The sodium salt of tolbutamide, in dosages ranging from 12.5 mg./kg. to 125 mg./kg. body weight, was administered to pregnant albino rats to determine its effect upon litter size, individual fetal weight, normal development of the young, and the fetal skeleton.
As the dosage level increased, a statistically significant decrease in fetal weight was observed. Tolbutamide administration had no detrimental effect upon the total number of implantations; however, a large number of resorptions occurred at the 125 mg./kg. level resulting in a decreased litter number.
The number of rats having litters with fetuses weighing less than three grams increased as the dosage increased from 12.5 mg./kg. to 100 mg./kg. levels.
No adverse effect on the maternal animal was noted except at the 100 mg./kg. and 125 mg./kg. levels. At these levels all animals experienced a localized tetanic response which varied in duration according to the level of injection.
The number of sternebrae, metacarpals, and metatarsals, as well as long bones, indicated that the number and size of bones varied inversely with increased dosage levels.
Normal skeletal development occurred despite dosages up to and including the 37.5 mg./kg. level. Abnormalities were observed from the 50 mg./kg. to the 125 mg./kg. level of administration.