Embryo-fetal developmental toxicity study of Diminazene aceturate and buparvaquone in rats

Abstract

The present study investigated the embryo-fetal toxicity of Diminazene aceturate (DAC) and Buparvaquone (BPQ), administered individually and in combination, at clinical therapeutic doses in pregnant rats. A total of 120 Wistar rats (40 males, 80 females) were used, with females assigned to four groups: control (normal saline), DAC (3.5 mg/kg), BPQ (2.5 mg/kg), and DAC + BPQ combination. Treatments were administered intramuscularly during gestation days (GD) 6, 9, 12, and 15 (combination group dosed on GD 6 and 12). No maternal mortality or significant clinical signs were observed across groups. Combination treatment resulted in the highest pregnancy rate and lowest fetal resorption. DAC-treated groups exhibited higher incidences of incomplete ossification, while BPQ treatment was associated with dumbbell-shaped vertebrae and delayed ossification of phalanges. No major visceral abnormalities were detected in fetuses. Haematological evaluation revealed elevated haemoglobin, packed cell volume, and erythrocyte count in DAC-BPQ-treated groups. Biochemical alterations included reduced ALT, BUN, creatinine, and CK levels, though these remained within non-adverse ranges. DAC, BPQ, and their combination at therapeutic doses were generally well tolerated during pregnancy and did not produce major teratogenic effects in rats. However, minor skeletal variations suggest that further studies may be warranted to assess potential long-term effects.