An oral (gavage) control embryo-fetal development study in the Wistar Hannover rat.
Many of the studies conducted to examine the developmental and reproductive toxicity potential of candidate pharmaceuticals use the Sprague-Dawley rat as the animal model. This is due in part to the large database for this outbred rat available for comparison of litter data, and the low incidence of fetal malformations and variations. The following study was conducted to generate information on potential embryo-fetal developmental defects and litter data in another outbred stock of rat, the Wistar Hannover. One hundred fifty pregnant female Wistar Hannover rats (Tac:Glx:WIfBR) were dosed orally once per day with distilled water from Gestation Days (GD) 6 through 17 covering the time from implantation to closure of the hard palate (GD0 = day of insemination). Caesarean sections were performed on Day 20 of gestation. All fetuses were examined for external, visceral and skeletal malformations and variations. Macroscopic and histomorphologic examinations were also completed for the F0 females at termination. The percent pregnant (88%) and litter size (average 10.6) were found to be lower than that commonly reported for the Sprague-Dawley rat (Crl:CD (SD)BR; 95.4% and 14.6, respectively). Pre-implantation loss (14.1%), post-implantation loss (7.4%) and percent resorptions (7.2%) occurred at a higher incidence than typically seen in the Sprague-Dawley rat (5.9, 5.6 and 5.1%, respectively). The average fetal body weights for both the female and male rats were lower than those typically seen in the Sprague-Dawley rat. External, visceral and skeletal examination of the F1 fetuses revealed numerous malformations and variations which also occurred at higher incidences than those reported for the Sprague-Dawley rat. Routine macroscopic and histomorphologic examination showed there were no changes that would be interpreted to have impaired mating performance, fertility or gestation. Thus, this study provides information on the reproductive effects and the background incidence of embryo-fetal development defects that could be used for comparison to those identified when using this outbred rat for developmental and reproductive toxicity studies, as well as for comparison to the more commonly used rat stock, the Sprague-Dawley rat. For the parameters evaluated, the Wistar Hannover rat had greater variability and an increased incidence of spontaneous malformations as compared to the Crl:CD (SD)BR Sprague-Dawley rat. These findings should be considered if this stock of rat is selected in the conduct of developmental and reproductive toxicity studies.
Liberati
Teresa A
TA
Department of Toxicology, Sanofi-Synthelabo Research, Division of Sanofi-Synthelabo, Inc., 9 Great Valley Parkway, Malvern, PA 19355, USA.
Roe
Barbara J
BJ
Feuston
Maureen H
MH
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000502:physiology; D004622:Embryo, Mammalian / Q000002:abnormalities*; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D008098:Litter Size / Q000502:physiology; D008297:Male; D023421:Models, Animal; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar / Q000196:embryology*; D012107:Research Design; D013997:Time Factors; D014781:Viscera / Q000002:abnormalities; D014867:Water / Q000008:administration & dosage
D014867:Water