Single Toxicity Evaluation of the Polygonati Rhizoma Preparata with Benzo[a]pyrene Contents in ICR Mice

구증황정(九蒸黃精)의 벤조피렌 함량과 마우스 단일투여 독성실험

  • Kim, Yong-Ung (Department of Herbal Pharmaceutical Engineering, College of Herbal Bio-Industry, Daegu-Haany University) ;
  • Roh, Seong-Soo (Department of Herbology, College of Oriental Medicine, Daegu-Haany University)
  • 김용웅 (대구한의대학교 한방산업대학 한방제약공학과) ;
  • 노성수 (대구한의대학교 한의과대학 본초학교실)
  • Received : 2010.11.19
  • Accepted : 2011.02.07
  • Published : 2011.02.25

Abstract

The object of this study was two. One was if Polygonati Rhizoma preparata had a benzo(a)pyrene, the other was to evaluate the single dose toxicity of 9 repetitive steaming and fermenting processed Polygonati Rhizoma, dried root parts of Polygonati Rhozoma preparata extract, in male and female mice. We measured a content of benzo(a)pyrene in Polygonati Rhozoma preparata using a method with HPLC/FLD. And for single dose toxicity, aqueous extracts of Polygonati Rhozoma preparata (EPP; Yield = 35.4 %) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for slight soft feces sporadically detected in EPP treated male mice at 1 day after administration. In addition, no EPP-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that benzo(a)pyrene was not existed in Polygonati Rhozoma preparata and the 50% lethal dose and approximate lethal dose of EPP aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines. However, it also observed that the possibilities of digestive disorders, like soft feces when administered over 500 mg/kg of EPP aqueous extracts in the present study.

Keywords

References

  1. 全國韓醫科大學共同敎材編纂委員會. 本草學. 서울, 永林社, pp 651-652, 2007.
  2. 中華本草 編委會. 中華本草. 上海, 上海科學技術出版社, pp 143-148, 1999.
  3. 許 浚. 東醫寶鑑. 서울, 法人文化社, pp 134-135, 2000.
  4. 서부일, 신순식 편저. 알기쉬운 한약포제학. 대구, 대원당기획 출판사, pp 309-311, 2007.
  5. 徐國均, 何宏賢主. 徐珞珊, 金蓉鸞編. 中國藥材學. 北京, 中國 醫藥科技出版社, pp 644-647, 1996.
  6. 안덕균, 김호철 편저. 韓藥炮製學. 서울, 一中社, pp 261-264, 2000.
  7. 肖培根主著. 新編中藥志. 北京, 化學工業出版社, pp 902-910, 2002.
  8. Lee, J.E., Kim, H.J., Choi, E.K., Chai, H.Y., Yun, Y.W., Kim, D.J., Nam, S.Y., Lee, B.J., Ahn, B.W., Kang, H.G., Kim, Y.B. Four-week repeated-dose toxicity study on Pinellia Extract. Korean J. Lab. Anim. Sci., 19: 127-141, 2003.
  9. 한국식품의약품안전청. 의약품 등의 독성시험기준. 서울, 한국식품의약품 안전청 고시 제 2009-116호, 2009.
  10. Irwin, S. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology 13: 222-257, 1968. https://doi.org/10.1007/BF00401402
  11. Dourish, C.T. Effects of drugs on spontaneous motor activity. In Experimental Psychopharmacology (A.J.GreenshawandC.T.Dourish,Ed.), Clifton, HumanaPress, pp 325-334, 1987.
  12. 王孝泰. 歷代中藥炮劑法滙典. 南昌, 江西科學技術出版社, pp 136-137, 1989.
  13. 楊東熙編著. 本草備要解析. 서울, 一中社, pp 40-41, 1991.
  14. 李時珍. 本草綱目 上卷. 北京, 人民衛生出版社 (一中社 影印), pp 718-721, 1982.
  15. 徐春甫. 古今醫統大全. 北京, 人民衛生出版社, pp 383-384, 745, 1994.
  16. 龔廷賢著, 陳柱杓譯. 對譯萬病回春. 서울, 法人文化社, pp 444-445, 2007.
  17. 李阡著, 安秉國譯. 國譯醫學入門卷二. 서울, 원풍문화사, p 828, 1982.
  18. Yee H., Yie T.A., Goldberg J., Wong K.M., Rom W.N. Immunohistochemical study of fibrosis and adenocarcinoma in dominant-negative p53 transgenic mice exposed to chrysotile asbestos and benzo(a)pyrene. J Environ Pathol Toxicol Oncol. 27: 267-276, 2008. https://doi.org/10.1615/JEnvironPatholToxicolOncol.v27.i4.30
  19. Li J.Z., Pan H.Y., Zheng J.W., Zhou X.J., Zhang P., Chen W.T., Zhang Z.Y. Benzo (a) pyrene induced tumorigenesity of human immortalized oral epithelial cells : transcription profiling. Chin Med J (Engl). 19: 1882-1890, 2
  20. Kometani T., Yoshino I., Miura N., Okazaki H., Ohba T., Takenaka T., Shoji F., Yano T., Maehara Y. Benzo[a]pyrene promotes proliferation of human lung cancer cells by accelerating the epidermal growth factor receptor signaling pathway. Cancer Lett. 278: 27-33, 2009. https://doi.org/10.1016/j.canlet.2008.12.017
  21. IARC, Polynuclear Aromatic Hydrocarbons Part I Chem and Environ Data 32: 211-224, 1983.
  22. IARC, IARC Monographs on the evaluation of carcinogenic risk of chemicals to human, volume 1-42, 1987.
  23. Plata, E.J., Murphy, W.H. Growth and haematologic properties of the BALB/wm strain of inbred mice. Lab. Anim. Sci., 22: 712-720, 1972.
  24. Yamaguchi, C., Fujita, S., Obara, T., Ueda, T. Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp. Anim., 32: 1-11, 1983.
  25. Lee, J.H., Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Lee, H.S., Ku, S.K. Single subcutaneous dose toxicity of $Polycan^{\circledR},a\beta$-glucan originated from Aureobasidium in mice. Lab. Anim. Res. 21: 299-305, 2005.
  26. Lee, H.S., Lee I.G., Ku S.K. Single oral dose toxicity study of water extracts of Picrorrhiza Rhizoma in mice. J. Toxicol. Pub. Health, 22: 117-126, 2006.
  27. Banks, W.J. Female reproductive system. In: Applied veterinary histology (W.J.Banks,Ed.) Baltimore, Williams&Wilkins, pp 506-526, 1986.
  28. Pineda, M.H. Female reproductive system. In: Veterinary endocrinology and reproduction (L.E.McDonald and M.H. Pineda,Eds.), Philadelphia, Lea&Febiger, pp 303-354, 1989.
  29. U.S. Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.100. Acute Toxicity Testing Background. Washington, US EPA, 1998.