Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Genotoxicity Assessment of Erythritol by Using Short-term Assay

  • Chung, Young-Shin (Hoseo Toxicological Research Center, Hoseo University) ;
  • Lee, Michael (Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University)
  • Received : 2013.12.10
  • Accepted : 2013.12.17
  • Published : 2013.12.31
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Abstract

Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 ${\mu}g$/plate in bacterial reverse mutation tests, 5,000 ${\mu}g/ml$ in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y $tk^{+/-}$ cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y $tk^{+/-}$ cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo.

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References

  1. Shindou, T., Sasaki, Y., Miki, H., Eguchi, T., Hagiwara, K. and Ichikawa, T. (1988) Determination of erythritol in fermented foods by high performance liquid chromatography. Shokuhin Eiseigaku Zasshi, 29, 419-422. https://doi.org/10.3358/shokueishi.29.419
  2. Goossens, J. and Roper, H. (1994) Erythritol: A new bulk sweetener. Int. Food Ingredients, 1/2, 27-33.
  3. Munro, I.C., Berndt, W.O., Borzelleca, J.F., Flamm, G., Lynch, B.S., Kennepohl, E., Bar, E.A. and Modderman, J. (1998) Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. Food Chem. Toxicol., 36, 1139-1174. https://doi.org/10.1016/S0278-6915(98)00091-X
  4. Arrigoni, E., Brouns, F. and Amado, R. (2005) Human gut microbiota does not ferment erythritol. Br. J. Nutr., 94, 643-646. https://doi.org/10.1079/BJN20051546
  5. Hino, H., Kasai, S., Hattori, N. and Kenjo, K. (2000) A case of allergic urticaria caused by erythritol. J. Dermatol., 27, 163-165. https://doi.org/10.1111/j.1346-8138.2000.tb02143.x
  6. FDA/CFSAN. (2001) Agency Response Letter: GRAS Notice No. GRN 000076. FDA, Washington.
  7. Chung, Y.S., Lee, S.J., Choi, S.A., Lee, J.H., Ryu, J.C. and Hong, E.K. (2004) Genotoxicity study of water extract of Anemarrhena asphodeloid and Phellodendron amurense in bacterial and mammalian cell systems. Toxicol. Res., 20, 43-47.
  8. Maron, D.M. and Ames, B.N. (1983) Revised methods for the Salmonella mutagenicity test. Mutat. Res., 113, 173-215. https://doi.org/10.1016/0165-1161(83)90010-9
  9. Hong, M.Y., Kim, J.Y., Lee, Y.M. and Lee, M. (2005) Assessment of sensitivity of photo-chromosomal assay in the prediction of photo-carcinogenicity. Toxicol. Res., 21, 99-105.
  10. Dean, B. J. and Danford, N. (1984) Assays for the detection of chemically-induced chromosome damage in cultured mammalian cells. In Mutagenicity testing - a practical approach (S. Venitt and J. M. Parry, Ed.), IRL Press Limited, Oxford, pp. 187-232.
  11. Kirsch-Volders, M., Sofuni, T., Aardema, M., Albertini, S., Eastmond, D., Fenech, M., Ishidate M. Jr., Kirchner, S., Lorge, E., Morita, T., Norppa, H., Surralles, J., Vanhauwaert, A. and Wakata, A. (2003) Report from the in vitro micronucleus assay working group. Mutat. Res., 540, 153-163. https://doi.org/10.1016/j.mrgentox.2003.07.005
  12. Oliver, J., Meunier, J.R., Awogi, T., Elhajouji, A., Ouldelhkim, M.C., Bichet, N., Thybaud, V., Lorenzon, G., Marzin, D. and Lorge, E. (2006) SFTG international collaborative study on in vitro micronucleus test V. Using L5178Y cells. Mutat. Res., 607, 125-152. https://doi.org/10.1016/j.mrgentox.2006.04.004
  13. Fenech, M. (2000) The in vitro micronucleus technique. Mutat. Res., 455, 81-95. https://doi.org/10.1016/S0027-5107(00)00065-8
  14. Kim, J.Y., Koh, W.S. and Lee, M. (2006) Validation of photocomet assay as a model for the prediction of photocarcinogenicity. Toxicol. Res., 22, 423-429.
  15. Schmid, W. (1975) The micronucleus test. Mutat. Res., 31, 9-15. https://doi.org/10.1016/0165-1161(75)90058-8
  16. Richardson, C., Williams, D.A., Allen, J.A., Amphlett, G., Chanter, D.O. and Phillips, B. (1989) Analysis of data from in vitro cytogenetics assays, In : Statistical evaluation of mutagenicity test data (Kirkland, D.J. edit.), Cambridge University Press, Cambridge, pp. 141-154.
  17. McCann, J., Horn, L. and Kaldoer, J. (1984) An evaluation of Salmonella (Ames) test data in the published literature: application of statistical procedures and analysis of mutagenicity potency. Mutat. Res., 134, 1-47. https://doi.org/10.1016/0165-1110(84)90013-7
  18. OECD/OCDE. (1997) OECD Guidelines for the Testing of Chemicals. TG No. 471 'Bacterial Reverse Mutation Test'. OECD, pp. 1-11.
  19. Lorge, E., Thybaud, V., Aardema, M.J., Oliver, J., Wakata, A., Lorenzon, G. and Marzin, D. (2006) SFTG international collaborative study on in vitro micronucleus test I. General conditions and overall conclusions of the study. Mutat. Res., 607, 13-36. https://doi.org/10.1016/j.mrgentox.2006.04.006
  20. Fenech, M. and Morley, A.A. (1985) Measurement of micro-nuclei in lymphocytes. Mutat. Res., 147, 29-36. https://doi.org/10.1016/0165-1161(85)90015-9
  21. Moon, H.J., Jeya, M., Kim, I.W. and Lee, J.K. (2010) Biotechnological production of erythritol and its applications. Appl. Microbiol. Biotechnol., 86, 1017-1025. https://doi.org/10.1007/s00253-010-2496-4
  22. Tandel, K.R. (2011) Sugar substitutes: Health controversy over perceived benefits. J. Pharmacol. Pharmacother., 2, 236-243. https://doi.org/10.4103/0976-500X.85936
  23. Bryan, G.T., Erturk, E. and Yoshida, O. (1970) Production of urinary bladder carcinomas in mice by sodium saccharin. Science, 168, 1238-1240. https://doi.org/10.1126/science.168.3936.1238
  24. Magnuson, B.A., Burdock, G.A., Doull, J., Kroes, R.M., Marsh, G.M., Pariza, M.W., Spencer, P.S., Waddell, W.J., Walker, R. and Williams, G.M. (2007) Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit. Rev. Toxicol., 37, 629-727. https://doi.org/10.1080/10408440701516184
  25. Takayama, S., Sieber, S.M., Adamson, R.H., Thorgeirsson, U.P., Dalgard, D.W., Arnold, L.L., Cano, M., Eklund, S. and Cohen, M.S. (1998) Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer. J. Natl. Cancer Inst., 90, 19-25. https://doi.org/10.1093/jnci/90.1.19
  26. Whysner, J. and Williams, G.M. (1996) Saccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion. Pharmacol. Ther., 71, 225-252. https://doi.org/10.1016/0163-7258(96)00069-1
  27. Butchko, H.H., Stargel, W.W., Comer, C.P., Mayhew, D.A., Benninger, C., Blackburn, G.L., de Sonneville, L.M., Geha, R.S., Hertelendy, Z., Koestner, A., Leon, A.S., Liepa, G.U., McMartin, K.E., Mendenhall, C.L., Munro, I.C., Novotny, E.J., Renwick, A.G., Schiffman, S.S., Schomer, D.L., Shaywitz, B.A., Spiers, P.A., Tephly, T.R., Thomas, J.A. and Trefz, F.K. (2002) Aspartame: review of safety. Regul. Toxicol. Pharmacol., 35, S1-93. https://doi.org/10.1006/rtph.2002.1542
  28. Pezzuto, J.M., Compadre, C.M., Swanson, S.M., Nanayakkara, D. and Kinghorn, A.D. (1985) Metabolically activated steviol, the aglycone of stevioside, is mutagenic. Proc. Natl. Acad. Sci. U. S. A., 82, 2478-2482. https://doi.org/10.1073/pnas.82.8.2478
  29. Benford, D.J., DiNovi, M. and Schlatter, J. (2006) Safety evaluation of certain food additives: Steviol glycosides. WHO Food Additives Series (World Health Organization Joint FAO/WHO Expert Committee on Food Additives (JECFA)), 54, 140.
  30. Kawamura, Y., Saito, Y., Imamura, M. and Modderman, J.P. (1996) Mutagenicity studies on erythritol in bacterial reversion assay systems and in chinese hamster fibroblast cells. Regul. Toxicol. Pharmacol., 24, S261-S263. https://doi.org/10.1006/rtph.1996.0107
  31. OECD/OCDE. (2010) OECD Guidelines for the Testing of Chemicals. TG No. 487 'In Vitro Mammalian Cell Micronucleus Test'. OECD, pp. 1-24.

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