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

Nitrate/Nitrite Toxicity
Who Is At Risk?

Learning Objectives

Upon completion of this section, you will be able to

• describe drinking water exposure risk to nitrates and nitrites and
• identify the population most susceptible to nitrates and nitrites.

Introduction

About 1% to 2% of the U.S. population that uses drinking water from public water systems might be exposed to nitrates in excess of the EPA‑recommended maximum concentration. EPA has estimated that approximately 1.2% of community water wells and 2.4% of private wells exceed the nitrate standard. Residents in as many as 603,000 homes may consume drinking water from nitrate-contaminated domestic wells. Although suppliers of public water sources are required to monitor nitrate concentrations regularly, few rural wells are routinely tested for nitrates (8).

Infants Are at Highest Risk

Infants younger than 4 months of age who are fed formula diluted with water from rural domestic wells are especially prone to developing health effects from nitrate exposure (21). The high pH of the infant gastrointestinal system favors the growth of nitrate-reducing bacteria, particularly in the stomach and especially after ingestion of contaminated waters. The stomach of adults is typically too acidic to allow for significant bacterial growth and the resulting conversion of nitrate to nitrite.

A proportion of hemoglobin in young infants is still in the form of fetal hemoglobin. Fetal hemoglobin is more readily oxidized to methemoglobin (MHg) by nitrites than is adult hemoglobin. Therefore, infants, and especially premature infants, are particularly susceptible.

In addition, NADH-dependent methemoglobin reductase, the enzyme responsible for reduction of induced MHg back to normal hemoglobin, has only about half the activity in infants as in adults (22, 23).

Infection and inflammatory reactions can increase endogenous synthesis of nitrate in both infants and adults (4). Gastroenteritis with vomiting and diarrhea can exacerbate nitrite formation in infants. It has been reported to be a major contributor to MHg risk in infants independent of nitrate/nitrite ingestion (24–26). These factors combine to place young infants with diarrhea, who are fed formula diluted with nitrate‑contaminated well water, at the greatest risk for toxicity (10, 27).

Pregnancy

The pregnant woman and her fetus represent another high-risk group. Reproductive outcome studies done at sites with high nitrate levels in the water supply provide some evidence of maternal transfer of nitrate and nitrite. The pregnant woman and her fetus might be more sensitive to toxicity from nitrites or nitrates at or near the 30th week of pregnancy (28, 29).

Key Points

• About 1% to 2% of the U.S. population that uses drinking water from public water systems might be exposed to nitrates in excess of the EPA-recommended maximum concentration.
• Infants younger than 4 months of age are the highest risk group.

Progress Check