Vrednotenje mutagenega in karcinogenega potenciala izbranih barvil za lase in silico

Korošec, Sara (avtor), Jakopin, Žiga (mentor)

Barve za lase so prosto dostopne in predstavljajo velik delež kozmetične industrije. Z vidika uporabe je zelo pomembno, da so tako barve za lase kot tudi ostali kozmetični izdelki varni. Pri tem je predvsem pomembno, da kozmetični izdelki ne vsebujejo sestavin, ki so razvrščene kot rakotvorne, mutagene ali strupene za razmnoževanje. V diplomski nalogi smo se osredotočili na vrednotenje karcinogenega in mutagenega potenciala dvanajstih najpogosteje uporabljanih sestavin v oksidativnih barvah za lase. Nabor slednjih je bil narejen iz pregleda 30 različnih oksidativnih barv za lase. Testiranje kozmetičnih izdelkov in njihovih sestavin na živalih je od 2013 prepovedano, zato smo za oceno karcinogenosti in mutagenosti uporabili metode in silico. Slednje za napoved uporabijo fizikalno-kemijske lastnosti posamezne kemikalije ter strukturne alarme v njihovih strukturah. Temeljijo tudi na predpostavki, da imajo podobne spojine podobno delovanje. Programi, ki smo jih uporabili, so bili OncoLogic, Toxtree, T.E.S.T. in Derek Nexus. Napovedi smo primerjali z že znanimi podatki iz podatkovnih baz in z rezultati in vitro ter in vivo testov, opisanih v literaturi. S programom T.E.S.T. smo lahko napovedali le mutageni potencial, s programom OncoLogic pa le karcinogeni potencial, medtem ko ostala programa omogočata napoved obeh potencialov. Pravilnih napovedi karcinogenega potenciala je bilo zelo malo, saj se je pri večini primerov napoved razlikovala od podatkov iz literature; le-ti so bili negativni, napovedi pa pozitivne. V primeru napovedi karcinogenega potenciala sta imela največjo napovedno moč programa Derek Nexus in Toxtree, saj sta podala najmanj lažno pozitivnih rezultatov, medtem ko OncoLogic ni podal nobene pravilne napovedi. Rezultati in vitro ter in vivo študij mutagenosti so velikokrat neskladni. Za napoved mutagenega delovanja in vitro pri bakterijah se najpogosteje uporablja Amesov test. Pri primerjavi rezultatov, pridobljenih v Amesovem testu, z našimi in silico napovedmi, smo opazili, da sta največ pravilnih napovedi podala programa Derek Nexus in Toxtree, nato pa T.E.S.T. Splošno lahko pripišemo programoma Derek Nexus in Toxtree najvišjo napovedno moč, saj sta pri največ sestavinah pravilno napovedala tako mutageni kot tudi karcinogeni potencial. Potrebno se je zavedati, da ta sklep sloni le na manjšem številu pravilnih napovedi karcinogenega potenciala in nekaj pravilnih napovedi mutagenega potenciala. In silico ter in vitro metode so trenutno edina alternativa in vivo študijam, vendar njihova napovedna moč še zdaleč ni tako dobra, kar lahko zaključimo tudi iz primerjave rezultatov. Za ustrezno vrednotenje kozmetičnih sestavin bo v prihodnosti potrebno razviti še bolj natančne QSAR modele.

• Jezik: Slovenski jezik
• Ključne besede: mutagenost, karcinogenost, in silico metode, barvila za lase, QSAR
• Vrsta gradiva: Diplomsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2019
• PID: 20.500.12556/RUL-109328
• Datum objave v RUL: 30.08.2019

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: In silico evaluation of mutagenic and carcinogenic potencial of selected hair dyes

Izvleček

Hair dyes are easily accessible and represent a big part of the cosmetic industry. Given their frequent use, hair dyes as well as other cosmetic products must be safe. Specifically, cosmetic products are not allowed to contain substances that are carcinogenic, mutagenic or toxic to reproduction. In this thesis, we focused on carcinogenic and mutagenic aspect of twelve most frequently represented substances used in oxidative hair dyes. The selection of the latter was conducted from a review of 30 different oxidative hair dyes. Since 2013, cosmetic products and their ingredients are not allowed to be tested on animals, therefore we used in silico methods to predict their carcinogenic and mutagenic potential. These methods are based on physico-chemical properties of certain chemical and its structural alerts. Furthermore, they are also based on the following presumption; those substances, which are structurally related also share the same mechanism of action. In our research, we used the following programmes: OncoLogic, Toxtree, T.E.S.T. and Derek Nexus. We compared the generated predictions with results from databases and data obtained from in vitro and in vivo studies. While T.E.S.T. only predicts mutagenicity and OncoLogic only predicts carcinogenicity, other two programmes are capable of predicting mutagenicity as well as carcinogenicity. Only a few predictions in terms of carcinogenicity potential were correct, because in most other cases the prediction differed from the data from literature. When assessing the carcinogenic potential, programmes Derek Nexus and Toxtree possess the highest predictive strength, because they predicted the least false positive results, as opposed to OncoLogic, which failed to generate correct predictions. Most of the mutagenicity results from in vitro and in vivo studies are contradictory. Ames test in bacteria is most frequently used test for predicting in vitro mutagenicity. By comparing results from the Ames test we found out that Derek Nexus and Toxtree were able to generate the most correct predictions, when compared with T.E.S.T. Overall; the highest predictive strength can evidently be assigned to Derek Nexus and Toxtree. However, one has to bear in mind that this decision is based only on a few examples of correct predictions for carcinogenicity potential and some correct predictions for mutagenicity potential. In silico and in vitro methods represent a good as well as the only alternative to in vivo studies, but their predictive strength is still rather low, which we can see from comparing the results. In the future more accurate QSAR models should be developed for appropriate evaluation of cosmetic ingredients.

• Ključne besede: mutagenicity, carcinogenicity, in silico methods, hair dyes, QSAR