Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro

Eur J Pharm Biopharm. 2008 May;69(1):214-22. doi: 10.1016/j.ejpb.2007.10.002. Epub 2007 Oct 5.


The safety of topical application of Australian tea tree Oil (TTO) is confounded by a lack of transdermal penetration data, which adequately informs opinions and recommendations. In this study we applied TTO in its pure form and as a 20% solution in ethanol in vitro to human epidermal membranes from three different donors, mounted in horizontal Franz-type diffusion cells, using normal 'in use' dosing conditions (10 mg/cm2). In addition, we examined the effect of partially occluding the application site on the penetration of TTO components. Our data showed that only a small quantity of TTO components, 1.1-1.9% and 2-4% of the applied amount following application of a 20% TTO solution and pure TTO, respectively, penetrated into or through human epidermis. The largest TTO component penetrating the skin was terpinen-4-ol. Following partial occlusion of the application site, the penetration of terpinen-4-ol increased to approximately 7% of the applied TTO. Measurement of the rate of evaporation of tea tree oil from filter paper (7.4 mg/cm2) showed that 98% of the oil evaporated in 4 hours. Overall, it is apparent that the penetration of TTO components through human skin is limited.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical / methods*
  • Cyclohexane Monoterpenes
  • Cyclohexenes / chemistry
  • Diffusion
  • Dosage Forms*
  • Epidermis / metabolism
  • Female
  • Humans
  • Monoterpenes / chemistry
  • Risk Assessment
  • Skin / drug effects*
  • Skin / metabolism
  • Skin / pathology
  • Solubility
  • Surface Properties
  • Tea Tree Oil / administration & dosage*
  • Technology, Pharmaceutical / methods
  • Terpenes / chemistry
  • Time Factors


  • Cyclohexane Monoterpenes
  • Cyclohexenes
  • Dosage Forms
  • Monoterpenes
  • Terpenes
  • alpha-terpineol
  • terpinenol-4
  • Tea Tree Oil