Skip to main content
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2005 May;62(5):330–336. doi: 10.1136/oem.2004.017129

The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry

H Kafferlein 1, C Ferstl 1, A Burkhart-Reichl 1, K Hennebruder 1, H Drexler 1, T Bruning 1, J Angerer 1
PMCID: PMC1741015  PMID: 15837855

Abstract

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.

Full Text

The Full Text of this article is available as a PDF (132.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angerer J., Göen T., Krämer A., Käfferlein H. U. N-methylcarbamoyl adducts at the N-terminal valine of globin in workers exposed to N,N-dimethylformamide. Arch Toxicol. 1998 Apr;72(5):309–313. doi: 10.1007/s002040050507. [DOI] [PubMed] [Google Scholar]
  2. Chang Ho-Yuan, Tsai Ching-Yi, Lin Yu-Qun, Shih Tung-Sheng, Lin Yun-Chin. Urinary biomarkers of occupational N,N-dimethylformamide (DMF) exposure attributed to the dermal exposure. J Expo Anal Environ Epidemiol. 2004 May;14(3):214–221. doi: 10.1038/sj.jea.7500316. [DOI] [PubMed] [Google Scholar]
  3. Ducatman A. M., Conwill D. E., Crawl J. Germ cell tumors of the testicle among aircraft repairmen. J Urol. 1986 Oct;136(4):834–836. doi: 10.1016/s0022-5347(17)45096-8. [DOI] [PubMed] [Google Scholar]
  4. Gescher A. Metabolism of N,N-dimethylformamide: key to the understanding of its toxicity. Chem Res Toxicol. 1993 May-Jun;6(3):245–251. doi: 10.1021/tx00033a001. [DOI] [PubMed] [Google Scholar]
  5. Hellwig J., Merkle J., Klimisch H. J., Jäckh R. Studies on the prenatal toxicity of N,N-dimethylformamide in mice, rats and rabbits. Food Chem Toxicol. 1991 Mar;29(3):193–201. doi: 10.1016/0278-6915(91)90037-8. [DOI] [PubMed] [Google Scholar]
  6. Kennedy G. L., Jr Biological effects of acetamide, formamide, and their mono and dimethyl derivatives: an update. Crit Rev Toxicol. 2001 Mar;31(2):139–222. doi: 10.1080/200140911116861. [DOI] [PubMed] [Google Scholar]
  7. Käfferlein H. U., Angerer J. Determination of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in the general population using gas chromatography-mass spectrometry. J Environ Monit. 1999 Oct;1(5):465–469. doi: 10.1039/a903039e. [DOI] [PubMed] [Google Scholar]
  8. Käfferlein H. U., Angerer J. N-methylcarbamoylated valine of hemoglobin in humans after exposure to N,N-dimethylformamide: evidence for the formation of methyl isocyanate? Chem Res Toxicol. 2001 Jul;14(7):833–840. doi: 10.1021/tx000230r. [DOI] [PubMed] [Google Scholar]
  9. Käfferlein H. U., Angerer J. Simultaneous determination of two human urinary metabolites of N,N-dimethylformamide using gas chromatography-thermionic sensitive detection with mass spectrometric confirmation. J Chromatogr B Biomed Sci Appl. 1999 Nov 12;734(2):285–298. doi: 10.1016/s0378-4347(99)00372-2. [DOI] [PubMed] [Google Scholar]
  10. Käfferlein H. U., Göen T., Müller J., Wrbitzky R., Angerer J. Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry. Int Arch Occup Environ Health. 2000 Mar;73(2):113–120. doi: 10.1007/s004200050016. [DOI] [PubMed] [Google Scholar]
  11. Lareo A. C., Perbellini L. Biological monitoring of workers exposed to N-N-dimethylformamide. II. Dimethylformamide and its metabolites in urine of exposed workers. Int Arch Occup Environ Health. 1995;67(1):47–52. doi: 10.1007/BF00383132. [DOI] [PubMed] [Google Scholar]
  12. Lauwerys R. R., Kivits A., Lhoir M., Rigolet P., Houbeau D., Buchet J. P., Roels H. A. Biological surveillance of workers exposed to dimethylformamide and the influence of skin protection on its percutaneous absorption. Int Arch Occup Environ Health. 1980;45(3):189–203. doi: 10.1007/BF00380783. [DOI] [PubMed] [Google Scholar]
  13. Moorman W. J., Ahlers H. W., Chapin R. E., Daston G. P., Foster P. M., Kavlock R. J., Morawetz J. S., Schnorr T. M., Schrader S. M. Prioritization of NTP reproductive toxicants for field studies. Reprod Toxicol. 2000 Jul-Aug;14(4):293–301. doi: 10.1016/s0890-6238(00)00089-7. [DOI] [PubMed] [Google Scholar]
  14. Mráz J., Nohová H. Absorption, metabolism and elimination of N,N-dimethylformamide in humans. Int Arch Occup Environ Health. 1992;64(2):85–92. doi: 10.1007/BF00381474. [DOI] [PubMed] [Google Scholar]
  15. Mráz J., Nohová H. Percutaneous absorption of N,N-dimethylformamide in humans. Int Arch Occup Environ Health. 1992;64(2):79–83. doi: 10.1007/BF00381473. [DOI] [PubMed] [Google Scholar]
  16. Mráz J., Simek P., Chvalová D., Nohová H., Smigolová P. Studies on the methyl isocyanate adducts with globin. Chem Biol Interact. 2004 Jun 30;148(1-2):1–10. doi: 10.1016/j.cbi.2003.06.003. [DOI] [PubMed] [Google Scholar]
  17. Mráz J., Turecek F. Identification of N-acetyl-S-(N-methylcarbamoyl)cysteine, a human metabolite of N,N-dimethylformamide and N-methylformamide. J Chromatogr. 1987 Mar 6;414(2):399–404. doi: 10.1016/0378-4347(87)80064-6. [DOI] [PubMed] [Google Scholar]
  18. Mráz Jaroslav, Dusková Sárka, Gálová Eva, Nohová Hana, Brabec Marek. Biological monitoring of N, N-dimethylformamide. Reference value for N-methylcarbamoyl adduct at the N-terminal valine of globin as a biomarker of chronic occupational exposure. Int Arch Occup Environ Health. 2002 Sep 20;75 (Suppl):S93–S96. doi: 10.1007/s00420-002-0387-4. [DOI] [PubMed] [Google Scholar]
  19. Mráz Jaroslav, Dusková Sárka, Gálová Eva, Nohová Hana, Krausová Pavla, Linhart Igor, Simek Petr. Improved gas chromatographic-mass spectrometric determination of the N-methylcarbamoyl adduct at the N-terminal valine of globin, a metabolic product of the solvent N,N-dimethylformamide. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Oct 5;778(1-2):357–365. doi: 10.1016/s0378-4347(01)00455-8. [DOI] [PubMed] [Google Scholar]
  20. Saillenfait A. M., Payan J. P., Beydon D., Fabry J. P., Langonne I., Sabate J. P., Gallissot F. Assessment of the developmental toxicity, metabolism, and placental transfer of N,N-dimethylformamide administered to pregnant rats. Fundam Appl Toxicol. 1997 Sep;39(1):33–43. doi: 10.1006/faat.1997.2343. [DOI] [PubMed] [Google Scholar]
  21. Sakai T., Kageyama H., Araki T., Yosida T., Kuribayashi T., Masuyama Y. Biological monitoring of workers exposed to N,N-dimethylformamide by determination of the urinary metabolites, N-methylformamide and N-acetyl-S-(N-methylcarbamoyl) cysteine. Int Arch Occup Environ Health. 1995;67(2):125–129. doi: 10.1007/BF00572236. [DOI] [PubMed] [Google Scholar]
  22. Slatter J. G., Rashed M. S., Pearson P. G., Han D. H., Baillie T. A. Biotransformation of methyl isocyanate in the rat. Evidence for glutathione conjugation as a major pathway of metabolism and implications for isocyanate-mediated toxicities. Chem Res Toxicol. 1991 Mar-Apr;4(2):157–161. doi: 10.1021/tx00020a006. [DOI] [PubMed] [Google Scholar]
  23. Wrbitzky R., Angerer J., Lehnert G. External and internal monitoring in workers exposed to N,N-dimethylformamide. Int Arch Occup Environ Health. 1996;68(6):508–510. doi: 10.1007/BF00377877. [DOI] [PubMed] [Google Scholar]
  24. Wrbitzky R., Angerer J. N,N-dimethylformamide--influence of working conditions and skin penetration on the internal exposure of workers in synthetic textile production. Int Arch Occup Environ Health. 1998 Jul;71(5):309–316. doi: 10.1007/s004200050286. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES