International archives of occupational and environmental health · 2003
Human experimental exposure to N-methyl-2-pyrrolidone (NMP): toxicokinetics of NMP, 5-hydroxy- N-methyl-2-pyrrolidone, N-methylsuccinimide and 2-hydroxy- N-methylsuccinimide (2-HMSI), and biological monitoring using 2-HMSI as a biomarker.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jönsson B A G, Akesson B
Аннотация
OBJECTIVE: N-methyl-2-pyrrolidone (NMP) is a strong and selective organic solvent with an extensive and increasing use. It has been reported to be a compound that is toxic to the reproductive system. The aim of this study was to evaluate toxicokinetics parameters for NMP and its metabolites, 5-hydroxy- N-methyl-2- pyrrolidone (5-HNMP), N-methylsuccinimide (MSI) and 2-hydroxy- N-methylsuccinimide (2-HMSI), and to develop a method for biological monitoring of NMP exposure that uses 2-HMSI as a biomarker.
METHODS: Six healthy, male volunteers were exposed to NMP in an exposure chamber for 8 h at concentrations of 10, 25 and 50 mg/m(3). In addition, three of the subjects were exposed a second time at 50 mg/m(3). Air levels were monitored by Amberlite XAD-7 sampling and gas chromatography (GC) analysis. Levels of NMP and the metabolites in plasma and urine were analysed by GC or GC with mass spectrometry detection.
RESULTS: The concentration of 2-HMSI in plasma and urine rose during exposure and reached a peak approximately 15 h after the end of exposure. It then decayed according to a one-compartment model with a half-time of about 18 h. There were very close correlations between the NMP air levels, on the one hand, and concentrations of 2-HMSI in plasma (r=0.98) and creatinine-adjusted urinary 2-HMSI levels (r=0.96), on the other. The renal clearances were 0.13, 1.4, 0.12 and 1.2 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The total clearances were 11.4, 3.2, 8.5 and 1.1 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The apparent volumes of distribution were 41, 28, 120 and 28 l for NMP, 5-HNMP, MSI and 2-HMSI, respectively.
CONCLUSIONS: Toxicokinetics parameters for NMP, 5-HNMP, MSI and 2-HMSI have been estimated. Furthermore, 2-HMSI is applicable as a biomarker of exposure to NMP, and the levels in plasma and urine may be used to indicate an exposure over three days.
METHODS: Six healthy, male volunteers were exposed to NMP in an exposure chamber for 8 h at concentrations of 10, 25 and 50 mg/m(3). In addition, three of the subjects were exposed a second time at 50 mg/m(3). Air levels were monitored by Amberlite XAD-7 sampling and gas chromatography (GC) analysis. Levels of NMP and the metabolites in plasma and urine were analysed by GC or GC with mass spectrometry detection.
RESULTS: The concentration of 2-HMSI in plasma and urine rose during exposure and reached a peak approximately 15 h after the end of exposure. It then decayed according to a one-compartment model with a half-time of about 18 h. There were very close correlations between the NMP air levels, on the one hand, and concentrations of 2-HMSI in plasma (r=0.98) and creatinine-adjusted urinary 2-HMSI levels (r=0.96), on the other. The renal clearances were 0.13, 1.4, 0.12 and 1.2 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The total clearances were 11.4, 3.2, 8.5 and 1.1 l/h for NMP, 5-HNMP, MSI and 2-HMSI, respectively. The apparent volumes of distribution were 41, 28, 120 and 28 l for NMP, 5-HNMP, MSI and 2-HMSI, respectively.
CONCLUSIONS: Toxicokinetics parameters for NMP, 5-HNMP, MSI and 2-HMSI have been estimated. Furthermore, 2-HMSI is applicable as a biomarker of exposure to NMP, and the levels in plasma and urine may be used to indicate an exposure over three days.