The chemical N-nitrosodimethylamine, better known as NDMA, has recently been found in drinking water in the United States. This yellow, oily liquid is thought to produce a variety of adverse health effects in humans following both short- and long-term exposures. Health risks are suspected to occur at levels in the range of parts per billion (ppb) and parts per trillion (ppt).

Until 1978, NDMA was used in the production of liquid rocket fuel and manufacture of rubber in the United States. Although it isn't directly manufactured today, NDMA may be found in a number of products such as tobacco, beer, milk, cured meats (i.e., bacon, salami, jerky) and smoked fish. Cosmetics, cleaners and pesticides may also contain NDMA as a by-product of natural and manmade compounds. N-nitrosamines (including NDMA) have even been found at levels up to 387 ppb in rubber nipples from baby bottles, and were shown to migrate to the liquid contents of the bottle.1

New developments
Recently, NDMA has been detected in the effluent of drinking water and wastewater treatment plants, especially in areas known to be contaminated with rocket fuel wastes. The first documented concern in the United States surfaced in 1998 when California officials detected NDMA at concentrations around 150 ppt in a drinking water well in the northern region of the state.2 This finding prompted more investigations of drinking water wells in the state, yielding three more contaminated sites with concentrations ranging from 70-to-3,000 ppt. All of the wells positive for NDMA were taken out of service.

In 1999, yet another surprise surfaced for California officials. NDMA was found in treated drinking water at very low levels (10 ppt). This finding led to speculation that drinking water treatment processes may actually produce NDMA. Studies are currently focused on the possibility that NDMA production may result from the interaction of nitrite, ammonia and polymers used in water treatment. Others are investigating the possible role of chlorine in the production of NDMA, but these studies have all been inconclusive. For example, one preliminary study showed NDMA required the presence of chlorine to form, while another showed chlorine decreased levels of NDMA.2

Health effects
Following short-term exposures, NDMA is known to irritate the eyes, skin and respiratory tract. The most serious effects seem to occur with the liver, which may result in jaundice. Other symptoms include nausea, vomiting, diarrhea, abdominal cramps, headaches, fever, enlarged liver, reduced kidney and lung function, and malaise. Following long-term exposures, the liver may be permanently damaged due to cirrhosis or carcinogenic effects. Over time, NDMA exposures may lower the blood platelet count in humans and cause conditions associated with suppressed immunity.3

Little is known about the direct impact of NDMA on humans. Animal studies, however, show both ingested and inhaled exposures to NDMA produce a variety of tumors at multiple sites in rodents and non-rodent mammals. Animal studies also indicate the compound can cross the placental barrier between mother and child and increase the risk of lung, liver and kidney tumors in infants. An overall increase in infant mortality has been seen in rats following NDMA exposures. Other studies showed a link with skin, seminal vesicle and lymphatic system cancers.

Risk assessment
The first task in identifying the probable risk associated with NDMA is to determine the level of exposure where adverse effects occur. The problem is that exposures may occur from multiple sources, i.e., food, water, air and environmental pollutants and produce varied responses in different individuals. Symptoms may also be delayed and not be evident for years. The synergistic nature of NDMA effects combined with other pollutants are also not known; currently, the U.S. Environmental Protection Agency (USEPA) is evaluating the reference concentration for NDMA where health effects are likely to occur-a vital piece of information for estimating risk.

Another important question to answer is how much exposure to NDMA is due to water relative to other sources? In other words, what NDMA sources are most important relative to the associated heath risks? Considering levels in milk may range from 90-to-100 ppt (up to 3,559 for nonfat dry milk), and there are 50-to-7,700 ppt in beer, 2,600-to-2,700 ppt in bacon, and as much as 5,350 ppt in salami-the levels found in water seem relatively insignificant. The important thing to remember about water, however, is the relative dose consumed compared to other foods. Salami may be eaten rarely but water tends to be ingested on a constant, daily basis.

The amount of NDMA that results in health effects in humans is unknown; however, epidemiological studies have shown a clear connection between NDMA and cancer. A study in Finland showed people with a diet high in nitrosamine compounds (including NDMA) were more likely to develop colorectal cancer than others. The study followed 9,985 people for up to 24 years and found those consuming smoked and salted fish containing nitrosamines and other preservatives were nearly 2.6 times more at risk for cancer than individuals not consuming these foods.

Worldwide response
Health officials in the Netherlands are taking a proactive step in minimizing the public health risk due to NDMA exposures by setting guidelines that estimate the lifetime cancer risks associated with occupational exposures to a variety of carcinogens. A committee of the Health Council of the Netherlands calculated an additional risk of cancer in one's lifetime from NDMA exposures as 4 x 10-5 for 40 years if exposed to 0.002 micrograms per cubic meter (mg/m3)--or ppb--and 4 x 10-3 for 40 years of exposures at 0.2 mg/m3 .4

According to another published study, the maximum allowable 24-hour human intake of NDMA is 0.15 micrograms/kg.5 The maximum allowable concentration for NDMA in water is 5 mg/L (5 ppb) based on chronic experiments in mice.

Seeking a standard
At this time, recognition of NDMA as a problem in drinking water is so recent standardized tests for detection of the chemical haven't been developed. Currently, the California Department of Health Services (DHS) is working on the development of standard methods of analysis. A list of laboratories with specialized equipment capable of detecting low levels of NDMA, in the parts per trillion range, is available from the California DHS.6

Although no federal drinking water standards exist, the DHS has initiated an action level (an advisory level, not an enforceable standard) concentration in an effort to inform and protect the public from potential risks due to NDMA exposures. DHS has set a temporary action level of 0.002 ppb of NDMA in drinking water.7 This value corresponds to a theoretical 10-5 cancer risk (corresponding to up to one excess case of cancer per 100,000 people), assuming a 2 L per day ingestion rate over a 70-year lifetime. This means that if NDMA is found at concentrations above 0.002 ppb, the public water system is advised to notify the city council, or other local governing body, within 30 days.

DHS also recommends the utility inform its customers and consumers as soon as feasible about the presence and potential adverse health effects of NDMA. If the level of NDMA present in drinking water exceeds a 10-4 risk or at concentrations above 0.02 ppb, it's recommended the source be removed from service.

Treatment options
The good news is NDMA isn't very persistent in the environment as it readily degrades into harmless compounds when exposed to light. NDMA may be removed by activated carbon but this doesn't eliminate the compound. The NDMA-contaminated carbon thus creates a source of more concentrated exposures to NDMA if necessary precautions aren't taken. Contaminated carbon also poses a disposal problem where NDMA might again be released into the environment. The compound is, however, sensitive to ultraviolet light and is rapidly eliminated when exposed.

Conclusion
The USEPA has classified NDMA as a "probable human carcinogen." The carcinogenic effect of NDMA has been classified as a medium hazard. The USEPA states that individuals are most likely to be exposed to NDMA in occupational settings such as in the rubber, tannery, fish processing, dye, and surfactant industries. Other exposures may be from cigarette smoke and contaminated air. Drinking water is listed as a potential exposure route but how prevalent this route is hasn't been determined.

References
1. Havery, D.C. and T. Fazio, "Survey of baby bottle rubber nipples for volatile N-nitrosamines." Journal for the Association of Official Analytical Chemists, 1983. 66(6): p. 1500-3.
2. Orange County Water District, "Background information on N-Nitrosodimethylamine (NDMA)." 2000, OCWD Online. www.ocwd.com/pages/ndma.htm
3. Desjardins, R., M. Fournier, F. Denizeau, and K. Krzystyniak, "Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice." Journal of Toxicology and Environmental Health, 1992. 37(3): p. 351-61.
4. Health Council of the Netherlands, "Executive summary: N-Nitrosodimethylamine (NDMA)." 1995: www.gr.nl
5. Litvinov, N.N., D. Parfenov Iu, V.M. Voronin, and V.S. Zhurkov, "Calculation of maximum allowable concentration of N- nitrosodimethylamine and N-nitrosodiethylamine based on chronic experiments in mice." Gigiena I Sanitarria, 1990(4): p. 33-6.
6. California Department of Health Services, "NDMA laboratory analysis. 2000, California DHS." www.dhs.cahwnet.gov/ps/ddwem/chemicals/ndma/
ndmalabs.htm
7. California Department of Health Services, "Drinking water action level for NDMA." 2000. www.dhs.cahwnet.gov