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.
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.
Hagiwara
Akihiro
A
Daiyu-kai Institute of Medical Science, 64 Goura, Nishiazai, Ichinomiya 491-0113, Japan. hagiwara@daiyu-kai.com
Imai
Norio
N
Doi
Yuko
Y
Nabae
Kyoko
K
Hirota
Takeshi
T
Yoshino
Hiroko
H
Kawabe
Mayumi
M
Tsushima
Yoko
Y
Aoki
Hiromitsu
H
Yasuhara
Kazuo
K
Koda
Takatoshi
T
Nakamura
Mikio
M
Shirai
Tomoyuki
T
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
D002273:Carcinogens; D005505:Food Coloring Agents; D002338:Carotenoids; C099823:norbixin; D010634:Phenobarbital