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Benzalkonium chloride
Benzalkonium chloride
Benzalkonium chloride
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Benzalkonium chloride
Names
Other names
N-Alkyl-N-benzyl-N,N-dimethylammonium chloride; Alkyldimethylbenzylammonium chloride; ADBAC; BC50 BC80
Identifiers
ChEBI
ChEMBL
EC Number
  • 264-151-6
KEGG
RTECS number
  • BO3150000
UNII
Properties
Variable
Molar mass Variable
Appearance
  • 100% is white or yellow powder; gelatinous lumps;
  • BC50 (50%) and BC80 (80%) solutions are colourless to pale yellow solutions.
Density 0.98 g/cm3
Very soluble
Pharmacology
D08AJ01 (WHO)
Hazards
GHS labelling:
GHS05: CorrosiveGHS07: Exclamation markGHS09: Environmental hazard
Danger
H302, H312, H314, H410
P260, P264, P270, P273, P280, P301+P312, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P322, P330, P363, P391, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
3
0
0
Flash point 250 °C (482 °F; 523 K) (if solvent based)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Benzalkonium chloride (BZK, BKC, BAK, BAC), also known as alkyldimethylbenzylammonium chloride (ADBAC) is a type of cationic surfactant. It is an organic salt classified as a quaternary ammonium compound. ADBACs have three main categories of use: as a biocide, a cationic surfactant, and a phase transfer agent.[1] ADBACs are a mixture of alkylbenzyldimethylammonium chlorides, in which the alkyl group has various even-numbered alkyl chain lengths.

Solubility and physical properties

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Depending on purity, benzalkonium chloride ranges from colourless to a pale yellow (impure). Benzalkonium chloride is readily soluble in ethanol and acetone. Dissolution in water is ready, upon agitation. Aqueous solutions should be neutral to slightly alkaline. Solutions foam when shaken. Concentrated solutions have a bitter taste and a faint almond-like odour.[citation needed]

Standard concentrates are manufactured as 50% and 80% w/w solutions, and sold under trade names such as BC50, BC80, BAC50, BAC80, etc. The 50% solution is purely aqueous, while more concentrated solutions require incorporation of rheology modifiers (alcohols, polyethylene glycols, etc.) to prevent increases in viscosity or gel formation under low temperature conditions.

Cationic surfactant

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Benzalkonium chloride possesses surfactant properties, dissolving the lipid phase of the tear film and increasing drug penetration,[2] making it a useful excipient, but at the risk of causing damage to the surface of the eye.[3]

  • Laundry detergents and treatments.
  • Softeners for textiles.

Phase transfer agent

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Main article: Phase transfer catalysis

Benzalkonium chloride is a mainstay of phase-transfer catalysis, an important technology in the synthesis of organic compounds, including drugs.[citation needed]

Bioactive agents

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Especially for its antimicrobial activity, benzalkonium chloride is an active ingredient in many consumer products:

Benzalkonium chloride is also used in many non-consumer processes and products, including as an active ingredient in surgical disinfection. A comprehensive list of uses includes industrial applications.[9]

During the course of the COVID-19 pandemic, from time to time there have been shortages of hand cleaner containing ethanol or isopropanol as active ingredients. The FDA has stated that benzalkonium chloride is eligible as an alternative for use in the formulation of healthcare personnel hand rubs.[10] However, in reference to the FDA rule, the CDC states that it does not have a recommended alternative to ethanol or isopropanol as active ingredients, and adds that "available evidence indicates benzalkonium chloride has less reliable activity against certain bacteria and viruses than either of the alcohols."[11]

In November 2020 the Journal of Hospital Infection published a study on benzalkonium chloride formulations; it was found that laboratory and commercial disinfectants with as little as 0.13% benzalkonium chloride inactivated the SARS-CoV-2 virus within 15 seconds of contact, even in the presence of a soil or hard water.[12] This resulted in a growing consensus that BZK sanitizers are just as effective as alcohol-based sanitizers despite the CDC guidelines.[13]

As a hand sanitizer, use of BZK may be advantageous over ethanol in some situations because it has significantly more residual antibacterial action on the skin after initial application.[14] Benzalkonium chloride has demonstrated persistent antimicrobial activity for up to four hours after contact whereas ethanol-based sanitizer demonstrate skin protection for only 10 minutes post-application.[15]

Medicine

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Benzalkonium chloride is a frequently used preservative in eye drops. Typical concentrations range from 0.004% to 0.01%.[16] Stronger concentrations can be caustic[17] and cause irreversible damage to the corneal endothelium.[18]

Avoiding the use of benzalkonium chloride solutions while contact lenses are in place is discussed in the literature.[19][20]

Due to its antimicrobial activity[21] when applied to skin, some topical medications for acne vulgaris have benzalkonium chloride added to increase the products' efficiency or shelf-life.[22][23]

Benzalkonium chloride has also been shown to be a spermicide.[24] In Russia and China, a very dilute solution is used as a contraceptive. Tablets are inserted vaginally, or a gel is applied, resulting in local spermicidal contraception.[25][26] It is not a reliable method, and can cause irritation.

Beekeeping

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This chemical is used in beekeeping for the treatment of rotten diseases of the brood.[27]

Adverse effects

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Although historically benzalkonium chloride has been ubiquitous as a preservative in ophthalmic preparations, its ocular toxicity and irritant properties,[28] in conjunction with consumer demand, have led pharmaceutical companies to increase production of preservative-free preparations, or to replace benzalkonium chloride with preservatives which are less harmful.[29]

Many mass-marketed inhaler and nasal spray formulations contain benzalkonium chloride as a preservative, despite substantial evidence that it can adversely affect ciliary motion, mucociliary clearance, nasal mucosal histology, human neutrophil function, and leukocyte response to local inflammation.[30] Although some studies have found no correlation between use of benzalkonium chloride in concentrations at or below 0.1% in nasal sprays and drug-induced rhinitis,[31] others have recommended that benzalkonium chloride in nasal sprays be avoided.[32][33] In the United States, nasal steroid preparations that are free of benzalkonium chloride include budesonide, triamcinolone acetonide, dexamethasone, and Beconase and Vancenase aerosol inhalers.[30]

Benzalkonium chloride is an irritant to middle ear tissues at typically used concentrations. Inner ear toxicity has been demonstrated.[34]

Occupational exposure to benzalkonium chloride has been linked to the development of asthma.[35] In 2011, a large clinical trial designed to evaluate the efficacy of hand sanitizers based on different active ingredients in preventing virus transmission amongst schoolchildren was re-designed to exclude sanitizers based on benzalkonium chloride due to safety concerns.[36]

Benzalkonium chloride has been in common use as a pharmaceutical preservative and antimicrobial since the 1940s. While early studies confirmed the corrosive and irritant properties of benzalkonium chloride, investigations into the adverse effects of, and disease states linked to, benzalkonium chloride have only surfaced during the past 30 years.[citation needed]

Toxicology

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RTECS lists the following acute toxicity data:[37]

Organism Route of exposure Dose (LD50)
Rat Intravenous 13.9 mg/kg
Rat Oral 240 mg/kg
Rat Intraperitoneal 14.5 mg/kg
Rat Subcutaneous 400 mg/kg
Mouse Subcutaneous 64 mg/kg

Benzalkonium chloride is a human skin and severe eye irritant.[38] It is a respiratory toxicant, immunotoxicant, gastrointestinal toxicant, and neurotoxicant.[39][40][41]

Benzalkonium chloride formulations for consumer use are dilute solutions. Concentrated solutions are toxic to humans, causing corrosion/irritation to the skin and mucosa, and death if taken internally in sufficient volumes. 0.1% is the maximum concentration of benzalkonium chloride that does not produce primary irritation on intact skin or act as a sensitizer.[42]

Poisoning by benzalkonium chloride is recognised in the literature.[43] A 2014 case study detailing the fatal ingestion of up to 8.1 oz (240 ml) of 10% benzalkonium chloride in a 78-year-old male also includes a summary of the currently published case reports of benzalkonium chloride ingestion. While the majority of cases were caused by confusion about the contents of containers, one case cites incorrect pharmacy dilution of benzalkonium chloride as the cause of poisoning of two infants.[44] In 2018 a Japanese nurse was arrested and admitted to having murdered approximately 20 patients at a hospital in Yokohama by injecting benzalkonium chloride into their intravenous drip bags.[45][46]

Benzalkonium chloride poisoning of domestic pets has been recognised as a result of direct contact with surfaces cleaned with disinfectants using benzalkonium chloride as an active ingredient.[47]

Biological activity

[edit]

The antimicrobial activity is dependent on the chain length. For example, yeast and fungi are most affected by C12, gram positive by C14, and gram negative by C16.[48]

The greatest biocidal activity is associated with the C12 dodecyl and C14 myristyl alkyl derivatives. The mechanism of bactericidal/microbicidal action is thought to be due to disruption of intermolecular interactions. This can cause dissociation of cellular membrane lipid bilayers, which compromises cellular permeability controls and induces leakage of cellular contents. Other biomolecular complexes within the bacterial cell can also undergo dissociation. Enzymes, which finely control a wide range of respiratory and metabolic cellular activities, are particularly susceptible to deactivation. Critical intermolecular interactions and tertiary structures in such highly specific biochemical systems can be readily disrupted by cationic surfactants.[citation needed]

Benzalkonium chloride solutions are fast-acting biocidal agents with a moderately long duration of action. They are active against bacteria and some viruses, fungi, and protozoa. Bacterial spores are considered to be resistant. Solutions are bacteriostatic or bactericidal according to their concentration. Gram-positive bacteria are generally more susceptible than gram-negative bacteria. Its activity depends on the surfactant concentration and also on the bacterial concentration (inoculum) at the moment of the treatment.[49] Activity is not greatly affected by pH, but increases substantially at higher temperatures and prolonged exposure times.

In a 1998 study using the FDA protocol, a non-alcohol sanitizer with benzalkonium chloride as the active ingredient met the FDA performance standards, while Purell, a popular alcohol-based sanitizer, did not. The study, which was undertaken and reported by a leading US developer, manufacturer and marketer of topical antimicrobial pharmaceuticals based on quaternary ammonium compounds, found that their own benzalkonium chloride-based sanitizer performed better than alcohol-based hand sanitizer after repeated use.[50]

Newer formulations using benzalkonium blended with various quaternary ammonium derivatives can be used to extend the biocidal spectrum and enhance the efficacy of benzalkonium based disinfection products.[citation needed] Formulation techniques have been used to great effect in enhancing the virucidal activity of quaternary ammonium-based disinfectants such as Virucide 100 to typical healthcare infection hazards such as hepatitis and HIV.[citation needed] The use of appropriate excipients can also greatly enhance the spectrum, performance and detergency, and prevent deactivation under use conditions.[citation needed] Formulation can also help minimise deactivation of benzalkonium solutions in the presence of organic and inorganic contamination.[citation needed]. However, recent studies have demonstrated the capacity of environmental microorganisms to develop reduced susceptibility to benzalkonium chloride by employing strategies such as modifying bacterial membranes: increasing pump activity, and reducing the expression of certain porins.[51]

Degradation

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Biodegradation pathways of BAC with Fenton process (H2O2/Fe2+)[52]

Benzalkonium chloride degradation follows consecutive debenzylation, dealkylation, and demethylation steps producing benzyl chloride, an alkyl dimethyl amine, dimethylamine, a long chain alkane, and ammonia.[52] The intermediates, major, and minor products can then be broken down into CO2, H2O, NH3, and Cl–. The first step to the biodegradation of BAC is the fission or splitting of the alkyl chain from the quaternary nitrogen as shown in the diagram. This is done by abstracting the hydrogen from the alkyl chain by using a hydroxyl radical leading to a carbon centered radical. This results in dimethylbenzylamine as the first intermediate and dodecanal as the major product.[52]

From here, dimethylbenzylamine can be oxidized to benzoic acid using the Fenton process. The trimethyl amine group in dimethylbenzylamine can be cleaved to form a benzyl that can be further oxidized to benzoic acid. Benzoic acid uses hydroxylation (adding a hydroxyl group) to form p-hydroxybenzoic acid. Dimethylbenzylamine can then be converted into ammonia by performing demethylation twice, which removes both methyl groups, followed by debenzylation, removing the benzyl group using hydrogenation.[52] The diagram[which?] represents suggested pathways of the biodegradation of BAC for both the hydrophobic and the hydrophilic regions of the surfactant. Since stearalkonium chloride is a type of BAC, the biodegradation process should happen in the same manner.

Regulation

[edit]

Benzalkonium chloride is classed as a Category III antiseptic active ingredient by the United States Food and Drug Administration (FDA). Ingredients are categorized as Category III when "available data are insufficient to classify as safe and effective, and further testing is required”.

In September 2016, the FDA announced a ban on nineteen ingredients in consumer antibacterial soaps citing a lack of evidence for safety and effectiveness.[53] A ban on three additional ingredients, including benzalkonium chloride, was deferred at that time to allow ongoing studies to be completed.

Benzalkonium chloride was deferred from further rulemaking in the 2019 FDA Final Rule on safety and effectiveness of consumer hand sanitizers, "to allow for the ongoing study and submission of additional safety and effectiveness data necessary to make a determination" on whether it met these criteria for use in OTC hand sanitizers, but the agency indicated it did not intend to take action to remove benzalkonium chloride-based hand sanitizers from the market.[54] There is acknowledgement that more data are required on its safety, efficacy, and effectiveness, especially with relation to:

  • Human pharmacokinetic studies, including information on its metabolites
  • Studies on animal absorption, distribution, metabolism, and excretion
  • Data to help define the effect of formulation on dermal absorption
  • Carcinogenicity
  • Studies on developmental and reproductive toxicology
  • Potential hormonal effects
  • Assessment of the potential for development of bacterial resistance
  • Risks of using it as a contraceptive method.

However, recent studies have demonstrated the capacity of environmental microorganisms to develop reduced susceptibility to benzalkonium chloride by employing strategies such as modifying bacterial membranes: increasing pump activity, and reducing the expression of certain porins.[55]

See also

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References

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Further reading

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Benzalkonium chloride

View on Grokipedia
from Grokipedia
Benzalkonium chloride is a quaternary compound and cationic consisting of a mixture of alkylbenzyldimethylammonium chlorides, where the alkyl chains typically range from C8 to C18, with an approximate molecular formula of C6H5CH2N(CH3)2RCl and a molecular weight of about 354 g/mol. It appears as a hygroscopic white to pale yellow powder or gelatinous lumps with a characteristic , and is highly soluble in and but less so in . This compound is widely recognized for its broad-spectrum properties, effectively targeting , fungi, , and some viruses by disrupting cell membranes, denaturing proteins, and inactivating enzymes. Benzalkonium chloride has been employed for nearly a century in diverse applications due to its efficacy as a and . In the pharmaceutical and medical fields, it serves as an in over-the-counter antiseptics for minor cuts and abrasions, as well as a in , nasal sprays, and solutions. In cosmetics and , it is incorporated into shampoos, conditioners, body lotions, and hand sanitizers to prevent microbial growth and provide activity. Industrially, it functions as a in cleaning products, , , and fabric softeners, highlighting its versatility across domestic, medical, and commercial sectors. Despite its utility, benzalkonium chloride raises safety concerns related to and environmental impact. It is corrosive to the skin, eyes, and , and can cause severe irritation or burns upon direct contact or inhalation, with potential for if ingested. The U.S. (FDA) has classified it as a Category III for certain uses, indicating insufficient data to determine safety and effectiveness for consumer applications like hand rubs, though it remains approved for specific topical products. Additionally, its persistence in and potential to promote underscore ongoing regulatory scrutiny and the need for cautious use.

History and production

Discovery and development

Benzalkonium chloride was first identified in 1935 by German pathologist and bacteriologist , who discovered its properties as a quaternary ammonium compound during research at I.G. Farbenindustrie. Domagk's seminal work demonstrated the compound's broad-spectrum activity against and fungi, positioning it as a promising alternative to harsher disinfectants like . This breakthrough built on prior explorations of synthetic cationic , leading to the compound's recognition as a key advancement in chemistry. Early commercialization followed soon after, with patents filed in the mid- describing the synthesis and applications of alkylbenzyldimethylammonium , the chemical name for benzalkonium . It was marketed under trade names such as Zephiran by Winthrop Chemical Company and Roccal by various producers, emphasizing its non-irritating profile for skin and mucosal use. By the late and into the 1940s, the U.S. approved its incorporation into medical formulations, including as a in and antiseptics, which spurred initial adoption in healthcare settings. Following , production expanded significantly through efforts by chemical manufacturers, enabling cost-effective large-scale synthesis and distribution. This post-war growth facilitated widespread use in the across hospitals, laboratories, and industrial applications as a reliable . By the , benzalkonium chloride had transitioned into consumer products, appearing in household cleaners and personal care items like soaps and mouthwashes, driven by its efficacy as a cationic and its established safety profile for everyday use.

Chemical synthesis

Benzalkonium chloride is synthesized primarily through a quaternization reaction, a where a tertiary amine reacts with an alkylating agent to form a quaternary ammonium salt. The most common industrial method involves the reaction of with an alkyldimethylamine, such as dimethyldodecylamine or a thereof, in a like or without solvent under controlled conditions. This process yields the chloride salt directly, with the general reaction represented as: C6H5CH2Cl+(CH3)2NR→C6H5CH2N(CH3)2R+Cl−\mathrm{C_6H_5CH_2Cl + (CH_3)_2NR \rightarrow C_6H_5CH_2N(CH_3)_2R^+ Cl^-} where R denotes an alkyl chain typically ranging from C8 to C18. An alternative laboratory synthesis quaternizes N,N-dimethylbenzylamine with an alkyl chloride, such as dodecyl chloride, in the presence of a solvent like ethanol to facilitate the reaction. The reaction mixture is heated to 70–100°C and stirred for 7–10 hours to ensure complete conversion, often using excess alkylating agent to drive the equilibrium toward the product. In industrial settings, variations employ mixtures of tertiary amines with predominant alkyl chain lengths of C12–C14 to optimize the surfactant properties and efficacy of the final product, as these chains balance solubility and antimicrobial performance. Following the quaternization, purification steps are essential to isolate the product from unreacted precursors and byproducts. Common methods include with solvent washes, such as , followed by recrystallization to achieve high purity (>99%). For commercial production, of the amine feedstock precedes the reaction, and post-reaction processing may involve freezing and filtration to remove impurities, ensuring the solution meets formulation standards without further in standard processes. The resulting benzalkonium chloride is typically obtained as a or , ready for dilution and application.

Chemical properties

Molecular structure

Benzalkonium chloride is a class of quaternary salts characterized by the general \ceC6H5CH2N(CH3)2RCl\ce{C6H5CH2N(CH3)2RCl}, where R denotes a linear alkyl chain typically ranging from 8 to 18 carbon atoms. This formula represents a family of homologues rather than a single compound, with the variable alkyl substituent conferring flexibility in applications. The molecule exists as an ionic compound, comprising a quaternary cation [\ceC6H5CH2N(CH3)2R]+[\ce{C6H5CH2N(CH3)2R}]^+ and a chloride anion \ceCl−\ce{Cl^-}. The cation's nitrogen atom is bonded to four alkyl groups: a benzyl moiety (\ceC6H5CH2−\ce{C6H5CH2-}), two methyl groups (\ceCH3\ce{CH3}), and the longer alkyl chain (R), rendering it permanently positively charged. This amphiphilic architecture features a hydrophobic tail provided by the alkyl chain R and the partially hydrophobic benzyl group, contrasted with a hydrophilic head group at the charged quaternary nitrogen. In commercial formulations, benzalkonium chloride is supplied as a mixture of these homologues, with the alkyl chain distribution often dominated by the C12_{12} (dodecyl) and C14_{14} (tetradecyl) variants, typically comprising C12_{12} (40-70%) and C14_{14} (around 30%), alongside lesser amounts of other chain lengths from C8_8 to C18_{18}. These variations in chain length composition influence the compound's physical characteristics, such as melting point and solubility, without altering the core quaternary structure. The structural representation highlights the benzyl group's phenyl ring, which exhibits delocalization of π-electrons across the aromatic system, stabilizing the overall cation. This can be depicted as: \chemfig∗∗6(−=−=−=)−\chemfigCH2−N+(CH3)2−([−CH2−]n−CH3)\cewith Cl−\chemfig{**6(-=-=-=)} - \chemfig{CH_2 - N^+(CH_3)_2 - ([-CH_2-]_n-CH_3)} \quad \ce{with\ Cl^-} where the hexagon denotes the resonant benzene ring and n ≈ 8-18 for the alkyl chain.

Physical and chemical properties

Benzalkonium chloride is typically supplied as a colorless to pale yellow viscous liquid or a white to yellowish-white waxy solid or gel, with the physical form varying based on the predominant alkyl chain length in the mixture—shorter chains (e.g., C12) yield more liquid-like consistencies, while longer chains (e.g., C16-C18) result in solids or semi-solids. It is highly soluble in water (up to 500 g/L at 20°C) and , but practically insoluble in and acetone. Key physical properties include a of approximately 0.98 g/cm³ and a of 800 kg/m³. It has a high exceeding 100°C at 760 mmHg, though it decomposes upon heating above 140-250°C without boiling, contributing to its low volatility. Chemically, benzalkonium chloride is stable under normal ambient conditions in neutral to mildly alkaline environments and shows resistance to in 7 buffered aqueous solutions, though degradation can occur under prolonged UV exposure. It undergoes slow in strong acidic conditions, with about 10% degradation observed under severe acid stress (0.1 M HCl at 70°C). The compound is incompatible with anionic , forming insoluble precipitates that reduce efficacy. Aqueous solutions of benzalkonium chloride (1-10% concentration) exhibit a pH range of 6.0-9.0. Its amphiphilic structure enables significant reduction in surface tension, measuring approximately 28 mN/m at 1 g/L and 20°C.

Applications

Surfactant and emulsifying agent

Benzalkonium chloride serves as a cationic surfactant that adsorbs at interfaces between air-water or oil-water phases, reducing surface tension to promote foam formation and stabilize emulsions in oil-water systems. This adsorption occurs due to its amphiphilic structure, where the hydrophobic alkyl chain extends into the non-polar phase and the hydrophilic quaternary ammonium head group remains in the aqueous phase, enabling effective wetting, dispersing, and emulsifying actions in various formulations. Aqueous solutions of benzalkonium chloride exhibit low surface tension and readily foam when agitated, contributing to its detergent-like properties. In non-biological applications, benzalkonium chloride is incorporated into such as shampoos and conditioners for enhanced spreading and mixing of ingredients, as well as into detergents and fabric softeners to improve cleaning and softening performance. Its emulsifying capabilities help maintain stable oil-in-water or water-in-oil dispersions in these products, preventing and ensuring uniform texture. The cationic character of benzalkonium chloride allows it to bind selectively to negatively charged surfaces, such as hair or fabric fibers, imparting conditioning effects like smoothness and reduced in products or softness in textiles. This binding also neutralizes electrical charges, preventing static cling in fabrics during softening processes. The efficiency of these interactions is influenced by its (CMC), which for the C12 homolog is approximately 3.8 mM in aqueous solutions, marking the threshold where molecules aggregate into micelles and alter and interfacial behavior.

Phase transfer agent

Benzalkonium chloride functions as a (PTC) in by leveraging its to extract anions from an aqueous phase into an organic phase, thereby facilitating reactions between immiscible solvents and accelerating nucleophilic substitutions. This ion-transfer mechanism enhances the availability of reactive anions in the organic medium, where they can interact more effectively with electrophiles, often under milder conditions than traditional . Common applications include the of and , notably in the conducted under PTC conditions, where benzalkonium chloride enables efficient O-alkylation by shuttling alkoxide ions across phases. For instance, in the synthesis of ethers from alkyl and , the catalyst promotes high yields while minimizing side reactions. Similarly, it supports displacements, exemplified by the general scheme RX (org) + CN⁻ (aq) → RCN (org) + X⁻ (aq), where R represents an and X a , allowing nucleophilic attack in biphasic systems. Another key example is the Darzens glycidic ester condensation, in which α-halo esters react with carbonyl compounds under basic aqueous conditions to form epoxy esters, with the PTC improving reaction rates and . The advantages of employing benzalkonium chloride as a PTC include the elimination of hazardous or toxic solvents, such as dipolar aprotic media, and the use of only catalytic quantities (typically 1-5 mol%), which is enabled by its ability to form micelles that concentrate at phase interfaces. Its properties contribute to this micellar enhancement, promoting efficient ion transport without requiring stoichiometric amounts. These features make it particularly valuable in scalable , as demonstrated in processes like the alkaline of , where benzalkonium chloride has shown superior performance over other quaternary ammonium salts.

Disinfectant and preservative

Benzalkonium chloride serves as a broad-spectrum antimicrobial agent widely employed in non-medical disinfection and preservation applications due to its cationic surfactant properties that disrupt microbial cell membranes. It effectively kills bacteria, fungi, and some enveloped viruses at low concentrations, typically ranging from 0.01% to 0.1%, by inserting into lipid bilayers and causing leakage of cellular contents. This mechanism provides rapid bactericidal and fungicidal action, making it suitable for preventing microbial growth in various industrial and consumer products. In terms of antimicrobial spectrum, benzalkonium chloride exhibits greater efficacy against compared to , owing to the latter's outer membrane barrier that reduces penetration. It shows limited activity against bacterial s and mycobacteria, which possess robust protective structures like spore coats or waxy cell walls. Despite these limitations, its broad activity supports its use in systems, including pools and cooling towers, where it controls algal and bacterial at concentrations around 0.01-0.05%. Additionally, it functions as a in paints, inks, and such as and solutions, inhibiting microbial contamination during storage and use. Formulations commonly incorporate benzalkonium chloride at 0.013-0.1% to balance and , with its stability enhanced in neutral to slightly alkaline environments ( 5-9), where it remains hydrolytically stable and retains activity over extended periods. This -dependent longevity ensures reliable preservation in aqueous-based products like disinfectants for industrial cooling systems and consumer formulations.

Medical and pharmaceutical uses

Benzalkonium chloride serves as a key in various medical and pharmaceutical formulations to prevent microbial , particularly in multidose products where sterility is essential. In ophthalmic solutions, it is commonly used at concentrations of 0.005% to 0.02% to inhibit bacterial, fungal, and growth, ensuring the safety of for conditions like or . For example, Alcon's procedural , such as MYDRIACYL® Solution, incorporate 0.01% benzalkonium chloride as a alongside active ingredients like tropicamide. Similarly, in nasal sprays and injectables, concentrations around 0.01% to 0.02% are employed; nasal products benefit from its broad-spectrum activity against pathogens in aqueous formulations, while small-volume parenteral injectables, like certain suspensions (e.g., Celestone Soluspan at 0.02% w/v), use it to maintain sterility during multi-dose administration. In topical applications within healthcare settings, benzalkonium chloride is utilized as an agent in cleansers, hand sanitizers, and urological irrigants, often at concentrations up to 0.2% for contact to provide protection without compromising tissue viability. It appears in over-the-counter products like wipes and lubricating gels for insertion, where 0.02% formulations help reduce infection risk during urological procedures. For instance, in the treatment of , it is included as a (e.g., 0.0025% in otic solutions) to support the delivery of antibiotics directly to the , aiding resolution of bacterial infections. Since the , benzalkonium chloride has been adopted in surgical disinfection and preserved ophthalmic preparations, evolving into a staple in modern OTC topical for minor and disinfection. While effective, prolonged exposure in sensitive areas like the eyes may lead to mild in some patients, prompting the development of preservative-free alternatives for long-term use. Similar concerns exist for prolonged use in nasal decongestant sprays, which has been associated with nasal irritation, swelling, mucosal damage, and rebound congestion in some studies, although a comprehensive safety review has concluded that benzalkonium chloride is safe and well-tolerated in intranasal products at concentrations up to 0.1% for both short- and long-term use (see Health and safety section for details).

Other industrial and agricultural uses

Benzalkonium chloride serves as an in oilfield waters, where it effectively controls algal growth and removes associated to prevent in systems. In cooling systems, it functions as a alongside its properties, mitigating microbiologically influenced corrosion in CO2-saturated environments by inhibiting bacterial adhesion and metal degradation. Additionally, it acts as an in plastics, reducing surface charge accumulation during manufacturing and improving material handling. In , benzalkonium chloride is applied as a for post-harvest preservation of fruits, where it suppresses fungal and delays decay by reducing microbial load on surfaces. It is also used in for hive disinfection, particularly against bacterial pathogens like those causing , with 0.5-1% solutions employed to sterilize equipment and surfaces. This application has been supported under EPA guidelines for pesticidal disinfectants since the 1970s, allowing its use in apiaries for preventive sanitation. Emerging uses include for control, where benzalkonium chloride disinfects water systems and equipment at concentrations around 250-500 mg/L to combat bacterial and fungal pathogens, though its application remains limited by environmental and regulatory restrictions on residue levels.

Biological activity

Mechanism of action

Benzalkonium chloride, a ammonium compound, primarily exerts its effects through disruption of the bacterial cytoplasmic . The positively charged ammonium group electrostatically binds to the negatively charged components of the bacterial , such as phospholipids and lipopolysaccharides. This binding is facilitated by the molecule's amphiphilic nature, featuring a hydrophilic cationic head and a hydrophobic alkyl tail. Following initial binding, the hydrophobic tail inserts into the , destabilizing the membrane structure and increasing its permeability. This insertion leads to the formation of pores or lesions in the membrane, resulting in the leakage of essential intracellular components, such as ions, proteins, and , ultimately causing cell lysis and death. The process is concentration-dependent, with bactericidal activity observed at concentrations exceeding the (MIC), typically ranging from 1 to 10 µg/mL for susceptible bacterial strains. In addition to membrane disruption, benzalkonium chloride induces secondary effects by penetrating the compromised cell envelope and interacting with intracellular targets. It inhibits key enzyme activities, such as ATPase, by denaturing proteins and disrupting their function, which impairs energy metabolism. Furthermore, it interferes with DNA and RNA synthesis, likely through binding to nucleic acids or associated proteins, halting replication and transcription processes. Bacterial resistance to benzalkonium chloride can develop through mechanisms that mitigate these effects, including the overexpression of efflux pumps that actively expel the compound from the cell, reducing intracellular accumulation. Biofilm formation also contributes to resistance by creating a protective matrix that limits penetration and binding to individual cells.

Antimicrobial spectrum and efficacy

Benzalkonium chloride (BAC) exhibits a broad , demonstrating strong activity against such as , where it disrupts bacterial cell membranes leading to rapid cell death. It shows moderate against like , though the outer membrane of these organisms provides some resistance, requiring higher concentrations for effective killing. BAC is highly effective against enveloped viruses, including and , due to its ability to destabilize envelopes, but it shows reduced against non-enveloped viruses compared to enveloped ones. Additionally, it displays good fungicidal activity against species like , with varying by chain length homologues (e.g., C12 for fungi), and algicidal activity against various algae species. Efficacy is commonly assessed through (MIC) and (MBC) values, which quantify the lowest concentrations needed to inhibit or kill microorganisms. For S. aureus, typical MIC values range from 0.5 to 2 µg/mL, with MBC values often similar or slightly higher, indicating bactericidal action at low doses. In contrast, like Pseudomonas aeruginosa require higher concentrations, with MIC values around 64 µg/mL, reflecting greater intrinsic resistance. These metrics highlight BAC's potency against susceptible pathogens while underscoring challenges with resilient species. Several factors influence BAC's antimicrobial efficacy, including pH, organic load, and temperature. Optimal performance occurs at neutral to slightly alkaline pH (6-8), where the cationic nature of BAC facilitates strong interactions with microbial surfaces; efficacy decreases at extreme pH levels due to altered ionization. High organic loads, such as proteins or debris, reduce effectiveness by binding to BAC and preventing contact with microbes. Temperature enhances activity in the range of 20-25°C, as higher mobility aids penetration, though efficacy can diminish at elevated temperatures above 40°C. Post-2020 studies have revealed emerging concerns regarding reduced efficacy against resistant strains, particularly methicillin-resistant S. aureus (MRSA), where repeated exposure leads to elevated MIC values (e.g., doubling from 5 to 10 µg/mL) and cross-resistance with antibiotics via overexpression. This co-selection of resistance underscores the need for judicious use to maintain long-term performance.

Health and safety

Adverse effects

Benzalkonium chloride (BAK) commonly causes skin irritation and allergic contact dermatitis of the type IV hypersensitivity reaction upon topical exposure, particularly in products like antiseptics, cosmetics, and medical wipes. These reactions manifest as erythema, pruritus, and eczematous lesions at the site of contact, with irritant effects occurring more frequently than true allergic sensitization due to BAK's detergent-like properties disrupting the skin barrier. In ophthalmic formulations, BAK frequently induces transient stinging and burning sensations upon instillation, attributed to its disruption of corneal epithelial cells and tear film stability. Specific risks include corneal toxicity from eye drops containing 0.01% BAK, which can lead to superficial punctate characterized by epithelial defects and fluorescein staining, especially with frequent use in patients. Prolonged use of decongestant nasal sprays preserved with BAK has been associated with nasal irritation, mucosal swelling, damage including , squamous , and reduced , and may contribute to rebound congestion (rhinitis medicamentosa), exacerbating symptoms in chronic rhinosinusitis. However, rhinitis medicamentosa is primarily attributed to the decongestant active ingredient (such as oxymetazoline), and BAK's role is debated; some safety reviews conclude that BAK is safe and well tolerated in intranasal products at concentrations up to 0.1%, with conflicting data often confounded by other ingredients. Adverse reactions affect approximately 1-5% of users, with rates of contact allergy ranging from 1.6% to 12.1% in patch-tested populations, and incidence rising in atopic individuals due to their compromised skin barrier. Case studies from the 2010s, including those on preservative-free ophthalmic and nasal products, highlight resolution of symptoms upon switching formulations, underscoring BAK's role in these effects. Mitigation strategies include using diluted concentrations below 0.01% where possible, performing patch testing to confirm allergic , and replacing BAK with gentler preservatives such as polyquaternium-1, which exhibits lower in ocular tissues. Preservative-free single-dose formats are recommended for sensitive patients to minimize exposure.

Toxicology in humans and animals

Benzalkonium chloride demonstrates moderate acute systemic toxicity via , with an LD50 value of approximately 240 mg/kg in rats. Dermal exposure shows low systemic , with an LD50 of approximately 1400 mg/kg in rats, attributable to limited absorption despite its irritant properties. is higher, with an LC50 of about 0.053 mg/L (53 mg/m³) for a 4-hour exposure in rats, primarily affecting the before systemic effects manifest. Chronic exposure profiles in mammals indicate potential reproductive risks, as evidenced by reduced in mice following oral doses greater than 50 mg/kg/day over extended periods. No clear evidence of carcinogenicity has been established, and the International Agency for Research on Cancer (IARC) has not classified benzalkonium chloride as carcinogenic to humans. High-dose studies in rodents have revealed liver and effects, including elevated organ weights and histopathological changes such as tubular in kidneys and hepatocellular alterations, typically at doses exceeding 50 mg/kg/day in subchronic oral administrations. As of 2024, the U.S. Food and Drug Administration (FDA) has deferred further rulemaking on benzalkonium chloride for use in consumer rubs, pending additional safety and effectiveness data. For human occupational exposure, the (OSHA) has not established a (PEL) for benzalkonium chloride. The American Conference of Governmental Industrial Hygienists (ACGIH) recommends a (TLV) of 0.2 mg/m³ as a time-weighted average for related quaternary ammonium compounds.

Environmental impact

Degradation and persistence

Benzalkonium chloride (BAC) undergoes limited abiotic degradation in aqueous environments. Photolysis occurs slowly under (UV) irradiation, with a degradation rate of approximately 0.0928 h⁻¹ observed for C12 homologs in , corresponding to a of about 7.5 hours under simulated conditions; however, in natural surface waters with lower UV intensity, half-lives extend to several days. is negligible at neutral , where BAC solutions remain stable across a wide pH range (typically 5–9), showing no significant loss of activity even under autoclaving conditions. Biotic degradation of BAC is mediated primarily by microbial communities in aerobic environments, such as in systems. Bacteria like species cleave the alkyl chains through dealkylation, yielding benzyldimethylamine (BDMA) as a key metabolite, which is substantially less toxic than the parent compound. In moving bed reactors simulating processes, degradation half-lives range from 12 hours for C12 homologs to 20 hours for C14 homologs, with near-complete removal achieved through combined adsorption and . BAC exhibits high persistence under anaerobic conditions, where is minimal; studies in anaerobic aquatic systems over 12 months show no significant degradation, implying half-lives exceeding 360 days. Additionally, its cationic nature promotes strong adsorption to sediments and , with log Koc values often >4, reducing and limiting further environmental transport or degradation. Degradation products and residual BAC are commonly monitored using high-performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LC-MS), which provide separation and identification of homologs and metabolites like BDMA with high sensitivity and specificity.

Ecological effects and regulation

Benzalkonium chloride poses significant ecological risks, particularly to aquatic ecosystems, where it exhibits high toxicity to organisms such as , , and . Acute toxicity studies report LC50 values ranging from 0.1 to 1 mg/L for and species, indicating very toxic effects even at low concentrations. This toxicity arises from its properties, which disrupt cell membranes and impair respiration and reproduction in exposed organisms. The compound also demonstrates potential for bioaccumulation in sediments, where it sorbs strongly due to its cationic nature, leading to long-term exposure for benthic communities. Concentrations in sediments can reach levels that affect microbial communities and nutrient cycling. Furthermore, benzalkonium chloride contributes to the development of in environments by selecting for resistant bacterial strains, including those carrying resistance genes. This selective pressure exacerbates the spread of resistant pathogens through environmental pathways. In terms of regulation, the U.S. Environmental Protection Agency (EPA) has classified benzalkonium chloride as a under the Federal , , and Act (FIFRA) since its early registrations in the mid-20th century, requiring reregistration and environmental risk assessments for antimicrobial uses. In the , under regulation and Cosmetics Regulation (EC) No 1223/2009, its concentration in cosmetic products is restricted to a maximum of 0.1% for preservatives with alkyl chains of C14 or less, due to concerns over and environmental persistence. In 2025, introduced AB 916, proposing a ban on benzalkonium chloride in consumer hand soaps and body washes by 2028 to mitigate ecological and health risks from overuse in disinfectants; however, the bill did not advance and failed during the legislative session. Environmental monitoring reveals benzalkonium chloride at concentrations of 0.01–10 µg/L in rivers and effluents globally, with higher levels (up to 37 µg/L) near discharge points. In plants, removal efficiencies typically reach 90% or higher through to during processes, though residual amounts persist in effluents and . These detections underscore the need for targeted surveillance in high-use areas like urban and effluents. To mitigate these impacts, biodegradable alternatives such as (3%) and (≥70%) are promoted for disinfection, as they degrade rapidly without persistent residues. International guidelines, including those from the (WHO), emphasize proper treatment of hospital effluents containing disinfectants to meet discharge standards, recommending dilution, , and disinfection to prevent environmental release. Such measures, combined with ecopharmacovigilance strategies, aim to reduce inputs and promote sustainable use.

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/Benzalkonium-Chloride
  2. https://www.inchem.org/documents/icsc/icsc/eics1584.htm
  3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9827944/
  4. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d1f06aa6-2264-4ac1-a9a4-8ca9be1c9ca8&audience=consumer
  5. https://pmc.ncbi.nlm.nih.gov/articles/PMC3991986/
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC8363107/
  7. https://pmc.ncbi.nlm.nih.gov/articles/PMC6581159/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC7269367/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC6986023/
  10. https://pmc.ncbi.nlm.nih.gov/articles/PMC6011824/
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC9826383/
  12. https://www.researchgate.net/figure/Gerhard-Domagk-who-discovered-the-disinfection-properties-of-benzalkonium-chloride_fig8_349947613
  13. https://jamanetwork.com/journals/jamasurgery/fullarticle/549189
  14. https://www.irjmets.com/uploadedfiles/paper//issue_4_april_2024/52990/final/fin_irjmets1713290319.pdf
  15. https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6684f842c9c6a5c07a246005/original/a-short-overview-of-benzalkonium-chloride-in-pharmaceutical-sector-safety-environmental-impact-and-alternatives.pdf
  16. https://www.sciencedirect.com/science/article/abs/pii/S0223523499002160
  17. https://www.spectrumchemical.com/media/flowchart/B1068_-_flowchart.pdf
  18. https://patents.google.com/patent/CN106946716A/en
  19. https://patents.google.com/patent/EP1505058A1/en
  20. https://patents.google.com/patent/CN104151172A/en
  21. https://www.sigmaaldrich.com/US/en/product/sial/12060
  22. https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2022.973680/full
  23. https://www.ema.europa.eu/en/documents/report/benzalkonium-chloride-used-excipient-report-published-support-questions-answers-benzalkonium_en.pdf
  24. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0712969.htm
  25. https://www.carlroth.com/medias/SDB-273L-GB-EN.pdf
  26. https://www.drugs.com/monograph/benzalkonium.html
  27. https://www.chemicalbook.com/ProductChemicalPropertiesCB1712971_EN.htm
  28. https://www.biolinscientific.com/blog/what-are-surfactants-and-how-do-they-work?update_2025=1
  29. https://www.nbinno.com/article/cationic-surfactants/specialty-cationic-surfactants-exploring-benzalkonium-chlorides-versatility-xo
  30. https://www.sciencedirect.com/topics/mathematics/cationic-surfactant
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC6942038/
  32. https://www.specialchem.com/cosmetics/inci-ingredients/benzalkonium-chloride
  33. https://periodical.knowde.com/benzalkonium-chloride-in-cosmetics-and-personal-care-products/
  34. https://ri.conicet.gov.ar/bitstream/handle/11336/49183/CONICET_Digital_Nro.c7b02bec-3cf4-43c7-9d57-b06834aee665_D.pdf?sequence=5&isAllowed=y
  35. https://www.sciencedirect.com/science/article/pii/S0065316008601203
  36. https://pubs.acs.org/doi/10.1021/ja00792a025
  37. https://www.scirp.org/journal/paperinformation?paperid=7449
  38. https://pubs.rsc.org/en/content/articlehtml/2024/gc/d4gc05070c
  39. https://pmc.ncbi.nlm.nih.gov/articles/PMC6588108/
  40. https://pmc.ncbi.nlm.nih.gov/articles/PMC10217790/
  41. https://pmc.ncbi.nlm.nih.gov/articles/PMC10099023/
  42. https://nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=P1005J4P.TXT
  43. https://wwwcourses.sens.buffalo.edu/ce457_527/ce457_pro/Disinfectants.doc
  44. https://www.scielo.br/j/aib/a/ZdHfvTDt9TVKLk34fZWvd3K/?format=pdf&lang=en
  45. https://eyewiki.org/Preservatives_in_Topical_Ophthalmic_Medications
  46. https://www.myalcon.com/professional/cataract-surgery/procedural-eye-drops/
  47. https://www.ema.europa.eu/en/documents/scientific-guideline/questions-and-answers-benzalkonium-chloride-used-excipient-medicinal-products-human-use_en.pdf
  48. https://ptacts.uspto.gov/ptacts/public-informations/petitions/1550762/download-documents?artifactId=FyCysZFtcg64_bS28PVfJYB8-fVUfceOVhTs7WS3Tz17PI_9iPrReaA
  49. https://www.drugs.com/cdi/benzalkonium-chloride.html
  50. https://pubmed.ncbi.nlm.nih.gov/10864037/
  51. https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/20799slr012_floxin_lbl.pdf
  52. https://www.pharmacytimes.com/view/eye-catching-study-the-truth-about-benzalkonium-chloride
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC8277985/
  54. https://pubmed.ncbi.nlm.nih.gov/10566570/
  55. https://pubmed.ncbi.nlm.nih.gov/14726922/
  56. https://www.sciencedirect.com/science/article/pii/S0048969720350555
  57. https://www.researchgate.net/publication/312039896_Corrosion_inhibition_and_anti-bacterial_efficacy_of_benzalkonium_chloride_in_artificial_CO2-saturated_oilfield_produced_water
  58. https://www.irosurfactant.com/product/cationic/bkc/
  59. https://pubmed.ncbi.nlm.nih.gov/23572782/
  60. https://lfi-naas.org.ua/wp-content/uploads/2024/08/NTB-131-128-138.pdf
  61. https://www.epa.gov/pesticide-registration/selected-epa-registered-disinfectants
  62. https://www.merckvetmanual.com/exotic-and-laboratory-animals/aquaculture/production-medicine-and-biosecurity-in-aquaculture
  63. https://pmc.ncbi.nlm.nih.gov/articles/PMC7237276/
  64. https://www.sciencedirect.com/topics/immunology-and-microbiology/benzalkonium-chloride
  65. https://synapse.patsnap.com/article/what-is-the-mechanism-of-benzalkonium-chloride
  66. https://pmc.ncbi.nlm.nih.gov/articles/PMC3344204/
  67. https://pubmed.ncbi.nlm.nih.gov/28444329/
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC7350379/
  69. https://journals.asm.org/doi/10.1128/cmr.12.1.147
  70. https://go.drugbank.com/drugs/DB11105
  71. https://microbewiki.kenyon.edu/index.php/Antiseptic_efficacy_of_benzalkonium_chloride
  72. https://www.mdpi.com/2673-947X/2/4/20
  73. https://ami-journals.onlinelibrary.wiley.com/doi/full/10.1111/jam.14118
  74. https://www.icjournal.org/DOIx.php?id=10.3947/ic.2024.0097
  75. https://ijmmtd.org/html-article/10547
  76. https://www.sciencedirect.com/science/article/abs/pii/S0740002021000058
  77. https://www.mdpi.com/2079-6382/12/8/1244
  78. https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.722219/full
  79. https://pmc.ncbi.nlm.nih.gov/articles/PMC10319159/
  80. https://pubmed.ncbi.nlm.nih.gov/15186375/
  81. https://www.dovepress.com/the-use-of-preservatives-in-dry-eye-drops-peer-reviewed-fulltext-article-OPTH
  82. https://journals.sagepub.com/doi/10.1345/aph.1P268
  83. https://pubmed.ncbi.nlm.nih.gov/21905766/
  84. https://pmc.ncbi.nlm.nih.gov/articles/PMC7014950/
  85. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c6cbe63b-a81c-4f8f-b51f-e6b35e6c1bf8&type=pdf
  86. https://pubmed.ncbi.nlm.nih.gov/18715840/
  87. https://www.e-lactancia.org/media/papers/BenzalconioBF-JAMColTox1989-Johnson_.pdf
  88. https://www.fda.gov/drugs/drug-safety-and-availability/fda-issues-final-rule-safety-and-effectiveness-consumer-antiseptic-rub-products
  89. https://www.sciencedirect.com/science/article/abs/pii/S0304389425012270
  90. https://journals.asm.org/doi/10.1128/AEM.01255-14
  91. https://www.researchgate.net/publication/280923876_Biodegradation_of_benzalkonium_chlorides_singly_and_in_mixtures_by_a_Pseudomonas_sp_isolated_from_returned_activated_sludge
  92. https://www.sciencedirect.com/science/article/pii/S0304389423021180
  93. https://pmc.ncbi.nlm.nih.gov/articles/PMC7467655/
  94. https://www.sciencedirect.com/science/article/abs/pii/S0301479717301834
  95. https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.5484
  96. https://www.researchgate.net/publication/275383025_Analysis_of_Residual_Products_in_Benzalkonium_Chloride_by_High-Performance_Liquid_Chromatography
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC9839631/
  98. https://www.sciencedirect.com/science/article/pii/S0147651320309556
  99. https://www.sciencedirect.com/science/article/pii/S014765132301117X
  100. https://www.sciencedirect.com/science/article/abs/pii/S0048969723001420
  101. https://www.tandfonline.com/doi/abs/10.1080/10643389.2021.1889284
  102. https://archive.epa.gov/pesticides/reregistration/web/pdf/adbac_red.pdf
  103. https://echa.europa.eu/cosmetics-preservatives/-/legislationlist/substance/external/100.063.913
  104. https://legiscan.com/CA/text/AB916/id/3183963
  105. https://www.sciencedirect.com/science/article/abs/pii/S0048969725014238
  106. https://sustainability.wayne.edu/news/toxic-household-cleaners-and-better-environmental-options-cleaning-and-killing-the-coronavirus-41968
  107. https://www.who.int/docs/default-source/wpro---documents/countries/china/covid-19-briefing-nhc/8-annex-5-guideline-for-site-specific-disinfection.pdf?sfvrsn=d0be3679_2
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