Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons.

Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life.

Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications.

Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood.

Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

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The Broad Scope of Health Effects from Chronic Arsenic Exposure: Update on a Worldwide Public Health Problem

Arsenic Exposure and Toxicology: A Historical Perspective

Heavy metals in drinking water: Occurrences, implications, and future needs in developing countries.

Arsenic in drinking water is an established cause of lung cancer, and preliminary evidence suggests that ingested arsenic may also cause nonmalignant lung disease. Antofagasta is the second largest city in Chile and had a distinct period of very high arsenic exposure that began in 1958 and lasted until 1971, when an arsenic removal plant was installed. This unique exposure scenario provides a rare opportunity to investigate the long-term mortality impact of early-life arsenic exposure. In this study, we compared mortality rates in Antofagasta in the period 1989-2000 with those of the rest of Chile, focusing on subjects who were born during or just before the peak exposure period and who were 30-49 years of age at the time of death. For the birth cohort born just before the high-exposure period (1950-1957) and exposed in early childhood, the standardized mortality ratio (SMR) for lung cancer was 7.0 [95% confidence interval (CI), 5.4-8.9; p<0.001] and the SMR for bronchiectasis was 12.4 (95% CI, 3.3-31.7; p<0.001). For those born during the high-exposure period (1958-1970) with probable exposure in utero and early childhood, the corresponding SMRs were 6.1 (95% CI, 3.5-9.9; p<0.001) for lung cancer and 46.2 (95% CI, 21.1-87.7; p<0.001) for bronchiectasis. These findings suggest that exposure to arsenic in drinking water during early childhood or in utero has pronounced pulmonary effects, greatly increasing subsequent mortality in young adults from both malignant and nonmalignant lung disease.

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Increased mortality from lung cancer and bronchiectasis in young adults after exposure to arsenic in utero and in early childhood

Arsenic toxicity is a worldwide health concern as several millions of people are exposed to this toxicant via drinking water, and exposure affects almost every organ system in the body including the brain. Recent studies have shown that even low concentrations of arsenic impair neurological function, particularly in children. This review will focus on the current epidemiological evidence of arsenic neurotoxicity in children and adults, with emphasis on cognitive dysfunction, including learning and memory deficits and mood disorders. We provide a cohesive synthesis of the animal studies that have focused on neural mechanisms of dysfunction after arsenic exposure including altered epigenetics; hippocampal function; glucocorticoid and hypothalamus-pituitary-adrenal axis (HPA) pathway signaling; glutamatergic, cholinergic and monoaminergic signaling; adult neurogenesis; and increased Alzheimer’s-associated pathologies. Finally, we briefly discuss new studies focusing on therapeutic strategies to combat arsenic toxicity including the use of selenium and zinc.

/pdf/the-effects-of-arsenic-exposure-on-neurological-and-2r567476nr.pdf

The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review

Between 2001 and 2003, the authors studied pregnancy outcomes and infant mortality among 202 married women in West Bengal, India. Reproductive histories were ascertained using structured interviews. Arsenic exposure during each pregnancy, including all water sources used, was assessed; this involved measurements from 409 wells. Odds ratios for spontaneous abortion, stillbirth, neonatal mortality, and infant mortality were estimated with logistic regression based on the method of generalized estimating equations. Exposure to high concentrations of arsenic (> or =200 microg/liter) during pregnancy was associated with a sixfold increased risk of stillbirth after adjustment for potential confounders (odds ratio (OR) = 6.07, 95% confidence interval (CI): 1.54, 24.0; p = 0.01). Arsenic-related skin lesions were found in 12 women who had a substantially increased risk of stillbirth (OR = 13.1, 95% CI: 3.17, 54.0; p = 0.002). The odds ratio for neonatal death was 2.81 (95% CI: 0.73, 10.8). No association was found between arsenic exposure and spontaneous abortion (OR = 1.01, 95% CI: 0.38, 2.70) or overall infant mortality (OR = 1.33, 95% CI: 0.43, 4.04). This study adds to the limited evidence that exposure to high concentrations of arsenic during pregnancy increases the risk of stillbirth. However, there was no indication of the increased rates of spontaneous abortion and overall infant mortality that have been reported in some studies.

https://faculty.washington.edu/heagerty/Courses/VA-longitudinal/private/vonEhrenstein-AJE2006.pdf

Pregnancy Outcomes, Infant Mortality, and Arsenic in Drinking Water in West Bengal, India

Background: Very little evidence exists concerning the possible impairment of children’s intellectual function in relation to arsenic exposure in utero and during childhood. Methods: We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001–2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates. Results: Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, 0.14, 0.28; P for trend 0.02), the object assembly test (0, 0.16, 0.24; P for trend 0.03), and the picture completion test (0, 0.15, 0.26; P for trend 0.02). These findings correspond to relative declines of 12% (95% confidence interval 0.4% to 24%) in the vocabulary test, 21% (0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood. Conclusions: Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in schoolaged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function. (Epidemiology 2007;18: 44 –51)

Children's intellectual function in relation to arsenic exposure.

Background: Very little evidence exists concerning the possible impairment of children's intellectual function in relation to arsenic exposure in utero and during childhood. Methods: We conducted a cross-sectional study among 351 children age 5 to 15 years who were selected from a source population of 7683 people in West Bengal, India, in 2001-2003. Intellectual function was assessed with 6 subtests from the Wechsler Intelligence Scale for Children as well as with the Total Sentence Recall test, the Colored Progressive Matrices test, and a pegboard test. Arsenic in urine and lifetime water sources (including during the pregnancy period) were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regression analyses based on the method of generalized estimating equations incorporating relevant covariates. Results: Stratifying urinary arsenic concentrations into tertiles, we found associations between arsenic and reductions in the adjusted scores of the vocabulary test (0, -0.14, -0.28; P for trend = 0.02), the object assembly test (0, -0.16, -0.24; P for trend = 0.03), and the picture completion test (0, -0.15, -0.26; P for trend = 0.02). These findings correspond to relative declines of 12% (95% confidence interval =0.4% to 24%) in the vocabulary test, 21% (-0.8% to 42%) in the object assembly test, and of 13% (0.3% to 24%) in the picture completion test in the upper urinary arsenic tertile. However, we did not find evidence of an association between test results and arsenic water concentrations during pregnancy or childhood. Conclusions: Current arsenic concentrations in urine, which reflect all sources of recent exposure, including water and food, were associated with small decrements in intellectual testing in schoolaged children in West Bengal. We did not see associations between long-term water arsenic concentrations and intellectual function.

S Das

Papers

Pregnancy Outcomes, Infant Mortality, and Arsenic in Drinking Water in West Bengal, India

Children's intellectual function in relation to arsenic exposure.

Children's intellectual function in relation to arsenic exposure. Commentary