Are atranols the only skin sensitizers in oakmoss, a systematic investigation using non-animal methods

Authors: AVONTO, CRISTINA - University Of Mississippi; CHITTIBOYINA, AMAR - University Of Mississippi; KHAN, SHABANA - University Of Mississippi; DALE, OLIVIA - University Of Mississippi; PARCHER, JON - University Of Mississippi; Wang, Mei; KHAN, IKHLAS - University Of Mississippi

Submitted to: Toxicology In Vitro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/11/2021
Publication Date: 11/17/2020
Citation: Avonto, C., Chittiboyina, A.G., Khan, S.I., Dale, O.R., Parcher, J.F., Wang, M., Khan, I.A. 2020. Are atranols the only skin sensitizers in oakmoss, a systematic investigation using non-animal methods. Toxicology In Vitro. 70. Article e105053. https://doi.org/10.1016/j.tiv.2020.105053.
DOI: https://doi.org/10.1016/j.tiv.2020.105053

Interpretive Summary: The absolute of the lichen oak moss is a commercially significant natural product used in exotic perfumes, cosmetics, and personal care products. Contrarily, oak moss absolute is also known to contain many allergens, such as atranol(ATR) and chloroatranol (ClATR) being identified as the main skin allergens in oakmoss. Although atranols skin sensitization potential has been repeatedly demonstrated, further evidence points toward the presence of multiple skin sensitizers in addition to the atranols. The present work was to investigate the skin sensitization potential of main atranols and atranol-like oakmoss costituents using a combination of chemical and in vitro methods to gain a better understanding of the mechanism of action of oakmoss and its constituents on the molecular initiating event (MIE) leading to skin sensitization and further biological pathways. Unknown compounds were isolated and identified by NMR and GC/MS. A combination of four non-animal methods was investigated. Based on weight of evidence, both ATR and ClATR were confirmed as potential skin sensitizers. Also, potential new candidate sensitizers in oakmoss were identified.

Technical Abstract: Oakmoss and treemoss absolutes are the major natural extracts of concern as potential source of of skin sensitizers in cosmetics and personal care products (PCP). Two single constituents, atranol and chloroatranol, have been identified as primary culprits in both lichens, and industrial self-regulation has been proposed to limit their contents to less than 100 ppm. Nonetheless, evidence points to the presence of additional candidate skin sensitizers in these multicomponent extracts. These observations, along with a lack of data from non-animal alternative methods and the chemical variability of commercial absolutes, prompted further investigation of oakmoss absoluts along with altranol-like compounds in these extracts. The major chemical constituents of a commercial sample were identified by two independent analytical techniques, GC/MS and HPLC/DAD-MS. The crude oakmoss extract and pure compounds were assayed with two in chemico methods (HTS-DCYA and DPRA) to gauge their chemical reactivity. Activation of inflammatory responses in vitro was investigated by KerationSensTM and human cell line activation test (h-CLAT). Based on weight of evidence, orcinol, ethyl orsellinate, and usnic acid were classified as candidate sensitizers, along with both atranols and oakmoss extract.