A Dose-Response and Susceptibility Investigation of Skin Keratoses and Hyperpigmentation due to Ingestion of Arsenic in Drinking Water

EPA Grant Number: R826137
Title: 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: Hiscock, Michael
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: Human Health , Drinking Water , Health Effects , Water


The proposed study will be conducted in West Bengal, India where a large population is exposed to drinking water containing arsenic. This study will focus on effects at low doses and will be of immediate value for arsenic risk assessment.

The key objectives of the proposed reasearch are to establish the dose-response relationship for skin keratoses and hyperpigmentation caused by ingestion of inorganic arsenic in drinking water, and to identify if susceptibility varies according to arsenic methylation efficiency and nutritional factors.

The study will build upon a unique cross-sectional epidemiological study previously conducted in the arsenic exposed region of West Bengal, India. This study examined over 7000 participants, more than 400 of whom were found to have arsenic induced skin lesions. Some cases resulted from drinking water containing very high arsenic levels, but about 280 cases were reported to consume water containing between 10 and 500 µg/L. Two hundred of these cases, along with age and sex matched controls, will be identified for further medical examination and detailed exposure assessment. Potential susceptibility factors will be assessed, including arsenic methylation efficiency based on urinary assays, and nutritional status as determined by blood measurements of macronutrients, vitamins, minerals, and amino acids. Nutritional status will also be assessed by body mass measurements and analysis of general dietary patterns.

The proposed research will produce key information regarding skin keratoses and hyperpigmentation, two early endpoints of arsenic-associated pathology. Arsenic skin lesions are an early biomarker of effect from chronic exposure because they usually appear 5 to 15 years after exposure commences. It is expected that the study will yield critical dose-response information for arsenic caused skin lesions, and where a threshold might lie. It will also identify potential susceptibility factors, and thereby reduce the uncertainty in generalizing risk to other populations. Since arsenic skin lesions are the most frequently occurring and earliest endpoint of chronic inorganic arsenic ingestion , and since the evidence suggest they may also be markers of subsequent cancer risks, this study will make a significant contribution to a fuller scientific understanding about the human health effects of consuming drinking water containing low levels of arsenic.

Publications and Presentations:

Publications have been submitted on this project: View all 7 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 5 journal articles for this project

Supplemental Keywords:

drinking water, exposure assessment, risk assessment, health effects, metabolism, carcinogen, heavy metals, case-control study,, 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, ingestion, monitoring, public water systems, risk assessment, biomarkers, carcinogenesis, dose-response models, health risks, human health effects, exposure and effects, age-related differences, dose-response, exposure, gender, case-control study, community water system, skin keratoses, survey, India, urinary assays, dermatology, effects, cancer risks, human exposure, hyperpigmentation, public health, quantifying exposure, residential populations, susceptibility, toxicity testing, dietary questionnaire, dietary sources, environmental toxicant, harmful environmental agents, metabolism, toxic environmental contaminants, water quality, hepatic endpoints, arsenic exposure, biological markers, dietary exposure, dietary ingestion exposures, drinking water contaminants, keratoses, predictive toxicology, skin cancer, nutritional factors, micronutrients, age, biomarker data, biomedical research, cancer risk, dose dependency, drinking water system, exposure assessment, heavy metals, long-term exposure

Relevant Websites:

http://socrates.berkeley.edu/~asrg exit EPA

Progress and Final Reports:

  • 1998
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001
  • Final Report