Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 7632-00-0 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Sodium nitrite
  • NITROUS ACID, SODIUM SALT
  • DIAZOTIZING SALTS

Human Toxicity Excerpts

  • HUMAN EXPOSURE STUDIES: Human volunteers given sodium nitrite intravenously produced a maximum methemoglobin level of 7% after a dose of 2.7 mg NO2-/kg and 30% after a dose of 8 mg/kg ... The first symptoms of oral nitrite poisoning develop within 15 to 45 minutes. [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]
  • HUMAN EXPOSURE STUDIES: Symptoms of nitrite poisoning and MetHb formation after ingestion ranged from 0.4 to > 200 mg/kg bw, expressed as nitrite ion ... MetHb formation in different cases varied from 7.7 up to 79% ... /It was deduced that/ cyanosis occurred at MetHb concentration above 10%, and other symptoms at > 20% ... /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]
  • HUMAN EXPOSURE STUDIES: The effect of sodium nitrite on subpopulations (young and old) of isolated neonatal and adult red blood cells was studied. MetHb formation increased with NaNO2 concentration in all subpopulations. Red blood cells treated with NaNO2 were less fragile. Changes in protein composition occurred after NaNO2 treatment. The membrane-bound Hb increased with increasing NaNO2 concentration. When compared with adult red blood cells, neonatal red blood cells seemed more susceptible to MetHb formation, to decrease in fragility, and to oxidative denaturation of spectrins and band-3-proteins. Increased susceptibility of neonatal cells to oxidative injury and MetHb formation may contribute to their shorter life-span when compared to adult cells. This susceptibility may also be related to lower MetHb reductase activity in neonatal cells. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]
  • SIGNS AND SYMPTOMS: Signs and symptoms of nitrite poisoning include intense cyanosis, nausea, vertigo, vomiting, collapse, spasms of abdominal pain, tachycardia, tachypnea, coma, convulsions and death. Injection and inflammation of gastric and intestinal mucosa are described at autopsy. /Inorganic nitrite salts/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-315]
  • SIGNS AND SYMPTOMS: Symptomatology: Prompt fall in blood pressure. Headache which is persistent and throbbing, with assoc palpitations and visual disturbances. Skin is flushed and perspiring, later cold and cyanotic. Ingestion of nitrites may cause colic and diarrhea ... hyperpnea; later dyspnea and slow breathing ... incr intraocular tension and intracranial pressure. /Nitrite/ [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-323]
  • SIGNS AND SYMPTOMS: ACUTE ... SYMPTOMS: Inhalation--Blue lips or finger nails. Blue skin. Confusion. Convulsions. Dizziness. Headache. Nausea. Unconsciousness; Eyes--Redness. Pain; Ingestion--Rapid pulse. (See Inhalation). [IPCS, CEC; International Chemical Safety Card on Sodium nitrite. (October 2000). Available from http://www.inchem.org/documents/icsc/icsc/eics1120.htm as of October 23, 2006. ]
  • SIGNS AND SYMPTOMS: ... /Sodium nitrite/ is irritating to the eyes. The substance may cause effects on the cardiovascular system and blood, resulting in lower blood pressure and the formation of methemoglobin. Exposure may result in death. The effects may be delayed ... [IPCS, CEC; International Chemical Safety Card on Sodium nitrite. (October 2000). Available from http://www.inchem.org/documents/icsc/icsc/eics1120.htm as of October 23, 2006. ]
  • SIGNS AND SYMPTOMS: The major acute toxic effect of nitrate and nitrite poisoning is methemoglobinemia. Blood is the target organ. Methemoglobin reduces the oxygen-carrying capacity of the blood and in addition, it shifts the oxyhemoglobin dissociation curve to the left interfering with the unloading of oxygen. Hypotension and collapse may also occur ... Hematological effects include blue-greyish cyanosis that may appear within a few minutes to 45 minutes or more after exposure. Stupor, coma and convulsions in severe poisoning due to severe hypoxia. Tachycardia, hypotension and collapse may also occur. Nausea, vomiting and abdominal pain may be seen ... The diagnosis is based on: the clinical presentation of the patient, mainly a central cyanosis in absence of cardiac or pulmonary cause; the brownish color of blood and high levels of methemoglobinemia (which correlate well with clinical symptoms) ... /Nitrate and nitrite poisoning/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]
  • SIGNS AND SYMPTOMS: The major acute toxic effect from nitrite is development of methemoglobinemia, a condition where more than 10% of the hemoglobin is transformed into methemoglobin. When the conversion exceeds 70% the condition can be fatal. Nitrite may also cause sudden fall in blood pressure due to its vasodilating properties. These effects are reversible. The major concern of possible long-term effects of exposure to nitrate and nitrite is associated with formation of nitroso compounds, many of which are carcinogenic. This formation may take place wherever nitrite and nitrosable compounds are present, but it is favored by acidic conditions or the presence of some bacteria. The gastrointestinal tract and especially the stomach is regarded as the main formation site, but nitrosation reactions can also take place in an infected urinary bladder ... /Nitrate and nitrite poisoning/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]
  • SIGNS AND SYMPTOMS: The principal mechanism of nitrite toxicity is the oxidation of the ferrous iron (Fe2+) in deoxyhemoglobin to the ferric (Fe3+) valence state, producing methemoglobin. Methemoglobin cannot reversibly bind or transport circulating oxygen. Depending on the percentage of total methemoglobin in oxidized form, the clinical picture is one of oxygen deprivation with cyanosis, cardiac dysrhythmias and circulatory failure, and progressive central nervous system (CNS) effects. CNS effects can range from mild dizziness and lethargy to coma and convulsions. ... A chocolate-brown or slate-gray central cyanosis (involving the trunk and proximal portions of the limbs, as well as the distal extremities, mucous membranes, and lips) is one of the hallmarks of methemoglobinemia. This cyanosis is due to the dark chocolate-brown color of methemoglobin itself and can become noticeable at a concentration of 10%–15% of total hemoglobin. /Nitrates and nitrites/ [ATSDR; Case Studies in Environmental Medicine. NITRATE/NITRITE TOXICITY.p 9-11. Course: SS3054. Revision Date: January 2001 Original Date: October 1991 Expiration Date: January 2007. Available at http://www.atsdr.cdc.gov/HEC/CSEM/nitrate/docs/nitrate_nitrite.pdf as of November 26, 2006 ]
  • SIGNS AND SYMPTOMS: In large doses, nitrite is an excellent vasodilator because of its relaxing action on vascular smooth muscle; hypotension and shock can result. Systolic flow murmurs can be heard on auscultation in persons with severe methemoglobinemia, which can develop with too-rapid intravenous administration of sodium nitrite (used as an antidote for cyanide and hydrogen sulfide poisoning) or sodium nitroprusside (used in hypertensive crisis therapy). In patients who have inhaled volatile nitrites, transient electrocardiographic changes (T-wave inversions and ST-segment depression) might be noted. /Nitrates and nitrites/ [ATSDR; Case Studies in Environmental Medicine. NITRATE/NITRITE TOXICITY. p 11. Course: SS3054. Revision Date: January 2001 Original Date: October 1991 Expiration Date: January 2007. Available at http://www.atsdr.cdc.gov/HEC/CSEM/nitrate/docs/nitrate_nitrite.pdf as of November 26, 2006 ]
  • SIGNS AND SYMPTOMS: Metabolic acidosis develops in cases of severe methemoglobinemia, especially in young infants or when hypotension and shock are present. Dyspnea and tachypnea are common findings in patients with significant methemoglobinemia. Respiratory tract irritation can occur in patients who abuse volatile nitrites. /Nitrates and nitrites/ [ATSDR; Case Studies in Environmental Medicine. NITRATE/NITRITE TOXICITY. p 11. Course: SS3054. Revision Date: January 2001 Original Date: October 1991 Expiration Date: January 2007. Available at http://www.atsdr.cdc.gov/HEC/CSEM/nitrate/docs/nitrate_nitrite.pdf as of November 26, 2006 ]
  • CASE REPORTS: A 78 year old man was found comatose, apneic, and asystolic after closed-spaced smoke inhalation. He was successfully resuscitated to pulse and blood pressure at the scene. A cyanide component to the poisoning was suspected and two 300 mg doses of sodium nitrite were administered, resulting in significant hypotension. Although high methemoglobin levels were not induced, when added to simultaneously obtained carboxyhemoglobin levels, the total amount of non-oxygen transporting hemoglobin remained nearly constant for about 4-1/2 hr before hyperbaric oxygen therapy could be administered. The patient later died in multi-organ system failure. Admission whole blood cyanide level was only 0.34 ug/mL. These sodium nitrite adverse effects can be avoided by slow intravenous infusion and by administering only recommended doses. In smoke inhalation victims with suspected cyanide poisoning, sodium thiosulfate should be administered first, and sodium nitrite withheld until after the patient is receiving hyperbaric oxygen therapy. When available, hydroxocobalamin (which neither induces methemoglobinemia nor causes hypotension) may be the specific cyanide antidote of choice for victims of smoke inhalation. [Hall AH et al; J Toxicol Clin Exp 9 (1): 3-9 (1989) ]
  • CASE REPORTS: ... A fatal case of a 17-year-old nurse who probably ingested 1 g sodium nitrite (= 670 mg NO2-) as a tablet. In contrast, an adult survived without lasting problems after ingestion of 9.7 g NO2- (as sodium nitrite). [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]
  • CASE REPORTS: The development of methemoglobinemia was investigated in three patients after eating meat contaminated with excessive nitrites. In two patients (41-year old woman and her 19-year old son), the blood gas analysis showed hypoxia, and the blood samples were dark brown. After treatment with 35% oxygen and methylene blue the patients improved symptomatically. Methemoglobin concentration, measured at a later stage due to delayed diagnosis, were respectively 23% in the woman and 7.7% in the son. The third patient revealed a profound hypoxia and dark brown colored blood. In this case, the MetHb concentration was measured immediately and found to be 66%. Following treatment with high concentration of oxygen and 1% methylene blue the patient recovered consciousness and the cyanosis cleared within minutes. The meat which had been consumed was analyzed and reported to contain 15,000 mg nitrite/kg in the first two cases and 10,000 mg/kg in the third case. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]
  • CASE REPORTS: ... A case of methemoglobinemia caused by the accidental contamination of drinking-water with sodium nitrite. The patient had a MetHb concentration of 49%. The amount of sodium nitrite ingested was estimated to be 0.7 g. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]
  • CASE REPORTS: ... Two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite /are described/. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulfate at a concentration of 15 g/L. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia. [Ellis M et al; Isr J Med Sci 28 (5): 289-91 (1992) ]
  • CASE REPORTS: ... a case of fatal methemoglobinemia (MetHb-emia) resulting from application of liniment solution containing large quantities of sodium nitrite /is described/. As a remedial treatment of atopic dermatitis, the liniment solution was applied all over the boy's body. Autopsy findings showed no significant macroscopic or microscopic findings except blood tinted chocolate brown color and chronic atopic dermatitis over the whole surface of the body. Quantitation of the methemoglobin (MetHb) in the blood was performed using spectrophotometer; MetHb concentration of the blood was 76%. Ion chromatographic determination revealed a nitrite concentration of 1 mg/L in the serum... [Saito T et al; J Forensic Sci 41 (1): 169-71 (1996) ]
  • CASE REPORTS: ... This report summarizes the investigation of an incident of methemoglobinemia in five members of a household in New York who became ill after eating a meal seasoned with a white crystalline substance from a plastic bag labeled "Refined Iodized Table Salt". The findings underscore the need for proper storage of hazardous materials to avoid unintentional ingestion and the importance of collaboration by multiple agencies to address a potential public health emergency. [Centers for Disease Control and Prevention (CDC); MMWR Morb Mortal Wkly Rep 51 (29): 639-42 (2002) ]
  • EPIDEMIOLOGY STUDIES: ... A causative connection between nitrate/nitrite and cancer through the formation of N-nitroso compounds is suspected. The role of nitrate and nitrite in the etiology of cancer in humans, especially gastric cancer, is addressed in numerous studies ... Epidemiological studies seeking to find correlation between frequency of cancer and nitrate intake with food and water ... do not support the hypothesis of a straightforward cause and effect association between nitrate exposure and cancer risk. /Nitrate and nitrite/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 25, 2006. ]
  • EPIDEMIOLOGY STUDIES: An accidental food poisoning outbreak occurred resulting in the death of 14 of the 22 affected persons. Chemical analysis of food materials revealed the presence of sodium nitrite and potassium arsenate. Analysis of urine, gastric contents, liver and kidney, collected at the time of autopsy, confirmed the presence of these chemical substances in high concentrations. ... the food poisoning occurred due to the accidental use of sodium nitrite and potassium arsenate instead of table salt in the preparation of tamarind (Tamarindus indica) soup. [Gautami S et al; J Toxicol Clin Toxicol 33 (2): 131-3 (1995) ]
  • ALTERNATIVE and IN VITRO TESTS: The effect of different concentrations (0, 0.1, 0.2, 0.4, and 0.8 mg/ml) of sodium nitrite on the anti-tumor activity of natural killer (NK) cells isolated from human peripheral blood was examined. Sodium nitrite induced significant inhibition (25.3-66.6%) of NK cell activity against WEHI-164 cells. This reduction in NK cell cytotoxicity was found to be partially due to inhibition of NK cell production of interferon-gamma (25.7-92.8%) and tumor necrosis factor-alpha (26.6-76.6%). In addition, exposure to sodium nitrite resulted in a significant decrease (17.5-81.1%) in proliferation of control and interleukin-2-stimulated NK cells. Furthermore, the release of granzyme A and N-acetyl-beta-D-glucosaminidase by NK cells was also decreased by 21.7-72.2% and 33.5-81.2%, respectively. Therefore, sodium nitrite is of environmental concern in view of its inhibitory effects on NK cell activity that might contribute to tumor promotion in vivo. [Abuharfeil N et al; Arch Toxicol 75 (5): 291-6 (2001) ]
  • GENOTOXICITY: Unscheduled DNA synthesis (UDS) was determined in leukocytes of 10 human subjects after the consumption of meals containing varying amt of nitrate, nitrites or nitrosamines. In 6/10 subjects, UDS was significantly incr but no correlation was found with dietary nitrate, nitrite and nitrosamine levels or with blood nitrosamine levels. /Nitrates, nitrites and nitrosamines/ [European Chemicals Bureau; IUCLID Dataset, Sodium nitrate, containing in the dry state more than 16.3 per cent by weight of nitrogen (7631-99-4) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]
  • OTHER TOXICITY INFORMATION: Acute nitrate toxicity is almost always seen in infants rather than adults when it results from ingestion of well waters and vegetables high in nitrates ... /It was/ deduced that infants were prone to upset stomachs and achlorhydria. As result, stomach pH increased in alkalinity allowing nitrate-reducing organisms to enter and to reduce nitrates to nitrites. A gastric pH above 4 supports nitrate-reducing organisms ... Immature enzyme systems may also be of importance ... Fetal hemoglobin (hemoglobin F) is oxidized by nitrite to methemoglobin at rate twice as rapid as adult hemoglobin (hemoglobin A). Furthermore, enzymatic capacity of erythrocytes of newborn infants to reduce methemoglobin to hemoglobin appears less than that of adults. Difference is probably due to developmental deficiency in activity of DPNH-methemoglobin reductase (diphosphopyridine nucleotide). As opposed to adults, several clinical, physiologic and metabolic factors predispose infants to development of methemoglobinemia and acute nitrate poisoning. /Nitrates and Nitrites/ [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 420]
  • OTHER TOXICITY INFORMATION: Several factors or conditions can influence the formation of gastric tumors. The correlation between nitrate intake and tumor incidence involves several factors which influence the reduction of nitrate to nitrite. These factors ... involve the biotransformation of nitrate, presence of thiocyanate (smokers versus non-smokers), iodide, age (increasing salivary nitrate and nitrite levels with increasing age), conditions for bacterial growth in the GI tract (pH of the stomach or type of indigestible material in the diet), and antacid medication ... Factors influencing the formation of carcinogenic N-nitroso compounds are also important in correlating nitrite or nitrite intake with gastric tumor incidence. Factors influencing nitrosation of amines and amides ... include the role of thiocyanate, high salt intake, pH of the stomach, vitamin C or other dietary components, medication (cimetidine and other antacid), and gastric lesions or disorders ... The majority of the studies revealed no correlation, or in some cases a negative correlation, between nitrate intake and gastric cancer. A high intake of certain vegetables, although an important source of nitrate, seemed to be associated with a lower risk of gastric cancer. Protective factors such as ascorbic acid simultaneously present in these foods may be involved. /Nitrate and nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 31, 2006. ]
  • OTHER TOXICITY INFORMATION: Dermal toxicity has only been reported in humans when the skin integrity has been affected, eg in case of burning. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]
  • OTHER TOXICITY INFORMATION: Methylene blue has a protective effect against nitrite-induced MetHb formation and may therefore be used as an antidote in nitrite intoxications. It is also used to verify whether certain toxic effects are mediated by nitrite and MetHb or by other compounds ... MetHb was not a good quantitative criterion for nitrite intake. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]
  • OTHER TOXICITY INFORMATION: Decreased excretion of 17-hydroxy and 17-ketosteroids occurred in urine of humans upon ingestion of 0.5 mg NaNO2/kg bw/day in cooked vegetables for 9 days. These results indicated a decreased production of adrenal steroid, in line with experiments reported in rabbits ... They also support a causal relationship between the administration of nitrite and the hypertrophy of the adrenal zona glomerulosa in rats. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]
  • OTHER TOXICITY INFORMATION: As there was no quantitative evidence of the endogenous formation of carcinogenic N-nitroso compounds at intake levels of nitrite and nitrosatable precursors achievable in the diet, a quantitative risk assessment of nitrite on the basis of endogenously formed N-nitroso compounds was not considered to be appropriate. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 31, 2006. ]

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Non-Human Toxicity Excerpts

  • LABORATORY ANIMALS: Acute Exposure: Single dose of 30 mg/kg of sodium nitrite iv caused methemoglobinemia in dogs. /From table/ [Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2416]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Testing of sodium nitrite on rabbit corneas by application of 0.08 molar soln after removal of corneal epithelium, or by injection into stroma, has caused no local injury. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 840]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Sodium nitrite /is/ not irritating /to/ rabbit skin ... [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Sodium nitrite /is/ moderately irritating /to/ rabbit eyes ... Irrigation of the treated eye 30 to 60 seconds after application ... had little effect on the overall effects, which were primarily of conjunctival irritation. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Groups of 10 male and 10 female Alpk:AP (Wistar) rats were exposed nose only for 4 hr to sodium nitrite aerosols, generated from soln in deionized water, at target concn of 10 or 100 mg/cu m ... Controls killed after exposure and blood taken for measurement of methemoglobin, the remaining animals were maintained for 14 days, and then subject to a full post-mortem examination. During exposure signs typically seen in restrained animals were somewhat more severe in treated animals. Methemoglobin was significantly incr above concurrent control values only in females exposed to 10 mg/cu m. However, the incr was judged to be not hematologically significant as the value was within the range seen for control animals of this age. Further there was no significant incr in males ... [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Dogs administered a single dose of 1 to 2 g sodium nitrite/kg of sausage showed an increased respiration and heart rate, changes of the ECG, methemoglobinemia within 1 to 2 hr, increased concentration of sodium, decreased concentration of potassium and increased aspartate aminotransferase (ASAT) activity in serum. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: ... In female rats ... a single dose was compared with a more continuous administration of the same dose. Using methemoglobinemia as a parameter, doses of 160 mg sodium nitrite/kg bw or 320 mg/kg bw divided into smaller doses over time (3 intervals of 15 minutes, followed by 4 intervals of 30 minutes) appeared to be less toxic than single doses of 40 or 80 mg/kg bw ... 2 doses of 100 mg sodium nitrite/kg bw administered to rats at 2-hour interval caused a high mortality, whereas all animals survived at a 4-hour interval. The difference in toxicity could be related to the elimination half-life of MetHb which was reported to be 90 minutes in rats. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: Clinical signs of acute /sodium nitrite/ intoxication in rodents included vasodilatation, lowering of the blood pressure, decrease in vitamin A content in the liver, and functional disturbance of the thyroid gland. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Acute Exposure: The effect of nitrite on blood pressure and heart rate was studied in anesthetized (non-telemetric method) and free-moving rats (biotelemetry system). In anesthetized rats, sodium nitrite (NaNO2) (10-1,000 umol/kg), infused over 5 min, induced a dose-related decrease in blood pressure. The maximal decrease in mean arterial blood pressure (MAP), caused by 1,000 umol/kg NaNO2 and measured 15 min after infusion was 55.9+/-3.2% (n = 3). After NaNO2 infusion, in the plasma, rapid conversion of nitrite into nitrate was observed. However, sodium nitrate (NaNO3, 100 umol/kg) did not decrease blood pressure and there was no conversion of nitrate into nitrite. Free-moving rats received KNO2 which was added to drinking water (36 mmolL) for a period of 3 days. KNO2 decreased the MAP and increased the heart rate during the rat's activity phase at night but not during their resting phase in the day. An equal concentration of potassium (KCl, 36 mmol/L added to drinking water) for 3 days did not decrease blood pressure. It is concluded that nitrite decreases blood pressure in rats, which probably induces, by renin-angiotensin system activation, hypertrophy of the adrenal zona glomerulosa. [Vleeming W et al; Food Chem Toxicol 35 (6): 615-9 ]**PEER REVIEWED** PubMed Abstract
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Vitamin A and E levels in the blood serum, and also in liver were determined in 80 weaned piglets or feeder pigs. The effects of sodium nitrate were studied, and 5 experiments were designed to assess the effects of sodium nitrite or potassium nitrite, all administered in the drinking water or added to dry complete feed mixtures for 20 to 42 days. In no case (including that of potassium nitrite intake at 1.8 g/kg body mass for 28 days) was this supplementation found to exert adverse effects on the metabolism of vitamins A and E. Some indication of a downward trend in vitamin A and E levels in the serum and liver was found in 4 experiments. There were no adverse effects on either health status or gains in body mass. Toxic effects were produced by administration of 31 mg nitrite/kg body mass in the drinking water. Consideration was also given to the development and course of methemoglobinemia. [Dvorak M; Acta Vet Brno 53 (3-4): 159-68 (1984) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 90-day toxicity study in Wistar rats, the incidence and degree of hypertrophy of the adrenal zona glomerulosa observed at a dose level of 5.4 mg/kg bw/day, expressed as nitrite ion, were not significantly different from that among controls, whereas at higher dose levels the hypertrophy was both significant and dose-related. In another 90-day toxicity study carried out by other investigators with a different Wistar substrain, slight hypertrophy of the adrenal zona glomerulosa was seen from 28 days onwards, but only at dose levels three times as high. The NOEL for hypertrophy in these studies was 5.4 mg/kg bw/day, expressed as nitrite ion. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 31, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: Groups of 10 male and 10 female /Fischer 344/ rats were given 20 mL of water each day, containing /0, 500, 1,250, 2,500, 5,000 or 10,000 ppm/ of sodium nitrite /for 42 days/ ... There were some fatalities in the groups given 5,000 and 10,000 ppm sodium nitrite. Body weight gain was reduced at 10,000 ppm only. Abnormal blood coloration (methemoglobinemia) was seen in the 5,000 and 10,000 ppm group. On the basis of this study, 2,500 ppm was considered to be the maximum tolerated dose. /Sodium nitrite 98.5%/ [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In two 2-week toxicity studies, chickens were fed a diet containing ... 0 or 18 to 60 mg/kg bw/day sodium nitrite. The test animals showed growth retardation, enlarged thyroid glands and decreased vitamin A content in the liver despite the vitamin A-rich diet. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 7-day study, groups of 6- or 55-week old mice (5/group) were administered by gastric intubation 0 or 110 mg sodium nitrite/kg bw. A decrease in the forced running distance, abnormalities in the ECG and ultramicroscopic changes of the heart muscle were observed. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 6-week study, rats (10/sex/group) received 0, 0.06, 0.125, 0.25, 0.5 or 1% sodium nitrite via drinking-water, equivalent to 0, 60, 125, 250, 500 or 1,000 mg/kg bw/day. Moderate growth depression was observed at 1000 mg/kg bw. At autopsy, a marked change in color (brown) of the blood and spleen due to methemoglobinemia was noted at the two highest dose groups. The maximum tolerated dose was 0.25% in drinking-water. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 2-month study, male rats (8/group) received 0, 100, 300 or 2,000 mg sodium nitrite/L in drinking-water, equivalent to 0, 10, 30 or 200 mg/kg bw/day. Abnormalities in the electroencephalogram (EEG) were observed in the highest dose group and to a lesser extent in the other dose groups. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: In a 16-week toxicity study, 1-month old male rats (8/group) received 0 or 200 mg sodium nitrite/L via the drinking-water (equivalent to 0 or 20 mg/kg bw/day). The methemoglobin levels in the treated animals ranged from 0.5 to 3.1%, in comparison with 0 to 1.2% in the control group. A higher incidence of pulmonary lesions was noticed in the treated group. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Subchronic or Prechronic Exposure: ... Changes /were reported/ in urinary steroid excretion of rabbits caused by parenteral administration of 10 mg sodium nitrite/kg (NaNO2/kg) bw/day for 18 days. The changes consisted of a time-dependent decrease in the urinary excretion of 17-hydroxy-, 17-keto- and 17-ketogenic steroid. Oral administration of 20 mg NaNO2/kg bw/day for 14 days also caused a decreased urinary excretion of 17-hydroxy and 17-ketosteroids. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Squid contains high levels of naturally occurring amines such as dimethylamine (DMA), trimethylamine, and trimethylamine-N-oxide (TMAO). The hepatotoxicity and hepatocarcinogenicity of squid with or without exogenous nitrite were investigated in rats. Acute necrosis including polymorphogenic neutrophil infiltration, hemorrhage and cholangiofibrosis were observed in the livers of most rats fed squid. Hepatocellular carcinoma was induced in 2/12 rats (16%) by feeding 10% squid in the diet for 10 months. The incidence of hepatocellular carcinoma was increased to 4/10 rats (33%) when 0.3% sodium nitrite (NaNO2) was added to the diet. At the end of the experiment a marked elevation of serum gamma-glutamyl transpeptidase (gamma-GT) was observed in the nitrite treatment group (L-alanine aminotransferase and aspartate-aminotransferase were not changed) ... [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 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. In the first week of treatment the following hematological parameters were reduced: 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, leukemias and testicular interstitial cell tumors. Leukemias 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 tumors was reduced in a dose-related manner, which corelated with a similar trend in body weights. [Grant D, Butler WH; Food Chem Toxicol 27 (9): 565-72 (1989) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Mice chronically exposed to sodium nitrite at 1,000 and 2,000 mg/L in dirnking water showed reduced motor activity. EEG recordings from implanted electrodes revealed major changes in brain electric activity in rats receiving nitrite at 100 to 2,000 mg/L ... Chronic exposure of rats to sodium nitrite at 2,000 and 3,000 mg/L in drinking for 2 yr was associated with distinct pathologic changes in heart and lung tissues. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 420]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Groups of 50 male and 50 female F344/N rats were exposed to 0, 750, 1,500 or 3,000 ppm sodium nitrite (equivalent to average daily doses of approximately 35, 70 or 130 mg/kg to males and 40, 80 or 150 mg/kg to females) in drinking water for 2 yr ... Groups of 50 male and 50 B6C3F1 female mice were exposed to 0, 750, 1500 or 3000 ppm sodium nitrite (equivalent to average daily doses of approximately 60, 120 or 220 mg/kg to males and 45, 90 or 165 mg/kg to females) in drinking water for 2 yr ... There was no evidence of carcinogenic activity of sodium nitrite in male or female F344/N rats exposed to 750, 1500, or 3000 ppm. There was no evidence of carcinogenic activity in male B6C3F1 mice exposed to 750, 1,500 or 3,000 ppm. There was equivocal evidence of carcinogenic activity of sodium nitrite in female B6C3F1 mice based on positive trend in the incidences of squamous cell papilloma or carcinoma (combined of the forstomach). [Toxicology & Carcinogenesis Studies of Sodium Nitrite in F344/N Rats and B6C3F1 Mice p.8 Technical Report Series No. 495 (2001) NIH Publication No. 01-3954 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: 50 Fischer 344 rats per sex per group /were given sodium nitrite/ daily at 0, 0.125, 0.25% (0, 17, 29.5 g) in 20 mL drinking water /for/ 104 wk ... Body weight was reduced in both treated female groups and in high dose males. Mortality was reduced in males over the whole study. No treatment group showed a significant increase in the incidence of any specific tumor compared to the relevant controls ... [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: In ... /an/ experiment with 2-month old rats (12 in the nitrite and 9 in the control group), sodium nitrite was administered /in drinking water/ at levels of 0 or 2000 mg/L for 14 months. The methemoglobin levels fluctuated from 1 to 35% in comparison to 0 to 1% in the control group. Animals receiving nitrite had lower body and liver weights, decreased vitamin E levels in serum, and higher red blood cells reduced glutathione levels, while the lungs of all animals exhibited severe lesions. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: In a carcinogenicity study, F344 rats (50/sex/group) received in drinking-water concentrations of 0, 0.125 or 0.25% sodium nitrite for 2 years. No carcinogenic effects were observed. A significant decrease in tumor incidence was found in the high-dose females as compared to controls. Part of this decrease was accounted for by mononuclear cell leukemia which has a rather high spontaneous frequency (about 25%) in this rat strain. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: In a long-term carcinogenicity study, inbred mice (200/group) were administered 0 or 0.2% sodium nitrite/L (NaNO2/L) in drinking-water. One hundred mice were exposed in utero to 0.2% NaNO2 (during pregnancy and suckling) and continued on 0.2% NaNO2 in their drinking-water during weanling. Routine histological examination revealed that NaNO2 had no apparent effect on CNS tumor formation irrespective of the length of exposure. This finding contradicted previous suggestive evidence that nitrite may be a causative factor in cerebral glioma, since these VM mice are especially susceptible to spontaneous glioma formation. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: In a 2-year toxicity study, groups of male rats (8/group) received drinking-water containing 0, 100, 1,000, 2,000 or 3,000 mg sodium nitrite/L. There was no significant differences in growth, development, mortality or total hemoglobin levels between the control and treated groups. However, the methemoglobin levels in the groups receiving sodium nitrite at 1000, 2,000, and 3,000 mg/L were raised significantly throughout the study and averaged 5%, 12% and 22% of total hemoglobin, 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 narrowed as is usually seen at that age. Changes in the lungs consisted of dilatation of the bronchi with infiltration of lymphocytes and alveolar hyperinflation. These changes were observed in rats receiving 1,000, 2,000 and 3,000 mg sodium nitrite/L drinking-water. The NOEL in this study was 100 mg/L sodium nitrite, equivalent to 10 mg sodium nitrite/kg bw/day, or 6.7 mg/kg bw/day expressed as nitrite ion. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Dose-dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 15 6-week-old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose-dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high-dose combination. In a second short-term experiment conducted for sequential observation, necrosis and strong inflammation were found in the forestomach epithelium shortly after commencing combined treatment with 1.0% AsA and 0.2% NaNO2, followed by hyperplasia, whereas there were no obvious effects in the glandular stomach. In addition, after a 4 hr treatment with 1.0% AsA and 0.2% NaNO2, a slight increase in the 8-hydroxy-deoxyguanosine levels in the forestomach epithelium was observed by high-performance liquid chromatography and an electrochemical detection system, albeit without statistical significance. In vitro, electron spin resonance demonstrated nitric oxide formation during incubation with NaNO2 and AsA under acidic conditions. Thus, NaNO2 was demonstrated to exert promoter action in the forestomach, with AsA acting as a strong copromoter through cytotoxicity and regenerative cell proliferation, possibly mediated by oxidative DNA damage, but the combined treatment with NaNO2 and AsA had little influence on glandular stomach carcinogenesis. [Okazaki K et al; Cancer Sci 97 (3): 175-82 (2006) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: ... Effects of combined treatment with NaAsA or ascorbic acid (AsA) and sodium nitrite (NaNO2) on carcinogenesis were examined in F344 male rats with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) pre-treatment. Groups of 20 or 15 rats, respectively, aged 6 weeks, were given a single intra-gastric administration of 150 mg/kg body weight of MNNG in DMSO:water = 1:1 or the vehicle alone by stomach tube. Starting 1 week later, they received supplements of 1% NaAsA or 1% AsA in the diet and 0.3% NaNO2 in drinking water in combination, each of the individual chemicals alone, or basal diet until the end of week 52. In MNNG-treated animals, incidences of forestomach papillomas and carcinomas were significantly enhanced in the NaNO2 alone group (84 and 47%, respectively) as compared with the basal diet group (30 and 10%), with further significant increase in carcinomas occurring with additional NaAsA (79%, p<0.05) or AsA (85%, p<0.05) treatment. In animals without MNNG, all animals in the NaNO2 group demonstrated mild hyperplasia, additional administration of NaAsA or AsA remarkably enhancing the grade of hyperplasia, and resulting in 53% and 20% incidences, respectively, of papillomas. Thus NaNO2 was demonstrated to exert promoter action for forestomach carcinogenesis, with NaAsA and AsA acting as co-promoters. The results strongly indicate that combined treatment with NaAsA or AsA and NaNO2 may induce forestomach carcinomas in the long term. [Yoshida Y et al; Int J Cancer 56 (1): 124-8 (1994) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity: Dose-dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 15 6-week-old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose-dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high-dose combination... [Okazaki K et al; Cancer Sci 97 (3): 175-82 (2006) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Pregnant ICR mice were given drinking water containing sodium nitrite at a concn of either 100 or 1000 mg/L on days 7 to 18 of gestation. There were no significant differences between treated and control groups in measures of developmental toxicity, eg, litter size, fetal weight and number of resorbed or dead fetuses. The incidences of external and skeletal malformations in fetuses of treated groups were not significantly different from those in the controls. No significant increase was observed in the frequency of gaps and breaks of liver cell chromosomes in fetuses exposed in utero to sodium nitrite. Teratogenic and mutagenic effects of sodium nitrite were absent in mice at the doses used. [Shimada T; Arch Environ Health 44 (1): 59-63 (1989) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Effects of nitrate (doses of 600 and 1,200 mg/kg/day during 14 days) and sodium nitrite (60 and 120 mg/kg/day during 14 days) on germ cells of male mice were investigated /by/ ... stomach intubation. The germ cell stages analysed were spermatids (for the heritable effects) and differentiating and stem cell spermatogonia (for direct effects). A lack of heritable translocation, sperm abnormalities, as well as morphological changes, such as changes in the eyes, coat color, testes and body weight, was demonstrated in F1 males originating from treated P males. Significant effects in treated males were found with respect to: (1) sex chromosomal univalency in the diakinesis metaphase I stage after the treatment of stem spermatogonia (both doses of sodium nitrate and the higher dose of sodium nitrite), (2) sperm head abnormalities after treatment of differentiating spermatogonia (the higher dose of sodium nitrite and both doses of sodium nitrate), and (3) fertility after treatment of spermatids (the higher dose of sodium nitrite). Nonmutagenic effects and possible carcinogenic potential of the tested doses are discussed. [Alvanti CD et al; Mutat Res 204 (4): 689-95 (1988) ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: ... Rats received sodium nitrite at 100 mg/kg in drinking water daily during their entire life span over three generations; no evidence of chronic toxicity, carcinogenicity, or teratogenicity ... found. [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 420]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Pregnant cows received by infusion for 30 minutes 7, 9.5 or 12 mg NO2-/kg bw. Treatment with nitrite resulted in a dose-related conversion of maternal Hb into MetHb, a 30 to 50% decrease in mean arterial blood pressure, an increase in heart rate with dose-related recovery periods, and a decrease of partial oxygen tension (pO2) of maternal blood. Fetal changes included a small increase in MetHb content, variable changes in heart rate (tachycardia and bradycardia), and decreases in fetal pO2, with considerable differences between animals. All calves were born alive. Three cows calved early, 2 to 3 days after the highest nitrite dose. The hematological and cardiovascular data suggest that these 3 fetuses experienced a more serious hypoxemic stress than the other fetuses. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Sodium nitrite (NaNO2) admin in the drinking water to Long-Evans rats during pregnancy and lactation /day 0 gestation to day 20 of lactation/ severely affected erythropoietic development, growth and mortality in their offspring. Pregnant rats were maintained throughout gestation on 0.5, 1, 2, or 3 g NaNO2/L. There were no significant differences between treated and control litters at birth. Thereafter, pups of treated dams on 2 and 3 g NaNO2/L gained less weight, progressively became severely anemic, and began to die by the third week postpartum. By the second week postpartum, hemoglobin levels, RBC count and mean corpuscular vol of these pups were all drastically reduced compared to controls. Blood smears showed marked anisocytosis and hypochromasia. Gross chylous serum lipemia and fatty liver degeneration were noted. Histopathology demonstrated cytoplasmic vacuolization of centrilobular hepatocytes and decr hematopoiesis in bone marrow and spleen. Admin of 1 g NaNO2/L resulted in hematological effects but did not affect growth or mortality. NaNO2 (0.5 g/L) was at or near the no observed effect level. Cross-fostering indicated that treatment during the lactational period was more instrumental in producing lesions than treatment during the gestational period. The data presented are consistent with the lactational induction of severe iron deficiency in the neonate. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Developmental or Reproductive Toxicity: Long-Evans rats were given sodium nitrite (NaNO2) daily at 0, 2.0, 3.0 g/L in drinking water from day 0 of gestation to day 20 of lactation ... Neonatal rats from dams receiving 2 or 3 g/NaNO2/L ... suffered severe microcytic anemia as well as growth retardation and high mortality. Lipemia, fatty liver damage, decr erythropoiesis of spleen and bone marrow, and reduced plasma and tissue iron levels were noted in affected pups. These effects were all consistent with the characteristics of iron deficiency ... It was found that admin of exogenous iron supplement to pups of treated mothers reversed the amenia and other effects of nitrite toxicity ... in unsupplemented littermates. Mothers of affected pups were themselves anemic ... Severe iron deficiency in pups of nitrite-treated mothers was demonstrated and these mothers produced milk of reduced iron content. It appears then that nitrite-consuming dams have a reduced capacity to transfer iron to their pups. The nitrite-associated toxicities in the pups are actually a result of iron deficiency. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • LABORATORY ANIMALS: Neurotoxicity: Behavioral changes /of 45- to 55-day old male Long-Evans Hooded rats (18 to 24 animals/group)/ were studied 25 minutes after administration of sodium nitrite (NaNO2) (75 mg/kg bw) and the histopathology of the brains was performed 24 hr after dosing. Severe motor incoordination was produced by immersing the animals in water for 10 minutes before testing, but not when they received mild foot shocks 10 minutes before testing. The MetHb formed after nitrite administration was determined after these pretreatments. No changes in MetHb due to pretreatment were detected. Evidence of a prolonged effect of nitrite on cells in the hippocampal formation was noted which resembled changes in other cases of ischemia. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: Chromosomal aberration tests in vitro were carried out on Chinese hamster cells grown in culture with sodium nitrate and sodium nitrite and were positive. [ISHIDATE M, ODASHIMA S; MUTAT RES 48: 337 (1977) ]**PEER REVIEWED**
  • GENOTOXICITY: The Drosphila wing somatic mutation and recombination test was applied to a series of chemicals to determine its suitability in genotoxicity screening. Chronic feeding of three day old larvae with a concentration of 72.5 mM sodium nitrite led to a positive result for the small single spots in two independent experiments. Data on induction of large single spots and twin spots were inconclusive. [Graf U et al; Mutat Res 222 (4): 359-73 (1989) ]**PEER REVIEWED**
  • GENOTOXICITY: Endo-reduplication has also been reported /induced by sodium nitrite/ ... Sodium nitrite induced a sharp increase in "aberrant cells" obtained from human embryonic lung tissue ... In a mouse lymphoma L5178Y thymidine kinase locus assay, sodium nitrite was positive at concentrations ranging from 0.02 to 1 mmol/L, indicating a relatively weak response in comparison with known mutagenic and carcinogenic compound ... [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: Administration of about 210 mg sodium nitrite/kg bw in drinking-water to nonpregnant or 5 to 18 days pregnant rats ... induced chromosome aberrations in bone marrow of both non-pregnant and pregnant animals as well as in the embryonic liver. The ratio of the number of metaphases with aberrations in treated and control animals, was higher for embryonic liver in comparison to adult bone marrow. This higher incidence may have resulted from higher numbers of cells in mitosis by shorter cell cycle times in embryonic tissues ... [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: /In a/ heritable translocation assay, male C3H mice /were given sodium nitrite by/ gavage /at/ 60 and 120 mg/kg/day /for/ 3 or 14 days ... No heritable defects were identified were seen in F1 offspring of treated males-either in morphology of sperm or in clinical condition. The sex ratio of offspring from "semisterile" treated males was affected. In the treated males (parents) sex chromosome univalency was incr at 60 and 120 mg/kg/day, as were sperm head abnormalities. Unscheduled DNA synthesis (indicating repair of damaged DNA) was not incr in sperm of treated males. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: In a study with mouse cells, sodium nitrite without metabolic activation did not lead to an increase in single strand breaks, but a dose-related increase in gene mutations and chromosome aberrations was found at relatively high doses. According to the authors, the mutagenic activity was probably due to deamination of DNA and not to nitrosamine formation, since nitro-sodimethylamine without metabolic activation did not change the mutation frequency to any significant extent. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: /In a/ dominant lethal assay, male C3H mice /were given sodium nitrite by/ gavage /at/ 0 and 50 mg/kg/day /for/ 5 days ... Sodium nitrite significantly reduced (to 80% controls 100%) number of pregnancies in females mated with treated males only in wk 2 after treatment. However, pre and post implantation losses were not increased at any time, nor were numbers of corpora lutea per pregnancy, implants per pregnancy or number of live embryos per pregnancy. This study was negative for dominant lethal effects. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: Syrian hamsters were administered orally sodium nitrite on day 11 or 12 of gestation. An increase in drug-resistant mutations (8-AG and ouabain) was found in cells cultured from hamsters embryos ... A dose-dependent increase in micronucleus formation was found, although no increased number of chromosome aberrations was detected ... Transformation in embryonic cells occurred in vitro, while in vivo implantation of the transformed cells led to neoplasms. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: Mutagenic activity of nitrite ... has been reported in bacterial systems such as Escherichia coli and several Salmonella typhimurium strains ... Positive results in mutagenic studies have been reported with various fungi such as Aspergillus species and Neurospora crassa, yeast (Saccharomyces cerevisiae), tobacco mosaic virus and bacteriophage T4 ... Sodium nitrite showed mutagenic effects in the Ames test with different Salmonella typhimurium strains ... /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: The addition of sodium nitrite (NaNO2) (5 to 20 mM) for 72 hr to mouse BALB/c3T3 cells resulted in the induction of transformed foci (type III) in a dose-dependent manner. The cells isolated from the NaNO2-induced transformed loci produced progressively growing tumours when inoculated subcutaneously into (immunodeficient) nude mice at an inoculation size of 1×10+6 cells per spot, whereas untreated cells did not. The possibility that NaNO2 reacts with cellular or medium components to produce carcinogenic N-nitroso compounds which in turn might induce cell transformation was examined and rejected. Thus nitrite, itself seems to have a cell transforming activity. Recent evidence suggest that NO2- is produced by the activated macrophages of mammals ... [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: Sodium nitrite administered in an acid environment (pH about 5), induced an increase in 6-thioguanine (6TG) mutants in V79 hamster cells in vitro. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: No mutagenic activity was found in two in vivo tests, a host-mediated assay with the Escherichia coli K 12 uvr B/rec A DNA repair and a micronucleus test with mice. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 30, 2006. ]**PEER REVIEWED**
  • GENOTOXICITY: ... Untreated Bisphenol A (4,4'isopropylidenediphenol: BPA) did not exhibit any mutagenicity. However, the mixture of BPA and sodium nitrite after incubation at pH 3.0 showed strong mutagenic activity toward Salmonella typhimurium strains TA100 and TA98 either with or without a metabolic activation system (S9 mix). The clastogenic properties of nitrite-treated and untreated BPA were analyzed by a micronucleus test with male ICR mice. A single gastric intubation of nitrite-treated BPA induced a significantly higher frequency of micronucleated reticulocytes (MNRETs) in mice. The results of analysis of electron spin resonance (ESR) suggest that the expression of the mutagenic activity of nitrite-treated BPA is related to the generation of radicals in the reaction mixture. By applying 1H and 13C NMR, AB-MS and APCI/LC/MS, ... two compounds, 3-nitrobisphenol A and 3,3'-dinitro-bisphenol A, /were identified/. These compounds were synthesized by the reaction of BPA with nitric acid. 3,3'-Dinitro-bisphenol induced a significantly greater frequency of MNRETs in male ICR mice. ... [Masuda S et al; Mutat Res 585 (1-2): 137-46 (2005) ]**PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: The small intestine of Wistar rats was perfused continuously with 100 mL of sodium nitrite solution, during which the rat was under urethane anesthesia. The rate of this in situ perfusion in the apparatus-intestine system was 20 mL/min and the perfusion lasted 1hr. Sodium nitrite was poorly absorbed (10% of the administered dose), but inhibited the activity of Na+/K+-ATPase and alkaline phosphatase. It had no effect on the lactic acid level, pointing to normal level of oxygen in the intestine, but evidently reducing the utilization of oxygen by this tissue. Using metabolism inhibitors added to the perfusion fluid (ouabain, sodium azide, phenylalanine) and during functional ischemia of the intestine produced by occlusion of the superior mesenteric artery during perfusion, it was possible to determine the site and nature of the action of sodium nitrite. Nitrite acts on the plasma membrane of the enterocytes providing a possibility for producing lability of these membranes which is associated with changes in transport function. The structure of other membrane lipids such as membranes of lysosomes or mitochondria might be changed. An interaction with the respiratory chain was found. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • ALTERNATIVE and IN VITRO TESTS: Stomach contents of rats and guinea-pigs were incubated with carbaryl, carbofuran or methylurea and sodium nitrite. Less than 1% and 19 to 37% nitrosation of the amides occurred in the stomach contents of rats (pH 4 to 5) and guinea-pigs (pH 1.2 to 2.6), respectively.[WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Nitrite converts hemoglobin ... into methemoglobin ... If this change is sufficiently complete animals may die of tissue anoxia; clinical signs are seen when about 20% of hemoglobin is converted into methemoglobin and become progressively more severe as proportion increases, death occurring when level reaches about 80%. /Inorganic nitrite salts/ [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 66]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Fasting increases susceptibility to ... nitrite poisoning ... Cattle fed on an adequate diet can tolerate ... intake of ... nitrite sufficient to cause a 50% conversion of hemoglobin to methemoglobin ... /Inorganic nitrite salts/ [Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 67]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: ... Ruminants and mink in Norway were reported to have malignant liver lesions after eating ration that contained fish meal preserved by addition of nitrite. /Inorganic nitrite salts/ [Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Cleveland: The Chemical Rubber Co., 1972., p. 154]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: In rats ... /sodium nitrite/ crosses placental barrier to generate methemoglobin in fetus. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-315]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: ... Vasodilatory properties ... and consequent stimulation of aldosterone production in the adrenal ... /and/ alterations in adrenally synthesized hormones have been reported for sodium nitrite. [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 27, 2006. ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: In rats ... /sodium nitrite/ crosses placental barrier to generate methemoglobin in fetus. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-315]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: Nitrate and nitrite given orally are absorbed and transferred to the blood in the upper part of the gastrointestinal tract. Abundant pectin in the food may delay absorption which may then occur lower down in the intestine, with possible increased risk for microbial transformation of nitrate into nitrite. /Nitrate and nitrite/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]**PEER REVIEWED**
  • OTHER TOXICITY INFORMATION: in the 1960s it was found that some batches of fish meal which had been treated with sodium nitrite for preservation caused toxic liver injury in sheep. The cause of the injury was traced to nitrosodimethylamine (NDMA) which had formed in the fish meal. [Bingham, E.; Cohrssen, B.; Powell, C.H.; Patty's Toxicology Volumes 1-9 5th ed. John Wiley & Sons. New York, N.Y. (2001)., p. 4:633]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Rabbit oral 186 mg/kg [Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3266]**PEER REVIEWED**
  • LD50 Mouse ip 158 mg/kg [Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3266]**PEER REVIEWED**
  • LD50 Mouse oral 175 mg/kg [Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3266]**PEER REVIEWED**
  • LD50 Rat iv 65 mg/kg [Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3266]**PEER REVIEWED**
  • LD50 Rat oral 85 mg/kg [Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3266]**PEER REVIEWED**
  • LC50 Rat inhalation 5.5 mg/L/4 hr [European Chemicals Bureau; IUCLID Dataset, Sodium nitrite (7632-00-0) (2000 CD-ROM edition). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of October 26, 2006. ]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • In mice given 400, 800, or 1200 mg sodium nitrite orally in drinking water 99.1 to 99.5% of the dose was eliminated. The remaining nitrite was transformed into nitrate & recovered from the liver & muscle. [CANTONI C ET AL; ARCH VET ITAL 32 (1-2): 7 (1981) ]**PEER REVIEWED**
  • Nitrate and nitrite given orally are absorbed and transferred to the blood in the upper part of the gastrointestinal tract. Abundant pectin in the food may delay absorption which may then occur lower down in the intestine, with possible increased risk for microbial transformation of nitrate into nitrite. /Nitrate and nitrite/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]**PEER REVIEWED**
  • Regardless of route of exposure, nitrate and nitrite are rapidly transferred into the blood. Nitrite is gradually oxidized to nitrate which is readily distributed into most body fluids (urine, saliva, gastric juice, sweat, ileostomy fluid). Distribution of nitrate into plasma, erythrocytes, saliva and urine following an oral dose of sodium nitrate has been demonstrated ... /Nitrate and nitrite/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]**PEER REVIEWED**
  • ... Transplacental passage of nitrite occurred in pregnant rats given doses at 2.5-50 mg/kg orally ... [National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977., p. 420]**PEER REVIEWED**
  • In rats ... /sodium nitrite/ crosses placental barrier to generate methemoglobin in fetus. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-315]**PEER REVIEWED**
  • Nitrite rapidly disappeared from a buffered solution at pH<5, simulating gastric conditions, and the rate of disappearance was enhanced by the presence of food ... Nitrite may also react with gastric contents (eg, nitrosation) or be reduced by the GI flora. A large part of nitrite entering the GI tract may thus disappear before absorption takes place ... Absorption of nitrite from the GI tract of rats was slower than that of nitrate. Forty five minutes after intragastric instillation of (13)N-labelled nitrite, radioactivity was higher in the stomach and lower in the liver, kidneys, bladder and eviscerated carcass, than in similar experiments with (13)N-labelled nitrate ... Nitrite was not absorbed from the caecum and large intestine of rats ... Gastric absorption of nitrite was noted in labelling and gastric emptying studies using rats and mice ... In rats, 63% of nitrite loss from the stomach was due to emptying and 37% to other processes ... Gastric absorption of nitrite seemed faster in mice than in rats. In vivo, the rate of absorption was about 4.5 times greater than the rate of chemical degradation. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • Nitrite is normally absent from the body fluids and tissues of laboratory animals ... The extensive pre-systemic metabolism of nitrite results in an absolute bioavailability (ie the percentage of the dose reaching the systemic circulation) considerably lower than 100%. Intravenous injections and intratracheal instillation of (13)N-labelled nitrite in mice and rabbits resulted in homogenous distribution of radioactivity in the heart, kidneys, liver, stomach, intestines, lungs and bladder (ranging from 4.2 to 10.5%) within 5 minutes. The (13)N was equally distributed in plasma and red blood cells with 15 to 20% of the plasma (13)N bound to proteins ... Thirty minutes after iv injection of nitrite, low levels of nitrite were detected in blood and saliva of dogs ... Nitrite can cross the placenta of rats and guinea-pigs: nitrite injected into pregnant animals appeared after a lag of approximately 20 minutes in fetal blood but at a lower concentration than in maternal blood ... /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • Iv injections of 20 mg/kg sodium nitrite in dogs, sheep or ponies resulted in nitrate plasma concentrations of 40 to 100 mg/L (0.6 to 1.6 mmol/L) in all three species within minutes. [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • Urinary and fecal excretion of nitrite are very low since most of the nitrite that enters the bloodstream or passes down the GI tract is rapidly converted to nitrate, bound to the GI contents, or reduced by enteric bacteria. Nitrite is not secreted in significant amounts in saliva or bile ... In a balance study in rats, Na(15)NO2 was administered at a level of 1.6% in the diet, as a single or multiple dose. Within 72 hr after administration of the single dose, 68% and 12% of the (15)N dose was excreted in urine and feces, respectively. After multiple dosing, 59% of the administered (15)N was excreted in urine and 19% in feces. Some 10% of the dose was excreted in urine as (15)N-nitrite ... The rapid decline in blood concentrations of nitrite was attributed to the reactivity of nitrite with haemoglobin and other endogenous compounds, a hypothesis which is supported by the increased nitrate level after intravenous administration of nitrite ... In humans ... nitrite may be absorbed from the GI tract since part of the ingested nitrate is converted to nitrite in the oral cavity and stomach ... and high MetHb levels in young infants ingesting large amounts of nitrate have been reported ... Low levels of nitrite have been detected in the feces of humans ... Ntrite incubated with fresh feces under anaerobic conditions was rapidly converted by the fecal microflora, suggesting that nitrite excretion may well be higher than what is actually detected. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • ... Significantly higher amount of nitrate-reducing bacteria, nitrite and nitroso compounds in fasting gastric juice of patients with partial gastrectomy than in normal controls. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**

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Metabolism/Metabolites

  • ... Intestinal bacteria were involved in the reduction of nitrite ... Absorbed nitrite is rapidly oxidized to nitrate in the blood by a mammalian process ... The process of nitrate generation parallels the methemoglobin (MetHb) formation ... Nitrite oxidation to nitrate may also occur in the stomach prior to absorption, as demonstrated in vitro for mice. However, under in vivo conditions, nitrite is probably absorbed from the stomach before large quantities of nitrate are formed. /Nitrite/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**
  • ... Nitrite may be further reduced to nitrogen by bacteria under some conditions. In blood, nitrite transforms hemoglobin to methemoglobin and is simultaneously oxidized to nitrate. Normally methemoglobin gradually reverts to hemoglobin through enzymatic reactions. Nitrite has vasodilating properties, probably through transformation into nitric oxide (NO) or a NO-containing molecule acting as a signal factor for smooth muscle relaxation. Nitrite easily transforms into a nitrosating agent in an acidic environment and can react with a variety of compounds, eg ascorbic acid, amines, amides. Nitrosation can also be mediated by bacteria, eg in the stomach. Some reaction products are carcinogenic (eg most nitrosoamines and amides). /Nitrate and nitrite/ [IPCS; Poisons Information Monograph G016: Nitrates and nitrites. (September 1996). Available from: http://www.inchem.org/documents/pims/chemical/pimg016.htm as of October 24, 2006. ]**PEER REVIEWED**
  • No or very slight increase in blood nitrosamine level was found in human subjects after consumption of nitrate-, nitrite-, and/or amine-rich meals /Nitrate, nitrite, and amine/ [WHO; WHO Food Additives Series 35 (844): Nitrite. Available from: http://www.inchem.org/documents/jecfa/jecmono/v35je13.htm as of October 27, 2006. ]**PEER REVIEWED**

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TSCA Test Submissions

  • None found

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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