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.
This study was conducted to assess the potential for orally administered diethylene glycol to cause developmental toxicity. The oral route of administration corresponds to the most hazardous potential human route of exposure to DEG. The CD-1 mouse was selected as the test animal for this study based on evidence for DEG-induced teratogenicity in the CD-1 mouse reported by the National Toxicology Program in a continuous breeding study, as well as the paucity of developmental toxicity data.
Diethylene glycol (DEG, CAS No. 111-46-6) was administered by gavage to timed-pregnant Swiss (CD-1) mice (26-31 per group) on gestational days 6-15 at dose levels of 0, 1250, 5000, or 10,000 mg/kg body weight/day. Animals were observed daily for clinical signs of toxicity. Food and water consumption and body weights were determined on GD 0, 3, 6, 9, 12, 15, and 17. All animals were killed on GD 17 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development.
Maternal body weights did not differ significantly between the control group and any of the DEG-treated groups. Relative (g/kg body weight/day) water intake was significantly increased over control for every interval starting at GD 6 in the 5000 and 10,000 mg/kg/day DEG treated animals. Maternal animals given 10,000 mg/kg/day of DEG had significantly decreased relative (g/kg body weight/day) food consumption from GD 6 to 12.
One maternal animal treated with 10,000 mg/kg/day of DEG was sacrificed in extremis on gd 10. Necropsy and histopathologic examinations revealed evidence of renal degeneration and suggested that morbidity was due to toxicity produced by DEG. Necropsy of maternal animals on GD 17 showed that animals from the 5000 and 10,000 mg/kg/day DEG groups had significantly increased absolute (g) and relative (% body weight) kidney weights when compared to control animals. At 10,000 mg/kg/day, renal lesions (renal tubular degeneraion) were noted in 2/27 females which survived to scheduled 11% (3/28) of the pregnant females at the high dose showed evidence of renal pathology as compared to 0/20 pregnant females from the vehicle control group.
No effects of DEG were observed on pre- or post-implantation loss. The mean fetal body weight per dose group on GD 17 was associated with a significant decreasing linear trend (99%, 96%, and 85% of control from the low to high dose) and mean fetal body weight was significantly decreased in the highdose group (0.865 g) when compared to controls (1.012 g). Examination of the fetuses for external, visceral and skeletal malformations did not reveal any significant effects between dose groups. The decrease in fetal body weight indicated developmental toxicity at the 10,000 mg/kg/day exposure level of DEG.
In summary, there was no maternal or developmental toxicity at 1250 mg/kg/day of DEG. The mid-dose (5000 mg/kg/day DEG) produced significant maternal toxicity, but no clear evidence of developmental toxicity. The high dose (10,000 mg/kg/day DEG) caused the death of I out of 28 pregnant dams, maternal toxicity and developmental toxicity.