Nitrate and nitrite

(endorsed 2011)

Guideline

Nitrate: Based on health considerations, the guideline value of 50 mg-NO/L (as nitrate) has been set to protect bottle-fed infants under 3 months of age. Up to 100 mg-NO/L can be safely consumed by adults and children over 3 months of age.

Where a water supply has between 50 and 100 mg-NO/L nitrate, active measures are required to ensure that those caring for infants are aware of the need to use alternative water sources in making up bottle feeds for babies under 3 months of age. Water may be used for bottle-fed infants if the nitrate concentration is between 50 and 100 mg/L, but medical authorities need to be increasingly vigilant and the water must also be known to be microbiologically safe.

Nitrite: Based on health considerations, the concentration of nitrite in drinking water should not exceed 50 mg-NO/L (as nitrite).

General description

Nitrate and nitrite ions are naturally occurring oxides of nitrogen that make up part of the nitrogen cycle.

Nitrate is formed from the oxidation of organic wastes such as manure, by the action of nitrogen-fixing bacteria in soils, or from lightning strikes through air. Nitrates are also manufactured for use in explosives and inorganic fertilisers.

Intensification of farming practices and sewage effluent disposal to streams have led to increasing amounts of nitrate in some waters, particularly groundwater.

The nitrite ion is relatively unstable and can be formed by the reduction of nitrate in poorly oxygenated waters. It is rapidly oxidised to nitrate and is seldom present in well oxygenated or chlorinated supplies. Chemical and biological processes can result in further reduction to various compounds, including ammonia, or oxidation back to nitrate.

Food, particularly vegetables and cured meat, is the major source of nitrate intake for humans.

Typical values in Australian drinking water

In major Australian reticulated supplies, nitrate concentrations range up to 51 mg NO3/L\text{NO}_3\text{/L}, with typical concentrations usually less than 0.15 mg NO3/L\text{NO}_3\text{/L}. Nitrite is generally not present in significant concentrations, although operational difficulties in chloramination can lead to nitrite formation due to the action of nitrifying bacteria.

Very high nitrate concentrations (up to 1300 mg NO3/L\text{NO}_3\text{/L}) have been recorded in some groundwater supplies in rural areas.

Treatment of drinking water

Conventional water treatment is not effective for nitrate removal. Nitrate reduction facilities are expensive to operate and involve the use of anion exchange resins.

Measurement

The nitrate concentration in drinking water can be determined by a colorimetric procedure following reduction of nitrate to nitrite using a cadmium column (APHA Method 4500-NO3\text{NO}_3 Part E 1992). The limit of determination is 0.01 mg/L. Nitrite can be determined separately using the same procedure but without the reduction column (APHA Method 4500-NO2\text{NO}_2 Part B 1992). Alternatively, nitrate and nitrite can be determined using ion chromatography (APHA Method 4110 Part B 1992).

Health considerations

The toxicity of nitrate to humans is thought to be solely due to its reduction to nitrite. The major biological effect of nitrite in humans is its involvement in the oxidation of normal haemoglobin to methaemoglobin, which is unable to transport oxygen to the tissues. This condition is called methaemoglobinaemia. Young infants are more susceptible to methaemoglobin formation than older children and adults. Other susceptible groups include pregnant women and people with a deficiency of glucose-6-phosphate dehydrogenase or methaemoglobin reductase.

Recently the World Health Organization (WHO 2007) reviewed the toxicity and health information for nitrate and nitrite and retained the drinking water guideline of 50 mg NO3/L\text{NO}_3\text{/L} based on epidemiological evidence for methaemoglobinaemia in infants because it is protective for bottle-fed infants and consequently for other parts of the population. The WHO recommended that water should not be used for bottle-fed infants when nitrate levels are above 100 mg/L, but that it may be used if medical authorities are increasingly vigilant when the nitrate concentration is between 50 and 100 mg/L. However, the water must also be known to be microbiologically safe. This caveat was included because the dose response data for methaemoglobin formation is complicated by the more-often-than-not concomitant presence of bacterial contamination and the fact that nitrite formation from nitrate in infants is markedly enhanced by gastrointestinal infections. Indeed some cases of infant methaemoglobinaemia have been described in which increased endogenous nitrite synthesis as a result of gastrointestinal infection appeared to be the only causative factor (FAO/WHO 1996, WHO 2007).

The central role that gastrointestinal infection plays in the aetiology of the disease has lead to an opinion that exogenous nitrate in drinking water is not a significant contributor to the prevalence of methaemoglobinaemia, and that current limits of nitrate in drinking water based solely on the health threat of infantile methaemoglobinaemia may be unnecessarily strict (Avery 1999). Indeed, a recent exposure assessment based on drinking water nitrate levels greater than 50 mg NO3/L\text{NO}_3\text{/L} could not identify an exposure-response relationship that related drinking water nitrate level to methaemoglobinaemia (Fewtrell 2004). Nevertheless the collective data indicate that concentrations less than the current 51 mg NO3/L\text{NO}_3\text{/L} are not commonly associated with methaemoglobinaemia (Fan and Steinberg 1996, FAO/WHO 1996, WHO 2007).

In animals, laboratory experiments suggest that neither nitrite nor nitrate acts directly as a carcinogen. There is concern that nitrite may react with foods rich with secondary amines to form N-nitroso compounds in the stomach: many of these compounds are known to be carcinogenic in animals. Some epidemiological evidence suggests a relationship between nitrate and gastric cancer in humans, but this has not been confirmed in more definitive analytical studies.

Nitrate is not mutagenic in tests with bacteria and mammalian cells in vitro. Chromosome aberrations have been observed in the bone marrow of rats but may be due to the formation of N-nitroso compounds. Nitrite is mutagenic in both in vivo and in vitro experiments using mammalian cells.

Derivation of guideline

The guideline value of 50 mg NO3/L\text{NO}_3\text{/L} for nitrate is set to protect young infants, the most sensitive group (USEPA 1990, WHO 2007). Up to 100 mg NO3/L\text{NO}_3\text{/L} can be used by adults and children over 3 months of age without significant health effects.

If the value of 50 mg NO3/L\text{NO}_3\text{/L} is exceeded, the relevant health authority or drinking water regulator should be informed so that parents can be advised to use rainwater or bottled water in making up feeds for babies under 3 months of age. Water with concentrations up to 100 mg NO3/L\text{NO}_3\text{/L} may be used if medical authorities are vigilant and the water is free of microbial contamination (WHO 2007).

The guideline level for nitrite of 3 mg NO3/L\text{NO}_3\text{/L} is based on a relative potency for nitrite and nitrate with respect to methaemoglobin formation. WHO (2007) developed the same value for nitrite based on human data that show methaemoglobinaemia caused in infants by doses of nitrite ranging from 0.4 to more than 200 mg/kg of bodyweight. The guideline (rounded value) was derived by using the lowest level of the range (0.4 mg/kg of bodyweight), a bodyweight of 5 kg for an infant and a drinking-water consumption of 0.75 litre.

Because it is possible that nitrate and nitrite may occur simultaneously in drinking-water, and the two have a common toxic effect (methaemoglobinaemia), these compounds should be considered together when judging compliance with the Guidelines. The sum of the ratios of the concentration (C) of each to its guideline value (GV) should not exceed unity (WHO 2007). This is a standard screening risk assessment approach based on the assumption of dose additivity. Thus for infants:

References

APHA Method 4110 Part B (1992). Determination of ions by ion chromatography: ion chromatography with chemical suppression of eluant conductivity. Standard Methods for the Examination of Water and Wastewater, 18th edition. American Public Health Association, Washington.

APHA Method 4500-NO3\text{NO}_3 Part E (1992). Nitrogen (nitrate): Cadmium reduction method. Standard Methods for the Examination of Water and Wastewater, 18th edition. American Public Health Association, Washington.

APHA Method 4500-NO2\text{NO}_2 Part B (1992). Nitrogen (nitrite): Colorimetric method. Standard Methods for the Examination of Water and Wastewater, 18th edition. American Public Health Association, Washington.

Avery AA (1999). Infantile methemoglobinemia: reexamining the role of drinking water nitrates. Environmental Health Perspectives, 107(7):583-586.

FAO/WHO (1996). Toxicological evaluation of certain food additives and contaminants: Nitrate. Prepared by the Forty-fourth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), Geneva, World Health Organization, International Programme on Chemical Safety (WHO Food Additive Series 35).

Fan AM, SteinbergVE (1996). Health implications of nitrate and nitrite in drinking water: An update on methemoglobinemia occurrence and reproductive and developmental toxicity. Regulatory Toxicology and Pharmacology, 23(1):35-43.

Fewtrell L (2004). Drinking-water nitrate, methemoglobinemia, and global burden of disease: a discussion. Environmental Health Perspectives, 112(14):1371-1374.

USEPA (United States Environmental Protection Agency) (1990). Drinking water criteria document on Nitrate/Nitrite. Report TR-1242-608 from ICAIR Life Systems Inc, Cleveland, Ohio. Prepared for Criteria and Standards Division Office of Drinking Water, USEPA, Washington DC.

WHO (World Health Organization) (2007). Nitrate and nitrite in drinking-water: Background document for development of WHO Guidelines for Drinking-water Quality, WHO, Geneva, Switzerland.

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Australian Drinking Water Guidelines 6 2011, v3.9

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