Reduction of teratogenic effects of ethylenethiourea in rats by interaction with sodium nitrite in vivo

Nitrites are present in a wide variety of foods and their daily intake in man has been estimated at 1·5 mg. Ethylenethiourea (ETU), a major food contaminant resulting from degradation of ethylenebisdithiocarbamate fungicides, is a potent rat teratogen. The co-administration of ETU (60 or 40 mg/kg) and NaNO₂ (80 mg/kg) to rats by gavage on day 15 of gestation resulted in a higher survival of progeny than occurred with the corresponding dose of ETU alone. In a second study, ETU (60 mg/kg) and NaNO₂ (80, 100 or 120 mg/kg) were administered, either individually or in combination, as a single dose on day 13 of gestation. Administered alone, NaNO₂ did not produce any teratogenic response in full-term foetuses, whereas ETU produced a high incidence of various anomalies. However, the combined dosing resulted in the elimination of almost all the anomalies. The reducing effect of NaNO₂ on ETU-induced malformations was reversed when the animals were pretreated with 200 mg ascorbic acid/kg or 360 mg sodium ascorbate/kg. Since both of these are well-known inhibitors of N-nitrosation reactions, it was presumed that the simultaneous oral dosing of ETU and NaNO₂ resulted in the formation of N-nitrosoethylenethiourea.