The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats
Yoshio OtaToshio ImaiJun-ichi OnoseShigeaki TakamiYoung-Man ChoMasao HiroseAkiyoshi Nishikawa
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2009 Volume 34 Issue 3 Pages 305-313

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Abstract

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 γ-glutamyl transpeptidase (γ-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.

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© 2009 The Japanese Society of Toxicology
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