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 (EGEE), 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% w/v EGEE in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 0.76, 1.50, and 2.6 g/kg/d.
There were no effects on body weights during the continuous cohabitation portion of the study. Two females died in both the control and high dose groups. Water consumption was unchanged by the addition of EGEE.
No pairs in the 2% EGEE group had any litters of pups, live or dead. In the middle dose group (1% EGEE), the number of litters/fertile pair was reduced by 35%, there were nearly equal to 2.6 live pups/litter vs. a control mean of 9.8, the proportion of pups born alive was reduced by 50%, and the weight of the live pups, adjusted for litter size, was reduced by 12%. The fertility indices in the low dose (0.5% EGEE) were not affected.
Task 3 crossover mating trials were conducted with the controls and both the 2% EGEE and 1% EGEE groups. With the 2% EGEE mice, no litters were delivered of treated females mated with control males, while 5/18 control females delivered a litter after mating with a treated male (significantly less than the 17/20 control x control matings). The proportion born alive, the sex ratio, and the adjusted live pup weight were not affected when one parent had been exposed to 2% EGEE.
For the 1% EGEE mice, 78% of control pairs were fertile (bore any young), while only 44% of matings were fertile if the male had consumed 1% EGEE. The fertility of treated females x control male matings was not different from that of controls. Litters from control dams mated with treated males were not different from controls, while litters from treated females x control males had pups that were 12% lighter than controls, when adjusted for litter size.
After the last Task 3 mating, and 7 days of lavage for vaginal cytology, the F0 mice from the control, 1% and 2% EGEE groups were killed and necropsied. The 15% reduction in female body weight at 2% EGEE may be related to the fact that these animals never were pregnant. Adjusted liver weight was increased in the 1% EGEE-treated females females, while adjusted brain weight was decreased in 2% EGEE-treated females by 10%. In males, liver weight was unchanged, while adjusted brain weight was decreased by 5% and 8% in the 1%EGEE and 2% EGEE groups, respectively. Absolute testis weights in the middle and high-dose groups were reduced by 11% and 35%, respectively. Relative epididymis and seminal vesicle weights were reduced in the 2% EGEE group by 18% and 12%, respectively. Abnormal sperm forms were increased by nearly equal to 2.5-fold at 1% EGEE, and by nearly equal to 13-fold at 2% EGEE from a control value of 3.3%. Also at 2% EGEE, sperm motility was reduced by 40% and epididymal sperm density was down by 19%. In the 2% EGEE group, vaginal cycle length was increased to 5.5 days, from a control value of 4.6 days.
An analysis of the second generation was not conducted in this study.
In conclusion, EGEE was clearly toxic to reproduction in both F0 male and female mice at 1% and 2% in drinking water, based on reduced pup numbers and weight in Task 2, fertility and pup weight effects in Task 3, and alterations in estrous cyclicity and epididymal sperm parameters at necropsy.