Fifty-two week chronic toxicity of enzymatically decomposed rutin in Wistar rats.
The chronic toxicity of enzymatically decomposed rutin, which consists mainly of isoquercitrin, was evaluated in male and female Wistar rats with dietary administration at concentrations of 0%, 0.04%, 0.2%, 1% and 5% for 52 weeks. No toxicological findings were found in the mortality, body weights, food consumption, hematology, clinical biochemistry or organ weights in either sex. Obvious clinical signs were chromaturia that could be attributed to the color of test substance in the 5% groups of both sexes. Coloration of the urine collected over 24h in the 1% and 5% groups of both sexes was noted. Increased daily urinary calcium excretion was observed in the 5% groups of both sexes and an increase in urinary calcium concentration was observed in the male 5% group. On histopathological examination, incidences of mineralization, inflammatory cell debris, inflammatory cell infiltration and/or transitional cell hyperplasia in the renal pelvis were increased in the 5% male group, whereas treated females showed no apparent difference in these incidences. Based on the above findings, the no observed adverse effect level (NOAEL) was estimated to be 1% in both sexes (542.4 mg/kg body weight/day for males and 674.0mg/kg body--weight/day for females).
Tamura
T
T
Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co Ltd, Azumino, Nagano 399-8305, Japan. toru_tamura@pharm.kissei.co.jp
Mitsumori
K
K
Muto
S
S
Kasahara
H
H
Kobayashi
S
S
Okuhara
Y
Y
Hayashi
M
M
Nagasawa
T
T
Onozato
T
T
Kuroda
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000652:urine; D004032:Diet; D004435:Eating / Q000187:drug effects; D005260:Female; D005503:Food Additives; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000652:urine; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011794:Quercetin / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012431:Rutin / Q000378:metabolism / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D036401:Toxicity Tests, Chronic
D005503:Food Additives; C016527:isoquercitrin; D012431:Rutin; D011794:Quercetin; D002118:Calcium