Dams at 125 mg/kg-BW per day or greater completed parturition more than 28 h after controls, all of whom delivered by time zero (0730 on PCD 23) (Table 2). Mean times to complete parturition were 2.5, 6.7, 22.2, and 28.4 h for 31.25, 62.5, 125, and 250 mg/kg-BW per day groups, respectively. Delivery times for dams dosed with 125 and 250 mg/kg-BW differed from times for dams dosed at 62.5 mg/kg-BW per day or lower (P < 0.0005) but were not statistically different from each other (P = 0.1847). Five of eight dams treated with 125 mg/kg-BW per day delivered at least one stillborn pup.
The rate of stillbirths at this dose range was 12% ± 4% (mean ± SEM) of the number of fetal implants. In the 250 mg/kg-BW per day dose group, one dam died during prolonged delivery and two dams did not deliver any live pups. The group of five remaining dams treated with 250 mg/kg-BW per day delivered stillborn pups at a rate of 32% ± 7% of the number of fetal implants.
Offspring Effects During Neonatal and Infantile Life
On PCD 25, body weights for pups of both sexes from treated dams were lower than control pups at 62.5 mg/kgBW per day (female pups P = 0.03), 125 mg/kg-BW per day (male, P = 0.0019; female, P = 0.0002), and 250 mg/ kg-BW per day (both sexes, P < 0.0001; Fig. 3). Effects on pup weight were transient and body weights did not differ among groups at weaning except for reduced weight in females dosed at 250 mg/kg-BW per day (P = 0.041).
TABLE 2. Maternal PZ dosing effects on overall pup survivorship expressed as percentages (mean ± SEM) of live pups where the number of uterine implantation scars (according to litter) was 100%.
a Number of hours to delivery completion after initiation of observations. *P < 0.05 when compared to controls of the same age.
**P < 0.001 when compared to controls of the same age.