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Toxicological information

Exposure related observations in humans: other data

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Administrative data

exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
Biomonitoring of N-ethyl-2-pyrrolidone in automobile varnishers
S. Koslitz, S. Meier, B. K. Schindler, T. Weiß, H.M. Koch, T. Brüning, H.U. Käfferlein
Bibliographic source:
Toxicology Letters 231 (2014) 142–146

Materials and methods

Type of study / information:
Biomonitoring study
Endpoint addressed:
other: exposure at the workplace
GLP compliance:
not specified


Ethical approval:
not specified
Details on study design:
Spot urine samples from 14 workers in a varnishing plant of a German automobile manufacturer were collected. The majority of the workers (n = 12) carried out regular working tasks consisting of loading, detaching and packing varnished automobile parts and refilling the spraying system with lacquers. These workers wore cotton gloves during handling of the parts. Respiratory protection was provided and used by the workers when they were refilling the sprayer system. In addition, these workers wore solvent-resistant gloves beneath regular rubber gloves. The latter were used for grip only. Refilling the sprayer system was a short-term working task where break-through times for NMP of the solvent resistant
inner gloves (>480 min) was not reached. Two workers carried out particular working tasks consisting of manually disassembling and cleaning spraying nozzles, screws and nuts with different solvent mixtures, containing up to 100% N-alkylpyrrolidones. These workers used the same protective measures as described above (solvent resistant inner and rubber outer gloves, respiratory protection). It is important to mention that the varnishes and solvents contained NMP (known due to compulsory labeling) but no information was available whether they also contained NEP. Urine samples were collected midweek pre-shift, post-shift and pre-shift on the following day to address the different elimination half-lives of 5-HNEP and 2-HESI. All workers worked a regular 8-h work shift. Additionally, nine non-exposed employees from the medical department of the same company served as controls and provided midweek post-shift urine specimens. All samples were frozen and stored at -20°C until analysis. Information about workplace, working tasks, personal protection equipment, confounders outside the work place (e.g., the use of paints and lacquers at home), age, sex, body weight and smoking habits were collected by questionnaire.

Results and discussion

The median urinary level of 5-HNEP in control individuals of the plant was 0.03 mg/L. The median post-shift level reported here in workers with regular
working tasks was approximately 5-fold higher (0.15 mg/L). The maximum observed level of urinary 5-HNEP was 5.55 mg/L in these workers. Differences between controls and exposed workers were also observed for 2-HESI. The median background urinary level in the controls from this plant was 0.03 mg/L, whereas median concentrations of 2-HESI in samples from the non-exposed general population were <0.005 mg/L (<5 mg/L, Schindler et al.,2012). Again, post-shift exposure in workers with regular working tasks in the varnishing department of the plant presented here were considerably higher (0.19 mg/L) with a maximum level of 6.40 mg 2-HESI per liter urine. No differences were found between median post-shift levels of 5-HNEP and those in pre-shift urine samples on the same day (0.13 mg/L) and the following day (0.14 mg/L). The same was also true for 2-HESI. Maximum urinary levels of 4.04 and 8.45 mg/L were observed for 2-HESI in the pre-shift samples of day 2. Continuously increasing concentrations, however, were not expected for 5-HNEP. Nevertheless, in the particular case of the two cleaners the level of 5-HNEP in pre-shift samples of the following day (5.2 and 31.0 mg/L) were unexpectedly high. These increased pre-shift levels probably reflect the relevance of dermal absorption of NEP in terms of a delayed absorption, distribution and elimination and compared to oral or inhalation exposure.

Applicant's summary and conclusion

The authors of the study concluded that they were able to show that workers can be exposed to NEP during varnishing tasks in the automobile industry.
Executive summary:


N-alkyl-2-pyrrolidones are important organic solvents for varnishes in industry. This study investigated exposure to N-ethyl-2-pyrrolidone (NEP) in varnishing of hard plastic components in an automobile plant. Two specific biomarkers of exposure, 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), were analyzed in urine samples of 14 workers. For this purpose, pre-shift, post-shift and next day pre-shift urine samples were collected midweek. Twelve workers performed regular work tasks (loading, wiping and packing), whereas two workers performed special work tasks including cleaning the sprayer system with organic solvents containing N-alkyl-2-pyrrolidones. Spot urine samples of nine non-exposed persons of the same plant served as controls. Median post-shift urinary levels of workers with regular work tasks (5-HNEP: 0.15 mg/L; 2-HESI: 0.19 mg/L) were 5-fold higher compared to the controls (0.03 mg/L each). Continuously increasing metabolite levels, from preshift via post-shift to pre-shift samples of the following day, were observed in particular for the two workers with the special working tasks. Maximum levels were 31.01 mg/L (5-HNEP) and 8.45 mg/L (2-HESI). No clear trend was evident for workers with regular working tasks. In summary, the authors concluded that they were able to show that workers can be exposed to NEP during varnishing tasks in the automobile industry.