Diethylene glycol monoethyl ether (DGMEE; greater than 99% pure) was evaluated in the Reproductive Assessment by Continuous Breeding protocol. Task 1 (dose-range finding) was performed using eight male and 8 female Swiss CD-l mice (8 weeks of age) per dose group, which were given 0.0, 1.0, 2.0, 3.0, 4.0 and 5.0% DGMEE in their drinking water (deionized/filtered) for 14 days. During the 14-day exposure, one male in the 5.0% DGMEE group exhibited dehydration on days 8-10 and exhibited dehydration and tremors prior to death on day 11. The % weight gain for the sexes combined was significantly reduced in the 4.0% DGMEE group relative to the 0.0, 1.0 and 2.0% DGMEE groups and in the 5.0% DGMEE group relative to the 0.0, 1.0, 2.0 and 3.0% DGMEE groups. Based on the acute toxicity results (Task 1), drinking water levels of 0.0, 0.25, 1.25 and 2.5% DGMEE were selected for the continuous breeding phase of the study (Task 2).
Continuous exposure of CD-l mice (11 weeks of age at outset) to up to 2.5% DGMEE had no effect on the number of pairs able to produce at least one litter. In addition, DGMEE had no influence on the number of litters per pair, live pups per litter, proportion of pups born alive, or sex (males/total) of pups born alive. In contrast, continuous exposure to the low dose of DGMEE did significantly reduce the adjusted mean live male pup weight and exposure to 2.5% DGMEE significantly reduced the adjusted mean live female pup weight relative to the control group.
Due to the minimal effects of DGMEE on fertility and reproductive performance in the Task 2 parental mice (F0 generation), the second generation was evaluated in only the control and high dose groups (Task 4). Each weanling was maintained on the same treatment as their Task 2 parents. Body weights of the F1 male and female offspring continuously exposed to 2.5% DGMEE were slightly depressed at birth, at weaning and at 74 + 10 days of age relative to control F1 male and female offspring. At 74 + 10 days of age, a male and female from different litters within treatment groups were cohabited for one week. The pairs were then separated and the females allowed to deliver their litters. Continuous exposure of the mice to DGMEE had no statistically significant effects on mating behavior, fertility rate, number of live pups per litter, proportion of pups born alive, sex males/total of pups born alive or live pup weight.
The 0.0 and 2.5% DGMEE F1 parental mice were necropsied at the conclusion of Task 4. Sperm assessment indicated no significant differences in the sperm concentration or % abnormal sperm in the cauda epididymis between male mice exposed to 0.0 or 2.5% DGMEE. Conversely, sperm samples from mice in the 2.5% DGMEE group had significantly fewer motile sperm than did the controls. Although body weight was unaffected, the adjusted liver weight was significantly increased and the adjusted brain weight was significantly decreased in males and females exposed to 2.5% DGMEE relative to controls.
Under the conditions of this reproductive study, diethylene glycol monoethyl ether (at doses as high as 2.5% in the drinking water) was not a reproductive toxicant in either F0 or F1 breeding pairs of Swiss CD-l mice, although DGMEE was associated with significantly decreased sperm motility in the F1 males. DGMEE (2.5% in the drinking water) increased liver weight and decreased brain weight in both sexes of the F1 generation.
NTIS# PB85137123