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Sample records for low-dose inorganic arsenic

  1. Arsenic, inorganic

    Integrated Risk Information System (IRIS)

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

  2. Low doses of arsenic, via perturbing p53, promotes tumorigenesis.

    PubMed

    Ganapathy, Suthakar; Li, Ping; Fagman, Johan; Yu, Tianqi; Lafontant, Jean; Zhang, Guojun; Chen, Changyan

    2016-09-01

    In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure. PMID:27425828

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

    SciTech Connect

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

    2005-09-01

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

  4. Proteomic Analysis of Low Dose Arsenic and Ionizing Radiation Exposure on Keratinocytes

    PubMed Central

    Berglund, Susanne R.; Santana, Alison R.; Li, Dan; Rice, Robert H.; Rocke, David M.; Goldberg, Zelanna

    2008-01-01

    Human exposure to arsenic and ionizing radiation occur environmentally at low levels. While the human health effects of arsenic and ionizing radiation have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent ionizing radiation especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic and/or low dose ionizing radiation exposure, resulting in differential proteomic expression based on 2DGE, immunoblotting and statistical analysis. Seven proteins were identified that passed a rigorous statistical screen for differential expression in 2DGE and also passed a strict statistical screen for follow-up immunoblotting. These included: α-enolase, epidermal-fatty acid binding protein, heat shock protein 27, histidine triad nucleotide-binding protein 1, lactate dehydrogenase A, protein disulfide isomerase precursor and S100A9. Four proteins had combined effects that were different than would be expected based on the response to either individual toxicant. These data demonstrate a possible reaction to the combined insult that is substantially different from that of either separate treatment. Several proteins had different responses than what has been seen from high dose exposures, adding to the growing literature suggesting that the cellular responses to low dose exposures are distinct. PMID:19294697

  5. 29 CFR 1910.1018 - Inorganic arsenic.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 6 2012-07-01 2012-07-01 false Inorganic arsenic. 1910.1018 Section 1910.1018 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS (CONTINUED) Toxic and Hazardous Substances § 1910.1018 Inorganic arsenic. (a) Scope...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  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 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...

  14. 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...

  15. 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...

  16. A market basket survey of inorganic arsenic in food.

    PubMed

    Schoof, R A; Yost, L J; Eickhoff, J; Crecelius, E A; Cragin, D W; Meacher, D M; Menzel, D B

    1999-08-01

    Dietary arsenic intake estimates based on surveys of total arsenic concentrations appear to be dominated by intake of the relatively non-toxic, organic arsenic forms found in seafood. Concentrations of inorganic arsenic in food have not been not well characterized. Accurate dietary intake estimates for inorganic arsenic are needed to support studies of arsenic's status as an essential nutrient, and to establish background levels of exposure to inorganic arsenic. In the market basket survey reported here, 40 commodities anticipated to provide at least 90% of dietary inorganic arsenic intake were identified. Four samples of each commodity were collected. Total arsenic was analysed using an NaOH digestion and inductively coupled plasma-mass spectrometry. Separate aliquots were analysed for arsenic species using an HCl digestion and hydride atomic absorption spectroscopy. Consistent with earlier studies, total arsenic concentrations (all concentrations reported as elemental arsenic per tissue wet weight) were highest in the seafoods sampled (ranging from 160 ng/g in freshwater fish to 2360 ng/g in saltwater fish). In contrast, average inorganic arsenic in seafood ranged from less than 1 ng/g to 2 ng/g. The highest inorganic arsenic values were found in raw rice (74 ng/g), followed by flour (11 ng/g), grape juice (9 ng/g) and cooked spinach (6 ng/g). Thus, grains and produce are expected to be significant contributors to dietary inorganic arsenic intake. PMID:10506007

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

    SciTech Connect

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

    1989-11-01

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

  18. Low-dose Arsenic induces chemotherapy protection via p53/NF-κB-mediated metabolic regulation

    PubMed Central

    Ganapathy, Suthakar; Xiao, Shaowen; Seo, Seog-Jin; Lall, Rajuli; Yang, Mei; Xu, Teng; Su, Hang; Shadfan, Miriam; Ha, Chul S.; Yuan, Zhi-Min

    2015-01-01

    Most chemotherapeutical drugs kill cancer cells chiefly by inducing DNA damage, which unfortunately also causes undesirable injuries to normal tissues, mainly due to p53 activation. We report a novel strategy of normal tissue-protection that involves p53/NF-κB coordinated metabolic regulation. Pretreatment of untransformed cells with low doses of arsenic induced concerted p53 suppression and NF-κB activation, which elicited a marked induction of glycolysis. Significantly, this metabolic shift provided cells effective protection against cytotoxic chemotherapy, coupling the metabolic pathway to cellular resistance. Using both in vitro and in vivo models, we demonstrated an absolute requirement of functional p53 in arsenic-mediated protection. Consistently, a brief arsenic-pretreatment selectively protected only normal tissues but not tumors from toxicity of chemotherapy. An indispensable role of glycolysis in protecting normal tissues was demonstrated by using an inhibitor of glycolysis, 2-deoxyglucose, which almost totally abolished low-dose arsenic-mediated protection. Together, our work demonstrates that low-dose arsenic renders normal cells and tissues resistance to chemotherapy-induced toxicity by inducting glycolysis. PMID:23524579

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2003-01-01

    Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development. PMID:12896845

  1. Methylation of inorganic arsenic by murine fetal tissue explants.

    PubMed

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

    2016-07-01

    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 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 h 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

  2. 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

  3. 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...

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

    PubMed Central

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

    2016-01-01

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

  5. 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,...

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

    PubMed

    Farmer, J G; Johnson, L R

    1990-05-01

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

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

    PubMed Central

    Farmer, J G; Johnson, L R

    1990-01-01

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

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  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. 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...

  14. 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...

  15. 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.

  16. 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

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

    EPA Science Inventory

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

  18. 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 ...

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

    PubMed

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

    2016-12-15

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

  20. Occurrence of inorganic arsenic in edible Shiitake (Lentinula edodes) products.

    PubMed

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

    2014-09-01

    The present study reports arsenic speciation analysis in edible Shiitake (Lentinula edodes) products. The study focused on the extraction, and accurate quantification of inorganic arsenic (iAs), the most toxic form of arsenic, which was selectively separated and determined using anion exchange LC-ICPMS. A wide variety of edible Shiitake products (fresh mushrooms, food supplements, canned and dehydrated) were purchased and analysed. A cultivated Shiitake grown under controlled conditions was also analysed. The extraction method showed satisfactory extraction efficiencies (>90%) and column recoveries (>85%) for all samples. Arsenic speciation revealed that iAs was the major As compound up to 1.38 mg As kg(-1) dm (with a mean percentage of 84% of the total arsenic) and other organoarsenicals were found as minor species. Shiitake products had high proportions of iAs and therefore should not be ignored as potential contributors to dietary iAs exposure in populations with a high intake of Shiitake products. PMID:24731333

  1. 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

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

    PubMed

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

    2012-10-01

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

  3. 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.

  4. 77 FR 72858 - Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-06

    ... AGENCY Toxicological Review of Inorganic Arsenic (Cancer and Noncancer Effects): In Support of Summary... toxicological review of inorganic arsenic (cancer and noncancer effects) in support of the IRIS program. SUMMARY... toxicological review of chronic exposure to iAs (cancer and noncancer effects), which EPA intends to post in...

  5. 75 FR 7477 - Draft Toxicological Review of Inorganic Arsenic: In Support of the Summary Information on the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-19

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

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

    PubMed Central

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

    2011-01-01

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

  7. 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. PMID:19350943

  8. 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

  9. 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.

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

    2013-01-01

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

  12. METABOLISM AND DISPOSITION OF INORGANIC ARSENIC IN LABORATORY ANIMALS AND HUMANS

    EPA Science Inventory

    The carcinogenicity of inorganic arsenic in humans, particulary in the lung and skin, has been reasonably well established through epidemiological investigations. owever, there is no substantial experimental evidence for carcinogenicity in animals to support the human studies. tu...

  13. 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...

  14. 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 ...

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

    PubMed

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

    2016-11-01

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

  16. 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. PMID:24360462

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed

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

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient. PMID:9644328

  2. 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. PMID:27416995

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

    PubMed

    Yokoi, Katsuhiko; Konomi, Aki

    2012-07-01

    The UK Food Standards Agency and its counterparts in other countries have warned consumers not to eat hijiki (Sargassum fusiforme; synonym Hizikia fusiformis), a Sargasso seaweed, because it contains large amounts of inorganic arsenic. We investigated dietary exposure of hijiki in weaning male F344/N rats fed an AIN-93G diet supplemented with 3% (w/w) hijiki powder for 7 weeks, compared with those fed only an AIN-93G diet. Body weight, body temperature, blood and tissue arsenic concentrations, plasma biochemistry and hematological parameters were measured. We found that feeding rats a 3% hijiki diet led to a marked accumulation of arsenic in blood and tissues, and evoked a high body temperature and abnormal blood biochemistry including elevated plasma alkaline phosphatase activity and inorganic phosphorus, consistent with arsenic poisoning. These findings should prompt further investigations to identify the health hazards related to consumption of hijiki and related Sargassum species in humans. PMID:22561181

  4. INTEGRATED QUANTITATIVE CANCER RISK ASSESSMENT OF INORGANIC ARSENIC

    EPA Science Inventory

    This paper attempts to make an integrated risk assessment of arsenic, using data on humans exposed to arsenic via inhalation and ingestion. he data useful for making an integrated analysis and data gaps are discussed. rsenic provides a rare opportunity to compare the cancer risk ...

  5. 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

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

    PubMed

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

    2015-03-01

    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. PMID:25649028

  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. 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

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

    PubMed Central

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

    1977-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-06-01

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

  12. 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...

  13. 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...

  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. 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...

  16. 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....

  17. 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...

  18. 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...

  19. 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

  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. Accumulation, transformation, and release of inorganic arsenic by the freshwater cyanobacterium Microcystis aeruginosa.

    PubMed

    Wang, Zhenhong; Luo, Zhuanxi; Yan, Changzhou

    2013-10-01

    Arsenic (As) as a major hazardous metalloid was affected by phytoplankton in many aquatic environments. The toxic dominant algae Microcystis aeruginosa was exposed to different concentrations of inorganic arsenic (arsenate or arsenite) for 15 days in BG11 culture media. Arsenic accumulation, toxicity, and speciation in M. aeruginos as well as the changes of As species in media were examined. M. aeruginosa has a general well tolerance to arsenate and a definite sensitivity to arsenite. Additionally, arsenate actively elevated As methylation by the algae but arsenite definitely inhibited it. Interestingly, the uptake of arsenite was more pronounced than that of arsenate, and it was correlated to the toxicity. Arsenate was the predominant species in both cells and their growth media after 15 days of exposure to arsenate or arsenite. However, the amount of the methylated As species in cells was limited and insignificantly affected by the external As concentrations. Upon uptake of the inorganic arsenic, significant quantities of arsenate as well as small amounts of arsenite, DMA, and MMA were produced by the algae and, in turn, released back into the growth media. Bio-oxidation was the first and primary process and methylation was the minor process for arsenite exposures, while bioreduction and the subsequent methylation were the primary metabolisms for arsenate exposures. Arsenic bioaccumulation and transformation by M. aeruginosa in aquatic environment should be paid more attention during a period of eutrophication. PMID:23636594

  2. 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

  3. 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.

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2014-10-01

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

  6. VALIDATION OF AN EMISSION MEASUREMENT METHOD FOR INORGANIC ARSENIC FROM STATIONARY SOURCES: PROPOSED METHOD 108. LABORATORY AND FIELD TEST EVALUATION

    EPA Science Inventory

    The United States Environmental Protection Agency (USEPA) has listed inorganic arsenic emissions as a hazardous air pollutant. USEPA proposed Method 108 for the measurement of these emissions from stationary sources has been subjected to validation studies in this work. Laborator...

  7. 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)...

  8. 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...

  9. Concentrations of total and inorganic arsenic in fresh fish, mollusks, and crustaceans from the Gulf of Thailand.

    PubMed

    Ruangwises, Suthep; Ruangwises, Nongluck

    2011-03-01

    Concentrations of total and inorganic arsenic were determined in 120 samples of eight marine animals collected from the Gulf of Thailand between March and May 2008. Two species with the highest annual catch from each of four marine animal groups were analyzed: fish (Indo-Pacific mackerel and goldstripe sardine), bivalves (green mussel and blood cockle), cephalopods (pharaoh cuttlefish and Indian squid), and crustaceans (banana prawn and swimming crab). Concentrations of inorganic arsenic based on wet weight ranged from 0.012 μg/g in Indian squids to 0.603 μg/g in blood cockles. Average percentages of inorganic arsenic with respect to total arsenic ranged from 1.2% in banana prawns to 7.3% in blood cockles. Blood cockles also exhibited the highest levels of total arsenic (5.26 ± 2.01 μg/g) and inorganic arsenic (0.352 ± 0.148 μg/g). The levels of inorganic arsenic in the study samples were much lower than the Thai regulatory limit of 2 μg/g (wet wt) and hence are safe for human consumption. PMID:21375883

  10. 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). PMID:26992513

  11. 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.

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed

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

    2002-05-15

    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 microg-As/L for arsenite and 1080 microg-As/L for arsenate, and acid mine drainage samples reached 13 000 microg-As/L for arsenite and 3700 microg-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. PMID:12038832

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. Response of pepper plants (Capsicum annum L.) on soil amendment by inorganic and organic compounds of arsenic.

    PubMed

    Száková, Jirina; Tlustos, Pavel; Goessler, Walter; Pavlíková, Daniela; Schmeisser, Ernst

    2007-01-01

    The influence of soil contamination by inorganic and organic arsenic compounds on uptake, accumulation, and transformation of arsenic in pepper (Capsicum annum L.) was investigated in greenhouse pot experiments under controlled conditions. Pepper plants were cultivated in substrate amended by aqueous solutions of arsenite, arsenate, methylarsonic acid (MA), and dimethylarsinic acid (DMA) applied individually into cultivation substrate at concentrations of 15 mg As per kg of substrate. The plant availability of the arsenicals increased in the order arsenite = arsenate < MA < DMA. The highest arsenic concentrations were found in roots followed by stems, leaves, and fruits regardless of arsenic compound applied. In the control samples of pepper fruits, As(III), As(V), and DMA were present (25%, 37%, and 39% of the water-extractable arsenic). In control stems + leaves and roots, As(V) was the major compound (63% and 53% in a phosphate buffer extract) followed by As(III) representing 33% and 42%. Additionally, low concentrations (not exceeding 5%) of DMA and MA were detected as well. In all the soils analyzed after the first harvest of pepper fruits, arsenate was the dominating compound followed by arsenite. Methylarsonic acid, methylarsonous acid, and DMA were present at varying concentrations depending on the individual soil treatments. In the treated plants, the arsenic compounds in plant tissues reflected predominantly the extractable portions of arsenic compounds present in soil after amendment, and this pattern was more significant in the first part of vegetation period. The results confirmed the ability of generative parts of plants to accumulate preferably organic arsenic compounds, whereas in the roots and aboveground biomass, mainly inorganic arsenic species are present. Evidently, the source of soil arsenic contamination affects significantly the extractable portions of arsenic compounds in soil and subsequently the distribution of arsenic compounds within

  17. Quantitative Mass Spectrometry Reveals Changes in Histone H2B Variants as Cells Undergo Inorganic Arsenic-Mediated Cellular Transformation.

    PubMed

    Rea, Matthew; Jiang, Tingting; Eleazer, Rebekah; Eckstein, Meredith; Marshall, Alan G; Fondufe-Mittendorf, Yvonne N

    2016-07-01

    Exposure to inorganic arsenic, a ubiquitous environmental toxic metalloid, leads to carcinogenesis. However, the mechanism is unknown. Several studies have shown that inorganic arsenic exposure alters specific gene expression patterns, possibly through alterations in chromatin structure. While most studies on understanding the mechanism of chromatin-mediated gene regulation have focused on histone post-translational modifications, the role of histone variants remains largely unknown. Incorporation of histone variants alters the functional properties of chromatin. To understand the global dynamics of chromatin structure and function in arsenic-mediated carcinogenesis, analysis of the histone variants incorporated into the nucleosome and their covalent modifications is required. Here we report the first global mass spectrometric analysis of histone H2B variants as cells undergo arsenic-mediated epithelial to mesenchymal transition. We used electron capture dissociation-based top-down tandem mass spectrometry analysis validated with quantitative reverse transcription real-time polymerase chain reaction to identify changes in the expression levels of H2B variants in inorganic arsenic-mediated epithelial-mesenchymal transition. We identified changes in the expression levels of specific histone H2B variants in two cell types, which are dependent on dose and length of exposure of inorganic arsenic. In particular, we found increases in H2B variants H2B1H/1K/1C/1J/1O and H2B2E/2F, and significant decreases in H2B1N/1D/1B as cells undergo inorganic arsenic-mediated epithelial-mesenchymal transition. The analysis of these histone variants provides a first step toward an understanding of the functional significance of the diversity of histone structures, especially in inorganic arsenic-mediated gene expression and carcinogenesis. PMID:27169413

  18. 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. PMID:26506262

  19. 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

  20. 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

  1. 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. PMID:24360440

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2016-05-01

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

  4. 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

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

    PubMed

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

    2010-10-01

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

  6. 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.

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

    PubMed

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

    2016-03-01

    Dietary uptake could be the primary route of arsenic (As) bioaccumulation in marine fish, but the bioavailability of inorganic and organic As remains elusive. In this study, we investigated the trophic transfer and bioavailability of As in herbivorous rabbitfish Siganus fuscescens and carnivorous seabass Lateolabrax japonicus. Rabbitfish were fed with one artificial diet or three macroalgae, whereas seabass were fed with one artificial diet, one polychaete, or two bivalves for 28 days. The six spiked fresh prey diets contained different proportions of inorganic As [As(III) and As(V)] and organic As compounds [methylarsenate (MMA), dimethylarsenate (DMA), and arsenobetaine (AsB)], and the spiked artificial diet mainly contained As(III) or As(V). We demonstrated that the trophic transfer factors (TTF) of As in both fish were negatively correlated with the concentrations of inorganic As in the diets, while there was no relationship between TTF and the AsB concentrations in the diets. Positive correlation was observed between the accumulated As concentrations and the AsB concentrations in both fish, suggesting that organic As compounds (AsB) were more trophically available than inorganic As. Furthermore, the biotransformation ability of seabass was higher than that in rabbitfish, which resulted in higher As accumulation in seabass than in rabbitfish. Our study demonstrated that different prey with different inorganic/organic As proportions resulted in diverse bioaccumulation of total As in different marine fish. PMID:26835720

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

    PubMed

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

    2016-09-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-05-18

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

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

    SciTech Connect

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

    2015-07-01

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

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

    PubMed Central

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

    2012-01-01

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

  13. Nephroprotective effect of astaxanthin against trivalent inorganic arsenic-induced renal injury in wistar rats

    PubMed Central

    Wang, Xiaona; Zhao, Haiyuan; Shao, Yilan; Wang, Pei; Wei, Yanru; Zhang, Weiqian; Jiang, Jing; Chen, Yan

    2014-01-01

    Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy. PMID:24611105

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

    PubMed

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

    2016-08-01

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

  15. 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. PMID:26106064

  16. 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...

  17. 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...

  18. 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...

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

    PubMed

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

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Sigrist, Mirna E.; Beldoménico, Horacio R.

    2004-07-01

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

  1. Arsenic

    MedlinePlus

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

  2. 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 ...

  3. 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. PMID:24313911

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

    PubMed

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

    2014-10-15

    Arsenic (As) can exist in the environment in several different forms, each having unique chemical characteristics that influence its toxicity and potential for human and ecological exposure. Within the last decade or so, the focus on speciated As (both the inorganic and organic forms) and its potential toxicity has led to an increased availability of data on speciated As in different food types. To gain an understanding of these developments and the current science, we evaluated the state of knowledge regarding As speciation in food and calculated the average levels of several species of As measured in food. Because inorganic arsenic (inAs) is considered the most toxicologically important form of As, we focused our analysis on papers presenting information on total inAs and speciated inAs (inAs(3+) or inAs(5+)). We also evaluated speciated As forms (e.g., monomethylarsonic and dimethylarsinic acid) when presented with inAs information. Publications were drawn from the peer-reviewed literature and reports by authoritative health agencies. While a great deal of speciation data were identified, including over 6500 unique inAs data points, unclear study methodology and inconsistencies between studies introduced uncertainty into the analysis of these data. Despite these limitations, our analysis demonstrates that inAs in foods can vary widely by type and even by sample, with mean inAs concentrations ranging from undetectable (in milk) to 11,000 μg/kg (in seaweed/algae). We found a high percentage of non-measurable As in many food types, suggesting that the limits of detection of speciated As must be considered to accurately estimate dietary As exposure. The applicability of our analysis is limited by the inconsistencies and uncertainties in the available data; calculations of inAs dietary intake should be tailored to the study population of interest and should consider study quality. PMID:25089691

  5. 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. PMID:23994116

  6. 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...

  7. 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

  8. 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

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

    PubMed Central

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

    2009-01-01

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

  10. 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.

  11. Simple and fast colorimetric detection of inorganic arsenic selectively adsorbed onto ferrihydrite-coated silica gel using silver nanoplates.

    PubMed

    Siangproh, Weena; Chailapakul, Orawan; Songsrirote, Kriangsak

    2016-06-01

    The optical detection for inorganic arsenic (As) semi-quantitative determination is presented by using silver nanoplates (AgNPls). The color of AgNPs is immediately changed in the presence of As(III) and As(V) with the same sensitivity. To improve the selectivity of AgNPls for As detection, ferrihydrite-coated silica gel (SiO2-Fh) was specifically exploited as adsorbent for arsenic prior to As detection by AgNPls. The developed method provides the detection limit of 0.5ppm with the detection range between 0.5ppm and 30.0ppm for As determination observed with naked eye, and allows to determine total inorganic arsenic. This is the first report of As detection approach combining As removal technology together with nanotechnology. This combined technique provides a rapid, sensitive and selective method for monitoring As levels in aqueous samples, and can be employed as a testing field kit to screen arsenic contamination outside of a laboratory. PMID:27130109

  12. [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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Huang, Jen-How; Matzner, Egbert

    2007-09-01

    To identify the role of the forest floor in arsenic (As) biogeochemistry, concentrations and fluxes of inorganic and organic As in throughfall, litterfall and forest floor percolates at different layers were investigated. Nearly 40% of total As(total) input (5.3g Asha(-1)yr(-1)) was retained in Oi layer, whereas As(total) fluxes from Oe and Oa layers exceeded the input by far (10.8 and 20g Asha(-1)yr(-1), respectively). Except dimethylarsinic acid (DMA), fluxes of organic As decreased with depth of forest floor so that <10% of total deposition (all <0.3g Asha(-1)yr(-1)) reached the mineral soil. All forest floor layers are sinks for most organic As. Conversely, Oe and Oa layers are sources of As(total), arsenite, arsenate and DMA. Significant correlations (r>/=0.43) between fluxes of As(total), arsenite, arsenate or DMA and water indicate hydrological conditions and adsorption-desorption as factors influencing their release from the forest floor. The higher net release of arsenite from Oe and Oa and of DMA from Oa layer in the growing than dormant season also suggests microbial influences on the release of arsenite and DMA. PMID:17624646

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

    PubMed

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

    2016-07-01

    Chronic exposure to inorganic arsenic (iAs) in the human population is associated with various internal cancers and other adverse outcomes. The purpose of this study was to estimate a population-scale exposure risk attributable to iAs consumptions by linking a stochastic physiological-based pharmacokinetic (PBPK) model and biomonitoring data of iAs in urine. The urinary As concentrations were obtained from a total of 1,043 subjects living in an industrial area of Taiwan. The results showed that the study subjects had an iAs exposure risk of 27 % (the daily iAs intake for 27 % study subjects exceeded the WHO-recommended value, 2.1 μg iAs day(-1) kg(-1) body weight). Moreover, drinking water and cooked rice contributed to the iAs exposure risk by 10 and 41 %, respectively. The predicted risks in the current study were 4.82, 27.21, 34.69, and 64.17 %, respectively, among the mid-range of Mexico, Taiwan (this study), Korea, and Bangladesh reported in the literature. In conclusion, we developed a population-scale-based risk model that covered the broad range of iAS exposure by integrating stochastic PBPK modeling and reverse dosimetry to generate probabilistic distribution of As intake corresponding to urinary As measured from the cohort study. The model can also be updated as new urinary As information becomes available. PMID:27048329

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

    PubMed

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

    2015-12-23

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

  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. 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

  1. 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

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

    PubMed

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

    2013-11-15

    Egg-shell membrane (ESM) is a promising adsorbent for heavy metal uptake. However, carboxylic groups on ESM surface barrier arsenic adsorption. Herein, ESM is modified by esterification and the methyl esterified egg-shell membrane (MESM) possesses positive charge within pH 1-9. As a novel green sorbent material, MESM exhibits 200-fold improvement on sorption capacity of arsenate with respect to bare ESM. It presents an ultra-high selectivity of 256:1 toward arsenate against arsenite. At pH 6, 100% sorption efficiency is achieved for 2 μg L(-1) As(V) by 10 mg MESM, while virtually no adsorption of As(III) is observed. This provides great potential for selective sorption of arsenate in the presence of arsenite. By loading 4.0 mL sample within 0.05-5.00 μg L(-1) As(V) followed by elution with 300 μL HCl (1.5 mol L(-1)), a detection limit of 15 ng L(-1) is obtained along with a RSD of 3.5% at 0.5 μg L(-1). Total inorganic arsenic is achieved by converting As(III) to As(V) and following the same sorption process. This procedure is applied for arsenate determination and inorganic arsenic speciation in Hijiki and water samples. The results are confirmed by graphite furnace atomic absorption spectrometry and spiking recovery. PMID:24148462

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

    PubMed

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

    2016-09-01

    Arsenic exposure has been implicated as a risk factor for cardiovascular diseases, metabolic disorders, and cancer, yet the role mitochondrial dysfunction plays in the cellular mechanisms of pathology is largely unknown. To investigate arsenic-induced mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), we exposed rat aortic smooth muscle cells (A7r5) to inorganic arsenic (iAs(III)) and its metabolite monomethylarsonous acid (MMA(III)) and compared their effects on mitochondrial function and oxidative stress. Our results indicate that MMA(III) is significantly more toxic to mitochondria than iAs(III). Exposure of VSMCs to MMA(III), but not iAs(III), significantly decreased basal and maximal oxygen consumption rates and concomitantly increased compensatory extracellular acidification rates, a proxy for glycolysis. Treatment with MMA(III) significantly increased hydrogen peroxide and superoxide levels compared to iAs(III). Exposure to MMA(III) resulted in significant decreases in mitochondrial ATP, aberrant perinuclear clustering of mitochondria, and decreased mitochondrial content. Mechanistically, we observed that mitochondrial superoxide and hydrogen peroxide contribute to mitochondrial toxicity, as treatment of cells with MnTBAP (a mitochondrial superoxide dismutase mimetic) and catalase significantly reduced mitochondrial respiration deficits and cell death induced by both arsenic compounds. Overall, our data demonstrates that MMA(III) is a mitochondria-specific toxicant that elevates mitochondrial and non-mitochondrial sources of ROS. PMID:27327130

  4. 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...

  5. 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

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

    PubMed

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

    2015-01-01

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

  7. 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.

  8. 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...

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

    PubMed

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

    2008-10-01

    The purpose of this paper was to use derivative anodic stripping chronopotentiometry (dASCP) as a sensitive and accurate technique, to determine the concentrations of dissolved As (III) and As (V) in coastal seawater samples from the Straits of Messina, the Ionian and the Tyrrhenian seas, and to investigate the relationship between the anthropogenic activities on the coastal areas and the concentration of dissolved inorganic arsenic in seawaters. The obtained data indicated that As (V) was the most abundant species, with concentration ranging from 26.7 to 307 nM, whereas As (III) levels were lower than 48 nM in all the samples. In particular, As (III) and As (V) levels significantly decreased from high to low anthropogenic activities zones (p < 0.00001, ANOVA), with the reference samples, from a wildlife reserve, showing the lowest values. Furthermore it was observed that human activities influenced inorganic arsenic speciation, since the zones that received high human input presented the highest As(V)/As (III) ratio. PMID:18058034

  10. Arsenic

    MedlinePlus

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

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

    PubMed

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

    2016-09-01

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

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

    EPA Science Inventory

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

  13. 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. PMID:25347547

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

    PubMed

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

    2008-09-01

    In order to characterize the different sources of exposure to arsenic (As), urinary excretion of total As, the sum of inorganic As+MMA+DMA determined by the hydride generation-atomic absorption spectrophotometry technique, and the species As3, As5, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine were determined in 49 workers at a steel foundry, with presumed occupational exposure to As, and 50 subjects from the general population, all males. No evidence of occupational exposure to As resulted from environmental monitoring performed in the foundry, although the analysis of minerals used as raw materials showed the presence of As, particularly in fossils and fine ores. The urinary concentrations of As3, MMA, DMA, the sum of inorganic As+MMA+DMA and total As were not different in the two groups, while arsenobetaine appeared significantly higher in the controls than in the workers. The different species of urinary As were all significantly correlated. Urinary excretion of As3 was associated with the consumption of mineral water and with residence in an industrial zone, while MMA, DMA, arsenobetaine, the sum of inorganic As+MMA+DMA and total As urinary excretion were associated with the consumption of crustaceans and/or shellfish 3 days or less before urine collection. Multiple regression analysis confirmed these results. In conclusion, in populations with a high consumption of seafood, living in areas characterized by coastal/marine As pollution, only speciation of As can identify a prevalent role of environmental sources, like the consumption of seafood contaminated by As, in determining urinary As excretion, and exclude an occupational origin of the exposure. PMID:18657289

  16. 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

  17. 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.

  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. PMID:8043317

  19. SPECIAL REPORT ON INGESTED INORGANIC ARSENIC: SKIN CANCER; NUTRITIONAL ESSENTIALITY (SAB REVIEW DRAFT)

    EPA Science Inventory

    A technical panel of EPA's Risk Assessment Forum has studied three special issues regarding certain health effects, particularly skin cancer, associated with arsenic ingestion: (1) the validity of the Taiwan study and its use for dose-response assessment in the U.S. population, (...

  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. TIME DEPENDENCE OF ACCUMULATION AND BINDING OF INORGANIC AND ORGANIC ARSENIC SPECIES IN RABBIT ERYTHROCYTES

    EPA Science Inventory

    The uptake by rabbit erythrocytes of 0.4 mM arsenite, As(III), arsenate, As(V), monomethylarsinate, MMA(V) and dimethylarsonate, DNM(V) were compared over 24 hours. n membrane-free hemolysate, the protein-to-cytosol ratio was determined by ultrafiltration and arsenic species were...

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

    PubMed

    Xu, Xiaofan; Drobná, Zuzana; Voruganti, V Saroja; Barron, Keri; González-Horta, Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Cerón, Roberto Hernández; Morales, Damián Viniegra; Terrazas, Francisco A Baeza; Ishida, María C; Gutiérrez-Torres, Daniela S; Saunders, R Jesse; Crandell, Jamie; Fry, Rebecca C; Loomis, Dana; García-Vargas, Gonzalo G; Del Razo, Luz M; Stýblo, Miroslav; Mendez, Michelle A

    2016-09-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Ezeh, Vivian C; Harrop, Todd C

    2013-03-01

    The EPA has established a maximum contaminant level (MCL) of 10 ppb for arsenic (As) in drinking water requiring sensitive and selective detection methodologies. To tackle this challenge, we have been active in constructing small molecules that react specifically with As(3+) to furnish a new fluorescent species (termed a chemodosimeter). We report in this contribution, the synthesis and spectroscopy of two small-molecule fluorescent probes that we term ArsenoFluors (or AFs) as As-specific chemodosimeters. The AFs (AF1 and AF2) incorporate a coumarin fluorescent reporter coupled with an As-reactive benzothiazoline functional group. AFs react with As(3+) to yield the highly fluorescent coumarin-6 dye (C6) resulting in a 20-25-fold fluorescence enhancement at λem ∼ 500 nm with detection limits of 0.14-0.23 ppb in tetrahydrofuran (THF) at 298 K. The AFs also react with common environmental As(3+) sources such as sodium arsenite in a THF/CHES (N-cyclohexyl-2-aminoethanesulfonic acid) (1:1, pH 9, 298 K) mixture resulting in a modest fluorescence turn-ON (1.5- to 3-fold) due to the quenched nature of coumarin-6 derivatives in high polarity solvents. Bulk analysis of the reaction of the AFs with As(3+) revealed that the C6 derivatives and the Schiff-base disulfide of the AFs (SB1 and SB2) are the ultimate end-products of this chemistry with the formation of C6 being the principle photoproduct responsible for the As(3+)-specific turn-ON. It appears that a likely species that is traversed in the reaction path is an As-hydride-ligand complex that is a putative intermediate in the proposed reaction path. PMID:23421428

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

    PubMed

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

    2016-04-15

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

  6. COMMONALITIES IN METABOLISM OF ARSENICALS

    EPA Science Inventory

    Elucidating the pathway of inorganic arsenic metabolism shows that some of methylated arsenicals formed as intermediates and products are reactive and toxic species. Hence, methylated arsenicals likely mediate at least some of the toxic and carcinogenic effects associated with e...

  7. A dose-response analysis of skin cancer from inorganic arsenic in drinking water

    SciTech Connect

    Brown, K.G.; Boyle, K.E.; Chen, C.W.; Gibb, H.J. )

    1989-12-01

    A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3)) if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).

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

    EPA Science Inventory

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

  9. 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

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

    PubMed

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

    2016-05-01

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

  11. 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,...

  12. [A quantitative assessment of health risk induced by occupational exposure to inorganic arsenic].

    PubMed

    Szymczak, W

    1997-01-01

    The risk of neoplastic disease, primarily lung cancer, induced by occupational, inhalation exposure to nonorganic arsenic was assessed. In order to identify individual risk in the linear dose-response relationship which would serve as a basis for the risk assessment among persons exposed occupationally, the author also analysed the latest epidemiological studies performed in Sweden, as well as repeated analyses of American studies. This allowed to diminish individual risk by several times. It is thought that a diminished value of individual risk is, in the light of the most up-to-date epidemiological studies, closer to the reality than the value proposed by the Environmental Protection Agency (EPA). Having the value of individual risk related to occupational exposure, equal 1.79 x 10(-4), lung cancer risk after forty years of employment under the exposure level within the range of currently binding MAC values for arsenic (0.05 mg/m3) accounts for 8.95 x 10(-3), thus slightly exceeding the adopted value of 1 x 10(3). Whereas a new value, proposed by the Expert Group for Chemical Factors of the International Commission for Updating the list of MAC and MAI values in 1996, equals 0.01, so the risk for a forty-year employment accounts for 1.79 x 10(-3), in fact the value corresponding to that already approved. In addition, the assessment indicated that smoking increases by 4-6 times the risk of lung cancer induced by exposure to arsenic. PMID:9558633

  13. Contribution of water, bread, and vegetables (raw and cooked) to dietary intake of inorganic arsenic in a rural village of Northern Chile.

    PubMed

    Díaz, Oscar Pablo; Leyton, Irma; Muñoz, Ociel; Núñez, Nelson; Devesa, Vicenta; Súñer, Maria Angeles; Vélez, Dinoraz; Montoro, Rosa

    2004-03-24

    Total and inorganic As contents of cooked vegetables obtained from an arsenic endemic area of Chile were analyzed. Inorganic As intake from those foods, bread, and water was estimated. The study was performed in two different periods, in which the water used by the population for drinking and cooking purposes contained 0.572 (first period) or 0.041 microg mL(-)(1) (second period). In the first period, the FAO/WHO reference intake was exceeded by all of the persons interviewed. In the second period, the reference intake was exceeded by all of the persons interviewed ages 13-15. The foods studied contributed 4% (first period) or 25% (second period) of the inorganic As intake. The results show the contribution of food to inorganic As intake and the risk to which those ages 15 or younger are exposed. PMID:15030245

  14. Biosorption of inorganic and organic arsenic from aqueous solution by Acidithiobacillus ferrooxidans BY-3.

    PubMed

    Yan, Lei; Yin, Huanhuan; Zhang, Shuang; Leng, Feifan; Nan, Wenbin; Li, Hongyu

    2010-06-15

    The traditional techniques for removing low concentration arsenic are unsuitable. The biosorption characteristics of arsenite (iAs(III)) and monomethyl arsonate (MMA(V)) from aqueous solution by Acidithiobacillus ferrooxidans BY-3 (At. f BY-3) were investigated as a function of pH, contact time, initial arsenic concentration, biomass dosage and temperature in this study. Results indicated that Langmuir isotherm model fitted better than Freundlich model to the equilibrium data. Analysis of kinetic data showed that the biosorption processes of both iAs(III) and MMA(V) involved pseudo-second-order kinetics. The thermodynamic parameters such as DeltaG(o), DeltaH(o) and DeltaS(o) of the biosorption process showed that the adsorption of iAs(III) and MMA(V) onto At. f BY-3 was feasible, spontaneous and endothermic under the examined conditions. The competitive biosorption of iAs(III) and MMA(V) in binary mixture system was evaluated, and the results indicated that At. f BY-3 favored MMA(V) biosorption. Fourier-transform infrared spectroscopy (FT-IR) showed -OH and -NH groups were involved in the biosorption process. PMID:20122794

  15. 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.

  16. 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. PMID:20695441

  17. 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 ...

  18. Development of an ion chromatography-inductively coupled plasma-mass spectrometry method to determine inorganic arsenic in liver from chickens treated with roxarsone.

    PubMed

    Conklin, Sean D; Shockey, Nohora; Kubachka, Kevin; Howard, Karyn D; Carson, Mary C

    2012-09-19

    Roxarsone, (4-hydroxy-3-nitrophenyl)arsonic acid, is an arsenic-containing compound that has been approved as a feed additive for poultry and swine since the 1940s; however, little information is available regarding residual arsenic species present in edible tissues. We developed a novel method for the extraction and quantification of arsenic species in chicken liver. A strongly basic solution solubilized the liver, and ultrafiltration removed macromolecules and particulate material. Ion chromatography separated the species [arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid, (4-hydroxy-3-aminophenyl)arsonic acid, (4-hydroxy-3-acetaminophenyl)arsonic acid, and roxarsone] in the extracts, which were then detected by inductively coupled plasma-mass spectrometry. The extraction oxidized most arsenite to arsenate. For fortification concentrations at 2 μg kg(-1) and above, recoveries ranged from 70 to 120%, with relative standard deviations from 7 to 34%. We detected roxarsone, its 3-amino and 3-acetamido metabolites, inorganic arsenic, and additional unknown arsenic species in livers from roxarsone-treated chickens. Both the originating laboratory and a second laboratory validated the method. PMID:22897610

  19. DNA-strand breaks induced by dimethylarsinic acid, a metabolite of inorganic arsenics, are strongly enhanced by superoxide anion radicals.

    PubMed

    Rin, K; Kawaguchi, K; Yamanaka, K; Tezuka, M; Oku, N; Okada, S

    1995-01-01

    We previously reported that dimethylarsinic acid (DMAA), a major metabolite of inorganic arsenics, induced DNA single-strand breaks (ssb) both in vivo and in cultured alveolar type II (L-132) cells in vitro, possibly via the production of dimethylarsenic peroxyl radicals. Here, the interaction of superoxide anion radicals (O2-) in the induction of ssb in L-132 cells was investigated using paraquat, an O2(-)-producing agent. A significant enhancement of ssb formation was observed in the DMAA-exposed cells when coexposed to paraquat. This enhancement occurred even when post-exposed to DMAA after washing, suggesting that the DMAA exposure caused some modification of DNA such as DNA-adducts, which was recognized by active oxygens to form ssb. An experiment with UV-irradiation, which was likely to induce ssb at the modified region, supported the possibility of DNA modification by DMAA exposure. An ESR study indicated that O2- produced by paraquat in DMAA-exposed cells was more consumed than in non-exposed cells, assumingly through the reaction with the dimethylarsenic-modified region of DNA. The species of active oxygens were estimated by using diethyldithiocarbamate, aminotriazole, diethylmaleate, hydrogen peroxide (H2O2), gamma-irradiation and ethanol. O2- but neither H2O2 nor hydroxyl radicals was very likely to contribute to the ssb-enhancing action of paraquat. PMID:7735248

  20. 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.

  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%. PMID:27451169

  2. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

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

  3. 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. 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. PMID:26681408

  5. 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. PMID:26990091

  6. 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

  7. 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

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

    EPA Science Inventory


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

  9. Arsenic in Food

    MedlinePlus

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

  10. 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.

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

    PubMed

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

    2016-10-15

    In this study, we report on model simulations performed using the newly developed exposure tool, MERLIN-Expo, in order to assess inorganic arsenic (iAs) exposure to adults resulting from past emissions by non-ferrous smelters in Belgium (Northern Campine area). Exposure scenarios were constructed to estimate external iAs exposure as well as the toxicologically relevant As (tAs, i.e., iAs, MMA and DMA) body burden in adults living in the vicinity of the former industrial sites as compared to adults living in adjacent areas and a reference area. Two scenarios are discussed: a first scenario studying exposure to iAs at the aggregated population level and a second scenario studying exposure at the individual level for a random sub-sample of subjects in each of the three different study areas. These two scenarios only differ in the type of human related input data (i.e., time-activity data, ingestion rates and consumption patterns) that were used, namely averages (incl. probability density functions, PDFs) in the simulation at population level and subject-specific values in the simulation at individual level. The model predictions are shown to be lower than the corresponding biomonitoring data from the monitoring campaign. Urinary tAs levels in adults, irrespective of the area they lived in, were under-predicted by MERLIN-Expo by 40% on average. The model predictions for individual adults, by contrast, under-predict the biomonitoring data by 7% on average, but with more important under-predictions for subjects at the upper end of exposure. Still, average predicted urinary tAs levels from the simulations at population level and at individual level overlap, and, at least for the current case, lead to similar conclusions. These results constitute a first and partial verification of the model performance of MERLIN-Expo when dealing with iAs in a complex site-specific exposure scenario, and demonstrate the robustness of the modelling tool for these situations. PMID:27113276

  12. 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). PMID:24209302

  13. *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...

  14. Low Dose Effects in Psychopharmacology: Ontogenetic Considerations

    PubMed Central

    Spear, Linda Patia; Varlinskaya, Elena I.

    2005-01-01

    Low doses of psychoactive drugs often elicit a behavioral profile opposite to that observed following administration of more substantial doses. Our laboratory has observed that these effects are often age-specific in rats. For instance, whereas moderate to high doses of the dopamine agonist apomorphine increase locomotion, suppressed locomotor activity is seen following low dose exposure, with this low dose effect not emerging consistently until adolescence. A somewhat earlier emergence of a low dose “paradoxical” effect is seen with the 5HT1a receptor agonist, 8-OH-DPAT, with late preweanling, but not neonatal, rats showing increases in ingestive behavior at low doses but suppression at higher doses. In contrast to these ontogenetic increases in expression of low dose drug effects, low dose facilitation of social behavior is seen following ethanol only in adolescent rats and not their mature counterparts, although suppression of social interactions at higher doses is seen at both ages. This hormesis-like low dose stimulation appears related in part to overcompensation, with brief social suppression preceding the subsequent stimulation response, and also bears a number of ontogenetic similarities to acute tolerance, a well characterized, rapidly emerging adaptation to ethanol. Implications of these and other ontogenetic findings for studies of hormesis are discussed. PMID:19330157

  15. 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.

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

    PubMed

    Sengupta, Mrinal K; Dasgupta, Purnendu K

    2011-12-15

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

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

    PubMed

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

    2016-01-01

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

  19. 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

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

    PubMed Central

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

    2012-01-01

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

  1. Low dose mercury toxicity and human health.

    PubMed

    Zahir, Farhana; Rizwi, Shamim J; Haq, Soghra K; Khan, Rizwan H

    2005-09-01

    Post Minamata incident there has been awareness about mercury toxicity even among the general public. Previous researches contributed a vast amount of data regarding acute mercury exposure, but gradually information about the low dose [Ninomiya, T., Ohmori, H., Hashimoto, K., Tsuruta, K., Ekino, S., 1995. Expansion of methylmercury poisoning outside minamata: an epidemiological study on chronic methylmercury poisoninig outside of Minamata. Environ. Res. 70 (1) 47-50; Lebel, J., Mergler, D., Lucotte, M., Amorim, M., Dolbec, J., Miranda, D., Arantes, G., Rheault, I., Pichet, P., 1996. Evidence of early nervous system dysfunction in Amazonian populations exposed to low-levels of methylmercury. Neurotoxicology 17 (1) 157-167] of mercury toxicity has been trickling in. With mercury contaminating rain-, ground- and sea-water no one is safe. Polluted water leads to mercury laced fish, meat and vegetable. In aquatic environments, inorganic mercury is microbiologically transformed into lipophilic organic compound 'methylmercury'. This transformation makes mercury more prone to biomagnification in food chains. Consequently, populations with traditionally high dietary intake of food originating from fresh or marine environment have highest dietary exposure to mercury. Extensive research done on locals across the globe have already established this, persons who routinely consume fish or a particular species of fish are at an increased risk of methylmercury poisoning. The easy access of the toxicant to man through multiple pathways air, water, food, cosmetic products and even vaccines increase the exposure. Foetus and children are more susceptible towards mercury toxicity. Mothers consuming diet containing mercury pass the toxicant to foetus and to infants through breast milk. Decreased performance in areas of motor function and memory has been reported among children exposed to presumably safe mercury levels. Similarly, disruption of attention, fine motor function and verbal

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

    PubMed

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

    2013-09-01

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

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

    PubMed

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

    2010-01-01

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

  4. Ferric ion induced enhancement of ultraviolet vapour generation coupled with atomic fluorescence spectrometry for the determination of ultratrace inorganic arsenic in surface water.

    PubMed

    Wang, Yuelong; Lin, Lingling; Liu, Jixin; Mao, Xuefei; Wang, Jianhua; Qin, Deyuan

    2016-02-21

    A novel method of ultraviolet vapour generation (UVG) coupled with atomic fluorescence spectrometry (AFS) was developed for the determination of ultratrace inorganic arsenic (iAs) in surface water. In this work, different ferric species were utilised for the first time as an enhancement reagent for the ultraviolet vapour generation of As(III), and their UVG efficiencies for volatile species of arsenic were investigated. 15 mg L(-1) of ferric chloride provided the greatest enhancement of approximately 10-fold, using 20% acetic acid combined with 4% formic acid with 30 s ultraviolet irradiation at 200 mL min(-1) Ar/H2 flow rate. Under the optimised conditions, the linear range was 1.0 μg L(-1)-100.0 μg L(-1), and the spiked recoveries were 92%-98%. The limit of detection was 0.05 μg L(-1) for iAs, and the relative standard deviation (RSD) value of the repeated measurements was 2.0% (n = 11). This method was successfully applied to the determination of ultratrace iAs in tap water, river water, and lake water samples using 0.2% H2SO4 (v : v) as the sample preserver. The obtained values for the water samples of certified reference materials (CRMs) including GSB-Z50004-200431, GBW08605 and GBW(E)080390 were all within the certified ranges. PMID:26765360

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

    PubMed

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

    2008-04-01

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

  6. 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.

  7. Toxicological Characterization of the Inorganic and Organic Arsenic Metabolite Thio-DMAV in Cultured Human Lung Cells

    PubMed Central

    Bartel, Marc; Ebert, Franziska; Leffers, Larissa; Karst, Uwe; Schwerdtle, Tanja

    2011-01-01

    We synthesised and toxicologically characterised the arsenic metabolite thiodimethylarsinic acid (thio-DMAV). Successful synthesis of highly pure thio-DMAV was confirmed by state-of-the-art analytical techniques including 1H-NMR, HPLC-FTMS, and HPLC-ICPMS. Toxicological characterization was carried out in comparison to arsenite and its well-known trivalent and pentavalent methylated metabolites. It comprised cellular bioavailability as well as different cytotoxicity and genotoxicity end points in cultured human A549 lung cells. Of all arsenicals investigated, thio-DMAV exerted the strongest cytotoxicity. Moreover, thio-DMAV did not induce DNA strand breaks and an increased induction of both micronuclei and multinucleated cells occurred only at beginning cytotoxic concentrations, indicating that thio-DMAV does not act via a genotoxic mode of action. Finally, to assess potential implications of thio-DMAV for human health, further mechanistic studies are urgently necessary to identify the toxic mode of action of this highly toxic, unusual pentavalent organic arsenical. PMID:22007210

  8. 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...

  9. 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...

  10. 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...

  11. 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. PMID:26003714

  12. Low Dose Effects: Benefit or Harm?

    PubMed

    Woloschak, Gayle E

    2016-03-01

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

  13. 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

  14. 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

  15. 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.’

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

    PubMed

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

    2014-03-18

    A high-capacity diffusive gradients in thin films (DGT) technique has been developed for measurement of total dissolved inorganic arsenic (As) using a long shelf life binding gel layer containing hydrous zirconium oxide (Zr-oxide). Both As(III) and As(V) were rapidly accumulated in the Zr-oxide gel and could be quantitatively recovered by elution using 1.0 M NaOH for freshwater or a mixture of 1.0 M NaOH and 1.0 M H2O2 for seawater. DGT uptake of As(III) and As(V) increased linearly with deployment time and was independent of pH (2.0-9.1), ionic strength (0.01-750 mM), the coexistence of phosphate (0.25-10 mg P L(-1)), and the aging of the Zr-oxide gel up to 24 months after production. The capacities of the Zr-oxide DGT were 159 μg As(III) and 434 μg As(V) per device for freshwater and 94 μg As(III) and 152 μg As(V) per device for seawater. These values were 5-29 times and 3-19 times more than those reported for the commonly used ferrihydrite and Metsorb DGTs, respectively. Deployments of the Zr-oxide DGT in As-spiked synthetic seawater provided accurate measurements of total dissolved inorganic As over the 96 h deployment, whereas ferrihydrite and Metsorb DGTs only measured the concentrations accurately up to 24 and 48 h, respectively. Deployments in soils showed that the Zr-oxide DGT was a reliable and robust tool, even for soil samples heavily polluted with As. In contrast, As in these soils was underestimated by ferrihydrite and Metsorb DGTs due to insufficient effective capacities, which were likely suppressed by the competing effects of phosphate. PMID:24528281

  17. 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. PMID:25618730

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    1977-01-01

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

  1. [Complications of low-dose amiodarone].

    PubMed

    Feigl, D; Gilad, R; Katz, E

    1991-11-15

    Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated. PMID:1752553

  2. Low-dose radiation exposure and carcinogenesis.

    PubMed

    Suzuki, Keiji; Yamashita, Shunichi

    2012-07-01

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

  3. Arsenic Toxicity in Male Reproduction and Development

    PubMed Central

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-01-01

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

  4. Arsenic Toxicity in Male Reproduction and Development.

    PubMed

    Kim, Yoon-Jae; Kim, Jong-Min

    2015-12-01

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

  5. Cancer in Experimental Animals Exposed to Arsenic and Arsenic Compounds

    PubMed Central

    Tokar, Erik J.; Benbrahim-Tallaa, Lamia; Ward, Jerold M.; Lunn, Ruth; Sams, Reeder L.; Waalkes, Michael P.

    2011-01-01

    Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, like mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC 2009). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals. PMID:20812815

  6. Culmination of Low-Dose Pesticide Effects

    PubMed Central

    2013-01-01

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

  7. Effects of inorganic arsenic exposure on glucose transporters and insulin receptor in the hippocampus of C57BL/6 male mice.

    PubMed

    Rodríguez, V M; Limón-Pacheco, J H; Del Razo, L M; Giordano, M

    2016-01-01

    Children and adolescent populations chronically exposed to high doses of inorganic arsenic (iAs) in drinking water in some regions around the world have shown behavioral and memory deficits. Recent studies have also associated iAs exposure with dysregulation of glucose metabolism. The hippocampus is a cerebral region well known for its role in learning and memory. Studies in vitro and in vivo have shown that the hippocampus is vulnerable to iAs exposure, and to changes in glucose metabolism. The glucose transporters (GLUTs) and insulin receptor (IR) regulate glucose metabolism in brain; they are expressed by hippocampal cells, and alterations in these proteins have been associated with memory deficits. The aims of this study were to evaluate the effects of iAs exposure via drinking water (DW) on GLUT1, GLUT3 and insulin receptor (INSR) mRNA expression in the hippocampus, on performance in a spatial memory task, and on peripheral glucose regulation. C57Bl/6 male mice were exposed to 50 mg iAs/L via DW for one, two, or three months. The qRT-PCR analyses indicated that, compared to a control group, GLUT1 and GLUT3 mRNA levels were decreased, while INSR mRNA levels were increased in the hippocampus of iAs exposed animals. The levels of iAs and its methylated species in the hippocampus of the iAs-exposed group were significantly higher than in controls. Mice exposed to iAs learned the spatial task but showed increased latency to find the submerged platform 48 h after the last training session; these animals also showed dysregulation of peripheral glucose. These results suggest that the effects of iAs exposure on a spatial memory task performance could be mediated by disruptions of glucose regulation in the CNS. PMID:26876454

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

    PubMed

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

    2016-09-15

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

  9. 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.

  10. 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.

  11. 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.

  12. LINKING MOLECULAR EVENT TO CELLULAR RESPONSES AT LOW DOSE EXPOSURES

    EPA Science Inventory

    Defining low dose radiation cancer risks is limited by our ability to measure and directly correlate relevant cellular and molecular responses occurring at low dose and dose rate with tumor formation. This deficiency has led to conservative risk assessments based on low dose ext...

  13. 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...

  14. 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

  15. 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.

  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. PMID:25281102

  17. 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

  18. 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...

  19. Contraception. Low-dose pill launched.

    PubMed

    1993-01-01

    At a vibrant ceremony in Kampala, Uganda, the Minister of Women in Development, Youth and Culture launched the new low-dose oral contraceptive Pilplan which provides women more options for birth spacing. Diplomats, physicians, government officials, and business leaders attended the ceremony at the Sheraton Hotel Kampala. A dance group did an interpretation of "Women in Uganda: Gaining Momentum." The Minister considered the introduction of this new pill as a turning point for reproductive rights. A baseline survey among Ugandan women has shown that although almost all women were familiar with the pill, only 36% have ever used it and only 15% were currently using it. 80% thought that pill use was preferable to having an unplanned pregnancy. These findings convinced the Minister that ignorance and misconception keep women from using the pill. The government, health providers, and others need to educate women about Pilplan and how to use it correctly. A bilateral agreement between the Ministry of Health and USAID set in motion a social marketing project which has now launched two contraceptive methods: Pilplan in 1993 and the Protector condom in 1990. USAID vowed to continue to support Pilplan, particularly if men could also help in supporting birth spacing. A Uganda-based pharmaceutical firm will distribute Pilplan in Uganda through pharmacies, clinics, and health facilities. Pilplan targets all middle- to low-income women. PMID:12319754

  20. Engineering the Soil Bacterium Pseudomonas putida for Arsenic Methylation

    PubMed Central

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

    2013-01-01

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

  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. 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...

  3. 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...

  4. AN INTRALABORATORY COMPARATIVE STUDY OF HYDRIDE GENERATION AND GRAPHITE FURNACE ATOMIC ABSORPTION TECHNIQUES FOR DETERMINING ORGANIC AND INORGANIC ARSENIC IN COMPLEX WASTEWATERS

    EPA Science Inventory

    A detailed intralaboratory comparison of the determination of arsenic in complex wastewater samples by hydride generation and graphite furnace atomic absorption techniques has been conducted. Two hydride generation techniques were employed. One consisted of the use of sodium boro...

  5. Arsenic concentration and speciation in infant formulas and first foods

    PubMed Central

    Jackson, Brian P.; Taylor, Vivien F.; Punshon, Tracy; Cottingham, Kathryn L.

    2012-01-01

    Arsenic exposure to humans is pervasive, and, increasingly, studies are revealing adverse health effects at ever lower doses. Drinking water is the main route of exposure for many individuals; however, food can be a significant source of arsenic to an individual, especially if their diet is rice-based. Infants are particularly susceptible to dietary exposure, since many first foods contain rice and they have a low body mass. Here we report on arsenic concentration and speciation in infant formulas and first foods. Speciation is essential for food analysis because of the much greater toxicity of inorganic arsenic species and the possibility that arsenic in food (unlike water) may be present in either inorganic or organic forms. Infant milk formulas were low in total arsenic (2.2–12.6 ng g−1, n=15). Non-dairy formulas were significantly higher in arsenic than dairy-based formulas. Arsenic in formula was almost exclusively inorganic and predominantly arsenic(V). Arsenic concentration in purees (n=41) and stage 3 foods (n=18) ranged from 0.3–22 ng g−1. Rice-fortified foods had significantly higher total arsenic concentrations than non rice-based foods. Again arsenic speciation was predominantly inorganic; arsenic(III) was the main species with lower concentrations of DMA and arsenic(V) also present. These data confirm that infants are exposed to arsenic via diet, and suggest that careful attention to diet choices may limit this. PMID:22701232

  6. Environmental biochemistry of arsenic

    SciTech Connect

    Tamaki, S.; Frankenberger, W.T. Jr. )

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  7. 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. PMID:22074737

  8. Arsenic round the world: a review.

    PubMed

    Mandal, Badal Kumar; Suzuki, Kazuo T

    2002-08-16

    This review deals with environmental origin, occurrence, episodes, and impact on human health of arsenic. Arsenic, a metalloid occurs naturally, being the 20th most abundant element in the earth's crust, and is a component of more than 245 minerals. These are mostly ores containing sulfide, along with copper, nickel, lead, cobalt, or other metals. Arsenic and its compounds are mobile in the environment. Weathering of rocks converts arsenic sulfides to arsenic trioxide, which enters the arsenic cycle as dust or by dissolution in rain, rivers, or groundwater. So, groundwater contamination by arsenic is a serious threat to mankind all over the world. It can also enter food chain causing wide spread distribution throughout the plant and animal kingdoms. However, fish, fruits, and vegetables primarily contain organic arsenic, less than 10% of the arsenic in these foods exists in the inorganic form, although the arsenic content of many foods (i.e. milk and dairy products, beef and pork, poultry, and cereals) is mainly inorganic, typically 65-75%. A few recent studies report 85-95% inorganic arsenic in rice and vegetables, which suggest more studies for standardisation. Humans are exposed to this toxic arsenic primarily from air, food, and water. Thousands and thousands of people are suffering from the toxic effects of arsenicals in many countries all over the world due to natural groundwater contamination as well as industrial effluent and drainage problems. Arsenic, being a normal component of human body is transported by the blood to different organs in the body, mainly in the form of MMA after ingestion. It causes a variety of adverse health effects to humans after acute and chronic exposures such as dermal changes (pigmentation, hyperkeratoses, and ulceration), respiratory, pulmonary, cardiovascular, gastrointestinal, hematological, hepatic, renal, neurological, developmental, reproductive, immunologic, genotoxic, mutagenetic, and carcinogenic effects. Key research

  9. 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.

  10. 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 ...