Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Nitrate/Nitrite Toxicity
What Is the Biological Fate of Nitrate?

Learning Objectives

Upon completion of this section, you will be able to describe

• the mean intake of nitrates by persons in the United States and
• how nitrates are metabolized and excreted.

Introduction

Nitrate and nitrite levels in the body are the result of internal nitrate production and external sources. Intake of some amount of nitrates is a normal part of the nitrogen cycle in humans. The mean intake of nitrate per person in the United States is about 40–100 mg/day (in Europe it is about 50–140 mg/day). In the proximal small intestine, nitrate is rapidly and almost completely absorbed (bioavailability at least 92%) (31).

Approximately 60% to 70% of an ingested nitrate dose is excreted in urine within the first 24 hours. About 25% is excreted in saliva through an active blood nitrate transport system and potentially is reabsorbed. Half-lives of parent nitrate compounds are usually less than 1 hour; half-lives of metabolites range from 1 hour to 8 hours (35, 36). Nitrate may also be synthesized endogenously from nitric oxide (especially in the case of inflammation), which reacts to form nitrite (22, 31).

Metabolism of Nitrates to Nitrites

In vivo conversion of nitrates to nitrites significantly enhances nitrates’ toxic potency. The major metabolic pathway for nitrate is conversion to nitrite, and then to ammonia. Approximately 5%–10% of the total nitrate intake is converted to nitrite by bacteria in the saliva, stomach, and small intestine. This reaction is pH dependent, with no nitrate reduction occurring below pH 4 or above pH 9. This is the main reason why infants are more susceptible to nitrite toxicity from elevated nitrate/nitrite ingestion. Another potential metabolic pathway is the reaction of nitrite with endogenous molecules to form N-nitroso compounds, which may have toxic or carcinogenic effects (22).

Key Points

• Intake of some amount of nitrates is a normal part of the nitrogen cycle in humans.
• In vivo conversion of nitrates to nitrites significantly enhances nitrates’ toxic potency.

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