Teratogenicity of flubendazole in rats

Flubendazole, the p-fluoroderivative of mebendazole, was suspended in deionized water, and administered by gavage once daily to pregnant rats on days 8 through 15 of pregnancy at 0 (control), 2.5, 10, 40 or 160 mg/kg. Fetuses were removed on day 21 of pregnancy by caesarian section, and examined by routine teratological methods. The highest dose (160 mg/kg) was embryocidal and resulted in a significant increase in the fetal resorption rate. There was a dose-dependent decrease in fetal body weights which was significant at 40 mg/kg or more. The 40 and 160 mg/kg doses induced significant fetal (gross, skeletal and internal) malformations. A variety of gross malformations occurred, i.e. encephalocele, cranial meningocele, omphalocele, ectrodactyly, club foot, defects in tail, anal atresia, shortened backbone and Spina bifida occulta. The skeletal malformations mainly affected the vertebrae and ribs. The most frequently observed internal malformation was hydrocephaly, followed by anophthalmia and/or microphthalmia.