Health effects of N-Nitrosodimethylamine
n-Nitrosodimethylamine is commonly known as NDMA. It is a yellow liquid which has no distinct odor. It is produced in the US only for use as a research chemical. NDMA was used to make rocket fuel, but this use was stopped after unusually high levels of this compound were found in air, water, and soil samples collected near a rocket fuel manufacturing plant. NDMA is, however, unintentionally formed during various manufacturing processes at many industrial sites and in air, water and soil from reactions involving other chemicals called alkylamines. Alkylamines are both natural and man-made compounds which are found widely distributed throughout the environment.
NDMA does not persist in the environment. When NDMA is released into the atmosphere, it breaks down in sunlight in a matter of minutes. When released to soil surfaces, NDMA may evaporate into air, break down upon exposure to sunlight, or sink into deeper soil. NDMA should break down within a few months in deep soil. When NDMA is released into water, it may break down upon exposure to sunlight or break down by natural biological processes. The rate of breakdown in water is not known.
Exposure to n-Nitrosodimethylamine
Information suggests that the general population may be exposed to NDMA from a wide variety of sources, including environmental, consumer, and occupational sources. At this time, NDMA has been found in at least 1 out of 1177 hazardous waste sites on the National Priorities List (NPL) in the US. Under certain conditions, NDMA may be found in outdoor air, surface waters (rivers and lakes, for example), and soil.
The primary sources of human exposure to NDMA are tobacco smoke, chewing tobacco, diet (cured meats [particularly bacon], beer, fish, cheese, and other food items), toiletry and cosmetic products (for example, shampoos and cleansers), interior air of cars, and various other household goods, such as detergents and pesticides. In addition, NDMA can form in the stomach during digestion of alkylamine-containing foods. Alkylamines are naturally occurring compounds which are found in some drugs and in a variety of foods.
Infants may be exposed to NDMA from the use of rubber baby bottle nipples and pacifiers which may contain very small amounts of NDMA, from ingestion of contaminated infant formulas, and from breast milk of some nursing mothers. Very low levels of NDMA have been found in some samples of human breast milk.
Occupational exposure may happen in a large number of places including industries such as tanneries, pesticide manufacturing plants, rubber and tire manufacturing plants, alkylamine manufacture/use industries, fish processing industries, foundries, and dye manufacturing plants. Researchers making or handling NDMA may also be exposed to this compound if it passes through the rubber gloves they wear during laboratory work. NDMA has been found in groundwater samples, in amounts of 10 parts NDMA per billion parts of water, at one or more hazardous waste sites on the National Priorities List (NPL). No information is available about contamination of soil, drinking water, irrigation water, sewers, storm drains, or the human food chain with NDMA near NPL sites.
Pathways in the body
NDMA can enter the body when a person breathes air that contains NDMA or when a person eats food or drinks water contaminated with NDMA. NDMA can also enter the body through the skin after contact with rubber articles that contain NDMA. Experiments in animals have shown that after being given by mouth, NDMA enters the bloodstream and goes to many organs of the body in a matter of minutes. In the liver, NDMA is broken down into other substances, most of which leave the body within 24 hours in air exhaled from the lungs and in urine, along with the NDMA that is not broken down. Little is known about what happens to NDMA that enters the body through the skin or through contaminated air. Although vapors of NDMA are broken down within minutes after exposure to sunlight, if NDMA is spilled at a waste site and evaporates, a person nearby can be exposed to NDMA before it disappears from the air. The most important and probably the most harmful way of coming into contact with NDMA seems to be by eating contaminated food or drinking contaminated water.
You should know that one way to learn whether a chemical will harm people is to determine how the body absorbs, uses, and releases the chemical. For some chemicals, animal testing may be necessary. Animal testing may also help identify such health effects as cancer or birth defects. Without laboratory animals, scientists would lose a basic method for getting information needed to make wise decisions that protect public health. Scientists have the responsibility to treat research animals with care and compassion. Scientists must comply with strict animal care guidelines because laws today protect the welfare of research animals.
Additionally, there are vigorous national and international efforts to develop alternatives to animal testing. The efforts focus on both in vitro and in silico approaches and methods. For example, the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences (NIEHS) created the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) in 1998. The role of NICEATM is to serve the needs of high quality, credible science by facilitating development and validation—and regulatory and public acceptance—of innovative, revised test methods that reduce, refine, and replace the use of animals in testing while strengthening protection of human health, animal health and welfare, and the environment. In Europe, similar efforts at developing alternatives to animal based testing are taking place under the aegis of the European Centre for the Validation of Alternative Methods (ECVAM).
NDMA is very harmful to the liver of animals and humans. People who were intentionally poisoned on one or several occasions with unknown levels of NDMA in beverage or food died of severe liver damage accompanied by internal bleeding. Animals that ate food, drank water, or breathed air containing high levels of NDMA over a period of days or several weeks also developed serious, non-cancerous, liver disease. When rats, mice, hamsters, and other animals ate food, drank water, or breathed air containing lower levels of NDMA for periods more than several weeks, liver cancer and lung cancer as well as non-cancerous liver damage occurred. The high level short-term and low level long-term exposures that caused non-cancerous liver damage and/or cancer in animals also usually resulted in internal bleeding and death.
Although there are no reports of NDMA causing cancer in humans, it is reasonable to expect that exposure to NDMA by eating, drinking, or breathing could cause cancer in humans. Mice that were fed NDMA during pregnancy had offspring that were born dead or died shortly after birth. However, it is not known whether NDMA could cause the death of human babies whose mothers are exposed during pregnancy. It should be realized that exposure to NDMA does not mean that any effect on health will definitely occur.
The presence of NDMA can be detected in blood and urine by a test, but this test is not usually available and has not been used as a test for human exposure or to predict possible health effects.
Levels of exposure
The levels of NDMA in air, water, or food that result in health effects in people are unknown. Short-term expose of animals to air containing levels of 16 parts per million (ppm) NDMA produces liver damage and death. Toxic effects of long-term exposure of animals to air containing NDMA are unknown. Short-term or long-term exposure of animals to water or food containing NDMA is also associated with serious effects, such as liver disease and death, at levels ranging from 5 to 50 ppm in water and 5 to 100 ppm in food.
Disclaimer: This article is taken wholly from, or contains information that was originally published by, the Agency for Toxic Substances and Disease Registry. Topic editors and authors for the Encyclopedia of Earth may have edited its content or added new information. The use of information from the Agency for Toxic Substances and Disease Registry should not be construed as support for or endorsement by that organization for any new information added by EoE personnel, or for any editing of the original content.