Developmental toxic effects of N-ethyl-2-pyrrolidone administered orally to rats.
The developmental toxicity of N-ethyl-2-pyrrolidone (NEP) was studied in Sprague-Dawley rats after oral administration. Pregnant rats were given NEP at doses of 0 (distilled water), 50, 250, 500 and 750 mg kg(-1) day(-1), by gavage (5 ml kg(-1)), on gestational days (GD) 6-20. Maternal toxicity, as evidenced by reduction in body weight gain and food consumption, was observed in all NEP groups at the beginning of treatment (GD 6-9). The incidence of resorptions was significantly increased at 500 mg kg(-1) day(-1), and reached 83% at 750 mg kg(-1) day(-1). There was a dose-related decrease in fetal weight, which was significantly lower than control at 250 mg kg(-1) day(-1) and higher doses. The incidence of malformed fetuses per litter and the number of litters with malformed fetuses were significantly increased at 500 and 750 mg kg(-1) day(-1). Malformations mainly consisted of edema, anal atresia with absent tail, cardiovascular defects and fused cervical arches. Ossification of skull bones and sternebrae was significantly reduced at 500 and 750 mg kg(-1) day(-1). The incidence of supernumerary ribs was significantly elevated at 250 mg kg(-1) day(-1) and higher doses. In conclusion, NEP administered by gavage is embryotoxic and teratogenic at maternal toxic doses.
Saillenfait
A M
AM
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, B.P. 27, 54501 Vandoeuvre, France. anne-marie.saillenfait@inrs.fr
Gallissot
F
F
Sabaté
J P
JP
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D005260:Female; D005333:Fetus / Q000187:drug effects*; D000077287:Levetiracetam; D010889:Piracetam / Q000031:analogs & derivatives / Q000633:toxicity; D011247:Pregnancy; D011760:Pyrrolidinones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
C523727:N-ethyl-2-pyrrolidone; D011760:Pyrrolidinones; D000077287:Levetiracetam; C038678:N-methylpyrrolidone; D010889:Piracetam