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Nitrate and Nitrite in Drinking Water (1995)

Chapter: 5 RISK CHARACTERIZATION

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Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
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5

Risk Characterization

This chapter combines information from the hazard-identification, dose-response assessment, and exposure-assessment chapters to determine what magnitudes of human exposure to nitrate and nitrite might produce adverse health effects.

When EPA evaluated the toxicity of nitrate and nitrite for the purpose of establishing drinking-water criteria, it did not assign a weight-of-evidence classification for their carcinogenic potential (EPA 1990a). EPA concluded that there are no convincing data to suggest that nitrate or nitrite is associated with any adverse effect other than methemoglobinemia, and it identified a no-observed-adverse-effect level (NOAEL) for nitrate of 10 mg of nitrate nitrogen per liter ( 1.6 mg/kg-day) on the basis of epidemiologic studies (Walton 1951). That value is equivalent to nitrate at 44 mg/L. To obtain a reference dose (RfD) from the NOAEL, an uncertainty factor of 1 was used because the NOAEL was derived from studies in humans of the most sensitive subpopulation. For nitrite, EPA

Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×

assumed that the conversion rate of nitrate to nitrite by gastrointestinal tract bacteria in infants is about 10%, from which an RfD of 1 mg of nitrite nitrogen per liter (0.16 mg/kg-day) was calculated. That value is equivalent to nitrite at 3.3 mg/L. The MCLGs for nitrate and nitrite are based on those RfDs. Assuming water consumption of 0.64 L/d by a 4-kg infant, the MCLGs for nitrate nitrogen and nitrite nitrogen are 10 mg/L and 1 mg/L, respectively.

CANCER RISKS

The subcommittee concludes that exposure to the nitrate and nitrite concentrations found in drinking water in the United States is unlikely to contribute to human cancer risk. That conclusion is based on the following observations:

  • For more than 99% of the U.S. population, about 97% of nitrate intake comes from the diet (99% in the case of vegetarians) and about 99% of nitrite intake comes from the diet. Attempting to limit nitrate or nitrite exposure on the basis of carcinogenicity would implicate the diet, and vegetables in particular, as the primary source of risk for most of the U.S. population. Any theoretical cancer risk should be weighed against the benefits of eating vegetables.

  • Epidemiologic studies provide inadequate evidence of an association between nitrate exposure from drinking water in the United States and cancer risk.

  • Studies in laboratory animals do not support an association between nitrate exposure and cancer risk or between nitrite exposure and cancer risk in the absence of concurrent exposure to nitrosatable amines.

Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
  • Studies in laboratory animals support an association between combined exposure to nitrite and nitrosatable amines and cancer risk because of endogenous formation of nitrosamines. Cancer risk associated with endogenous nitrosamine formation is a function of four factors: the amount of nitrite ingested or formed from nitrate, the amount of nitrosatable substances ingested, the rate of in vivo nitrosation, and the carcinogenic potency of the resulting nitrosamine. Each of those factors varies over a range of a factor of 100 or more. Nitrate or nitrite intake from drinking water is unlikely to be a rate-limiting step. As a result, calculating useful estimates of potential cancer risk solely on the basis of nitrate or nitrite exposure is not possible in the absence of supporting epidemiologic data or a physiologically based pharmacokinetic model that would permit analysis of the complex relationships between exogenous and endogenously formed nitrate, nitrite, and N-nitroso compounds.1

  • Endogenous nitrate formation occurs at about 1 mg/kg-day. That rate constitutes some 50% of total nitrate exposure for most of the U.S. population. Regulating exogenous nitrate exposure from water on the basis of carcinogenicity is inconsistent with such a rate of endogenous nitrate formation.

The subcommittee concludes that the incremental contribution of nitrate and nitrite from drinking water in the United States to total nitrate and nitrite exposure is negligible and unlikely to contribute to human cancer risk. The current maximum-contaminant-level goals of nitrate at 44 mg/L (nitrate nitrogen at 10 mg/L) and nitrite at 3.3 mg/L (nitrite nitrogen at 1 mg/L) are adequate to protect human health.

1  

See Appendix A for a discussion of how a physiologically based pharmaco-kinetic model could be developed to assess the risk of cancer associated withexposure to nitrate.

Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×

NONCANCER RISKS

Available data are inadequate to support an association between nitrate and nitrite exposure from drinking water and any non-cancer effects other than methemoglobinemia in infants. That conclusion is based on the following observations:

  • No studies in humans have demonstrated adverse health effects that can be attributed to nitrate or nitrite toxicity other than methemoglobinemia in infants.

  • There is scant evidence from laboratory animals of developmental effects attributable to nitrate. One study reported deficits in neurobehavioral development when pregnant rats and their offspring received a low dosage of nitrate, 7.5 mg/kg-day. That is the lowest dosage at which adverse health effects of nitrate or nitrite have been reported in laboratory animals. The study had several limitations, and it is not known whether the neurobehavioral effects reported in rats can be extrapolated to humans; however, if so, converting the dosage to an adult human dosage yields 317 mg of nitrate per day, which is equivalent to the total dietary intake of a typical pregnant woman. That dosage is therefore unlikely to pose a threat to the fetus. The adverse effects reported in rats might have resulted from exposure after birth; the equivalent human infant nitrate dosage is about 23 mg/day. If an infant drinks 850 mL of formula prepared with water that contains nitrate at 44 mg/L each day, more than 23 mg of nitrate would be received each day. It would be inappropriate to classify nitrate as a developmental toxicant on the basis of this limited experimental evidence, although the results suggest that further studies of such effects should be conducted.

  • Methemoglobinemia in infants is the only adverse effect that has been associated with nitrate exposure. It can occur as a result

Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×

of exposure to nitrate-contaminated water or to vegetables with high concentrations of nitrate or as a result of increased endogenous nitrate synthesis in cases of infection. There are very few published reports of methemoglobinemia occurring in infants whose drinking water contains nitrate at less than 50 mg/L, and none of the reported cases occurred in the United States.

The subcommittee concludes that limiting infant exposure to nitrate would be a sensible public-health measure. It could be accomplished by minimizing exposure to both foods and water that are high in nitrate and by protecting infants from infection. Infection is the major contributor to methemoglobinemia from nitrate exposure; the incremental contribution of drinking water is negligible. However, in view of the uncertain quality of historical data and the absence of current data—the absence of which might be due in part to the lack of requirements for reporting cases of methemoglobinemia—it is prudent to maintain EPA's current MCLGs of nitrate at 44 mg/L (nitrate nitrogen at 10 mg/L) and nitrite at 3.3 mg/L (nitrite nitrogen at 1 mg/L). These MCLGs are adequate to protect human health from the potential consequences of exposure to nitrate and nitrite in public water supplies because they are based on human data derived from the most sensitive subpopulation and because no cases of methemoglobinemia have been reported in the United States at dosages below the MCLGs. The MCLGs for nitrate and nitrite are identical with their MCLs because the technology needed to implement the MCLGs is considered available and inexpensive.

Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
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Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 45
Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 46
Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 47
Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 48
Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 49
Suggested Citation:"5 RISK CHARACTERIZATION." National Research Council. 1995. Nitrate and Nitrite in Drinking Water. Washington, DC: The National Academies Press. doi: 10.17226/9038.
×
Page 50
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