To cause methemoglobinemia, nitrate must be converted to nitrite. The conversion is performed by bacteria in the mouth and stomach. The extent of toxicity of nitrate depends on the extent to which it is converted to nitrite, which depends on the concentration and type of bacteria in the mouth and stomach. In adults, the acidity of the stomach is usually great enough that bacterial growth and the consequent conversion of nitrate to nitrite are negligible; probably about 5% of a dose of nitrate is reduced to nitrite, on average (ECETOC 1988), and methemoglobinemia is rare. In infants, however, the low gastric acidity is thought to favor the growth of nitrate-reducing bacteria, and infants are the group most susceptible to methemoglobinemia. Most infant victims of methemoglobinemia have reportedly been fed infant formula mixed with well water that contained high concentrations of nitrate, but cases have also been associated with the consumption of spinach and carrots, which are high in nitrate and nitrite (Bruning-Fann and Kaneene 1993). However, several authors have reported that achlorhydria and gastric nonsterility are rare in infants, even infants with methemoglobinemia (Bodo 1955; Simon et al. 1962; Agunod et al. 1969); that observation suggests a role of pathways other than gastrointestinal nitrite synthesis. Other investigators have reported that infant gastric acidity is low enough to support bacterial growth (EPA 1990a). Hegesh and Shiloah (1982) studied newborns hospitalized for acute diarrhea and found no correlation between ingestion of food or water containing high concentrations of nitrate or nitrite and methemoglobinemia; they concluded that endogenous synthesis of nitrite resulting from diarrhea was the principal cause of infantile methemoglobinemia. Thus, diarrhea apparently can be a major cause of infant methemoglobinemia unrelated to the nitrate content of food and water (endogenous synthesis is discussed in Chapter 4).

A 1990 EPA publication (EPA 1990a) provides a thorough review of the literature available on the occurrence of methemoglo-



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