Chemical speciation of arsenic in urine of patients with blackfoot disease

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Although extensive epidemiological study has implicated high arsenic content in artesian well water of the endemic area bears some important connection with the disease, the etiology of the disease is still not clarified. In this study, attention is paid to chemical speciation of arsenic in order to find out whether the concentrations of arsenic species in urine of Blackfoot disease patients are different from those of controls. Experimental results indicate that the total arsenic, inorganic arsenic, monomethylarsonic acid, and other forms of arsenic in the urine of patients are significantly higher than those of the contols. The possible connection of those arsenic species with the etiology of the disease is discussed.     

Trace elements in hair of blackfoot disease

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Though extensive epidemiological study has implicated that high arsenic content in artesian well water of the endemic area, bears some important connection with the disease, the etiology of the disease is still unknown. In this study, attention is paid to multielement determination in order to find out whether the trace elements in hair of Blackfoot disease patients are different from those of the controls. Experimental results indicate that the concentrations of As and Se in hair of patients are significantly higher than those of the controls, but Ca and Zn are significantly lower than those of the controls. The possible connection of these elements with the etiology of the disease is discussed.     

Arsenic concentration in the urine of patients with Blackfoot disease and Bowen’s disease

Extensive epidemiological study implicates that high arsenic content in artesian well water is the causal factor responsible for Blackfoot disease. We determine the arsenic concentration in urine samples of patients with Blackfoot and Bowen’s diseases and examine whether there exists any discrepancy of urinary arsenic concentrations among patients and the normal population. The analyses were made by hydride atomic absorption spectrophotometry (AAS) and the analytical reliability of the method was checked with a standard urine sample (ORTHO Bi-Level Urine Metal Control). The results show that the mean urinary arsenic concentration in 100 healthy adults is 63.4±29.7 μg/L, and those means for 23 and 11 patients with Blackfoot disease and Bowen’s disease are 75.7±39.1 μg/L (P vs controls >0.05) and 201±58 μg/L (P vs controls <0.001), respectively. From the analytical results obtained, we cannot conclude that urinary arsenic is associated with Blackfoot disease, as was disclosed from the epidemiological studies. However, urinary arsenic concentrations are possibly very closely associated with Bowen’s disease.     

Arsenic,selenium, and zinc in patients with blackfoot disease

Blackfoot disease is a peripheral vascular disease resulting in gangrene of the lower extremities. Extensive epidemiological study implicates that high arsenic content in artesian well water is the responsible causal factor of the disease. In the present study the concentrations of arsenic, selenium, and zinc in the body fluids and hair of patients with Blackfoot disease, in comparison to age- and sex-matched normal controls, are investigated. Two analytical techniques that include atomic absorption spectrometry and neutron activation analysis were used for the analysis of urine, serum, hair, and whole blood. The analytical results indicate that hair arsenic of the patients is significantly higher than that of the controls, but still below the critical value of 1 μg/g. In addition, the patients showed significantly lower concentrations of Se and Zn in the urine and blood than the normal controls. The possible connection of these elements with the etiology of the disease is discussed.     

An Epidemiologic Study of Arsenic-Related Skin Disorders and Skin Cancer and the Consumption of Arsenic-Contaminated Well Waters in Huhhot,Inner Mongolia,China

Well-use histories were obtained and dermatological examinations were conducted for 3,179 of the 3,228 (98.5%) residents of 3 villages in Inner Mongolia with well water arsenic levels as high as 2,000 ppb (ug/L). Eight persons were found to have skin cancer, 172 had hyperkeratoses, 121 had dyspigmentation, 94 had both hyperkeratoses and dyspigmentation, and, strikingly, none had Blackfoot disease. All 8 subjects with skin cancer also had both hyperkeratoses and dyspigmentation. Arsenic levels were measured for 184 wells and individual well-use histories were obtained. Arsenic exposure histories were summarized as both highest arsenic concentration (highest exposure level for at least 1-year duration) and cumulative arsenic exposure (ppb-years). Sixty-nine percent of the participants had highest arsenic concentrations below 100 ppb; 71% had cumulative arsenic exposures below 2,000 ppb-years. Exposure-response analyses included frequency-weighted, simple linear regression, and most-likely estimate (hockey-stick) models. Skin cancer cases were only found for those with a highest arsenic concentration greater than 150 ppb, and those with exposure less than 150 ppb had a statistically significant deficit. A frequency-weighted model showed a threshold at 150 ppb, and a hockey-stick model showed a threshold at 122 ppb. Considerations of duration, age, latency, and misclassification did not appear to markedly affect the analysis. The non-malignant skin findings showed thresholds of 40–50 ppb in the hockey-stick models. Application of these analytic models to the data from other epidemiological studies of arsenic ingestion and malignant and non-malignant skin disorders can be used to examine patterns of arsenic carcinogenicity.     

Arsenic exposure levels of petrochemical workers in three workplace settings in Rayong Province,Thailand

Background: Crude oil and natural gas are often contaminated with arsenic. As a carcinogen, arsenic contamination in the workplace is of concern, particularly when urinary arsenic levels are higher than the standard. The aim of this study was to identify exposure sources of arsenic among petrochemical workers. Methods: A total of 188 operators and 30 office workers participated in the study. Ninety-three workplace air samples, three main meals in five consecutive days, and drinking water were collected from each participant. Urine was collected at the end of the day after the last food sample was collected from each subject. Urine samples where arsenic concentration exceeded 100 mg/L were further analyzed to identify species. Results: The average arsenic concentrations in operators' and office workers' food and urine were 0.55 ± 1.00 and 0.49 ± 0.67 mg/kg; and 76.43 ± 107.36 and 149.92 ± 200.28 mg/L, respectively. The arsenic concentrations in air and water were well below their standards. The urinary arsenic correlated well with arsenic in the food but not in the air and water. Conclusion: Occupational exposure to arsenic among operators and office workers was lower than 1% TLV (Threshold limit value) and did not differ significantly. The major source of arsenic exposure Q2 was food.     

Arsenic Concentrations in the Surface,Well, and Drinking Waters of the Hisarcik,Turkey, Area

Arsenic is one of the most important water pollutants because of its carcinogenicity. The association between arsenical poisoning and the development of internal malignancies and skin cancer is well known. The U.S. Environmental Protection Agency (USEPA) sets maximum contaminant level goals at zero for carcinogens. In this study are presented groundwater arsenic concentrations in the area of naturally rich boron sources of Turkey. Water samples were collected from the Hisarcik, Turkey, area, which has a large boron mine. An inductively coupled plasma/mass spectrometry method was used to analyze arsenic concentrations in water samples. The arsenic levels in water ranged from no detectable amounts to 3.00 mg As/L (mean: 0.46 ± 0.07SD). This mean As level exceeds by a factor of 10 the USEPA's current Maximum Contaminant Level of 0.05 mgAs/L. Some possible health problems associated with consumption of arsenic-contaminated water are discussed and public health interventions proposed.     

Baseline and sodium arsenite-induced sister chromatid exchanges in cultured lymphocytes from patients with Blackfoot disease and healthy persons

Summary A significantly higher frequency of baseline sister chromatid exchange (SCE) was found in the cultured lymphocytes of 13 Blackfoot disease patients (BFP) in comparison with that of healthy persons (HP). Twelve of these BFP consumed well water containing a high concentration of arsenic for 15 years or longer and had switched to drinking tap water 12 years before the time of this study. Sodium arsenite was found to be effective in increasing the SCE frequency and delaying the cell growth of the lymphocytes from both BFP and HP. However, the SCE increment induced by sodium arsenite as well as the progression of the cell divisions in the cultured lymphocytes showed no significant difference between BFP and HP.     

Epidemiological associations between arsenic and cancer in Argentina

The population of a large central area of Argentina is affected by a syndrome designed as “regional and endemic chronic hydroarsenicism.” A number of types of neoplasms, especially of skin, urinary bladder, and of digestive system, occur with higher frequency in these areas. Drinking water in some of the affected areas contains from 0.1 to 1.2 mg/L of As.     

Simultaneous determination of Zn,Cd, Pb,and Cu in urine of patients with blackfoot disease using anodic stripping voltammetry

Blackfoot disease (BFD) is an endemic peripheral vascular disorder resulting in gangrene of the lower extremities, especially the feet, among residents in a limited area on the southwest coast of Taiwan. In the present study, the concentrations of zinc, cadmium, lead, and copper in urine of BFD patients with matched normal controls are investigated by differential pulse anodic stripping voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The analytical results indicate that urinary copper, cadmium, and lead of the BFD patients are significantly higher than those of the controls. In addition, the patients showed a significantly lower concentration of zinc in the urine than the normal controls. The possible connection of these elements with the etiology of the disease is discussed.     

Physicochemical and elemental contamination assessment in groundwater samples of Khairpur Mir's,Pakistan

Drinking water contaminated with arsenic poses serious threat to the human health. The present study was aimed for quality assessment of the groundwater of Khairpur Mir's in respect with arsenic and other elemental contamination like Fe, Cu, Co, and Ni. The presence of the trace elements in groundwater from different sources in the study area was measured by using atomic absorption spectroscopy. For arsenic analysis hydride generation technique (MHS-15) was used with detection limit of 0.02 µg l^?1. Elevated level of arsenic was observed in most of the samples as compared to recommended value of World Health Organization (WHO) guidelines (10 µg l^?1). However, levels of Fe, Cu, Co, and Ni in hand pump (HP) water samples was found in the range of 4–1610 µg l^?1, 0–556 µg l^?1, 0–230 µg l^?1, and 0–700 µg l^?1, respectively. Whereas in tube well (TW) water samples the observed values are 5–1620 µg l^?1, 0–50 µg l^?1, 4–110 µg l^?1, and 0–360 µg l^?1 for Fe, Cu, Co, and Ni, respectively. Significant difference was observed between TW and HP water samples. It was concluded that the level of arsenic found was very high up to 13 fold more than the WHO recommended limit in study area. While the levels of other elements was noted within the safe limit.     

基于Wnt信号通路探讨氟砷混合暴露的生物暴露限值

慢性氟砷联合中毒是全世界的一个重大公共卫生问题,影响着数千万人.目前该病病因清楚,但发病机制未明,且无特效治疗方法,因此,早期预防尤为重要.生物暴露限值旨在探讨外源化学物引起机体有害效应的最高容许浓度.为了探讨氟砷混合暴露的生物暴露限值(BEL),本研究通过比较对照及氟砷联合暴露地区环境介质中的氟、砷含量,分析氟、砷与Wnt信号通路关键蛋白的剂量-效应及剂量-反应关系,利用基准剂量法估算氟砷混合暴露的生物暴露限值.结果表明: 氟砷联合暴露地区煤、黏土、室内空气、室外空气、辣椒、大米中的氟含量以及煤、黏土、室外空气、辣椒、大米中的砷含量均高于对照;随着氟、砷暴露水平的增加,糖原合酶激酶3β(GSK3β)、β-连环蛋白(β-catenin)含量以及Wnt/β连环蛋白信号通路拮抗蛋白(DKK1)、GSK3β、β-catenin的异常检出率逐渐增加,但DKK1含量显著降低;基于Wnt信号通路,氟砷混合暴露的生物暴露限值UF为0.52 mg·g^-1Cr,UAs为6.59 μg·g^-1Cr.本研究对于早期预防氟砷联合中毒引起的机体损伤具有重要的指导意义.     

How Creditable are Cancer Risk Estimates from the S.W. Taiwan Database for Arsenic in Drinking Water?

A database of cancer mortality and arsenic concentrations in village wells in an arseniasis-endemic area of southwestern Taiwan has been the predominant source of information for risk assessments of U.S. Environmental Protection Agency and two National Research Council reports on arsenic and drinking water. A limitation of the data, however, is that exposure is ecological, that is, cancer mortality cannot be matched with arsenic exposure on an individual basis, just grouped by village. The resultant potential for bias is examined by comparing dose-response analyses of villages divided into two groups, those with well concentrations in a narrow range and the remainder. The narrow range group suggests a flat or downward change in risk in the low dose range, whereas the other group indicates increasing risk. More disturbingly, however, the dose-response data are highly dispersed for both groups and the dose-response curve predicts background bladder/lung cancer levels much higher than a southwestern Taiwan comparison population. This may be due to a large variability between villages of the study area in bladder/lung cancer not directly attributable to arsenic. Including the comparison population in the dose-response analysis artificially anchors the dose-response curve at a background level inconsistent with the study population and likely just biases the slope factor upward.     

Arsenic transport between water and sediments

Arsenic discharged into the Moira River has accumulated in the sediments of Moira Lake during the past century. The chronology of arsenic concentrations in the sediments, established using Pb-210 dating, has a subsurface concentration maximum (> 1000 g g^–1) that reflects higher inputs to the lake 15 to 45 years ago. The distribution coefficient (K_d) of arsenic in the surficial sediments was low (4000–6000 L kg^–1) and decreased below the sediment water interface. Higher concentrations of exchangeable As also were extracted deeper in the sediments. As a result, arsenic is mobile in the sediment column and the flux of arsenic via diffusion and particle resuspension from the sediments into the water is greater than current external loading from the Moira River. Less than 20% of the external input of arsenic is buried in the lake sediments. Using these flux measurements and a one dimensional model of arsenic transport in the sediment column, we constructed the history of arsenic exchange between water and sediments throughout the past century. The simulations predict that arsenic input into the water from the sediments has been > 20 % of external loading for the past 25 years and will continue to be important in the future as diffusion and resuspension regenerate arsenic from the mixed layer of the sediments into the overlying water.     

Dietary Arsenic Intake in Taiwanese Districts with Elevated Arsenic in Drinking Water

Inorganic arsenic in dietary staples (i.e., yams and rice) may have substantially contributed to exposure and adverse health effects observed in an endemic Taiwanese population historically exposed to arsenic in drinking water. Observations of this population were used by the U.S. Environmental Protection Agency to derive toxicity values that form the basis for arsenic risk assessment and various regulations in the United States. However, data were previously insufficient to accurately estimate dietary intake. Rice and yam samples collected in 1993 and 1995 from Taiwanese districts with endemic arsenic were analyzed for total arsenic and for inorganic and organic mono and dimethylarsenic. The acid digestion techniques used in the analyses are among the best to preserve organic arsenic in the test sample. Furthermore, concurrent analyses of the proportion of inorganic arsenic in split samples of rice and yams collected in the 1995 investigation were in good agreement, despite using a different digestion method. These data support a likely mean dietary intake of 50?µg/day with a range of 15 to 211?µg/day. Consideration of dietary intake may result in a downward revision of the assumed potency of ingested arsenic as reflected in EPA's toxicity values.     

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics

ObjectiveTo clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China.MethodsA case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0–510.2 μg/L, and that in the mechanical well water was 167 μg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS).ResultsADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478−0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014–2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls.ConclusionADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.     

Arsenic Ingestion and Bladder Cancer Mortality—What Do the Dose-Response Relationships Suggest About Mechanism?

The Black–Foot Disease (BFD) endemic area of SW Taiwan has historically been the principal data source for assessing cancer risks from arsenic in drinking water in the United States, most recently in a 42–village ecological study. The data showed a discontinuity for bladder cancer risk at about 400 μg/L. A proposed explanation was that the arsenic–dependent bladder cancer risk was found only for those villages that were dependent on water from the artesian well aquifer (As > 350 μg/L and co–contamination with humic acids) and not for those villages receiving water from the shallow aquifer (As < 350 μg/L without humic acids). The humic acids were present from the algae that grew in the uncovered tanks holding the artesian water. The risk factors (slopes) developed from these subpopulations of the SW Taiwan study were applied to the data from an ecological study of median groundwater arsenic concentration and bladder cancer mortality in 133 U.S. counties dependent on groundwater to determine the slope most predictive of U.S. experience for bladder cancer mortality and arsenic ingestion (Lamm et al. 2004 Lamm, S H, Engel, AKruse, M B. 2004. Arsenic in drinking water and bladder cancer mortality in the United States: An analysis based on 133 U.S. counties and 30 years of observation.. J Occup Environ Med, 46(3): 298–306. [PUBMED][INFOTRIEVE][CSA][Crossref], [PubMed], [Web of Science ®] [Google Scholar]).The U.S. data excluded the SW Taiwan slope estimate derived from the artesian well–dependent subpopulation but were consistent with the slope estimate derived from the subpopulation using shallow aquifer water. Both the SW Taiwan data in the absence of high arsenic levels (< 350 μg/L) and humic acids and the U.S. 133–county data with As < 60 μg/L are consistent with no increased bladder cancer mortality risk from drinking water arsenic concentrations in the exposure range of observation. These analytic results are consistent with both co–carcinogenesis and high–exposure (hundreds of μ g/L As) dependence models of toxicological mode–of–action. These dose–response relationships should influence prioritization in the remediation of arsenic–contaminated drinking water supplies.     

Noncancer risk assessment of arsenic safe and unsafe water uses: Bayesian estimation on cohort study

Cancer and noncancer risk of arsenic exposure depends on arsenic intake through drinking water and diets. The present study evaluated the probability of noncancer effects of arsenic exposure from drinking water and diets in a cohort of 82 participants in arsenic-endemic rural areas, considering arsenic-safe and arsenic-unsafe water uses for three consecutive years. The risk assessment included the collection of last 24 hours' diet replica and urine of the participants followed by total arsenic analysis of the same. Toxic dose emerging from exposure duration is a nonlinear variable. So, Bayesian estimation of the data for noncancer risk assessment of the variable arsenic consumption was performed. In spite of using arsenic-safe water, we observed arsenic consumption and release. Participants with skin lesions had more arsenic in urine than participants without skin lesions. Future risk for participants without skin lesions was twice due to less arsenic release in urine. For the first time, Bayesian simulation was used to assess noncancer risk on a cohort for a consecutive three-year study. A significant finding was the higher assessed noncancer risk of the participants without skin lesions than the participants with skin lesions.     

Development of suitable hydroponics system for phytoremediation of arsenic-contaminated water using an arsenic hyperaccumulator plant Pteris vittata

In this study, we found that high-performance hydroponics of arsenic hyperaccumulator fern Pteris vittata is possible without any mechanical aeration system, if rhizomes of the ferns are kept over the water surface level. It was also found that very low-nutrition condition is better for root elongation of P. vittata that is an important factor of the arsenic removal from contaminated water. By the non-aeration and low-nutrition hydroponics for four months, roots of P. vittata were elongated more than 500 mm. The results of arsenate phytofiltration experiments showed that arsenic concentrations in water declined from the initial concentrations (50?μg/L, 500?μg/L, and 1000?μg/L) to lower than the detection limit (0.1?μg/L) and about 80% of arsenic removed was accumulated in the fern fronds. The improved hydroponics method for P. vittata developed in this study enables low-cost phytoremediation of arsenic-contaminated water and high-affinity removal of arsenic from water.     

Role of JAK/STAT signaling in neuroepithelial stem cell maintenance and proliferation in the Drosophila optic lobe

Human urine contains a large number of proteins and peptides (the urinary proteome). Global analysis of the human urinary proteome is important for understanding urinary tract diseases. Bladder cancer is the most common urological cancer with higher incidence rates in endemic areas of Blackfoot disease (BFD) in southern Taiwan. The aim of this study was to use the proteomic approach to establish urinary protein biomarkers of bladder cancer. ADAM28, identified by proteomic approaches and confirmed by Western blotting, showed significant differences compared with normal individuals, so it may be a biomarker of bladder cancer.