Safety and efficacy of combined essential oils for the skin barrier properties: In vitro, ex vivo and clinical studies

Abstract Objective To evaluate the safety and the synergistic effects of tea tree, lavender, eucalyptus and tangerine essential oils in combination on the skin using in vitro, ex vivo and clinical studies. Methods The phototoxicity was predicted using 3T3 neutral red uptake phototoxicity test (OECD TG 432). Skin penetration was evaluated by confocal Raman microspectroscopy using direct application of essential oils to pig ears. For the clinical studies, 40 participants were enrolled and randomized in three groups: (1) lavender, eucalyptus and tangerine, (2) the same essential oils plus melaleuca and (3) placebo group. The skin was evaluated by noninvasive techniques before and after a 90‐day period of topical use. Results The essential oils were non‐phototoxic, but the tangerine oil showed dose‐dependent cytotoxicity (IC50: 33.1 µg/ml), presenting 35% of penetration in the viable epidermis. On the contrary, 17.7 µg/ml in combination was applied per day in the clinical study and the penetration rate for the combinations (10%, 1.77 µg/ml achieving the viable epidermis) guaranteed the safety, since in the clinical study, the application of the four essential oils improved skin barrier and morphologic skin characteristics, as well as increased skin hydration and decreased sebum levels, with no unwanted effects reported. Conclusions All essential oils studied were considered non‐cytotoxic or non‐phototoxic separately except tangerine, which present a dose‐dependent cytotoxicity. Finally, the essential oils in combination in an appropriate amount were safe and effective in the improvement of the hydrolipidic balance and morphological properties of the skin.