Effect of Safe Water on Arsenicosis: A Follow-up Study.

BACKGROUND: Arsenic pollution in groundwater, used for drinking purposes, has been envisaged as a problem of global concern. Treatment options for the management symptoms of chronic arsenicosis are limited. Mitigation option available for dealing with the health problem of ground water arsenic contamination rests mainly on supply of arsenic safe water in arsenic-endemic region of Indo-Bangladesh subcontinent. Limited information is available regarding the long-term effect of chronic arsenic toxicity after stoppage of consumption of arsenic-containing water. OBJECTIVE: The current study was, therefore, done to assess, objectively, the effect of drinking arsenic safe water (<50 µg/L) on disease manifestation of arsenicosis. RESULTS: Manifestations of various skin lesions and systemic diseases associated with chronic arsenic exposure were ascertained initially by carrying on baseline study on 208 participants in Nadia (Cohort-I, with skin lesion and Cohort-II, without skin lesion) using a scoring system, as developed by us, and compared objectively at the end of each year for 3 year follow-up period. All the participants who had arsenic contaminated drinking water source in their houses were supplied with arsenic removal filters for getting arsenic-free water during the follow-up period. In participants belonging to Cohort-I, the skin score was found to improve significantly at the end of each year, and it was found to be reduced significantly from 2.17 ± 1.09 to 1.23 ± 1.17; P < 0.001 at the end of 3 year's intervention study indicating beneficial effect of safe water on skin lesions. The systemic disease symptom score was also found to improve, but less significantly, at the end of 3 years in both the cohorts. Most important observation during the follow-up study was persistence of severe symptoms of chronic lung disease and severe skin lesion including Bowen's disease in spite of taking arsenic-safe water. Further, death could not be prevented to occur because of lung cancer and severe lung disease. CONCLUSION: It is, therefore, an urgent need to make arrangement for availability of safe water source among the arsenic-affected people in the district. Many of the people in the affected villages are not aware of contamination of their home tube wells with arsenic. Awareness generation and motivation of the people for testing their drinking water sources for arsenic and environmental interventions like rain water harvesting, ground water recharge, and restricting excessive use of ground water for domestic and agricultural purposes are also important to prevent further exposure of arsenic to these people.

Role of folic Acid on symptoms of chronic arsenic toxicity.

BACKGROUND: Chronic arsenic toxicity (Arsenicosis) due to drinking of arsenic contaminated ground water is a global problem. However, its treatment is unsatisfactory. Methylation of arsenic facilitates its urinary excretion. Persons with relatively lower proportion of urinary dimethyl arsenic acid (DMA) are found to have at greater risk of developing symptoms of arsenicosis including its complications. The biochemical pathway responsible for methylation of arsenic is a folate-dependent pathway. Studies in rodents and humans suggest that folate nutritional status influences the metabolism of arsenic. METHODS: The present study compares the effect of giving folic acid on 32 arsenicosis patients during a 6-month period and comparing the results with clinical effect of taking only arsenic-free safe water on 45 age and sex-matched arsenic-affected people for the same period. RESULTS: There was significant improvement of arsenical skin lesion score of both patients treated with folic acid (2.96 ± 1.46 to 1.90 ± 0.90, P < 0.001) and arsenic free safe water (2.91 ± 1.26 to 1.62 ± 1.05, P < 0.001) for a period of 6 months. Significant improvement in systemic disease score was also observed from the baseline systemic score in folic acid treated group (4.78 ± 3.43 to 1.00 ± 1.56, P < 0.001) and the group treated with arsenic-free water (1.87 ± 2.11 to 0.82 ± 1.62, P < 0.001). However, there was a significant increased improvement of systematic disease score in the folic acid treated group compared to the control group taking arsenic free water (P < 0.001). CONCLUSIONS: This study provides evidence that folic acid treatment in arsenicosis cases could help in reducing clinical symptoms of arsenicosis.

Human urothelial micronucleus assay to assess genotoxic recovery by reduction of arsenic in drinking water: a cohort study in West Bengal, India.

Chronic exposure to arsenic through drinking water affects nearly 26 million individuals in West Bengal, India. Cytogenetic biomarkers like urothelial micronucleus (MN) are extensively used to monitor arsenic exposed population. In 2004-2005, 145 arsenic exposed individuals and 60 unexposed controls were surveyed of which 128 exposed individuals and 54 unexposed controls could be followed up in 2010-2011. In 2004-2005, the extent of arsenic content in the drinking water was 348.23 ± 102.67 µg/L, which was significantly lowered to 5.60 ± 10.83 µg/L in 2010-2011. Comparing the data obtained between 2004-2005 and 2010-2011, there was a significant decline in the MN frequency, when assayed in 2010-2011 compared to 2004-2005. Hence, we infer that urothelial MN can be utilized as a good biomarker in detecting remedial effects from toxicity of the low dose of arsenic through drinking water.

Arsenic exposure induces genomic hypermethylation.

Gene-specific hypermethylation has previously been detected in Arsenic exposed persons. To monitor the level of whole genome methylation in persons exposed to different levels of Arsenic via drinking water, DNA was extracted from peripheral blood mononuclear cells of 64 persons. Uptake of methyl group from (3)H labeled S-Adenosyl Methionine after incubation of DNA with SssI methylase was measured. Results showed statistically significant (P = 0.0004) decrease in uptake of (3)H methyl group in the persons exposed to 250-500 microg/L arsenic, indicating genomic hypermethylation.

Occurrence of arsenicosis in a rural village of Cambodia.

Ninety-seven subjects belonging to 40 families in a village in Cambodia were examined in a health camp where all the cases with skin disease assembled. These people had evidences of chronic arsenic exposure from reports of testing of water samples and of hair and/or nail studied. Seventy cases were diagnosed to be suffering from arsenicosis (Clinically and laboratory confirmed according to WHO criteria) as all these cases had evidences of pigmentation and/or keratosis characteristic of arsenicosis and history of exposure of arsenic contaminated water and/or elevated level of arsenic in hair and/or in nail. Highest number of cases belonged to age group of 31 to 45 yrs, both the sexes are more or less affected equally. Evidence of both pigmentation and keratosis were found in 60 cases (85.7%) while only pigmentation and only keratosis was found in 6 (8.5%) and 4 (5.7%) cases respectively. It was interesting to find 37.04% of children below the age of 16 years had skin lesions of arsenicosis. The youngest child having definite evidence of keratosis and pigmentation was aged 8 years, though two children aged 4 and 5 yrs had feature of redness and mild thickening of the palms. The minimum and maximum arsenic values detected in the nails were 1.06 and 69.48 mg/Kg respectively and the minimum and maximum arsenic values in hair were 0.92 and 25.6 mg/Kg respectively. No correlation was observed between arsenic concentration in drinking water and arsenic level in nail and hair. This is the first report of clinical and laboratory confirmed cases of arsenicosis in Cambodia.

Effect of drinking arsenic contaminated water in children.

OBJECTIVE: Chronic arsenic toxicity due to drinking of arsenic contaminated water is a major environmental health hazard throughout the world including India. Though lot of information is available on health effects due to chronic arsenic toxicity in adults, knowledge of such effect on children is scanty. A review of available literature has been made to highlight the problem in children. REVIEW METHODS: Scientific publication in journals, monograph, thesis and proceedings of conferences on arsenic in regard to epidemiological, clinical and psychometric studies were reviewed. RESULTS: Skin abnormalities including pigmentation change and keratosis are the diagnostic signs of chronic arsenic toxicity in adults. Incidence of skin manifestations vary between 1.9-37.1% in various arsenic exposed children populations in different regions of the world. Occurrence of chronic lung disease including pulmonary interstitial fibrosis was described in arsenic exposed children in Chile. Affection of intellectual function is also reported from Thailand, Bangladesh and India. CONCLUSION: Chronic arsenic toxicity due to drinking of arsenic contaminated water causes significant morbidity in children in different parts of the world.

Seasonal variation of arsenic concentrations in tubewells in west Bengal, India.

This study was conducted to monitor the changes in arsenic concentration during different seasons in a one-year period during 2002-2003 in selected tubewells in an arsenic-affected area in the district of South 24 Parganas in West Bengal, India, and to map the location of the wells. Seasonal variations in concentrations of arsenic in water were measured from 74 selected tubewells, ranging in depth from 40 to 500 feet. Water samples were collected from these wells during winter, summer, monsoon, and the following winter in 2002-2003. A global positioning system was used for locating the tubewells, and a geographic information system was used for mapping. There was evidence of seasonal variation in concentrations of arsenic in water (p=0.02) with the minimum average concentration occurring in the summer season (694 microg/L) and the maximum in the monsoon season (906 microg/L). From the winter of 2002 to the winter of 2003, arsenic concentrations increased, irrespective of the depth of the tubewells, from an average of 464 microg/L to 820 microg/L (p<0.001). This extent of variation in arsenic concentration, if confirmed, has important implications for both epidemiological research and mitigation programmes.

Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water.

BACKGROUND: Arsenic is a unique human carcinogen in that it causes lung cancer by exposure through ingestion (in drinking water) as well as through inhalation. Less is known about nonmalignant pulmonary disease after exposure to arsenic in drinking water. METHODS: We recruited 108 subjects with arsenic-caused skin lesions and 150 subjects without lesions from a population survey of over 7000 people in an arsenic-exposed region in West Bengal, India. Thirty-eight study participants who reported at least 2 years of chronic cough underwent high-resolution computed tomography (CT); these scans were read by investigators in India and the United States without knowledge of the presence or absence of skin lesions. RESULTS: The mean (+/-standard deviation) bronchiectasis severity score was 3.4 (+/-3.6) in the 27 participants with skin lesions and 0.9 (+/-1.6) in the 11 participants without these lesions. In subjects who reported chronic cough, CT evidence of bronchiectasis was found in 18 (67%) participants with skin lesions and 3 (27%) subjects without skin lesions. Overall, subjects with arsenic-caused skin lesions had a 10-fold increased prevalence of bronchiectasis compared with subjects who did not have skin lesions (adjusted odds ratio=10; 95% confidence interval=2.7-37). CONCLUSIONS: These results suggest that, in addition to being a cause of lung cancer, ingestion of high concentrations of arsenic in drinking water may be a cause of bronchiectasis.

Decrements in lung function related to arsenic in drinking water in West Bengal, India.

During 1998-2000, the authors investigated relations between lung function, respiratory symptoms, and arsenic in drinking water among 287 study participants, including 132 with arsenic-caused skin lesions, in West Bengal, India. The source population involved 7,683 participants who had been surveyed for arsenic-related skin lesions in 1995-1996. Respiratory symptoms were increased among men with arsenic-caused skin lesions (versus those without lesions), particularly "shortness of breath at night" (odds ratio (OR) = 2.8, 95% confidence interval (CI): 1.1, 7.6) and "morning cough" (OR = 2.8, 95% CI: 1.2, 6.6) in smokers and "shortness of breath ever" (OR = 3.8, 95% CI: 0.7, 20.6) in nonsmokers. Among men with skin lesions, the average adjusted forced expiratory volume in 1 second (FEV1) was reduced by 256.2 ml (95% CI: 113.9, 398.4; p < 0.001) and the average adjusted forced vital capacity (FVC) was reduced by 287.8 ml (95% CI: 134.9, 440.8; p < 0.001). In men, a 100-microg/liter increase in arsenic level was associated with a 45.0-ml decrease (95% CI: 6.2, 83.9) in FEV1 (p = 0.02) and a 41.4-ml decrease (95% CI: -0.7, 83.5) in FVC (p = 0.054). Women had lower risks than men of developing skin lesions and showed little evidence of respiratory effects. In this study, consumption of arsenic-contaminated water was associated with respiratory symptoms and reduced lung function in men, especially among those with arsenic-related skin lesions.

Effect of chronic intake of arsenic-contaminated water on liver.

The hepatotoxic effect of arsenic when used in therapeutic dose has long been recognized. We described the nature and degree of liver involvement and its pathogenesis due to prolonged drinking of arsenic-contaminated water in West Bengal, India. From hospital-based studies on 248 cases of arsenicosis, hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The portal fibrosis was characterized by expansion of portal zones with streaky fibrosis, a few of which contained leash of vessels. However, portal hypertension was found in smaller number of cases. A cross-sectional epidemiological study was carried out on 7683 people residing in arsenic-affected districts of West Bengal. Out of these, 3467 and 4216 people consumed water-containing arsenic below and above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001). The incidence of hepatomegaly was found to have a linear relationship proportionate to increasing exposure of arsenic in drinking water in both sexes (P < 0.001). In an experimental study, BALB/C mice were given water contaminated with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at 3-month intervals. We observed progressive reduction of hepatic glutathione and enzymes of anti-oxidative defense system associated with lipid peroxidation. Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15 months. Our studies show that prolong drinking of arsenic-contaminated water is associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to be caused by arsenic induced oxystress.

Nutritional factors and susceptibility to arsenic-caused skin lesions in West Bengal, India.

There has been widespread speculation about whether nutritional deficiencies increase the susceptibility to arsenic health effects. This is the first study to investigate whether dietary micronutrient and macronutrient intake modulates the well-established human risk of arsenic-induced skin lesions, including alterations in skin pigmentation and keratoses. The study was conducted in West Bengal, India, which along with Bangladesh constitutes the largest population in the world exposed to arsenic from drinking water. In this case-control study design, cases were patients with arsenic-induced skin lesions and had < 500 microg/L arsenic in their drinking water. For each case, an age- and sex-matched control was selected from participants of a 1995-1996 cross-sectional survey, whose drinking water at that time also contained < 500 microg/L arsenic. Nutritional assessment was based on a 24-hr recall for major dietary constituents and a 1-week recall for less common constituents. Modest increases in risk were related to being in the lowest quintiles of intake of animal protein [odds ratio (OR) = 1.94; 95% confidence interval (CI), 1.05-3.59], calcium (OR = 1.89; 95% CI, 1.04-3.43), fiber (OR = 2.20; 95% CI, 1.15-4.21), and folate (OR = 1.67; 95% CI, 0.87-3.2). Conditional logistic regression suggested that the strongest associations were with low calcium, low animal protein, low folate, and low fiber intake. Nutrient intake was not related to arsenic exposure. We conclude that low intake of calcium, animal protein, folate, and fiber may increase susceptibility to arsenic-caused skin lesions. However, in light of the small magnitude of increased risks related to these dietary deficiencies, prevention should focus on reducing exposure to arsenic.

Arsenic in drinking water and skin lesions: dose-response data from West Bengal, India.

BACKGROUND: Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation. METHODS: We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field. RESULTS: The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations. CONCLUSIONS: The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.

Family correlations of arsenic methylation patterns in children and parents exposed to high concentrations of arsenic in drinking water.

We investigated the evidence of a familial contribution to urinary methylation patterns in families ingesting arsenic in drinking water. Arsenic methylation can be assessed by measuring urinary levels of inorganic arsenic (InAs) and its methylated metabolites, monomethylarsonate (MMA), and dimethylarsinate (DMA). Methylation activity is reflected in the ratios: InAs/methylated arsenic (InAs/metAs) and MMA/DMA. Eleven families from Chile were selected because of their long-term exposure to very high levels of arsenic in drinking water (735-762 microg/L). Each family consisted of a father, a mother, and two children. We measured urinary arsenic and its methylated metabolites for each participant (n = 44). The intraclass correlation coefficients showed that 13-52% of the variations in the methylation patterns were from being a member of a specific family. Family correlations were calculated for father-mother, parent-child, and sibling-sibling pairs. Methylation patterns correlated strongly between siblings [r = 0.78 for InAs/metAs, 95% confidence interval (CI), 0.34-0.94; r = 0.82 for MMA/DMA, 95%CI, 0.43-0.95] compared to lower correlations in father-mother pairs (r = 0.18, r = -0.01, respectively), after adjustment for total urinary arsenic, age, and sex. Family correlations were not notably altered when adjustments were made for specific blood micronutrients (methionine, homocysteine, folate, vitamin B6, selenium, and vitamin B12 potentially related to methylation. We also report on a family pedigree with high prevalence of arsenic-induced effects. Participants from this family had low InAs/metAs values, which is consistent with increased toxicity of trivalent methylated arsenic species. Despite our small sample size, we observed that methylation patterns aggregate in families and are correlated in siblings, providing evidence of a genetic basis for the variation in arsenic methylation. Larger studies with more extensive pedigrees will need to be conducted to confirm these findings.