Cumulative Arsenic Exposure Research Articles

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

ABSTRACT 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 methylation capability and hypertension risk in subjects living in arseniasis-hyperendemic areas in southwestern Taiwan

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. 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 >or=140 mm Hg and/or diastolic blood pressure >or=90 mm Hg. Urinary arsenic species were determined by high-performance liquid chromatography-hydride generator and atomic absorption spectrometry. Primary arsenic methylation index [PMI, defined as monomethylarsonic acid (MMA(V)) divided by (As(III)+As(V))] and secondary arsenic methylation index (SMI, defined as dimethylarsinic acid divided by MMA(V)) were used as indicators for arsenic methylation capability. 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(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. Inefficient arsenic methylation ability may be related with hypertension risk.

Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA(V)) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA(V) (MMA%) was calculated by dividing with total arsenic species in urine, including arsenite, arsenate, MMA(V), and dimethylarsinic acid (DMA(V)). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% (> or =16.5%) and high homocysteine levels (> or =12.7 micromol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 micromol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.

Lung Cancer Development in Primary Smelter Workers: A Nested Case-Referent Study

The objective of this study was to study the impact of work-related exposure to mainly arsenic and lead versus smoking in primary smelter workers developing lung cancer. In a cohort of 3979 primary smelter workers, 46 subjects had contracted respiratory malignancies. They were compared with 141 age-matched male referents by conditional logistic regression analysis. Cases showed a significantly higher smoking rate as compared with referents: odds ratio (OR) = 4.0; 95% confidence interval (CI) = 1.6-10.1; P = 0.003. When restricted to smokers (33 cases, 63 referents), the cumulative air arsenic exposure index, but not the lead exposure indices, was significantly higher among the cases: OR = 1.07; 95% CI = 1.02-1.11; P = 0.005. Cumulative arsenic exposure and smoking were identified as risk factors for the development of lung cancer; lead exposure, however, was not.

Plasma-transforming growth factor-alpha expression in residents of an arseniasis area in Taiwan

Epidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5±38.2 pg ml−1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1±5.6 pg ml−1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population.

Genetic Polymorphisms of Oxidative and Antioxidant Enzymes and Arsenic-Related Hypertension

The association of 4 genetic polymorphisms, NAD(P)H oxidase, manganese superoxide dismutase (MnSOD), catalase, and endothelial nitric oxide synthase (e-NOS), was assessed with arsenic-related hypertension risk among 79 hypertensive cases and 213 controls in an arseniasis-hyperendemic area of Taiwan. Overall, MnSOD polymorphism significantly increased the risk of hypertension regardless of arsenic exposure. NADPH oxidase and eNOS polymorphisms were significantly associated with hypertension risk in the high arsenic exposure group; however, catalase polymorphism was not associated with hypertension. Groups were further stratified by triglyceride levels to evaluate whether the cumulative arsenic exposure combined the three polymorphisms together. The adjusted adds ratios (ORs) of at least two risk factors of the cumulative arsenic exposure and MnSOD, NADPH oxidase, and eNOS three-polymorphism combination versus any one risk factor of them were 0.8 (95% CI 0.3–2.3) for individuals with low triglyceride levels (<110 mg/dl) and 2.5 (95% CI 1.0–6.01) for high-triglyceride groups (>110 mg/dl), respectively. These results suggested that the NADPH oxidase, MnSOD, and e-NOS polymorphisms, but not catalase, might play a role in the development of arsenic-related hypertension, especially in subjects with high triglyceride levels.

Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan

Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (As III) and arsenate (As V), monomethylarsonic acid (MMA V), and dimethylarsinic acid (DMA V) were determined. Primary methylation index [PMI = MMA V/(As III + As V)] and secondary methylation index (SMI = DMA V/MMA V) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMA V. The multivariate-adjusted odds ratios for CAE of 0, 0.1–15.4, and >15.4 mg/L × year were 1.00, 3.41 (0.74–15.78), and 4.62 (0.96–22.21), respectively ( P < 0.05, trend test); and for PMI ≤ 1.77 and SMI > 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI ≤ 6.93, and PMI ≤ 1.77 and SMI ≤ 6.93 were 1.00, 2.93 (0.90–9.52), 2.85 (1.05–7.73), and 3.60 (1.12–11.56), respectively ( P < 0.05, trend test). It was concluded that individuals with a higher arsenic exposure and a lower capacity to methylate inorganic arsenic to DMA V have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan.

Arsenic Methylation and Skin Cancer Risk in Southwestern Taiwan

Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.

Genetic Polymorphism in p53 Codon 72 and Skin Cancer in Southwestern Taiwan

The Pro/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case–control study in southwestern Taiwan. From 1996 to 1999, 93 newly-diagnosed skin cancer patients at the National Cheng-Kung University (NCKU) Hospital and 71 community controls matched on residence were recruited in southwestern Taiwan. The genotype of p53 codon 72 (Arg/Arg, Arg/Pro, or Pro/Pro) was determined for all subjects by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). A questionnaire was administered to each subject for collection of demographic information, personal habits, disease history, diet information, and other relevant questions. The Pro/Pro (homozygous) genotype was more frequent in skin cancer patients (cases, 20%; controls, 12%; P = 0.37). Subjects with the susceptible genotype Pro/Pro and heterozygous (intermediate) genotype Pro/Arg had 2.18 and 0.99 times risk of skin cancer than the wild type Arg/Arg (95% confidence interval, 0.74–4.38; 95% confidence interval, 0.44–2.21), respectively. Compared with subjects with 18.5<BMI<23, subjects with BMI>18.5 had 5.78 times risk of skin cancer (95% confidence interval, 1.06 to 31.36) after adjusting for other risk factors. There was no interaction between BMI and genotype, but the sample size was small. The risk of skin cancer did not significantly vary by tumor cell-type. The risk of skin cancer is increased in individuals with the Pro/Pro genotype. Larger, confirmatory studies are needed to clarify the role of constitutional polymorphisms in p53 and skin cancer risk.

Arsenic methylation and bladder cancer risk in Taiwan.

The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan. From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976. Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.

Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic villages in Taiwan

The association between long-term arsenic exposure and peripheral vascular disease has been well documented in our previous epidemiologic studies. The purpose of this study was to evaluate whether long-term arsenic exposure could be associated with ischemic heart disease (IHD). A total of 462 subjects living in the blackfoot disease-hyperendemic villages along the southwestern coast of Taiwan and characterized by long-term arsenic exposure from drinking artesian well water was studied. The subjects were recruited from an epidemiologic cohort who participated in a health examination. IHD was diagnosed by coding the resting electrocardiograms with the Minnesota code. History of arsenic exposure was estimated through information obtained from a personal interview according to a structured questionnaire and the arsenic content in artesian well water of the villages. Cumulative arsenic exposure (CAE) was calculated as the sum of the products multiplying the arsenic concentration in artesian well water (mg/l) by the duration of drinking the water (years) in consecutive periods of living in the different villages. Among the subjects, 78 cases (16.9%) were diagnosed as having IHD. The prevalence rates of IHD for the age groups of 30–39, 40–49, 50–59, and ≥60 years were 4.9, 7.5, 16.8, and 30.7%, respectively ( P<0.001). For those with CAE of 0, 0.1–14.9 and ≥15 mg/l-years, the prevalence rates of IHD were 5.2, 10.9 and 24.1%, respectively ( P<0.001). The odds ratios (95% confidence intervals) for IHD were 1.60 (0.48, 5.34), and 3.60 (1.11, 11.65), respectively, for those with CAE of 0.1–14.9 and ≥15.0 mg/l-years, when compared with those lacking drinking water exposure to arsenic after multivariate adjustment. It is concluded that IHD in the arseniasis-hyperendemic villages in Taiwan was associated with long-term arsenic exposure.

Determinants of inorganic arsenic methylation capability among residents of the Lanyang Basin, Taiwan: arsenic and selenium exposure and alcohol consumption

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As i) and the overall inorganic and organic arsenic in urine (overall As i+o) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum α-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.

Biological gradient between long-term arsenic exposure and carotid atherosclerosis.

Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of > or =20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological gradient.

The incidence of type 2 diabetes mellitus in Taiwan

Currently, diabetes mellitus is the fifth leading cause of death in Taiwan. The trends of diabetes mortality is increasing steadily. Epidemiologic studies also showed increasing prevalence of diabetes mellitus over the past few decades. The incidence of diabetes mellitus in Taiwan has only been studied in recent 10 years. The areas that have been included as study areas for diabetes incidence are Kin-Chen (Kinmen), Chu-Dung, Pu-Tzu, Pu-Li and Pu-Tai. The reported incidence rates ranged from 1.0 to 4.0% per year for people with varying degrees of baseline plasma glucose levels not reaching the diagnosis of diabetes mellitus according to the criteria of the World Health Organization. Age, baseline glucose level, and obesity are important predictors for the development of diabetes mellitus. In the Pu-Tai study, which was aimed at following a group of people who had been living in the hyperendemic villages of blackfoot disease and had been exposed to arsenic from drinking artesian well water, the incidence of diabetes mellitus was calculated to be 27.4 per 1000 person years. The incidence of diabetes mellitus in these arseniasis-hyperendemic villages correlated with age, body mass index and cumulative arsenic exposure.

Long-Term Arsenic Exposure and Incidence of Non-Insulin-Dependent Diabetes Mellitus: A Cohort Study in Arseniasis-Hyperendemic Villages in Taiwan

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

Long-term arsenic exposure and incidence of non-insulin-dependent diabetes mellitus: a cohort study in arseniasis-hyperendemic villages in Taiwan.

Diabetes prevalence in arseniasis-hyperendemic villages in Taiwan has been reported to be significantly higher than in the general population. The aim of this cohort study was to further evaluate the association between ingested inorganic arsenic and the incidence of non-insulin-dependent diabetes mellitus in these villages. A total of 446 nondiabetic residents in these villages were followed biannually by oral glucose tolerance test. Diabetes is defined as a fasting plasma glucose level > or = 7.8 mmol/L and/or a 2-hr post-load glucose level > or = 11.1 mmol/L. During the follow-up period of 1499.5 person-years, 41 cases developed diabetes, showing an overall incidence of 27.4/1,000 person-years. The incidence of diabetes correlated with age, body mass index, and cumulative arsenic exposure. The multivariate-adjusted relative risks were 1.6, 2.3, and 2.1 for age > or = 55 versus < 55 years, a body mass index ¿Greater/Equal to] 25 versus < 25 kg/m(2), and a cumulative arsenic exposure > or = 17 versus < 17 mg/L-years, respectively. The incidence density ratios (95% confidence intervals) between the hyperendemic villages and the two nonendemic control townships were 3.6 (3.5-3.6), 2.3 (1.1-4.9), 4.3 (2.4-7.7), and 5.5 (2.2-13.5), respectively, for the age groups of 35-44, 45-54, 55-64, and 65-74 years. The findings are consistent with our previous cross-sectional observation that ingested inorganic arsenic is diabetogenic in human beings.

Drinking water arsenic in Utah: A cohort mortality study.

The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted.

Drinking Water Arsenic in Utah: A Cohort Mortality Study

The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted.

URINARY LEVELS OF INORGANIC AND ORGANIC ARSENIC METABOLITES AMONG RESIDENTS IN AN ARSENIASIS-HYPERENDEMIC AREA IN TAIWAN

In order to elucidate whether urinary levels of inorganic and organic arsenic metabolites are associated with previous exposure to high-arsenic artesian well water, a total of 302 residents of age 30 yr or older were recruited from three arseniasis-hyperendemic villages in Taiwan. Most study subjects had stopped consuming high-arsenic artesian well water for more than 20 yr. The mean total arsenic (Ast) determined by inductively cout pled plasma mass spectrometer (ICPMS) was 267.05 +/- 20.95 mug/L, and the mean level of inorganic arsenic and its metabolites (Ast) was 86.08 +/- 3.43 mug/L. In the multivariate analysis, urinary dimethylarsinic acid (DMA) levels were significantly inversely associated with age, with women exhibiting significantly lower urinary amounts of arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMA), organic arsenic (Aso), and Ast compared to men. After adjustment for age and sex, previous cumulative arsenic exposure through consumption of artesian well water was significantly associated with elevated urinary levels of MMA and DMA, but not As(III) + As(V), Asot, and Ast. In the multivariate analysis, the percentage of As in As was significantly higher in men than women, but this was not significantly associated with age. The percentage of As(III) + As(V) in As increased significantly with age, while the reverse was noted with DMA in Asi. Women had a significantly higher DMA percentage but lower As(III) + As(V) and MMA percentages in Asi than men. After adjustment for age and sex, the percentages of As(III) + As(V) in Asi were significantly inversely associated with previous arsenic exposure through consumption of artesian well water. Data suggested that women seem to possess a more efficient arsenic methylation capability than men, and aging diminishes this methylation capability; furthermore, the higher the cumulative arsenic exposure, the greater is the body burden of inorganic arsenic, mainly in the form of MMA and DMA.

Lipid profile and peripheral vascular disease in arseniasis-hyperendemic villages in Taiwan.

To examine whether lipid abnormalities contributed to the endemic peripheral vascular disease (PVD) in villages where arseniasis was hyperendemic in Taiwan, the authors studied 533 adults with Doppler ultrasound and lipid profiles including total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, apolipoprotein AI, and apolipoprotein B. Among them, 63 had PVD based on an ankle-brachial index < 0.90. Long-term arsenic exposure indices including cumulative arsenic exposure in mg/L-years, duration of drinking artesian well water in years, and duration of living in arseniasis-hyperendemic villages in years were calculated from detailed history obtained through standardized interviews based on a structured questionnaire and arsenic concentration in well water. Possible confounders including age, sex, body mass index, cigarette smoking, and disease status of diabetes mellitus and hypertension were considered in the analyses. None of the lipid profiles differed significantly between the presence and absence of PVD. The odds ratios for PVD did not differ among different quintiles of lipid profiles with the lowest quintile as the referent. However, a significant dose-response relation was found for the long-term arsenic exposure indices. The multivariate-adjusted odds ratios for cumulative arsenic exposure of 0.1 approximately 19.9 and > or = 20 mg/L-years were 2.77 and 4.68, respectively, compared with the unexposed. These results suggest that the PVD in arseniasis-hyperendemic villages is correlated with ingested inorganic arsenic and not with the lipid profiles.