Single Dose Oral Toxicity and Genotoxicological Safety Study of Ssanghwa-tang Fermented with Lactobacillus acidophyllus

유산균 발효 쌍화탕에 대한 단회 투여 경구 독성 및 유전 독성 연구

  • Chung, Tae-Ho (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine) ;
  • Shim, Ki-Shuk (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine) ;
  • Kim, Dong-Seon (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine) ;
  • Lee, Jae-Hoon (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine) ;
  • Ma, Jin-Yeul (Center for Herbal Medicine Improvement Research, Korea Institute of Oriental Medicine)
  • 정태호 (한국한의학연구원 신한방제제연구센터) ;
  • 심기석 (한국한의학연구원 신한방제제연구센터) ;
  • 김동선 (한국한의학연구원 신한방제제연구센터) ;
  • 이재훈 (한국한의학연구원 신한방제제연구센터) ;
  • 마진열 (한국한의학연구원 신한방제제연구센터)
  • Received : 2010.10.11
  • Accepted : 2011.01.05
  • Published : 2011.01.30

Abstract

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

Keywords

References

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