In chemico evaluation of tea tree essential oils as skin sensitizers: Impact of the chemical composition on aging and generation of reactive species

Authors: AVONTO, CRISTINA - University Of Mississippi; CHITTIBOYINA, AMAR - University Of Mississippi; WANG, MEI - University Of Mississippi; VASQUEZ, YELKAIRA - University Of Mississippi; RUA, DIEGO - Us Food & Drug Administration (FDA); KHAN, IKHLAS - University Of Mississippi

Submitted to: Chemical Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2016
Publication Date: 6/10/2016
Citation: Avonto, C., Chittiboyina, A.G., Wang, M., Vasquez, Y., Rua, D., Khan, I.A. 2016. In chemico evaluation of tea tree essential oils as skin sensitizers: Impact of the chemical composition on aging and generation of reactive species. Chemical Research in Toxicology. 29:1108-1117.

Interpretive Summary: A new method called “HTS-DCYA assay” successfully enabled the identification of potential skin sensitizers from complex mixtures, such as essential oils. The obtained data are in agreement with findings from clinical and in vivo reports of increased sensitization potential of aged tea tree oils. This method and approach may serve as an important tool in prescreening of such complex mixtures to validate and prioritize in vivo experiments, thus helping minimizing the number and cost of in vivo assays, which is of great importance for regulatory risk assessment.

Technical Abstract: Tea tree oil (TTO) is a popular skin remedy obtained from the leaves of Melaleuca alternifolia, M. linariifolia or M dissitiflora. Due to the commercial importance ofTTO, substitution or adulteration with other tea tree species (such as cajeput, niaouli, manuka and kanuka oils) is common and may pose significant risk along with perceived health benefits. The distinctive nature, qualitative and quantitative compositional variation of these oils is responsible for the various phar­ macological as well as adverse effects. Authentic TTOs (especially aged ones) have been identified as potential skin sensi­ tizers, while reports of adverse allergic reactions to the other tea trees essential oils are less frequent. Chemical sensitizers are usually electrophilic compounds, and in chemica methods have been developed to identify skin allergens in terms of their ability to bind to biological nucleophiles. However, little information is available on the assessment of sensitization potential of mixtures such as essential oils due to their complexity. In the present study, ten "tea tree" oils and six major TTO constituents have been investigated for their sensitization potential using a fluorescence in chemica method. The reactivity of authentic TTOs was found to correlate with the age of the oils, while the majority of non-authentic TTOs were less reactive, even after aging. Further thio-trapping experiments with DCYA and characterization by UHPLC-DAD-MS led to the identification of several possible DCYA-adducts which can be used to infer the structure of the candidate reactive species. The major TTO components terpinolene, a.-terpinene and terpinene-4-ol were unstable under accelerated aging conditions, which led to formation of several DCYA-adducts.