title: Absence of liver tumor promoting effects of annatto extract (norbixin), a natural carotenoid food color, in a medium-term liver carcinogenesis bioassay using male F344 rats.
abstract: Modifying potential of annatto extract (norbixin) on liver carcinogenesis was investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given annatto extract at dietary levels of 0, 0.03, 0.1 and 0.3%, or phenobarbital sodium at 0.05% as a positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. There were no deaths related to annatto extract ingestion, and the treatment had no effects on body weights, or food and water consumption. Statistically significant increases of absolute and relative liver weights were apparent in the 0.1 and 0.3% groups. However, annatto extract did not significantly increase the quantitative values for glutathione S-transferase placental form positive liver cell foci observed after DEN initiation, in clear contrast to the positive control case. The results thus demonstrate that annatto extract at a dietary level of 0.3% (200 mg/kg/day) lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.
authors.affiliation: Daiyu-kai Institute of Medical Science, 64 Goura, Nishiazai, Ichinomiya 491-0113, Japan. hagiwara@daiyu-kai.com
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Norio
authors.initials: N
authors.lastname: Imai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nabae
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirota
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yoshino
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawabe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tsushima
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Aoki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yasuhara
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Koda
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002338:Carotenoids / Q000633:toxicity*; D004195:Disease Models, Animal; D005505:Food Coloring Agents; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D005505:Food Coloring Agents; D002338:Carotenoids; C099823:norbixin; D010634:Phenobarbital