COMPARISON OF GENE EXPRESSION IN KIDNEY AND URINARY BLADDER FROM RATS TREATED WITH DIMETHYLARSINIC ACID

EPA Science Inventory

Arsenic is widespread in the environment and a human carcinogen. A major metabolite of inorganic arsenic (iAs) in most species, including humans, is dimethylarsinic acid (DMA), which is also used as a pesticide. Unlike iAs, DMA induces urinary bladder tumors in rats. DMA is belie...

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

EPA Science Inventory

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

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

EPA Science Inventory

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

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

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

EPA Science Inventory

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

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

EPA Science Inventory

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

Effect of Dietary Treatment with Dimethylarsinous Acid (DMAIII) on the Urinary Bladder Epithelium of Arsenic (+3 Oxidation State) Methyltransferase (As3mt) Knockout and C57BL/6 Wild Type Female Mice

EPA Science Inventory

Abstract Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder. It produces urothelial cytotoxicity and proliferation in rats and mice. DMAv, a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the...

Arsenic Exposure in Relation to Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

PubMed

Tsinovoi, Cari L; Xun, Pengcheng; McClure, Leslie A; Carioni, Vivian M O; Brockman, John D; Cai, Jianwen; Guallar, Eliseo; Cushman, Mary; Unverzagt, Frederick W; Howard, Virginia J; He, Ka

2018-01-01

The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States. We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species. The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident. A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research. © 2017 American Heart Association, Inc.

Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water

PubMed Central

Hong, Young-seoub; Ye, Byeong-jin; Kim, Yu-mi; Kim, Byoung-gwon; Kang, Gyeong-hui; Kim, Jeong-jin; Song, Ki-hoon; Kim, Young-hun

2017-01-01

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents. PMID:29186890

Dietary administration of sodium arsenite to rats: Relations between dose and urinary concentrations of methylated and thio-metabolites and effects on the rat urinary bladder epithelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.

2010-04-15

Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in drinking water is carcinogenic to humans, inducing skin, urinary bladder and lung tumors. In vivo, inorganic arsenic is metabolized to organic methylated arsenicals including the highly toxic dimethylarsinous acid (DMA{sup III}) and monomethylarsonous acid (MMA{sup III}). Short-term treatment of rats with 100 mug/g trivalent arsenic (As{sup III}) as sodium arsenite in the diet or in drinking water induced cytotoxicity and necrosis of the urothelial superficial layer, with increased cell proliferation and hyperplasia. The objectives of this study were to determine if these arsenic-induced urothelial effects are dosemore » responsive, the dose of arsenic at which urothelial effects are not detected, and the urinary concentrations of the arsenical metabolites. We treated female F344 rats for 5 weeks with sodium arsenite at dietary doses of 0, 1, 10, 25, 50, and 100 ppm. Cytotoxicity, cell proliferation and hyperplasia of urothelial superficial cells were increased in a dose-responsive manner, with maximum effects found at 50 ppm As{sup III}. There were no effects at 1 ppm As{sup III}. The main urinary arsenical in As{sup III}-treated rats was the organic arsenical dimethylarsinic acid (DMA{sup V}). The thio-metabolites dimethylmonothioarsinic acid (DMMTA{sup V}) and monomethylmonothioarsinic acid (MMMTA{sup V}) were also found in the urine of As{sup III}-treated rats. The LC{sub 50} concentrations of DMMTA{sup V} for rat and human urothelial cells in vitro were similar to trivalent oxygen-containing arsenicals. These data suggest that dietary As{sup III}-induced urothelial cytotoxicity and proliferation are dose responsive, and the urothelial effects have a threshold corresponding to the urinary excretion of measurable reactive metabolites.« less

DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

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

PubMed

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

2016-05-09

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-As(IMM), of urinary inorganic As species, arsenite (As(III)) and arsenate (As(V)), 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.

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

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.

Urinary arsenic speciation profile in ethnic group of the Atacama desert (Chile) exposed to variable arsenic levels in drinking water.

PubMed

Yáñez, Jorge; Mansilla, Héctor D; Santander, I Paola; Fierro, Vladimir; Cornejo, Lorena; Barnes, Ramón M; Amarasiriwardena, Dulasiri

2015-01-01

Ethnic groups from the Atacama Desert (known as Atacameños) have been exposed to natural arsenic pollution for over 5000 years. This work presents an integral study that characterizes arsenic species in water used for human consumption. It also describes the metabolism and arsenic elimination through urine in a chronically exposed population in northern Chile. In this region, water contained total arsenic concentrations up to 1250 μg L(-1), which was almost exclusively As(V). It is also important that this water was ingested directly from natural water sources without any treatment. The ingested arsenic was extensively methylated. In urine 93% of the arsenic was found as methylated arsenic species, such as monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. The original ingested inorganic species [As(V)], represent less than 1% of the total urinary arsenic. Methylation activity among individuals can be assessed by measuring primary [inorganic As/methylated As] and secondary methylation [MMA/DMA] indexes. Both methylation indexes were 0.06, indicating a high biological converting capability of As(V) into MMA and then MMA into DMA, compared with the control population and other arsenic exposed populations previously reported.

RECENT ADVANCES IN ARSENIC CARCINOGENESIS: MODES OF ACTION, ANIMAL MODEL SYSTEMS AND METHYLATED ARSENIC METABOLITES

EPA Science Inventory

Abstract:

Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer -skin, lung, urinary bladder, liver and kidney. Tumors can be produced from eit...

Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

EPA Science Inventory

Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

Renal, hepatic, pulmonary and adrenal tumors induced by prenatal inorganic arsenic followed by dimethylarsinic acid in adulthood in CD1 mice

PubMed Central

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

2012-01-01

Inorganic arsenic, an early life carcinogen in humans and mice, can initiate lesions promotable by other agents in later life. The biomethylation product of arsenic, dimethylarsinic acid (DMA), is a multi-site tumor promoter. Thus, pregnant CD1 mice were given drinking water (0 or 85 ppm arsenic) from gestation day 8 to 18 and after weaning male offspring received DMA (0 or 200 ppm; drinking water) for up to 2 years. No renal tumors occurred in controls or DMA alone treated mice while gestational arsenic exposure plus later DMA induced a significant renal tumor incidence of 17% (primarily renal cell carcinoma). Arsenic plus DMA or arsenic alone also increased renal hyperplasia over control but DMA alone did not. Arsenic alone, DMA alone and arsenic plus DMA all induced urinary bladder hyperplasia (33–35%) versus control (2%). Compared to control (6%), arsenic alone tripled hepatocellular carcinoma (20%), and arsenic plus DMA doubled this rate again (43%), but DMA alone had no effect. DMA alone, arsenic alone, and arsenic plus DMA increased lung adenocarcinomas and adrenal adenomas versus control. Overall, DMA in adulthood promoted tumors/lesions initiated by prenatal arsenic in the kidney and liver, but acted independently in the urinary bladder, lung and adrenal. PMID:22230260

Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

INDUCTION OF URINARY BLADDER PATHOLOGY IN MALE AND FEMALE C3H MICE EXPOSED TO SODIUM ARSENITE FROM GESTATION THROUGH YOUNG ADULTHOOD

EPA Science Inventory

Epidemiology studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Recently, an in utero animal model was developed to characterize the carcinogenic properties of inorganic arsen...

Low-level inorganic arsenic exposure and neuropsychological functioning in American Indian elders.

PubMed

Carroll, Clint R; Noonan, Carolyn; Garroutte, Eva M; Navas-Acien, Ana; Verney, Steven P; Buchwald, Dedra

2017-07-01

Inorganic arsenic at high and prolonged doses is highly neurotoxic. Few studies have evaluated whether long-term, low-level arsenic exposure is associated with neuropsychological functioning in adults. To investigate the association between long-term, low-level inorganic arsenic exposure and neuropsychological functioning among American Indians aged 64-95. We assessed 928 participants in the Strong Heart Study by using data on arsenic species in urine samples collected at baseline (1989-1991) and results of standardized tests of global cognition, executive functioning, verbal learning and memory, fine motor functioning, and speed of mental processing administered during comprehensive follow-up evaluations in 2009-2013. We calculated the difference in neuropsychological functioning for a 10% increase in urinary arsenic with adjustment for sex, age, education, and study site. The sum of inorganic and methylated arsenic species (∑As) in urine was associated with limited fine motor functioning and processing speed. A 10% increase in ∑As was associated with a .10 (95% CI -.20, -.01) decrease on the Finger Tapping Test for the dominant hand and a .13 decrease (95% CI -.21, -.04) for the non-dominant hand. Similarly, a 10% increase in ∑As was associated with a .15 (95% CI -.29, .00) decrease on the Wechsler Adult Intelligence Scale-Fourth Edition Coding Subtest. ∑As was not associated with other neuropsychological functions. Findings indicate an adverse association between increased urinary arsenic fine motor functioning and processing speed, but not with other neuropsychological functioning, among elderly American Indians. Copyright © 2017 Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Chao-Yuan; Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan; Su, Chien-Tien

2012-08-01

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

GENE EXPRESSION PROFILING OF RESPONSES TO DIMETHYLARSINIC ACID IN FEMALE F344 RAT UROTHELIUM

EPA Science Inventory

Arsenic is a human carcinogen and epidemiologic evidence implicates it in the development of urinary bladder cancer. Even though several mechanisms have been proposed for arsenic carcinogenicity, the mode of action of inorganic arsenic (iAs) is confounded by the limited availabil...

TISSUE DOSIMETRY, METABOLISM AND EXCRETION OF PENTAVALENT AND TRIVALENT DIMETHYLATED ARSENIC IN MICE AFTER ORAL ADMINISTRATION

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were...

Unusual arsenic metabolism in Giant Pandas.

PubMed

Braeuer, Simone; Dungl, Eveline; Hoffmann, Wiebke; Li, Desheng; Wang, Chengdong; Zhang, Hemin; Goessler, Walter

2017-12-01

The total arsenic concentration and the arsenic speciation in urine and feces samples of the two Giant Pandas living at Vienna zoo and of their feed, bamboo, were determined with ICPMS and HPLC-ICPMS. Urine was the main excretion route and accounted for around 90% of the ingested arsenic. The urinary arsenic concentrations were very high, namely up to 179 μg/L. Dimethylarsinic acid (DMA) was the dominating arsenic compound in the urine samples and ranged from 73 to 92% of the total arsenic, which is unusually high for a terrestrial mammal. The feces samples contained around 70% inorganic arsenic and 30% DMA. The arsenic concentrations in the bamboo samples were between 16 and 920 μg/kg dry mass. The main arsenic species in the bamboo extracts was inorganic arsenic. This indicates that the Giant Panda possesses a unique way of very efficiently methylating and excreting the provided inorganic arsenic. This could be essential for the survival of the animal in its natural habitat, because parts of this area are contaminated with arsenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2016-01-01

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

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

EPA Science Inventory

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

EXCRETION OF ARSENIC IN URINE AS A FUNCTION OF EXPOSURE TO ARSENIC IN DRINKING WATER

EPA Science Inventory

Urinary arsenic (As) concentrations were evaluated as a biomarker of exposure in a U.S. population chronically exposed to inorganic As (InAs) in their drinking water. Ninety-six individuals who consumed drinking water with As concentrations of 8-620 microg/L provided first mornin...

Chronic early childhood exposure to arsenic is associated with a TNF-mediated proteomic signaling response.

PubMed

Smeester, Lisa; Bommarito, Paige A; Martin, Elizabeth M; Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Fry, Rebecca C

2017-06-01

Exposure to inorganic arsenic (iAs) in drinking water is a global public health concern and is associated with a range of health outcomes, including immune dysfunction. Children are a particularly sensitive population to the effects of inorganic arsenic, yet the biological mechanisms underlying adverse health outcomes are understudied. Here we used a proteomic approach to examine the effects of iAs exposure on circulating serum protein levels in a cross-sectional children's cohort in Mexico. To identify iAs-associated proteins, levels of total urinary arsenic (U-tAs) and its metabolites were determined and serum proteins assessed for differences in expression. The results indicate an enrichment of Tumor Necrosis Factor-(TNF)-regulated immune and inflammatory response proteins that displayed decreased expression levels in relation to increasing U-tAs. Notably, when analyzed in the context of the proportions of urinary arsenic metabolites in children, the most robust response was observed in relation to the monomethylated arsenicals. This study is among the first serum proteomics assessment in children exposed to iAs. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of Exposure to Arsenic in Residential Soil

PubMed Central

Tsuji, Joyce S.; Van Kerkhove, Maria D.; Kaetzel, Rhonda S.; Scrafford, Carolyn G.; Mink, Pamela J.; Barraj, Leila M.; Crecelius, Eric A.; Goodman, Michael

2005-01-01

In response to concerns regarding arsenic in soil from a pesticide manufacturing plant, we conducted a biomonitoring study on children younger than 7 years of age, the age category of children most exposed to soil. Urine samples from 77 children (47% participation rate) were analyzed for total arsenic and arsenic species related to ingestion of inorganic arsenic. Older individuals also provided urine (n = 362) and toenail (n = 67) samples. Speciated urinary arsenic levels were similar between children (geometric mean, geometric SD, and range: 4.0, 2.2, and 0.89–17.7 μg/L, respectively) and older participants (3.8, 1.9, 0.91–19.9 μg/L) and consistent with unexposed populations. Toenail samples were < 1 mg/kg. Correlations between speciated urinary arsenic and arsenic in soil (r = 0.137, p = 0.39; n = 41) or house dust (r = 0.049, p = 0.73; n = 52) were not significant for children. Similarly, questionnaire responses indicating soil exposure were not associated with increased urinary arsenic levels. Relatively low soil arsenic exposure likely precluded quantification of arsenic exposure above background. PMID:16330356

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire.

PubMed

Bommarito, Paige A; Martin, Elizabeth; Smeester, Lisa; Palys, Thomas; Baker, Emily R; Karagas, Margaret R; Fry, Rebecca C

2017-10-01

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes. Copyright © 2017. Published by Elsevier Inc.

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

PubMed Central

2012-01-01

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

Effect of Sodium Arsenite Dose Administered in the Drinking Water on the Urinary Bladder Epithelium of Female Arsenic (+3 oxidation state) Methyltransferase Knockout Mice

EPA Science Inventory

The enzyme arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes reactions converting inorganic arsenic to methylated metabolites, some of which are highly cytotoxic. In a previous study, we evaluated whether the As3mt null genotype in mice modified cytotoxic and proli...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.

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) frommore » 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.« less

DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis.

PubMed

Ahsan, Habibul; Chen, Yu; Wang, Qiao; Slavkovich, Vesna; Graziano, Joseph H; Santella, Regina M

2003-07-20

Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. An estimated 50-70 million people in Bangladesh have been chronically exposed to arsenic from drinking water and are at risk of skin and other cancers. We undertook the first study to examine whether genetic susceptibility, as determined by the codon 751 SNP (A-->C) of the DNA repair gene XPD, influences the risk of arsenic-induced hyperkeratotic skin lesions, precursors of skin cancer, in a case-control study of 29 hyperkeratosis cases and 105 healthy controls from the same community in an area of Bangladesh. As expected, there was a monotonic increase in risk of hyperkeratosis in relation to urinary arsenic measures but the XPD genotype was not independently associated with the risk. However, the increase in hyperkeratosis risk in relation to urinary arsenic measures genotype was borderline significant for urinary total arsenic (P for trend=0.06) and statistically significant for urinary creatinine adjusted arsenic (P for trend=0.01) among subjects with the XPD A allele (AA) but not among subjects with the other XPD genotypes. Among AA carriers, the risk for the highest arsenic exposed group compared with the lowest was more than 7-fold for urinary total arsenic and about 11-fold for urinary creatinine adjusted arsenic. In conclusion, our findings suggest that the DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. Future larger studies are needed to confirm this novel finding and investigate how combinations of different candidate genes and/or other host and environmental factors may influence the risk of arsenic induced skin and other cancers.

GENE EXPRESSION CAN DIFFERENTIATE CARCINOGENIC FROM NON-CARCINOGENIC DOSES OF DIMETHYLARSINIC ACID (DMAv) IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS

EPA Science Inventory

Arsenic is an environmental concern worldwide, and drinking arsenic contaminated water has been associated with increased incidences of skin, lung and bladder cancer. Dimethylarsinic acid (DMAv) is a major metabolite of inorganic arsenic in rodents and humans and is the predomina...

Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh.

PubMed

Hata, Akihisa; Yamanaka, Kenzo; Habib, Mohamed Ahsan; Endo, Yoko; Fujitani, Noboru; Endo, Ginji

2012-05-01

Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. The median iAs concentration in drinking water was 55 μgAs/L (range <0.5-332 μgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7-32.3), 1.8 (<0.5-3.3), 13.7 (5.6-25.0), and 88.6 μgAs/L (47.9-153.4 μgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration.

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

Arsenic Metabolites and Methylation Capacity Among Individuals Living in a Rural Area with Endemic Arseniasis in Inner Mongolia, China.

PubMed

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

2016-04-01

More than 0.3 million individuals are subject to chronic exposure to arsenic via their drinking water in Inner Mongolia, China. To determine arsenic methylation capacity profiles for such individuals, concentrations of urinary arsenic metabolites were measured for 548 subjects using high-performance liquid chromatography and a hydride generator combined with inductively coupled plasma-mass spectrometry. Mean urinary concentrations of dimethylarsonic acid (DMA), monomethylarsonic acid (MMA), inorganic arsenic (iAs), and total arsenic (TAs) were 200.50, 46.71, 52.96, and 300.17 μg/L, respectively. The %iAs, %DMA, and %MMA were 15.98, 69.72, and 14.29%. Mean urinary %iAs and %MMA were higher in males, while urinary %DMA was higher in females. There was a strong positive correlation between %iAs and %MMA, with negative correlations between %iAs and %DMA, and %iAs and %MMA. In addition, %iAs and %MMA were positively associated with total arsenic in drinking water (WAs), while %DMA was negatively related with WAs. Regression analysis indicated that the primary methylation index (PMI) and secondary methylation index (SMI) generally decreased with increasing WAs. Females had a higher arsenic methylation capacity compared to males. Younger subjects had lower primary arsenic methylation capacity. However, the secondary arsenic methylation capacity was hardly affected by age. Moreover, both primary and secondary arsenic methylation capacities were negatively related to WAs.

Urinary arsenic levels influenced by abandoned mine tailings in the Southernmost Baja California Peninsula, Mexico.

PubMed

Colín-Torres, Carlos G; Murillo-Jiménez, Janette M; Del Razo, Luz M; Sánchez-Peña, Luz C; Becerra-Rueda, Oscar F; Marmolejo-Rodríguez, Ana J

2014-10-01

Gold has been mined at San Antonio-El Triunfo, (Baja California Sur, Mexico) since the 18th century. This area has approximately 5,700 inhabitants living in the San Juan de Los Planes and El Carrizal hydrographic basins, close to more than 100 abandoned mining sites containing tailings contaminated with potentially toxic elements such as arsenic. To evaluate the arsenic exposure of humans living in the surrounding areas, urinary arsenic species, such as inorganic arsenic (iAs) and the metabolites mono-methylated (MMA) and di-methylated arsenic acids (DMA), were evaluated in 275 residents (18-84 years of age). Arsenic species in urine were analyzed by hydride generation-cryotrapping-atomic absorption spectrometry, which excludes the non-toxic forms of arsenic such as those found in seafood. Urinary samples contained a total arsenic concentration (sum of arsenical species) which ranged from 1.3 to 398.7 ng mL(-1), indicating 33% of the inhabitants exceeded the biological exposition index (BEI = 35 ng mL(-1)), the permissible limit for occupational exposure. The mean relative urinary arsenic species were 9, 11 and 80% for iAs, MMA and DMA, respectively, in the Los Planes basin, and 17, 10 and 73%, respectively, in the El Carrizal basin. These data indicated that environmental intervention is required to address potential health issues in this area.

METABOLSM OF PENTAVALENT AND TRIVALENT DIMETHYLARSENIC ARSENIC IN THE MOUSE

EPA Science Inventory

Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen after chronic exposure in either drinking water or the diet. DMA(V) is also a major urinary metabolite of mammals exposed to inorganic arsenic. In mice, iv and po administration of [¹⁴C]-DMA(V) results in rapi...

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

PubMed

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

2015-02-01

Chronic diseases, including coronary heart disease (CHD), have been associated with ingestion of drinking water with high levels of inorganic arsenic (> 1,000 μg/L). However, associations have been inconclusive in populations with lower levels (< 100 μg/L) of inorganic arsenic exposure. We conducted a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of CHD. This study included 555 participants with 96 CHD events diagnosed between 1984 and 1998 for which individual lifetime arsenic exposure estimates were determined using data from structured interviews and secondary data sources to determine lifetime residence, which was linked to a geospatial model of arsenic concentrations in drinking water. These lifetime arsenic exposure estimates were correlated with historically collected urinary arsenic concentrations. A Cox proportional-hazards model with time-dependent CHD risk factors was used to assess the association between time-weighted average (TWA) lifetime exposure to low-level inorganic arsenic in drinking water and incident CHD. We estimated a positive association between low-level inorganic arsenic exposure and CHD risk [hazard ratio (HR): = 1.38, 95% CI: 1.09, 1.78] per 15 μg/L while adjusting for age, sex, first-degree family history of CHD, and serum low-density lipoprotein levels. The risk of CHD increased monotonically with increasing TWAs for inorganic arsenic exposure in water relative to < 20 μg/L (HR = 1.2, 95% CI: 0.6, 2.2 for 20-30 μg/L; HR = 2.2; 95% CI: 1.2, 4.0 for 30-45 μg/L; and HR = 3, 95% CI: 1.1, 9.1 for 45-88 μg/L). Lifetime exposure to low-level inorganic arsenic in drinking water was associated with increased risk for CHD in this population.

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

EPA Science Inventory

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

Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite.

PubMed

Li, Jinlong; Duan, Xiaoxu; Dong, Dandan; Zhang, Yang; Zhao, Lu; Li, Wei; Chen, Jinli; Sun, Guifan; Li, Bing

2017-09-01

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO 2 ). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO 2 groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What's more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid. Copyright © 2016 Elsevier GmbH. All rights reserved.

Urinary arsenic levels in the French adult population: the French National Nutrition and Health Study, 2006-2007.

PubMed

Saoudi, Abdessattar; Zeghnoun, Abdelkrim; Bidondo, Marie-Laure; Garnier, Robert; Cirimele, Vincent; Persoons, Renaud; Fréry, Nadine

2012-09-01

The French Nutrition and Health Survey (ENNS) was conducted to describe dietary intakes, nutritional status, physical activity, and levels of various biomarkers for environmental chemicals (heavy metals and pesticides) in the French population (adults aged 18-74 years and children aged 3-17 years living in continental France in 2006-2007). The aim of this paper was to describe the distributions of total arsenic and the sum of iAs+MMA+DMA in the general adult population, and to present their main risk factors. In the arsenic study, 1500 and 1515 adults (requested to avoid seafood intake in the previous 3 days preceding urine collection) were included respectively for the analysis of the sum of inorganic arsenic (iAs) and its two metabolites, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), and for the total arsenic. Results were presented as geometric means and selected percentiles of urinary arsenic concentrations (μg/L) and creatinine-adjusted urinary arsenic (μg/g of creatinine) for total arsenic, and the sum of inorganic arsenic and metabolites (iAs+MMA+DMA). The geometric mean concentration of the sum of iAs+MMA+DMA in the adult population living in France was 3.34 μg/g of creatinine [3.23-3.45] (3.75 μg/L [3.61-3.90]) with a 95th percentile of 8.9 μg/g of creatinine (10.68 μg/L). The geometric mean concentration of total arsenic was 11.96 μg/g of creatinine [11.41-12.53] (13.42 μg/L [12.77-14.09]) with a 95th percentile of 61.29 μg/g of creatinine (72.75 μg/L). Urinary concentrations of total arsenic and iAS+MMA+DMA were influenced by sociodemographic and economic factors, and by risk factors such as consumption of seafood products and of wine. In our study, covariate-adjusted geometric means demonstrated several slight differences, due to consumption of fish, shellfish/crustaceans or wine. This study provides the first reference value for arsenic in a representative sample of the French population not particularly exposed to high levels of arsenic (10 μg/g of creatinine). It shows that urinary arsenic concentrations in the French adult population (in particular concentrations of iAs+MMA+DMA) were relatively low compared with foreign data. Copyright © 2012 Elsevier B.V. All rights reserved.

Arsenic exposure and type 2 diabetes: results from the 2007-2009 Canadian Health Measures Survey.

PubMed

Feseke, S K; St-Laurent, J; Anassour-Sidi, E; Ayotte, P; Bouchard, M; Levallois, P

2015-06-01

Inorganic arsenic and its metabolites are considered dangerous to human health. Although several studies have reported associations between low-level arsenic exposure and diabetes mellitus in the United States and Mexico, this association has not been studied in the Canadian population. We evaluated the association between arsenic exposure, as measured by total arsenic concentration in urine, and the prevalence of type 2 diabetes (T2D) in 3151 adult participants in Cycle 1 (2007-2009) of the Canadian Health Measures Survey (CHMS). All participants were tested to determine blood glucose and glycated hemoglobin. Urine analysis was also performed to measure total arsenic. In addition, participants answered a detailed questionnaire about their lifestyle and medical history. We assessed the association between urinary arsenic levels and T2D and prediabetes using multivariate logistic regression while adjusting for potential confounders. Total urinary arsenic concentration was positively associated with the prevalence of T2D and prediabetes: adjusted odds ratios were 1.81 (95% CI: 1.12-2.95) and 2.04 (95% CI: 1.03-4.05), respectively, when comparing the highest (fourth) urinary arsenic concentration quartile with the lowest (first) quartile. Total urinary arsenic was also associated with glycated hemoglobin levels in people with untreated diabetes. We found significant associations between arsenic exposure and the prevalence of T2D and prediabetes in the Canadian population. Causal inference is limited due to the cross-sectional design of the study and the absence of long-term exposure assessment.

Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

EPA Science Inventory

Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Huang, Chao-Yuan

Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain riskmore » factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.« less

THE URINARY BLADDER EXHIBITS A U-SHAPED GENOMIC DOSE-RESPONSE FOLLOWING SHORT- AND LONG-TERM EXPOSURE OF MICE TO ARSENATE IN DRINKING WATER

EPA Science Inventory

A number of studies have demonstrated increased urinary bladder tumor incidence in populations exposed to inorganic arsenic in drinking water at concentrations on the order of several hundred micrograms per liter, but experimental animal studies at much higher concentrations have...

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

PubMed Central

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

2005-01-01

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

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

PubMed

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

2017-09-01

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO 2 ) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

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

EPA Science Inventory

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

Concentrations of urinary arsenic species in relation to rice and seafood consumption among children living in Spain.

PubMed

Signes-Pastor, Antonio J; Vioque, Jesus; Navarrete-Muñoz, Eva M; Carey, Manus; García de la Hera, Manoli; Sunyer, Jordi; Casas, Maribel; Riaño-Galán, Isolina; Tardón, Adonina; Llop, Sabrina; Amorós, Rubén; Amiano, Pilar; Bilbao, José R; Karagas, Margaret R; Meharg, Andrew A

2017-11-01

Inorganic arsenic (i-As) has been related to wide-ranging health effects in children, leading to lifelong concerns. Proportionally, dietary i-As exposure dominates in regions with low arsenic drinking water. This study aims to investigate the relation between rice and seafood consumption and urinary arsenic species during childhood and to assess the proportion of urinary i-As metabolites. Urinary arsenic species concentration in 400 4-year-old children living in four geographical areas of Spain, in addition to repeated measures from 100 children at 7 years of age are included in this study. Rice and seafood products intake was collected from children's parents using a validated food frequency questionnaire (FFQ). At 4 years of age, children's urine i-As and monomethylarsonic acid (MMA) concentrations increased with rice product consumption (p-value = 0.010 and 0.018, respectively), and urinary arsenobetaine (AsB) with seafood consumption (p = 0.002). Four-year-old children had a higher consumption of both rice and seafood per body weight and a higher urinary %MMA (p-value = 0.001) and lower % dimethylarsinic acid (DMA) (p-value = 0.017). This study suggests increased dietary i-As exposure related to rice product consumption among children living in Spain, and the younger ones may be especially vulnerable to the health impacts of this exposure also considering that they might have a lower i-As methylation capacity than older children. In contrast, seafood consumption did not appear to influence the presence of potentially toxic arsenic species in this population of children. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico.

PubMed

Laine, Jessica E; Bailey, Kathryn A; Rubio-Andrade, Marisela; Olshan, Andrew F; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H; Stýblo, Miroslav; García-Vargas, Gonzalo G; Fry, Rebecca C

2015-02-01

Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.

HPLC-ICP-MS speciation analysis of arsenic in urine of Japanese subjects without occupational exposure.

PubMed

Hata, Akihisa; Endo, Yoko; Nakajima, Yoshiaki; Ikebe, Maiko; Ogawa, Masanori; Fujitani, Noboru; Endo, Ginji

2007-05-01

The toxicity and carcinogenicity of arsenic depend on its species. Individuals living in Japan consume much seafood that contains high levels of organoarsenics. Speciation analysis of urinary arsenic is required to clarify the health risks of arsenic intake. There has been no report of urinary arsenic analysis in Japan using high performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We performed speciation analysis of urinary arsenic for 210 Japanese male subjects without occupational exposure using HPLC-ICP-MS. The median values of urinary arsenics were as follows: sodium arsenite (AsIII), 3.5; sodium arsenate (AsV), 0.1; monomethylarsonic acid (MMA), 3.1; dimethylarsinic acid (DMA), 42.6; arsenobetaine (AsBe), 61.3; arsenocholine, trimethylarsine oxide, and unidentified arsenics (others), 5.2; and total arsenic (total As), 141.3 microgAs/l. The median creatinine-adjusted values were as follows: AsIII, 3.0; AsV, 0.1; MMA, 2.6; DMA, 35.9; AsBe, 52.1; others 3.5; and total As, 114.9 microgAs/g creatinine. Our findings indicate that DMA and AsBe levels in Japan are much higher than those found in Italian and American studies. It appears that the high levels of DMA and AsBe observed in Japan may be due in part to seafood intake. ACGIH and DFG set the BEI and BAT values for occupational arsenic exposure as 35 microgAs/l and 50 microgAs/l, respectively, using the sum of inorganic arsenic (iAs), MMA, and DMA. In the general Japanese population, the sums of these were above 50 microgAs/l in 115 (55%) samples. We therefore recommend excluding DMA concentration in monitoring of iAs exposure.

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

PubMed Central

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

2014-01-01

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

Differences in Urinary Arsenic Metabolites between Diabetic and Non-Diabetic Subjects in Bangladesh

PubMed Central

Nizam, Saika; Kato, Masashi; Yatsuya, Hiroshi; Khalequzzaman, Md.; Ohnuma, Shoko; Naito, Hisao; Nakajima, Tamie

2013-01-01

Ingestion of inorganic arsenic (iAs) is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons) and non-diabetic controls (180 persons) were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L) and controls (85.8 μg/L). The percentage of urinary iAs (iAs%) was significantly lower in cases (8.6%) than in controls (10.4%), while that of dimethylarsinic acid (DMA%) was higher in cases (82.6%) than in controls (79.9%). This may have been due to the higher secondary methylation index (SMI) in the former (11.6) rather than the latter (10.0). Adjusting for matching factors (sex and unions), and the additional other covariates (age and water arsenic) significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects. PMID:23481591

A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

PubMed Central

Li, Zhigang; Perry, Ann E.; Spencer, Steven K.; Gandolfi, A. Jay; Karagas, Margaret R.

2013-01-01

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association. Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178 PMID:23872349

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

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

PubMed

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

2004-10-01

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

Urinary Arsenic Speciation in Children and Pregnant Women from Spain.

PubMed

Signes-Pastor, Antonio J; Carey, Manus; Vioque, Jesus; Navarrete-Muñoz, Eva M; Rodríguez-Dehli, Cristina; Tardón, Adonina; Begoña-Zubero, Miren; Santa-Marina, Loreto; Vrijheid, Martine; Casas, Maribel; Llop, Sabrina; Gonzalez-Palacios, Sandra; Meharg, Andrew A

2017-01-01

Inorganic arsenic (i-As) is a non-threshold human carcinogen that has been associated with several adverse health outcomes. Exposure to i-As is of particular concern among pregnant women, infants and children, as they are specifically vulnerable to the adverse health effects of i-As, and in utero and early-life exposure, even low to moderate levels of i-As, may have a marked effect throughout the lifespan. Ion chromatography-mass spectrometry detection (IC-ICP-MS) was used to analyse urinary arsenic speciation, as an exposure biomarker, in samples of 4-year-old children with relatively low-level arsenic exposure living in different regions in Spain including Asturias, Gipuzkoa, Sabadell and Valencia. The profile of arsenic metabolites in urine was also determined in samples taken during pregnancy (1st trimester) and in the children from Valencia of 7 years old. The median of the main arsenic species found in the 4-year-old children was 9.71 μg/l (arsenobetaine-AsB), 3.97 μg/l (dimethylarsinic acid-DMA), 0.44 μg/l (monomethylarsonic acid-MMA) and 0.35 μg/l (i-As). Statistically significant differences were found in urinary AsB, MMA and i-As according to the study regions in the 4-year-old, and also in DMA among pregnant women and their children. Spearman's correlation coefficient among urinary arsenic metabolites was calculated, and, in general, a strong methylation capacity to methylate i-As to MMA was observed.

A population-based case-control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA.

PubMed

Gilbert-Diamond, Diane; Li, Zhigang; Perry, Ann E; Spencer, Steven K; Gandolfi, A Jay; Karagas, Margaret R

2013-10-01

Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. We conducted a population-based case-control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.

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

PubMed Central

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.

2016-01-01

Abstract 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

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: application of salivary and urinary biomarkers.

PubMed

Hinhumpatch, Pantip; Navasumrit, Panida; Chaisatra, Krittinee; Promvijit, Jeerawan; Mahidol, Chulabhorn; Ruchirawat, Mathuros

2013-12-15

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r=0.56, P<0.001) and arsenic concentration in urine (r=0.50, P<0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (~4-fold, P<0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (~3-fold, P<0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. © 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yokohira, Masanao; Arnold, Lora L.; Pennington, Karen L.

Arsenic (+ 3 oxidation state) methyltransferase (As3mt) catalyzes reactions which convert inorganic arsenic to methylated metabolites. This study determined whether the As3mt null genotype in the mouse modifies cytotoxic and proliferative effects seen in urinary bladders of wild type mice after exposure to inorganic arsenic. Female wild type C57BL/6 mice and As3mt KO mice were divided into 3 groups each (n = 8) with free access to a diet containing 0, 100 or 150 ppm of arsenic as arsenite (As{sup III}). During the first week of As{sup III} exposure, As3mt KO mice exhibited severe and lethal systemic toxicity. At termination,more » urinary bladders of both As3mt KO and wild type mice showed hyperplasia by light microscopy. As expected, arsenic-containing granules were found in the superficial urothelial layer of wild type mice. In As3mt KO mice these granules were present in all layers of the bladder epithelium and were more abundant and larger than in wild type mice. Scanning electron microscopy of the bladder urothelium of As3mt KO mice treated with 100 ppm As{sup III} showed extensive superficial necrosis and hyperplastic changes. In As3mt KO mice, livers showed severe acute inflammatory changes and spleen size and lymphoid areas were decreased compared with wild type mice. Thus, diminished arsenic methylation in As3mt KO mice exacerbates systemic toxicity and the effects of As{sup III} on the bladder epithelium, showing that altered kinetic and dynamic behavior of arsenic can affect its toxicity.« less

Differences of urinary arsenic metabolites and methylation capacity between individuals with and without skin lesions in Inner Mongolia, Northern China.

PubMed

Zhang, Qiang; Li, Yongfang; Liu, Juan; Wang, Da; Zheng, Quanmei; Sun, Guifan

2014-07-18

Incomplete arsenic (As) methylation has been considered a risk factor of As-related diseases. This study aimed to examine the difference of urinary As metabolites and the methylation capacity between subjects with and without skin lesions. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analyzed. The percentage of each As species (iAs%, MMA%, and DMA%), the primary methylation index (PMI) and secondary methylation index (SMI) were calculated. The results showed that subjects with skin lesions have higher levels of urinary iAs (99.08 vs. 70.63 μg/g Cr, p = 0.006) and MMA (69.34 vs. 42.85 μg/g Cr, p = 0.016) than subjects without skin lesions after adjustment for several confounders. Significant differences of urianry MMA% (15.49 vs. 12.11, p = 0.036) and SMI (0.74 vs. 0.81, p = 0.025) were found between the two groups. The findings of the present study suggest that subjects with skin lesions may have a lower As methylation capacity than subjects without skin lesions.

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

PubMed Central

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

2014-01-01

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes. We previously reported an association of diabetes and urinary concentration of dimethylarsinite (DMAsIII), a toxic product of arsenic methylation by arsenic ( +3 oxidation state) methyltransferase (AS3MT). Here we examine associations between AS3MT polymorphism, arsenic metabolism and diabetes. Fasting blood glucose, oral glucose tolerance and self-reported diagnoses were used to identify diabetic individuals. Inorganic arsenic and its metabolites were measured in urine. Genotyping analysis focused on six polymorphic sites of AS3MT. Individuals with M287T and G4965C polymorphisms had higher levels of urinary DMAsIII and were more frequently diabetic than the respective wild-type carriers, although the excess was not statistically significant. Odds ratios were 11.4 (95% confidence interval (CI) 2.2–58.8) and 8.8 (95% CI 1.6–47.3) for the combined effects of arsenic exposure >75th percentile and 287T and 4965C genotypes, respectively. Carriers of 287T and 4965C may produce more DMAsIII and be more likely to develop diabetes when exposed to arsenic. PMID:23093101

Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

PubMed

Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

2015-01-01

Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-05-01

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

Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

PubMed

Yin, Jinbao; Liu, Su; Yu, Jing; Wu, Bing

2017-07-01

Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

Concentration-and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks

EPA Science Inventory

Inorganic arsenic (AsD is a known human bladder carcinogen. The objective of this study was to examine the concentration dependence of the genomic response to ASi in the urinary bladders of mice. C57BL/6J mice were exposed for 1 or 12 weeks to arsenate in drinking water at concen...

Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: Application of salivary and urinary biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinhumpatch, Pantip; Navasumrit, Panida; Chulabhorn Graduate Institute, Laksi, Bangkok

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations withmore » other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.« less

Methylation of inorganic arsenic in different mammalian species and population groups.

PubMed

Vahter, M

1999-01-01

Thousands of people in different parts of the world are exposed to arsenic via drinking water or contaminated soil or food. The high general toxic of arsenic has been known for centuries, and research during the last decades has shown that arsenic is a potent human carcinogen. However, most experimental cancer studies have failed to demonstrate carcinogenicity in experimental animals, indicating marked variation in sensitivity towards arsenic toxicity between species. It has also been suggested that there is a variation in susceptibility among human individuals. One reason for such variability in toxic response may be variation in metabolism. Inorganic arsenic is methylated in humans as well as animals and micro-organisms, but there are considerable differences between species and individuals. In many, but not all, mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are more rapidly excreted in urine than is the inorganic arsenic, especially the trivalent form (AsIII, arsenite) which is highly reactive with tissue components. Absorbed arsenate (AsV) is reduced to trivalent arsenic (AsIII) before the methyl groups are attached. It has been estimated that as much as 50-70% of absorbed AsV is rapidly reduced to AsIII, a reaction which seems to be common for most species. In most experimental animal species, DMA is the main metabolite excreted in urine. Compared to human subjects, very little MMA is produced. However, the rate of methylation varies considerably between species, and several species, e.g. the marmoset monkey and the chimpanzee have been shown not to methylate inorganic arsenic at all. In addition, the marmoset monkey accumulates arsenic in the liver. The rat, on the other hand, has an efficient methylation of arsenic but the formed DMA is to a large extent accumulated in the red blood cells. As a result, the rat shows a low rate of excretion of arsenic. In both human subjects and rodents exposed to DMA, about 5% of the dose is excreted in the urine as trimethylarsine oxide. It is obvious from studies on human volunteers exposed to specified doses of inorganic arsenic that the rate of excretion increases with the methylation efficiency, and there are large inter-individual variations in the methylation of arsenic. Recent studies on people exposed to arsenic via drinking water in northern Argentina have shown unusually low urinary excretion of MMA. Furthermore, children had a lower degree of methylation of arsenic than adults. Some studies indicate a lower degree of arsenic methylation in men than in women, especially during pregnancy. Whether the observed differences in methylation of arsenic are associated with variations in the susceptibility of arsenic remains to be investigated.

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).

Maternal Arsenic Exposure, Arsenic Methylation Efficiency, and Birth Outcomes in the Biomarkers of Exposure to ARsenic (BEAR) Pregnancy Cohort in Mexico

PubMed Central

Laine, Jessica E.; Bailey, Kathryn A.; Rubio-Andrade, Marisela; Olshan, Andrew F.; Smeester, Lisa; Drobná, Zuzana; Herring, Amy H.; Stýblo, Miroslav; García-Vargas, Gonzalo G.

2014-01-01

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization’s recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations. Citation: Laine JE, Bailey KA, Rubio-Andrade M, Olshan AF, Smeester L, Drobná Z, Herring AH, Stýblo M, García-Vargas GG, Fry RC. 2015. Maternal arsenic exposure, arsenic methylation efficiency, and birth outcomes in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Mexico. Environ Health Perspect 123:186–192; http://dx.doi.org/10.1289/ehp.1307476 PMID:25325819

A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

PubMed Central

Li, Yongfang; Wang, Da; Li, Xin; Zheng, Quanmei; Sun, Guifan

2015-01-01

Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects) residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%), primary methylation index (PMI) and secondary methylation index (SMI) were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI) and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors. PMID:25837203

Bioaccessibility and excretion of arsenic in Niu Huang Jie Du Pian pills

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koch, Iris; Sylvester, Steven; Lai, Vivian W.-M.

2007-08-01

Traditional Chinese medicines (TCMs) often contain significant levels of potentially toxic elements, including arsenic. Niu Huang Jie Du Pian pills were analyzed to determine the concentration, bioaccessibility (arsenic fraction soluble in the human gastrointestinal system) and chemical form (speciation) of arsenic. Arsenic excretion in urine (including speciation) and facial hair were studied after a one-time ingestion. The pills contained arsenic in the form of realgar, and although the total arsenic that was present in a single pill was high (28 mg), the low bioaccessibility of this form of arsenic predicted that only 4% of it was available for absorption intomore » the bloodstream (1 mg of arsenic per pill). The species of arsenic that were solubilized were inorganic arsenate (As(V)) and arsenite (As(III)) but DMAA and MMAA were detected in urine. Two urinary arsenic excretion peaks were observed: an initial peak several (4-8) hours after ingestion corresponding to the excretion of predominantly As(III), and a larger peak at 14 h corresponding predominantly to DMAA and MMAA. No methylated As(III) species were observed. Facial hair analysis revealed that arsenic concentrations did not increase significantly as a result of the ingestion. Arsenic is incompletely soluble under human gastrointestinal conditions, and is metabolized from the inorganic to organic forms found in urine. Bioaccessible arsenic is comparable to the quantity excreted. Facial hair as a bio-indicator should be further tested.« less

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

PubMed

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

2017-02-01

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

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-06-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed Central

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-01-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively. PMID:12782488

Associations between Methylated Metabolites of Arsenic and Selenium in Urine of Pregnant Bangladeshi Women and Interactions between the Main Genes Involved.

PubMed

Skröder, Helena; Engström, Karin; Kuehnelt, Doris; Kippler, Maria; Francesconi, Kevin; Nermell, Barbro; Tofail, Fahmida; Broberg, Karin; Vahter, Marie

2018-02-01

It has been proposed that interactions between selenium and arsenic in the body may affect their kinetics and toxicity. However, it is unknown how the elements influence each other in humans. We aimed to investigate potential interactions in the methylation of selenium and arsenic. Urinary selenium (U-Se) and arsenic (U-As) were measured using inductively coupled plasma mass spectrometry (ICPMS) in samples collected from pregnant women ( n =226) in rural Bangladesh at gestational weeks (GW) 8, 14, 19, and 30. Urinary concentrations of trimethyl selenonium ion (TMSe) were measured by HPLC-vapor generation-ICPMS, as were inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA). Methylation efficiency was assessed based on relative amounts (%) of arsenic and selenium metabolites in urine. Genotyping for the main arsenite and selenium methyltransferases, AS3MT and INMT, was performed using TaqMan probes or Sequenom. Multivariable-adjusted linear regression analyses indicated that %TMSe (at GW8) was positively associated with %MMA (β=1.3, 95% CI: 0.56, 2.0) and U-As, and inversely associated with %DMA and U-Se in producers of TMSe ( INMT rs6970396 AG+AA, n =74), who had a wide range of urinary TMSe (12-42%). Also, %TMSe decreased in parallel to %MMA during pregnancy, especially in the first trimester (-0.58 %TMSe per gestational week). We found a gene-gene interaction for %MMA ( p -interaction=0.076 for haplotype 1). In analysis stratified by INMT genotype, the association between %MMA and both AS3MT haplotypes 1 and 3 was stronger in women with the INMT GG (TMSe nonproducers, 5th-95th percentile: 0.2-2%TMSe) vs. AG+AA genotype. Our findings for Bangladeshi women suggest a positive association between urinary %MMA and %TMSe. Genes involved in the methylation of selenium and arsenic may interact on associations with urinary %MMA. https://doi.org/10.1289/EHP1912.

Dose-dependent urinary phenotype of inorganic arsenic methylation in mice with a focus on trivalent methylated metabolites.

PubMed

García-Montalvo, Eliud A; Valenzuela, Olga L; Sánchez-Peña, Luz C; Albores, Arnulfo; Del Razo, Luz M

2011-11-01

Inorganic arsenic (iAs) exposure has been associated with the increased risk of various forms of cancer and of non-cancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate. The results of metabolic and toxicity studies using mice have been entirely applicable to other species including humans. The goal of this study was to investigate the phenotype for the trivalent and pentavalent arsenic metabolites in relation to arsenite dose via immediate analysis of fresh urine samples, while preventing the oxidation of unstable methylated AsIII-containing metabolites. Female mice (C57BL/6) received sodium arsenite by gavage at doses of 0, 3, 6 or 10 mg As/kg/day for 9 days, after which trivalent methylated arsenicals were detected in 100% of urine samples; these arsenicals were not detected in the urine of control mice. The amount of DMAsIII detected in urine depended on the dose of arsenite administered and was determined to be 50.2%, 31.4% and 16.5% of the total urinary arsenic in mice exposed to 3, 6, or 10 mg/kg/day, respectively. This relationship is consistent with the hypothesis of inhibition or saturation of iAs methylation. Understanding the in vivo production of MAsIII and DMAsIII in mice exposed to iAs could aid in developing a biologically based dose-response model for iAs.

Arsenic Metabolism in Children Differs From That in Adults

PubMed Central

Skröder Löveborn, Helena; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-01-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12. Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children’s arsenic methylation; an increase in Ery-Se from the 5–95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and −3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5–95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5–95th percentile: −1.9 pp, P  =  .001) and positively associated with %DMA (5–95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. PMID:27056082

AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

PubMed

Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

2014-07-01

Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

Low-level arsenic exposure: nutritional and dietary predictors in first-grade Uruguayan children

PubMed Central

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

2016-01-01

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5–8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-hour dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9 µg/L) and household water (water As: median 0.45 µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on ”nutrient dense” dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. PMID:26828624

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

PubMed

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

2016-05-01

Arsenic exposure in children is a public health concern but is understudied in relation to the predictors, and effects of low-level exposure. We examined the extent and dietary predictors of exposure to inorganic arsenic in 5-8 year old children from Montevideo, Uruguay. Children were recruited at school; 357 were enrolled, 328 collected morning urine samples, and 317 had two 24-h dietary recalls. Urinary arsenic metabolites, i.e. inorganic arsenic (iAs), methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were measured using high-performance liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICP-MS), and the sum concentration (U-As) used for exposure assessment. Proportions of arsenic metabolites (%iAs, %MMA and %DMA) in urine were modelled in OLS regressions as functions of food groups, dietary patterns, nutrient intake, and nutritional status. Exposure to arsenic was low (median U-As: 9.9µg/L) and household water (water As: median 0.45µg/L) was not a major contributor to exposure. Children with higher consumption of rice had higher U-As but lower %iAs, %MMA, and higher %DMA. Children with higher meat consumption had lower %iAs and higher %DMA. Higher scores on "nutrient dense" dietary pattern were related to lower %iAs and %MMA, and higher %DMA. Higher intake of dietary folate was associated with lower %MMA and higher %DMA. Overweight children had lower %MMA and higher %DMA than normal-weight children. In summary, rice was an important predictor of exposure to inorganic arsenic and DMA. Higher meat and folate consumption, diet rich in green leafy and red-orange vegetables and eggs, and higher BMI contributed to higher arsenic methylation capacity. Copyright © 2016 Elsevier Inc. All rights reserved.

Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study.

PubMed

Hsu, Ling-I; Hsieh, Fang-I; Wang, Yuan-Hung; Lai, Tai-Shuan; Wu, Meei-Maan; Chen, Chien-Jen; Chiou, Hung-Yi; Hsu, Kuang-Hung

2017-12-01

Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified. The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study. 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively. Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration. Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan's National Health Insurance database 1998 to 2011. HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression. We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 10 4 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria. Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured. This study describes the temporal relationship between arsenic concentrations ≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Analysis of maternal polymorphisms in arsenic (+3 oxidation state)-methyltransferase AS3MT and fetal sex in relation to arsenic metabolism and infant birth outcomes: Implications for risk analysis.

PubMed

Drobná, Zuzana; Martin, Elizabeth; Kim, Kyung Su; Smeester, Lisa; Bommarito, Paige; Rubio-Andrade, Marisela; García-Vargas, Gonzalo G; Stýblo, Miroslav; Zou, Fei; Fry, Rebecca C

2016-06-01

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the metabolism of inorganic arsenic (iAs). Polymorphisms of AS3MT influence adverse health effects in adults, but little is known about their role in iAs metabolism in pregnant women and infants. The relationships between seven single nucleotide polymorphisms (SNPs) in AS3MT and urinary concentrations of iAs and its methylated metabolites were assessed in mother-infant pairs of the Biomarkers of Exposure to ARsenic (BEAR) cohort. Maternal alleles for five of the seven SNPs (rs7085104, rs3740400, rs3740393, rs3740390, and rs1046778) were associated with urinary concentrations of iAs metabolites, and alleles for one SNP (rs3740393) were associated with birth outcomes/measures. These associations were strongly dependent upon the male sex of the fetus but independent of fetal genotype for AS3MT. These data highlight a potential sex-dependence of the relationships among maternal genotype, iAs metabolism and infant health outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women.

PubMed

Pineda-Belmontes, Cristina P; Hernández-Ramírez, Raúl U; Hernández-Alcaraz, César; Cebrián, Mariano E; López-Carrillo, Lizbeth

2016-04-01

To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.

Inorganic arsenic exposure increased expression of Fas and Bax gene in vivo and vitro.

PubMed

He, Yuefeng; Zhang, Ruobing; Xiaoxiao, Song; Li, Shang; Xinan, Wu; Huang, Dahai

2018-06-01

Accumulating evidences have shown that apoptosis plays an important role in mediating the therapeutic effects and toxicity of arsenic. Fas and Bax genes are critical regulatory genes for apoptosis. In this study, we investigated the association between levels of Fas and Bax expression and the three arsenic species (inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in vivo and vitro. Three arsenic species in urine were measured and levels of Fas and Bax expression were examined by the quantitative real-time PCR (qPCR) for all subjects. We found that Fas and Bax mRNA expression in the exposed group were significantly higher than that in the control group. The levels of gene expression were positively correlated with the concentrations of urinary iAs, MMA and DMA in all subjects. Sodium arsenite induced Fas and Bax mRNA expression, then MMA and DMA did not induce mRNA expression in MDA-MB-231 and XWLC-05 cells. The findings of the present study indicated that iAs, MMA, and DMA had different effects on expression of Bax and Fas gene. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun; Wei, Yudan; Feng, Hongqi; Wang, Cheng; Wei, Wei; Ding, Yunpeng; Sun, Dianjun

2012-02-15

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06mg-year), medium (1.37-3.55mg-year), and high (4.26-48.13mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

Glutathione-S-transferase-omega [MMA(V) reductase] knockout mice: Enzyme and arsenic species concentrations in tissues after arsenate administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chowdhury, Uttam K.; Zakharyan, Robert A.; Hernandez, Alba

Inorganic arsenic is a human carcinogen to which millions of people are exposed via their naturally contaminated drinking water. Its molecular mechanisms of carcinogenicity have remained an enigma, perhaps because arsenate is biochemically transformed to at least five other arsenic-containing metabolites. In the biotransformation of inorganic arsenic, GSTO1 catalyzes the reduction of arsenate, MMA(V), and DMA(V) to the more toxic + 3 arsenic species. MMA(V) reductase and human (hGSTO1-1) are identical proteins. The hypothesis that GST-Omega knockout mice biotransformed inorganic arsenic differently than wild-type mice has been tested. The livers of male knockout (KO) mice, in which 222 bp ofmore » Exon 3 of the GSTO1 gene were eliminated, were analyzed by PCR for mRNA. The level of transcripts of the GSTO1 gene in KO mice was 3.3-fold less than in DBA/1lacJ wild-type (WT) mice. The GSTO2 transcripts were about two-fold less in the KO mouse. When KO and WT mice were injected intramuscularly with Na arsenate (4.16 mg As/kg body weight); tissues removed at 0.5, 1, 2, 4, 8, and 12 h after arsenate injection; and the arsenic species measured by HPLC-ICP-MS, the results indicated that the highest concentration of the recently discovered and very toxic MMA(III), a key biotransformant, was in the kidneys of both KO and WT mice. The highest concentration of DMA(III) was in the urinary bladder tissue for both the KO and WT mice. The MMA(V) reducing activity of the liver cytosol of KO mice was only 20% of that found in wild-type mice. There appears to be another enzyme(s) other than GST-O able to reduce arsenic(V) species but to a lesser extent. This and other studies suggest that each step of the biotransformation of inorganic arsenic has an alternative enzyme to biotransform the arsenic substrate.« less

[Exploration of Epigenetic Changes and DNA Methylation Markers Associated with Liver Tumors Induced by Inorganic Arsenite Exposure in Mice].

PubMed

Suzuki, Takehiro; Nohara, Keiko

2015-01-01

Naturally occurring inorganic arsenic is known to increase the risk of cancers of the skin and several other organs, including the urinary bladder, lung, and liver. Epidemiological studies have also indicated that gestational arsenic exposure is associated with increased incidences of cancers in several organs, including the bladder and liver, in adulthood. Previous studies have shown that epigenetic changes are involved in arsenic-induced carcinogenesis. Among epigenetic changes, DNA methylation changes that are specific to arsenic-induced tumors would be useful for distinguishing such tumors from tumors induced by other factors and for clarifying arsenic carcinogenesis. It has been reported that gestational arsenic exposure of C3H mice, whose males tend to spontaneously develop liver tumors, increases the incidence of tumors in the male offspring. Using the same experimental protocol, we found a number of regions where the DNA methylation status was altered in the liver tumors compared with the normal liver tissues by the methylated DNA immunoprecipitation (MeDIP)-CpG island microarray method. Among such regions, we demonstrated using real-time methylation-specific PCR and bisulfite sequencing that a gene body region of the oncogene Fosb underwent alteration in DNA methylation following gestational arsenic exposure. We also showed that the Fosb expression level significantly increased following gestational arsenic exposure. These findings suggest that the DNA methylation status of the Fosb region is implicated in tumor augmentation and can also be utilized for characterizing tumors induced by gestational arsenic exposure.

Creatinine, diet, micronutrients, and arsenic methylation in West Bengal, India.

PubMed

Basu, Arin; Mitra, Soma; Chung, Joyce; Guha Mazumder, D N; Ghosh, Nilima; Kalman, David; von Ehrenstein, Ondine S; Steinmaus, Craig; Liaw, Jane; Smith, Allan H

2011-09-01

Ingested inorganic arsenic (InAs) is methylated to monomethylated (MMA) and dimethylated metabolites (DMA). Methylation may have an important role in arsenic toxicity, because the monomethylated trivalent metabolite [MMA(III)] is highly toxic. We assessed the relationship of creatinine and nutrition--using dietary intake and blood concentrations of micronutrients--with arsenic metabolism, as reflected in the proportions of InAS, MMA, and DMA in urine, in the first study that incorporated both dietary and micronutrient data. We studied methylation patterns and nutritional factors in 405 persons who were selected from a cross-sectional survey of 7,638 people in an arsenic-exposed population in West Bengal, India. We assessed associations of urine creatinine and nutritional factors (19 dietary intake variables and 16 blood micronutrients) with arsenic metabolites in urine. Urinary creatinine had the strongest relationship with overall arsenic methylation to DMA. Those with the highest urinary creatinine concentrations had 7.2% more arsenic as DMA compared with those with low creatinine (p < 0.001). Animal fat intake had the strongest relationship with MMA% (highest tertile animal fat intake had 2.3% more arsenic as MMA, p < 0.001). Low serum selenium and low folate were also associated with increased MMA%. Urine creatinine concentration was the strongest biological marker of arsenic methylation efficiency, and therefore should not be used to adjust for urine concentration in arsenic studies. The new finding that animal fat intake has a positive relationship with MMA% warrants further assessment in other studies. Increased MMA% was also associated, to a lesser extent, with low serum selenium and folate.

Individual differences in arsenic metabolism and lung cancer in a case-control study in Cordoba, Argentina

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmaus, Craig, E-mail: craigs@berkeley.ed; School of Public Health, University of California, Berkeley, CA; Yuan Yan

2010-09-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer wasmore » also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p = 0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine {beta}-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.« less

The relationships between arsenic methylation and both skin lesions and hypertension caused by chronic exposure to arsenic in drinking water.

PubMed

Wei, Binggan; Yu, Jiangping; Wang, Jing; Yang, Linsheng; Li, Hairong; Kong, Chang; Xia, Yajuan; Wu, Kegong

2017-07-01

The associations between arsenic exposure, arsenic methylation, and the prevalence of skin lesions and hypertension are investigated. The results indicate that the HS (hypertension and skin lesions) group and the S (skin lesions) group have higher urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinous acid) and%MMA, and lower SMI (secondary arsenic methylation index) compared to the H (hypertension) and N (without both hypertension and skin lesions) groups. The arsenic content in water which caused H may be lower than that which caused HS and S. In addition, the odds ratios suggest that higher urinary concentrations of iAs and MMA, %iAs, %MMA and PMI elevate the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. However, higher%DMA and SMI, and lower%MMA increase the prevalence of both hypertension and skin lesions compared to that of only skin lesions. It can be concluded that skin lesions subjects have higher prevalence of hypertension. Hypertension subjects may have higher prevalence of skin lesions. Lower%DMA and SMI, higher%iAs, %MMA and PMI enhance the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. Moreover, iAs and MMA may have higher toxicity and lead to both hypertension and skin lesions than to only hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-10-01

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

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

PubMed

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

2017-08-01

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yuanyuan; Gao, Yanhui; Zhao, Lijun

2012-02-15

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68–45.71 mg-year) andmore » non-arsenicosis group without skin lesions, which further divided into low (0.00–1.06 mg-year), medium (1.37–3.55 mg-year), and high (4.26–48.13 mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity. -- Highlights: ► Three regions are selected as the areas affected by endemic arsenicosis of China. ► We first examine changes in serum TRX1 among individuals exposed to arsenic. ► A positive correlation was seen between serum TRX1 and total water arsenic intake. ► The same relationship was seen between serum TRX1 and urinary arsenic species. ► TRX as early biomarker of arsenicosis can be detected before skin lesions occur.« less

Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

PubMed Central

Argos, Maria; Chen, Lin; Jasmine, Farzana; Tong, Lin; Pierce, Brandon L.; Roy, Shantanu; Paul-Brutus, Rachelle; Gamble, Mary V.; Harper, Kristin N.; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Slavkovich, Vesna; Baron, John A.; Graziano, Joseph H.; Kibriya, Muhammad G.

2014-01-01

Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity. Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation. Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation. Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10–11) and blood arsenic concentrations (p = 1.48 × 10–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci. Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions. Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884 PMID:25325195

Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic.

PubMed

Molin, Marianne; Ulven, Stine Marie; Meltzer, Helle Margrete; Alexander, Jan

2015-01-01

Fish and seafood are main contributors of arsenic (As) in the diet. The dominating arsenical is the organoarsenical arsenobetaine (AB), found particularly in finfish. Algae, blue mussels and other filter feeders contain less AB, but more arsenosugars and relatively more inorganic arsenic (iAs), whereas fatty fish contain more arsenolipids. Other compounds present in smaller amounts in seafood include trimethylarsine oxide (TMAO), trimethylarsoniopropionate (TMAP), dimethylarsenate (DMA), methylarsenate (MA) and sulfur-containing arsenicals. The toxic and carcinogenic arsenical iAs is biotransformed in humans and excreted in urine as the carcinogens dimethylarsinate (DMA) and methylarsonate (MA), producing reactive intermediates in the process. Less is known about the biotransformation of organoarsenicals, but new insight indicates that bioconversion of arsenosugars and arsenolipids in seafood results in urinary excretion of DMA, possibly also producing reactive trivalent arsenic intermediates. Recent findings also indicate that the pre-systematic metabolism by colon microbiota play an important role for human metabolism of arsenicals. Processing of seafood may also result in transformation of arsenicals. Copyright © 2015 Elsevier GmbH. All rights reserved.

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

PubMed

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

2016-11-01

Chronic arsenic (As) exposure decreases adult and children's ability to methylate inorganic As (iAs); however, few studies have examined children's sex differences. We measured urinary concentrations of iAs, monomethylarsonic (MMA), and dimethylarsinic (DMA) acids, and calculated the primary (PMI: MMA/iAs) and secondary (SMI: DMA/MMA) methylation capacity indexes in 591 children 6-8 years in Torreón, Mexico. We determined iAs, MMA, and DMA by hydride generation cryotrapping AAS. Lineal regression models estimated associations between methylation capacity and total As (TAs) or iAs. Interactions with sex were tested at p<0.10. Boys had significantly higher TAs levels, (58.4µg/L) than girls (46.2µg/L). We observed negative associations between TAs and PMI (β=-0.039; p<0.18) and SMI (β=-0.08; p=0.002) with significant sex differences; PMI reduction was significant in boys (β=-0.09; p=0.02) but not in girls (β=0.021; p=0.63), p for interaction=0.06. In contrast, SMI reduction was significantly more pronounced in girls. Furthermore, negative associations PMI (β=-0.19; p<0.001) and SMI (β=-0.35; p<0.001) were a function of urinary iAs levels, independently of TAs; however, the reduction in PMI was more pronounced in boys (β=-0.24; p<0.001; girls β=-0.15; p<0.001), p for interaction=0.04. A significant negative association was observed between SMI and iAs levels without significant sex differences. TAs and iAs associations with metabolite percentages were in good agreement with those observed with methylation indexes. Our results suggest that iAs plays an important role in reducing As methylation ability and that significant sex differences are present in As metabolism. These differences merit further investigation to confirm our findings and their potential implications for arsenic toxicity in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Arsenic Metabolism in Children Differs From That in Adults.

PubMed

Skröder Löveborn, Helena; Kippler, Maria; Lu, Ying; Ahmed, Sultan; Kuehnelt, Doris; Raqib, Rubhana; Vahter, Marie

2016-07-01

Arsenic toxicity in adults is associated with methylation efficiency, influenced by factors such as gender, genetics, and nutrition. The aim of this study was to evaluate influencing factors for arsenic metabolism in children. For 488 children (9 years), whose mothers participated in a study on arsenic exposure during pregnancy (nested into the MINIMat trial) in rural Bangladesh, we measured urinary concentrations of inorganic arsenic (iAs) and its metabolites methylarsonic acid (MMA) and dimethylarsinic acid (DMA) by HPLC-HG-ICPMS. Methylation efficiency was assessed by relative amounts (%) of the metabolites. We evaluated the impact of factors such as maternal urinary metabolite pattern, arsenic exposure, gender, socioeconomic status, season of sampling, and nutritional factors, including erythrocyte selenium (Ery-Se), and plasma folate and vitamin B12.Children had higher %DMA and lower %iAs in urine compared to their mothers, unrelated to their lower exposure [median urinary arsenic (U-As) 53 vs 78 µg/l]. Surprisingly, selenium status (Ery-Se) was strongly associated with children's arsenic methylation; an increase in Ery-Se from the 5-95th percentile was associated with: +1.8 percentage points (pp) for %iAs (P  =  .001), +1.4 pp for %MMA (P  =  .003), and -3.2 pp for %DMA (P  <  .001). Despite this, Ery-Se was positively associated with U-As (5-95th percentile: +41 µg/l, P  =  .026). As expected, plasma folate was inversely associated with %iAs (5-95th percentile: -1.9 pp, P  =  .001) and positively associated with %DMA (5-95th percentile: +2.2 pp, P  =  .008). Children methylated arsenic more efficiently than their mothers. Also influencing factors, mainly selenium and folate, differed. This warrants further research. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Arsenic Methylation and Lung and Bladder Cancer in a Case-control Study in Northern Chile

PubMed Central

Melak, Dawit; Ferreccio, Catterina; Kalman, David; Parra, Roxana; Acevedo, Johanna; Pérez, Liliana; Cortés, Sandra; Smith, Allan H; Yuan, Yan; Liaw, Jane; Steinmaus, Craig

2014-01-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200 μg/L (median=60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. PMID:24296302

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.

The impact of a rice based diet on urinary arsenic.

PubMed

Cascio, Claudia; Raab, Andrea; Jenkins, Richard O; Feldmann, Joerg; Meharg, Andrew A; Haris, Parvez I

2011-02-01

Rice is elevated in arsenic (As) compared to other staple grains. The Bangladeshi community living in the United Kingdom (UK) has a ca. 30-fold higher consumption of rice than white Caucasians. In order to assess the impact of this difference in rice consumption, urinary arsenicals of 49 volunteers in the UK (Bangladeshi n = 37; white Caucasians n = 12) were monitored along with dietary habits. Total urinary arsenic (As(t)) and speciation analysis for dimethylarsinic acid (DMA), monomethylarsonic acid (MA) and inorganic arsenic (iAs) was conducted. Although no significant difference was found for As(t) (median: Bangladeshis 28.4 µg L(-1)) and white Caucasians (20.6 µg L(-1)), the sum of medians of DMA, MA and iAs for the Bangladeshi group was found to be over 3-fold higher (17.9 µg L(-1)) than for the Caucasians (3.50 µg L(-1)). Urinary DMA was significantly higher (p < 0.001) in the UK Bangladeshis (median: 16.9 µg DMA L(-1)) than in the white Caucasians (3.16 µg DMA L(-1)) as well as iAs (p < 0.001) with a median of 0.630 µg iAs L(-1) for Bangladeshi and 0.250 µg iAs L(-1) for Caucasians. Cationic compounds were significantly lower in the Bangladeshis (2.93 µg L(-1)) than in Caucasians (14.9 µg L(-1)). The higher DMA and iAs levels in the Bangladeshis are mainly the result of higher rice consumption: arsenic is speciated in rice as both iAs and DMA, and iAs can be metabolized, through MA, to DMA by humans. This study shows that a higher dietary intake of DMA alters the DMA/MA ratio in urine. Consequently, DMA/MA ratio as an indication of methylation capacity in populations consuming large quantities of rice should be applied with caution since variation in the quantity and type of rice eaten may alter this ratio.

Biological monitoring of occupational exposure to inorganic arsenic

PubMed Central

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

1999-01-01

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.   PMID:10658539

Biological monitoring of occupational exposure to inorganic arsenic.

PubMed

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

1999-12-01

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

TISSUE DISTRIBUTION AND URINARY EXCRETION OF INORGANIC ARSENIC AND ITS METHYLATED METABOLITES IN C57BL/6 MICE FOLLOWING SUBCHRONIC EXPOSURE TO ARSENATE (ASV) IN DRINKING WATER

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for AsV because its trivalent metabolites hav...

Tissue Distribution And Urinary Excretion Of Inorganic Arsenic And Its Methylated Metabolites In C57BL6 Mice Following Subchronic Exposure To Arsenate In Drinking Water

EPA Science Inventory

The relationship of exposure and tissue concentration of parent chemical and metabolites over prolonged exposure is a critical issue for chronic toxicities mediated by metabolite(s) rather than parent chemical alone. This is an issue for As^V because its trivalent meta...

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agusa, Tetsuro; Center for Marine Environmental Studies; Iwata, Hisato, E-mail: iwatah@agr.ehime-u.ac.j

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As{sup V} thanmore » the wild homo type. Higher percentage of DMA{sup V} in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As{sup V} to As{sup III}. Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.« less

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam.

PubMed

Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Minh, Tu Binh; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke

2010-02-01

To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST omega1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST omega2 (GSTO2) Asn142Asp, GST pi1 (GSTP1) Ile105Val, GST mu1 (GSTM1) wild/null, and GST theta1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As(V) than the wild homo type. Higher percentage of DMA(V) in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As(V) to As(III). Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population. Copyright 2009 Elsevier Inc. All rights reserved.

Health Risk Assessment and Urinary Excretion of Children Exposed to Arsenic through Drinking Water and Soils in Sonora, Mexico.

PubMed

García-Rico, Leticia; Meza-Figueroa, Diana; Jay Gandolfi, A; Del Rivero, Carlos Ibañez; Martínez-Cinco, Marco A; Meza-Montenegro, Maria M

2018-05-02

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7 μg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27 mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7 μg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Environmental exposure to arsenic and chromium in an industrial area.

PubMed

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

2017-04-01

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

Low-to-Moderate Arsenic Exposure and Respiratory Health in American Indian Communities.

PubMed

Powers, Martha; Sanchez, Tiffany R; Grau-Perez, Maria; Yeh, Fawn; Francesconi, Kevin; Goessler, Walter; George, Christine M; Heaney, Christopher; Best, Lyle G; Umans, Jason; Brown, Robert H; Navas-Acien, Ana

2018-04-01

Exposure to inorganic arsenic, through drinking naturally-contaminated water, is an established cause of lung cancer. Evidence on the impact of arsenic exposure on lung function, however, is less conclusive. The evidence available, mostly from populations exposed to water arsenic levels >100 μg/L, suggests that arsenic exposure is associated with lower lung function. Prospective studies and studies examining low-to-moderate levels of water arsenic exposure (<50 μg/L) the level relevant for U.S. populations, are very limited. We evaluated the association between chronic low-to-moderate arsenic exposure with lung function and disease in an American Indian population. The Strong Heart Study is a multicenter prospective study of cardiovascular disease and its risk factors among American Indian adults. The present analysis, in 2,166 adults, used urinary arsenic measurements at baseline (1989-1991) and lung symptoms and function assessment by standardized spirometry at the second examination (1993-1995). We evaluated associations between arsenic exposure and airflow obstruction, defined as ratio of forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity (FVC) of less than 0.70, and restrictive pattern, defined as FEV 1 /FVC ratio greater than 0.70 and FVC less than 80% predicted; respiratory symptoms; and self-reported physician diagnosis of nonmalignant respiratory disease. The prevalence of airflow obstruction between 1993 and 1995 was 21.4% (463/2,166); restrictive pattern was 14.5% (314/2,166). Median urinary arsenic concentrations were higher in participants with airflow obstruction (11.0 μg/g creatinine) compared to those without obstruction (9.8 μg/g creatinine), and higher in those with restrictive pattern (12.0 μg/g) compared to those without restrictive pattern (9.4 μg/g). The odds ratio (95% confidence interval) for obstructive and restrictive patterns comparing the 75th to 25th percentile of arsenic was 1.13 (0.96-1.32) and 1.27 (1.01-1.60), respectively, after adjustment for age, sex, education, study site, smoking status, smoking pack-year, estimated glomerular filtration rate, tuberculosis, and body mass index. Emphysema, cough 4-6 times a day, phlegm, and stopping for breath were also positively associated with arsenic. In this American Indian population, exposure to low-to-moderate levels of inorganic arsenic, as measured in urine, was positively associated with restrictive pattern as measured by spirometry, self-reported emphysema diagnosis, self-reported shortness of breath, and more frequent cough and phlegm among those with cough, independent of smoking status. These findings suggest that low-to-moderate arsenic exposure can contribute to nonmalignant lung disease, and may be associated with restrictive lung disease.

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ameer, Syeda Shegufta

Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by themore » urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for molecular responses in blood. • Arsenic is associated with decreased gene expression and increased DNA methylation. • Arsenic related pathways differed to some extent due to arsenic metabolism efficiency.« less

Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study

PubMed Central

Newman, Jonathan D.; Navas-Acien, Ana; Kuo, Chin-Chi; Guallar, Eliseo; Howard, Barbara V.; Fabsitz, Richard R.; Devereux, Richard B.; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Best, Lyle T.; Tellez-Plaza, Maria

2016-01-01

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45–74 years in 1989–1991 were reexamined in 1993–1995 and 1997–1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure. PMID:27810857

Characterization of intracellular inclusions in the urothelium of mice exposed to inorganic arsenic.

PubMed

Dodmane, Puttappa R; Arnold, Lora L; Muirhead, David E; Suzuki, Shugo; Yokohira, Masanao; Pennington, Karen L; Dave, Bhavana J; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2014-01-01

Inorganic arsenic (iAs) is a known human carcinogen at high exposures, increasing the incidences of urinary bladder, skin, and lung cancers. In most mammalian species, ingested iAs is excreted mainly through urine primarily as dimethylarsinic acid (DMA(V)). In wild-type (WT) mice, iAs, DMA(V), and dimethylarsinous acid (DMA(III)) exposures induce formation of intramitochondrial urothelial inclusions. Arsenite (iAs(III)) also induced intranuclear inclusions in arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice. The arsenic-induced formation of inclusions in the mouse urothelium was dose and time dependent. The inclusions do not occur in iAs-treated rats and do not appear to be related to arsenic-induced urothelial cytotoxicity. Similar inclusions in exfoliated urothelial cells from humans exposed to iAs have been incorrectly identified as micronuclei. We have characterized the urothelial inclusions using transmission electron microscopy (TEM), DNA-specific 4',6-diamidino-2-phenylindole (DAPI), and non-DNA-specific Giemsa staining and determined the arsenical content. The mouse inclusions stained with Giemsa but not with the DAPI stain. Analysis of urothelial mitochondrial- and nuclear-enriched fractions isolated from WT (C57BL/6) and As3mt KO mice exposed to arsenate (iAs(V)) for 4 weeks showed higher levels of iAs(V) in the treated groups. iAs(III) was the major arsenical present in the enriched nuclear fraction from iAs(V)-treated As3mt KO mice. In conclusion, the urothelial cell inclusions induced by arsenicals appear to serve as a detoxifying sequestration mechanism similar to other metals, and they do not represent micronuclei.

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

PubMed

García-Rico, Leticia; Tejeda-Valenzuela, Lourdes

2013-07-01

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

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

PubMed

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

2014-01-01

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

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. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiang, Chien-I; Huang, Ya-Li; Chen, Wei-Jen

The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Glnmore » by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on UC.« less

Transplacental Arsenic Carcinogenesis in Mice

PubMed Central

Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

2007-01-01

Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from day 8 to 18 of gestation, and the offspring were observed for up to two years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans and investigating a potential transplacental component of the human carcinogenic response to arsenic should be a research priority. PMID:17306315

Environmental arsenic exposure of schoolchildren in a former tin mining and smelting community of southern Thailand.

PubMed

Vitayavirasak, Banjong; Rakwong, Kittiya; Chatchawej, Warangkana

2005-01-01

Risk behavior and environmental sources of exposure to arsenic for 10-year-old schoolchildren were studied in a high exposure area and a low exposure area of Ron Phibun Subdistrict, Ron Phibun District, Nakhon Si Thammarat Province and compared to those in a control area. Arsenic concentrations of surface soil, ambient air and drinking water to which subjects in the high exposure group, the low exposure group and the control group were exposed, were significantly different (p < 0.05). Similarly, urinary concentrations of total arsenic and the sum of inorganic arsenic and its metabolites were significantly higher in the study groups than the control group. The arsenic content of locally grown agricultural produce was small with the exception of freshwater snails (Sinotaia ingallsiana). Drinking water and surface soil were found to be the main sources of exposure. The exposure was mediated by the subjects' risk behavior, such as playing with soil and no hand-washing before eating. The estimated cancer risk from arsenic for the schoolchildren in the study area was between 10(-5)-10(-6) which meant that their risk of developing cancer was probable. Measures to reduce the cancer risk are recommended.

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

PubMed

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

2017-05-01

Background: Exposure to inorganic arsenic (InAs) has been documented as a risk factor for lung cancer. This study examined the association between InAs exposure, its metabolism, and lung cancer occurrence. Methods: We followed 1,300 residents from an arseniasis area in Taiwan, determined urinary InAs metabolites, and identified 39 lung cancer cases. Cox proportional hazards model was performed. Results: The results demonstrated that participants with either the primary methylation index [monomethylarsonic acid (MMA)/InAs] or the secondary methylation index [dimethylarsenic acid (DMA)/MMA] lower than their respective median values were at a higher risk of lung cancer (HRs from 3.41 to 4.66) than those with high methylation capacity. The incidence density of lung cancer increased from 79.9/100,000 (year -1 ) to 467.4/100,000 (year -1 ) for residents with low methylation capacity and from 0 to 158.5/100,000 (year -1 ) for residents with high methylation capacity when the arsenic exposure dose increased from 2 to 10 ppb to ≥200 ppb, respectively. The analyses revealed a dose-response relationship between lung cancer occurrence and increasing arsenic concentrations in drinking water as well as cumulative arsenic exposure (monotonic trend test; P < 0.05 and P < 0.05, respectively) among the residents with low methylation capacity. The relationship between arsenic exposure and lung cancer among high methylators was not statistically significant. Conclusions: Hypomethylation responses to InAs exposure may dose dependently increase lung cancer occurrence. Impact: The high-risk characteristics observed among those exposed should be considered in future preventive medicine and research on arsenic carcinogenesis. Cancer Epidemiol Biomarkers Prev; 26(5); 756-61. ©2016 AACR . ©2016 American Association for Cancer Research.

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melak, Dawit; Ferreccio, Catterina; Kalman, David

2014-01-15

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung andmore » 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.« less

Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population.

PubMed

de la Rosa, Rosemarie; Steinmaus, Craig; Akers, Nicholas K; Conde, Lucia; Ferreccio, Catterina; Kalman, David; Zhang, Kevin R; Skibola, Christine F; Smith, Allan H; Zhang, Luoping; Smith, Martyn T

2017-07-01

Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

78 FR 42086 - Draft Guidance for Industry on Arsenic in Apple Juice: Action Level; Supporting Document for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-15

... Level for Arsenic in Apple Juice; A Quantitative Assessment of Inorganic Arsenic in Apple Juice... Arsenic in Apple Juice'' (the draft supporting document) and ``A Quantitative Assessment of Inorganic... document entitled ``A Quantitative Assessment of Inorganic Arsenic in Apple Juice.'' The draft guidance...

PATHWAY OF INORGANIC ARSENIC METABOLISM

EPA Science Inventory

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

The Association of Urine Arsenic with Prevalent and Incident Chronic Kidney Disease: Evidence from the Strong Heart Study

PubMed Central

Zheng, Laura Y.; Umans, Jason G.; Yeh, Fawn; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K; Bandeen-Roche, Karen; Guallar, Eliseo; Howard, Barbara V.; Weaver, Virginia M.; Navas-Acien, Ana

2016-01-01

Background Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults. Methods We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study (SHS) in 3,851 adults aged 45–74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as eGFR≤60 mL/min/1.73m2, kidney transplant or dialysis. Results CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted OR (95% CI) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR 0.4 (0.3, 0.4)). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR 3.8 and 1.8). The adjusted HR of incident CKD for an IQR in ΣAs was 1.2 (1.03, 1.41). The corresponding HR for inorganic arsenic, monomethylarsonate and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3) and 1.2 (1.0, 1.4). Conclusions The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relationship between arsenic and kidney disease development. PMID:25929811

Transient and permanent changes in DNA methylation patterns in inorganic arsenic-mediated epithelial-to-mesenchymal transition

PubMed Central

Eckstein, Meredith; Rea, Matthew; Fondufe-Mittendorf, Yvonne N.

2017-01-01

Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic changes to cells correlate with changes in chromatin structure and gene expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesenchymal transition and the impact of epigenetic alterations in this process are limited. In this study we used high-resolution microarray analysis to measure the changes in DNA methylation in cells undergoing inorganic arsenic-induced epithelial-to-mesenchymal transition, and on the reversal of this process, after removal of the inorganic arsenic exposure. We found that cells exposed to chronic, low-dose inorganic arsenic exposure showed 30,530 sites were differentially methylated, and with inorganic arsenic withdrawal several differential methylated sites were reversed, albeit not completely. Furthermore, these changes in DNA methylation mainly correlated with changes in gene expression at most sites tested but not at all. This study suggests that DNA methylation changes on gene expression are not clear-cut and provide a platform to begin to uncover the relationship between DNA methylation and gene expression, specifically within the context of inorganic arsenic treatment. PMID:28336213

Application of ICP-MS and HPLC-ICP-MS for diagnosis and therapy of a severe intoxication with hexavalent chromium and inorganic arsenic.

PubMed

Heitland, Peter; Blohm, Martin; Breuer, Christian; Brinkert, Florian; Achilles, Eike Gert; Pukite, Ieva; Köster, Helmut Dietrich

2017-05-01

ICP-MS and HPLC-ICP-MS were applied for diagnosis and therapeutic monitoring in a severe intoxication with a liquid containing hexavalent chromium (Cr(VI)) and inorganic arsenic (iAs). In this rare case a liver transplantation of was considered as the only chance of survival. We developed and applied methods for the determination of Cr(VI) in erythrocytes and total chromium (Cr) and arsenic (As) in blood, plasma, urine and liver tissue by ICP-MS. Exposure to iAs was diagnosed by determination of iAs species and their metabolites in urine by anion exchange HPLC-ICP-MS. Three days after ingestion of the liquid the total Cr concentrations were 2180 and 1070μg/L in whole blood and plasma, respectively, and 4540μg/L Cr(VI) in erythrocytes. The arsenic concentration in blood was 206μg/L. The urinary As species concentrations were <0.5, 109, 115, 154 and 126μg/L for arsenobetaine, As(III), As(V), methylarsonate (V) and dimethylarsinate (V), respectively. Total Cr and As concentrations in the explanted liver were 11.7 and 0.9mg/kg, respectively. Further analytical results of this case study are tabulated and provide valuable data for physicians and toxicologists. Copyright © 2017. Published by Elsevier GmbH.

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.

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

EPA Science Inventory

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

Blood Pressure Changes in Relation to Arsenic Exposure in a U.S. Pregnancy Cohort

PubMed Central

Farzan, Shohreh F.; Chen, Yu; Wu, Fen; Jiang, Jieying; Liu, Mengling; Baker, Emily; Korrick, Susan A.

2015-01-01

Background Inorganic arsenic exposure has been related to the risk of increased blood pressure based largely on cross-sectional studies conducted in highly exposed populations. Pregnancy is a period of particular vulnerability to environmental insults. However, little is known about the cardiovascular impacts of arsenic exposure during pregnancy. Objectives We evaluated the association between prenatal arsenic exposure and maternal blood pressure over the course of pregnancy in a U.S. population. Methods The New Hampshire Birth Cohort Study is an ongoing prospective cohort study in which > 10% of participant household wells exceed the arsenic maximum contaminant level of 10 μg/L established by the U.S. EPA. Total urinary arsenic measured at 24–28 weeks gestation was measured and used as a biomarker of exposure during pregnancy in 514 pregnant women, 18–45 years of age, who used a private well in their household. Outcomes were repeated blood pressure measurements (systolic, diastolic, and pulse pressure) recorded during pregnancy. Results Using linear mixed effects models, we estimated that, on average, each 5-μg/L increase in urinary arsenic was associated with a 0.15-mmHg (95% CI: 0.02, 0.29; p = 0.022) increase in systolic blood pressure per month and a 0.14-mmHg (95% CI: 0.02, 0.25; p = 0.021) increase in pulse pressure per month over the course of pregnancy. Conclusions In our U.S. cohort of pregnant women, arsenic exposure was associated with greater increases in blood pressure over the course of pregnancy. These findings may have important implications because even modest increases in blood pressure impact cardiovascular disease risk. Citation Farzan SF, Chen Y, Wu F, Jiang J, Liu M, Baker E, Korrick SA, Karagas MR. 2015. Blood pressure changes in relation to arsenic exposure in a U.S. pregnancy cohort. Environ Health Perspect 123:999–1006; http://dx.doi.org/10.1289/ehp.1408472 PMID:25793356

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Songbo; Wu, Jie; Li, Yuanyuan

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, whilemore » 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.« less

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh.

PubMed

Rodrigues, Ema G; Kile, Molly; Hoffman, Elaine; Quamruzzaman, Quazi; Rahman, Mahmuder; Mahiuddin, Golam; Hsueh, Yumei; Christiani, David C

2012-05-01

We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

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 ...

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-Hernández A, De Vizcaya-Ruíz A, Del Razo LM. 2013. Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic. Environ Health Perspect 121:1090–1096; http://dx.doi.org/10.1289/ehp.1205994 PMID:23757599

Urinary Arsenic Metabolites in Children and Adults Exposed to Arsenic in Drinking Water in Inner Mongolia, China

PubMed Central

Sun, Guifan; Xu, Yuanyuan; Li, Xin; Jin, Yaping; Li, Bing; Sun, Xiance

2007-01-01

Background We report the concentrations and distributions of urinary arsenic (As) metabolites in 233 residents exposed to 20, 90, or 160 μg/L inorganic arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia, China, that formed one control and two exposed groups. Methods We used hydride generation-atomic absorption spectrometry (HGAAS) to determine iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Results The concentrations of each urinary As species in the two exposed groups were significantly higher than in the control group for both children and adults. Both children and adults in exposed groups had higher percent iAs and MMA and lower percent DMA, and low primary and secondary methylation indices (PMI and SMI, respectively) than those in the control group. However, children showed significant increases in percent DMA and the SMI as well as decreases in the percent MMA when the iAs exposure level increased from 90 to 160 μg/L. In addition, children in the two exposed groups showed lower percent MMA but higher percent DMA and higher SMI than adults in the same exposed group. No significant differences in As metabolite concentrations and distributions were found between males and females in each group. A significant correlation was also found in the SMI between 11 pairs of children and their mothers from the 160-μg/L–exposed group. Conclusions Children had higher a capacity for secondary methylation of As than adults when exposed to the same concentrations of iAs in drinking water. Exposure to As may increase the capacity for methylation in children to some extent. PMID:17450238

Urinary and dietary analysis of 18,470 bangladeshis reveal a correlation of rice consumption with arsenic exposure and toxicity.

PubMed

Melkonian, Stephanie; Argos, Maria; Hall, Megan N; Chen, Yu; Parvez, Faruque; Pierce, Brandon; Cao, Hongyuan; Aschebrook-Kilfoy, Briseis; Ahmed, Alauddin; Islam, Tariqul; Slavcovich, Vesna; Gamble, Mary; Haris, Parvez I; Graziano, Joseph H; Ahsan, Habibul

2013-01-01

We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (β=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (β=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. This study suggests that rice intake may be a source of arsenic exposure beyond drinking water.

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

PubMed Central

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

2012-01-01

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

Dimethylarsinic acid in drinking water changed the morphology of urinary bladder but not the expression of DNA repair genes of bladder transitional epithelium in F344 rats.

PubMed

Wang, Amy; Wolf, Douglas C; Sen, Banalata; Knapp, Geremy W; Holladay, Steven D; Huckle, William R; Caceci, Thomas; Robertson, John L

2009-06-01

Inorganic arsenic increases urinary bladder transitional cell carcinoma in humans. In F344 rats, dimethylarsinic acid (DMA[V]) increases transitional cell carcinoma. Arsenic-induced inhibition of DNA repair has been reported in cultured cell lines and in lymphocytes of arsenic-exposed humans, but it has not been studied in urinary bladder. Should inhibition of DNA damage repair in transitional epithelium occur, it may contribute to carcinogenesis or cocarcinogenesis. We investigated morphology and expression of DNA repair genes in F344 rat transitional cells following up to 100 ppm DMA(V) in drinking water for four weeks. Mitochondria were very sensitive to DMA(V), and swollen mitochondria appeared to be the main source of vacuoles in the transitional epithelium. Real-time reverse transcriptase polymerase chain reaction (Real-Time RT PCR) showed the mRNA levels of tested DNA repair genes, ataxia telangectasia mutant (ATM), X-ray repair cross-complementing group 1 (XRCC1), excision repair cross-complementing group 3/xeroderma pigmentosum B (ERCC3/XPB), and DNA polymerase beta (Polbeta), were not altered by DMA(V). These data suggested that either DMA(V) does not affect DNA repair in the bladder or DMA(V) affects DNA repair without affecting baseline mRNA levels of repair genes. The possibility remains that DMA(V) may lower damage-induced increases in repair gene expression or cause post-translational modification of repair enzymes.

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,...

Transient and permanent changes in DNA methylation patterns in inorganic arsenic-mediated epithelial-to-mesenchymal transition.

PubMed

Eckstein, Meredith; Rea, Matthew; Fondufe-Mittendorf, Yvonne N

2017-09-15

Chronic low dose inorganic arsenic exposure causes cells to take on an epithelial-to-mesenchymal phenotype, which is a crucial process in carcinogenesis. Inorganic arsenic is not a mutagen and thus epigenetic alterations have been implicated in this process. Indeed, during the epithelial-to-mesenchymal transition, morphologic changes to cells correlate with changes in chromatin structure and gene expression, ultimately driving this process. However, studies on the effects of inorganic arsenic exposure/withdrawal on the epithelial-to-mesenchymal transition and the impact of epigenetic alterations in this process are limited. In this study we used high-resolution microarray analysis to measure the changes in DNA methylation in cells undergoing inorganic arsenic-induced epithelial-to-mesenchymal transition, and on the reversal of this process, after removal of the inorganic arsenic exposure. We found that cells exposed to chronic, low-dose inorganic arsenic exposure showed 30,530 sites were differentially methylated, and with inorganic arsenic withdrawal several differential methylated sites were reversed, albeit not completely. Furthermore, these changes in DNA methylation mainly correlated with changes in gene expression at most sites tested but not at all. This study suggests that DNA methylation changes on gene expression are not clear-cut and provide a platform to begin to uncover the relationship between DNA methylation and gene expression, specifically within the context of inorganic arsenic treatment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Total and inorganic arsenic in fish samples from Norwegian waters.

PubMed

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

2012-01-01

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

Human arsenic poisoning issues in central-east Indian locations: biomarkers and biochemical monitoring.

PubMed

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

2007-03-01

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

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

PubMed

Ruangwises, Nongluck; Saipan, Piyawat; Ruangwises, Suthep

2012-12-01

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

Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of seafood.

PubMed

Molin, M; Ulven, S M; Dahl, L; Telle-Hansen, V H; Holck, M; Skjegstad, G; Ledsaak, O; Sloth, J J; Goessler, W; Oshaug, A; Alexander, J; Fliegel, D; Ydersbond, T A; Meltzer, H M

2012-01-01

Seafood is the predominant food source of several organoarsenic compounds. Some seafood species, like crustaceans and seaweed, also contain inorganic arsenic (iAs), a well-known toxicant. It is unclear whether human biotransformation of ingested organoarsenicals from seafood result in formation of arsenicals of health concern. The present controlled dietary study examined the urinary excretion of arsenic compounds (total arsenic (tAs), iAs, AB (arsenobetaine), dimethylarsinate (DMA) and methylarsonate (MA)) following ingestion of a single test meal of seafood (cod, 780 μg tAs, farmed salmon, 290 μg tAs or blue mussel, 690 μg tAs or potato (control, 110 μg tAs)) in 38 volunteers. The amount of ingested tAs excreted via the urine within 0-72 h varied significantly among the groups: Cod, 74% (52-92%), salmon 56% (46-82%), blue mussel 49% (37-78%), control 45% (30-60%). The estimated total urinary excretion of AB was higher than the amount of ingested AB in the blue mussel group (112%) and also ingestion of cod seemed to result in more AB, indicating possible endogenous formation of AB from other organoarsenicals. Excretion of iAs was lower than ingested (13-22% of the ingested iAs was excreted in the different groups). Although the ingested amount of iAs+DMA+MA was low for all seafood groups (1.2-4.5% of tAs ingested), the urinary DMA excretion was high in the blue mussel and salmon groups, counting for 25% and 11% of the excreted tAs respectively. In conclusion our data indicate a possible formation of AB as a result of biotransformation of other organic arsenicals. The considerable amount of DMA excreted is probably not only due to methylation of ingested iAs, but due to biotransformation of organoarsenicals making it an inappropriate biomarker of iAs exposure in populations with a high seafood intake. Copyright © 2011 Elsevier Inc. All rights reserved.

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

PubMed

Hernández-Zavala, Araceli; Valenzuela, Olga L; Matousek, Tomás; Drobná, Zuzana; Dĕdina, Jirí; García-Vargas, Gonzalo G; Thomas, David J; Del Razo, Luz M; Stýblo, Miroslav

2008-12-01

The concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues. In this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans. Exfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12-17 pg As for analysis of As species in BECs. All urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine. These results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs.

Urinary and Dietary Analysis of 18,470 Bangladeshis Reveal a Correlation of Rice Consumption with Arsenic Exposure and Toxicity

PubMed Central

Melkonian, Stephanie; Argos, Maria; Hall, Megan N.; Chen, Yu; Parvez, Faruque; Pierce, Brandon; Cao, Hongyuan; Aschebrook-Kilfoy, Briseis; Ahmed, Alauddin; Islam, Tariqul; Slavcovich, Vesna; Gamble, Mary; Haris, Parvez I.; Graziano, Joseph H.; Ahsan, Habibul

2013-01-01

Background We utilized data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, to evaluate the association of steamed rice consumption with urinary total arsenic concentration and arsenical skin lesions in the overall study cohort (N=18,470) and in a subset with available urinary arsenic metabolite data (N=4,517). Methods General linear models with standardized beta coefficients were used to estimate associations between steamed rice consumption and urinary total arsenic concentration and urinary arsenic metabolites. Logistic regression models were used to estimate prevalence odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations between rice intake and prevalent skin lesions at baseline. Discrete time hazard models were used to estimate discrete time (HRs) ratios and their 95% CIs for the associations between rice intake and incident skin lesions. Results Steamed rice consumption was positively associated with creatinine-adjusted urinary total arsenic (β=0.041, 95% CI: 0.032-0.051) and urinary total arsenic with statistical adjustment for creatinine in the model (β=0.043, 95% CI: 0.032-0.053). Additionally, we observed a significant trend in skin lesion prevalence (P-trend=0.007) and a moderate trend in skin lesion incidence (P-trend=0.07) associated with increased intake of steamed rice. Conclusions This study suggests that rice intake may be a source of arsenic exposure beyond drinking water. PMID:24260455

The factors influencing urinary arsenic excretion and metabolism of workers in steel and iron smelting foundry.

PubMed

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

2014-01-01

In order to evaluate the degree of arsenic (As) exposure and the factors influencing urinary As excretion and metabolism, 192 workers from a steel and iron smelting plant, with different type of work in production such as roller, steel smelting, iron smelting and metallic charge preparation, were recruited. Information about characteristics of each subject was obtained by questionnaire and inorganic As (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were determined. The results showed that steel smelters had significantly higher concentrations of DMA and total As (TAs) than rollers and metallic charge preparation workers, and iron and steel smelters had a higher value of primary methylation index and lower proportion of the iAs (iAs%) than rollers and metallic charge preparation workers. In steel smelters, urinary As level exceeded the biological exposure index (BEI) limit for urinary As of 35 μg/l by 65.52%, and higher than metallic charge preparation workers (35.14%). The individuals consumed seafood in recent 3 days had a higher TAs than the individuals without seafood consumption. Multivariate logistic regression analysis showed that different jobs, taken Chinese medicine of bezoar and seafood consumption in recent 3 days were significantly associated with urinary TAs exceeded BEI limit value 35 μg/l. Our results suggest that workers in steel and iron smelting plant had a lower level of As exposure, and seafood consumption and taking Chinese medicine of bezoar also could increase the risk of urinary TAs exceeded BEI limit value.

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...

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...

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

PubMed

Lin, M C; Liao, C M

2008-02-01

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

Arsenic (+3 Oxidation State) Methyltransferase and the Methylation of Arsenicals

PubMed Central

Thomas, David J.; Li, Jiaxin; Waters, Stephen B.; Xing, Weibing; Adair, Blakely M.; Drobna, Zuzana; Devesa, Vicenta; Styblo, Miroslav

2008-01-01

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 process. Intermediates and products formed in this pathway may be more reactive and toxic than inorganic arsenic. Like all metabolic pathways, understanding the pathway for arsenic methylation involves identification of each individual step in the process and the characterization of the molecules which participate in each step. Among several arsenic methyltransferases that have been identified, arsenic (+3 oxidation state) methyltransferase is the one best characterized at the genetic and functional levels. This review focuses on phylogenetic relationships in the deuterostomal lineage for this enzyme and on the relation between genotype for arsenic (+3 oxidation state) methyltransferase and phenotype for conversion of inorganic arsenic to methylated metabolites. Two conceptual models for function of arsenic (+3 oxidation state) methyltransferase which posit different roles for cellular reductants in the conversion of inorganic arsenic to methylated metabolites are compared. Although each model accurately represents some aspects of enzyme’s role in the pathway for arsenic methylation, neither model is a fully satisfactory representation of all the steps in this metabolic pathway. Additional information on the structure and function of the enzyme will be needed to develop a more comprehensive model for this pathway. PMID:17202581

Exposure assessment of the population in Poland to the toxic effects of arsenic compounds present in rice and rice based products

PubMed

Mania, Monika; Rebeniak, Małgorzata; Szynal, Tomasz; Starska, Krystyna; Wojciechowska-Mazurek, Maria; Postupolski, Jacek

Rice is a staple food for many people in the world and an important ingredient for production of food for infants and young children. According to European Food Safety Authority (EFSA), cereals, primarily rice and rice products, are an important source of human exposure to inorganic arsenic, which has been classified by the International Agency for Research on Cancer (IARC) as group I carcinogen. Arsenic is present in rice and rice products mainly as an inorganic form being more toxic than organic compounds The aim of the study was to determine the total and inorganic arsenic content in rice, rice-based products including food for infants and young children available on the market in Poland and thus to estimate consumer exposure to inorganic arsenic from these groups of foodstuffs A total of 62 samples of rice and rice products from trade, including a group of rice products for infants and young children, were tested. Contents of total and inorganic arsenic were determined by using hydride generation atomic absorption spectrometry (HGAAS), after dry mineralization of samples and reduction of arsenic to arsenic hydride with sodium borohydride. To extract the inorganic arsenic forms, the samples were subjected to hydrolysis in concentrated HCl and then reduced in the presence of hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of different groups of populations (adults and children), was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL05) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 µg/kg body weight (b.w.) per day) Mean content of total and inorganic arsenic in investigated rice samples was 0.12 mg/kg (median: 0.09 mg/kg; 90th percentile 0.22 mg/kg) and 0.04 mg/kg (median: 0.03 mg/kg, 90th percentile 0.07 mg/kg). Brown rice was found to be more highly contaminated with both total and inorganic arsenic than white rice. Mean contamination of brown rice with total arsenic and inorganic arsenic was: 0.18 mg/kg (median: 0.12 mg/kg, 90th percentile: 0.32 mg/kg) and 0.05 mg/kg (median: 0.05 mg/kg, 90th percentile: 0.07 mg/kg). In turn for the white rice contamination was lower, mean total arsenic content: 0.10 mg/kg (median: 0.08 mg/kg, 90th percentile: 0.19 mg/kg) and mean inorganic arsenic: 0.03 mg/kg (median: 0.03 mg/kg, 90th percentile: 0.06 mg/kg). Contamination of rice-based products both total and inorganic arsenic was similar to those reported for rice, except rice wafers (mean: 0.24 mg/kg and 0.13 mg/kg). In the group of products for infants and young children obtained results were low – mean total arsenic content was 0.06 mg/kg and inorganic arsenic 0.02 mg/kg. The estimated average adult and children’s exposure to inorganic arsenic with rice and rice products was less than 1% of the BMDL05. Intake of inorganic arsenic by 12-month-old infants with ricebased products intended for this group of population was at 6% BMDL05 Based on the obtained results, it was found that the content of total and inorganic arsenic in investigated samples of rice and rice products did not pose a health risk even though contamination levels in some individual samples were significant

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...

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 this...

29 CFR 1910.1018 - Inorganic arsenic.

Code of Federal Regulations, 2010 CFR

2010-07-01

... container in the change-room which prevents dispersion of inorganic arsenic outside the container. (vi) The.... (vii) The employer shall assure that the containers of contaminated protective clothing and equipment... apply precautionary labels to all shipping and storage containers of inorganic arsenic, and to all...

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 this...

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 identical...

Total and inorganic arsenic in fish, seafood and seaweeds--exposure assessment.

PubMed

Mania, Monika; Rebeniak, Małgorzata; Szynal, Tomasz; Wojciechowska-Mazurek, Maria; Starska, Krystyna; Ledzion, Ewa; Postupolski, Jacek

2015-01-01

According to the European Food Safety Authority (EFSA), fish, seafood and seaweeds are foodstuffs that significantly contribute to dietary arsenic intake. With the exception of some algal species, the dominant compounds of arsenic in such food products are the less toxic organic forms. Both the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and EFSA recommend that speciation studies be performed to determine the different chemical forms in which arsenic is present in food due to the differences in their toxicity. Knowing such compositions can thus enable a complete exposure assessment to be made. Determination of total and inorganic arsenic contents in fish, their products, seafood and seaweeds present on the Polish market. This was then followed by an exposure assessment of consumers to inorganic arsenic in these foodstuffs. Total and inorganic arsenic was determined in 55 samples of fish, their products, seafood as well as seaweeds available on the market. The analytical method was hydride generation atomic absorption spectrometry (HGAAS), after dry ashing of samples and reduction of arsenic to arsenic hydride using sodium borohydride. In order to isolate only the inorganic forms of arsenic prior to mineralisation, samples were subjected to concentrated HCl hydrolysis, followed by reduction with hydrobromic acid and hydrazine sulphate after which triple chloroform extractions and triple 1M HCl re-extractions were performed. Exposure of adults was estimated in relation to the Benchmark Dose Lower Confidence Limit (BMDL0.5) as set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) that resulted in a 0.5% increase in lung cancer (3.0 μg/kg body weight (b.w.) per day). Mean total arsenic content from all investigated fish samples was 0.46 mg/kg (90th percentile 0.94 mg/kg), whilst the inorganic arsenic content never exceeded the detection limit of the analytical method used (0.025 mg/kg). In fish products, mean total arsenic concentration was 1.48 mg/kg (90th percentile: 2.42 mg/kg), whilst in seafood they were 0.87 mg/ kg (90th percentile: 2.23 mg/kg), for inorganic arsenic contamination at the 90th percentile was 0.043 mg/kg with most results however being less than 0.025 mg/kg. The highest inorganic arsenic levels were determined in the Hijiki algal species samples (102.7 mg/kg), whereas the other algal samples gave a mean inorganic concentration of 0.41 mg/kg (90th percentile 0.86 mg/kg). The estimated average adults exposure to inorganic arsenic in fish, seafood and seaweeds was less than 0.5% of the lowest BMDL0.5 dose. Only for the Hijiki seaweed it was at 4.9% BMDL0.5. Results demonstrate that dietary arsenic intake from fish, seafood and seaweed along with all their products do not constitute a significant health threat to consumers apart from the seaweed species Hizikia fusiformis in which over 40% of all the inorganic arsenic compounds were found.

Influence of dietary selenium on the disposition of arsenate in the female B6C3F{sub 1} mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenyon, E.M.; Hughes, M.F.; Levander, O.A.

1997-06-27

Interactions between arsenic (As) and selenium (Se) at the metabolic level are multifaceted and complex. These interactions are of practical significance because populations in various parts of the world are simultaneously exposed to inorganic As in drinking water and Se mainly in the diet at varying levels. The primary goal of this study was to investigate whether differing dietary Se status would alter the profile of urinary metabolites or their time course for elimination after exposure to arsenate [As(V)]. Weanling female 86C3F, mice were maintained for 28 d on either a control diet of powdered rodent meal sufficient in Semore » (A 0.2 ppm) or Torula yeast-based (TYB) diets deficient (B, 0.02 ppm Se), sufficient (C, 0.2 ppm Se), or excessive (D, 2.0 ppm Se) in Se; mice then received by oral gavage 5 mg (As)/kg as sodium [{sup 73}As] arsenate. The time course for elimination of total arsenic and metabolites in urine was measured over a 48-h period, and total arsenic was determined in feces and tissues at 48 h. Mice on the Se excess diet excreted a significantly higher percentage of urinary As as inorganic As, with a significantly decreased ratio of organic to inorganic As compared to Se-sufficient mice, suggesting that As methylation was decreased. Mice on the Se-deficient diet appeared to eliminate As(V), arsenite, and dimethylarsinic acid (DMA) in urine more slowly than Se-sufficient mice; however, further studies are required to confirm this finding. Mice on the Se-sufficient meal diet (A) excreted significantly less (by percent) arsenate-derived radioactivity in urine and more in feces compared to mice on the Se-sufficient TYB diet (C), with total elimination being similar for both groups. This indicates that mice on the meal diet absorbed significantly less As(V) than mice on the TYB diet, and this may be due to more fiber or {open_quotes}bulk{close_quotes} in the meal diet. 35 refs., 6 figs., 6 tabs.« less

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...

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

USDA-ARS?s Scientific Manuscript database

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...

78 FR 56719 - Draft Guidance for Industry on Arsenic in Apple Juice: Action Level; Supporting Document for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... Level for Arsenic in Apple Juice; A Quantitative Assessment of Inorganic Arsenic in Apple Juice... Juice,'' and a risk assessment document entitled ``A Quantitative Assessment of Inorganic Arsenic in...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Paul-Yann; Lin, Yung-Lun; Huang, Chin-Chin

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 glycosaminoglycanmore » 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 the mouse bladder. ► Inorganic arsenic increases Sp1 while decreases NQO-1 protein expression in the mouse whole bladder.« less

Impaired arsenic metabolism in children during weaning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faengstroem, Britta; Hamadani, Jena; Nermell, Barbro

2009-09-01

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

Automated system for on-line determination of dimethylarsinic and inorganic arsenic by hydride generation-atomic fluorescence spectrometry.

PubMed

Chaparro, L L; Ferrer, L; Cerdà, V; Leal, L O

2012-09-01

A multisyringe flow-injection approach has been coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS) with UV photo-oxidation for dimethylarsinic (DMA), inorganic As and total As determination, depending on the pre-treatment given to the sample (extraction or digestion). The implementation of a UV lamp allows on-line photo-oxidation of DMA and the following arsenic detection, whereas a bypass leads the flow directly to the HG-AFS system, performing inorganic arsenic determination. DMA concentration is calculated by the difference of total inorganic arsenic and measurement of the photo-oxidation step. The detection limits for DMA and inorganic arsenic were 0.09 and 0.47 μg L(-1), respectively. The repeatability values accomplished were of 2.4 and 1.8%, whereas the injection frequencies were 24 and 28 injections per hour for DMA and inorganic arsenic, respectively. This method was validated by means of a solid reference material BCR-627 (muscle of tuna) with good agreement with the certified values. Satisfactory results for DMA and inorganic arsenic determination were obtained in several water matrices. The proposed method offers several advantages, such as increasing the sampling frequency, low detection limits and decreasing reagents and sample consumption, which leads to lower waste generation.

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...

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy.

PubMed

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-02-09

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20-44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79-4.00]), GSTT gene (GMR: 0.68 [0.52-0.80]), consumption of tap water (GMR: 1.35 [1.02-1.77]), seafood (GMR: 1.44 [1.11-1.88]), whole milk (GMR: 1.34 [1.04-1.73]), and fruit/vegetables (GMR: 1.37 [1.03-1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources.

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy

PubMed Central

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-01-01

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20–44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79–4.00]), GSTT gene (GMR: 0.68 [0.52–0.80]), consumption of tap water (GMR: 1.35 [1.02–1.77]), seafood (GMR: 1.44 [1.11–1.88]), whole milk (GMR: 1.34 [1.04–1.73]), and fruit/vegetables (GMR: 1.37 [1.03–1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources. PMID:29425136

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

PubMed

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

2013-02-01

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

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

PubMed Central

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

2012-01-01

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

Fact Sheet on Arsenic

EPA Pesticide Factsheets

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

Gene Expression of Normal Human Epidermal Keratinocytes Modulated by Trivalent Arsenicals

EPA Science Inventory

Chronic exposure to inorganic arsenic (iAs) is associated with the development of benign and malignant human skin lesions including nonmelanoma skin cancers. The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (...

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

PubMed Central

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

2016-01-01

Background: Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. Objective: We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Methods: Among 706 mother–infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Results: Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7–6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: –0.19, –0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: –0.82, –0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: –111.6, –14.2) in birth weight, though the association was null in the other strata. Conclusions: Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Citation: Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299–1307; http://dx.doi.org/10.1289/ehp.1510065 PMID:26955061

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

PubMed

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

2016-08-01

Studies suggest that arsenic exposure influences birth outcomes; however, findings are mixed. We assessed in utero arsenic exposure in relation to birth outcomes and whether maternal prepregnancy weight and infant sex modified the associations. Among 706 mother-infant pairs exposed to low levels of arsenic through drinking water and diet, we assessed in utero arsenic exposure using maternal second-trimester urinary arsenic, maternal prepregnancy weight through self-report, and birth outcomes from medical records. Median (interquartile range) of total urinary arsenic [tAs; inorganic arsenic (iAs) + monomethylarsonic acid (MMA) + dimethylarsinic acid (DMA)] was 3.4 μg/L (1.7-6.0). In adjusted linear models, each doubling of tAs was associated with a 0.10-cm decrease (95% CI: -0.19, -0.01) in head circumference. Results were similar for MMA and DMA. Ln(tAs) and ln(DMA) were positively associated with birth length in infant males only; among males, each doubling of tAs was associated with a 0.28-cm increase (95% CI: 0.09, 0.46) in birth length (pinteraction = 0.04). Results were similar for DMA. Additionally, arsenic exposure was inversely related to ponderal index, and associations differed by maternal weight. Each ln(tAs) doubling of tAs was associated with a 0.55-kg/m3 lower (95% CI: -0.82, -0.28, p < 0.001) ponderal index for infants of overweight/obese, but not normal-weight, mothers (pinteraction < 0.01). Finally, there was a significant interaction between maternal weight status, infant sex, and arsenic exposure on birth weight (pinteraction = 0.03). In girls born of overweight/obese mothers, each doubling of tAs was associated with a 62.9-g decrease (95% CI: -111.6, -14.2) in birth weight, though the association was null in the other strata. Low-level arsenic exposure may affect fetal growth, and the associations may be modified by maternal weight status and infant sex. Gilbert-Diamond D, Emond JA, Baker ER, Korrick SA, Karagas MR. 2016. Relation between in utero arsenic exposure and birth outcomes in a cohort of mothers and their newborns from New Hampshire. Environ Health Perspect 124:1299-1307; http://dx.doi.org/10.1289/ehp.1510065.

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

PubMed

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

2016-01-01

Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008-2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104-111; http://dx.doi.org/10.1289/ehp.1408742.

Arsenic methylation capacity is associated with breast cancer in northern Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Carrillo, Lizbeth; Hernández-Ramírez, Raúl Ulises; Gandolfi, A. Jay

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case–control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined bymore » HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29 μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA OR{sub Q5vs.Q1} = 2.63; 95%CI 1.89,3.66; p for trend < 0.001; PMI OR{sub Q5vs.Q1} = 1.90; 95%CI 1.39,2.59, p for trend < 0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA OR{sub Q5vs.Q1} = 0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI OR{sub Q5vsQ1} = 0.42, 95%CI 0.31,0.59, p for trend < 0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. - Highlights: • Arsenic methylation capacity is associated to an increased breast cancer (BC) risk. • Women with higher capacity to methylate arsenic to MMA were at higher BC risk. • Women with higher capacity to methylate arsenic to DMA were at lower BC risk. • Associations occurred at urinary As levels near the biological exposure index.« less

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

PubMed Central

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

2015-01-01

Background Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. Objective This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. Methods We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008–2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. Results After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Conclusions Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Citation Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104–111; http://dx.doi.org/10.1289/ehp.1408742 PMID:26068977

Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

PubMed

Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

2013-12-01

Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

A novel biosensor selective for organoarsenicals.

PubMed

Chen, Jian; Zhu, Yong-Guan; Rosen, Barry P

2012-10-01

Organoarsenicals used as herbicides and growth promoters for farm animals are degraded to inorganic arsenic. Available bacterial whole-cell biosensors detect only inorganic arsenic. We report a biosensor selective for the trivalent organoarsenicals methylarsenite and phenylarsenite over inorganic arsenite. This sensor may be useful for detecting degradation of arsenic-containing herbicides and growth promoters.

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...

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

PubMed

Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

2014-01-01

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

INFLUENCE OF DIETARY ARSENIC ON URINARY ARSENIC METABOLITE EXCRETION

EPA Science Inventory

Influence of Dietary Arsenic on Urinary Arsenic Metabolite Excretion

Cara L. Carty, M.S., Edward E. Hudgens, B.Sc., Rebecca L. Calderon, Ph.D., M.S.P.H., Richard Kwok, M.S.P.H., Epidemiology and Biomarkers Branch/HSD, NHEERL/US EPA; David J. Thomas, Ph.D., Pharmacokinetics...

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

PubMed

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

2015-04-24

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

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

PubMed

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

2015-12-15

Inorganic mercury and arsenic encompasses a term which includes As(III), As(V) and Hg(II) species. These metal ions have been extensively studied due to their toxicity related issues. Different analytical methods are used to monitor inorganic mercury and arsenic in a variety of samples at trace level. The present study reviews various analytical techniques available for detection of inorganic mercury and arsenic with particular emphasis on electrochemical methods especially stripping voltammetry. A detailed critical evaluation of methods, advantages of electrochemical methods over other analytical methods, and various electrode materials available for mercury and arsenic analysis is presented in this review study. Modified carbon paste electrode provides better determination due to better deposition with linear and improved response under studied set of conditions. Biological materials may be the potent and economical alternative as compared to macro-electrodes and chemically modified carbon paste electrodes in stripping analysis of inorganic mercury and arsenic. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2008-10-01

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

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

PubMed Central

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

2016-01-01

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

A COMPARISON OF URINARY ARSENIC SPECIATION VIA DIRECT NEBULIZATION AND ON-LINE PHOTOOXIDATION-HYDRIDE GENERATION WITH DETECTION BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

EPA Science Inventory

Arsenic speciation continues to be important in assessing human and environmental exposure risk. Urinary arsenic analysis provides information on recent arsenic exposure. In this study, two sample introduction pathways: direct nebulization (DN) and hydride generation (HG) were ut...

Health risk assessment of inorganic arsenic intake of Ronphibun residents via duplicate diet study.

PubMed

Saipan, Piyawat; Ruangwises, Suthep

2009-06-01

To assess health risk from exposure to inorganic arsenic via duplicate portion sampling method in Ronphibun residents. A hundred and forty samples (140 subject-days) were collected from participants in Ronphibun sub-district. Inorganic arsenic in duplicate diet sample was determined by acid digestion and hydride generation-atomic absorption spectrometry. Deterministic risk assessment is referenced throughout the present paper using United States Environmental Protection Agency (U.S. EPA) guidelines. The average daily dose and lifetime average daily dose of inorganic arsenic via duplicate diet were 0.0021 mg/kg/d and 0.00084 mg/kg/d, respectively. The risk estimates in terms of hazard quotient was 6.98 and cancer risk was 1.26 x 10(-3). The results of deterministic risk characterization both hazard quotient and cancer risk from exposure inorganic arsenic in duplicate diets were greater than safety risk levels of hazard quotient (1) and cancer risk (1 x 10(-4)).

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

PubMed

Rahman, M Azizur; Hasegawa, H

2011-10-15

Rice is the staple food for the people of arsenic endemic South (S) and South-East (SE) Asian countries. In this region, arsenic contaminated groundwater has been used not only for drinking and cooking purposes but also for rice cultivation during dry season. Irrigation of arsenic-contaminated groundwater for rice cultivation has resulted high deposition of arsenic in topsoil and uptake in rice grain posing a serious threat to the sustainable agriculture in this region. In addition, cooking rice with arsenic-contaminated water also increases arsenic burden in cooked rice. Inorganic arsenic is the main species of S and SE Asian rice (80 to 91% of the total arsenic), and the concentration of this toxic species is increased in cooked rice from inorganic arsenic-rich cooking water. The people of Bangladesh and West Bengal (India), the arsenic hot spots in the world, eat an average of 450g rice a day. Therefore, in addition to drinking water, dietary intake of arsenic from rice is supposed to be another potential source of exposure, and to be a new disaster for the population of S and SE Asian countries. Arsenic speciation in raw and cooked rice, its bioavailability and the possible health hazard of inorganic arsenic in rice for the population of S and SE Asia have been discussed in this review. Copyright © 2011 Elsevier B.V. All rights reserved.

Heavy metal, total arsenic, and inorganic arsenic contents of algae food products.

PubMed

Almela, C; Algora, S; Benito, V; Clemente, M J; Devesa, V; Súñer, M A; Vélez, D; Montoro, R

2002-02-13

The total arsenic, inorganic arsenic, lead, cadmium, and mercury contents of 18 algae food products currently on sale in Spain were determined. The suitability of the analytical methodologies for this type of matrix was confirmed by evaluating their analytical characteristics. The concentration ranges found for each contaminant, expressed in milligrams per kilogram of dry weight, were as follows: total arsenic, 2.3-141; inorganic arsenic, 0.15-88; lead, < 0.05-1.33; cadmium, 0.03-1.9; and mercury, 0.004-0.04. There is currently no legislation in Spain regarding contaminants in algae food products, but some of the samples analyzed revealed Cd and inorganic As levels higher than those permitted by legislation in other countries. Given the high concentrations of inorganic As found in Hizikia fusiforme, a daily consumption of 1.7 g of the product would reach the Provisional Tolerable Weekly Intake recommended by the WHO for an average body weight of 68 kg. A more comprehensive study of the contents and toxicological implications of the inorganic As present in the algae food products currently sold in Spain may be necessary, which might then be the basis for the introduction of specific sales restrictions.

Interaction of plasma glutathione redox and folate deficiency on arsenic methylation capacity in Bangladeshi adults

PubMed Central

Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Slavkovich, Vesna; Ilievski, Vesna; Levy, Diane; Alam, Shafiul; Siddique, Abu B.; Parvez, Faruque; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Inorganic arsenic (InAs) is metabolized through a series of methylation reactions catalyzed by arsenic(III)-methyltransferase (AS3MT), resulting in the generation of monomethylarsonic (MMAs) and dimethylarsinic acids (DMAs). AS3MT activity requires the presence of the methyl donor S-adenosylmethionine (SAM), a product of folate-dependent one-carbon metabolism, and a reductant. Although glutathione (GSH), the primary endogenous antioxidant, is not required for As methylation, GSH stimulates As methylation rates in vitro. However, the relationship between GSH redox and As methylation capacity in humans is unknown. We wished to test the hypothesis that a more oxidized plasma GSH redox status is associated with decreased As methylation capacity, and examine whether these associations are modified by folate nutritional status. Concentrations of plasma GSH and GSSG, plasma folate, total blood As (bAs), total urinary As (uAs), and uAs metabolites were assessed in a cross-sectional study of n = 376 Bangladeshi adults who were chronically exposed to As in drinking water. We observed that a decreased plasma GSH/GSSG ratio (reflecting a more oxidized redox state) was significantly associated with increased urinary %MMA, decreased urinary %DMA, and increased total bAs in folate-deficient individuals (plasma folate ≤ 9.0 nmol/L). Concentrations of plasma GSH and GSSG were independently associated with increased and decreased As methylation capacity, respectively. No significant associations were observed in folate-sufficient individuals, and interactions by folate status were statistically significant. Our findings suggest that GSH/GSSG redox regulation might contribute to the large interindividual variation in As methylation capacity observed in human populations. PMID:24726863

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.

DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMASIII AND DMASIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC

EPA Science Inventory

DETERMINATION OF URINARY TRIVALENT ARSENICALS (MMAsIII and DMAsIII) IN INDIVIDUALS CHRONICALLY EXPOSED TO ARSENIC.
L. M. Del Razo1, M. Styblo2, W. R. Cullen3, and D.J. Thomas4.
1Toxicology Section, Cinvestav-IPN, Mexico, D.F., 2Univ. North Carolina, Chapel Hill, NC; 3Uni...

Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical Hospital, Taichung, Taiwan; Huang, Ya-Li

2013-04-15

Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profilesmore » were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.« less

Arsenic Concentrations and Speciation in Shellfishes from Korea

NASA Astrophysics Data System (ADS)

Yoon, C.; Yoon, H.

2005-12-01

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

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

PubMed

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

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Association of Arsenic Methylation Capacity with Developmental Delays and Health Status in Children: A Prospective Case-Control Trial

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Mei; Chen, Wei-Jen; Lee, Chih-Ying; Chien, Ssu-Ning; Shiue, Horng-Sheng; Huang, Shiau-Rung; Lin, Ming-I.; Mu, Shu-Chi; Hsieh, Ru-Lan

2016-11-01

This case-control study identified the association between the arsenic methylation capacity and developmental delays and explored the association of this capacity with the health status of children. We recruited 120 children with developmental delays and 120 age- and sex-matched children without developmental delays. The health status of the children was assessed using the Pediatric Quality of Life Inventory (PedsQL) and Pediatric Outcomes Data Collection Instrument (PODCI). The arsenic methylation capacity was determined by the percentages of inorganic arsenic (InAs%), monomethylarsonic acid (MMAV%), and dimethylarsinic acid (DMAV%) through liquid chromatography and hydride generation atomic absorption spectrometry. Developmental delays were significantly positively associated with the total urinary arsenic concentration, InAs%, and MMAV%, and was significantly negatively associated with DMAV% in a dose-dependent manner. MMAV% was negatively associated with the health-related quality of life (HRQOL; -1.19 to -1.46, P < 0.01) and functional performance (-0.82 to -1.14, P < 0.01), whereas DMAV% was positively associated with HRQOL (0.33-0.35, P < 0.05) and functional performance (0.21-0.39, P < 0.01-0.05) in all children and in those with developmental delays. The arsenic methylation capacity is dose-dependently associated with developmental delays and with the health status of children, particularly those with developmental delays.

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

PubMed

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

2017-01-01

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

Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity.

PubMed

Jansen, Rick J; Argos, Maria; Tong, Lin; Li, Jiabei; Rakibuz-Zaman, Muhammad; Islam, Md Tariqul; Slavkovich, Vesna; Ahmed, Alauddin; Navas-Acien, Ana; Parvez, Faruque; Chen, Yu; Gamble, Mary V; Graziano, Joseph H; Pierce, Brandon L; Ahsan, Habibul

2016-02-01

Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity. The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species. Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles. ©2015 American Association for Cancer Research.

Association between Arsenic Exposure from Drinking Water and Longitudinal Change in Blood Pressure among HEALS Cohort Participants.

PubMed

Jiang, Jieying; Liu, Mengling; Parvez, Faruque; Wang, Binhuan; Wu, Fen; Eunus, Mahbub; Bangalore, Sripal; Newman, Jonathan D; Ahmed, Alauddin; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; Slavkovich, Vesna; Argos, Maria; Scannell Bryan, Molly; Farzan, Shohreh F; Hayes, Richard B; Graziano, Joseph H; Ahsan, Habibul; Chen, Yu

2015-08-01

Cross-sectional studies have shown associations between arsenic exposure and prevalence of high blood pressure; however, studies examining the relationship of arsenic exposure with longitudinal changes in blood pressure are lacking. We evaluated associations of arsenic exposure in relation to longitudinal change in blood pressure in 10,853 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Arsenic was measured in well water and in urine samples at baseline and in urine samples every 2 years after baseline. Mixed-effect models were used to estimate the association of baseline well and urinary creatinine-adjusted arsenic with annual change in blood pressure during follow-up (median, 6.7 years). In the HEALS population, the median water arsenic concentration at baseline was 62 μg/L. Individuals in the highest quartile of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in systolic blood pressure compared with those in the reference group (β = 0.48 mmHg/year; 95% CI: 0.35, 0.61, and β = 0.43 mmHg/year; 95% CI: 0.29, 0.56 for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models. Likewise, individuals in the highest quartile of baseline arsenic exposure had a greater annual increase in diastolic blood pressure for water arsenic and urinary creatinine-adjusted arsenic, (β = 0.39 mmHg/year; 95% CI: 0.30, 0.49, and β = 0.45 mmHg/year; 95% CI: 0.36, 0.55, respectively) compared with those in the lowest quartile. Our findings suggest that long-term arsenic exposure may accelerate age-related increases in blood pressure. These findings may help explain associations between arsenic exposure and cardiovascular disease.

Dilution of rice with other gluten free grains to lower inorganic arsenic in foods for young children in response to European Union regulations provides impetus to setting stricter standards

PubMed Central

Donaldson, Emily; Signes-Pastor, Antonio J.

2018-01-01

There has been an increasing realisation that young infants are exposed to elevated concentrations of the carcinogen inorganic arsenic, relative to adults. This is because many infant food products are rice based, and rice is ~10-fold elevated in inorganic arsenic compared to most other foods. The European Commission (EC) has acted on this concern setting stricter standards for infants, 100 μg of inorganic arsenic per kg of food (100 μg/kg), as compared to adults (200 μg/kg), for rice based foods, a law that was brought into place in 1st January 2016. Here we investigate how this law has impacted on inorganic arsenic in baby food products in the UK market, and compare the findings to previous baby food surveys taken before and just after the law came into place. We find that for a wide range of UK infant products that the new regulations are being adhered to, with all samples surveyed, being under 100 μg/kg inorganic arsenic. The prevalence of pure rice products had decreased in the UK, and there appears to be careful sourcing of the rice used in these products to ensure conformity with regulations. There has been an increased presence of mixed cereal products, with rice and maize as the main ingredient, appearing on the UK market, with varying rice contents for infant porridges, cakes and mueslis, with the latter being a relatively innovative product for infant foods. There was a highly significant correlation (P<0.0001) between rice content and inorganic arsenic concentration across all infant foods. When UK infant rice cakes, breakfast cereals and porridges were compare to their general, i.e. not labelled specifically for being for infant consumption, equivalent it was found that the adult foods generally exceeded the 100 μg/kg inorganic arsenic standard for infant foods. Thus, infants should not be given rice products not specifically labelled as being for them if a lower inorganic arsenic diet is to be maintained. PMID:29547635

DNA methylation changes in Mexican children exposed to arsenic from two historic mining areas in San Luis potosí.

PubMed

Alegría-Torres, Jorge Alejandro; Carrizales-Yánez, Leticia; Díaz-Barriga, Fernando; Rosso-Camacho, Fernando; Motta, Valeria; Tarantini, Letizia; Bollati, Valentina

2016-12-01

Arsenic is a carcinogen and epimutagen that threatens the health of exposed populations worldwide. In this study, we examined the methylation status of Alu and long interspersed nucleotide elements (LINE-1) and their association with levels of urinary arsenic in 84 Mexican children between 6 and 12 years old from two historic mining areas in the State of San Luis Potosí, Mexico. Urinary arsenic levels were determined by atomic absorption spectrophotometry and DNA methylation analysis was performed in peripheral blood leukocytes by bisulfite-pyrosequencing. The geometric mean of urinary arsenic was 26.44 µg/g Cr (range 1.93-139.35). No significant differences in urinary arsenic or methylation patterns due to gender were observed. A positive correlation was found between urinary arsenic and the mean percentage of methylated cytosines in Alu sequences (Spearman correlation coefficient r = 0.532, P < 0.001), and a trend of LINE-1 hypomethylation was also observed (Spearman correlation coefficient r = -0.232, P = 0.038) after adjustment for sex and age. A linear regression model showed an association with log-normalized urinary arsenic for Alu (β = 1.05, 95% CI: 0.67; 1.43, P < 0.001) and LINE-1 (β = -0.703, 95% CI: -1.36; -0.38, P = 0.038). Despite the low-level arsenic exposure, a subtle epigenetic imbalance measured as DNA methylation was detected in the leukocytes of Mexican children living in two historic mining areas. Environ. Mol. Mutagen. 57:717-723, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Arsenic concentrations in Baltic Sea sediments close to chemical munitions dumpsites

NASA Astrophysics Data System (ADS)

Bełdowski, Jacek; Szubska, Marta; Emelyanov, Emelyan; Garnaga, Galina; Drzewińska, Anna; Bełdowska, Magdalena; Vanninen, Paula; Östin, Anders; Fabisiak, Jacek

2016-06-01

In addition to natural sources and land-originated pollution, the Baltic Sea has another anthropogenic source of arsenic in bottom sediments-arsenic-based Chemical Warfare Agents (CWA). To examine the potential usage of arsenic contents results for monitoring the leakage from chemical weapons, sediment samples were collected from officially reported and potential chemical weapon dumpsites located in the Baltic Sea, and total and inorganic arsenic concentrations were analyzed. Results showed an elevated arsenic content in dumpsite areas compared to reference areas. Correlations of arsenic with other metals and organic matter were studied to elucidate any unusual behavior of arsenic in the dumpsites. In the area of the Bornholm Deep, such behavior was observed for inorganic arsenic. It appears that in close vicinity of dumped munitions, the inorganic arsenic concentration of sediments is not correlated with either organic matter content or authigenic minerals formation, as is commonly observed elsewhere. Investigations on CWA concentrations, performed within the CHEMSEA (Chemical Munition Search and Assesment) project, allowed us to compare the results of arsenic concentrations with the occurrence of arsenic-containing CWA.

Human exposure to arsenic from drinking water in Vietnam.

PubMed

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

2014-08-01

Vietnam is an agricultural country with a population of about 88 million, with some 18 million inhabitants living in the Red River Delta in Northern Vietnam. The present study reports the chemical analyses of 68 water and 213 biological (human hair and urine) samples conducted to investigate arsenic contamination in tube well water and human arsenic exposure in four districts (Tu Liem, Dan Phuong, Ly Nhan, and Hoai Duc) in the Red River Delta. Arsenic concentrations in groundwater in these areas were in the range of <1 to 632 μg/L, with severe contamination found in the communities Ly Nhan, Hoai Duc, and Dan Phuong. Arsenic concentrations were markedly lowered in water treated with sand filters, except for groundwater from Hoai Duc. Human hair samples had arsenic levels in the range of 0.07-7.51 μg/g, and among residents exposed to arsenic levels ≥50 μg/L, 64% of them had hair arsenic concentrations higher than 1 μg/g, which is a level that can cause skin lesions. Urinary arsenic concentrations were 4-435 μg/g creatinine. Concentrations of arsenic in hair and urine increased significantly with increasing arsenic content in drinking water, indicating that drinking water is a significant source of arsenic exposure for these residents. The percentage of inorganic arsenic (IA) in urine decreased with age, whereas the opposite trend was observed for monomethylarsonic acid (MMA) in urine. Significant co-interactions of age and arsenic exposure status were also detected for concentrations of arsenic in hair and the sum of IA, MMA, and dimethylarsinic acid (DMA) in urine and %MMA. In summary, this study demonstrates that a considerable proportion of the Vietnamese population is exposed to arsenic levels of chronic toxicity, even if sand filters reduce exposure in many households. Health problems caused by arsenic ingestion through drinking water are increasingly reported in Vietnam. © 2013 Elsevier B.V. All rights reserved.

Use status and metabolism of realgar in Chinese patent medicine.

PubMed

Li, Yongfang; Wang, Da; Xu, Yuanyuan; Liu, Boying; Zheng, Yi; Yang, Boyi; Fan, Shujun; Zhi, Xueyuan; Zheng, Quanmei; Sun, Guifan

2015-04-08

Realgar is widely used in combination with other herbs as Chinese patent medicine to treat a wide range of diseases in China. It is also a well known arsenical toxicant. Chronic arsenic poisoning events caused by long-term usage of realgar-containing medicines have been reported in literatures. Given to the paradoxical role of realgar, comprehensive outline of its usage status in Chinese patent medicine might provide basal data for evaluating its toxicology risks in populations. Unfortunately, the relevant information is limited. Also, a metabolic process after intake of realgar-containing medicine in humans is poorly understood. The Traditional Chinese Patent Medicine Prescription Database was reviewed to get the information on the usage status of realgar. Realgar powder was dissolved in different pH-value solutions (1, 3, 5, 7, 9 and 11) to determine the soluble arsenic concentrations from realgar. Ten volunteers aged 24-26 years old were recruited to take four pills of Niu Huang Jie Du Pian (NHJDP), a very common Chinese patent medicine with realgar, to analyze the arsenic metabolism after exposure to realgar-containing medicine. The four pills were taken according to the medical instruction. Concentrations of soluble arsenic from realgar and urinary arsenic metabolites in humans were determined by hydride generation atomic absorption spectrometry. A total of 191 (2.25%) realgar-containing traditional Chinese patent medicines were obtained from the database, and almost 86.91% of them were for oral application. 73 (38.22%) medicines were found to be available for children. The mass fraction of arsenic in realgar-containing medicine ranged from 0.11% to 27.52%. According to medical instructions, the amount of average daily arsenic intake ranged from 0.47 to 2895.53mg. Nearly 86% medicines with daily intake of arsenic >10mg. Only inorganic arsenic (iAs) was detected from realgar in dissolution experiment and the levels of soluble iAs increased with pH values. After intake NHJDP, arsenic excretion in urine significantly increased, with a maximum excretion of iAs and monomethylarsonic acid at 6h post-ingestion and a peak excretion of dimethylarsinic acid at 9h post-ingestion. Arsenic methylation capacity was decreased after intake NHJDP. Females carried a more efficient arsenic methylation process than males. Realgar is widely used in traditional Chinese medicine. The arsenic solubility from realgar may be enhanced under alkaline conditions. The levels of urinary arsenic metabolites significantly increased while the arsenic methylation capacity significantly decreased after intaking realgar-containing medicine, which may suggest that a potential health hazard exists if people use arsenical medicines for long-term. Copyright © 2015. Published by Elsevier Ireland Ltd.

Arsenic Speciation in Plankton Organisms from Contaminated Lakes: Transformations at the Base of the Freshwater Food Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caumette, Guilhem; Koch, Iris; Estrada, Esteban

2012-02-06

The two complementary techniques high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) and X-ray absorption near edge structure (XANES) analysis were used to assess arsenic speciation in freshwater phytoplankton and zooplankton collected from arsenic-contaminated lakes in Yellowknife (Northwest Territories, Canada). Arsenic concentrations in lake water ranged from 7 {micro}g L{sup -1} in a noncontaminated lake to 250 {micro}g L{sup -1} in mine-contaminated lakes, which resulted in arsenic concentrations ranging from 7 to 340 mg kg{sup -1} d.w. in zooplankton organisms (Cyclops sp.) and from 154 to 894 mg kg{sup -1} d.w. in phytoplankton. The main arsenic compounds identified by HPLC-ICP-MSmore » in all plankton were inorganic arsenic (from 38% to 98% of total arsenic). No other arsenic compounds were found in phytoplankton, but zooplankton organisms showed the presence of organoarsenic compounds, the most common being the sulfate arsenosugar, up to 47% of total arsenic, with traces of phosphate sugar, glycerol sugar, methylarsonate (MMA), and dimethylarsinate (DMA). In the uncontaminated Grace Lake, zooplankton also contained arsenobetaine (AB). XANES characterization of arsenic in the whole plankton samples showed AsV-O as the only arsenic compound in phytoplankton, and AsIII-S and AsV-O compounds as the two major inorganic arsenic species in zooplankton. The proportion of organoarsenicals and inorganic arsenic in zooplankton depends upon the arsenic concentration in lakes and shows the impact of arsenic contamination: zooplankton from uncontaminated lake has higher proportions of organoarsenic compounds and contains arsenobetaine, while zooplankton from contaminated area contains mostly inorganic arsenic.« less

Methylated Arsenic in the Southern North Sea

NASA Astrophysics Data System (ADS)

Millward, G. E.; Kitts, H. J.; Comber, S. D. W.; Ebdon, L.; Howard, A. G.

1996-07-01

Water samples collected in the southern North Sea in August 1988 (mid-summer), April 1989 (spring), September/October 1989 (late summer) and May 1990 were analysed for dissolved inorganic arsenic, monomethylarsenic (MMA) and dimethylarsenic (DMA). In mid-summer 1988, both MMA and DMA were observed throughout the southern North Sea, with lowest concentrations of dissolved inorganic arsenic (mean 6·48 nmol l -1) and the highest proportions of methylated arsenic (29%) being found in highly productive continental coastal waters. In April 1989, waters of the North Sea had a mean inorganic arsenic concentration of 12 nmol l -1and methylated species were not detected, even though phytoplankton blooms were present. Shipboard phytoplankton incubation studies (in May 1990) revealed that uptake of dissolved inorganic arsenic occurred at a rate of 0·57 nmol l -1 day -1, but the appearance of dissolved methylated species was not observed. During September/October 1989, while MMA and DMA were present in all sectors of the North Sea, the relative proportion of methylated compounds (11%) in continental coastal waters was less than mid-summer 1988. It was shown that estuarine, porewater and atmospheric inputs of arsenic species were relatively small during the observational periods, and that almost all of the methylated compounds originated from decaying algal tissue. Demethylation of DMA and MMA throughout winter contributed to the dissolved inorganic arsenic pool. The results are discussed in the context of the development of a predictive model for the cycling of arsenic in the North Sea.

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

PubMed

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

2012-04-01

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

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer.

PubMed

Hsueh, Yu-Mei; Su, Chien-Tien; Shiue, Horng-Sheng; Chen, Wei-Jen; Pu, Yeong-Shiau; Lin, Ying-Chin; Tsai, Cheng-Shiuan; Huang, Chao-Yuan

2017-09-01

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04-0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06-2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou Province, China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, J.C.; Wang, J.P.; Zheng, B.S.

2005-08-07

Coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-borne arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those inmore » the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age ({lt} 20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation.« less

Expression of arsenic resistance genes in the obligate anaerobe Bacteroides vulgatus ATCC 8482, a gut microbiome bacterium

PubMed Central

Li, Jiaojiao; Mandal, Goutam; Rosen, Barry P.

2016-01-01

The response of the obligate anaerobe Bacteroides vulgatus ATCC 8482, a common human gut microbiota, to arsenic was determined. B. vulgatus ATCC 8482 is highly resistant to pentavalent As(V) and methylarsenate (MAs(V)). It is somewhat more sensitive to trivalent inorganic As(III) but 100-fold more sensitive to methylarsenite (MAs(III)) than to As(III). B. vulgatus ATCC 8482 has eight continuous genes in its genome that we demonstrate form an arsenical-inducible transcriptional unit. The first gene of this ars operon, arsR, encodes a putative ArsR As(III)-responsive transcriptional repressor. The next three genes encode proteins of unknown function. The remaining genes, arsDABC, have well-characterized roles in detoxification of inorganic arsenic, but there are no known genes for MAs(III) resistance. Expression of each gene after exposure to trivalent and pentavalent inorganic and methylarsenicals was analyzed. MAs(III) was the most effective inducer. The arsD gene was the most highly expressed of the ars operon genes. These results demonstrate that this anaerobic microbiome bacterium has arsenic-responsive genes that confer resistance to inorganic arsenic and may be responsible for the organism's ability to maintain its prevalence in the gut following dietary exposure to inorganic arsenic. PMID:27040269

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

PubMed

Ruangwises, Suthep; Ruangwises, Nongluck; Saipan, Piyawat

2011-02-01

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

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

PubMed

Ruangwises, Suthep; Saipan, Piyawat

2010-03-01

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

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

PubMed Central

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

2016-01-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex-specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID:26883664

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

PubMed Central

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

2015-01-01

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

Environmental arsenic exposure and serum matrix metalloproteinase-9.

PubMed

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

2013-03-01

The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake was estimated. Urine was speciated for arsenic, and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking, and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike's Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9 than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure evaluated using all three exposure metrics was positively associated with MMP-9.

Environmental arsenic exposure and serum matrix metalloproteinase-9

PubMed Central

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

2014-01-01

The objective of this study was to evaluate the relationship between environmental arsenic exposure and serum matrix metalloproteinase (MMP)-9, a biomarker associated with cardiovascular disease and cancer. In a cross-sectional study of residents of Arizona, USA (n=215) and Sonora, Mexico (n=163), drinking water was assayed for total arsenic, and daily drinking water arsenic intake estimated. Urine was speciated for arsenic and concentrations were adjusted for specific gravity. Serum was analyzed for MMP-9 using ELISA. Mixed model linear regression was used to assess the relation among drinking water arsenic concentration, drinking water arsenic intake, urinary arsenic sum of species (the sum of arsenite, arsenate, monomethylarsonic acid and dimethylarsinic acid), and MMP-9, controlling for autocorrelation within households. Drinking water arsenic concentration and intake were positively associated with MMP-9, both in crude analysis and after adjustment for gender, country/ethnicity, age, body mass index, current smoking and diabetes. Urinary arsenic sum of species was positively associated with MMP-9 in multivariable analysis only. Using Akaike’s Information Criterion, arsenic concentration in drinking water provided a better fitting model of MMP-9, than either urinary arsenic or drinking water arsenic intake. In conclusion, arsenic exposure was positively associated with MMP-9 using all three exposure metrics evaluated. PMID:23232971

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

PubMed

Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

2011-12-01

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

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

PubMed

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

2017-01-06

A new rapid monitoring method by means of high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) following the heat-assisted extraction was developed for measurement of total inorganic arsenic species in rice flour. As(III) and As(V) eluted at the same retention time and completely separated from organoarsenic species by an isocratic elution program on a reversed phase column. Therefore, neither ambiguous oxidation of arsenite to arsenate nor the integration of two peaks were necessary to determine directly the target analyte inorganic arsenic. Rapid injection allowed measuring 3 replicates within 6min and this combined with a quantitative extraction of all arsenic species from rice flour by a 15min HNO 3 -H 2 O 2 extraction makes this the fastest laboratory based method for inorganic arsenic in rice flour. Copyright © 2016 Elsevier B.V. All rights reserved.

ASSESSING ARSENIC EXPOSURE AND SKIN HYPERKERATOSIS IN INNER MONGOLIA, CHINA

EPA Science Inventory

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

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 ...

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

EPA Pesticide Factsheets

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

Arsenic Release from Foodstuffs upon Food Preparation.

PubMed

Cheyns, Karlien; Waegeneers, Nadia; Van de Wiele, Tom; Ruttens, Ann

2017-03-22

In this study the concentration of total arsenic (As) and arsenic species (inorganic As, arsenobetaine, dimethylarsinate, and methylarsonate) was monitored in different foodstuffs (rice, vegetables, algae, fish, crustacean, molluscs) before and after preparation using common kitchen practices. By measuring the water content of the foodstuff and by reporting arsenic concentrations on a dry weight base, we were able to distinguish between As release effects due to food preparation and As decrease due to changes in moisture content upon food preparation. Arsenic species were released to the broth during boiling, steaming, frying, or soaking of the food. Concentrations declined with maxima of 57% for total arsenic, 65% for inorganic As, and 32% for arsenobetaine. On the basis of a combination of our own results and literature data, we conclude that the extent of this release of arsenic species is species specific, with inorganic arsenic species being released most easily, followed by the small organic As species and the large organic As species.

Arsenic-induced dyslipidemia in male albino rats: comparison between trivalent and pentavalent inorganic arsenic in drinking water.

PubMed

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

2015-06-05

Recent epidemiological evidences indicate close association between inorganic arsenic exposure via drinking water and cardiovascular diseases. However, the exact mechanism of this arsenic-mediated increase in cardiovascular risk factors remains enigmatic. In order to investigate the effects of inorganic arsenic exposure on lipid metabolism, male albino rats were exposed to 50, 100 and 150 ppm arsenic as sodium arsenite and 100, 150 and 200 ppm arsenic as sodium arsenate respectively in their drinking water for 12 weeks. Dyslipidemia induced by the two arsenicals exhibited different patterns. Hypocholesterolemia characterised the effect of arsenite at all the doses, but arsenate induced hypercholesterolemia at the 150 ppm As dose. Hypertriglyceridemia was the hallmark of arsenate effect whereas plasma free fatty acids (FFAs) was increased by the two arsenicals. Reverse cholesterol transport was inhibited by the two arsenicals as evidenced by decreased HDL cholesterol concentrations whereas hepatic cholesterol was increased by arsenite (100 ppm As), but decreased by arsenite (150 ppm As) and arsenate (100 ppm As) respectively. Brain cholesterol and triglyceride were decreased by the two arsenicals; arsenate decreased the renal content of cholesterol, but increased renal content of triglyceride. Arsenite, on the other hand, increased the renal contents of the two lipids. The two arsenicals induced phospholipidosis in the spleen. Arsenite (150 ppm As) and arsenate (100 ppm As) inhibited hepatic HMG CoA reductase. At other doses of the two arsenicals, hepatic activity of the enzyme was up-regulated. The two arsenicals however up-regulated the activity of the brain enzyme. We observed positive associations between tissue arsenic levels and plasma FFA and negative associations between tissue arsenic levels and HDL cholesterol. Our findings indicate that even though sub-chronic exposure to arsenite and arsenate through drinking water produced different patterns of dyslipidemia, our study identified two common denominators of dyslipidemia namely: inhibition of reverse cholesterol transport and increase in plasma FFA. These two denominators (in addition to other individual perturbations of lipid metabolism induced by each arsenical), suggest that in contrast to strengthening a dose-dependent effect phenomenon, the two forms of inorganic arsenic induced lipotoxic and non-lipotoxic dyslipidemia at "low" or "medium" doses and these might be responsible for the cardiovascular and other disease endpoints of inorganic arsenic exposure through drinking water.

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

PubMed

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

2012-01-01

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

40 CFR 61.180 - Applicability and designation of sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade arsenic...

40 CFR 61.180 - Applicability and designation of sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61... metallic arsenic production plant and to each arsenic trioxide plant that processes low-grade arsenic...

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

PubMed Central

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

2011-01-01

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

Association of cadmium and arsenic exposure with salivary telomere length in adolescents in Terai, Nepal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fillman, Toki, E-mail: tokif@humeco.m.u-tokyo.ac.jp; Shimizu-Furusawa, Hana, E-mail: hana-shimizu@umin.ac.jp; Ng, Chris Fook Sheng, E-mail: chrisng-tky@umin.ac.jp

Background: Cadmium and arsenic are ubiquitous metals commonly found in the environment which can harm human health. A growing body of research shows telomere length as a potential biomarker of future disease risk. Few studies have examined the effects of metals on telomere length and none have focused on adolescents. Objectives: In this study, the impact of cadmium and arsenic on salivary telomere length was studied in adolescents in Terai, Nepal. Methods: Adolescents aged 12–16 years old (n=351)were recruited where questionnaire interviews and both saliva and urine collection took place. Telomere length was determined by quantitative polymerase chain reaction usingmore » DNA extracted from saliva. Urinary cadmium and arsenic concentration were measured by inductively coupled plasma mass spectrometry. Multivariable linear regression was used to examine associations between urinary metals and salivary telomere length. Results: The geometric means and standard deviations of cadmium and arsenic were 0.33±0.33 μg/g creatinine and 196.0±301.1 μg/g creatinine, respectively. Urinary cadmium concentration was negatively associated with salivary telomere length after adjustment for confounders (β=−0.24, 95% CI −0.42,−0.07). Arsenic showed positive associations with telomere length but did not reach statistical significance. Conclusions: This is the first study to demonstrate that cadmium may shorten adolescent telomeres, even at exposure levels that may be considered low. These results agree with prior experimental and adult epidemiological studies, and also help identify the mechanism of DNA damage by cadmium. This study expanded current evidence on the harmful effects of cadmium exposure on telomere length even to adolescents. - Highlights: • This is the first study examining metal exposure on telomere length in adolescents. • Urinary cadmium levels were similar to non-industrially polluted levels in Asia. • Urinary arsenic levels were as high as groundwater arsenic polluted areas in Asia. • Urinary cadmium was negatively associated with salivary telomere length. • Urinary arsenic was not significantly associated with salivary telomere length.« less

Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

PubMed

Piñol, S; Sala, A; Guzman, C; Marcos, S; Joya, X; Puig, C; Velasco, M; Velez, D; Vall, O; Garcia-Algar, O

2015-11-01

Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries.

GENE EXPRESSION DOSE-RESPONSE IN THE BLADDERS OF MICE EXPOSED TO ARSENIC IN DRINKING WATER FOR 13 WEEKS

EPA Science Inventory

The association between drinking water exposures to inorganic arsenic and life-threatening tumors in the human is strongest for bladder cancer. To investigate the mode of action for inorganic arsenic carcinogenicity in the bladder, a study was conducted to characterize the dose-r...

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

EPA Pesticide Factsheets

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

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)...

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...

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

EPA Pesticide Factsheets

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

Determination of Inorganic Arsenic in a Wide Range of Food Matrices using Hydride Generation - Atomic Absorption Spectrometry.

PubMed

de la Calle, Maria B; Devesa, Vicenta; Fiamegos, Yiannis; Vélez, Dinoraz

2017-09-01

The European Food Safety Authority (EFSA) underlined in its Scientific Opinion on Arsenic in Food that in order to support a sound exposure assessment to inorganic arsenic through diet, information about distribution of arsenic species in various food types must be generated. A method, previously validated in a collaborative trial, has been applied to determine inorganic arsenic in a wide variety of food matrices, covering grains, mushrooms and food of marine origin (31 samples in total). The method is based on detection by flow injection-hydride generation-atomic absorption spectrometry of the iAs selectively extracted into chloroform after digestion of the proteins with concentrated HCl. The method is characterized by a limit of quantification of 10 µg/kg dry weight, which allowed quantification of inorganic arsenic in a large amount of food matrices. Information is provided about performance scores given to results obtained with this method and which were reported by different laboratories in several proficiency tests. The percentage of satisfactory results obtained with the discussed method is higher than that of the results obtained with other analytical approaches.

Arsenic in Food

MedlinePlus

... It is found in water, air, food, and soil in organic and inorganic forms. The FDA has ... of arsenic compounds in water, food, air, and soil: organic and inorganic (these together are referred to ...

Availability of arsenic in human milk in women and its correlation with arsenic in urine of breastfed children living in arsenic contaminated areas in Bangladesh.

PubMed

Islam, Md Rafiqul; Attia, John; Alauddin, Mohammad; McEvoy, Mark; McElduff, Patrick; Slater, Christine; Islam, Md Monirul; Akhter, Ayesha; d'Este, Catherine; Peel, Roseanne; Akter, Shahnaz; Smith, Wayne; Begg, Stephen; Milton, Abul Hasnat

2014-12-04

Early life exposure to inorganic arsenic may be related to adverse health effects in later life. However, there are few data on postnatal arsenic exposure via human milk. In this study, we aimed to determine arsenic levels in human milk and the correlation between arsenic in human milk and arsenic in mothers and infants urine. Between March 2011 and March 2012, this prospective study identified a total of 120 new mother-baby pairs from Kashiani (subdistrict), Bangladesh. Of these, 30 mothers were randomly selected for human milk samples at 1, 6 and 9 months post-natally; the same mother baby pairs were selected for urine sampling at 1 and 6 months. Twelve urine samples from these 30 mother baby pairs were randomly selected for arsenic speciation. Arsenic concentration in human milk was low and non-normally distributed. The median arsenic concentration in human milk at all three time points remained at 0.5 μg/L. In the mixed model estimates, arsenic concentration in human milk was non-significantly reduced by -0.035 μg/L (95% CI: -0.09 to 0.02) between 1 and 6 months and between 6 and 9 months. With the progression of time, arsenic concentration in infant's urine increased non-significantly by 0.13 μg/L (95% CI: -1.27 to 1.53). Arsenic in human milk at 1 and 6 months was not correlated with arsenic in the infant's urine at the same time points (r = -0.13 at 1 month and r = -0.09 at 6 month). Arsenite (AsIII), arsenate (AsV), monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA) and arsenobetaine (AsB) were the constituents of total urinary arsenic; DMA was the predominant arsenic metabolite in infant urine. We observed a low arsenic concentration in human milk. The concentration was lower than the World Health Organization's maximum permissible limit (WHO Permissible Limit 15 μg/kg-bw/week). Our findings support the safety of breastfeeding even in arsenic contaminated areas.

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 substances. Copyright © 2015 Elsevier B.V. All rights reserved.

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

The effect of association between inefficient arsenic methylation capacity and demographic characteristics on the risk of skin lesions.

PubMed

Rasheed, Hifza; Kay, Paul; Slack, Rebecca; Gong, Yun Yun

2018-01-15

This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090μgL -1 . The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10μgL -1 with a daily arsenic intake of 3.23±3.75mgday -1 from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48μgg -1 Cr), MMA (106.38±135.04 vs. 35.43±39.97μgg -1 Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

A review on environmental factors regulating arsenic methylation in humans.

PubMed

Tseng, Chin-Hsiao

2009-03-15

Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers.

Effects of Inorganic Arsenic, Methylated Arsenicals, and Arsenobetaine on Atherosclerosis in the apoE−/− Mouse Model and the Role of As3mt-Mediated Methylation

PubMed Central

Negro Silva, Luis Fernando; Lemaire, Maryse; Lemarié, Catherine A.; Plourde, Dany; Bolt, Alicia M.; Chiavatti, Christopher; Bohle, D. Scott; Slavkovich, Vesna; Graziano, Joseph H.; Lehoux, Stéphanie

2017-01-01

Background: Arsenic is metabolized through a series of oxidative methylation reactions by arsenic (3) methyltransferase (As3MT) to yield methylated intermediates. Although arsenic exposure is known to increase the risk of atherosclerosis, the contribution of arsenic methylation and As3MT remains undefined. Objectives: Our objective was to define whether methylated arsenic intermediates were proatherogenic and whether arsenic biotransformation by As3MT was required for arsenic-enhanced atherosclerosis. Methods: We utilized the apoE−/− mouse model to compare atherosclerotic plaque size and composition after inorganic arsenic, methylated arsenical, or arsenobetaine exposure in drinking water. We also generated apoE−/−/As3mt−/− double knockout mice to test whether As3MT-mediated biotransformation was required for the proatherogenic effects of inorganic arsenite. Furthermore, As3MT expression and function were assessed in in vitro cultures of plaque-resident cells. Finally, bone marrow transplantation studies were performed to define the contribution of As3MT-mediated methylation in different cell types to the development of atherosclerosis after inorganic arsenic exposure. Results: We found that methylated arsenicals, but not arsenobetaine, are proatherogenic and that As3MT is required for arsenic to induce reactive oxygen species and promote atherosclerosis. Importantly, As3MT was expressed and functional in multiple plaque-resident cell types, and transplant studies indicated that As3MT is required in extrahepatic tissues to promote atherosclerosis. Conclusion: Taken together, our findings indicate that As3MT acts to promote cardiovascular toxicity of arsenic and suggest that human AS3MT SNPs that correlate with enzyme function could predict those most at risk to develop atherosclerosis among the millions that are exposed to arsenic. https://doi.org/10.1289/EHP806 PMID:28728140

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

PubMed Central

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

2016-01-01

Background: Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown. Objectives: Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone. Methods: We evaluated 3,329 participants ≥ 6 years old from the 2003–2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake. Results: After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p-trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p-trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer. Conclusions: Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003–2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic exposure in the U.S. population. Citation: Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien A. 2017. Poultry consumption and arsenic exposure in the U.S. population. Environ Health Perspect 125:370–377; http://dx.doi.org/10.1289/EHP351 PMID:27735790

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

PubMed

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

2017-03-01

Arsenicals (roxarsone and nitarsone) used in poultry production likely increase inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and roxarsone or nitarsone concentrations in poultry meat. However, the association between poultry intake and exposure to these arsenic species, as reflected in elevated urinary arsenic concentrations, is unknown. Our aim was to evaluate the association between 24-hr dietary recall of poultry consumption and arsenic exposure in the U.S. population. We hypothesized first, that poultry intake would be associated with higher urine arsenic concentrations and second, that the association between turkey intake and increased urine arsenic concentrations would be modified by season, reflecting seasonal use of nitarsone. We evaluated 3,329 participants ≥ 6 years old from the 2003-2010 National Health and Nutrition Examination Survey (NHANES) with urine arsenic available and undetectable urine arsenobetaine levels. Geometric mean ratios (GMR) of urine total arsenic and DMA were compared across increasing levels of poultry intake. After adjustment, participants in the highest quartile of poultry consumption had urine total arsenic 1.12 (95% CI: 1.04, 1.22) and DMA 1.13 (95% CI: 1.06, 1.20) times higher than nonconsumers. During the fall/winter, participants in the highest quartile of turkey intake had urine total arsenic and DMA 1.17 (95% CI: 0.99, 1.39; p -trend = 0.02) and 1.13 (95% CI: 0.99, 1.30; p -trend = 0.03) times higher, respectively, than nonconsumers. Consumption of turkey during the past 24 hr was not associated with total arsenic or DMA during the spring/summer. Poultry intake was associated with increased urine total arsenic and DMA in NHANES 2003-2010, reflecting arsenic exposure. Seasonally stratified analyses by poultry type provide strong suggestive evidence that the historical use of arsenic-based poultry drugs contributed to arsenic exposure in the U.S. Nigra AE, Nachman KE, Love DC, Grau-Perez M, Navas-Acien A. 2017. Poultry consumption and arsenic exposure in the U.S. Environ Health Perspect 125:370-377; http://dx.doi.org/10.1289/EHP351.

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

PubMed Central

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

2013-01-01

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

Inorganic arsenic levels in rice milk exceed EU and US drinking water standards.

PubMed

Meharg, Andrew A; Deacon, Claire; Campbell, Robert C J; Carey, Anne-Marie; Williams, Paul N; Feldmann, Joerg; Raab, Andrea

2008-04-01

Under EU legislation, total arsenic levels in drinking water should not exceed 10 microg l(-1), while in the US this figure is set at 10 microg l(-1) inorganic arsenic. All rice milk samples analysed in a supermarket survey (n = 19) would fail the EU limit with up to 3 times this concentration recorded, while out of the subset that had arsenic species determined (n = 15), 80% had inorganic arsenic levels above 10 microg l(-1), with the remaining 3 samples approaching this value. It is a point for discussion whether rice milk is seen as a water substitute or as a food, there are no EU or US food standards highlighting the disparity between water and food regulations in this respect.

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...

Substantial contribution of biomethylation to aquifer arsenic cycling

USGS Publications Warehouse

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

2015-01-01

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

Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow

EPA Science Inventory

Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA ...

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

USGS Publications Warehouse

Fishman, M.

1977-01-01

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

Folate and Cobalamin Modify Associations between S-adenosylmethionine and Methylated Arsenic Metabolites in Arsenic-Exposed Bangladeshi Adults123

PubMed Central

Howe, Caitlin G.; Niedzwiecki, Megan M.; Hall, Megan N.; Liu, Xinhua; Ilievski, Vesna; Slavkovich, Vesna; Alam, Shafiul; Siddique, Abu B.; Graziano, Joseph H.; Gamble, Mary V.

2014-01-01

Chronic exposure to inorganic arsenic (InAs) through drinking water is a major problem worldwide. InAs undergoes hepatic methylation to form mono- and dimethyl arsenical species (MMA and DMA, respectively), facilitating arsenic elimination. Both reactions are catalyzed by arsenic (+3 oxidation state) methyltransferase (AS3MT) using S-adenosylmethionine (SAM) as the methyl donor, yielding the methylated product and S-adenosylhomocysteine (SAH), a potent product-inhibitor of AS3MT. SAM biosynthesis depends on folate- and cobalamin-dependent one-carbon metabolism. With the use of samples from 353 participants in the Folate and Oxidative Stress Study, our objective was to test the hypotheses that blood SAM and SAH concentrations are associated with arsenic methylation and that these associations differ by folate and cobalamin nutritional status. Blood SAM and SAH were measured by HPLC. Arsenic metabolites in blood and urine were measured by HPLC coupled to dynamic reaction cell inductively coupled plasma MS. In linear regression analyses, SAH was not associated with any of the arsenic metabolites. However, log(SAM) was negatively associated with log(% urinary InAs) (β: −0.11; 95% CI: −0.19, −0.02; P = 0.01), and folate and cobalamin nutritional status significantly modified associations between SAM and percentage of blood MMA (%bMMA) and percentage of blood DMA (%bDMA) (P = 0.02 and P = 0.01, respectively). In folate- and cobalamin-deficient individuals, log(SAM) was positively associated with %bMMA (β: 6.96; 95% CI: 1.86, 12.05; P < 0.01) and negatively associated with %bDMA (β: −6.19; 95% CI: −12.71, 0.32; P = 0.06). These findings suggest that when exposure to InAs is high, and methyl groups are limiting, SAM is used primarily for MMA synthesis rather than for DMA synthesis, contributing additional evidence that nutritional status may explain some of the interindividual differences in arsenic metabolism and, consequently, susceptibility to arsenic toxicity. PMID:24598884

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

PubMed

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

2013-11-01

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

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...

Arsenic exposure and oral cavity lesions in Bangladesh.

PubMed

Syed, Emdadul H; Melkonian, Stephanie; Poudel, Krishna C; Yasuoka, Junko; Otsuka, Keiko; Ahmed, Alauddin; Islam, Tariqul; Parvez, Faruque; Slavkovich, Vesna; Graziano, Joseph H; Ahsan, Habibul; Jimba, Masamine

2013-01-01

To evaluate the relationship between arsenic exposure and oral cavity lesions among an arsenic-exposed population in Bangladesh. We carried out an analysis utilizing the baseline data of the Health Effects of Arsenic Exposure Longitudinal Study, which is an ongoing population-based cohort study to investigate health outcomes associated with arsenic exposure via drinking water in Araihazar, Bangladesh. We used multinomial regression models to estimate the risk of oral cavity lesions. Participants with high urinary arsenic levels (286.1 to 5000.0 μg/g) were more likely to develop arsenical lesions of the gums (multinomial odds ratio = 2.90; 95% confidence interval, 1.11 to 7.54), and tongue (multinomial odds ratio = 2.79; 95% confidence interval, 1.51 to 5.15), compared with those with urinary arsenic levels of 7.0 to 134.0 μg/g. Higher level of arsenic exposure was positively associated with increased arsenical lesions of the gums and tongue.

STABILITY: AN INVESTIGATION OF AS(III)/AS(V) STABILITY IN IRON RICH DRINKING WATER MATRICES

EPA Science Inventory

Arsenic in drinking water is predominantly inorganic arsenic. The two oxidation states of inorganic arsenic are As(III)(pKa=9.3) and As(V)(pKa2=6.9). The distribution of As(III) and AS(V) in a water is dependent on the redox potential of the water. The actual distribution can ...

Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Shu-Mei

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293more » age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR = 0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A + A/G and DNMT3A rs34048824 T/T + T/C genotypes had significantly higher OR for ccRCC [OR = 2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan. - Highlights: • High urinary total arsenic level or polymorphism of DNMT1 increased the OR of ccRCC. • High risk genotypes of combination of DNMT1 and DNMT3A increased the OR of ccRCC. • A joint effect of urinary total arsenic level and DNMTs genotypes may affect ccRCC.« less

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

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

EPA Pesticide Factsheets

On February 19, 2010, the draft IRIS Toxicological Review of Inorganic Arsenic (Cancer) external review draft document and the charge to external peer reviewers were released for public review and comment. The draft document and the charge to external peer reviewers were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the Toxicological Review of Inorganic Arsenic and the charge to external peer reviewers are posted on this site. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical. An assessment of noncancer health effects of inorganic arsenic will be released for external peer review and public comment at a later date.

Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chia-Chang; Department of Urology, Taipei Medical University—Shuang Ho Hospital, Taipei, Taiwan; Huang, Yung-Kai

2013-10-01

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C, IL-8 − 251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquidmore » chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α − 308 G/A, IL-6 − 174 G/C and IL-8 − 251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α − 308 A/A and IL-8 − 251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose–response joint effect of TNF-α − 308 A/A or IL-8 − 251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 − 251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 − 251 T/T genotype for each SD increase in DMA%. - Highlights: • Joint effect of the TNF-α -308 A/A genotype and urinary total arsenic affected UC. • Joint effect of the IL-8 -251 T/T genotype and urinary total arsenic affected UC. • Urinary total arsenic level, TNF-α -308 A/A and IL-8 -251 T/T genotype affected UC.« less

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...

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,...

Total arsenic concentrations in Chinese children's urine by different geographic locations, ages, and genders.

PubMed

Zhang, Xuan; Wang, Beibei; Cui, Xiaoyong; Lin, Chunye; Liu, Xitao; Ma, Jin

2018-06-01

Little is known about the variation of Chinese children's exposure to arsenic by geography, age, gender, and other potential factors. The main objective of this study was to investigate the total arsenic concentration in Chinese children's urine by geographic locations, ages, and genders. In total, 259 24-h urine samples were collected from 210 2- to 12-year-old children in China and analyzed for total arsenic and creatinine concentrations. The results showed that the upper limit (upper limit of the 90% confidence interval for the 97.5 fractile) was 27.51 µg/L or 55.88 µg/g creatinine for Chinese children. The total urinary arsenic levels were significantly different for children in Guangdong, Hubei, and Gansu provinces (P < 0.05), where the upper limits were 24.29, 58.70, and 44.29 µg/g creatinine, respectively. In addition, the total urinary arsenic levels were higher for 2- to 7-year-old children than for 7- to 12-year-old children (P < 0.05; the upper limits were 59.06 and 44.29 µg/g creatinine, respectively) and higher for rural children than for urban children (P < 0.05; the upper limits were 59.06 and 50.44 µg/g creatinine, respectively). The total urinary arsenic levels for boys were not significantly different from those for girls (P > 0.05), although the level for boys (the upper limit was 59.30 µg/g) was slightly higher than that for girls (the upper limit was 58.64 µg/g creatinine). Because the total urinary arsenic concentrations are significantly different for general populations of children in different locations and age groups, the reference level of total urinary arsenic might be dependent on the geographic site and the child's age.

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

EPA Pesticide Factsheets

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

29 CFR 1926.1118 - Inorganic arsenic.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Toxic and Hazardous Substances § 1926.1118 Inorganic arsenic. Note: The requirements applicable to construction work under this section are identical...

Nutritional Influences on One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity.

PubMed

Saxena, Roheeni; Bozack, Anne K; Gamble, Mary V

2018-05-23

Exposure to inorganic arsenic (InAs) via drinking water and/or food is a considerable worldwide problem. Methylation of InAs generates monomethyl (MMAs III+V )- and dimethyl (DMAs III+V )-arsenical species in a process that facilitates urinary As elimination; however, MMA is considerably more toxic than either InAs or DMAs. Emerging evidence suggests that incomplete methylation of As to DMAs, resulting in increased MMAs, is associated with increased risk for a host of As-related health outcomes. The biochemical pathway that provides methyl groups for As methylation, one-carbon metabolism (OCM), is influenced by folate and other micronutrients, including choline and betaine. Individuals and species differ widely in their ability to methylate As. A growing body of research, including cell-culture, animal-model, and epidemiological studies, has demonstrated the role of OCM-related micronutrients in As methylation. This review examines the evidence that nutritional status and nutritional interventions can influence the metabolism and toxicity of As, with a primary focus on folate. Expected final online publication date for the Annual Review of Nutrition Volume 38 is August 21, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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

EPA Pesticide Factsheets

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

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arsenic Speciation of Solvent-Extracted Leachate from New and Weathered CCA-Treated Wood

PubMed Central

KHAN, BERNINE I.; SOLO - GABRIELE, HELENA M.; DUBEY, BRAJESH K.; TOWNSEND, TIMOTHY G.; CAI, YONG

2009-01-01

For the past 60 yr, chromate-copper-arsenate (CCA) has been used to pressure-treat millions of cubic meters of wood in the United States for the construction of many outdoor structures. Leaching of arsenic from these structures is a possible health concern as there exists the potential for soil and groundwater contamination. While previous studies have focused on total arsenic concentrations leaching from CCA-treated wood, information pertaining to the speciation of arsenic leached is limited. Since arsenic toxicity is dependent upon speciation, the objective of this study was to identify and quantify arsenic species leaching from new and weathered CCA-treated wood and CCA-treated wood ash. Solvent-extraction experiments were carried out by subjecting the treated wood and the ash to solvents of varying pH values, solvents defined in the EPA’s Synthetic Precipitation Leaching Procedure (SPLP) and Toxicity Characteristic Leaching Procedure (TCLP), rainwater, deionized water, and seawater. The generated leachates were analyzed for inorganic As(III) and As(V) and the organoarsenic species, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), using high-performance liquid chromatography followed by hydride generation and atomic fluorescence spectrometry (HPLC–HG-AFS). Only the inorganic species were detected in any of the wood leachates; no organoarsenic species were found. Inorganic As(V) was the major detectable species leaching from both new and weathered wood. The weathered wood leached relatively more overall arsenic and was attributed to increased inorganic As(III) leaching. The greater presence of As(III) in the weathered wood samples as compared to the new wood samples may be due to natural chemical and biological transformations during the weathering process. CCA-treated wood ash leached more arsenic than unburned wood using the SPLP and TCLP, and ash samples leached more inorganic As(III) than the unburned counterparts. Increased leaching was due to higher concentrations of arsenic within the ash and to the conversion of some As(V) to As(III) during combustion. PMID:15461159

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

PubMed

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

2016-03-01

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

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

Strong positive associations between seafood, vegetables, and alcohol with blood mercury and urinary arsenic levels in the Korean adult population.

PubMed

Park, Sunmin; Lee, Byung-Kook

2013-01-01

Blood mercury and urinary arsenic levels are more than fivefold greater in the Korean population compared with those of the United States. This may be related to the foods people consumed. Therefore, we examined the associations between food categories and mercury and arsenic exposure in the Korean adult population. Data regarding nutritional, biochemical, and health-related parameters were obtained from a cross-sectional study, the 2008-2009 Korean National Health and Nutrition Examination Survey (3,404 men and women age ≥ 20 years). The log-transformed blood mercury and urinary arsenic levels were regressed against the frequency tertiles of each food group after covariate adjustment for sex, age, residence area, education level, smoking status, and drinking status using food-frequency data. Blood mercury levels in the high consumption groups compared to the low consumption groups were elevated by about 20 percents with salted fish, shellfish, whitefish, bluefish, and alcohol, and by about 9-14 percents with seaweeds, green vegetables, fruits and tea, whereas rice did not affect blood mercury levels. Urinary arsenic levels were markedly increased with consumption of rice, bluefish, salted fish, shellfish, whitefish, and seaweed, whereas they were moderately increased with consumption of grains, green and white vegetables, fruits, coffee, and alcohol. The remaining food categories tended to lower these levels only minimally. In conclusion, the typical Asian diet, which is high in rice, salted fish, shellfish, vegetables, alcoholic beverages, and tea, may be associated with greater blood mercury and urinary arsenic levels. This study suggests that mercury and arsenic contents should be monitored and controlled in soil and water used for agriculture to decrease health risks from heavy-metal contamination.

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

EPA Pesticide Factsheets

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

ARSENIC AND THE EPIGENOME: LINKED BY METHYLATION(Thailand)

EPA Science Inventory

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

Inorganic Arsenic Emissions from Glass Manufacturing Plants: National Emission Standards for Hazardous Air Pollutants (NESHAP) -- 40 CFR Part 61 Subpart N

EPA Pesticide Factsheets

Learn about the NESHAP for inorganic arsenic from glass manufacturing plants by reading the rule summary, the rule history, the code of federal regulations text, additional resources and related rules

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 ...

BIOMARKERS OF EXPOSURE: A CASE STUDY WITH INORGANIC ARSENIC

EPA Science Inventory

Inorganic arsenic (iAs) is a human toxicant and carcinogen that is found in the environment as a natural contaminant and from anthropogenic sources. Most mammalian species metabolize iAs by reduction to trivalent species followed by oxidative methylation to pentavalent species. ...

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...

40 CFR 61.183 - Emission monitoring.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.183 Emission monitoring. (a... arsenic trioxide and metallic arsenic process emission stream that exits from a control device. (b) The...

40 CFR 61.183 - Emission monitoring.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.183 Emission monitoring. (a... arsenic trioxide and metallic arsenic process emission stream that exits from a control device. (b) The...

Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.

PubMed

Rager, Julia E; Auerbach, Scott S; Chappell, Grace A; Martin, Elizabeth; Thompson, Chad M; Fry, Rebecca C

2017-10-16

Prenatal inorganic arsenic (iAs) exposure influences the expression of critical genes and proteins associated with adverse outcomes in newborns, in part through epigenetic mediators. The doses at which these genomic and epigenomic changes occur have yet to be evaluated in the context of dose-response modeling. The goal of the present study was to estimate iAs doses that correspond to changes in transcriptomic, proteomic, epigenomic, and integrated multi-omic signatures in human cord blood through benchmark dose (BMD) modeling. Genome-wide DNA methylation, microRNA expression, mRNA expression, and protein expression levels in cord blood were modeled against total urinary arsenic (U-tAs) levels from pregnant women exposed to varying levels of iAs. Dose-response relationships were modeled in BMDExpress, and BMDs representing 10% response levels were estimated. Overall, DNA methylation changes were estimated to occur at lower exposure concentrations in comparison to other molecular endpoints. Multi-omic module eigengenes were derived through weighted gene co-expression network analysis, representing co-modulated signatures across transcriptomic, proteomic, and epigenomic profiles. One module eigengene was associated with decreased gestational age occurring alongside increased iAs exposure. Genes/proteins within this module eigengene showed enrichment for organismal development, including potassium voltage-gated channel subfamily Q member 1 (KCNQ1), an imprinted gene showing differential methylation and expression in response to iAs. Modeling of this prioritized multi-omic module eigengene resulted in a BMD(BMDL) of 58(45) μg/L U-tAs, which was estimated to correspond to drinking water arsenic concentrations of 51(40) μg/L. Results are in line with epidemiological evidence supporting effects of prenatal iAs occurring at levels <100 μg As/L urine. Together, findings present a variety of BMD measures to estimate doses at which prenatal iAs exposure influences neonatal outcome-relevant transcriptomic, proteomic, and epigenomic profiles.

Grain Unloading Of Arsenic Species In Rice

EPA Science Inventory

Rice (Oryza sativa) is the staple food for over half the world's population yet may represent a significant dietary source of inorganic arsenic (As), a nonthreshold, class 1 human carcinogen. Rice grain As is dominated by the inorganic species, and the organic species dim...

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....

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...

HEALTH EFFECTS FROM CHRONIC EXPOSURE TO ARSENIC VIA DRINKING WATER IN INNER MONGOLIA

EPA Science Inventory

Arsenite and arsenate are widely present in natural waters. The inorganic forms , especially arsenite, are believed to be the most toxic species. Methylation is often considered to be the primary detoxification pathway for the metaboliism of inorganic arsenic. Recently studi...

Application of titanium dioxide in arsenic removal from water: A review.

PubMed

Guan, Xiaohong; Du, Juanshan; Meng, Xiaoguang; Sun, Yuankui; Sun, Bo; Hu, Qinghai

2012-05-15

Natural arsenic pollution is a global phenomenon and various technologies have been developed to remove arsenic from drinking water. The application of TiO(2) and TiO(2)-based materials in removing inorganic and organic arsenic was summarized. TiO(2)-based arsenic removal methods developed to date have been focused on the photocatalytic oxidation (PCO) of arsenite/organic arsenic to arsenate and adsorption of inorganic and organic arsenic. Many efforts have been taken to improve the performance of TiO(2) by either combing TiO(2) with adsorbents with good adsorption property in one system or developing bifunctional adsorbents with both great photocatalytic ability and high adsorption capacity. Attempts have also been made to immobilize fine TiO(2) particles on supporting materials like chitosan beads or granulate it to facilitate its separation from water. Among the anions commonly exist in groundwater, humic acid and bicarbonate have significant influence on TiO(2) photocatalyzed oxidation of As(III)/organic arsenic while phosphate, silicate, fluoride, and humic acid affect arsenic adsorption by TiO(2)-based materials. There has been a controversy over the TiO(2) PCO mechanisms of arsenite for the past 10 years but the adsorption mechanisms of inorganic and organic arsenic onto TiO(2)-based materials are relatively well established. Future needs in TiO(2)-based arsenic removal technology are proposed. Copyright © 2012 Elsevier B.V. All rights reserved.

PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

EPA Science Inventory

Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

40 CFR 61.185 - Recordkeeping requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.185 Recordkeeping... arsenic to the atmosphere between the time of discovery and the time corrective action was taken. (c) Each... ambient inorganic arsenic concentrations at all sampling sites and other data needed to determine such...

40 CFR 61.185 - Recordkeeping requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.185 Recordkeeping... arsenic to the atmosphere between the time of discovery and the time corrective action was taken. (c) Each... ambient inorganic arsenic concentrations at all sampling sites and other data needed to determine such...

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...

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

PubMed

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

2017-11-01

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

Determination of arsenic species in edible periwinkles (Littorina littorea) by HPLC-ICPMS and XAS along a contamination gradient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whaley-Martin, K. J.; Koch, I.; Reimer, K. J.

Arsenic is naturally found in the tissues of marine animals, usually as the non-toxic arsenical arsenobetaine, but exposure to elevated arsenic concentrations in the environment may alter the arsenic species distribution within tissues of the organism. This study examined the arsenic species in the tissues of the marine periwinkle (Littorina littorea) along an arsenic concentration gradient in the sediment. The arsenicals in L. littorea were examined using the complementary analytical methods high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC–ICPMS) and X-ray absorption spectroscopy (XAS). Total arsenic concentrations in the periwinkle tissues ranged from 56 to 840more » mg · kg -1 dry weight (equivalent to 13 to 190 mg · kg -1 wet weight). Inorganic arsenicals were found to be positively correlated with total arsenic concentrations (R 2 = 0.993) and reached 600 mg · kg -1 dry weight, the highest reported to date in marine organisms. These high inorganic arsenic concentrations within this low trophic organism pose a potential toxicological risk to higher trophic consumers.« less

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...

The importance of being thiomethylated: formation, fate, and effects of methylated thioarsenicals

EPA Science Inventory

AbstractAlthough inorganic arsenic has long been recognized as a potent toxicant and carcinogen in humans, recent evidence shows that at least some of its effects are mediated by methylated metabolites. Elucidating the conversion of inorganic arsenic to mono-, di-, and tri-methyl...

Reproductive Effects Assessment Group's Report on the Mutagenicity of Inorganic Arsenic

EPA Science Inventory

Various inorganic compounds of arsenic have been tested for mutagenicity in a variety of test systems ranging in complexity from bacteria to peripheral lymphocytes of exposed human beings. Although a great deal of the data are contradictory, the weight of evidence supports the fo...

MODES OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC - MOVING TOWARDS A MORE QUANTITATIVE RISK ASSESSMENT

EPA Science Inventory

Arsenic exposures can lead to human tumors in skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical¬macromolecular interaction are (1) binding of trivalent arsenicals to sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

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.

Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomez-Rubio, Paulina; Roberge, Jason; Arendell, Leslie

2011-04-15

Human arsenic methylation efficiency has been consistently associated with arsenic-induced disease risk. Interindividual variation in arsenic methylation profiles is commonly observed in exposed populations, and great effort has been put into the study of potential determinants of this variability. Among the factors that have been evaluated, body mass index (BMI) has not been consistently associated with arsenic methylation efficiency; however, an underrepresentation of the upper BMI distribution was commonly observed in these studies. This study investigated potential factors contributing to variations in the metabolism of arsenic, with specific interest in the effect of BMI where more than half of themore » population was overweight or obese. We studied 624 adult women exposed to arsenic in drinking water from three independent populations. Multivariate regression models showed that higher BMI, arsenic (+ 3 oxidation state) methyltransferase (AS3MT) genetic variant 7388, and higher total urinary arsenic were significantly associated with low percentage of urinary arsenic excreted as monomethylarsonic acid (%uMMA) or high ratio between urinary dimethylarsinic acid and uMMA (uDMA/uMMA), while AS3MT genetic variant M287T was associated with high %uMMA and low uDMA/uMMA. The association between BMI and arsenic methylation efficiency was also evident in each of the three populations when studied separately. This strong association observed between high BMI and low %uMMA and high uDMA/uMMA underscores the importance of BMI as a potential arsenic-associated disease risk factor, and should be carefully considered in future studies associating human arsenic metabolism and toxicity.« less

In Vivo Exposure to Inorganic Arsenic Alters Differentiation-Specific Gene Expression of Adipose-Derived Mesenchymal Stem/Stromal Cells in C57BL/6J Mouse Model

PubMed Central

Shearer, Joseph J.; Figueiredo Neto, Manoel; Umbaugh, C. Samuel; Figueiredo, Marxa L.

2017-01-01

Abstract The number of mesenchymal stem cell (MSC) therapeutic modalities has grown in recent years. Adipose-derived mesenchymal stem/stromal cells (ASCs) can be isolated and expanded relatively easily as compared with their bone-marrow counterparts, making them a particularly promising source of MSCs. And although the biological mechanisms surrounding ASCs are actively being investigated, little is known about the effects that in vivo environmental exposures might have on their ability to properly differentiate. Therefore, we hypothesized that ASCs isolated from mice exposed to inorganic arsenic (iAs) would have an altered response towards adipogenic, osteogenic, and/or chondrogenic differentiation. To test this hypothesis, C57BL/6J male mice were provided drinking water containing 0, 300, or 1000 ppb iAs. ASCs were then isolated and differentiated, which was assessed by immunocytochemistry and real-time quantitative PCR (RT-qPCR). Our results showed that total urinary arsenic equilibrated within 1 week of exposure to iAs and was maintained throughout the study. ASCs isolated from each exposure group maintained differentiation capabilities for each lineage. The magnitude of differentiation-specific gene expression, however, appeared to be concentration dependent. For osteogenesis and chondrogenesis, differentiation-specific gene expression decreased, whereas adipogenesis showed a biphasic response with an initial decrease followed by an increase in adipogenic-related gene expression following iAs exposure. These results suggest that the level in which differentiation-specific genes are induced within these stromal cells might be sensitive to environmental contaminants. These findings highlight the need to take into account potential environmental exposures prior to selecting stromal cell donors, so ASCs can achieve optimal efficiency in regenerative therapy applications. PMID:28206643

*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...

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

EPA Pesticide Factsheets

EPA's Office of Research and Development (ORD), Office of Pesticide Programs (OPP), and Office of Water (OW) requested the SAB to provide advice to the Agency on several issues about the mode of carcinogenic action of various arsenic species and the implications of these issues for EPA's assessment of the cancer hazard and risks of organic and inorganic arsenic. The panel will review an OPP Science Issue Paper (with an attachment prepared by ORD) and a revised hazard and dose response assessment/characterization for inclusion in the Integrated Risk Information System (IRIS) prepared by OW. Inorganic arsenic is used for hardening copper and lead alloys. It also is used in glass manufacturing as a decolorizing and refining agent, as a component of electrical devices, in the semiconductor industry, and as a catalyst in the production of ethylene oxide.

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. Copyright © 2012 Elsevier Inc. All rights reserved.

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...

29 CFR 1910.1018 - Inorganic arsenic.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Coveralls or similar full-body work clothing; (ii) Gloves, and shoes or coverlets; (iii) Face shields or... possibility of skin or eye irritation from exposure to inorganic arsenic wash their hands and face prior to... well your respirator fits your face is very important, your employer is required to conduct fit tests...

29 CFR 1910.1018 - Inorganic arsenic.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Coveralls or similar full-body work clothing; (ii) Gloves, and shoes or coverlets; (iii) Face shields or... possibility of skin or eye irritation from exposure to inorganic arsenic wash their hands and face prior to... well your respirator fits your face is very important, your employer is required to conduct fit tests...

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...

A Prospective Study of Arsenic Exposure, Arsenic Methylation Capacity, and Risk of Cardiovascular Disease in Bangladesh

PubMed Central

Wu, Fen; Liu, Mengling; Parvez, Faruque; Slavkovich, Vesna; Eunus, Mahbub; Ahmed, Alauddin; Argos, Maria; Islam, Tariqul; Rakibuz-Zaman, Muhammad; Hasan, Rabiul; Sarwar, Golam; Levy, Diane; Graziano, Joseph

2013-01-01

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk. Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk. Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS). Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking. Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk. PMID:23665672

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...

Comparative Distribution and Retention of Arsenic in Arsenic (+3 Oxidation State) Methyltransferase Knockout and Wild Type Mice

EPA Science Inventory

The mouse arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a ~ 43 kDa protein that catalyzes conversion of inorganic arsenic into methylated products. Heterologous expression of AS3MT or its silencing by RNA interference controls arsenic methylation phenotypes...

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Chen, Baowei; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

2012-09-28

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100 ppm As(V). DMPS (2800 ppm) co-administered in the diet significantly reduced the As(V)-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA. Copyright © 2012. Published by Elsevier Ireland Ltd.

THE REACTIVE OXYGEN SPECIES (ROS) THEORY OF ARSENIC CARCINOGENESIS

EPA Science Inventory

Arsenic is a human carcinogen in skin, lung, liver, urinary bladder
and kidney. At this time, there is not a scientific consensus on the
mechanisms/modes of action for arsenic carcinogenesis. Proposed
mechanisms/modes of action for arsenic carcinogenesi...

PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTLY WITH DNA

EPA Science Inventory

PROXIMATE OR ULTIMATE GENOTOXIC FORMS OF ARSENIC: METHYLATED ARSENIC(III) SPECIES THAT REACT DIRECTL Y WITH DNA.

Abstract:

Although inorganic arsenic (iAs), arsenite or arsenate, is genotoxic, there has been no demonstration that iAs or a methylated metabolite...

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...

Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.

EPA Science Inventory

Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and ovi...

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

... Environmental Assessment (NCEA) within the EPA's Office of Research and Development (ORD). The Toxicological Review of Inorganic Arsenic was submitted to the EPA's Science Advisory Board (SAB) for external peer... IRIS IRIS is a human health assessment program that evaluates quantitative and qualitative risk...

Total and inorganic arsenic in Mid-Atlantic marine fish and shellfish and implications for fish advisories.

PubMed

Greene, Richard; Crecelius, Eric

2006-10-01

Sampling was conducted in 2002 to determine the total concentration and chemical speciation of arsenic in several marine fish and shellfish species collected from the Delaware Inland Bays and the Delaware Estuary, both of which are important estuarine waterbodies in the US Mid-Atlantic region that support recreational and commercial fishing. Edible meats from summer flounder (Paralicthys dentatus), striped bass (Marone saxatilis), Atlantic croaker (Micropogonias undulates), and hard clam (Mercenaria mercenaria) were tested. Total arsenic was highest in summer flounder, followed by hard clam, then striped bass, and finally, Atlantic croaker. Total arsenic was higher in summer flounder collected during the spring, as these fish migrated into the Inland Bays from the continental shelf, compared with levels in summer flounder collected during the fall, after these fish had spent the summer in the Inland Bays. Similarly, striped bass collected in the early spring close to the ocean had higher total arsenic levels compared with levels detected in striped bass collected later during the year in waters with lower salinity. Speciation of arsenic revealed low concentrations (0.00048-0.02 microg/g wet wt) of toxic inorganic arsenic. Dimethylarsinic acid was more than an order of magnitude greater in hard clam meats than in the other species tested, a finding that was 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 consumption advisory is not warranted.

IDENTIFYING CRITICAL CYSTEINE RESIDUES IN ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes methylation of inorganic arsenic to mono, di, and trimethylated arsenicals. Orthologous AS3MT genes in genomes ranging from simple echinoderm to human predict a protein with five conserved cysteine (C) residues. In ...

SELENIUM MODIFIES THE METABOLISM AND TOXICITY OF ARSENIC IN PRIMARY RAT HEPATOCYTES

EPA Science Inventory

ABSTRACT
Selenium Modifies the Metabolism and Toxicity of Arsenic in Primary Rat Hepatocytes. Miroslav Styblo, David J. Thomas (2000) Toxicol. Appl. Pharmacol.
Arsenic and selenium are metalloids with similar chemical properties and metabolic fates. Inorganic arsenic (iAs...

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...

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

PubMed Central

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

2014-01-01

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

Arsenic geochemistry and human health in South East Asia

PubMed Central

McCarty, Kathleen M.; Hanh, Hoang Thi; Kim, Kyoung-Woong

2011-01-01

Arsenic occurs naturally in many environmental components and enters the human body through several exposure pathways. Natural enrichment of arsenic may result in considerable contamination of soil, water, and air. Arsenic in groundwater can exceed values hundreds of time higher than the concentration recommended for drinking water. Such exposure levels indicate a serious potential health risk to individuals consuming raw groundwater. Human activities that have an impact on the environment may increase the distribution of inorganic arsenic. Abandoned mines are of great concern due to the extremely high arsenic concentrations detected in mine drainage and tailings. Diet, drinking water, air, soil, and occupational exposures are all sources of inorganic arsenic for humans. Interdisciplinary efforts to better characterize the transport of arsenic and reactants that facilitate their release to the environment are important for human health studies. Multi-disciplinary efforts are needed to study diet, infectious disease, genetics, and cultural practices unique to each region to better understand human health risk and to design public health interventions. PMID:21714384

COMPARISON OF IN VITRO AND IN VIVO RESPONSES TO ARSENIC: GENE EXPRESSION PROFILING IN NORMAL HUMAN EPIDERMAL KERATINOCYTES AND HYPERKERATOSES FROM ARSENIC-EXPOSED HUMANS

EPA Science Inventory

Chronic exposure to arsenic is positively associated with skin, urinary bladder, lung, liver and kidney cancer development in humans. Elucidating the mode of action of arsenic carcinogenesis is a complicated issue as target cells are exposed to different toxic species of arsenic....

Ground water arsenic contamination in West Bengal, India: a risk of sub-clinical toxicity in cattle as evident by correlation between arsenic exposure, excretion and deposition.

PubMed

Bera, Asit Kumar; Rana, Tanmoy; Das, Subhshree; Bhattacharya, Debasis; Bandyopadhyay, Subhasish; Pan, Diganta; De, Sumanta; Samanta, Srikanta; Chowdhury, Atalanta Narayan; Mondal, Tapan Kumar; Das, Subrata Kumar

2010-11-01

Arsenic contamination of ground water in West Bengal, India, is a great concern for both human and livestock populations. Our study investigated and correlated the arsenic concentration in the drinking water, urinary excretion and deposition of total arsenic in hair of cattle at an arsenic contaminated zone in West Bengal. The results of our study indicated that the average concentration of arsenic in tube well water in contaminated villages ranged from 0.042 to 0.251 ppm and a statistical significant (p < 0.01) difference was seen when compared to samples from a non-contaminated zone. The arsenic concentration in urine and hair of cattle ranged between 0.245-0.691 ppm and 0.461-0.984 ppm, respectively. A close relationship was found between the total arsenic in drinking water urinary excretion (r² = 0.03664, p < 0.05) and the arsenic concentration in hair (r² = 0.03668, p < 0.05). Our findings indicate that quantification of arsenic concentration in cattle urine and hair can serve as biomarkers for both present and past exposure in cattle population.

ARSENIC URINARY METABOLITES: BIOMARKER STUDY

EPA Science Inventory

A population of adults and children with ranges of 10 to 300 g/l of arsenic in their drinking water will have their urine analyzed for total and speciated arsenic. A sample of 30 families will be selected based on tap water analyses for arsenic. This sample will comprise 50% adul...

Arsenic Metabolites, Including N-Acetyl-4-hydroxy-m-arsanilic Acid, in Chicken Litter from a Roxarsone-Feeding Study Involving 1600 Chickens.

PubMed

Yang, Zonglin; Peng, Hanyong; Lu, Xiufen; Liu, Qingqing; Huang, Rongfu; Hu, Bin; Kachanoski, Gary; Zuidhof, Martin J; Le, X Chris

2016-07-05

The poultry industry has used organoarsenicals, such as 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, ROX), to prevent disease and to promote growth. Although previous studies have analyzed arsenic species in chicken litter after composting or after application to agricultural lands, it is not clear what arsenic species were excreted by chickens before biotransformation of arsenic species during composting. We describe here the identification and quantitation of arsenic species in chicken litter repeatedly collected on days 14, 24, 28, 30, and 35 of a Roxarsone-feeding study involving 1600 chickens of two strains. High performance liquid chromatography separation with simultaneous detection by both inductively coupled plasma mass spectrometry and electrospray ionization tandem mass spectrometry provided complementary information necessary for the identification and quantitation of arsenic species. A new metabolite, N-acetyl-4-hydroxy-m-arsanilic acid (N-AHAA), was identified, and it accounted for 3-12% of total arsenic. Speciation analyses of litter samples collected from ROX-fed chickens on days 14, 24, 28, 30, and 35 showed the presence of N-AHAA, 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), inorganic arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), and ROX. 3-AHPAA accounted for 3-19% of the total arsenic. Inorganic arsenicals (the sum of As(III) and As(V)) comprised 2-6% (mean 3.5%) of total arsenic. Our results on the detection of inorganic arsenicals, methylarsenicals, 3-AHPAA, and N-AHAA in the chicken litter support recent findings that ROX is actually metabolized by the chicken or its gut microbiome. The presence of the toxic metabolites in chicken litter is environmentally relevant as chicken litter is commonly used as fertilizer.

Urinary arsenic and porphyrin profile in C57BL/6J mice chronically exposed to monomethylarsonous acid (MMAIII) for two years.

PubMed

Krishnamohan, Manonmanii; Qi, Lixia; Lam, Paul K S; Moore, Michael R; Ng, Jack C

2007-10-01

Arsenicals are proven carcinogens in humans and it imposes significant health impacts on both humans and animals. Recently monomethylarsonous acid (MMA(III)), the toxic metabolite of arsenic has been identified in human urine and believed to be more acutely toxic than arsenite and arsenate. Arsenic also affects the activity of a number of haem biosynthesis enzymes. As a part of 2-year arsenic carcinogenicity study, young female C57BL/6J mice were given drinking water containing 0, 100, 250 and 500 microg/L arsenic as MMA(III)ad libitum. 24 h urine samples were collected at 0, 1, 2, 4, 8 weeks and every 8 weeks for up to 104 weeks. Urinary arsenic speciation and porphyrins were measured using HPLC-ICP-MS and HPLC with fluorescence detection respectively. DMA(V) was a major urinary metabolite detected. Significant dose-response relationship was observed between control and treatment groups after 1, 4, 24, 32, 48, 56, 88, 96 and 104 weeks. The level of uroporphyrin in 250 and 500 microg As/L group is significantly different from the control group after 4, 8, 16, 32, 56, 72, 80, 96 and 104 weeks. Coproporphyrin I level in 500 microAs/L group is significantly different from control group after 8, 24, 32, 40, 56, 72, 80, 88 and 104 weeks. After 4 weeks the level of coproporphyrin III concentration significantly increased in all the treatment groups compared to the control except week 16 and 48. Our results show urinary DMA(V) and porphyrin profile can be used as an early warning biomarker for chronic MMA(III) exposure before the onset of cancer.

Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes formation of mono-, di-, and tri-methylated metabolites of inorganic arsenic. Distribution and retention of arsenic were compared in adult female As3mt knockout mice and wild-type C57BL/6 mice using a regimen in whi...

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

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 ...

ARSENIC (III) METHYLATED SPECIES REACT WITH DNA DIRECTLY AND COULD BE PROXIMATED/ULTIMATE GENOTOXIC FORMS OF ARSENIC

EPA Science Inventory

ARSENIC(III) METHYLATED SPECIES REACT WITH DNA DIRECTL Y AND COULD BE PROXIMATE/ULTIMATE GENOTOXIC FORMS OF ARSENIC


Arsenite and arsenate (iAs, inorganic arsenic) have been thought to act as genotoxicants without reacting directly with DNA; neither iAs nor As(V) m...

Total arsenic determination and speciation in infant food products by ion chromatography-inductively coupled plasma-mass spectrometry.

PubMed

Vela, Nohora P; Heitkemper, Douglas T

2004-01-01

Health risk associated with dietary arsenic intake may be different for infants and adults. Seafood is the main contributor to arsenic intake for adults while terrestrial-based food is the primary source for infants. Processed infant food products such as rice-based cereals, mixed rice/formula cereals, milk-based infant formula, applesauce and puree of peaches, pears, carrots, sweet potatoes, green beans, and squash were evaluated for total and speciated arsenic content. Arsenic concentrations found in rice-based cereals (63-320 ng/g dry weight) were similar to those reported for raw rice. Results for the analysis of powdered infant formula by inductively coupled plasma-mass spectrometry (ICP-MS) indicated a narrow and low arsenic concentration range (12 to 17 ng/g). Arsenic content in puree infant food products, including rice cereals, fruits, and vegetables, varies from <1 to 24 ng/g wet weight. Sample treatment with trifluoroacetic acid at 100 degrees C were an efficient and mild method for extraction of arsenic species present in different food matrixes as compared to alternative methods that included sonication and accelerated solvent extraction. Extraction recoveries from 94 to 128% were obtained when the summation of species was compared to total arsenic. The ion chromatography (IC)-ICP-MS method selected for arsenic speciation allowed for the quantitative determination of inorganic arsenic [As(III) + As(V)], dimethylarsinic acid (DMA), and methylarsonic acid (MMA). Inorganic arsenic and DMA are the main species found in rice-based and mixed rice/formula cereals, although traces of MMA were also detected. Inorganic arsenic was present in freeze-dried sweet potatoes, carrots, green beans, and peaches. MMA and DMA were not detected in these samples. Arsenic species in squash, pears, and applesauce were not detected above the method detection limit [5 ng/g dry weight for As(III), MMA, and DMA and 10 ng/g dry weight for As(V)].

A need for determination of arsenic species at low levels in cereal-based food and infant cereals. Validation of a method by IC-ICPMS.

PubMed

Llorente-Mirandes, Toni; Calderón, Josep; Centrich, Francesc; Rubio, Roser; López-Sánchez, José Fermín

2014-03-15

The present study arose from the need to determine inorganic arsenic (iAs) at low levels in cereal-based food. Validated methods with a low limit of detection (LOD) are required to analyse these kinds of food. An analytical method for the determination of iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA) in cereal-based food and infant cereals is reported. The method was optimised and validated to achieve low LODs. Ion chromatography-inductively coupled plasma mass spectrometry (IC-ICPMS) was used for arsenic speciation. The main quality parameters were established. To expand the applicability of the method, different cereal products were analysed: bread, biscuits, breakfast cereals, wheat flour, corn snacks, pasta and infant cereals. The total and inorganic arsenic content of 29 cereal-based food samples ranged between 3.7-35.6 and 3.1-26.0 μg As kg(-1), respectively. The present method could be considered a valuable tool for assessing inorganic arsenic contents in cereal-based foods. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

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...

Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CD1 Mice

EPA Science Inventory

Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the bi...

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

EPA Science Inventory

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

Glutathione Modulates Recominant Rat Arsenic (+3 Oxidation State) Methyltransferase-Catalyzed Formation of Trimethylarsine Oxide and Trimethylarsine

EPA Science Inventory

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

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

EPA Science Inventory

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

ADVANCED APPROACHES TO ARSINE ATOMIZATION FOR AS SPECIATION BY CRYOFOCUSING WITH ATOMIC ABSORPTION AND ATOMIC FLUORESCENCE DETECTORS

EPA Science Inventory

Human metabolism of inorganic arsenic (iAs) yields methylated arsenicals that contain arsenic in +3 or +5 oxidation state. Trivalent methylated arsenicals are significantly more toxic than their pentavalent counterparts. Therefore, determination of tri- and pentavalent forms of m...

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

EPA Science Inventory

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

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

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

EPA Science Inventory

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

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENIC EXPOSURES

EPA Science Inventory

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

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

EPA Science Inventory

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

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

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

EPA Science Inventory

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

PROTEOMIC PROFILING OF CULTURED HUMAN BLADDER CELLS AFTER TRIVALENT ARSENICAL EXPOSURES

EPA Science Inventory

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

Arsenic: a roadblock to potential animal waste management solutions.

PubMed

Nachman, Keeve E; Graham, Jay P; Price, Lance B; Silbergeld, Ellen K

2005-09-01

The localization and intensification of the poultry industry over the past 50 years have incidentally created a largely ignored environmental management crisis. As a result of these changes in poultry production, concentrated animal feeding operations (CAFOs) produce far more waste than can be managed by land disposal within the regions where it is produced. As a result, alternative waste management practices are currently being implemented, including incineration and pelletization of waste. However, organic arsenicals used in poultry feed are converted to inorganic arsenicals in poultry waste, limiting the feasibility of waste management alternatives. The presence of inorganic arsenic in incinerator ash and pelletized waste sold as fertilizer creates opportunities for population exposures that did not previously exist. The removal of arsenic from animal feed is a critical step toward safe poultry waste management.

Hypomethylation of inflammatory genes (COX2, EGR1, and SOCS3) and increased urinary 8-nitroguanine in arsenic-exposed newborns and children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phookphan, Preeyaphan; Navasumrit, Panida

Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylationmore » of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p < 0.01). A follow-up study in these prenatally arsenic-exposed children showed a significant hypomethylation of these genes in salivary DNA (p < 0.01). In vitro experiments confirmed that arsenite treatment at short-term high doses (10–100 μM) and long-term low doses (0.5–1 μM) in human lymphoblasts (RPMI 1788) caused promoter hypomethylation of these genes, which was in concordance with an increase in their mRNA expression. Additionally, the level of urinary 8-nitroguanine was significantly higher (p < 0.01) in exposed newborns and children, by 1.4- and 1.8-fold, respectively. Arsenic accumulation in toenails was negatively correlated with hypomethylation of these genes and positively correlated with levels of 8-nitroguanine. These results indicated that early-life exposure to arsenic causes hypomethylation of COX2, EGR1, and SOCS3, increases mRNA expression of these genes, and increases 8-nitroguanine formation. These effects may be linked to mechanisms of arsenic-induced inflammation and cancer development later in life. - Highlight: • Early-life arsenic exposure caused promoter hypomethylation of COX2, EGR1 and SOCS3. • Hypomethylation of these genes is associated with increased mRNA expression. • Arsenite treatment in vitro showed hypomethylation and increased mRNA expression. • Arsenic-exposed newborns and children had higher levels of urinary 8-nitroguanine. • Urinary 8-nitroguanine correlated with hypomethylation and mRNA expression.« less

Effects of industrial processing on essential elements and regulated and emerging contaminant levels in seafood.

PubMed

Rasmussen, Rie Romme; Søndergaard, Annette Bøge; Bøknæs, Niels; Cederberg, Tommy Licht; Sloth, Jens Jørgen; Granby, Kit

2017-06-01

Mitigation of contaminants in industrial processing was studied for prawns (cooked and peeled), Greenland halibut (cold smoked) and Atlantic salmon (cold smoked and trimmed). Raw prawns had significantly higher cadmium, chromium, iron, selenium and zinc content in autumn than in spring, while summer levels typically were intermediate. Peeling raw prawns increased mercury concentration but reduced the concentration of all other elements including inorganic arsenic, total arsenic, chromium, zinc, selenium but especially cadmium, copper and iron (p < 0.05), however interaction between seasons and processing was observed. Non-toxic organic arsenic in raw Greenland halibut (N = 10) and salmon (N = 4) did not transform to carcinogenic inorganic arsenic during industrial cold smoking. Hence inorganic arsenic was low (<0.003 mg/kg wet weight) in both raw and smoked fillets rich in organic arsenic (up to 9.0 mg/kg for farmed salmon and 0.7 mg/kg for wild caught Greenland halibut per wet weight). Processing salmon did not significantly change any levels (calculated both per wet weight, dry weight or lipid content). Cold smoking decreased total arsenic (17%) and increased PCB congeners (10-22%) in Greenland halibut (wet weight). However PFOS, PCB and PBDE congeners were not different in processed Greenland halibut when corrected for water loss or lipid content. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective speciation and determination of inorganic arsenic in water, food and biological samples.

PubMed

Tuzen, Mustafa; Saygi, Kadriye Ozlem; Karaman, Isa; Soylak, Mustafa

2010-01-01

A procedure for the speciation of arsenic(III) and arsenic(V) in natural water samples has been established in the presented work. Arsenic(III) ions were quantitatively recovered on Alternaria solani coated Diaion HP-2MG resin at pH 7, while the recoveries of arsenic(V) was below 10%. Arsenic(V) in the mixing solution containing As(III) and As(V) was reduced by using KI and L(+) ascorbic acid solution, then the procedure was applied to determination of total arsenic. Arsenic(V) was calculated as the difference between the total arsenic content and As(III) content. The determination of arsenic was performed by using hydride generation atomic absorption spectrometry. The influences of some alkali, earth alkali and transition metals on the biosorption of arsenic(III) were investigated. The preconcentration factor was 35. The detection limits for As(III) (N=20, k=3) was found as 11 ng L(-1). The relative standard deviation and relative error of the determinations were found to be lower than 7% and 4%, respectively. The accuracy of the method was confirmed with certified reference materials. The method was successively applied for the determination and speciation of inorganic arsenic in water, food and biological samples. Copyright 2009 Elsevier Ltd. All rights reserved.

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...

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...

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

Determination of inorganic arsenic in algae using bromine halogenation and on-line nonpolar solid phase extraction followed by hydride generation atomic flourescence spectrometry

USDA-ARS?s Scientific Manuscript database

Accurate, stable and fast analysis of toxic inorganic arsenic (iAs) in complicated and arsenosugar-rich algae matrix is always a challenge. Herein, a novel analytical method for iAs in algae was reported, using bromine halogenation and on-line nonpolar solid phase extraction (SPE) followed by hydrid...

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...

Inter-laboratory validation of an inexpensive streamlined method to measure inorganic arsenic in rice grain

USDA-ARS?s Scientific Manuscript database

With the establishment by CODEX of a 200 ng/g limit of inorganic arsenic (iAs) in polished rice grain, more analyses of iAs will be necessary to ensure compliance in regulatory and trade applications, to assess quality control in commercial rice production, and to conduct research involving iAs in r...

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.

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...

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

PubMed

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

2014-10-01

In the recent National Research Council report on conducting a dose-response assessment for inorganic arsenic, the committee remarked that mode of action data should be used, to the extent possible, to extrapolate below the observed range for epidemiological studies to inform the shape of the dose-response curve. Recent in vitro mode of action studies focused on understanding the development of bladder cancer following exposure to inorganic arsenic provide data to inform the dose-response curve. These in vitro data, combined with results of bladder cancer epidemiology studies, inform the dose-response curve in the low-dose region, and include values for both pharmacokinetic and pharmacodynamic variability. Integration of these data provides evidence of a range of concentrations of arsenic for which no effect on the bladder would be expected. Specifically, integration of these results suggest that arsenic exposures in the range of 7-43 ppb in drinking water are exceedingly unlikely to elicit changes leading to key events in the development of cancer or noncancer effects in bladder tissue. These findings are consistent with the lack of evidence for bladder cancer following chronic ingestion of arsenic water concentrations <100 ppb in epidemiological studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coronado-Gonzalez, Jose Antonio; Razo, Luz Maria del; Garcia-Vargas, Gonzalo

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,more » 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.« less

75 FR 27554 - Science Advisory Board Staff Office; Request for Nominations of Experts for the SAB Arsenic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... Nominations of Experts for the SAB Arsenic Review Panel AGENCY: Environmental Protection Agency (EPA). ACTION... (IRIS) assessment for inorganic arsenic (noncancer). DATES: Nominations should be submitted by June 7...://www.epa.gov/sab . SUPPLEMENTARY INFORMATION: EPA is revising an assessment for arsenic in support of...

METHYLATED TRIVALENT ARSENICALS AS CANDIDATE ULTIMATE GENOTOXIC FORMS OF ARSENIC: INDUCTION OF CHROMOSOMAL MUTATIONS BUT NOT GENE MUTATIONS

EPA Science Inventory

ABSTRACT
Arsenic is a prevalent human carcinogen whose mutagenicity has not been characterized fully. Exposure to either form of inorganic arsenic, AsIII or AsV, can result in the formation of at least four organic metabolites: monomethylarsonic acid, monomethylarsonous aci...

Renin–angiotensin–aldosterone system related gene polymorphisms and urinary total arsenic is related to chronic kidney disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Wei-Jen; Huang, Ya-Li; Shiue, Horng-Sheng

A recent study demonstrated that an increased risk of chronic kidney disease (CKD) was associated with high urinary total arsenic levels. However, whether genomic instability is related to CKD remains unclear. An association between CKD and genetic polymorphisms of regulation enzymes of the renin–angiotensin–aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), and aldosterone synthase (CYP11B2) has not been shown. The aim of the present study was to investigate the relationship between arsenic, genetic polymorphisms of RAAS enzymes and CKD. A total of 233 patients and 449 age- and gender-matched controls were recruitedmore » from the Taipei Medical University Hospital, Taipei Municipal Wan Fang Hospital and the Shin Kong Wu Ho-Su Memorial Hospital. Concentrations of urinary arsenic were determined by a high-performance liquid chromatography-linked hydride generator, and atomic absorption spectrometry. Polymorphisms of ACE(I/D), AGT(A[− 20]C), (T174M), (M235T), AT1R(A1166C) and CYP11B2(C[− 344]T) were examined by polymerase chain reaction and restriction fragment length polymorphism. Subjects carrying the CYP11B2 TT genotype had a higher odds ratio (OR), 1.39 (0.96–2.01), of CKD; while those with the AGT(A[− 20]C) CC genotype had an inverse OR of CKD (0.20 (0.05–0.81)), and a high-risk genotype was defined as A/A + A/C for AGT(A[− 20C]) and T/T for CYP11B2(C[− 344]T). The trend test showed a higher OR for CKD in patients who had either high urinary total arsenic levels or carried the high-risk genotype, or both, compared to patients with low urinary total arsenic levels, who carried the low-risk genotype, and could also be affected by the hypertension or diabetes status. - Highlights: • AGT(− 20 C) and CYP11B2(− 344 T) genotypes were significantly associated with CKD. • Combined effect of high-risk genotypes and high urinary total arsenic on OR of CKD. • Combined effect on the CKD was modified by the hypertension and diabetes status.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClintock, Tyler R.; Department of Environmental Medicine, New York University School of Medicine, New York, NY; Department of Urology, New York University School of Medicine, New York, NY

2014-04-01

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

Difference of toxicity and accumulation of methylated and inorganic arsenic in arsenic-hyperaccumulating and -hypertolerant plants.

PubMed

Huang, Ze-Chun; Chen, Tong-Bin; Lei, Mei; Liu, Ying-Ru; Hu, Tian-Dou

2008-07-15

The arsenic (As) hyperaccumulators, Pteris vittata and Pteris cretica and an As-tolerant plant Boehmeria nivea, were selected to compare the toxicity, uptake, and transportation of inorganic arsenate (As(V)) and its methylated counterpart dimethylarsinic acid (DMA). The XANES method was used to elucidate the effect of As species transformation on As toxicity and accumulation characteristics. Significantly higher toxicity and lower accumulation of DMAthan inorganic As(V) was shown in the As hyperaccumulators and the As-tolerant plant. Reduction of As(V) was commonly found in the plants. Arsenic complexation with thiols, which have less mobility in plants and usually occur in As-tolerant plants, was also found in rhizoids of P. cretica. Plants with greater ability to form As-thiolate have lower ability for upward transport of As. Demethylation of DMA occurred in the three plants. The DMA component decreased from the rhizoids to the fronds in both hyperaccumulators, while this tendency is reverse in B. nivea.

Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium.

PubMed

Suzuki, Shugo; Arnold, Lora L; Pennington, Karen L; Kakiuchi-Kiyota, Satoko; Cohen, Samuel M

2009-06-30

Arsenite (As(III)), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of As(III) and dimethylarsinous acid (DMA(III)) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as l-ascorbate and N-acetylcysteine, did not inhibit As(III)-induced cytotoxicity but they were more effective at inhibiting DMA(III)-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100ppm As(III). Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by As(III) treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit As(III)-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

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...

40 CFR 61.171 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions... equipment used to collect particulate matter emissions. Converter arsenic charging rate means the hourly rate at which arsenic is charged to the copper converters in the copper converter department based on...

THE ROLE OF ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE IN ARSENIC METABOLISM

EPA Science Inventory

Arsenic (As) is widely distributed in the environment. Epidemiological studies have linked chronic exposures to inorganic As (iAs) to adverse health effects such as skin lesions, peripheral neuropathy, cardiovascular, hepatic and renal disorders, diabetes mellitus, skin cancer,...

40 CFR 61.171 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions... equipment used to collect particulate matter emissions. Converter arsenic charging rate means the hourly rate at which arsenic is charged to the copper converters in the copper converter department based on...

A STUDY OF THE INTERCONVERSION OF METHYLATED ARSENIC OXIDES TO METHYLATED ARSENIC SULFIDES IN SOLUTIONS CONTAINING FREE SULFIDE

EPA Science Inventory

Evidence suggests that thiolated arsenicals are urinary metabolites in both humans and rats. These thiolated species may be formed in the digestive system or as metabolites within the body. The role they may play in the overall toxicity of arsenic is an active area of research....

Assessment of chemical and biological significance of arsenical species in the Maurice River drainage basin (N. J. ). Part II. Partitioning of arsenic into bottom sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faust, S.D.; Winka, A.J.; Belton, T.

1987-01-01

A laboratory study was conducted on the partitioning of four arsenical species onto organic and sandy bottom sediments of Union Lake, N.J. Sandy sediments released more arsenic and sorbed less arsenic than the organic sediments. Organic sediments generally sorbed inorganic As species better than organic As species.

Arsenic and diabetes: current perspectives.

PubMed

Huang, Chun Fa; Chen, Ya Wen; Yang, Ching Yao; Tsai, Keh Sung; Yang, Rong Sen; Liu, Shing Hwa

2011-09-01

Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose-response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM) in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM). These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with respect to human exposure to arsenic in the environment. Moreover, the experimental studies were limited to the use of arsenic concentrations much higher than those relevant to human exposure. Further prospective epidemiological studies might help to clarify this controversy. The issues about environmental exposure assessment and appropriate biomarkers should also be considered. Here, we focus on the review of mechanism studies and discuss the currently available evidence and conditions for the association between environmental arsenic exposure and the development of DM. Copyright © 2011. Published by Elsevier B.V.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Fen; Department of Environmental Medicine, New York University School of Medicine, New York, NY; Jasmine, Farzana

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

40 CFR 61.186 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... at least 30 days prior notice of each reference opacity level determination required in § 61.183(a...

40 CFR 61.186 - Reporting requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... at least 30 days prior notice of each reference opacity level determination required in § 61.183(a...

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...

The Chemistry and Metabolism of Arsenic

EPA Science Inventory

I. IntrodctionA century of study of the process by which many organisms convert inorganic arsenic into an array of methylated metabolites has answered many questions and has posed some new ones. The capacity of microorganisms to. form volatile arsenic compounds was first recogniz...

Arsenic Methylation, Oxidative Stress and Cancer - Is there a Link?

EPA Science Inventory

Arsenic is a multiorgan human carcinogen. The best-known example of this effect occurred in subgroups of the Taiwanese population who were chronically exposed to high levels of naturally occurring arsenic in drinking water and developed cancers of the skin, lung, urinary bladde...

Individual variability in the human metabolism of an arsenic-containing carbohydrate, 2',3'-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-beta-D-riboside, a naturally occurring arsenical in seafood.

PubMed

Raml, Reingard; Raber, Georg; Rumpler, Alice; Bauernhofer, Thomas; Goessler, Walter; Francesconi, Kevin A

2009-09-01

We report studies on the variability in human metabolism of an oxo-arsenosugar involving the ingestion of a chemically synthesized arsenosugar and quantitative determination of the arsenic metabolites in urine and serum by HPLC coupled with arsenic-selective mass spectrometric detection (ICPMS, inductively coupled plasma mass spectrometry). The total, four-day, urinary excretion of arsenic for six volunteers ranged widely from ca. 4-95%. The arsenic metabolites present in the urine also showed great variability: high arsenic excretion was accompanied by almost complete biotransformation of the ingested oxo-arsenosugar into a multitude of metabolites (>10), whereas the subjects that excreted low amounts of arsenic produced low quantities of metabolites relative to unchanged oxo-arsenosugar and its thio-analogue. Major arsenic urinary metabolites were dimethylarsinate (DMA) and possible intermediates in the degradation of arsenosugar to DMA, namely, dimethylarsinoylethanol (DMAE) and dimethylarsinoylacetate (DMAA) present both as their oxo- and thio-analogues. Thio-DMAE and thio-DMAA were also found in blood serum indicating that these species were formed in the liver rather than on storage of the urine in the bladder. The large variability in the way individuals metabolize arsenosugars has implications for risk assessment of arsenic intake from seafood.

T05 DETERMINATION OF REDUCED ARSENIC-THIO SPECIES IN WATERS BY ION CHROMATOGRAPHY-INDUCTIVELY-COUPLED PLASMA-MASS SSPECTROMETRY (IC-ICP-MS).

EPA Science Inventory

Elevated arsenic concentrations in ground water are a significant concern for human health, because they may lead to increased arsenic exposure via drinking water. As the inorganic arsenic species arsenite (As(III)) and arsenate (As(V)) are known carcinogens, it is desirable to r...

Speciation analysis of inorganic arsenic by magnetic solid phase extraction on-line with inductively coupled mass spectrometry determination.

PubMed

Montoro Leal, P; Vereda Alonso, E; López Guerrero, M M; Cordero, M T Siles; Cano Pavón, J M; García de Torres, A

2018-07-01

Arsenic, one of the main environmental pollutants and potent natural poison, is a chemical element that is spread throughout the Earth's crust. It is well known that the toxicity of arsenic is highly dependent on its chemical forms. Generally, the inorganic species are more toxic than its organics forms, and As(III) is 60 times more toxic than As(V). In environmental waters, arsenic exists predominantly in two chemical forms: As(III) and As(V). In view of these facts, fast, sensitive, accurate and simple analytical methods for the speciation of inorganic arsenic in environmental waters are required. In this work, a new magnetic solid phase extraction with a hydride generation system was coupled on line with inductively coupled plasma mass spectrometry (MSPE-HG-ICP-MS). The new system was based on the retention of As(III) and As(V) in two knotted reactors filled with (Fe 3 O 4 ) magnetic nanoparticles functionalized with [1,5-bis (2-pyridyl) 3-sulfophenylmethylene] thiocarbonohydrazide (PSTH-MNPs). As(III) and total inorganic As were sequentially eluted in different reduction conditions. The concentration of As(V) was obtained by subtracting As(III) from total As. The system runs in a fully automated way and the method has proved to have a wide linear range and to be precise, sensitive and fast. The detection limits found were 2.7 and 3.2 ng/L for As(III) and total As, respectively; with relative standard deviations (RSDs) of 2.5% and 2.7% and a sample throughput of 14.4 h -1 . In order to validate the developed method, several certified reference samples of environmental waters including sea water, were analyzed and the determined values were in good agreement with the certified values. The proposed method was successfully applied to the speciation analysis of inorganic arsenic in well-water and sea water. Copyright © 2018 Elsevier B.V. All rights reserved.

DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS.

EPA Science Inventory

Dose-dependent alteration of oxidative stress and DNA repair gene expression by Dimethylarsinic acid [DMA(V)] in transitional epithelium of urinary bladder from female F344 rats.
Arsenic (As) is a major concern as millions of people are at risk from drinking arsenic contaminat...

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.

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 autonomousmore » 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 valuable model for arsenic-induced lung cancer.« less

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 mediated through changes in membrane fluidity brought about by changes in the concentration of cholesterol in the microsomes. © 2014 Wiley Periodicals, Inc.

Field and laboratory arsenic speciation methods and their application to natural-water analysis

USGS Publications Warehouse

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

2004-01-01

The toxic and carcinogenic properties of inorganic and organic arsenic species make their determination in natural water vitally important. Determination of individual inorganic and organic arsenic species is critical because the toxicology, mobility, and adsorptivity vary substantially. Several methods for the speciation of arsenic in groundwater, surface-water, and acid mine drainage sample matrices using field and laboratory techniques are presented. The methods provide quantitative determination of arsenite [As(III)], arsenate [As(V)], monomethylarsonate (MMA), dimethylarsinate (DMA), and roxarsone in 2-8min at detection limits of less than 1??g arsenic per liter (??g AsL-1). All the methods use anion exchange chromatography to separate the arsenic species and inductively coupled plasma-mass spectrometry as an arsenic-specific detector. Different methods were needed because some sample matrices did not have all arsenic species present or were incompatible with particular high-performance liquid chromatography (HPLC) mobile phases. The bias and variability of the methods were evaluated using total arsenic, As(III), As(V), DMA, and MMA results from more than 100 surface-water, groundwater, and acid mine drainage samples, and reference materials. Concentrations in test samples were as much as 13,000??g AsL-1 for As(III) and 3700??g AsL-1 for As(V). Methylated arsenic species were less than 100??g AsL-1 and were found only in certain surface-water samples, and roxarsone was not detected in any of the water samples tested. The distribution of inorganic arsenic species in the test samples ranged from 0% to 90% As(III). Laboratory-speciation method variability for As(III), As(V), MMA, and DMA in reagent water at 0.5??g AsL-1 was 8-13% (n=7). Field-speciation method variability for As(III) and As(V) at 1??g AsL-1 in reagent water was 3-4% (n=3). ?? 2003 Elsevier Ltd. All rights reserved.

Speciation of the Bioaccessible Fraction of Arsenic in Rice using IC-ICP-MS

EPA Science Inventory

Dietary arsenic exposure occurs mainly through drinking water and food; therefore, both aspects should be incorporated into any aggregate exposure assessment. Drinking water exposures are predominantly inorganic arsenic (AsIng) while dietary exposures are made up of a diverse se...

SPECIATION OF ARSENIC IN TARGET FOODS AND COMPOSITE DIET SAMPLES

EPA Science Inventory

For the general population, food may surpass drinking water as the major source of ingestion of total elemental arsenic. Accurate assessments of inorganic arsenic intake via food are needed to understand the relative contributions of drinking water and foods to human exposures t...

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 ...

THE ROLE OF FLAVONOIDS IN MODULATION OF THE METABOLISM OF ARSENIC

EPA Science Inventory

The biotransformation of inorganic arsenic (iAs) in humans produces trivalent and pentavalent methylated species. The pattern and extent of iAs conversion is critical for the overall toxicity and adverse health effects associated with arsenic exposure. Our previous work showed a ...

THE CELLULAR METABOLISM AND SYSTEMIC TOXICITY OF ARSENIC

EPA Science Inventory

Abstract

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

GENOTYPE AND PHENOTYPE IN THE METABOLISM, TOXICITY AND CARCINOGENICITY OF ARSENIC

EPA Science Inventory

This research will study the role of genetic factors in the expression of arsenic toxicity. The project will determine whether the interindividual variation in response is related to differences in the capacity to metabolize inorganic arsenic, if these differences in metabolic c...

THE ROLE OF VALENCE AND METHYLATION STATE ON THE ACTIVITY OF ARSENIC DURING MITOSIS

EPA Science Inventory

Trivalent methylated arsenicals are much more potent DNA damaging agents, clastogens, and large deletion mutagens than are their inorganic and pentavalent counterparts. Previously we had noticed that many of the arsenicals induced "c-type" anaphases characteristic of spindle pois...

Species Specific Bio-accessibility Estimates of Arsenic in US Consumed Rice

EPA Science Inventory

Inorganic arsenic (iAs) has been classified as a Class I carcinogen by the International Agency for Research on Cancer (IARC). For non-occupationally exposed individuals, the two predominant exposure routes for arsenic are drinking water and diet. Drinking water exposures conta...

Establishment of a method for determination of arsenic species in seafood by LC-ICP-MS.

PubMed

Zmozinski, Ariane V; Llorente-Mirandes, Toni; López-Sánchez, José F; da Silva, Márcia M

2015-04-15

An analytical method for determination of arsenic species (inorganic arsenic (iAs), methylarsonic acid (MA), dimethylarsinic acid (DMA), arsenobetaine (AB), trimethylarsine oxide (TMAO) and arsenocholine (AC)) in Brazilian and Spanish seafood samples is reported. This study was focused on extraction and quantification of inorganic arsenic (iAs), the most toxic form. Arsenic speciation was carried out via LC with both anionic and cationic exchange with ICP-MS detection (LC-ICP-MS). The detection limits (LODs), quantification limits (LOQs), precision and accuracy for arsenic species were established. The proposed method was evaluated using eight reference materials (RMs). Arsenobetaine was the main species found in all samples. The total and iAs concentration in 22 seafood samples and RMs ranged between 0.27-35.2 and 0.02-0.71 mg As kg(-1), respectively. Recoveries ranging from 100% to 106% for iAs, based on spikes, were achieved. The proposed method provides reliable iAs data for future risk assessment analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Environmental concerns of roxarsone in broiler poultry feed and litter in Maryland, USA.

PubMed

Fisher, Daniel J; Yonkos, Lance T; Staver, Kenneth W

2015-02-17

Roxarsone has been used extensively in the broiler chicken industry. We reviewed the environmental concerns of this usage. To summarize, arsenic added to poultry feed as roxarsone ends up in poultry litter. Fresh litter contains predominately roxarsone, whereas aged litter contains predominately inorganic arsenic. Soil arsenic concentrations from long-term poultry litter applications can exceed Maryland arsenic soil background remediation standards. Due to continued soil accumulation, arsenic-amended litter use as fertilizer is thought to be unsustainable. Surface-applied roxarsone-amended litter does not influence deep aquifer arsenic concentrations but is transported as inorganic arsenic to receiving waters and very shallow groundwater after precipitation. Arsenic in some receiving waters and sediments from agriculturally dominated watersheds have levels above established criteria. Arsenic in fish and shellfish is mostly organic. Phosphorus-based nutrient management will tend to limit PL application rates in areas that have over-applied phosphorus relative to crop needs, resulting in decreased rates of arsenic application and accumulation. Despite most arsenic in surface soils being tightly bound, as surface soils become more enriched in arsenic, the potential for downward movement increases but is limited in most soils due to the high capacity for binding of arsenic to clay minerals and oxides of iron and aluminum in subsoil horizons. In 2012, Maryland passed a law banning the use of arsenic additives except nitarsone in poultry feed. In 2013, the USFDA withdrew approval of roxarsone, carbarsone, and arsanilic but is reviewing nitarsone.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-06-15

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

Speciation and Localization of Arsenic in White and Brown Rice Grains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meharg, Andrew A.; Lombi, Enzo; Williams, Paul N.

2008-06-30

Synchrotron-based X-ray fluorescence (S-XRF) was utilized to locate arsenic (As) in polished (white) and unpolished (brown) rice grains from the United States, China, and Bangladesh. In white rice As was generally dispersed throughout the grain, the bulk of which constitutes the endosperm. In brown rice As was found to be preferentially localized at the surface, in the region corresponding to the pericarp and aleurone layer. Copper, iron, manganese, and zinc localization followed that of arsenic in brown rice, while the location for cadmium and nickel was distinctly different, showing relatively even distribution throughout the endosperm. The localization of As inmore » the outer grain of brown rice was confirmed by laser ablation ICP?MS. Arsenic speciation of all grains using spatially resolved X-ray absorption near edge structure (?-XANES) and bulk extraction followed by anion exchange HPLC?ICP?MS revealed the presence of mainly inorganic As and dimethylarsinic acid (DMA). However, the two techniques indicated different proportions of inorganic:organic As species. A wider survey of whole grain speciation of white (n = 39) and brown (n = 45) rice samples from numerous sources (field collected, supermarket survey, and pot trials) showed that brown rice had a higher proportion of inorganic arsenic present than white rice. Furthermore, the percentage of DMA present in the grain increased along with total grain arsenic.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Ya-Tang; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan; Genomics Research Center, Academia Sinica, Taiwan

Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan weremore » recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.« less

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico.

PubMed

Del Razo, Luz M; García-Vargas, Gonzalo G; Valenzuela, Olga L; Castellanos, Erika Hernández; Sánchez-Peña, Luz C; Currier, Jenna M; Drobná, Zuzana; Loomis, Dana; Stýblo, Miroslav

2011-08-24

Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.

Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico

PubMed Central

2011-01-01

Background Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico. Methods We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity. Results The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance. Conclusions Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII. PMID:21864395

THE VALENCE AND METHYLATION STATE OF ARSENIC DETERMINES ITS POTENCY IN INTERACTION WITH THE MITOTIC APPARATUS

EPA Science Inventory

We have previously shown that the cytotoxic and genotoxic potency of arsenicals is dependent upon their valence and methylation state. Trivalent methylated arsenicals are much more potent DNA damaging agents than are their inorganic and pentavalent counterparts. Furthermore, thei...

Arsenic uptake in organic rice production systems

USDA-ARS?s Scientific Manuscript database

Arsenic in rice is known to be a problem in some rice-producing countries that have high levels of inorganic arsenic naturally occurring in water resources. However, it was never considered an issue for USA produced rice until international market surveys were published, indicating some USA rice sam...

Arsenic and Environmental Health: State of the Science and Future Research Opportunities

EPA Science Inventory

Background: Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting ...

ARSENIC MODE OF ACTION AND DEVELOPING A BBDR MODEL

EPA Science Inventory

The current USEPA cancer risk assessment for inorganic arsenic is based on a linear extrapolation of the epidemiological data from exposed populations in Taiwan. However, proposed key events in the mode of action (MoA) for arsenic-induced cancer (which may include altered DNA me...

Trends in urinary arsenic among the U.S. population by drinking water source: Results from the National Health and Nutritional Examinations Survey 2003-2014.

PubMed

Welch, Barrett; Smit, Ellen; Cardenas, Andres; Hystad, Perry; Kile, Molly L

2018-04-01

In 2001, the United States revised the arsenic maximum contaminant level for public drinking water systems from 50µg/L to 10µg/L. This study aimed to examine temporal trends in urinary arsenic concentrations in the U.S. population from 2003 to 2014 by drinking water source among individuals aged 12 years and older who had no detectable arsenobetaine - a biomarker of arsenic exposure from seafood intake. We examined data from 6 consecutive cycles of the National Health and Nutrition Examination Survey (2003-2014; N=5848). Total urinary arsenic (TUA) was calculated by subtracting arsenobetaine's limit of detection and detectable arsenocholine from total arsenic. Additional sensitivity analyses were conducted using a second total urinary arsenic index (TUA2, calculated by adding arsenite, arsenate, monomethylarsonic acid, dimethylarsinic acid). We classified drinking water source using 24-h dietary questionnaire data as community supply (n=3427), well or rain cistern (n=506), and did not drink tap water (n=1060). Geometric means (GM) of survey cycles were calculated from multivariate regression models adjusting for age, gender, race/ethnicity, BMI, income, creatinine, water source, type of water consumed, recent smoking, and consumption of seafood, rice, poultry, and juice. Compared to 2003-2004, adjusted TUA was 35.5% lower in 2013-2014 among the general U.S. Stratified analysis by smoking status indicated that the trend in lower TUA was only consistent among non-smokers. Compared to 2003-2004, lower adjusted TUA was observed in 2013-2014 among non-smoking participants who used community water supplies (1.98 vs 1.16µg/L, p<0.001), well or rain cistern users (1.54 vs 1.28µg/L, p<0.001) and who did not drink tap water (2.24 vs 1.53µg/L, p<0.001). Sensitivity analyses showed consistent results for participants who used a community water supplier and to a lesser extent those who did not drink tap water. However, the sensitivity analysis showed overall exposure stayed the same or was higher among well or rain cistern users. Finally, the greatest decrease in TUA was among participants within the highest exposure percentiles (e.g. 95th percentile had 34% lower TUA in 2013/2014 vs 2003/2004, p<0.001). Overall, urinary arsenic levels in the U.S. population declined over a 12-year period that encompassed the adoption of the revised Arsenic Rule. The most consistent trends in declining exposure were observed among non-smoking individuals using public community water systems. These results suggest regulation and prevention strategies to reduce arsenic exposures in the U.S. may be succeeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic, chemical, and field management strategies for reducing accumulation of arsenic in rice grains

USDA-ARS?s Scientific Manuscript database

There is public concern over amounts of arsenic contained in rice grains and foods. The World Health Organization (WHO) has set a CODEX limit of 0.2 ppm inorganic arsenic (iAs) in milled white rice, and a lower limit of 0.1 ppm for baby food products. Arsenic is of greater concern in rice than oth...

Arsenic metabolism and cancer risk: A meta-analysis.

PubMed

Gamboa-Loira, Brenda; Cebrián, Mariano E; Franco-Marina, Francisco; López-Carrillo, Lizbeth

2017-07-01

To describe the studies that have reported association measures between risk of cancer and the percentage distribution of urinary inorganic arsenic (iAs) metabolites by anatomical site, in non-ecological epidemiological studies. Studies were identified in the PubMed database in the period from 1990 to 2015. Inclusion criteria were: non-ecological epidemiological study, with histologically confirmed cancer cases, reporting the percentage distribution of inorganic arsenic (iAs), monomethylated (MMA) and dimethylated (DMA) metabolites, as well as association measures with confidence intervals (CI) between cancer and %iAs and/or %MMA and/or %DMA. A descriptive meta-analysis was performed by the method of the inverse of the variance for the fixed effects model and the DerSimonian and Laird's method for the random effects model. Heterogeneity was tested using the Q statistic and stratifying for epidemiological design and total As in urine. The possibility of publication bias was assessed through Begg's test. A total of 13 eligible studies were found, most of them were performed in Taiwan and focused on skin and bladder cancer. The positive association between %MMA and various types of cancer was consistent, in contrast to the negative relationship between %DMA and cancer that was inconsistent. The summary risk of bladder (OR=1.79; 95% CI: 1.42, 2.26, n=4 studies) and lung (OR=2.44; 95% CI: 1.57, 3.80, n=2 studies) cancer increased significantly with increasing %MMA, without statistical heterogeneity. In contrast, lung cancer risk was inversely related to %DMA (OR=0.58; 95% CI: 0.36, 0.93, n=2 studies), also without significant heterogeneity. These results were similar after stratifying by epidemiological design and total As in urine. No evidence of publication bias was found. These findings provide additional support that methylation needs to be taken into account when assessing the potential iAs carcinogenicity risk. Copyright © 2017. Published by Elsevier Inc.

Arsenic levels in the groundwater of Korea and the urinary excretion among contaminated area.

PubMed

Park, Jung-Duck; Choi, Seong-Jin; Choi, Byung-Sun; Lee, Choong-Ryeol; Kim, Heon; Kim, Yong-Dae; Park, Kyung-Soo; Lee, Young-Jo; Kang, Seojin; Lim, Kyung-Min; Chung, Jin-Ho

2016-09-01

Drinking water is a main source of human exposure to arsenic. Hence, the determination of arsenic in groundwater is essential to assess its impact on public health. Here, we report arsenic levels in the groundwater of 722 sites covering all six major provinces of Korea. Water was sampled in two occasions (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured with highly sensitive inductively coupled plasma-mass spectrometry method (limit of detection, 0.1 μg/l) to encompass the current drinking water standard (<10 μg/l). Seasonal variation was negligible, but the geographical difference was prominent. Total arsenic in groundwater ranged from 0.1 to 48.4 μg/l. A 88.0-89.0% of sites were <2.0 μg/l and the remaining ones generally did not exceed 10 μg/l (6.4-7.0%, 2.0-4.9 μg/l; 2.4-3.0%, 5.0-9.9 μg/l). However, some areas (1.0-9.2%) exhibited >10 μg/l. Notably, urinary arsenic excretion of people around these regions was markedly higher compared with non-contaminated areas (<5 μg/l) (79.7±5.2 μg/g (N=122) vs 68.4±5.4 μg/g (N=65) creatinine, P=0.052). All stratified analysis also revealed higher urinary excretion, where a statistically significant difference was noted for non-smokers (85.9±12.7 vs 54.0±6.3, P=0.030), suggesting that arsenic-contaminated groundwater may contribute to its systemic exposure.

Preliminary analysis of in utero low-level arsenic exposure and fetal growth using biometric measurements extracted from fetal ultrasound reports.

PubMed

Davis, Matthew A; Higgins, John; Li, Zhigang; Gilbert-Diamond, Diane; Baker, Emily R; Das, Amar; Karagas, Margaret R

2015-03-30

Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero. Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth measures (converted to Z-scores based on reference populations for estimated fetal weight, head, and other body measures) at approximately 18 weeks of gestation. In a preliminary cross-sectional analysis of 223 out of 272 pregnancies, maternal urinary arsenic concentration (excluding arsenobetaine) was associated with a reduction in head circumference Z-score (Spearman correlation coefficient, rs = -0.08, p-value = 0.21) and a stronger association was observed among female fetuses at approximately 18 weeks of gestation (rs = - 0.21, p-value < 0.05). Although, associations were attenuated in adjusted analyses - among female fetuses a 1 μg/L increase in maternal urinary arsenic concentration was associated with a decrease of 0.047 (95% CI: -0.115, 0.021) in head circumference and 0.072 (95% CI: -0.151, 0.007) decrease in biparietal head diameter Z-score. Our study demonstrates that useful data can be extracted directly from electronic medical records for epidemiologic research. We also found evidence that exposure to low-level arsenic may be associated with reduced head circumference in a sex dependent manner that warrants further investigation.

Urinary arsenic, pesticides, heavy metals, phthalates, polyaromatic hydrocarbons, and polyfluoroalkyl compounds are associated with sleep troubles in adults: USA NHANES, 2005-2006.

PubMed

Shiue, Ivy

2017-01-01

Links between environmental chemicals and human health have emerged, but the effects on sleep health were less studied. Therefore, the aim of the present study was to investigate the relationships of different sets of environmental chemicals and common sleep troubles in a national and population-based setting. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, serum measurements, lifestyle factors, self-reported sleep troubles, and urinary environmental chemical concentrations. Statistical analyses including descriptive statistics, t-test, chi-square test, and survey-weighted logistic regression models were performed. Of all 5563 Americans aged 18-85, 2331 (42.0%) had wake-up at night, 2914 (52.5%) felt unrested during the day, 740 (13.4%) had leg jerks while sleeping, and 1059 (19.1%) had leg cramps for 2+ times a month. Higher levels of urinary arsenic, phthalates, and polyfluoroalkyl compounds were associated with wake-up at night. Higher levels of urinary 4-tert-octylphenol and polyfluoroalkyl compounds were associated with being unrested during the day. Higher levels of urinary arsenic, polyaromatic hydrocarbons, and polyfluoroalkyl compounds were associated with leg jerks while sleeping. Higher levels of urinary pesticides, heavy metals, phthalates, and polyaromatic hydrocarbons were associated with leg cramps while sleeping. However, there were no significant associations with other environmental chemicals such as parabens, bisphenol A, benzophenone-3, triclosan, perchlorate, nitrate, or thiocyanate. Eliminating arsenic, heavy metals, phthalate, pesticides, polyaromatic hydrocarbons, and polyfluoroalkyl compounds to improve sleep health might be considered while understanding the biological pathway with a longitudinal or experimental approach in future research would be suggested.

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%. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

SPECIATION OF ARSENIC IN BIOLOGICAL MATRICES BY AUTOMATED HG-AAS WITH MULTIPLE MICROFLAME QUARTZ TUBE ATOMIZER (MULTIATOMIZER)

EPA Science Inventory

Analyses of arsenic (As) species in body fluids and tissues of individuals chronically exposed to inorganic arsenic (iAs) provide essential information about the exposure level and pattern of iAs metabolism. This information facilitates the risk assessment of disorders associated...

IN-FIELD PRESERVATION OF ARSENIC SPECIES IN DRINKING WATER USING EDTA

EPA Science Inventory

The two predominant inorganic arsenic species found in drinking waters are As(III) and As(V). As(III) is commonly associated with ground waters while As(V) is associated with surface waters. The efficiency of arsenic removal from a drinking water supply is dependent on the oxid...

SEPARATION OF TOXICOLOGICALLY RELEVANT ARSENICALS IN URINE USING A NEW SOLID PHASE EXTRACTION TECHNIQUE

EPA Science Inventory

Abstract - Metabolism and toxicity of arsenicals are critically influenced by the oxidation state of As. In human urine, inorganic and methylated arsenicals contain both As(III) and As(V). Because As(III) is easily oxidized, a method is needed to preserve the native oxidation sta...

THE ROLE OF MEMBRANE TRANSPORTERS IN THE CELLULAR METABOLISM OF ARSENIC

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (AS3MT) catalyzes methylation of inorganic arsenic (iAs) in humans. In this pathway iAs is converted to mono- (MAs) and dimethylated (DMAs) metabolites containing either As^III or As^V. Because toxicities and meta...

ACCUMULATION AND METABOLISM OF ARSENIC IN MICE AFTER REPEATED ADMINISTRATION OF ARSENATE

EPA Science Inventory

Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate, Hughes, M. F., Kenyon, E. M., Edwards, B. C., Mitchell, C. T., Del Razo, L. M., and Thomas,
D. J.

The human carcinogen inorganic arsenic (iAs) is a pervasive environmental ...

40 CFR 61.174 - Test methods and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Arsenic Emissions From Primary Copper Smelters § 61.174 Test methods and procedures. (a) To determine... converter arsenic charging rate as follows: (1) Collect daily grab samples of copper matte and any lead... determine the weight percent of inorganic arsenic contained in each sample. (3) Calculate the converter...

SHRNA SILENCING OF AS3MT EXPRESSION MINIMIZES ARSENIC METHYLATION CAPACITY OF HEPG2 CELLS

EPA Science Inventory

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

Associations between Blood and Urine Arsenic Concentrations and Global Levels of Post-Translational Histone Modifications in Bangladeshi Men and Women

PubMed Central

Howe, Caitlin G.; Liu, Xinhua; Hall, Megan N.; Slavkovich, Vesna; Ilievski, Vesna; Parvez, Faruque; Siddique, Abu B.; Shahriar, Hasan; Uddin, Mohammad N.; Islam, Tariqul; Graziano, Joseph H.; Costa, Max; Gamble, Mary V.

2016-01-01

Background: Exposure to inorganic arsenic is associated with numerous adverse health outcomes, with susceptibility differing by sex. Although evidence from in vitro studies suggests that arsenic alters post-translational histone modifications (PTHMs), evidence in humans is limited. Objectives: The objectives were to determine: a) if arsenic exposure is associated with global (percent) levels of PTHMs H3K36me2, H3K36me3, and H3K79me2 in a sex-dependent manner, and b) if %PTHMs are stable when arsenic exposure is reduced. Methods: We examined associations between arsenic, measured in blood and urine, and %PTHMs in peripheral blood mononuclear cells from 317 participants enrolled in the Bangladesh Folic Acid and Creatine Trial (FACT). We also examined the stability of %PTHMs after the use of arsenic-removal water filters (n = 60). Results: Associations between natural log–transformed (ln) urinary arsenic, adjusted for creatinine (uAsCr), and %H3K36me2 differed significantly between men and women (p = 0.01). ln(uAsCr) was positively associated with %H3K36me2 in men [β = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with %H3K36me2 in women (β = –0.05; 95% CI: –0.12, 0.02, p = 0.19). The patterns of associations with blood arsenic were similar. On average, water filter use was also associated with reductions in %H3K36me2 (p < 0.01), but this did not differ significantly by sex. Arsenic was not significantly associated with %H3K36me3 or %H3K79me2 in men or women. Conclusions: Arsenic exposure was associated with %H3K36me2 in a sex-specific manner but was not associated with %H3K36me3 or %H3K79me2. Additional studies are needed to assess changes in %H3K36me2 after arsenic removal. Citation: Howe CG, Liu X, Hall MN, Slavkovich V, Ilievski V, Parvez F, Siddique AB, Shahriar H, Uddin MN, Islam T, Graziano JH, Costa M, Gamble MV. 2016. Associations between blood and urine arsenic concentrations and global levels of post-translational histone modifications in Bangladeshi men and women. Environ Health Perspect 124:1234–1240; http://dx.doi.org/10.1289/ehp.1510412 PMID:26967670

Elevated childhood exposure to arsenic despite reduced drinking water concentrations--A longitudinal cohort study in rural Bangladesh.

PubMed

Kippler, Maria; Skröder, Helena; Rahman, Syed Moshfiqur; Tofail, Fahmida; Vahter, Marie

2016-01-01

The aim of this study was to evaluate the massive efforts to lower water arsenic concentrations in Bangladesh. In our large mother-child cohort in rural Matlab, we measured the arsenic concentrations (and other elements) in drinking water and evaluated the actual exposure (urinary arsenic), from early gestation to 10 years of age (n=1017). Median drinking water arsenic decreased from 23 (2002-2003) to <2 μg/L (2013), and the fraction of wells exceeding the national standard (50 μg/L) decreased from 58 to 27%. Still, some children had higher water arsenic at 10 years than earlier. Installation of deeper wells (>50 m) explained much of the lower water arsenic concentrations, but increased the manganese concentrations. The highest manganese concentrations (~900 μg/L) appeared in 50-100 m wells. Low arsenic and manganese concentrations (17% of the children) occurred mainly in >100 m wells. The decrease in urinary arsenic concentrations over time was less apparent, from 82 to 58 μg/L, indicating remaining sources of exposure, probably through food (mean 133 μg/kg in rice). Despite decreased water arsenic concentrations in rural Bangladesh, the children still have elevated exposure, largely from food. Considering the known risks of severe health effects in children, additional mitigation strategies are needed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Arsenic speciation in edible mushrooms.

PubMed

Nearing, Michelle M; Koch, Iris; Reimer, Kenneth J

2014-12-16

The fruiting bodies, or mushrooms, of terrestrial fungi have been found to contain a high proportion of the nontoxic arsenic compound arsenobetaine (AB), but data gaps include a limited phylogenetic diversity of the fungi for which arsenic speciation is available, a focus on mushrooms with higher total arsenic concentrations, and the unknown formation and role of AB in mushrooms. To address these, the mushrooms of 46 different fungus species (73 samples) over a diverse range of phylogenetic groups were collected from Canadian grocery stores and background and arsenic-contaminated areas. Total arsenic was determined using ICP-MS, and arsenic speciation was determined using HPLC-ICP-MS and complementary X-ray absorption spectroscopy (XAS). The major arsenic compounds in mushrooms were found to be similar among phylogenetic groups, and AB was found to be the major compound in the Lycoperdaceae and Agaricaceae families but generally absent in log-growing mushrooms, suggesting the microbial community may influence arsenic speciation in mushrooms. The high proportion of AB in mushrooms with puffball or gilled morphologies may suggest that AB acts as an osmolyte in certain mushrooms to help maintain fruiting body structure. The presence of an As(III)-sulfur compound, for the first time in mushrooms, was identified in the XAS analysis. Except for Agaricus sp. (with predominantly AB), inorganic arsenic predominated in most of the store-bought mushrooms (albeit with low total arsenic concentrations). Should inorganic arsenic predominate in these mushrooms from contaminated areas, the risk to consumers under these circumstances should be considered.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Metabolism and disposition of arsenic species after repeated oral dosing with sodium arsenite in drinking water. II. Measurements in pregnant and fetal CD-1 mice.

PubMed

Twaddle, Nathan C; Vanlandingham, Michelle; Beland, Frederick A; Doerge, Daniel R

2018-05-01

Arsenic is ubiquitous in the earth's crust, and human diseases are linked with exposures that are similar to dietary intake estimates. Metabolic methylation of inorganic arsenic facilitates excretion of pentavalent metabolites and decreases acute toxicity; however, tissue binding of trivalent arsenic intermediates is evidence for concomitant metabolic activation. Pregnant and fetal CD-1 mice comprise a key animal model for arsenic carcinogenesis since adult-only exposures have minimal effects. This study evaluated inorganic arsenic and its metabolites in pentavalent and trivalent states in blood and tissues from maternal and fetal CD-1 mice after repeated administration of arsenite through drinking water. After 8 days of exposure, DMA species were ubiquitous in dams and fetuses. Despite the presence of MMA III in dams, none was observed in any fetal sample. This difference may be important in assessing fetal susceptibility to arsenic toxicity because MMA production has been linked with human disease. Binding of DMA III in fetal tissues provided evidence for metabolic activation, although the role for such binding in arsenic toxicity is unclear. This study provides links between administered dose, metabolism, and internal exposures from a key animal model of arsenic toxicity to better understand risks from human exposure to environmental arsenic. Copyright © 2018. Published by Elsevier Ltd.

Metal mixtures in urban and rural populations in the US: The Multi-Ethnic Study of Atherosclerosis and the Strong Heart Study.

PubMed

Pang, Yuanjie; Peng, Roger D; Jones, Miranda R; Francesconi, Kevin A; Goessler, Walter; Howard, Barbara V; Umans, Jason G; Best, Lyle G; Guallar, Eliseo; Post, Wendy S; Kaufman, Joel D; Vaidya, Dhananjay; Navas-Acien, Ana

2016-05-01

Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS). We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (∑As). All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (∑As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (∑As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, ∑As). LDA indicated that ∑As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants. In SHS, the ∑As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, ∑As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US. Copyright © 2016 Elsevier Inc. All rights reserved.

Arsenic methylation capacity is associated with breast cancer in northern Mexico.

PubMed

López-Carrillo, Lizbeth; Hernández-Ramírez, Raúl Ulises; Gandolfi, A Jay; Ornelas-Aguirre, José Manuel; Torres-Sánchez, Luisa; Cebrian, Mariano E

2014-10-01

Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case-control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63; 95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for trend <0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42, 95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. Copyright © 2014 Elsevier Inc. All rights reserved.

40 CFR 61.160 - Applicability and designation of source.

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Inorganic Arsenic Emissions From Glass Manufacturing Plants § 61.160 Applicability and designation... commercial arsenic as a raw material. This subpart does not apply to pot furnaces. (b) Rebricking is not...

40 CFR 142.62 - Variances and exemptions from the maximum contaminant levels for organic and inorganic chemicals.

Code of Federal Regulations, 2011 CFR

2011-07-01

... be required to convert Arsenic III to Arsenic V. 5 To obtain high removals, iron to arsenic ratio... Exchange 6=Lime Softening (not BAT for systems Corrosion... corrosion control treatment requirements for lead and copper in §§ 141.81 and 141.82 to avoid an...

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

EPA Science Inventory

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

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

EPA Science Inventory

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

DIRECT-ACTING, DNA-DAMAGING AS (III)-METHYLATED SPECIES: IMPLICATIONS FOR A CARCINOGENIC MECHANISM OF ACTION OF ARSENICALS

EPA Science Inventory

Direct-acting, DNA-damaging As (III)-methylated species: implications for a carcinogenic . mechanism of action of arsenicals

Inorganic arsenic (iAs, arsenite and arsenate) has been thought to act as a carcinogen without reacting directly with DNA; neither iAs nor the As(...

High arsenic groundwater: mobilization, metabolism and mitigation--an overview in the Bengal Delta Plain.

PubMed

Bhattacharyya, Rupa; Chatterjee, Debashis; Nath, Bibhash; Jana, Joydev; Jacks, Gunnar; Vahter, Marie

2003-11-01

The widespread occurrence of high inorganic arsenic in natural waters is attributed to human carcinogen and is identified as a major global public health issue. The scale of the problem in terms of population exposure (36 million) and geographical area coverage (173 x 10(3) Km2) to high arsenic contaminated groundwater (50-3200 microgL(-1)) compared to the National drinking water standard (50 microgL(-1)) and WHO recommended provisional limit (10 microgL(-1)) is greatest in the Holocene alluvium and deltaic aquifers of the Bengal Delta Plain (Bangladesh and West Bengal, India). This large-scale 'natural' high arsenic groundwater poses a great threat to human health via drinking water. Mobilization, metabolism and mitigation issues of high arsenic groundwater are complex and need holistic approach for sustainable development of the resource. Mobilization depends on the redox geochemistry of arsenic that plays a vital role in the release and subsequent transport of arsenic in groundwater. Metabolism narrates the biological response vis-à-vis clinical manifestations of arsenic due to various chemical and biological factors. Mitigation includes alternative source for safe drinking water supply. Drinking water quality regulatory standards as well as guidelines are yet to cover risk assessments for such metal toxicity. Lowering of the ingested inorganic arsenic level and introduction of newer treatment options (implementation of laterite, the natural material) to ensure safe water supply (arsenic free and/or low arsenic within permissible limit) are the urgent need to safe guard the mass arsenic poisoning and internal arsenic related health problems.

Assessment of arsenic in Australian grown and imported rice varieties on sale in Australia and potential links with irrigation practises and soil geochemistry.

PubMed

Fransisca, Yunnita; Small, Darryl M; Morrison, Paul D; Spencer, Michelle J S; Ball, Andrew S; Jones, Oliver A H

2015-11-01

Chronic dietary exposure to arsenic, particularly the inorganic forms (defined as elemental arsenic, predominantly As(3+) and As(5+), and all its inorganic compounds except arsine), is a matter of concern for human health. Ingestion of arsenic usually occurs via contaminated water but recent studies show there is also a risk of exposure from food, particularly Asian rice (Oryza sativa). Australia is a rice growing country, contributing around 2% of the world rice trade, and a large proportion of the population consumes rice regularly. In the present study we investigated concentrations of arsenic in both Australian grown and imported rice on sale in Australia and examined the potential links with irrigation practises and soil geochemistry. The results indicated a wide spread of arsenic levels of 0.09-0.33 mg kg(-1), with Australian grown Arborio and sushi varieties of O. sativa containing the highest mean value of ∼0.22 mg kg(-1). Arsenic levels in all samples were below the 1 mg kg(-1) limit set by Food Standards Australia New Zealand. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inverse association between toenail arsenic and body mass index in a population of welders.

PubMed

Grashow, Rachel; Zhang, Jinming; Fang, Shona C; Weisskopf, Marc G; Christiani, David C; Kile, Molly L; Cavallari, Jennifer M

2014-05-01

Recent data show that arsenic may play a role in obesity-related diseases. However, urinary arsenic studies report an inverse association between arsenic level and body mass index (BMI). We explored whether toenail arsenic, a long-term exposure measure, was associated with BMI in 74 welders with known arsenic exposure. BMI showed significant inverse associations with toenail arsenic (p=0.01), which persisted in models adjusted for demographics, diet and work history. It is unclear whether low arsenic biomarker concentrations in high BMI subjects truly reflect lower exposures, or instead reflect internal or metabolic changes that alter arsenic metabolism and tissue deposition. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of indigenous soil microbes in arsenic mitigation from contaminated alluvial soil of India.

PubMed

Majumder, Aparajita; Bhattacharyya, Kallol; Kole, S C; Ghosh, Sagarmoy

2013-08-01

Selected arsenic-volatilizing indigenous soil bacteria were isolated and their ability to form volatile arsenicals from toxic inorganic arsenic was assessed. Approximately 37 % of AsIII (under aerobic conditions) and 30 % AsV (under anaerobic conditions) were volatilized by new bacterial isolates in 3 days. In contrast to genetically modified organism, indigenous soil bacteria was capable of removing 16 % of arsenic from contaminated soil during 60 days incubation period while applied with a low-cost organic nutrient supplement (farm yard manure).

Co-exposure to methylmercury and inorganic arsenic in baby rice cereals and rice-containing teething biscuits.

PubMed

Rothenberg, Sarah E; Jackson, Brian P; Carly McCalla, G; Donohue, Alexis; Emmons, Alison M

2017-11-01

Rice is an important dietary source for methylmercury (MeHg), a potent neurotoxin, and inorganic arsenic (As), a human carcinogen. Rice baby cereals are a dietary source of inorganic As; however, less is known concerning MeHg concentrations in rice baby cereals and rice teething biscuits. MeHg concentrations were measured in 36 rice baby cereals, eight rice teething biscuits, and four baby cereals manufactured with oats/wheat (n = 48 total). Arsenic (As) species, including inorganic As, were determined in rice baby cereals and rice teething biscuits (n = 44/48), while total As was determined in all products (n = 48). Rice baby cereals and rice teething biscuits were on average 61 and 92 times higher in MeHg, respectively, and 9.4 and 4.7 times higher in total As, respectively, compared to wheat/oat baby cereals. For a 15-g serving of rice baby cereal, average MeHg intake was 0.0092μgday -1 (range: 0.0013-0.034μgday -1 ), while average inorganic As intake was 1.3μgday -1 (range: 0.37-2.3μgday -1 ). Inorganic As concentrations in two brands of rice baby cereal (n = 12/36 boxes of rice cereal) exceeded 100ng/g, the proposed action level from the U.S. Food and Drug Administration. Log 10 MeHg and inorganic As concentrations in rice baby cereals were strongly, positively correlated (Pearson's rho = 0.60, p < 0.001, n = 36). Rice-containing baby cereals and teething biscuits were a dietary source of both MeHg and inorganic As. Studies concerning the cumulative impacts of MeHg and inorganic As on offspring development are warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Arsenic methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y.-K.; Tseng, C.-H.; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Background: Cumulative arsenic exposure (CAE) from drinking water has been shown to be associated with hypertension in a dose-response pattern. This study further explored the association between arsenic methylation capability and hypertension risk among residents of arseniasis-hyperendemic areas in Taiwan considering the effect of CAE and other potential confounders. Method: There were 871 subjects (488 women and 383 men) and among them 372 were diagnosed as having hypertension based on a positive history or measured systolic blood pressure {>=} 140 mm Hg and/or diastolic blood pressure {>=} 90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generatormore » and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA{sup V}) divided by (As{sup III} + As{sup V})] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA{sup V}) were used as indicators for arsenic methylation capability. Results: The level of urinary arsenic was still significantly correlated with cumulative arsenic exposure (CAE) calculated from a questionnaire interview (p = 0.02) even after the residents stopped drinking the artesian well water for 2-3 decades. Hypertensive subjects had higher percentages of MMA{sup V} and lower SMI than subjects without hypertension. However, subjects having CAE > 0 mg/L-year had higher hypertension risk than those who had CAE = 0 mg/L-year disregard a high or low methylation index. Conclusion: Inefficient arsenic methylation ability may be related with hypertension risk.« less

Accumulation features of arsenic species in various fishes collected from coastal cities in Korea

NASA Astrophysics Data System (ADS)

Choi, Sung-Deuk; Son, Hee-Sik; Choi, Minkyu; Park, Min-Kyu

2015-12-01

In this study, 36 fish species were collected from three coastal cities in Korea to investigate levels and patterns of six arsenicals (arsenite: As (III), arsenate: As (V), arsenocholine: AsC, arsenobetaine: AsB, monomethylarsonic acid: MMA, and dimethylarsinic acid: DMA). The levels of ∑6 As in the different fish species varied substantially, ranging from 0.02 μg As/g ww (Islaeli carp) to 9.65 μg As/g ww (Skate ray) with a median of 0.40 μg As/g ww. All the arsenicals in marine fishes showed higher levels than those in freshwater fishes due to fish feed living in saline water. Overall, marine carnivorous fishes seem to be more contaminated with arsenic. For all the fish samples, AsB (mean fraction: 90.6%) was dominant among the six arsenicals, indicating biomethylation of inorganic arsenic and accumulation of AsB. Fish species with high water contents showed elevated levels of As (III), but there was no further significant correlations between arsenicals and water/lipid contents. Concentrations of As (V) were significantly lower than those of As (III), which implies that As (V) is reduced during biomethylation of inorganic arsenic. Consequently, we hypothesize that the toxicity of arsenic (mainly derived from As (III)) can be increased by the reduction of As (V), especially for the fish species with higher water contents.

Comparison of on-site field measured inorganic arsenic in rice with laboratory measurements using a field deployable method: Method validation.

PubMed

Mlangeni, Angstone Thembachako; Vecchi, Valeria; Norton, Gareth J; Raab, Andrea; Krupp, Eva M; Feldmann, Joerg

2018-10-15

A commercial arsenic field kit designed to measure inorganic arsenic (iAs) in water was modified into a field deployable method (FDM) to measure iAs in rice. While the method has been validated to give precise and accurate results in the laboratory, its on-site field performance has not been evaluated. This study was designed to test the method on-site in Malawi in order to evaluate its accuracy and precision in determination of iAs on-site by comparing with a validated reference method and giving original data on inorganic arsenic in Malawian rice and rice-based products. The method was validated by using the established laboratory-based HPLC-ICPMS. Statistical tests indicated there were no significant differences between on-site and laboratory iAs measurements determined using the FDM (p = 0.263, ά = 0.05) and between on-site measurements and measurements determined using HPLC-ICP-MS (p = 0.299, ά = 0.05). This method allows quick (within 1 h) and efficient screening of rice containing iAs concentrations on-site. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

PubMed Central

Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

2016-01-01

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

Accumulation of arsenic in leaves and grain are affected by variety and soil arsenic

USDA-ARS?s Scientific Manuscript database

The arsenic (As) levels in rice grains and food products can reach toxic levels when produced under certain growing conditions found mostly in Asia. The World Health Organization (WHO) recently set a CODEX limit of 0.2 ppm inorganic As in milled white rice, and lower limits are expected to be set f...

Probabilistic Modeling of Dietary Arsenic Exposure and Dose and Evaluation with 2003-2004 NHANES Data

EPA Science Inventory

Dietary exposure from food to toxic inorganic arsenic (iAs) in the general U.S. population has not been well studied. The goal of this research was to quantify dietary arsenic As exposure and analyze the major contributors to total As (tAs) and iAs. Another objective was to com...

SPECIATION ANALYSIS OF ARSENIC IN BIOLOGICAL MATRICES BY AUTOMATED HYDRIDE GENERATION-CRYOTRAPPING-ATOMIC ABSORPTION SPECTROMETRY WITH MULTIPLE MICROFLAME QUARTZ TUBE ATOMIZER (MULTIATOMIZER)

EPA Science Inventory

Abstract Analyses of arsenic (As) species in tissues and body fluids of individuals chronically exposed to inorganic arsenic (iAs) provide essential information about the exposure level and pattern of iAs metabolism. We have previously described an oxidation state-specifi...

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

PubMed Central

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

2016-01-01

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

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

EPA Pesticide Factsheets

EPA's Science Advisory Board (SAB) conducted a review of the scientific basis supporting the human health cancer hazard and dose-response assessment of inorganic arsenic that will appear on the Integrated Risk Information System (IRIS) database. EPA revised the assessment and is now returning the assessment to the SAB and releasing the document to the public for a focused review of EPA's responses to the SAB recommendations. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical.

Volatilization of Arsenic from Polluted Soil by Pseudomonas putida Engineered for Expression of the arsM Arsenic(III) S-Adenosine Methyltransferase Gene

PubMed Central

2015-01-01

Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 μM arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 ± 2.2% DMAs(V), 25 ± 1.4% MAs(V) and 10 ± 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 ± 1.0%) and trimethylarsine (TMAs(III)) (10 ± 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products. PMID:25122054

Volatilization of arsenic from polluted soil by Pseudomonas putida engineered for expression of the arsM Arsenic(III) S-adenosine methyltransferase gene.

PubMed

Chen, Jian; Sun, Guo-Xin; Wang, Xiao-Xue; Lorenzo, Víctor de; Rosen, Barry P; Zhu, Yong-Guan

2014-09-02

Even though arsenic is one of the most widespread environmental carcinogens, methods of remediation are still limited. In this report we demonstrate that a strain of Pseudomonas putida KT2440 endowed with chromosomal expression of the arsM gene encoding the As(III) S-adenosylmethionine (SAM) methyltransfase from Rhodopseudomonas palustris to remove arsenic from contaminated soil. We genetically engineered the P. putida KT2440 with stable expression of an arsM-gfp fusion gene (GE P. putida), which was inserted into the bacterial chromosome. GE P. putida showed high arsenic methylation and volatilization activity. When exposed to 25 μM arsenite or arsenate overnight, most inorganic arsenic was methylated to the less toxic methylated arsenicals methylarsenate (MAs(V)), dimethylarsenate (DMAs(V)) and trimethylarsine oxide (TMAs(V)O). Of total added arsenic, the species were about 62 ± 2.2% DMAs(V), 25 ± 1.4% MAs(V) and 10 ± 1.2% TMAs(V)O. Volatilized arsenicals were trapped, and the predominant species were dimethylarsine (Me2AsH) (21 ± 1.0%) and trimethylarsine (TMAs(III)) (10 ± 1.2%). At later times, more DMAs(V) and volatile species were produced. Volatilization of Me2AsH and TMAs(III) from contaminated soil is thus possible with this genetically engineered bacterium and could be instrumental as an agent for reducing the inorganic arsenic content of soil and agricultural products.

The effect of the Environmental Protection Agency maximum contaminant level on arsenic exposure in the USA from 2003 to 2014: an analysis of the National Health and Nutrition Examination Survey (NHANES).

PubMed

Nigra, Anne E; Sanchez, Tiffany R; Nachman, Keeve E; Harvey, David; Chillrud, Steven N; Graziano, Joseph H; Navas-Acien, Ana

2017-11-01

The current US Environmental Protection Agency (EPA) maximum contaminant level (MCL) for arsenic in public water systems (10 µg/L) took effect in 2006. Arsenic is not federally regulated in private wells. The impact of the 2006 MCL on arsenic exposure in the US, as confirmed through biomarkers, is presently unknown. We evaluated national trends in water arsenic exposure in the US, hypothesizing that urinary arsenic levels would decrease over time among participants using public water systems but not among those using well water. We further estimated the expected number of avoided lung, bladder, and skin cancer cases. We evaluated 14,127 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2014 with urinary dimethylarsinate (DMA) and total arsenic available. To isolate water exposure, we expanded a residual-based method to remove tobacco and dietary contributions of arsenic. We applied EPA risk assessment approaches to estimate the expected annual number of avoided cancer cases comparing arsenic exposure in 2013-2014 vs. 2003-2004. Among public water users, fully adjusted geometric means (GMs) of DMA decreased from 3.01 µg/L in 2003-2004 to 2.49 µg/L in 2013-2014 (17% reduction; 95% confidence interval 10%, 24%; p-trend<0.01); no change was observed among well water users (p-trend= 0.35). Assuming these estimated exposure reductions will remain similar across a lifetime, we estimate a reduction of 200 to 900 lung and bladder cancer cases per year depending on the approach used. The decline in urinary arsenic among public water but not private well users in NHANES 2003-2014 indicates that the implementation of the current MCL has reduced arsenic exposure in the US population. Our study supports prior work showing that well water users are inadequately protected against drinking water arsenic, and confirms the critical role of federal drinking water regulations in reducing toxic exposures and protecting human health. This work was supported by the National Institute of Environmental Health Sciences (1R01ES025216, R01ES021367, 5P30ES009089 and P42ES010349). A. E. Nigra was supported by 5T32ES007322.

Cooking rice in excess water reduces both arsenic and enriched vitamins in the cooked grain.

PubMed

Gray, Patrick J; Conklin, Sean D; Todorov, Todor I; Kasko, Sasha M

2016-01-01

This paper reports the effects of rinsing rice and cooking it in variable amounts of water on total arsenic, inorganic arsenic, iron, cadmium, manganese, folate, thiamin and niacin in the cooked grain. We prepared multiple rice varietals both rinsed and unrinsed and with varying amounts of cooking water. Rinsing rice before cooking has a minimal effect on the arsenic (As) content of the cooked grain, but washes enriched iron, folate, thiamin and niacin from polished and parboiled rice. Cooking rice in excess water efficiently reduces the amount of As in the cooked grain. Excess water cooking reduces average inorganic As by 40% from long grain polished, 60% from parboiled and 50% from brown rice. Iron, folate, niacin and thiamin are reduced by 50-70% for enriched polished and parboiled rice, but significantly less so for brown rice, which is not enriched.

Arsenic and its compounds in mushrooms: A review.

PubMed

Falandysz, Jerzy; Rizal, Leela M

2016-10-01

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

Arsenic Methylation in Arabidopsis thaliana Expressing an Algal Arsenite Methyltransferase Gene Increases Arsenic Phytotoxicity

PubMed Central

Tang, Zhong; Lv, Yanling; Chen, Fei; Zhang, Wenwen; Rosen, Barry P.; Zhao, Fang-Jie

2016-01-01

Arsenic (As) contamination in soil can lead to elevated transfer of As to the food chain. One potential mitigation strategy is to genetically engineer plants to enable them to transform inorganic As to methylated and volatile As species. In this study, we genetically engineered two ecotypes of Arabidopsis thaliana with the arsenite (As(III)) S-adenosylmethyltransferase (arsM) gene from the eukaryotic alga Chlamydomonas reinhardtii. The transgenic A. thaliana plants gained a strong ability to methylate As, converting most of the inorganic As into dimethylarsenate [DMA(V)] in the shoots. Small amounts of volatile As were detected from the transgenic plants. However, the transgenic plants became more sensitive to As(III) in the medium, suggesting that DMA(V) is more phytotoxic than inorganic As. The study demonstrates a negative consequence of engineered As methylation in plants and points to a need for arsM genes with a strong ability to methylate As to volatile species. PMID:26998776

Prevalence of Chronic Diseases in Adults Exposed to Arsenic-Contaminated Drinking Water

PubMed Central

Zierold, Kristina M.; Knobeloch, Lynda; Anderson, Henry

2004-01-01

Inorganic arsenic is naturally occurring in groundwaters throughout the United States. This study investigated arsenic exposure and self-report of 9 chronic diseases. We received private well-water samples and questionnaires from 1185 people who reported drinking their water for 20 or more years. Respondents with arsenic levels of 2 μg/L or greater were statistically more likely to report a history of depression, high blood pressure, circulatory problems, and bypass surgery than were respondents with arsenic concentrations less than 2 μg/L. PMID:15514231

Evaluation of the fate of arsenic-contaminated groundwater at different aquifers of Thar coalfield Pakistan.

PubMed

Ali, Jamshed; Kazi, Tasneem G; Baig, Jameel A; Afridi, Hassan I; Arain, Mariam S; Ullah, Naeem; Brahman, Kapil D; Arain, Sadaf S; Panhwar, Abdul H

2015-12-01

In present study, the ground water at different aquifers was evaluated for physicochemical parameters, iron, total arsenic, total inorganic arsenic and arsenic species (arsenite and arsenate). The samples of groundwater were collected at different depths, first aquifer (AQ1) 50-60 m, second aquifer (AQ2) 100-120 m, and third aquifer (AQ3) 200-250 m of Thar coalfield, Pakistan. Total inorganic arsenic was determined by solid phase extraction using titanium dioxide as an adsorbent. The arsenite was determined by cloud point extraction using ammonium pyrrolidinedithiocarbamate as a chelating reagent, and resulted complex was extracted by Triton X-114. The resulted data of groundwater were reported in terms of basic statistical parameters, principal component, and cluster analysis. The resulted data indicated that physicochemical parameters of groundwater of different aquifers were exceeded the World Health Organization provisional guideline for drinking water except pH and SO4(2-). The positive correlation was observed between arsenic species and physicochemical parameters of groundwater except F(-) and K(+), which might be caused by geochemical minerals. Results of cluster analysis indicated that groundwater samples of AQ1 was highly contaminated with arsenic species as compared to AQ2 and AQ3 (p > 0.05).

Presence of organoarsenicals used in cotton production in agricultural water and soil of the Southern United States

USGS Publications Warehouse

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

2002-01-01

Arsenicals have been used extensively in agriculture in the United States as insecticides and herbicides. Mono- and disodium methylarsonate and dimethylarsinic acid are organoarsenicals used to control weeds in cotton fields and as defoliation agents applied prior to cotton harvesting. Because the toxicity of most organoarsenicals is less than that of inorganic arsenic species, the introduction of these compounds into the environment might seem benign. However, biotic and abiotic degradation reactions can produce more problematic inorganic forms of arsenic, such as arsenite [As(III)] and arsenate [As(V)]. This study investigates the occurrences of these compounds in samples of soil and associated surface and groundwaters. Preliminary results show that surface water samples from cotton-producing areas have elevated concentrations of methylarsenic species (>10 ??g of As/L) compared to background areas (<1 ??g of As/L). Species transformations also occur between surface waters and adjacent soils and groundwaters, which also contain elevated arsenic. The data indicate that point sources of arsenic related to agriculture might be responsible for increased arsenic concentrations in local irrigation wells, although the elevated concentrations did not exceed the new (2002) arsenic maximum contaminant level of 10 ??g/L in any of the wells sampled thus far.

Arsenic in freshwater fish in the Chihuahua County water reservoirs (Mexico).

PubMed

Nevárez, Myrna; Moreno, Myriam Verónica; Sosa, Manuel; Bundschuh, Jochen

2011-01-01

Water reservoirs in Chihuahua County, Mexico, are affected by some punctual and non-punctual geogenic and anthropogenic pollution sources; fish are located at the top of the food chain and are good indicators for the ecosystems pollution. The study goal was to: (i) determine arsenic concentration in fish collected from the Chuviscar, Chihuahua, San Marcos and El Rejon water reservoirs; (ii) to assess if the fishes are suitable for human consumption and (iii) link the arsenic contents in fish with those in sediment and water reported in studies made the same year for these water reservoirs. Sampling was done in summer, fall and winter. The highest arsenic concentration in the species varied through the sampling periods: Channel catfish (Ictalurus punctatus) with 0.22 ± 0.15 mg/kg dw in winter and Green sunfish (Lepomis cyanellus) with 2.00 ± 0.15 mg/kg dw in summer in El Rejon water reservoir. A positive correlation of arsenic contents was found through all sampling seasons in fish samples and the samples of sediment and water. The contribution of the weekly intake of inorganic arsenic, based on the consumption of 0.245 kg fish muscles/body weight/week was found lower than the acceptable weekly intake of 0.015 mg/kg/body weight for inorganic arsenic suggested by FAO/WHO.

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). Copyright © 2014 Elsevier B.V. All rights reserved.

METHYLATION OF ARSENIC BY RECOMBINANT HUMAN AS3MT/287M AND AS3MT/287T POLYMORPHS

EPA Science Inventory

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). AS3MT polymorphism is, in part, responsible for interindividual differences in iAs metabolism. AS3MT/M287T polymorphism that is found in ~ 10% of C...

Arsenic biotransformation by a cyanobacterium Nostoc sp. PCC 7120.

PubMed

Xue, Xi-Mei; Yan, Yu; Xiong, Chan; Raber, Georg; Francesconi, Kevin; Pan, Ting; Ye, Jun; Zhu, Yong-Guan

2017-09-01

Nostoc sp. PCC 7120 (Nostoc), a typical filamentous cyanobacterium ubiquitous in aquatic system, is recognized as a model organism to study prokaryotic cell differentiation and nitrogen fixation. In this study, Nostoc cells incubated with arsenite (As(III)) for two weeks were extracted with dichloromethane/methanol (DCM/MeOH) and the extract was partitioned between water and DCM. Arsenic species in aqueous and DCM layers were determined using high performance liquid chromatography - inductively coupled plasma mass spectrometer/electrospray tandem mass spectrometry (HPLC-ICPMS/ESIMSMS). In addition to inorganic arsenic (iAs), the aqueous layer also contained monomethylarsonate (MAs(V)), dimethylarsinate (DMAs(V)), and the two arsenosugars, namely a glycerol arsenosugar (Oxo-Gly) and a phosphate arsenosugar (Oxo-PO4). Two major arsenosugar phospholipids (AsSugPL982 and AsSugPL984) were detected in DCM fraction. Arsenic in the growth medium was also investigated by HPLC/ICPMS and shown to be present mainly as the inorganic forms As(III) and As(V) accounting for 29%-38% and 29%-57% of the total arsenic respectively. The total arsenic of methylated arsenic, arsenosugars, and arsenosugar phospholipids in Nostoc cells with increasing As(III) exposure were not markedly different, indicating that the transformation to organoarsenic in Nostoc was not dependent on As(III) concentration in the medium. Our results provide new insights into the role of cyanobacteria in the biogeochemical cycling of arsenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-12-07

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

Magnetic ferrite particles combined with electrothermal atomic absorption spectrometry for the speciation of low concentrations of arsenic.

PubMed

López-García, Ignacio; Marín-Hernández, Juan José; Hernández-Córdoba, Manuel

2018-05-01

Freshly in situ prepared ferrite particles were used for the micro-solid phase extraction of arsenic species. When the separation was carried out at pH 8, inorganic arsenic (As(III) + As(V)) and monomethylarsonic acid (MMA) were retained in the magnetic material. A second aliquot was treated with 2,3 dimercapto propanol, leading to the retention of As(V)+MMA, while a third aliquot was first treated with sodium thiosulphate, in which case only inorganic arsenic passed to the solid phase. In all cases, the solid residue collected by a magnet was suspended in a dilute nitric acid solution containing Triton X-100 and introduced into the electrothermal atomizer to obtain the analytical signal of arsenic. The use of palladium as a chemical modifier allowed calibration to be carried out with aqueous standards. The detection limit was 0.02µgL -1 arsenic for a 10mL sample volume. The procedure was applied to waters and herbal infusions, and its reliability was evaluated by analyzing eleven certified reference materials for which speciation data are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

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

The relation between rice consumption, arsenic contamination, and prevalence of diabetes in South Asia

PubMed Central

Hassan, Fatima Ismail; Niaz, Kamal; Khan, Fazlullah; Maqbool, Faheem; Abdollahi, Mohammad

2017-01-01

Rice is the major staple food for about two billion people living in Asia. It has been reported to contain considerable amount of inorganic arsenic which is toxic to pancreatic beta cells and disrupt glucose homeostasis. Articles and conference papers published between 1992 and 2017, indexed in Scopus, PubMed, EMBASE, Google, and Google scholar were used. Arsenic exposure has been associated with increased blood glucose and insulin levels, or decreased sensitization of insulin cells to glucose uptake. Several studies have shown the association between inorganic arsenic exposure and incidence of diabetes mellitus. Considerable amounts of arsenic have been reported in different types of rice which may be affected by cultivation methods, processing, and country of production. Use of certain microbes, fertilizers, and enzymes may reduce arsenic uptake or accumulation in rice, which may reduce its risk of toxicity. Combined exposure to contaminated rice, other foods and drinking water may increase the risk of diabetes in these countries. Maximum tolerated daily intake of arsenic contaminated rice (2.1 µg/day kg body weight) has been set by WHO, which may be exceeded depending on its content in rice and amount consumed. Hence, increased prevalence of diabetes in South Asia may be related to the consumption of arsenic contaminated rice depending on its content in the rice and daily amount consumed. In this review, we have focused on the possible relation between rice consumption, arsenic contamination, and prevalence of diabetes in South Asia. PMID:29285009

Arsenic exposure, genetic susceptibility and leukocyte telomere length in an Italian young adult population.

PubMed

Borghini, Andrea; Faita, Francesca; Mercuri, Antonella; Minichilli, Fabrizio; Bustaffa, Elisa; Bianchi, Fabrizio; Andreassi, Maria Grazia

2016-09-01

Arsenic-induced health effects may be associated with critically shortened telomeres. However, few data are available on the effects of arsenic exposure on telomere length. The aim of this study was to investigate the effects of chronic arsenic exposure on leukocyte telomere length (LTL) as well as the contribution of common polymorphisms in genes implicated in arsenic metabolism (GSTT1 and GSTM1) and DNA repair (hOGG1 and XRCC1). A group of 241 healthy subjects was enrolled from four areas of Italy known to be affected by natural or anthropogenic arsenic pollution. Urine samples were tested for inorganic As (iAs), monomethylarsinic (MMA) and dimethylarsinic acid (DMA). LTL was evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Genotyping was carried out by PCR-RFLP on leukocyte DNA. In multiple linear regression analysis, LTL was significantly and inversely correlated with age (β = -0.231, P = 0.006) and showed a certain trend toward significance with iAs urinary concentration (log10 iAs, β = -0.106, P = 0.08). The genotype distribution showed significant associations between GSTT1 and the As concentration (log10 iAs, P = 0.01) and metabolite patterns (log10 DMA, P = 0.05) in the urine. However, GST genes did not interact with arsenic exposure in the modulation of LTL. Conversely, the combined presence of a higher level of iAs + MMA + DMA ≥ 19.3 μg/l (F = 6.0, P interaction = 0.01), Asi ≥ 3.86 (F = 3.9, P interaction = 0.04) μg/l, iAs + MMA + DMA ≥ 15 μg/l (F = 4.2, P interaction = 0.04) and hOGG1 Cys allele was associated with a significantly lower LTL. An interaction between XRCC1 Arg399Gln and arsenic exposure was also observed (all P interaction = 0.04). These findings suggest that telomere shortening may represent a mechanism that contributes to arsenic-related disease. The interaction of hOGG1 and XRCC1 DNA repair polymorphisms and exposure enhances telomeric DNA damage. Future studies are warranted to understand better the epidemiologic impact of arsenic on telomere function as well as to identify the subgroups of exposed subjects who need better health surveillance. © The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

40 CFR 141.51 - Maximum contaminant level goals for inorganic contaminants.

Code of Federal Regulations, 2010 CFR

2010-07-01

...: Contaminant MCLG (mg/l) Antimony 0.006 Arsenic zero 1 Asbestos 7 Million fibers/liter (longer than 10 µm... Nitrogen). Selenium 0.05 Thallium .0005 1 This value for arsenic is effective January 23, 2006. Until then...

Arsenolysis and Thiol-Dependent Arsenate Reduction

EPA Science Inventory

Conversion of arsenate to arsenite is a critical event in the pathway that leads from inorganic arsenic to a variety of methylated metabolites. The formation of methylated metabolites influences distribution and retention of arsenic and affects the reactivity and toxicity of thes...

Intercomparison of analytical methods for arsenic speciation in human urine.

PubMed

Crecelius, E; Yager, J

1997-06-01

An intercomparison exercise was conducted for the quantification of arsenic species in spiked human urine. The primary objective of the exercise was to determine the variance among laboratories in the analysis of arsenic species such as inorganic As (As+3 and As+5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). Laboratories that participated had previous experience with arsenic speciation analysis. The results of this interlaboratory comparison are encouraging. There is relatively good agreement on the concentrations of these arsenic species in urine at concentrations that are relevant to research on the metabolism of arsenic in humans and other mammals. Both the accuracy and precision are relatively poor for arsenic concentrations of less than about 5 micrograms/l.

Organic Arsenicals as Functional Motifs in Polymer and Biomaterials Science.

PubMed

Tanaka, Joji; Davis, Thomas P; Wilson, Paul

2018-05-28

Arsenic (As) exhibits diverse (bio)chemical reactivity and biological activity depending upon its oxidation state. However, this distinctive reactivity has been largely overlooked across many fields owing to concerns regarding the toxicity of arsenic. Recently, a clinical renaissance in the use of arsenicals, including organic arsenicals that are known to be less toxic than inorganic arsenicals, alludes to the possibility of broader acceptance and application in the field of polymer and biomaterials science. Here, current examples of polymeric/macromolecular arsenicals are reported to stimulate interest and highlight their potential as a novel platform for functional, responsive, and bioactive materials. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inorganic arsenic impairs differentiation and functions of human dendritic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier

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.more » 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 inducing necrosis ► Arsenite (0.1 to 0.5 μM) slightly reduces endocytotic activity of immature DCs ► Arsenite (0.1 to 0.5 μM) represses expression of IL-12p70 and IL-23 in activated DCs ► Arsenite (0.1 to 0.5 μM) reduces the ability of DCs to activate human T lymphocytes.« less

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

USGS Publications Warehouse

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

2002-01-01

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

Arsenic Speciation in Blue Mussels (Mytilus edulis) Along a Highly Contaminated Arsenic Gradient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whaley-Martin, K.J.; Koch, I.; Moriarty, M.

2012-11-01

Arsenic is naturally present in marine ecosystems, and these can become contaminated from mining activities, which may be of toxicological concern to organisms that bioaccumulate the metalloid into their tissues. The toxic properties of arsenic are dependent on the chemical form in which it is found (e.g., toxic inorganic arsenicals vs nontoxic arsenobetaine), and two analytical techniques, high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and X-ray absorption spectroscopy (XAS), were used in the present study to examine the arsenic species distribution in blue mussels (Mytilus edulis) obtained from an area where there is a strongmore » arsenic concentration gradient as a consequence of mining impacted sediments. A strong positive correlation was observed between the concentration of inorganic arsenic species (arsenic compounds with no As-C bonds) and total arsenic concentrations present in M. edulis tissues (R{sup 2} = 0.983), which could result in significant toxicological consequences to the mussels and higher trophic consumers. However, concentrations of organoarsenicals, dominated by arsenobetaine, remained relatively constant regardless of the increasing As concentration in M. edulis tissue (R{sup 2} = 0.307). XANES bulk analysis and XAS two-dimensional mapping of wet M. edulis tissue revealed the presence of predominantly arsenic-sulfur compounds. The XAS mapping revealed that the As(III)-S and/or As(III) compounds were concentrated in the digestive gland. However, arsenobetaine was found in small and similar concentrations in the digestive gland as well as the surrounding tissue suggesting arsenobetaine may being used in all of the mussel's cells in a physiological function such as an intracellular osmolyte.« less

Enzyme-assisted extraction and liquid chromatography mass spectrometry for the determination of arsenic species in chicken meat.

PubMed

Liu, Qingqing; Peng, Hanyong; Lu, Xiufen; Le, X Chris

2015-08-12

Chicken is the most consumed meat in North America. Concentrations of arsenic in chicken range from μg kg(-1) to mg kg(-1). However, little is known about the speciation of arsenic in chicken meat. The objective of this research was to develop a method enabling determination of arsenic species in chicken breast muscle. We report here enzyme-enhanced extraction of arsenic species from chicken meat, separation using anion exchange chromatography (HPLC), and simultaneous detection with both inductively coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESIMS). We compared the extraction of arsenic species using several proteolytic enzymes: bromelain, papain, pepsin, proteinase K, and trypsin. With the use of papain-assisted extraction, 10 arsenic species were extracted and detected, as compared to 8 detectable arsenic species in the water/methanol extract. The overall extraction efficiency was also improved using a combination of ultrasonication and papain digestion, as compared to the conventional water/methanol extraction. Detection limits were in the range of 1.0-1.8 μg arsenic per kg chicken breast meat (dry weight) for seven arsenic species: arsenobetaine (AsB), inorganic arsenite (As(III)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), inorganic arsenate (As(V)), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone), and N-acetyl-4-hydroxy-m-arsanilic acid (NAHAA). Analysis of breast meat samples from six chickens receiving feed containing Roxarsone showed the presence of (mean±standard deviation μg kg(-1)) AsB (107±4), As(III) (113±7), As(V) (7±2), MMA (51±5), DMA (64±6), Roxarsone (18±1), and four unidentified arsenic species (approximate concentration 1-10 μg kg(-1)). Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-04-01

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

Dietary micronutrient intake and its relationship with arsenic metabolism in Mexican women

PubMed Central

López-Carrillo, Lizbeth; Gamboa-Loira, Brenda; Becerra, Wendy; Hernández-Alcaraz, César; Hernández-Ramírez, Raúl Ulises; Gandolfi, A. Jay; Franco-Marina, Francisco; Cebrián, Mariano E.

2017-01-01

Introduction Concentrations of inorganic arsenic (iAs) metabolites in urine present intra-and interindividual variations, which are determined not only by the magnitude of exposure to iAs, but also by differences in genetic, environmental and dietary factors. Objective To evaluate whether differences in dietary intake of selected micronutrients are associated with the metabolism of iAs. Methods The intake of 21 micronutrients was estimated for 1027 women living in northern Mexico using a food frequency questionnaire. Concentration of urinary metabolites of iAs was determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and the proportion of iAs metabolites was calculated (%iAs, monomethylarsonic acid [%MMA] and dimethylarsinic acid [%DMA]), as well as ratios corresponding to the first (MMA/iAs), second (DMA/MMA) and total methylation (DMA/iAs). Results After adjustment for covariates, it was found that methionine, choline, folate, vitamin B12, Zn, Se and vitamin C favor elimination of iAs mainly by decreasing the %MMA and/or increasing %DMA in urine. Conclusions Our results confirm that diet contributes to the efficiency of iAs elimination. Further studies are needed to assess the feasibility of dietary interventions that modulate the metabolism of iAs and the consequent risk of diseases related to its exposure. PMID:27565879