Skip to main content
NCBI home page
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2005 Mar;62(3):151–156. doi: 10.1136/oem.2004.016089

Total body burden arising from a week's repeated dermal exposure to N,N-dimethylformamide

H Chang 1, C Tsai 1, Y Lin 1, T Shih 1, W Lin 1
PMCID: PMC1740980  PMID: 15723879

Abstract

Background: Hazardous chemicals and their metabolites may accumulate in the body following repeated airborne exposures and skin contact.

Aims: To estimate the contribution of skin absorption to total body burden of N,N-dimethylformamide (DMF) across a working week in two groups with similar levels of respiratory exposure but dissimilar skin contact.

Methods: Twenty five workers in a synthetic leather (SL) factory, 20 in a copper laminate circuit board (CLCB) factory, and 20 age and sex matched non-DMF exposed subjects, were recruited. Environmental monitoring of DMF exposure via respiratory and dermal routes, as well as biological monitoring of pre-shift urinary N-methylformamide (U-NMF), were performed for five consecutive working days.

Results: Environmental and biological monitoring showed no detectable exposure in controls. The average airborne DMF concentration (geometric mean (GM) 3.98 ppm, geometric standard deviation (GSD) 1.91 ppm), was insignificantly lower for SL workers than for CLCB workers (GM 4.49, GSD 1.84 ppm). Dermal DMF exposure and U-NMF values, however, were significantly higher for SL workers. A significant pattern of linear accumulation was found across a five day work cycle for SL workers but not for CLCB workers.

Conclusions: Dermal exposure to DMF over five consecutive days of occupational exposure can result in the accumulation of a significant DMF body burden. The long term exposure response under both repeated and intermittent conditions of substantial skin exposure is worthy of note.

Full Text

The Full Text of this article is available as a PDF (236.2 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. Brindley C., Gescher A., Ross D. Studies of the metabolism of dimethylformamide in mice. Chem Biol Interact. 1983 Aug 1;45(3):387–392. doi: 10.1016/0009-2797(83)90085-6. [DOI] [PubMed] [Google Scholar]
  3. Calvert G. M., Fajen J. M., Hills B. W., Halperin W. E. Testicular cancer, dimethylformamide, and leather tanneries. Lancet. 1990 Nov 17;336(8725):1253–1254. doi: 10.1016/0140-6736(90)92870-n. [DOI] [PubMed] [Google Scholar]
  4. Chang H-Y, Lin C-C, Shih T-S, Chan H., Chou J-S, Huang Y-S. Evaluation of the protective effectiveness of gloves from occupational exposure to 2-methoxyethanol using the biomarkers of 2-methoxyacetic acid levels in the urine and plasma. Occup Environ Med. 2004 Aug;61(8):697–702. doi: 10.1136/oem.2003.011171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang Ho-Yuan, Shih Tung-Sheng, Cheng Ching-Chang, Tsai Ching-Yi, Lai Jim-Shoung, Wang Ven-Shing. The effects of co-exposure to methyl ethyl ketone on the biological monitoring of occupational exposure to N,N-dimethylformamide. Int Arch Occup Environ Health. 2003 Feb 4;76(2):121–128. doi: 10.1007/s00420-002-0371-z. [DOI] [PubMed] [Google Scholar]
  6. Chang Ho-Yuan, Shih Tung-Sheng, Guo Yueliang Leon, Tsai Ching-Yi, Hsu Ping-Chi. Sperm function in workers exposed to N,N-dimethylformamide in the synthetic leather industry. Fertil Steril. 2004 Jun;81(6):1589–1594. doi: 10.1016/j.fertnstert.2003.10.033. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Chivers C. P. Disulfiram effect from inhalation of dimethylformamide. Lancet. 1978 Feb 11;1(8059):331–331. doi: 10.1016/s0140-6736(78)90105-8. [DOI] [PubMed] [Google Scholar]
  9. Cox N. H., Mustchin C. P. Prolonged spontaneous and alcohol-induced flushing due to the solvent dimethylformamide. Contact Dermatitis. 1991 Jan;24(1):69–70. doi: 10.1111/j.1600-0536.1991.tb01644.x. [DOI] [PubMed] [Google Scholar]
  10. Fail P. A., George J. D., Grizzle T. B., Heindel J. J. Formamide and dimethylformamide: reproductive assessment by continuous breeding in mice. Reprod Toxicol. 1998 May-Jun;12(3):317–332. doi: 10.1016/s0890-6238(98)00011-2. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Glennemeler K. A., Denver R. J. Sublethal effects of chronic exposure to an organochlorine compound on northern leopard frog (Rana pipiens) tadpoles. Environ Toxicol. 2001;16(4):287–297. [PubMed] [Google Scholar]
  13. Goh V. H., Chia S. E., Ong C. N. Effects of chronic exposure to low doses of trichloroethylene on steroid hormone and insulin levels in normal men. Environ Health Perspect. 1998 Jan;106(1):41–44. doi: 10.1289/ehp.9810641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hansen E., Meyer O. Embryotoxicity and teratogenicity study in rats dosed epicutaneously with dimethylformamide (DMF). J Appl Toxicol. 1990 Oct;10(5):333–338. doi: 10.1002/jat.2550100505. [DOI] [PubMed] [Google Scholar]
  15. Johanson G., Boman A. Percutaneous absorption of 2-butoxyethanol vapour in human subjects. Br J Ind Med. 1991 Nov;48(11):788–792. doi: 10.1136/oem.48.11.788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kestell P., Gill M. H., Threadgill M. D., Gescher A., Howarth O. W., Curzon E. H. Identification by proton NMR of N-(hydroxymethyl)-N-methylformamide as the major urinary metabolite of N,N-dimethylformamide in mice. Life Sci. 1986 Feb 24;38(8):719–724. doi: 10.1016/0024-3205(86)90586-2. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. Lyle W. H., Spence T. W., McKinneley W. M., Duckers K. Dimethylformamide and alcohol intolerance. Br J Ind Med. 1979 Feb;36(1):63–66. doi: 10.1136/oem.36.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mráz J., Jheeta P., Gescher A., Hyland R., Thummel K., Threadgill M. D. Investigation of the mechanistic basis of N,N-dimethylformamide toxicity. Metabolism of N,N-dimethylformamide and its deuterated isotopomers by cytochrome P450 2E1. Chem Res Toxicol. 1993 Mar-Apr;6(2):197–207. doi: 10.1021/tx00032a009. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Nomiyama T., Nakashima H., Chen L. L., Tanaka S., Miyauchi H., Yamauchi T., Sakurai H., Omae K. N,N-dimethylformamide: significance of dermal absorption and adjustment method for urinary N-methylformamide concentration as a biological exposure item. Int Arch Occup Environ Health. 2001 Apr;74(3):224–228. doi: 10.1007/s004200000207. [DOI] [PubMed] [Google Scholar]
  26. Poet Torka S., Weitz Karl K., Gies Richard A., Edwards Jeffrey A., Thrall Karla D., Corley Richard A., Tanojo Hanafi, Hui Xiaoying, Maibach Howard I., Wester Ronald C. PBPK modeling of the percutaneous absorption of perchloroethylene from a soil matrix in rats and humans. Toxicol Sci. 2002 May;67(1):17–31. doi: 10.1093/toxsci/67.1.17. [DOI] [PubMed] [Google Scholar]
  27. Pope C. A., 3rd Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who's at risk? Environ Health Perspect. 2000 Aug;108 (Suppl 4):713–723. doi: 10.1289/ehp.108-1637679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sartorelli P. Dermal exposure assessment in occupational medicine. Occup Med (Lond) 2002 May;52(3):151–156. doi: 10.1093/occmed/52.3.151. [DOI] [PubMed] [Google Scholar]
  29. Scailteur V., de Hoffmann E., Buchet J. P., Lauwerys R. Study on in vivo and in vitro metabolism of dimethylformamide in male and female rats. Toxicology. 1984 Jan;29(3):221–234. doi: 10.1016/0300-483x(84)90023-4. [DOI] [PubMed] [Google Scholar]
  30. Shih Tung-Sheng, Chou Tzu-Chieh, Chang Ho-Yuan, Wu Cheng-Chao, Wang Peng-Yau. Accumulation of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) among workers occupationally exposed to carbon disulfide for 1 week. Sci Total Environ. 2003 Jun 1;308(1-3):37–47. doi: 10.1016/S0048-9697(02)00617-4. [DOI] [PubMed] [Google Scholar]
  31. Thrall Karla D., Weitz Karl K., Woodstock Angela D. Use of real-time breath analysis and physiologically based pharmacokinetic modeling to evaluate dermal absorption of aqueous toluene in human volunteers. Toxicol Sci. 2002 Aug;68(2):280–287. doi: 10.1093/toxsci/68.2.280. [DOI] [PubMed] [Google Scholar]
  32. Wrbitzky R. Liver function in workers exposed to N,N-dimethylformamide during the production of synthetic textiles. Int Arch Occup Environ Health. 1999 Jan;72(1):19–25. doi: 10.1007/s004200050329. [DOI] [PubMed] [Google Scholar]

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

RESOURCES