Developmental toxicity of diacetoxyscirpenol in the mouse

Mycotoxins (frequently referred to as secondary metabolites of toxigenic fungi) are commonly found in foodstuffs and are important because of their association with disease. The mycotoxin diacetoxyscirpenol, or 3-hydroxy-4,15-diacetoxy-12,13-epoxytrichothec-9-ene (DAS), is produced by numerous species of Fusarium and is reportedly toxic to humans and animals. The teratogenic potential of DAS was determined in time-mated ICR mice. DAS (dissolved in a 1:9 mixture of propylene glycol/saline) was administered intraperitoneally to pregnant mice at levels of 1.0, 1.5, 2.0, 3.0 and 6.0 mg/kg body weight in a single dose on one of gestation days 7-11 during the period of organogenesis. Term fetuses were examined for anomalies by routine teratologic procedures. Reabsorption frequency was dose-related and occurred as follows: 100% at 6.0 mg/kg on all gestation days tested; 90-99% at 3.0 mg/kg on days 7-9 and 100% on days 10 and 11; 26-51% at 2.0 mg/kg on days 7-9 and 100% on days 10 and 11; 9-77% at 1.5 mg/kg on days 7-10 and 100% on day 11; 7-34% at 1.0 mg/kg on days 7-11. A significant reduction in mean fetal body weight and a variety of fetal malformations (i.e. external and skeletal) were observed following maternal exposure to DAS. This is the first report to implicate this mycotoxin as a teratogen.