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Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, the prenatal developmental toxicity of ETBE was determined in rabbits. New Zealand white rabbits were given ETBE by gavage at 100, 300, or 1,000 mg/kg/day on gestational days (GDs) 6-27, and the pregnancy outcome was determined on GD 28. Neither death nor abortion occurred in the pregnant rabbits at any dose. Slightly and significantly suppressed maternal body-weight gain and transiently decreased maternal food consumption were found at 1,000 mg/kg/day during the administration period. At this dose, no changes in clinical or macroscopic finding were noted in dams. No treatment-related changes were observed in any dam treated at 300 mg/kg/day or less. There was no significant effect of ETBE on the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, incidences of pre- and postimplantation loss, viability of fetuses, fetal body weight, sex ratio of fetuses, or weights of gravid uteri. No significant difference was detected in the incidences of fetuses with malformations or variations between the ETBE-treated and control groups. Also, no adverse effects on the progress of ossification were noted in fetuses of dams given ETBE. Based on these findings, it is concluded that the no observed adverse effect levels of ETBE were 300 mg/kg/day for dams and 1,000 mg/kg/day for fetuses in rabbits.

A uterine choriocarcinoma was found in a 49-wk-old virgin Donryu rat given intrauterine administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). The tumor was macroscopically present as a bloody cystic mass and microscopically composed of 2 kinds of cells: small basophilic cells similar to cytotrophoblasts in the rat placenta and large cells with big nuclei resembling giant trophoblasts. The giant cells were positive for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), although immunohistochemical examination was negative or nonspecific for chorionic gonadotrophins, including beta human chorionic gonadotrophin (beta hCG), human placental lactogen (hPL), and placental glycoprotein (SP-1), or for placental alkaline phosphatase (ALP). However, the animal exhibited a slight mammotropic status. The results thus suggest a choriocarcinoma nature for this uterine tumor and that the tumor cells secrete a weakly mammotrophic hormone.