Ocena varnosti izvlečka navadne konoplje (Cannabis sativa) z visoko vsebnostjo kanabidiola kot kozmetične sestavine z uporabo pristopa s pragom toksikološkega tveganja

Lipovec, Anamarija (author), Tavčar, Eva (mentor), Jakopin, Žiga (comentor)

Navadna konoplja (Cannabis Sativa L.) in njeni izvlečki so vse bolj prisotni v kozmetičnih izdelkih. Poznamo več kot 700 varietet konoplje, najbolj pogosto pa jo sistematiziramo na podvrste glede na vsebnost psihoaktivnega kanabinoida Δ9-tetrahidrokanabinola na industrijsko (manj kot 0,3 %) in indijsko (več kot 0,3 %). Cilj te diplomske naloge je oceniti varnost izvlečka navadne konoplje z visoko vsebnostjo kanabidiola (CBD). Pogosto raziskovan način pridobivanja izvlečka konoplje je ekstrakcija s superkritičnim ogljikovim dioksidom, s katerim je bil pridobljen tudi naš proučevan izvleček konoplje kultivarja Helena. Varnost izvlečka kot kozmetične sestavine smo ocenili z uporabo pristopa s pragom toksikološkega tveganja (TTC), ki temelji na razvrstitvi spojin glede na njihovo kemijsko strukturo v tri Cramerjeve razrede toksičnosti. V programu ChemDraw smo spojinam iz izvlečka najprej narisali kemijske strukture in pridobili vrednosti nekaterih fizikalno-kemijskih parametrov (logP, logS, molekulska masa). Te smo kasneje potrebovali za izračune, na podlagi katerih smo ocenili varnost izvlečka. Nato smo spojine s pomočjo programa Toxtree razvrstili v Cramerjeve razrede, ki imajo pripisano vsak svojo vrednost TTC. Z izračunano hitrostjo difuzije spojine skozi kožo smo jim ocenili potencialni obseg absorpcije in izračunali sistemsko izpostavljenost. Nazadnje smo vrednosti, pridobljene s pristopom TTC, primerjali še z izračunanim varnim dnevnim odmerkom iz eksperimentalno pridobljenih vrednosti NOAEL (najvišji odmerek, pri katerem še ne pride do pojava neželenih učinkov) iz literature. Ugotovili smo, da so vrednosti TTC, ki so določene za posamezne Cramerjeve razrede, mnogo nižje od vrednosti varne dnevne izpostavljenosti. Od vseh spojin proučevanega izvlečka je le ena spojina, in sicer CBD, presegel vrednost TTC, ki je pripisana Cramerjevemu razredu, v katerega je spojina uvrščena. Vendar je bila ta v primerjavi z varnim dnevnim odmerkom še vedno mnogo manjša. Zato smo zaključili, da je proučevan izvleček kot kozmetična sestavina varen za uporabo.

• Language: Slovenian
• Keywords: izvleček konoplje, pristop TTC, dnevna varna izpostavljenost, ocena varnosti, potencialni obseg absorpcije
• Work type: Bachelor thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2025
• PID: 20.500.12556/RUL-171424
• Publication date in RUL: 26.08.2025

Secondary language

• Language: English
• Title: Safety assessment of hemp (Cannabis sativa) extract with high content of cannabidiol as a cosmetic ingredient using the threshold of toxicological concern approach

Abstract

The use of hemp (Cannabis Sativa L.) and hemp extracts in cosmetic products is increasingly common. While there are over 700 known varieties of cannabis, it is most commonly classified into subspecies based on the content of the psychoactive cannabinoid Δ9-tetrahydrocannabinol, where hemp contains less than 0.3 % and indica contains more than 0.3 %. The aim of this thesis is to assess the safety of a hemp extract with a high content of cannabidiol (CBD). Supercritical carbon dioxide extraction is a frequently explored method for obtaining hemp extract and was also used to obtain the extract of the hemp cultivar Helena that we studied. The safety of the extract as a cosmetic ingredient was assessed using the threshold of toxicological concern (TTC) approach based on categorising compounds according to their chemical structure into three Cramer classes of toxicity. We used ChemDraw to plot the chemical structures of the extract compounds and to obtain the values of certain physicochemical parameters (logP, logS, molecular weight). These were required for the calculations used to assess the safety of the extract. Next, Toxtree was used to categorise the compounds into Cramer classes, each with its own TTC value. Based on the calculated rate of diffusion of each compound through the skin, we estimated the potential extent of their absorption and calculated the systemic exposure. Finally, the values obtained using the TTC approach were compared with the calculated safe daily dose based on experimentally derived NOAEL values (the highest dose at which no adverse effects occur) from the literature. We found that the TTC values for each Cramer class were much lower than the safe daily exposure values. Of all the compounds in the studied extract, only one compound, namely CBD, exceeded the TTC value assigned to the Cramer class into which the compound is classified. However, this value was still significantly lower than the safe daily dose. We therefore concluded that the studied extract is safe for use as a cosmetic ingredient.

• Keywords: hemp extract, TTC approach, safe daily exposure, safety assessment, potential extent of absorption