Diethylphthalate (DEP) was tested for reproductive toxicity in the standard Continuous Breeding design using Swiss CD-1 mice. Data collected in the Task 1 dose-range-finding study (body weight, clinical signs, food and water consumptions) were used to select concentrations of 0.0, 0.25, 1.25, and 2.5% in feed for the main study. Feed consumption was not affected by the presence of DEP. These concentrations in feed gave calculated consumption estimates of 0.34, 1.77, and 3.64 g DEP/kg body weight/day.
DEP consumption had no adverse effect on the mean number of litters/pair, the number of live pups/litter, the viability of the pups, or pup body weight adjusted for litter size. In fact, the number of pups/litter were increased at the low and middle doses by 32% and 14%, respectively. We attribute this to the fact that the value for the controls was nearly equal to 25% below historical values for this strain.
Because there was no observable change in fertility or reproductive outcome, Task 3 (the crossover mating trial to determine the affected sex) was not conducted. The second generation was tested using the F1 mice from the control and high dose groups.
There was no difference between these two groups in terms of body weights or viability of the F1 pups at birth, weaning, or at the start of the week of mating (pnd 74 ± 10). All 20 pairs of mice mated in both groups, and 95% of those delivered live young (in both groups). The DEP litters had 14% fewer pups; viability and pup weight adjusted for litter size were unchanged.
After the F2 pups were evaluated and discarded, the F1 adults were killed and necropsied. Treated females weighed 8% less, while adjusted liver weight was increased by 28%. Treated males weighed 12% less than their respective controls, while their liver weight and prostate weight, both adjusted for body weight, were increased by 18% and 32%, respectively. Epididymal sperm concentration was reduced by 30%, while the percent motile sperm and the proportion of abnormal forms were unaffected by DEP.
In summary, DEP had no effect on F0 reproductive performance, while producing moderate reproductive effects in the second generation in the presence of mild body weight gain inhibitions and moderate increases in liver weight.
NTIS #PB85118636