toxreviewТоксикологический вестникToxicological Review0869-79223034-4611Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0869-7922-2026-34-4-254-263wmfujwtoxreview-1152Research ArticleПРОФИЛАКТИЧЕСКАЯ ТОКСИКОЛОГИЯPREVENTIVE TOXICOLOGYМолекулярные механизмы гематотоксичности фенола и его синергическое взаимодействие с бензолом в условиях профессиональной экспозиции (обзор литературы)Molecular mechanisms of phenol hematotoxicity and its synergistic interaction with benzene under occupational exposure conditions (literature review)https://orcid.org/0000-0002-8284-0008ШабардинаЛада ВладимировнаShabardinaLada V.

Научный сотрудник отдела токсикологии и биопрофилактики ФБУН ЕМНЦ ПОЗРПП Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: lada.shabardina@mail.ru

Researcher at the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: lada.shabardina@mail.ru

lada.shabardina@mail.ruhttps://orcid.org/0000-0002-1871-8593МинигалиеваИльзира АмировнаMinigalievaIlzira A.

Доктор биологических наук, зав. отделом токсикологии и биопрофилактики ФБУН ЕМНЦ ПОЗРПП Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: ilzira@ymrc.ru

Dr. Sci. (Biology), Head of the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ilzira@ymrc.ru

ilzira@ymrc.ruhttps://orcid.org/0000-0002-4694-0175БатеневаВлада АндреевнаBatenevaVlada A.

Младший научный сотрудник. отдела токсикологии и биопрофилактики ФБУН ЕМНЦ ПОЗРПП Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: bateneva@ymrc.ru

Junior Researcher at the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: bateneva@ymrc.ru

bateneva@ymrc.ruhttps://orcid.org/0009-0002-3278-4885БаженовВладислав АлександровичBazhenovVladislav A.

Лаборант отдела токсикологии и биопрофилактики ФБУН ЕМНЦ ПОЗРПП Роспотребнадзора, 620014, Екатеринбург, Россия

e-mail: vlabajenoxv@yandex.ru

Research Assistant at the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: vlabajenoxv@yandex.ru

vlabajenoxv@yandex.ruФБУН «Екатеринбургский медицинский научный центр профилактики и охраны здоровья рабочих промпредприятий» РоспотребнадзораРоссияYekaterinburg Medical Research Center for Prophylaxis and Health Protection of Industrial WorkersRussian Federation202616092026344254263Copyright © Шабардина Л.В., Минигалиева И.А., Батенева В.А., Баженов В.А., 20262026Шабардина Л.В., Минигалиева И.А., Батенева В.А., Баженов В.А.Shabardina L.V., Minigalieva I.A., Bateneva V.A., Bazhenov V.A.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/1152

Фенол относится к широко распространённым промышленным загрязнителям воздуха рабочей зоны, однако его гематотоксичность и механизмы взаимодействия с бензолом при комбинированной профессиональной экспозиции остаются недостаточно изученными.

Цель настоящего обзора – систематический анализ современных научных данных о токсикокинетике, молекулярных механизмах гематотоксичности фенола и оценка его взаимодействия с бензолом в условиях профессиональной экспозиции.

Проведён поиск публикаций в базах PubMed, Scopus, Web of Science и eLIBRARY.RU в соответствии с руководством PRISMA. Из 136 рассмотренных публикаций для окончательного анализа было отобрано 47 работ.

Фенол способен к локальной биоактивации в костном мозге, для тканей которого характерна высокая активность сульфатаз и миелопероксидазы при низкой активности сульфотрансфераз, что приводит к образованию высокореактивных метаболитов. Эти соединения ингибируют топоизомеразу IIα, нарушают эритроидную дифференцировку, подавляют иммунные клетки и индуцируют окислительный стресс. Выявлено, что генетические полиморфизмы ферментов детоксикации и репарации ДНК могут модулировать индивидуальную восприимчивость к гематотоксическому действию фенола и его метаболитов. Кроме того, при комбинированном воздействии фенол и бензол могут вступать в синергическое взаимодействие.

Заключение

Заключение. Полученные данные свидетельствуют о необходимости комплексного изучения механизмов токсичности фенола и усовершенствования гигиенических нормативов с учётом комбинированного действия и генетической предрасположенности, а также внедрения расширенного биомониторинга (определение специфических метаболитов в моче и крови, цитогенетический анализ, углублённое обследование групп риска) у работников коксохимических и нефтехимических производств.

Вклад авторов

Вклад авторов: Шабардина Л.В., Батенева В.А. – сбор материала, обработка данных, написание текста; Минигалиева И.А. – концепция и дизайн исследования; Баженов В.А. – сбор и обработка данных. Все соавторы – утверждение окончательного варианта статьи, ответственность за целостность всех её частей.

Конфликт интересов

Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов в связи с публикацией данной статьи.

Финансирование

Финансирование. Исследование не имело финансовой поддержки.

Поступила

Поступила: 07 апреля 2026 / Принята к печати: 03 августа 2026 / Опубликована: 16 сентября 2026

Phenol is a widespread industrial workplace air pollutant but its hematotoxic effects and the mechanisms of its interaction with benzene during combined occupational exposure remain insufficiently studied.

The purpose of this review is to systematize current research data on toxicokinetics and molecular mechanisms of phenol’s hematotoxicity, as well as to assess its interaction with benzene under occupational exposure conditions.

A literature search was conducted in the PubMed, Scopus, Web of Science, and eLIBRARY.RU databases in accordance with the PRISMA guidelines. Out of 136 reviewed publications, 47 papers were selected for the review.

Phenol can undergo local bioactivation in the bone marrow, where tissues are characterized by high sulfatase and myeloperoxidase activity coupled with low sulfotransferase activity. This leads to the formation of highly reactive metabolites. These compounds inhibit topoisomerase IIα, disrupt erythroid differentiation, suppress immune cells, and induce oxidative stress. It has been revealed that genetic polymorphisms in detoxification and DNA repair enzymes can modulate individual susceptibility to the hematotoxic effects of phenol and its metabolites. Furthermore, in case of the combined exposure to phenol and benzene, the chemicals can act synergistically.

Conclusions

Conclusions. The obtained data indicate the need for a comprehensive study of the mechanisms of phenol toxicity and for the improvement of hygienic standards, taking into account combined exposure effects and genetic predisposition. It is also necessary to implement expanded biomonitoring (including the determination of specific metabolites in urine and blood, cytogenetic analysis, and in depth examination of high risk groups) among workers in coke and petrochemical industries.

Authors’ contribution

Authors’ contribution: Shabardina L.V., Bateneva V.A. – data collection and processing, text writing; Minigalieva I.A. – study concept and design; Bazhenov V.A. – data collection and processing. All co‑authors approved the final version of the article and are responsible for the integrity of all its parts.

Conflict of interest

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding

Funding. The study had no financial support.

Received

Received: April 07, 2026 / Accepted: August 3, 2026 / Published: September 16, 2026

фенолгематотоксичностьпрофессиональная экспозициябензолсинергизмбиоактивацияметаболизмобзорphenolhematotoxicityoccupational exposurebenzenesynergismbioactivationmetabolismreviewReferencesZeng H., Qiu Z., Domínguez-Huerta A., Hearne Z., Chen Z., Li C.J. An adventure in sustainable cross-coupling of phenols and derivatives via carbon-oxygen bond cleavage. ACS Catal. 2016; 7(1): 510–9. https://doi.org/10.1021/acscatal.6b02964Zeng H., Qiu Z., Domínguez-Huerta A., Hearne Z., Chen Z., Li C.J. An adventure in sustainable cross-coupling of phenols and derivatives via carbon-oxygen bond cleavage. ACS Catal. 2016; 7(1): 510–9. https://doi.org/10.1021/acscatal.6b02964Sun M., Li X., Geng M., Zhou X., Zhang Z., Nie H., et al. Associations of coke oven emission exposure with pulmonary function, blood pressure, blood cell parameters, and biochemical indices in coking workers: a cross-sectional pilot study. Environ. Sci. Process Impacts. 2025; 27(1): 91–103. https://doi.org/10.1039/d4em00306c https://elibrary.ru/ehpdfsSun M., Li X., Geng M., Zhou X., Zhang Z., Nie H., et al. Associations of coke oven emission exposure with pulmonary function, blood pressure, blood cell parameters, and biochemical indices in coking workers: a cross-sectional pilot study. Environ. Sci. Process Impacts. 2025; 27(1): 91–103. https://doi.org/10.1039/d4em00306c https://elibrary.ru/ehpdfsRai A., Chakrabarty J., Dutta S. Phycoremediation of pollutants from coke-oven wastewater using Tetraspora sp. NITD 18 and estimation of macromolecules from spent biomass. J. Water Process Eng. 2021; 39: 101746. https://doi.org/10.1016/j.jwpe.2020.101746 https://elibrary.ru/hskgexRai A., Chakrabarty J., Dutta S. Phycoremediation of pollutants from coke-oven wastewater using Tetraspora sp. NITD 18 and estimation of macromolecules from spent biomass. J. Water Process Eng. 2021; 39: 101746. https://doi.org/10.1016/j.jwpe.2020.101746 https://elibrary.ru/hskgexXue J., Ma Y., Feng Z., Ji C., Wang Q. Screening analysis and fine-scale spatial health risks assessment of phenols and PAHs in soils surrounding the coking industry. Environ. Geochem. Health. 2025; 47(7): 281. https://doi.org/10.1007/s10653-025-02598-3 https:/elibrary.ru/arvrcyXue J., Ma Y., Feng Z., Ji C., Wang Q. Screening analysis and fine-scale spatial health risks assessment of phenols and PAHs in soils surrounding the coking industry. Environ. Geochem. Health. 2025; 47(7): 281. https://doi.org/10.1007/s10653-025-02598-3 https:/elibrary.ru/arvrcySawahata T., Neal R.A. Biotransformation of phenol to hydroquinone and catechol by rat liver microsomes. Mol. Pharmacol. 1983; 23(2): 453–60.Sawahata T., Neal R.A. Biotransformation of phenol to hydroquinone and catechol by rat liver microsomes. Mol. Pharmacol. 1983; 23(2): 453–60.Powley M.W., Carlson G.P. Cytochrome P450 isozymes involved in the metabolism of phenol, a benzene metabolite. Toxicol. Lett. 2001; 125(1–3): 117–23. https://doi.org/10.1016/s0378-4274(01)00441-6 https://elibrary.ru/ascccfPowley M.W., Carlson G.P. Cytochrome P450 isozymes involved in the metabolism of phenol, a benzene metabolite. Toxicol. Lett. 2001; 125(1–3): 117–23. https://doi.org/10.1016/s0378-4274(01)00441-6 https://elibrary.ru/ascccfTabrett C.A., Coughtrie M.W. Phenol sulfotransferase 1A1 activity in human liver: kinetic properties, interindividual variation and re-evaluation of the suitability of 4-nitrophenol as a probe substrate. Biochem. Pharmacol. 2003; 66(11): 2089–97. https://doi.org/10.1016/s0006-2952(03)00582-3 https://elibrary.ru/etaoovTabrett C.A., Coughtrie M.W. Phenol sulfotransferase 1A1 activity in human liver: kinetic properties, interindividual variation and re-evaluation of the suitability of 4-nitrophenol as a probe substrate. Biochem. Pharmacol. 2003; 66(11): 2089–97. https://doi.org/10.1016/s0006-2952(03)00582-3 https://elibrary.ru/etaoovKolanczyk R.C., Solem L.E., Schmieder P.K., McKim J.M. 3rd. A comparative study of Phase I and II hepatic microsomal biotransformation of phenol in three species of Salmonidae: Hydroquinone, catechol, and phenylglucuronide formation. Fishes. 2024; 9(7): 1–20. https://doi.org/10.3390/fishes9070284 https://elibrary.ru/jrnmoiKolanczyk R.C., Solem L.E., Schmieder P.K., McKim J.M. 3rd. A comparative study of Phase I and II hepatic microsomal biotransformation of phenol in three species of Salmonidae: Hydroquinone, catechol, and phenylglucuronide formation. Fishes. 2024; 9(7): 1–20. https://doi.org/10.3390/fishes9070284 https://elibrary.ru/jrnmoiShangari N., Chan T.S., O’Brien P.J. Sulfation and glucuronidation of phenols: implications in coenzyme Q metabolism. Methods Enzymol. 2005; 400: 342–59. https://doi.org/10.1016/S0076-6879(05)00020-0 https://elibrary.ru/xscpdmShangari N., Chan T.S., O’Brien P.J. Sulfation and glucuronidation of phenols: implications in coenzyme Q metabolism. Methods Enzymol. 2005; 400: 342–59. https://doi.org/10.1016/S0076-6879(05)00020-0 https://elibrary.ru/xscpdmRothman N., Bechtold W.E., Yin S.N., Dosemeci M., Li G.L., Wang Y.Z., et al. Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene. Occup. Environ. Med. 1998; 55(10): 705–11. https://doi.org/10.1136/oem.55.10.705Rothman N., Bechtold W.E., Yin S.N., Dosemeci M., Li G.L., Wang Y.Z., et al. Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene. Occup. Environ. Med. 1998; 55(10): 705–11. https://doi.org/10.1136/oem.55.10.705EPA. Toxicological Review of Phenol (CAS No. 108-95-2) [IRIS]. Washington; 2002. Available at: https://iris.epa.gov/static/pdfs/0088tr.pdfEPA. Toxicological Review of Phenol (CAS No. 108-95-2) [IRIS]. Washington; 2002. Available at: https://iris.epa.gov/static/pdfs/0088tr.pdfMichałowicz J., Duda W. Phenols – sources and toxicity. Pol. J. Environ. Stud. 2007; 16(3): 347–62. https://elibrary.ru/mfikyzMichałowicz J., Duda W. Phenols – sources and toxicity. Pol. J. Environ. Stud. 2007; 16(3): 347–62. https://elibrary.ru/mfikyzLouei Monfared A., Jaafari A., Sheibani M.T. Histological and histometrical evidences for phenol immunotoxicity in mice. Comp. Clin. Path. 2012; 23(3): 529–34. https://doi.org/10.1007/s00580-012-1645-9Louei Monfared A., Jaafari A., Sheibani M.T. Histological and histometrical evidences for phenol immunotoxicity in mice. Comp. Clin. Path. 2012; 23(3): 529–34. https://doi.org/10.1007/s00580-012-1645-9Medinsky M.A., Kenyon E.M., Seaton M.J., Schlosser P.M. Mechanistic considerations in benzene physiological model development. Environ. Health Perspect. 1996; 104(Suppl. 6): 1399–404. https://doi.org/10.1289/ehp.961041399Medinsky M.A., Kenyon E.M., Seaton M.J., Schlosser P.M. Mechanistic considerations in benzene physiological model development. Environ. Health Perspect. 1996; 104(Suppl. 6): 1399–404. https://doi.org/10.1289/ehp.961041399Ross D. Metabolic basis of benzene toxicity. Eur. J. Haematol. Suppl. 1996; 60: 111–8. https://doi.org/10.1111/j.1600-0609.1996.tb01656.xRoss D. Metabolic basis of benzene toxicity. Eur. J. Haematol. Suppl. 1996; 60: 111–8. https://doi.org/10.1111/j.1600-0609.1996.tb01656.xSchlosser P.M., Bond J.A., Medinsky M.A. Benzene and phenol metabolism by mouse and rat liver microsomes. Carcinogenesis. 1993; 14(12): 2477–86. https://doi.org/10.1093/carcin/14.12.2477 https://elibrary.ru/imuhvbSchlosser P.M., Bond J.A., Medinsky M.A. Benzene and phenol metabolism by mouse and rat liver microsomes. Carcinogenesis. 1993; 14(12): 2477–86. https://doi.org/10.1093/carcin/14.12.2477 https://elibrary.ru/imuhvbMonks T.J., Butterworth M., Lau S.S. The fate of benzene-oxide. Chem. Biol. Interact. 2010; 184(1-2): 201–6. https://doi.org/10.1016/j.cbi.2009.12.025Monks T.J., Butterworth M., Lau S.S. The fate of benzene-oxide. Chem. Biol. Interact. 2010; 184(1-2): 201–6. https://doi.org/10.1016/j.cbi.2009.12.025Eastmond D.A., Smith M.T., Ruzo L.O., Ross D. Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase. Mol. Pharmacol. 1986; 30(6): 674–9.Eastmond D.A., Smith M.T., Ruzo L.O., Ross D. Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase. Mol. Pharmacol. 1986; 30(6): 674–9.Low L.K., Lambert C.E., Meeks J.R., Naro P.A., Mackerer C.R. Tissue-specific metabolism of benzene in Zymbal gland and other solid tumor target tissues in rats. J. Am. Coll. Toxicol. 1995; 14(1): 40–60. https://doi.org/10.3109/10915819509008680Low L.K., Lambert C.E., Meeks J.R., Naro P.A., Mackerer C.R. Tissue-specific metabolism of benzene in Zymbal gland and other solid tumor target tissues in rats. J. Am. Coll. Toxicol. 1995; 14(1): 40–60. https://doi.org/10.3109/10915819509008680Schattenberg D.G., Stillman W.S., Gruntmeir J.J., Helm K.M., Irons R.D., Ross D. Peroxidase activity in murine and human hematopoietic progenitor cells: potential relevance to benzene-induced toxicity. Mol. Pharmacol. 1994; 46(2): 346–51.Schattenberg D.G., Stillman W.S., Gruntmeir J.J., Helm K.M., Irons R.D., Ross D. Peroxidase activity in murine and human hematopoietic progenitor cells: potential relevance to benzene-induced toxicity. Mol. Pharmacol. 1994; 46(2): 346–51.Ross D., Siegel D., Schattenberg D.G., Sun X.M., Moran J.L. Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity. Environ. Health Perspect. 1996; 104(Suppl. 6): 1177–82. https://doi.org/10.1289/ehp.961041177Ross D., Siegel D., Schattenberg D.G., Sun X.M., Moran J.L. Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity. Environ. Health Perspect. 1996; 104(Suppl. 6): 1177–82. https://doi.org/10.1289/ehp.961041177Eastmond D.A., Smith M.T., Irons R.D. An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure. Toxicol. Appl. Pharmacol. 1987; 91(1): 85–95. https://doi.org/10.1016/0041-008x(87)90196-7Eastmond D.A., Smith M.T., Irons R.D. An interaction of benzene metabolites reproduces the myelotoxicity observed with benzene exposure. Toxicol. Appl. Pharmacol. 1987; 91(1): 85–95. https://doi.org/10.1016/0041-008x(87)90196-7Smith M.T., Yager J.W., Steinmetz K.L., Eastmond D.A. Peroxidase-dependent metabolism of benzene’s phenolic metabolites and its potential role in benzene toxicity and carcinogenicity. Environ. Health Perspect. 1989; 82: 23–9. https://doi.org/10.1289/ehp.898223Smith M.T., Yager J.W., Steinmetz K.L., Eastmond D.A. Peroxidase-dependent metabolism of benzene’s phenolic metabolites and its potential role in benzene toxicity and carcinogenicity. Environ. Health Perspect. 1989; 82: 23–9. https://doi.org/10.1289/ehp.898223Smith M.T. Overview of benzene-induced aplastic anaemia. Eur. J. Haematol. Suppl. 1996; 60: 107–10. https://doi.org/10.1111/j.1600-0609.1996.tb01655.xSmith M.T. Overview of benzene-induced aplastic anaemia. Eur. J. Haematol. Suppl. 1996; 60: 107–10. https://doi.org/10.1111/j.1600-0609.1996.tb01655.xChen H., Eastmond D.A. Topoisomerase inhibition by phenolic metabolites: a potential mechanism for benzene’s clastogenic effects. Carcinogenesis. 1995; 16(10): 2301–7. https://doi.org/10.1093/carcin/16.10.2301 https://elibrary.ru/imvvtxChen H., Eastmond D.A. Topoisomerase inhibition by phenolic metabolites: a potential mechanism for benzene’s clastogenic effects. Carcinogenesis. 1995; 16(10): 2301–7. https://doi.org/10.1093/carcin/16.10.2301 https://elibrary.ru/imvvtxWu X.R., Xue M., Li X.F., Wang Y., Wang J., Han Q.L., et al. Phenolic metabolites of benzene inhibited the erythroid differentiation of K562 cells. Toxicol. Lett. 2011; 203(3): 190–9. https://doi.org/10.1016/j.toxlet.2011.03.012Wu X.R., Xue M., Li X.F., Wang Y., Wang J., Han Q.L., et al. Phenolic metabolites of benzene inhibited the erythroid differentiation of K562 cells. Toxicol. Lett. 2011; 203(3): 190–9. https://doi.org/10.1016/j.toxlet.2011.03.012Yu C.H., Li Y., Zhao X., Yang S.Q., Li L., Cui N.X., et al. Benzene metabolite 1,2,4-benzenetriol changes DNA methylation and histone acetylation of erythroid-specific genes in K562 cells. Arch. Toxicol. 2019; 93(1): 137–47. https://doi.org/10.1007/s00204-018-2333-6 https://elibrary.ru/rhpwdtYu C.H., Li Y., Zhao X., Yang S.Q., Li L., Cui N.X., et al. Benzene metabolite 1,2,4-benzenetriol changes DNA methylation and histone acetylation of erythroid-specific genes in K562 cells. Arch. Toxicol. 2019; 93(1): 137–47. https://doi.org/10.1007/s00204-018-2333-6 https://elibrary.ru/rhpwdtBukowska B., Kowalska S. Phenol and catechol induce prehemolytic and hemolytic changes in human erythrocytes. Toxicol. Lett. 2004; 152(1): 73–84. https://doi.org/10.1016/j.toxlet.2004.03.025 https://elibrary.ru/kklmqpBukowska B., Kowalska S. Phenol and catechol induce prehemolytic and hemolytic changes in human erythrocytes. Toxicol. Lett. 2004; 152(1): 73–84. https://doi.org/10.1016/j.toxlet.2004.03.025 https://elibrary.ru/kklmqpZhao Z., He X., Bi Y., Xia Y., Tao N., Li L., et al. Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo in human promyelocytic leukemic cell lines and ex vivo in human blood neutrophils. Drug Metab. Dispos. 2009; 37(2): 282–91. https://doi.org/10.1124/dmd.108.023192Zhao Z., He X., Bi Y., Xia Y., Tao N., Li L., et al. Induction of CYP4F3 by benzene metabolites in human white blood cells in vivo in human promyelocytic leukemic cell lines and ex vivo in human blood neutrophils. Drug Metab. Dispos. 2009; 37(2): 282–91. https://doi.org/10.1124/dmd.108.023192Irons R.D. Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow. Environ. Health Perspect. 1981; 39: 39–49. https://doi.org/10.1289/ehp.813939Irons R.D. Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow. Environ. Health Perspect. 1981; 39: 39–49. https://doi.org/10.1289/ehp.813939Das A., Chakrabarty S., Choudhury D., Chakrabarti G. 1,4-Benzoquinone (PBQ) induced toxicity in lung epithelial cells is mediated by the disruption of the microtubule network and activation of caspase-3. Chem. Res. Toxicol. 2010; 23(6): 1054–66. https://doi.org/10.1021/tx1000442 https://elibrary.ru/mzbpgzDas A., Chakrabarty S., Choudhury D., Chakrabarti G. 1,4-Benzoquinone (PBQ) induced toxicity in lung epithelial cells is mediated by the disruption of the microtubule network and activation of caspase-3. Chem. Res. Toxicol. 2010; 23(6): 1054–66. https://doi.org/10.1021/tx1000442 https://elibrary.ru/mzbpgzSnyder R., Dimitriadis E., Guy R., Hu P., Cooper K., Bauer H., et al. Studies on the mechanism of benzene toxicity. Environ. Health Perspect. 1989; 82: 31–5. https://doi.org/10.1289/ehp.898231Snyder R., Dimitriadis E., Guy R., Hu P., Cooper K., Bauer H., et al. Studies on the mechanism of benzene toxicity. Environ. Health Perspect. 1989; 82: 31–5. https://doi.org/10.1289/ehp.898231Shu N., Lorentzen L.G., Davies M.J. Reaction of quinones with proteins: Kinetics of adduct formation, effects on enzymatic activity and protein structure, and potential reversibility of modifications. Free Radic. Biol. Med. 2019; 137: 169–80. https://doi.org/10.1016/j.freeradbiomed.2019.04.026Shu N., Lorentzen L.G., Davies M.J. Reaction of quinones with proteins: Kinetics of adduct formation, effects on enzymatic activity and protein structure, and potential reversibility of modifications. Free Radic. Biol. Med. 2019; 137: 169–80. https://doi.org/10.1016/j.freeradbiomed.2019.04.026Zeman K., Tchórzewski H., Baj Z., Nowak Z., Majewska E., Pokoca L., et al. The effects of occupational exposure to hydrocarbons on some immune parameters of workers of the phenol division of a petrochemical plant. Pol. J. Occup. Med. 1990; 3(4): 399–407.Zeman K., Tchórzewski H., Baj Z., Nowak Z., Majewska E., Pokoca L., et al. The effects of occupational exposure to hydrocarbons on some immune parameters of workers of the phenol division of a petrochemical plant. Pol. J. Occup. Med. 1990; 3(4): 399–407.Shen M., Lan Q., Zhang L., Chanock S., Li G., Vermeulen R., et al. Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity. Carcinogenesis. 2006; 27(10): 2083–9. https://doi.org/10.1093/carcin/bgl061 https://elibrary.ru/imtapzShen M., Lan Q., Zhang L., Chanock S., Li G., Vermeulen R., et al. Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity. Carcinogenesis. 2006; 27(10): 2083–9. https://doi.org/10.1093/carcin/bgl061 https://elibrary.ru/imtapzJafari Roshan S., Mansoori Y., Hosseini S.R., Sabour D., Daraei A. Genetic variations in ATM and H2AX loci contribute to risk of hematological abnormalities in individuals exposed to BTEX chemicals. J. Clin. Lab. Anal. 2022; 36(4): e24321. https://doi.org/10.1002/jcla.24321 https://elibrary.ru/cmmmjnJafari Roshan S., Mansoori Y., Hosseini S.R., Sabour D., Daraei A. Genetic variations in ATM and H2AX loci contribute to risk of hematological abnormalities in individuals exposed to BTEX chemicals. J. Clin. Lab. Anal. 2022; 36(4): e24321. https://doi.org/10.1002/jcla.24321 https://elibrary.ru/cmmmjnRamírez-Lopera V., Uribe-Castro D., Bautista-Amorocho H., Silva-Sayago J.A., Mateus-Sánchez E., Ardila-Barbosa W.Y., et al. The effects of genetic polymorphisms on benzene-exposed workers: A systematic review. Health Sci. Rep. 2021; 4(3): e327. https://doi.org/10.1002/hsr2.327 https://elibrary.ru/odxywjRamírez-Lopera V., Uribe-Castro D., Bautista-Amorocho H., Silva-Sayago J.A., Mateus-Sánchez E., Ardila-Barbosa W.Y., et al. The effects of genetic polymorphisms on benzene-exposed workers: A systematic review. Health Sci. Rep. 2021; 4(3): e327. https://doi.org/10.1002/hsr2.327 https://elibrary.ru/odxywjNourozi M.A., Neghab M., Bazzaz J.T., Nejat S., Mansoori Y., Shahtaheri S.J. Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity. Arch. Toxicol. 2018; 92(6): 1983–90. https://doi.org/10.1007/s00204-017-2104-9 https://elibrary.ru/bzrcidNourozi M.A., Neghab M., Bazzaz J.T., Nejat S., Mansoori Y., Shahtaheri S.J. Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity. Arch. Toxicol. 2018; 92(6): 1983–90. https://doi.org/10.1007/s00204-017-2104-9 https://elibrary.ru/bzrcidKoop D.R., Laethem C.L., Schnier G.G. Identification of ethanol-inducible P450 isozyme 3a (P450IIE1) as a benzene and phenol hydroxylase. Toxicol. Appl. Pharmacol. 1989; 98(2): 278–8. https://doi.org/10.1016/0041-008x(89)90233-0Koop D.R., Laethem C.L., Schnier G.G. Identification of ethanol-inducible P450 isozyme 3a (P450IIE1) as a benzene and phenol hydroxylase. Toxicol. Appl. Pharmacol. 1989; 98(2): 278–8. https://doi.org/10.1016/0041-008x(89)90233-0Medinsky M.A., Kenyon E.M., Schlosser P.M. Benzene: a case study in parent chemical and metabolite interactions. Toxicology. 1995; 105(2-3): 225–33. https://doi.org/10.1016/0300-483x(95)03217-4 https://elibrary.ru/aphdwhMedinsky M.A., Kenyon E.M., Schlosser P.M. Benzene: a case study in parent chemical and metabolite interactions. Toxicology. 1995; 105(2-3): 225–33. https://doi.org/10.1016/0300-483x(95)03217-4 https://elibrary.ru/aphdwhMedinsky M.A., Sabourin P.J., Lucier G., Birnbaum L.S., Henderson R.F. A physiological model for simulation of benzene metabolism by rats and mice. Toxicol. Appl. Pharmacol. 1989; 99(2): 193–206. https://doi.org/10.1016/0041-008x(89)90002-1Medinsky M.A., Sabourin P.J., Lucier G., Birnbaum L.S., Henderson R.F. A physiological model for simulation of benzene metabolism by rats and mice. Toxicol. Appl. Pharmacol. 1989; 99(2): 193–206. https://doi.org/10.1016/0041-008x(89)90002-1Barale R., Marrazzini A., Betti C., Vangelisti V., Loprieno N., Barrai I. Genotoxicity of two metabolites of benzene: phenol and hydroquinone show strong synergistic effects in vivo. Mutat. Res. 1990; 244(1): 15–20. https://doi.org/10.1016/0165-7992(90)90101-oBarale R., Marrazzini A., Betti C., Vangelisti V., Loprieno N., Barrai I. Genotoxicity of two metabolites of benzene: phenol and hydroquinone show strong synergistic effects in vivo. Mutat. Res. 1990; 244(1): 15–20. https://doi.org/10.1016/0165-7992(90)90101-oLegathe A., Hoener B.A., Tozer T.N. Pharmacokinetic interaction between benzene metabolites, phenol and hydroquinone, in B6C3F1 mice. Toxicol. Appl. Pharmacol. 1994; 124(1): 131–8. https://doi.org/10.1006/taap.1994.1016Legathe A., Hoener B.A., Tozer T.N. Pharmacokinetic interaction between benzene metabolites, phenol and hydroquinone, in B6C3F1 mice. Toxicol. Appl. Pharmacol. 1994; 124(1): 131–8. https://doi.org/10.1006/taap.1994.1016Schlosser M.J., Shurina R.D., Kalf G.F. Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase. Environ. Health Perspect. 1989; 82: 229–37. https://doi.org/10.1289/ehp.8982229Schlosser M.J., Shurina R.D., Kalf G.F. Metabolism of phenol and hydroquinone to reactive products by macrophage peroxidase or purified prostaglandin H synthase. Environ. Health Perspect. 1989; 82: 229–37. https://doi.org/10.1289/ehp.8982229Lau S.S., Kuhlman C.L., Bratton S.B., Monks T.J. Role of hydroquinone-thiol conjugates in benzene-mediated toxicity. Chem. Biol. Interact. 2010; 184(1–2): 212–7. https://doi.org/10.1016/j.cbi.2009.12.016Lau S.S., Kuhlman C.L., Bratton S.B., Monks T.J. Role of hydroquinone-thiol conjugates in benzene-mediated toxicity. Chem. Biol. Interact. 2010; 184(1–2): 212–7. https://doi.org/10.1016/j.cbi.2009.12.016Bratton S.B., Lau S.S., Monks T.J. Identification of quinol thioethers in bone marrow of hydroquinone/phenol-treated rats and mice and their potential role in benzene-mediated hematotoxicity. Chem. Res. Toxicol. 1997; 10(8): 859–65. https://doi.org/10.1021/tx960208rBratton S.B., Lau S.S., Monks T.J. Identification of quinol thioethers in bone marrow of hydroquinone/phenol-treated rats and mice and their potential role in benzene-mediated hematotoxicity. Chem. Res. Toxicol. 1997; 10(8): 859–65. https://doi.org/10.1021/tx960208rSubrahmanyam V.V., Doane-Setzer P., Steinmetz K.L., Ross D., Smith M.T. Phenol-induced stimulation of hydroquinone bioactivation in mouse bone marrow in vivo: possible implications in benzene myelotoxicity. Toxicology. 1990; 62(1): 107–16. https://doi.org/10.1016/0300-483x(90)90035-fSubrahmanyam V.V., Doane-Setzer P., Steinmetz K.L., Ross D., Smith M.T. Phenol-induced stimulation of hydroquinone bioactivation in mouse bone marrow in vivo: possible implications in benzene myelotoxicity. Toxicology. 1990; 62(1): 107–16. https://doi.org/10.1016/0300-483x(90)90035-f

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