Nakano Masahiko, Takahashi Hisaaki, Koura Seiko, Chung Catherine, Tafazoli Shahrzad, Roberts Ashley
NC Planning & Development Division, Mitsubishi Gas Chemical Co., Inc., 5-2, Marunouchi 2-chome, Chiyoda-ku, Tokyo, Japan.
Central Laboratories, New Drug Research Center, Inc., 452-1, Toiso, Eniwa-shi, Hokkaido, Japan.
Regul Toxicol Pharmacol. 2014 Oct;70(1):107-21. doi: 10.1016/j.yrtph.2014.06.024. Epub 2014 Jul 1.
The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.
吡咯喹啉醌二钠盐（BioPQQ™）作为一种补充食品成分的潜在用途，在一系列大鼠口服毒性研究中进行了评估，包括急性研究、14天初步研究和28天重复剂量研究，以及13周亚慢性研究。BioPQQ™的半数致死剂量在雄性大鼠中为1000 - 2000mg/kg体重（bw），在雌性大鼠中为500 - 1000mg/kgbw。在14天的研究中，高剂量的BioPQQ™仅导致雌性大鼠相对肾重量增加并伴有相关组织病理学变化，而在雌性动物后续的28天研究中导致尿蛋白和晶体增加。这些发现是可逆的，在恢复期内得到缓解。在13周的研究中，观察到一些临床化学指标变化和组织病理学改变，这些被认为没有毒理学意义，因为这些水平在历史对照范围内，不依赖剂量，在对照组中以相似频率出现，或仅在对照组中出现。基于这些发现，确定大鼠中BioPQQ™的未观察到有害作用水平为100mg/kgbw/天，这是13周研究中测试的最高剂量。
