Antimicrobial Quaternary Ammonium Compounds can be Toxic

Quaternary ammonium compounds (QACs), also known as quats, are widely used in various products for their antimicrobial, preservative, and cleaning properties. These include disinfectants, personal care items, and household goods.

Research conducted before and during the COVID-19 pandemic has shown a significant increase in human exposure to QACs, particularly because these chemicals can easily attach to airborne particles and dust. One study found QACs in over 90% of residential dust samples collected during the pandemic, with concentrations much higher than those measured before COVID-19 and closely linked to how frequently homes were disinfected.

In addition to increased indoor exposure, environmental releases of QACs have also risen. The heightened use of cleaning and disinfecting products during the pandemic has led to more QACs entering the environment, raising concerns about their potential health and ecological effects. As QACs can persist in dust and other environmental media, monitoring and managing their levels is essential to protect both human health and the environment.

QACs include hundreds of chemicals and mixtures used in:

• Antimicrobial products
• Antistatic agents
• Biomedical instruments
• Cleaning products
• Dispersants
• Personal care products
• Pesticide products
• Preservatives
• Sanitary wipes, including surface, baby, hand, and disinfecting wipes
• Softening agents
• Surfactants
• Textiles

QACs were frequently used as replacement chemicals in over-the-counter hand and body washes after the 2016 FDA ban on 19 active ingredients, including triclosan and triclocarban.

The original FDA rule also included benzalkonium chloride and benzethonium chloride, but they were removed from the final rule to allow manufacturers more time to submit data on their safety and effectiveness.

A 2018 study concluded that benzalkonium chloride and benzethonium chloride are more toxic to environmental model organisms than triclosan and triclocarban and should not be considered safer alternatives in this respect.

Suspected or known adverse health outcomes from QACs include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs’ role in antimicrobial resistance has also been demonstrated.

QAC exposure routes from products and other sources, via pathways indoors and outdoors.

Common Subclasses of QACs and Associated Products^a.

A Structures of some of these subclasses are shown in Figure S1. QAC product types are excerpts from the larger product Table S1. Chemical functions are derived from product ingredient information on manufacturer websites, EPA’s CompTox Dashboard,25 general understanding of QAC uses and applications as described above, and the Handbook of Applied Surface and Colloid Chemistry, Vol. 1.26 Abbreviations by others: *, Benzalkonium chloride as BAC (see further discussion in the text); **, chloride salt of DADMAC C10:C10 as DDAC.

Proposed ADME routes for QACs based on in vitro and in vivo data on some subgroups of QACs in humans and animal

Environmental Research Recommendations

• Conduct comprehensive monitoring of wastewater influent, effluent and biosolids, as well as impacted surface waters, to better understand the fate and transport of QACs in the environment and potential sources and exposure pathways for biota.
• Perform experimental and theoretical research on the physicochemical properties, environmental and biological behavior, and fate and transport of a wide array of QACs.
• In particular the persistence of QACs in soil/sediment needs to be better understood.

Human Health Research Recommendations

• Conduct quantitative exposure surveys and collect comprehensive biomonitoring data on QACs and QAC metabolites in blood, urine, and feces (e.g., in the general public through NHANES and in highly exposed populations via National Institute for Occupational Safety and Health (NIOSH) or the Nurses’ Health Study.
• Study QACs in indoor environments to better characterize human exposure (dermal, inhalation, and ingestion) directly from products and through routes such as household air and dust.
• Additional research on metabolic fate will help us better understand how the human body absorbs, distributes, metabolizes, and excretes QACs.
• Human epidemiological and animal toxicity studies of respiratory, immune, reproductive, developmental, and other sensitive endpoints should be conducted to replicate and expand on current findings in animal models.

Policy Recommendations

• Include QACs on lists of contaminants of emerging concern used for reporting, monitoring, assessment, etc. This should also include QACs not registered as antimicrobials but used in large quantities or detected in the environment.
• Regulate QACs consistently across different uses and agencies and consider exposure from multiple sources when evaluating allowable concentrations, formulations, and conditions of use.
• Require full disclosure of the exact QACs used in all products, their functions (including for non-antimicrobial use such as material preservation or odor control), and production volumes.
• Develop a generally agreed-upon definition of the entire class of QACs, perhaps with the help of the National Academies of Science and Medicine, to better understand the scope of the problem and support research and policy initiatives.
• Revisit QACs on the EPA Safer Chemical Ingredient List to ensure that they have been assessed for endpoints of concern identified for other QACs.
• Finalize the FDA assessments regarding safety and effectiveness of benzalkonium chloride and benzethonium chloride in over-the-counter hand and body washes.
• Establish a more rigorous process to incorporate academic findings in investigations of health or environmental hazards of QACs carried out by regulatory agencies.
• Immediately address the known threat of antimicrobial resistance.
• An example would be product labeling requirements such as “To reduce the public health threat of antimicrobial resistance, use this product only when disinfection is necessary and not for general cleaning”.
• Manufacturers should also be discouraged from implying a health benefit of QAC use in coatings and other durable product treatments without supporting evidence that these treatments are effective in reducing the transmission of infectious diseases.

The Bottom Line

Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal.

Reference

Arnold, William A et al. “Quaternary Ammonium Compounds: A Chemical Class of Emerging Concern.” Environmental science & technology vol. 57,20 (2023): 7645-7665. doi:10.1021/acs.est.2c08244 Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works https://creativecommons.org/licenses/by-nc-nd/4.0/).

Wait, there’s more!

Alternatives

• Guidelines During COVID-19: The CDC and WHO recommend washing hands with soap and water for at least 20 seconds, especially after being in public or after coughing and sneezing. If soap isn't available, using ethyl or isopropyl alcohol-based hand sanitizers is advised.
• Effective Alcohol Concentrations: Hand sanitizers are most effective when they contain 60-80% alcohol, which effectively kills viruses and bacteria. Higher concentrations do not necessarily improve effectiveness and can sometimes be less effective.
• Safety Risks: Overusing sanitizers can lead to skin irritation and serious toxicity. Methanol-based products are highly toxic and should be avoided.
• Alternative Sanitization Methods: When soap, water, or alcohol-based sanitizers aren't available, options like sand, soil, ash, seawater, sunlight, and 40% alcohol spirits can be used for hand hygiene.
• Best Practices: Use hand sanitizers in moderation, choose products with the recommended alcohol concentrations, and select reputable brands to ensure safety and effectiveness.
  
  

References

Kweon, Hyukmin et al. “Analysis of Consumer Exposure Cases for Alcohol-Based Disinfectant and Hand Sanitizer Use against Coronavirus Disease 2019 (COVID-19).” International journal of environmental research and public health vol. 19,1 100. 23 Dec. 2021, doi:10.3390/ijerph19010100

Meyers, C et al. “Ethanol and isopropanol inactivation of human coronavirus on hard surfaces.” The Journal of hospital infection vol. 107 (2021): 45-49. doi:10.1016/j.jhin.2020.09.026