Watanabe Eri, Kodama Terutaka, Masuyama Takeshi, Tsubuku Shoji, Otabe Akira, Mochizuki Masahiro, Nakajima Madoka, Masumori Shoji, Bernard Bruce K
Toxicology and Pathology, Nonclinical Developmental Research Department, Pharmaceutical Research Laboratories, Pharmaceutical Company, Ajinomoto Co., Inc., Kawasaki, Kanagawa, Japan.
Int J Toxicol. 2008;27 Suppl 3:1-9. doi: 10.1080/10915810802513361.
A single-dose oral toxicity lethal-dose study was conducted to examine the toxicity of capsinoids contained in CH-19 Sweet extract. CH-19 Sweet extract was administered once by gavage to SPF (Crl:CD(SD)) Sprague-Dawley male and female rats at dose levels of 0 (vehicle), 5, 10, or 20 ml/kg of body weight (BW). The concentration of capsinoids in the CH-19 Sweet extract was 71.25 mg/ml; this resulted in administered dose levels of capsinoids of 356.25, 712.5, and 1425 mg/kg BW, respectively. The toxicity of CH-19 Sweet extract by single oral administration was low; only transient salivation or decreased spontaneous movement was observed on the day of administration at > or =10 ml/kg BW. It was concluded that the lethal dose of CH-19 Sweet extract was estimated to be higher than 20 ml/kg (1425 mg/kg as capsinoids) for both males and females since no deaths were observed at any dose in this study. A bacterial reverse mutation test of CH-19 Sweet extract was performed employing Salmonella typhimurium and Escherichia coli and using the preincubation method. Treatment with CH-19 Sweet extract did not increase the number of revertant colonies compared with negative controls either in the presence (+S9) or absence (-S9) of metabolic activation. An in vitro chromosome aberration test was conducted using Chinese hamster lung cultured cells (CHL/IU). Treatment with CH-19 Sweet extract failed to induce chromosome aberrations in either short-term or continuous treatment scenarios, with or without metabolic activation (-S9, +S9). In an in vivo micronucleus test using BDF(1) male mice, CH-19 Sweet extract failed to increase the incidence of micronucleated polychromatic erythrocytes (MNPCEs) or decrease the ratio of polychromatic erythrocytes (PCEs) in any of the treatment groups. These results suggest the absence of mutagenicity as well as in vitro and in vivo clastogenicity of capsinoids contained in CH-19 Sweet extract.
进行了一项单剂量口服毒性致死剂量研究，以检测CH-19甜椒提取物中辣椒素类物质的毒性。将CH-19甜椒提取物以0（赋形剂）、5、10或20 ml/kg体重（BW）的剂量水平通过灌胃法一次性给予SPF（Crl:CD(SD)）斯普拉格-道利雄性和雌性大鼠。CH-19甜椒提取物中辣椒素类物质的浓度为71.25 mg/ml；这导致辣椒素类物质的给药剂量水平分别为356.25、712.5和1425 mg/kg BW。单次口服CH-19甜椒提取物的毒性较低；在给药当天，当剂量≥10 ml/kg BW时，仅观察到短暂流涎或自发活动减少。由于在本研究中任何剂量下均未观察到死亡，因此得出结论：CH-19甜椒提取物对雄性和雌性的致死剂量估计均高于20 ml/kg（以辣椒素类物质计为1425 mg/kg）。采用鼠伤寒沙门氏菌和大肠杆菌，运用预孵育法对CH-19甜椒提取物进行了细菌回复突变试验。在有（+S9）或无（-S9）代谢活化条件下，与阴性对照相比，用CH-19甜椒提取物处理均未增加回复菌落数。使用中国仓鼠肺细胞（CHL/IU）进行了体外染色体畸变试验。在有或无代谢活化（-S9，+S9）的情况下，无论是短期还是连续处理，用CH-19甜椒提取物处理均未诱导染色体畸变。在使用BDF(1)雄性小鼠的体内微核试验中，CH-19甜椒提取物在任何处理组中均未增加微核多染红细胞（MNPCEs）的发生率或降低多染红细胞（PCEs）比率。这些结果表明CH-19甜椒提取物中所含辣椒素类物质不存在致突变性以及体外和体内的断裂剂活性。
