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Ethylene oxide: evaluation of genotoxicity data and an exploratory assessment of genetic risk |
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| Authors: | A. T. Natarajan R. J. Preston V. Dellarco L. Ehrenberg W. Generoso S. Lewis A. D. Tates |
| Affiliation: | a Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Wassenaarseweg 72, 2300 RA, Leiden, The Netherlands b Chemical Industry Institute of Toxicology, Department of Cellular and Molecular Toxicology, P.O. Box 12137, 6 Davis Drive, Research Triangle Park, NC 27709, USA c Human Health Assessment Group, Office of Health and Environmental Assessment (RD-689), U.S. Environmental Protection Agency, 401 M St., SW, Washington, DC 20460, USA d Department of Radiobiology, University of Stockholm, S-10691, Stockholm, Sweden e Oak Ridge National Laboratory, Biology Division, P.O. Box Y, Oak Ridge, TN 37831-6050, USA f Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC 27709, USA |
| Abstract: | A risk estimate of the heritable effects of ethylene oxide exposure, using the parallelogram approach, as suggested by Frits Sobels, is described. The approach is based on available data on the ethylene oxide-induced responses for the same genetic endpoint in somatic cells of both laboratory animals and humans, and for germ cell mutations in the same laboratory animal. Human germ cell effects are estimated. The available data sets for this approach were evaluated. We consider this as complementary to the genetic risk assessment carried out by U.S. EPA scientists, in which the risk from heritable (reciprocal) translocations induced by ethylene oxide was estimated. In the present study we restricted our assessment to dominant mutations. The sensitivity factor relating mouse to man was based on ethylene oxide-induced HPRT mutant frequencies in lymphocytes in vivo. From this comparison, it could be concluded that occupational exposure for 1 year to 1 ppm ethylene oxide would lead to a risk of a dominantly inherited disease in the offspring of 4 × 10−4 above the background level. The uncertainty interval of this figure is quite large (0.6–28) × 10−4. The values are compatible with the existing estimates of the corresponding risk from exposure to low LET radiation when the genotoxic potency ratio of ethylene oxide and radiation is considered. This risk estimation approach has allowed us to identify additional data that are required for a more complete risk estimation of the heritable effects of ethylene oxide, or indeed any mutagenic chemical. |
| Keywords: | Ethylene oxide Dominant heritable effect Genetic risk assessment |
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