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Reproductive effects of diethylene glycol and diethylene glycol monoethyl ether in Swiss CD-1 mice assessed by a
J Williams1, J R Reel, J D George
1Developmental and Reproductive Toxicology Group, National Toxicology Program, NIEHS, Research Triangle Park, North Carolina 27709.
Abstract:
Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) were evaluated for reproductive toxicity in CD-1 mice using a continuous breeding protocol. Compounds were administered in the drinking water at 0, 0.35, 1.75, and 3.5% w/v (DEG) or 0, 0.25 1.25, and 2.5% w/v (DEGEE). Exposure of the breeding pairs to 3.5% DEG for 14 weeks produced statistically significant decreases in the number of litters per pair, live pups per litter, proportion of pups born alive, and live pup weight. There was also a significant increase in the cumulative days to litter and a significant decrease in the number of pairs producing the third, fourth, and fifth litters for the 3.5% DEG-exposed mice. A crossover mating trial of the F0 mice to determine the affected sex was inconclusive, but suggested that offspring development was compromised in females exposed to 3.5% DEG. Slight maternal (F0) toxicity was noted for the 3.5 DEG group (7% decrease in body weight). The F1 generation, at 3.5% DEG, had decreased body weights at birth and exhibited poor postnatal survival. At the intermediate dose of DEG, body weights of both sexes were depressed at weaning, at onset of mating, and at necropsy. However, no adverse effects on reproduction were observed. DEGEE had no effect on reproduction in the F0 or F1 generation mice despite a 34% decrease in cauda epididymal sperm motility in the F1 males at 2.5% DEGEE. Other signs of toxicity observed in these F1 mice included increased relative liver weights. These data indicate that DEG is a reproductive toxicant in Swiss mice affecting fertility and reproductive performance, albeit at high doses (equivalent to 6.1 g/kg/day). However, its monoethyl derivative, DEGEE, is without adverse effects on fertility and reproductive performance.
Insights
Diethylene glycol (DEG) is a reproductive toxicant in mice, impacting fertility and offspring survival at high doses. Diethylene glycol monoethyl ether (DEGEE) showed no adverse reproductive effects, even with decreased sperm motility in males.
Area of Science:
- Toxicology
- Reproductive Toxicology
- Environmental Health
Background:
- Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) are industrial chemicals with potential health implications.
- Understanding their reproductive toxicity is crucial for risk assessment and public safety.
Purpose of the Study:
- To evaluate the reproductive toxicity of DEG and DEGEE in CD-1 mice using a continuous breeding protocol.
- To determine the effects on fertility, reproductive performance, and offspring development.
Main Methods:
- CD-1 mice were exposed to varying concentrations of DEG (0-3.5%) or DEGEE (0-2.5%) in drinking water.
- A continuous breeding protocol was employed, assessing multiple generations (F0 and F1).
- Reproductive parameters, pup viability, body weight, and maternal toxicity were monitored.
Main Results:
- High-dose DEG (3.5%) significantly reduced litter size, pup viability, and pup weight, with maternal toxicity observed.
- DEG exposure also led to increased days to litter and reduced breeding success in F0 mice.
- DEGEE did not affect reproductive parameters in either generation, despite causing decreased sperm motility and increased liver weight in F1 males at the highest dose.
Conclusions:
- Diethylene glycol (DEG) is confirmed as a reproductive toxicant in mice, affecting fertility and offspring health at high exposure levels.
- Diethylene glycol monoethyl ether (DEGEE) demonstrated a lack of reproductive toxicity in this study.
- These findings highlight the differential toxicity profiles of DEG and its derivative, DEGEE.