Human experimental exposure study on the uptake and urinary elimination of N-methyl-2-pyrrolidone (NMP) during simulated workplace conditions

Bader, M; Wrbitzky, R; Blaszkewicz, M; van Thriel, C

HERO ID

3539722

Reference Type

Journal Article

Year

2007

Language

English

PMID

17103143

HERO ID 3539722
In Press No
Year 2007
Title Human experimental exposure study on the uptake and urinary elimination of N-methyl-2-pyrrolidone (NMP) during simulated workplace conditions
Authors Bader, M; Wrbitzky, R; Blaszkewicz, M; van Thriel, C
Journal Archives of Toxicology
Volume 81
Issue 5
Page Numbers 335-346
Abstract A human experimental study was carried out with 16 volunteers to examine the elimination of N-methyl-2-pyrrolidone (NMP) after exposure to the solvent under simulated workplace conditions. The NMP concentrations were 10, 40 and 80 mg/m(3) for 2 x 4 h with an exposure-free interval of 30 min. Additionally, a peak exposure scenario (25 mg/m(3) baseline, 160 mg/m(3) peaks for 4 x 15 min, time-weighted average: 72 mg/m(3)) was tested. The influence of physical activity on the uptake and elimination of NMP was studied under otherwise identical exposure conditions but involving moderate workload on a bicycle ergometer (75 W for 6 x 10 min). The peak times and biological half-lives of urinary NMP and its main metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in urine were analysed as well as the interrelationships between exposure and biomarkers. All analytes showed a close correlation between their post-shift peak concentrations and airborne NMP. An exposure to the current German workplace limit value of 80 mg/m(3) under resting conditions resulted in urinary peak concentrations of 2,400 microg/L NMP, 117 mg/g creatinine 5-HNMP and 32 mg/g creatinine 2-HMSI (workload conditions: 3,400 microg/L NMP, 150 mg/g creatinine 5-HNMP, 44 mg/g creatinine 2-HMSI). Moderate workload enhanced the total uptake of NMP by approximately one third. Differences between the estimated and the observed total amount of urinary metabolites point to a significant contribution of dermal absorption on the uptake of NMP. This aspect, together with the influence of physical workload, should be considered for the evaluation of a biological limit value for NMP.
Doi 10.1007/s00204-006-0161-6
Pmid 17103143
Wosid WOS:000246269900004
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English