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EPIDEMIOLOGICAL, TOXICOLOGICAL AND MOLEСULAR-GENETIC ASPECTS OF ENDOCRINE DISRUPTING CHEMICALS IN THE CHEMICAL SAFETY PROBLEM


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Abstract

The literature review has shown the problem of endocrine disrupting chemicals (EDC) to be associated with their wide distribution in the environment, the abundance, and variety of the chemical structure. Three leading mechanisms of EDCs action are identified as follows: imitation of the naturally occurring hormones action, blocking of receptors within the target cells of hormones, the impact of their kinetics in the body. Epidemiological studies indicate an increase in diseases caused by a disorder of the hormonal system. They are associated with the effect of EDCs. Substances that are completely dissimilar in chemical structure can cause the same effects. According to WHO [6], it is impossible, based on the chemical structure, to determine whether a substance is a disruptor of the endocrine system. However, some structural features determine the estrogenic, thyreogenic and glucocorticoid activity of chemicals. Hence, the need to differentiate the specific (primary) effect of a chemical substance on the endocrine system and the indirect (secondary) effect on it via other mechanisms comes to the fore. In own research, specific mechanisms were shown to be determined in the experiment when studying the complexity of effects, taking into account the processes of adaptation and decompensation, and identifying the effects manifested with the lowest doses. One of the methodological approaches can be the developed “structure-biotransformation-activity” prediction system aimed at revealing the primary types of effects: using quantum-chemical calculations and the plausible reasoning class (called the JSM-reasoning in honour of John Stuart Mill) logico-combinatorial method, it was possible to identify structural fragments of substances responsible for the manifestation of carcinogenic, allergenic effects, methemoglobin formation, etc. The results of clinical studies show the use of pharmacological drugs as models for in vivo study of the effects of EDC to allow not only studying atypical mechanisms of the impact of EDCs from the point of view of molecular genetics but also to predict the individual susceptibility to them taking into account polymorphism of candidate genes. The EDCs problem poses the need for a complex of interdisciplinary research, including three main relationships: exposure assessment-biomonitoring data-the prevalence of endocrine-dependent diseases, taking into account the qualitative and quantitative contribution of individual endocrine disrupters to the development of an ecologically dependent endocrine pathology using molecular genetic methods.


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