Biological monitoring and health effects of low-level exposure to N-methyl-2-pyrrolidone: a cross-sectional study.
OBJECTIVE
To examine the value of urinary 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in a population of workers exposed to N-methyl-2-pyrrolidone (NMP) and to look for health effects of exposure to this organic solvent.


METHODS
Airborne NMP was determined according to the NIOSH method. Urinary 5-HNMP and 2-HMSI (after and before next shift) were determined by liquid chromatography with tandem mass spectrometry. Outcomes were effects on lung, kidney, skin and mucous membranes, nervous system, haematopoiesis and liver determined by clinical examination and laboratory measurements. Univariate statistical methods and multiple regressions were used to analyse results. Skin resorption, smoking and other potential confounders were taken into account.


RESULTS
Three hundred twenty-seven workers were eligible out of which 207 workers (63%) participated. Ninety-one of these worked with NMP. Occupational exposure to NMP did often not occur daily and ranged from non-detectable to 25.8 mg/m3 (median = 0.18). Urinary 2-HMSI (mg/l; before next shift) was the best biomarker of exposure to NMP, explaining about 70% of the variance, but most likelihood ratios did not allow for ruling exposure in or out, at these low levels of exposure. Creatinine adjustment did not improve the results clearly. No clear and consistent health effects could be associated with NMP exposure. No indication for a bias due to non-participation was found.


CONCLUSIONS
Biological monitoring, primarily urinary 2-HMSI (mg/l; before next shift), is of value to estimate exposure to NMP even when exposure is irregular and low. Likelihood ratios of urinary 5-HMNP or 2-HMSI are, however, not quite satisfactory at these low levels. No irritant or other health effects were found.
Vincent
V
Haufroid
Veronika K
VK
Jaeger
Stefan
S
Jeggli
Rolf
R
Eisenegger
Alfred
A
Bernard
Drita
D
Friedli
Dominique
D
Lison
Philipp
P
Hotz
D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D003430:Cross-Sectional Studies; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D011760:Pyrrolidinones / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity / Q000652:urine*; D013388:Succinimides / Q000652:urine*; D013557:Switzerland; D013723:Teratogens / Q000032:analysis / Q000378:metabolism* / Q000633:toxicity; D055815:Young Adult
C107901:2-hydroxy-N-methylsuccinimide; C107902:5-hydroxy-N-methylpyrrolidone; D000395:Air Pollutants, Occupational; D011760:Pyrrolidinones; D013388:Succinimides; D013723:Teratogens; C038678:N-methylpyrrolidone