Lead Section: Hypochlorous acid (HOCl) is a weak acid with powerful antimicrobial properties, formed when chlorine dissolves in water and partially dissociates. Initially discovered in 1834 by French chemist Antoine Jérôme Balard, and later refined through electrochemical methods by Michael Faraday, HOCl has garnered significant attention for its efficacy as a disinfectant, especially in recent years amid the COVID-19 pandemic. Its broad-spectrum antimicrobial action makes it a valuable asset in healthcare, agriculture, and sanitation, owing to its safety, non-toxicity, and effectiveness against a range of pathogens, including antibiotic-resistant bacteria and viruses. Chemically, hypochlorous acid serves as a potent oxidizer and disrupts the cell membranes of microorganisms, rendering them inactive. Despite its efficacy, maintaining a stable HOCl solution presents challenges, as it tends to revert to saltwater under normal storage conditions. Innovations in production methods, such as electrolysis and fermentation, as well as advanced stabilization techniques, have improved the commercial viability of medical-grade HOCl solutions. These advancements are essential for its application in healthcare settings, where HOCl is utilized for wound care, disinfection, and even in eye care and veterinary products approved by the U.S. Food and Drug Administration (FDA). Hypochlorous acid is notable not only for its external applications but also as a naturally occurring substance within the human immune system. White blood cells produce HOCl to combat invading pathogens, underscoring its compatibility and safety for human use. Its antimicrobial action extends to wound healing, where it targets biofilm formation and accelerates the healing process without being cytotoxic to human cells. Additionally, HOCl is employed in various forms, including sprays, wet wipes, and aerosolized applications, to disinfect environments effectively. The use of HOCl is regulated by multiple agencies, including the FDA and the U.S. Department of Agriculture (USDA), which recognize its safety and efficacy for medical, agricultural, and disinfection purposes. Despite its benefits, some controversies exist regarding its stability and the potential for cytotoxicity at higher concentrations. Ongoing research and technological innovations continue to enhance its stability and broaden its applications, solidifying hypochlorous acid’s role as a critical component in modern disinfection and healthcare practices.
History
Hypochlorous acid (HOCl) was first discovered in 1834 by the French chemist Antoine Jérôme Balard (1802–1876). Balard made this discovery by adding a dilute suspension of mercury(II) oxide in water to a flask containing chlorine gas, resulting in the formation of HOCl[1][2]. He also named the acid and its compounds. Despite being relatively easy to produce, maintaining a stable solution of hypochlorous acid has proven to be challenging[2]. Later in the 19th century, the renowned scientist Michael Faraday developed a successful technique for generating hypochlorous acid from saltwater through a process known as electrochemical activation[1]. This process remains in use today for the production of HOCl. In recent years, hypochlorous acid has gained significant attention for its disinfectant properties, particularly during the COVID-19 pandemic. Research indicates that HOCl is highly effective in sanitizing against the COVID-19 virus, offering a practical, inexpensive, and nontoxic disinfectant solution suitable for daily use in various settings[3][4]. The compound has also found applications in healthcare, agriculture, and sanitation due to its safety and efficacy[5].
Chemical Composition and Properties
Hypochlorous acid (HOCl) is a weak acid formed when chlorine dissolves in water and partially dissociates, yielding the hypochlorite anion (ClO−)[2]. It cannot be isolated from its aqueous solutions due to rapid equilibration with its precursor, chlorine[2]. The acid and its conjugate base, hypochlorite, are potent oxidizers and serve as the primary disinfection agents in chlorine solutions[2]. The synthesis of hypochlorous acid is straightforward, typically involving the electrolysis of a saline solution, which can include common ingredients like salt, water, and vinegar[5]. This electrolysis process yields a stable and potent disinfectant that is effective against a broad spectrum of microorganisms[6]. Hypochlorous acid is notable for its strong antimicrobial properties. It disrupts the cell membranes of microorganisms, including bacteria and viruses, rendering them inactive[5]. This mechanism makes it a valuable disinfectant in various applications, including healthcare, sanitation, and agriculture[5][3]. In terms of stability, the efficacy of hypochlorous acid can be influenced by the pH of the solution. It is crucial to maintain the pH within its natural range to ensure optimal performance and to prevent any potential harm to the skin[7]. Moreover, hypochlorous acid’s antimicrobial action extends to the medical field, where it has been shown to inactivate a range of pathogens, including antibiotic-resistant bacteria and viruses[8]. Its safety profile, environmental benignity, and lack of harmful residues make it an attractive alternative to conventional disinfectants[8][9]. Hypochlorous acid is also present naturally in the human immune system. White blood cells produce HOCl as a defense mechanism against invading pathogens, underscoring its efficacy and safety for human use[2].
Production Methods
Electrolysis
The most common method for producing hypochlorous acid is through the electrolysis of saline solutions. This process was first explained by Michael Faraday in the 1830s, when he developed the Laws of Electrolysis[10]. By conducting electrical current across two electrodes in a salt brine solution, various products can be generated, including chlorine gas, sodium hypochlorite (bleach), and hypochlorous acid[10]. Adjusting the chemical conditions, such as adding hydrochloric acid (HCl) to the saline solution, can help stabilize the production of hypochlorous acid, although its stability remains a challenge[11][2].
Fermentation
One method to produce medical-grade hypochlorous acid (HOCl) involves the use of fermentors, where high cell density microbial cultivations can be performed under carefully controlled conditions[12]. Fermentation processes have been optimized over the decades to produce bulk amino acids, and similar principles can be adapted for HOCl production. These processes involve multiple steps: cultivation of microbial production strains, removal of cells by centrifugation or ultrafiltration, separation and purification of the product from the fermented broth, evaporation and drying, and finally, wastewater treatment[12].
Stabilization Techniques
One of the significant challenges in producing medical-grade hypochlorous acid is maintaining its stability. While HOCl is a powerful disinfectant, it is notoriously unstable, often reverting back to salt water under normal storage conditions[2]. Innovations in continuous flow electrochemical cells have made it possible to produce more stable solutions, allowing for commercial and industrial applications[2]. Companies like Pure&Clean have developed unique processes and use quality ingredients to produce highly stable HOCl solutions, including rare HOCl Hydrogel products for medical applications[13].
pH Considerations
The stability and effectiveness of hypochlorous acid solutions are highly dependent on maintaining a proper pH balance. Products with a pH within its natural range ensure that HOCl works optimally without causing harm to the skin or losing its disinfecting capabilities[7]. This is crucial for both the stability of the active ingredient and its efficacy as a disinfectant.
Environmental and Biological Factors
The production and use of hypochlorous acid also intersect with environmental and biological considerations. External factors, referred to as the ‘skin exposome,’ affect the structure and function of the skin and its cellular components. Hypochlorous acid serves multiple roles, including as an innate immune factor and a topical chemopreventive agent against solar UV-induced skin cancer[14]. Its production methods must, therefore, account for these complex interactions to ensure safety and efficacy in medical applications.
Mechanisms of Action
Hypochlorous acid (HOCl) is a multifaceted compound with significant roles in the innate immune system, environmental toxicology, and as a topical chemopreventive agent against solar UV-induced skin cancer[14]. Its mechanisms of action are diverse and involve complex interactions at the cellular and molecular levels. HOCl is produced by the enzyme myeloperoxidase, which uses hydrogen peroxide (H2O2) and chloride ions (Cl-) as substrates[15]. This production process is essential for bacterial killing, although the precise mechanisms are not fully understood. Studies have indicated that while HOCl is a potent oxidant with low specificity at high concentrations, it can selectively inhibit bacterial cell division within phagocytes[15]. Upon exposure to HOCl, bacterial cells undergo several morphological and biochemical changes. These include enhanced surface adhesion, increased production of extracellular polymeric substance (EPS) matrix, and the upregulation of cyclic-di-GMP (c-di-GMP) by diguanylate cyclases (DCGs). Additionally, HOCl influences transcriptional regulators associated with the stress response to HOCl exposure[16]. These adaptations help bacteria survive under adverse conditions by enhancing tolerance and biofilm formation. In the context of wound healing, HOCl exhibits potent antimicrobial properties by targeting biofilm formation and increasing the killing rate of common wound pathogens. However, its cytotoxicity remains a point of contention in wound care applications[17]. Furthermore, in non-myeloid cells, chloride ions can enhance antiviral innate immune responses by increasing intracellular HOCl levels[18]. This highlights the broad spectrum of biological activities and potential therapeutic applications of HOCl.
Applications in Healthcare
Hypochlorous acid (HOCl) has gained widespread recognition in healthcare for its versatility and efficacy as a disinfectant and wound care agent. It is particularly valued for being a relatively inexpensive, nontoxic, noncorrosive, and well-studied compound, with extensive applications across various healthcare settings[3].
Eye Care and Veterinary Applications
The FDA has also approved HOCl for use in eye care products, underscoring its safety and efficacy in treating eye infections[19]. Additionally, HOCl is commonly used in veterinary care products, where it aids in wound healing and infection control in animals[19].
Wound Care
One of the primary uses of HOCl in healthcare is in wound care. The U.S. Food and Drug Administration (FDA) has approved products with hypochlorous acid as the main active ingredient for treating wounds and various infections in both humans and pets[2][19]. HOCl is utilized for its ability to eradicate biofilm and accelerate wound healing without being cytotoxic to human cells, making it an ideal candidate for managing chronic wounds and scar treatment in dermatologic and plastic surgery procedures[17]. It operates by altering the protective protein coats of pathogens, causing them to lose their structure and aggregate, thus enhancing the body’s natural healing processes[3][4].
Disinfection
HOCl is also extensively used for disinfection purposes in healthcare environments. The U.S. Environmental Protection Agency has recommended several disinfectants against COVID-19, including hypochlorous acid, due to its effectiveness in destroying the cell walls of microbes or viruses, thereby inactivating them[3]. It is commonly employed in various forms, including liquid sprays, wet wipes, and aerosolized applications[2]. Recent studies have indicated its suitability for fogging and aerosolized applications in disinfection chambers, which is especially beneficial for sanitizing indoor settings such as offices, hospitals, and healthcare clinics[2].
Dermatology
In dermatology, hypochlorous acid is lauded for its gentleness on the skin while being harsh on harmful bacteria. It is recommended by skin experts for combating common bacterial skin problems like acne, eczema, and psoriasis. HOCl-based products can disinfect the skin, reduce inflammation, and speed up natural healing processes, making it a valuable addition to skincare routines[4][20]. Its non-toxic nature allows for safe application on even sensitive skin, highlighting its versatility in treating a variety of dermatological conditions[5].
Food Service and Water Distribution
Beyond healthcare, HOCl finds application in food service and water distribution industries. Specialized equipment is often used to generate weak solutions of HOCl from water and salt to disinfect food preparation surfaces and water supplies, ensuring safety and hygiene in these settings[2].
Safety and Regulatory Guidelines
FDA Approvals and Usage
Hypochlorous acid (HOCl) has garnered significant attention for its safety and efficacy in various applications, especially in healthcare and medical settings. The U.S. Food and Drug Administration (FDA) has approved hypochlorous acid for use in wound healing and wound care, as well as in eye care products and veterinary care products[19]. Furthermore, the FDA recognizes HOCl as a preservative in saline solutions[2]. The chemical is used in multiple forms including liquid sprays, wet wipes, and aerosolized applications[2].
USDA and Organic Production
In addition to FDA endorsements, hypochlorous acid is approved by the U.S. Department of Agriculture (USDA) for use in organic crop production[19]. The USDA National Organic Program (NOP) has outlined that electrolyzed water, another term for hypochlorous acid, is a type of chlorine material allowed in organic production and handling[21]. This approval is rooted in the USDA’s broader regulatory framework which includes directives for safe and suitable ingredients used in the production of meat, poultry, and egg products[21].
Food Contact Notification
Hypochlorous acid is also recognized under the Food Contact Notification (FCN) 1811 by the FDA. This notification permits the use of electrolytically generated hypochlorous acid as an antimicrobial agent in the production and preparation of various food items including whole or cut meat, poultry, fish, seafood, fruits, vegetables, and shell eggs[21]. This regulatory green light underscores the versatility and safety of HOCl in food-related applications.
Efficacy in Disinfection
HOCl’s safety profile extends to its use in disinfection. Studies have demonstrated its suitability for fogging and aerosolized applications to disinfect indoor settings such as offices, hospitals, and healthcare clinics[2]. Adjustments in concentration and pH levels pre-fogging ensure effective pathogen inactivation, leading to substantial reductions in viral infectivity and RNA titers on surfaces[3].
Toxicity and Safety Data
The safety of hypochlorous acid is further validated by its low toxicity. The reported LD50 (lethal dose) ranges between 0.0104–0.156 ppm, and a concentration of 2.6 ppm has shown to cause 100% growth inhibition within five minutes[2]. These metrics highlight its high efficacy at low concentrations, making it a balanced choice for safety and performance in various applications. By adhering to these safety and regulatory guidelines, hypochlorous acid has established itself as a reliable and safe solution for medical, agricultural, and disinfection purposes.
Comparison with Other Antiseptics
Hypochlorous acid (HOCl) has been gaining attention in the medical field for its robust antimicrobial properties and ability to disrupt biofilms effectively, making it a viable option for various medical applications such as wound irrigation and the treatment of diabetic foot ulcers[7]. Compared to traditional antiseptics, HOCl offers a unique balance of efficacy and safety. While it is highly effective in eradicating microbes, concerns have been raised regarding its cytotoxicity, which can influence wound healing outcomes[17]. When correctly diluted, hypochlorous acid is both harsh on harmful bacteria and gentle on the skin, including sensitive skin types. This is a distinct advantage over other antiseptics, which can often cause skin irritation and other adverse reactions. Dermatologists recommend HOCl-based products for common skin issues like acne, eczema, and psoriasis, as it helps disinfect the skin, reduce inflammation, and speed up the natural healing process[20]. In the context of environmental disinfection, HOCl proves to be a potent agent against bacteria, viruses, and fungi, comparable to, or even surpassing, traditional disinfectants. However, unlike many conventional products that can lead to microbial resistance and environmental harm, HOCl is safe for human tissues and environmentally benign. It does not require special handling for toxic waste disposal, which is a significant advantage in maintaining ecological balance[8]. Furthermore, the stability and purity of HOCl solutions can vary based on the manufacturing process. Some products are manufactured in state-of-the-art facilities adhering to ISO 9001:2015 and GMP guidelines, ensuring high-quality and stable HOCl formulations. These formulations can be tailored for specific markets, including healthcare, commercial, and cosmetic applications[9]. Despite its benefits, the adoption of HOCl over other antiseptics is also influenced by economic considerations. While some customers find it to be a cost-effective solution, there are mixed opinions regarding the residue it can leave behind, as well as its overall safety and quality[22]. Nonetheless, in hospital settings, HOCl is increasingly used for its effectiveness against superbugs and its role in comprehensive infection control strategies[1].
Recent Advances and Research
In recent years, there have been significant advancements in the production and application of hypochlorous acid (HOCl) for medical use. One notable advancement is the electrochemical production of sodium hypochlorite (NaOCl) from salty wastewater, which is more sustainable and environmentally friendly compared to traditional methods that rely on hazardous chemicals and generate toxic waste. This method requires careful control of operating conditions such as current density, flow rate, inert electrode spacing, and electrolyte concentration to optimize conversion efficiency and prevent electrode fouling and degradation[23]. Electrolysis technology, which was first explained by Michael Faraday in the 1830s, remains a foundational technique in the production of hypochlorous acid. By conducting an electrical current across two electrodes in a salt brine solution, various oxidants including chlorine gas, sodium hypochlorite, hypochlorous acid, and hydrogen gas can be produced[10]. Despite the relative ease of production, maintaining a stable hypochlorous acid solution has historically been challenging. However, recent advancements have enabled the cost-effective production and maintenance of stable hypochlorous acid solutions for commercial use[2]. Hypochlorous acid has shown promising results in various medical applications due to its strong antimicrobial properties. It can penetrate the cell walls and membranes of bacterial cells through passive diffusion, causing rapid ATP hydrolysis and disrupting essential cellular processes[16]. This makes hypochlorous acid an effective disinfectant against pathogens, including the COVID-19 virus, which can persist on various surfaces for extended periods[3]. Studies have reviewed the effectiveness of hypochlorous acid in different settings, concluding that it can be a highly predictable disinfectant for daily use in office environments[3]. Moreover, hypochlorous acid has been identified as a potent agent in wound care. A stabilized HOCl solution has demonstrated dose-dependent favorable effects on fibroblast and keratinocyte migration, suggesting it could become a future gold standard in wound care and scar management in dermatologic and plastic surgery procedures[17]. Additionally, hypochlorous acid is gaining attention in the skincare industry. As an antimicrobial agent that can combat both COVID-19 and acne, it is being replicated for use in various skin care products[4]. Its microbicidal activities have been evaluated, and the results indicate strong stability and effectiveness[24]. These advancements highlight the growing significance of hypochlorous acid in medical and commercial applications, driven by ongoing research and technological innovations.
Future Directions
The future of medical-grade hypochlorous acid (HOCl) solutions appears promising, particularly in the fields of disinfection and wound care. Recent studies and developments suggest several potential advancements and applications for HOCl technology.
Stability Enhancements
One of the primary challenges with hypochlorous acid solutions has been maintaining their stability over time. Traditional HOCl solutions tend to degrade quickly, reverting back to saltwater and losing their disinfecting properties[2]. Future research aims to develop more stable formulations that retain their efficacy for extended periods, which would facilitate wider distribution and usage, especially in healthcare settings[13]. By leveraging advanced engineering processes, such as those used by Pure&Clean, companies are already making strides in creating more stable and effective HOCl solutions[13].
Expanded Applications in Disinfection
Given its superior efficacy and safety profile compared to traditional disinfectants like bleach, HOCl is poised for broader application in various disinfection scenarios. The advent of COVID-19 has spurred interest in using HOCl for fogging and aerosolized applications to sanitize hospitals and other high-touch areas[19]. Future research will likely focus on optimizing these applications to enhance their practicality and effectiveness[19]. Additionally, there is ongoing interest in using HOCl within disinfection chambers and for cleaning indoor environments such as offices, hospitals, and healthcare clinics[2].
Advances in Wound Care
In wound care, hypochlorous acid has already been approved by the U.S. Food and Drug Administration (FDA) for treating wounds and infections in humans and pets[2]. Future directions may include further refinement of HOCl-based products to enhance their antimicrobial effectiveness and reduce healing times. Studies have shown that formulations with specific pH ranges can be particularly effective as topical antimicrobials, suggesting that fine-tuning the pH balance could lead to more potent wound care solutions[25].
Regulatory and Safety Considerations
As the use of HOCl expands, regulatory frameworks will need to adapt to ensure safety and efficacy. The National Organic Program (NOP) under the USDA has already recognized electrolyzed water, which includes hypochlorous acid, as permissible in organic production and handling[21]. Continued updates and clarifications in regulatory policies will be essential as new formulations and applications emerge.
Integration in Healthcare Settings
Healthcare professionals must continue to educate themselves about the benefits and limitations of hypochlorous acid as a disinfectant, especially in the context of combating superbugs and ensuring patient safety[1]. The cost-effectiveness and non-toxicity of HOCl make it an attractive option for daily use in medical environments[3]. Future research could focus on optimizing delivery systems, such as automated dispensers and integrated cleaning protocols, to maximize its utility in these settings.
