One-year chronic toxicity of madder color in F344 rats--induction of preneoplastic/neoplastic lesions in the kidney and liver.
To evaluate chronic toxicity of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., F344 rats were fed diet containing 0%, 0.2%, 1.0% or 5.0% MC for 53 weeks. Hematological changes including anemia and serum biochemical alterations indicating hepatotoxicity were demonstrated at 5.0% in both sexes. Relative weights of the liver were significantly increased from 1.0% in both sexes, and those of the kidney were significantly increased from 1.0% in males and from 0.2% in females. Histopathologically, atypical renal tubule hyperplasias were increased at 1.0% or higher in both sexes in association with increase of cell proliferative activity in the tubules. A renal cell adenoma was observed in a male rat receiving 5.0% MC. In addition, glutathione S-transferase placental form-positive liver cell foci were significantly increased at 5.0% in both sexes. These results indicate that MC has chronic toxicity targeting kidney, liver and blood cells. Moreover, the results strongly suggest that MC may have the carcinogenic potential in the kidney and the liver.
Inoue
Kaoru
K
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. k-inoue@nihs.go.jp
Shibutani
Makoto
M
Masutomi
Naoya
N
Toyoda
Kazuhiro
K
Takagi
Hironori
H
Takahashi
Miwa
M
Fujimoto
Hitoshi
H
Hirose
Masao
M
Nishikawa
Akiyoshi
A
D000818:Animals; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D007668:Kidney / Q000166:cytology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage* / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D045470:Rubia / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
D010936:Plant Extracts; C438508:madder color