Bengt Akesson1, Martin A Carnerup, Bo A G Jönsson. 1. Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Vincent Haufroid; Veronika K Jaeger; Stefan Jeggli; Rolf Eisenegger; Alfred Bernard; Drita Friedli; Dominique Lison; Philipp Hotz Journal: Int Arch Occup Environ Health Date: 2014-08 Impact factor: 3.015
Authors: Nadin Ulrich; Daniel Bury; Holger M Koch; Maria Rüther; Till Weber; Heiko-Udo Käfferlein; Tobias Weiss; Thomas Brüning; Marike Kolossa-Gehring Journal: Int Arch Occup Environ Health Date: 2018-08-22 Impact factor: 3.015