title: A thirteen-week oral toxicity study of annatto extract (norbixin), a natural food color extracted from the seed coat of annatto (Bixa orellana L.), in Sprague-Dawley rats.
abstract: A subchronic oral toxicity study of annatto extract (norbixin), a natural food color, was conducted. Groups of 10 male and 10 female Sprague-Dawley rats were fed annatto extract at dietary levels of 0, 0.1, 0.3 and 0.9% for 13 weeks. There were no treatment-related adverse effects on body weight, food and water consumption, ophthalmology and hematology data. Blood biochemical analysis revealed changes in rats of both sexes confined to the 0.9% and 0.3% groups, including increased alkaline phosphatase, phospholipid, total protein, albumin and albumin/globulin ratio. Marked elevation in absolute and relative liver weights was also found in both sexes of the 0.9% and 0.3% groups, but not the 0.1% group. Hepatocyte hypertrophy was evident and an additional electron microscopic examination demonstrated this to be linked to abundant mitochondria after exposure to a dietary level of 0.9% annatto extract for 2 weeks. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) was judged to be a dietary level of 0.1% (69 mg/kg body weight/day for males, 76 mg/kg body weight/day for females) of annatto extract (norbixin) under the present experimental conditions.
authors.affiliation: Daiyu-kai Institute of Medical Science, 64 Goura, Nishiazai, 491-0113, Ichinomiya, Japan. hagiwara@daiyu-kai.com
authors.forename: A
authors.initials: A
authors.lastname: Hagiwara
authors.forename: N
authors.initials: N
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Ichihara
authors.forename: M
authors.initials: M
authors.lastname: Sano
authors.forename: S
authors.initials: S
authors.lastname: Tamano
authors.forename: H
authors.initials: H
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Yasuhara
authors.forename: T
authors.initials: T
authors.lastname: Koda
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D031212:Bixaceae; D001798:Blood Proteins / Q000032:analysis; D002338:Carotenoids / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D006984:Hypertrophy; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D010936:Plant Extracts; D002338:Carotenoids; C054041:annatto; C099823:norbixin; D000469:Alkaline Phosphatase