Teratogenic potential of the mycotoxin, citreoviridin, in rats

Abstract

Citreoviridin produced by the fungus Penicillium citreo-viride was administered by gavage to groups of 9–16 pregnant Fisher 344 rats either on days 8–11 (group A) or on days 12–15 (group B) of gestation. Doses of 0, 5, 10 or 15 mg/kg body weight were given daily in a constant volume of 1 ml/kg body weight in dimethylsulphoxide. Six rats in each high-dose group died during the dosing period. Compared with control groups, mean daily feed consumption was significantly reduced in the 10- and 15-mg/kg animals in both groups A and B. Weight gain during pregnancy in both groups was reduced with increasing dosage; dams in control groups gained an average of 75 g/rat compared with 30 g overall gain in group A, or 9 g overall gain in group B, both at a dose of 15 mg/kg. Male and female pup weights were reduced with increasing dosage for both groups A and B. The post-implantation foetal loss rate was significantly increased to 33% in group A high-dose animals. The main effect of citreoviridin on skeletal development in both groups A and B was one of retardation. No internal abnormalities were observed in group A pups. Some smaller than average pups from dams in group B that were treated with the high dose of citreoviridin had slightly dilated lateral ventricles of the brain and, in some cases, a palate defect. The foetotoxicity induced by citreoviridin was observed only at doses that also induced maternal toxicity.