Diethylene glycol diethyl ether was evaluated for developmental toxicity in artificially inseminated, New Zealand White rabbits. DGDE was dissolved in distilled water to provide doses of 0, 50, 200 and 400 mg/kg, and subsequently administered daily by gavage from gestational days 6 through 19.
DGDE treatment did not adversely influence maternal viability. The only exception was that one of the 27 confirmed pregnant dams (3.7%) in the 400 mg/kg group died on gd 15. Necropsy of that animal indicated that its death was related to DGDE exposure. The pregnancy incidence was similar across dose groups and ranged from 85.7% to 88.6%.
Clinical signs of toxicity were observed during treatment with the greatest occurrence in the high dose group. Ataxia, coma, dyspnea and postdosing vocalization predominated at 400 mg DGDE/kg/day. Weight loss (greater than or equal to 150 g/day) occurred in both the control and treated animals.
Maternal body weight was similar among dose groups on gd 0 as well as throughout the treatment and post-treatment periods. When weight gain was compared, however, dams exposed to 400 mg DGDE/kg had significantly lower weight gain than controls during the treatment period. Liver and gravid uterine weights did not differ among dose groups.
There was no effect of treatment on embryo viability. The incidences of resorptions and fetal deaths were similar among the treatment groups. In addition, the number of live fetuses per litter and average fetal body weight per litter (both sexes) were not affected by DGDE treatment. Nonetheless. when fetal body weights were analyzed by sex, female weight manifested a significant decreasing trend which was related to the statistically nonsignificant, weight reduction in the 400 mg/kg/day dose group, In addition, embryo/fetal morphogenesis was not observably altered by DGDE treatment, based on the findings of external, visceral and skeletal examinations of gd 30 fetuses.
In conclusion, embryonic and fetal development of the NZW rabbit was not sensitive to DGDE as tested in the present study at maternally toxic doses. Although clearcut developmental effects were not identified for DGDE, the significant decreasing trend in body weight of female fetuses at 400 mg/kg/day is marginal evidence of DGDE-induced developmental toxicity. Since maternal toxicity was also observed at the high dose, the 200 mg/kg/day dose represents a no observed effect level for both DGDE induced developmental and maternal toxicities.