Potency of N-methyl-2-pyrrolidone main metabolites to induce developmental toxic effects in rats
Saillenfait, AM; Sabate, JP; Gallissot, F
HERO ID
3564264
Reference Type
Journal Article
Subtype
Abstract
Year
2006
Language
English
| HERO ID | 3564264 |
|---|---|
| Material Type | Abstract |
| In Press | No |
| Year | 2006 |
| Title | Potency of N-methyl-2-pyrrolidone main metabolites to induce developmental toxic effects in rats |
| Authors | Saillenfait, AM; Sabate, JP; Gallissot, F |
| Journal | Reproductive Toxicology |
| Volume | 22 |
| Issue | 2 |
| Page Numbers | 282 |
| Abstract | N-methyl-2-pyrrolidone (NMP) is a widely used industrial solvent. It was shown to be embryolethal and teratogenic when given to rats, by oral route, at doses of 500 mg/kg and greater. The aim of this study was to determine the role of NMP major metabolites in NMP-induced developmental toxic effects. Sprague–Dawley rats (20–24 per group) were given with 5-hydroxy-N-methylpyrolidone (5-HNMP), N-methylsuccinimide (NMS), or 2-hydroxy-N-methylsuccinimide (2-HNMS), by gavage, on Days 6–20 of gestation. The doses tested were: 0, 250, 500, 750 and 1000 mg/kg for 5-HNMP; 0, 500, 750, 1000, and 1250 mg/kg for NMS; and 0, 250, 500, 1000, and 1500 mg/kg for 2-HNMS. The dams were euthanized on Day 21 of gestation, and the fetuses were submitted to external examination. No sign of maternal or developmental toxicity was noted at any dose of 5-HNMP. NMS caused a significant increase in the incidence of resorptions and malformations (essentially anasarca) at 1250 mg/kg, in the presence of maternal toxicity (decreased food consumption and body weight gain). Reduced fetal weight was also found at 1000 and 1250 mg/kg. 2-HNMS did not produce adverse effect on embryo-fetal development up to the dose of 1500 mg/kg, while maternal toxicity was observed at the beginning of treatment from 500 mg/kg. Although NMS exhibited an embryotoxic potential at high doses, our results indicate that the three metabolites tested are not responsible for the prenatal toxicity of NMP. |
| Is Certified Translation | No |
| Dupe Override | No |
| Conference Location | September 3-6, 2006 |
| Conference Name | 34th Annual Conference of the European Teratology Society |
| Conference Date | Abano Terme, Padova, Italy |
| Is Public | Yes |
| Language Text | English |
| Keyword | Pregnancy; Animals; Rats, Sprague-Dawley; Pyrrolidinones/TOXICITY/METABOLISM; Solvents/TOXICITY/METABOLISM; Abnormalities/ETIOLOGY; Dose-Response Relationship, Drug; NO CAS RN; 26138-58-9 |