The carcinogenic potential of ethyl carbamate (urethane): Risk assessment at human dietary exposure levels

Abstract

Summary-Ethyl carbamate is found in fermented foods: bread contains 3-15 ng/g, stone-fruit brandies 200-20,000 ngfg, and about one-third of table-wine samples analysed contained more than 10 ng/g. In animals, ethyl carbamate is degraded to C0 2 , H 2 0 and NH 3 , with intermediate formation ofethanol. This degradation has been shown tobe inhibited (postponed) in the mouse by ethanol concentrations in the blood of about 0.15% and higher. A quantitatively minor pathway involves a two-step oxidation of the ethyl group to vinyl carbamate and epoxyethyl carbamate, the postulated electrophilic moiety that reacts with DNA. This reaction is probably the mode of the mutagenic action observed in many cellular and animal systems. The fact that only vinyl carbamate, but not ethyl carbamate, is mutagenic in a standard Ames test is probably because there is insufficient production of the intermediate oxidation product in the standard test. Consistent with this metabolism is the carcinogenic activity of ethyl carbamate in various animal species and in different organs; this activity can be seen even after a single high dose in early life. Quantitative analysis of the total tumour incidences after chronic exposure of rats and mice to 0.1-12.5 mg ethyl carbamate/kg body weightjday in the drinking-water showed a dose-related increase. The main target organs were the mammary gland (female rats and mice having similar susceptibilities) and the Jung (mice only). On the basis of sex-and organ-specific tumour data and with a linear extrapolation to a negligible increase of the lifetime tumour incidence by 0.0001% ( one additional tumour in one milüon individuals exposed for life), a "virtually safe dose .. of 20 to 80 ng/kg body weight/day was estimated. The daily burden reached under normal dietary habits without alcoholic beverages is in the range of about 20 ng/kg body weightfday. Regular table-wine consumption would increase the risk by a factor of up to five. Regular drinking of 20 to 40 ml stone-fruit brandy per day could raise the calculated lifetime tumour risk to near 0.01%.

Growth and Arginine Metabolism of the Wine Lactic Acid BacteriaLactobacillus buchneriandOenococcus oeniat Different pH Values and Arginine Concentrations

“…However, some wines have been reported to have arginine levels as high as 2 to 5 g liter Ϫ1 after alcoholic fermentation (4,10,27). In a recent long-term study of the formation of EC in (24). Considering these values, addition of citrulline to the EC precursor pool by arginine-degrading MLB may lead to exceeding existing or future voluntary or legal EC limits.…”

Ethyl carbamate and hydrocyanic acid in food and beverages - Scientific Opinion of the Panel on Contaminants

“…It can be found in fermented foods and beverages like spirits, wine, beer, bread, soy sauce and yoghurt (Conacher and Page, 1986;Dennis et al, 1989;Battaglia et al, 1990;Schlatter and Lutz, 1990;Zimmerli and Schlatter, 1991;Sen et al, 1992;Sen et al, 1993;Benson and Beland, 1997;Kim et al, 2000). The structure and two routes of the formation of ethyl carbamate are illustrated in Figure 1.…”

Quantification of ethyl carbamate in soy sauce consumed in Korea and estimated daily intakes by age

“…Kim et al 3 reported that Koreans were exposed to up to 2.8 µg EC day −1 , which is not a negligible amount considering the 'virtually safe dose' suggested by Schlatter and Lutz. 4 Although the contribution of soy sauce to daily EC intake was rated second highest among Korean food items, the range of EC levels in soy sauce (ND-73.3 µg kg −1 , where ND denotes 'not detected') was found to be about four times broader than that in kimchi (ND-16.2 µg kg −1 ). 3 Kimchi, a fermented vegetable product made with varying amounts of different ingredients, including Korean cabbage, red pepper, garlic and other vegetables, is an important source of EC owing to its high daily consumption by Koreans.…”