RESUMO
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 300â¯mg/kg body weight in Sprague-Dawley rats.
