Developmental toxicity of N-methyl-2-pyrrolidone administered orally to rats.
The developmental toxicity of N-methyl-2-pyrrolidone (NMP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NMP at doses of 0 (distilled water), 125, 250, 500, and 750 mg/kg/day, by gavage, on gestational days (GD) 6 through 20. Significant decreases in maternal body weight gain and food consumption during treatment, and a reduction in absolute weight gain were observed at 500 and 750 mg/kg. The incidence of resorptions per litter was significantly higher than control at 500 mg/kg, and rose to 91% at 750 mg/kg. Examination of the foetuses revealed treatment-related malformations, including imperforate anus and absence of tail, anasarca, and malformations of the great vessels and of the cervical arches. The incidence of malformed foetuses per litter, and of litters with malformed foetuses was significantly increased at 500 and 750 mg/kg. At 250 mg/kg, one foetus showed malformations similar to those recorded at higher dosages. There was a dose-related decrease in foetal body weights (male, female, and total) that reached statistical significance at 250 mg/kg. A significant increase in incomplete ossification of skull bones and of sternebrae was also present at 500 and 750 mg/kg. In summary, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 250 and 125 mg/kg/day, respectively. Thus, oral administration of NMP produced developmental toxicity below maternally toxic levels.
Saillenfait
A M
AM
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, BP No. 27, 54501 Vandoeuvre, France. anne-marie.saillenfait@inrs.fr
Gallissot
F
F
Langonné
I
I
Sabaté
J P
JP
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D005865:Gestational Age; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D015430:Weight Gain / Q000187:drug effects
D011760:Pyrrolidinones; D013723:Teratogens; C038678:N-methylpyrrolidone