Teratogenicity of secalonic acid D in rats

Teratogenic effects of secalonic acid D (SAD), a toxic fungal metabolite, produced by P. oxalicum has been studied in rats. Crystalline SAD was injected as a single subcutaneous dose (25 mg/kg) on one of the gestation day 6-10, 12 or 14. Pregnant rats were treated with 15 mg/kg SAD on gestation day 10. Both doses produced teratogenic and fetotoxic effects, although the effects produced with the lower dose were less marked. Treatment on days 9 and 10 resulted in increased fetal resorptions and decreased fetal body weights. The highest number of resorptions, greatest depression of fetal body weights and largest number of malformations occurred when SAD was injected on day 10. Anophthalmia (days 9 and 10), exencephaly (day 9) and defects in limbs, digits and tail (day 10) were the major gross malformations. The main internal soft tissue defects were hydronephrosis (days 9 and 10) and tracheo-esophageal fistula and renal agenesis (day 10). Major skeletal defects involved the vertebrae and ribs. For all of the abnormalities observed, administration of SAD on day 10 of gestation produced the most marked effects in rats.