The Developmental Toxicity of Diethylene Glycol Dimethyl Ether in Mice

The Developmental Toxicity of Diethylene Glycol Dimethyl Etherin Mice. PRICE, C. J., KIMMEL, C. A., GEORGE, J. D., AND MARR,M. C. (1987). Fundam. Appl. Toxicol. 8, 115–126. Diethyleneglycol dimethyl ether (diEGdiME) is structurally related toseveral compounds which produce reproductive and developmentaltoxicity, including teratogenicity in laboratory animals. Inthe present study, diEGdiME (0, 62.5, 125, 250, or 500 mg/kg/day)was administered by gavage in distilled water to timed-pregnantCD-1 mice during major organogenesis [gestational days (gd)6–15]. Clinical status of treated females was monitoreddaily during treatment and on gd 17. At sacrifice (gd 17), pregnancywas confirmed by uterine examination for 20–24 dams pergroup; each live fetus was examined for external, visceral,and skeletal malformations. No maternal deaths, morbidity, ortreatment-related clinical signs were observed. Reduced maternalweight gain during treatment at 250 mg/kg/day was primarilyattributed to compromised pregnancy status resulting in reducedgravid uterine weight. Maternal weight gain during gestationcorrected for gravid uterine weight, and relative liver weight(% body weight) were not affected. Average fetal body weight/litterwas significantly reduced at 125 mg/kg/day. The percentageof postimplantation loss/litter (5, 8, 7, 12, and 50% for controlthrough high dose) and the percentage of malformed live fetuses/litter(0.4, 0, 2, 24, and 96%) were significantly increased at 250mg/kg/day. Developmental defects involved primarily the neuraltube, limbs and digits, craniofacial structures, abdominal wall,cardiovascular system, urogenital organs, and both the axialand appendicular skeleton. In summary, oral administration ofdiEGdiME during major organogenesis did not produce any distinctivesigns of maternal toxicity, but did produce selective and profoundadverse effects upon fetal growth, viability, and morphologicaldevelopment at 125 mg/kg/day.