Perinatal toxicity of allisartan isoproxil in SD rats

OBJECTIVE:To observe the toxic effects of allisartan isoproxil(ALS-3) on maternal SpragueDawley (SD) rats during pregnancy,lactation period,the growth and development,and the reproduction of their offsprings.METHODS:ALS-3 was administered by intragastric method at a dose level of 0(control),30,90 or 270 mg/kg from day 15 of gestation to day 21 after parturition to examine the effects of ALS-3 on the reproductive capacity in the maternal rats and the growth and development of the offsprings.RESULTS:A pregnant rat(270 mg/kg) died due to dystocia.No obvious abnormality was observed in other maternal rats(F0) sacrificed 21 days after delivery.The body weight of F1 offspring on PND 7 and PND 21 in the 270 mg/kg group decreased significantly compared with control group (P0.05),and the body weight of Fl offsprings at other age and F2 offsprings in every test group showed no significant difference with control group(P0.05).Compared with control group,the breast feeding mortality of Fl offsprings in the 270 mg/kg group was significantly increased,while F2 offsprings in the 90 mg/kg group decreased(P0.01).Other indexes showed no significant difference compared with control group(P0.05).CONCLUSION:ALS-3 at 270 mg/kg had obvious toxic effects on lactation of F0 generation and growth or development of F1 offsprings before weaning.However no effects on the functional,behavioral or learning abilities or reproductive performance in offsprings were observed in the 30 and 90 mg/kg groups.