PMID- 17370238
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20161124
IS  - 0260-437X (Print)
IS  - 0260-437X (Linking)
VI  - 27
IP  - 6
DP  - 2007 Nov-Dec
TI  - Comparative developmental toxicities of the three major metabolites of 
      N-methyl-2-pyrrolidone after oral administration in rats.
PG  - 571-81
AB  - The developmental toxicity of the three main metabolites of 
      N-methyl-2-pyrrolidone (NMP) was studied in Sprague-Dawley rats. Pregnant rats 
      were given 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP; 0, 250, 500, 750 or 1000 mg 
      kg(-1) day(-1)), N-methylsuccinimide (MSI; 0, 500, 750, 1000 or 1250 mg kg(-1) 
      day(-1)), or 2-hydroxyN-methylsuccinimide (2-HMSI; 0, 250, 500, 1000 or 1500 mg 
      kg(-1) day(-1)), by gavage, on gestational days (GD) 6-20. No evidence of 
      maternal toxicity was observed in dams given 5-HNMP. Administration of 2-HMSI 
      resulted in overt maternal toxicity at 500 mg kg(-1) day(-1) and higher doses, as 
      indicated by a significant reduction in weight gain and food consumption at the 
      beginning of treatment. There was no evidence of embryo/fetal toxicity in any of 
      the groups treated with 5-HNMP or 2-HMSI. MSI produced marked developmental 
      toxicity in the presence of maternal effects. Maternal body weight gain and food 
      consumption were affected at 750 mg kg(-1) day(-1) MSI, and above. A significant 
      increase in post-implantation loss occurred at 1250 mg kg(-1) day(-1) MSI, and 
      the incidence of fetuses with external or with visceral malformations was 
      significantly increased at 1000 and 1250 mg kg(-1) day(-1) MSI. Malformations 
      mainly consisted of anasarca, cardiovascular defects and diaphragmatic hernia. 
      Fetal weight was significantly reduced at 1000 and 1250 mg kg(-1) day(-1). The 
      incidence of skeletal variations (predominantly cervical ribs, and delayed 
      ossification of skull bones and sternebrae) was significantly elevated at 750 mg 
      kg(-1) day(-1) and higher doses. However, MSI was much less potent than the 
      parent compound. These results indicate that the embryotoxic and teratogenic 
      effects of NMP are not attributable to these metabolites.
FAU - Saillenfait, A M
AU  - Saillenfait AM
AD  - Institut National de Recherche et de Securite, Avenue de Bourgogne, BP 27, 54501 
      Vandoeuvre, France. anne-marie.saillenfait@inrs.fr
FAU - Sabate, J P
AU  - Sabate JP
FAU - Gallissot, F
AU  - Gallissot F
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Appl Toxicol
JT  - Journal of applied toxicology : JAT
JID - 8109495
RN  - 0 (2-hydroxy-N-methylsuccinimide)
RN  - 0 (5-hydroxy-N-methylpyrrolidone)
RN  - 0 (N-methylsuccinimide)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Solvents)
RN  - 0 (Succinimides)
RN  - JR9CE63FPM (N-methylpyrrolidone)
SB  - IM
MH  - *Abnormalities, Drug-Induced
MH  - Administration, Oral
MH  - Animals
MH  - Biotransformation
MH  - Body Weight/drug effects
MH  - Bone and Bones/abnormalities/drug effects
MH  - Cardiovascular Abnormalities/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Eating/drug effects
MH  - Embryonic Development/drug effects
MH  - Female
MH  - Fetal Death/*chemically induced
MH  - Fetal Weight/drug effects
MH  - Fetus/*drug effects
MH  - Gestational Age
MH  - Hernia, Diaphragmatic/chemically induced
MH  - Pregnancy
MH  - Pyrrolidinones/administration & dosage/metabolism/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Solvents/administration & dosage/metabolism/*toxicity
MH  - Succinimides/administration & dosage/metabolism/*toxicity
EDAT- 2007/03/21 09:00
MHDA- 2007/12/14 09:00
CRDT- 2007/03/21 09:00
PHST- 2007/03/21 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/03/21 09:00 [entrez]
AID - 10.1002/jat.1238 [doi]
PST - ppublish
SO  - J Appl Toxicol. 2007 Nov-Dec;27(6):571-81. doi: 10.1002/jat.1238.