The developmental toxicity of diethylene glycol dimethyl ether in mice

Diethylene glycol dimethyl ether (diEGdiME) is structurally related to several compounds which produce reproductive and developmental toxicity, including teratogenicity in laboratory animals. In the present study, diEGdiME (0, 62.5, 125, 250, or 500 mg/kg/day) was administered by gavage in distilled water to timed-pregnant CD-1 mice during major organogenesis [gestational days (gd) 6-15]. Clinical status of treated females was monitored daily during treatment and on gd 17. At sacrifice (gd 17), pregnancy was confirmed by uterine examination for 20-24 dams per group; each live fetus was examined for external, visceral, and skeletal malformations. No maternal deaths, morbidity, or treatment-related clinical signs were observed. Reduced maternal weight gain during treatment at greater than or equal to 250 mg/kg/day was primarily attributed to compromised pregnancy status resulting in reduced gravid uterine weight. Maternal weight gain during gestation corrected for gravid uterine weight, and relative liver weight (% body weight) were not affected. Average fetal body weight/litter was significantly reduced at greater than or equal to 125 mg/kg/day. The percentage of postimplantation loss/litter (5, 8, 7, 12, and 50% for control through high dose) and the percentage of malformed live fetuses/litter (0.4, 0, 2, 24, and 96%) were significantly increased at greater than or equal to 250 mg/kg/day. Developmental defects involved primarily the neural tube, limbs and digits, craniofacial structures, abdominal wall, cardiovascular system, urogenital organs, and both the axial and appendicular skeleton. In summary, oral administration of diEGdiME during major organogenesis did not produce any distinctive signs of maternal toxicity, but did produce selective and profound adverse effects upon fetal growth, viability, and morphological development at greater than or equal to 125 mg/kg/day.