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.