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22.08.2018 | Original Article | Ausgabe 8/2018 Open Access

International Archives of Occupational and Environmental Health 8/2018

Metabolites of the alkyl pyrrolidone solvents NMP and NEP in 24-h urine samples of the German Environmental Specimen Bank from 1991 to 2014

International Archives of Occupational and Environmental Health > Ausgabe 8/2018
Nadin Ulrich, Daniel Bury, Holger M. Koch, Maria Rüther, Till Weber, Heiko-Udo Käfferlein, Tobias Weiss, Thomas Brüning, Marike Kolossa-Gehring
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00420-018-1347-y) contains supplementary material, which is available to authorized users.
The original version of this article was revised due to a retrospective Open Access order.
A correction to this article is available online at https://​doi.​org/​10.​1007/​s00420-019-01506-4.



The aim of this study was to get a first overview of the exposure to the solvents and reproductive toxicants N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) in Germany. NMP and NEP metabolite concentrations were determined in 540 24-h urine samples of the German Environmental Specimen Bank collected from 1991 to 2014. With these data we were able to investigate NMP/NEP exposures over time and to evaluate associated risks.


NMP metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) and NEP metabolites 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI) were determined by stable isotope dilution analysis using solid phase extraction followed by derivatization (silylation) and GC–EI–MS/MS.


We were able to quantify 5-HNMP and 2-HMSI in 98.0 and 99.6% and 5-HNEP and 2-HESI in 34.8 and 75.7% of the samples. Metabolite concentrations were rather steady over the timeframe investigated, even for NEP which has been introduced as an NMP substitute only in the last decade. Calculated median daily intakes in 2014 were 2.7 µg/kg bw/day for NMP and 1.1 µg/kg bw/day for NEP. For the combined risk assessment of NMP and NEP exposure, the hazard index based on the human biomonitoring assessment I values (HBM I values) was less than 0.1.


Based on the investigated subpopulation of the German population, individual and combined NMP and NEP exposures were within acceptable ranges in the investigated timeframe. Sources of NEP exposure in the 90s and 00s remain elusive.

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