Background: N,N-dimethylformamide (DMF) was recently prioritised for field studies by the National Toxicology Program based on the potency of its reproductive toxic effects. Aims: To measure accurately exposure to DMF in occupational settings. Methods: 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. Results: 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. Conclusions: 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.

The choice of the biomonitoring method depends mainly on the purpose for which the measurement is conducted. For evaluation of acute exposures or to assess safety measures in the working area, an updated version of the traditional method of Kimmerle and Eben (1975a, b) for the determination of total NMF in urine is sufficient. For risk assessment after exposure to DMF, the determination of AMCC should be carried out, since AMCC, but not total NMF, is supposed to be related to the toxicity of DMF. However, there is still a need to develop an easier, more sensitive and more selective method for the determination of AMCC in urine until AMCC can be considered for regulatory purposes in occupational settings.

The method permits the simultaneous quantification of the N‐terminal haemoglobin adducts N‐(2‐hydroxyethyl)valine (HEV), N‐(2‐hydroxypropyl)valine (HPV), N‐(2‐cyanoethyl)valine (CEV), N‐(2‐carbonamide ethyl)valine (AAV), and N‐(2‐hydroxy‐2‐carbonamide ethyl)valine (GAV) of the carcinogens ethylene oxide, propylene oxide, acrylonitrile, acrylamide, as well as of glycidamide the metabolite of acrylamide in blood. The adducts which are covalently bound to the N‐terminal valine of the globin chain are cleaved off from the globin chain by a modified Edman degradation. The resulting pentafluorophenyl thiohydantoine derivatives of the valine adducts are extracted with diethyl ether, purified and then subjected to tandem mass spectrometric detection. To protect the vicinal hydroxyl group of the glycidamide adduct, the modified Edman degradation is followed by a second derivatization using sulphuric acetone. For calibration, standards are prepared in non‐smoker pooled globin, adding solutions of dipeptide standards simulating the adduct‐bearing latter two N‐terminal amino acids of the haemoglobin chain. They are processed in the same way as the samples to be analyzed. As internal standards, solutions of isolated globin, which has prior been transformed with the deuterated compounds d 3 ‐acrylo‐nitrile, d 3 ‐acrylamide or d 3 ‐propylene oxide, are used. As internal standard for glycidamide, the d 8 ‐labeled, acetonized pentafluorophenyl thiohydantoine of the glycidamide valine adduct is used.

The method permits the simultaneous quantification of the N‐terminal haemoglobin adducts N‐(2‐hydroxyethyl)valine (HEV), N‐(2‐hydroxypropyl)valine (HPV), N‐(2‐cyanoethyl)valine (CEV), N‐(2‐carbonamide ethyl)valine (AAV), and N‐(2‐hydroxy‐2‐carbonamide ethyl)valine (GAV) of the carcinogens ethylene oxide, propylene oxide, acrylonitrile, acrylamide, as well as of glycidamide the metabolite of acrylamide in blood. The adducts which are covalently bound to the N‐terminal valine of the globin chain are cleaved off from the globin chain by a modified Edman degradation. The resulting pentafluorophenyl thiohydantoine derivatives of the valine adducts are extracted with diethyl ether, purified and then subjected to tandem mass spectrometric detection. To protect the vicinal hydroxyl group of the glycidamide adduct, the modified Edman degradation is followed by a second derivatization using sulphuric acetone. For calibration, standards are prepared in non‐smoker pooled globin, adding solutions of dipeptide standards simulating the adduct‐bearing latter two N‐terminal amino acids of the haemoglobin chain. They are processed in the same way as the samples to be analyzed. As internal standards, solutions of isolated globin, which has prior been transformed with the deuterated compounds d3‐acrylo‐nitrile, d 3 ‐acrylamide or d 3 ‐propylene oxide, are used. As internal standard for glycidamide, the d 8 ‐labeled, acetonized pentafluorophenyl thiohydantoine of the glycidamide valine adduct is used.