Biomonitoring of Exposure to <italic>N</italic>-Methyl-2-Pyrrolidone in Workers of the Automobile Industry

Abstract

N-methyl-2-pyrrolidone (NMP) is an important organic solvent for varnishes in industry. NMP has been previously shown to be a developmental toxicant in rodents. This study reports current exposures to NMP in the spraying department of an automobile plant using biological monitoring. Two specific metabolites, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methyl-succinimide (2-HMSI), were analyzed in 69 urine samples of 14 workers exposed to NMP and 9 nonexposed controls. Three different working tasks ('loading' and 'cleaning' of the sprayer system and 'wiping/packing' of the sprayed materials) and three sampling times (preshift, postshift, and preshift of the following day) were studied in exposed workers. Median exposures of 5-HNMP and 2-HMSI in postshift urine of exposed workers were 0.91 and 0.52mg g(-1) creatinine, respectively, whereas median levels in controls were below the limit of detection. Decreased levels of 5-HNMP were observed in preshift urine samples on the following day (0.39mg g(-1) creatinine) in exposed workers, while the concentration of 2-HMSI did not change (0.49mg g(-1) creatinine). Highest exposures occurred during sprayer cleaning with a maximum level of 8.31mg g(-1) creatinine of 5-HNMP in postshift urine. In contrast to 'wipers/packers', no decrease in 5-HNMP could be observed in preshift urine samples on day 2 of the 'loaders' and 'cleaners'. Overall, exposure in terms of 5-HNMP postshift and 2-HMSI preshift of the following day were well below the current biological limit values of the European Union (70 and 20mg g(-1) creatinine). Our results provide initial data on NMP exposure in the automobile industry and suggest that the analysis of 5-HNMP in preshift samples also provides essential information, particularly in situations involving direct handling of liquid NMP-containing formulations.

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

“…Median NMP metabolite levels (5-HNMP 30.3 µg/L, 2-HMSI 38.8 µg/L) were generally higher than NEP metabolite levels (5-HNEP < LOQ, 2-HESI 6.1 µg/L) while 95th percentiles were higher for NEP (5-HNEP: 212 µg/L, 2-HESI: 230 µg/L) than NMP (5-HNMP: 98.1 µg/L, 2-HMSI: 100 µg/L). Metabolite concentrations were in the same range as those from a pilot population (Schindler et al 2012) and reference populations (Meier et al 2013; Koslitz et al 2014) of occupationally non-exposed individuals.…”

Evaluation of Skin Absorption Potential of Chemicals Relevant to Painting Trades

“…Therefore, it is unlikely that only limiting the exposure of N -methyl-2-pyrrolidone through the inhalation route will ensure a safe work environment, but the exposure through the dermal route also needs to be considered. N -Methyl-2-pyrrolidone is a polar solvent and is used as a solvent for water-based paints. , Acute irritant contact dermatitis of the hands was reported following exposure to workers handling the solvent . Moreover, N -methyl-2-pyrrolidone is believed to cause reproductive toxicity. , Because of its toxicity issues, replacement of this chemical has been suggested by a less toxic one .…”

“…N-Methyl-2-pyrrolidone is a polar solvent and is used as a solvent for water-based paints. 17,52 Acute irritant contact dermatitis of the hands was reported following exposure to workers handling the solvent. 53 Moreover, N-methyl-2-pyrrolidone is believed to cause reproductive toxicity.…”

The European Human Biomonitoring Initiative (HBM4EU): Human biomonitoring guidance values (HBM-GVs) for the aprotic solvents N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP)

“…After 96 h, the metabolites of NEP were detected in all urine samples analysed and mean urinary excretion fractions were 28.9% for 5-HNEP (F UE (96 h): 0.289) and 21.6% for 2-HESI (F UE (96 h): 0.216). The described main metabolites 5-HNMP and 2-HMSI for NMP as well as 5-HNEP and 2-HESI for NEP are each substance-specific for the parent compound (Deutsche Forschungsgemeinschaft (DFG), 2008; Käfferlein et al, 2013 ; Meier et al, 2013 ) and thus suitable as exposure biomarkers. The simultaneous determination of the two main metabolites of NMP and NEP offers the advantage of being able to investigate two biomarkers with different elimination behaviour.…”