IN VITRO METHODS FOR IDENTIFICATION OF CHEMICALS WITH ENDOCRINE DISRUPTION POTENTIAL

• Published in: Physiological research Vol. 67; no. 5; p. 2P
• Main Authors: Kejlová, K, Dvořáková, M, Rucki, M, Jírová, D
• Format: Journal Article
• Language: English
• Published: Praha Institute of Physiology 01-09-2018
• Subjects: Androgen receptors; Antimicrobial agents; Bioaccumulation; Bisphenol A; Cosmetics; Endocrine disruptors; Endocrine system; Food chains; Household products; Packaging materials; Side effects; Structure-activity relationships; Czech Republic
• ISSN: 0862-8408; 1802-9973

Global concerns have been raised in the last decades over the possible adverse effects resulting from exposure to chemicals with potential to interfere with the endocrine system in wildlife and humans. Interaction of exogenous substances with human receptors is a significant initiation event on molecular level that leads to various complex effects. The physiological receptor mechanism may be affected either by direct receptor binding of the exogenous ligand to the receptor, resulting in activation (agonistic activity) or inhibition (antagonistic activity), or by consequent modulation of associated signaling pathways regulation. Endocrine disruptors may act in low nanomolar concentrations similarly to endogenous hormones and have been associated with adverse effects, such as endocrine system disturbances and consequent developmental, reproductive and immune disorders. Sources of exposure to endocrine disruptors may be products coming from industry or agriculture and include consumer products, e.g. food packaging materials, household products, thermopaper, plastics, cosmetics or toys. Certain substances may be persistent, resulting in their bioaccumulation in the food chain as well as in the human organism and others, on the contrary, may be quickly metabolized and act for a limited time. These facts complicate the detection of negative effects of endocrine disruptors in vivo. Development and use of in silico screening tools and fast and cheap in vitro methods is therefore most effective for first-level screening of potential endocrine disruption, allowing for a rapid initial prioritization and sorting of chemicals for further evaluation in mechanistically based screens. In our recent studies of the interactions of chemicals with human estrogen and androgen receptors, the battery of available tests included the OECD QSAR Toolbox, Stably Transfected Transactivation In Vitro Assay to Detect Estrogen Receptor Agonists (OECD TG 455) and yeast-based microplate assay (in compliance with Draft ISO/DIS 19040). Selected bisphenols and phthalates were tested in a pilot study. In vitro results correlated well with in silico prediction for phthalates, while the predictions for bisphenols differed slightly. The results revealed that bisphenol A analogues should be further tested as they may show similar or higher activity in vivo comparing to bisphenol A, which has been recently legislatively regulated. Further studies involved testing of newly developed antimicrobials based on nanosilver and phtalocyanines or selected rare earth elements, which have not shown any endocrine activity. The in vitro methods demonstrated great advantage in hazard assessment of chemicals over in vivo studies as they enable to test separate substances without the background of complex hormonal system of a living organism subjected to a cocktail of potential endocrine disruptors from the environment.