Developmental Toxicity of Aspirin Prenatally Given to Rats: Assessment in Sic: Wistar‐KY Rats

Abstract

S1c:Wistar-KY rats were administered orally with 62.5, 125, 187.5 or 250 mg/kg aspirin suspended with 0.5 % CMC-Na on days 9-1 1 of gestation (plug t = day 0). Suppression of maternal weight gain and food consumption during treatment was observed at and over 187.5 mg/kg. At term, the fetal mortality increased at and over 187.5 mg/kg and the fetal weight was lowered at and over 125 mg/kg. Among 15 live fetuses at 250 mg/kg, 4 had external malformations. In the skeletal examination (double staining), skeletal anomalies increased at and over 187.5 mg/kg. The skeletal variations such as vertebral anomalies, fused costal cartilages and increased presacral vertebrae were often encountered and delayed ossification was also found at and over 125 mg/kg. The internal anomalies tended to increase at and over 187.5 mg/kg. The live birth rate was significantly lower at 187.5 mg/kg than that in controls, and all pups, except for 3 from a dam, died before weaning. At 125 mg/kg, the pivoting locomotion on day 7 post partum was poorer as compared with controls. The physical and functional development at 62.5 mg/kg was not changed. There were no significant effects on male offspring in the open-field, rotarod, under-water T-maze and avoidance learning tests. However, in the Biel T-maze test (9-10 weeks of age), the aspirin-treated groups showed more errors and the increased elapsed time on the 1st trial day than controls. These results indicate that aspirin may induce a slight learning defect on rat offspring even at the non-teratogenic dose and the Biel T-maze test is more sensitive than any other learning tests given in this study.