Sodium nitrite

Endpoint summary

Additional information

NTP (2001) reported about the toxicology and carcinogenesis studies of sodium nitrite drinking water studies in rats and mice.

14-week rat study: Groups of 10 male and 10 female rats were exposed to 0, 375, 750, 1,500, 3,000, or 5,000 ppm sodium nitrite (equivalent to average daily doses of approximately 30, 55, 115, 200, or 310 mg sodium nitrite/kg body weight to males and 40, 80, 130, 225, or 345 mg/kg to females) in drinking water. Clinical pathology study groups of 15 male and 15 female rats were exposed to the same concentrations for 70 or 71 days. One female exposed to 3,000 ppm died before the end of the study. Body weights of males exposed to 3,000 or 5,000 ppm and females exposed to 5,000 ppm were significantly less than those of the controls. Water consumption by 5,000 ppm males and 3,000 and 5,000 ppm females was less than that by the controls at weeks 2 and 14. Clinical findings related to sodium nitrite exposure included brown discoloration in the eyes and cyanosis of the mouth, tongue, ears, and feet of males exposed to 3,000 or 5,000 ppm and of females exposed to 1,500 ppm or greater. Reticulocyte counts were increased in males and females exposed to 3,000 or 5,000 ppm. The erythron was decreased on day 19 but increased by week 14 in males and females exposed to 5,000 ppm. Methemoglobin concentrations were elevated in almost all exposed groups throughout the 14 week study. The relative kidney and spleen weights of males and females exposed to 3,000 or 5,000 ppm were significantly greater than those of the controls. Sperm motility in 1,500 and 5,000 ppm males was significantly decreased. Increased erythropoietic activity in the bone marrow of exposed males and females was observed. The incidences of squamous cell hyperplasia of the forestomach in 5,000 ppm males and females were significantly increased. The LOAEL for male rats was 115 mg/kg and the LOAEL for female rats was found to be 225 mg/kg bw. A no-observed-adverse-effect level was not achieved.

14-week mouse study: Groups of 10 male and 10 female mouse were exposed to 0, 375, 750, 1,500, 3,000, or 5,000 ppm sodium nitrite (equivalent to average daily doses of approximately 90, 190, 345, 750, or 990 mg/kg to males and 120, 240, 445, 8 40, or 1,230 mg/kg to females) in drinking water. No clinical signs of toxicity were noted. Body weights of 990 mg/kg bw/day males were significantly less than those of the controls. Water consumption by males exposed to 1,500 ppm or greater was slightly less than that by the controls at week 13. All mice survived until the end of the study. There were increased incidences of squamous cell hyperplasia of the forestomach in 990 mg/kg bw/day males and 1230 mg/kg bw/day females. Relative spleen weights of 750 and 990 mg/kg bw/day males and absolute and relative heart, kidney, liver, and spleen weights of 840 and 1230 mg/kg bw/day females were greater than those of the control groups. There were increased incidences of extramedullary hematopoiesis of the spleen in 750 and 990 mg/kg bw/day males and 445 mg/kg bw/day or greater females, and degeneration of the testis in 750 and 990 mg/kg bw/day males. Sperm motility was decreased in 990 mg/kg bw/day males, and the estrous cycles of 445 and 1230 mg/kg bw/day females were significantly longer than in the controls. The LOAEL for male mice was 750 mg/kg bw and the LOAEL for female mice was 445 mg/kg bw. NOAELs were not identified.

In the two-year chronic toxicity/carcinogenicity study male and female rats were exposed to 0, 750, 1500 or 3000 ppm sodium nitrite (equivalent to average daily doses of approximately 0, 35, 70 or 130 mg/kg bw/day in males and 0, 40, 80 or 150 mg/kg bw/day in females) in drinking water. There were no clinical findings related to exposure. Methaemoglobin levels were measured at two weeks and three months. At both 2 weeks and three months, methaemoglobin levels were high at night when the rats were actively feeding and drinking and low during the day when the rats were less active. Methaemoglobin levels tended to increase with increasing dosage. The NOAELs for male rats were found to be 130 mg/kg bw for male rats and 150 mg/kg bw for female rats.

In the two-year chronic toxicity/carcinogenicity study male and female mice were exposed to 0, 750, 1500 or 3000 ppm sodium nitrite (equivalent to average daily doses of approximately 0, 60, 120 or 220 mg/kg bw/day for males and 0, 45, 90 or 165 mg/kg bw/day for females) in drinking water. There were no clinical findings related to exposure. At 12 months, no significant increase in methaemoglobin level was observed in either sex at any dose. NOAELs were found to be 220 mg/kg bw for male and 165 mg/kg bw for female mice.

Shuval and Gruener (1977) reported about health effects of nitrates in water. Sodium nitrite was offered via the drinking water in daily concentrations of 100, 200, 2000 or 3000 mg/l (= 10, 100, 250 or 350 mg/kg bw). Male rats were used; study duration: 2 years. There were no significant differences in growth, development, mortality or total haemoglobin levels between the control and treated groups. However, the methaemoglobin levels in the groups receiving 100, 250 and 350 mg/kg bw/day sodium nitrite were raised significantly throughout the study and averaged 5, 12 and 22% of total haemoglobin, respectively. The main histopathological changes occurred in the lungs and heart. Focal degeneration and fibrosis of the heart muscle were observed in animals receiving the highest dose of nitrite. The coronary arteries were thin and dilated in these aged animals, instead of thickened and narrow as is usually seen at that age. Changes in the lungs consisted of dilatation of the bronchi with infiltration of lymphocytes and alveolar hyperinflation. Such changes were observed in rats receiving 100, 250 and 350 mg/kg bw/day sodium nitrite. The NOEL was found to be 10 mg/kg bw for male rats.

Justification for classification or non-classification

After repeated administration the prominent effect is damage of the blood (methemoglobin formation).