Diethylene glycol diethyl ether was evaluated for developmental toxicity in timed-pregnant CD-l mice. DGDE was administered daily in distilled water by gavage at 0, 300, 1500, 3000 and 4500 mg/kg on gestational days 6 through 15.
Maternal toxicity was evident in dams exposed to DGDE at doses greater than or equal to 1500 mg/kg/day . CNS function was highly sensitive to treatment as evidenced by ataxia, coma and lethargy in a majority of the dams dosed. Mortality among confirmed--pregnant animals occurred with incidences of 0% (0/29), 0% (0/24), 8.6% (3/35), 11.8% (4/34) and 100% (14/14) in the control through high-dose groups, respectively. Deaths occurred early during the dosing period (gd 6-9), and all deaths at the high dose were preceded by evidence of severe CNS depression.
There were no effects of treatment on any of the parameters that indicate changes in the numbers of resorptions, nonlive implants, fetal deaths as well as live fetuses. Average fetal body weight per litter was significantly lower at 3000 mg/kg DGDE when compared with the control group. The incidence of major malformations was low in all groups and was dose independent. The 1500 mg/kg/day dose was a no observed effect level for developmental toxicity.
In conclusion, development of the CD-1 mouse is not sensitive to DGDE administered by gavage at maternally nontoxic doses. A NOEL for DGDE-induced developmental toxicity was 1500 mg/kg/day , a dose which produced maternal CNS depression and lethality (8.6%). The lowest dose given, 300 mg/kg/day, represented a NOEL for DGDE-induced maternal toxicity.