title: Studies of the toxicological potential of capsinoids: II. A 26-week daily gavage dosing toxicity study of CH-19 Sweet extract in rats.
abstract: A 26-week oral toxicity study of capsinoids-containing CH-19 Sweet extract was conducted in Sprague-Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg/day. The concentration of capsinoids in the CH-19 Sweet extract employed was 71.25 to 73.15 mg/ml, resulting in dose levels of capsinoids of 89.06 to 91.44, 178.13 to 182.88, and 356.25 to 365.75 mg/kg, respectively. Adverse test article-related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 ml/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, liver weights, and in the incidence and severity of hepatocellular focal necrosis. No test substance-related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology, or urinalysis. No adverse test article-related changes were observed in low- or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no observed adverse effect level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 ml/kg/day in males and 5.0 ml/kg/day in females (178.13 to 182.88 mg/kg and 356.25 to 365.75 mg/kg as capsinoids, respectively).
authors.affiliation: Toxicology and Pathology, Nonclinical Developmental Research Department, Pharmaceutical Research Laboratories, Pharmaceutical Company, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan. terutaka kodama@ajinomoto.com
authors.forename: Terutaka
authors.initials: T
authors.lastname: Kodama
authors.forename: Eri
authors.initials: E
authors.lastname: Watanabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Masuyama
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsubuku
authors.forename: Akira
authors.initials: A
authors.lastname: Otabe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Bernard
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002211:Capsaicin / Q000737:chemistry; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; 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
chemical_list: D010936:Plant Extracts; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002211:Capsaicin