A review and biological risk assessment of sodium saccharin.

Dietary sodium saccharin is associated with bladder tumors when fed at high levels to the male rat. Under these conditions urinary pH, sodium concentration, and volume are elevated and proliferative changes are present in the urothelium. Extensive epidemiological studies have shown that saccharin does not increase the risk of bladder cancer in humans and laboratory investigations have shown that sodium saccharin is not mutagenic and does not bind to DNA. Recent research indicates that the urothelium in male rats is damaged under conditions of high urinary pH and sodium levels by a mechanism that involves alpha 2u-globulin and possibly silicate crystalluria. These studies and their implications for human health risk are reviewed.