Developmental Toxicity of N-Methylformamide Administered by Gavage to CD Rats and New Zealand White Rabbits

N-Methylformamide (NMF) is a metabolite of dimethylformamide(DMF), a solvent with wide applications in the chemical industry.The potential developmental toxicity of NMF was evaluated inCD rats and New Zealand white rabbits. Pregnant rats and rabbitswere dosed once daily by gavage on Gestation Days 6–15and 6–18, respectively. Doses for rats were 0, 1, 5, 10,or 75 mg/kg; doses for rabbits were 0, 5, 10, or 50 mg/kg. Cesareansections were performed on rats and rabbits on Gestation Days20 and 29, respectively. No treatment-related maternal deathsor clinical signs occurred in either species. Body weight gainand food consumption were depressed in rats given 75 mg/kg andrabbits given 50 mg/kg. Fetal viability was reduced at 75 mg/kgin rats and at 50 mg/kg in rabbits. In rats, a significant increasein the incidence of malformations including cephalocele andstern-oschisis was observed in fetuses from the 75 mg/kg group.In addition, a developmental delay was indicated by reductionof fetal weight and by a significant increase in the occurrenceof incomplete ossification of various skeletal structures. Inthe rabbit, fetal body weight was reduced at 50 mg/kg. Malformationsobserved at 50 mg/kg included gastroschisis, cephalocele, domedhead, flexed paw, and skull and sternum anomalies. The lowest-observed-adverse-effectlevels for maternal and developmental toxicity in the rat andrabbit were 75 and 50 mg/kg, respectively. The no-observed-adverse-effectlevel for maternal and developmental toxicity in the rat andrabbit was 10 mg/kg.