Ethylene glycol, a chemical which causes skeletal malformations in rats, was administered by gavage to sperm positive CD rats (7 per group for two doses and seven sacrifice times; i.e., 14 groups) on gestational days 6 through 15 at doses of 0 or 2500 mg/kg/day . Subsequently, two groups of dams were killed on gd 18 or 20, and fetal skeletons were double-stained and examined for degree of ossification in selected regions as well as for skeletal malformations. Other groups of dams were allowed to deliver their litters which were fostered to untreated dams on postnatal day 1. Pups were sacrificed by litter on pnd 1, 4, 14, 21 or 63. Pup skeletons were double-stained and examined for degree of ossification and skeletal malformations.
Maternal body weight after initiation of dosing and weight gain during gestation were significantly below controls in the gd 18 and pnd 1 EG groups. Corrected maternal weight gain was reduced in the gd 18 EG group only. Gd 20 and pnd 63 EG groups had significantly decreased weight gain during treatment. When all groups were pooled, maternal weights during and after treatment as well as maternal weight gain during treatment and gestation after EG exposure were all significantly below controls. No difference in gestational day of delivery between controls and the EG-treated dams was seen.
Fetal weights per litter were significantly decreased with EG treatment in the gd 18 and 20 groups. There was no increase in % resorptions per litter in EG treated dams sacrificed on gd 18 or 20. No significant effects of treatment were seen for pup body weight in any of the individual or combined postnatal groups except that body weight on pnd 1 for all postnatal EG groups combined was significantly below controls. Number of live pups per litter were significantly lower on pnd 1 in the pnd 1 EG group only. Percent fetuses/pups with skeletal malformations per litter were significantly increased in all EG groups except for the pnd 63 group, with a predominance of axial skeletal defects. Percent total ossification, percent sternebrae ossified and percent vertebral centra ossified were significantly reduced in the EG groups but were not significantly different when co-varied by body weight on gd 18, 20 or pnd 63. All were significantly lower than controls in the pnd 1 through pnd 21 groups. There was no effect of dose or body weight on ossification of fore or hindlimb digits.
In conclusion, ethylene glycol treatment caused developmental delays and apparent malformations in the perinatal rat skeleton which were resolved by pnd 63.