DOI QR코드

DOI QR Code

Comparative Study on the EC50 Value in Single and Mixtures of Dimethylformamide, Methyl Ethyl Ketone, and Toluene

  • Kim, Ki-Woong (Occupational Safety and Health Research Institute, KOSHA) ;
  • Won, Yong Lim (Occupational Safety and Health Research Institute, KOSHA) ;
  • Park, Dong Jin (Occupational Safety and Health Research Institute, KOSHA) ;
  • Kim, Doh-Hee (Research Institute, Seoul Medical Center) ;
  • Song, Kwan Young (Department of Neurosurgery, Seoul Medical Center)
  • Received : 2014.09.02
  • Accepted : 2014.09.19
  • Published : 2014.09.30

Abstract

The aim of this research was to improve our understanding of human toxicity due to exposure to DMF, MEK, or TOL individually as compared to exposure to DMF-MEK or DMF-TOL mixtures, by comparing $EC_{50}$ values as well as the morphological changes in HepG2 cells treated with these substances. We found that there was marked cell necrosis in the groups treated with mixtures than in those treated with the compounds alone, and that the amount of cell death and the $EC_{50}$ value were more dependent on MEK and TOL than on DMF. Moreover, analysis of the changes in effective concentration curves revealed that MEK had an antagonistic effect on the human toxicity of DMF, whereas TOL had a synergistic effect. Accordingly, these results suggest that in workplaces involved in the manufacture of synthetic leather, mixtures of DMF and TOL should be avoided as much as possible in order to minimize environmental toxicity and protect the health of the workers.

Keywords

References

  1. Lee, B.W. (2012) Globally harmonized system of classification and labeling of chemicals. 2012 Proceeding of Korean Society of Pesticide Science Spring Conference, pp 52-64.
  2. National Institute of Environmental Research (NIER). (2011) Notification 2011-29 of the National Institute of Environmental Research.
  3. Ministry of Employment and Labor (MoEL). (2013) Notification 2013-38 of the Ministry of Employment and Labor.
  4. Wolf, P., Hartl, F., Brischwein, M. and Wolf, B. (2011) Determination of dynamic doxorubicin-EC50 value in an automated high-content workstation for cellular assays. Toxicol. Vitro, 25, 1889-1894. https://doi.org/10.1016/j.tiv.2011.05.031
  5. Luan, F., Xu, X., Liu, H. and Cordeiro, M.N. (2013) Prediction of the baseline toxicity of non-polar narcotic chemical mixtures by QSAR approach. Chemosphere, 90, 1980-1986. https://doi.org/10.1016/j.chemosphere.2012.10.065
  6. Yang, R.S., Thomas, R.S., Gustafson, D.L., Campain, J., Benjamin, S.A., Verhaar, H.J. and Mumtaz, M.M. (1998) Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling. Environ. Health Perspect., 106 Suppl 6, 1385-1393.
  7. Kim, K.W. and Chung, Y.H. (2013) Hepatotoxicity in rats treated with dimethylformamide or toluene or both. Toxicol. Res., 29, 187-193. https://doi.org/10.5487/TR.2013.29.3.187
  8. Kim, K.W., Won, Y.L., Park, D.J., Lee, J.S., Han, I.S. and Lee, S.H. (2014) Changes in physico-chemical properties of single and mixture state of DMF, MEK and toluene in synthetic leather factories. J. Korean Soc. Occup. Environ. Hyg., 24, 238-245. https://doi.org/10.15269/JKSOEH.2014.24.2.238
  9. Korean Standard (KS). (2007) Determination of boiling temperature for chemical agents. Method KS M 1071-2. Korean Standard Association, Seoul.
  10. Korean Standard (KS). (1977) Test methods for density and relative density of chemical products. Method KS M 0004. Korean Standard Association, Seoul.
  11. Korean Standard (KS). (2012) Petroleum products and crude petroleum-Determination of vapour pressure-Reid method. Method KS M ISO 3007. Korean Standard Association, Seoul.
  12. Korean Standard (KS). (2008) Testing methods for flash point of crude oil and petroleum products-Determination of flash point-Tag closed cup method. Methods KS M 2010. Korean Standard Association, Seoul.
  13. American Standard Test Method. (2009) Concentration limits of flammability of chemicals (vapors and gases). ASTM E 681-09.
  14. National Institute of Occupational Safety and Health (NIOSH). (2003) NIOSH manual of analytical methods (3rd supplement), tp://www.msdshazcom.com/nmam/nmampub.html.
  15. IPCS. (1991) Dimethylformamide. Environmental Health Criteria 114. World Health Organization, Geneva, pp. 21-23.
  16. Kennedy, G.L. (2012) Toxicology of dimethyl and monomethyl derivatives of acetamide and formamide: a second update. Crit. Rev. Toxicol., 42, 793-826. https://doi.org/10.3109/10408444.2012.725028
  17. IPCS. (1985) Toluene. Environmental Health Criteria 52. World Health Organization, Geneva, pp. 49-54.
  18. IPCS. (1993) Methyl ethyl ketone. Environmental Health Criteria 143. World Health Organization, Geneva, pp. 49-57.
  19. Chang, H.Y., Yun, Y.D., Yu, Y.C., Shih, T.S., Lin, M.S., Kuo, H.W. and Chen, K.M. (2005) The effects of simultaneous exposure to methyl ethyl ketone and toluene on urinary biomarkers of occupational N,N-dimethylforamide exposure. Toxicol. Lett., 155, 385-395. https://doi.org/10.1016/j.toxlet.2004.11.005
  20. Croute, F., Poinsot, J., Gaubin, Y., Beau, B., Simon, V., Murat, J.C. and Soleilhavoup, J.P. (2002) Volatile organic compounds cytotoxicity and expression of HSP72, HSP90 and GRP78 stress proteins in cultured human cells. Biochem. Biophys. Acta, 1591, 147-155. https://doi.org/10.1016/S0167-4889(02)00271-9
  21. Connell, D.W., Braddock, R.D. and Mani, S.V. (1993) Prediction of the partition coefficient of lipophilic compounds in the air-mammal tissue system. Sci. Total Environ., Suppl Pt 2, 1383-1396.

Cited by

  1. Combined Toxic Effects of Polar and Nonpolar Chemicals on Human Hepatocytes (HepG2) Cells by Quantitative Property - Activity Relationship Modeling vol.32, pp.4, 2016, https://doi.org/10.5487/TR.2016.32.4.337