RECONSIDERATION OF THE GENETIC RISK ASSESSMENT FOR ETHYLENE-OXIDE EXPOSURES

The US Environmental Protection Agency (EPA) developed a genetic risk assessment model for exposures to ethylene oxide utilizing data on the induction of reciprocal translocations in mole germ cells [Rhomberg e t al. 1990]. This particular approach served as a reasonable initial a ttempt, albeit somewhat limited with regard to endpoint and only parti ally attentive to the mechanisms of induction of genetic alterations a nd the behavior of chromosomes during meiosis. The present paper discu sses the scientific basis for a reassessment of the EPA model, providi ng data and hypotheses related to effective dose to the target cells a nd shape of the dose-response relationship at low doses, and dose rate s. While the present genetic risk assessment approach is discussed in terms of ethylene oxide, it would be applicable to most mutagenic chem icals. The outcome of the discussion is that the generic risk for expo sed males from reciprocal translocation induction will be negligible a t low doses since the dose-response curve is likely to be a function o f the square of the dose. In addition, the proportion of genetically u nbalanced live born offspring in humans arising from reciprocal transl ocation carriers is less than 10% of the frequency formed through meio tic segregation and fertilization for such carriers. Simply from a con sideration of mechanism-namely, the very high probability of DNA repai r prior to the next S-phase for a resting oocyte-it would be predicted that there would be a very low to negligible frequency of translocati ons in Female germ cells from ethylene oxide exposure. It is further s tressed that additional components of a genetic risk model require a c onsideration of all germ cell stages in the mole, and the inclusion of calculations for point and deletion mutations. Some indications of li kely response are presented with these points in mind. (C) 1995 Wiley- Liss, Inc.