Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Evaluation of the Genetic Toxicity of Synthetic Chemical (XVIII)-in vitro Mouse Lymphoma Assay and in vivo Supravital Micronucleus Assay with Butylated Hydroxytoluene (BHT)

  • Kim, Youn-Jung (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology) ;
  • Ryu, Jae-Chun (Cellular and Molecular Toxicology Laboratory, Korea Institute of Science and Technology)
  • Published : 2007.09.30
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Abstract

Butylated hydroxytoluene (BHT) is widely used antioxidant food additives. It has been extensively studied for potential toxicities. BHT appears adverse effects in liver and thyroid. In this study, we evaluated the genetic toxicity of BHT with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vivo mouse supravital micronucleus (MN) assay. BHT did not appear the significantly results in the absence and presence of metabolic activation system with MLA. Also, in vivo testing of BHT yielded negative results with supravital MN assay. These results suggest that BHT itself was not generally considered genotoxic.

Keywords

References

  1. JECFA. Toxicological evaluation of certain food additives and contaminants in food. Who Food Additives Series. No. 35, pp. 3-86. Joint FAO/WHO Expert Committee on Food Additives. Geneva (1996)
  2. FDA. Number of brand name products in each product code, cosmetic product formulation data. In Division of Cosmetics Technology. pp. 33-34. Food and Drug Administration, Washington, DC (1981)
  3. Sherwin-Williams. BHT: The versatile antioxidant for today and tomorrow (Bull. A Ox12). Cleveland, OH(1992)
  4. ILSI. Butylated Hydroxytoluene (BHT). A Monograph. International Life Sciences Institute, Washington, DC (1984)
  5. IARC. IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 40, Some Naturally Occurring and Synthetic Food Components, Furocoumarins and Ultraviolet Radiation. Butylated hydroxytoluene (BHT). pp. 161-206. International Agency for Research on Cancer, Lyon (1986)
  6. Kahl, R. Synthetic antioxidants: biochemical actions and interference with radiation, toxic compounds, chemical mutagens and chemical carcinogens. Toxicology 33:185-228 (1984) https://doi.org/10.1016/0300-483X(84)90038-6
  7. WHO. Toxicological evaluation of certain food additives and contaminants. In Food Additives Series, 21. World Health Organization Cambridge (1987)
  8. Witschi, H., Williamson, D. & Lock, S. Enhancement of urethan tumorigenesis in mouse lung by butylated hydroxytoluene. J Nation Can Inst 58:301-305 (1977) https://doi.org/10.1093/jnci/58.2.301
  9. Lindenschrnidt, R. C. et al. The effects of dietary butylated hydroxytoluene on liver and colon tumor development in mice. Toxicology 38:151-160 (1986) https://doi.org/10.1016/0300-483X(86)90116-2
  10. Maeura, Y. & Williams, G. M. Enhancing effect of butylated hydroxytoluene on the development of liver altered foci and neoplasms induced by N-2-fluoremyl-acetamide in rats. Food Cosmet Toxicol 22:191-198 (1984) https://doi.org/10.1016/0278-6915(84)90126-1
  11. Imaida, K. et al. Promoting activities of butylated hydroxyanisole, butylated hydroxytoluene and sodium -1-ascordsate on forestomach and urinary bladder carcinogenesis initiated with the methylnitrosourea in F344 male rats. Gann 75:769-775 (1984)
  12. Williams, G. M., McQueen, C. A. & Tong, C. Toxicity studies of butylated hydroxyanisole and butylated hydroxytoluene. I. Genetic and cellular effects. Food Chem Toxicol 28:793-798 (1990) https://doi.org/10.1016/0278-6915(90)90051-N
  13. Yamasaki, H. Role of disrupted gap junctional intercellular communication in detection and characterization of carcinogens. Mutat Res 365:91-105 (1996) https://doi.org/10.1016/S0165-1110(96)90014-7
  14. Kinae, N. et al. Studies on the toxicity of pulp and paper mill effluents -1. Mutagenicity of the sediment samples derived from Kraft paper mills. Water Res 15:17-24 (1981) https://doi.org/10.1016/0043-1354(81)90177-9
  15. Brusick, D. Genotoxicity of phenotic antioxidants. Toxicol Indust Health 9:223-230 (1993) https://doi.org/10.1177/0748233793009001-216
  16. Alekperov, U. K., Abutalybov, M. G. & Bagirova, A. D. Ionol modification of natural and induced chromosome aberrations in Crepis capillaris L. Doklady Biological Sciences 220:31-32 (1975)
  17. Prasad, O. & Kamra, O. P. Radiosensitization of Drosophila sperm by commonly used food additivesbutylated hydroxyanisole and butylated hydroxytoluene. Inter J Rad Biol 25:67-72 (1974) https://doi.org/10.1080/09553007414550071
  18. Paschin, Y. V. & Bahitova, L. M. Inhibition of the mutagenicity of benzol a pyrene in the V79/HGPRT system by bioantioxidants. Mutat Res 137:57-59 (1984) https://doi.org/10.1016/0165-1218(84)90113-7
  19. Nakagawa, Y., Hiraga, K. & Suga, T. Biological fate of butylated hydroxytoluene (BHT) binding of BHT of nucleic acid in vivo. Biochem Pharmacol 29:1304-1306 (1980) https://doi.org/10.1016/0006-2952(80)90290-7
  20. Bruce, W. R. & Heddle, J. A. The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella and sperm abnormality assays. Canad J Genetic Cytol 21:319-333 (1979) https://doi.org/10.1139/g79-036
  21. Epstein, S. S. et al. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol Appl Pharmacol 23:288-325 (1972) https://doi.org/10.1016/0041-008X(72)90192-5
  22. Clive, D. et al. Consensus agreement regarding protocol issues discussed during the mouse lymphoma workshop: Portland, Oregon, May 7, 1994. Environ Mol Mutagen 25:165-168 (1995) https://doi.org/10.1002/em.2850250211
  23. Moore, M. et al. Mouse lymphoma thymidine kinase gene mutation assay: meeting of the International Workshop on Genotoxicity Testing, San Francisco, 2005, recommendations for 24-h treatment. Mutat Res 627:36-40 (2007) https://doi.org/10.1016/j.mrgentox.2006.08.013
  24. Bomhard, E. M., Bremmer, J. N. & Herbold. B. A. Review of the mutagenicity/genotoxicity of butylated hydroxytoluene. Mutat Res 277:187-200 (1992) https://doi.org/10.1016/0165-1110(92)90043-9
  25. Ames, B. N. et al. Carcinogens are mutagens : a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci USA 70:2281-2285 (1973)
  26. Clements, J. Gene mutation assays in mammalian cells, In O'Hare, S & Atterwill, C. K. (Ed.), Methods in Molecular Biology, Vol. 43, in vitro Toxicity Testing Protocols. Humana Press Inc. Totowa, NJ. 277-286 (1990)
  27. Robinson, W. D. et al. Statistical evaluation of bacterial/ mammalian fluctuation tests, in Statistical Evaluation of Mutagenicity Test Data (Kirkland, D. J., ed.). Cambridge University Press. Cambridge, UK, 102-140 (1990)
  28. Hayashi, M. et al. The micronucleus assay with mouse peripheral blood reticulocytes using acridine orange-coated slides. Mutat Res 245:245-249 (1990) https://doi.org/10.1016/0165-7992(90)90153-B