20.500.12556/RUL-186556 Ocena varnosti izvlečka virginskega nepozebnika (Hamamelis virginiana) kot kozmetične sestavine z uporabo pristopa s pragom toksikološkega tveganja Safety assessment of witch hazel (Hamamelis virginiana) extract as a cosmetic ingredient using the threshold of toxicological concern approach Virginski nepozebnik (Hamamelis virginiana), uvrščen v družino nepozebnikovk (Hamamelidaceae), je priznano uporabljan na področju tradicionalne medicine ter sodobne dermatologije in kozmetologije. Njegove adstringentne, antibakterijske, antioksidativne, protivnetne in pomirjujoče lastnosti omogočajo lajšanje vnetnih kožnih stanj in poškodb kože. V kozmetičnih izdelkih se največkrat uporablja za nego in vlaženje kože ter blaženje razdražene kože in lasišča. V diplomski nalogi smo ocenili varnost izvlečka virginskega nepozebnika kot kozmetične sestavine z uporabo pristopa s pragom toksikološkega tveganja (TTC), ki na osnovi kemijske strukture spojin le-te razvrsti v Cramer-jeve razrede toksičnosti. Za vsakega izmed treh razredov je pripisana vrednost TTC. Z uporabo literature smo preučili kvalitativno in kvantitativno sestavo listov in lubja izvlečka ter na podlagi fizikalno – kemijskih lastnosti posamičnih sestavin, pridobljenimi s programom ChemOffice, izračunali njihov potencialni obseg absorpcije ter dnevno sistemsko izpostavljenost. Ugotovili smo, da večina sestavin izvlečka ne predstavlja tveganja za zdravje, saj njihova sistemska izpostavljenost ne presega mejnih vrednosti TTC, z izjemo hamamelitanina v izvlečku lubja nepozebnika, ki pa mejno vrednost TTC presega. Za spojine z neznano koncentracijo smo na osnovi vrednosti TTC in potencialnega obsega absorpcije določili maksimalno dopustno koncentracijo, v kateri so lahko prisotne v izvlečku. Za nekatere spojine smo uspeli pridobiti eksperimentalne vrednosti NOAEL iz toksikoloških študij in vivo, s pomočjo katerih smo izračunali varne dnevne odmerke. Ugotovili smo, da so varni dnevni odmerki v primerjavi z vrednostmi TTC in vrednostmi sistemske izpostavljenosti, večji. Predvsem pa velike razlike med vrednostmi NOAEL ter vrednostmi Cramer-jevih razredov toksičnosti nakazujejo konzervativnost pristopa TTC, ki je sicer uporaben, kadar na voljo ni dovolj eksperimentalnih podatkov o toksičnosti določene spojine. Kljub temu smo lahko na podlagi izračunov in dobljenih rezultatov ocenili, da je izvleček virginskega nepozebnika varen za uporabo v kozmetičnih izdelkih. Witch hazel (Hamamelis virginiana), classified as a member of a witch hazel family (Hamamelidaceae), is recognized for its use in traditional medicine as well as modern dermatology and cosmetology. Its adstringent, antibacterial, antioxidant, anti-inflammatory, and soothing properties help relieve inflammatory skin conditions and skin damage. In cosmetics products it is most often used in skin care, for skin moisturizing and soothing irritated skin and scalp. In this thesis, we assessed the safety of witch hazel extract as a cosmetic ingredient using the threshold of toxicological concern approach (TTC), which classifies compounds into Cramer toxicity classes based on their chemical structure. A TTC value is assigned to each of the three classes. Using the literature data, we examined the qualitative and quantitative composition of the leaves and bark of the extract, and based on the physico-chemical properties of the compounds using the ChemOffice software, we calculated the potential absorption range and daily systemic exposure. We found out that most of the extract's components do not pose a health risk, as their systemic exposure does not exceed the TTC limit values, with the exception of hamamelitannin in witch hazel bark extract, which exceeds the TTC limit value. For compounds with unknown concentrations, we determined the maximum permissible concentration in which they can be present in the extract based on the TTC value and the potential absorption range. For some compounds, we were able to obtain experimental NOAEL values from in vivo toxicological studies, which were used to calculate safe daily doses. We found out that the safe daily doses are higher compared to the TTC values and systemic exposure values. Especially, the large differences between the NOAEL values and the Cramer toxicity class values indicate the conservatism of the TTC approach, which is otherwise useful when the experimental data on the toxicity of a particular compound is insufficient. However, based on our calculations and results obtained, we were able to assess that the witch hazel extract is safe for use in cosmetic products. izvleček virginskega nepozebnika Cramer-jevi razredi toksičnosti potencialni obseg absorpcije sistemska izpostavljenost varni dnevni odmerek ocena varnosti witch hazel extract Cramer toxicity classification potential absorption systemic exposure safe daily dose safety assessment true false false [S. Babnik] Slovenski jezik Angleški jezik Diplomsko delo/naloga 2026-09-03 07:45:10 2026-09-03 07:45:23 2026-09-04 04:30:41 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 665.58(043.2) 127906 289883395 33080.pdf 33080.pdf 1 19B086403B44E27A4DCC439F038B8AA1 844a7998e7be2ada5458120b37a8880bf1ea5a8a0fc532395ab2ab8badabcc31 3f38fedb-a75a-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=245828 33081.pdf 33081.pdf 1 A6E436D02B46C282340DB24ED131AD0C ebb726d3962763349e751df79ef9d4b14640808e37c8d5654734e36f91840969 402f57f2-a75a-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=245829 Fakulteta za farmacijo 0 0 0