binemia in infants, children, and adults, including case reports, reports of surveys, clinical studies, and epidemiologic studies. The subcommittee could find no studies of nitrate-induced methemoglobinemia reported since the 1990 EPA publication. The absence of reports might in part be due to the lack of requirements for reporting cases of methemoglobinemia. In addition, the studies reviewed by EPA are of uncertain quality largely because of the lack of controls for the presence of confounding factors.
Nitrate and nitrite have been tested for carcinogenicity in laboratory animals, and epidemiologic studies of human cancer rates among populations with high nitrate or nitrite exposure concentrations have been performed. In general, nitrate and nitrite are not carcinogenic in laboratory animals when administered in the absence of nitrosatable amines. When nitrite and nitrosatable amines are administered together, however, carcinogenic nitrosamines can be formed in the stomach and lead to various tumors. Similar results have not been reported for simultaneous administration of nitrate and nitrosatable amines. Nitrosamine formation is inhibited by antioxidants, such as vitamin C and vitamin E. Results of epidemiologic studies have not supported an association between high nitrate or nitrite exposure from drinking water in the United States and increased cancer rates in humans. Both the animal and human studies are reviewed in detail in publications of EPA (EPA 1990a) and the European Chemical Industry Ecology and Toxicology Centre (ECETOC 1988). Human studies reported since the EPA review are also included here. The subcommittee could find no animal-carcinogenicity studies reported since the 1990 EPA publication.