Biomonitoring of the industrial alkyl pyrrolidone solvents NMP and NEP: specific metabolites in 24-hour urine samples from the German Environmental Specimen Bank (1996/2012)

Abstract

N-Methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) are multi-purpose organic solvents in<BR>industry. Both are developmental and teratogenic toxicants in rodents. NMP is classified as a REACh substanceof very high concern. Because of their toxicological profile and their broad application resulting in a possibleexposure of the general population, NMP and NEP were chosen as target substances for the cooperationproject between the German Federal Ministry for the Environment, Nature Conservation, Building and NuclearSafety (BMUB) and the German Chemical Industry Association (VCI) aiming to establish human biomonitoring(HBM) methods for "newŁ substances of interest. NMP and NEP are metabolized to 5-hydroxy-N-alkyl-2-pyrrolidones (5-HNMP, 5-HNEP) and 2-hydroxy-N-alkylsuccinimides (2-HMSI, 2-HESI). We analyzed thesespecific metabolites in 24-hour urine samples from the German Environmental Specimen Bank. For thispurpose, 20 randomly selected samples collected in 1996 and in 2012, respectively, were analyzed by asensitive and specific GC-MS/MS method with isotope dilution quantification. We detected NMP metabolites in100% and NEP metabolites in 95% of all samples. Despite the considerable differences in the elimination halftimesof the alkyl pyrrolidone metabolites, the correlations between the metabolites were rather strong (NMP:r=0.51; NEP: r=0.67). An exposure determined through one metabolite is thus confirmed by the other129metabolite. Median NMP metabolite levels were comparable between 1996 (5-HNMP 50 ìg/L, 2-HMSI 46 ìg/L)and 2012 (5-HNMP 39 ìg/L, 2-HMSI 41 ìg/L). Surprisingly, urinary levels of NEP metabolites were approx. 10times higher in 1996 (5-HNEP 14 ìg/L, 2-HESI 42 ìg/L) as compared to 2012 (5-HNEP ~1 ìg/L, 2-HESI 5ìg/L). We would have expected a reverse trend for NEP since NEP has only recently been introduced into themarket as a substitute for NMP. The sources of past and present exposures to NMP and NEP warrant furtherinvestigations. <BR>Quelle: 24th Annual Meeting ofThe International Society of Exposure Science: Exposure Science Integration to Protect Ecological Systems,Human Well-Being, and Occupational Health; Abstrct Book ISES 2014 / International Society of Exposure Science, Cincinnati: 2014, S. 128