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Sample records for low-dose inorganic arsenic

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

    SciTech Connect

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

    1997-10-01

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

  2. 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

  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. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  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. Inorganic Arsenic and Human Prostate Cancer

    PubMed Central

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

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

  15. Low dose of arsenic trioxide triggers oxidative stress in zebrafish brain: expression of antioxidant genes.

    PubMed

    Sarkar, Shuvasree; Mukherjee, Sandip; Chattopadhyay, Ansuman; Bhattacharya, Shelley

    2014-09-01

    treated fish. It is concluded that even a low dose of arsenic trioxide is toxic enough to induce significant oxidative stress in zebrafish brain.

  16. In vitro Assays of Inorganic Arsenic Methylation

    PubMed Central

    Drobna, Zuzana; Styblo, Miroslav; Thomas, David J.

    2009-01-01

    Inorganic arsenic is extensively metabolized to produce mono-, di-, and trimethylated products. The formation of these metabolites produces a variety of intermediates that differ from inorganic arsenic in terms of patterns of distribution and retention and in toxic effects. In order to elucidate the pathway for arsenic methylation, it was necessary to develop a reliable in vitro assay system in which the formation of methylated metabolites could be monitored. Here, in vitro assay system that uses the postmicrosomal supernate from rat liver is used as the source of the enzymatic activity that catalyzes methylation reactions. This system can be used to study the requirements for methylation reactions (e.g., identifying the donor of methyl groups) and for screening of compounds as potential activators or inhibitors of arsenic methylation. PMID:20440380

  17. IRIS Toxicological Review of Inorganic Arsenic (Cancer) ...

    EPA Pesticide Factsheets

    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 internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the Toxicological Review of Inorganic Arsenic and the charge to external peer reviewers are posted on this site. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical. An assessment of noncancer health effects of inorganic arsenic will be released for external peer review and public comment at a later date.

  18. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... would occur if the employee were not using a respirator. (iii) The employer shall collect full shift... exposures to inorganic arsenic, without regard to the use of respirators, are in excess of the permissible... respirators. All persons entering a regulated area shall be supplied with a respirator, selected in...

  19. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... would occur if the employee were not using a respirator. (iii) The employer shall collect full shift... exposures to inorganic arsenic, without regard to the use of respirators, are in excess of the permissible... respirators. All persons entering a regulated area shall be supplied with a respirator, selected in...

  20. Inorganic arsenic: A non-genotoxic carcinogen.

    PubMed

    Cohen, Samuel M; Chowdhury, Aparajita; Arnold, Lora L

    2016-11-01

    Inorganic arsenic induces a variety of toxicities including cancer. The mode of action for cancer and non-cancer effects involves the metabolic generation of trivalent arsenicals and their reaction with sulfhydryl groups within critical proteins in various cell types which leads to the biological response. In epithelial cells, the response is cell death with consequent regenerative proliferation. If this continues for a long period of time, it can result in an increased risk of cancer. Arsenicals do not react with DNA. There is evidence for indirect genotoxicity in various in vitro and in vivo systems, but these involve exposures at cytotoxic concentrations and are not the basis for cancer development. The resulting markers of genotoxicity could readily be due to the cytotoxicity rather than an effect on the DNA itself. Evidence for genotoxicity in humans has involved detection of chromosomal aberrations, sister chromatid exchanges in lymphocytes and micronucleus formation in lymphocytes, buccal mucosal cells, and exfoliated urothelial cells in the urine. Numerous difficulties have been identified in the interpretation of such results, including inadequate assessment of exposure to arsenic, measurement of micronuclei, and potential confounding factors such as tobacco exposure, folate deficiency, and others. Overall, the data strongly supports a non-linear dose response for the effects of inorganic arsenic. In various in vitro and in vivo models and in human epidemiology studies there appears to be a threshold for biological responses, including cancer.

  1. DOES DISSOLVED INORGANIC CARBON PLAY A ROLE IN ARSENIC MOBILIZATION?

    EPA Science Inventory

    Recent experimental results provide evidence that dissolved inorganic carbon plays a direct role in mobilizing arsenic in anoxic aquatic environments. This hypothesis is partially supported by observed correlations between elevated levels of arsenic and alkalinity in a ground wa...

  2. Methylation of Inorganic Arsenic by Murine Fetal Tissue Explants

    PubMed Central

    Broka, Derrick; Ditzel, Eric; Quach, Stephanie; Camenisch, Todd D.

    2016-01-01

    Although it is generally believed that the developing fetus is principally exposed to inorganic arsenic and the methylated metabolites from the maternal metabolism of arsenic, little is known about whether the developing embryo can autonomously metabolize arsenic. This study investigates inorganic arsenic methylation by murine embryonic organ cultures of the heart, lung, and liver. mRNA for AS3mt, the gene responsible for methylation of arsenic, was detected in all of embryonic tissue types studied. In addition, methylated arsenic metabolites were generated by all three tissue types. The fetal liver explants yielded the most methylated arsenic metabolites (~7% of total arsenic/ 48 hr incubation) while the heart, and lung preparations produced slightly greater than 2% methylated metabolites. With all tissues the methylation proceeded mostly to the dimethylated arsenic species. This has profound implications for understanding arsenic-induced fetal toxicity, particularly if the methylated metabolites are produced autonomously by embryonic tissues. PMID:26446802

  3. 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.

  4. 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

  5. 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...

  6. IRIS Toxicological Review of Inorganic Arsenic (Cancer) ...

    EPA Pesticide Factsheets

    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 now returning the assessment to the SAB and releasing the document to the public for a focused review of EPA's responses to the SAB recommendations. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical.

  7. 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,...

  8. Total and inorganic arsenic in Iranian rice.

    PubMed

    Cano-Lamadrid, Marina; Munera-Picazo, Sandra; Burló, Francisco; Hojjati, Mohammad; Carbonell-Barrachina, Ángel A

    2015-05-01

    It is well known that arsenic (As) exposure, particularly to inorganic species (i-As), has adverse effects on humans. Nowadays, the European Union (EU) has still not regulated the maximum residue limit of As in commercial samples of rice and rice-based products, although it is actively working on the topic. The European Food Safety Authority (EFSA) is collecting data on total arsenic (t-As) and i-As from different rice-producing regions not only from EU countries but also from other parts of the world to finally set up this maximum threshold. As Iran is a rice-producing country, the aim of this work was to evaluate the contents of t-As and i-As in 15 samples of Iranian white, nonorganic, and aromatic rice collected from the most important rice-producing regions of the country. The means of t-As and i-As were 120 and 82 μg/kg, respectively. The experimental i-As mean in Iranian rice was below the Chinese standard for the i-As in rice, 150 μg/kg, and the Food and Agriculture Organization of the United Nations (FAO) limit, 200 μg/kg. Therefore, Iranian rice seems to have reasonable low i-As content and it is safe to be marketed in any market, including China and the EU.

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. Low-Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus-Induced Autoimmune Myocarditis in Mice

    PubMed Central

    Nyland, Jennifer F.; Fairweather, DeLisa; Shirley, Devon L.; Davis, Sarah E.; Rose, Noel R.; Silbergeld, Ellen K.

    2012-01-01

    Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model. PMID:21984480

  20. 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.

  1. 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.

  2. Low dose of arsenic trioxide inhibits multidrug resistant-related P-glycoprotein expression in human neuroblastoma cell line.

    PubMed

    Liu, Ling; Li, Yang; Xiong, Xilin; Qi, Kai; Zhang, Chi; Fang, Jianpei; Guo, Haixia

    2016-12-01

    This study investigated arsenic trioxide (As2O3), cisplatin (DDP) and etoposide (Vp16) on the anticancer effects and P-glycoprotein (P-gp) expression in neuroblastoma (NB) SK-N-SH cells. The potential influence of As2O3, DDP and Vp16 currently included in NB routine treatment protocols on cytotoxicity in SK-N-SH cells was measured by flow cytometry and drug half-maximal inhibitory concentration (IC50) was established. Moreover, chemotherapeutic agent-mediated changes of cellular expression levels of resistant-related P-gp, was monitored using western blotting. The data showed that As2O3, DDP and Vp16 significantly inhibited the growth and survival of the SK-N-SH cells at different concentration. Notably, the levels of apoptosis were upregulated in SK-N-SH cells with an acceleration of the exposure time and the concentration of As2O3, DDP and Vp16. As2O3, DDP and Vp16 were observed with their IC50 values on SK-N-SH cells being 3 µM, 8 and 100 µg/ml, respectively. Flow cytometry analysis showed that As2O3 at low concentrations in SK-N-SH cells led to enhanced accumulation of cell populations in G2/M phase with increasing the exposure time, and increased levels of apoptosis. In contrast, we observed that SK-N-SH cell populations arrested in S phase by DDP and Vp16. In vitro examination revealed that following pretreatment of SK-N-SH cells with As2O3, the expression of P-gp was not increased. The expression of P-gp downregulation were noted following the group treated by As2O3 at 2 and 3 µM. Exposed to As2O3 at 3 µM for 72 h, SK-N-SH cells exhibited lower expression of P-gp than 2 µM As2O3 for 72 h. In contrast, the expression of P-gp was upregulated by DDP and VP16. In summary, SK-N-SH cells were responsive to chemotherapeutic agent-induced apoptosis in a dose-dependent and time-dependent manner. In particular, ours findings showed that low dose of As2O3 markedly reduced the P-gp expression and increased apoptotic cell death in human NB cell line.

  3. Differential modulation of cellular antioxidant status in zebrafish liver and kidney exposed to low dose arsenic trioxide.

    PubMed

    Sarkar, Shuvasree; Mukherjee, Sandip; Chattopadhyay, Ansuman; Bhattacharya, Shelley

    2017-01-01

    Zebrafish were exposed to a nonlethal dose (1/350LC50; 50µg/L) of As2O3 and sampled at 7, 15, 30, 60 and 90 days of treatment. The oxidative stress response was assessed in terms of time-dependent histopathological changes, lipid peroxidation, GSH status, activities of detoxification enzymes and expression of antioxidant genes in liver and kidney. As2O3 treatment enhanced lipid peroxidation except at day 90 in liver and day 30 in kidney. Glutathione depleted significantly in the liver except on day 30; whereas in kidney, it increased initially but thereafter depleted significantly. The liver GST activity was high until day 30, low on day 60 and high on day 90. On the other hand, activity of GST in kidney remained high throughout the exposure. GR activity in liver decreased initially but augmented from 30 days onwards whereas in kidney it remained high until 30 days of exposure. Significant increase in GPx and CAT activities in liver and kidney confirmed oxidative stress in zebrafish which correlated with mRNA expression of antioxidant genes. Upregulation in mRNA level of Cu-Zn Sod in liver and kidney was prominent. Gpx1 upregulation was more conspicuous in kidney as compared to liver while the pattern of Cat expression was almost similar in both the organs. Among the mitochondrial genes, expression of Cox1 was significantly high only after 90 days in liver, while in kidney it enhanced at 7, 30 and 60 days of arsenic exposure. Ucp2 was upregulated in liver after 15 days of exposure but significantly downregulated at day 90; in kidney it remained unchanged at other time points except at day 90. An overall increased expression of Bcl2 further confirmed As2O3 induced oxidative stress in zebrafish liver and kidney. The pattern of mRNA expression of Nrf2 was not uniform and was in accordance to its downstream antioxidant genes. Present findings elucidate that low dose of As2O3 exposure induces a time dependent differential modulation of antioxidant status in liver and

  4. 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...

  5. 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

  6. 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 ...

  7. IRIS Toxicological Review of Ingested Inorganic Arsenic (2005 ...

    EPA Pesticide Factsheets

    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 for EPA's assessment of the cancer hazard and risks of organic and inorganic arsenic. The panel will review an OPP Science Issue Paper (with an attachment prepared by ORD) and a revised hazard and dose response assessment/characterization for inclusion in the Integrated Risk Information System (IRIS) prepared by OW. Inorganic arsenic is used for hardening copper and lead alloys. It also is used in glass manufacturing as a decolorizing and refining agent, as a component of electrical devices, in the semiconductor industry, and as a catalyst in the production of ethylene oxide.

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

    PubMed

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

    2017-03-08

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

  9. 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.

  10. 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.

  11. 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.

  12. Total and inorganic arsenic in dietary supplement supplies in northern Mexico.

    PubMed

    García-Rico, Leticia; Tejeda-Valenzuela, Lourdes

    2013-07-01

    The aim of this study was to evaluate the presence of total and inorganic arsenic in dietary supplements composed of herbal plants and seaweed, and to determine the potential toxicological risk. Total arsenic was determined by dry ashing and hydride generation atomic absorption spectrometry, and inorganic arsenic was determined by acid digestion, solvent extraction, and hydride generation atomic absorption spectrometry. Total and inorganic arsenic in the supplements ranged from 0.07 to 8.31 mg kg(-1) dry weight and from 0.14 to 0.28 mg kg(-1) dry weight, respectively. Daily intake of total arsenic ranged from 0.05 to 12.46 μg day(-1). Inorganic arsenic intake ranged from 0.21 to 0.83 μg day(-1), values that are below the Benchmark Dose Lower Confidence Limit recommended by the Word Health Organization. Therefore, there appears to be a low risk of adverse effects resulting from excess inorganic arsenic intake from these supplements. This is the first study conducted in Mexico that investigates total and inorganic arsenic in dietary supplements. Although the results do not suggest toxicological risk, it is nonetheless important considering the toxicity of inorganic arsenic and the increasing number consumer preferences for dietary supplements. Moreover, it is important to improve and ensure the safety of dietary supplements containing inorganic arsenic.

  13. 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.

  14. 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

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

    PubMed Central

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

    1998-01-01

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

  16. Inorganic arsenic and trace elements in Ghanaian grain staples.

    PubMed

    Adomako, Eureka E; Williams, Paul N; Deacon, Claire; Meharg, Andrew A

    2011-10-01

    A total of 549 samples of rice, maize, wheat, sorghum and millet were obtained from markets in Ghana, the EU, US and Asia. Analysis of the samples, originating from 21 countries in 5 continents, helped to establish global mean trace element concentrations in grains; thus placing the Ghanaian data within a global context. Ghanaian rice was generally low in potentially toxic elements, but high in essential nutrient elements. Arsenic concentrations in rice from US (0.22 mg/kg) and Thailand (0.15 mg/kg) were higher than in Ghanaian rice (0.11 mg/kg). Percentage inorganic arsenic content of the latter (83%) was, however, higher than for US (42%) and Thai rice (67%). Total arsenic concentration in Ghanaian maize, sorghum and millet samples (0.01 mg/kg) was an order of magnitude lower than in Ghanaian rice, indicating that a shift from rice-centric to multigrain diets could help reduce health risks posed by dietary exposure to inorganic As.

  17. 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.

  18. 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.

  19. 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.

  20. Inorganic arsenic can be potent granulotoxin in mammalian neutrophils in vitro.

    PubMed

    Taheri, Masumeh; Mehrzad, Jalil; Afshari, Reza; Saleh-Moghaddam, Massoud; Mahmudy Gharaie, Mohamad Hosein

    2016-09-01

    An important outcome arising out of occupational/environmental exposure to arsenic (As) is immunotoxicity. To determine the impact of inorganic As on innate immune cells, effects of a low dose of NaAsO2 (i.e. 20 ng As/ml) on select parameters associated with human and bovine neutrophils (PMN) were evaluated in vitro. PMN isolated from the blood of healthy individuals and cows (n = 8/treatment) were pre-incubated with NaAsO2 for 12 h before effects on PMN phagocytosis, transcription of TLR2, TLR4 and CD64 in human PMN - as well as on phagocytosis-dependent/-independent cell chemiluminescence (CL), phagocytosis and killing of Staphylococcus aureus and Escherichia coli, PMN H2O2 production and necrosis and TLR4 transcription in bovine PMN - were assessed. Relative to control (no As) PMN, treatment with As significantly decreased phagocytic capacity and CD64 mRNA, but increased TLR2 and TLR4 mRNA, in human PMN. In bovine PMN, while As also led to increased TLR4 mRNA abundance, it resulted in decreases in phagocytosis-dependent and -independent CL, PMN H2O2 production, PMN phagocytosis and killing of both E. coli and S. aureus by PMN. Considering the broad roles of PMN in immunology, the results of these studies increase our understanding of functional consequences of As exposure in inducing immunotoxicity and increasing susceptibility to (infectious) diseases in mammals.

  1. 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.

  2. 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

  3. Use of mode of action data to inform a dose-response assessment for bladder cancer following exposure to inorganic arsenic.

    PubMed

    Gentry, P R; Yager, J W; Clewell, R A; Clewell, H J

    2014-10-01

    In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies.

  4. 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.

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

    PubMed Central

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

    2016-01-01

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

  6. RE: Request for Correction - SAB Workgroup Review of Draft IRIS Assessment for Inorganic Arsenic

    EPA Pesticide Factsheets

    Request from Lynn Bergeson for the correction of information in the draft EPA document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS).

  7. 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.

  8. 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.

  9. Notification of SAB Workgroup Public Meeting for the Toxicological Review of Inorganic Arsenic

    EPA Pesticide Factsheets

    Organic Arsenical Products Task Force (OAPTF), a group of registrants of pesticide products that contain monosodium methanearsonate (MSMA), to request that the Science Advisory Board (SAB) reschedule the public meeting of a workgroup to conduct a review of the draft document entitled Toxicological Review of Inorganic Arsenic

  10. RE: Notification of SAB Workgroup Public Meeting for the Toxicological Review of Inorganic Arsenic

    EPA Pesticide Factsheets

    Request from the Organic Arsenical Products Task Force for the Science Advisory Board to reschedule the public meeting of a workgroup to conduct a review of the draft document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS).

  11. 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 ...

  12. 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...

  13. 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.

  14. 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

    ... 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 CFR... obtaining information (29 U.S.C. 657). The information collection requirements in the Inorganic...

  15. Biological monitoring of occupational exposure to inorganic arsenic

    PubMed Central

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

    1999-01-01

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

  16. Ethanol enhances tumor angiogenesis in vitro induced by low-dose arsenic in colon cancer cells through hypoxia-inducible factor 1 alpha pathway.

    PubMed

    Wang, Lei; Son, Young-Ok; Ding, Songze; Wang, Xin; Hitron, John Andrew; Budhraja, Amit; Lee, Jeong-Chae; Lin, Qinchen; Poyil, Pratheeshkumar; Zhang, Zhuo; Luo, Jia; Shi, Xianglin

    2012-12-01

    Health effects due to environmental exposure to arsenic are a major global health concern. Arsenic has been known to induce carcinogenesis and enhance tumor development via complex and unclear mechanism. Ethanol is also a well-established risk factor for many malignancies. However, little is known about the effects of coexposure to arsenic and ethanol in tumor development. In this study, we investigate the signaling and angiogenic effect of coexposure of arsenic and ethanol on different colon cancer cell lines. Results show that ethanol markedly enhanced arsenic-induced tumor angiogenesis in vitro. These responses are related to intracellular reactive oxygen species (ROS) generation, NADPH oxidase activation, and upregulation of PI3K/Akt and hypoxia-inducible factor 1 alpha (HIF-1α) signaling. We have also found that ethanol increases the arsenic-induced expression and secretion of angiogenic signaling molecules such as vascular endothelial growth factor, which further confirmed the above observation. Antioxidant enzymes inhibited arsenic/ethanol-induced tumor angiogenesis, demonstrating that the responsive signaling pathways of coexposure to arsenic and ethanol are related to ROS generation. We conclude that ethanol is able to enhance arsenic-induced tumor angiogenesis in colorectal cancer cells via the HIF-1α pathway. These results indicate that alcohol consumption should be taken into consideration in the investigation of arsenic-induced carcinogenesis in arsenic-exposed populations.

  17. Inorganic arsenic in seafood: does the extraction method matter?

    PubMed

    Pétursdóttir, Ásta H; Gunnlaugsdóttir, Helga; Krupp, Eva M; Feldmann, Jörg

    2014-05-01

    Nine different extraction methods were evaluated for three seafood samples to test whether the concentration of inorganic arsenic (iAs) determined in seafood is dependent on the extraction method. Certified reference materials (CRM) DOLT-4 (Dogfish Liver) and TORT-2 (Lobster Hepatopancreas), and a commercial herring fish meal were evaluated. All experimental work described here was carried out by the same operator using the same instrumentation, thus eliminating possible differences in results caused by laboratory related factors. Low concentrations of iAs were found in CRM DOLT-4 (0.012±0.003mgkg(-1)) and the herring fish meal sample (0.007±0.002mgkg(-1)) for all extraction methods. When comparing the concentration of iAs in CRM TORT-2 found in this study and in the literature dilute acids, HNO3 and HCl, showed the highest extracted iAs wheras dilute NaOH (in 50% ethanol) showed significantly lower extracted iAs. However, most other extraction solvents were not statistically different from one another.

  18. 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.

  19. 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

  20. 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...

  1. 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

  2. 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.

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

    PubMed

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

    2010-04-01

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

  4. 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

  5. Hybrid flow system for automatic dynamic fractionation and speciation of inorganic arsenic in environmental solids.

    PubMed

    Zhang, Yanlin; Miró, Manuel; Kolev, Spas D

    2015-03-03

    An integrated flow analysis system and protocol are proposed for the first time for automatic dynamic flow-through fractionation of inorganic arsenic (arsenite and arsenate) in environmental solids in combination with its real-time speciation. Four extractants (i.e., (1) 0.05 M ammonium sulfate, (2) 0.05 M ammonium dihydrogen phosphate, (3) 0.2 M ammonium oxalate, and (4) a mixture of 0.2 M ammonium oxalate and 0.1 M ascorbic acid at 96 °C) are applied sequentially to the sample to measure bioaccessible inorganic arsenic associated with (1) nonspecifically sorbed phases, (2) specifically sorbed phases, (3) amorphous plus poorly crystalline hydrous oxides of iron and aluminum, and (4) well-crystallized hydrous oxides of Fe and Al, respectively. The kinetic extraction profiles of arsenite and total inorganic arsenic are obtained for each extractant by automatic collection of a given number of its aliquots (subfractions) exposed to the solid sample. Arsenite and total inorganic arsenic in each subfraction are converted to arsine sequentially by hydride generation at pH 4.50 and in 1.14 M hydrochloric acid, respectively. Arsine is absorbed into a potassium permanganate solution, the discoloration of which is related to the concentration of the corresponding arsenic species. The proposed method is successfully validated by analyzing a soil reference material (NIST 2710a) and a sediment sample.

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

    PubMed

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

    2017-02-11

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

  7. 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

  8. Total and inorganic arsenic in the fauna of the Guadalquivir estuary: environmental and human health implications.

    PubMed

    Suñer, M A; Devesa, V; Muñoz, O; López, F; Montoro, R; Arias, A M; Blasco, J

    1999-12-06

    To evaluate the impact on fauna of the release of toxic waste from the tailings dam operated by the Boliden Apirsa S.L company at Aznalcóllar, Seville (Spain) a study was carried out of total and inorganic arsenic contents in 164 samples from six different estuary species, including molluscs, crustaceans and fish, collected at six sampling stations distributed along the estuary and mouth of the River Guadalquivir. The contents found, expressed in micrograms per gram wet weight, were as follows. Total arsenic: Crassostrea angulata--giant cupped oyster (2.44 +/- 0.45); Scrobicularia plana--peppery furrow (2.50 +/- 0.73); Palaemon longirostris--delta prawn (1.33 +/- 0.54); Uca tangeri--AfroEuropean fiddler crab (1.76 +/- 0.08); Melicertus kerathurus--shrimp (3.60 +/- 1.92); and Liza ramada--mullet (0.65 +/- 0.38). Inorganic arsenic: C. angulata (0.09 +/- 0.02); S. plana (0.38 +/- 0.23); P. longirostris (0.04 +/- 0.01); U. tangeri (0.22 +/- 0.03); M. kerathurus (0.03 +/- 0.01); and L. ramada (0.03 +/- 0.03). The levels of total As are comparable to those obtained by other authors. With respect to inorganic arsenic, only S. plana and U. tangeri present high levels of inorganic arsenic. This may be due to the fact that these organisms live in estuary sediments, reservoirs of inorganic arsenic, and ingest particles of sediments during feeding. Because of the lack of information for this area concerning previous levels of total and inorganic arsenic in the species analysed, it was not possible to establish the impact on the fauna of the River Guadalquivir estuary of the toxic spill resulting from the failure of the mine tailings dam at Aznalcóllar. With respect to the implications to human health as a result of consumption of species from the Guadalquivir estuary, only with the species Scrobicularia plana, as a high consumption of this mollusc might, in some cases, exceed the maximum tolerable intake for inorganic arsenic indicated by the FAO/WHO. Consumption of the

  9. Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample

    PubMed Central

    Baron, Patrick A.; Raber, Georg; Francesconi, Kevin A.; Navas-Acien, Ana; Love, David C.

    2013-01-01

    Background: Inorganic arsenic (iAs) causes cancer and possibly other adverse health outcomes. Arsenic-based drugs are permitted in poultry production; however, the contribution of chicken consumption to iAs intake is unknown. Objectives: We sought to characterize the arsenic species profile in chicken meat and estimate bladder and lung cancer risk associated with consuming chicken produced with arsenic-based drugs. Methods: Conventional, antibiotic-free, and organic chicken samples were collected from grocery stores in 10 U.S. metropolitan areas from December 2010 through June 2011. We tested 116 raw and 142 cooked chicken samples for total arsenic, and we determined arsenic species in 65 raw and 78 cooked samples that contained total arsenic at ≥ 10 µg/kg dry weight. Results: The geometric mean (GM) of total arsenic in cooked chicken meat samples was 3.0 µg/kg (95% CI: 2.5, 3.6). Among the 78 cooked samples that were speciated, iAs concentrations were higher in conventional samples (GM = 1.8 µg/kg; 95% CI: 1.4, 2.3) than in antibiotic-free (GM = 0.7 µg/kg; 95% CI: 0.5, 1.0) or organic (GM = 0.6 µg/kg; 95% CI: 0.5, 0.8) samples. Roxarsone was detected in 20 of 40 conventional samples, 1 of 13 antibiotic-free samples, and none of the 25 organic samples. iAs concentrations in roxarsone-positive samples (GM = 2.3 µg/kg; 95% CI: 1.7, 3.1) were significantly higher than those in roxarsone-negative samples (GM = 0.8 µg/kg; 95% CI: 0.7, 1.0). Cooking increased iAs and decreased roxarsone concentrations. We estimated that consumers of conventional chicken would ingest an additional 0.11 µg/day iAs (in an 82-g serving) compared with consumers of organic chicken. Assuming lifetime exposure and a proposed cancer slope factor of 25.7 per milligram per kilogram of body weight per day, this increase in arsenic exposure could result in 3.7 additional lifetime bladder and lung cancer cases per 100,000 exposed persons. Conclusions: Conventional chicken meat had higher i

  10. 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...

  11. 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...

  12. 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...

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. A Study on Extraction Method of Inorganic Arsenic Species in Abandoned Mine Soils of Korea

    NASA Astrophysics Data System (ADS)

    Shin, M.; Yoon, H.; Suh, J.

    2006-12-01

    It is important to determine the concentration of many toxic elements in environmental samples. However, the total concentration provides no information concerning the fate of the elements. Environmental fate, behavior, bioavailability, and toxicity of metals often vary dramatically with the chemical forms (species) in which metals exist. For example, inorganic arsenite [As (III)] and arsenate [As (V)] are toxic while methylarsonic acid [MMA(V)] and dimethylarseinic acid [DMA(V)] are less toxic. Thus, the assessments of environmental impact and human health risk solely based on the measurements of total element concentration become no longer reliable. It is important to identify and quantify individual chemical species of the element. A method to separate two inorganic arsenic species As(III) and As(V) by SPE HG-ICP-AES has been developed, based on extraction with a mixture of 1 mol phosphoric acid and 0.1 mol ascorbic acid. Hydride generation method by ICP-AES improved effectively the detection limit of the arsenic. Extraction instruments used in this study were the microwave system (Milestone 1200 Mega) and the ultrasound extraction method (Sonic Dismembrator 500, Fisher scientific). The separation of arsenic species was achieved on the anion exchange cartridge (Accell Plus QMA, Waters) with ammonium dihydrogen phosphate as mobile phase. SPE HG--ICP-AES coupled technique was applied to analyzed extracts of contaminated soil and SRM 2710. Analysis is performed as soon as possible (approximately within 1hour) after extraction. SPE HG--ICP-AES analysis showed the majority of solid phase arsenic to be arsenate (AsV), with AsIII accounting for <3% of extracted total inorganic arsenic. SRM 2710 (Montana soil) is not detected the AsIII. Both arsenite (AsIII) and arsenate (AsV) is increasing, according as size decreases (<64μm, 64-200μm, 2mm- 200μm). The extraction efficiency of contaminated soil samples, relative to the total arsenic concentration, varied from 15 to

  20. 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.

  1. 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.

  2. SHRNA-MEDIATED SILENCING OF AS3MT EXPRESSION MODULATES THE CAPACITY OF HEPG2 CELLS TO METHYLATE INORGANIC ARSENIC

    EPA Science Inventory

    Several methyltransferases have been linked to the oxidative methylation of inorganic arsenic (iAs) in mammalian cells. However, the relative contributions of these enzymes to the overall capacity of cells to methylate iAs have not been characterized. Arsenic (+3 oxidation state)...

  3. 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...

  4. Inorganic arsenic speciation by differential pulse anodic stripping voltammetry using thoria nanoparticles-carbon paste electrodes.

    PubMed

    Pereira, F J; Vázquez, M D; Debán, L; Aller, A J

    2016-05-15

    Two novel thoria (ThO2) nanoparticles-carbon paste electrodes were used to evaluate an anodic stripping voltammetric method for the direct determination of arsenite and total inorganic arsenic (arsenite plus arsenate) in water samples. The effect of Ag((I)), Cu((II)), Hg((II)), Sb((III)) and Se((IV)) ions on the electrochemical response of arsenic was assayed. The developed electroanalytical method offers a rapid procedure with improved analytical characteristics including good repeatability (3.4%) at low As((III)) concentrations, high selectivity, lower detection limit (0.1 μg L(-1)) and high sensitivity (0.54 μA μg(-1) L). The analytical capability of the optimized method was demonstrated by the determination of arsenic in certified reference materials (trace elements in natural water, trace elements in water and coal fly ash).

  5. 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.

  6. RE: Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System -- Comments Submitted for Review by the SAB Workgroup

    EPA Pesticide Factsheets

    Submission of comments by the Organic Arsenical Products Task Force on the draft document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS).

  7. 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).

  8. 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.

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

    PubMed

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

    2016-12-01

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

  10. 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.

  11. 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

  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. 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...

  16. 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

  17. 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.

  18. 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.

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

    SciTech Connect

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

    2015-07-01

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

  20. Voltammetric methods for determination and speciation of inorganic arsenic in the environment--a review.

    PubMed

    Mays, Douglas E; Hussam, Abul

    2009-07-30

    The measurement of inorganic arsenic in the environment has received considerable attention over the past 40+ years due to its toxicity and prevalence in drinking water. This paper provides an overview of voltammetric techniques used since 2001. More than fifty papers from refereed analytical chemistry journals on the speciation and measurement of inorganic arsenic (As(III) and As(V)) in practical and environmental samples are included. The present review shows that stripping voltammetry is a sensitive and inexpensive technique. The new approaches include development of novel measurement protocols through media variation, development and use of new boron doped diamond electrodes modified with metals, nano Au-modified electrodes on carbon or carbon nano-tubes, novel rotating disc and vibrating electrodes to enhance mass transfer, and modified Hg(l) and thin film Bi on carbon for cathodic stripping voltammetry are discussed. Although, majority of the papers were of exploratory in nature, the trend towards developing a commercial standalone instrument for field use is still in progress.

  1. 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.

  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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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

    ... Integrated Risk Information System (IRIS) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of... Integrated Risk Information System (IRIS)'' (EPA/635/R-10/001). The draft document was prepared by the... Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System...

  9. 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...

  10. 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...

  11. 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.

  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. Is it possible to agree on a value for inorganic arsenic in food? The outcome of IMEP-112.

    PubMed

    de la Calle, M B; Baer, I; Robouch, P; Cordeiro, F; Emteborg, H; Baxter, M J; Brereton, N; Raber, G; Velez, D; Devesa, V; Rubio, R; Llorente-Mirandes, T; Raab, A; Feldmann, J; Sloth, J J; Rasmussen, R R; D'Amato, M; Cubadda, F

    2012-11-01

    Two of the core tasks of the European Union Reference Laboratory for Heavy Metals in Feed and Food (EU-RL-HM) are to provide advice to the Directorate General for Health and Consumers (DG SANCO) on scientific matters and to organise proficiency tests among appointed National Reference Laboratories. This article presents the results of the 12th proficiency test organised by the EU-RL-HM (IMEP-112) that focused on the determination of total and inorganic arsenic in wheat, vegetable food and algae. The test items used in this exercise were: wheat sampled in a field with a high concentration of arsenic in the soil, spinach (SRM 1570a from NIST) and an algae candidate reference material. Participation in this exercise was open to laboratories from all around the world to be able to judge the state of the art of the determination of total and, more in particular, inorganic arsenic in several food commodities. Seventy-four laboratories from 31 countries registered to the exercise; 30 of them were European National Reference Laboratories. The assigned values for IMEP-112 were provided by a group of seven laboratories expert in the field of arsenic speciation analysis in food. Laboratory results were rated with z and ζ scores (zeta scores) in accordance with ISO 13528. Around 85 % of the participants performed satisfactorily for inorganic arsenic in vegetable food and 60 % did for inorganic arsenic in wheat, but only 20 % of the laboratories taking part in the exercise were able to report satisfactory results in the algae test material.

  14. 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 ...

  15. Inorganic arsenic in rice-based products for infants and young children.

    PubMed

    Signes-Pastor, Antonio J; Carey, Manus; Meharg, Andrew A

    2016-01-15

    Inorganic arsenic (Asi) is a chronic, non-threshold carcinogen. Rice and rice-based products can be the major source of Asi for many subpopulations. Baby rice, rice cereals and rice crackers are widely used to feed infants and young children. The Asi concentration in rice-based products may pose a health risk for infants and young children. Asi concentration was determined in rice-based products produced in the European Union and risk assessment associated with the consumption of these products by infants and young children, and compared to an identical US FDA survey. There are currently no European Union or United States of America regulations applicable to Asi in food. However, this study suggests that the samples evaluated may introduce significant concentration of Asi into infants' and young children's diets. Thus, there is an urgent need for regulatory limits on Asi in food, especially for baby rice-based products.

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

    PubMed Central

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

    2016-01-01

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

  17. Inorganic and total arsenic contents in rice-based foods for children with celiac disease.

    PubMed

    Munera-Picazo, Sandra; Ramírez-Gandolfo, Amanda; Burló, Francisco; Carbonell-Barrachina, Angel Antonio

    2014-01-01

    Celiac disease is an autoimmune disease that affects the villi of the small intestine causing abdominal pain, gas, diarrhea, or bad absorption due to gluten intolerance. The only treatment for this disease consists of a lifelong gluten free diet; this is, celiac people cannot consume products containing gluten, such as wheat, barley, and rye, but they can use rice and corn. Thus, rice flour is mainly used for the manufacturing of the basic products of this population. Unfortunately, rice can contain high contents of total (t-As) and inorganic (i-As) arsenic. The current study demonstrated that products for celiac children with a high percentage of rice contained high concentrations of arsenic (256 and 128 μg kg⁻¹). The daily intake of i-As ranged from 0.61 to 0.78 μg kg⁻¹ body weight (bw) in children up to 5 y of age; these values were below the maximum value established by the EFSA Panel (8.0 μg kg⁻¹ bw per day), but it should be considered typical of populations with a high exposure to this pollutant. Finally, legislation is needed to improve the labeling of these special rice-based foods for celiac children; label should include information about percentage, geographical origin, and cultivar of the used rice.

  18. 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.

  19. Survey of inorganic arsenic in marine animals and marine certified reference materials by anion exchange high-performance liquid chromatography-inductively coupled plasma mass spectrometry.

    PubMed

    Sloth, Jens J; Larsen, Erik H; Julshamn, Kåre

    2005-07-27

    A method for the determination of inorganic arsenic in seafood samples using high-performance liquid chromatography-inductively coupled plasma mass spectrometry is described. The principle of the method relied on microwave-assisted alkaline dissolution of the sample, which at the same time oxidized arsenite [As(III)] to arsenate [As(V)], whereby inorganic arsenic could be determined as the single species As(V). Anion exchange chromatography using isocratic elution with aqueous ammonium carbonate as the mobile phase was used for the separation of As(V) from other coextracted organoarsenic compounds, including arsenobetaine. The stability of organoarsenic compounds during the sample pretreatment was investigated, and no degradation/conversion to inorganic arsenic was detected. The method was employed for the determination of inorganic arsenic in a variety of seafood samples including fish, crustaceans, bivalves, and marine mammals as well as a range of marine certified reference materials, and the results were compared to values published in the literature. For fish and marine mammals, the results were in most cases below the limit of detection. For other sample types, inorganic arsenic concentrations up to 0.060 mg kg(-)(1) were found. In all samples, the inorganic arsenic content constituted less than 1% of the total arsenic content.

  20. Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells.

    PubMed

    Ebert, Franziska; Leffers, Larissa; Weber, Till; Berndt, Svenia; Mangerich, Aswin; Beneke, Sascha; Bürkle, Alexander; Schwerdtle, Tanja

    2014-04-01

    Thio-dimethylarsinic acid (thio-DMA(V)) has recently been identified as human metabolite after exposure toward both the human carcinogen inorganic arsenic and arsenosugars, which are the major arsenical constituents of marine algae. This study aims to get further insight in the toxic modes of action of thio-DMA(V) in cultured human urothelial cells. Among others effects of thio-DMA(V) on eight cell death related endpoints, cell cycle distribution, genotoxicity, cellular bioavailability as well as for the first time its impact on DNA damage induced poly(ADP-ribosyl)ation were investigated and compared to effects induced by arsenite. The data indicate that thio-DMA(V) exerts its cellular toxicity in a similar or even lower concentration range, however most likely via different mechanisms, than arsenite. Most interestingly, thio-DMA(V) decreased damage-induced cellular poly(ADP-ribosyl)ation by 35,000-fold lower concentrations than arsenite. The inhibition of this essential DNA-damage induced and DNA-repair related signaling reaction might contribute to inorganic arsenic induced toxicity, at least in the bladder. Therefore, and also because thio-DMA(V) is to date by far the most toxic human metabolite identified after arsenosugar intake, thio-DMA(V) should contemporary be fully (also in vivo) toxicologically characterized, to assess risks to human health related to inorganic arsenic but especially arsenosugar dietary intake.

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

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

    PubMed Central

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

    2017-01-01

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

  4. 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

  5. RE:RE: Comments on the Draft US EPA Document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS).

    EPA Pesticide Factsheets

    Letter from the Organic Arsenical Products Task Force expressing concern about aspects of the Science Advisory Board Workgroup's review of a draft document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS) and decision not to grant more time to prepare for meeting.

  6. Comments on the Draft U.S. EPA Document Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System (IRIS)

    EPA Pesticide Factsheets

    The Organic Arsenical Products Task Force (OAPTF) hereby submits the appended list of materials from the scientific literature on inorganic arsenic for inclusion in the U.S. Environmental Protection Agency's (EPA) docket maintained in support of the Summary Information on the Integrated Risk Information System (IRIS) Report (Report)

  7. Comments on the Draft Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the Integrated Risk Information System

    EPA Pesticide Factsheets

    Comments from the members of the SAB Arsenic Review Panel on the draft Toxicological Review of Inorganic Arsenic in Support of Summary Information on the Integrated Risk Information System (IRIS) document that will be review by a Work Group of the Chartered SAB.

  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. 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.

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

    PubMed

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

    2007-01-15

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

  11. [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

  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. High resolution profile of inorganic aqueous geochemistry and key redox zones in an arsenic bearing aquifer in Cambodia.

    PubMed

    Richards, Laura A; Magnone, Daniel; Sovann, Chansopheaktra; Kong, Chivuth; Uhlemann, Sebastian; Kuras, Oliver; van Dongen, Bart E; Ballentine, Christopher J; Polya, David A

    2017-07-15

    Arsenic contamination of groundwaters in South and Southeast Asia is a major threat to public health. In order to better understand the geochemical controls on the mobility of arsenic in a heavily arsenic-affected aquifer in northern Kandal Province, Cambodia, key changes in inorganic aqueous geochemistry have been monitored at high vertical and lateral resolution along dominant groundwater flow paths along two distinct transects. The two transects are characterized by differing geochemical, hydrological and lithological conditions. Arsenic concentrations in groundwater are highly heterogenous, and are broadly positively associated with iron and negatively associated with sulfate and dissolved oxygen. The observed correlations are generally consistent with arsenic mobilization by reductive-dissolution of iron (hydr)oxides. Key redox zones, as identified using groupings of the PHREEQC model equilibrium electron activity of major redox couples (notably ammonium/nitrite; ammonium/nitrate; nitrite/nitrate; dissolved oxygen/water) have been identified and vary with depth, site and season. Mineral saturation is also characterized. Seasonal changes in groundwater chemistry were observed in areas which were (i) sandy and of high permeability; (ii) in close proximity to rivers; and/or (iii) in close proximity to ponds. Such changes are attributed to monsoonal-driven surface-groundwater interactions and are consistent with the separate provenance of recharge sources as identified using stable isotope mixing models.

  15. 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.

  16. Total and inorganic arsenic in foods of the first Hong Kong total diet study.

    PubMed

    Chung, Stephen Wai-cheung; Lam, Chi-ho; Chan, Benny Tsz-pun

    2014-04-01

    Arsenic (As) is a metalloid that occurs in different inorganic and organic forms, which are found in the environment from both natural occurrence and anthropogenic activity. The inorganic forms of As (iAs) are more toxic as compared with the organic As, but so far most of the occurrence data in food collected in the framework of official food control are still reported as total As without differentiating the various As species. In this paper, total As and iAs contents of 600 total diet study (TDS) samples, subdivided into 15 different food groups, were quantified by high-resolution inductively coupled plasma mass spectrometry (HR-ICP/MS) and hydride generation (HG) ICP/MS respectively. The method detection limits for both total As and iAs were 3 μg As kg(-1). As the samples were prepared for TDS, food items were purchased directly from the market or prepared as for normal consumption, i.e. table ready, in the manner most representative of and consistent with cultural habits in Hong Kong as far as practicable. The highest total As and iAs content were found in 'fish, seafood and their products' and 'vegetables and their products' respectively. Besides, this paper also presents the ratios of iAs and total As content in different ready-to-eat food items. The highest ratio of iAs to total As was found in 'vegetables and their products'. It is likely that iAs in vegetables maintained its status even after cooking.

  17. A rapid monitoring method for inorganic arsenic in rice flour using reversed phase-high performance liquid chromatography-inductively coupled plasma mass spectrometry.

    PubMed

    Narukawa, Tomohiro; Chiba, Koichi; Sinaviwat, Savarin; Feldmann, Jörg

    2017-01-06

    A new rapid monitoring method by means of high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) following the heat-assisted extraction was developed for measurement of total inorganic arsenic species in rice flour. As(III) and As(V) eluted at the same retention time and completely separated from organoarsenic species by an isocratic elution program on a reversed phase column. Therefore, neither ambiguous oxidation of arsenite to arsenate nor the integration of two peaks were necessary to determine directly the target analyte inorganic arsenic. Rapid injection allowed measuring 3 replicates within 6min and this combined with a quantitative extraction of all arsenic species from rice flour by a 15min HNO3-H2O2 extraction makes this the fastest laboratory based method for inorganic arsenic in rice flour.

  18. 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.

  19. 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...

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

    PubMed

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

    2016-07-01

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

  1. 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.

  2. 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

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

    PubMed

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

    2016-12-22

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

  5. 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...

  6. 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

  7. 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

  8. 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.

  9. Fact Sheet on Arsenic

    EPA Pesticide Factsheets

    Arsenic is a naturally occurring element that is found in combination with either inorganic or organic substances to form many different compounds. Inorganic arsenic compounds are found in soils, sediments, and groundwater.

  10. Arsenic

    MedlinePlus

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

  11. 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...

  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. 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.

  14. 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...

  15. Femtomolar level sensing of inorganic arsenic(III) in water and in living-systems using a non-toxic fluorescent probe.

    PubMed

    Dey, Biswajit; Mukherjee, Priyanka; Mondal, Ranjan Kumar; Chattopadhyay, Asoke Prasun; Hauli, Ipsit; Mukhopadhyay, Subhra Kanti; Fleck, Michel

    2014-12-14

    A highly selective femtomolar level sensing of inorganic arsenic(III) as arsenious acid has been accomplished in water medium and in living-systems (on pollen grains of Tecoma stans; Candida albicans cells (IMTECH No. 3018) and Peperomia pellucida stem section) using a non-toxic fluorescent probe of a Cu(II)-complex.

  16. FINGERPRINTING INORGANIC ARSENIC AND ORGANOARSENIC COMPOUNDS IN IN SITU OIL SHALE RETORT AND PROCESS VOTERS USING A LIQUID CHROMATOGRAPH COUPLED WITH AN ATOMIC ABSORPTION SPECTROMETER AS A DETECTOR

    SciTech Connect

    Fish, Richard H.; Brinckman, Frederick E.; Jewett, Kenneth L.

    1981-07-01

    Inorganic arsenic and organoarsenic compounds were speciated in seven oil shale retort and process waters, including samples from simulated, true and modified in situ processes, using a high performance liquid chromatograph automatically coupled to a graphite furnace atomic absorption detector. The molecular forms of arsenic at ppm levels (({micro}g/mL) in these waters are identified for the first time, and shown to include arsenate, methylarsonic acid and phenylarsonic acid. An arsenic-specific fingerprint chromatogram of each retort or process water studied has significant impliestions regarding those arsenical species found and those marginally detected, such as dimethylarsinic acid and the suspected carcinogen arsenite. The method demonstrated suggests future means for quantifying environmental impacts of bioactive organometal species involved in oil shale retorting technology.

  17. 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

  18. Effects on operant learning and brain acetylcholine esterase activity in rats following chronic inorganic arsenic intake.

    PubMed

    Nagaraja, T N; Desiraju, T

    1994-05-01

    1. Very young and adult Wistar rats were given As5+, 5 mg arsenic kg-1 body weight day-1 (sodium arsenate). 2. Operant learning was tested in a Skinner box at the end of exposure and, in the case of developing animals, also after a recovery period. 3. Acetylcholine esterase (AChE) activity was estimated in discrete brain regions of these animals. 4. The animals exposed to arsenic took longer to acquire the learned behaviour and to extinguish the operant. AChE activity was inhibited in some regions of the brain.

  19. Inorganic arsenic trioxide induces gap junction loss in association with the downregulation of connexin43 and E-cadherin in rat hepatic "stem-like" cells.

    PubMed

    Hsiao, Pi-Jung; Jao, Jo-Chi; Tsai, Jin-Lian; Chang, Wen-Tsan; Jeng, Kuo-Shyang; Kuo, Kung-Kai

    2014-02-01

    Chronic exposure to inorganic arsenic trioxide causes tumors of the skin, urinary bladder, lung, and liver. Several cancer initiators and promoters have been shown to alter cell-cell signaling by interference with gap junction intercellular communication (GJIC) and/or modulation of cell adhesion molecules, such as connexin43 (Cx43), E-cadherin, and β-catenin. The aim of this study was to determine whether the disruption of cell-cell interactions occurs in liver epithelial cells after exposure to arsenic trioxide. WB-F344 cells were treated with arsenic trioxide (6.25-50 μM) for up to 8 hours, and gap junction function was analyzed using the scrape-load/dye transfer assay. In addition, the changes in mRNA and protein levels of Cx43, E-cadherin, and β-catenin were determined. A significant dose- and time-dependent decrease in GJIC was observed when WB-F344 cells were exposed to arsenic trioxide (p < 0.05). Consistent with the inhibition of GJIC, cells' exposure to arsenic trioxide resulted in dose- and time-dependent decreases in Cx43 and E-cadherin mRNA expression and protein levels. However, arsenic trioxide did not alter the mRNA or protein levels of β-catenin. In an immunofluorescence study, nuclei were heavily stained with anti-β-catenin antibody, indicating significant nuclear translocation. In this study, we also demonstrated that arsenic trioxide-induced GJIC loss was a reversible process. Taken together, these data support the hypothesis that disruption of cell-cell communication may contribute to the tumor-promoting effect of inorganic arsenic trioxide.

  20. 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...

  1. 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.

  2. 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.

  3. 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

  4. Determination of inorganic arsenic species in natural waters--benefits of separation and preconcentration on ion exchange and hybrid resins.

    PubMed

    Ben Issa, Nureddin; Rajaković-Ognjanović, Vladana N; Jovanović, Branislava M; Rajaković, Ljubinka V

    2010-07-19

    A simple method for the separation and determination of inorganic arsenic (iAs) species in natural and drinking water was developed. Procedures for sample preparation, separation of As(III) and As(V) species and preconcentration of the total iAs on fixed bed columns were defined. Two resins, a strong base anion exchange (SBAE) resin and a hybrid (HY) resin were utilized. The inductively-coupled plasma-mass spectrometry method was applied as the analytical method for the determination of the arsenic concentration in water. The governing factors for the ion exchange/sorption of arsenic on resins in a batch and a fixed bed flow system were analyzed and compared. Acidity of the water, which plays an important role in the control of the ionic or molecular forms of arsenic species, was beneficial for the separation; by adjusting the pH values to less than 8.00, the SBAE resin separated As(V) from As(III) in water by retaining As(V) and allowing As(III) to pass through. The sorption activity of the hydrated iron oxide particles integrated into the HY resin was beneficial for bonding of all iAs species over a wide range of pH values from 5.00 to 11.00. The resin capacities were calculated according to the breakthrough points in a fixed bed flow system. At pH 7.50, the SBAE resin bound more than 370 microg g(-1) of As(V) while the HY resin bound more than 4150 microg g(-1) of As(III) and more than 3500 microg g(-1) of As(V). The high capacities and selectivity of the resins were considered as advantageous for the development and application of two procedures, one for the separation and determination of As(III) (with SBAE) and the other for the preconcentration and determination of the total arsenic (with HY resin). Methods were established through basic analytical procedures (with external standards, certified reference materials and the standard addition method) and by the parallel analysis of some samples using the atomic absorption spectrometry-hydride generation

  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. Sex differences in the reduction of arsenic methylation capacity as a function of urinary total and inorganic arsenic in Mexican children.

    PubMed

    Torres-Sánchez, Luisa; López-Carrillo, Lizbeth; Rosado, Jorge L; Rodriguez, Valentina M; Vera-Aguilar, Eunice; Kordas, Katarzyna; García-Vargas, Gonzalo G; Cebrian, Mariano E

    2016-11-01

    Chronic arsenic (As) exposure decreases adult and children's ability to methylate inorganic As (iAs); however, few studies have examined children's sex differences. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids, and calculated the primary (PMI: MMA/iAs) and secondary (SMI: DMA/MMA) methylation capacity indexes in 591 children 6-8 years in Torreón, Mexico. We determined iAs, MMA, and DMA by hydride generation cryotrapping AAS. Lineal regression models estimated associations between methylation capacity and total As (TAs) or iAs. Interactions with sex were tested at p<0.10. Boys had significantly higher TAs levels, (58.4µg/L) than girls (46.2µg/L). We observed negative associations between TAs and PMI (β=-0.039; p<0.18) and SMI (β=-0.08; p=0.002) with significant sex differences; PMI reduction was significant in boys (β=-0.09; p=0.02) but not in girls (β=0.021; p=0.63), p for interaction=0.06. In contrast, SMI reduction was significantly more pronounced in girls. Furthermore, negative associations PMI (β=-0.19; p<0.001) and SMI (β=-0.35; p<0.001) were a function of urinary iAs levels, independently of TAs; however, the reduction in PMI was more pronounced in boys (β=-0.24; p<0.001; girls β=-0.15; p<0.001), p for interaction=0.04. A significant negative association was observed between SMI and iAs levels without significant sex differences. TAs and iAs associations with metabolite percentages were in good agreement with those observed with methylation indexes. Our results suggest that iAs plays an important role in reducing As methylation ability and that significant sex differences are present in As metabolism. These differences merit further investigation to confirm our findings and their potential implications for arsenic toxicity in children.

  7. 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 ...

  8. 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.

  9. 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.

    PubMed

    Liu, Jie; 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 17beta-hydroxysteroid dehydrogenase-7 (HSD17beta7; involved in estradiol production) and decreased expression of HSD17beta5 (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.

  10. 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

  11. 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.

  12. New diffusive gradients in a thin film technique for measuring inorganic arsenic and selenium(IV) using a titanium dioxide based adsorbent.

    PubMed

    Bennett, William W; Teasdale, Peter R; Panther, Jared G; Welsh, David T; Jolley, Dianne F

    2010-09-01

    A new diffusive gradients in a thin film (DGT) technique, using a titanium dioxide based adsorbent (Metsorb), has been developed and evaluated for the determination of dissolved inorganic arsenic and selenium. As(III), As(V), and Se(IV) were found to be quantitatively accumulated by the adsorbent (uptake efficiencies of 96.5-100%) and eluted in 1 M NaOH (elution efficiencies of 81.2%, 75.2%, and 88.7%). Se(VI) was not quantitatively accumulated by the adsorbent (<20%). Laboratory DGT validation experiments gave linear mass uptake over time (R(2) >or= 0.998) for As(III), As(V), and Se(IV). Consistent uptake occurred over pH (3.5-8.5) and ionic strength (0.0001-0.75 mol L(-1) NaNO(3)) ranges typical of natural waters, including seawater. Field deployments of DGT probes with various diffusive layer thicknesses confirmed the use of the technique in situ, allowing calculation of the diffusive boundary layers and an accurate measurement of inorganic arsenic. Reproducibility of the technique in field deployments was good (relative standard deviation <8%). Limits of detection (4 day deployments) were 0.01 microg L(-1) for inorganic arsenic and 0.05 microg L(-1) for Se(IV). The results of this study confirmed that DGT with Metsorb was a reliable and robust method for the measurement of inorganic arsenic and the selective measurement of Se(IV) within useful limits of accuracy.

  13. 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.

  14. Inorganic species of arsenic in soil solution determined by microcartridges and ferrihydrite-based diffusive gradient in thin films (DGT).

    PubMed

    Moreno-Jiménez, Eduardo; Six, Laetitia; Williams, Paul N; Smolders, Erik

    2013-01-30

    The bioavailability of soil arsenic (As) is determined by its speciation in soil solution, i.e., arsenite [As(III)] or arsenate [As(V)]. Soil bioavailability studies require suitable methods to cope with small volumes of soil solution that can be speciated directly after sampling, and thereby minimise any As speciation change during sample collection. In this study, we tested a self-made microcartridge to separate both As species and compared it to a commercially available cartridge. In addition, the diffusive gradient in thin films technique (DGT), in combination with the microcartridges, was applied to synthetic solutions and to a soil spiked with As. This combination was used to improve the assessment of available inorganic As species with ferrihydrite(FH)-DGT, in order to validate the technique for environmental analysis, mainly in soils. The self-made microcartridge was effective in separating As(III) from As(V) in solution with detection by inductively coupled plasma optical emission spectrometry (ICP-OES) in volumes of only 3 ml. The DGT study also showed that the FH-based binding gels are effective for As(III) and As(V) assessment, in solutions with As and P concentrations and ionic strength commonly found in soils. The FH-DGT was tested on flooded and unflooded As spiked soils and recoveries of As(III) and As(V) were 85-104% of the total dissolved As. This study shows that the DGT with FH-based binding gel is robust for assessing inorganic species of As in soils.

  15. 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.

  16. Molecular modifications induced by inorganic arsenic in Vicia faba investigated by FTIR, FTNIR spectroscopy and genotoxicity testing.

    PubMed

    Boccia, P; Meconi, C; Mecozzi, M; Sturchio, E

    2013-01-01

    Exposure to inorganic arsenic (iAs) through drinking water is a major public health concern affecting most countries. Epidemiologic studies showed a significant association between consumption of iAs through drinking water and different types of cancer. However, the exact mechanisms underlying As-induced cancer and other diseases are not yet well understood. The aim of this study is to determine the effects of exposure iAs (20 or 30 mg/L) on Vicia faba seedlings in terms of phytotoxicity, genotoxicity, and spectroscopy by investigation of molecular modifications using infrared (FTIR) and near infrared (FTNIR) spectroscopy. Further, the mitigation effects of a precursor of glutathione (GSH), N-acetylcysteine (NAC), were also assessed. Spectroscopic and genotoxicity analysis demonstrated that specific molecular changes were directly correlated with iAs exposure. Comet assay in Vicia faba showed significant effects at concentrations of 20 and 30 mg/L, depending on the structural changes involving nucleic acids as identified by FTIR and FTNIR spectroscopy. Results of phytotoxicity and micronuclei tests were significant only at higher iAs concentrations (30 mg/L), where an antioxidant effect of NAC was noted. The two spectroscopic techniques demonstrated molecular modifications predominantly associated with chemical interactions of iAs with biomolecules such as nucleic acids, carbohydrates, lipids, and proteins in Vicia faba. Our findings suggest that further studies are required to better understand the mechanisms underlying toxicity produced by different As chemical forms in vegetal and agricultural species.

  17. 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.

  18. 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.

  19. Inorganic Arsenic Determination in Food: A Review of Analytical Proposals and Quality Assessment Over the Last Six Years.

    PubMed

    Llorente-Mirandes, Toni; Rubio, Roser; López-Sánchez, José Fermín

    2017-01-01

    Here we review recent developments in analytical proposals for the assessment of inorganic arsenic (iAs) content in food products. Interest in the determination of iAs in products for human consumption such as food commodities, wine, and seaweed among others is fueled by the wide recognition of its toxic effects on humans, even at low concentrations. Currently, the need for robust and reliable analytical methods is recognized by various international safety and health agencies, and by organizations in charge of establishing acceptable tolerance levels of iAs in food. This review summarizes the state of the art of analytical methods while highlighting tools for the assessment of quality assessment of the results, such as the production and evaluation of certified reference materials (CRMs) and the availability of specific proficiency testing (PT) programmes. Because the number of studies dedicated to the subject of this review has increased considerably over recent years, the sources consulted and cited here are limited to those from 2010 to the end of 2015.

  20. Inorganic arsenic speciation in natural mineral drinking waters by flow-through anodic stripping chronopotentiometry.

    PubMed

    Jedryczko, Dominika; Pohl, Pawel; Welna, Maja

    2016-04-01

    A simple and inexpensive method for chemical speciation of inorganic As in natural mineral drinking waters by using anodic stripping chronopotentiometry (ASCP) in an electrochemical flow-through cell with an Au wire as the working electrode was described in the present work. The presented method is an attractive alternative to laborious and time-consuming procedures requiring pre-separation of various forms of As before their detection by other flow-through and non flow-through stripping methods. The limits of detection were found to be 0.42 µg L(-1) for As(III) and 0.55 µg L(-1) for As(V), obtained at the deposition potentials of -350 mV and -1600 mV, respectively. The accuracy of the method was assessed by the spiking-and-recovery experiments for particular water samples and the recoveries found, being in range from 99% to 105% for As(III) and from 104% to 106% for As(V), respectively, were quantitative. The proposed method was successfully applied to speciation analysis of inorganic As in water samples with a high content of Cu.

  1. 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%.

  2. Enhancing acupuncture by low dose naltrexone.

    PubMed

    Hesselink, Jan M Keppel; Kopsky, David J

    2011-06-01

    To find appropriate and effective treatment options for chronic pain syndromes is a challenging task. Multimodal treatment approach has been gaining acceptance for chronic pain. However, combining treatments, such as acupuncture, with rational pharmacology is still in its infancy. Acupuncture influences the opioid and cannabinoid system through releasing endogenous receptor ligands. Low dose naltrexone also acts on both these systems, and upregulates the opioid and cannabinoid receptors. The authors hypothesise that low dose naltrexone could enhance the pain-relieving effect of acupuncture.

  3. 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...

  4. 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).

  5. 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

  6. 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

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

    PubMed

    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 10μM Cd for 11weeks (CTPE) or 5μM iAs for 29weeks (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.

  8. Inorganic and Total Arsenic Contents in Rice and Rice-Based Foods Consumed by a Potential Risk Subpopulation: Sportspeople.

    PubMed

    Cano-Lamadrid, M; Munera-Picazo, S; Burgos-Hernández, A; Burló, F; Carbonell-Barrachina, Ángel A

    2016-04-01

    One of the main routes of exposure to inorganic arsenic (i-As) in humans is food, especially rice and rice-based products. There are certain groups of consumers that could be highly exposed to i-As. Maximum levels of i-As have been issued for infants and young children by the European Union, but perhaps other groups are also at risk. Sportspeople could be one of those groups, due to their specific nutritional requirements, especially its high consumption of cereals, such as rice. Because of the well-known relationship between rice and i-As, the intake of i-As by sportspeople deserved especial attention and was estimated in Spain. This study demonstrated that rice-based products reached a maximum i-As content of 178 μg/kg, with a mean for all studied products of 56 μg/kg; the maximum contents were found in rice cakes (149 μg/kg) and brown rice (111 μg/kg). The estimated daily intake of i-As were 0.16 and 0.18 μg/kg bw (body weight)/d, in sportsmen and sportswomen, respectively. These values were below the BMDL01 , 0.3 to 8.0 μg/kg bw/d; thus, it can be concluded that the sportspeople group is not at a significant risk regarding the intake of i-As. However, further studies are needed to evaluate their whole diet and not only rice-based products. Finally, it is important to claim that companies producing rice products include as much information as possible about the rice used in their products, including rice percentage and geographical origin.

  9. 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.

  10. 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

  11. 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.

  12. Health benefits from low-dose irradiation

    SciTech Connect

    Luckey, T.D.

    1996-12-31

    Whole-body exposures of mice and humans show no harm from low doses of ionizing radiation. Forty reports show statistically significant, p < 0.01, beneficial effects when cancer and total mortality rates were examined in mice. In vitro experiments indicate that radiogenic metabolism, adaptive repair mechanisms, such as DNA repair enzymes, and the essential nature of ionizing radiation are responsible for part of this activity. However, overwhelming evidence shows that low-dose irradiation increases immune competence. Such data negate the linear concept, which has no reliable whole-animal data to support it in the low-dose range. Cell culture data are not pertinent; such cells do not have a complete immune system.

  13. 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.

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

    PubMed

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

    2015-06-01

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

  15. *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...

  16. On-line speciation analysis of inorganic arsenic in complex environmental aqueous samples by pervaporation sequential injection analysis.

    PubMed

    Boonjob, Warunya; Miró, Manuel; Kolev, Spas D

    2013-12-15

    A proof of concept of a novel pervaporation sequential injection (PSI) analysis method for automatic non-chromatographic speciation analysis of inorganic arsenic in complex aqueous samples is presented. The method is based on hydride generation of arsine followed by its on-line pervaporation-based membrane separation and CCD spectrophotometric detection. The concentrations of arsenite (As(III)) and arsenate (As(V)) are determined sequentially in a single sample zone. The leading section of the sample zone merges with a citric acid/citrate buffer solution (pH 4.5) for the selective reduction of As(III) to arsine while the trailing section of the sample zone merges with hydrochloric acid solution to allow the reduction of both As(III) and As(V) to arsine at pH lower than 1. Virtually identical analytical sensitivity is obtained for both As(III) and As(V) at this high acidity. The flow analyzer also accommodates in-line pH detector for monitoring of the acidity throughout the sample zone prior to hydride generation. Under optimal conditions the proposed PSI method is characterized by a limit of detection, linear calibration range and repeatability for As(III) of 22 μg L(-1) (3sblank level criterion), 50-1000 μg L(-1) and 3.0% at the 500 μg L(-1) level and for As(V) of 51 μg L(-1), 100-2000 μg L(-1) and 2.6% at the 500 μg L(-1) level, respectively. The method was validated with mixed As(III)/As(V) standard aqueous solutions and successfully applied to the determination of As(III) and As(V) in river water samples with elevated content of dissolved organic carbon and suspended particulate matter with no prior sample pretreatment. Excellent relative recoveries ranging from 98% to 104% were obtained for both As(III) and As(V).

  17. 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...

  18. Mammography-oncogenecity at low doses.

    PubMed

    Heyes, G J; Mill, A J; Charles, M W

    2009-06-01

    Controversy exists regarding the biological effectiveness of low energy x-rays used for mammography breast screening. Recent radiobiology studies have provided compelling evidence that these low energy x-rays may be 4.42 +/- 2.02 times more effective in causing mutational damage than higher energy x-rays. These data include a study involving in vitro irradiation of a human cell line using a mammography x-ray source and a high energy source which matches the spectrum of radiation observed in survivors from the Hiroshima atomic bomb. Current radiation risk estimates rely heavily on data from the atomic bomb survivors, and a direct comparison between the diagnostic energies used in the UK breast screening programme and those used for risk estimates can now be made. Evidence highlighting the increase in relative biological effectiveness (RBE) of mammography x-rays to a range of x-ray energies implies that the risks of radiation-induced breast cancers for mammography x-rays are potentially underestimated by a factor of four. A pooled analysis of three measurements gives a maximal RBE (for malignant transformation of human cells in vitro) of 4.02 +/- 0.72 for 29 kVp (peak accelerating voltage) x-rays compared to high energy electrons and higher energy x-rays. For the majority of women in the UK NHS breast screening programme, it is shown that the benefit safely exceeds the risk of possible cancer induction even when this higher biological effectiveness factor is applied. The risk/benefit analysis, however, implies the need for caution for women screened under the age of 50, and particularly for those with a family history (and therefore a likely genetic susceptibility) of breast cancer. In vitro radiobiological data are generally acquired at high doses, and there are different extrapolation mechanisms to the low doses seen clinically. Recent low dose in vitro data have indicated a potential suppressive effect at very low dose rates and doses. Whilst mammography is a low

  19. Low dose naltrexone therapy in multiple sclerosis.

    PubMed

    Agrawal, Y P

    2005-01-01

    The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

  20. 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.’

  1. 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.

  2. Low dose aprotinin and low dose tranexamic acid in elective cardiac surgery with cardiopulmonary bypass.

    PubMed

    Waldow, Thomas; Krutzsch, Diana; Wils, Michael; Plötze, Katrin; Matschke, Klaus

    2009-01-01

    The antifibrinolytic agents aprotinin and tranexamic acid have both been proven to be efficient in reducing postoperative blood loss and transfusion requirements in patients in cardiac surgery. In light of recent safety issues regarding aprotinin, this single-centre study compared efficacy and safety of low dose aprotinin (2 million KIU, pump-prime volume only) and low dose tranexamic acid (1 g, pump-prime volume) in 708 consecutive patients from two prospective registers undergoing elective cardiac procedures with cardiopulmonary bypass (CPB). Incidences of postoperative complications showed no significant differences between groups. Postoperative blood loss and transfusion requirements were significantly lower in aprotinin compared to tranexamic acid patients. Overall, both antifibrinolytic low dose regimens are safe components of perioperative patient management in elective cardiac surgery with CPB. Cardiac procedures requiring longer CPB times might benefit from the administration of low dose aprotinin.

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

    PubMed

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

    2012-04-01

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

  4. 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

  5. Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.

    PubMed

    Honar, H; Riazi, K; Homayoun, H; Sadeghipour, H; Rashidi, N; Ebrahimkhani, M R; Mirazi, N; Dehpour, A R

    2004-01-01

    Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. Systemic administration of ultra-low doses of naltrexone (100 fg/kg-10 ng/kg) significantly potentiated the anticonvulsant effect of morphine at 0.5 mg/kg while higher degrees of opioid receptor antagonism blocked this effect. Moreover, inhibition of opioid-induced excitatory signaling by naltrexone (1 ng/kg) unmasked a strong anticonvulsant effect for very low doses of morphine (1 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of opioid receptor signaling can exert strong seizure-protective effects even at very low levels of opioid receptor activation. However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.

  6. 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...

  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.

  8. Reduction of inorganic compounds with molecular hydrogen by Micrococcus lactilyticus. I. Stoichiometry with compounds of arsenic, selenium, tellurium, transition and other elements.

    PubMed

    WOOLFOLK, C A; WHITELEY, H R

    1962-10-01

    Woolfolk, C. A. (University of Washington, Seattle) and H. R. Whiteley. Reduction of inorganic compounds with molecular hydrogen by Micrococcus lactilyticus. I. Stoichiometry with compounds of arsenic, selenium, tellurium, transition and other elements. J. Bacteriol. 84:647-658. 1962.-Extracts of Micrococcus lactilyticus (Veillonella alcalescens) oxidize molecular hydrogen at the expense of certain compounds of arsenic, bismuth, selenium, tellurium, lead, thallium, vanadium, manganese, iron, copper, molybdenum, tungsten, osmium, ruthenium, gold, silver, and uranium, as well as molecular oxygen. Chemical and manometric data indicate that the following reductions are essentially quantitative: arsenate to arsenite, pentavalent and trivalent bismuth to the free element, selenite via elemental selenium to selenide, tellurate and tellurite to tellurium, lead dioxide and manganese dioxide to the divalent state, ferric to ferrous iron, osmium tetroxide to osmate ion, osmium dioxide and trivalent osmium to the metal, uranyl uranium to the tetravalent state, vanadate to the level of vanadyl, and polymolybdate ions to molybdenum blues with an average valence for molybdenum of +5. The results of a study of certain other hydrogenase-containing bacteria with respect to their ability to carry out some of the same reactions are also presented.

  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.

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. Effects of low doses of radiation.

    PubMed

    Fry, R J

    1996-06-01

    This is a brief review of what is known from experimental studies about the effects of low doses of radiation, and approaches that might improve risk estimates are discussed. The dose-response relationships for cancer induction by radiation vary markedly between tissues. The evidence suggests that 1) the induction of the initial events is dependent on the cell type because the size and/or the number of targets and how the cells handle the initial lesions differs between cell types; and 2) there are marked differences among tissues how initial lesions are expressed and proceed to overt cancer. The recent findings about adaptive responses are discussed in the context of what they contribute to our understanding about the response to irradiation. Lastly, the possibility of extending the approach of determining "The probability of causation," which Vic Bond played such an important role in establishing, is raised.

  15. 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.

  16. 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.

  17. Low Dose Ionizing Radiation Modulates Immune Function

    SciTech Connect

    Nelson, Gregory A.

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  18. 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.

  19. Simultaneous speciation of inorganic arsenic, selenium and tellurium in environmental water samples by dispersive liquid liquid microextraction combined with electrothermal vaporization inductively coupled plasma mass spectrometry.

    PubMed

    Liu, Ying; He, Man; Chen, Beibei; Hu, Bin

    2015-09-01

    A new method based on dispersive liquid liquid microextraction (DLLME) combined with electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP-MS) was developed for the simultaneous speciation of inorganic arsenic (As), selenium (Se) and tellurium (Te) with sodium diethyldithiocarbamate (DDTC) as both chelating reagent and chemical modifier. As(III), Se(IV) and Te(IV) were transformed into DDTC-chelates at pH 7 and extracted into the fine droplets formed by injecting the binary solution of bromobenzene (extraction solvent) and methanol (dispersive solvent) into the sample solution. After phase separation by centrifugation, As(III), Se(IV) and Te(IV) preconcentrated in the organic phase were determined by ETV-ICP-MS. Total inorganic As, Se and Te were obtained by reducing As(V), Se(VI) and Te(VI) to As(III), Se(IV) and Te(IV) with L-cysteine, which were then subjected to the same DLLME-ETV-ICP-MS process. The concentration of As(V), Se(VI), Te(VI) were calculated by subtracting the concentration of As(III), Se(IV) and Te(IV) from the total inorganic As, Se and Te, respectively. The main factors affecting the microextraction efficiency and the vaporization behavior of target species were investigated in detail. Under the optimal conditions, the limits of detection were 2.5, 8.6 and 0.56 ng L(-1) for As(III), Se(IV) and Te(IV), respectively, with the relative standard deviations (n=7) of 8.5-9.7%. The developed method was applied to the speciation of inorganic As, Se and Te in Certified Reference Materials of GSBZ50004-88, GBW(E)080395 and GBW(E)080548 environmental waters, and the determined values are in good agreement with the certified values. The method was also successfully applied to the simultaneous speciation of inorganic As, Se and Te in different environmental water samples with the recoveries in the range of 86.3-107% for the spiked samples.

  20. TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ACUTE ORAL ADMINISTRATION OF ARSENATE

    EPA Science Inventory

    ABSTRACT The relationship of exposure dose and tissue concentration of parent chemical and metabolites is a critical issue in cases where toxicity may be mediated by a metabolite or parent chemical and metabolite acting together. This has emerged as an issue for inorganic ars...

  1. 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. PMID:27747248

  2. 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

  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. 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.

  5. Accumulation and transformation of inorganic and organic arsenic in rice and role of thiol-complexation to restrict their translocation to shoot

    PubMed Central

    Mishra, Seema; Mattusch, Jürgen; Wennrich, Rainer

    2017-01-01

    Environmental contamination of arsenic (As) and its accumulation in rice (Oryza sativa L.) is of serious human health concern. In planta speciation of As is an important tool to understand As metabolism in plants. In the present study, we investigated root to shoot As translocation and speciation in rice exposed to inorganic and methylated As. Arsenate (AsV) and methylarsonate (MAV) were efficiently reduced to arsenite (AsIII) and MAIII, respectively in rice root and shoot but no trivalent form of dimethylarsinate (DMAV) was detected. Further, up to 48 and 83% of root As in AsV and MAV exposed plants, respectively were complexed with various thiols showing up to 20 and 16 As species, respectively. Several mixed As- and MA-complexes with hydroxymethyl-phytochelatin, DesGly-phytochelatin, hydroxymethyl-GSH and cysteine were identified in rice. Despite high complexation in roots, more As was translocated to shoots in MAV exposed plants than AsV, with shoot/root As transfer factor being in order DMAV > MAV > AsV. Moreover, in shoots 78% MAIII and 71% AsIII were present as weakly bound species which is alarming, as MAIII has been found to be more cytotoxic than AsIII for human and it could also be an important factor inducing straighthead (spikelet sterility disorder) in rice. PMID:28094280

  6. 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.

  7. 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.

  8. 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).

  9. Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa.

    PubMed

    Otani, Atsushi; Kojima, Hiroshi; Guo, Congrong; Oishi, Akio; Yoshimura, Nagahisa

    2012-01-01

    The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.

  10. SPE HG-AAS method for the determination of inorganic arsenic in rice--results from method validation studies and a survey on rice products.

    PubMed

    Rasmussen, Rie R; Qian, Yiting; Sloth, Jens J

    2013-09-01

    The present paper describes the development, validation and application of a method for inorganic arsenic (iAs) determination in rice samples. The separation of iAs from organoarsenic compounds was done by off-line solid-phase extraction (SPE) followed by hydride generation atomic absorption spectrometry (HG-AAS) detection. This approach was earlier developed for seafood samples (Rasmussen et al., Anal Bioanal Chem 403:2825-2834, 2012) and has in the present work been tailored for rice products and further optimised for a higher sample throughput and a lower detection limit. Water bath heating (90 °C, 60 min) of samples with dilute HNO3 and H2O2 solubilised and oxidised all iAs to arsenate (As(V)). Loading of buffered sample extracts (pH 6 ± 1) followed by selective elution of arsenate from a strong anion exchange SPE cartridge enabled the selective iAs quantification by HG-AAS, measuring total arsenic (As) in the SPE eluate. The in-house validation gave mean recoveries of 101-106% for spiked rice samples and in two reference samples. The limit of detection was 0.02 mg kg(-1), and repeatability and intra-laboratory reproducibility were less than 6 and 9%, respectively. The SPE HG-AAS method produced similar results compared to parallel high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (ICP-MS) analysis. The SPE separation step was tested collaboratively, where the laboratories (N = 10) used either HG-AAS or ICP-MS for iAs determination in a wholemeal rice powder. The trial gave satisfactory results (HorRat value of 1.6) and did not reveal significant difference (t test, p > 0.05) between HG-AAS and ICP-MS quantification. The iAs concentration in 36 rice samples purchased on the Danish retail market varied (0.03-0.60 mg kg(-1)), with the highest concentration found in a red rice sample.

  11. [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.

  12. 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.

  13. Neuroblastoma cell death is induced by inorganic arsenic trioxide (As(2)O(3)) and inhibited by a normal human bone marrow cell-derived factor.

    PubMed

    Gesundheit, Benjamin; Malach, Lea; Or, Reuven; Hahn, Talia

    2008-12-01

    Three phenotypically distinct cell types are present in human neuroblastomas (NB) and NB cell lines: I-type stem cells, N-type neuroblastic precursors, and S-type Schwannian/melanoblastic precursors. The stimulation of human N-type neuroblastoma cell proliferation by normal human bone marrow monocytic cell conditioned medium (BMCM) has been demonstrated in vitro, a finding consistent with the high frequency of bone marrow (BM) metastases in patients with advanced NB. Inorganic arsenic trioxide (As(2)O(3)), already clinically approved for the treatment of several hematological malignancies, is currently under investigation for NB. Recent studies show that As(2)O(3) induces apoptosis in NB cells. We examined the impact of BMCM on growth and survival of As(2)O(3)-treated NB cell lines, to evaluate the response of cultured NB cell variants to regulatory agents. We studied the effect of BMCM on survival and clonogenic growth of eleven As(2)O(3)-treated NB cell lines grown in sparsely seeded, non-adherent, semi-solid cultures. As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines. BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action. Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.

  14. 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...

  15. 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

  16. 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.

  17. Arsenic speciation, distribution, and bioaccessibility in shrews and their food.

    PubMed

    Moriarty, Maeve M; Koch, Iris; Reimer, Kenneth J

    2012-04-01

    Shrews (Sorex cinereus) collected at a historic mine in Nova Scotia, Canada, had approximately twice the arsenic body burden and 100 times greater daily intake of arsenic compared with shrews from a nearby uncontaminated background site. Shrews store arsenic as inorganic and simple methylated arsenicals. Much of the arsenic associated with their primary food source, i.e., small invertebrates, may be soil adsorbed to their exoskeletons. A physiologically based extraction test estimated that 47 ± 2% of invertebrate arsenic is bioaccessible in the shrew gastrointestinal tract. Overall, shrews appear to be efficient at processing and excreting inorganic arsenic.

  18. 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.

  19. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice

    PubMed Central

    Lim, S.; Jatakanon, A.; Gordon, D.; Macdonald, C.; Chung, K. F.; Barnes, P.

    2000-01-01

    BACKGROUND—Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS—In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 µg beclomethasone dipropionate (BDP) daily and inhaled β2 agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 µg BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 µg BDP) over a six month period was examined.
RESULTS—One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION—There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.

 PMID:10992535

  20. 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...

  1. 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...

  2. 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.

  3. 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)

  4. Bradycardia following a single low dose of trazodone.

    PubMed

    Li, Tien-Chun; Chiu, Hsiu-Wen; Ho, Kai-Jen; Tzeng, Dong-Sheng

    2011-03-01

    Symptomatic bradycardia following a single low dose of oral trazodone is rare. Herein, we report the case of a patient with major depressive disorder who developed and was able to resolve symptomatic bradycardia following administration of a single low dose of trazodone 50mg, and then discontinuation. This is the first case report of symptomatic bradycardia which might be attributed to a single lowest dose of trazodone in the world.

  5. Low-dose cyclophosphamide-induced acute hepatotoxicity

    PubMed Central

    Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul

    2013-01-01

    Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described. Case Report: We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide. Conclusions: Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment. PMID:24023976

  6. 77 FR 5061 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Inorganic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ...; Inorganic Arsenic Standard ACTION: Notice. SUMMARY: The Department of Labor (DOL) is submitting the..., ``Inorganic Arsenic Standard,'' to the Office of Management and Budget (OMB) for review and approval for... . SUPPLEMENTARY INFORMATION: The purpose of the Inorganic Arsenic Standard is to protect workers from the...

  7. 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).

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. Speciation analysis of inorganic arsenic in river water by Amberlite IRA 910 resin immobilized in a polyacrylamide gel as a selective binding agent for As(V) in diffusive gradient thin film technique.

    PubMed

    Rolisola, Ana M C M; Suárez, Carlos A; Menegário, Amauri A; Gastmans, Didier; Kiang, Chang H; Colaço, Camila D; Garcez, Daniel L; Santelli, Ricardo E

    2014-09-07

    In this study, a method is proposed for the selective retention of As(V) using diffusive gradient in thin film (DGT) samplers containing a strongly basic anion exchange resin (Amberlite IRA 910) supported on a polyacrylamide gel. In addition, the total arsenic content is determined by ferrihydrite gel discs. Subsequently, the concentration of As(III) was obtained by determining the difference between the total As and As(V). DGT experiments showed linear accumulation of As(V) (up to 280 ng) until a deployment time of 8 h deployment (R(2) > 0.99). The retention of As(V) was appropriate (97.9-112.3%) between pH 5 and 9. For a solution with an ionic strength ranging from 0.001 to 0.05 mol L(-1), the As(V) uptake ranged from 90-120%. The proposed method was applied for the speciation of arsenic in river water. For the analysis of spiked samples collected at the Furnas stream, the recoveries of total arsenic content ranged between 103.9% and 118.8%. However, the recoveries of As(III) and As(V) were 43.3-75.2% and 147.3-153.4%, respectively. These differences were probably because of the oxidation of As(III) to As(V) during deployments. For spiked samples collected at the Ribeirão Claro, the recoveries of dissolved As(III), As(V) and As(T) were 103.1%, 108.0% and 106.3%, respectively. Thus, the DGT technique with Amberlite IRA 910 resin as the binding phase can be employed for the in situ redox speciation of inorganic arsenic.

  13. Sequential extraction of inorganic arsenic compounds and methyl arsenate in human urine using mixed-mode monolithic silica spin column coupled with gas chromatography-mass spectrometry.

    PubMed

    Namera, Akira; Takeuchi, Akito; Saito, Takeshi; Miyazaki, Shota; Oikawa, Hiroshi; Saruwatari, Tatsuro; Nagao, Masataka

    2012-09-01

    A sequential analytical method was developed for the detection of arsenite, arsenate, and methylarsenate in human urine by gas chromatography-mass spectrometry (GC-MS). The combination of a derivatization of trivalent arsenic compounds by 2,3-dithio-1-propanol (British antilewisite; BAL) and a reduction of pentavalent arsenic compounds (arsenate and methylarsenate) were accomplished to carry out the analysis of arsenic compounds in urine. The arsenic derivatives obtained using BAL were extracted in a stepwise manner using a monolithic spin column and analyzed by GC-MS. A linear curve was observed for concentrations of arsenic compounds of 2.0 to 200 ng/mL, where the correlation coefficients of calibration curves were greater than 0.996 (for a signal-to-noise (S/N) ratio >10). The detection limits were 1 ng/mL (S/N > 3). Recoveries of the targets in urine were in the range 91.9-106.5%, and RSDs of the intra- and interday assay for urine samples containing 5, 50, and 150 ng/mL of arsenic compounds varied between 2.95 and 13.4%. The results from real samples obtained from a patient suspected of having ingested As containing medications using this proposed method were in good agreement with those obtained using high-performance liquid chromatography with inductively coupled plasma mass spectrometry.

  14. Low-dose CT via convolutional neural network

    PubMed Central

    Chen, Hu; Zhang, Yi; Zhang, Weihua; Liao, Peixi; Li, Ke; Zhou, Jiliu; Wang, Ge

    2017-01-01

    In order to reduce the potential radiation risk, low-dose CT has attracted an increasing attention. However, simply lowering the radiation dose will significantly degrade the image quality. In this paper, we propose a new noise reduction method for low-dose CT via deep learning without accessing original projection data. A deep convolutional neural network is here used to map low-dose CT images towards its corresponding normal-dose counterparts in a patch-by-patch fashion. Qualitative results demonstrate a great potential of the proposed method on artifact reduction and structure preservation. In terms of the quantitative metrics, the proposed method has showed a substantial improvement on PSNR, RMSE and SSIM than the competing state-of-art methods. Furthermore, the speed of our method is one order of magnitude faster than the iterative reconstruction and patch-based image denoising methods. PMID:28270976

  15. [Mechanism of cytogenetic adaptive response induced by low dose radiation].

    PubMed

    Cai, L; Liu, S

    1990-11-01

    Cytogenetic observation on human lymphocytes indicated that pre-exposure of 10, 50 and 75 mGy X-rays could induced the adaptive response. Experimental results with different temperature treatment showed that the adaptive response induced by low dose radiation could be enhanced by 41 degrees C and 43 degrees C, but inhibited by 4 degrees C in addition the treatment by 41 degrees C for one hour could also cause the adaptive response as did low dose radiation. Results showed that adaptive response induced by low dose radiation (10 or 50 mGy X-rays) could be eliminated by the protein synthesis inhibitor, implying that the adaptive response is related with the metabolism of cells, especially with the production of certain protective proteins.

  16. Screening for lung cancer with low-dose CT.

    PubMed

    Coche, E

    2008-01-01

    Lung cancer represents the leading cause of cancer-related mortality in the world. In the past, many attempts were made to detect the disease at an early stage and subsequently reduce its mortality. Chest X-ray was abandoned for this purpose. For several years low-dose computed tomography has been introduced as a potential tool for early screening in a high-risk population. As demonstrated in several papers, the task is not easy and researchers are faced with many difficulties. This paper reviews mainly the role of low-dose CT for early cancer screening. Results of past and current trials, controversies related to the high rate of lung nodules, cost-effectiveness, and delivered radiation dose to the patient are presented. Finally some limitations of low dose CT for lung cancer detection are explained.

  17. 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.

  18. 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.

  19. 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.

  20. Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

    PubMed

    Paquette, Jay; Olmstead, Mary C; Olmstead, Mary

    2005-12-01

    Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.

  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. 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.

  3. 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

  4. 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.

  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. PMID:27621948

  6. Low dose naltrexone: side effects and efficacy in gastrointestinal disorders.

    PubMed

    Ploesser, Jennifer; Weinstock, Leonard B; Thomas, Erin

    2010-01-01

    Use of low dose naltrexone has been advocated for a variety of medical problems. Only a few articles published in peer review journals have documented side effects of low dose naltrexone. The purpose of this study was to determine the frequency of adverse effects of low dose naltrexone in patients who have been treated for a variety of gastrointestinal disorders. The secondary purpose was to determine global efficacy in a retrospective survey. Patients (206) form a single gastroenterologist's clinical practice who had been prescribed naltrexone were mailed a survey to evaluate the side effects and efficacy of naltrexone. Patients had either irritable bowel syndrome without evidence for small intestinal bacterial overgrowth, chronic idiopathic constipation, or inflammatory bowel disease. Patients with diarrhea were given 2.5 mg daily, constipation 2.5 mg twice daily, and inflammatory bowel disease 4.5 mg daily. In the patients who returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121 (61.2%) patients who had side effects, 58 had one or more neurological complaints, and 32 had one or more gastrointestinal side effects. In the patients with side effects, 24/74 (32.4%) had short lived symptoms. Low dose naltrexone was terminated owing to side effects in 20/74 patients (27.0%). In 13 patients with idiopathic irritable bowel syndrome, 2 were markedly worse. In 85 patients with irritable bowel syndrome-small intestinal bacterial overgrowth, 15 were markedly improved, 32 were moderately worse, and 1 was markedly worse. In 12 patients with chronic constipation, 7 were markedly improved, 1 was moderately improved, 1 was mildly improved, and 4 were unchanged. Low dose naltrexone frequently has side effects but in most is tolerable. It appears to be helpful for a member of patients with gastrointestinal disorders.

  7. 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 ...

  8. Evaluation and application of the diffusive gradients in thin films technique using a mixed-binding gel layer for measuring inorganic arsenic and metals in mining impacted water and soil.

    PubMed

    Huynh, Trang; Zhang, Hao; Noller, Barry

    2012-11-20

    The diffusive gradients in thin films (DGT) equipped with a Chelex or ferrihydrite binding gel has been designed to enable the measurement of either labile metal species or inorganic arsenic, respectively. In the mine impacted environment, metals and metalloids commonly coexist in a variety of species. This study, for the first time reports the performance of the DGT with a mixed-binding layer (MBL), consisting of Chelex and ferrihydrite for measurements of both metals and arsenic in a single assay. The MBL that consists of a combination of Chelex and ferrihydrite at a ratio of 1:2 has the greatest binding capacity for arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), and zinc (Zn). The elemental concentrations measured by using MBL-DGT (C(DGT)) were comparable (92-104%) with the original test solution concentrations (C(SOL)). The measurement of As by using MBL-DGT was consistent across a wide pH range (3-8) and ionic strength (0.001-0.1 M). At high pH (9), As measurement was slightly affected (∼80%). The measurements of Cd, Pb, and Zn were affected at low pH (<3) and high pH (9). Measurements of Cd, Cu, and Pb were affected at low ionic strength (0.001 M). At high ionic strength (0.1 M), measurements of Cd; Cu and Pb were slightly affected. The capacity of MBL-DGT for quantitative measurement in a multielements solution is effectively limited to 15 μg for As and 70 μg for metals per MBL-DGT device. Good correlations (p < 0.01) between MBL-DGT measurements and ferrihydrite or Chelex DGT were obtained for As, Cd, Cu, Pb, and Zn in water and soil with exception for Cd and Cu (p < 0.05) when deployed in soil.

  9. 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.

  10. Influence of low-dose and low-dose-rate ionizing radiation on mutation induction in human cells

    NASA Astrophysics Data System (ADS)

    Yatagai, F.; Umebayashi, Y.; Suzuki, M.; Abe, T.; Suzuki, H.; Shimazu, T.; Ishioka, N.; Iwaki, M.; Honma, M.

    This is a review paper to introduce our recent studies on the genetic effects of low-dose and low-dose-rate ionizing radiation (IR). Human lymphoblastoid TK6 cells were exposed to γ-rays at a dose-rate of 1.2 mGy/h (total 30 mGy). The frequency of early mutations (EMs) in the thymidine kinase ( TK) gene locus was determined to be 1.7 × 10 -6, or 1.9-fold higher than the level seen in unirradated controls [Umebayashi, Y., Honma, M., Suzuki, M., Suzuki, H., Shimazu, T., Ishioka, N., Iwaki, M., Yatagai, F., Mutation induction in cultured human cells after low-dose and low-dose-rate γ-ray irradiation: detection by LOH analysis. J. Radiat. Res., 48, 7-11, 2007]. These mutants were then analyzed for loss of heterozygosity (LOH) events. Small interstitial-deletion events were restricted to the TK gene locus and were not observed in EMs in unirradated controls, but they comprised about half of the EMs (8/15) after IR exposure. Because of the low level of exposure to IR, this specific type of event cannot be considered to be the direct result of an IR-induced DNA double strand break (DSB). To better understand the effects of low-level IR exposure, the repair efficiency of site-specific chromosomal DSBs was also examined. The pre γ-irradiation under the same condition did not largely influence the efficiency of DSB repair via end-joining, but enhanced such efficiency via homologous recombination to an about 40% higher level (unpublished data). All these results suggest that DNA repair and mutagenesis can be indirectly influenced by low-dose/dose-rate IR.

  11. 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.

  12. 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.

  13. 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.

  14. Low Dose Naltrexone in the Treatment of Fibromyalgia.

    PubMed

    Metyas, Samy K; Yeter, Karen; Solyman, John; Arkfeld, Daniel

    2017-03-21

    Fibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. A significant number of fibromyalgia patients do not respond adequately to the current drugs (pregabalin, milnacipran, duloxetine) approved for fibromyalgia treatment by the Food and Drug Administration (FDA). Thus, there is still a need for adjunctive therapies. Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. Treatment with low dose naltrexone may be an effective, highly tolerable and inexpensive treatment for fibromyalgia. Further controlled trials are needed.

  15. Response of human fibroblasts to low dose rate gamma irradiation

    SciTech Connect

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-11-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to ..gamma.. radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D/sub 0/) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury.

  16. Low Dose, Low Energy 3d Image Guidance during Radiotherapy

    NASA Astrophysics Data System (ADS)

    Moore, C. J.; Marchant, T.; Amer, A.; Sharrock, P.; Price, P.; Burton, D.

    2006-04-01

    Patient kilo-voltage X-ray cone beam volumetric imaging for radiotherapy was first demonstrated on an Elekta Synergy mega-voltage X-ray linear accelerator. Subsequently low dose, reduced profile reconstruction imaging was shown to be practical for 3D geometric setup registration to pre-treatment planning images without compromising registration accuracy. Reconstruction from X-ray profiles gathered between treatment beam deliveries was also introduced. The innovation of zonal cone beam imaging promises significantly reduced doses to patients and improved soft tissue contrast in the tumour target zone. These developments coincided with the first dynamic 3D monitoring of continuous body topology changes in patients, at the moment of irradiation, using a laser interferometer. They signal the arrival of low dose, low energy 3D image guidance during radiotherapy itself.

  17. Low-dose computed tomography to diagnose fetal bone dysplasias.

    PubMed

    Montoya Filardi, A; Guasp Vizcaíno, M; Gómez Fernández-Montes, J; Llorens Salvador, R

    We present a case of cleidocranial dysplasia diagnosed by low-dose fetal computed tomography (CT) in the 25th week of gestation. Severe bone dysplasia was suspected because of the fetus' low percentile in long bones length and the appearance of craniosynostosis on sonography. CT found no abnormalities incompatible with life. The effective dose was 5 mSv, within the recommended range for this type of examination. Low-dose fetal CT is a new technique that makes precision study of the bony structures possible from the second trimester of pregnancy. In Spain, abortion is legal even after the 22nd week of gestation in cases of severe fetal malformations. Therefore, in cases in which severe bone dysplasia is suspected, radiologists must know the strategies for reducing the dose of radiation while maintaining sufficient diagnostic quality, and they must also know which bony structures to evaluate.

  18. Gamma regularization based reconstruction for low dose CT.

    PubMed

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-09-07

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l0-norm and l1-norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms.

  19. 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.

  20. Low Dose Sarin Leads To Murine Cardiac Dysfunction

    DTIC Science & Technology

    2010-03-01

    reduced heart rate at smooth muscle level; at exocrine glands , it causes secretions in the lung, nasal, oral, and sweat glands . Among clinical effects...smooth muscles, skeletal muscles, most exocrine glands , the central nervous system (CNS), and the cardiac system (central and ganglionic afferents...sarin need to 8 be critically analyzed at low doses to help provide early diagnosis. Similarly, functional and structural changes in the heart

  1. Secondary infertility due to use of low-dose finasteride.

    PubMed

    Şalvarci, Ahmet; Istanbulluoğlu, Okan

    2013-02-01

    Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.

  2. 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.

  3. 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.

  4. Radiation crosslinking of CMC-Na at low dose and its application as substitute for hydrogel

    NASA Astrophysics Data System (ADS)

    Liu, Pengfei; Peng, Jing; Li, Jiuqiang; Wu, Jilan

    2005-04-01

    The slight radiation-crosslinked CMC-Na as a substitute for hydrogel was prepared by gamma irradiation below gelation dose. The effects of various parameters such as absorbed dose, concentration of inorganic salts, pH, swelling temperature and swelling time on the swelling ratio in water were investigated in detail. This kind of slight crosslinked CMC-Na showed good water absorption below 60°C, whereas, it became solution when heated up to 70°C. Such CMC-Na gel is different from the true gel that is insoluble in boiled water; nevertheless, it can be used as hydrogel at room temperature and produced at low dose. Due to its low cost, it might be useful for its application in agriculture or others.

  5. 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

  6. Low-dose dasatinib rescues cardiac function in Noonan syndrome

    PubMed Central

    Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

    2016-01-01

    Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

  7. 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.

  8. Therapeutic rationale for low dose doxepin in insomnia patients

    PubMed Central

    Katwala, Jigar; Kumar, Ananda K; Sejpal, Jaykumar J; Terrence, Marcelle; Mishra, Manish

    2013-01-01

    Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian cycle. The stimulation of the H1 receptor is thought to play an important role in mediating arousal. Doxepin has a high affinity for the H1 receptor, making it a selective H1 antagonist at low dose and it has been shown to display sedating properties. Compared to other sedative antidepressant, low dose doxepin is the only tricyclic drug which has been evaluated by well-designed, randomised, double blind, placebo controlled studies in both adult and elderly patients. Doxepin is not designated as controlled substance/unscheduled drugs and thus may be of special advantage to use in patients with a history of substance abuse. Hence, well-documented therapeutic efficacy, tolerability and lack of important adverse effects make the low dose doxepin as a unique, rational drug for the treatment of insomnia in adult and elderly patients.

  9. MELODI: the 'Multidisciplinary European Low-Dose Initiative'.

    PubMed

    Belli, M; Salomaa, S; Ottolenghi, A

    2011-02-01

    The importance of research to reduce uncertainties in risk assessment of low and protracted exposures is now recognised globally. In Europe a new initiative, called 'Multidisciplinary European LOw Dose Initiative' (MELODI), has been proposed by a 'European High Level and Expert Group on low-dose risk research' (www.hleg.de), aimed at integrating national and EC (Euratom) efforts. Five national organisations: BfS (DE), CEA (FR), IRSN (FR), ISS (IT) and STUK (FI), with the support of the EC, have initiated the creation of MELODI by signing a letter of intent. In the forthcoming years, MELODI will integrate in a step-by-step approach EU institutions with significant programmes in the field and will be open to other scientific organisations and stakeholders. A key role of MELODI is to develop and maintain over time a strategic research agenda (SRA) and a road map of scientific priorities within a multidisciplinary approach, and to transfer the results for the radiation protection system. Under the coordination of STUK a network has been proposed in the 2009 Euratom Programme, called DoReMi (Low-Dose Research towards Mutidisciplinary Integration), which can help the integration process within the MELODI platform. DoReMi and the First MELODI Open Workshop, organised by BfS in September 2009, are now important inputs for the European SRA.

  10. 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.

  11. 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.

  12. 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 (...

  13. 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

  14. 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.

  15. 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.

  16. Arsenic ingestion and internal cancers: a review

    SciTech Connect

    Bates, M.N.; Smith, A.H.; Hopenhayn-Rich, C. )

    1992-03-01

    Inorganic arsenic is known to cause skin cancer by ingestion and lung cancer by inhalation. However, whether arsenic ingestion causes internal cancers is still a matter of debate. This paper has reviewed the epidemiologic literature that bears on this question. Published studies of populations who have ingested arsenic in medicines, wine substitutes, or water supplies, as well as workers exposed to arsenic by inhalation, were considered in terms of whether the observed associations might be explained by the presence of biases, the consistency of the evidence, and the biologic plausibility of the associations. Many studies were found to be uninformative because of low statistical power or potential biases. The most informative studies, which were from Taiwan and Japan, involved exposure to arsenic in drinking water. These studies strongly suggest that ingested inorganic arsenic does cause cancers of the bladder, kidney, lung, and liver, and possibly other sites. However, confirmatory studies are needed.82 references.

  17. Animal Studies of Residual Hematopoietic and Immune System Injury from Low Dose/Low Dose Rate Radiation and Heavy Metals.

    DTIC Science & Technology

    1998-09-01

    accidents and industrial accidents (e.g., Chernobyl ) who receive high doses of radiation over a relatively short period of time, there are thousands of...several years after exposure may have been terminated. Examples of such groups include those affected by the fallout near Chernobyl , those living near...cohorts (e.g., Chernobyl victims) particular damage from low dose irradiation, especially membrane damage and mismatched DNA repair. Dosimetric Problems

  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. New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

    PubMed

    Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

    2016-04-01

    A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods.

  20. European low-dose radiation risk research strategy: future of research on biological effects at low doses.

    PubMed

    Salomaa, Sisko; Averbeck, Dietrich; Ottolenghi, Andrea; Sabatier, Laure; Bouffler, Simon; Atkinson, Michael; Jourdain, Jean-René

    2015-04-01

    In 2009, the European High Level and Expert Group identified key policy and scientific questions to be addressed through a strategic research agenda for low-dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). In 2010, the DoReMi Network of Excellence was launched in the Euratom 7th Framework Programme. DoReMi has acted as an operational tool for the sustained development of the MELODI platform during its early years. A long-term Strategic Research Agenda for European low-dose radiation risk research has been developed by MELODI. Strategic planning of DoReMi research activities is carried out in close collaboration with MELODI. The research priorities for DoReMi are designed to focus on objectives that are achievable within the 6-y lifetime of the project and that are in areas where stimulus and support can help progress towards the longer-term strategic objectives.

  1. BIPHASIC REGULATION OF BASE EXCISION DNA REPAIR BY LOW DOSE ARSENIC. (R826135)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. 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...

  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. Urinary arsenic metabolites of subjects exposed to elevated arsenic present in coal in Shaanxi Province, China.

    PubMed

    Gao, Jianwei; Yu, Jiangping; Yang, Linsheng

    2011-06-01

    In contrast to arsenic (As) poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP) induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions), who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China), were reported. The urinary arsenic species, including inorganic arsenic (iAs) [arsenite (iAsIII) and arsenate (iAsV)], monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), were determined by high-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectroscopy (ICP-MS). The relative distributions of arsenic species, the primary methylation index (PMI=MMAV/iAs) and the secondary methylation index (SMI=DMAV/MMAV) were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  8. 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.

  9. 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...

  10. Questions and Answers: Apple Juice and Arsenic

    MedlinePlus

    ... in its juice than any other company. Does organic apple juice have less arsenic than non-organic apple juice? The FDA is unaware of any ... States. Is the arsenic in apple juice predominantly organic or inorganic? Due to limited data available to ...

  11. 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.

  12. Low doses and thresholds in genotoxicity: from theories to experiments.

    PubMed

    Zito, R

    2001-09-01

    The absence of threshold in the action of genotoxic carcinogens was theoretically postulated more than thirty years ago, but continuously challenged for scientific and practical reasons. The direct experimental demonstration of the presence of a threshold for genotoxic damage is precluded by the insufficient sensitivity of the biological methods presently available. In the last twenty years the sensitivity of the methods for quantitative determination of the DNA adducts of the carcinogens was enormously improved, demonstrating linearity of the dose/adducts pattern over dose intervals of more than million-fold. The arguments more often advanced for the presence of a threshold for genotoxic carcinogens were mainly based on the action of intracellular scavengers, detoxification enzymes and repair systems, being able to block completely the genotoxic carcinogens at very low doses. This hypothesis is disproved by the constant presence of DNA adducts at extremely low doses of different carcinogens, whatever their chemical structure can be. On the other hand if genotoxic damage results from damage to proteins involved in cell division, like tubulin, there is a threshold dose for such genotoxic effects. The detailed knowledge of the genotoxicity mechanism is therefore needed for a sound carcinogenic risk assessment. Most of the genotoxic carcinogens, or their metabolites, damage directly the DNA. In this case the absence of threshold must be assumed, not only for theoretical reasons, but for the results of the experiments quantitatively relating DNA damage and very low doses of carcinogens. For the sake of clarity the "adjectivated" thresholds, like practical pragmatic, apparent and operational, must disappear from documents analysing the carcinogenic risk.

  13. Low-dose fixed-target serial synchrotron crystallography.

    PubMed

    Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

    2017-04-01

    The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

  14. 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

  15. 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.

  16. Water Intoxication Following Low-Dose Intravenous Cyclophosphamide

    PubMed Central

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung

    2007-01-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention. PMID:24459501

  17. Water intoxication following low-dose intravenous cyclophosphamide.

    PubMed

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung; Kim, Gheun-Ho

    2007-06-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention.

  18. 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.

  19. 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...

  20. Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation.

    PubMed

    Webster, Lynn R

    2007-08-01

    Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Low-dose endotoxemia and human neuropsychological functions.

    PubMed

    Krabbe, Karen Suárez; Reichenberg, Abraham; Yirmiya, Raz; Smed, Annelise; Pedersen, Bente Klarlund; Bruunsgaard, Helle

    2005-09-01

    Epidemiological data demonstrate an association between systemic low-grade inflammation defined as 2- to 3-fold increases in circulating inflammatory mediators and age-related decline in cognitive function. However, it is not known whether small elevations of circulating cytokine levels cause direct effects on human neuropsychological functions. We investigated changes in emotional, cognitive, and inflammatory parameters in an experimental in vivo model of low-grade inflammation. In a double-blind crossover study, 12 healthy young males completed neuropsychological tests before as well as 1.5, 6, and 24 h after an intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two experimental sessions. Endotoxin administration had no effect on body temperature, cortisol levels, blood pressure or heart rate, but circulating levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7-fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and the lymphocyte count declined. In this model, low-dose endotoxemia did not affect cognitive performance significantly but declarative memory performance was inversely correlated with cytokine increases. In conclusion, our findings demonstrate a negative association between circulating IL-6 and memory functions during very low-dose endotoxemia independently of physical stress symptoms, and the hypothalamo-pituitary-adrenal axis.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. Arsenic and its compounds in mushrooms: A review.

    PubMed

    Falandysz, Jerzy; Rizal, Leela M

    2016-10-01

    The purpose of this article is to review the detail concentration of arsenic in some species of mushrooms as well as organic and inorganic forms of arsenic in the substrates where wild and cultivated edible mushrooms grow. We also briefly review the molecular forms of arsenic in mushrooms. There is still a lack of experimental data from the environment for a variety of species from different habitats and for different levels of geogenic arsenic in soil. This information will be useful for mushrooms consumers, nutritionists, and food regulatory agencies by describing ways to minimize arsenic content in edible mushrooms and arsenic intake from mushroom meals.

  11. Thiolated arsenicals in arsenic metabolism: Occurrence, formation, and biological implications.

    PubMed

    Sun, Yuzhen; Liu, Guangliang; Cai, Yong

    2016-11-01

    Arsenic (As) is a notoriously toxic pollutant of health concern worldwide with potential risk of cancer induction, but meanwhile it is used as medicines for the treatment of different conditions including hematological cancers. Arsenic can undergo extensive metabolism in biological systems, and both toxicological and therapeutic effects of arsenic compounds are closely related to their metabolism. Recent studies have identified methylated thioarsenicals as a new class of arsenic metabolites in biological systems after exposure of inorganic and organic arsenicals, including arsenite, dimethylarsinic acid (DMA(V)), dimethylarsinous glutathione (DMA(III)GS), and arsenosugars. The increasing detection of thiolated arsenicals, including monomethylmonothioarsonic acid (MMMTA(V)), dimethylmonothioarsinic acid (DMMTA(V)) and its glutathione conjugate (DMMTA(V)GS), and dimethyldithioarsinic acid (DMDTA(V)) suggests that thioarsenicals may be important metabolites and play important roles in arsenic toxicity and therapeutic effects. Here we summarized the reported occurrence of thioarsenicals in biological systems, the possible formation pathways of thioarsenicals, and their toxicity, and discussed the biological implications of thioarsenicals on arsenic metabolism, toxicity, and therapeutic effects.

  12. 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.

  13. 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.

  14. Arsenic in rice: a cause for concern.

    PubMed

    Hojsak, Iva; Braegger, Christian; Bronsky, Jiri; Campoy, Cristina; Colomb, Virginie; Decsi, Tamas; Domellöf, Magnus; Fewtrell, Mary; Mis, Nataša Fidler; Mihatsch, Walter; Molgaard, Christian; van Goudoever, Johannes

    2015-01-01

    Inorganic arsenic intake is likely to affect long-term health. High concentrations are found in some rice-based foods and drinks widely used in infants and young children. In order to reduce exposure, we recommend avoidance of rice drinks for infants and young children. For all of the rice products, strict regulation should be enforced regarding arsenic content. Moreover, infants and young children should consume a balanced diet including a variety of grains as carbohydrate sources. Although rice protein-based infant formulas are an option for infants with cows' milk protein allergy, the inorganic arsenic content should be declared and the potential risks should be considered when using these products.

  15. Arsenic speciation in marine fish and shellfish from American Samoa.

    PubMed

    Peshut, Peter J; Morrison, R John; Brooks, Barbara A

    2008-03-01

    We speciated arsenic compounds in marine fish and shellfish from two islands of the United States Territory of American Samoa in the South Pacific, and found that inorganic arsenic occurred as a minor fraction. The proportion of inorganic arsenic was generally far below the levels of prevailing assumptions typically used in human health risk assessments when only total arsenic is analysed. Fish and shellfish were collected from Tutuila and Ofu between May 2001 and March 2002 (n=383 individual specimens, with 117 composites); sites were selected based on habitat type and were representative of those frequented by local fishers. These islands have moderately developed reef fish fisheries among artisanal fishers, are far removed from any industrial or mining sources of arsenic, and presented an opportunity to study arsenic variations in marine biota from un-impacted environments. Target species were from various trophic levels and are among those frequently harvested for human consumption. We found evidence that arsenic concentrated in some marine species, but did not tend to follow classic trophic patterns for biomagnification or bioaccumulation. For the majority of samples, inorganic arsenic was less than 0.5% of total arsenic, with only a few samples in the range of 1-5%, the latter being mollusks which are recognized to have unusually high arsenic levels in general. This work supports the importance of speciation analysis for arsenic, because of the ubiquitous occurrence of arsenic in the environment, and its variable toxicity depending on chemical form.

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

    PubMed

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

    2013-10-01

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

  17. 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.

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

    PubMed Central

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

    2013-01-01

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

  19. 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,...

  20. Integrating experimental (in vitro and in vivo) neurotoxicity studies of low-dose thimerosal relevant to vaccines.

    PubMed

    Dórea, José G

    2011-06-01

    There is a need to interpret neurotoxic studies to help deal with uncertainties surrounding pregnant mothers, newborns and young children who must receive repeated doses of Thimerosal-containing vaccines (TCVs). This review integrates information derived from emerging experimental studies (in vitro and in vivo) of low-dose Thimerosal (sodium ethyl mercury thiosalicylate). Major databases (PubMed and Web-of-science) were searched for in vitro and in vivo experimental studies that addressed the effects of low-dose Thimerosal (or ethylmercury) on neural tissues and animal behaviour. Information extracted from studies indicates that: (a) activity of low doses of Thimerosal against isolated human and animal brain cells was found in all studies and is consistent with Hg neurotoxicity; (b) the neurotoxic effect of ethylmercury has not been studied with co-occurring adjuvant-Al in TCVs; (c) animal studies have shown that exposure to Thimerosal-Hg can lead to accumulation of inorganic Hg in brain, and that (d) doses relevant to TCV exposure possess the potential to affect human neuro-development. Thimerosal at concentrations relevant for infants' exposure (in vaccines) is toxic to cultured human-brain cells and to laboratory animals. The persisting use of TCV (in developing countries) is counterintuitive to global efforts to lower Hg exposure and to ban Hg in medical products; its continued use in TCV requires evaluation of a sufficiently nontoxic level of ethylmercury compatible with repeated exposure (co-occurring with adjuvant-Al) during early life.

  1. 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

  2. Early outcomes following low dose naltrexone enhancement of opioid detoxification.

    PubMed

    Mannelli, Paolo; Patkar, Ashwin A; Peindl, Kathleen; Gottheil, Edward; Wu, Li-Tzy; Gorelick, David A

    2009-01-01

    Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post-detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven-day follow-up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow-up treatment modalities designed to address opioid dependence.

  3. 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.

  4. Surrogates of Protection in Repeated Low-Dose Challenge Experiments

    PubMed Central

    Long, Dustin M.; Hudgens, Michael G.; Wu, Chih-Da

    2015-01-01

    A critical step toward developing a successful vaccine to control the human immunodeficiency virus (HIV) pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of HIV, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered. PMID:25628249

  5. 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.

  6. Quantifying exploratory low dose compounds in humans with AMS.

    PubMed

    Dueker, Stephen R; Vuong, Le T; Lohstroh, Peter N; Giacomo, Jason A; Vogel, John S

    2011-06-19

    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 (14)C 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.

  7. Low dose ionizing radiation detection using conjugated polymers

    SciTech Connect

    Silva, E.A.B.; Borin, J.F.; Nicolucci, P.; Graeff, C.F.O.; Netto, T. Ghilardi; Bianchi, R.F.

    2005-03-28

    In this work, the effect of gamma radiation on the optical properties of poly[2-methoxy-5-(2{sup '}-ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) is studied. The samples were irradiated at room temperature with different doses from 0 Gy to 152 Gy using a {sup 60}Co gamma ray source. For thin films, significant changes in the UV-visible spectra were only observed at high doses (>1 kGy). In solution, shifts in absorption peaks are observed at low doses (<10 Gy), linearly dependent on dose. The shifts are explained by conjugation reduction, and possible causes are discussed. Our results indicate that MEH-PPV solution can be used as a dosimeter adequate for medical applications.

  8. 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.

  9. Transcriptome profiling of mice testes following low dose irradiation

    PubMed Central

    2013-01-01

    Background Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types in the adult testis. Methods Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were selected for further analysis. These transcripts were separated into clusters and their cellular origin was determined. Immunohistochemistry and in silico quantification was further used to study cellular changes post-irradiation (pi). Results We identified a subset of transcripts (n = 988) where changes in expression pi can be explained by changes in cellularity. We separated the transcripts into five unique clusters that we associated with spermatogonia, spermatocytes, early spermatids, late spermatids and somatic cells, respectively. Transcripts in the somatic cell cluster showed large changes in expression pi, mainly caused by changes in cellularity. Further investigations revealed that the low dose irradiation seemed to cause Leydig cell hyperplasia, which contributed to the detected expression changes in the somatic cell cluster. Conclusions The five clusters represent gene expression in distinct cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production and inadequate inhibin signalling due to missing germ cells. PMID:23714422

  10. Cardiovascular risks associated with low dose ionizing particle radiation.

    PubMed

    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 ((1)H; 0.5 Gy, 1 GeV) and iron ion ((56)Fe; 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 (56)Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56)Fe 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.

  11. 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.

  12. 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

  13. Cardiovascular Risks Associated with Low Dose Ionizing Particle Radiation

    DOE PAGES

    Yan, Xinhua; Sasi, Sharath P.; Gee, Hannah; ...

    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

  14. 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.

  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. Evaluation of a low-dose progestagen as a contraceptive.

    PubMed

    Iizuka, R; Hayashi, M; Kamouchi, Y; Yamanaka, K

    1971-01-01

    In order to evaluate the safety and effectiveness of a low-dose progestagen oral contraceptive, 46 women were administered 0.25 mg daily of a synthetic gestagen, R-2453 (17alpha-methyl delta 9-19 norprogesterone) for 1-12 months for a total of 189 cycles. The pill was found to be safe and completely effective with no pregnancies occurring in the study group. The length of the bleeding cycle was found to be prolonged under this treatment, to an average of 40 days . Bleeding duration and amount were generally the same as those before treatment, except in 3 cases where irregular bleeding prompted discontinuance of the pill use. Basal body temperature patterns were measured and found to be atypical biphasic in 17.3% of the cases, high temperature monophasic in 47.2%, and irregular in 34.6%. Routine blood, kidney and liver function tests were normal. Pregnandiol excretion before withdrawal bleeding was low in all but 1 case. Cervical mucus was also low and no crystal formation was observed. In the nidation menstrual stage the endometrial glands were few in number and adenomeres were small in size. In glandular cells, supranuclear vacuoles were found and interstices were coarse and edematous. Histological examinations in the implantation phase showed some alterations but their relationship to the contraceptive mechanism of this pill is not clear. Low-dose progestagens appear to be highly effective contraceptive agents that do not suppress ovulatory activity but their prescription must take careful note of dosage and formulas.

  17. 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...

  18. 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...

  19. 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

  20. 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...

  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. 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.

  3. Mineral arsenicals in traditional medicines: Orpiment, realgar, and arsenolite

    PubMed Central

    Liu, Jie; Lu, Yuanfu; Wu, Qin; Goyer, Robert A; Waalkes, Michael P.

    2009-01-01

    Mineral arsenicals have long been used in traditional medicines for various diseases, yet arsenic can be highly toxic and carcinogenic. Arsenic in traditional medicines typically comes from deliberate addition for therapeutic purposes, mainly in the form of mineral arsenicals including orpiment (As2S3), realgar (As4S4), and arsenolite (contains arsenic trioxide, As2O3). Inorganic arsenic is now accepted in Western medicine as a first line chemotherapeutic agent against certain hematopoietic cancers. This minireview analyzes the pharmacology and toxicology of these arsenicals used in traditional medicines. Orpiment and realgar are less soluble and poorly absorbed from the gastrointestinal tract, while the bioavailability of arsenic trioxide is similar to inorganic arsenic salts like sodium arsenite. Pharmacological studies show that arsenic trioxide and realgar are effective against certain malignancies. Orpiment and realgar are used externally for various skin diseases. Realgar is frequently included as an ingredient in oral traditional remedies for its antipyretic, antiinflammatory, antiulcer, anticonvulsive and anti-schistosmiasis actions, but the pharmacological basis for this inclusion still remains to be fully justified. Toxicological studies show that cardiovascular toxicity is the major concern for arsenic trioxide, and the gastrointestinal and dermal adverse effects may occur after prolonged use of mineral arsenicals. Little is known about possible secondary cancers resulting from the long-term use of any of these arsenicals. Similar to the safety evaluation of seafood arsenicals, total arsenic content alone appears to be insufficient for mineral arsenical safety evaluation. Arsenic speciation, bioavailability, and toxicity/benefit should be considered in evaluation of mineral arsenical-containing traditional medicines. PMID:18463319

  4. 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.

  5. Ultra low-dose CT attenuation correction in PET SPM

    NASA Astrophysics Data System (ADS)

    Wang, Shyh-Jen; Yang, Bang-Hung; Tsai, Chia-Jung; Yang, Ching-Ching; Lee, Jason J. S.; Wu, Tung-Hsin

    2010-07-01

    The use of CT images for attenuation correction (CTAC) allows significantly shorter scanning time and a high quality noise-free attenuation map compared with conventional germanium-68 transmission scan because at least 10 4 times greater of photon flux would be generated from a CT scan under standard operating condition. However, this CTAC technique would potentially introduce more radiation risk to the patients owing to the higher radiation exposure from CT scan. Statistic parameters mapping (SPM) is a prominent technique in nuclear medicine community for the analysis of brain imaging data. The purpose of this study is to assess the feasibility of low-dose CT (LDCT) and ultra low-dose CT (UDCT) in PET SPM applications. The study was divided into two parts. The first part was to evaluate of tracer uptake distribution pattern and quantity analysis by using the striatal phantom to initially assess the feasibility of AC for clinical purpose. The second part was to examine the group SPM analysis using the Hoffman brain phantom. The phantom study is to simulate the human brain and to reduce the experimental uncertainty of real subjects. The initial studies show that the results of PET SPM analysis have no significant differences between LDCT and UDCT comparing to the current used default CTAC. Moreover, the dose of the LDCT is lower than that of the default CT by a factor of 9, and UDCT can even yield a 42 times dose reduction. We have demonstrated the SPM results while using LDCT and UDCT for PET AC is comparable to those using default CT setting, suggesting their feasibility in PET SPM applications. In addition, the necessity of UDCT in PET SPM studies to avoid excess radiation dose is also evident since most of the subjects involved are non-cancer patients or children and some normal subjects are even served as a comparison group in the experiment. It is our belief that additional attempts to decrease the radiation dose would be valuable, especially for children and

  6. Ergogenic effects of low doses of caffeine on cycling performance.

    PubMed

    Jenkins, Nathan T; Trilk, Jennifer L; Singhal, Arpit; O'Connor, Patrick J; Cureton, Kirk J

    2008-06-01

    The purpose of this experiment was to learn whether low doses of caffeine have ergogenic, perceptual, and metabolic effects during cycling. To determine the effects of 1, 2, and 3 mg/kg caffeine on cycling performance, differentiated ratings of perceived exertion (D-RPE), quadriceps pain intensity, and metabolic responses to cycling exercise, 13 cyclists exercised on a stationary ergometer for 15 min at 80% VO, then, after 4 min of active recovery, completed a 15-min VO2peak performance ride 60 min after ingesting caffeine or placebo. Work done (kJ/kg) during the performance ride was used as a measure of performance. D-RPE, pain ratings, and expired-gas data were obtained every 3 min, and blood lactate concentrations were obtained at 15 and 30 min. Compared with placebo, caffeine doses of 2 and 3 mg/kg increased performance by 4% (95% CI: 1.0-6.8%, p = .02) and 3% (95% CI: -0.4% to 6.8%, p = .077), respectively. These effects were ergogenic, on average, but varied considerably in magnitude among individual cyclists. There were no effects of caffeine on D-RPE or pain throughout the cycling task. Selected metabolic variables were affected by caffeine, consistent with its known actions. The authors conclude that caffeine preparations of 2 and 3 mg/kg enhanced performance, but future work should aim to explain the considerable interindividual variability of the drug's ergogenic properties.

  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).

  8. Standardization and optimization of CT protocols to achieve low dose.

    PubMed

    Trattner, Sigal; Pearson, Gregory D N; Chin, Cynthia; Cody, Dianna D; Gupta, Rajiv; Hess, Christopher P; Kalra, Mannudeep K; Kofler, James M; Krishnam, Mayil S; Einstein, Andrew J

    2014-03-01

    The increase in radiation exposure due to CT scans has been of growing concern in recent years. CT scanners differ in their capabilities, and various indications require unique protocols, but there remains room for standardization and optimization. In this paper, the authors summarize approaches to reduce dose, as discussed in lectures constituting the first session of the 2013 UCSF Virtual Symposium on Radiation Safety and Computed Tomography. The experience of scanning at low dose in different body regions, for both diagnostic and interventional CT procedures, is addressed. An essential primary step is justifying the medical need for each scan. General guiding principles for reducing dose include tailoring a scan to a patient, minimizing scan length, use of tube current modulation and minimizing tube current, minimizing tube potential, iterative reconstruction, and periodic review of CT studies. Organized efforts for standardization have been spearheaded by professional societies such as the American Association of Physicists in Medicine. Finally, all team members should demonstrate an awareness of the importance of minimizing dose.

  9. Low dose radiation damage effects in silicon strip detectors

    NASA Astrophysics Data System (ADS)

    Wiącek, P.; Dąbrowski, W.

    2016-11-01

    The radiation damage effects in silicon segmented detectors caused by X-rays have become recently an important research topic driven mainly by development of new detectors for applications at the European X-ray Free Electron Laser (E-XFEL). However, radiation damage in silicon strip is observed not only after extreme doses up to 1 GGy expected at E-XFEL, but also at doses in the range of tens of Gy, to which the detectors in laboratory instruments like X-ray diffractometers or X-ray spectrometers can be exposed. In this paper we report on investigation of radiation damage effects in a custom developed silicon strip detector used in laboratory diffractometers equipped with X-ray tubes. Our results show that significant degradation of detector performance occurs at low doses, well below 200 Gy, which can be reached during normal operation of laboratory instruments. Degradation of the detector energy resolution can be explained by increasing leakage current and increasing interstrip capacitance of the sensor. Another observed effect caused by accumulation of charge trapped in the surface oxide layer is change of charge division between adjacent strips. In addition, we have observed unexpected anomalies in the annealing process.

  10. 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.

  11. Low dose radiation-induced endothelial cell retraction.

    PubMed

    Kantak, S S; Diglio, C A; Onoda, J M

    1993-09-01

    We characterized in vitro the effects of gamma-radiation (12.5-100 cGy) on pulmonary microvascular endothelial cell (PMEC) morphology and F-actin organization. Cellular retraction was documented by phase-contrast microscopy and the organization of actin microfilaments was determined by immunofluorescence. Characterization included radiation dose effects, their temporal duration and reversibility of the effects. A dose-dependent relationship between the level of exposure (12.5-100 cGy) and the rate and extent of endothelial retraction was observed. Moreover, analysis of radiation-induced depolymerization of F-actin microfilament stress fibres correlated positively with the changes in PMEC morphology. The depolymerization of the stress fibre bundles was dependent on radiation dose and time. Cells recovered from exposure to reform contact inhibited monolayers > or = 24 h post-irradiation. Concomitantly, the depolymerized microfilaments reorganized to their preirradiated state as microfilament stress fibres arrayed parallel to the boundaries of adjacent contact-inhibited cells. The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Our data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema.

  12. 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

  13. Pb low doses induced genotoxicity in Lactuca sativa plants.

    PubMed

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

    2017-03-01

    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L(-1) significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L(-1) and presence of micronuclei (MN) were detected for 20 mg L(-1). Also, cell cycle impairment was observed for doses as low as 0.05 mg L(-1) and 0.5 mg L(-1) (mostly G2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays.

  14. 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.

  15. Pharmacogenetics of Low Dose Clonidine in Irritable Bowel Syndrome

    PubMed Central

    Camilleri, Michael; Busciglio, Irene; Carlson, Paula; McKinzie, Sanna; Burton, Duane; Baxter, Kari; Ryks, Michael; Zinsmeister, Alan R.

    2009-01-01

    Objectives Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) sensorimotor functions. We aimed to determine whether candidate ADR-SER genes affect GI responses to low dose clonidine (CLO) in humans. Methods Forty healthy and 120 irritable bowel syndrome (IBS) participants received CLO, 0.1mg or 0.15mg b.i.d., for 6 days. At baseline and post-clonidine, we measured: gastric volume (GV); satiation volume; rectal compliance, sensation thresholds and ratings with distensions. Genetic variations tested were: α2A (C-1291G), α2C (Del 332-325), GNβ3 (C825T) and SLC6A4 (5-HTT-LPR). Results CLO reduced volume to satiation (p=0.002), postprandial GV (p<0.001), sensation threshold for pain (<0.001); CLO increased rectal compliance (p=0.024). There were significant associations between post-CLO responses and gene variations for Δ GV (α2A and SLC6A4), rectal sensation of gas (α2A, GNβ3), urgency (α2A); and pain (GNβ3 and SLC6A4); and rectal compliance (SLC6A4). Conclusion α2A, GNβ3 and SLC6A4 genotypes significantly modify responses to clonidine on sensory and motor GI functions in health and IBS. PMID:19309415

  16. Benzodiazepine dependence and its treatment with low dose flumazenil.

    PubMed

    Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth

    2014-02-01

    Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future.

  17. 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.

  18. 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.

  19. 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.

  20. Occurrence and distribution of arsenic in soils and plants

    PubMed Central

    Walsh, Leo M.; Sumner, Malcolm E.; Keeney, Dennis R.

    1977-01-01

    Inorganic arsenicals have been used in agriculture as pesticides or defoliants for many years and, in localized areas, oxides of arsenic have contaminated soils as a result of fallout from ore-smelting operations and coal-fired power plants. Use of inorganic arsenicals is no longer permitted in most agricultural operations, and recent air pollution controls have markedly reduced contamination from smelters. Thus, this paper will concentrate on the effect of past applications on arsenic accumulation in soil, phytotoxicity to and uptake by plants as influenced by soil properties, and alleviation of the deleterious effects of arsenic. Once incorporated into the soil, inorganic arsenical pesticides and arsenic oxides revert to arsenates, except where the soil is under reducing conditions. The arsenate ion has properties similar to that of orthophosphate, and is readily sorbed by iron and aluminum components. This reaction greatly restricts the downward movement (leaching) of arsenic in soils and the availability of arsenic to plants. Several methods of estimating plant available arsenic in soils have been developed. They involve extraction of the soil with reagents used to estimate phosphorus availability. This extractable arsenic is reasonably well correlated with reduced plant growth by, and plant uptake of arsenic. For most plants, levels of arsenic in the edible portion of the plant are well below the critical concentration for animal or human consumption, even when severe phytotoxicity occurs. Alleviation of arsenic phytotoxicity has been attempted by increasing the soil pH, by use of iron or aluminum sulfate, by desorbing arsenate with phosphate and subsequent leaching, and by cultural practices such as deep plowing. Only limited benefits have accrued from these procedures the cost of which is often prohibitively high. Since attempts to reduce arsenic toxicity have not been very successful, its excessive accumulation in soils should be avoided. PMID:908315

  1. 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.

  2. Cellular arsenic transport pathways in mammals.

    PubMed

    Roggenbeck, Barbara A; Banerjee, Mayukh; Leslie, Elaine M

    2016-11-01

    Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors. Considerable inter-individual variability in susceptibility to arsenic-induced disease and toxicity exists, and the reasons for such differences are incompletely understood. Transport pathways that influence the cellular uptake and export of arsenic contribute to regulating its cellular, tissue, and ultimately body levels. In the current review, membrane proteins (including phosphate transporters, aquaglyceroporin channels, solute carrier proteins, and ATP-binding cassette transporters) shown experimentally to contribute to the passage of inorganic, methylated, and/or glutathionylated arsenic species across cellular membranes are discussed. Furthermore, what is known about arsenic transporters in organs involved in absorption, distribution, and metabolism and how transport pathways contribute to arsenic elimination are described.

  3. Health Effects of Chronic Arsenic Exposure

    PubMed Central

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

    2014-01-01

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

  4. Low-dose ethanol aggravates allergic dermatitis in mice.

    PubMed

    Sakazaki, Fumitoshi; Ogino, Hirofumi; Arakawa, Tomohiro; Okuno, Tomofumi; Ueno, Hitoshi

    2014-08-01

    Alcohol injures dendritic cells and suppresses cellular immunity, while some evidence indicates that drinking alcohol aggravates allergic asthma. This study investigated the effect of low doses of ethanol in enhancing allergic reactions in the skin of mice. Liquid food containing alcohol was administered to conventional NC/Nga mice to induce alcoholic hepatic steatosis, and spontaneous dermatitis was evaluated. BALB/c mice were administered approximately 1 g/kg body weight of ethanol by gavage, and contact hypersensitivity (CHS) or active cutaneous anaphylaxis (ACA) was induced. Spleens were collected 24 h after the elicitation of CHS and mRNA expressions of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-10, and IL-18 were measured by quantitative RT-PCR. Alcohol-containing diet exaggerated spontaneous dermatitis in conventional NC/Nga mice and contact hypersensitivity in BALB/c mice. Ethanol administered by gavage for 5 days enhanced contact hypersensitivity in BALB/c mice. Ethanol administration with gavage also enhanced ACA of BALB/c mice. Ethanol did not affect mRNA expression of IFN-γ and IL-4, but did enhance IL-6, IL-10, and IL-18 mRNA expression. Histological evaluation revealed an absence of hepatic steatosis in mice administered ethanol by gavage for 5 days. In ethanol-administered mice, inflamed areas presented as lesions or a local extreme accumulation of mononuclear cells in the epidermis. These findings suggest that ethanol enhances the expression of inflammatory cytokines independently from T helper (Th)1/Th2 cytokine phenotypes, causing abnormalities in the epidermis resulting in exacerbated allergic reactivity.

  5. Low dose TBT exposure decreases amphipod immunocompetence and reproductive fitness.

    PubMed

    Jacobson, Therese; Sundelin, Brita; Yang, Gongda; Ford, Alex T

    2011-01-17

    The antifouling agent tributyltin (TBT) is a highly toxic pollutant present in many aquatic ecosystems. Despite of regulations on the usage of TBT, it remains in high concentrations in sediments both in harbors and in off-shore sites. The toxicity of TBT in mollusks is well documented. However, adverse effects in other aquatic organisms, such as crustaceans, are less well known. This study is an effort to assess the effects of environmentally realistic concentrations of TBT on an ecologically important species in Swedish fresh and brackish water ecosystems, the benthic amphipod Monoporeia affinis. Field collected animals were exposed during gonad maturation to TBT (70 and 170 ng/g sediment d wt) for five weeks in static microcosms with natural sediment. Exposure concentrations were chosen to reflect effects at concentrations found in Swedish coastal sediment, but below expected effects on survival. TBT exposure resulted in a statistically significant adverse effect on oocyte viability and a doubling of the prevalence of microsporidian parasites in females, from 17% in the control to 34% in the 170 ng TBT/g sediment d wt exposure. No effects on survival were observed. Borderline significant effects were observed on male sexual maturation in the 70 ng TBT/g d wt exposure and on ecdysteroid levels in the 170 ng/g sediment d wt exposure. Both reproduction and parasite infection effects are of ecological importance since they have the potential to affect population viability in the field. This study gives further evidence to the connection between low dose contaminant exposure and increases in microsporidian parasite infection.

  6. 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

  7. 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.

  8. Urinary arsenic speciation and its correlation with 8-OHdG in Chinese residents exposed to arsenic through coal burning

    SciTech Connect

    Li, X.; Pi, J.B.; Li, B.; Xu, Y.Y.; Jin, Y.P.; Sun, G.F.

    2008-10-15

    In contrast to arsenicosis caused by consumption of water contaminated by naturally occurring inorganic arsenic, human exposure to this metalloid through coal burning has been rarely reported. In this study, arsenic speciation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in urine were determined in the Chinese residents exposed to arsenic through coal burning in Guizhou, China, an epidemic area of chronic arsenic poisoning caused by coal burning. The urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic (tAs) of high-arsenic exposed subjects were significantly higher than those of low-arsenic exposed residents. A biomarker of oxidative DNA damage, urinary 8-OHdG level was significantly higher in high-arsenic exposed subjects than that of low exposed. Significant positive correlations were found between 8-OHdG levels and concentrations of iAs, MMA, DMA and tAs, respectively. In addition, a significant negative correlation was observed between 8-OHdG levels and the secondary methylation ratio (DMA/(MMA + DMA)). The results suggest that chronic arsenic exposure through burning coal rich in arsenic is associated with oxidative DNA damages, and that secondary methylation capacity is potentially related to the susceptibility of individuals to oxidative DNA damage induced by arsenic exposure through coal burning in domestic living.

  9. Substantial contribution of biomethylation to aquifer arsenic cycling

    USGS Publications Warehouse

    Maguffin, Scott C.; Kirk, Matthew F.; Daigle, Ashley R.; Hinkle, Stephen R.; Jin, Qusheng

    2015-01-01

    Microbes play a prominent role in transforming arsenic to and from immobile forms in aquifers1. Much of this cycling involves inorganic forms of arsenic2, but microbes can also generate organic forms through methylation3, although this process is often considered insignificant in aquifers4, 5, 6, 7. Here we identify the presence of dimethylarsinate and other methylated arsenic species in an aquifer hosted in volcaniclastic sedimentary rocks. We find that dimethylarsinate is widespread in the aquifer and its concentration correlates strongly with arsenite concentration. We use laboratory incubation experiments and an aquifer injection test to show that aquifer microbes can produce dimethylarsinate at rates of about 0.1% of total dissolved arsenic per day, comparable to rates of dimethylarsinate production in surface environments. Based on these results, we estimate that globally, biomethylation in aquifers has the potential to transform 100 tons of inorganic arsenic to methylated arsenic species per year, compared with the 420–1,250 tons of inorganic arsenic that undergoes biomethylation in soils8. We therefore conclude that biomethylation could contribute significantly to aquifer arsenic cycling. Because biomethylation yields arsine and methylarsines, which are more volatile and prone to diffusion than other arsenic species, we further suggest that biomethylation may serve as a link between surface and subsurface arsenic cycling.

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

    PubMed Central

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

    2008-01-01

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

  11. 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

  12. Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction

    NASA Astrophysics Data System (ADS)

    Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.

    2015-03-01

    Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

  13. 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.

  14. 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

    Direct solid sample analysis with graphite furnace atomic absorption spectrometry (SS-GF AAS) was investigated initially with the intention of developing a method for the determination of total As in fish and other seafood. A mixture of 0.1% Pd+0.06% Mg+0.06% Triton X-100 was used as the chemical modifier, added in solution over the solid samples, making possible the use of pyrolysis and atomization temperatures of 1200 °C and 2400 °C, respectively. The sample mass had to be limited to 0.25 mg, as the integrated absorbance did not increase further with increasing sample mass. Nevertheless, the recovery of As from several certified reference materials was of the order of 50% lower than the certified value. Strong molecular absorption due to the phosphorus monoxide molecule (PO) was observed with high-resolution continuum source AAS (HR CS AAS), which, however, did not cause any spectral interference. A microwave-assisted digestion with HNO3/H2O2 was also investigated to solve the problem; however, the results obtained for several certified reference materials were statistically not different from those found with direct SS-GF AAS. Accurate values were obtained using inductively coupled plasma mass spectrometry (ICP-MS) to analyze the digested samples, which suggested that organic As compounds are responsible for the low recoveries. HPLC-ICP-MS was used to determine the arsenobetaine (AB) concentration. Accurate results that were not different from the certified values were obtained when the AB concentration was added to the As concentration found by SS-GF AAS for most certified reference materials (CRM) and samples, suggesting that SS-GF AAS could be used as a fast screening procedure for inorganic As determination in fish and seafood.

  15. A Simple Low-dose X-ray CT Simulation from High-dose Scan.

    PubMed

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong; Ma, Jianhua

    2015-10-01

    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.

  16. [Epidemiology of digestive complications associated with use of low-dose aspirin].

    PubMed

    Czernichow, Pierre; Merle, Véronique

    2004-04-01

    Low-dose aspirin (< 330 mg/d) is recommended for the prevention of myocardial infarction or ischemic stroke. Six to 12% of the general population is exposed to low-dose aspirin. The most frequently studied digestive complications are bleeding peptic ulcers, whose risk is increased twofold by low-dose aspirin treatment, and non-complicated peptic ulcers. History of bleeding or non-complicated peptic ulcer, alcohol intake, concomitant treatment with NSAID or calcic inhibitors are demonstrated risk factors of bleeding ulcer associated with low-dose aspirin. The role of enteric coating, of low-dose aspirin dose, of delay since low-dose aspirin treatment onset, and of Helicobacter pylori infection, remains controversial. Antisecretory drugs (H2 inhibitors, proton pump inhibitors), and nitroglycerin are associated with a decreased risk of bleeding ulcer. The protective effect of COX-2 inhibitors on the risk of bleeding ulcer is suppressed by concomitant treatment with low-dose aspirin. The risk of no- complicated peptic ulcer was increased by low-dose aspirin intake by a factor 2.9 in one study. Low-dose aspirin dose, infection by Helicobacter pylori, NSAID intake, and absence of enteric coating, are possible risk factors for non-complicated peptic ulcer. No association was retrieved with alcohol intake and peptic ulcer history.

  17. GENE EXPRESSION PROFILING OF NORMAL HUMAN BRONCHIAL EPITHELIAL CELLS EXPOSED TO TRIVALENT ARSENICALS AND DIMETHYLTHIOARSINIC ACID

    EPA Science Inventory

    Lung is a major target for arsenic carcinogenesis in humans. However, the carcinogenic mode of action of arsenicals is unknown. We investigated, in human bronchial epithelial (BEAS2B) cells, the effects of inorganic arsenic (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsi...

  18. Genomic-wide analysis of BEAS-2B cells exposed to Trivalent Arsenicals and Dimethylthioarsinic acid

    EPA Science Inventory

    Lung is a major target for arsenic carcinogenesis in humans by both oral and inhalation routes. However, the carcinogenic mode of action of arsenicals is unknown. We investigated the effects of inorganic arsenic (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (D...

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

    EPA Science Inventory

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

  20. METHYLATED ARSENICIII SPECIES ARE POTENTIAL PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC

    EPA Science Inventory

    METHYLATED ARSENIC(III) SPECIES ARE POTENTIAL PROXIMATE OR UL TIMA TE GENOTOXIC FORMS OF ARSENIC

    Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a genotoxicant without reacting directly with DNA; neither iAs nor As(V) methylated metabolites are e...

  1. EFFECTS OF DIETARY FOLATE ON ARSENIC-INDUCED GENE EXPRESSION IN MICE

    EPA Science Inventory

    Effects of Dietary Folate on Arsenic-induced Gene Expression in Mice

    Arsenic, a drinking water contaminant, is a known carcinogen. Human exposure to inorganic arsenic has been linked to tumors of skin, bladder, lung, and to a lesser extent, kidney and liver. Dietary fola...

  2. PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

    EPA Science Inventory

    Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

    Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

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

    EPA Science Inventory

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

  4. MEETING AT SAN DIEGO, CA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

    EPA Science Inventory

    Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and di-...

  5. MEETING AT CAMBRIDGE, MA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

    EPA Science Inventory

    Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and d...

  6. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

    EPA Science Inventory

    Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  9. Automated atomic absorption spectrometric determination of total arsenic in water and streambed materials

    USGS Publications Warehouse

    Fishman, M.

    1977-01-01

    An automated method to determine both inorganic and organic forms of arsenic In water, water-suspended mixtures, and streambed materials Is described. Organic arsenic-containing compounds are decomposed by either ultraviolet radiation or by suHurlc acid-potassium persulfate digestion. The arsenic liberated, with Inorganic arsenic originally present, is reduced to arsine with sodium borohydrlde. The arable Is stripped from the solution with the aid of nitrogen and Is then decomposed In a tube furnace heated to 800 ??C which Is placed in the optical path of an atomic absorption spectrometer. Thirty samples per hour can be analyzed to levels of 1 ??g arsenic per liter.

  10. 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

  11. Rapid screening of water soluble arsenic species in edible oils using dispersive liquid-liquid microextraction.

    PubMed

    López-García, Ignacio; Briceño, Marisol; Vicente-Martínez, Yesica; Hernández-Córdoba, Manuel

    2015-01-15

    A methodology for the non-chromatographic screening of the main arsenic species present in edible oils is discussed. Reverse dispersive liquid-liquid microextraction was used to extract water soluble arsenic compounds (inorganic arsenic, methylarsonate, dimethylarsinate and arsenobetaine) from the edible oils into a slightly acidic aqueous medium. The total arsenic content was measured in the extracts by electrothermal atomic absorption spectrometry using palladium as the chemical modifier. By repeating the measurement using cerium instead of palladium, the sum of inorganic arsenic and methylarsonate was obtained. The detection limit was 0.03 ng As per gram of oil. Data for the total and water-soluble arsenic levels of 29 samples of different origin are presented. Inorganic arsenic was not found in any of the samples marketed as edible oils.

  12. THE CELLULAR METABOLISM AND SYSTEMIC TOXICITY OF ARSENIC

    EPA Science Inventory

    Abstract

    Toxic Consequences of the Metabolism of Arsenic. David J. Thomas, Miroslav Styblo, and Shan Lin. (2001). Toxicol. Appl. Pharmacol. 000, xxx-yyy.
    Although it has been known for decades that humans and many other species metabolize inorganic arsenic to methyl ...

  13. Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation

    SciTech Connect

    Li, Chuan-Yaun

    2009-01-27

    “Molecular dissection of the roles of the SOD genes in mammalian response to low dose irradiation " was started on 09/01/03 and ended on 08/31/07. The primary objective of the project was to carry out mechanistic studies of the roles of the anti-oxidant SOD genes in mammalian cellular response to low dose ionizing radiation.

  14. [Risk and prevention of gastrointestinal complications due to low-dose aspirin and other antiplatelet agents].

    PubMed

    Bretagne, Jean-François

    2008-09-15

    Upper and lower gastrointestinal (GI) haemorrhages are the main complications associated with low-dose aspirin or anti-thrombotic drugs. In France, low-dose aspirin or anti-thrombotic agents use has been found in 30% of upper GI and 40% of lower GI bleeding episodes. Main causes of GI bleeding with low-dose aspirin are gastroduodenal peptic ulcer and colonic diverticulosis. Recent cohort studies have shown that the relative risk of GI bleeding with low-dose aspirin was comprised between 2 and 4 and the absolute risk comprised between 1 per 100 and 1 per 1000 aspirin users per year. Main risk factors for upper GI bleeding with low-dose aspirin are concomitant antiplatelet agents, anticoagulants, non steroidal anti-inflammatory drugs or steroids use, and recent history of complicated or non-complicated gastroduodenal ulcer. Helicobacter pylori infection increases the risk for upper GI bleeding with low-dose aspirin, but infection should be searched and treated only in patients with peptic ulcer. Despite eradication of H. pylori in the latter patients, gastroprotection with PPI is strongly recommended. In patients presenting with peptic ulcer bleeding with low-dose aspirin, aspirin should be continued in association with PPI rather than replaced with clopidogrel. Discontinuation of low-dose aspirin which exposes to increased cardiovascular complications and mortality should be avoided, even in cases of peptic ulcer bleeding.

  15. Low doses of glyphosate change the response of soybean to later glyphosate exposures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The stimulatory effect of low doses of toxic substances is known as hormesis. Many herbicides that cause severe injury to plants at recommended rates, promote growth or have other stimulatory effects at very low doses. The objective of this study was to evaluate glyphosate-induced hormesis in soyb...

  16. Effect of low doses of dietary rare earth elements on growth performance of broilers.

    PubMed

    He, M L; Wehr, U; Rambeck, W A

    2010-02-01

    The present study was designed to investigate effect of dietary rare earth elements (REE), including both organic and inorganic compounds, on growth performance of broilers. In experiment 1, a total of 180 male Ross broiler chicks were allocated to 72 pens with different assignment: four chicks per pen or individually. The following three treatment diets were applied: control, REE-chlorides at a dose of 40 mg/kg and REE-citrate at a dose of 70 mg/kg. Each treatment group had 24 pens containing both assignments (12 pens each). In experiment 2, a total of 72 male 3-day-old Ross broiler chicks were separated to four groups: control, REE-chlorides at a dose of 70 mg/kg and REE-citrate at doses of 70 mg/kg and 100 mg/kg. In experiment 1, dietary REE-citrate improved body weight gain during the overall period by 5.0% (p < 0.05) while the increase with REE-chloride was not significant. In experiment 2, growth effects (p < 0.05) were only found in the period from day 21 to slaughter with all REE forms, and feed conversion ratio was improved by 3.4% (p < 0.05) with REE-citrate. No significant effects of REE were found on chill weight, percentages of breast meat, thigh weight, drumstick weight and wing weight. Concentrations of La and Ce in the liver and muscles were very low, accounting for 0.11-0.76 and 0.02-0.30 mg/kg respectively. There was weak tendency for a dose-response relationship especially in the groups supplemented with REE-chlorides. The main blood serum biochemical parameters were not significantly affected by REE in the diets. The results suggest that dietary supplementation of low doses of REE-citrates might improve growth performance of broilers without affecting carcass composition and health of the broilers.

  17. Arsenic species and leaching characters in tea (Camellia sinensis).

    PubMed

    Yuan, Chungang; Gao, Erle; He, Bin; Jiang, Guibin

    2007-12-01

    Tea is one of the most popular non-alcoholic beverages consumed in the world. Arsenic including species totalling to 47 Chinese tea samples from 18 tea-producing provinces in China were analyzed. By simulating the infusion process, leaching characters, effects of extraction time and temperature on arsenic extraction were investigated. Total amount of arsenic in tea leaf samples was in the range below the detection limit to 4.81 microg/g. Leaching of arsenic was strongly affected by extraction time and temperature. Because arsenic leaching ability by hot water was low and most of the arsenic was left in tea leaf residues after infusion, the concentration of arsenic in tea infusion was low even when some original tea leaf samples contained high level of arsenic. The major species in tea infusion were inorganic arsenic form (arsenite As(III) and arsenate As(V)). Compared with the amount of arsenic in infusion, more organic arsenic species were found in the original tea leaf samples. The contents of extractable inorganic arsenic in tea leaf samples were in the range below the detection limit to 226 ng/g. Considering ingestion dose and assuming one person (60 kg body weight) consumes 10 g of Chinese tea per day, the maximum inorganic arsenic contribution from tea infusion is 2.26 microg, which is equal to 0.038 microg/kg/d excluding water contribution. This value only accounts for 1.8% of provisional tolerable weekly intake (PTWI) (2.1 microg/kg/d) recommended by the Food and Agriculture Organization/World Health Organization [FAO/WHO, 1989. Evaluation of certain food additives and contaminants. Thirty-third Report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series No. 776, Geneva, World Health Organization].

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2014-01-01

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

  20. Arsenic geochemistry of groundwater in Southeast Asia.

    PubMed

    Kim, Kyoung-Woong; Chanpiwat, Penradee; Hanh, Hoang Thi; Phan, Kongkea; Sthiannopkao, Suthipong

    2011-12-01

    The occurrence of high concentrations of arsenic in the groundwater of the Southeast Asia region has received much attention in the past decade. This study presents an overview of the arsenic contamination problems in Vietnam, Cambodia, Lao People's Democratic Republic and Thailand. Most groundwater used as a source of drinking water in rural areas has been found to be contaminated with arsenic exceeding the WHO drinking water guideline of 10 μg·L(-1). With the exception of Thailand, groundwater was found to be contaminated with naturally occurring arsenic in the region. Interestingly, high arsenic concentrations (> 10 μg·L(-1)) were generally found in the floodplain areas located along the Mekong River. The source of elevated arsenic concentrations in groundwater is thought to be the release of arsenic from river sediments under highly reducing conditions. In Thailand, arsenic has never been found naturally in groundwater, but originates from tin mining activities. More than 10 million residents in Southeast Asia are estimated to be at risk from consuming arsenic-contaminated groundwater. In Southeast Asia, groundwater has been found to be a significant source of daily inorganic arsenic intake in humans. A positive correlation between groundwater arsenic concentration and arsenic concentration in human hair has been observed in Cambodia and Vietnam. A substantial knowledge gap exists between the epidemiology of arsenicosis and its impact on human health. More collaborative studies particularly on the scope of public health and its epidemiology are needed to conduct to fulfill the knowledge gaps of As as well as to enhance the operational responses to As issue in Southeast Asian countries.

  1. Impact of life stage and duration of exposure on arsenic-induced proliferative lesions, neoplasia, and gene expression in male C3H mice.

    EPA Science Inventory

    Previous studies have demonstrated increased liver and adrenal tumor incidence in male mice exposed gestationally to 85 ppm inorganic arsenic via the dams’ drinking water. To further characterize age susceptibility to arsenic carcinogenesis we have administered 85 ppm sodium ars...

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

    EPA Science Inventory

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

  3. Concentration and chemical status of arsenic in the early placentas of arsenate-dosed hamsters

    SciTech Connect

    Hanlon, D.P.; Ferm, V.H.

    1987-04-01

    The authors determined the concentration and chemical status of arsenic in the placentas of hamsters following continuous exposure via the osmotic minipump to minimally and frankly teratogenic doses of arsenate. Close to 70% of the placental arsenic is bound to macromolecules, two-thirds of which is dialyzable. The remaining 30% of arsenic consists of low molecular weight species, predominantly inorganic arsenic. This mix is the same for minimally teratogenic and frankly teratogenic doses of arsenate.

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

    SciTech Connect

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

    2007-01-15

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

  5. Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice

    PubMed Central

    Rodriguez, Karina F.; Ungewitter, Erica K.; Crespo-Mejias, Yasmin; Liu, Chang; Nicol, Barbara; Kissling, Grace E.; Yao, Humphrey Hung-Chang

    2015-01-01

    Background Mice exposed to high levels of arsenic in utero have increased susceptibility to tumors such as hepatic and pulmonary carcinomas when they reach adulthood. However, the effects of in utero arsenic exposure on general physiological functions such as reproduction and metabolism remain unclear. Objectives We evaluated the effects of in utero exposure to inorganic arsenic at the U.S. Environmental Protection Agency (EPA) drinking water standard (10 ppb) and at tumor-inducing levels (42.5 ppm) on reproductive end points and metabolic parameters when the exposed females reached adulthood. Methods Pregnant CD-1 mice were exposed to sodium arsenite [none (control), 10 ppb, or 42.5 ppm] in drinking water from gestational day 10 to birth, the window of organ formation. At birth, exposed offspring were fostered to unexposed dams. We examined reproductive end points (age at vaginal opening, reproductive hormone levels, estrous cyclicity, and fertility) and metabolic parameters (body weight changes, hormone levels, body fat content, and glucose tolerance) in the exposed females when they reached adulthood. Results Arsenic-exposed females (10 ppb and 42.5 ppm) exhibited early onset of vaginal opening. Fertility was not affected when females were exposed to the 10-ppb dose. However, the number of litters per female was decreased in females exposed to 42.5 ppm of arsenic in utero. In both 10-ppb and 42.5-ppm groups, arsenic-exposed females had significantly greater body weight gain, body fat content, and glucose intolerance. Conclusion Our findings revealed unexpected effects of in utero exposure to arsenic: exposure to both a human-relevant low dose and a tumor-inducing level led to early onset of vaginal opening and to obesity in female CD-1 mice. Citation Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. 2016. Effects of in utero exposure to arsenic during the second half of gestation on reproductive end points and metabolic

  6. Urinary Arsenic and Insulin Resistance in US Adolescents

    PubMed Central

    Peng, Qing; Harlow, Siobán D.; Park, Sung Kyun

    2015-01-01

    Chronic arsenic exposure has been associated with increased diabetes risk in adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic-related diabetes. Although limited evidence in adults found no association between arsenic and IR, the association in adolescents is largely unknown. We examined the association between urinary arsenic and insulin resistance in US adolescents. Eight hundred thirty five adolescents aged 12-19 years, with complete data on urinary arsenic (total arsenic, inorganic arsenic and dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were identified from the National Health and Nutrition Examination Survey (NHANES) cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting for intra-cluster correlation arising from the complex survey design were used to estimate the association between the updated Homeostasis Model Assessment (HOMA2)-IR and each type of arsenic. After adjusting for potential confounders, including urinary creatinine, sociodemographic factors, BMI, waist circumference, and arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile range increases in total arsenic, inorganic arsenic and DMA were associated with 1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9) increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association with diabetes in adults and potential role in insulin resistance, our findings do not support the hypothesis that arsenic exposure at levels common in the US contributes to insulin resistance in adolescents. Whether higher doses and longer exposure duration are required for appreciable influence on insulin resistance, or that arsenic does not act through insulin resistance to induce diabetes needs further investigation.1 PMID:25845984

  7. Urinary arsenic and insulin resistance in US adolescents.

    PubMed

    Peng, Qing; Harlow, Siobán D; Park, Sung Kyun

    2015-06-01

    Chronic arsenic exposure has been associated with increased diabetes risk in adults. Insulin resistance (IR) has been proposed as a mechanism of arsenic-related diabetes. Although limited evidence in adults found no association between arsenic and IR, the association in adolescents is largely unknown. We examined the association between urinary arsenic and insulin resistance in US adolescents. Eight hundred thirty five adolescents aged 12-19 years, with complete data on urinary arsenic (total arsenic, inorganic arsenic and dimethylarsenic acid (DMA)), fasting glucose, insulin and key covariates were identified from the National Health and Nutrition Examination Survey (NHANES) cycles 2003/2004 through 2009/2010. Generalized additive mixed models accounting for intra-cluster correlation arising from the complex survey design were used to estimate the association between the updated Homeostasis Model Assessment (HOMA2)-IR and each type of arsenic. After adjusting for potential confounders, including urinary creatinine, sociodemographic factors, BMI, waist circumference, and arsenobetaine, arsenic exposure was not associated with HOMA2-IR. Interquartile range increases in total arsenic, inorganic arsenic and DMA were associated with 1.5% (95% CI: -2.0, 5.2), 1.1% (95% CI: -1.5, 3.8) and 0.25% (95% CI: -2.3, 2.9) increases in HOMA2-IR, respectively. In conclusion, despite arsenic's association with diabetes in adults and potential role in insulin resistance, our findings do not support the hypothesis that arsenic exposure at levels common in the US contributes to insulin resistance in adolescents. Whether higher doses and longer exposure duration are required for appreciable influence on insulin resistance, or that arsenic does not act through insulin resistance to induce diabetes needs further investigation.

  8. Both Phosphorus Fertilizers and Indigenous Bacteria Enhance Arsenic Release into Groundwater in Arsenic-Contaminated Aquifers.

    PubMed

    Lin, Tzu-Yu; Wei, Chia-Cheng; Huang, Chi-Wei; Chang, Chun-Han; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2016-03-23

    Arsenic (As) is a human carcinogen, and arsenic contamination in groundwater is a worldwide public health concern. Arsenic-affected areas are found in many places but are reported mostly in agricultural farmlands, yet the interaction of fertilizers, microorganisms, and arsenic mobilization in arsenic-contaminated aquifers remains uncharacterized. This study investigates the effects of fertilizers and bacteria on the mobilization of arsenic in two arsenic-contaminated aquifers. We performed microcosm experiments using arsenic-contaminated sediments and amended with inorganic nitrogenous or phosphorus fertilizers for 1 and 4 months under aerobic and anaerobic conditions. The results show that microcosms amended with 100 mg/L phosphorus fertilizers (dipotassium phosphate), but not nitrogenous fertilizers (ammonium sulfate), significantly increase aqueous As(III) release in arsenic-contaminated sediments under anaerobic condition. We also show that concentrations of iron, manganese, potassium, sodium, calcium, and magnesium are increased in the aqueous phase and that the addition of dipotassium phosphate causes a further increase in aqueous iron, potassium, and sodium, suggesting that multiple metal elements may take part in the arsenic release process. Furthermore, microbial analysis indicates that the dominant microbial phylum is shifted from α-proteobacteria to β- and γ-proteobacteria when the As(III) is increased and phosphate is added in the aquifer. Our results provide evidence that both phosphorus fertilizers and microorganisms can mediate the release of arsenic to groundwater in arsenic-contaminated sediments under anaerobic condition. Our study suggests that agricultural activity such as the use of fertilizers and monitoring phosphate concentration in groundwater should be taken into consideration for the management of arsenic in groundwater.

  9. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

    PubMed Central

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-01-01

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen. PMID:26515758

  10. Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation.

    PubMed

    Kim, Rae-Kwon; Kim, Min-Jung; Seong, Ki Moon; Kaushik, Neha; Suh, Yongjoon; Yoo, Ki-Chun; Cui, Yan-Hong; Jin, Young Woo; Nam, Seon Young; Lee, Su-Jae

    2015-10-30

    Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

  11. Human Arsenic Poisoning Issues in Central-East Indian Locations: Biomarkers and Biochemical Monitoring

    PubMed Central

    Pandey, Piyush Kant; Yadav, Sushma; Pandey, Madhurima

    2007-01-01

    The study reports the use of three biomarkers i.e. total arsenic in hair and nails, total arsenic in blood, and total arsenic in urine to identify or quantify arsenic exposure and concomitant health effects. The main source of arsenic was inorganic exposure through drinking water. The arsenic levels and the health effects were analyzed closely in a family having maximum symptoms of arsenic. Based on the result of this study it is reported that there exist a correlation between the clinically observable symptoms, the blood and urine arsenic level, and the arsenic intake through drinking water. An intensive study on the urinary arsenic levels was carried out in which the urine levels of arsenic and the urine sufficiency tests were performed. A composite picture of body burden of arsenic has been obtained by carrying out a complete biochemical analysis of a maximum affected family. This confirms pronounced chronic exposure of the arsenic to these people. A combined correlation study on the arsenic levels measured in whole blood, urine, hair, nails and age present a remarkable outcome. Accordingly, the arsenic levels in blood are negatively correlated with the urine arsenic levels, which indicate either the inadequacy of the renal system in cleaning the blood arsenic or a continuous recirculation of the accumulated arsenic. This is an important conclusion about arsenical metabolism in humans. The study also raises the issues of the prospects of complete elimination of the accumulated arsenic and the reversibility of the health effects. Based on the work in Kourikasa village we report that there are very remote chances of complete purging of arsenic and thus reversibility of the health effects owing to various factors. The paper also discusses the various issues concerning the chronic arsenic poisoning management in the affected locations. PMID:17431310

  12. The Inhibitory Effects of Low-Dose Ionizing Radiation in IgE-Mediated Allergic Responses

    PubMed Central

    Nam, Seon Young; Yang, Kwang Hee; Kim, Cha Soon; Lee, In Kyung; Kim, Ji Young

    2015-01-01

    Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro. PMID:26317642

  13. Hijacking membrane transporters for arsenic phytoextraction

    PubMed Central

    LeBlanc, Melissa S.; McKinney, Elizabeth C.; Meagher, Richard B.; Smith, Aaron P.

    2012-01-01

    Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator. PMID:23108027

  14. Urinary excretion of arsenic following rice consumption.

    PubMed

    Meharg, A A; Williams, P N; Deacon, C M; Norton, G J; Hossain, M; Louhing, D; Marwa, E; Lawgalwi, Y; Taggart, M; Cascio, C; Haris, P

    2014-11-01

    Patterns of arsenic excretion were followed in a cohort (n = 6) eating a defined rice diet, 300 g per day d.wt. where arsenic speciation was characterized in cooked rice, following a period of abstinence from rice, and other high arsenic containing foods. A control group who did not consume rice were also monitored. The rice consumed in the study contained inorganic arsenic and dimethylarsinic acid (DMA) at a ratio of 1:1, yet the urine speciation was dominated by DMA (90%). At steady state (rice consumption/urinary excretion) ∼40% of rice derived arsenic was excreted via urine. By monitoring of each urine pass throughout the day it was observed that there was considerable variation (up to 13-fold) for an individual's total arsenic urine content, and that there was a time dependent variation in urinary total arsenic content. This calls into question the robustness of routinely used first pass/spot check urine sampling for arsenic analysis.

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

    PubMed

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

    2014-08-01

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

  16. Magentite nanoparticle for arsenic remotion.

    NASA Astrophysics Data System (ADS)

    Viltres, H.; Odio, O. F.; Borja, R.; Aguilera, Y.; Reguera, E.

    2017-01-01

    Inorganic As (V) and As (III) species are commonly found in groundwater in many countries around the world. It is known that arsenic is highly toxic and carcinogenic, at present exist reports of diverse countries with arsenic concentrations in drinking water higher than those proposed by the World Health Organization (10 μg/L). It has been reported that adsorption strategies using magnetic nanoparticles as magnetite (<20 nm) proved to be very efficient for the removal of arsenic in drinking water. Magnetic nanoparticles (magnetite) were prepared using a co-precipitation method with FeCl3 and FeCl2 as metal source and NaOH aqueous solution as precipitating agent. Magnetite nanoparticles synthesized were put in contact with As2O3 and As2O5 solutions at room temperature to pH 4 and 7. The nanoparticles were characterized by FT-IR, DRX, UV-vis, and XRF. The results showed that synthesized magnetite had an average diameter of 11 nm and a narrow size distribution. The presence of arsenic on magnetite nanoparticles surface was confirmed, which is more remarkable when As (V) is employed. Besides, it is possible to observe that no significant changes in the band gap values after adsorption of arsenic in the nanoparticles.

  17. Groundwater arsenic in Chimaltenango, Guatemala.

    PubMed

    Lotter, Jason T; Lacey, Steven E; Lopez, Ramon; Socoy Set, Genaro; Khodadoust, Amid P; Erdal, Serap

    2014-09-01

    In the Municipality of Chimaltenango, Guatemala, we sampled groundwater for total inorganic arsenic. In total, 42 samples were collected from 27 (43.5%) of the 62 wells in the municipality, with sites chosen to achieve spatial representation throughout the municipality. Samples were collected from household faucets used for drinking water, and sent to the USA for analysis. The only site found to have a concentration above the 10 μg/L World Health Organization provisional guideline for arsenic in drinking water was Cerro Alto, where the average concentration was 47.5 μg/L. A health risk assessment based on the arsenic levels found in Cerro Alto showed an increase in noncarcinogenic and carcinogenic risks for residents as a result of consuming groundwater as their primary drinking water source. Using data from the US Geological Survey and our global positioning system data of the sample locations, we found Cerro Alto to be the only site sampled within the tertiary volcanic rock layer, a known source of naturally occurring arsenic. Recommendations were made to reduce the levels of arsenic found in the community's drinking water so that the health risks can be managed.

  18. Modeling Low-Dose-Rate Effects in Irradiated Bipolar-Base Oxides

    SciTech Connect

    Cirba, C.R.; Fleetwood, D.M.; Graves, R.J.; Michez, A.; Milanowski, R.J.; Saigne, F.; Schrimpf, R.D.; Witczak, S.C.

    1998-10-26

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in bipolar junction transistors. Multiple-trapping simulations show that space charge limited transport is partially responsible for low-dose-rate enhancement. At low dose rates, more holes are trapped near the silicon-oxide interface than at high dose rates, resulting in larger midgap voltage shifts at lower dose rates. The additional trapped charge near the interface may cause an exponential increase in excess base current, and a resultant decrease in current gain for some NPN bipolar technologies.

  19. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  20. Noise reduction with low dose CT data based on a modified ROF model.

    PubMed

    Zhu, Yining; Zhao, Mengliu; Zhao, Yunsong; Li, Hongwei; Zhang, Peng

    2012-07-30

    In order to reduce the radiation exposure caused by Computed Tomography (CT) scanning, low dose CT has gained much interest in research as well as in industry. One fundamental difficulty for low dose CT lies in its heavy noise pollution in the raw data which leads to quality deterioration for reconstructed images. In this paper, we propose a modified ROF model to denoise low dose CT measurement data in light of Poisson noise model. Experimental results indicate that the reconstructed CT images based on measurement data processed by our model are in better quality, compared to the original ROF model or bilateral filtering.

  1. Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

    NASA Technical Reports Server (NTRS)

    Johnston, A.; Barnes, C.

    1995-01-01

    Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

  2. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  3. Arsenic Concentrations and Speciation in Shellfishes from Korea

    NASA Astrophysics Data System (ADS)

    Yoon, C.; Yoon, H.

    2005-12-01

    Speciation of arsenic has received significant attention over the past 20 years in both mechanistic and exposure assessment research. Because the toxicity of arsenic is related to its oxidation state and its chemical forms, the determination of the total arsenic contents in a sample is not adequate to allow its impact on living organisms to be estimated. The inorganic arsenic species, arsenite (As3+) and arsenate (As5+), have been classified as carcinogenic and the methylated forms, monomethyl arsonic acid (MMA) and dimethyl arsinic acid (DMA) have recently been identified as cancer promoters. The highly methylated compounds like as arsenobetaine (AsB) and arsenocholine (AsC) are considered to be nontoxic. Although organisms in marine environment contain high amounts of total arsenic (ppm level), it is not usually present as inorganic arsenic or simple methylated forms well known as one of the toxic species. Arsenobetaine is the dominant species in marine animals and arsenosugars are most abundant in marine algae. This study aims to clarify those arsenic species present in the whole body of eleven different shellfishes from Korea. And those arsenic species were separated and measured by characterization using high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) coupled system. The separation of arsenic species was achieved on anion exchange column and cation exchange column using phosphate and pyridine eluent, respectively. The ultrasonic extraction was employed for extraction of arsenic from whole body of shellfishes. The method was validated by analyzing three certified reference materials (DORM-2, TORT-2, 1566b). Total arsenic concentrations ranged from 0.1 mg/kg dry mass to 21.7 mg/kg dry mass. Most marine shellfishes contained higher arsenobetaine and arsenocholine with the exception of two shellfishes living in river. The lower amounts of inorganic arsenic species were also found in the some sample extracts

  4. Impaired arsenic metabolism in children during weaning

    SciTech Connect

    Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro; Grander, Margaretha; Palm, Brita; Vahter, Marie

    2009-09-01

    Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 {mu}g/L, range 2.4-940 {mu}g/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.

  5. Arsenic mobilization and immobilization in paddy soils

    NASA Astrophysics Data System (ADS)

    Kappler, A.; Hohmann, C.; Zhu, Y. G.; Morin, G.

    2010-05-01

    Arsenic is oftentimes of geogenic origin and in many cases bound to iron(III) minerals. Iron(III)-reducing bacteria can harvest energy by coupling the oxidation of organic or inorganic electron donors to the reduction of Fe(III). This process leads either to dissolution of Fe(III)-containing minerals and thus to a release of the arsenic into the environment or to secondary Fe-mineral formation and immobilisation of arsenic. Additionally, aerobic and anaerobic iron(II)-oxidizing bacteria have the potential to co-precipitate or sorb arsenic during iron(II) oxidation at neutral pH that is usually followed by iron(III) mineral precipitation. We are currently investigating arsenic immobilization by Fe(III)-reducing bacteria and arsenic co-precipitation and immobilization by anaerobic iron(II)-oxidizing bacteria in batch, microcosm and rice pot experiments. Co-precipitation batch experiments with pure cultures of nitrate-dependent Fe(II)-oxidizing bacteria are used to quantify the amount of arsenic that can be immobilized during microbial iron mineral precipitation, to identify the minerals formed and to analyze the arsenic binding environment in the precipitates. Microcosm and rice pot experiments are set-up with arsenic-contaminated rice paddy soil. The microorganisms (either the native microbial population or the soil amended with the nitrate-dependent iron(II)-oxidizing Acidovorax sp. strain BoFeN1) are stimulated either with iron(II), nitrate, or oxygen. Dissolved and solid-phase arsenic and iron are quantified. Iron and arsenic speciation and redox state in batch and microcosm experiments are determined by LC-ICP-MS and synchrotron-based methods (EXAFS, XANES).

  6. Biotransformation and biomethylation of arsenic by Shewanella oneidensis MR-1.

    PubMed

    Wang, Juan; Wu, Mingyin; Lu, Gan; Si, Youbin

    2016-02-01

    The resistance of Shewanella oneidensis MR-1 to toxic arsenic was investigated by measuring the growth of the bacteria in the presence of As(III) and As(V) in different growth media. The bacteria were shown to biotransform arsenic through the partial methylation of inorganic arsenic into methylated metabolites. This biotransformation of inorganic arsenic by S. oneidensis MR-1 was affected by the methyl donor, the composition of the medium, and the presence of Fe(III). The relative content of methylated arsenic in the medium containing S-adenosyl methionine as the methyl donor was greater than that in the medium containing methylcobalamin. The biotransformation process driven by Fe-reducing bacteria, and occurred in combination with microbially mediated As-Fe reduction in the presence of Fe(III). The results demonstrate that S. oneidensis MR-1 methylates inorganic arsenic into less toxic organoarsenic compounds. This process has potential applications in the bioremediation of environmental arsenic, and the results provide new insights into the control of in situ arsenic pollution.

  7. Bioaccessibility and degradation of naturally occurring arsenic species from food in the human gastrointestinal tract.

    PubMed

    Chávez-Capilla, Teresa; Beshai, Mona; Maher, William; Kelly, Tamsin; Foster, Simon

    2016-12-01

    Humans are exposed to organic arsenic species through their diet and therefore, are susceptible to arsenic toxicity. Investigating the transformations occurring in the gastrointestinal tract will influence which arsenic species to focus on when studying metabolism in cells. Using a physiologically based extraction test, the bioaccessibility of arsenic species was determined after the simulated gastrointestinal digestion of rice, seaweed and fish. Pure standards of the major arsenic species present in these foodstuffs (arsenic glutathione complexes, arsenosugars and short chain fatty acids) were also evaluated to assess the effect of the food matrix on bioaccessibility and transformation. Approximately 80% of arsenic is released from these foodstuffs, potentially becoming available. Hydrolysis and demethylation of arsenic glutathione complexes and arsenosugars standards was observed, but no transformations occurred to arsenosugars present in seaweed. Demethylation of MA and DMA from rice occurs increasing the amount of inorganic arsenic species available for metabolism.

  8. ARSENIC AND THE EPIGENOME: LINKED BY METHYLATION(Thailand)

    EPA Science Inventory

    Inorganic arsenic (iAs) is an environmental toxicant currently poisoning millions of people worldwide. The most common route of As exposure in humans is through the consumption of drinking water contaminated with iAs from natural, geologic sources. Inorganic As exists in drinking...

  9. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    PubMed Central

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  10. Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

    Cancer.gov

    A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

  11. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... protective equipment. Employee rotation is not required as a control strategy before respiratory protection... revised and updated at least annually to reflect the current status of the program. (h) Respiratory... respiratory protection program in accordance with § 1910.134(b) through (d) (except (d)(1)(iii)), and...

  12. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... effects; respiratory irritation; nervous system effects; and acute toxicity effects. (iii) Employers shall... protective equipment. Employee rotation is not required as a control strategy before respiratory protection... revised and updated at least annually to reflect the current status of the program. (h)...

  13. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... effects; respiratory irritation; nervous system effects; and acute toxicity effects. (iii) Employers shall... protective equipment. Employee rotation is not required as a control strategy before respiratory protection... revised and updated at least annually to reflect the current status of the program. (h)...

  14. An evaluation of human ADME and mass balance studies using regular or low doses of radiocarbon.

    PubMed

    Roffel, A F; van Marle, S P; van Lier, J J; Hartstra, J; van Hoogdalem, E-J

    2016-12-01

    There has been increased interest in conducting human absorption, distribution, metabolism, and excretion (ADME) studies with low doses (up to 0.1 MBq) as opposed to regular doses (1.85-3.7 MBq) of radiocarbon ((14) C). This is due to the fact that low-dose human ADME studies may be conducted without dosimetry calculations and will lead to lower human radiation exposure. Here, we sought to compare the outcomes of low-dose versus regular-dose human ADME studies in healthy volunteers. Forty oral human ADME studies conducted at PRA were surveyed, among which 12 were low-dose studies. The fraction of drug material absorbed was 67% ± 7% in the regular-dose studies (data for 13 studies) versus 39% ± 16% in the low-dose studies (data for 5 studies). The average total recovery of (14) C in excreta was 93% ± 5% for regular-dose studies, and 21 of 28 such studies showed recoveries more than 90%. For low-dose studies, average total recovery was 89% ± 9%, and 6 of 12 studies showed recoveries more than 90%. Metabolite profiling was successful in all cases reported (13 regular-dose studies and 5 low-dose studies). There was no obvious relationship between the total recoveries of (14) C in excreta and the proportion of (14) C excreted in feces, or between the total recoveries and the plasma elimination half-lives for parent or total (14) C, neither in the low-dose nor the regular-dose studies. A significant correlation was found between the fraction absorbed and the recovery in feces in the low-dose but not in the regular-dose studies, and no correlation was found between the fractions absorbed and the total recoveries in both types of studies. Low-dose studies were more often conducted on drugs that had a plasma elimination half-life of parent drug more than 100 hours (5 of 12 studies) than regular-dose studies (1 of 26 studies). We conclude that both low-dose as well as regular-dose human ADME studies provide adequate data to support decision making for further

  15. Concentrations and speciation of arsenic in groundwater polluted by warfare agents.

    PubMed

    Daus, Birgit; Hempel, Michael; Wennrich, Rainer; Weiss, Holger

    2010-11-01

    Groundwater polluted with phenylarsenicals from former warfare agent deposits and their metabolites was investigated with respect to the behavior of relevant arsenic species. Depth profiles at the estimated source and at about 1km downgradient from the source zone were sampled. The source zone is characterized by high total arsenic concentrations up to 16mgL(-1) and is dominated by organic arsenic compounds. The concentrations in the downgradient region are much lower (up to 400μgL(-1)) and show a high proportion of inorganic arsenic species. Iron precipitation seems to be an effective mechanism to prevent dispersion of inorganic arsenic as well as phenylarsonic acid. Reductive conditions were observed in the deeper zone with predominant occurrence of trivalent arsenic species. The inorganic species are in redox equilibrium, whereas the phenylarsenic compounds have variable proportions. Methylphenylarsinic acid was identified in groundwater in traces which indicates microbial degradation activity.

  16. Low-Dose Naltrexone: A New Therapy Option for Complex Regional Pain Syndrome Type I Patients.

    PubMed

    Sturn, Kayla M; Collin, Michael

    2016-01-01

    Naltrexone (an opioid antagonist) has long been used in patients overcoming alcohol and opioid dependency. However, at doses one-tenth of those commonly prescribed for the above conditions, an unexpected effect occurs that aids in alleviating pain. Although there are currently no randomized clinical trials supporting the use of low-dose naltrexone, we present a case study describing the impact of compounding low-dose naltrexone that has dramatically improved the patient's pain symptoms which were refractory to other treatments.

  17. [The advance of model of action in low-dose chronic benzene exposure induced hematotoxicity].

    PubMed

    Gao, Chen; Zhang, Zhengbao; Chen, Liping; Chen, Wen

    2015-09-01

    Benzene is classified as Group 1 carcinogen by IARC. It has been found that benzene induces hematotoxicity even in low dose exposure. The identification of key events during benzene induced hematotoxicty leads to adjustment of occupational exposure limits of benzene. In this review, we focus on the exposure, metabolism, target organs, key epigenetic changes, toxicty effects and end points of low-dose chronic benzene exposure induced hematotoxicity and finally discuss the perspectives on the future study of this area.

  18. Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

    SciTech Connect

    Seth, Isheeta; Joiner, Michael C.; Tucker, James D.

    2015-01-01

    Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

  19. Use of MOS structures for the investigation of low-dose-rate effects in bipolar transistors

    SciTech Connect

    Belyakov, V.V.; Pershenkov, V.S.; Shalnov, A.V.; Shvetzov-Shilovsky, I.N.

    1995-12-01

    A possible physical mechanism for bipolar transistor low-dose-rate irradiation response is discussed. This mechanism is described in terms of shallow electron traps in oxide. The experimental results on positive charge build-up at low dose-rates and small electric field in oxide are presented. The use of MOS transistor in bipolar mode for investigation of surface peripheral recombination current in bipolar transistor and extraction of MOS structure physical parameters is described.

  20. Low-dose Ketamine Versus Morphine for Acute Pain In the ED: A Randomized Controlled Trial

    DTIC Science & Technology

    2015-03-01

    Original Contribution Low-dose ketamine vs morphine for acute pain in the ED: a randomized controlled trial☆,☆☆ Joshua P. Miller, MD a,b,⁎, Steven G...numeric rating scale (NRS) pain scores, in patients receiving low-dose ketamine (LDK) or morphine (MOR) for acute pain in the emergency department...convenience sample of patients aged 18 to 59 years with acute abdominal, flank, low back, or extremity pain were enrolled. Subjects were consented and