Evaluation of exposure biomarkers from percutaneous absorption of N-methyl-2-pyrrolidone.
OBJECTIVE
The aim of this study was to evaluate different biomarkers of exposure to N-methyl-2-pyrrolidone (NMP), a widely used industrial chemical. For this purpose, differences in toxicokinetics between men and women and between pure and water-mixed NMP were evaluated after dermal absorption.


METHODS
Six female and six male volunteers (groups 1 and 2) were topically exposed for 6 hours to 300 mg of NMP. An additional group of six male volunteers (group 3) was exposed to 300 mg of NMP in a 50% water solution. Blood and urine were sampled before, during, and up to 9 days after the exposure. Plasma and urine were analyzed using mass spectrometry.


RESULTS
For groups 1 and 2, 16% and 18% of the applied dose were recovered in the urine as the sum of NMP and its metabolites. For group 3, 4% was recovered. The maximal concentration of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) was 10, 8.1, and 2.1 micromol/l for groups 1, 2 and 3, respectively, in plasma and 420, 360 and 62 micromol/l in urine adjusted for density. For 2-hydroxy-N-methylsuccinimide (2-HMSI), the maximal concentration was 5.4, 4.5, and 1.3 micromol/l for groups 1, 2 and 3, in plasma, respectively, and 110, 82 and 19 micromol/l in urine adjusted for density. For 5-HNMP there was a difference in time to reach the maximal concentration depending on whether pure NMP or 50% NMP in water was used. No such difference was seen for 2-HMSI. The differences in kinetics between male and female volunteers were small.


CONCLUSIONS
Preferably 2-HMSI should be used as the biomarker of exposure to NMP.
Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
Bengt
B
Akesson
Martin A
MA
Carnerup
Bo A G
BA
Jönsson
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011760:Pyrrolidinones / Q000032:analysis* / Q000633:toxicity; D013548:Sweden
D015415:Biomarkers; D011760:Pyrrolidinones; C038678:N-methylpyrrolidone