A 13-week subchronic toxicity study of dietary administered morin in F344 rats.
A subchronic toxicity study of a flavonoid morin was performed in both sexes of F344 rats with dietary administration at concentrations of 0%, 0.625%, 1.25%, 2.5% and 5% (w/w) for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any group. Although a slight tendency for increase in food intake was noted in both sexes of the 2.5% and 5.0% groups, slight non-significant body weight decrease was observed in 5.0% males. Significant increases in alanine transaminase (ALT; over 2.5%), alkali phosphatase (ALP; 1.25% and 5.0%) and relative liver weights (1.25% and 2.5%) in males and in gamma-glutamyl transpeptidase (gamma-GT), aspartate transaminase (AST), ALT, relative liver weights in the 2.5% and 5.0% females and ALP in 5.0% females were noted. Increased urea nitrogen and relative kidney weights at dose of 1.25% and above and creatinine at 5.0% were observed also in females. On histopathological observation, hepatocyte hypertrophy was detected in 3 of 10 5.0% females. Based on the above findings, the no-observed-adverse-effect level (NOAEL) for both sexes was estimated to be 0.625% (299 and 356 mg/kg b.w./day for males and females, respectively).
Cho
Y-M
YM
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-Ku, Tokyo 158-8501, Japan. ymcho@nihs.go.jp
Onodera
H
H
Ueda
M
M
Imai
T
T
Hirose
M
M
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004435:Eating / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D005723:gamma-Glutamyltransferase / Q000097:blood; D047309:Flavones
D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D005419:Flavonoids; D005723:gamma-Glutamyltransferase; C008548:morin; D047309:Flavones