Ethylene Glycol Monoethyl Ether Acetate (EGEEA), a common chemical and solvent used in industry and in consumer goods, was tested for reproductive toxicity in Swiss CD-1 mice using the RACB protocol. It was part of a series of glycol ethers and congeners evaluated for structure-activity correlations using this design. Data collected on body weights, clinical signs, and food/water consumption during the dose-range-finding segment (Task 1) were used to set concentrations for the main study (Task 2) at 0.5%, 1.0%, and 2.0% EGEEA in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 0.93, 1.86, and 3.0 g/kg/d.
During Task 2, body weights were slightly reduced (less than 10%) only at the top dose, the same level at which water consumption was reduced by nearly equal to 20%. During Task 2, the mean number of litters per pair was reduced in the middle and high dose groups by 8% and 70%, respectively. The number of live pups/litter in these groups was reduced by 27% and 98%. In these two dose groups, the adjusted live pup weight also was reduced, by 5% and 13%, respectively. Thus, animals consuming 1% or 2% EGEEA delivered fewer, lighter pups in the presence of no or modest changes in body weight.
The Task 3 crossover used control and 2% EGEEA mice, and found that the EGEEA-treated females produced fewer fertile matings, and these had 94% fewer pups, and only 7% of them were born alive. There were no effects seen with EGEEA-treated males.
The control and 2% EGEEA F0 mice were killed and necropsied. There were no treatment-related changes in female body or organ weights, while treated males weighed 7% less than controls, and absolute testis weight was reduced by 9%. While there were no changes in sperm motility or density, the % abnormal forms doubled in the 2% EGEEA group at necropsy (from a control level of 3% abnormal forms).
There were insufficient live pups from the 2% EGEEA group to provide pups for an evaluation of the second generation at that concentration, so in Task 4, mice were evaluated from the control, 0.5% EGEEA-treated, and 1% EGEEA-treated groups. There was no indication of treatment-related reductions in growth to weaning, or in growth to mating at 74 ± 10 days of age. At the mating trial, there was a 50% reduction in the number of pairs that were confirmed sperm positive in the 1% group, but no change in the fertility of those pairs, and no change in the pup indices as a result of those matings.
After delivery of the F2's, all the mice were killed, and the F1's were necropsied. While there were no reductions in body weight, there was a 6% reduction in female relative liver weight at 1%. In males, liver weight was increased by 9% and 7% in the 0.5% and 1% EGEEA-treated groups, respectively, while epididymis weight was reduced by 9% in the 1% EGEEA group. Cauda epididymal sperm density was reduced by 30% at the top dose.
In summary, EGEEA was a reproductive toxicant in F0 mice, based on the large reductions in pup number in treated females and increased abnormal sperm in males. It was also a reproductive toxicant in the F1's, reducing epididymis weight and sperm number. The effects in the second generation were seen in the presence of changes in liver weight.
NTIS# PB86139565