Ethyl carbamate: analytical methodology, occurrence, formation, biological activity and risk assessment

Abstract

Ethyl carbamate (EC) is a genotoxic compound in vitro and in vivo, it binds covalently to DNA and is an animal carcinogen. Today, EC is mainly found as a natural trace constituent in different alcoholic beverages and in fermented food items. Data on analytical methodology and the levels of EC in different food items are summarized and the daily burden of humans is estimated. Under normal dietary habits excluding alcoholic beverages, the unavoidable daily intake is 10-20 ng/kg b.w. On the basis of the evaluation of all toxicity data and its mode of action a conventional risk assessment of EC indicates that this level represents a negligible lifetime cancer risk (less than 0.0001%). Individual habits may greatly enhance the risk. Regular drinking of table wine (500 ml/day) would increase the risk up to 5 times, regular drinking of stone-fruit distillates (20-40 ml/day) would raise the calculated hypothetical tumor risk to near 0.01%. Human exposure to carcinogenic compounds should be as low as reasonably achievable. In order to take reliable measures to reduce EC levels in beverages and foods, it is crucial to know the mode of its formation. For its natural formation the presence of ethanol is absolutely required. In stone-fruit distillates hydrogen cyanide together with photochemically active substances are crucial to form EC. The main part of EC is formed after the distillation involving photochemical reactions. In wine (and probably bread) significant EC formation seems to depend on heat treatment. While in distillates hydrogen cyanide is the most important single precursor, in wine different carbamyl compounds, mainly urea, seem to be involved in EC formation. Despite this apparent difference a common EC formation pathway is discussed for all alcoholic beverages by assuming cyanic-/isocyanic acid as an important ultimate reactant with ethanol. Some ideas are presented as to the possible course of future work.