Dose-response study of the carcinogenicity of dietary sodium nitrite and morpholine in rats and hamsters

Abstract

Long-term feeding studies were conducted in Sprague-Dawley rats and Syrian golden hamsters using various dietary concentrations of nitrite and morpholine (up to 1000 ppm of each) or N-nitrosomorpholine (5 or 50 ppm). Most combinations of the two chemicals induced a high incidence of hepatocellular carcinoma in rats and a lower incidence in hamsters. The highest level of nitrite and morpholine (1000 ppm of each) had a stronger potential for carcinogenesis in both rats and hamsters than did a dietary level of 50 ppm of preformed N-nitrosomorpholine. Nitrite and morpholine also induced angiosarcomas in both species, most frequently in the liver, with the lung as the next most common site. The nitrite concentration in the diet seemed to have a greater effect on the incidence of hepatocellular carcinoma and angiosarcoma in the rat than did the concentration of morpholine. Dietary concentrations of 5 ppm each of nitrite and morpholine induced hepatocellular carcinoma and angiosarcoma in some rats. High concentrations of sodium nitrite alone were associated with a relatively high incidence of lymphoreticular tumours.