CARCINOGENIC RISKS OF INORGANIC ARSENIC IN PERSPECTIVE

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dos e-response relationships between different target organs. Inhaled or i ngested arsenic causes cancer in humans but not in other species. Inha led arsenic primarily induces lung cancer, whereas ingested arsenic in duces cancer at multiple sites, including the skin and various other o rgans. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exp osures in some instances. To understand what might explain these incon sistencies, we reviewed several hypotheses about the mechanism of canc er induction by arsenic. Arsenic disposition does not provide satisfac tory explanations. Induction of cell proliferation by arsenic is a mec hanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.