Ethylene Glycol Diethyl Ether (CAS No. 629-14-1) Administered to New Zealand White Rabbits on Gestational Days 6 Through 19
Report Date: Oct. 16, 1987
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Ethylene glycol diethyl ether, a member of the glycol ether class of industrial solvents, was evaluated for toxic and teratogenic effects in timed-pregnant New Zealand White rabbits. Animals were exposed to EGDE in water, by gavage on gestational days 6 through 19 and sacrificed on gd 30. Prior to initiation of the teratology study, a preliminary study was conducted in order to establish appropriate doses for use in the teratology study. Based on the results of the preliminary study, doses of 0, 25, 50 and 100 mg/kg/day EGDE were administered in the teratology study.
The teratology study was conducted using a three replicate design, with 12-14 animals assigned to each dose group in each replicate. A total of 26-32 does (i.e., confirmed-pregnant females) per treatment group were evaluated in the study, with the following results:
- A no observed effect level for maternal toxicity was 100 mg/kg/day based on gestational and corrected maternal body and liver weight.
- EGDE had a minimal effect on maternal weight gain during treatment (gd 6-19 and gravid uterine weight at 100 mg/kg/day that appeared to be secondary to an increased incidence of resorptions).
- A no effect level for developmental toxicity was observed at 25 mg/kg/day .
- A significant increase in the percent of litters with one or more malformed fetuses (all malformations combined) was observed at 50 mg/kg/day . A significant increase in the percent resorptions per litter, the percent malformed fetuses per litter (all malformations combined), and in the number of litters with one or more fetuses with external, visceral, or skeletal malformations occurred at 100 mg/kg/day .
In conclusion, exposure of timed-pregnant New Zealand White rabbits to EGDE during gestation resulted in clearcut evidence of developmental toxicity at doses of 50 mg/kg/day and above, in the absence of clearcut maternal toxicity.