nsc-141537 and Fetal-Resorption

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.

Topics: Abnormalities, Drug-Induced; Animals; Bone and Bones; Female; Fetal Resorption; Injections, Intraperitoneal; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Pregnancy; Sesquiterpenes; Teratogens; Trichothecenes