pharmacokinetics ofNMP inplasma andurine

Objectives-To studytheacuteeffects of exposure totheincreasingly usedsolvent, N-methyl-2-pyrrolidone (NMP) inmale volunteers. Further,to determinethe NMP concentration inplasmaandurine duringandafter theexposure. Methods-Sixmale volunteers were exposed foreighthourson fourdifferent daysto 0,10,25,and 50mg/mlNMP. Plasmawas collected andurinewas sampledduringand afterthe exposure. Changesinnasalvolumewere measured by acoustic rhinometryand in airway resistance byspirometry. Results-Theeight-hour experimental exposure to10,25,and50mg/m3didnot inducediscomfort to eyes or upper airways. Acutechanges innasalvolumewere notfound,andno changesinthespirometricdatacouldbe registered. The elimination curves suggested a non-linear patternandattheendofexposure showed mean (range) halflifes ofNMP inplasma ofabout40 (2.9-5.8) hoursandinurine 45 (3.5-6.6) hours.The unmetabolised NMP foundinurinesamplescollected during exposure andatthesubsequent 44 hourscorresponded to about2% ofthe calculated absorbeddose.At theendof theexposure there was a closecorrelation betweenexposures andtheplasmaconcentration andurinary excretion ofNMP. Conclusions-NMP was absorbed throughtherespiratory tractandreadily eliminated fromthebody,mainlybybiotransformation to other compounds. Exposureto10,25,or 50mg/m3NMP did notcause nose, eye, or airwayirritation. Thus,NMP isa mildirritant. (Occup Environ Med1997;54:236-240)