title: Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and urine following oral administration of NMP to rats.
abstract: The primary aims were to study the metabolism in rats and to determine the biological levels after one oral developmentally toxic dose of N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. Non-pregnant female Sprague-Dawley rats were given an oral single dose of either a non-toxic dose of 125 mg NMP/kg (group 1) by gavage or a developmentally toxic dose of 500 mg/kg (group 2). Blood plasma (7 rats per time point) and urine (10 rats per time point) were sampled up to 72 h after administration and analyzed using mass spectrometry. In both plasma and urine NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP), N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide (2-HMSI) and 2-pyrrolidone (2-P) were identified. In urine 48% of the administered dose was recovered as 5-HNMP and 2-5% as 2-HMSI. The total recovery in urine was 53-59%. The peak concentrations for NMP in plasma were 1.2 and 6.9 mmol/l, 0.42 and 0.76 mmol/l for 5-HNMP, 0.07 and 0.31 mmol/l for MSI and for 2-HMSI the concentrations were 0.02 and 0.05 mmol/l for groups 1 and 2, respectively. In summary, the same metabolites were found in rats as in humans and the biological levels were reported for NMP and its metabolites after oral exposure to a developmentally toxic dose and one non-toxic dose of NMP.
authors.affiliation: Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University Hospital, SE-221 85 Lund, Sweden. martin.carnerup@ymed.lu.se
authors.forename: Martin A
authors.initials: MA
authors.lastname: Carnerup
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Saillenfait
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D005260:Female; D013058:Mass Spectrometry; D011247:Pregnancy; D011760:Pyrrolidinones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000493:pharmacokinetics*
chemical_list: D011760:Pyrrolidinones; D012997:Solvents; C038678:N-methylpyrrolidone