Grantee Research Project Results
Final Report: A Dose-Response and Susceptibility Investigation of Skin Keratoses and Hyperpigmentation due to Ingestion of Arsenic in Drinking Water
EPA Grant Number: R826137Title: A Dose-Response and Susceptibility Investigation of Skin Keratoses and Hyperpigmentation due to Ingestion of Arsenic in Drinking Water
Investigators: Smith, Allan H.
Institution: University of California - Berkeley
EPA Project Officer: Packard, Benjamin H
Project Period: September 5, 1997 through September 4, 2000 (Extended to October 31, 2001)
Project Amount: $861,788
RFA: Arsenic Health Effects Research (1997) RFA Text | Recipients Lists
Research Category: Drinking Water , Human Health , Water
Objective:
The investigators have completed the first detailed assessment of the dose-response relationship of arsenic-induced keratoses and hyperpigmentation at low doses. A key objective of the study included determining if susceptibility varies by arsenic methylation capability and nutritional factors, such as methionine and cysteine. Arsenic methylation was assessed by urinary assays. Nutritional status was determined by blood measurements of key macronutrients and micronutrients, as well as by analysis of a dietary questionnaire.Summary/Accomplishments (Outputs/Outcomes):
A case-control study was recently completed that takes advantage of the largest population-based survey conducted of a district in West Bengal, India, with elevated inorganic arsenic levels in its drinking water supplies. The source of the arsenic is geologic. Potential participants for the case-control study were identified from the 1995 cross-sectional survey for further medical examination and detailed arsenic exposure assessment. The cross-sectional survey included more than 7,000 participants and measured the residents' current arsenic concentration in their tubewell water supplies. All individuals identified with keratoses and/or hyperpigmentation in the survey, and exposed to < 500 µg/L of arsenic, comprised the case group for this investigation. The control group consisted of lesion-free individuals randomly selected from the cross-sectional survey database, matched on age and sex. The information used in the earlier survey of arsenic in drinking water was expanded to include information from all current and past water sources used in households and work sites.
Data obtained from personal interviews and chemical analyses of drinking water samples were used to assess arsenic exposure. The interviews consisted of questions about lifetime residential history, water sources at home and work, and fluid consumption. The clinical exam involved various dermatologic, neurologic, and respiratory endpoints. A number of participants suspected to have an arsenic-induced skin lesion were photographed. A dietary questionnaire supplemented with results of blood assays was used to ascertain the participants' nutritional status. Urinary assays were used to determine arsenic methylation efficiency.
The interviews and sample collection commenced in June 1998, and ended in January 2000. Participation was excellent (88 percent in cases and 94 percent in controls). Ultimately, 192 cases and 213 controls participated. Key preliminary results on the dose-response relation showed that: (1) strong dose-response trends with peak and average exposures were found based on known years of exposure (test for trend with peak and average exposures, p < 0.0001); (2) these trends remained after adjusting for sex, age, smoking status, socioeconomic factors, and body mass index; (3) the proportion of cases confirmed as definite or probable by photograph was 87 percent (an implication of this finding is that keratoses and hyperpigmentation are the best biomarkers of long-term effect); and (4) some cases who initially were thought to have consumed very low arsenic levels actually were exposed to higher concentrations in past decades.
With regard to nutrition, a publication is nearing completion that shows that cases of skin lesions occur over a wide range of intake of macronutrients and micronutrients. There was, however, evidence for some risk modification related to animal protein and vegetable intake, with risks approximately doubled for those in the lowest quintile of intake. Analysis continues concerning blood micronutrients.
For the first time, the dose-response relation of skin lesions and arsenic ingestion at low doses was characterized using a detailed exposure assessment. It also was the first study to confirm cases by photograph.
Interviewing and sample collection has been completed for 405 total participants. Data entry and editing have been completed, and the investigators now are preparing scientific reports for publication regarding the dose-response relation, arsenic methylation capability, and nutritional factors. A key paper on the dose-response relation has been submitted for publication.
Journal Articles on this Report : 4 Displayed | Download in RIS Format
| Other project views: | All 7 publications | 5 publications in selected types | All 5 journal articles |
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Guha Mazumder DN, Haque R, Ghosh N, De BK, Santra A, Chakroborty D, Smith AH. Arsenic levels in drinking water and the prevalence of skin lesions in West Bengal, India. International Journal of Epidemiology<\em> 1998;27(5):871-77. |
R826137 (1999) R826137 (2000) R826137 (Final) |
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Haque R, Mazumder DNG, Samanta S, Ghosh N, Kalman D, Smith MM, Mitra S, Santra A, Lahiri S, Das S, De BK, Smith AH. Arsenic in drinking water and skin lesions: dose-response data from West Bengal, India. Epidemiology 2003;14(2):174-182. |
R826137 (Final) |
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von Ehrenstein OS, Mazumder DNG, Yuan Y, Samanta S, Balmes J, Sil A Ghosh N, Hira-Smith M, Haque R, Purushothamam R, Lahiri S, Das S, Smith AH. Decrements in lung function related to arsenic in drinking water in West Bengal, India. American Journal of Epidemiology 2005;162(6):533-541. |
R826137 (Final) |
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von Ehrenstein OS, Jenny AM, Basu A, Smith KR, Hira-Smith M, Smith AH. Capacity building in environmental health research in India and Nepal. International Journal of Occupational and Environmental Health 2006;12(4):300-306. |
R826137 (Final) |
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Supplemental Keywords:
arsenic, health effects, epidemiology, case-control study, dose-response, drinking water, human health, susceptibility, metabolism, carcinogen, nutrition, diet, metals, West Bengal, India., Health, RFA, Scientific Discipline, Water, Toxics, POLLUTANTS/TOXICS, National Recommended Water Quality, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Risk Assessments, genetic susceptability, Environmental Chemistry, Arsenic, Disease & Cumulative Effects, Drinking Water, Environmental Monitoring, Water Pollutants, community water system, dietary exposure, health effects, health risks, heavy metals, metabolism, quantifying exposure, toxic environmental contaminants, hepatic endpoints, biological markers, harmful environmental agents, ingestion, toxicity testing, water quality, urinary assays, dermatology, age-related differences, biological threshold, human exposure, risk assessment, cancer risks, carcinogenesis, dietary ingestion exposures, dose dependency, monitoring, susceptibility, drinking water system, drinking water contaminants, exposure, gender, residential populations, skin cancer susceptibility, nutritional factors, micronutrients, age, biomedical research, dietary sources, dose-response models, keratoses, predictive toxicology, skin cancer, survey, effects, dose-response, environmental toxicant, human health effects, public water systems, dietary questionnaire, arsenic exposure, biomarker data, biomarkers, cancer risk, exposure assessment, hyperpigmentation, long-term exposure, public health, skin keratoses, case-control study, IndiaProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.