Ethyl carbamate

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Ethyl carbamate
Skeletal formula of ethyl carbamate
Chemical name Ethyl carbamate
Chemical formula C3H7NO2
Molecular mass 89.09 g/mol
CAS number 51-79-6
Density 1.056 g/cm3
Melting point 49 °C
Boiling point 185 °C
SMILES
Disclaimer and references

Ethyl carbamate (also called urethane) is a substance first prepared in the nineteenth century. Structurally it is an ester of carbamic acid, i. e., ethyl carbamate as shown. Urethane itself is: (NH2-COOC2H5) and is not a component of polyurethanes.

Contents

[edit] Synthesis

This ethyl ester is a white crystalline substance produced by the action of ammonia on ethyl carbonate or by heating urea nitrate and ethyl alcohol (Merck 1989).

Other carbamates include methyl carbamate (urethylane, m. p. 52-54°C)(HSDB 2006b), butyl carbamate(HSDB 2006c), and phenyl carbamate (m. p. 149-152°C) (Dean 1985), which can also be prepared from the corresponding chloroformate and ammonia.

[edit] Properties

These esters are white, crystalline solids at room temperature. Except for the phenyl carbamate, they sublime at moderate temperatures; methyl carbamate sublimes at room temperatures. The first two and urethane are very soluble in water, benzene, and ether (HSBD 2006a,b,c).

[edit] Uses

In the past urethane has been produced commercially in the United States for well over 30 years. It has been used as an antineoplastic agent and for other medicinal purposes. It saw relatively heavy use in the treatment of multiple myeloma before it was found to be toxic and largely ineffective.[1] By US FDA regulations urethane has been withdrawn from pharmaceutical use. Formerly, cross linking agents for permanent press textile treatments were synthesized from urethane(NTP 2005). Although reports made to the USEPA for the Toxics Release Inventory indicate that over 100,000 pounds of urethane was used in 2004 (USEPA 2006); this is probably in error, because of incorrect reporting. Small quantities of this ester are also used in laboratories as an anesthetic for animals (VCU 2006). The other carbamates (methyl, butyl, and phenyl) are only used in small quantities for research purposes.

[edit] Occurrence of Urethane in Beverages and Food

After 1984, studies showed that various alcoholic beverages contained traces (15 ppb to 12 ppm) of urethane (Segal 1988). Later studies have shown that other foods and beverages that are prepared by fermentation processes also contain trace amounts of urethane. For example, bread has been found to contain 2 ppb (Haddon, et. al. 1994), while as much a 20 ppb has been found in some samples of soy sauce (Matsudo, et. al., 1993). It has been shown that urethane forms from the reaction of alcohol (ethanol) with urea.

Image:EtOH_plus_urea.png

This reaction is much faster at higher temperatures, and, therefore, higher concentrations of urethane are found in beverages that are heated in processing, such as dessert wines, fruit brandies, and whiskey. The urea in wines results from the metabolism of arginine or citrulline by yeast or other organisms. Although this process can not be eliminated, it can be minimized by controlling fertilization of grape vines, minimizing heat exposure, and other actions (Butzke & Bisson 1997). Traces of methyl carbamate have also been found in wines. In 1988, wine and other alcoholic beverage manufacturers agreed to control the levels of urethane in wine to less than 15 ppb, and in stronger alcoholic drinks to less than 125 ppb (Segal 1988). Other countries have set limits on the concentration of urethane in alcoholic beverages (see the German record: Urethan).

[edit] Hazards

Urethane is not acutely toxic to humans, as shown by its use as a medicine. Acute toxicity studies show that the lowest fatal dose in rats, mice, and rabbits equals 1.2 grams/kg. or more. When urethane was used medicinally, about 50 percent of the patients exhibited nausea and vomiting, and long time use lead to gastroenteric hemorrhages(USEPA 1979). The compound has almost no odor and a cooling, saline, bitter taste (HSDB 2006a).

Studies with rats, mice, and hamsters has shown that urethane will cause cancer when it is administered orally, injected, or applied to the skin, but no adequate studies of urethane-caused cancer in humans has been reported (IARC,1974). The International Agency for Research on Cancer has stated that urethane can be “reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals.” (NTP 2005). This evaluation has lead to the following US regulatory actions:

NESHAP: Listed as a Hazardous Air Pollutant (HAP) Comprehensive Environmental Response, Compensation, and Liability Act Reportable Quantity (RQ) = 100 lb Emergency Planning and Community Right-To-Know Act EPA’s Toxics Release Inventory A listed substance subject to RCRA reporting requirements RCRA Listed Hazardous Waste: substance - U238

[edit] References

  1. Butzke, C E & L F Bisson, “Ethyl Carbamate Preventative Action Manual” from Depart. of Viticulture & Enology, U. of CA, Davis, CA, for US FDA, 1997 accessed May 13, 2006 at http://www.cfsan.fda.gov/~frf/ecaction.html
  2. Dean, JA (editor), Lange’s Handbook of Chemistry, 13th Ed., 1985, p. 7-586, #p191.
  3. HSDB National Library of Medicine, Hazardous Data Bank, Ethyl Carbamate 2006a, accessed May 13, 2006 at http://toxnet.nlm.nih.gov/
  4. Haddon W F, M I Mancini, M Mclaren, A Effio, L A Harden, R I Egre, & J L Bradford; Cereal Chemistry; 71 (2).. 207-215, 1994; accessed May 12, 2006 at http://toxnet.nlm.nih.gov
  5. HSDB National Library of Medicine, Hazardous Data Bank, Methyl Carbamate 2006b, accessed May 13, 2006 at http://toxnet.nlm.nih.gov
  6. HSDB National Library of Medicine, Hazardous Data Bank, Butyl Carbamate 2006c, accessed May 13, 2006 at http://toxnet.nlm.nih.gov
  7. Matsudo T, T Aoki, K Abe, N Fukuta, T Higuchi, M Sasaki & K Uchida, J Agric Food Chem; 41 (3). 352-356(1993); accessed May 12, 2006 at http://toxnet.nlm.nih.gov
  8. Merck S. Budavari (editor), The Merck Index, 11th Edition, no. 9789, 1989.
  9. NTP National Toxicology Program, NIEHS, National Institutes of Health, “Eleventh Report on Carcinogens, Urethane”, 2005: accessed May 13,2006 at: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s184uret.pdf
  10. OTS EPA. Office of Toxic Substances, “Chemical Hazard Information Profile Urethane, CAS No. 51-79-6 , U.S. EPA, Washington, D.C., 12 pages, 26 references, 1979, accessed May 13, 2006 at http://toxnet.nlm.nih.gov
  11. Segal, M “Too Many Drinks Spiked with Urethane” US Food and Drug Administration, September 1988, accessed at http://www.cfsan.fda.gov/~frf/fc0488ur.html.
  12. USEPA Toxic Release Inventory, Urethane Data 2004 (released April 12, 2006).
  13. VCU Virginia Commonwealth University, The Chemical/Biological Safety Section (CBSS) of the Office of Environmental Health and Safety, “Working with Urethane” 2006 accessed May 13,2006 at http://www.vcu.edu/oehs/chemical/biosafe/urethane.pdf.
  14. Holland JR, Hosley H, Scharlau C, Carbone PP, Frei E, Brindley CO, Hall TC, Shnider BI, Gold GL, Lasagna L, Owens AH Jr, Miller SP. A controlled trial of urethane treatment in multiple myeloma. Blood. 1966 Mar;27(3):328-42

[edit] See also


[edit] External links

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