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청목향 Aristolochiae radix에 있어 F344 랫드의 독성
Toxicity of Aristolochiae radix in F344 rats

김충용   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 김용범   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 양병철   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 이종화   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 정문구   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 양기화   (국립독성연구원  ); 장동덕   (국립독성연구원  ); 한상섭   (한국화학연구원 부설 안전성평가연구소CC0186998  ); 강부현   (한국화학연구원 부설 안전성평가연구소CC0186998  );
  • 초록

    13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.


  • 주제어

    Aristolochiae radix .   aristolochic acid .   stomach .   urinary bladder .   F344 rats.  

  • 참고문헌 (11)

    1. 허옥순, 이진하, 김세은, 주인선, 신동우, 이정호, 김지연, 강숙경, 이형규, 백승화, 문병우, 김진수. 유통 방기의 화학적 분석. The Annual Report of KFDA 2000. 4. 111-118 
    2. Cosyns JP. Aristolochic acid and chinese herbs nephropathy. Drug Safety 2003, 26, 33-48 
    3. Hashimoto K, Higuch M, Makino B, Sakakibara I, Komatsu Y, Maruno M, Okada M. Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants. J Ethnopharmacol 1999, 64, 185-189 
    4. Mengs U. On the histopathogenesis of rat forestomach carcinoma caused by aristolochic acid. Arch Toxicol 1983, 52, 209-220 
    5. Nortier JN, Martinez MC, Schmeiser HH, Arlt VM, Bieler CA, Petein M, Depierreux MF, Depauw L, Abramowicz D, Vereerstraeten P, Vanherweghem JL. Urothelial carcinoma associated with the use of a chinese herb (Aristolochia Fanchi). New Engl J Med 2000, 342, 1686-1692 
    6. 황명실, 박미선, 문지영, 이지선, 염영나, 이효민, 신동환, 강진석, 윤은경, 최미나, 육미영, 장동덕, 길광섭, 김승희, 양기화. 아리스톨로크산 함유 생약제에 대한 안전성평가연구, The Annual Report of KFDA 2001, 5, 568-578 
    7. WHO. B. Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene(Aristolochia species and aristolochic acids), IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 2002, 82, 69-128 
    8. Arlt VM, Stiborova M, Schmeiser HH. Aristolochic acid as a probable human cancer hazard in herbal remedies : a review, Mutagenesis 2002, 17, 265-277 
    9. Graham ML, Rajat T, Terry C, Peter G, Gharies DP. Nephropathy caused by chinese herbs in the UK. Lancet 1999, 354, 481-482 
    10. Mengs U, Lang W, Poch JA. The Carcinogenic action of aristolochic acid in rats. Arch Toxicol 1982, 51, 107-119 
    11. Mengs U, Stotzem CD. Toxicity of aristolochic acid - a subacute study in male rats. Med Sci Res 1992, 20, 223-224 

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