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Arsenic in Drinking Water (1999) / Chapter Skim
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Executive Summary
Pages 1-9

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From page 1...
... A wide variety of adverse health effects, including skin and internal cancers and cardiovascular and neurological effects, have been attributed to chronic arsenic exposure, primarily from drinking water. EPA's interim maximum contaminant level (MCL)
From page 2...
... The Subcommittee's Evaluation Health Effects The subcommittee concludes that there is sufficient evidence from human epidemiological studies in Taiwan, Chile, and Argentina that chronic ingestion of inorganic arsenic causes bladder and lung cancer, as well as skin cancer. With minor exceptions, epidemiological studies for cancer are based on populations exposed to arsenic concentrations in drinking water of at least several hundred micrograms per liter.
From page 3...
... Future studies on the beneficial effects of arsenic in experimental animals should carefully monitor the amount and speciation of arsenic in diets and water, use biomarkers to assess arsenic exposure and bioavailability, and use techniques that assess the toxicity and benefits of arsenic in a more specific manner than is possible through measurement of growth and reproductive success. In humans, the concentration of arsenic in total parenteral nutrition (TPN)
From page 4...
... The mechanism of action by which arsenic induces noncancer effects is centered on its inhibitory effects on cellular respiration at the level of the mitochondrion. Hepatotoxicity is a major health effect related to decreased cellular respiration.
From page 5...
... A greater understanding is needed of the inter-relationships between arsenic's effects on cellular respiration and its effects on biochemical processes, including methylation, formation of reactive oxygen species, oxidative stress, and protein stress response. Variation in Human Sensitivity Human sensitivity to the toxic effects of inorganic arsenic exposure is likely to vary based on genetics, metabolism, diet, health status, sex, and other possible factors.
From page 6...
... Standard reference materials are needed to analyze arsenic species in urine. Other Considerations Assessment of arsenic exposure via drinking water is often based on the measurements of arsenic concentrations in drinking water and assumptions regarding the amount of water consumed.  Such data are estimates, the uncertainty of which will depend on the method used.
From page 7...
... Therefore, the subcommittee's characterization of risks at the current MCL is based on observed epidemiological findings, experimental data on the mode of action of arsenic, and available information on the variations in human susceptibility. In the absence of a well-designed and well-conducted epidemiological study that includes individual exposure assessments, the subcommittee concluded that ecological studies from the arsenic endemic area of Taiwan provide the best available empirical human data for assessing the risks of arsenic-induced cancer.
From page 8...
... The subcommittee also concludes that the choice of model for statistical analysis can have a major impact on estimated cancer risks at low-dose exposures, especially when the model accounts for age as well as concentration.  Applying different statistical models to the Taiwanese male bladder-cancer data revealed that a more stable and reliable fit is provided by Poisson regression models that characterized the log relative risk as a linear function of exposure. The estimation of risk at low doses using those models is substantially higher than that using the multistage Weibull model.
From page 9...
... The potential effect of measurement error and confounding on the dose-response curve and associated confidence limits should be further addressed. To assist in the application of cancer data observed in different populations to cancer risks predicted for the United States, information on nutritional factors in study populations that pertains to susceptibility to arsenic-induced cancer should be investigated.


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