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 Monomethyl Ether (EGME), 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. In a preliminary study using concentrations of 0.5% to 2.0% EGME in drinking water, all treated mice were infertile. Thus follow-up study was designed to more accurately define the dose-response curve. Data from the previous study, plus 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 0.1%, 0.2%, and 0.4% EGME in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 159, 336, and 619 mg/kg/d.
During Task 2, 1 male died in the control group, and 2, 2, 1, and 4 females died in the control-to-high-dose EGME groups, respectively. Only 1 of the remaining 16 high-dose pairs had a litter, while the fertility rate in the other groups was unchanged by EGME consumption. Female body weight during Task 2 was reduced, which reflects the lack of pregnancy-induced body weight increases. The number of litters/pair was reduced by 30% at 0.2% EGME, while the number of live pups/litter was reduced by 18% and 77% in the low dose and middle dose groups, respectively. No live pups were delivered at 0.4% EGME. Pup weight adjusted for litter size was reduced by 6% in the middle dose group. Cumulative days to litter was increased for all litters at all doses; for the 0.1% and 0.2% EGME groups, the last litter was delivered 8 and 11 days after the controls, respectively.
The middle dose group was used in a Task 3 crossover to determine the affected sex. There was a 66% reduction in pups delivered to treated females, and the pup adjusted body weight was reduced by 6%. No adverse effects were seen in litters of treated males. After delivery and assessment of the litters, these F0 mice were killed and necropsied. Body and organ weights were unaffected by 0.2% EGME consumption, but estrous cycle length was increased from 4.8 days (controls) to 5.6 days.
For a second generation mating, there were only sufficient mice from the 0.1% EGME group. Thus, F1 mice from the last litter of the control and 0.1% EGME groups were reared to mating at 74 ± 10 days of age. Only 5/20 EGME pairs mated and only 2/20 bore a litter (vs. 19/20 for controls for both endpoints). In those two litters, 75% of the pups were live-born (vs. 99% for controls). Other changes were not significant, probably due to the low number of animals involved.
After litter delivery and subsequent vaginal lavage, the F1 mice were killed and necropsied. While female body weight was unchanged by 0.1% EGME consumption, adjusted liver weight was reduced by 11%. In males, no body weight difference was found, but EGME consumption reduced weights of seminal vesicles, epididymis and prostate by 11%, 12%, and 20% respectively. Epididymal sperm parameters and estrous cycle length were unchanged by 0.1% EGME exposure.
In summary, these concentrations (0.1% to 0.4%) of EGME produced marked reductions in fertility and reproductive indices, while leaving body weights unchanged. Because of the reduced liver weight in the F1 females, it must be concluded that the reproductive effects seen in this study occurred in the presence of some somatic toxicity.