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Scientific justification of the group hygiene norm for the cluster of alkylbenzyldimethylammonium chloride compounds in the air of the working area

ISSN 2223-6775 Ukrainian journal of occupational health Vol.18, No 2, 2022


https://doi.org/10.33573/ujoh2022.02.107

Scientific justification of the group hygiene norm for the cluster of alkylbenzyldimethylammonium chloride compounds in the air of the working area

Turkina V.A., Kuzminov B.P., Alyokhina T.A.
Danylo Halytsky Lviv National University


Full article (PDF), UKR

Introduction. Poor regulation of active substances in disinfectants in Ukraine holds their legalization on the national market. Cluster approach in the hygienic regulation practice is one of the ways to address this issue.

Research purpose is to establish group-based hygiene regulations for the benzalkonium chloride (BC) cluster.

Research materials and methods. The subject of research is BC homologues. The research is based on the analysis of national and international scientific publications and legislative acts regarding BC toxic effects and hygienic regulations.

Results. BC is a mixture of the benzalkonium chloride compounds homologues. The homologues ratio in a mixture plays a key role in assigning CAS numbers to BC. The average lethal doses with oral administration for all BC homologues are below 500 mg/kg. BC skin and oral absorption does not exceed 10%. BC does not affect reproductive system and does not cause neonatal development abnormalities; it has no carcinogenic and mutagenic properties. Typical adverse effects of BC are related to compound irritant activity. Pursuant to EU regulation 1907/2006, substances with similar physicochemical, toxicological and ecotoxicological properties can be considered as a cluster. The data for reference substance of the cluster make it possible to predict the impact of other substances from this group on human health and environment. In case of BC, alkyl (C12-C16) dimethylbenzylammonium chloride was chosen as the reference substance. In Ukraine, the hygienic regulation sets 0.5 mg/m3 as occupational exposure limit for this substance. Following the clusters principle, it is advisable to introduce group hygiene regulations for all BC homologues based on alkyl (C12-C16) dimethylbenzylammonium chloride.

Conclusions. The implementation of cluster approach when developing exposure limits for chemical compounds in environmental medium makes it possible to introduce group hygienic regulations of 0.5 mg/m3 as occupational exposure limit for all BC homologues.

Keywords:

References

  1. The official site of The Ministry of Health of Ukraine, (2022), "Open data", available at: https://moz.gov.ua/vidkriti-dani.
  2. Hora, P., Pati, S., McNamara, P. and Arnold, W. (2020), "Increased Use of Quaternary Ammonium Compounds during the SARS-CoV-2 Pandemic and Beyond: Consideration of Environmental Implications", Environmental Science & Technology Letters, Vol. 7, No. 9, pp.622-631, https://doi.org/10.1021/acs.estlett.0c00437
  3. The official site of The U.S. Environmental Protection Agency, (2006), "Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)", available at: https://www3.epa.gov/pesticides/chem_search/reg_actions/reregistration/red_G-2_3-Aug-06.pdf
  4. The official site of The Cabinet of Ministers, (2008), "Addition VI for Regulation (EC) no 1272/2008 of the European Parliament and of the Council", available at: https://www.kmu.gov.ua/storage/app/sites/1/55-GOEEI/es-12722008.pdf
  5. Uematsu, M., Kumagami, T., Shimoda, K., Kusano, M., Teshima, M., Sasaki, H. and Kitaoka, T. (2010), "Influence of Alkyl Chain Length of Benzalkonium Chloride on Acute Corneal Epithelial Toxicity", Cornea, Vol. 29, No. 11, pp.1296-1301, https://doi.org/10.1097/ICO.0b013e3181dc81b6
  6. Jono, K., Takayama, T., Kuno, M. and Higashide, E. (1986), "Effect of alkyl chain length of benzalkonium chloride on the bactericidal activity and binding to organic materials", Chemical and Pharmaceutical Bulletin, Vol. 34, No. 10, pp. 4215-4224, https://doi.org/10.1248/cpb.34.4215
  7. Merianos, J., (1991), "Quaternary Ammonium Antimicrobial Compounds", in S. Block (ed.), Disinfection, Sterilisation, and Preservation 4th ed., USA, pp. 225-255
  8. Osimitz, T. and Droege, W. (2021), "Quaternary ammonium compounds: perspectives on benefits, hazards, and risk", Toxicology Research and Application, Vol. 5, pp. 239784732110490, https://doi.org/10.1177/23978473211049085
  9. Seguin, R., Herron, J., Lopez, V., Dempsey, J. and Xu, L. (2019), "Metabolism of Benzalkonium Chlorides by Human Hepatic Cytochromes P450", Chemical Research in Toxicology, Vol. 32, No. 12, pp. 2466-2478, https://doi.org/10.1021/acs.chemrestox.9b00293
  10. The official site of The European Chemicals Agency, (2015), "Assessment Report - Alkyl (C12-16) Dimethylbenzyl Ammonium Chloride Product-type 8 (Wood Preservative) European Chemicals Agency", available at: https://echa.europa.eu/documents/10162/b9030b10-c8af-211b-456a-4f4b11d509b7
  11. Kuzminov, B.P., Turkina, V.A., Lukasevich, N.Ph., Zhuk, S.Sh., Lapovets, N.Ye, Pryzyhley, G.V. and Grushka, O.I. (2021), "Experimental justification of hygienic regulations of alkyl (C 12-16) Dimethylbenzylamonium of chloride in the conditions of production application", Aktualni problemy profilaktichnoi medicine, Vol. 21, pp 54-63.
  12. Choi, H., Lee, Y., Lim, C., Kim, Y., Lee, I., Jo, J., Lee, H., Cha, H., Woo, H. and Seo, D. (2020), "Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats", Particle and Fibre Toxicology, Vol. 17, No. 1, https://doi.org/10.1186/s12989-020-0339-8
  13. Świercz, R., Hałatek, T., Wąsowicz, W., Kur, B., Grzelińska, Z. and Majcherek, W. (2008), "Pulmonary Irritation After Inhalation Exposure to Benzalkonium Chloride in Rats", International Journal of Occupational Medicine and Environmental Health, Vol. 21, No. 2, pp. 157-163, https://doi.org/10.2478/v10001-008-0020-1
  14. Świercz, R., Hałatek, T., Stetkiewicz, J., Wąsowicz, W. , Kur, B., Grzelińska, Z. and Majcherek, W. (2013), "Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride", International Journal of Occupational Medicine and Environmental Health, Vol. 26, pp. 647-656, https://doi.org/10.2478/s13382-013-0137-8
  15. Kim, S. H., Kwon, D. Lee, S., Son, S.W., Kwon J. T., Kim P. J. , Lee Y. H. and Jung Y. S. (2020), "Concentration- and Time-Dependent Effects of Benzalkonium Chloride in Human Lung Epithelial Cells: Necrosis, Apoptosis, or Epithelial Mesenchymal Transition", Toxics, Vol. 8, No. 1, pp. 17, https://doi.org/10.3390/toxics8010017
  16. Wentworth, A. B., Yiannias, J.A., Davis, M. D. P., and Killian J.M., (2016), "Benzalkonium Chloride", Dermatitis, Vol. 27, No. 1. pp. 14-20, https://doi.org/10.1097/DER.0000000000000160
  17. Luz, A., DeLeo, P., Pechacek, N. and Freemantle, M. (2020), "Human health hazard assessment of quaternary ammonium compounds: Didecyl dimethyl ammonium chloride and alkyl (C12-C16) dimethyl benzyl ammonium chloride", Regulatory Toxicology and Pharmacology, Vol. 116, pp. 104717. https://doi.org/10.1016/j.yrtph.2020.104717
  18. The official site of the United State Government, (2019), "Pesticides; Technical Amendment to Data Requirements for Antimicrobial Pesticides", available at: https://www.regulations.gov/document/EPA-HQ-OPP-2018-0668-0004
  19. Dumas, O., Boggs, K., Quinot, C., Varraso, R., Zock, J., Henneberger, P., Speizer, F., Le Moual, N. and Camargo, C., (2019), "Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study", American Journal of Industrial Medicine, Vol. 63, No. 1, pp. 44-50, https://doi.org/10.1002/ajim.23067
  20. Preller, L., Doekes, G., Heederik, D., Vermeulen, R., Vogelzang, P. and Boleij, J. (1997), "Disinfectant Use as a Risk Factor for Atopic Sensitization and Symptoms Consistent With Asthma: an Epidemiological Study", Chest, Vol. 112, No. 2, pp. 16, https://doi.org/10.1016/S0012-3692(15)53056-0
  21. Vandenplas, O., D'Alpaos, V., Evrard, G., Jamart, J., Thimpont, J., Huaux, F. and Renauld, J., (2013), "Asthma related to cleaning agents: a clinical insight", BMJ Open, Vol. 3, No. 9, pp. e003568, https://doi.org/10.1136/bmjopen-2013-003568
  22. Lakind, J. and Goodman, M., (2019), "Methodological evaluation of human research on asthmagenicity and occupational cleaning: a case study of quaternary ammonium compounds ("quats")", Allergy, Asthma & Clinical Immunology, Vol. 15, No. 1, https://doi.org/10.1186/s13223-019-0384-8
  23. The Cabinet of Ministers of Ukraine, (2006), Postanova KMU no 908 vid 03.07.2006 . Pro zatverdzhennya poryadku reyestracii (perereyestracii) dezinfikciynyh zasobiv. Resolution of The Cabinet of Ministers of Ukraine no 908 at 03.07.2006. On approval of the procedure for registration (reregistration) of disinfectants. The Cabinet of Ministers of Ukraine, Kiev, Ukraine, available at: https://zakon.rada.gov.ua/laws/show/908-2006-%D0%BF#Text
  24. The Ministry of Health of Ukraine, (2020), Nakas MOZ Ukrainy no 1596 vid 14.07.2020. Pro zatverdzhennya gigiyenichnyh reglamentiv dopustymogo vmistu himichnyh i biologichnyh rechovyn u povitri robochoi zony. Order of the Ministry of Health of Ukraine no 1596 at 14.07.2020. On the approval of hygienic regulations for the permissible content of chemical and biological substances in the air of the working area, The Ministry of Health of Ukraine, Kiev, Ukraine, available at: https://zakon.rada.gov.ua/laws/show/z0741-20#Text
  25. The official site of the State institution "O.M. Marzieiev Institute For Pablic Health" (2012), " Regulation (EC) no 528/2012 of the European Parliament and of the Council about using of biocidal agents", available at: http://www.health.gov.ua/docs/presentation/regl528_2012.pdf
  26. The official site of the European Chemical Agency, (2022), "Guidance on the Biocidal Products Regulation Volume I: Identity of the active substance/physico-chemical properties/analytical methodology - Information Requirements, Evaluation and Assessment. Parts A+B+C", available at: https://echa.europa.eu/documents/10162/2324906/bpr_guidance_vols_i_part_abc_en.pdf/31b245e5-52c2-f0c7-04db-8988683cbc4b?t=1648547577294
  27. Merchel Piovesan Pereira, B. and Tagkopoulos, I., (2019), " Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance", Applied and Environmental Microbiology, Vol. 85, No. 13, https://doi.org/10.1128/AEM.00377-19
  28. The official site of the United States European Protection Agency, (2022), "About List N: Disinfectants for Coronavirus (COVID-19)", available at: https://www.epa.gov/coronavirus/about-list-n-disinfectants-coronavirus-covid-19-0
  29. The official site of the National Toxicology Program, "Biocides & Potential Respiratory Health Outcomes", available at: https://ntp.niehs.nih.gov/whatwestudy/assessments/noncancer/ongoing/biocides/index.htm
  30. Dotson, G.S., Lotter, J.T., Zisook, R.E., Gaffney, S. H., Maier, A. and Colvin, J., (2020), "Setting occupational exposure limits for antimicrobial agents: A case study based on a quaternary ammonium compound-based disinfectant", Toxicology and Industrial Health, Vol. 36, No. 9, pp. 619-633, https://doi.org/10.1177/0748233720970438
  31. The official site of the Organisation for Economic Cooperation and Development, (2014), "Guidance on grouping of chemicals, second edition", available at: https://www.oecd.Org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono(2014)4&doclanguage=en
  32. Escher, S. E., Kamp, H. and Bennekou, S.H. et al., (2019), "Towards grouping concepts based on new approach methodologies in chemical hazard assessment: the read-across approach of the EU-ToxRisk project", Arch Toxicol, Vol. 93, pp. 3643-3667, https://doi.org/10.1007/s00204-019-02591-7
  33. An official website of European Union, (2006), "Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006", available at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02006R1907ї-20140410
  34. The Cabinet of Ministers of Ukraine, (2022), Nakaz KMU no 712 vid 24.06.2022 . Pro vnesennya zminy do Polozhennya pro gigienichnu reglamentaciyu ta derzhavnu reyestraciyu nebezpechyh faktjriv. Order of The Cabinet of Ministers of Ukraine no 712 at 24.06.2022 . On amending the Regulation on hygienic regulations and state registration of dangerous factors. The Cabinet of Ministers of Ukraine, Kiev, Ukraine, available at: https://www.kmu.gov.ua/npas/pro-vnesennya-zmini-do-polozhennya-pro-gigiyenichnu-reglamentaciyu-ta-s712-240622