Teratogenicity of secalonic acid D in mice.

Teratogenicity and fetotoxicity of secalonic acid D, a toxic fungal metabolite produced by Penicillium oxalicum, were investigated with pregnant CD1 mice. The compound was administered ip on d 7-15 of pregnancy. A dose-dependent reduction in weight gain of mothers receiving all doses of secalonic acid D and an increase in resorptions of implanted embryos of dams treated with more than 5 mg/kg secalonic acid D occurred. The latter effect was nearly 100% at 15 or 9 mg/kg given in NaHCO3 with or without dimethyl sulfoxide (DMSO), respectively. A corresponding decrease in the percent of live fetuses and a decrease in the average fetal body weight on d 19 of pregnancy also occurred. Multiple gross, skeletal, and visceral anomalies were noted in fetuses born to mothers receiving 10 mg/kg or more in NaHCO3 containing DMSO. In NaHCO3 alone, the minimum teratogenic dose was 6 mg/kg. Major malformations included cleft palate, cleft lip, open eyelids, missing phalangeal ossification centers, and shortened mandibles. The results indicated that secalonic acid D is embryocidal and teratogenic as well as fetotoxic when given to female CD1 mice during pregnancy.