Safety of Topical Essential Oil Herbal Ointments: A Phase I Randomized Controlled Trial

Abstract

Background and Aim: Plants hold significant promise for dermatological applications. However, the potential for phytochemicals, particularly essential oils, to cause skin irritation or sensitization necessitates rigorous safety evaluation for products derived from medicinal plants. This Phase I study was therefore designed to investigate the safety profile of three novel herbal ointment formulations prepared from essential oils on the healthy human skin of volunteers. Methods: An open-label, randomized controlled Phase I trial was conducted with 30 healthy volunteers in Ethiopia. Participants were randomly assigned (10 each) to one of the three investigational herbal ointments in a 1:1:1 ratio. For each participant, placebo (vehicle), 2%, and 5% concentrations of the allocated investigational product were applied concurrently using an occlusive patch test, followed by a photo-patch test and a repeated open application test (ROAT). Participants were followed for 14 days to monitor for skin reactions and adverse events. The primary endpoint was the occurrence of serious adverse reactions (SAR) associated with investigational products. Results: All 30 enrolled participants completed the study with full adherence to the required procedures as per the protocol. No serious adverse reaction related to the investigational herbal products (IHPs) were observed throughout the trial. A total of six non-serious adverse events were recorded among five study participants, none of which was assessed as related to the IHPs. Baseline and end-of-study laboratory parameters and vital signs remained stable, with no clinically significant abnormalities detected. Conclusion: The trial was registered under the number PACTR202311887239866.