Human experimental exposure study on the uptake and urinary elimination of N-methyl-2-pyrrolidone (NMP) during simulated workplace conditions.
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.
Bader
Michael
M
Department of Occupational Medicine, Hannover Medical School, OE 5370, Carl-Neuberg-Str 1, 30625, Hannover, Germany. bader.michael@mh-hannover.de
Wrbitzky
Renate
R
Blaszkewicz
Meinolf
M
van Thriel
Christoph
C
D000280:Administration, Inhalation; D000328:Adult; D000395:Air Pollutants, Occupational / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test / Q000379:methods; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D016273:Occupational Exposure / Q000032:analysis* / Q000517:prevention & control; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D012146:Rest / Q000502:physiology; D013223:Statistics as Topic; D013388:Succinimides / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D013723:Teratogens / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D013997:Time Factors; D014116:Toxicology / Q000379:methods; D016526:Workload; D017132:Workplace
C107901:2-hydroxy-N-methylsuccinimide; C107902:5-hydroxy-N-methylpyrrolidone; D000395:Air Pollutants, Occupational; D011760:Pyrrolidinones; D013388:Succinimides; D013723:Teratogens; D003404:Creatinine; C038678:N-methylpyrrolidone