Jönsson B A G, Akesson B
Department of Occupational and Environmental Medicine, Institute of Laboratory Medicine, University Hospital, 221 85 Lund, Sweden.
Int Arch Occup Environ Health. 2003 May;76(4):267-74. doi: 10.1007/s00420-003-0438-5. Epub 2003 Apr 3.
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.
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.
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.
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.
N-甲基-2-吡咯烷酮（NMP）是一种强效且具有选择性的有机溶剂，其使用范围广泛且不断增加。据报道，该化合物对生殖系统有毒性。本研究的目的是评估NMP及其代谢产物5-羟基-N-甲基-2-吡咯烷酮（5-HNMP）、N-甲基琥珀酰亚胺（MSI）和2-羟基-N-甲基琥珀酰亚胺（2-HMSI）的毒代动力学参数，并开发一种以2-HMSI作为生物标志物的NMP暴露生物监测方法。
6名健康男性志愿者在暴露舱中分别以10、25和50mg/m³的浓度暴露于NMP 8小时。此外，其中3名受试者以50mg/m³的浓度再次暴露。通过Amberlite XAD-7采样和气相色谱（GC）分析监测空气水平。血浆和尿液中NMP及其代谢产物的水平通过GC或GC与质谱检测进行分析。
血浆和尿液中2-HMSI的浓度在暴露期间升高，并在暴露结束后约15小时达到峰值。然后根据一室模型衰减，半衰期约为18小时。一方面，NMP空气水平与血浆中2-HMSI浓度（r = 0.98）和肌酐校正后的尿2-HMSI水平（r = 0.96）之间存在非常密切的相关性。NMP、5-HNMP、MSI和2-HMSI的肾清除率分别为0.13、1.4、0.12和1.2 l/h。NMP、5-HNMP、MSI和2-HMSI的总清除率分别为11.4、3.2、8.5和1.1 l/h。NMP、5-HNMP、MSI和2-HMSI的表观分布容积分别为41、28、120和28 l。
已估算出NMP、5-HNMP、MSI和2-HMSI的毒代动力学参数。此外，2-HMSI可作为NMP暴露的生物标志物，血浆和尿液中的水平可用于指示三天内的暴露情况。
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