The developmental toxicity of triethylene glycol dimethyl ether in mice

Triethylene glycol dimethyl ether (triEGdiME) is structurally related to several compounds which produce reproductive and developmental toxicity, including teratogenicity in laboratory animals. In the present study, triEGdiME (0, 250, 500, or 1000 mg/kg/day) was administered by gavage to timed-pregnant CD-1 mice during major organogenesis (Gestational Days (gd) 6-15). Maternal clinical 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 skeletal malformations. No maternal death or morbidity was observed. Clinical signs of toxicity including piloerection were minor. Maternal weight gain during treatment, gestation, and maternal weight gain during gestation corrected for gravid uterine weight were not affected. Gravid uterine weight decreased in a dose-related manner, indicating compromised pregnancy status. Relative maternal liver weight (% body wt) was significantly increased over controls at doses greater than or equal to 500 and 1000 mg/kg/day. Average fetal body weight per litter was significantly reduced at doses greater than or equal to 500 mg/kg/day. The percentage malformed live fetuses per litter (0.3, 0, 0.8, and 11.1%) was significantly increased at 1000 mg/kg/day. Major malformations affected primarily the development of the neural tube, craniofacial structures, and the axial skeleton. In summary, oral administration of triEGdiME during major organogenesis produced only marginal signs of altered maternal status, as evidenced by an increase in maternal liver weight, and caused selective adverse effects upon fetal growth and morphological development at doses greater than or equal to 500 mg/kg/day.