Dipropylene glycol is a high production glycol used in the manufacture of nitrocellulose solvent, lacquers, paints, printing inks, and shellac varnishes. In general, the toxicity of the glycols decreases as the molecular weight of the molecule increases. Therefore, it could be predicted that DPG would be less toxic than low molecular weight glycols such as ethylene glycol. Since there is a lack of data with which to confirm this hypothesis, this study was conducted to assess the potential for DPG to cause developmental toxicity and to compare its toxicity to other glycols. DPG (CAS No. 25265-71-8) was administered by gavage to timed-pregnant CD rats (20-25/group) on gestational days (gd) 6-15 at dose levels of 0, 800, 2000, or 5000 mg/kg body weight/day. Animals were observed daily for clinical signs of toxicity. Food and water weights and body weights were reported on gd 0, 3, 6, 9, 12, 15, 18, and 20. All animals were killed on gd 20 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development.
The mid-dose (2000 mg/kg/day DPG) produced maternal lethality in 1 out of 25 pregnant animals while the high dose (5000 mg/kg/day) caused the death of 2 out of 22 pregnant animals. Maternal body weights were significantly decreased in the 5000 mg/kg/day group from gd 9 through gd 20. Maternal body weight gain of the animals exposed to 5000 mg/kg/day was significantly reduced across the treatment period and across gestation. Corrected maternal weight gain (gestation gain minus gravid uterine weight) was also significantly reduced in the 5000 mg/kg/day group. Absolute (g/day) and relative (grams/kg body weight/day) food consumption of animals in the 5000 mg/kg/day group were significantly decreased from control for the intervals from gd 6 to 9 and gd 9 to 12. As a result, the absolute and relative food consumption was decreased during treatment (gd 6 to 15) and across gestation (gd 0 to 20). Absolute food consumption was decreased in the animals from the 2000 mg/kg/day group from gd 6 to 9. Relative water consumption by the animals in the 5000 mg/kg/day group was increased for all measurement periods between gd 9 and gd 18. Relative liver weight of the maternal animals was significantly increased in the animals exposed to 2000 and 5000 mg/kg/day of DPG.
No effects of DPG were observed on pre- or post-implantation loss. The mean male and female body weights per litter were associated with a significant decreasing linear trend, but mean male and female body weights were not significantly different from control in the exposed groups. Examination of the fetuses for external, visceral and skeletal malformations and variations did not reveal any significant effects among dose groups.
In summary, there was no maternal or developmental toxicity at 800 mg/kg/day of DPG. Maternal toxicity and lethality were observed at 2000 and 5000 mg/kg/day, but developmental toxicity was not observed even at these maternally lethal exposures.