Appel M J, van Veen H A, Vietsch H, Salaheddine M, Nuijens J H, Ziere B, de Loos F
TNO Quality of Life, Business Unit Toxicology and Applied Pharmacology, P.O. Box 360, 3700 AJ Zeist, The Netherlands.
Food Chem Toxicol. 2006 Jul;44(7):964-73. doi: 10.1016/j.fct.2005.11.012. Epub 2006 Jan 19.
The oral toxicity of recombinant human lactoferrin (rhLF) produced in the milk of transgenic cows was investigated in Wistar rats by daily administration via oral gavage for 13 consecutive weeks, 7 days per week. The study used four groups of 20 rats/sex/dose. The control group received physiological saline and the three test groups received daily doses of 200, 600 and 2000 mg of rhLF per kg body weight. Clinical observations, growth, food consumption, food conversion efficiency, water consumption, neurobehavioural testing, ophthalmoscopy, haematology, clinical chemistry, renal concentration test, urinalysis, organ weights and gross examination at necropsy and microscopic examination of various organs and tissues were used as criteria for detecting the effects of treatment. Overall, no treatment-related, toxicologically significant changes were observed. The few findings that may be related to the treatment (lower cholesterol in high-dose females, lower urinary pH in high-dose males and females and very slightly higher kidney weight in high-dose females) were considered of no toxicological significance. Based on the absence of treatment-related, toxicologically relevant changes, the no-observed-adverse-effect level (NOAEL) was considered to be at least 2000 mg/kg body weight/day.
通过每周7天、连续13周经口灌胃给药，在Wistar大鼠中研究了转基因奶牛乳汁中产生的重组人乳铁蛋白（rhLF）的口服毒性。该研究使用了四组，每组20只大鼠/性别/剂量。对照组接受生理盐水，三个试验组分别接受每千克体重每日200、600和2000毫克rhLF的剂量。临床观察、生长情况、食物消耗、食物转化效率、水消耗、神经行为测试、检眼镜检查、血液学、临床化学、肾脏浓缩试验、尿液分析、器官重量以及尸检时的大体检查和各种器官及组织的显微镜检查被用作检测治疗效果的标准。总体而言，未观察到与治疗相关的、具有毒理学意义的变化。少数可能与治疗相关的发现（高剂量雌性大鼠胆固醇降低、高剂量雄性和雌性大鼠尿液pH值降低以及高剂量雌性大鼠肾脏重量略高）被认为无毒理学意义。基于未观察到与治疗相关的、具有毒理学相关性的变化，未观察到有害作用水平（NOAEL）被认为至少为2000毫克/千克体重/天。
