title: Lack of hinokitiol (beta-thujaplicin) carcinogenicity in F344/DuCrj rats.
abstract: Chronic toxicity and carcinogenicity of hinokitiol (beta-thujaplicin), used as an antibiotic and fungicidal agent of a food additive, was examined in both sexes of F344/DuCrj (F344) rats. In this chronic toxicity study, groups of 10 rats of each sex were given a diet containing hinokitiol at doses of 0, 0.005, 0.015 and 0.05% for 52 weeks. No treatment-related adverse effects were noted in the survival rate, general condition, body weights, food consumption, urinalysis, hematology and clinical chemistry. Slight but significant elevation of spleen and liver weights was noted in both sexes given 0.05% hinokitiol, along with an increase in hemosiderin deposits in male spleens, related to chelator binding of iron, together with slight centrilobular hypertrophy of male hepatocytes. However, these alterations were negligible and not toxicologically significant. In the carcinogenicity study, groups of 50 female and 50 male rats were given a diet containing hinokitiol at doses of 0, 0.005, 0.015 and 0.05% (excluding 0.005% in females). No treatment-related changes in survival rate, general condition, body weight, food consumption, hematology and organ weights were noted. Detailed histopathological examination revealed no treatment-related increase in the incidences of any neoplastic lesions. The results demonstrate that hinokitiol is not carcinogenic in F344 rats of either sex.
authors.affiliation: DIMS Institute of Medical Science, Inc., Nishiazai, Ichinomiya, Japan.
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: Seiko
authors.initials: S
authors.lastname: Tamano
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Ichihara
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005503:Food Additives / Q000633:toxicity*; D008297:Male; D039821:Monoterpenes / Q000633:toxicity*; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D014334:Tropolone / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D005503:Food Additives; D039821:Monoterpenes; D014334:Tropolone; C009479:beta-thujaplicin