medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2018-97-3-197-203medlit-515Research ArticleГИГИЕНА ОКРУЖАЮЩЕЙ СРЕДЫENVIRONMENTAL HYGIENEЭпидемиологические, токсикологические и молекулярно-генетические аспекты разрушителей эндокринной системы в проблеме химической безопасностиEpidemiological, toxicological and moleсular-genetic aspects of endocrine disrupting chemicals in the chemical safety problemСиницынаОксана ОлеговнаSinitsynaOksana O.

Доктор мед. наук, проф., член-корр. РАН, зам. директора по научной работе ФГБУ «Центр стратегического планирования и управления медико-биологическими рисками здоровью» Минздрава России. 

e-mail: labtox@sysin.ru

MD, Ph.D., Dr. Sci., professor, corresponding member of RAS, Deputy Director for research work of the Centre for Strategic Planning and Management of Biomedical Health Risks, Moscow, 119992, Russian Federation. 

e-mail: labtox@sysin.ru

labtox@sysin.ruРахманинЮ. А.RakhmaninYu. A.noemail@neicon.ruЖолдаковаЗ. И.ZholdakovaZ. I.noemail@neicon.ruАксеноваМ. Г.AksenovaM. G.noemail@neicon.ruКирилловА. В.KirillovA. V.noemail@neicon.ruБурдС. Г.BurdS. G.noemail@neicon.ruИльюковаИ. И.IlyukovaI. I.noemail@neicon.ruФГБУ «Центр стратегического планирования и управления медико-биологическими рисками здоровью» Минздрава РоссииCentre for Strategic Planning and Management of Biomedical Health RisksФГБОУ ВО «Российский национальный исследовательский медицинский университет» им. Н.И. Пирогова Минздрава РоссииN.I. Pirogov Russian National Research Medical UniversityРеспубликанское унитарное предприятие «Научно-практический центр гигиены»Scientific Practical Centre of Hygiene201814102020973197203Copyright © Синицына О.О., Рахманин Ю.А., Жолдакова З.И., Аксенова М.Г., Кириллов А.В., Бурд С.Г., Ильюкова И.И., 20202020Синицына О.О., Рахманин Ю.А., Жолдакова З.И., Аксенова М.Г., Кириллов А.В., Бурд С.Г., Ильюкова И.И.Sinitsyna O.O., Rakhmanin Y.A., Zholdakova Z.I., Aksenova M.G., Kirillov A.V., Burd S.G., Ilyukova I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rjhas.ru/jour/article/view/515

Обзор литературы показал, что проблема разрушителей эндокринной системы (эндокринных разрушителей) связана с их широким распространением в окружающей среде, многочисленностью и многообразием химической структуры. Выделены 3 ведущих механизма действия эндокринных разрушителей: имитация действия естественных гормонов, блокирование рецепторов в клетках-мишенях гормонов, воздействие на их кинетику в организме. Эпидемиологические исследования свидетельствуют о росте заболеваний, вызванных нарушением гормональной системы. Их связывают с воздействием эндокринных разрушителей. Вещества, абсолютно несхожие по химической структуре, могут вызывать одинаковые эффекты. По мнению ВОЗ [6], невозможно, основываясь на химической структуре, определить, является ли вещество разрушителем эндокринной системы. Однако существуют некоторые структурные особенности, которые определяют эстрогенную, тиреогенную и глюкокортикоидную активность химических веществ. Отсюда на первый план выступает необходимость дифференцировать специфическое (первичное) действие химического вещества на эндокринную систему и опосредованное (вторичное) влияние на неё через другие механизмы. В собственных исследованиях показано, что специфические механизмы следует определять в эксперименте при изучении комплекса эффектов с учётом процессов адаптации и декомпенсации и выявления эффектов, проявляющихся при наименьших дозах. Одним из методических подходов может служить система прогноза «структура – биотрансформация – активность», направленная на выявление первичных видов эффектов: с помощью квантово-химических расчётов и логико-комбинаторного метода ДСМ удалось выявить структурные фрагменты веществ, ответственные за проявление канцерогенных, аллергенных эффектов, метгемоглобинобразования и др. Результаты проведённых клинических исследований свидетельствуют, что использование фармакологических препаратов в качестве модельных для изучения in vivo эффектов эндокринных разрушителей позволяет не только изучать нетипичные с точки зрения молекулярной генетики механизмы воздействия эндокринных разрушителей, но и прогнозировать индивидуальную чувствительность к ним с учётом полиморфизма кандидатных генов. Проблема эндокринных разрушителей определяет необходимость комплексных междисциплинарных исследований, в том числе включающих 3 основных звена: оценку экспозиции, данные биомониторинга, распространённость эндокринозависимых заболеваний с учётом качественного и количественного вклада отдельных разрушителей эндокринной системы в развитие эколого-зависимой эндокринной патологии с использованием молекулярно-генетических методов исследования.

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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The authors declare that there are no conflicts of interest present.