Workgroup report: Drinking-water nitrate and health--recent findings and research needs

Ward, M.H., deKok, T.M., Levallois, P., Brender, J., Gulis, G., Nolan, B.T., VanDerslice, J. and International Society for Environmental, E. (2005) Environmental Health Perspectives, 113 (11); 1607-14.

A symposium took place in August 2004 in New York on drinking water nitrate and health examining recent findings and research needs. This article summarises the symposium discussions and recommends potential areas for future research. The epidemiological evidence for drinking water nitrate and the risk of specific cancers is discussed as well as adverse reproductive outcomes and other health outcomes with consideration of the current regulatory limit for nitrate in drinking water. The U.S. Environmental Protection Agency (EPA) maximum contaminant level (MCL) for nitrate in drinking water is 10 mg/L nitrate-nitrogen (nitrate-N) which is equivalent to 45 mg/L as nitrate, and the World Health Organization (WHO) guideline level is 50 mg/L as nitrate.

Due to human alteration of the nitrogen cycle, nitrate is gradually increasing in our water resources and is the most common chemical contaminant in the world's groundwater aquifers. It is estimated that 42% of the U.S. population uses groundwater for their drinking water. Recent data suggests that about 22% of domestic wells in agricultural areas in the U.S. exceed the MCL. In the European Union, nitrate levels have been found to exceed the WHO guideline in about one-third of groundwater bodies for which there is data available.

When nitrate is ingested it is reduced to nitrite which binds to haemoglobin to form methemoglobin (MetHb). The condition methemoglobinemia occurs when elevated levels of MetHb interfere with the oxygen-carrying capacity of the blood. Infants are particularly susceptible to developing methemoglobinemia. The U.S. EPA MCL and the WHO guideline levels for nitrate were set to protect infants from developing methemoglobinemia. The risk of methemoglobinemia in infants depends on many factors, not just the ingestion of nitrate in drinking water. There have been varying results in studies that have considered the relationship between nitrate levels in drinking water and MetHb levels in infants. Whether nitrate exposure alone causes methemoglobinemia has been recently questioned. The interactions and importance of factors that lead to methemoglobinemia including nitrate in drinking water need to be clarified.

Nitrate is a precursor in the formation of N -nitroso compounds (NOC); this is a class of genotoxic compounds. There have been several studies that show a direct relationship between nitrate intake and endogenous formation of NOC. NOC are potent animal carcinogens and can induce tumours at multiple organ sites including the oesophagus, stomach, colon, bladder, lymphatics and hematopoietic system. There are very few well-designed epidemiological studies on drinking water nitrate and cancer risk to drawn firm conclusions. Most of the studies have been of a weaker ecological design linking the incidence or mortality rates to drinking water nitrate levels at the town or county level rather than at the individual level. Results of studies have been mixed with some showing positive associations with the development of cancers, some showing no associations and others showing inverse associations.

There have been at least 10 studies considering the relationship between drinking water nitrate and adverse reproductive outcomes. Results from theses studies are also mixed. Studies have examined relationships between drinking water nitrate and spontaneous abortions, stillbirths, premature birth or intrauterine growth retardation as well as congenital malformations, in particular malformations of the central nervous system and specifically neural tube defects. Other health outcomes studied include thyroid hypertrophy, genotoxic effects, type-1 childhood diabetes, increased blood pressure and acute respiratory tract infections in children.

It was concluded that more experimental studies need to be undertaken on healthy individuals and on susceptible subgroups with medical conditions that increase endogenous nitrosation. The limited numbers of epidemiological studies that have considered intake of nitrosation precursors and/or inhibitors have found elevated risks of colon cancers and neural tube defects associated with drinking water containing nitrate concentrations below the regulatory limit. Several authors have suggested that the current nitrate standard could be safely raised to 15-20 mg/L nitrate-N with no increase in methemoglobinemia cases. However before any changes to the standards are considered, a clearer understanding is needed of the conditions under which nitrate in drinking water poses a risk of methemoglobinemia, as well as the role of nitrate as a risk factor for cancer and adverse reproductive outcomes.