Lina B A, Bär A
TNO-Nutrition and Food Research Institute, Zeist, 3700 AJ, The Netherlands.
Regul Toxicol Pharmacol. 1998 Apr;27(2):178-88. doi: 10.1006/rtph.1998.1223.
The toxicity of gamma-cyclodextrin (gamma-CD), a cyclic polymer of eight alpha-1,4-linked glucopyranosyl units with potential applications as a food ingredient, was examined in a 2-week pilot study followed by a 13-week oral toxicity study in Wistar rats. In the 2-week study, the test substance was administered to groups of 5 male rats at dietary levels of 0, 5, 10, 15, and 20%. In the 13-week study, groups of 20 rats/sex received diets with 0, 1.5, 5, or 20% gamma-CD. In each study, a comparison group receiving a diet with 20% lactose also was included. The 13-week study also included satellite groups of 10 rats/sex for the control and 20% gamma-CD groups. These satellite groups were kept on a standard, cereal-based rodent diet for a 4-week recovery period after termination of the treatment period. Parameters measured during the two studies were clinical signs, body weights, food and water intake, clinicochemical parameters, organ weights, and gross observation at necropsy. In the 13-week study, ophthalmoscopic and hematological examinations, urine and feces analyses, and histopathological examination of standard organs and tissues were conducted. There were no treatment-related mortalities in either study. Soft stools and, in the 13-week study, infrequent occurrences of diarrhea were noted in the lactose group at the beginning of treatment. Among the gamma-CD groups, soft stools occurred in only a few animals of the high-dose groups (>/=10% gamma-CD) during the first few days of treatment. Mean body weights tended to be slightly reduced in males of the 20% gamma-CD and 20% lactose groups. However, food efficiency was not affected by treatment except in the 13-week study in males of the 20% gamma-CD group during the first week of treatment. The hematological examinations and the semiquantitative urinalyses (conducted in the 13-week study) and the clinicochemical investigations (both studies) did not reveal any changes that could be attributed to gamma-CD treatment. Except for a slight cecal enlargement, which is commonly observed in rodents upon ingestion of incompletely absorbed carbohydrates, organ weights did not exhibit relevant changes as a result of gamma-CD treatment. On histopathological examination (13-week study), no treatment-related abnormalities were found. In conclusion, the ingestion of gamma-CD for 13 weeks at dietary levels of up to 20% (corresponding to intakes of 11.4 and 12.7 g/kg body wt/day for male and female rats, respectively) was well tolerated and did not produce any signs of toxicity.
γ-环糊精（γ-CD）是一种由8个α-1,4-连接的吡喃葡萄糖基单元组成的环状聚合物，具有作为食品成分的潜在应用价值。在一项为期2周的预试验研究之后，对Wistar大鼠进行了为期13周的经口毒性研究，以检测γ-环糊精的毒性。在为期2周的研究中，将受试物质以0%、5%、10%、15%和20%的膳食水平给予每组5只雄性大鼠。在为期13周的研究中，每组20只大鼠（雌雄各半）分别接受含0%、1.5%、5%或20%γ-环糊精的饲料。在每项研究中，还设立了一个接受含20%乳糖饲料的对照组。为期13周的研究还包括每组10只大鼠（雌雄各半）的卫星组，分别用于对照组和20%γ-环糊精组。在治疗期结束后，这些卫星组在标准的谷类啮齿动物饲料上饲养4周恢复期。在两项研究中测量的参数包括临床症状、体重、食物和水摄入量、临床化学参数、器官重量以及尸检时的大体观察。在为期13周的研究中，还进行了眼科和血液学检查、尿液和粪便分析以及标准器官和组织的组织病理学检查。两项研究中均未出现与治疗相关的死亡情况。在治疗开始时，乳糖组出现软便，在为期13周的研究中，偶尔出现腹泻。在γ-环糊精组中，仅在高剂量组（≥10%γ-环糊精）的少数动物在治疗的头几天出现软便。20%γ-环糊精组和20%乳糖组雄性大鼠的平均体重有轻微下降趋势。然而，除了在为期13周的研究中，20%γ-环糊精组雄性大鼠在治疗的第一周食物效率受到影响外，食物效率不受治疗影响。血液学检查、半定量尿液分析（在为期13周的研究中进行）和临床化学检查（两项研究）均未发现任何可归因于γ-环糊精治疗的变化。除了在啮齿动物摄入未完全吸收的碳水化合物时常见的盲肠轻微肿大外，γ-环糊精治疗未导致器官重量出现相关变化。组织病理学检查（为期13周的研究）未发现与治疗相关的异常情况。总之，在膳食水平高达20%（分别相当于雄性和雌性大鼠每天摄入11.4和12.7 g/kg体重）的情况下，连续13周摄入γ-环糊精耐受性良好，未产生任何毒性迹象。
