The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Ethylene Glycol (EG), an industrial chemical precursor, solvent, and component of antifreezes and numerous other consumer products, was tested for reproductive toxicity in Swiss CD-1 mice using the RACB protocol. It was part of a large structure-activity series of glycol ethers and congeners evaluated using this design, generating data on compounds for which there were few or no reproductive data in the open literature. Food and water consumption,body weight and clinical sign data from Task 1 were used to set levels for the Task 2 at 0.0, 0.25%, 0.50%, and 1.0% EG in drinking water. Based on water consumption data collected during Task 2, these concentrations produced calculated EG consumptions of approximately 400, 850, and 1700 mg/kg/d.
There was no EG-related depression of body weight during the cohabitation phase of the study. For the cohabitation phase, the total number of litters/pair was reduced by 9% at the high dose, and the mean number of pups/litter was reduced by nearly equal to 5%. Pup weight (both absolute and adjusted for litter size) was also reduced at the middle and top doses by 3% and 7%, respectively. The relatively small degree of change in pup number contributed to the decision not to conduct a Task 3 crossover mating to determine the affected sex. Thus, the F0 mice were killed at the end of the cohabitation phase (Task 2), and discarded without necropsy.
It was noted during the nursing period that selected high-dose F1's had abnormal facial development. Selected affected animals were necropsied at weaning, and their skeletons stained with Alizarin Red S. Rib/vertebral and facial bone abnormalities were noted in the treated skeletons, and were absent from the controls. The remaining mice from the control and high dose groups were evaluated by an F1 mating trial at 74 ± 10 days of age. There were no significant effects of EG consumption on the number or viability of F2 pups. Pup weight adjusted for litter size was reduced by 5%, a change of borderline significance (p=0.064). After the F2 litters were born, the F1 adults were killed and necropsied. Terminal body weight was not changed, but there was a nearly equal to 8.5% reduction in brain weight in both sexes, and a 9% reduction in relative liver weight for females.
These data show that EG, at sufficient doses, can reduce litter size and pup weight without affecting F0 body weight. Of potentially more interest, however, were the skeletal terata induced by 1% EG consumption. This study served to identify those effects, and stimulated a follow-up study.
NTIS # PB84241108