G-7%NANA是N-乙酰神经氨酸(NANA),含有7%的唾液酸从糖巨肽(GMP)分离,牛奶的化合物。由于NANA可能具有免疫毒性,确保长期管理安全的必要性已经提高。在这项研究中,使用G-7%NANA对大鼠进行90天重复口服剂量毒性试验,剂量为0,1250,2500和5000mg/kg/天.建立了基于物质给药引起的显著变化的毒性测定标准,用于估计NOEL。NOAEL和LOAEL适用于这项研究。在分析免疫学标记时,没有观察到明显的变化,即使在高剂量组中观察到其他显着变化。根据制定的毒性测定标准,男性和女性的NOEL被确定为2500毫克/千克/天,女性的NOAEL被确定为5000毫克/千克/天。毒性测定标准,首次应用于重复剂量毒性测试,可以为更清楚地区分NOEL和NOAEL提供基础;然而,毒性确定标准需要补充,根据重复剂量毒性测试的更多经验,增加区分不良反应和非不良反应。
G-7%
NANA is N-acetylneuraminic acid(
NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since
NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7%
NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests.