Degradation products of monoterpenes are the sensitizing agents in tea tree oil

Am J Contact Dermat. 1999 Jun;10(2):68-77. doi: 10.1016/s1046-199x(99)90002-7.


Background: Patients using tea tree oil (TTO) topically may become sensitized to this natural remedy. More than 30 cases have been documented in the literature since 1991.

Objective: Freshly distilled, as well as oxidized TTO, some fractions, and single constituents were used for experimental sensitization in guinea pigs. TTO was stored on a window sill to study the influence of light, oxygen, and warmth. The oxidized oil and different fractions were devoted to experimental sensitization in guinea pigs to determine their sensitizing potency. Fifteen constituents were patch tested in TTO-sensitive patients to find how many may play a role as contact allergens.

Methods: Guinea pigs were sensitized by a modified FCA-method (Freund's complete adjuvant) with freshly distilled TTO, oxidized TTO, the monoterpene and sesquiterpene fraction, and 1, 8-cineole. TTO-sensitive patients were tested with 15 typical constituents and degradation products. Gas chromatographic analysis was used to detect degradation products of the deteriorated TTO.

Results: Fresh TTO was revealed to be a very weak sensitizing material whereas oxidized TTO was 3 times stronger. The monoterpene fraction showed to be a stronger sensitizer than the sesquiterpene fraction. All 11 patients reacted mostly with a ++-plus or even a -plus reaction to alpha-terpinene, terpinolene and ascaridol. alpha-Phellandrene became positive in four patients, myrcene in only two. Gas chromatographic analyses showed that the formation of peroxides increased within 4 days from less than 50 to more than 500 ppm. Peroxides, epoxides and endoperoxides were formed. Deterioration products of alpha-terpinene were found to be mainly p-cymene, ascaridol, isoascaridol, a ketoperoxide, and colorless crystals that likely were 1,2,4-trihydroxy menthane. The p-cymene content increased dramatically from 2% to 11.5%. alpha- and gamma-terpinene, as well as terpinolene, were reduced to one half of their former concentration. Ascaridol and isoascaridol have never before been found in TTO.

Conclusion: Tea tree oil kept in open and closed bottles or other containers undergoes photooxidation within a few days to several months, leading to the creation of degradation products that are moderate to strong sensitizers. Peroxides, epoxides and endoperoxides, like ascaridol and 1,2,4-trihydroxy menthane, are formed. These must be considered responsible for the development of allergic contact dermatitis seen in individuals treating themselves with the oil. A test series with 15 characteristic constituents is recommended for patch testing.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Anti-Infective Agents, Local / adverse effects*
  • Anti-Infective Agents, Local / analysis*
  • Anti-Infective Agents, Local / chemistry
  • Chromatography, Gas
  • Dermatitis, Atopic / chemically induced*
  • Drug Stability
  • Female
  • Guinea Pigs
  • Humans
  • Immunization
  • Light
  • Male
  • Middle Aged
  • Oils, Volatile / adverse effects*
  • Oils, Volatile / analysis*
  • Oils, Volatile / chemistry
  • Oxidation-Reduction
  • Patch Tests / methods
  • Plant Oils / adverse effects*
  • Plant Oils / analysis*
  • Plant Oils / chemistry
  • Sensitivity and Specificity
  • Species Specificity
  • Tea Tree Oil
  • Terpenes / adverse effects*
  • Terpenes / analysis*
  • Terpenes / chemistry


  • Anti-Infective Agents, Local
  • Oils, Volatile
  • Plant Oils
  • Terpenes
  • Tea Tree Oil