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The method of read-across as a basis for group standardization of harmful compounds in the air of the working area (as exemplified by dialkyldimethylammonium chlorides С8-С10 homologues)

ISSN 2223-6775 Ukrainian journal of occupational health Vol.19, No 2, 2023

The method of read-across as a basis for group standardization of harmful compounds in the air of the working area (as exemplified by dialkyldimethylammonium chlorides C8-C10 homologues)

Turkina V.A., Alyokhina T.A.
Danylo Halytsky Lviv National Medical University, Lviv

Full article (PDF): ENG / UKR

Introduction. The situation of recent years during the SARS-CoV-2 pandemic has aggravated the problem of an insufficient number of approved hygienic standards of active substances included in disinfectants. This, in turn, has become a deterrent to the introduction of such agents into practice. For the proper organization of chemical safety of the workforce new methods of substantiating hygienic standards need to be developed. One of the ways to overcome the outlined higher problem, which will significantly speed up the resolution of the situation, is the introduction of read-across as an express method of substantiating the maximum permissible concentrations for a group (cluster) of compounds.

The purpose of the research is to substantiate the possibilities of developing group regulations for this cluster of compounds in the air of the working area based on data about the physicochemical and toxicological characteristics of dialkyldimethylammonium chloride С810 homologues.

Results. Similar chemical structure of dialkyldimethylammonium chloride C8-C10 homologues determines their similarity in terms of physicochemical and toxicological properties. All substances are solids in their aggregate state, dissolve well in water, have the ability to penetrate biological membranes and disrupt their integrity. According to parameters of acute oral toxicity, dialkyldimethylammonium chloride C8-C10 homologues belong to moderately hazardous substances – hazard class 3, do not cause systemic toxicity; the main negative manifestation of their influence is an irritating effect which further provokes signs of general toxicity. The substances do not have carcinogenic, mutagenic effects, they do not affect reproductive function. The most studied representative of the cluster is didecyldimethylammonium chloride (DC10DAC), which is accepted as a standard (analogue) for all dialkyldimethylammonium chloride C8-C10 homologues. In Ukraine a temporary hygienic standard for didecyldimethylammonium chloride in the air of the working area (approximately safe exposure level, ASEL) has been approved at the level of 0.2 mg/m3, where the limiting criteria for harmfulness are pronounced irritating effect on the skin and mucous membranes of the eyes and an acute inhalation effect. The calculation standard for quaternary ammonium compounds proposed by Dotson G.S. et al. is 0.1 mg/m3. Both standards belong to the II class of safety.

Conclusions. The read-across method allows for accepting didecyldimethylammonium chloride (DC10DAC) as a standard (analogue) for all dialkyldimethylammonium chloride C8-C10 homologues. The hygienic regulation of the permissible content of didecyldimethylammonium chloride obtained on the basis of additional experimental studies as a result of the application of the cluster approach will be legitimate for dioctyldimethylammonium chloride (DC8DAC); octyldecyldimethylammonium chloride (DC8-10DAC), didecyldimethylammonium chloride (DC10DAC) and their mixtures with different percentage ratios.

Keywords: dialkyldimethylammonium chloride C8-C10 homologues, dialkyl(C8-C10)dimethylammonium chloride, dioctyldimethylammonium chloride, didecyldimethylammonium chloride, read-across, hygienic standard, cluster approach, group hygienic regulation.


  1. Draft didecyl dimethyl ammonium chloride (DDAC) occupational and Residential Exposure Assessment [Internet]. Arlington: Office of Pesticide Programs Antimicrobials Division U.S. Environmental Protection Agency; 2006 [cited 2023 Apr 26]. Available from:
  2. Hora PI, Pati SG, McNamara PJ, Arnold WA. Increased use of quaternary ammonium compounds during the SARS-COV-2 pandemic and beyond: Consideration of environmental implications. Environmental Science & Technology Letters. 2020;7(9):622–31. DOI:
  3. Escher SE, Kamp H, Bennekou SH, Bitsch A, Fisher C, Graepel R, et al. Towards grouping concepts based on new approach methodologies in chemical hazard assessment: The read-across approach of the EU-toxrisk project. Archives of Toxicology. 2019;93(12):3643–67. DOI:
  4. Guidance on grouping of chemicals. OECD Environment Health and Safety Publication. Series on Testing and Assessment No. 80 [Internet]. Paris: Environment Directorate Organisation for Economic Co-operation and Development; 2007 [cited 2023Apr26]. Available from:
  5. Guidance on information requirements and chemical safety assessment. Chapter R.6: QSARs and grouping of chemicals [Internet]. European Chemicals Agency; 2008 [cited 2023Apr26]. Available from:
  6. Read-Across Assessment Framework (RAAF). Considerations on multi-constituent substances and UVCBs. [Internet]. European Chemicals Agency; 2017 [cited 2023Apr26]. Available from:
  7. Korshun MN, Verbilov AA. [Toxicological substantitation of the maximum admissible content of fluorides in air of working area]. Modern problems of toxicology. 2005;2005(4):71-6. Ukrainian.
  8. Turkina VA, Kuzminov BP, Alyokhina TA. [Scientific justification of the group hygiene norm for the cluster of alkylbenzyldimethylammonium chloride compounds in the air of the working area]. Ukrainian Journal of Occupational Health. 2022;18(2):107–18. Ukrainian.
  9. Benkova M, Soukup O, Prchal L, Sleha R, Eleršek T, Novak M, et al. Synthesis, antimicrobial effect and lipophilicity activity dependence of three series of dichained N alkylammonium salts. Chemistry Select. 2019;4(41):12076–84. DOI:
  10. Proposed Re-evaluation Decision. Didecyl Dimethyl Ammonium Chloride Cluster (DDAC) [Internet]. Government of Canada Publications - [cited 2023 Apr 26]. Available from:
  11. Juergensen L, Busnarda J., Caux P-Y, Kent RA. Fate, behavior, and aquatic toxicity of the fungicide DDAC in the Canadian environment. Environmental Toxicology. 2000;3(15):174–200. DOI:<174::AID-TOX4>3.0.CO;2-P.
  12. Luz A, DeLeo P, Pechacek N, Freemantle M. Human health hazard assessment of quaternary ammonium compounds: Didecyl dimethyl ammonium chloride and alkyl (C12–C16) dimethyl benzyl ammonium chloride. Regulatory Toxicology and Pharmacology. 2020;116:104717.
  13. Mozrzymas A. On the head group effect on critical micelle concentration of cationic surfactants using molecular connectivity indices and atomic partial charges. Journal of Solution Chemistry. 2019;48(6):875–90. DOI:
  14. Farn RJ. Chemistry and technology of surfactants. Oxford: Blackwell Pub.; 2006. DOI:
  15. Kihara Koji, Yoshikawa Shinichi, Nishio Yumi, Furuta Taro. Existence of an optimal concentration for bactericidal activity of quaternary ammonium compounds. Biocontrol Science. 1997;2(2):61–6. DOI:
  16. Zhou C, Wang Y. Structure–activity relationship of cationic surfactants as antimicrobial agents. Current Opinion in Colloid & Interface Science. 2020;45:28–43. DOI:
  17. Patlewicz GY, Rodford RA, Ellis G, Barratt MD. A QSAR model for the eye irritation of cationic surfactants. Toxicology in Vitro. 2000;14(1):79–84. DOI:
  18. Registration dossier [Internet]. European Chemicals Agency. [cited 2023 Apr 26]. Available from:
  19. Dioctyldimethylammonium chloride [Internet]. United States Environmental Protection Agency [cited 2023 Apr 26]. Available from:
  20. Decyldimethyloctylammonium chloride [Internet]. [cited 2023Apr26]. Available from:
  21. Octyl decyl dimethyl ammonium chloride [Internet]. United States Environmental Protection Agency [cited 2023 Apr 26]. Available from:
  22. Didecyldimethylammonium chloride [Internet]. European Chemicals Agency. [cited 2023 Apr 26]. Available from:
  23. Didecyldimethylammonium chloride [Internet]. United States Environmental Protection Agency [cited 2023Apr26]. Available from:
  24. Hrubec TC, Seguin RP, Xu L, Cortopassi GA, Datta S, Hanlon AL, et al. Altered toxicological endpoints in humans from common quaternary ammonium compound disinfectant exposure. Toxicology Reports. 2021;8:646–56. DOI:
  25. Quaternary ammonium compounds, di-C8-10-alkyldimethyl, chlorides [Internet]. European Chemicals Agency [cited 2023 Apr26]. Available from:
  26. Song IS, Choi MK, Shim WS, Shim CK. Transport of organic cationic drugs: Effect of ion-pair formation with bile salts on the biliary excretion and pharmacokinetics. Pharmacology & Therapeutics. 2013;138(1):142–54. DOI:
  27. Osimitz TG, Droege W. Adverse outcome pathway for antimicrobial quaternary ammonium compounds. Journal of Toxicology and Environmental Health, Part A. 2022;85(12):494–510. DOI:
  28. Ohnuma A, Yoshida T, Horiuchi H, Fukumori J, Tomita M, Kojima S, et al. Altered pulmonary defense system in lung injury induced by didecyldimethylammonium chloride in mice. Inhalation Toxicology. 2011;23(8):476–85. DOI:
  29. Lukáč Miloš, Pisárčik Martin, Devínsky Ferdinand. Cationic amphiphiles: Self-assembling systems for biomedicine and Pharmacies. Nova Science Publishers Incorporated; 2017.
  30. Peyneau M, de Chaisemartin L, Gigant N, Chollet-Martin S, Kerdine-Römer S. Quaternary ammonium compounds in hypersensitivity reactions. Frontiers in Toxicology. 2022;4. DOI:
  31. Association of Occupational and Environmental Clinic [Internet]. Washington: AOEC [cited 2023 Apr 26]. Available from:
  32. Hostetler KA, Fisher LC, Burruss BL. Prenatal developmental toxicity of alkyl dimethyl benzyl ammonium chloride and didecyl dimethyl ammonium chloride in cd rats and New Zealand white rabbits. Birth Defects Research. 2021;113(12):925–44. DOI:
  33. Pauluhn J, Mohr U. Review article: Inhalation studies in laboratory animals—current concepts and alternatives. Toxicologic Pathology. 2000;28(5):734–53. DOI:
  34. Shusterman D, Matovinovic E, Salmon A. Does Haber's law apply to human sensory irritation? Inhalation Toxicology. 2006;18(7):457–71. DOI:
  35. Zhminko PG, Voronina VM, Svitlyi SS, Rudaya LO. [Toxicological substantiation for Didecyldimethylammonium Chloride Occupational Exposure Standard]. Ukrainian Journal of Modern Toxicological Aspects. 2020;88(1):54–60. DOI: Ukrainian.
  36. Dotson GS, Lotter JT, Zisook RE, Gaffney SH, Maier A, Colvin J. Setting occupational exposure limits for antimicrobial agents: A case study based on a quaternary ammonium compound-based disinfectant. Toxicology and Industrial Health. 2020;36(9):619–33. DOI:
  37. On the approval of hygienic regulations on the permissible content of chemical and biological substances in the air of the working area]. Order of the Ministry of Health Protection of Ukraine No.1596 [Internet] 2020 July 14 [cited 2023 Apr 28]. Available from: Ukrainain.