PDF(Pubmed)
Abstract：
PD-00105 corresponds to a compound initially identified in the fruit of Alpinia oxyphylla Miq., obtained by chemical synthesis and proposed to be use in dietary supplements for its potential neuroprotective properties. The aim of this study was to perform a toxicological evaluation of PD-00105 in accordance with the testing strategy recommended by food regulatory authorities. All studies were conducted in accordance with Good Laboratory Practice (GLP), and followed the Organization for Economic Co-operation and Development (OECD) test guidelines for chemicals. Studies included a bacterial reverse mutation test, one in vitro micronucleus test in mammalian cells, and a repeated dose 90-day oral toxicity study. No sign of toxicity was observed in the two genotoxicity tests. The test item induced a significant liver and kidney toxicity at high doses (50 and 100 mg/kg BW/day), highlighted by significant increases in liver and kidney absolute and relative weights, associated with histopathological findings and concomitant changes in hematology and clinical chemistry. Increases in alanine aminotransferase, alkaline phosphatase, total protein, albumin, globulin, cholesterol, LDL, and HDL have been measured in these two groups. However, findings observed in the low-dose group (10 mg/kg BW/day) were considered as minimal and non-adverse, and were limited to an increase in liver weight in males and in kidneys weight in females, without concomitant changes in blood chemistry. The No Observed Adverse Effect Level (NOAEL) of PD-00105 was established as 10 mg/kg BW/day under the conditions of this study. This study substantiates the use of PD-00105 in dietary supplements at doses of 10 mg/day, taking into account a safety margin factor for dose conversion to humans.
摘要：
PD-00105对应于最初在谷草果实中鉴定的化合物。,通过化学合成获得，并因其潜在的神经保护特性而建议用于膳食补充剂。这项研究的目的是根据食品监管机构建议的测试策略对PD-00105进行毒理学评估。所有研究均按照良好实验室规范(GLP)进行。并遵循了经济合作与发展组织（OECD）的化学品测试指南。研究包括细菌回复突变试验,一种哺乳动物细胞的体外微核试验，和重复剂量90天口服毒性研究。在两种遗传毒性试验中均未观察到毒性迹象。在高剂量（50和100mg/kgBW/天）下，该测试项目诱导了显着的肝和肾毒性，肝脏和肾脏的绝对和相对重量显着增加，与组织病理学发现以及血液学和临床化学的伴随变化有关。丙氨酸转氨酶增加，碱性磷酸酶,总蛋白质，白蛋白,球蛋白,胆固醇,LDL,在这两组中测量了HDL和HDL。然而,在低剂量组（10mg/kg体重/天）中观察到的发现被认为是最小的和非不利的，并且仅限于男性肝脏重量和女性肾脏重量的增加，没有伴随的血液化学变化。在本研究条件下,PD-00105的未观察到的不良反应水平(NOAEL)确定为10mg/kgBW/天。这项研究证实了PD-00105在膳食补充剂中的使用剂量为10毫克/天，考虑到剂量转换为人类的安全裕度因素。
