Ethyl carbamate. Documentation of proposed values of occupational exposure limits (OELs)
Journal Title: Podstawy i Metody Oceny Środowiska Pracy - Year 2015, Vol 31, Issue 3
Abstract
Ethyl carbamate (urethane, CAS 51-79-6) is a solid, odorless and soluble in water and organic solvents. In an environment it occurs as a natural product produced during alcoholic fermentationof foods and beverages containing alcohol. They could be the main source of exposure of the generalpopulation. The technical formulations of ethyl carbamate, obtained through organic synthesis,achieve a high chemical purity. Ethyl carbamate is mainly used as an intermediatein organic synthesis (including manufacturing amino resin), and its aqueous solutions assolvents for pesticides, fumigants, cosmetics and pharmaceuticals used in veterinary medicine.In Poland, occupational exposure to ethyl carbamate (inhalation and/or skin contact) occurs inseveral plants producing and using it, and many people are exposed every year.In humans, no acute poisoning with ethyl carbamate was noticed. There is no information in theavailable literature about epidemiological data and chronic toxicity in humans occupationallyexposed.The LD50 value of ethyl carbamate given intragastrically to rats is 1810 mg/kg of body weight. Inacute intoxication in animals, narcosis and sedation (used in veterinary medicine) and narcoticeffects were observed. Ethyl carbamate did not show irritation and sensitization for animals.Subchronic exposure of rats and mice on ethyl carbamate administered in drinking water (with concentrations of 110 — 10.000 ppm, or in doses of 8 — 622 mg/kg/day for rats and 18.3 — 1667 mg/kg/ day for mice) resulted in, depending on the size of the exposure, immunosuppressive activity. Inanimals, observed nephropathy and cardiomyopathy were also, and in males also damages toliver were observed. In addition to the immunotoxicity in mice, proliferation changes in the genitaltract and in the lungs were observed .After 2-year exposure of mice for ethyl carbamate in drinking water (with concentrations of 10to 90 ppm, corresponding to a dose of 1.17 to 12 mg/kg/day) the toxic effects for liver, heart,lung, and uterus were observed. Ethyl carbamate in concentration in water 30 or 90 ppm (4 or12 mg/kg /day) caused an increasing number of deaths of animals.Based on the results of standardized tests, ethyl carbamate is classifi ed as a substance with a weakmutagenic and genotoxic effects.The results of subchronic and chronic toxicity studies of ethyl carbamate administered in variousways and various species of laboratory animals show its carcinogenic effect. The compound wasfound as a cause of cancer of lung, liver, blood vessels and skin, and lymphomas and leukemia. Ethyl carbamate cause a negative impact on fertility. It has embryotoxic, fetotoxic and teratogeniceffects. Ethyl carbamate is absorbed into an organism rapidly and completely after exposure in different ways and is immediately subjected to distribution in a body. Majority of ethyl carbamate (90%)is metabolized to ethanol, ammonia and carbon dioxide, which is excreted in the expired air.About 5% of ethyl carbamate is transformed by CYP2E1 to the vinyl carbamate and then to vinylcarbamate epoxide which, by binding to DNA and RNA, is responsible for the genotoxic andcarcinogenic effects of the compound. The excretion of metabolites in the urine and faeces is lowand amounts 2 — 8% and 0.3 — 1%, respectively.Ethyl carbamate classifi ed by IARC (2010) as 2.A group — agents probably carcinogenic to humans.The European Union classifi ed it as 1.B group — substances that can cause cancer. The maximum allowable concentration (MAC) for ethyl carbamate was not set in any country. SCOEL did not established OEL values, since the compound is in Group A carcinogenicity, i.e., genotoxic carcinogens with no establish limit values based on health effect. Ethyl carbamate causes the cancer in rats and mice in many target organs following administration to a differently ways. Ethyl carbamate is toxic, mutagenic or clastogenic, especially in the presence of a metabolic activation.The risk of additional lung cancer was estimated on the basis of experimental data (2-year exposureof mice, p.o.):– 10-3 to 40 years of exposure to ethyl carbamateat a concentration of 0.0093 (≈ 0.01) mg/m3– 10-4 to 40 years of exposure to ethyl carbamateat a concentration of 0.00093 (≈0.001) mg/m3– 10-5 to 40 years of exposure to ethyl carbamateat a concentration of 0.000093(≈ 0.0001) mg/m[sup]3[/sup].Based on this estimation it is proposed to accept the MAC-TWA value for ethyl carbamate at risk10-4 or 0.001 mg/m[sup]3[/sup]. There is no reason to determine the value of short-term exposure limit(STEL) and the biological exposure index (BEI). Additional labeling as „Carc. 1.B”, “Ft — fetotoxicity”and „skin — absorption of substances through the skin may be similarly important, as withinhalation” was proposed.
Authors and Affiliations
Jadwiga Szymańska, Elżbieta Bruchajzer
Keywords
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