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Developmental Toxicity of Aspirin Prenatally Given to Rats: Assessment in Slc: Wistar‐KY Rats
Author(s) -
OKAMOTO Masaharu,
KIHARA Takahide,
TANIMURA Takashi
Publication year - 1988
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1988.tb00965.x
Subject(s) - offspring , aspirin , medicine , fetus , gestation , weaning , developmental toxicity , ossification , endocrinology , pregnancy , surgery , biology , genetics
Slc:Wistar‐KY rats were administered orally with 62.5, 125, 187.5 or 250mg/kg aspirin suspended with 0.5 % CMC‐Na on days 9–11 of gestation (plug += 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.