Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Regenera Pharma, Nes-Ziona, Israel.
Food Chem Toxicol. 2018 Feb;112:168-177. doi: 10.1016/j.fct.2017.12.036. Epub 2017 Dec 27.
Mastic gum is used for health products and in the food industry, and is being tested for several clinical indications. Nevertheless, information on its safety is scarce. Our aim was to test the local and systemic toxicity of RPh201, a botanical extract of gum mastic, and to assess the toxicokinetic profile of the mastic gum constituents masticadienonic acid (MDA) and isomasticadienonic acid (IMDA). 340 Sprague-Dawley rats were administered twice weekly subcutaneously with placebo or different doses of RPh201 for 6 months with an interim group at 3 months and a 4-week recovery group. No systemic toxicity was observed with RPh201. Local injection site reactions were observed in all animals, with comparable severity and frequency in the placebo and high dose groups. However, given the relative increase in tissue reaction in the high dose group, these changes were attributed to RPh201 administration. Nevertheless, considering the minor local irritation effects and clear trend for reversibility, the effects were not judged to be adverse. The toxicokinetic study revealed that the MDA and IMDA exposure increased with dose and the increase was supra-proportional on all days. This study supports a "no observed adverse effect level" (NOAEL) of 300 mg/kg body weight in Sprague-Dawley rats.
乳香树胶被用于保健品和食品工业，并且正在针对多种临床适应证进行测试。然而，关于其安全性的信息却很少。我们的目的是测试 RPh201（乳香树胶的植物提取物）的局部和全身毒性，并评估乳香树胶成分乳香酸（MDA）和异乳香酸（IMDA）的毒代动力学特征。340 只 Sprague-Dawley 大鼠每周两次经皮下给予安慰剂或不同剂量的 RPh201，共 6 个月，其中包括一个 3 个月的中期组和一个 4 周恢复期组。RPh201 未观察到全身毒性。所有动物均观察到局部注射部位反应，安慰剂和高剂量组的严重程度和频率相当。然而，鉴于高剂量组组织反应的相对增加，这些变化归因于 RPh201 的给药。然而，考虑到轻微的局部刺激作用和明显的可逆趋势，这些作用不被认为是有害的。毒代动力学研究表明，MDA 和 IMDA 的暴露量随剂量增加而增加，并且在所有天数上呈超比例增加。这项研究支持在 Sprague-Dawley 大鼠中，300mg/kg 体重是“无观察到不良效应水平”（NOAEL）。
