Oral exposure to inorganic arsenic: evaluation of its carcinogenic and non-carcinogenic effects

Inorganic arsenic, which is extensively metabolised in humans into even more toxic methylated arsenicals, is a potent carcinogen, causing tumours of the skin, lung, urinary bladder, and other organs. It also induces a number of non-cancer effects. Consumption of drinking water highly contaminated by arsenic causes serious health problems in some countries in southeastern Asia, and arsenic poses problems for drinking-water safety worldwide. Existing risk assessments are based on epidemiological studies from regions with high exposure concentrations (in the mg/L range). It is a matter of debate whether these findings are useful at predicting arsenic-induced effects at low concentrations. In recent years numerous epidemiological studies on cancer and non-cancer effects of inorganic arsenic have been published. This work aims at reviewing recent toxicological and epidemiological data on inorganic arsenic with emphasis on effects at low exposure concentrations. Information obtained from epidemiological studies is supplemented with mechanistic data from in vitro and in vivo studies. Various modes of action for arsenic carcinogenicity are discussed. The information gathered was used to evaluate the reliability of existing cancer-risk assessments and to improve current assessments of non-cancer health effects. A tolerable daily dose, based on epidemiological studies on arsenic-induced skin disorders, is presented.