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estimate the magnitude of the risk. The forum identified three sources of uncertainty and controversy, however, with respect to the assessment of risk from ingestion of arsenic (EPA 1988, p. 3): (1) Evidence of human carcinogenicity is primarily from epidemiological studies conducted in other countries, and its applicability to the U.S. population is uncertain. (2) The primary tumor response in those studies is skin cancer, which is more likely to be detected and successfully treated than many other forms of cancer. (3) Limited animal evidence suggests that arsenic might be an essential nutrient, raising the possibility that reducing the level of arsenic below some critical level (as yet unspecified) might result in a decrement of health in some way (as yet unknown).

The forum concluded that the epidemiological studies conducted in Taiwan on arsenic in drinking water (Tseng et al. 1968) and confirmatory studies (Albores et al. 1979; Cebrian et al. 1983) demonstrate that inorganic arsenic is a human carcinogen by the oral route (group A by EPA's classification scheme) (EPA 1988, p.3). The forum also concluded that the Taiwanese studies provide a reasonable basis for quantitative risk assessment of skin cancer in the United States, despite many uncertainties. Those two conclusions affirm the adequacy of the evidence to address the first two steps (i.e., hazard identification and dose-response assessment) of the four-step risk-assessment paradigm developed by the National Research Council (NRC 1983). EPA's group A classification for hazard identification does not refer to potency but to the strength of the evidence for human carcinogenicity. The result of the dose-response assessment is an estimated increase of U.S. lifetime skin-cancer risk of 3-7 x 10-5 (µg/L)-1 (i.e., 3-7 additional cases of skin cancer per 100,000 persons for each microgram of inorganic arsenic per liter in the drinking water). The "3" and "7" are not statistical bounds, but the outcomes from data on females and males, respectively. A value of 5 x 10-5 (µg/L)-1 has been used to estimate skin-cancer risk for both sexes in the United States. An implicit assumption in those values, which are a consequence of the methodology of EPA's risk-assessment guidelines, is that at low arsenic concentrations the risk of skin cancer increases linearly with the arsenic concentration in drinking water. The forum noted that assumption as a source of uncertainty, stating that the dose-response curve might be less than linear and might not pass through the origin. The forum pointed out, but did not explore in depth, epidemiological evidence of an association between inorganic arsenic and internal cancers (EPA 1988, Appendix C) and concluded that more studies are needed to determine if arsenic is a nutritional requirement in humans (EPA 1988, p. 40).

The remainder of this section examines each chapter of the special report to highlight what was done and how it was done, issues that were or were not resolved, and the remaining sources of uncertainty and possible data gaps.



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