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 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.