toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2025-33-5-316-327tdxbnatoxreview-1021Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYКонтрольные уровни биомаркеров экспозиции вредных химических веществ в биосредах работающих во вредных условиях трудаReference levels of biomarkers of toxic chemicals in biosamples of workers operating under harmful working conditionshttps://orcid.org/0000-0002-2911-1260УколовАнтон ИгоревичUkolovAnton I.

Кандидат хим. наук, заведующий отделом токсикологии ФГУП «НИИ гигиены, профпатологии и экологии человека» ФМБА России, 188663, Ленинградская обл. г. пос. Кузьмоловский, Россия

e-mail: ukolov.ai@gpech.ru

PhD, head of department of toxicology, Scientific Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of Russia, Leningrad region, Kuzmolovsky urban settlement, 188663, Russian Federation

e-mail: ukolov.ai@gpech.ru

ukolov.ai@gpech.ruhttps://orcid.org/0009-0000-6619-2744ОрловаОльга ИгоревнаOrlovaOlga I.

Кандидат хим. наук, ведущий научный сотрудник ФГУП «НИИ гигиены, профпатологии и экологии человека» ФМБА России, 188663, Ленинградская область, г. пос. Кузьмоловский, Россия

e-mail: orlova@yandex.ru

PhD, leading researcher, Scientific Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of Russia, Leningrad region, Kuzmolovsky urban settlement, 188663, Russian Federation

e-mail: orlova@yandex.ru

orlova@yandex.ruhttps://orcid.org/0000-0002-3276-8036БариновВладимир АлександровичBarinovVladimir A.

Доктор мед. наук, профессор, главный научный сотрудник ФГБУ НКЦТ им. С.Н. Голикова ФМБА России, 192019, Санкт-Петербург, Россия

e-mail: vladbar50@yandex.ru

Dr.Sci, professor, chief researcher, Scientific and Clinical Center of Toxicology of Federal Medical Biological Agency of Russia, St. Petersburg, 192019, Russian Federation

e-mail: vladbar50@yandex.ru

vladbar50@yandex.ruhttps://orcid.org/0000-0003-0776-7434РадиловАндрей СтаниславовичRadilovAndrei S.

Доктор мед. наук, профессор, и. о. директора ФГУП «НИИ гигиены, профпатологии и экологии человека» ФМБА России, 188663, Ленинградская область, г. пос. Кузьмоловский, Россия

e-mail: a.radilov@icloud.com

Dr. Sci., Professor, Acting director of Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of Russia, Leningrad region, Kuzmolovsky urban settlement, 188663, Russian Federation

e-mail: a.radilov@icloud.com

a.radilov@icloud.comФГУП «Научно-исследовательский институт гигиены, профпатологии и экологии человека» ФМБА России; ФГБУ «Научно-клинический центр токсикологии имени академика С.Н. Голикова ФМБА России»РоссияScientific Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of Russia; Golikov Research Clinical Center of Toxicology of the Federal Medical Biological Agency of RussiaRussian FederationФГУП «Научно-исследовательский институт гигиены, профпатологии и экологии человека» ФМБА РоссииРоссияScientific Research Institute of Hygiene, Occupational Pathology and Human Ecology of the Federal Medical Biological Agency of RussiaRussian FederationФГБУ «Научно-клинический центр токсикологии имени академика С.Н. Голикова ФМБА России»РоссияGolikov Research Clinical Center of Toxicology of the Federal Medical Biological Agency of RussiaRussian Federation202524112025335316327Copyright © Уколов А.И., Орлова О.И., Баринов В.А., Радилов А.С., 20252025Уколов А.И., Орлова О.И., Баринов В.А., Радилов А.С.Ukolov A.I., Orlova O.I., Barinov V.A., Radilov A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.toxreview.ru/jour/article/view/1021Введение

Введение. Впервые введено и теоретически обосновано понятие величин «контрольных уровней биомаркеров» (КУБ) ряда вредных химических веществ, превышение которых свидетельствует о возрастающем химическом риске здоровью работающих и может служить основой предиктивной промышленной медицины и персонализации подходов к проведению медицинского обследования.

Цель исследования – обоснование, с использованием литературных данных, контрольных уровней биомаркеров вредных химических веществ органической природы: этиленоксида, эпихлоргидрина, трихлорэтана, фенола, три- и тетрахлорэтилена, ди- и тетрахлорметана, бензола, толуола, стирола, диметилбензолов, смесей предельных углеводородов C6H14–C10H22, винилхлорида, бутанола-1, ацетона, N,N-диметилформамида и N-нитрозодиметиламина.

Материал и методы

Материал и методы. Исходные данные для обоснования были получены из научных статей, монографий, материалов Агентства по регистрации токсичных веществ и заболеваний (ASTDR, США), Российского регистра потенциально опасных химических и биологических веществ, содержащих информацию о физико-химических свойствах, токсичности и опасности химических веществ.

Результаты

Результаты. Обоснование контрольных уровней биомаркеров вредных химических веществ выполнено двумя способами: 1-й – путём анализа литературных данных о содержании биомаркеров в биологических средах организма работающих в производственных условиях с различными уровнями экспозиции для установления математических зависимостей между параметрами, которые могут быть экстраполированы на уровень ПДКр.з.; 2-й – путём анализа литературных данных о содержании эндогенных биомаркеров в биологических средах организма, превышение которых может служить критерием причастности к группе работающих, здоровье которых подвержено повышенному химическому риску.

Ограничения исследования

Ограничения исследования. Обоснование контрольных уровней проведено только для ряда органических соединений с использованием литературных данных о наблюдавшихся концентрациях веществ в воздухе рабочей зоны и концентрациях в биологических средах работающих.

Заключение

Заключение. В данной статье впервые введено понятие и обоснованы контрольные уровни биомаркеров вредных химических веществ в крови и моче работающих во вредных условиях труда. Предложено обоснование контрольных уровней биомаркеров 17 вредных химических веществ органической природы, которые составляют значительную часть химической нагрузки на работников предприятий отечественной промышленности.

Соблюдение этических стандартов. Данное исследование не требует заключения этического комитета.

Участие авторов

Участие авторов: Уколов А.И., Радилов А.С. – концепция и дизайн исследования; Орлова О.И. – сбор и обработка данных; Уколов А.И., Орлова О.И. – написание текста; Баринов В.А., Радилов А.С. – редактирование.

Благодарность

Благодарность. Авторы выражают благодарность С.В. Тряшкину – заместителю начальника Управления научно-технологического обеспечения химической, биологической и радиационной безопасности ФМБА России за содействие в формулировании проблемы обоснования контрольных уровней биомаркеров.

Конфликт интересов

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Поступила в редакцию

Поступила в редакцию: 12 мая 2025 / Поступила после исправления: 15 сентября 2025 / Принята в печать: 02 октября 2025 / Опубликована: 19 ноября 2025

Introduction

Introduction. For the first time, the concept was introduced and a theoretical justification was carried out for the values of “biomarkers’ control levels” (BCL) of a number of harmful chemicals, the excess of which indicates an increased chemical risk to the health of workers and can serve as the basis for predictive industrial medicine and personalization of approaches to medical examination.

The aim of the study was to substantiate, using literature data, indicative control levels of biomarkers of harmful chemicals of organic nature: ethylene oxide, epichlorohydrin, trichloroethane, phenol, tri- and tetrachloroethylene, di- and tetrachloromethane, benzene, toluene, styrene, dimethylbenzenes, mixtures of limit hydrocarbons C6H14–C10H22, vinyl chloride, butanol-1, acetone, N,N-dimethylformamide and N-nitrosodimethylamine.

Material and methods

Material and methods. The initial data for substantiation were obtained from scientific articles, monographs, materials from the Agency for Toxic Substances and Disease Registry (ATSDR, USA), the Russian Register of Potentially Hazardous Chemical and Biological Substances containing information on the physico-chemical properties, toxicity and hazards of chemicals.

Results

Results. The substantiation of the approximate control levels of biomarkers of hazardous chemicals is carried out in two ways: first – by analyzing the literature data on the content of biomarkers in the biological environments of the body working in industrial conditions with different exposure levels to establish mathematical relationships between parameters that can be extrapolated to the OEL level; second – by analyzing literature data on the content of endogenous biomarkers in the biological environment of the body, the excess of which can serve as a criterion for classifying as a group of workers whose health is at increased chemical risk.

Limitations

Limitations. The control levels were justified only for a number of organic compounds using literature data on the observed concentrations of substances in the air of the work area and concentrations in the biological environments of workers.

Conclusion

Conclusion. In this work, the concept of reference levels of biomarkers of hazardous chemicals in the blood and urine of workers in harmful working conditions is introduced for the first time. The rationale for the control levels of biomarkers of 17 hazardous chemicals of an organic nature, which make up a significant part of the chemical burden on employees of domestic industry enterprises, is proposed.

Compliance with ethical standards: This study does not require approval by the ethics committee.

Аuthors’ сontribution

Аuthors’ сontribution: Ukolov A.I., Radilov A.S. – сoncept and design of the study; Orlova O.I. – data collection and processing; Ukolov A.I., Orlova O.I. – writing the text; BarinovV.A., Radilov A.S. – editing. All co-authors are responsible for approving the final version of the article and ensuring the integrity of all parts of the article.

Acknowledgment

Acknowledgment. The authors are grateful to S.V. Tryashkin, Deputy Head of the Department of Scientific and Technological Support for Chemical, Biological and Radiation Safety of the FMBA of Russia, for valuable comments on the goals and principles of substantiating biomarker levels.

Conflict of interests

Conflict of interests. The authors declare no conflicts of interest.

Funding

Funding. The study had no sponsorship.

Received

Received: May 12, 2025 / Revised: September 15, 2025 / Accepted: October 2, 2025 / Published: November 19, 2025

биомаркерыбиологический мониторингмедицинское обследованиебиологические ПДКbiomarkersbiological monitoringmedical examinationbiological exposure indicesReferencesУколов А.И., Радилов А.С. О развитии идей биологического контроля производственного воздействия вредных химических веществ (дискуссия). Медицина труда и промышленная экология. 2022; 62(11): 740–6.Ukolov A.I., Radilov A.S. On the development of ideas for biological control of industrial exposure to harmful chemicals (discussion). Medicina truda i promy`shlennaya ekologiya. 2022; 62(11): 740–6. (in Russian)Порядок применения результатов медико-биологических исследований для доказательства причинения вреда здоровью населения негативным воздействием химических факторов среды обитания: методические рекомендации 2.1.10.3165–14. М.; 2014. 66 с.The procedure for applying the results of biomedical research to prove harm to public health caused by the negative effects of chemical factors of the environment: methodological recommendations 2.1.10.3165-14. Moscow. (in Russian)OECD (2022), Occupational Biomonitoring Guidance Document, OECD Series on Testing and Assessment, No. 370, OECD Publishing, Paris.OECD (2022), Occupational Biomonitoring Guidance Document, OECD Series on Testing and Assessment, No. 370, OECD Publishing, Paris.Саноцкий И.В., Уланова И.П., Авилова Г.Г., Ткачева Т.А. и др. Биологический контроль производственного воздействия вредных веществ: Методические рекомендации № 5205-90. М.; 1990. 30 с.Sanotsky I.V., Ulanova I.P., Avilova G.G., Tkacheva T.A. and others. Biological control of industrial exposure to harmful substances: Methodological recommendations No. 5205-90. Moscow; 1990. 30. (in Russian)Межгосударственный стандарт. Система стандартов безопасности труда. Вредные вещества. Классификация и общие требования безопасности (ГОСТ 12.1.007–76).Interstate standard. A system of occupational safety standards. Harmful substances. Classification and general safety requirements (GOST 12.1.007-76).Руководство по оценке риска здоровью населения при воздействии химических веществ, загрязняющих среду обитания. Руководство Р 2.1.10.3968–23.Guidelines for assessing the risk to public health when exposed to chemicals that pollute the environment. Manual R 2.1.10.3968-23.(in Russian)Уколов А.И. Комбарова М.Ю., Рейнюк В.Л., Баринов В.А., Радилов А.С. Анализ перспективных направлений совершенствования методической части системы биологического мониторинга на потенциально химически опасных объектах (аналитический обзор). Токсикологический вестник. 2024; 32(3): 137–61.Ukolov A.I. Kombarova M.Yu., Reynyuk V.L., Barinov V.A., Radilov A.S. Analysis of promising areas for improving the methodological part of the biological monitoring system at potentially chemically hazardous sites (analytical review). Toksikologicheskii vestnik. 2024; 32(3): 137–61. (in Russian)Меньшиков В.В. Лабораторный специалист и клиническая интерпретация лабораторных результатов. Клиническая лабораторная диагностика. 2014; 59(5): 60–4.Menshikov V.V. Laboratory specialist and clinical interpretation of laboratory results. Klinicheskaya laboratornaya diagnostika. 2014; 59(5): 60–4. (in Russian)Barr D.B., Wilder L.C., Caudill S.P., Gonzalez A.J., Needham L.L., Pirkle J.L. Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005; 113(2): 192–200. https://doi.org/10.1289/ehp.7337Barr D.B., Wilder L.C., Caudill S.P., Gonzalez A.J., Needham L.L., Pirkle J.L. Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005; 113(2): 192–200. https://doi.org/10.1289/ehp.7337WHO 1996. Biological Monitoring of Chemical Exposure in the Workplace. Vol 1. Geneva: World Health Organization.WHO 1996. Biological Monitoring of Chemical Exposure in the Workplace. Vol 1. Geneva: World Health Organization.Koh S.B., Cha B.S., Park J.K., Chang S.H., Chang S.J. The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver. Yonsei Med J. 2002; 43(4): 491–9.Koh S.B., Cha B.S., Park J.K., Chang S.H., Chang S.J. The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver. Yonsei Med J. 2002; 43(4): 491–9.Käfferlein H.U., Ferstl C., Burkhart-Reichl A., Hennebrüder K., Drexler H., Brüning T., Angerer J. The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry. Occup Environ Med. 2005; 62(5): 330–6.Käfferlein H.U., Ferstl C., Burkhart-Reichl A., Hennebrüder K., Drexler H., Brüning T., Angerer J. The use of biomarkers of exposure of N,N-dimethylformamide in health risk assessment and occupational hygiene in the polyacrylic fibre industry. Occup Environ Med. 2005; 62(5): 330–6.Wang V.S., Shih T.S., Cheng C.C., Chang H.Y., Lai J.S., Lin C.C. Evaluation of current biological exposure index for occupational N, N-dimethylformamide exposure from synthetic leather workers. J Occup Environ Med. 2004; 46(7): 729–36.Wang V.S., Shih T.S., Cheng C.C., Chang H.Y., Lai J.S., Lin C.C. Evaluation of current biological exposure index for occupational N, N-dimethylformamide exposure from synthetic leather workers. J Occup Environ Med. 2004; 46(7): 729–36.Agency for Toxic Substances and Disease Registry (ATSDR). 2022. Toxicological Profile for Acetone. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.Agency for Toxic Substances and Disease Registry (ATSDR). 2022. Toxicological Profile for Acetone. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.Swiercz R., Korsak Z., Rydzynski K. Kinetics of n-butyl alcohol and m-xylene in blood during single and combined inhalation exposure in rats. Int J Occup Med Environ Health. 1995; 8(4): 361–5.Swiercz R., Korsak Z., Rydzynski K. Kinetics of n-butyl alcohol and m-xylene in blood during single and combined inhalation exposure in rats. Int J Occup Med Environ Health. 1995; 8(4): 361–5.Lin Y.S., Vermeulen R., Tsai C.H., Waidyanatha S., Lan Q., Rothman N., Smith M.T. Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers. Environ Health Perspect. 2007; 115(1): 28–34.Lin Y.S., Vermeulen R., Tsai C.H., Waidyanatha S., Lan Q., Rothman N., Smith M.T. Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers. Environ Health Perspect. 2007; 115(1): 28–34.Boogaard P.J., van Sittert N.J. Biological monitoring of exposure to benzene: a comparison between S-phenylmercapturic acid, trans,trans-muconic acid, and phenol. Occupational and Environmental Medicine. 1995; 52: 611–20.Boogaard P.J., van Sittert N.J. Biological monitoring of exposure to benzene: a comparison between S-phenylmercapturic acid, trans,trans-muconic acid, and phenol. Occupational and Environmental Medicine. 1995; 52: 611–20.Шаяхметов С.Ф., Журба О.М., Алексеенко А.Н., Меринов А.В., Дорогова В.Б. Биологический мониторинг хлорорганических углеводородов в производстве винилхлорида и поливинилхлорида. Медицина труда и промышленная экология. 2017; (1): 39–42.Shayakhmetov S.F., Zhurba O.M., Alekseenko A.N., Merinov A.V., Dorogova V.B. Biological monitoring of organochlorine hydrocarbons in the production of vinyl chloride and polyvinyl chloride. Occupational Medicina truda i promy`shlennaya e`kologiya. 2017; (1): 39–42. (in Russian)Inoue O., Seiji K., Kawai T. et al. Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: Comparison among three xylene isomers and toluene. Int Arch Occup Environ Health. 1993; 64: 533–9.Inoue O., Seiji K., Kawai T. et al. Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: Comparison among three xylene isomers and toluene. Int Arch Occup Environ Health. 1993; 64: 533–9.Casanova M., Deyo D.F., Heck H. Dichloromethane (methylene chloride): metabolism to formaldehyde and formation of DNA-protein cross-links in B6C3F1 mice and Syrian golden hamsters. Toxicol Appl Pharmacol. 1992; 114(1): 162–5.Casanova M., Deyo D.F., Heck H. Dichloromethane (methylene chloride): metabolism to formaldehyde and formation of DNA-protein cross-links in B6C3F1 mice and Syrian golden hamsters. Toxicol Appl Pharmacol. 1992; 114(1): 162–5.Уколов А.И., Мигаловская Е.Д., Радилов А.С. Хроматомасс-спектрометрическое исследование биологических образцов крыс подвергавшихся воздействию алифатических углеводородов с числом атомов углерода от 6 до 10. Биомедицинский журнал. Medline.ru. 2015; 16: 335–43.Ukolov A.I., Migalovskaya E.D., Radilov A.S. Chromatograph-mass spectrometric study of biological samples of rats exposed to aliphatic hydrocarbons with the number of carbon atoms from 6 to 10. Biomedicinskij zhurnal Medline.ru. 2015; 16: 335–43. (in Russian)Triebig G., Stark T., Ihrig A., Dietz M.C. Intervention study on acquired color vision deficiencies in styrene-exposed workers. J Occup Environ Med. 2001; 43(5): 494–500.Triebig G., Stark T., Ihrig A., Dietz M.C. Intervention study on acquired color vision deficiencies in styrene-exposed workers. J Occup Environ Med. 2001; 43(5): 494–500.Manautou J.E., Campion S.N., Aleksunes L.M. 9.08 – Regulation of Hepatobiliary Transporters during Liver Injury, Editor(s): Charlene A. McQueen, Comprehensive Toxicology (Second Edition), Elsevier, 2010: 175–220.Manautou J.E., Campion S.N., Aleksunes L.M. 9.08 – Regulation of Hepatobiliary Transporters during Liver Injury, Editor(s): Charlene A. McQueen, Comprehensive Toxicology (Second Edition), Elsevier, 2010: 175–220.Mehendale M., 7.19 – Halogenated Hydrocarbons, Editor(s): Charlene A. McQueen, Comprehensive Toxicology (Second Edition). Elsevier; 2010: 459-–74.Mehendale M., 7.19 – Halogenated Hydrocarbons, Editor(s): Charlene A. McQueen, Comprehensive Toxicology (Second Edition). Elsevier; 2010: 459-–74.Ghittori G. et al. Biological Monitoring of Workers Exposed to Carbon Tetrachloride Vapor. Appl Occup Environ Hyg. 1994; 9: 353–7.Ghittori G. et al. Biological Monitoring of Workers Exposed to Carbon Tetrachloride Vapor. Appl Occup Environ Hyg. 1994; 9: 353–7.Waksman J.C., Phillips S.D. Biologic markers of exposure to chlorinated solvents. Clin Occup Environ Med. 2004; 4(3): 413–21.Waksman J.C., Phillips S.D. Biologic markers of exposure to chlorinated solvents. Clin Occup Environ Med. 2004; 4(3): 413–21.Ikeda M., Ukai H., Kawai T, Inoue O., Maejima Y., Fukui Y., Ohashi F., Okamoto S. Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene. Toxicol Lett. 2008; 179(3): 148–54. https://doi.org/10.1016/j.toxlet.2008.05.003Ikeda M., Ukai H., Kawai T, Inoue O., Maejima Y., Fukui Y., Ohashi F., Okamoto S. Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene. Toxicol Lett. 2008; 179(3): 148–54. https://doi.org/10.1016/j.toxlet.2008.05.003Imbriani M., Niu Q., Negri S., Ghittori S. Trichloroethylene in urine as biological exposure index. Ind Health. 2001; 39(3): 225–30. https://doi.org/10.2486/indhealth.39.225Imbriani M., Niu Q., Negri S., Ghittori S. Trichloroethylene in urine as biological exposure index. Ind Health. 2001; 39(3): 225–30. https://doi.org/10.2486/indhealth.39.225Jha A., Jobby R., Kudale S., Modi N., Dhaneshwar A., Desai N. Biodegradation of phenol using hairy roots of Helianthus annuus L. International Biodeterioration & Biodegradation. 2013; 77: 106–13.Jha A., Jobby R., Kudale S., Modi N., Dhaneshwar A., Desai N. Biodegradation of phenol using hairy roots of Helianthus annuus L. International Biodeterioration & Biodegradation. 2013; 77: 106–13.Hirakawa B. Epichlorohydrin. Editor(s): Philip Wexler, Encyclopedia of Toxicology (Second Edition). Elsevier; 2005: 228–9.Hirakawa B. Epichlorohydrin. Editor(s): Philip Wexler, Encyclopedia of Toxicology (Second Edition). Elsevier; 2005: 228–9.de Rooij B.M., Boogaard P.J., Commandeur J.N., Vermeulen N.P. 3-Chloro-2-hydroxypropylmercapturic acid and α-chlorohydrin as biomarkers of occupational exposure to epichlorohydrin. Environ Toxicol Pharmacol. 1997; 3(3): 175–85.de Rooij B.M., Boogaard P.J., Commandeur J.N., Vermeulen N.P. 3-Chloro-2-hydroxypropylmercapturic acid and α-chlorohydrin as biomarkers of occupational exposure to epichlorohydrin. Environ Toxicol Pharmacol. 1997; 3(3): 175–85.Niot-Mansart V., Muhamedi A., Arnould J.P. A competitive ELISA detecting 7-methylguanosine adduct induced by N-nitrosodimethylamine exposure. Hum Exp Toxicol. 2005; 24(2): 89–94.Niot-Mansart V., Muhamedi A., Arnould J.P. A competitive ELISA detecting 7-methylguanosine adduct induced by N-nitrosodimethylamine exposure. Hum Exp Toxicol. 2005; 24(2): 89–94.Gallo V., Khan A., Gonzales C., Phillips D.H., Schoket B., Györffy E., Anna L., Kovács K., Møller P., Loft S., Kyrtopoulos S., Matullo G., Vineis P. Validation of biomarkers for the study of environmental carcinogens: a review. Biomarkers. 2008; 13(5): 505–34.Gallo V., Khan A., Gonzales C., Phillips D.H., Schoket B., Györffy E., Anna L., Kovács K., Møller P., Loft S., Kyrtopoulos S., Matullo G., Vineis P. Validation of biomarkers for the study of environmental carcinogens: a review. Biomarkers. 2008; 13(5): 505–34.Topp H., Sander G., Heller-Schöch G., Schöch G. Determination of 7-methylguanine, N2,N2-dimethylguanosine, and pseudouridine in ultrafiltrated serum of healthy adults by high-performance liquid chromatography. Anal Biochem. 1987; 161(1): 49–56.Topp H., Sander G., Heller-Schöch G., Schöch G. Determination of 7-methylguanine, N2,N2-dimethylguanosine, and pseudouridine in ultrafiltrated serum of healthy adults by high-performance liquid chromatography. Anal Biochem. 1987; 161(1): 49–56.Scherer G., Urban M., Hagedorn H.W., Serafin R., Feng S., Kapur S. et al. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878(27): 2520–8.Scherer G., Urban M., Hagedorn H.W., Serafin R., Feng S., Kapur S. et al. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878(27): 2520–8.Frigerio G., Mercadante R., Polledri E., Missineo P., Campo L., Fustinoni S. An LC-MS/MS method to profile urinary mercapturic acids, metabolites of electrophilic intermediates of occupational and environmental toxicants. J Chromatogr B Analyt Technol Biomed Life Sci. 2019; 1117: 66–76.Frigerio G., Mercadante R., Polledri E., Missineo P., Campo L., Fustinoni S. An LC-MS/MS method to profile urinary mercapturic acids, metabolites of electrophilic intermediates of occupational and environmental toxicants. J Chromatogr B Analyt Technol Biomed Life Sci. 2019; 1117: 66–76.Eckert E., Schmid K., Schaller B., Hiddemann-Koca K., Drexler H., Göen T. Mercapturic acids as metabolites of alkylating substances in urine samples of German inhabitants. Int J Hyg Environ Health. 2011; 214(3): 196–204.Eckert E., Schmid K., Schaller B., Hiddemann-Koca K., Drexler H., Göen T. Mercapturic acids as metabolites of alkylating substances in urine samples of German inhabitants. Int J Hyg Environ Health. 2011; 214(3): 196–204.Stevens J.F., Maier C.S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res. 2008; 52(1): 7–25.Stevens J.F., Maier C.S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol Nutr Food Res. 2008; 52(1): 7–25.

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