Subhankar Das

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 &mgr;g/liter for cases and 180 &mgr;g/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 &mgr;g/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.

Hepatic Damage Caused by Chronic Arsenic Toxicity in Experimental Animals

Objective: Noncirrhotic fibrosis of the liver is common in subjects chronically consuming ground water geologically contaminated with arsenic, but the mechanism of the hepatic fibrosis is not known. Because lipid peroxidation has been implicated in the development of several other forms of hepatic fibrosis, including iron and copper overload, we have explored the roles of oxidative stress and lipid peroxidation in the causation of hepatic fibrosis in a murine model of chronic arsenic toxicity. Methods: Male BALB/c mice were given drinking water contaminated with arsenic (3.2 mg/L) or arsenic-free (<0.01 mg/L, control) ad libitum. Mice were sacrificed at 3, 6, 9, 12, and 15 months for examination of hepatic histology and assays of hepatic reduced glutathione content, lipid peroxidation, enzymes of the antioxidant defense system, and membrane-bound sodium/potassium ATPase (Na+/K+ ATPase). Results: After 12 months of arsenic feeding, the liver weights increased significantly as did serum aspartate aminotransferase and alanine aminotransferase. After 6 months of arsenic feeding, hepatic glutathione and the enzymes glucose-6-phosphate dehydrogenase and glutathione peroxidase were significantly lower than those of the control group. Hepatic catalase activity was significantly reduced at 9 months in the arsenic-fed group, while glutathione-S-transferase and glutathione reductase activities were also significantly reduced at 12 and 15 months. Plasma membrane Na+/K+ ATPase activity was reduced after 6 months while lipid peroxidation increased significantly after 6 months of arsenic feeding. Liver histology remained normal for the first 9 months, but showed fatty infiltration after 12 months of arsenic feeding. Histologic evidence of fibrosis was observed after 15 months. Conclusion: We have demonstrated hepatic fibrosis due to long-term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferase and alanine aminotransferase elevated at 12 months and hepatic fibrosis at 15 months. The murine model is proposed as relevant to epidemic human toxicity in areas of arsenic contamination.

Randomized Placebo-Controlled Trial of 2,3-Dimercapto-1-propanesulfonate (DMPS) in Therapy of Chronic Arsenicosis Due to Drinking Arsenic-Contaminated Water

Background: Chronic arsenic toxicity, producing various clinical manifestations, is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. 2,3-Dimercapto-1-propanesulfonate, a chelating agent, increases excretion of arsenic in urine to several times the prechelation concentration but the therapeutic efficacy of 2,3-dimercapto-1-propanesulfonate in the management of chronic arsenic toxicity has been incompletely evaluated. We investigated the clinical use of 2,3-dmercapto-1-propanesulfonate in such patients. Methods: Twenty-one consecutive patients with chronic arsenicosis were individually randomized into 2 groups: 11 patients (9 males and 2 females, age 30.63 ± 11.4 years) received 2,3-dimercapto-1-propanesulfonate 100-mg capsules 4 times a day for 1 week and repeated in the 3rd, 5th, and 7th week with no drug during the intervening period. The other 10 patients (5 males and 5 females, age 34.4 ± 14.41 years) were given placebo capsules (resembling 2,3-dimercapto-1-propanesulfonate) in the same schedule. The consumption of arsenic-contaminated water was terminated by all 21 subjects. Initial and posttreatment urinary arsenic excretion was determined in all cases. Sequential excretion of urinary arsenic was determined during the treatment of 2 drug- and 1 placebo-treated cases. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigation including liver function test and skin biopsy were also done before and after the treatment. Drug-associated toxicity was tabulated. Results: Therapy with 2,3-dimercapto-1-propanesulfonate caused significant improvement in the clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90 ± 2.84 to 3.27 ± 1.73; p < 0.0001. Exposure cessation alone with placebo treatment also reduced clinical scores (8.50 ± 1.96 to 5.40 ± 2.12; p < 0.003), but the posttreatment total clinical score of 2,3-dimercapto-1-propanesulfonate-treated patients (3.27 ± 1.73) was significantly lower than that of placebo-treated patients (5.40 ± 2.12; p < 0.01). The most significant improvement was noted in regard to the clinical scores of weakness, pigmentation, and lung disease. No difference was noted between groups in the hematological and biochemical parameters (which were normal) and skin histology before and after treatment. No 2,3-dimercapto-1-propanesulfonate-related adverse effects were noted. Total urinary excretion of arsenic in 2,3-dimercapto-1-propanesulfonate-treated cases increased significantly following drug therapy, with no increase in placebo-treated cases. Conclusion: 2,3-Dimercapto-1-propanesulfonate treatment caused significant improvement in the clinical score of patients suffering from chronic arsenic toxicity. Increased urinary excretion of arsenic during the period of therapy is the possible cause of this improvement.

Natural history following arsenic exposure: A study in an arsenic endemic area of West Bengal, India

Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.

Natural history following arsenic exposure

Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.

Chapter 29 – Natural history following arsenic exposure: A study in an arsenic endemic area of West Bengal, India

Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.Publisher Summary A significant number of arsenicosis patients show evidence of dermatological manifestations in spite of apparently consuming arsenic (As)–free water for a prolonged period. New skin lesions appeared in a few cases without known exposure. A number of these people show feature of chronic lung disease (CLD). However, there was no monitoring of exposure during the follow-up period, and it is possible that the exposure occurred either because of unmeasured or undetermined water sources or perhaps from the food contaminated with As. A more detailed follow-up of larger cohorts is needed to fully elucidate the health effects of As following termination of exposure.