In silico methods for the detection of endocrine disruptors in food

Abstract

During the twentieth century, the world experienced an enormous technological and industrial development which, however, had several negative effects, such as an increase in risks to human health due to the products and/or waste deriving from the industry. In particular, among them, we find a class of substances called "Endocrine Disrupting Chemicals" (EDCs), a heterogeneous group of chemicals characterized by the ability to interfere with the functioning of the endocrine system through several mechanisms. The main source of exposure to EDCs for humans is represented by food, but it is not the only one: in fact, it is possible to come into contact with these molecules also through the environment, such as air, water, and soil, or the use of different products, such as detergents, cosmetics, clothes, and toys. The spectrum of pathologies related to these compounds is very broad and includes tumors, birth effects, metabolic disorders, reproductive function problems in males and females, and many others. However, the consequences on human and animal health and the effects on the environment of these chemicals are not yet fully verified. Many points, including the biological mechanisms, the mechanisms of action, the risk factors, and the entire spectrum of pathologies potentially associated with exposure to EDCs, still need to be clarified. The vastness of the problem requires the collaboration of experts, scientists, governments, and international agencies. A rationalization of efforts is also necessary, to fill those gaps in current knowledge that are of critical importance. It is necessary to obtain solid scientific knowledge regarding: i) the levels of environmental pollution; ii) the exposure extent of the population and in particular of certain risk groups; iii) the relationship between the absorbed dose and the occurrence of negative effects; iv) the mechanism of action of these chemicals; and v) the development of in vitro and in vivo experimental tests capable of both identifying with sufficient sensitivity and characterizing accurately the effects on endocrine balance. In this context, computational methods can be used to study the mechanisms and modes of action underlying the toxicity of endocrine disruptors chemicals. They are based on the premise that the chemical and physical properties and the bioavailability and toxicity of a chemical depend on its intrinsic nature (structure-activity relationship) and they can be directly predicted from its molecular structure and/or from similar structures with known functions and effects. In this broad and complex context, this PhD thesis wants to highlight the criticality of the endocrine disruptors problem and the relative negative effects on human health, and the usefulness of the computational methods for detecting endocrine disruptors in food, for understanding their mechanism of action, and for preventing their possible negative effects on human, animal, plant one health. In more detail, the aim is to detect the possible endocrine disruptors in food using in silico methods.