A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats.
A chronic toxicity study of kojic acid (KA) was performed using male F344 rats by dietary administration at concentrations of 0 (control), 0.5 and 2.0% for 55 weeks. Body weight gain was suppressed in the 2.0% group. The major hematological findings were decreased red blood cell (RBC) count and hematocrit (Ht) values at both 0.5 and 2.0%. In serum biochemistry, increased aspartate transaminase (AsT), alanine transaminase (AlT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GTP) levels were detected in the 0.5 and 2.0% groups. Histopathologically, single cell necrosis of hepatocytes and proliferation of bile ductules in both treatment groups, and hypertrophy of hepatocytes, granulomas and proliferation of bile ducts in the 2.0% group were increased in incidence, and numbers and areas of glutathione-S-transferase placental-form (GST-P) positive foci were increased in the liver of the 2.0% group. In the thyroids, diffuse follicular cell hyperplasia at 0.5 and 2.0% and focal follicular cell hyperplasia and follicular adenoma at 2.0% were increased. A thyroid follicular carcinoma was also observed at 2.0%. Additionally, increased incidences of hyaline casts and basophilic tubules in the kidneys at 2.0% and microgranulomas containing crystals in the lung in both treatment groups were noted. At 2.0%, hypertrophy of cortical cells in zona fasciculata was also increased in the adrenals. In conclusion, no observed adverse effect level of KA was below 0.5%, which is equivalent to 227 mg/kg body weight/day in male rats.
Ota
Yoshio
Y
Division of Pathology, National Institute of Health Sciences, Tokyo.
Imai
Toshio
T
Onose
Jun-Ichi
J
Takami
Shigeaki
S
Cho
Young-Man
YM
Hirose
Masao
M
Nishikawa
Akiyoshi
A
D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D049108:Cell Enlargement / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects* / Q000473:pathology; D005503:Food Additives / Q000633:toxicity*; D006400:Hematocrit; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D011753:Pyrones / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D036401:Toxicity Tests, Chronic; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000975:Antioxidants; D005503:Food Additives; D011753:Pyrones; C011890:kojic acid; D005723:gamma-Glutamyltransferase