Chronic toxicity of sodium nitrite in the male F344 rat

A long-term feeding study was carried out in rats with sodium nitrite. The test substance was administered as part of a reduced-protein diet to groups of 50, 6-wk-old, male F344 rats at dose levels of 0.2 or 0.5% (w/w) sodium nitrite for up to 115 wk. A control group of 20 males received the reduced-protein diet alone. Throughout the study, there was a dose-related decrease in the rates of body-weight gains and a corresponding decrease in body weights among animals fed sodium nitrite in the diet. Food intakes of rats in the low-dose group were slightly raised over most of the study. In the high-dose group, food intakes were reduced during the first month, but thereafter were similar to those of the control group. This reduction in food intake together with the lower body weights in the nitrite-treated animals, may indicate a reduction in food utilization. In the first week of treatment the following haematological parameters were reduced: red blood cell count, haematocrit and haemoglobin concentration. The red blood cell count continued to fall for 8 wk, then slowly returned to normal by wk 52. A dose-related reduction was noted in both the incidence and time of onset of lymphomas, leukaemias and testicular interstitial cell tumours. Leukaemias were only found in animals with lymphoma, indicating an association between the two lesions. Under the conditions described in this study, sodium nitrite was found not to be carcinogenic when fed to rats in the diet for up to 115 wk, but rather that the incidence of tumours was reduced in a dose-related manner, which correlated with a similar trend in body weights.