People are becoming more and more aware of the harmful effects of UV radiation, which results in increased use of cosmetic products for sun protection that contain UV filters as active ingredients. These can also be found in other cosmetic products, which is why we are often exposed to them. As they are so widely used, they can also be found in groundwater, waste water and rivers. The question is whether these ingredients are safe for people or they pose a threat to human health. This thesis evaluates the endocrine and reproductive toxicity of chosen cinnamates and their metabolites through in silico methods. The results are then compared with already published in vitro and in vivo studies. The chosen cinnamates are 2-ethylhexyl methoxycinnamate and isoamyl methoxycinnamate. Both are allowed as UV filters on the European as well as the American market. Most cosmetic products contain 2-ethylhexyl methoxycinnamate while the isoamyl methoxycinnamate is used less often. The research was done with the use of in silico methods which could in the future replace in viro and in vivo research and reduce animal testing. The potential metabolites of the chosen cinnamates and their metabolic pathways were predicted with the Meteor Nexus program. The predicted metabolites were used for additional research. With the Endocrine Disruptome program and VEGA (Estrogen Receptor Relative Binding Affinity model) we have predicted the binding affinity of cinnamates and their metabolites to 12 different nuclear receptors. With the use of the Derek Nexus program, VEGA (Developmental Toxicity model) and TEST we have predicted the different aspects of the reproductive toxicity of the chosen cinnamates and their metabolites. Predictions made with the Meteor Nexus program matched the data in literature for some of the metabolites. Most of the predicted metabolites however, could not be found in literature while we have found certain metabolites in literature that the program did not predict. While studying the endocrine effects, the program predicted medium level of likelihood of binding one or both cinnamates and all or some metabolites to the thyroid receptor, androgen receptor in the antagonist conformation and glucocorticoid receptor. The software predicted inactivity for the estrogen receptor. The results of the prediciton for reproductive and developmental toxicity were inconclusive for both cinnamates and conclusive only for the 2-EH metabolite, which has also been confirmed by the existing studies. In silico methods have proven themselves useful in early stages of research or while processing large quantities of data. However, at this time
they are not reliable enough to be able to replace in vivo and in vitro research. In the future they will require further upgrades and expert evaluation of the obtained results.
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