Ahn Mi Young, Joo Hyo Jin, Kim Jin Sik, Yeon Yong, Ryu Hyeon Yeol, Choi Byung Gil, Song Kyung Seuk, Kim Sang Ho, Park Myeong Kyu, Jo You Young
Department of Agricultural Biology, National Institute of Agricultural Sciences, RDA, 166 Nongsaengmyung-Ro, Iseo-Myun, Wanju-Gun, 55365 Korea.
Korea Conformity Labortories, Incheon, Korea.
Toxicol Res. 2020 Feb 14;36(4):319-328. doi: 10.1007/s43188-020-00037-2. eCollection 2020 Oct.
We performed general toxicity studies of (two-spotted cricket) glycosaminoglycan (GbG), including a single, 4-week repeated oral dose toxicity test in ICR mice, and short-term genotoxicity tests. The mutagenic potential of the purified GbG was non-genotoxic when it was evaluated using short-term genotoxicity tests, namely Ames, chromosome aberration (CA), and micronuclei (MN) tests. In and assays, GbG did not produce any mutagenic response in the absence or presence of S9 mix with five bacterial strains (TA98, TA100, TA1535, TA1537, and WP2uvrA). Chromosome aberration test showed that GbG had no significant effect on Chinese hamster ovary (CHO) cells. In mouse micronuclei tests after twice oral treatments per day for two days, no significant alteration in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice intraperitoneally administered with GbG at doses of 15.63, 31.25, or 62.50 mg/kg. These results indicate that GbG has no mutagenic potential in these in vitro and in vivo systems. After GbG was orally administered at doses of 20, 40, 80, and 160 mg/kg for a single oral dose toxicity study and at 0, 40, 80, and 160 mg/kg bw/day for 4-week oral dose toxicity study, there were no observed clinical signs or deaths related to treatment in any group tested. Therefore, the approximate lethal oral dose of GbG was considered to be higher than 160 mg/kg in mice. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), or gross pathology were detected. Microscopic examination did not identify any treatment-related histopathologic changes in organs of GbG-treated mice in the high dose group. These results indicate that the no-observed adverse effect level (NOAEL) of GbG is higher than 160 mg/kg bw/day in mice.
我们对(双斑蟋蟀)糖胺聚糖(GbG)进行了一般毒性研究,包括在ICR小鼠中进行单次为期4周的重复口服剂量毒性试验以及短期遗传毒性试验。当使用短期遗传毒性试验(即Ames试验、染色体畸变(CA)试验和微核(MN)试验)评估纯化后的GbG的致突变潜力时,其无遗传毒性。在Ames试验中,无论有无S9混合物存在,GbG与五种菌株(TA98、TA100、TA1535、TA1537和WP2uvrA)均未产生任何诱变反应。染色体畸变试验表明,GbG对中国仓鼠卵巢(CHO)细胞无显著影响。在每天口服两次、连续两天的小鼠微核试验中,腹腔注射剂量为15.63、31.25或62.50 mg/kg的GbG的ICR雄性小鼠中,未观察到多染性红细胞微核发生率有显著变化。这些结果表明,GbG在这些体外和体内系统中无诱变潜力。在单次口服剂量毒性研究中,以20、40、80和160 mg/kg的剂量口服GbG,在为期4周的口服剂量毒性研究中,以0、40、80和160 mg/kg bw/天的剂量口服GbG,在所测试的任何组中均未观察到与治疗相关的临床体征或死亡。因此,GbG对小鼠的近似致死口服剂量被认为高于160 mg/kg。在整个给药期间,未检测到饮食消耗、眼科检查结果、器官重量、临床病理学(血液学、临床化学、凝血和尿液分析)或大体病理学有显著变化。显微镜检查未发现高剂量组GbG处理小鼠的器官中有任何与治疗相关的组织病理学变化。这些结果表明,GbG对小鼠的未观察到不良反应水平(NOAEL)高于160 mg/kg bw/天。