In Massachusetts, the TURA SAB considers petitions to add or delete chemicals from the TURA chemical list. In reviewing the science about DDAC and ADBAC, the SAB had concerns related to these substances, including respiratory system irritation and inflammation including outcomes consistent with occupational asthma and work-exacerbated asthma; corrosive effects; hazard for aquatic life; and environmental fate and persistence. The SAB had additional concerns for reproductive effects and neural tube development.

QACs are associated with both acute (short-term) and chronic (long-term) health effects. Exposure can occur by inhalation, dermal, and oral routes. QACs pose concerns for people using them for cleaning both in the home and in the workplace. In addition, the residues from treated surfaces, including utensils, countertops, equipment, and appliances, can migrate to food, resulting in ingestion by humans.

The majority of data that regulatory agencies have used to make recommendations on use and health and safety are based on the individual chemical. However, many of these product formulations typically contain several different QAC substances, in addition to other ingredients that may be irritating or sensitizing.[9]

Acute (Short-term) Health Effects

EPA classifies five types of acute exposures (oral, dermal, inhalation, skin and eye irritation) into four Toxicity Categories, Category I being the highest hazard. ADBAC and DDAC are acutely toxic through the oral, dermal, and inhalation exposure routes. EPA classifies both substances in Toxicity Category II for the oral and inhalation route, and Toxicity Category III for the dermal route.

Irritant: Eyes, nose, throat, or lung irritation have all been reported among workers exposed to QACs. For skin and eye irritation EPA has categorized DDAC and ADBAC as Toxicity Category I: Corrosive. According to the European Union’s harmonized classification they are considered irritants and corrosive to the skin and eyes.

Chronic (Long-term) Health Effects

Chronic occupational health hazards associated with using QACs include dermal irritation that may lead to skin sensitization, and an increased risk of asthma.[10],[11],[12],[13] The Association of Occupation and Environmental Clinics (AOEC) lists both DDAC and ADBAC as asthmagens and respiratory sensitizers.[14],[15]

Respiratory Effects/Asthma: Surveillance studies, case reports, and animal studies indicate that DDAC and ADBAC are associated with respiratory system irritation and inflammation including outcomes consistent with occupational asthma and work-exacerbated asthma. Recent studies have suggested that occupational exposure to cleaning agents and disinfectants containing DDAC and ADBAC may cause work-related asthma, chronic obstructive pulmonary disease, and other respiratory illnesses in occupations such as laundry workers, pharmacists, janitors, nursing/medical assistants, health technicians, and housekeepers.[16],[17] Exposure to QACs was found to significantly increase the risk of nasal symptoms and physician diagnosed asthma at work more than any other potentially hazardous exposures including glutaraldehyde, latex gloves, or chlorinated/bleach products.[18]

Dermal Effects: ADBAC and DDAC are highly irritating to the skin, and long-term exposure may result in skin sensitization or allergic dermatitis. There have been several cases in which workers reported symptoms of skin sensitization. More recent animal studies have documented that mice dermally exposed to these substances developed not only irritation but also allergic sensitization.[19]

Emerging Evidence

Reproductive/Developmental Effects: Some emerging evidence has suggested that exposure to QACs such as DDAC and ADBAC may affect reproduction and development in animals.[20] The SAB noted during their review that these early studies are concerning and warrant follow-up, but that the evidence was not yet conclusive. Mice experienced adverse effects after exposure to a ready-to-use product that contained both ADBAC and DDAC, including decreased fertility, fewer pregnancies, reduced number of offspring, disruption of hormone-regulated processes such as ovulation, and birth defects.[21],[22] [23] [24] Exposure to a disinfectant containing both ADBAC and DDAC was associated with delayed neural tube closing in both mice and rats.[25]

Other Human Health Effects: A human biomonitoring study of 43 random volunteers detected measurable concentrations of QACs in the blood of 80% of participants and identified correlations between levels of QACs, cellular disruption and specific biomarkers related to human health.[26] This was the first study to measure QACs in human blood and to find evidence that QAC concentrations may influence important biomarkers. Some recent studies have shown that QACs can worsen inflammation and disrupt overall cellular function and regulation.[27] [28]

Environmental Fate

QACs usually go down the drain and to wastewater treatment plants, which remove some but not all of the QACs prior to discharge to the environment. QACs have been found in surface waters, soil, sediments, and wastewater sludge. Researchers have raised concerns for microorganisms and aquatic organisms as well as the impact of QACs on wastewater treatment plants. DDAC and ADBAC are recognized as toxic to aquatic life. They are considered immobile in soil by both EPA and ECHA. Due to their low volatility, they are expected to bind to sediments and soils. There are also concerns that the overuse of DDAC, ADBAC, and other QACs could lead to development of antibiotic-resistant bacteria.

QACs have also been detected on surfaces long after being used, and in household dust, meaning they may have the potential to persist in the environment, our workplaces, and our homes. A recent study detected 19 different QAC substances in residential dust samples. QACs, the majority of which were ADBAC substances, were found in over 90% of samples taken. When compared to pre-COVID dust samples, the level of QAC concentrations had nearly doubled.[29]

There are numerous suitable alternatives to QACs for disinfecting applications. These include chemical alternatives as well as non-chemical disinfecting technologies. Safer active disinfectant ingredients include hydrogen peroxide, alcohol (isopropyl alcohol or ethanol), caprylic acid, citric acid, and lactic acid.[30] The TURI Laboratory has investigated the performance of many of these products in addition to other safer alternative disinfectants. Review more information on alternatives and TURI’s list of safer disinfectant products. Listed below are some of the safer active ingredients and disinfecting technologies available as alternatives to QACs. All products must be used in accordance with the manufacturer’s label directions, including dilution rates and dwell time on surfaces, in order to ensure proper disinfection.

Caprylic Acid: Caprylic or octanoic acid is a natural agent produced by the distillation of coconut or palm kernel oils. In its pure form it is a colorless and corrosive liquid.

Citric Acid: Citric acid is a naturally occurring substance that can be extracted from pineapple waste and citrus fruits. It is used as an active ingredient in antimicrobial products and can be corrosive in its concentrated form.

Hydrogen Peroxide: Hydrogen peroxide is a clear liquid in its concentrated form that is fairly inexpensive and is easily accessible at most stores. Products that contain hydrogen peroxide as the only active ingredient are generally considered safer alternatives. However, products that contain hydrogen peroxide and peroxyacetic acid together are asthmagens and respiratory sensitizers and are not considered safer alternatives.[31]

L-Lactic Acid: L-Lactic acid is a naturally occurring organic acid that can be used in a variety of applications and on various surfaces as an antimicrobial solution. At the highest level of purification, lactic acid is a colorless and odorless liquid. Concentrated L-Lactic Acid is corrosive and a severe skin and eye irritant.

Additional alternative chemicals

In addition, other active ingredients and disinfecting technologies are useful in some circumstances.

Alcohols: Alcohols such as isopropanol (IPA) and ethanol (ethyl alcohol) are clear colorless liquids in their pure form; they evaporate quickly and are best used for spot cleaning. 70% IPA is also commonly referred to as rubbing alcohol. Concentrated alcohols are flammable and exposure may cause nausea, dizziness, headache, and irritating effects to the skin, eyes, and throat.

Aqueous Ozone: Aqueous ozone is a water-based sanitizer that has been used for years primarily for drinking water disinfection. Only requiring water and electricity, the solution is produced at the point of use in an ozone generator. The technology can be hard piped for large production facilities, smaller portable equipment, and handheld spray bottle devices. Aqueous ozone has a short shelf life as the ozone readily reverts back to oxygen. Ozone gas is on the TURA list of Toxic or Hazardous Substances, and chemical and inhalation exposure at high concentrations can cause respiratory irritation and exacerbate asthma.

Hypochlorous Acid: Hypochlorous acid is a chlorine solution that can be generated by dissolving concentrated sodium dichloroisocyanurate (NaDCC) tablets in water, or by using electrolyzed water systems, which use salt and, in some instances, vinegar, in water that is electrolyzed in small units. Hypochlorous acid has a short shelf life and a slightly acidic pH between 4.5 and 6.0. Chlorine solutions have inherent hazards, but TURI lab testing has found that airborne chlorine is lower for hypochlorous acid solutions than for bleach (sodium hypochlorite) solutions. For more information on hypochlorous acid, see TURI’s fact sheet.

Non-chemical alternatives

Non-chemical technologies for disinfection include UV light and steam.

Steam: High temperature, low-moisture or dry steam does not leave a residue or chemical film, and is effective and suitable for many surfaces. The use of a pressurized system to generate steam at a high temperature creates a risk of burns.

UV Light: UVC light may be appropriate for specific disinfecting applications. For example, it can be used to disinfect unoccupied medical rooms and high-tech electronic devices and can be used inside air ducts to disinfect the air. UV light exposure can be hazardous for the eyes and skin.

ADBAC and DDAC are active ingredients for use in antimicrobial products registered with the U.S. EPA and other agencies around the world. These QACs are regulated under the U.S. EPA FIFRA, the European Biocidal Products Regulation (BPR), Health Canada (HC), and the California Department of Pesticide Regulation (CA DPR). California’s Scientific Guidance Panel recently listed QACs as Priority Chemicals under its Biomonitoring Program.

In Massachusetts, after reviewing the science and the hazards of QACs, the TURA Science Advisory Board recommended in May 2021 that certain DDAC and ADBAC chemicals be added to the TURA list of Toxic or Hazardous Substances. The next steps in the TURA process will include a policy analysis and consideration by the TURA Advisory Committee and TURA Administrative Council.[32]

Chemicals Included in SAB Recommendation

November 2021

References for Quaternary Ammonium Compounds Fact Sheet
[1]United States Environmental Protection Agency, List N: Disinfectants for Use Against SARS-CoV-2 (COVID-19): https://cfpub.epa.gov/wizards/disinfectants/

[2] Vereshchagin, A.N.; Frolov, N.A.; Egorova, K.S.; Seitkalieva, M.M.; Ananikov, V.P. Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials. Int. J. Mol. Sci. 2021, 22, 6793. https://doi.org/10.3390/ijms22136793

[3] USEPA/Office of Pesticide Programs; Didecyl Dimethyl Ammonium Chloride (DDAC) Final Work Plan, Registration Review: Initial Docket Case Number 3003, March 2017. Docket Number EPA-HQ-OPP-2015-0740

[4] United States Environmental Protection Agency (2017) Alkyls Dimethyl Benzyl Ammonium Chloride (ADBAC) Final Work Plan, Registration Review: Initial Docket, Case Number 03050, Docket Number EPA-HQ-OPP-2015-0737.

[5] ECHA; Didecyldimethylammonium chloride (7173-51-5). Registered Data Dossier. Helsinki, Finland: European Chemicals Agency. Accessed at: https://echa.europa.eu/registration-dossier/-/registereddossier/5864/4/2

[6] ECHA; Didecyldimethylammonium chloride (7173-51-5). Registered Data Dossier. Helsinki, Finland: European Chemicals Agency. Accessed at: https://echa.europa.eu/registration-dossier/-/registereddossier/5864/4/2

[7] Stepan Company, Stepanquat 8358: https://zh.stepan.com/content/stepan-dot-com/en/products-markets/product/STEPANQUAT8358.html

[8] Global Antiseptics And Disinfectants Market Report, 2021-2028 (grandviewresearch.com)

[9] Quinn MM, Henneberger PK, Braun B, Delclos GL, Fagan K, Huang V, et al. Cleaning and disinfecting environmental surfaces in health care: toward an integrated framework for infection and occupational illness prevention. Am J Infect Control. 2015;43:424–34.

[10] Vandenplas, O., D’Alpaos, V., Evrard, G., Jamart, J.,Thimpont, J., Huaux, F., Renauld, J., (2013) Asthma related to cleaning agents: a clinical insight. British Medical Journal (http://dx.doi.org/10.1136/

bmjopen-2013-003568

[11] Preller L, Doekes G, Heederik D, Vermeulen R, Vogelzang PF, Boleij JS. Disinfectant use as a risk factor for atopic sensitization and symptoms consistent with asthma: an epidemiological study. Eur Respir J. 1996 Jul;9(7):1407-13. doi: 10.1183/09031936.96.09071407. PMID: 8836651.

[12] Dumas O, Boggs KM, Quinot C, Varraso R, Zock JP, Henneberger PK, Speizer FE, Le Moual N, Camargo CA Jr. Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study. Am J Ind Med. 2020 Jan;63(1):44-50. doi: 10.1002/ajim.23067. Epub 2019 Nov 6. PMID: 31692020; PMCID: PMC6891131.

[13] Bernstein, Jonathan, et al (1994) A combined respiratory and cutaneous hypersensitivity syndrome induced by work exposure to quaternary amines. Journal of Allergy and Clinical Immunology

[14] Association of Occupational and Environmental Clinics (AOEC) Exposure code lookup for Didecyl Dimethyl Ammonium Chloride (CAS 7173-51-5) accessed on 8/17/20: http://www.aoecdata.org/ExpCodeLookup.aspx

[15] Association of Occupational and Environmental Clinics (AOEC) Exposure code lookup for Alkyl Dimethylbenzyl ammonium chloride (CAS #: 68424-85-1) accessed on 10/14/20: http://www.aoecdata.org/ExpCodeLookup.aspx

[16] Dumas O, Varraso R, Boggs KM, et al. Association of Occupational Exposure to Disinfectants With Incidence of Chronic Obstructive Pulmonary Disease Among US Female Nurses. JAMA Netw Open. 2019;2(10):e1913563. doi:10.1001/jamanetworkopen.2019.13563

[17] Dumas O, Boggs KM, Quinot C, Varraso R, Zock JP, Henneberger PK, Speizer FE, Le Moual N, Camargo CA Jr. Occupational exposure to disinfectants and asthma incidence in U.S. nurses: A prospective cohort study. Am J Ind Med. 2020 Jan;63(1):44-50. doi: 10.1002/ajim.23067. Epub 2019 Nov 6. PMID: 31692020; PMCID: PMC6891131.

[18] Gonzalez M, Jégu J, Kopferschmitt MC, Donnay C, Hedelin G, Matzinger F, Velten M, Guilloux L, Cantineau A, de Blay F. Asthma among workers in healthcare settings: role of disinfection with quaternary ammonium compounds. Clin Exp Allergy. 2014 Mar;44(3):393-406. doi: 10.1111/cea.12215. PMID: 24128009.

[19] Anderson, S. E., Shane, H., Long, C., Lukomska, E., Meade, B. J., & Marshall, N. B. (2016). Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride. Journal of Immunotoxicology, 13(4), 557–566. https://doi-org.umasslowell.idm.oclc.org/10.3109/1547691X.2016.1140854

[20] Melin, V. E., Potineni, H., Hunt, P., Griswold, J., Siems, B., Werre, S. R., & Hrubec, T. C. (2014). Exposure to common quaternary ammonium disinfectants decreases fertility in mice. Reproductive Toxicology, 50, 163–170. https://doi-org.umasslowell.idm.oclc.org/10.1016/j.reprotox.2014.07.071

[21] Melin, V. E., Melin, T. E., Dessify, B. J., Nguyen, C. T., Shea, C. S., & Hrubec, T. C. (2016). Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes. Reproductive Toxicology (Elmsford, N.Y.), 59, 159–166. https://doi-org.umasslowell.idm.oclc.org/10.1016/j.reprotox.2015.10.006

[22] Hrubec TC, Melin VE, Shea CS, et al. Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents. Birth Defects Res. 2017;109(14):1166-1178. doi:10.1002/bdr2.1064

[23] Melin, V. E., Potineni, H., Hunt, P., Griswold, J., Siems, B., Werre, S. R., & Hrubec, T. C. (2014). Exposure to common quaternary ammonium disinfectants decreases fertility in mice. Reproductive Toxicology, 50, 163–170. https://doi-org.umasslowell.idm.oclc.org/10.1016/j.reprotox.2014.07.071

[24] Melin VE, Melin TE, Dessify BJ, Nguyen CT, Shea CS, Hrubec TC. Quaternary ammonium disinfectants cause subfertility in mice by targeting both male and female reproductive processes. Reprod Toxicol. 2016 Jan;59:159-66. doi: 10.1016/j.reprotox.2015.10.006. Epub 2015 Nov 12. PMID: 26582257

[25] Hrubec TC, Melin VE, Shea CS, et al. Ambient and Dosed Exposure to Quaternary Ammonium Disinfectants Causes Neural Tube Defects in Rodents. Birth Defects Res. 2017;109(14):1166-1178. doi:10.1002/bdr2.1064

[26] Hrubec TC, et al. (2020) Altered Toxicological Endpoints in Humans with Quaternary Ammonium Compound Exposure doi: https://doi.org/10.1101/2020.07.15.20154963

[27] Herron, J.; Reese, R. C.; Tallman, K. A.; Narayanaswamy, R.; Porter, N. A.; Xu, L., Identification of environmental quaternary ammonium compounds as direct inhibitors of cholesterol biosynthesis. Toxicol. Sci. 2016, 151, 261-270.

[28] Datta, S.; He, G.; Tomilov, A.; Sahdeo, S.; Denison, M. S.; Cortopassi, G., In vitro evaluation of mitochondrial function and estrogen signaling in cell lines exposed to the antiseptic cetylpyridinium chloride. Environ. Health Perspect. 2017, 125, 087015-087015.

[29] Guomao Zheng, Gabriel M. Filippelli, and Amina Salamova Increased Indoor Exposure to Commonly Used Disinfectant during the COVID-19 Pandemic, Environmental Science & Technology Letters 2020 7 (10), 760-765 DOI: 10.1021/acs.estlett.0c00587

[30] https://www.epa.gov/pesticide-labels/dfe-certified-disinfectants

[31] Association of Occupational and Environmental Clinics (AOEC) Exposure Code 050.480 “Mixture of Hydrogen Peroxide and Peroxyacetic Acid” Accessed 9/21/2021: http://www.aoecdata.org/ExpCodeLookup.aspx

[32]https://www.turi.org/content/download/11795/186838/file/Decision-making%20under%20TURA%20-%20October%202018.pdf