Ethylene Glycol Diethyl Ether (CAS No. 629-14-1) Administered to CD-1 Mice on Gestational Days 6 Through 15
Report Date: Aug. 25, 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 CD-1 mice. Animals were exposed to EGDE in water, by gavage on gestational days 6 through 15 and sacrificed on gd 17. 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, 50, 150, 500, and 1000 mg/kg/day EGDE were administered in the teratology study.
The teratology study was conducted using a two-replicate design, with 12-14 animals assigned to each dose group in each replicate. Females were weighed and observed during daily treatment for clinical signs of toxicity. On gd 17, the gravid uterus of each dam was weighed, and the number and status of uterine implantation sites were recorded. Each live fetus was weighed, sexed, and examined for external, visceral, and skeletal malformations. A total of 22-24 dams (i.e., confirmed-pregnant females) per treatment group were evaluated in the study, with the following results:
- A no effect level for maternal toxicity was observed at 500 mg/kg/day . Significant maternal toxicity in the form of reduced body weight and body weight gain was observed at 1000 mg/kg/day . This effect appeared to be secondary to embryofetal toxicity at the 1000 mg/kg/day dose level.
- A no effect level for developmental toxicity was observed at 50 mg/kg/day . A significant increase in the percent litters with one or more malformed fetuses was observed at 150 mg/kg/day , whereas a significant increase in other measures of developmental toxicity was observed at doses of 500 mg/kg/day and above.
- At 500 and 1000 mg/kg/day , a dose-related increase in the incidence of craniofacial malformations, similar to those seen after exposure of experimental animals to other glycol ethers, was observed.
In conclusion, EGDE administered to pregnant CD-l mice during the period of major organogenesis marginally increased malformation incidence at 150 mg/kg/day and produced other signs of significant developmental toxicity in the absence of significant maternal toxicity at doses of 500 mg/kg/day and above. Significantly reduced prenatal viability and fetal body weight and a significant increase in teratogenicity was observed at 1000 mg/kg/day in the presence of significant maternal toxicity that was secondary to reduced gravid uterine weight. Thus, it appears that exposure to EGDE may selectively affect the developing organism.