In everyday life, we are continuously exposed to various chemicals present in household and personal care products, such as parabens, bisphenols, alkylphenols and UV filters. These substances are known endocrine-disrupting chemicals, whereas their halogenated derivatives formed during disinfection processes, have received relatively little scientific attention to date. The aim of this doctoral dissertation was to investigate the endocrine-disrupting potential of halogenated derivatives of parabens, bisphenols, alkylphenol ethoxylates and UV filters and compare their activity to that of their parent compounds as well as to examine the immunomodulatory effects of selected UV filters.
To this end, we synthesized a library of halogenated derivatives of selected phenolic compounds, predicted to form under environmental conditions, and evaluated their agonistic or antagonistic effects on the thyroid receptor (TR) and the aryl hydrocarbon receptor (AhR). Results showed that halogenation frequently increased modulation of TR, with dihalogenated derivatives generally exhibiting stronger activity than monohalogenated ones, and brominated compounds displaying greater potency than their chlorinated counterparts. Dihalogenated BPF derivative emerged as the most potent agonists, while halogenated parabens containing longer side chain emerged as the most potent antagonists. The same library was also assessed for activity on AhR, where only certain halogenated bisphenol derivatives acted as agonists. Antagonistic activity was observed only in monohalogenated parabens with longer side chains, while further halogenation nullified these effects.
Furthermore, we evaluated the immunomodulatory properties of eight commonly used organic UV filters on monocytic cell line, monocyte derived macrophages, and peripheral blood mononuclear cells. Among the tested compounds, avobenzone appeared to have the strongest effect on the secretion of pro-inflammatory cytokines. To further explore this, we investigated the impact of avobenzone on the differentiation of monocytes into Langerhans-like cells. Our findings indicate that avobenzone, at non-toxic concentrations, influences both the differentiation and functional activity of these skin-resident immune cells, which are directly exposed to UV filters.
Overall, the results of this dissertation demonstrate that halogenated transformation products are stronger in vitro TR and AhR modulators than their parent compounds, and that selected organic UV filters exhibit immunomodulatory activity. The doctoral research contributed to a more comprehensive toxicological profile of these chemicals, thereby supporting their safer use.
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