Grantee Research Project Results
2000 Progress 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 Period Covered by this Report: September 5, 1999 through September 4, 2000
Project Amount: $861,788
RFA: Arsenic Health Effects Research (1997) RFA Text | Recipients Lists
Research Category: Drinking Water , Human Health , Water
Objective:
The first detailed assessment of the dose-response relationship of arsenic-induced keratoses and hyperpigmentation at low doses has been completed by our group. Key objectives of the study also 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.Progress Summary:
Recently, we completed a case-control study 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 our present 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 will be used to ascertain the participants' nutritional status. Urinary assays will be used to determine arsenic methylation efficiency.
Preliminary Findings:
The interviews and sample collection commenced June 1998, and ended December 1999. Participation was excellent (93 percent in cases and 97 percent in controls). Ultimately, 192 cases and 213 controls participated. Key preliminary results on the dose-response relation are listed below:
? 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).
? These trends remained after adjusting for sex, age, smoking status, socioeconomic factors, and body mass index.
? The proportion of cases confirmed as definite or probable by photograph was high (87 percent). An implication of this finding is that keratoses and hyperpigmentation are the best biomarkers of long-term effect.
? Some cases who were initially thought to have consumed very low arsenic levels actually were exposed to higher concentrations in past decades.
Significance of Findings. For the first time, the dose-response relation of skin lesions and arsenic ingestion at low doses was characterized using a detailed exposure assessment. This also was the first study to confirm cases by photograph.
Future Activities:
Interviewing and sample collection has been completed for 405 total participants. Data entry and editing have been completed, and we are now preparing scientific reports for publication regarding the dose-response relation, arsenic methylation capability, and nutritional factors.Journal Articles on this Report : 1 Displayed | Download in RIS Format
Other project views: | All 7 publications | 5 publications in selected types | All 5 journal articles |
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Type | Citation | ||
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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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Supplemental Keywords:
arsenic, health effects, epidemiology, case-control study, dose-response, exposure assessment, risk assessment, drinking water, human health, susceptibility, metabolism, carcinogen, nutrition, diet, metals, heavy metals, West Bengal, India., RFA, Health, Scientific Discipline, Toxics, Water, POLLUTANTS/TOXICS, National Recommended Water Quality, Environmental Chemistry, Health Risk Assessment, Arsenic, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Environmental Monitoring, genetic susceptability, Water Pollutants, Drinking Water, biological threshold, health effects, risk assessment, ingestion, public water systems, monitoring, biomarkers, carcinogenesis, dose-response models, health risks, human health effects, exposure and effects, age-related differences, dose-response, exposure, gender, case-control study, skin keratoses, community water system, survey, India, urinary assays, dermatology, effects, human exposure, public health, quantifying exposure, residential populations, susceptibility, toxicity testing, cancer risks, hyperpigmentation, dietary questionnaire, environmental toxicant, harmful environmental agents, toxic environmental contaminants, dietary sources, metabolism, hepatic endpoints, water quality, biological markers, dietary exposure, predictive toxicology, skin cancer, keratoses, arsenic exposure, dietary ingestion exposures, drinking water contaminants, nutritional factors, micronutrients, biomedical research, exposure assessment, long-term exposure, cancer risk, skin cancer susceptibility, age, biomarker data, dose dependency, drinking water systemRelevant Websites:
http://socrates.berkeley.edu/~asrg ExitProgress 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.