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 in CD rats and New Zealand white rabbits. Pregnant rats and rabbits were dosed once daily by gavage on Gestation Days 6-15 and 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. Cesarean sections were performed on rats and rabbits on Gestation Days 20 and 29, respectively. No treatment-related maternal deaths or clinical signs occurred in either species. Body weight gain and food consumption were depressed in rats given 75 mg/kg and rabbits given 50 mg/kg. Fetal viability was reduced at 75 mg/kg in rats and at 50 mg/kg in rabbits. In rats, a significant increase in the incidence of malformations including cephalocele and sternoschisis was observed in fetuses from the 75 mg/kg group. In addition, a developmental delay was indicated by reduction of fetal weight and by a significant increase in the occurrence of incomplete ossification of various skeletal structures. In the rabbit, fetal body weight was reduced at 50 mg/kg. Malformations observed at 50 mg/kg included gastroschisis, cephalocele, domed head, flexed paw, and skull and sternum anomalies. The lowest-observed-adverse-effect levels for maternal and developmental toxicity in the rat and rabbit were 75 and 50 mg/kg, respectively. The no-observed-adverse-effect level for maternal and developmental toxicity in the rat and rabbit was 10 mg/kg.
Toxicology Research Laboratories, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, Indiana 46140, USA.
S L
SL
Kelich
M D
MD
Mercieca
R C
RC
Pohland
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005328:Fetal Viability / Q000187:drug effects; D005559:Formamides / Q000008:administration & dosage / Q000633:toxicity*; D007441:Intubation, Gastrointestinal; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012744:Sex Ratio; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D000970:Antineoplastic Agents; D005559:Formamides; D013723:Teratogens; C002950:methylformamide