medlitГигиена и санитарияHygiene and Sanitation0016-99002412-0650Federal Scientific Center of Hygiene named after F.F. Erisman10.47470/0016-9900-2020-99-8-792-802medlit-44Research ArticleМЕДИЦИНА ТРУДАOCCUPATIONAL HEALTHГенотоксические биомаркеры у сотрудников патологоанатомических лабораторий, работающих с формальдегидом (систематический обзор)Genotoxic biomarkers in employees of pathomorphological laboratories working with formaldehyde (systematic review)https://orcid.org/0000-0002-7226-5505ЕреминаНаталья ВахитовнаEreminaNatal'ya V.

Кандидат биол. наук, ст. науч. сотр. лаб. лекарственной токсикологии ФГБНУ «НИИ фармакологии им. В.В. Закусова», 125315, Москва.

e-mail: neremina@panacelalabs.com

MD, Ph.D., senior research of the Laboratory of Drug Toxicology of the Zakusov Institute of Pharmacology, Moscow, 125315, Russian Federation.

e-mail: neremina@panacelalabs.com

neremina@panacelalabs.comhttps://orcid.org/0000-0002-7673-8672ЖанатаевА. К.ZhanataevAliy K.noemail@neicon.ruhttps://orcid.org/0000-0003-0218-8580ДурневА. Д.DurnevAndrey D.noemail@neicon.ruФГБНУ «Научно-исследовательский институт фармакологии имени В.В. Закусова»Zakusov Institute of Pharmacology202014092020998792802Copyright © Еремина Н.В., Жанатаев А.К., Дурнев А.Д., 20202020Еремина Н.В., Жанатаев А.К., Дурнев А.Д.Eremina N.V., Zhanataev A.K., Durnev A.D.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/44Введение

Введение. Проведён систематический обзор и анализ литературы, посвящённый генотоксическим обследованиям лиц, контактирующих с парами формальдегида (ФА) при работе в патоморфологических лабораториях медицинских учреждений. ФА классифицирован Международным агентством ВОЗ по исследованию рака как канцероген I класса. Опубликован ряд исследований, свидетельствующих о генотоксическом повреждении персонала патологоанатомических лабораторий, работающего с ФА, выявленного с помощью различных цитогенетических методов, использующихся для мониторинга биологических эффектов у людей, в частности, метода по учёту микроядер в лимфоцитах периферической крови и клетках буккального эпителия, метода по учёту хромосомных аберраций и метода «ДНК-комет».

Материал и методы

Материал и методы. Поиск литературы проводили до декабря 2019 г. с использованием базы данных научной литературы MedLine/PubMed (https://www.ncbi.nlm.nih.gov/PubMed). Ключевые термины поиска включали «formaldehyde laboratory micronuclei», «formaldehyde laboratory chromosomal aberration» или «formaldehyde laboratory DNA comet». Рассматривали полнотекстовые статьи, опубликованные на английском языке в журналах с присвоенными DOI.

Результаты

Результаты. Во всех исследованиях сообщалось о присутствии паров ФА на рабочем месте, при этом только в половине случаев уровень ФА находился не выше предельно допустимых значений. Средняя экспозиция формальдегидом за 8-часовой рабочий день составила 0,79 ± 0,43 мг/м3. Во всех исследованиях сообщалось о присутствии повышенного уровня исследуемых цитогенетических биомаркеров по сравнению с контролями. Суммарный анализ данных показал более чем 2,5-кратное превышение уровня микроядер в лимфоцитах периферической крови работников лабораторий по сравнению с контрольными группами (8,15 ± 2,57 vs. 3,56 ± 1,15‰; p < 0,05) и более чем 5-кратное превышение в случае уровня микроядер в буккальных эпителиоцитах (0,83 ± 0,09 vs. 0,16 ± 0,01‰; p < 0,05).

Заключение

Заключение. Таким образом, персонал патоморфологических лабораторий, контактирующий с парами ФА, подвергается потенциальному риску для жизни и здоровья, связанному с отдалёнными последствиями генотоксических воздействий.

Introduction

Introduction. A systematic review and analysis of literature on genotoxic examinations of individuals occupationally exposed to formaldehyde vapors (FAV) when working in pathomorphological laboratories of medical institutions has been performed. Formaldehyde is classified by the WHO International Agency for Research on Cancer as a class I carcinogen. Many studies have been published concerning testification of the genotoxic damage of pathomorphological laboratory personnel working with formaldehyde, identification using various biomonitoring cytogenetic methods, in particular, the micronucleus test in peripheral blood lymphocytes and buccal epithelial cells, a chromosomal aberrations test, and the DNA comet assay.

Material and methods

Material and methods. Literature was searched until December 2019 using the MedLine / PubMed database of scientific literature (https://www.ncbi.nlm.nih.gov/PubMed). Key search terms included formaldehyde laboratory micronuclei, formaldehyde laboratory chromosomal aberration, or formaldehyde laboratory DNA comet. Full-text articles published in English in journals with assigned DOIs were considered.

Results

Results. All studies reported the presence of FAV in the workplace, while in only half of the cases the level of formaldehyde was not higher than the maximum permissible values. The average exposure to formaldehyde over an 8-hour working day was 0.79 ± 0.43 mg/m3. All studies reported the presence of an increased level of the studied cytogenetic biomarkers compared to controls. A total analysis of the data showed more than a 2.5-fold excess in the level of micronuclei in the peripheral blood lymphocytes of laboratory workers compared with the control groups (8.15 ± 2.57 ‰ vs. 3.56 ± 1.15 ‰; p < 0.05), and more than a 5-fold excess in case of the level of micronuclei in buccal epithelial cells (0.83 ± 0.09 ‰ vs. 0.16 ± 0.01 ‰; p < 0.05).

Conclusion

Conclusion. Thus, pathomorphological laboratory personnel exposed to FAV is at potential risk to life and health from the long-term impact of genotoxic eff

формальдегидгенотоксичностьповреждения ДНКхромосомные аберрациимикроядраобзорformaldehydegenotoxicityDNA damagechromosomal aberrationsmicronucleireviewReferencesd’Ettorre G., Criscuolo M., Mazzotta M. Managing Formaldehyde indoor pollution in anatomy pathology departments. Work. 2017; 56(3): 397-402. https://doi.org/10.3233/WOR-172505d’Ettorre G., Criscuolo M., Mazzotta M. Managing Formaldehyde indoor pollution in anatomy pathology departments. Work. 2017; 56(3): 397-402. https://doi.org/10.3233/WOR-172505Fenech M., Nersesyan A., Knasmueller S. A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes. Mutat. Res. 2016; 770(Pt. A): 46-57. https://doi.org/10.1016/j.mrrev.2016.04.005Fenech M., Nersesyan A., Knasmueller S. A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes. Mutat. Res. 2016; 770(Pt. A): 46-57. https://doi.org/10.1016/j.mrrev.2016.04.005Swenberg J.A., Kerns W.D., Mitchell R.I., Gralla E.J., Pavkov K.L. Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 1980; 40(9): 3398-402.Swenberg J.A., Kerns W.D., Mitchell R.I., Gralla E.J., Pavkov K.L. Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 1980; 40(9): 3398-402.U.S. Environmental Protection Agency, Office of Air and Radiation. Report to Congress on Indoor Air Quality. Volume II. Assessment and Control of Indoor Air Pollution. EPA 400-1-89-001C. Washington: USEPAOAR; 1989.U.S. Environmental Protection Agency, Office of Air and Radiation. Report to Congress on Indoor Air Quality. Volume II. Assessment and Control of Indoor Air Pollution. EPA 400-1-89-001C. Washington: USEPAOAR; 1989.IARC Monographs on the Evaluation of Carcinogenic Risks to Human. Volume 88: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxy-2-propanol. Lyon: WHO; 2006.IARC Monographs on the Evaluation of Carcinogenic Risks to Human. Volume 88: Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxy-2-propanol. Lyon: WHO; 2006.IARC (International Agency for Research on Cancer). Formaldehyde. In: IARC, ed. A Review of Human Carcinogens, Chemical Agents and Related Occupations, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Part F of Vol. 100. Lyon: WHO; 2012: 401-35.IARC (International Agency for Research on Cancer). Formaldehyde. In: IARC, ed. A Review of Human Carcinogens, Chemical Agents and Related Occupations, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Part F of Vol. 100. Lyon: WHO; 2012: 401-35.NTP (National Toxicology Program). Report on Carcinogens. US Department of Health and Human Services, Public Health Service, National Toxicology Program, Formaldehyde. Research Triangle Park; 2011: 195-205.NTP (National Toxicology Program). Report on Carcinogens. US Department of Health and Human Services, Public Health Service, National Toxicology Program, Formaldehyde. Research Triangle Park; 2011: 195-205.Zhang L., Steinmaus C., Eastmond D.A., Xin X.K., Smith M.T. Formaldehyde exposure and leukemia: a new meta-analysis and potential mechanisms. Mutat. Res. 2009; 681(2-3): 150-68. https://doi.org/10.1016/j.mrrev.2008.07.002Zhang L., Steinmaus C., Eastmond D.A., Xin X.K., Smith M.T. Formaldehyde exposure and leukemia: a new meta-analysis and potential mechanisms. Mutat. Res. 2009; 681(2-3): 150-68. https://doi.org/10.1016/j.mrrev.2008.07.002Heck H.d., Casanova M. The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity. Regul. Toxicol. Pharmacol. 2004; 40(2): 92-106. https://doi.org/10.1016/j.yrtph.2004.05.001Heck H.d., Casanova M. The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity. Regul. Toxicol. Pharmacol. 2004; 40(2): 92-106. https://doi.org/10.1016/j.yrtph.2004.05.001Pyatt D., Natelson E., Golden R. Is inhalation exposure to formaldehyde a biologically plausible cause of lymphohematopoietic malignancies? Regul. Toxicol. Pharmacol. 2008; 51(1): 119-33. https://doi.org/10.1016/j.yrtph.2008.03.003Pyatt D., Natelson E., Golden R. Is inhalation exposure to formaldehyde a biologically plausible cause of lymphohematopoietic malignancies? Regul. Toxicol. Pharmacol. 2008; 51(1): 119-33. https://doi.org/10.1016/j.yrtph.2008.03.003Franks S.J. A mathematical model for the absorption and metabolism of formaldehyde vapour by humans. Toxicol. Appl. Pharmacol. 2005; 206(3): 309-20. https://doi.org/10.1016/j.taap.2004.11.012Franks S.J. A mathematical model for the absorption and metabolism of formaldehyde vapour by humans. Toxicol. Appl. Pharmacol. 2005; 206(3): 309-20. https://doi.org/10.1016/j.taap.2004.11.012National Toxicology Program. Final report on carcinogens background document for formaldehyde. Rep. Carcinog. Backgr. Doc. 2010; (10-5981): i-512.National Toxicology Program. Final report on carcinogens background document for formaldehyde. Rep. Carcinog. Backgr. Doc. 2010; (10-5981): i-512.Lu K., Ye W., Zhou L., Collins L.B., Chen X., Gold A. et al. Structural characterization of formaldehyde-induced cross-links between amino acids and deoxynucleosides and their oligomers. J. Am. Chem. Soc. 2010; 132(10): 3388-99. https://doi.org/10.1021/ja908282fLu K., Ye W., Zhou L., Collins L.B., Chen X., Gold A. et al. Structural characterization of formaldehyde-induced cross-links between amino acids and deoxynucleosides and their oligomers. J. Am. Chem. Soc. 2010; 132(10): 3388-99. https://doi.org/10.1021/ja908282fZhang L., Freeman L.E., Nakamura J., Hecht S.S., Vandenberg J.J., Smith M.T. et al. Formaldehyde and leukemia: epidemiology, potential mechanisms, and implications for risk assessment. Environ. Mol. Mutagen. 2010; 51(3): 181-91. https://doi.org/10.1002/em.20534Zhang L., Freeman L.E., Nakamura J., Hecht S.S., Vandenberg J.J., Smith M.T. et al. Formaldehyde and leukemia: epidemiology, potential mechanisms, and implications for risk assessment. Environ. Mol. Mutagen. 2010; 51(3): 181-91. https://doi.org/10.1002/em.20534Swenberg J.A., Moeller B.C., Lu K., Rager J.E., Fry R.C., Starr T.B. Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment. Toxicol. Pathol. 2013; 41(2): 181-9. https://doi.org/10.1177/0192623312466459Swenberg J.A., Moeller B.C., Lu K., Rager J.E., Fry R.C., Starr T.B. Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment. Toxicol. Pathol. 2013; 41(2): 181-9. https://doi.org/10.1177/0192623312466459Ye X., Ji Z., Wei C., McHale C.M., Ding S., Thomas R. et al. Inhaled formaldehyde induces DNA-protein crosslinks and oxidative stress in bone marrow and other distant organs of exposed mice. Environ. Mol. Mutagen. 2013; 54(9): 705-18. https://doi.org/10.1002/em.21821Ye X., Ji Z., Wei C., McHale C.M., Ding S., Thomas R. et al. Inhaled formaldehyde induces DNA-protein crosslinks and oxidative stress in bone marrow and other distant organs of exposed mice. Environ. Mol. Mutagen. 2013; 54(9): 705-18. https://doi.org/10.1002/em.21821Bonassi S., Norppa H., Ceppi M., Strömberg U., Vermeulen R., Znaor A. et al. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis. 2008; 29(6): 1178-83. https://doi.org/10.1093/carcin/bgn075Bonassi S., Norppa H., Ceppi M., Strömberg U., Vermeulen R., Znaor A. et al. Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries. Carcinogenesis. 2008; 29(6): 1178-83. https://doi.org/10.1093/carcin/bgn075Bonassi S., Znaor A., Ceppi M., Lando C., Chang W.P., Holland N. et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007; 28(3): 625-31. https://doi.org/10.1093/carcin/bgl177Bonassi S., Znaor A., Ceppi M., Lando C., Chang W.P., Holland N. et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007; 28(3): 625-31. https://doi.org/10.1093/carcin/bgl177Vodicka P., Polivkova Z., Sytarova S., Demova H., Kucerova M., Vodickova L. et al. Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis. 2010; 31(7): 1238-41. https://doi.org/10.1093/carcin/bgq056Vodicka P., Polivkova Z., Sytarova S., Demova H., Kucerova M., Vodickova L. et al. Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls. Carcinogenesis. 2010; 31(7): 1238-41. https://doi.org/10.1093/carcin/bgq056Mateuca R., Lombaert N., Aka P.V., Decordier I., Kirsch-Volders M. Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie. 2006; 88(11): 1515-31. https://doi.org/10.1016/j.biochi.2006.07.004Mateuca R., Lombaert N., Aka P.V., Decordier I., Kirsch-Volders M. Chromosomal changes: induction, detection methods and applicability in human biomonitoring. Biochimie. 2006; 88(11): 1515-31. https://doi.org/10.1016/j.biochi.2006.07.004Albertini R.J., Anderson D., Douglas G.R., Hagmar L., Hemminki K., Merlo F. et al. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety. Mutat. Res. 2000; 463(2): 111-72. https://doi.org/10.1016/s1383-5742(00)00049-1Albertini R.J., Anderson D., Douglas G.R., Hagmar L., Hemminki K., Merlo F. et al. IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety. Mutat. Res. 2000; 463(2): 111-72. https://doi.org/10.1016/s1383-5742(00)00049-1Collins A.R. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol. Biotechnol. 2004; 26(3): 249-61. https://doi.org/10.1385/MB:26:3:249Collins A.R. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol. Biotechnol. 2004; 26(3): 249-61. https://doi.org/10.1385/MB:26:3:249Ying C.J., Yan W.S., Zhao M.Y., Ye X.L., Xie H., Yin S.Y. et al. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class. Biomed. Environ. Sci. 1997; 10(4): 451-5.Ying C.J., Yan W.S., Zhao M.Y., Ye X.L., Xie H., Yin S.Y. et al. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class. Biomed. Environ. Sci. 1997; 10(4): 451-5.Vasudeva N., Anand C. Cytogenetic evaluation of medical students exposed to formaldehyde vapor in the gross anatomy dissection laboratory. J. Am. Coll. Health. 1996; 44(4): 177-9. https://doi.org/10.1080/07448481.1996.9937526Vasudeva N., Anand C. Cytogenetic evaluation of medical students exposed to formaldehyde vapor in the gross anatomy dissection laboratory. J. Am. Coll. Health. 1996; 44(4): 177-9. https://doi.org/10.1080/07448481.1996.9937526Costa S., Costa C., Madureira J., Valdiglesias V., Teixeira-Gomes A., Guedes de Pinho P. et al. Occupational exposure to formaldehyde and early biomarkers of cancer risk, immunotoxicity and susceptibility. Environ. Res. 2019; 179(Pt. A): 108740. https://doi.org/10.1016/j.envres.2019.108740Costa S., Costa C., Madureira J., Valdiglesias V., Teixeira-Gomes A., Guedes de Pinho P. et al. Occupational exposure to formaldehyde and early biomarkers of cancer risk, immunotoxicity and susceptibility. Environ. Res. 2019; 179(Pt. A): 108740. https://doi.org/10.1016/j.envres.2019.108740Costa S., García-Lestón J., Coelho M., Coelho P., Costa C., Silva S. et al. Cytogenetic and immunological effects associated with occupational formaldehyde exposure. J. Toxicol. Environ. Health A. 2013; 76(4-5): 217-29. https://doi.org/10.1080/15287394.2013.757212Costa S., García-Lestón J., Coelho M., Coelho P., Costa C., Silva S. et al. Cytogenetic and immunological effects associated with occupational formaldehyde exposure. J. Toxicol. Environ. Health A. 2013; 76(4-5): 217-29. https://doi.org/10.1080/15287394.2013.757212Ladeira C., Viegas S., Carolino E., Gomes M.C., Brito M. The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde. Environ. Mol. Mutagen. 2013; 54(3): 213-21. https://doi.org/10.1002/em.21755Ladeira C., Viegas S., Carolino E., Gomes M.C., Brito M. The influence of genetic polymorphisms in XRCC3 and ADH5 genes on the frequency of genotoxicity biomarkers in workers exposed to formaldehyde. Environ. Mol. Mutagen. 2013; 54(3): 213-21. https://doi.org/10.1002/em.21755Bouraoui S., Mougou S., Brahem A., Tabka F., Ben Khelifa H., Harrabi I. et al. A combination of micronucleus assay and fluorescence in situ hybridization analysis to evaluate the genotoxicity of formaldehyde. Arch. Environ. Contam. Toxicol. 2013; 64(2): 337-44. https://doi.org/10.1007/s00244-012-9828-6Bouraoui S., Mougou S., Brahem A., Tabka F., Ben Khelifa H., Harrabi I. et al. A combination of micronucleus assay and fluorescence in situ hybridization analysis to evaluate the genotoxicity of formaldehyde. Arch. Environ. Contam. Toxicol. 2013; 64(2): 337-44. https://doi.org/10.1007/s00244-012-9828-6Costa S., Pina C., Coelho P., Costa C., Silva S., Porto B. et al. Occupational exposure to formaldehyde: genotoxic risk evaluation by comet assay and micronucleus test using human peripheral lymphocytes. J. Toxicol. Environ. Health A. 2011; 74(15-16): 1040-51. https://doi.org/10.1080/15287394.2011.582293Costa S., Pina C., Coelho P., Costa C., Silva S., Porto B. et al. Occupational exposure to formaldehyde: genotoxic risk evaluation by comet assay and micronucleus test using human peripheral lymphocytes. J. Toxicol. Environ. Health A. 2011; 74(15-16): 1040-51. https://doi.org/10.1080/15287394.2011.582293Ladeira C., Viegas S., Carolino E., Prista J., Gomes M.C., Brito M. Genotoxicity biomarkers in occupational exposure to formaldehyde – the case of histopathology laboratories. Mutat. Res. 2011; 721(1): 15-20. https://doi.org/10.1016/j.mrgentox.2010.11.015Ladeira C., Viegas S., Carolino E., Prista J., Gomes M.C., Brito M. Genotoxicity biomarkers in occupational exposure to formaldehyde – the case of histopathology laboratories. Mutat. Res. 2011; 721(1): 15-20. https://doi.org/10.1016/j.mrgentox.2010.11.015Viegas S., Ladeira C., Nunes C., Malta-Vacas J., Gomes M., Brito M. et al. Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production. J. Occup. Med. Toxicol. 2010; 5(1): 25. https://doi.org/10.1186/1745-6673-5-25Viegas S., Ladeira C., Nunes C., Malta-Vacas J., Gomes M., Brito M. et al. Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production. J. Occup. Med. Toxicol. 2010; 5(1): 25. https://doi.org/10.1186/1745-6673-5-25Costa S., Coelho P., Costa C., Silva S., Mayan O., Santos L.S. et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology. 2008; 252(1-3): 40-8. https://doi.org/10.1016/j.tox.2008.07.056Costa S., Coelho P., Costa C., Silva S., Mayan O., Santos L.S. et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology. 2008; 252(1-3): 40-8. https://doi.org/10.1016/j.tox.2008.07.056Orsière T., Sari-Minodier I., Iarmarcovai G., Botta A. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat. Res. 2006; 605(1-2): 30-41. https://doi.org/10.1016/j.mrgentox.2006.01.006Orsière T., Sari-Minodier I., Iarmarcovai G., Botta A. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat. Res. 2006; 605(1-2): 30-41. https://doi.org/10.1016/j.mrgentox.2006.01.006Costa S., Carvalho S., Costa C., Coelho P., Silva S., Santos L.S. et al. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde. Mutagenesis. 2015; 30(4): 463-73. https://doi.org/10.1093/mutage/gev002Costa S., Carvalho S., Costa C., Coelho P., Silva S., Santos L.S. et al. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde. Mutagenesis. 2015; 30(4): 463-73. https://doi.org/10.1093/mutage/gev002Formaldehyde: Method 3500 (Issue 2). In: NIOSH (National Institute for Occupational Safety and Health), ed. NIOSH Manual of Analytical Method U.S. Department of Health and Human Services. Cincinnati, Ohio; 1994: 2-5.Formaldehyde: Method 3500 (Issue 2). In: NIOSH (National Institute for Occupational Safety and Health), ed. NIOSH Manual of Analytical Method U.S. Department of Health and Human Services. Cincinnati, Ohio; 1994: 2-5.NIOSH Manual of Analytical Methods. 2541. Formaldehyde by GC. Available at: https://www.cdc.gov/niosh/docs/2003-154/pdfs/2541.pdfNIOSH Manual of Analytical Methods. 2541. Formaldehyde by GC. Available at: https://www.cdc.gov/niosh/docs/2003-154/pdfs/2541.pdfAmerican Conference of Governmental Industrial Hygienists. TLV’s and BEI’s – Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH; 2017.American Conference of Governmental Industrial Hygienists. TLV’s and BEI’s – Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH; 2017.Bonassi S., El-Zein R., Bolognesi C., Fenech M. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis. 2011; 26(1): 93-100. https://doi.org/10.1093/mutage/geq075Bonassi S., El-Zein R., Bolognesi C., Fenech M. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis. 2011; 26(1): 93-100. https://doi.org/10.1093/mutage/geq075Hopf N.B., Bolognesi C., Danuser B., Wild P. Biological monitoring of workers exposed to carcinogens using the buccal micronucleus approach: A systematic review and meta-analysis. Mutat. Res. 2019; 781: 11-29. https://doi.org/10.1016/j.mrrev.2019.02.006Hopf N.B., Bolognesi C., Danuser B., Wild P. Biological monitoring of workers exposed to carcinogens using the buccal micronucleus approach: A systematic review and meta-analysis. Mutat. Res. 2019; 781: 11-29. https://doi.org/10.1016/j.mrrev.2019.02.006Suruda A., Schulte P., Boeniger M., Hayes R.B., Livingston G.K., Steenland K. et al. Cytogenetic effects of formaldehyde exposure in students of mortuary science. Cancer Epidemiol. Biomarkers Prev. 1993; 2(5): 453-60.Suruda A., Schulte P., Boeniger M., Hayes R.B., Livingston G.K., Steenland K. et al. Cytogenetic effects of formaldehyde exposure in students of mortuary science. Cancer Epidemiol. Biomarkers Prev. 1993; 2(5): 453-60.Zeller J., Neuss S., Mueller J.U., Kühner S., Holzmann K., Högel J. et al. Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions. Mutagenesis. 2011; 26(4): 555-61. https://doi.org/10.1093/mutage/ger016Zeller J., Neuss S., Mueller J.U., Kühner S., Holzmann K., Högel J. et al. Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions. Mutagenesis. 2011; 26(4): 555-61. https://doi.org/10.1093/mutage/ger016Bolognesi C., Knasmueller S., Nersesyan A., Thomas P., Fenech M. The HUMNxl scoring criteria for different cell types and nuclear anomalies in the buccal micronucleus cytome assay – an update and expanded photogallery. Mutat. Res. 2013; 753(2): 100-13. https://doi.org/10.1016/j.mrrev.2013.07.002Bolognesi C., Knasmueller S., Nersesyan A., Thomas P., Fenech M. The HUMNxl scoring criteria for different cell types and nuclear anomalies in the buccal micronucleus cytome assay – an update and expanded photogallery. Mutat. Res. 2013; 753(2): 100-13. https://doi.org/10.1016/j.mrrev.2013.07.002Fenech M., Holland N., Zeiger E., Chang W.P., Burgaz S., Thomas P. et al. The HUMN and HUMNxL international collaboration projects on human micronucleus assays in lymphocytes and buccal cells–past, present and future. Mutagenesis. 2011; 26(1): 239-45. https://doi.org/10.1093/mutage/geq051Fenech M., Holland N., Zeiger E., Chang W.P., Burgaz S., Thomas P. et al. The HUMN and HUMNxL international collaboration projects on human micronucleus assays in lymphocytes and buccal cells–past, present and future. Mutagenesis. 2011; 26(1): 239-45. https://doi.org/10.1093/mutage/geq051He J.L., Jin L.F., Jin H.Y. Detection of cytogenetic effects in peripheral lymphocytes of students exposed to formaldehyde with cytokinesis-blocked micronucleus assay. Biomed. Environ. Sci. 1998; 11(1): 87-92.He J.L., Jin L.F., Jin H.Y. Detection of cytogenetic effects in peripheral lymphocytes of students exposed to formaldehyde with cytokinesis-blocked micronucleus assay. Biomed. Environ. Sci. 1998; 11(1): 87-92.Shaham J., Gurvich R., Kaufman Z. Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde. Mutat. Res. 2002; 514(1-2): 115-23. https://doi.org/10.1016/s1383-5718(01)00334-5Shaham J., Gurvich R., Kaufman Z. Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde. Mutat. Res. 2002; 514(1-2): 115-23. https://doi.org/10.1016/s1383-5718(01)00334-5Santovito A., Schilirò T., Castellano S., Cervella P., Bigatti M.P., Gilli G. et al. Combined analysis of chromosomal aberrations and glutathione S-transferase M1 and T1 polymorphisms in pathologists occupationally exposed to formaldehyde. Arch. Toxicol. 2011; 85(10): 1295-302. https://doi.org/10.1007/s00204-011-0668-3Santovito A., Schilirò T., Castellano S., Cervella P., Bigatti M.P., Gilli G. et al. Combined analysis of chromosomal aberrations and glutathione S-transferase M1 and T1 polymorphisms in pathologists occupationally exposed to formaldehyde. Arch. Toxicol. 2011; 85(10): 1295-302. https://doi.org/10.1007/s00204-011-0668-3Jakab M.G., Klupp T., Besenyei K., Biró A., Major J., Tompa A. Formaldehyde-induced chromosomal aberrations and apoptosis in peripheral blood lymphocytes of personnel working in pathology departments. Mutat. Res. 2010; 698(1-2): 11-7. https://doi.org/10.1016/j.mrgentox.2010.02.015Jakab M.G., Klupp T., Besenyei K., Biró A., Major J., Tompa A. Formaldehyde-induced chromosomal aberrations and apoptosis in peripheral blood lymphocytes of personnel working in pathology departments. Mutat. Res. 2010; 698(1-2): 11-7. https://doi.org/10.1016/j.mrgentox.2010.02.015Musak L., Smerhovsky Z., Halasova E., Osina O., Letkova L., Vodickova L. et al. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand. J. Work Environ. Health. 2013; 39(6): 618-30. https://doi.org/10.5271/sjweh.3358Musak L., Smerhovsky Z., Halasova E., Osina O., Letkova L., Vodickova L. et al. Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand. J. Work Environ. Health. 2013; 39(6): 618-30. https://doi.org/10.5271/sjweh.3358Pala M., Ugolini D., Ceppi M., Rizzo F., Maiorana L., Bolognesi C. et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detect. Prev. 2008; 32(2): 121-6. https://doi.org/10.1016/j.cdp.2008.05.003Pala M., Ugolini D., Ceppi M., Rizzo F., Maiorana L., Bolognesi C. et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detect. Prev. 2008; 32(2): 121-6. https://doi.org/10.1016/j.cdp.2008.05.003Thomson E.J., Shackleton S., Harrington J.M. Chromosome aberrations and sister-chromatid exchange frequencies in pathology staff occupationally exposed to formaldehyde. Mutat. Res. 1984; 141(2): 89-93. https://doi.org/10.1016/0165-7992(84)90016-2Thomson E.J., Shackleton S., Harrington J.M. Chromosome aberrations and sister-chromatid exchange frequencies in pathology staff occupationally exposed to formaldehyde. Mutat. Res. 1984; 141(2): 89-93. https://doi.org/10.1016/0165-7992(84)90016-2Ogawa M., Kabe I., Terauchi Y., Tanaka S. A strategy for the reduction of formaldehyde concentration in a hospital pathology laboratory. J. Occup. Health. 2019; 61(1): 135-42. https://doi.org/10.1002/1348-9585.12018Ogawa M., Kabe I., Terauchi Y., Tanaka S. A strategy for the reduction of formaldehyde concentration in a hospital pathology laboratory. J. Occup. Health. 2019; 61(1): 135-42. https://doi.org/10.1002/1348-9585.12018Keshava N., Ong T.M. Occupational exposure to genotoxic agents. Mutat. Res. 1999; 437(2): 175-94. https://doi.org/10.1016/s1383-5742(99)00083-6Keshava N., Ong T.M. Occupational exposure to genotoxic agents. Mutat. Res. 1999; 437(2): 175-94. https://doi.org/10.1016/s1383-5742(99)00083-6Ladeira C., Pádua M., Veiga L., Viegas S., Carolino E., Gomes M.C. et al. Influence of serum levels of vitamins A, D, and E as well as vitamin D receptor polymorphisms on micronucleus frequencies and other biomarkers of genotoxicity in workers exposed to formaldehyde. J. Nutrigenet. Nutrigenomics. 2015; 8(4-6): 205-14. https://doi.org/10.1159/000444486Ladeira C., Pádua M., Veiga L., Viegas S., Carolino E., Gomes M.C. et al. Influence of serum levels of vitamins A, D, and E as well as vitamin D receptor polymorphisms on micronucleus frequencies and other biomarkers of genotoxicity in workers exposed to formaldehyde. J. Nutrigenet. Nutrigenomics. 2015; 8(4-6): 205-14. https://doi.org/10.1159/000444486Mierauskiene J., Lekevicius R., Lazutka J.R. Anticlastogenic effects of Aevitum intake in a group of chemical industry workers. Hereditas. 1993; 118(3): 201-4. https://doi.org/10.1111/j.1601-5223.1993.00201.xMierauskiene J., Lekevicius R., Lazutka J.R. Anticlastogenic effects of Aevitum intake in a group of chemical industry workers. Hereditas. 1993; 118(3): 201-4. https://doi.org/10.1111/j.1601-5223.1993.00201.xДурнев А.Д., Жанатаев А.К., Шредер О.В., Середенина В.С. Генотоксические поражения и болезни. Молекулярная медицина. 2013; (3): 3-19.Durnev A.D., Zhanataev A.K., Shreder O.V., Seredenina V.S. Genotoxic lesions and diseases. Molekulyarnaya meditsina. 2013; (3): 3-19. (in Russian)Дурнев А.Д. Антимутагенез и антимутагены. Физиология человека. 2018; 44(3): 116-37. https://doi.org/10.7868/S013116461803013XDurnev A.D. Antimutagenesis and antimutagens. Fiziologiya cheloveka. 2018; 44(3): 116-37. https://doi.org/10.7868/S013116461803013X (in Russian)

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