Arsenic: opportunity for risk assessment.

Arsenic is a human carcinogen that in small amounts is widely distributed in food and water. It has been regulated for almost 100 years worldwide and in the United States, on the judgment of the Royal Commission on Arsenic that a classical threshold of toxicity exists and that a daily intake of 400 micrograms/day is safe. Modern regulatory thinking in the United States has not accepted safe levels for carcinogens and is thus in conflict with the arsenic standard. Recent epidemics of arsenicism have quantitatively confirmed that threshold not only for the non-cancerous arsenical skin lesions but also for arsenical skin and internal cancers. Research shows that arsenic is a general gene inducer. Genes induced are involved in proliferation, recombination, amplification and the activation of viruses. This characterizes arsenic as an indirect carcinogen and provides a molecular basis for risk assessment and the observed threshold dose response. In the United States at present, about 300 cases of occupational arsenical cancer, declining in numbers, are known. Background arsenic below the drinking water standard is not known to have produced disease. The conspicuous nature of arsenical skin disease presents an unusual opportunity for a simplified survey of arsenical skin disease to support regulatory standards for arsenic.