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http://dx.doi.org/10.5487/TR.2013.29.4.249

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)
Publication Information
Toxicological Research / v.29, no.4, 2013 , pp. 249-255 More about this Journal
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.
Keywords
Erythritol; Ames assay; Chromosomal aberration test; Micronucleus assay; Comet assay; Genotoxicity;
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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.   DOI
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.   DOI   ScienceOn
4 Arrigoni, E., Brouns, F. and Amado, R. (2005) Human gut microbiota does not ferment erythritol. Br. J. Nutr., 94, 643-646.   DOI   ScienceOn
5 Hino, H., Kasai, S., Hattori, N. and Kenjo, K. (2000) A case of allergic urticaria caused by erythritol. J. Dermatol., 27, 163-165.   DOI
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.   과학기술학회마을
8 Maron, D.M. and Ames, B.N. (1983) Revised methods for the Salmonella mutagenicity test. Mutat. Res., 113, 173-215.   DOI   ScienceOn
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.   과학기술학회마을
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.   DOI   ScienceOn
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.   DOI   ScienceOn
13 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.   과학기술학회마을
14 Schmid, W. (1975) The micronucleus test. Mutat. Res., 31, 9-15.   DOI
15 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.
16 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.   DOI   ScienceOn
17 OECD/OCDE. (1997) OECD Guidelines for the Testing of Chemicals. TG No. 471 'Bacterial Reverse Mutation Test'. OECD, pp. 1-11.
18 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.   DOI
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.   DOI   ScienceOn
20 Fenech, M. and Morley, A.A. (1985) Measurement of micro-nuclei in lymphocytes. Mutat. Res., 147, 29-36.   DOI   ScienceOn
21 Tandel, K.R. (2011) Sugar substitutes: Health controversy over perceived benefits. J. Pharmacol. Pharmacother., 2, 236-243.   DOI   ScienceOn
22 Bryan, G.T., Erturk, E. and Yoshida, O. (1970) Production of urinary bladder carcinomas in mice by sodium saccharin. Science, 168, 1238-1240.   DOI   ScienceOn
23 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.   DOI   ScienceOn
24 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.   DOI   ScienceOn
25 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.   DOI   ScienceOn
26 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.   DOI   ScienceOn
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.   DOI   ScienceOn
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.   DOI   ScienceOn
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 OECD/OCDE. (2010) OECD Guidelines for the Testing of Chemicals. TG No. 487 'In Vitro Mammalian Cell Micronucleus Test'. OECD, pp. 1-24.
31 Fenech, M. (2000) The in vitro micronucleus technique. Mutat. Res., 455, 81-95.   DOI   ScienceOn