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Toxicological information

Health surveillance data

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Administrative data

health surveillance data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study which meets basic scientific principles. No data on ethical approval.

Data source

Reference Type:

Materials and methods

Study type:
biological exposure monitoring
measurement of biomarkers to assess the exposure from environmental sources.
Endpoint addressed:
basic toxicokinetics
Principles of method if other than guideline:
Measurement of accurately exposure to DMF in occupational settings. The main metabolites of DMF were measured in the urine and blood of workers exposed to DMF in the polyacrylic fibre industry.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): N,N-dimethylformamide

- Substance type: solvent
- Physical state: vapour
- Analytical purity: not applicable (exposure to DMF took place at the workplaces in a factory of polyacrylic fibre production)


Type of population:
Ethical approval:
not specified
only questionnaire information is mentioned
Details on study design:
Thirty five male workers exposed to DMF at different workplaces were studied with regard to their exposure to DMF.

Results and discussion

NMHb was the best biomarker of exposure for use in future risk assessments studies.

Any other information on results incl. tables

N-methylformamide = NMF in urine samples

The concentrations were analysed to be 8.0, 18.6, and 27.6 mg/L in workers exposed to low (group 1), medium (group 2), and high (group 3) concentrations of DMF, respectively. However, because of the wide range of NMF levels in every group, no statistically significant differences could be determined between all three groups. There were also no differences between smokers and non-smokers and between persons working in dry and wet spinning. The results clearly show the advantages and disadvantages of measuring NMF in urine. NMF is specific for occupational exposure to DMF. Because no NMF can be found in urine samples of non-exposed individuals, analysis of NMF is clearly suitable to distinguish between exposed and nonexposed persons. However, NMF cannot be used to categorise workers in different exposure groups, to identify particular working tasks with high exposures to DMF, or in risk assessment.

N-Acetyl-S-(N-methylcarbamoyl)cysteine = AMCC in urine samples

The concentrations were determined to be 6.2, 17.7, and 29.1 mg/L in workers exposed to low, medium, and high concentrations of DMF, respectively . In contrast to NMF, the differences between all three groups now were of borderline statistical significance (p = 0.04 for both volume and creatinine related concentrations). It might be due to a longer half-time of AMCC (24 -34 h) in comparison with NMF (4 -5 h). A detailed comparison between groups 1 and 2 and between groups 1 and 3 revealed p values of 0.08 and 0.02 for volume related concentrations, while for creatinine related concentrations p values of 0.03 were calculated. No statistical differences between smokers and non-smokers were found. The formation of AMCC is not totally specific for occupational exposure to DMF, However, single measurements of AMCC in urine can still be used to distinguish between occupationally exposed and nonexposed individuals, because AMCC concentrations are about 100 times higher in exposed workers than non-exposed individuals. Compared to NMF in urine, AMCC is more suitable to categorise and assess exposure of workers exposed to DMF, and AMCC measurements represent DMF exposure more accurately, which is expected from workplace conditions and questionnaires. The formation of AMCC is linked to the metabolic formation of methyl isocyanate (MIC) after exposure to DMF and more related to toxic effects caused by exposure to DMF.15 Therefore, the formation and measurement of AMCC is also more suitable from a toxicological point of view. However, measurements of AMCC—although preferable to those of NMF—are still limited to certain time points of urine sampling. In conclusion, AMCC cannot be recommended as a biomarker of exposure in health risk studies because of its short halflife. However, AMCC is—similar to NMF—an ideal biomarker of exposure for occupational hygiene control.

N-methylcarbamoylated haemoglobin = NMHb in blood samples

Hb adducts—if stable—are supposed to be biomarkers at the molecular level with a mean life span of about 120 days. Median concentration of NMHb in blood of exposed workers at all workplaces was determined to be 121.2 nmol/g globin (21.3–464.9 nmol/g). In contrast to urinary levels of NMF and AMCC, there was a clear statistically significant difference between all three groups of exposed workers for NMHb (p = 0.01). The concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. The difference in the mean adduct levels between group 1 and 2 is more pronounced than between groups 2 and 3. The result is based on the fact that workers of group 3 use protective measures more often (impermeable gloves, respiratory masks) than workers of group 2, because they belong to an exposure group with higher risk of exposure. The results show that the provided and applied protective measures—if used—are capable of decreasing the uptake of DMF at the workplace. NMHb is a biomarker of exposure on the molecular level and related to DMF toxicity. In contrast to NMF and AMCC, sampling for NMHb measurements is completely independent of specific time points. Exposure assessment can be carried out randomly 2–3 times per year, because the measurement does represent the mean exposure to DMF during the previous four months.

Applicant's summary and conclusion

Measurement of NMHb in blood is recommended rather than measurement of NMF and AMCC in urine to accurately assess exposure to DMF in health risk assessment. However, NMF and AMCC are useful biomarkers for occupational hygiene intervention. Further investigations regarding toxicity of DMF should focus on highly exposed persons in the polyacrylic fibre industry. Additional measurements in occupational settings other than the polyacrylic fibre industry are also recommended, since the population at risk and the production volume of DMF are high.
Executive summary:


"Exposure assessment can be carried out by the determination of urinary metabolites NMF and AMCC. However, less information is available using biomarkers on the molecular level, such as NMHb. Knowing that risk is linked to exposure, which in turn is dependent on particular working tasks, we analysed NMF, AMCC, and NMHb in workers exposed to DMF in the polyacrylic fibre industry at different workplaces. Main focus was on the suitability of the biomarkers in order to assess exposure, the identification of working tasks, which are associated with increased exposure to DMF, whether or not the expected exposure (questionnaire information) does reflect the true exposure to DMF determined by biological monitoring, and finally, which biomarkers are suitable for health risk assessment and occupational hygiene."


In 35 healthy workers employed in the polyacrylic fibre industry, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine, and N-methylcarbamoylated haemoglobin (NMHb) in blood were measured. Workplace documentation and questionnaire information were used to categorise workers in groups exposed to low, medium, and high concentrations of DMF.


All three biomarkers can be used to identify occupational exposure to DMF. However, only the analysis of NMHb could accurately distinguish between workers exposed to different concentrations of DMF. The median concentrations were determined to be 55.1, 122.8, and 152.6 nmol/g globin in workers exposed to low, medium, and high concentrations of DMF, respectively. It was possible by the use of NMHb to identify all working tasks with increased exposure to DMF. While fibre crimpers were found to be least exposed to DMF, persons washing, dyeing, or towing the fibres were found to be highly exposed to DMF. In addition, NMHb measurements were capable of uncovering working tasks, which previously were not associated with increased exposure to DMF; for example, the person preparing the fibre forming solution.