PMID- 12176097
OWN - NLM
STAT- MEDLINE
DCOM- 20021011
LR  - 20190901
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 40
IP  - 11
DP  - 2002 Nov
TI  - Developmental toxicity of N-methyl-2-pyrrolidone administered orally to rats.
PG  - 1705-12
AB  - 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.
FAU - Saillenfait, A M
AU  - Saillenfait AM
AD  - Institut National de Recherche et de Securite, Avenue de Bourgogne, BP No. 27, 
      54501 Vandoeuvre, France. anne-marie.saillenfait@inrs.fr
FAU - Gallissot, F
AU  - Gallissot F
FAU - Langonne, I
AU  - Langonne I
FAU - Sabate, J P
AU  - Sabate JP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Pyrrolidinones)
RN  - 0 (Teratogens)
RN  - JR9CE63FPM (N-methylpyrrolidone)
SB  - IM
MH  - Abnormalities, Drug-Induced
MH  - Administration, Oral
MH  - Animals
MH  - Bone and Bones/abnormalities
MH  - Dose-Response Relationship, Drug
MH  - Eating/drug effects
MH  - Female
MH  - Fetal Resorption/chemically induced
MH  - Gestational Age
MH  - No-Observed-Adverse-Effect Level
MH  - Pregnancy
MH  - Pyrrolidinones/administration & dosage/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Teratogens/*toxicity
MH  - Weight Gain/drug effects
EDAT- 2002/08/15 10:00
MHDA- 2002/10/12 04:00
CRDT- 2002/08/15 10:00
PHST- 2002/08/15 10:00 [pubmed]
PHST- 2002/10/12 04:00 [medline]
PHST- 2002/08/15 10:00 [entrez]
AID - S0278691502001151 [pii]
AID - 10.1016/s0278-6915(02)00115-1 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2002 Nov;40(11):1705-12. doi: 10.1016/s0278-6915(02)00115-1.