Ethyl carbamate (also known as urethane) is a carcinogen capable of inducing tumours at multiple sites in many animal species. It was recently upgraded (in 2007) to a Group 2A human carcinogen - the same carcinogen class as lead, mercury, acrylamide and diesel exhaust - by the World Health Organization's (WHO) International Agency for Research on Cancer (IARC). Used today in the production of fumigants, pesticides and textiles, prior to the 1940s it was administered therapeutically to humans as a hypnotic, and in the treatment of varicose veins and leukemia. It has since been demonstrated to be mutagenic (accumulated in the DNA), teratogenic (birth defect-causing) and carcinogenic in many different species.

The use of ethyl carbamate in about 100 million medical injections in Japan from 1950 until the procedure was stopped in 1975 has been described by one cancer researcher in a peer-reviewed journal as "the largest number (millions) of humans exposed to the largest doses of a pure carcinogen that is on record." Unfortunately, no epidemiological studies have been performed to determine the resulting cancer-causing effects on the Japanese of dosages that are "carcinogenic in mice." Source: Japanese Journal of Cancer Research 82, 1323-1324, December 1991.

EC or urethane forms in various alcoholic beverages as a result of reactions of certain precursors, primarily urea or cyanide, with ethanol. In wines, urea is produced as a natural by-product of yeast metabolism of arginine, a common amino acid in grape juice that provides a source of nitrogen for yeast. Yeast could metabolize the urea it produces to derive an additional source of nitrogen, but in wild and conventional commercial yeast this reaction is not dominant. If the urea produced is not re-consumed by the yeast as a nutrient, or if it is utilized inefficiently, it is secreted from the yeast into the wine, where it can react with ethanol and form ethyl carbamate (urethane).

Factors that influence the levels of urea produced include the amount of arginine and nitrogen present in fermentation, the particular yeast strain employed, and the temperature, among other factors. The reaction that produces urethane from urea and ethanol occurs exponentially faster at higher temperatures - the rate doubles with each 5°C elevation. Various fermented alcoholic beverages that are produced by processes that require heating (e.g., distilled spirits), or are subjected to heated environments during storage and shipping (or simply over time), are at significantly increased risk of higher levels of urethane. Urethane concentrations are found in many commonly consumed fermented beverages and foods, including wine, brandy, whisky, sake, bread, beer, soy sauce, bean curds, crackers and rolls.

Alcoholic beverages, particularly certain stone-fruit spirits and whiskies, tend to contain much higher concentrations of urethane. Heating (e.g., cooking) the beverage increases the ethyl carbamate content, and some concern exists over shipping wines to overseas markets in containers that tend to overheat. In addition, urethane has a tendency to accumulate in the human body from a number of daily dietary sources, e.g., alcohols, bread and other fermented grain products, soy sauce, orange juice and commonly consumed foods. Hence, exposure risk to human health is increasingly evaluated on the total EC intake from the daily diet (WHO refers to this as "margin of exposure" or MOE), of which alcoholic beverages often provide the most significant portion.

Studies in Korea (2000) and Hong Kong (2009) outline the extent of the accumulative exposure to EC in daily life. Fermented foods such as soy sauce, kimchi, soybean paste, breads, rolls, buns, crackers and bean curd, along with wine, sake and plum wine, were found to be the foods with the highest EC levels in traditional Asian diets.

In 2005, the JECFA (Joint FAO/WHO Expert Committee On Food Additives) risk assessment evaluation of EC concluded that the MOE intake of EC from daily food and alcoholic beverages combined is of concern and mitigation measures to reduce EC in some alcoholic beverages should continue. There is little doubt that EC in alcoholic beverages is very important to health authorities, while the cumulative daily exposure in the typical diet is also an issue of rising concern that merits closer observation. The Korean study concluded, "It would be desirable to closely monitor ethyl carbamate levels in Korean foods and find ways to reduce the daily intake."

1985:	Health Canada - The Canadian Health Protection Branch (following discoveries by the Liquor Control Board of Ontario) sets mandatory limits on Ethyl Carbamate levels in wine and alcohol and sets standards to which all alcoholic products must meet in order for importation.
1987:	U.S. wine and distilled spirits industry sets voluntary limits on Ethyl Carbamate levels for importation.
1988:	U.S. National Institutes of Health - National Toxicology Program (NTP) makes Ethyl Carbamate long-term study its highest priority.
1997:	U.S. FDA publishes Ethyl Carbamate Prevention Action Manual outlining methods to reduce Ethyl Carbamate formation.
1999:	World Health Organization Codex Committee puts Ethyl Carbamate on its toxins priority list for JECFA food contaminate risk assessment.
2002:	U.S. National Institutes of Health NTP long-term exposure study released. Carcinogenesis results indicate "Clear Evidence" of carcinogenicity. Final report released in August 2004.
2004:	U.S. FDA's Program Priorities include the development of a food policy on Ethyl Carbamate for 2004-2005.
2005:	World Heath Organization (FAO/WHO) : Joint FAO/WHO Expert Committee on Food Additives (JECFA) 64th Meeting issues risk assessment report on Ethyl Carbamate. JECFA evaluation states that "margin of exposure" intake from food and alcoholic beverages combined is of concern and mitigation measures to reduce ethyl carbamate in some alcoholic beverages should continue. This report will be presented to the CODEX committee for international food policy setting consideration in 2005.
2005:	United Kingdom Food Standards Agency - Survey on Ethyl Carbamate in Food and Beverages. Based on survey results the Agency is continuing to work with manufacturers to ensure that good manufacturing practices are in place to reduce the level of ethyl carbamate in alcoholic beverages.
October 2006:	European Food Safety Authority requests data and studies from member states on the presence of ethyl carbamate and cyanide in foods and beverages.
March 2007:	The World Health Organization's International Agency for Research on Cancer (IARC) re-classifies ethyl carbamate as a Group 2A carcinogen (probably carcinogenic to humans) from Group 2B (possibly carcinogenic). Other Group 2A carcinogens include acrylamide, PCBs, diesel engine exhaust, arsenic, mercury and mustard gas.