Evaluation of the developmental XXXX of @entity27390 in New Zealand white @entity95 .

@entity137 @entity853 @entity27390 @entity95 @entity409 @entity600 @entity1017 @entity204 @entity1907
Naturally mated female New Zealand White (NZW) @entity95 (24/group) received @entity27390 (35, 70, or 140 mg/kg/day) or vehicle (1 ml/kg deionized/distilled water) by gavage on gestational days (GD) 6 through 29. The study was conducted using a 2-replicate design. @entity1907 (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. One and four maternal @entity204 occurred at the low and high doses, respectively. Abortions or early deliveries were noted in 0, 2, 2, and 8 females in the 0, 35, 70, and 140-mg/kg/day dose groups, respectively. Other clinical signs associated with @entity27390 exposure were minimal: primarily reduced or absent fecal output at the high dose (2-13 animals/day). Also at the high dose, maternal body weight was significantly depressed on GD 21, 24, and 27 (87-90% of the control value); maternal body weight gain was significantly reduced for GD 12 to 15, 18 to 21, and 21 to 24 (treated animals gained less than 1 g, or lost up to 100 g). In addition, maternal body weight gain was reduced at the middle dose for GD 18 to 21. @entity1017 , corrected for gravid uterine weight, was unaffected. Relative maternal food consumption in the high-dose group was 34-59% of control intake from GD 12 through GD 24, but was comparable to controls thereafter. At termination (GD 30), confirmed-pregnant females (9-20 per group) were evaluated for clinical status, liver weights, and gestational outcome; live fetuses were examined for external, @entity600 and variations. @entity409 (absolute or relative to body weight) was unaffected by treatment, but gravid uterine weight at the high dose was 71% of the control value. A significantly increasing trend was noted for the percent non-live implants per litter. In addition, although not statistically significant from the control group, the values for the percent late fetal @entity204 per litter and percent non-live implants per litter in the 140-mg/kg/day group were higher than maximum historical values, suggesting an increase in late gestational @entity204 in the surviving high-dose animals. @entity27390 decreased the mean number of live fetuses per litter at the high dose to 66% of the control value. Mean fetal body weight per litter for males and the sexes combined was significantly decreased at the high dose; mean female fetal body weight was also decreased, although the difference did not reach statistical significance. There was no effect of treatment on the incidence of @entity853 or variations in animals surviving to scheduled necropsy. In summary, the no-observed-adverse-effect level (NOAEL) for maternal @entity137 was 70 mg/kg/day and the lowest-observed-adverse-effect level (LOAEL) was 140 mg/kg/day under the conditions of this study. Similarly, the NOAEL for developmental @entity137 was 70 mg/kg/day and the LOAEL was 140 mg/kg/day.
