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.
Triethylene glycol diacetate (TGDA) was tested in the Reproductive Assessment by Continuous Breedng (RACB) protocol using Swiss CD-1 mice, as part of a larger effort to evaluate a series of glycol ethers and their structural congeners and metabolites. Data gathered on body weights, clinical signs, and food and water consumption during the Task 1 dose-range-finding study were used to select concentrations for the continuous breeding phase (Task 2) of 0., 0.75%, 1.5%, and 3% w/v in drinking water. These concentrations produced calculated consumption estimates of nearly equal to 1.31, 2.62, and 5.25 g/kg/d.
Continuous exposure of adult F0 mice to these concentrations of TGD had no effect on the number of litters/pair, or the number or weight of live pups/litter. The proportion of pups born alive was not affected by these concentrations of TGDA.
Since no effects were observed in Task 2, Task 3, which determines the effected sex, was not conducted. The last litter from Task 2 was nursed until weaning, and then given water containing TGDA at the same concentration as their parents. Only the control and 3% TGDA groups were assessed in a second generation. Although viability was not adversely affected, pups nursed by dams receiving 3% TGDA weighed between 15 and 25% less than their controls at pnd 14 and 21. These differences in body weight had disappeared by the time of Task 4 mating at nearly equal to pnd 74.
In the second generation mating trial, there were no treatment-related effects on mating or fertility indices, or on the number of F2 pups, their viability, or weight adjusted for litter size.
After the F2 litters were delivered and evaluated, the F1 adults were killed and necropsied. There were no TGDA-related differences in body weight for either sex. In males and females, relative kidney weight was increased by nearly equal to 6-8%. No other treatment-related effects were found. Epididymal sperm concentration, motility, and morphology were unaffected by 3% TGDA consumption.
These data show that triethylene glycol diacetate had no detectable reproductive toxicity in Swiss mice at exposure levels that altered kidney weights and neonatal development.