one step derivatization with BAL for the iAs speciation in rice. This GC-MS/MS method would be a simple, useful and reliable measure for the iAs analysis in rice in the laboratories in which the expensive and element specific HPLC-ICP-MS is not available. PMID:27506365

  8. The Chemistry and Metabolism of Arsenic

    EPA Science Inventory

    I. IntrodctionA century of study of the process by which many organisms convert inorganic arsenic into an array of methylated metabolites has answered many questions and has posed some new ones. The capacity of microorganisms to. form volatile arsenic compounds was first recogniz...

  9. Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

    PubMed

    Piñol, S; Sala, A; Guzman, C; Marcos, S; Joya, X; Puig, C; Velasco, M; Velez, D; Vall, O; Garcia-Algar, O

    2015-11-01

    Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries.

  10. Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

    PubMed

    Piñol, S; Sala, A; Guzman, C; Marcos, S; Joya, X; Puig, C; Velasco, M; Velez, D; Vall, O; Garcia-Algar, O

    2015-11-01

    Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries. PMID:26431705

  11. Responses to Low Doses of Ionizing Radiation in Biological Systems

    PubMed Central

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems. To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses. The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed

  12. Reduction in urinary arsenic with bottled-water intervention.

    PubMed

    Josyula, Arun B; McClellen, Hannah; Hysong, Tracy A; Kurzius-Spencer, Margaret; Poplin, Gerald S; Stürup, Stefan; Burgess, Jefferey L

    2006-09-01

    The study was conducted to measure the effectiveness of providing bottled water in reducing arsenic exposure. Urine, tap-water and toenail samples were collected from non-smoking adults residing in Ajo (n=40) and Tucson (n=33), Arizona, USA. The Ajo subjects were provided bottled water for 12 months prior to re-sampling. The mean total arsenic (microg/L) in tap-water was 20.3+/-3.7 in Ajo and 4.0+/-2.3 in Tucson. Baseline urinary total inorganic arsenic (microg/L) was significantly higher among the Ajo subjects (n=40, 29.1+/-20.4) than among the Tucson subjects (n=32, 11.0+/-12.0, p<0.001), as was creatinine-adjusted urinary total inorganic arsenic (microg/g) (35.5+/-25.2 vs 13.2+/-9.3, p<0.001). Baseline concentrations of arsenic (microg/g) in toenails were also higher among the Ajo subjects (0.51+/-0.72) than among the Tucson subjects (0.17+/-0.21) (p<0.001). After the intervention, the mean urinary total inorganic arsenic in Ajo (n=36) dropped by 21%, from 29.4+/-21.1 to 23.2+/-23.2 (p=0.026). The creatinine-adjusted urinary total inorganic arsenic and toenail arsenic levels did not differ significantly with the intervention. Provision of arsenic-free bottled water resulted in a modest reduction in urinary total inorganic arsenic.

  13. Reduction in urinary arsenic with bottled-water intervention.

    PubMed

    Josyula, Arun B; McClellen, Hannah; Hysong, Tracy A; Kurzius-Spencer, Margaret; Poplin, Gerald S; Stürup, Stefan; Burgess, Jefferey L

    2006-09-01

    The study was conducted to measure the effectiveness of providing bottled water in reducing arsenic exposure. Urine, tap-water and toenail samples were collected from non-smoking adults residing in Ajo (n=40) and Tucson (n=33), Arizona, USA. The Ajo subjects were provided bottled water for 12 months prior to re-sampling. The mean total arsenic (microg/L) in tap-water was 20.3+/-3.7 in Ajo and 4.0+/-2.3 in Tucson. Baseline urinary total inorganic arsenic (microg/L) was significantly higher among the Ajo subjects (n=40, 29.1+/-20.4) than among the Tucson subjects (n=32, 11.0+/-12.0, p<0.001), as was creatinine-adjusted urinary total inorganic arsenic (microg/g) (35.5+/-25.2 vs 13.2+/-9.3, p<0.001). Baseline concentrations of arsenic (microg/g) in toenails were also higher among the Ajo subjects (0.51+/-0.72) than among the Tucson subjects (0.17+/-0.21) (p<0.001). After the intervention, the mean urinary total inorganic arsenic in Ajo (n=36) dropped by 21%, from 29.4+/-21.1 to 23.2+/-23.2 (p=0.026). The creatinine-adjusted urinary total inorganic arsenic and toenail arsenic levels did not differ significantly with the intervention. Provision of arsenic-free bottled water resulted in a modest reduction in urinary total inorganic arsenic. PMID:17366771

  14. Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

  15. THE ROLE OF VALENCE AND METHYLATION STATE ON THE ACTIVITY OF ARSENIC DURING MITOSIS

    EPA Science Inventory

    Trivalent methylated arsenicals are much more potent DNA damaging agents, clastogens, and large deletion mutagens than are their inorganic and pentavalent counterparts. Previously we had noticed that many of the arsenicals induced "c-type" anaphases characteristic of spindle pois...

  16. THE VALENCE AND METHYLATION STATE OF ARSENIC DETERMINES ITS POTENCY IN INTERACTION WITH THE MITOTIC APPARATUS

    EPA Science Inventory

    We have previously shown that the cytotoxic and genotoxic potency of arsenicals is dependent upon their valence and methylation state. Trivalent methylated arsenicals are much more potent DNA damaging agents than are their inorganic and pentavalent counterparts. Furthermore, thei...

  17. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals. PMID:24772825

  18. Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis

    PubMed Central

    Seed, Thomas M.; Inal, Cynthia E.

    2014-01-01

    Purpose Amifostine is a highly efficacious cytoprotectant when administered in vivo at high doses. However, at elevated doses, drug toxicity manifests for general, non-clinical radioprotective purposes. Various strategies have been developed to avoid toxic side-effects: The simplest is reducing the dose. In terms of protecting hematopoietic tissues, where does this effective, non-toxic minimum dose lie? Material and methods C3H/HEN mice were administered varying doses of amifostine (25–100 mg/kg) 30 min prior to cobalt-60 irradiation and euthanized between 4–14 days for blood and bone marrow collection and analyses. Results Under steady-state, amifostine had little effect on bipotential and multi-potential marrow progenitors but marginally suppressed a more primitive, lineage negative progenitor subpopulation. In irradiated animals, prophylactic drug doses greater than 50 mg/kg resulted in significant regeneration of bipotential progenitors, moderate regeneration of multipotential progenitors, but no significant and consistent regeneration of more primitive progenitors. The low amifostine dose (25 mg/kg) failed to elicit consistent and positive, radioprotective actions on any of the progenitor subtypes. Conclusions Radioprotective doses for amifostine appear to lie between 25 and 50 mg/kg. Mature, lineage-restricted progenitors appear to be more responsive to the protective effects of low doses of amifostine than the more primitive, multipotential progenitors. PMID:24597748

  19. Differentially Expressed Genes Associated with Low-Dose Gamma Radiation

    NASA Astrophysics Data System (ADS)

    Hegyesi, Hargita; Sándor, Nikolett; Schilling, Boglárka; Kis, Enikő; Lumniczky, Katalin; Sáfrány, Géza

    We have studied low dose radiation induced gene expression alterations in a primary human fibroblast cell line using Agilent's whole human genome microarray. Cells were irradiated with 60Co γ-rays (0; 0.1; 0.5 Gy) and 2 hours later total cellular RNA was isolated. We observed differential regulation of approximately 300-500 genes represented on the microarray. Of these, 126 were differentially expressed at both doses, among them significant elevation of GDF-15 and KITLG was confirmed by qRT-PCR. Based on the transcriptional studies we selected GDF-15 to assess its role in radiation response, since GDF-15 is one of the p53 gene targets and is believed to participate in mediating p53 activities. First we confirmed gamma-radiation induced dose-dependent changes in GDF-15 expression by qRT-PCR. Next we determined the effect of GDF-15 silencing on radiosensitivity. Four GDF-15 targeting shRNA expressing lentiviral vectors were transfected into immortalized human fibroblast cells. We obtained efficient GDF-15 silencing in one of the four constructs. RNA interference inhibited GDF-15 gene expression and enhanced the radiosensitivity of the cells. Our studies proved that GDF-15 plays an essential role in radiation response and may serve as a promising target in radiation therapy.

  20. Low dose CT perfusion using k-means clustering

    NASA Astrophysics Data System (ADS)

    Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

    2016-03-01

    We aim at improving low dose CT perfusion functional parameters maps and CT images quality, preserving quantitative information. In a dynamic CT perfusion dataset, each voxel is measured T times, where T is the number of acquired time points. In this sense, we can think about a voxel as a point in a T-dimensional space, where the coordinates of the voxels would be the values of its time attenuation curve (TAC). Starting from this idea, a k-means algorithm was designed to group voxels in K classes. A modified guided time-intensity profile similarity (gTIPS) filter was implemented and applied only for those voxels belonging to the same class. The approach was tested on a digital brain perfusion phantom as well as on clinical brain and body perfusion datasets, and compared to the original TIPS implementation. The TIPS filter showed the highest CNR improvement, but lowest spatial resolution. gTIPS proved to have the best combination of spatial resolution and CNR improvement for CT images, while k-gTIPS was superior to both gTIPS and TIPS in terms of perfusion maps image quality. We demonstrate k-means clustering analysis can be applied to denoise dynamic CT perfusion data and to improve functional maps. Beside the promising results, this approach has the major benefit of being independent from the perfusion model employed for functional parameters calculation. No similar approaches were found in literature.

  1. Dosimetric Study of a Low-Dose-Rate Brachytherapy Source

    NASA Astrophysics Data System (ADS)

    Rodríguez-Villafuerte, M.; Arzamendi, S.; Díaz-Perches, R.

    Carcinoma of the cervix is the most common malignancy - in terms of both incidence and mortality - in Mexican women. Low dose rate (LDR) intracavitary brachytherapy is normally prescribed for the treatment of this disease to the vast majority of patients attending public hospitals in our country. However, most treatment planning systems being used in these hospitals still rely on Sievert integral dose calculations. Moreover, experimental verification of dose distributions are hardly ever done. In this work we present a dosimetric characterisation of the Amersham CDCS-J 137Cs source, an LDR brachytherapy source commonly used in Mexican hospitals. To this end a Monte Carlo simulation was developed, that includes a realistic description of the internal structure of the source embedded in a scattering medium. The Monte Carlo results were compared to experimental measurements of dose distributions. A lucite phantom with the same geometric characteristics as the one used in the simulation was built. Dose measurements were performed using thermoluminescent dosimeters together with commercial RadioChromic dye film. A comparison between our Monte Carlo simulation, the experimental data, and results reported in the literature is presented.

  2. Sensitivity to low-dose radiation in radiosensitive wasted mice

    SciTech Connect

    Paunesku, T.; Protic, M.; Woloschak, G. E.

    1999-11-12

    Mice homozygous for the autosomal recessive wasted mutation (wst/wst) have abnormalities in T-lymphocytes and in the anterior motor neuron cells of the spinal cord, leading to sensitivity to low doses of ionizing radiation, hind limb paralysis, and immunodeficiency. This defect results in a failure to gain weight by 20 days and death at 28 days of age. The wasted mutation (previously mapped to mouse chromosome 2) is shown to be a 3-bp deletion in a T-cell-specific (and perhaps motor-neuron-specific) regulatory region (promoter) of the proliferating cell nuclear antigen (PCNA) gene on mouse chromosome 2. A regulatory element is also shown to be important in PCNA expression in T-lymphocytes and motor neuron cells afflicted by the 3-bp deletion in the PCNA promoter. The model is as follows: Absence of PCNA expression in the thymuses (and motor neurons) of wasted mice causes cellular apoptosis; this absence of expression is mediated by a positive transactor that can bind to the wild-type but not the wasted mutant PCNA promoter; the bound protein induces late expression of PCNA in T-lymphocytes and prevents onset of radiation sensitivity in the cells.

  3. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    PubMed

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  4. Algorithm-enabled low-dose micro-CT imaging.

    PubMed

    Han, Xiao; Bian, Junguo; Eaker, Diane R; Kline, Timothy L; Sidky, Emil Y; Ritman, Erik L; Pan, Xiaochuan

    2011-03-01

    Micro-computed tomography (micro-CT) is an important tool in biomedical research and preclinical applications that can provide visual inspection of and quantitative information about imaged small animals and biological samples such as vasculature specimens. Currently, micro-CT imaging uses projection data acquired at a large number (300-1000) of views, which can limit system throughput and potentially degrade image quality due to radiation-induced deformation or damage to the small animal or specimen. In this work, we have investigated low-dose micro-CT and its application to specimen imaging from substantially reduced projection data by using a recently developed algorithm, referred to as the adaptive-steepest-descent-projection-onto-convex-sets (ASD-POCS) algorithm, which reconstructs an image through minimizing the image total-variation and enforcing data constraints. To validate and evaluate the performance of the ASD-POCS algorithm, we carried out quantitative evaluation studies in a number of tasks of practical interest in imaging of specimens of real animal organs. The results show that the ASD-POCS algorithm can yield images with quality comparable to that obtained with existing algorithms, while using one-sixth to one quarter of the 361-view data currently used in typical micro-CT specimen imaging.

  5. Risk of cancer subsequent to low-dose radiation.

    PubMed

    Warren, S

    1980-10-01

    Prominent among media items related to the Three Mile Island episode were prophecies of future cancers. The credibility of some of these estimates are discussed. The average person has been exposed by the age of 50 to 2.5 rad (0.025 Gy) from natural background. We define low doses as under 25 rad (0.25 Gy). The most heavily exposed members of the general population during the Three Mile Island event received 83 mrad (0.83 mGy). Those exposed to 2500 mrad (25 mGy) would show no pathologically recognizable effects of radiation though there is evidence that chromosomal damage may occur with doses about 1 rad (0.01 Gy). An official stated among the consequences of the Three Mile Island accident that two additional cancer deaths would result. No epidemiologist could detect such an increase in the population at risk. It has been generally agreed that the linear hypothesis is useful for determining protection standards, not prognosis. Objective criteria for pathologic diagnosis of cause-effect relations are presented. PMID:7430985

  6. Information content of low-dose radiographs: Part 2

    SciTech Connect

    Morris, R.A.

    1997-10-01

    The previous paper described the concept of using the net number of information bits transmitted in a radiographic image as a measure of the contrast parameter of image quality. The concept is particularly useful when the image contrast is limited by the statistics of the photon fluence incident on the detector (low doses). The Wolfram Research Mathematica program (described in Ref. 1) that was used to simulate a noisy image of an object with two thicknesses and to calculate the resulting IC (information content). The only noise source in the simulation was fluctuations in the photon fluence incident on the detector. The results from the simulation were compared to data obtained from actual radiographs of a copper step wedge radiographed with 10 and 50 pulses from a 150-p, V x-ray machine. Good agreement between the simulation and experiment was obtained when the photon fluence was considered a free, adjustable parameter. This report extends the simulation described in Ref. 1 and shows how IC varies as the following radiographic parameters change: object thickness; object Z number; x-ray energy; and incident x-ray fluence.

  7. Functional modulation on macrophage by low dose naltrexone (LDN).

    PubMed

    Yi, Zhe; Guo, Shengnan; Hu, Xu; Wang, Xiaonan; Zhang, Xiaoqing; Griffin, Noreen; Shan, Fengping

    2016-10-01

    Previously it was confirmed that naltrexone, a non-peptide δ-opioid receptor selective antagonist is mainly used for alcoholic dependence and opioid addiction treatment. However, there is increasing data on immune regulation of low dose naltrexone (LDN). The aim of this work was to explore the effect of LDN on the phenotype and function of macrophage. The changes of macrophage after treatment with LDN were examined using flow cytometry (FCM); FITC-dextran phagocytosis and enzyme-linked immunosorbent assay (ELISA). We have found that LDN enhances function of macrophage as confirmed by up-regulating MHC II molecule and CD64 on macrophage while down-regulating CD206 expression. Furthermore the productions of TNF-α, IL-6, IL-1β, increased significantly. Macrophages in LDN treated group performed the enhanced phagocytosis. Therefore it is concluded that LDN could promote function of macrophage and this work has provided concrete data of impact on immune system by LDN. Especially the data would support interaction between CD4+T cell and macrophage in AIDS treatment with LDN in Africa (LDN has already been approved in Nigeria for the use in AIDS treatment). PMID:27561742

  8. Low-dose diclofenac, naproxen, and ibuprofen cohort study.

    PubMed

    Pérez-Gutthann, S; García-Rodríguez, L A; Duque-Oliart, A; Varas-Lorenzo, C

    1999-07-01

    The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (< or = 75 mg), 46,919 using naproxen (< or = 750 mg), and 54,830 using ibuprofen (< or = 1200 mg). Age, gender, and comorbidity were similar in the three cohorts. Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5-4.6), 2.3 (1.2-4.2), and 0.4 (0.04-1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.

  9. Role of heme Oxygenase-1 in low dose Radioadaptive response

    PubMed Central

    Bao, Lingzhi; Ma, Jie; Chen, Guodong; Hou, Jue; Hei, Tom K.; Yu, K.N.; Han, Wei

    2016-01-01

    Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1–10 cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5 cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells. PMID:26966892

  10. Personalized low dose CT via variable kVp

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Jin, Yannan; Yao, Yangyang; Wu, Mingye; Yan, Ming; Tao, Kun; Yin, Zhye; De Man, Bruno

    2015-03-01

    Computerized Tomography (CT) is a powerful radiographic imaging technology but the health risk due to the exposure of x-ray radiation has drawn wide concern. In this study, we propose to use kVp modulation to reduce the radiation dose and achieve the personalized low dose CT. Two sets of simulation are performed to demonstrate the effectiveness of kVp modulation and the corresponding calibration. The first simulation used the helical body phantom (HBP) that is an elliptical water cylinder with high density bone inserts. The second simulation uses the NCAT phantom to emulate the practical use of kVp modulation approach with region of interest (ROI) selected in the cardiac region. The kVp modulation profile could be optimized view by view based on the knowledge of patient attenuation. A second order correction is applied to eliminate the beam hardening artifacts. To simplify the calibration process, we first generate the calibration vectors for a few representative spectra and then acquire other calibration vectors with interpolation. The simulation results demonstrate the beam hardening artifacts in the images with kVp modulation can be eliminated with proper beam hardening correction. The results also show that the simplification of calibration did not impair the image quality: the calibration with the simplified and the complete vectors both eliminate the artifacts effectively and the results are comparable. In summary, this study demonstrates the feasibility of kVp modulation and gives a practical way to calibrate the high order beam hardening artifacts.

  11. Arsenic (+ 3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

    SciTech Connect

    Hughes, Michael F.; Edwards, Brenda C.; Herbin-Davis, Karen M.; Saunders, Jesse; Styblo, Miroslav; Thomas, David J.

    2010-12-15

    Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in which mice received daily oral doses of 0.5 mg of arsenic as arsenate per kilogram of body weight. Regardless of genotype, arsenic body burdens attained steady state after 10 daily doses. At steady state, arsenic body burdens in As3mt knockout mice were 16 to 20 times greater than in wild-type mice. During the post dosing clearance period, arsenic body burdens declined in As3mt knockout mice to {approx} 35% and in wild-type mice to {approx} 10% of steady-state levels. Urinary concentration of arsenic was significantly lower in As3mt knockout mice than in wild-type mice. At steady state, As3mt knockout mice had significantly higher fractions of the body burden of arsenic in liver, kidney, and urinary bladder than did wild-type mice. These organs and lung had significantly higher arsenic concentrations than did corresponding organs from wild-type mice. Inorganic arsenic was the predominant species in tissues of As3mt knockout mice; tissues from wild-type mice contained mixtures of inorganic arsenic and its methylated metabolites. Diminished capacity for arsenic methylation in As3mt knockout mice prolongs retention of inorganic arsenic in tissues and affects whole body clearance of arsenic. Altered retention and tissue tropism of arsenic in As3mt knockout mice could affect the toxic or carcinogenic effects associated with exposure to this metalloid or its methylated metabolites.

  12. Arsenic distribution and speciation in Daphnia pulex.

    PubMed

    Caumette, Guilhem; Koch, Iris; Moriarty, Maeve; Reimer, Kenneth J

    2012-08-15

    Rat Lake, Yellowknife, Northwest Territories, is situated on arsenic-rich tailings from a historical gold mine. The abundant zooplankton species Daphnia pulex in this lake was used to study the impact of arsenic at the base of the freshwater food web; the speciation and distribution of arsenic in D. pulex and its food sources; and the origin of formation of organoarsenicals in freshwater systems. The arsenic concentration in lake water was measured as 0.25 mg L(-1), while the zooplankton organisms contained up to 35 mg kg(-1) d.w. arsenic. Plankton samples were analyzed for arsenic speciation, by using X-ray Absorption Near Edge Structure (XANES) on the whole, dried samples and High Performance Liquid Chromatography coupled to Inductively Coupled Plasma Mass Spectrometry (HPLC-ICP-MS) on water extracts. XANES data suggest that D. pulex mainly contain inorganic arsenicals with 56% of arsenic with +5 oxidation state and 10% of arsenic with +3 oxidation state, but also 34% of organoarsenic compounds that were identified with HPLC-ICP-MS as monomethylarsonate (MMA), dimethylarsinate (DMA), and arsenosugars. The most abundant of the organoarsenicals was the glycerol sugar (Sugar 1). X-ray Fluorescence (XRF) mapping of D. pulex for arsenic distribution showed that arsenic was mainly distributed in the gut of the animal, where its concentration was ten times higher than in the surrounding tissues. Moreover, the analysis of residues from extractions targeting water-soluble and lipid-soluble arsenicals suggested that part of the measured arsenic signal comes from ingested sediments, phytoplankton, or other food sources. These food sources contain inorganic arsenic only, with As(V)-O in phytoplankton and As(III)-S in sediments, suggesting the possibility that the organoarsenicals compounds detected in the tissues of the organism are created by the Daphnia. PMID:22750169

  13. Metabolism of arsenic and its toxicological relevance.

    PubMed

    Watanabe, Takayuki; Hirano, Seishiro

    2013-06-01

    Arsenic is a worldwide environmental pollutant and a human carcinogen. It is well recognized that the toxicity of arsenicals largely depends on the oxidoreduction states (trivalent or pentavalent) and methylation levels (monomethyl, dimethyl, and trimethyl) that are present during the process of metabolism in mammals. However, presently, the specifics of the metabolic pathway of inorganic arsenicals have yet to be confirmed. In mammals, there are two possible mechanisms that have been proposed for the metabolic pathway of inorganic arsenicals, oxidative methylation, and glutathione conjugation. Oxidative methylation, which was originally proposed in fungi, is based on findings that arsenite (iAs(III)) is sequentially converted to monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) in both humans and in laboratory animals such as mice and rats. However, recent in vitro observations have demonstrated that arsenic is only methylated in the presence of glutathione (GSH) or other thiol compounds, which strongly suggests that arsenic is methylated in trivalent forms. The glutathione conjugation mechanism is supported by findings that have shown that most intracellular arsenicals are trivalent and excreted from cells as GSH conjugates. Since non-conjugated trivalent arsenicals are highly reactive with thiol compounds and are easily converted to less toxic corresponding pentavalent arsenicals, the arsenic-glutathione conjugate stability may be the most important factor for determining the toxicity of arsenicals. In addition, "being a non-anionic form" also appears to be a determinant of the toxicity of oxo-arsenicals or thioarsenicals. The present review discusses both the metabolism of arsenic and the toxicity of arsenic metabolites.

  14. THE ROLE OF ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE IN ARSENIC METABOLISM

    EPA Science Inventory

    Arsenic (As) is widely distributed in the environment. Epidemiological studies have linked chronic exposures to inorganic As (iAs) to adverse health effects such as skin lesions, peripheral neuropathy, cardiovascular, hepatic and renal disorders, diabetes mellitus, skin cancer,...

  15. Tissue dosimetry, metabolism and excretion of pentavalent and trivalent monomethylated arsenic in mice after oral administration

    PubMed Central

    Hughes, Michael F.; Devesa, Vicenta; Adair, Blakely M.; Styblo, Miroslav; Kenyon, Elaina M.; Thomas, David J.

    2008-01-01

    Exposure to monomethylarsonic acid (MMA(V)) and monomethylarsonous acid (MMA(III)) can result from their formation as metabolites of inorganic arsenic and by the use of the sodium salts of MMA(V) as herbicides. This study compared the disposition of MMA(V) and MMA(III) in adult female B6C3F1 mice. Mice were gavaged po with MMA(V), either unlabeled or labeled with 14C at two dose levels (0.4 or 40 mg As/kg). Other mice were dosed po with unlabeled MMA(III) at one dose level (0.4 mg As/kg). Mice were housed in metabolism cages for collection of excreta and sacrificed serially over 24 h for collection of tissues. MMA(V)-derived radioactivity was rapidly absorbed, distributed and excreted. By 8 h post-exposure, 80% of both doses of MMA(V) were eliminated in urine and feces. Absorption of MMA(V) was dose dependent; that is, there was less than a 100-fold difference between the two dose levels in the area under the curves for the concentration-time profiles of arsenic in blood and major organs. In addition, urinary excretion of MMA(V)-derived radioactivity in the low dose group was significantly greater (P < 0.05) than in the high dose group. Conversely, fecal excretion of MMA(V)-derived radioactivity was significantly greater (P < 0.05) in the high dose group than in the low dose group. Speciation of arsenic by hydride generation-atomic absorption spectrometry in urine and tissues of mice administered MMA(V) or MMA(III) found that methylation of MMA(V) was limited while the methylation of MMA(III) was extensive. Less than 10% of the dose excreted in urine of MMA(V)-treated mice was in the form of methylated products, whereas it was greater than 90% for MMA(III)-treated mice. In MMA(V)-treated mice, 25% or less of the tissue arsenic was in the form of dimethylarsenic, whereas in MMA(III)-treated mice, 75% or more of the tissue arsenic was in the form of dimethylarsenic. Based on urinary analysis, administered dose of MMA(V) did not affect the level of its metabolites

  16. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully.

  17. Health Risks From Low Doses and Low Dose-Rates of Ionizing Radiation. Session 5: Future of Radiation Protection Regulations.

    PubMed

    Cool, Donald A

    2016-03-01

    The system of radiological protection is a prospective approach to protection of individuals in all exposure situations. It must be applied equitably across all age groups and all populations. This is a very different circumstance from dose assessment for a particular individual where the unique characteristics of the individual and the exposure can be taken into account. Notwithstanding the ongoing discussions on the possible shape of the dose response at low doses and dose rates, the prospective system of protection has therefore historically used a linear assumption as a pragmatic, prudent and protective approach. These radiation protection criteria are not intended to be a demarcation between "safe" and "unsafe" and are the product of a risk-informed judgement that includes inputs from science, ethics, and experience. There are significant implications for different dose response relationships. A linear model allows for equal treatment of an exposure, irrespective of the previously accumulated exposure. In contrast, other models would predict different implications. Great care is therefore needed in separating the thinking around risk assessment from risk management, and prospective protection for all age groups and genders from retrospective assessment for a particular individual. In the United States, the prospective regulatory structure functions effectively because of assumptions that facilitate independent treatment of different types of exposures, and which provide pragmatic and prudent protection. While the a linear assumption may, in fact, not be consistent with the biological reality, the implications of a different regulatory model must be considered carefully. PMID:26808877

  18. Measurements of Arsenic in the Urine and Nails of Individuals Exposed to Low Concentrations of Arsenic in Drinking Water From Private Wells in a Rural Region of Québec, Canada.

    PubMed

    Gagnon, Fabien; Lampron-Goulet, Eric; Normandin, Louise; Langlois, Marie-France

    2016-01-01

    Chronic exposure to inorganic arsenic leads to an increased risk of cancer. A biological measurement was conducted in 153 private well owners and their families consuming water contaminated by inorganic arsenic at concentrations that straddle 10 μg/L. The relationship between the external dose indicators (concentration of inorganic arsenic in wells and daily well water inorganic arsenic intake) and the internal doses (urinary arsenic--sum of As(III), DMA, and MMA, adjusted for creatinine--and total arsenic in toenails) was evaluated using multiple linear regressions, controlling for age, gender, dietary sources of arsenic, and number of cigarettes smoked. It showed that urinary arsenic was associated with concentration of inorganic arsenic in wells (p < .001) and daily well water inorganic arsenic intake (p < .001) in adults, and with daily well water inorganic arsenic intake (p = .017) and rice consumption (p = .022) in children (n = 43). The authors' study reinforces the drinking-water quality guidelines for inorganic arsenic. PMID:26867295

  19. Evaluation of a low-dose neonatal chest radiographic system.

    PubMed

    Burton, E M; Kirks, D R; Strife, J L; Henry, G C; Kereiakes, J G

    1988-11-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad [0.009 vs 0.029 mGy]) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad [0.009 vs 0.037 mGy]). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

  20. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. PMID:27302731

  1. Evaluation of a low-dose neonatal chest radiographic system

    SciTech Connect

    Burton, E.M.; Kirks, D.R.; Strife, J.L.; Henry, G.C.; Kereiakes, J.G.

    1988-11-01

    A new low-dose chest radiographic system for use in the neonatal nursery was evaluated. This test system, composed of a Du Pont Kevlar fiber-front cassette, Quanta fast-detail screen, Cronex 4L film (wide latitude), and additional yttrium filtration (0.1 mm), reduced the radiation dose in neonatal chest radiography by 69% (0.9 vs 2.9 mrad (0.009 vs 0.029 mGy)) as compared with a conventional system without added yttrium filtration; the thyroid dose was reduced by 76% (0.9 vs 3.7 mrad (0.009 vs 0.037 mGy)). The cumulative dose reduction was achieved through a combination of factors, including (1) beam hardening by the added yttrium filter, (2) increased X-ray transmission through the Kevlar cassette, and (3) a fast film-screen combination. Scatter radiation at distances of 1 and 6 ft. (0.3 and 1.8 m) was negligible for both systems. Image sharpness was compared for the conventional system with and without added yttrium filtration and for the Kevlar system with yttrium. Although sharpness of bony detail was unchanged by adding yttrium filtration to the conventional system, a decrease in sharpness was noted with the Kevlar system. Because image sharpness was affected in the test system, we are not using the Kevlar-Cronex 4L system for mobile chest radiography in the neonatal intensive care unit, despite dose reductions. However, further study is recommended to determine if there is a slower film-screen combination with yttrium filtration that will not degrade image sharpness.

  2. [Relationship to Carcinogenesis of Repetitive Low-Dose Radiation Exposure].

    PubMed

    Ootsuyama, Akira

    2016-06-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose.

  3. Lung cancer risk at low doses of alpha particles.

    PubMed

    Hofmann, W; Katz, R; Zhang, C X

    1986-10-01

    A survey of inhabitant exposures arising from the inhalation of 222Rn and 220Rn progeny, and lung cancer mortality has been carried out in two adjacent areas in Guangdong Province, People's Republic of China, designated as the "high background" and the "control" area. Annual exposure rates are 0.38 working level months (WLM) per year in the high background, and 0.16 WLM/yr in the control area. In 14 yr of continuous study, from 1970 to 1983, age-adjusted mortality rates were found to be 2.7 per 10(5) living persons of all ages in the high background area, and 2.9 per 10(5) living persons in the control area. From this data, we conclude that we are unable to determine excess lung cancers over the normal fluctuations below a cumulative exposure of 15 WLM. This conclusion is supported by lung cancer mortality data from Austrian and Finnish high-background areas. A theoretical analysis of epidemiological data on human lung cancer incidence from inhaled 222Rn and 220Rn progeny, which takes into account cell killing as competitive with malignant transformation, leads to the evaluation of a risk factor which is either a linear-exponential or a quadratic-exponential function of the alpha-particle dose. Animal lung cancer data and theoretical considerations can be supplied to support either hypothesis. Thus we conclude that at our current stage of knowledge both the linear-exponential and the quadratic-exponential extrapolation to low doses seem to be equally acceptable for Rn-induced lung cancer risk, possibly suggesting a linear-quadratic transformation function with an exponential cell-killing term, or the influence of risk-modifying factors such as repair or proliferation stimuli.

  4. Low dose acute alcohol effects on GABAA receptor subtypes

    PubMed Central

    Wallner, Martin; Hanchar, H. Jacob; Olsen, Richard W.

    2010-01-01

    GABAA receptors (GABAARs) are the main inhibitory neurotransmitter receptors and have long been implicated in mediating at least part of the acute actions of ethanol. For example, ethanol and GABAergic drugs including barbiturates and benzodiazepines share many pharmacological properties. Besides the prototypical synaptic GABAAR subtypes, nonsynaptic GABAARs have recently emerged as important regulators of neuronal excitability. While high doses (≥100 mM) of ethanol have been reported to enhance activity of most GABAAR subtypes, most abundant synaptic GABAARs are essentially insensitive to ethanol concentrations that occur during social ethanol consumption (<30 mM). However, extrasynaptic δ and β3 subunit-containing GABAARs, associated in the brain with α4or α6 subunits, are sensitive to low millimolar ethanol concentrations, as produced by drinking half a glass of wine. Additionally, we found that a mutation in the cerebellar α6 subunit (α6R100Q), initially reported in rats selectively bred for increased alcohol sensitivity, is sufficient to produce increased alcohol-induced motor impairment and further increases of alcohol sensitivity in recombinant α6β3δ receptors. Furthermore, the behavioral alcohol antagonist Ro15-4513 blocks the low dose alcohol enhancement on α4/6/β3δ receptors, without reducing GABA-induced currents. In binding assays α4β3δ GABAARs bind [3H] Ro15-4513 with high affinity, and this binding is inhibited, in an apparently competitive fashion, by low ethanol concentrations, as well as analogs of Ro15-4513 that are active to antagonize ethanol or Ro15-4513’s block of ethanol. We conclude that most low to moderate dose alcohol effects are mediated by alcohol actions on alcohol/Ro15-4513 binding sites on GABAAR subtypes. PMID:16814864

  5. Effect of low-dose gaseous ozone on pathogenic bacteria

    PubMed Central

    2012-01-01

    Background Treatment of chronically infected wounds is a challenge, and bacterial environmental contamination is a growing issue in infection control. Ozone may have a role in these situations. The objective of this study was to determine whether a low dose of gaseous ozone/oxygen mixture eliminates pathogenic bacteria cultivated in Petri dishes. Methods A pilot study with 6 bacterial strains was made using different concentrations of ozone in an ozone-oxygen mixture to determine a minimally effective dose that completely eliminated bacterial growth. The small and apparently bactericidal gaseous dose of 20 μg/mL ozone/oxygen (1:99) mixture, applied for 5min under atmospheric pressure was selected. In the 2nd phase, eight bacterial strains with well characterized resistance patterns were evaluated in vitro using agar-blood in adapted Petri dishes (105 bacteria/dish). The cultures were divided into 3 groups: 1- ozone-oxygen gaseous mixture containing 20 μg of O3/mL for 5 min; 2- 100% oxygen for 5 min; 3- baseline: no gas was used. Results The selected ozone dose was applied to the following eight strains: Escherichia coli, oxacillin-resistant Staphylococcus aureus, oxacillin-susceptible Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii, Acinetobacter baumannii susceptible only to carbapenems, and Pseudomonas aeruginosa susceptible to imipenem and meropenem. All isolates were completely inhibited by the ozone-oxygen mixture while growth occurred in the other 2 groups. Conclusion A single topical application by nebulization of a low ozone dose completely inhibited the growth of all potentially pathogenic bacterial strains with known resistance to antimicrobial agents. PMID:23249441

  6. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    PubMed

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001) following arsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  7. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    PubMed

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-01

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001) following arsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process. PMID:26861378

  8. Grain Unloading Of Arsenic Species In Rice

    EPA Science Inventory

    Rice (Oryza sativa) is the staple food for over half the world's population yet may represent a significant dietary source of inorganic arsenic (As), a nonthreshold, class 1 human carcinogen. Rice grain As is dominated by the inorganic species, and the organic species dim...

  9. RECENT ADVANCES IN ARSENIC CARCINOGENESIS: MODES OF ACTION, ANIMAL MODEL SYSTEMS AND METHYLATED ARSENIC METABOLITES

    EPA Science Inventory


    Abstract:

    Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer -skin, lung, urinary bladder, liver and kidney. Tumors can be produced from eit...

  10. Acute arsenic poisoning in two siblings.

    PubMed

    Lai, Melisa W; Boyer, Edward W; Kleinman, Monica E; Rodig, Nancy M; Ewald, Michele Burns

    2005-07-01

    We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy. PMID:15995066

  11. 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.

  12. Compelling Issues Compounding the Understanding of Low Dose Radiation Effects: But Do They Matter?

    PubMed

    Morgan, William F

    2016-03-01

    Recent advances in low dose radiation research have raised a number of compelling issues that have compounded the understanding of low dose radiation effects. Here some of them are outlined: the linear no-threshold model for predicting effects at low radiation doses, dose rate effectiveness factor, attributability, and public perception of low dose radiation effects. The impact of changes in any of these hotly debated issues on radiation protection is considered.

  13. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    SciTech Connect

    Al-Qaisieh, Bashar; Mason, Josh; Bownes, Peter; Henry, Ann; Dickinson, Louise; Ahmed, Hashim U.; Emberton, Mark; Langley, Stephen

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  14. A Simple Low-dose X-ray CT Simulation from High-dose Scan

    PubMed Central

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong

    2015-01-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements. PMID:26543245

  15. Arsenic Methyltransferase

    EPA Science Inventory

    The metalloid arsenic enters the environment by natural processes (volcanic activity, weathering of rocks) and by human activity (mining, smelting, herbicides and pesticides). Although arsenic has been exploited for homicidal and suicidal purposes since antiquity, its significan...

  16. Arsenic and bladder cancer: observations and suggestions.

    PubMed

    Radosavljević, Vladan; Jakovljević, Branko

    2008-10-01

    Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.

  17. Arsenic concentration and speciation of the marine hyperaccumulator whelk Buccinum undatum collected in coastal waters of Northern Britain.

    PubMed

    Urgast, Dagmar S; Adams, Gillian C; Raab, Andrea; Feldmann, Jörg

    2010-05-01

    European whelks (Buccinum undatum) have shown to accumulate high levels of arsenic. Since the accumulation process is not well understood it is necessary to gain information about the geographical variability of the arsenic concentration in them. Here we show that the mean arsenic concentrations of the whelks are site specific and vary by a factor of 3.5 in ten different geographical locations. At fishing grounds where whelks exhibited low arsenic concentrations the arsenic concentration increased linearly with size, whereas the whelks with high arsenic levels from a different location showed no correlation. Although the overall arsenic concentration in the whelks differed between 45 and 655 mg kg(-1) d.w., the inorganic arsenic concentration did not exceed 0.4 mg kg(-1) d.w. The main arsenic compound is arsenobetaine, which is widely considered as non-toxic. The exposure to toxic inorganic arsenic when eating whelks cannot be estimated from their size or their total arsenic concentration.

  18. Determination of diphenylarsinic acid, phenylarsonic acid and inorganic arsenic in drinking water by graphite-furnace atomic-absorption spectrometry after simultaneous separation and preconcentration with solid-phase extraction disks.

    PubMed

    Hagiwara, Kenta; Inui, Tetsuo; Koike, Yuya; Nakamura, Toshihiro

    2013-01-01

    A simple method of graphite-furnace atomic-absorption spectrometry (GFAAS) after solid-phase extraction (SPE) was developed for the determination of diphenylarsinic acid (DPAA), phenylarsonic acid (PAA), and inorganic arsenic (iAs) in drinking water. This method involves the simultaneous collection of DPAA, PAA, and iAs using three stacked SPE disks, i.e., an Empore SDB-XD disk (the upper layer), an activated carbon disk (the middle layer), and a Cation-SR disk loaded with Zr and Ca (ZrCa-CED; the lower layer). A 200-mL aqueous sample was adjusted to pH 3 with nitric acid and passed through the SPE disks at a flow rate of 15 mL min(-1), to concentrate DPAA on the SDB-XD disk, PAA on the activated carbon disk, and iAs on the ZrCa-CED. The As compounds were eluted from the disks with 10 mL of ethanol containing 0.5 mol L(-1) ammonia solution for DPAA, 20 mL of 1 mol L(-1) ammonia solution for PAA, and 20 mL of 6 mol L(-1) hydrochloric acid for iAs. The eluates of DPAA, PAA, and iAs were diluted to 20, 25, and 25 mL, respectively, with deionized water, and then analyzed by GFAAS. The detection limits of As (three-times the standard deviation (n = 3) of the blank values) were 0.13 and 0.16 μg L(-1) at enrichment factors of 10 and 8, respectively, using a 200-mL water sample. Spike tests with 2 μg (10 μg L(-1)) of DPAA, PAA, and iAs in 200 mL of tap water and bottled drinking water showed good recoveries (96.1-103.8%).

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

    EPA Science Inventory

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

  20. The effects of repeated low-dose sarin exposure

    SciTech Connect

    Shih, T.-M. . E-mail: tsungming.a.shih@us.army.mil; Hulet, S.W.; McDonough, J.H.

    2006-09-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD{sub 5} dose of sarin (42 {mu}g/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD{sub 5} of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD{sub 5} of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD{sub 5} sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD{sub 5} sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD{sub 5} sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD{sub 5} sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0

  1. Direct solid sample analysis with graphite furnace atomic absorption spectrometry—a fast and reliable screening procedure for the determination of inorganic arsenic in fish and seafood.

    PubMed

    Zmozinski, Ariane V; Llorente-Mirandes, Toni; Damin, Isabel C F; López-Sánchez, José F; Vale, Maria Goreti R; Welz, Bernhard; Silva, Márcia M

    2015-03-01