Genotoxic effects of ethylene oxide and their relevance to human cancer.

The potential danger of ethylene oxide (EtO*) to human health has been discussed for several years. Although its mutagenic action has been known for a long time (1), it was not until 1967, when cytogenetic studies of workers occupationally exposed to EtO were published that serious attention was paid to its potential cancer risk (2). The toxicological interest in EtO is based, first of all, on the fact that this chemical, the simplest member of the class of epoxides, is widely used in the chemical industry. The consumption of EtO in Western Europe is ~2.5 x 10* tons per year, the USA annually produces ~ 800 000 tons and ~ 150 000 workers deal with it daily in different industrial processes (3). Examples of industrial processes include the production of ethylene glycol (antifreeze), as well as of synthetic fibers, films, detergents, etc. The sterilization of heat-sensitive medical materials by EtO is another important field of use for this chemical. Since EtO at room temperature is a colorless and odorless (below 700 p.p.m.) gas it is likely that those dealing with sterilization would inhale it. Furthermore, EtO is an alkylating agent, which may react directly with nucleophilic macromolecules (such as DNA, RNA and proteins) without requiring metabolic activation. The ability of EtO to alkylate (hydroxyethylate) DNA (4) and to introduce alkylations in haemoglobin (5) has been demonstrated. EtO may be considered as a model substance for the whole class of epoxides for studies of DNA and protein damage and for DNA repair mechanisms. Since EtO is produced metabolically by soil microorganisms from ethylene and by combustion of organic compounds, it is an environmental carcinogen. Moreover, ethylene is present as a pollutant in urban air and as a component of cigarette smoke. The inhalation of ethylene in animals results in exhalation of EtO (6,7). The genetic effects of epoxides, including EtO, and the problems connected with the risk estimation of epoxides have been reviewed by Ehrenberg and Hussain (8). Several recent reviews have summarized the toxicological and epidemiological data (9—12). In our review we will up-date the present knowledge with the emphasis on carcinogenic and genotoxic effects of EtO in experimental animals and occupationally exposed persons.