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

Nitrate/Nitrite Toxicity
What Are Nitrate and Nitrite?

Learning Objectives

Upon completion of this section, you will be able to

• describe what nitrates/nitrites are and
• identify sources of nitrates/nitrites.

Introduction

Nitrate (NO₃^-) and nitrite (NO₂^-) are naturally occurring inorganic ions that are part of the nitrogen cycle. Microbial action in soil or water decomposes wastes containing organic nitrogen into ammonia, which is then oxidized to nitrite and nitrate. Because nitrite is easily oxidized to nitrate, nitrate is the compound predominantly found in groundwater and surface waters. Contamination with nitrogen‑containing fertilizers (e.g. potassium nitrate and ammonium nitrate), or animal or human organic wastes, can raise the concentration of nitrate in water. Nitrate‑containing compounds in the soil are generally soluble and readily migrate with groundwater (2, 3).

Water Contamination

Shallow, rural domestic wells are those most likely to be contaminated with nitrates, especially in areas where nitrogen‑based fertilizers are in widespread use (4). Approximately 13 million households in the United States use private wells to supply their drinking water (5). In agricultural areas, nitrogen-based fertilizers are a major source of contamination for shallow groundwater aquifers that provide drinking water (6). A recent United States Geological Survey study showed that more than 8,200 wells nationwide were contaminated with nitrate levels above the U.S. Environmental Protection Agency (EPA) drinking water standard of 10 parts per million (ppm) (7). EPA has estimated that approximately 1.2% of community water wells and 2.4% of private wells exceed the nitrate standard (8).

Other sources of nitrate contamination are organic animal wastes and contamination from septic sewer systems, especially in wells less than 100 feet deep. During spring melt or drought conditions, both domestic wells and public water systems using surface water can show increased nitrate levels (9–11). Drinking water contaminated by boiler fluid additives may also contain increased levels of nitrites (12).

Food Contamination

Contaminated foodstuffs, prepared baby foods, and sausage preserved with nitrates and nitrites have caused exposure in children (13–15). Although vegetables are seldom a source of acute toxicity, they account for more than 70% of the nitrates in a typical human diet. Cauliflower, spinach, collard greens, broccoli, and root vegetables have naturally greater nitrate content than other plant foods do (16, 17). The remainder of the nitrate in a typical diet comes from drinking water (about 21%) and from meat and meat products (about 6%) in which sodium nitrate is used as a preservative and color-enhancing agent (18, 19). For infants who are bottle-fed, however, the major source of nitrate exposure is drinking water used to dilute formula.

Other Sources of Exposure

Nitrate or nitrite exposure can occur from certain medications and volatile nitrite inhalants. Accidental exposures to nitrites in chemical laboratories and ingestion in suicide attempts have been reported. Deliberate abuse of volatile nitrites (amyl, butyl, and isobutyl nitrites) frequently occurs. Nitrate or nitrite exposure also can occur from certain medications. Infants and children are especially susceptible to nitrate exposure through topical silver nitrate used in burn therapy.

Other medications implicated in cases of nitrate or nitrite toxicity are quinone derivatives (antimalarials), nitroglycerine, bismuth subnitrite (antidiarrheal), ammonium nitrate (diuretic), amyl and sodium nitrites (antidotes for cyanide and hydrogen sulfide poisoning), and isosorbide dinitrate/tetranitrates (vasodilators used in coronary artery disease therapy). Ammonium nitrate found in cold packs and nitrous gases used in arc welding are other possible sources of exposure. An ethyl nitrite folk remedy called “sweet spirits of nitre” has caused fatalities (20, 21).

Key Points

• Shallow, rural domestic wells are those most likely to be contaminated with nitrates, especially in areas where nitrogen‑based fertilizers are in widespread use.
• Other nitrate sources in well water include seepage from septic sewer systems, or other contaminants.
• Contaminated foodstuffs, prepared baby foods, and sausage preserved with nitrates and nitrites have caused exposure in children.
• Nitrate or nitrite exposure can occur from certain medications and volatile nitrite inhalants.

Progress Check