What happens after the activation of ascaridole? Reactive compounds and their implications for skin sensitization

Authors: CHITTIBOYINA, AMAR - University Of Mississippi; AVONTO, CRISTINA - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi

Submitted to: Chemical Research in Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2016
Publication Date: 8/11/2016
Citation: Chittiboyina, A.G., Avonto, C., Khan, I.A. 2016. What happens after the activation of ascaridole? Reactive compounds and their implications for skin sensitization. Chemical Research in Toxicology. 29:1488-1492. doi:10.1021/acs.chemrestox.6b00157.

Interpretive Summary: Ascaridole, the oxidative metabolite of a-terpinene, is considered to be one of the components responsible for contact allergy associated with essential oils derived from Chenopodium and Melaleuca (tea tree) species. The HTS-DCYA method was applied to understand the reported enhanced reactivity of activated ascaridole and possibly to identify the resulting elusive, radical or other reactive species. As a result, a substituted cyclohexenone was identified as potential electrophilic intermediate resulting in higher depletion of nucleophilic DCYA, along with several non-reactive byproducts of ascaridole via radical degradation mechanism.

Technical Abstract: To replace animal testing and to improve the prediction of skin sensitization, significant attention has been directed to the use of alternative methods. Along with induction of Nrf2 target gene and upregulation of CD86 and C54 markers, the direct peptide reactivity assay (DPRA), the regulatory agencies approved alternative in chemica method has been applied for understanding the sensitization capacity of activated ascaridole. Ascaridole, the oxidative metabolite of