Abstract for RACB85053

Ethylene Glycol Monobutyl Ether: Reproduction and Fertility Assessment in CD-1 Mice When Administered in Drinking Water

CASRN: 111-76-2
Chemical Formula: C6H14O2
Molecular Weight: 118.176
Report Date: May 1985


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 Monobutyl Ether (EGBE), 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% EGBE in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 0.72, 1.35, and 2.0 g/kg/d.

Excessive mortality (65%) was seen in the high-dose females during Task 2; 6/20 females died in the 1% group, and 1/20 in the control and 0.5% groups. Male mice in the middle and high dose groups showed less weight gain during Task 2. Water consumption was reduced in all treatment groups, by approximately 50%. The number of live pups/litter was reduced by 52% and 71% in the middle and high dose groups, respectively, and the proportion of pups born alive was reduced in these groups by nearly equal to 40% and 45%. As EGBE concentration increased, adjusted pup weight decreased by 5%, 11%, and 16%.

At the crossover mating trial, using the controls and the 1.0% EGBE group, EGBE-treated females delivered 34% fewer pups which weighed 12% less than control pups.

At necropsy after Task 3, F0 females from the 1.0% EGBE group weighed 10% less than controls, while the kidneys and liver (adjusted for body weight) weighed 17% and 21% more than controls. EGBE-treated F0 males weighed 9% less than controls, with kidneys that weighed 13% more than controls, and testes that weighed 8% less. There were no changes in sperm indices.

Due to the reduced fertility in the 1% EGBE group, insufficient animals were available to test the second generation at this dose. Thus, the second generation was evaluated using the 0.5% group and the controls. There was no indication of reduced body weight gain during maturation to mating at 74 ± 10 days of age. While there was no difference between the two groups in the proportion of pairs mating or becoming pregnant, there was a 5% reduction in the weight of the F2 pups.

At F1 necropsy, body weights were not different between the groups, although in females , liver weight and kidney weight were increased by 7% and 22%, respectively. In males, liver weight was increased by 9%.

In summary, EGBE was a reproductive toxicant, based on reductions in pup weight and litter size, but these occurred only at concentrations that reduced water intake and fluid consumption, altered liver and kidney weights and/or induced significant lethality (F0's). In F1's, reduced pup weight was seen concomitant with increased liver and kidney weight.