title: Modifications of azoxymethane-induced carcinogenesis and 90-day oral toxicities of 2-tetradecylcyclobutanone as a radiolytic product of stearic acid in F344 rats.
abstract: A 90-day oral toxicity test in rats was performed to evaluate the toxicity of 2-tetradecylcyclobutanone (2-tDCB), a unique radiolytic product of stearic acid. Six-week-old male and female F344 rats (n=15/group) were given 2-tDCB at concentrations of 0, 12, 60 and 300 ppm in a powder diet for 13 weeks. Slight dose-dependent increases in serum total protein and albumin in male rats were found, but these changes were not considered to be a toxic effect. The fasting, but not non-fasting, blood glucose levels of the male rats in the 300 ppm group and female rats in the 60 and 300 ppm groups were lower than those of the controls. Gas chromatography-mass spectrometry analysis showed dose-dependent accumulation of 2-tDCB in adipose tissue, notably in males. Next, we performed an azoxymethane (AOM)-induced two-stage carcinogenesis study. After injection of 6-week-old male F344 rats (n=30/group) once a week for 3 weeks, the animals received 2-tDCB at concentrations of 0, 10, 50 and 250 ppm in a powder diet for 25 weeks. The incidences of colon tumors for the 2-tDCB dosages were 34%, 45%, 40% and 37%, respectively, and were not statistically significant. These data suggest that 2-tDCB shows no toxic or tumor-modifying effects under the present conditions, and that the no-observed-adverse-effect level for 2-tDCB is 300 ppm in both sexes, equivalent to 15.5 mg/kg b.w./day in males and 16.5 mg/kg b.w./day in females.
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sato
authors.affiliation: Food Safety Division, National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
authors.forename: Setsuko
authors.initials: S
authors.lastname: Todoriki
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Ezar
authors.initials: E
authors.lastname: Hafez
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Uehara
authors.affiliation: Division of Alternative Toxicology Test, Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano, Kanagawa 257-8523, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Yamakage
authors.affiliation: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Motoyama Kamigamo, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Quantum-beam Chemical Biology, Radiation Research Center, Osaka Prefecture University, 1-2 Gakuen-cho, Sakai, Osaka 599-8570, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Furuta
authors.affiliation: Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Izumi
keywords: 2-tetradecylcyclobutanone; 90-day oral toxicity; colon carcinogenesis; food irradiation