Toxicity of Aristolochiae radix in F344 rats |
Choong-Yong Kim1, Yong-Bum Kim1, Byung-Chul Yang1, Jong-Hwa Lee1, Moon-Koo Chung1, Ki-Hwa Yang2, Dong-Deuk Jang2, Sang-Seop Han1, Boo-Hyon Kang1 |
1Toxicology Division, Korea Institute of Toxicology 2National Institute of Toxicology Research, Korea Food and Drug Administration |
청목향 Aristolochiae radix에 있어 F344 랫드의 독성 |
김충용1, 김용범1, 양병철1, 이종화1, 정문구1, 양기화2, 장동덕2, 한상섭1, 강부현1 |
1한국화학연구원 부설 안전성평가연구소 2국립독성연구원 |
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Abstract |
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. |
Key Words:
Aristolochiae radix, aristolochic acid, stomach, urinary bladder, F344 rats |
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