Diethylene Glycol (DEG), 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 large structure-activity series of glycol ethers and congeners evaluated using this design. F0 mice were exposed to drinking water containing 0.0, 0.35%, 1.75%, and 3.5% DEG. Based on water consumption data collected during the study, these concentrations produced calculated DEG consumptions of nearly equal to 612, 3062, and 6125 mg/kg/d.
While F0 body weight was unchanged by DEG consumption during the Task 2 mating period, the number of litters per pair was reduced by 12% at the top dose, and the number of live pups/litter was reduced by 32%. Pup weight adjusted for litter size was reduced by nearly equal to 12% at the top dose level. In a crossover mating to determine the affected sex, number of pups/litter was equivalent across the three groups, but adjusted pup weight was reduced by 10% in the control male x 3.5% DEG female mating. After the F1 mice were weaned, the control and 3.5% DEG F0 mice were killed and necropsied. There were no treatment-related changes in male organ weights or histopathology, while female body weight was reduced by 7% after 3.5% DEG consumption. Adjusted organ weights were unchanged.
For the F1 mating trial, exposed mice from the 1.75% group were used, because insufficient mice were available from the top dose, due to reduced fertility in that group. DEG at 1.75% did not affect pup survival to mating at pnd 74. There were no treatment-related alterations in the number or weight of F2 pups in the Task 4 mating trial. After all the F2 litters were born and the F1 females subjected to estrous cyclicity evaluation, the F1 mice were killed and necropsied. There was an 11% and 7% decrease in the body weights of the treated males and females, respectively. No organ weights were affected, nor were sperm indices changed.
In summary, diethylene glycol at 3.5% was a reproductive toxicant in Swiss mice, based on reductions in litters/pair, and in mean litter size. In F0 mice, this was unaccompanied by body weight loss, while in F1 mice, there was reduced body weight in the absence of a fertility effect.
NTIS #PB85212926/AS