Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
권호 표지
DOI QR코드

DOI QR Code

A Review on the Health Risks Associated with the Use of Products Containing Benzalkonium Chloride (BKC), Focusing on Humidifier Disinfectant Products

염화벤잘코늄(Benzalkonium chloride) 살균제의 용도 및 건강 위험에 대한 고찰 - 가습기 살균제를 중심으로

  • Kim, Jiwon (Department of Anthropology, Zanvyl Krieger School of Arts & Sciences, Johns Hopkins University) ;
  • Zoh, Kyung Ehi (Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University) ;
  • Kim, Hana (Department of Public Health Sciences, Graduate School of Public Health, Seoul National University) ;
  • Park, Dong-Uk (Department of Environmental Health, Korea National Open University)
  • 김지원 (존스 홉킨스 대학교 인류학과) ;
  • 조경이 (서울대학교 보건대학원 환경보건학과) ;
  • 김하나 (서울대학교 보건대학원 보건학과) ;
  • 박동욱 (한국방송통신대학교 보건환경학과)
  • Received : 2021.09.28
  • Accepted : 2021.11.29
  • Published : 2021.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Benzalkonium chloride (BKC) has been extensively used as a preservative in industrial products and in hygiene, medical, and cosmetic applications. Humidifier disinfectant (HD) products containing BKC have been used in South Korea. Objectives: This study was aimed to review types of products containing BKC, to summarize the regulations in the US, EU, Japan, and South Korea, and to review the health effects associated with the use of HD. Methods: We reviewed and summarized documents which were searched through PubMed and Google Scholar with the key words: BKC and asthma/contact dermatitis, humidifier disinfectant-associated lung injury (HDLI), and more. Results: Regulations in most countries including South Korea do not allow its use as disinfectants in spray-type of products for medicine, cosmetics, and household products. Two types of HD containing BKC (800~1,270 ppm) were marketed in South Korea from 1996~2003. Health effects reported from people who used products containing BKC were allergic contact dermatitis, erythema, and respiratory disease, including asthma. Two people who responded as HD users containing BKC only were confirmed to have developed asthma. HD-associated lung injury (HDLI) was reported by consumers who used both HD containing polyhexamethylene guanidine (PHMG) and HD containing BKC. Conclusions: In conclusion, the use of BKC as a biocide has to be controlled considering the route and pattern of exposure. Products containing BKC as preservatives were reviewed with exposure routes and sites in the human body such as skin, eyes, and the respiratory tract. HD containing BKC was clinically evaluated to be associated with asthma.

Keywords

References

  1. Park DU, Lee S, Lim HK, Kim SY, Kim J, Park J, et al. Comprehensive review on humidifier disinfectant (HD) products, focusing on the number of products and their disinfectant type. J Environ Health Sci. 2020; 46(5): 481-494. https://doi.org/10.5668/JEHS.2020.46.5.481
  2. Korea Environmental Industry & Technology Institute (KEITI). Comprehensive Supporting Portal for Humidifier Disinfectant Victims: Statistical Data. Available: https://www.healthrelief.or.kr/home/content/stats01/view.do [accessed 30 November 2021].
  3. Park DU, Ryu SH, Roh HS, Lee E, Cho HJ, Yoon J, et al. Association of high-level humidifier disinfectant exposure with lung injury in preschool children. Sci Total Environ. 2018; 616-617: 855-862. https://doi.org/10.1016/j.scitotenv.2017.10.237
  4. Purohit A, Kopferschmitt-Kubler MC, Moreau C, Popin E, Blaumeiser M, Pauli G. Quaternary ammonium compounds and occupational asthma. Int Arch Occup Environ Health. 2000; 73(6): 423-427. https://doi.org/10.1007/s004200000162
  5. United States. Environmental Protection Agency. Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC). Washington, D.C.: U.S. Environmental Protection Agency; 2006.
  6. Choi SM, Roh TH, Lim DS, Kacew S, Kim HS, Lee BM. Risk assessment of benzalkonium chloride in cosmetic products. J Toxicol Environ Health B Crit Rev. 2018; 21(1): 8-23. https://doi.org/10.1080/10937404.2017.1408552
  7. European Union. Biocidal Products Regulation. Brussels: European Parliament, Council of the European Union; 2012.
  8. European Commission. Commission Implementing Decision (EU) 2016/1950 of 4 November 2016 on the Non-Approval of Certain Biocidal Active Substances Pursuant to Regulation (EU) No 528/2012 of the European Parliament and of the Council. Available: https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX:32016D1950 [accessed 30 September 2021].
  9. European Union (EU). Regulation (EU) 528/2012- Annex V: List of Preservatives Allowed in Cosmetic Products. Available: https://ec.europa.eu/growth/tools-databases/cosing/pdf/COSING_Annex%20V_v2.pdf [accessed 30 September 2021].
  10. European Commission. Regulation (EC) No. 1223/2009 on Cosmetic Products - Annex III. Available: https://ec.europa.eu/health/sites/default/files/endocrine_disruptors/docs/cosmetic_1223_2009_regulation_en.pdf [accessed 30 September 2021].
  11. Cosmetic Ingredient Review Expert Panel. Annual review of cosmetic ingredient safety assessments: 2005/2006. Int J Toxicol. 2008; 27(Suppl 1): 77-142. https://doi.org/10.1080/10915810802032362
  12. US Food and Drug Administration, HHS. Safety and effectiveness of health care antiseptics; topical antimicrobial drug products for over-the-counter human use. Final rule. Fed Regist. 2017; 82(242): 60474-60503.
  13. Japan Ministry of Health and Welfare. Standards for Cosmetics, Notification No.331. Tokyo: Ministry of Health and Welfare, Japan; 2000.
  14. Korea Ministry of Food and Drug Safety. Regulations on Safety Standards for Cosmetics. No. 2020-12 (Amended on Feb 25, 2020). Available: https://www.mfds.go.kr/brd/m_211/view.do?seq=14453 [accessed 30 September 2021].
  15. Korea Ministry of Food and Drug Safety. Korean Manufacturing Standard for Medicine. No.2021-68 (Partly Amended and Enforced on August 9, 2021). Available: https://www.law.go.kr/%ED%96%89%EC%A0%95%EA%B7%9C%EC%B9%99/%EC%9D%98%EC%95%BD%EC%99%B8%ED%92%88%ED%91%9C%EC%A4%80%EC%A0%9C%EC%A1%B0%EA%B8%B0%EC%A4%80/(2021-68,20210809) [accessed 30 September 2021].
  16. Korea Ministry of Food and Drug Safety. Prior Notice 1: Modification Order for Approving Drugs Containing Benzalkonium Chlorides. Available: https://nedrug.mfds.go.kr/CCBAR01F012/getList/getItem?infoNo=20210099&infoClassCode=3 [accessed 30 September 2021].
  17. Korea Ministry of Food and Drug Safety. Prior Notice 2: Modification Order for Approving Drugs Containing Benzalkonium Chlorides. Available: https://nedrug.mfds.go.kr/CCBAR01F012/getList/ getItem?infoNo=20210133&infoClassCode=3 [accessed 30 September 2021].
  18. Korea Ministry of Environment. Standard for Consumer Chemical Products Designated as Products Subject to Safety Confirmation and their Safety and Labeling No.2021-150 (Partly Amended and Enforced on July 30, 2021). Available: https://www.law.go.kr/admRulSc.do?menuId=5&query=%EC%95%88%EC%A0%84%ED%99%95%EC%9D%B8%EB%8C%80%EC%83%81%EC%83%9D%ED%99%9C%ED%99%94%ED%95%99%EC%A0%9C%ED%92%88%20%EC%A7%80%EC%A0%95%20%EB%B0%8F%20%EC%95%88%EC%A0%84%C2%B7%ED%91%9C%EC%8B%9C%EA%B8%B0%EC%A4%80#AJAX [accessed 30 September 2021].
  19. Lewis RJ, Sax NI. Sax's Dangerous Properties of Industrial Materials, 12th ed. Oxford: Wiley-Blackwell; 2012.
  20. Willis CM, Stephens JM, Wilkinson JD. Experimentally-induced irritant contact dermatitis. Determination of optimum irritant concentrations. Contact Dermatitis. 1988; 18(1): 20-24. https://doi.org/10.1111/j.1600-0536.1988.tb05484.x
  21. Dao H Jr, Fricker C, Nedorost ST. Sensitization prevalence for benzalkonium chloride and benzethonium chloride. Dermatitis. 2012; 23(4): 162-166. https://doi.org/10.1097/der.0b013e318260d78d
  22. Fisher AA. Allergic contact dermatitis and conjunctivitis from benzalkonium chloride. Cutis. 1987; 39(5): 381-383.
  23. Suneja T, Belsito DV. Occupational dermatoses in health care workers evaluated for suspected allergic contact dermatitis. Contact Dermatitis. 2008; 58(5): 285-290. https://doi.org/10.1111/j.1600-0536.2007.01315.x
  24. Stanford D, Georgouras K. Allergic contact dermatitis from benzalkonium chloride in plaster of Paris. Contact Dermatitis. 1996; 35(6): 371-372. https://doi.org/10.1111/j.1600-0536.1996.tb02427.x
  25. Isaac J, Scheinman PL. Benzalkonium chloride: an irritant and sensitizer. Dermatitis. 2017; 28(6): 346-352. https://doi.org/10.1097/der.0000000000000316
  26. Oiso N, Fukai K, Ishii M. Irritant contact dermatitis from benzalkonium chloride in shampoo. Contact Dermatitis. 2005; 52(1): 54. https://doi.org/10.1111/j.0105-1873.2005.0483j.x
  27. Tartari F, Vincenzi C, Di Altobrando A, Bruni F, Neri I. Allergic contact dermatitis to benzalkonium chloride with erythema multiforme-like reaction in a child. Contact Dermatitis. 2020; 82(6): 397-399. https://doi.org/10.1111/cod.13481
  28. Ling T, Highet A. Irritant reactions to an antiseptic bath emollient. J Dermatol Treat. 2000; 11(4): 263-267. https://doi.org/10.1080/09546630050517216
  29. Krogsrud NE, Larsen AI. Airborne irritant contact dermatitis from benzalkonium chloride. Contact Dermatitis. 1997; 36(2): 112. https://doi.org/10.1111/j.1600-0536.1997.tb00430.x
  30. Mauleon C, Mauleon P, Chavarria E, de la Cueva P, Suarez R, Lazaro P. Airborne contact dermatitis from n-alkyl dimethylbenzylammonium chloride and n-alkyl dimethylethyl-benzylammonium chloride in a detergent. Contact Dermatitis. 2006; 55(5): 311-312.
  31. Freeman PD, Kahook MY. Preservatives in topical ophthalmic medications: historical and clinical perspectives. Expert Rev Ophthalmol. 2009; 4(1): 59-64. https://doi.org/10.1586/17469899.4.1.59
  32. Lee J. Glaucoma and ocular surface disease. J Korean Glaucoma Soc. 2019; 8(1): 33-35.
  33. Rasmussen CA, Kaufman PL, Kiland JA. Benzalkonium chloride and glaucoma. J Ocul Pharmacol Ther. 2014; 30(2-3): 163-169. https://doi.org/10.1089/jop.2013.0174
  34. Yu I. Medical treatment of glaucoma and ocular surface disease: from old to new. J Korean Glaucoma Soc. 2017; 6(1): 30-33.
  35. Orsini D, D'Arino A, Pigliacelli F, Assorgi C, Latini A, Cristaudo A. Allergic contact dermatitis to dorzolamide and benzalkonium chloride. Postepy Dermatol Alergol. 2018; 35(5): 538-539. https://doi.org/10.5114/ada.2018.73859
  36. Lee SJ, Kim M. Allergic contact dermatitis caused by dorzolamide eyedrops. Clin Ophthalmol. 2015; 9: 575-577. https://doi.org/10.2147/OPTH.S74555
  37. Datta S, Baudouin C, Brignole-Baudouin F, Denoyer A, Cortopassi GA. The eye drop preservative benzalkonium chloride potently induces mitochondrial dysfunction and preferentially affects LHON mutant cells. Invest Ophthalmol Vis Sci. 2017; 58(4): 2406-2412. https://doi.org/10.1167/iovs.16-20903
  38. Suzuki K, Teranishi S, Sagara T, Yoshino H, Nakayama M, Enoki M, et al. Safety and efficacy of benzalkonium chloride-optimized tafluprost in Japanese glaucoma patients with existing superficial punctate keratitis. J Glaucoma. 2015; 24(6): e145-e150. https://doi.org/10.1097/IJG.0000000000000020
  39. Sezgin Akcay BI, Guney E, Bozkurt TK, Topal CS, Akkan JC, unlu C. Effects of polyquaternium- and benzalkonium-chloride-preserved travoprost on ocular surfaces: an impression cytology study. J Ocul Pharmacol Ther. 2014; 30(7): 548-553. https://doi.org/10.1089/jop.2013.0248
  40. Cha SH, Lee JS, Oum BS, Kim CD. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Exp Ophthalmol. 2004; 32(2): 180-184. https://doi.org/10.1111/j.1442-9071.2004.00782.x
  41. George M, Joshi SV, Concepcion E, Lee H. Paradoxical bronchospasm from benzalkonium chloride (BAC) preservative in albuterol nebulizer solution in a patient with acute severe asthma. A case report and literature review of airway effects of BAC. Respir Med Case Rep. 2017; 21: 39-41. https://doi.org/10.1016/j.rmcr.2017.03.005
  42. Lee BH, Kim SH. Benzalkonium chloride induced bronchoconstriction in patients with stable bronchial asthma. Korean J Intern Med. 2007; 22(4): 244-248. https://doi.org/10.3904/kjim.2007.22.4.244
  43. Graf P, Enerdal J, Hallen H. Ten days' use of oxymetazoline nasal spray with or without benzalkonium chloride in patients with vasomotor rhinitis. Arch Otolaryngol Head Neck Surg. 1999; 125(10): 1128-1132. https://doi.org/10.1001/archotol.125.10.1128
  44. Lechien JR, Costa de Araujo P, De Marrez LG, Halloy JL, Khalife M, Saussez S. Contact allergy to benzalkonium chloride in patients using a steroid nasal spray: a report of 3 cases. Ear Nose Throat J. 2018; 97(1-2): E20-E22.
  45. Vandenplas O, D'Alpaos V, Evrard G, Jamart J, Thimpont J, Huaux F, et al. Asthma related to cleaning agents: a clinical insight. BMJ Open. 2013; 3(9): e003568. https://doi.org/10.1136/bmjopen-2013-003568
  46. The Mount Sinai Selikoff Centers for Occupational Health. Quaternary Ammonium Compounds in Cleaning Products: Health & Safety Information for Cleaners and Supervisors. Available: https://www.mountsinai.org/files/MSHealth/Assets/HS/Patient-Care/Service-Areas/Occupational-Medicine/QACsInfoforWorkers_18.pdf [accessed 30 September 2021].
  47. Park DU, Kwon JH, Park JH, Oh HB. Analysis of Components of Disinfectant Contained in Humidifier Disinfectant Products. Seoul: Special Committee for Examining the Cause of Tragedy caused by Humidifier Disinfectant (SCECTHD); 2020.
  48. KOSHA. Study on the Respiratory Toxicity of Biocide, Benzalknonium Chloride. Available: https://oshri.kosha.or.kr/oshri/publication/researchReportSearch.do?mode=view&articleNo=411076&article.offset=130&articleLimit=10 [accessed 30 September 2021].
  49. Johnson NF. Pulmonary toxicity of benzalkonium chloride. J Aerosol Med Pulm Drug Deliv. 2018; 31(1): 1-17. https://doi.org/10.1089/jamp.2017.1390