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15 years old was 6.9%, which was comparable to those found by the same examiner in arsenic-contaminated areas in Bangladesh, and that males had prevalence a twice as high as females, which could not be explained by the difference in the exposure level.
Elevated arsenic level in drinking water has become a public health threat in many developing countries. In lowland Nepal, known as Terai, where almost half (12 million) of the Nepalese population resides, the people have been using groundwater for all domestic purposes including drinking since 1990s.1 Although contamination of tube well water by arsenic in this area was first reported in 1999, only sporadic information on the situation have been published.1–4 Among such studies, it was reported that 29% of more than 20,000 tube wells had arsenic concentrations exceeding the World Health Organization (WHO) standard (10 µg/L),3 that the prevalence of arsenicosis varied between 1.3% and 5.1% among four independent surveys,4 and that approximately 0.5 million people in Terai were at risk of consuming water with an arsenic concentration > 50 µg/L.1 However, low sampling rates and/or selection biases (e.g., excluding those consuming uncontaminated water) in these surveys may have obscured the real situation. In this paper, we report the results of a community-based, cross-sectional, dose-response evaluation conducted in a "hot spot" area in lowland Nepal to examine the extent and health impact of arsenic contamination of groundwater.
The survey was conducted from December 2002 to February 2003 and in July–August 2003 in three communities in the Nawalparasi District in lowland Nepal. Since these communities are close to each other and share a similar environment and lifestyle, all data were treated en bloc. Except for some women who migrated from neighboring areas upon being married, most of the residents were indigenous to this area. Dermatologic examinations were conducted by one of the authors (AA), a physician having ample experience in diagnosing arsenicosis cases in Bangladesh, who was blind to the exposure condition of individuals. An arsenicosis case was defined as having skin manifestations, i.e., pigmentation changes and/or keratosis on the palms, the soles of the feet, or trunk,5 and was classified as a mild, moderate, or severe according to criteria previously described.6 Approximately 80% of the inhabitants voluntarily participated in the dermatologic examinations (Table 1
). Spot urine samples were collected from a subset of these participants, i.e., 106 husband and wife pairs who were more than 20 years old. Age differences in the couples were less than 10 years (to avoid possible confounding effects of age, which could be problematic in between-sex comparison7). Mean daily water consumption was measured in the both surveys (n = 45 for each sex in each survey) by providing a water bottle to be used for one day for drinking, a simple, field-applicable method as described elsewhere.8 The arsenic content of urine (Asu) and drinking water samples (Astw) from all the tube wells in use (n = 146, mean ± SD age of the tube wells = 10 ± 8 years) was measured by atomic absorption spectrophotometry with hydride generation with appropriate standard reference materials as previously described.7
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The tube wells were the only sources for drinking water in this area. The Astw ranged from 3 to 1,072 µg/L, with a mean (SD) of 403 (229) µg/L. A total of 97.9% of the tube wells had arsenic levels > 10 µg/L, the WHO limit; 87.6% had levels > 50 µg/L, the Nepal Interim Standard. Among the participants of dermatologic examinations, the overall prevalence of arsenicosis was 6.9%, with a significantly higher prevalence in males than in females and a virtually negligible prevalence among those less than 15 years old. In both sexes, mild cases of arsenicosis predominated and none was classified as severe (Table 1
). When the subset of the participants (n = 106 couples) was classified into groups for each sex by the urinary arsenic level, the prevalence significantly increased with the arsenic level in males, but not in females. The prevalence rate was significantly different between sexes of the high arsenic concentration group (Table 2). The mean ± SD daily water consumption averaged across the two surveys was 68 ± 7 and 63 ± 10 mL/kg/day in males and females, respectively. This small difference was statistically significant (P < 0.001), but was not reflected in Asu levels, presumably due to a relatively large variation in the Astw, as well to the creatinine correction, which may slightly overestimate the exposure in females.7
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The higher susceptibility of males to arsenic-induced skin lesions was consistent with the results of our previous report7 and another study.10 The analyses of arsenic exposure groups showed that male susceptibility remained even when the exposure levels were taken into account. The higher the exposure level, the greater the sex-related difference, suggesting that the difference is more related with the effect of arsenic than with intrinsic (background) prevalence in skin manifestations. The significant difference in water consumption (thus, in arsenic intake) appears too small (by only 8%) to account for the sex-related two-fold difference in the prevalence, further suggesting higher susceptibility in males. Since mean age of either husbands or wives was approximately 40 years, while the mean age of tube wells was only 10 years, presumably the husbands and wives were exposed to contaminated water for a similar length of period. Similar to our Bangladeshi survey,7 other possible confounders including sunlight exposure and cigarette smoking appeared to play minor roles in this sex-related difference. Thus, we would speculate that such a sex-related difference in susceptibility might have biologic origin, e.g., difference in the metabolism of arsenic, and is worthy of further study.
Received May 21, 2004. Accepted for publication August 26, 2004.
Acknowledgments: We thank all villagers in Goini and Kunwars for their hospitality and cooperation. Makhan Maharjan conducted fieldwork and laboratory and statistical analyses. Chiho Watanabe supervised the overall study, including the fieldwork. Akhtar Ahmad conducted the clinical examinations for arsenicosis. Ryutaro Ohtsuka managed the project and participated in the fieldwork. All authors cooperated in writing the report.
Financial support: This work was done as a part of the research project on "Health Effects of Environmental Arsenic Exposure in Lowland Nepal," and was supported by the Alliance for Global Sustainability Program, and the Ministry of Education, Culture, Sports, Science, and Technology in Japan. The sponsors had no role in the design of the study, collection, and interpretation of data, or preparation of the report.
* Address correspondence to Dr. Chiho Watanabe, Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: chiho{at}humeco.m.u-tokyo.ac.jp 
Authors’ addresses: Makhan Maharjan, Chiho Watanabe, and Ryu-taro Ohtsuka, Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan, E-mails: makhan_maharjan{at}hotmail.com, chiho{at}humeco.m.u-tokyo.ac.jp, and rohtsuka{at}humeco.m.u-tokyo.ac.jp. Sk. Aktar Ahmad, Department of Occupational and Environmental Health, National Institute of Preventive and Social Medicine, Mohakali, Dhaka-1212, Bangla-desh, E-mail: anon{at}mail.bdcom.com.
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  M. Maharjan, C. Watanabe, S. A. Ahmad, M. Umezaki, and R. Ohtsuka Mutual interaction between nutritional status and chronic arsenic toxicity due to groundwater contamination in an area of Terai, lowland Nepal J Epidemiol Community Health, May 1, 2007; 61(5): 389 - 394. [Abstract] [Full Text] [PDF]
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