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Teratogenic response of dimethylacetamide in rats
F R Johannsen1, G J Levinskas, J L Schardein
1Department of Medicine and Health Sciences, Monsanto Company, St. Louis, Missouri 63167.
Abstract:
Pregnant CD rats (25/group) were used to determine the teratogenic potential of dimethylacetamide (DMAC). DMAC was administered in deionized water once a day by gavage on Days 6 through 19 of gestation at dosages of 0, 65, 160, and 400 mg/kg/day. Cesarean sections were performed on all females on Gestation Day 20. No treatment-related effects were observed in survival, appearance, or behavior at necropsy. Mean maternal body weight gain was reduced significantly only at the 400 mg/kg/day level. Fetotoxicity manifested by increased postimplantation loss was seen at the 400 mg/kg/day level while reduction in mean fetal body weights was noted at the 160 and 400 mg/kg/day test levels. Developmental variations (reduced ossification and unossified skeletal variations) were increased at the 400 mg/kg/day test level and corresponded to the reduced fetal body weights which were observed. Treatment-related malformations of the heart, major vessels and oral cavity, and anasarca were seen at the 400 mg/kg/day DMAC level. No teratogenic effect of DMAC treatment was observed at or below dosage levels of 160 mg/kg/day.