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Vrednotenje parabenov in njihovih razgradnih produktov kot okoljskih endokrinih motilcev in silico
ID Mehle, Katarina (Author), ID Jakopin, Žiga (Mentor) More about this mentor... This link opens in a new window

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Abstract
Parabeni so najbolj pogosto uporabljeni konzervansi v kozmetični industriji. Najdemo jih tudi v farmacevtski in prehrambni industriji. Zaradi načina uporabe se težko izognemo vnosu parabenov v vodno okolje. V vodnem okolju so velikokrat prisotni halogeni elementi, kot sta klor in brom, s katerimi lahko reagirajo, kar vodi v nastanek halogeniranih razgradnih produktov. Ker parabene uvrščamo v skupino šibkih endokrinih motilcev, je zelo pomembno, da poznamo njihovo usodo v vodnem okolju ter njihov vpliv na žive organizme. V nalogi smo sedmim različnim parabenom, para-hidroksibenzojski kislini (PHBA) ter njihovim halogeniranim razgradnim produktom s pomočjo dveh programov, in sicer Endocrine disruptome in VegaNIC, napovedali okoljski vpliv, akutno toksičnost in endokrino delovanje. Na usodo parabenov v okolju pomembno vpliva vrednost logP. Zanimala nas je tudi verjetnost njihove biološke razgradnje, odpornost proti biodegradaciji in faktor bioakumulacije (BCF). Pri napovedovanju obstojnosti parabenov smo ugotovili, da se pri vseh pojavlja enak vzorec. Izvorni paraben ima največjo verjetnost biološke razgradnje. Mono- in diklorirani produkti imajo le malo verjetno biološko razgradnjo. Bromirani razgradni produkti so biološko nerazgradljivi, kar pomeni, da so v okolju veliko bolj obstojni v primerjavi z izvornimi parabeni. Kot najmanj obstojnega smo uvrstili metil paraben z najnižjo vrednostjo BCF. Najbolj obstojen je bil benzil paraben. Rezultati akutne toksičnosti so pokazali, da je najbolj toksičen benzil paraben, ki mu sledita butil paraben in izo-butil paraben. Najvišjo vrednost LC50 in tako najmanjšo toksičnost je izkazal metil paraben. Rezultati, pridobljeni z in silico metodami, so pokazali, da so bromirani derivati bolj akutno toksični kot klorirani derivati enakega parabena. Pri preučevanju endokrinega delovanja so rezultati pokazali, da je najvišja možnost vezave na androgenske in tiroidne receptorje (AR, AR an in TR ? in TR ß). Možnost vezave se ni povečevala z razgradnjo izvornega parabena. Na osnovi vseh rezultatov, pridobljenih s pomočjo računalniških programov, smo ocenili, da je najbolj varen metil paraben, saj je imel najnižjo vrednost logP, nizko akutno toksičnost ter nizko vrednost BCF, kar ga uvršča med snovi, ki se ne bioakumulirajo. Najbolj toksičen paraben je po dobljenih rezultatih benzil paraben in njegovi bromirani razgradni produkti, saj imajo visoko vrednost logP, so najbolj akutno toksični ter imajo visoko afiniteto vezave na androgenski receptor in srednjo možnost vezave na tiroidne receptorje. Parabeni so dolgo veljali za varne sestavine, vendar se v zadnjem času pojavlja vedno več raziskav, ki to trditev zavračajo. Vsekakor bi lahko rekli, da omenjeni konzervansi ne predstavljajo zelo visokega tveganja v okolju, saj se ne pojavljajo v zelo visokih koncentracijah, vendar bodo vsekakor potrebne še nadaljnje raziskave predvsem na področju njihovega endokrinega delovanja in povezave z nastankom raka dojk.

Language:Slovenian
Keywords:parabeni, halogeniranje, in silico napoved, endokrino delovanje, ekotoksikološki vpliv.
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2019
PID:20.500.12556/RUL-111226 This link opens in a new window
Publication date in RUL:26.09.2019
Views:1193
Downloads:261
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Secondary language

Language:English
Title:In silico evaluation of parabens and their degradation products as environmental endocrine disruptors
Abstract:
Parabens are the most commonly used preservatives in the cosmetic industry. We can find them in the pharmaceutical and food industry also. Because of their method of use, it is very difficult to avoid the intake of parabens in the aquatic environment. In the aquatic environment halogen elements, such as chlorine and bromine are present on many occasions. Parabens can react with chlorine and bromine which leads to the emergence of halogenated degradation products. Because parabens are classified in the group of weak endocrine disruptors, it is very important to know their path in the aquatic environment and their influence on live organisms. In the thesis, we predicted environmental influence, acute toxicity, and endocrine functioning for seven different parabens, para-hydroxybenzoic acid (PHBA), and their halogenated degradation products by means of two programs, i.e. Endocrine disruptome and VegaNIC. The logP value influences the path of parabens in the environment importantly. We were also interested in the probability of their biological degradation, resistance against biodegradation, and bioaccumulation factor (BCF). In predicting the resistance of parabens, we ascertained that there is the same pattern in all of them. The biggest probability of degradation is for the original paraben. Biological degradation of very little probability is characteristic for mono- and dichlorinated products. Brominated degradation products are biologically non-degradable, which means that they are far more resistant in the environment in comparison to the original parabens. We classified methylparaben with lowest BCF value as the least resistant. The most resistant was benzylparaben. The results of acute toxicity showed that the most toxic is benzylparaben. It is followed by butylparaben and iso-butylparaben. The highest LC50 value and thus the least toxicity proved methylparaben. The results gained by in silico methods showed that brominated derivatives are more acutely toxic as chlorinated derivatives of the same paraben. In researching endocrine functioning, the results showed that the highest probability is binding to androgen and thyroid receptors (AR, AR an and TR α and TR β). The possibility of binding did not increase by the degradation of the original paraben. On the basis of all results gained by means of computer programs, we estimated that the safest is methylparaben because it had the lowest logP value, low acute toxicity, and low BCF value which classifies it among substances who are not bioaccumulated. According to the results, the most toxic paraben is benzylparaben and its brominated degradation products because they have a high logP value, are the most acute toxic, and have a high affinity of binding to the androgenic receptor and the medium possibility of binding to thyroid receptors. Parabens were believed as safe ingredients for a long time. Lately, however, there is an increasing amount of research which rejects this hypothesis. We could surely say that the mentioned preservatives do not represent a very high risk in the environment because they do not emerge in very high concentrations. In the future, however, further research will be necessary mostly in the field of their endocrine functioning and the connection with the emergence of breast cancer.

Keywords:parabens, halogenation, in silico prediction, endocrine functioning, ecotoxicological influence

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