Theo Nash
The COVID-19 pandemic caused a surge in demand for hand sanitizers, leading to a search for effective non-alcoholic alternatives. Benzalkonium chloride (BKC) is a quaternary ammonium compound that has been evaluated as a potential alternative active ingredient to ethyl alcohol in hand sanitizers. While BKC has shown promising results in some studies, outperforming alcohol-based sanitizers in terms of reduced irritation and persistence, concerns have been raised about its potential side effects and toxicity. Additionally, bacteria can develop resistance to BKC, which is not the case with alcohol. This comparison between ethyl alcohol and benzalkonium chloride as effective disinfectants warrants further investigation.
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What You'll Learn
Benzalkonium chloride as an alternative to alcohol-based hand gels
Benzalkonium chloride-based hand sanitizers have emerged as a potential alternative to traditional alcohol-based hand gels. The active ingredient in most hand sanitizers is alcohol, typically ethyl alcohol or isopropyl alcohol, which has broad-spectrum antimicrobial properties. However, concerns about flammability, skin irritation, and accidental ingestion have spurred the development of alcohol-free alternatives.
Benzalkonium chloride, a quaternary ammonium compound, is one such alternative that has been evaluated in various studies. It is structured as a benzyl-dimethyl-ammonium chloride linked to alkyl chains (C12 and C14). One of the advantages of benzalkonium chloride-based hand sanitizers is their non-flammable nature, reducing the risk of fires and burns associated with alcohol-based products. Additionally, these sanitizers are less irritating to the skin, addressing the issue of skin dryness and contact dermatitis caused by frequent use of alcohol-based gels.
In terms of antimicrobial efficacy, research has yielded inconsistent findings. Some studies have shown that benzalkonium chloride-based sanitizers are equally effective in reducing bacterial counts as alcohol-based gels. However, other studies have reported variations in the range and duration of antimicrobial action. Benzalkonium chloride-based sanitizers have demonstrated greater sustained antibacterial activity, providing 2 to 4 hours of residual protection. On the other hand, long-term exposure to benzalkonium chloride has been associated with changes in microbial community structure and increased antimicrobial resistance.
Overall, benzalkonium chloride-based hand sanitizers offer a promising alternative to alcohol-based hand gels, particularly in situations where alcohol supply may be limited or when skin irritation is a concern. However, further research is needed to comprehensively understand the efficacy and potential long-term effects of benzalkonium chloride as an active ingredient in hand hygiene products.
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Effectiveness against SARS-CoV-2
The use of hand sanitizers has been one of the effective measures for reducing the transmission of infections, including SARS-CoV-2. The active ingredient in alcohol-based hand sanitizers (ABHS) is usually ethyl alcohol (70% to 80% v/v) or isopropyl alcohol (70% to 75% v/v). However, non-alcohol-based hand sanitizers (NABHS) may contain surfactants, including quaternary ammonium compounds such as benzalkonium chloride (BKC).
BKC has been used as an antimicrobial for decades due to its broad-spectrum activity against some bacteria, viruses, and fungi. It is also used as a preservative in the food industry, a surface disinfectant, an antiseptic, and a hand sanitizer in healthcare settings.
During the COVID-19 pandemic, there were occasional shortages of hand sanitizers containing ethanol or isopropanol as active ingredients. This led to a search for gentler, alcohol-free alternatives, and benzalkonium chloride emerged as a potential solution.
Several studies have demonstrated the effectiveness of benzalkonium chloride against SARS-CoV-2. For example, a study by Chin et al. (2020) found that BKC at a concentration of 0.1% could inactivate the virus on surfaces within 5 minutes. Another study by Ogilvie et al. (2021) showed that BKC at a concentration of 0.13% as commercially available hand sanitizing wipes rapidly inactivated the virus within 15 seconds of exposure. Furthermore, a study by BYU researchers, published in the Journal of Hospital Infection, found that benzalkonium chloride could kill 99.9% of the SARS-CoV-2 virus within 15 seconds.
In comparison to alcohol-based sanitizers, benzalkonium chloride has been shown to have significantly more residual antibacterial action on the skin after the initial application. It has demonstrated persistent antimicrobial activity for up to four hours after contact, while ethanol-based sanitizers provide skin protection for only 10 minutes post-application. Benzalkonium chloride can also be used in much lower concentrations and does not cause the same level of skin irritation or the "burn" feeling associated with alcohol-based sanitizers.
However, it is important to note that the CDC states that available evidence indicates benzalkonium chloride has less reliable activity against certain bacteria and viruses than alcohol-based sanitizers.
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Effectiveness against Staphylococcus aureus
The effectiveness of ethyl alcohol and benzalkonium chloride against Staphylococcus aureus has been compared in several studies. One study evaluated the effectiveness of a new commercially available hand sanitiser using 0.12% benzalkonium chloride (BZK) as the active ingredient in reducing transient skin contamination with Staphylococcus aureus in healthcare workers (HCWs), compared to a 70% ethanol-based hand sanitiser. The study found a significant decrease in transient S. aureus on the fingertips of HCWs in the BZK hand sanitiser use week compared to the 70% ethanol hand sanitiser use week.
Another study compared the antibacterial efficacy of 46 commercially available hand sanitisers, including those with 80% ethanol or 75% isopropyl alcohol, and those with benzalkonium chloride as the active ingredient. The results showed that formulations following World Health Organization-recommended ingredients or those including benzalkonium chloride displayed excellent antibacterial activity against Staphylococcus aureus.
In addition, a study by Bondurant et al. (2019) evaluated the persistent antibacterial efficacy of a hand sanitiser containing benzalkonium chloride on human skin at 1, 2, and 4 hours after application. The results demonstrated a significant reduction in transient Staphylococcus aureus bacterial skin contamination in healthcare workers.
However, it is important to note that ethyl alcohol has also been found to be effective against Staphylococcus aureus. Its effectiveness is attributed to its ability to denature proteins, which is a critical mechanism in destroying bacteria. The bactericidal activity of various concentrations of ethyl alcohol (ethanol) was examined against a variety of microorganisms, including Staphylococcus aureus.
In summary, both ethyl alcohol and benzalkonium chloride have been found to be effective against Staphylococcus aureus in different studies. The choice between the two may depend on various factors, such as skin irritation, availability, and personal preference.
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Toxicity and side effects
Benzalkonium chloride has been linked to several toxicities and side effects. It is a human skin and eye irritant, causing ocular toxicity. It is also a severe respiratory irritant and can cause or exacerbate asthma. Inner ear toxicity has been observed, along with adverse effects on ciliary motion, mucociliary clearance, nasal mucosal histology, human neutrophil function, and leukocyte response to local inflammation. It has also been associated with neurotoxicity, endocrine disruption, and non-reproductive organ system toxicity.
Occupational exposure to benzalkonium chloride has been linked to the development of asthma, and poisoning by ingestion is possible, with a case study detailing the fatal ingestion of 240ml of 10% benzalkonium chloride. Concentrated solutions are toxic to humans, causing corrosion and irritation to the skin and mucosa, and death if ingested in sufficient volumes. 0.1% is the maximum concentration that does not produce primary irritation on intact skin.
The use of benzalkonium chloride in consumer products has been restricted due to its potential hazards. It is still found in many household disinfectants and cleaning supplies, as well as in ophthalmic preparations and nasal sprays, despite concerns about its ocular toxicity and irritant properties.
Ethyl alcohol, on the other hand, has its own set of toxicities and side effects. It can cause acute alcohol intoxication, leading to metabolic abnormalities such as lactic acidosis, hypoglycemia, and hypokalemia. It can also affect the cardiovascular system, causing atrial and ventricular tachydysrhythmias and potentially leading to "holiday heart syndrome", which involves new-onset arrhythmias following acute ingestion.
Chronic alcohol abuse can lead to alcoholic hepatitis and acute-on-chronic liver failure. Heavy drinkers are at a much higher risk of heart failure compared to non-drinkers. Alcohol can also cause contractile dysfunction, increasing the risk of heart failure, stroke, and cardiac death.
Additionally, ethyl alcohol can affect the central nervous system, leading to altered mental status and potentially contributing to conditions such as trauma, sepsis, CNS infections, seizures, hypoxia, and metabolic derangements. It is important to note that ethyl alcohol is rapidly bactericidal and has broad-spectrum activity, but its efficacy decreases significantly when diluted below 50% concentration. The optimum bactericidal concentration is 60%-90% solutions in water.
In summary, both benzalkonium chloride and ethyl alcohol have their own sets of toxicities and side effects. Benzalkonium chloride has been linked to skin, eye, and respiratory irritation, asthma, inner ear toxicity, and potential endocrine disruption. Ethyl alcohol intoxication can cause metabolic abnormalities, cardiovascular issues, liver problems, and altered mental status. Proper use and handling are crucial for both substances to mitigate their respective side effects and toxicities.
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Antimicrobial resistance
Alcohol-based hand sanitizers are considered efficient alternatives to handwashing with water and soap. They are effective against a broad spectrum of microbes. However, limitations such as skin dryness, irritant contact dermatitis, and accidental ingestion have driven the need for effective non-alcoholic alternatives.
Benzalkonium chloride (BKC) is a quaternary ammonium compound with antimicrobial activities. It is a cationic surfactant that damages the cell membrane structural integrity of microbes. BKC-based hand sanitizers have been evaluated as a potential alternative to alcohol-based hand gels, with a focus on reduced irritation and improved persistence.
In a study comparing the effectiveness of benzalkonium chloride and ethanol-based hand sanitizers, healthcare workers used antimicrobial soap for handwashing and an ethanol-based sanitizer for the first week, followed by a BKC-based sanitizer in the subsequent week. The results showed that BKC-based sanitizers could effectively reduce transient Staphylococcus aureus bacterial skin contamination in healthcare workers.
Another study evaluated the antimicrobial properties of commercial hand sanitizers. Formulations containing 80% ethanol or 75% isopropyl alcohol, as well as those with benzalkonium chloride as the active ingredient, displayed excellent antibacterial activity. However, ethyl alcohol formulations performed better than benzalkonium chloride-containing sanitizers against SARS-CoV-2.
While benzalkonium chloride has broad-spectrum antimicrobial properties, some concerns have been raised about microbial resistance. There have been reports of bacterial tolerance and the potential for cross-resistant phenotypes to emerge with frequent exposure to benzalkonium chloride.
In summary, while both ethyl alcohol and benzalkonium chloride have antimicrobial properties, the available evidence suggests that ethyl alcohol-based sanitizers may be more effective against certain bacteria and viruses, including SARS-CoV-2. Benzalkonium chloride-based sanitizers are still effective alternatives, especially in mitigating bacterial skin contamination, but the potential for antimicrobial resistance warrants further investigation.
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Frequently asked questions
The active ingredient in hand sanitizers is ethyl alcohol, usually in a concentration of 70% to 80%, or isopropyl alcohol, in a concentration of 70% to 75%. However, non-alcohol-based hand sanitizers contain benzalkonium chloride as the active ingredient.
The antimicrobial action of alcohol is due to the denaturation of proteins. Absolute ethyl alcohol is a dehydrating agent, but it is less bactericidal than mixtures of alcohol and water because proteins are denatured more quickly in water.
Benzalkonium chloride-based sanitizers have been found to be just as effective as alcohol-based sanitizers. In a 1998 study, a non-alcohol sanitizer with benzalkonium chloride met the FDA performance standards, while a popular alcohol-based sanitizer did not. However, the CDC states that evidence indicates benzalkonium chloride has less reliable activity against certain bacteria and viruses than alcohol.
Benzalkonium chloride has been associated with antibiotic resistance in bacteria such as MRSA. Additionally, a few case reports have documented occupational asthma as a result of exposure to benzalkonium chloride.
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