Metabolites of the alkyl pyrrolidone solvents NMP and NEP in 24-h urine samples of the German Environmental Specimen Bank from 1991 to 2014
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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.
KeywordsHuman biomonitoring N-Methyl-2-pyrrolidone (NMP) N-Ethyl-2-pyrrolidone (NEP) German Environmental Specimen Bank (ESB) Exposure assessment Urinary metabolites
This study was financed by the German Environment Agency (Umweltbundesamt, Grant No. 3714 622006). We would like to acknowledge the teams of the ESB, of the University Hospital Muenster and of Fraunhofer IBMT for their excellent work in acquiring, handling, and storing of human samples for the German ESB. The development of the analytical method and its application in a population study are part of a large-scale 10-year project on the advancement of human biomonitoring in Germany. This project is a cooperation agreed in 2010 between the German Federal Ministry for Environment, Nature Conservation and Nuclear Safety (BMU) and the Verband der Chemischen Industrie e.V. (German Chemical Industry Association—VCI) and is managed by the German Environment Agency (UBA). In this cooperation project the analytical method development is financed by the Chemie Wirtschaftsförderungsgesellschaft mbH while the first application of the novel methodology in a population study is financed by the German Environment Agency. Experts from governmental scientific authorities, industry and science closely accompany and advise the project in selecting substances and developing methods.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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