The effects of cyclopiazonic acid on pregnancy and fetal development of Fischer rats

Abstract

To assess the potential effect of cyclopiazonic acid (CPA) on pregnancy and fetal development, Fischer-344 rats were dosed daily with 0, 1, 5, or 10 mg CPA/kg body weight on either d 8-11 or d 12-15 of pregnancy (sperm day = d 1). There were significant (p less than 0.05) decreases in feed consumption by high-dose dams of both groups. One high-dose rat in each group died prior to term, and signs of toxicity were observed in other high-dose animals. Animals that died had histologic lesions in the liver, spleen, kidney, and other organs. Remaining dams were killed on d 21. Compared to controls, there were no significant differences in pup weights, percentage pre- or postimplantation losses, or fetal deaths. Significant differences in skeletal development included retardation of ossification of cervical centra (d 12-15) and caudal vertebrae (d 8-11) in the two highest dose groups. Retardations of development were the most common manifestations of embryotoxicity. Since significant maternal toxicity occurred at the highest dose level in the absence of fetal malformations, the teratogenic potential of CPA is low.