Hypochlorous acid (HOCl) is a weak acid with strong disinfectant properties that plays a critical role in various fields including healthcare, environmental cleaning, and the food industry. Known for its potent efficacy in eliminating pathogens such as bacteria, viruses, fungi, and spores, HOCl has garnered attention for its application in wound care, its use as a preservative in saline solutions, and its effectiveness as a non-toxic disinfectant against COVID-19. The compound’s inherent characteristics, such as being non-irritating to human tissues and environmentally safe, alongside its approval by the U.S. Food and Drug Administration (FDA) and recommendation by the U.S. Environmental Protection Agency (EPA), underscore its significance in medical and environmental contexts. The historical development and understanding of HOCl’s chemical properties, alongside advancements in its production methods, have been crucial in overcoming challenges related to its stability and potential toxicity. Innovations such as single cell technology in electrolysis have enabled more stable and effective forms of HOCl, facilitating its widespread commercial use. Furthermore, the introduction of stable forms of hypochlorous acid, such as Brio HOCL™, signifies progress in maintaining the compound’s disinfecting power while ensuring safety for humans and minimal environmental impact. Regulatory endorsements by bodies such as the EPA and FDA have played pivotal roles in establishing the credibility and trust in HOCl’s effectiveness and safety for various applications. The compound’s regulation for use on food-contact surfaces and in products for treating wounds and infections reflects a comprehensive understanding of its beneficial properties and potential risks. These regulatory measures, along with ongoing research into optimizing production methods and expanding applications, highlight the dynamic evolution of hypochlorous acid’s role in public health and safety. Given its broad-spectrum antimicrobial activity, safety profile, and environmental benefits, hypochlorous acid represents a vital component in the fight against infectious diseases and in promoting sustainable disinfection practices. Its continued development and application across healthcare, agriculture, food safety, and domestic and industrial cleaning illustrate the compound’s versatility and importance in modern society. The future of hypochlorous acid research and application holds promise for enhancing public health, environmental protection, and safety in a world increasingly concerned with effective yet sustainable disinfection solutions.
Historical Background
Hypochlorous acid (HOCl), a substance known for its potent disinfectant properties, has played a pivotal role in various applications ranging from wound care to fighting off infections within the human body. The compound has been identified as a key player in the innate immune system, produced by white blood cells to combat pathogens[1]. Its efficacy as a disinfectant agent, capable of altering the protective protein coats of viruses and facilitating their inactivation, has been recognized and recommended by the US Environmental Protection Agency against pathogens such as COVID-19[2]. The significance of HOCl in medical and disinfection practices has been further solidified with the approval of products containing hypochlorous acid by the U.S. Food and Drug Administration (FDA). Since early 2016, these products have been authorized for treating wounds and various infections in both humans and pets, demonstrating the compound’s versatility and safety[3]. Additionally, hypochlorous acid has been adopted as a preservative for saline solutions, underlining its utility in healthcare settings[3]. Beyond its biological and medical applications, hypochlorous acid has been highlighted for its environmental benefits. As an active ingredient in electrolyzed water, it serves as a green cleaning and sanitizing solution. This application not only showcases HOCl’s effectiveness as a disinfectant but also its role in promoting environmentally friendly practices[1]. Recent advancements have introduced stable forms of hypochlorous acid, such as Brio HOCL™, enhancing its utility across various domains. These developments have addressed previous limitations related to the compound’s stability and potential toxicity, offering solutions that are safe for human tissues and do not harm the environment. The emergence of such technology underscores the potential of HOCl to inactivate a wide array of pathogens, including viruses, bacteria, endospores, fungi, and even prions, without contributing to resistance or environmental damage[4].
Chemical Properties
Hypochlorous acid (HOCl) is a significant chemical entity due to its strong oxidative properties, making it a potent disinfectant and a reactive substance in various chemical reactions[5][3]. Structurally, it comprises a chlorine atom bonded to oxygen and hydrogen atoms (Cl-O-H), manifesting its ability to act as an acid when dissolved in water. This dissolution leads to the partial dissociation of HOCl into the hypochlorite ion (OCl-) and hydrogen ion (H+), showcasing its nature as a weak acid[5][3]. HOCl’s role as a strong oxidizer allows it to form explosive mixtures under certain conditions, underscoring the need for careful handling and application of this chemical[5]. Its oxidative capacity is not limited to inorganic reactions; it also engages in reactions with organic molecules and biomolecules, highlighting its versatile reactivity[5]. This behavior is crucial for its effectiveness in disinfection and sterilization processes, where it targets and reacts with the cellular components of pathogens[3]. In aqueous solutions, HOCl exhibits a dynamic equilibrium, rapidly converting between its molecular form and its dissociated ions. This rapid equilibration with its precursor, chlorine, impedes the isolation of pure hypochlorous acid from such solutions, emphasizing the transient nature of HOCl in aqueous environments[3]. Its reactivity extends to bases, with which it reacts to form salts known as hypochlorites. Sodium hypochlorite (NaOCl), commonly known as bleach, is one such salt, produced by reacting hypochlorous acid with sodium hydroxide[5]. The chemical behavior of HOCl towards nucleic acids and proteins is of particular interest in the context of its disinfectant properties. It reacts slowly with DNA, RNA, and various nucleotides, with guanosine monophosphate (GMP) being notably more reactive due to the presence of both a heterocyclic NH group and an amino group that HOCl can target[3]. This selective reactivity is pivotal in understanding how HOCl can cause cross-linking and aggregation of proteins through the formation of Schiff bases, a process that underpins its mechanism of action against pathogens[3]. Despite its potent reactivity and beneficial applications, the stability of hypochlorous acid, particularly in aqueous solutions, poses challenges. The active compounds rapidly deteriorate back into saltwater, diminishing its disinfecting capability and complicating its transportation for widespread use[3]. This instability is a significant consideration in the development and application of hypochlorous acid-based disinfectants, driving research into more stable formulations that retain the chemical’s efficacy[4].
Production Methods
The production of hypochlorous acid (HOCl) has evolved over the years with significant advancements aimed at overcoming its inherent instability and maximizing its potent biocidal properties. The methods of production have varied, focusing on achieving stable hypochlorous acid solutions that can be used across various industries.
Electrochemical Activation
One of the primary methods for producing hypochlorous acid involves the electrochemical activation of a saturated salt solution, commonly referred to as brine. This process yields HOCl through the electrolysis of the saline solution[6]. Michael Faraday’s development of the Laws of Electrolysis in the 1830s laid the groundwork for this method, allowing for the generation of chlorine gas, sodium hypochlorite, hypochlorous acid, and other compounds by conducting electrical current across electrodes in a salt brine solution[7].
Single Cell Technology
A notable advancement in the electrolysis method is the development of single cell technology. Unlike previous methods that used membranes and high pressures, resulting in unstable byproducts, single cell technology generates a single stream of free chlorine without producing sodium hydroxide (NaOH) as a byproduct. This has led to more stable solutions of hypochlorous acid and greater control over the pH of the produced free chlorine[8]. The continuous flow electrochemical cells, a product of this technology, enable the commercialization of devices for in-situ generation of HOCl for disinfection purposes, significantly improving its stability and usability[3].
Acid-Driven Methods
Research has also explored methods involving the reaction of chlorine with water in the presence of acids. By adding acids to aqueous salts like sodium hypochlorite, a common commercial bleach solution, chlorine gas is generated, which then dissolves in water to form hypochlorous acid. This method shifts the reaction towards producing hypochlorous acid, leveraging chlorine’s significant oxidizing power, which is partly due to the chlorine atom in its molecule[9][10].
Innovations in Stability and Safety
Despite the relatively straightforward production of hypochlorous acid, maintaining a stable solution has been challenging. Recent years have seen innovations aimed at enhancing stability, such as methods providing air-free mixing to prevent destabilization of HOCl due to exposure to air, a known factor in its rapid deterioration. These methods avoid electrolysis or the use of chlorine gas, targeting the production process’s aspects that may contribute to the instability of the product[6]. The Box–Behnken design, a response surface methodology, has been employed to optimize the production process by studying the effects of various parameters like feed water flow rate, pH, temperature, and acid concentration. This approach not only improves the efficiency of hypochlorous acid production but also its consistency and stability, addressing its tendency to revert to salt water or convert to hypochlorite[11].
Commercialization and Use
Despite the challenges in stabilizing hypochlorous acid, technological advancements have reduced manufacturing costs, allowing for the bottling of hypochlorous acid water for home and commercial use. These developments have facilitated the wider adoption of hypochlorous acid in disinfection and its application across multiple industries, including medical, food service, and agriculture, among others[6][3].
Safety and Regulation
Hypochlorous acid (HOCl) is recognized for its role as a disinfectant and its involvement in various applications, including food safety and wound care. Given its widespread use, the safety and regulation of hypochlorous acid are of paramount importance to ensure public health and environmental protection.
Regulatory Status
In December 2020, the United States Environmental Protection Agency (EPA) made a significant decision regarding the regulation of hypochlorous acid. As detailed in the Hypochlorous Acid Interim Registration Review Decision, hypochlorous acid is registered for use as a disinfectant on food-contact surfaces in public eating places[12]. This registration underscores the EPA’s acknowledgment of hypochlorous acid’s efficacy as a disinfectant while emphasizing the need to regulate its use to prevent possible residue in food. The EPA proposed an exemption from the requirement of a tolerance for residues of hypochlorous acid on food-contact surfaces in public eating areas, aiming to address residues identified during the agency’s registration review program[12].
FDA Approval
The U.S. Food and Drug Administration (FDA) has also recognized the importance of hypochlorous acid, particularly in the domain of wound care and food safety. As of early 2016, the FDA approved products with hypochlorous acid as the main active ingredient for treating wounds and various infections in humans and pets. This approval extends to its use as a preservative for saline solutions[3]. Additionally, the FDA provides guidance on minimizing microbial food safety hazards for fresh-cut fruits and vegetables, indicating the antimicrobial activity of chlorine-based disinfectants, such as those containing hypochlorous acid[13].
Environmental and Human Health Considerations
Despite its beneficial applications, the current methods of disinfection, including those involving hypochlorous acid, can contribute to antimicrobial resistance, prove toxic to tissues, and cause environmental damage[4]. This has led to an increased focus on developing and utilizing forms of hypochlorous acid that are safe for human tissues and environmentally benign, as exemplified by the novel, stable form of hypochlorous acid (Brio HOCL™)[4]. This emphasis on safety is further supported by the principles of green chemistry, aiming to minimize the use and generation of hazardous substances[8].
Efficacy in Disinfection
The antimicrobial efficacy of hypochlorous acid depends significantly on its concentration and the pH level of the solution. It is more potent as a disinfectant at a lower pH, where hypochlorous acid predominates[14]. This property is utilized in industrial water treatment and disinfection practices to ensure efficient microbial control while considering environmental and safety impacts[14].
Modern Applications
Hypochlorous acid (HOCl) has found a wide range of applications in the modern world, thanks to its powerful disinfectant properties coupled with being non-toxic and environmentally friendly. This has led to its use across various industries, from healthcare to agriculture, demonstrating the compound’s versatility and effectiveness.
Healthcare and Medical Use
In the healthcare sector, HOCl is recognized for its efficacy in wound care and disinfection. The U.S. Food and Drug Administration (FDA) has approved products containing hypochlorous acid as the main active ingredient for treating wounds and various infections in humans and pets. These approvals underline the compound’s safety and effectiveness in medical applications[3]. Furthermore, HOCl is used as a preservative for saline solutions, showcasing its compatibility with sensitive medical formulations[3]. HOCl’s non-toxic and gentle nature has made it a staple in chronic wound care, eye care products, and even in veterinary care products. Its ability to eradicate biofilm also adds to its utility in healthcare settings, addressing complex microbial challenges[15].
Disinfection and Sanitization
The advent of the COVID-19 pandemic has underscored the need for effective and safe disinfectants. HOCl has emerged as a key player in this arena, with the ability to change the protective protein coat of viruses, leading to their deactivation. This mechanism of action, along with endorsements from the US Environmental Protection Agency against COVID-19, has positioned HOCl as a vital disinfectant in the fight against the virus[2]. HOCl is used in various forms, including liquid spray, wet wipes, and aerosolized applications, for disinfection purposes. Recent studies have shown its suitability for fog and aerosolized application in disinfection chambers and for indoor settings such as offices, hospitals, and healthcare clinics[3]. The use of hypochlorous vapor fogging has also shown virucidal activity against numerous types of viruses and bacteria, offering a method to disinfect large spaces efficiently[2].
Agriculture and Food Industry
In the agricultural sector and food industry, HOCl is utilized for sanitizing and maintaining the hygiene of food products. Its non-toxic properties make it an ideal choice for farming and restaurants, helping to prevent foodborne illnesses without leaving harmful residues[2].
Industrial and Domestic Cleaning
The role of HOCl in industrial and domestic cleaning cannot be overstated. Ready-to-Use (RTU) products adjust the pH of sodium hypochlorite solutions to create neutral pH hypochlorous acid solutions, making them safe and effective for a wide range of cleaning applications[16]. Additionally, the invention of air-free compositions of HOCl has contributed to the development of more stable solutions, enhancing its effectiveness and shelf life for cleaning purposes[6].
Green Cleaning Technology
Electrolyzed water, an industrial technology that uses electricity to change the chemical structure of salt, water, and vinegar into a disinfectant as effective as bleach but non-toxic, represents a significant advancement in green cleaning. HOCl, being the active ingredient in electrolyzed water, highlights its role in promoting environmentally friendly cleaning solutions[1][17][7].
Future Prospects and Research Directions
The future of hypochlorous acid (HOCl) research and application looks promising, driven by its significant role in disinfection and its potential in various fields. Given its efficiency as a disinfectant, particularly evident during the COVID-19 pandemic, and its environmentally friendly profile, HOCl stands as a critical component in the fight against pathogens[2][11]. The exploration of its efficacy, production methods, and applications continues to evolve, offering a fertile ground for scientific advancement and practical implementations.
Optimization of Production Methods
Recent innovations have shown that the stability of HOCl can be significantly improved through air-free production methods, avoiding the destabilization issues caused by acidic pH and exposure to air during the production process[6]. This advancement opens new research directions in the optimization of production methods, aiming to enhance the efficiency, reduce costs, and increase the accessibility of HOCl for various uses. Future studies might focus on refining these air-free mixing methods or exploring alternative production techniques that maintain the integrity and efficacy of HOCl.
Expanded Applications in Public Health and Safety
The broad-spectrum efficacy of HOCl against viruses, bacteria, endospores, and fungi, coupled with its safety for human tissues and minimal environmental impact, positions it as a versatile agent in public health[4]. Research into novel applications, such as area and wound decontamination, could revolutionize how we approach infection control, especially in light of the increasing threat of antibiotic-resistant pathogens. The development of stable forms of HOCl, like Brio HOCL™, indicates the potential for its expanded use in healthcare settings, public facilities, and even in routine home cleaning products[4].
Environmental Implications
Given its environment-friendly characteristics, HOCl offers a sustainable alternative to traditional disinfectants that may leave harmful chemical residues or contribute to the development of resistant pathogens[11][18]. Future research could explore its ecological benefits further, examining its impact on water and soil quality, its role in reducing hazardous waste, and its potential integration into eco-friendly disinfection protocols and products.
Technological Advancements
The advent of electrolyzed water (EW) as a method for producing HOCl highlights the intersection of technology and chemistry in developing effective disinfectants[11]. Research into the optimization of EW systems, including the exploration of feed water flow rate, pH, temperature, and other process parameters, could lead to more efficient and scalable production of HOCl[11]. Additionally, the integration of response surface methodology (RSM) designs, such as the Box–Behnken design, in studying the effects of these parameters presents an innovative approach to enhancing the production and application of HOCl[11].
