Effect of maternal administration of acetaminophen on the development of rat embryos

ABSTRACT

Acetaminophen a popular nonprescription analgesic-antipyretic drug, wasadministered orally to pregnant rats at a dose levels of 0 [control], 25, 50,100, 200 and 400 mg/kg/day on day 1 to 15 gestation. The dams were sacrificedon the day 21 of pregnancy and the fetuses were removed by cesarean sectionand examined. Body weight showed evidence of maternal toxicity as exhibitedby marked increase in liver weight and decreased body weight gain. Noincrease in the incidence of resorptions was observed even at 400 mg/kg, adose several-folds higher than those used in human clinical practice [10- 20mg/kg]. There was a dose-related decrease in fetal body weights which wasstatistically significant at 200 mg/kg or more. Examination of the fetusesrevealed insignificant increase in the incidence of gross, skeletal andinternal malformations at any dose level in comparison with the controls. However, one of the fetuses in the group which received 400 mg/kg showed shorttail and club foot. Thus, no evidence of embryocidal and teratogenic effectswas observed with this analgesic-antipyretic drug at the recommendedtherapeutic dose in rats. Acetaminophen may be considered the safestanalgesic- antipyretic drug during pregnancy