Safety assessement of common mallow (Malva sylvestris) extract as a cosmetic ingredient using the threshold of toxicological concern approach

Gozdni slezenovec (Malva Sylvestris) je zdravilna rastlina iz družine slezenovk in je ena najbolj uporabljenih rastlin v tradicionalni medicini. Z naraščanjem priljubljenosti naravne kozmetike se je uporaba izvlečka gozdnega slezenovca iz farmacije in medicine razširila tudi na področje kozmetologije. Izvleček se zaradi vlažilnega delovanja vgrajuje predvsem v izdelke za nego suhe kože, zasledimo pa ga tudi v kozmetiki za nego atopične kože in v ustnih vodicah, kjer predstavlja naravno alternativo pogostim protimikrobnim učinkovinam. Čeprav se rastlinski izvlečki smatrajo kot varni, pa na njihovo kompleksno zgradbo vplivajo predvsem dejavniki okolja, zato se je pred vgrajevanjem v kozmetične izdelke o njihovi varnosti potrebno prepričati. V diplomskem delu smo ocenili varnost izvlečka gozdnega slezenovca kot sestavine kozmetičnega izdelka, pri čemer smo uporabili pristop s pragom toksikološkega tveganja (TTC). Uporabljeni pristop temelji na razvrščanju spojin v Cramer-jeve razrede toksičnosti s predpisanimi vrednostmi mejne izpostavljenosti na osnovi njihove kemijske strukture. S pomočjo literature smo preučili kvalitativno in kvantitativno sestavo rastline in izvlečka gozdnega slezenovca ter na podlagi koncentracije in fizikalno-kemijskih lastnosti spojin izračunali parametre, potrebne za oceno potencialnega obsega absorpcije. Na osnovi slednjega smo nato lahko ocenili sistemsko izpostavljenost spojinam. Če podatki o koncentraciji spojin niso bili dostopni, smo maksimalno sistemsko izpostavljenost preračunali iz vrednosti TTC in potencialnega obsega absorpcije. Za nekatere spojine smo v literaturi uspeli najti tudi vrednosti NOAEL, s pomočjo katerih smo izračunali dnevni varni odmerek. Pri večini spojin je bila izračunana vrednost sistemske izpostavljenosti manjša od vrednosti TTC, pri skupini flavonoidov pa so bile izračunane vrednosti večje od dopustnih, saj smo pri računanju izpostavljenosti posameznim spojinam upoštevali najvišji skupni delež celotne skupine v izvlečku. Eksperimentalno določene vrednosti NOAEL v literaturi so bile znatno večje od vrednosti, ki so predpisane posameznim razredom s pristopom TTC. Kljub temu, da so izračunane vrednosti sistemske izpostavljenosti za določene spojine presegale vrednosti TTC, pa so bile znatno manjše od vrednosti NOAEL, na podlagi česar lahko zaključimo, da je uporaba izvlečka gozdnega slezenovca v mejah normale varna za uporabo in vgrajevanje v kozmetične izdelke.Common mallow (Malva Sylvestris) is a medicinal plant from the mallow family and is one of the most frequently used plants in traditional medicine. With the growing popularity of natural cosmetics, the use of common mallow extract has expanded from pharmacy and medicine to the field of cosmetology. Due to its moisturizing effect, the extract is primarily incorporated into products for dry skin. It can also be found in skin care cosmetics for atopic skin and in mouthwashes, where it represents a natural alternative to common antimicrobial agents. Although plant extracts are considered safe, their complex structure is primarily influenced by environmental factors, so it is necessary to ensure their safety before incorporating them into cosmetic products. In this thesis, we assessed the safety of common mallow extract as an ingredient of a cosmetic product, using the Threshold of Toxicological Concern (TTC) approach. The used approach is based on classifying compounds into Cramer classes of toxicity with set values of exposure limits (TTC values), taking into account their chemical structure. Using the available literature, we studied the qualitative and quantitative composition of the plant and the extract of the common mallow, and calculated the parameters necessary for assessing the potential range of absorption, based on the concentration and physicochemical properties of the compounds. Based on this, we were then able to assess the systemic exposure to the compounds. If data on the concentration of compounds were not available, we calculated the maximum systemic exposure from the TTC values and the potential range of absorption. For selected compounds, we were also able to find their NOAEL values in the literature, using which we calculated the daily safe dose. For most compounds, the calculated systemic exposure value was lower than the TTC value, except for the class of flavonoids, where the values exceeded the TTC value. Granted, we took into account the highest total concentration of the entire class in the extract when calculating the exposure to individual compounds. Experimentally determined NOAEL values in the literature were significantly higher than those calculated via the TTC approach. Despite the fact that the calculated values of systemic exposure for certain compounds exceeded the TTC values, they were significantly lower than the corresponding NOAEL values, on the basis of which we can conclude that the use of the common mallow extract is safe for use and incorporation into cosmetic products