Effects of deoxynivalenol (DON, vomitoxin) on in utero development in rats.
Deoxynivalenol (DON, vomitoxin), is one of the most common contaminants of cereal grains world-wide. The effects of DON on fetal development were assessed in Charles River Sprague-Dawley rats. Pregnant female rats were gavaged once daily with DON at doses of 0, 0.5, 1, 2.5, or 5 mg/kg body weight on gestation days (GD) 6-19. At cesarean section on GD 20, reproductive and developmental parameters were measured. All females survived to cesarean section. DON caused a dose-related increase in excessive salivation by the pregnant females, a reaction probably linked to the lack of emetic reflex in rats. At 5 mg/kg, feed consumption and mean body weight gain were significantly decreased throughout gestation, mean weight gain (carcass weight), and gravid uterine weight were significantly reduced, 52% of litters (12/23) were totally resorbed, the average number of early and late deaths per litter was significantly increased, average fetal body weight and crown-rump length were significantly decreased, the incidence of runts was significantly increased, and the ossification of fetal sternebrae, centra, dorsal arches, vertebrae, metatarsals, and metacarpals was significantly decreased. At 2.5 mg/kg, DON significantly decreased average fetal body weight, crown-rump length, and vertebral ossification. These effects may be secondary to maternal toxicity and the reduced size of the fetuses. The incidence of misaligned and fused sternebrae was significantly increased at 5.0 mg/kg. No adverse developmental effects were observed at 0.5 and 1.0 mg/kg. Dose-related increases in maternal liver weight-to-body weight ratios were observed in all treated groups (significant at 1, 2.5, and 5 mg/kg). The weight changes were correlated with dose-related cytoplasmic alterations of hepatocytes. The NOEL for maternal toxicity for this study is 0.5 mg/kg based on the dose-related increase in liver-body weight ratio at 1 mg/kg. The NOEL for fetal toxicity is 1 mg/kg based on the general reduction in fetal development at 2.5 and 5 mg/kg. DON is considered a teratogen at 5 mg/kg day in Sprague-Dawley rats based on the anomalous development of the sternebrae.
Collins
Thomas F X
TF
Center for Food Safety and Applied Nutrition, US Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD 20708, USA. tcollins@cfsan.fda.gov
Sprando
Robert L
RL
Black
Thomas N
TN
Olejnik
Nicholas
N
Eppley
Robert M
RM
Hines
Fred A
FA
Rorie
James
J
Ruggles
Dennis I
DI
D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D018568:Crown-Rump Length; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D047109:Fetal Development / Q000187:drug effects*; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D008099:Liver / Q000473:pathology; D009929:Organ Size; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects; D014255:Trichothecenes / Q000008:administration & dosage / Q000633:toxicity*; D014599:Uterus / Q000473:pathology
D014255:Trichothecenes; C007262:deoxynivalenol