The Developmental Toxicity of Triethylene Glycol Dimethyl Ether in Mice1

The Developmental Toxicity of Triethylene Glycol Dimethyl Etherin Mice. GEORGE, J. D., PRICE, C. J., KIMMEL, C. A., AND MARR,M. C. (1987). Fundam. Appl. Toxicol. 9, 173–181. Triethyleneglycol dimethyl ether (triEGdiME) is structurally related toseveral compounds which produce reproductive and developmentaltoxicity, including teratogenicity in laboratory animals. Inthe present study, triEGdiME (0, 250, 500, or 1000 mg/kg/day)was administered by gavage to timed-pregnant CD-I mice duringmajor organogenesis (Gestational Days (gd) 6– 15). Maternalclinical status was monitored daily during treatment. At sacrifice(gd 17), confirmed-pregnant females (26–28 per group)were evaluated for clinical Status and gestational outcome;each live fetus was examined for external, visceral, and skeletalmalformations. No maternal death or morbidity was observed.Clinical signs of toxicity including piloerection were minor.Maternal weight gain during treatment, gestation, and maternalweight gain during gestation corrected for gravid uterine weightwere not affected. Gravid uterine weight decreased in a dose-relatedmanner, indicating compromised pregnancy status. Relative maternalliver weight (% body wt) was significantly increased over controlsat doses 500 and 1000 mg/kg/day. Average fetal body weightper litter was significantly reduced at doses 500 mg/kg/day.The percent age malformed live fetuses per litter (0.3, 0, 0.8,and 11.1%) was significantly increased at 1000 mg/kg/day. Majormalformations affected primarily the development of the neuraltube, cranio facial structures, and the axial skeleton. In summary,oral administration of triEGdiME during major organogenesisproduced only marginal signs of altered maternal status, asevidenced by an increase in maternal liver weight, and causedselective adverse effects upon fetal growth and morphologicaldevelopment at doses 500 mg/kg/day.