Abstract
A study was made of the stage-specific teratogenicity in rat fetuses from dams given different dosages of aspirin throughout and also during 3 subdivided organogenetic periods of pregnancy (days 8-10, 11-13 and 15-17 of gestation). The stage-specific teratogenicity of the drug, from the aspect of the dam-fetus distribution pattern of salicylic acid during the respective periods of pregnancy was also determined. The stage when the malformations, typical of aspirin toxicity (cranioschisis, spondyloschisis, abdominal fissure, cleft palate) were most frequent was from day 8 to day 10 of gestation. Even in this period when the fetuses were most susceptible to this teratogen, however, the drug was not teratogenic unless it was ingested for 3 or more consecutive days. There were no significant alterations in the maternal plasma levels of salicylic acid during the respective periods. During the first 8-10 days of gestation, the fetal levels of salicylic acid remained significantly high (p<0.05) at any stage of measurement during the 10 hours after application of aspirin, compared with the maternal plasma levels. Furthermore, as pregnancy progressed, the amount of salicylic acid transferred to the fetuses tended to gradually decrease, despite of the fact that the maternal plasma levels of the agent remained fairly stable. On the other hand, the placental levels of salicylic acid tended to be increasingly elevated with the pregression of pregnancy. Thus, salicylic acid is most readily transferred to the fetuses at high concentrations at days 8-10 of gestation. Also, from the finding that aspirin proved to be teratogenic when the fetuses were exposed to a given period (3 days or more), the teratogenic action of aspirin is attributed to a direct action of this compound.
