## An endocrine active substance does not necessarily have to be an endocrine disruptor

In the environment in which we live, there are substances that, after entering the target cell, can alter the reaction cascade. These substances alter the cell's response to the hormone by a specific mechanism and thus acquire endocrine activity. Endocrine active substances are therefore able to interact with the normal function of naturally occurring hormones or interfere with them in a certain way. These substances can be of natural or artificial origin, and many of them are found in food and the environment (e.g. pesticides or industrial pollutants such as bisphenols, polychlorinated biphenyls, dioxins and others). When endocrine-active substance cause an undesirable effect in the body, it is called the endocrine disruptor. So, the definition of an endocrine disruptor could be a substance in the external environment that, after entering the body under certain circumstances, can behave like a hormone, altering intracellular signalling and thereby affecting the cell's response. The result of this process is an undesirable physiological effect on the organism, with such substances termed endocrine-disrupting chemicals (EDCs).

Whether the effect of an endocrine agent is undesirable depends on several factors. The first is the origin of the substance, with synthetic endocrine agents usually more likely to have adverse effects than natural ones. Furthermore, the dose or concentration of the substance to which the organism is exposed is important, as it does not always mean that a higher dose automatically brings worse effects. There are endocrine active substances that act at very low (nanomolar) concentrations and whose negative effects do not increase with increasing concentration. Examples are BPA that is used to make polycarbonate plastic and epoxy resins that are in turn used in plastic bottles and dental devices, and DEHP which is a phthalate used as a plasticizer to add flexibility to plastic. However, there are also substances whose effects increase with increasing concentration, such as per- and polyfluoroalkyl substances (PFAS). An equally important factor is the state of the body, which reflects the body's ability to deal with the possible negative effects of an endocrine-active substance. Here, it is true that an organism in a superior condition is more able to fight the adverse effects of substances and is thus better prepared for their excretion. Decisive for the evaluation of the effect of a substance is the duration of exposure. The longer exposure time to even low doses of a substance with potentially harmful effects could be more devastating compared to shorter exposure time to higher doses.

In the case of endocrine-disrupting substances, the effects of some of them may also be positive. One example is progesterone, a drug used in high-risk pregnancies to protect against spontaneous abortion or premature birth when the natural hormone levels are insufficient for the current pregnancy and the mother's body is unable to ensure the full term of the foetus. Another example of the positive effects of endocrine agents are medications for arthritis prescribed to menopausal women because they have lower levels of oestrogen than women of reproductive age, which leads to the development of this disease. Such drugs are used precisely because of their positive endocrine effects.