Results of a long-term carcinogenicity bioassay on Sprague-Dawley rats exposed to sodium arsenite administered in drinking water

Arsenic (As) is a metal found in nature whose acute and chronic toxic effects have been known for decades. Hundreds of millions of people are at risk of exposure to As and its various chemical forms which can occur in the occupational and general environment in air, water, soil, food, and medicines. Several epidemiological studies have shown that prolonged exposure to As can induce various types of malignant tumors in humans, namely, skin, lung, liver, kidney, and bladder cancers. These effects have been observed particularly in geographic areas where people are exposed to well water with high concentrations of As. While the risks of As at high concentrations are well documented, there is still a great deal of uncertainty regarding the risk of exposure to As at very low levels. This uncertainty is due to the absence of adequate epidemiological data and the insufficiency of experimental data currently available. Given the limited evidence demonstrating the carcinogenic potential of As in animals, a long-term carcinogenicity bioassay on sodium arsenite (NaAsO₂) was performed at the Cesare Maltoni Cancer Research Center (CMCRC) of the European Ramazzini Foundation (ERF). NaAsO₂ was administrated with drinking water at concentrations of 200, 100, 50, or 0 mg/L, for 104 weeks to Sprague-Dawley rats (50/sex/group), 8 weeks old at the start of the study. The animals were monitored until spontaneous death at which time each animal underwent complete necropsy. Histopathological evaluation of all pathological lesions and of all organs and tissues collected was routinely performed on each animal. The results demonstrate that in our experimental conditions NaAsO₂ induces sparse benign and malignant tumors among treated rats. The types of tumors observed are infrequent in the strain of Sprague-Dawley rats of the colony used in our laboratory, namely, lung adenomas and carcinomas, kidney adenomas/papillomas and carcinomas, and bladder carcinomas. Notably, an elevated incidence of these types of oncological lesions is also observed among people living in geographical areas where As is present at higher concentrations in drinking water.