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J Occup Health year 2000 volume 42 number 6 page 321 - 327
Classification Original
Title A Linear Pharmacokinetic Model Predicts Usefulness of N-Methyl-2-Pyrrolidone (NMP) in Plasma or Urine as a Biomarker for Biological Monitoring for NMP Exposure
Author Xiaofei E1, Yasuhiko WADA1, Jun-ichi NOZAKI1, 2, Hiroyuki MIYAUCHI3, Shigeru TANAKA4, Yukio SEKI4 and Akio KOIZUMI1, 2
Organization 1Department of Hygiene, Akita University School of Medicine, 2Department of
Health and Environmental Sciences, Kyoto University, School of Public Health, 3The Association of Industrial Health and 4School of Allied Health Sciences, Kitasato University
Keywords N-methyl-2-pyrrolidine, Pharmacokinetic modeling, Biological modeling
Correspondence A. Koizumi, Department of Health and Environmental Sciences, School of Public Health, Kyoto University, Kyoto 606-8501, Japan
Abstract A Linear Pharmacokinetic Model Predicts Usefulness of N-Methyl-2-Pyrrolidone (NMP) in Plasma or Urine as a Biomarker for Biological Monitoring for NMP Exposure: Xiaofei E, et al. Department of Hygiene, Akita University School of Medicine-N-methyl-2-pyrrolidone (NMP: C5H9NO:CAS number 872-50-4) is an increasingly used solvent due to the lack of ozone depleting activity. The aim of this study is to construct a simple pharmacokinetic model for NMP. In factory A, four workers who were exposed to NMP at 0.09-0.69 ppm for 12 h by time weighted average (TWA) were followed up for an entire workweek. Their NMP concentrations in plasma and urine were monitored during the observation period. Five volunteers were exposed to NMP during the observation of workers in the factory A for eight hours. NMP kinetics in plasma and urine were monitored for 2 d after exposure. Concentrations of NMP in plasma and urine as standardized by creatinine concentrations were used to construct a one compartment pharmacokinetic model. The model successfully simulated the kinetics in four workers and five volunteers. In the next step, the model was applied to eight workers in another factory: they were exposed to NMP for 12 h at 0.04 to 0.59 ppm by TWA. The model could successfully predict kinetics of NMP levels in plasma and urine at the end of work. The model was then applied to experimental exposure cases in the literature. The model successfully predicted the concentrations of NMP in plasma and urine at the exposure intensity level of 12 ppm X 8 h. These results imply that metabolic saturation does not occur up to the exposure intensity of 12 ppm X 8 h and demonstrate the usefulness of determinations of NMP in plasma and urine for biological monitoring.