title: Induction of kidney and liver cancers by the natural food additive madder color in a two-year rat carcinogenicity study.
abstract: Madder color (MC) extracted from the roots of Rubia tinctorum (madder root) has been used as a food coloring in Japan. Our previous studies revealed MC to have obvious subchronic and chronic toxicity and potent carcinogenicity targeting rat liver and kidney. In the present two-year carcinogenicity study, conducted to further elucidate the long-term effects of MC and its target organs, male and female F344 rats were fed diet containing 0%, 2.5%, and 5.0% MC for 104 weeks. Body weights were significantly decreased in treated groups of both sexes throughout the feeding period. However, survival rates at week 104 were higher in treated groups of both sexes than in controls. Relative weights of the kidneys and liver were significantly increased in treated groups of both sexes. Histopathologically, karyomegaly and atypical tubules/hyperplasias, as well as renal cell adenomas and carcinomas were significantly increased in treated groups of both sexes with dose-dependence. Moreover, the incidence of hepatocellular adenomas and/or carcinomas was increased significantly with a dose-relation in treated groups of both sexes. These data provide clear evidence that MC exerts unequivocal carcinogenicity against renal tubule cells and hepatocytes in rats.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. k-inoue@nihs.go.jp
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Hironori
authors.initials: H
authors.lastname: Takagi
authors.forename: Masao
authors.initials: M
authors.lastname: Hirose
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishikawa
mesh_terms: D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005503:Food Additives / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D045470:Rubia / Q000633:toxicity*; D012727:Sex Characteristics
chemical_list: D005503:Food Additives; D010936:Plant Extracts; C438508:madder color