Phthalates are found in many consumer products, including personal care products, pharmaceuticals, cosmetics and food packaging. Used as plasticizers are not chemically bound to plastic polymers. Therefore, we are largely exposed to them due to their leaking of products containing such prepared plastic. They also pose a danger to the environment. In the past years, research into the impact of potential chemical endocrine disruptors has increased. Phthalates also show harmful effects on the endocrine system, so in this master's thesis we focused on 26 selected phthalates and evaluated their endocrine disruption potential using in silico method.
For evaluation, we used the freely available computer program Endocrine Disruptome (ED), which allows the docking of compounds to the active sites of 18 structures of 14 different nuclear hormone receptors. The obtained results were compared with data from the professional literature. According to the obtained results and the availability of information in databases, phthalates were classified into four groups. Above all, we wanted to determine whether the program correctly predicts the binding of those phthalates that are already biologically evaluated. The first group includes phthalates, which are included in the list of potential hormone disruptors and the program predicted a medium or high probability of interactions with at least one receptor. This phthalates are benzyl butyl phthalate (BBP), diphenyl phthalate (DPhP) and dicyclohexyl phthalate (DCHP). The second group includes does who are also classified as potential endocrine disruptors and Endocrine Disruptome did not predict their interactions with medium or high probability. The highest number of tested phthalates was included in this group, dimethyl phthalate (DMP), diethyl phthalate (DEP), dipropyl phthalate (DPP), dibutyl phthalate (DBP), diisobutyl phthalate (DiBP), dimethoxyethyl phthalate (DMEP), dipentyl phthalate (DPeP), diisopentyl phthalate (DiPeP), dihexyl phthalate (DHP), di-(2-ethylhexyl) phthalate (DEHP), dioctyl phthalate (DOP), dinonyl phthalate (DNP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP) and ditridecyl phthalate (DTDP). The third group includes phthalates, which, according to the available data, do not cause effects on the endocrine system, nor have their harmful effects been predicted with the program. This group includes diallyl phthalate (DAP), diheptyl phthalate (DHpP), didecyl phthalate (DDcP) and di-(2-propylheptyl) phthalate (DPHP). In the last group are phthalates which according to the literature do not work on the endocrine system, but the program predicted harmful effects for them. These phthalates are: butyl cyclohexyl phthalate (BCHP), dibenzyl phthalate (DBzP), dimethyl cyclohexyl phthalate (DMCHP) and cyclohexyl isooctyl phthalate (CHIOP).
The in silico methods are easy to use and the toxicity of the compounds can be assessed before they are even synthesized. When interpreting the results, we must be aware that the action of compounds cannot be confirmed by method in silico alone. This can be confirmed by further in vitro and in vivo studies, which also applies to the binding of the studied phthalates to selected receptors and their potential endocrine function.
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