Safety assessment of icelandic moss (Cetraria islandica) extract as a cosmetic ingredient using the threshold of toxicological concern approach

Islandski lišaj, znan pod latinskim imenom Cetraria islandica, je v farmacevtski industriji ena izmed nepogrešljivih rastlin. Najpogosteje se uporablja v obliki rastlinskega izvlečka za zdravljenje vnetega grla in žrela ter umirjanje draženja zgornjih dihal. V izvlečku prisotne komponente pa so odgovorne za njegovo vedno bolj pogosto uporabo tudi v kozmetični industriji. Uporablja se lahko v različnih oblikah kozmetičnih izdelkov, primernih tako za uporabo na koži kot tudi na sluznicah ustne votline. Vsem rastlinskim izvlečkom je skupna izjemna pestrost kvalitativne in kvantitativne sestave, na kar v veliki meri vpliva okolje in pogoji gojenja. Zaradi tega moramo biti pri njihovi uporabi še toliko bolj previdni in upoštevati vsa priporočila ter navodila za uporabo, ki temeljijo na njihovi oceni varnosti. Oceno varnosti izvlečka islandskega lišaja smo v diplomski nalogi izvedli z uporabo pristopa s pragom toksikološkega tveganja (TTC), ki z razvrstitvijo v Cramer-jeve razrede toksičnosti spojinam določi mejno vrednost izpostavljenosti (vrednost TTC). Na osnovi literature smo preučili kvalitativno in kvantitativno sestavo rastline in izvlečka ter na podlagi fizikalno-kemijskih lastnosti posameznim spojinam določili potencialni obseg absorpcije. Dobljene vrednosti so nam skupaj s koncentracijo spojin v izvlečku služile za izračun sistemske izpostavljenosti v primeru uporabe kozmetičnega izdelka z vsebovanim izvlečkom. Prav zaradi pestre in zapletene kemijske sestave rastlinskih izvlečkov pa ti vsebujejo tudi spojine, katerih koncentracija je neznana. V tem primeru smo maksimalno dovoljeno sistemsko izpostavljenost spojinam določili na podlagi potencialnega obsega absorpcije in vrednosti TTC posameznega Cramer-jevega razreda. Za nekatere spojine smo s pomočjo vrednosti NOAEL izračunali še njihov dnevni varni odmerek, ki je bil v vseh primerih veliko večji od vrednosti TTC in potencialne sistemske izpostavljenosti preko izvlečka. Slednja je bila pri večini spojin nizka in tako ni presegla vrednosti TTC na podlagi razvrstitve v Cramer-jeve razrede toksičnosti, kar smo pripisali nizkemu obsegu absorpcije skozi kožo. Kljub temu so sistemske izpostavljenosti nekaterih spojin presegle mejne vrednosti, ki pa so zastavljene dokaj konservativno in so tako v nekaterih primerih že predlagane višje vrednosti. Ne glede na rahla odstopanja smo na podlagi vseh izračunov in dobljenih vrednosti ocenili preučevani izvleček islandskega lišaja kot varen za uporabo pod normalnimi pogoji uporabe.Icelandic moss, with the Latin name Cetraria islandica, is commonly used in the pharmaceutic industry. It is mostly used as a plant extract to soothe a sore throat and to heal upper respiratory tract infections. Due to the components present in the extract, it is lately also increasingly used in the cosmetic industry. The extract can be used in various types of cosmetic productsits properties are suitable for skin care cosmetics as well as for cosmetics intended for the mucous membranes. Extracts show a huge variation in qualitative and quantitative structure which is mainly affected by its environment and growing conditions. To this end, we must take extra care when handling the extract and follow the recommendations and instructions for use, based on the safety assessment. In this thesis we have conducted a safety assessment for the Icelandic moss extract with the use of the threshold of toxicological concern (TTC) approach, which evaluates the compounds with the implementation of the Cramer classification scheme providing the exposure limits (TTC values). We have examined the qualitative and quantitative compositions of the actual plant and extract based on the literature and determined the potential extent of absorption based on the physicochemical properties of each individual compound. These values in addition to the concentration of the compounds have enabled us to calculate the systemic exposure when using cosmetic products containing this extract. Due to the varied and complex chemical composition of the plant extract it is clear that they contain compounds, whose concentrations are not known. In this case, we have determined the maximal tolerated systemic exposure of the compounds based on the range of the absorption potential and the TTC values from the Cramer classification scheme. For some of the compounds, we have also calculated the acceptable daily intake by employing the NOAEL values, which in all cases were significantly higher than the TTC values and the potential systemic exposure via the extract. The latter was very low for most of the compounds and did not exceed the TTC values based on the Cramer classification scheme of systemic toxicity due to its low absorption through the skin. Still, some of the compounds showed systemic exposure above the permitted levels that are somewhat conservative and higher levels for these limits have already been recommended. Despite some slight deviation in the values, we have managed to declare the Icelandic moss extract to be safe to use under normal conditions, based on all calculations and acquired values