Biological monitoring of N-methyl-2-pyrrolidone using 5-hydroxy-N-methyl-2-pyrrolidone in plasma and urine as the biomarker.
OBJECTIVE
The aims were to study the toxicokinetics of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) in blood and urine after exposure to N-methyl-2-pyrrolidone (NMP) and to study the suitability of 5-HNMP as a biomarker for assessing NMP exposure.


METHODS
Six male volunteers were exposed for 8 hours to NMP concentrations of 0, 10, 25, and 50 mg/m3. Blood and urine were sampled before, during, and up to 40 hours after exposure. Aliquots of urine and plasma were purified, derivatized, and analyzed for 5-HNMP on a gas chromatograph/mass spectrometer in the electron impact mode.


RESULTS
The mean plasma concentration [P-(5-HNMP)] after 8-hour NMP exposure to 10, 25, and 50 mg/m3 was 8.0, 19.6, and 44.4 micromol/l, respectively. The mean urinary concentration [U-(5-HNMP)] for the 2 last hours of exposure was 17.7, 57.3, and 117.3 mmol/mol creatinine, respectively. The maximal P-(5-HNMP)and U-(5-HNMP) concentrations occurred 1 hour and 0-2 hours, respectively, after the exposure. The half-times of P-(5-HNMP) and U-(5-HNMP) were 6.3 and 7.3 hours, respectively. The 5-HNMP urinary concentrations were 58% of the calculated retained dose. There was a close correlation (r) between P-(5-HNMP) (r=0.98) and U-(5-HNMP) (r=0.97) with NMP exposure.


CONCLUSIONS
5-HNMP is an excellent biomarker for assessing exposure to NMP. Its plasma and urinary half-times (6-7 hours), the minimal risk for contamination during sampling in occupational settings, and the close correlation of P-(5-HNMP) and U-(5-HNMP) with NMP exposure makes 5-HNMP suitable for monitoring exposure to NMP. 5-HNMP in plasma is recommended.
Akesson
B
B
Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden. bengt.akesson@ymed.lu.se
Jönsson
B A
BA
D000328:Adult; D015415:Biomarkers; D004784:Environmental Monitoring / Q000379:methods; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis*; D016014:Linear Models; D008297:Male; D008452:Maximum Allowable Concentration; D011760:Pyrrolidinones / Q000032:analysis* / Q000378:metabolism*; D012997:Solvents / Q000032:analysis*; D013548:Sweden; D013723:Teratogens / Q000032:analysis*
C107902:5-hydroxy-N-methylpyrrolidone; D015415:Biomarkers; D011760:Pyrrolidinones; D012997:Solvents; D013723:Teratogens; C038678:N-methylpyrrolidone