Safety issues in the use of disinfectants based on polyhexamethyleneguanidine (literature review)

Cover Page

Cite item

Full Text

Abstract

The article presents data of the analysis of scientific literature on the toxicity and danger of polyhexamethylene guanidine (PHMG) and based on it disinfectants, which have been widely used for several decades. The COVID-19 pandemic has contributed to a sharp increase in the use of disinfectants, making it important to study the safety of these substances. The presented materials confirm the effectiveness of PHMG and its compounds against a wide range of bacteria, viruses and fungi. The article discusses the mechanism of the bactericidal action of guanidine polymers, based on the destruction of the bacterial cell wall due to the electrostatic effect of positively charged substance molecules on anionic groups on the cellular wall. Methods for using disinfectants based on PHMG for sanitizing various surfaces and media are shown.

The results of toxicological studies show that polyhexamethyleneguanidine compounds have low toxicity when taken orally, but pose a great danger to the respiratory system. With chronic exposure, they cause pulmonary fibrosis, a serious lung disease, associated with irreversible destruction of the lung architectonics, pulmonary insufficiency and impaired gas exchange due to excessive accumulation of proteins in the extracellular matrix. The use of disinfectants based on polyhexamethylene guanidine is not recommended for aerosol disinfection of indoor air in the presence of people. The presented data also indicate the need for additional toxicological studies to establish threshold doses of PHMG under inhalation exposure.

Contribution:
Lebed-Sharlevich Ya.I. — collection and processing of material, writing a text;
Mamonov R.A. — editing. All authors are responsible for the concept and design of the study, integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: May 19, 2023 / Accepted: September 26, 2023 / Published: October 30, 2023

About the authors

Yana I. Lebed-Sharlevich

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency

Author for correspondence.
Email: YaSharlevich@cspmz.ru
ORCID iD: 0000-0002-4249-1093

MD, PhD, Senior Researcher of the Centre for Strategic Planning of FMBA of Russia, Moscow, 119121, Russian Federation.

e-mail: YaSharlevich@cspmz.ru

 

Russian Federation

Roman A. Mamonov

Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency

Email: noemail@neicon.ru
ORCID iD: 0000-0002-6540-6015
Russian Federation

References

  1. Lindenbraten A.L., Sidorenko N.V., Gololobova T.V., Shestopalova T.N. The role of standard operating procedures in quality management of medical activities. Vestnik Roszdravnadzora. 2018; (6): 40–4. https://elibrary.ru/vnjjmm (in Russian)
  2. Gembitskiy P.A., Vointseva I.I. Polymeric Biocidal Preparation Polyhexamethyleneguanidine [Polimernyy biotsidnyy preparat poligeksametilenguanidin]. Zaporozh’e: Poligraf; 1998. (in Russian)
  3. Dias F.G.G., de Freitas Pereira L., Parreira R.L.T., Veneziani R.C.S., Bianchi T.C., de Paula Fontes V.F.N., et al. Evaluation of the antiseptic and wound healing potential of polyhexamethylene guanidine hydrochloride as well as its toxic effects. Eur. J. Pharm. Sci. 2021; 160: 105739. https://doi.org/10.1016/j.ejps.2021.105739
  4. Ochirov O.S., Razuvaeva Ya.G., Badmaev N.S., Stel’makh S.A., Mognonov D.M. Wound-healing effect of polyguanidine-based hydrogel. Byulleten’ Vostochno-Sibirskogo nauchnogo tsentra Sibirskogo otdeleniya Rossiyskoy akademii meditsinskikh nauk. 2016; 1(5): 117–20. https://elibrary.ru/wxbrsn (in Russian)
  5. Pan Y., Xia Q., Xiao H. Cationic polymers with tailored structures for rendering polysaccharide-based materials antimicrobial: An overview. Polymers. 2019; 11(8): 1283. https://doi.org/10.3390/polym11081283
  6. Heydarifard S., Pan Y., Xiao H., Nazhad M.M., Shipin O. Water-resistant cellulosic filter containing non-leaching antimicrobial starch for water purification and disinfection. Carbohydr. Polym. 2017; 163: 146–52. https://doi.org/10.1016/j.carbpol.2017.01.063
  7. Zhang H.L., Gao Y.B., Gai J.G. Guanidinium-functionalized nanofiltration membranes integrating anti-fouling and antimicrobial effects. J. Mater. Chem. A. 2018; 6(15): 6442–54. https://doi.org/10.1039/C8TA00342D
  8. Gandurina L.V., Latyshev N.S., Ivkin P.A. Jeffektivnost’ primenenija biocidnogo koaguljanta-poligeksametilenguanidin gidrohlorida v shemah ochistki prirodnyh vod. Vodoochistka. Vodopodgotovka. Vodosnabzhenie. 2012; (9): 34–7. https://elibrary.ru/pcvdgr (in Russian)
  9. Bogachuk G.P. Prikladnye aspekty primenenija perspektivnyh antiseptikov na osnove poligeksametilenguanidina (PGMG). Soobshhenie pervoe. Sbornik nauchnykh trudov Angarskogo gosudarstvennogo tekhnicheskogo universiteta. 2006; 2(1): 48–60. https://elibrary.ru/rdekmd (in Russian)
  10. Tarasevich V., Dobysh V., Karpinchik E., Agabekov V. Polymer biocides. Nauka i innovatsii. 2019; (11): 23–6. https://elibrary.ru/ltfdrh (in Russian)
  11. Oule M.K., Azinwi R., Bernier A.M., Kablan T., Maupertuis A.M., Mauler S., et al. Polyhexamethylene guanidine hydrochloride-based disinfectant: a novel tool to fight meticillin-resistant Staphylococcus aureus and nosocomial infections. Med. Microbiol. 2008; 57(Pt. 12): 1523–8. https://doi.org/10.1099/jmm.0.2008/003350-0
  12. Oule M.K., Quinn K., Dickman M., Bernier A.M., Rondeau S., De Moissac D., et al. Akwaton, polyhexamethylene-guanidine hydrochloride-based sporicidal disinfectant: a novel tool to fight bacterial spores and nosocomial infections. J. Med. Microbiol. 2012; 61(Pt. 10): 1421–7. https://doi.org/10.1099/jmm.0.047514-0
  13. Oule M.K., Staines K., Lightly T., Roberts L., Traore Y.L., Dickman M., et al. Fungicidal activity of AKWATON and in vitro assessment of its toxic effects on animal cells. J. Med. Microbiol. 2015; 64(Pt. 1): 59–66. https://doi.org/10.1099/jmm.0.079467-0
  14. Choi H., Kim K.J., Lee D.G. Antifungal activity of the cationic antimicrobial polymer-polyhexamethylene guanidine hydrochloride and its mode of action. Fungal. Biol. 2017; 121(1): 53–60. https://doi.org/10.1016/j.funbio.2016.09.001
  15. Panteleeva L.G. Virulicide activity of cationic surface-active materials and disinfection means on their base. Dezinfektsionnoe delo. 2006; (1): 34–8. https://elibrary.ru/jxrmbh (in Russian)
  16. Fedorova L.S., Pankratova G.P., Levchuk N.N., Chernyavskiy I.N., Efimov K.M., Dityuk A.I., et al. Desinfectants of polyguanidine with extended release and their use on practice in food industry enterprise. Dezinfektsionnoe delo. 2013; (3): 27–33. https://elibrary.ru/rapjdp (in Russian)
  17. Zhou Z.X., Wei D.F., Guan Y., Zheng A.N., Zhong J.J. Damage of Escherichia coli membrane by bactericidal agent polyhexamethylene guanidine hydrochloride: micrographic evidences. J. Appl. Microbiol. 2010; 108(3): 898–907. https://doi.org/10.1111/j.1365-2672.2009.04482.x
  18. Shandala M.G., Fedorova L.S., Pankratova G.P., Efimov K.M., Dityuk A.I., Snezhko A.G., et al. Hygienic substantiation of the development and use of polyguanidines as antimicrobial prophylactic means of the innovative class. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2015; 94(8): 77–81. https://elibrary.ru/vjzdhj (in Russian)
  19. Qian L., Xiao H., Zhao G., He B. Synthesis of modified guanidine-based polymers and their antimicrobial activities revealed by AFM and CLSM. ACS Appl. Mater. Interfaces. 2011; 3(6): 1895–901. https://doi.org/10.1021/am200094u
  20. Brzezinska M.S., Walczak M., Jankiewicz U., Pejchalová M. Antimicrobial activity of polyhexamethylene guanidine derivatives introduced into polycaprolactone. J. Polym. Environ. 2018; 26(2): 589–95. https://doi.org/10.1007/s10924-017-0974-9
  21. Dorozhkin V.I., Popov N.I., Bondarenko V.O., Khod’kova Yu.S., Likhikh T.N., Shul’ga M.A. Effectiveness of disinfectant based on polyhexamethylene guanidine hydrochloride. Rossiyskiy zhurnal «Problemy veterinarnoy sanitarii, gigieny i ekologii». 2020; (1): 24–9. https://doi.org/10.36871/vet.san.hyg.ecol.202001004 https://elibrary.ru/mrtkby (in Russian)
  22. Efimov K.M., Grigor’ev G.A., Gembitskiy P.A., Polikarpov N.A., Alov N.V. Investigation of biopag films adsorbed on metal and ceramic surfaces by x-ray photoelectron spectroscopy. Zhurnal fizicheskoy khimii. 2006; 80(2): 360–2. https://doi.org/10.1134/S0036024406020312 https://elibrary.ru/ljpuxl
  23. Lifentsova M.N., Gorpinchenko E.A. Efficiency of roksatsin in aerosol disinfection of the livestock buildings. Politematicheskiy setevoy elektronnyy nauchnyy zhurnal Kubanskogo gosudarstvennogo agrarnogo universiteta. 2016; (121): 1985–94. https://doi.org/10.21515/1990-4665-121-125 https://elibrary.ru/wwsmhd (in Russian)
  24. Malkov A.E. Aeron. Meditsinskaya sestra. 2014; (8): 38–9. https://elibrary.ru/syzbjr (in Russian)
  25. Fedorova L.S. Obosnovanie vybora dezinficirujushhih sredstv dlja profilaktiki koronavirusnoj infekcii. In: Control and Prevention of Healthcare-Associated Infections (HCAI-2020). Proceedings of the VIII Congress with International Participation [Kontrol’ i profilaktika infektsiy, svyazannykh s okazaniem meditsinskoy pomoshchi (ISMP-2020). Sbornik tezisov VIII Kongressa s mezhdunarodnym uchastiem]. Moscow; 2020. (in Russian)
  26. Johnston R. Antiviral and antibacterial coatings being tested on Prague trams and buses; 2020. Available at: https://www.expats.cz/czech-news/article/antiviral-and-antibacterial-coatings-being-tested-on-prague-trams-and-buses
  27. Deng C., Seidi F., Yong Q., Jin X., Li C., Zheng L., et al. Virucidal and biodegradable specialty cellulose nonwovens as personal protective equipment against COVID-19 pandemic. J. Adv. Res. 2022; 39: 147–56. https://doi.org/10.1016/j.jare.2021.11.002
  28. Tul’skaya E.A., Zholdakova Z.I., Sinitsyna O.O., Mamonov R.A. Toxicity and efficacy “Dezavid” and its analogs compared with other means of disinfection. Vodosnabzhenie i kanalizatsiya. 2013; (5-6): 44–50. https://elibrary.ru/rdkpuj (in Russian)
  29. Gotovskiy D.G., Petrov V.V., Shchigel’skaya E.S., Kondakova V.V. Comparative efficiency of bactericidal effects and toxicity of certain biopolymers. Veterinarnyy zhurnal Belarusi. 2021; (1): 6–10. https://elibrary.ru/mhprjj (in Russian)
  30. Zholdakova Z.I., Odintsov E.E., Kharchevnikova N.V., Belyaeva N.N., Tul’skaya E.A., Zaytsev N.A. Poligeksametilenguanidin gidrohdloid (PGMG-gidrohlorid). Toksikologicheskiy vestnik. 2004; (6): 35–6. https://elibrary.ru/vzlver (in Russian)
  31. Asiedu-Gyekye I.J., Mahmood S.A., Awortwe C., Nyarko A.K. A preliminary safety evaluation of polyhexamethylene guanidine hydrochloride. Int. J. Toxicol. 2014; 33(6): 523–31. https://doi.org/10.1177/1091581814553036
  32. Nadzharyan L.A., Karpinchik E.V., Tarasevich V.A., Kotelenets A.I. The study of the toxic properties of polyhexamethyleneguanidine hydrochloride and their formulation. Zdorov’e i okruzhayushchaya sreda. 2011; (19): 127–32. https://elibrary.ru/zatzkf (in Russian)
  33. Kondrashov V.A. Hygienic evaluation of a new polymer flocculant polyhexamethylene guanidine. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 1992; (3): 11–3. (in Russian)
  34. Lebedeva S.N., Ochirov O.S., Grigor’eva M.N., Zhamsaranova S.D., Stel’makh S.A., Mognonov D.M. Acute toxicity of hydrogel polyhexamethylene guanidine hydrochloride. Acta Biomedica Scientifica. 2020; 5(4): 103–7. https://doi.org/10.29413/ABS.2020-5.4.15 https://elibrary.ru/sliiqg (in Russian)
  35. Kim H.R., Hwang G.W., Naganuma A., Chung K.H. Adverse health effects of humidifier disinfectants in Korea: lung toxicity of polyhexamethylene guanidine phosphate. J. Toxicol. Sci. 2016; 41(6): 711–7. https://doi.org/10.2131/jts.41.711
  36. Park D.U., Park J., Yang K.W., Park J.H., Kwon J.H., Oh H.B. Properties of polyhexamethylene guanidine (PHMG) associated with fatal lung injury in Korea. Molecules. 2020; 25(14): 3301. https://doi.org/10.3390/molecules25143301
  37. Ahn J.J. The humidifier disinfectant incident and the self-examination of environmental toxicology and public health experts. Environ. Health Toxicol. 2015; 30: e2015016. https://doi.org/10.5620/eht.e2015016
  38. Jeon B.H., Park Y.J. Frequency of humidifier and humidifier disinfectant usage in Gyeonggi provine. Environ. Health Toxicol. 2012; 27: e2012002. https://doi.org/10.5620/eht.2012.27.e2012002
  39. Lee J.H., Kang H.J., Seol H.S., Kim C.K., Yoon S.K., Gwack J., et al. Refined exposure assessment for three active ingredients of humidifier disinfectants. Environ. Eng. Res. 2013; 18(4): 253–7. https://doi.org/10.4491/eer.2013.18.4.253
  40. Park D.U., Friesen M.C., Roh H.S., Choi Y.Y., Ahn J.J., Lim H.K., et al. Estimating retrospective exposure of household humidifier disinfectants. Indoor Air. 2015; 25(6): 631–40. https://doi.org/10.1111/ina.12180
  41. Song J.A., Park H.J., Yang M.J., Jung K.J., Yang H.S., Song C.W., et al. Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy. Food Chem. Toxicol. 2014; 69: 267–75. https://doi.org/10.1016/j.fct.2014.04.027
  42. Park S., Lee K., Lee E.J., Lee S.Y., In K.H., Kim H.K., et al. Humidifier disinfectant-associated interstitial lung disease in an animal model induced by polyhexamethylene guanidine aerosol. Am. J. Respir. Crit. Care Med. 2014; 190(6): 706–8. https://doi.org/10.1164/rccm.201404-0710LE
  43. Kim H.R., Lee K., Park C.W., Song J.A., Shin D.Y., Park Y.J., et al. Polyhexamethylene guanidine phosphate aerosol particles induce pulmonary inflammatory and fibrotic responses. Arch. Toxicol. 2016; 90(3): 617–32. https://doi.org/10.1007/s00204-015-1486-9
  44. Jung H.N., Zerin T., Podder B., Song H.Y., Kim Y.S. Cytotoxicity and gene expression profiling of polyhexamethylene guanidine hydrochloride in human alveolar A549 cells. Toxicol. In Vitro. 2014; 28(4): 684–92. https://doi.org/10.1016/j.tiv.2014.02.004
  45. Park Y.J., Jeong M.H., Bang I.J., Kim H.R., Chung K.H. Guanidine-based disinfectants, polyhexamethylene guanidine-phosphate (PHMG-P), polyhexamethylene biguanide (PHMB), and oligo (2-(2-ethoxy) ethoxyethyl guanidinium chloride (PGH) induced epithelial-mesenchymal transition in A549 alveolar epithelial cells. Inhal. Toxicol. 2019; 31(4): 161–6. https://doi.org/10.1080/08958378.2019.1624896
  46. Lee Y., Seo D. Toxicity of humidifier disinfectant polyhexamethylene guanidine hydrochloride by two-week whole body-inhalation exposure in rats. J. Toxicol. Pathol. 2020; 33(4): 265–77. https://doi.org/10.1293/tox.2020-0043

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Lebed-Sharlevich Y.I., Mamonov R.A.


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.