Abstract：
The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina\'s intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.
摘要：
重组人乳铁蛋白（rhLF，HelainarhLF,在成年SpragueDawley大鼠中通过每天一次的口服灌胃连续14天研究了在Komagataellaphafii中产生的Effera™）。该研究使用3-6只大鼠/性别/剂量的组。载体对照组接受柠檬酸钠缓冲液，试验组每天接受200、1000和2000mg的含rhLF的柠檬酸钠缓冲液/kg体重。使用每天2000mg/kg体重的牛LF作为比较对照。临床观察，体重,血液学,临床化学，铁参数,免疫表型,和尸检时的大体检查被用作检测所有组治疗效果的标准,并帮助选择未来毒理学研究的剂量水平.定量LF水平也被分析为生物利用度的指示。总的来说,通过每天一次口服灌胃14天给药HelainarhLF在大鼠中具有良好的耐受性，其水平高达2000mg/kg/天，或57×Helaina\在成人中的预期商业用途，并表明2000mg/kg/天的高剂量适用于未来的确定性毒理学研究。
