Alkyldimethylbenzylammonium chloride (ADBAC)

Other names: N-Alkyl-N-benzyl-N,N-dimethylammonium chloride; Alkyldimethylbenzylammonium chloride; ADBAC; BC50 BC80; Quaternary ammonium compounds; quats

Benzalkonium chlorides (BACs) are chemicals with widespread applications due to their broad-spectrum antimicrobial properties against bacteria, fungi, and viruses

CAS:68424-85-1; CAS:8001-54-5; CAS:85665-42-5; CAS:63449-41-2

CAS :68424-85-1 Chemical Name Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

CAS :8001-54-5; Chemical Name Quaternary ammonium compounds, alkylbenzyldimethyl, chlorides benzalkonium chloridebenzyl-C12-18 -alkyldimethylammonium chlorides

CAS :85665-42-5; Chemical Name Quaternary ammonium compounds, benzyl-C7-17-alkyldimethyl, chlorides; Synonyms: benzyl-C7-18 -alkyldimethylammonium chlorides

CAS :63449-41-2; Chemical Name Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides; Synonyms: benzyl-C8-18 -alkyldimethylammonium chlorides

CAS :68989-00-4; Chemical Name Quaternary ammonium compounds, benzyl-C10-16-alkyldimethyl,chlorides; Synonyms: benzyl-C10-16 -alkyldimethylammonium chloride

CAS :91080-30-7; Chemical Name Quaternary ammonium compounds, benzyl-C10-21-alkyldimethyl,chlorides; Synonyms: benzyl-C10-21 -alkyldimethylammonium chloride

CAS :85409-22-9; Chemical Name Quaternary ammonium compounds, benzyl-C12-14-alkyldimethyl,chlorides; Synonyms: benzyl-C12-14 -alkyldimethylammonium chlorides

CAS :68424-85-1; Chemical Name Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl,chlorides; Synonyms: benzyl-C12-16 -alkyldimethylammonium chlorides

CAS :68391-01-5; Chemical Name Quaternary ammonium compounds, benzyl-C12-18-alkyldimethyl,chlorides; Synonyms: benzyl-C12-18 -alkyldimethylammonium chlorides

CAS :68607-20-5; Chemical Name Quaternary ammonium compounds, benzyl-C16-18-alkyldimethyl,chlorides; Synonyms: benzyl-C16-18 -alkyldimethylammonium chlorides

CAS :91080-31-8; Chemical Name Quaternary ammonium compounds, benzyl-C16-22-alkyldimethyl,chlorides; Synonyms: benzyl-C16-22 -alkyldimethylammonium chlorides

CAS :61789-75-1; Chemical Name Quaternary ammonium compounds, benzyldimethyltallow alkyl, chlorides; Synonyms: benzyl(tallow alkyl)dimethylammonium chloride

CAS :61789-72-8; Chemical Name Quaternary ammonium compounds, benzyl(hydrogenated tallow alkyl)dimethyl,chlorides; Synonyms: benzyl(hydrogenated tallow alkyl)dimethylammonium chloride

CAS :61789-71-7; Chemical Name Quaternary ammonium compounds, benzylcoco alkyldimethyl, chlorides; Synonyms: benzyl(coconut oil alkyl)dimethylammonium chloride

CAS :61789-74-0; Chemical Name Quaternary ammonium compounds, benzyldimethylsoya alkyl, chlorides; Synonyms: benzyl(soybean oil alkyl)dimethylammonium chloride

Showing 1 – 10 of 12 results for “alkyl dimethyl ammonium chloride”

Benzyl-C8-18-alkyldimethylammonium chloride; CAS: 63449-41-2

Dimethyl di(hydrogenated tallow) ammonium chloride; CAS: 61789-80-8 | Synonyms: Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides

Benzalkonium chloride; CAS: 8001-54-5 | Synonyms: Quaternary ammonium compounds, alkylbenzyldimethyl, chlorides, alkyldimethylbenzylammonium chloride

Benzyl-C12-18-alkyldimethylammonium chloride; CAS: 68391-01-5

Quaternary ammonium compounds, benzylcoco alkyldimethyl, chlorides; CAS: 61789-71-7

Benzyl-C12-16-alkyldimethylammonium chloride, CAS: 68424-85-1

Benzyl-C12-18-alkyldimethylammonium chloride, CAS: 68391-01-5

Benzyl-C12-16-alkyldimethylammonium chloride, CAS: 68424-85-1

Alkyl dimethyl benzyl ammonium chloride, CAS: 63449-41-2

Benzyl-C12-18-alkyldimethylammonium chloride, CAS: 68391-01-5

Benzyl-C12-16-alkyldimethylammonium chloride, CAS: 68424-85-1

CAS-Nummer

8001-54-5 (Alkyl)

63449-41-2 (Alkyl: C8–C18)

68424-85-1 (Alkyl: C12–C16)

68391-01-5 (Alkyl: C12–C18)

Name Benzalkonium chloride, 50% in water

Alt. name alkyldimethylbenzylammonium chloride

CAS number 63449-41-2

Related CAS 55963-06-9, 68391-01-5, 68424-85-1, 8001-54-5, 8045-21-4

Benzalkyl quaternary ammonium surfactants:

CAS Registry Numbers: 8001-54-5, 85665-42-5, 63449-41-2,

68989-00-4, 91080-30-7, 85409-22-9, 68424-85-1, 68391-01-5,

68607-20-5, 91080-31-8, 61789-75-1, 61789-72-8, 61789-71-7,

61789-74-0.

Benzalkoniumchlorid; Alkylbenzyldimethylammoniumchlorid; Benzyldimethylalkylammoniumchlorid; BAC; N-Alkyl-N-benzyl-N,N-dimethylammoniumchlorid; BENZALKONIUM CHLORIDE (INCI)

Benzalkonium chloride

Synonym: Alkylbenzyldimethylammonium chloride, Alkyldimethylbenzylammonium chloride

CAS Number 63449-41-2 Linear Formula C6H5CH2N(CH3)2RCl (R=C8H17 to C18H37) Beilstein/REAXYS Number 4062599 EC Number 264-151-6 MDL number MFCD00145757 NACRES NA.22

Benzalkonium chloride is a quaternary ammonium compound used in pharmaceutical formulations as an antimicrobial preservative in applications similar to other cationic surfactants.

Solutions containing benzalkonium chloride are active against wide range of bacteria, yeasts and fungi.

Activity is more marked against Gram-positive than Gram-negative bacteria and minimal against bacterial endospores and acid-fast bacteria.

Benzalkonium chloride is usually non-irritating, non-sensitising and is well tolerated in the dilutions normally employed on the skin and mucous membranes.

However benzalkonium chloride has been associated with adverse effects when used in some pharmaceutical formulations.

BAC-50 Antimicrobial contains the active substance C12-C16 Alkyl dimethyl benzyl ammonium chloride (ADBAC).

The active is a cationic molecule offering good surfactant properties and can be formulated together with non-ionic and/or amphoteric surfactants.

ADBAC has a broad antimicrobial efficacy against gram-positive and gram-negative bacteria, yeast, and enveloped viruses. ADBAC maintains its efficacy across a broad pH-range.

Single-active C12-C16 ADBAC products are available at different active concentrations, C-chain distributions and solvent combinations.

Benzalkonium chloride appears to be the main preservative in ophthalmic preparations on the EU market.

Approximately 74% of ophthalmic preparations have benzalkonium chloride as a preservative.

It is used as an antimicrobial preservative in numerous medicinal products for nasal route of administration and in many preparations for inhalation use authorised on EU markets.

Only in limited cases the medicinal products that contain benzalkonium chloride are intended for cutaneous, oral, oromucosal, rectal, vaginal, auricular, intravenous/ subcutaneous and intramuscular/intralesional/intraarticular use.

Benzalkonium chloride has three main categories of use: as a biocide, a cationic surfactant, and phase transfer agent in the chemical industry.

It is widely used in cosmetics, wet wipes, hand and surface sanitisers. Benzalkonium chloride was found to be an effective method of contraception.

Lozenges containing benzalkonium chloride are used for the treatment of superficial infections of the mouth and throat.

Benzalkonium chloride is a quaternary ammonium antiseptic and disinfectant with actions and uses similar to those of other cationic surfactants.

It is also used as an antimicrobial preservative for pharmaceutical products.

Benzalkonium chloride is a mixture of alkylbenzyldimethylammonium chlorides, the alkyl groups mainly having chain lengths of C12, C14 and C16.

It is presented as a white or yellowish-white powder or Benzalkonium chloride used as an excipient gelatinous, yellowish-white fragments.

Benzalkonium chloride is hygroscopic. On heating it forms a clear molten mass

For most multidose aqueous nasal, ophthalmic and otic products, benzalkonium chloride is the preservative of choice.

Benzalkonium chloride is a preservative that is commonly used in ophthalmic preparations. It has been used in eye drops as a preservative since the 1950s and in 2011 it was still the most common preservative used in ophthalmic solutions.

It is an effective bactericidal and fungicidal agent that helps to minimise the growth of organisms in multidose containers.

Only a few medicinal products containing benzalkonium chloride are intended for other routes of administrations i.e. cutaneous, oral, oromucosal, rectal, vaginal, auricular and parenteral use.

Therefore the warnings will be developed only for the most commonly used routes of administration.

For other routes not mentioned in the proposal for update, the information included in the package leaflet should follow the same principles.

The acute toxicity (LD50) of benzalkonium chloride after oral administration was approximately

344 mg/kg while LD50 after dermal administration was 3.56 mL/kg (80% ethanol/water solution).

BENZALKONIUM CHLORIDE ICSC: 1584

Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl chlorides

Alkyldimethylbenzylammonium chloride

Alkyldimethyl(phenylmethyl) quaternary ammonium chloride

Ammonium alkyldimethyl(phenylmethyl) chloride

Ammonium alkyldimethylbenzyl chloride

What is Benzalkonium Chloride?

Benzalkonium Chloride is a powerful antiseptic and a cationic surfactant. Benzalkonium Chloride is also known as BZK, BKC, BAK, alkyl dimethyl benzyl ammonium chloride and ADBAC.

Our Benzalkonium Chloride products have proven efficacy against a broad spectrum of microorganisms (gram + and – & acid fast bacteria, yeasts, moulds and enveloped vira such as HIV, herpes and corona).

They are effective through a wide pH range, are surface active/adhesive cationic agents and do not add unpleasant odour/colour to finished formulations.

Benzalkonium chlorides (BACs), also known as alkyl dimethyl benzyl ammonium chlorides, alkyl dimethyl (phenylmethyl) quaternary ammonium chlorides, ammonium alkyl dimethyl (phenylmethyl) chlorides, or ammonium alkyl dimethyl benzyl chlorides, are a class of quaternary ammonium compounds (QACs)

They are usually commercialized as a mixture of compounds with different lengths for the alkyl chain, ranging from C8 to C18, with higher biocide activity for C12 and C14 derivatives

BACs were reported for the first time in 1935 by Gerhard Domagk, gaining the market as zephiran chlorides, and were marketed as promising and superior disinfectant and antiseptics.

In 1947, the first product containing BACs was registered with the Environmental Protection Agency (EPA) in the United States.

Since then, they have been used in a wide variety of products, both prescription and over the counter. Applications range from domestic to agricultural, industrial, and clinical.

Domestic applications include fabric softeners, personal hygiene and cosmetic products, such as shampoos, conditioners, and body lotions, as well as ophthalmic solutions and medications that use the nasal route of delivery.

BACs are also among the most common active ingredients in disinfectants used in residential, industrial, agricultural, and clinical settings.

Additional registered uses for BACs in the United States include applications on indoor and outdoor surfaces (walls, floors, toilets, etc.), agricultural tools and vehicles, humidifiers, water storage tanks, products for use in residential and commercial pools, decorative ponds and fountains, water lines and systems, pulp and paper products, and wood preservation.

The recommended or allowed concentrations of BACs in different products vary considerably according to the application.

With perhaps the exception of countries which adopted stricter regulations toward BAC use, discussed in the next section, the potential use of BACs is likely on the rise.

The global market for disinfectants alone, which includes BACs, is expected to grow over 6% from 2016 and reach over $8 billion by 2021.

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.

ADBACs are a mixture of alkylbenzyldimethylammonium chlorides, in which the alkyl group has various even-numbered alkyl chain lengths.

KEYWORDS: alkyl dimethyl benzyl ammonium chlorides, antiseptic, BACs, benzalkonium chlorides, QACs

Solubility and physical properties

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 slow.

Aqueous solutions should be neutral to slightly alkaline. Solutions foam when shaken. Concentrated solutions have a bitter taste and a faint almond-like odour.

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

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

Laundry detergents and treatments

Softeners for textiles

Phase transfer agent

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.

Bioactive agents

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

Pharmaceutical products such as eye, ear and nasal drops or sprays, as a preservative

Personal care products such as hand sanitizers, wet wipes, shampoos, soaps, deodorants and cosmetics

Skin antiseptics and wound wash sprays, such as Bactine.

Throat lozenges and mouthwashes, as a biocide

Spermicidal creams

Cleaners for floor and hard surfaces as a disinfectant, such as Lysol and Dettol antibacterial spray and wipes.

Algaecides for clearing of algae, moss, lichens from paths, roof tiles, swimming pools, masonry, etc.

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. An advantage of benzalkonium chloride, not shared by ethanol-based antiseptics or hydrogen peroxide antiseptic, is that it does not cause a burning sensation when applied to broken skin.

However, prolonged or repeated skin contact may cause dermatitis.

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.

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.

Medicine

Benzalkonium chloride is a frequently used preservative in eye drops; typical concentrations range from 0.004% to 0.01%. Stronger concentrations can be caustic and cause irreversible damage to the corneal endothelium.

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

In Russia and China, benzalkonium chloride is used as a contraceptive. Tablets are inserted vaginally, or a gel is applied, resulting in local spermicidal contraception.

It is not a failsafe method, and can cause irritation.

Beekeeping

It is used in beekeeping for the treatment of rotten diseases of the brood.

Adverse effects

Although historically benzalkonium chloride has been ubiquitous as a preservative in ophthalmic preparations, its ocular toxicity and irritant properties, 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.

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.

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, others have recommended that benzalkonium chloride in nasal sprays be avoided.

In the United States, nasal steroid preparations that are free of benzalkonium chloride include budesonide, triamcinolone acetonide, dexamethasone, and Beconase and Vancenase aerosol inhalers.

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

Occupational exposure to benzalkonium chloride has been linked to the development of asthma.

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.

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.

Benzalkonium chloride is a human skin and severe eye irritant. It is a suspected respiratory toxicant, immunotoxicant, gastrointestinal toxicant, and neurotoxicant.

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.

Poisoning by benzalkonium chloride is recognised in the literature. A 2014 case study detailing the fatal ingestion of up to 8.1 oz (240ml) 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.

In 2018 a Japanese nurse was arrested and admitted to having poisoned approximately 20 patients at a hospital in Yokohama by injecting benzalkonium chloride into their intravenous drip bags.

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.

Biological activity

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.

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.

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.

Advancements in the quality and efficacy of benzalkonium chloride in current non-alcohol hand sanitizers has addressed the CDC concerns regarding gram negative bacteria, with the leading products being equal if not more effective against gram negative, particularly New Delhi metallo-beta-lactamase 1 and other antibiotic resistant bacteria.

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.

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.

Formulation can also help minimise deactivation of benzalkonium solutions in the presence of organic and inorganic contamination.

Degradation

Biodegradation pathways of BAC with Fenton process (H2O2/Fe2+)[39]

Benzalkonium chloride degradation follows consecutive debenzylation, dealkylation, and demethylation steps producing benzyl chloride, alkyl dimethyl amine, dimethyl amine, long chain alkane, and ammonia.

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 benzyl dimethyl amine as the first intermediate and dodecanal as the major product.

From here, benzyl dimethyl amine 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.

Benzyldimethylamine can then be converted into ammonia by performing demethylation twice, which removes both methyl groups, followed by debenzylation, removing the benzyl group using hydrogenation.

The diagram 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

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”.

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.

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

In September 2016, the FDA announced a ban on nineteen ingredients in consumer antibacterial soaps citing a lack of evidence for safety and effectiveness.

A ban on three additional ingredients, including benzalkonium chloride, was deferred to allow ongoing studies to be completed.

In Europe, the European Commission (EC) is involved in the regulation of BACs.

Recent rules in the European market included a change in the maximum residual levels of BACs allowed in food products from 0.5 mg/kg to 0.1 mg/kg, values which will undergo an additional review by the end of 2019.

Additionally, recent changes in legislation, Decision (EU) 2016/1950 and the Biocidal Products Regulation (EU) no. 528/2012 (the BPR) (10, 11), meant that BACs are no longer approved for use in several biocidal products, such as consumer hand and body wash antiseptics, which is in contrast with current legislation in the United States.

In the United States, the Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA) share the role of regulating BACs.

Such agencies regularly update regulations based on current scientific data, occasionally limiting the use of compounds found not to be safe or effective.

Final determinations, however, can be delayed by requests from the industry sector that commercializes such products.

As an example, the FDA recently published three proposed and final decisions regarding the use of chemicals as consumer hand rub antiseptics, consumer hand and body wash antiseptics, and health care antiseptics.

The rules banned specific biocides, such as triclosan, or added additional and stricter regulatory approvals for several others, such as chlorhexidine, regarding the applications mentioned above.

In all instances, however, BACs were excluded from the decisions and granted deferral letters as requested by manufacturers.

The decisions granted manufacturers extra time to provide data to fill gaps related to safety and efficacy.

Since 2015, letters and recommendations have been moving back and forth between the FDA and manufacturers and their representatives, such as the American Cleaning Institute, Lonza America, and Henkel Consumer Goods, Inc.

Decisions to postpone any action regarding the regulation of BACs were taken based on the affirmation of lack of sufficient data in the literature.

Yet, multiple researchers have studied the safety aspects of BACs over the years, which include data on the toxicity to humans and the environment, as we discuss next.

Benzalkonium chloride (BAC) is a major non-alcohol-based active ingredient used for clinical, food line, and domestic household biocides.

A biocide is a general term for a chemical agent, that may be applied topically in/on living tissue (antiseptic) or on inanimate objects (disinfectant), in order to inhibit growth of (“-static”) or kill (“-cidal”) microorganisms .

In communities where people are in constant contact with one another and surfaces covered with microorganisms, hand hygiene is important for infection control.

Studies found the use of antiseptic hand sanitizers subdued the prevalence of the common cold, acute respiratory syndromes, gastroenteritis, viral influenza, and more.

Similarly, this practice is important in limiting hospital-acquired, or nosocomial, infections between patients and clinical staff by limiting spread of opportunists like Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSAs), and vancomycin-resistant Enterococcus (VREs).

For such preventative measures, there are a variety of hand sanitizers available with alcohol-based and alcohol-free antiseptic agents including ethanol, triclosan and benzalkonium chloride.

Recently alcohol-free hand sanitizers with triclosan or benzalkonium chloride have been gaining ground due to concerns that ethanol is dries out the skin, is too toxic, and there are frequent cases of intentional ingestion.

Additional concerns involve the extensive use of antiseptics risking the selective survival of antiseptic resistant pathogens, which may be simultaneously selecting for antibiotic resistance.

This theory of simultaneous or “cross-selection” suggests that selection of either antiseptic or antibiotic resistance will also select for the other, ultimately resulting in weaker antibacterial therapy and pressure for careful use of both biocides.

Despite speculations of evolving resistance mechanisms, BACs are extensively used biocides especially efficacious against enveloped microorganisms.

Quaternary Ammonium Compounds (QACs)

Benzalkonium chloride.

BACs are classified as Quaternary Ammonium Compounds, which are positively charged derivatives of ammonium compounds with the chemical formula NR4+, where R can be different carbon-hydrogen containing groups.

QACs are commonly used as antiseptic agents because of their cationic amphiphilic property, having a distinct hydrophobic and hydrophilic region, resulting from nucleophilic substitution of alkyldimethylamine and benzyl chloride.

BAC’s hydrophilic cationic region destabilizes the pathogen’s surface by forming electrostatic interactions with negatively charged components.

These interactions effectively outcompete the divalent cations, which normally stabilizes surface structures by linking adjacent negatively-charged components.

Once close contact is accomplished by the hydrophilic region, the BAC’s hydrophobic region proceeds to penetrate the hydrophobic bilayer to cause cell leakage and lysis.

The ultimate effect of BACs is to damage the pathogen’s membrane, thus for bacteria, disrupting essential cell processes like ATP synthesis or solute uptake.

Therefore BAC’s amphiphilicity is critical in interacting with and perturbing target membranes for efficacious antimicrobial action.

Susceptible Microorganisms

The key component of BAC’s antimicrobial activity is membrane destruction, which is most effective against Gram-positive bacteria, some Gram-negative bacteria, some enveloped viruses, fungi, yeasts and protozoa.

Non-sporulating Gram-positive bacteria

A three-dimensional image of the surface of an enveloped measles virus.

General comparison of Gram-positive (a) and Gram-negative (b) bacterial cell wall structure.

Staphylococcus aureus is a Gram-positive bacterium that can survive on antiseptic-free hands for at least 150 minutes, which is enough time for it to spread and persist as a leading cause of nosocomial infections.

However, S. aureus is readily killed with BACs because their cell walls are chiefly composed of slightly-negatively-charged peptidoglycan and techoic acids.

These surface structures also lack effective permeability properties and allow uptake of more BACs and other antimicrobial substances.

Enveloped viruses

Some viruses require a lipid envelope, which serves a dual function: first, as a protective barrier from harsh environmental conditions of pH or desiccation, and secondly as an undesirable target for BAC-based antiseptics.

Therefore, enveloped viruses like human immunodeficiency virus (HIV), hepatitis B virus (HBV), influenza virus, measles virus, vaccinia virus, meningopneumonitis virus, Semliki Forest virus, canine distemper virus, rabies virus, fowl laryngotracheitis, and feline pneumonitis virus are all susceptible to BACs.

Impermeability of Benzalkonium Chloride

In particular, impermeability by additional or architecturally-complex surface layers in addition to the cellular membrane are commonly exhibited by a variety of microorganisms that render BAC less efficacious.

Not only is BAC prevented from causing cell lysis, but the uptake of BAC and other active agents in hand sanitizers is severely inhibited.

Therefore, even at high concentrations, BACs tend to be “non-cidal” and are rather bacteriostatic, mycobacteriostatic, and sporostatic.

Bacteriostatic

Pseudomonas aeruginosa is a Gram-negative bacterium with reduced sensitivity to BACs, and is of clinical importance as a common opportunistic pathogen causing nosocomial respiratory tract infections like pneumonia.

Generally, Gram-negative bacteria like P. aeruginosa are less permeable to QACs than non-sporulating, non-mycobacterial Gram-positive organisms.

This marked difference in uptake regulation by Gram-negative bacteria is mediated by structural differences including an outer membrane, porins, and efflux pumps.

While inner membranes have a conventional phospholipid bilayer, the outer leaflet of an outer membrane is composed of lipopolysaccharides (LPS).

The outer membrane’s reduced permeability is a result of strong LPS-LPS lateral interactions, where a highly anionic “R-core” region on the LPS links interacts with soluble divalent cations to link LPS molecules together.

The outer membrane’s hydrophobic core has greater London dispersion forces as LPS has up to seven hydrocarbon tails per molecule compared to two per each phospholipid molecule of the inner membrane.

Small porins studding this outer membrane facilitates diffusion of hydrophilic solutes, but can strictly restrict larger molecules of BAC.

Additionally, efflux proteins in the inner membrane may actively pump out BACs that make it past the outer membrane.

Although P. aeruginosa is only a model organism and there have been reports of BAC efficaciously destructing the outer membranes of other Gram-negative species, P. aeruginosa maximizes BAC impermeability as an antiseptic-resistance measure.

Schematic diagram of Mycobacterial cell wall structure.

Mycobacteriostatic

Mycobacteria are some of the most antiseptic-resistant opportunistic pathogens, characterized by highly hydrophobic cell walls of a complex mycoyl arabinogalactan-peptidoglycan skeletal architecture.

Although the specific component conferring antiseptic resistance remains undecided, experiments involving cell wall synthesis inhibitors suggests that a cell wall component like lipid content is responsible.

Further studies supports the idea of lipid content determining BAC (im)permeability, as species with high lipid content like Mycobacterium tuberculosis were found to be less antiseptic sensitive than Mycobacterium phlei with lower lipid content.

Sporostatic

Clostridium difficile is a major spore forming bacteria, causing 15-55% of all nosocomial diarrheas.

Similar to Gram-negative and myco- bacteria, additional impermeability layers of complex spore coat(s) hinders the permeability and activity of BACs.

Roles Classification

Chemical Role(s): surfactant: A substance which lowers the surface tension of the medium in which it is dissolved, and/or the interfacial tension with other phases, and, accordingly, is positively adsorbed at the liquid/vapour and/or at other interfaces.

detergent: A surfactant (or a mixture containing one or more surfactants) having cleaning properties in dilute solutions.

Biological Role(s): antibacterial agent: A substance (or active part thereof) that kills or slows the growth of bacteria.

disinfectant: An antimicrobial agent that is applied to non-living objects to destroy harmful microorganisms or to inhibit their activity.

Application(s): detergent: A surfactant (or a mixture containing one or more surfactants) having cleaning properties in dilute solutions.

antiseptic drug: A substance used locally on humans and other animals to destroy harmful microorganisms or to inhibit their activity (cf. disinfectants, which destroy microorganisms found on non-living objects, and antibiotics, which can be transported through the lymphatic system to destroy bacteria within the body).

benzalkonium chloride (CHEBI:3020) has role antibacterial agent (CHEBI:33282)

benzalkonium chloride (CHEBI:3020) has role antiseptic drug (CHEBI:48218)

benzalkonium chloride (CHEBI:3020) has role detergent (CHEBI:27780)

benzalkonium chloride (CHEBI:3020) has role disinfectant (CHEBI:48219)

benzalkonium chloride (CHEBI:3020) has role surfactant (CHEBI:35195)

benzalkonium chloride (CHEBI:3020) is a organic chloride salt (CHEBI:36094)

benzalkonium chloride (CHEBI:3020) is a quaternary ammonium salt (CHEBI:35273)

INNs Sources

benzalkonii chloridum LINGUA LATINA

benzalkonium chloride

chlorure de benzalkonium Français

cloruro de benzalconio Español ChemIDplus

Synonyms

ADBAC ChEBI

Alkyl dimethylbenzyl ammonium chloride

Alkylbenzyldimethylammonium chloride

Alkyldimethyl(phenylmethyl)quaternary ammonium chlorides

Alkyldimethylbenzylammonium chloride

Benzalkonium chloride

benzalkonium chlorides

Benzalkonium Chloride Solutions

BC50: 50% Benzalkonium Chloride Solutions

BC50: Low foam

BC80: 80% Benzalkonium Chloride Solutions

BC80: Low foam

BAC70 WLF: Winterised, low foam oilfield biocide

Benzalkonium Chloride Solutions can be tailored to your specific industrial requirements.

Please CONTACT US for variations on concentration, solvents and other additives.

BIOCIDAL PROPERTIES:

Benzalkonium chloride is a member of the quaternary ammonium class of biocides, recognised for its dual biocidal and detergency properties.

Its biocidal efficacy depends on its capacity to act as a cationic surfactant in binding to and disrupting cellular and intracellular membranes, and associated biochemical processes.

Functions such as cell adhesion, cell signaling, selective permeability to ions and nutritional organic molecules ensure cellular survival through its ability to interact with and respond effectively to environmental stimuli.

Disruption of these processes ensures a high level of activity against bacteria, algae, fungi and enveloped viruses at exceptionally low concentrations.

BC50 passes stringent BS EN 1276 microbicidal testing (high organic contamination, hard water conditions) at a dilution of 1:1250, giving a 5-log kill (1:100,000 bacterial survival) against a range of the most problematic organisms.

CHARACTERISTICS OF BENZALKONIUM CHLORIDE DISINFECTANTS:

Benzalkonium chloride is widely used in the formulation of disinfectants and cleaner-sanitisers for the hospital, livestock, food & dairy and personal hygiene sectors.

Offers rapid, safe, powerful antimicrobial activity at low ppm

Strong detergency ensures ease of removal of organic soil which harbours microbes

Ease of formulation for biocidal activity under high organic contamination conditions

Compatible with non-ionic, amphoteric and cationic surface-active agents

Displays synergistic activity with other classes of biocide & excipients

Retains activity in highly acid to highly alkaline formulations

High molecular stability with retention of activity at extremes of temperature

Lends itself well to formulation optimisation for hard water conditions

Retains biocidal activity in aqueous and organic solvents

Benzalkonium chloride disinfectants are non-toxic, non-tainting & odour-free at typical use dilutions

For Quat-Chem disinfection products based on quaternary ammonium compounds, please click here.

INDUSTRIAL APPLICATIONS:

For industrial applications of benzalkonium chloride, please click here.

ENVIRONMENTAL CHARACTERISTICS:

Quaternary ammonium compounds display a high level of biodegradability when tested in accordance with OECD test protocol 301C.

It is not known to accumulate in the natural environment under normal use conditions.

Like all detergents, ADBAC is highly toxic to marine organisms under laboratory conditions, but does not bio-accumulate in organisms.

In the natural environment it is readily deactivated by clays and humic substances which neutralises its aquatic toxicity and prevent its migration across environmental compartments.

Synonyms: Alkyl dimethyl benzyl ammonium chloride, ADBAC, BC50, BAC 50, BKC 50, BC80, BAC 80, BKC 80

REGULATORY:

Alkyl dimethyl benzyl ammonium chloride has been pre-registered under REACH regulation and notified under the Biocidal Product Directive 98/8/EC (ref: N501).

Regulatory process names

Benzalkonium chloride

Cosmetic Products Regulation, Annex V – Allowed Preservatives

Quaternary ammonium compounds, alkylbenzyldimethyl, chlorides

Pre-Registration process, Other

IUPAC names

Alkyldimethylbenzylammonium chloride

ammonium, alkylbenzyldimethyl-,chloride

Benzalkonium Chlorid

benzalkonium chloride

Benzalkonium chloride, alkyl distribution C8-C16

Benzalkónium-klorid

benzyl-dimethyl-tetradecylazanium chloride

benzyl-dodecyl-dimethylazanium chloride

N-alkyl(C8-C16)dimethylbenzylammonium chloride

Quaternary ammonium compounds, alkylbenzyldimethyl, chlorides

Other names

Benzalkonium chloride

Benzalkonium Chloride C16

Other identifiers: 12741-06-9

CAS number: 39434-18-9

CAS number: 59890-14-1

CAS number: 75635-12-0

CAS number: 8001-54-5

CAS number: 8011-91-4

CAS number: 8036-90-6

CAS number: 8039-63-2

CAS number: 8045-21-4

Alkylbenzyldimethylammonium chlorides with alkyl chain lengths of C8, C10, C12, C14, C16 and C18

Benzalkonium chloride

C8-18-Alkydimethylbenzyl ammonium chlorides

Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides

quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides

Translated names

(C8-18)alkylbenzyldimetylammoniumklorid (no)

(C8-18)alkylbenzyldimetylammoniumklorid (sv)

(C8-18)alkyylibentsyylidimetyyliammoniumkloridi (fi)

chlorki czwartorzedowych zwiazków amoniowych – chlorki benzylo(C8-18)alkilodimetyloamonium (pl)

composti di ammonio quaternario, benzil-C8-18-alchildimetil, cloruri (it)

compostos de amónio quaternário, benzil-C8-18-alquildimetil, cloretos (pt)

composés d’ammonium quaternaire, benzyl-C8-18-alkyldiméthyle, chlorures (fr)

compuestos de amonio cuaternario, bencil-C8-18-alquildimetil, cloruros (es)

compusi de amoniu cuaternari, benzil-C8-18-alildimetil, cloruri (ro)

ketvirtiniai amonio junginiai, benzil-C8-18-alkildimetil-, chloridai (lt)

kvarterne amonijeve spojine, benzil-C8-18-alkildimetil kloridi (sl)

kvarterni amonijevi spojevi,benzil-C8-18-alkildimetil, kloridi (hr)

kvarterní amoniové sloučeniny, alkyl(C8-C18)(benzyl) dimethylamonium-chlorid (cs)

kvartérne amóniové zlúčeniny, (C8-18-alkyl)(benzyl)di(metyl)amónium-chloridy (sk)

Kvaternaarsete bensüül-C 8-18-alküüldimetüülammooniumiühendite kloriidid (et)

kvaterner ammónium vegyületek, benzil-C8-18-alkildimetilammónium-klorid (hu)

kvaternääriset ammoniumyhdisteet, bentsyyli-C8-18-alkyylidimetyylikloridit (fi)

kvaternære ammoniumforbindelser, benzyl-C8-18-alkyldimethyl-, chlorider (da)

kvaternære ammoniumforbindelser, benzyl-C8-18-alkyldimetyl, klorider (no)

quaternaire ammoniumverbindingen, benzyl-C8-18-alkyldimethyl, chloriden (nl)

Quaternäre Ammoniumverbindungen, Benzyl-C8-18-alkyldimethyl-, Chloride (de)

četraizvietotie amonija savienojumi, benzil-C8-C18-alkildimetil-hlorīdi (lv)

χλωρίδια των βενζυλο-C8-18-αλκυλοδιμεθυλο τεταρτοταγών ενώσεων αμμωνίου (el)

кватернерни амониеви съединения, бензил-C8-18-aлкилдиметил, хлориди (bg)

CAS names

Alkylbenzyldimethylammonium chlorides, benzyl-C8-18-alkyldimethyl

IUPAC names

Alkylbenzyldimethylammonium chlorides, benzyl-C8-18-alkyldimethyl

Alkyldimethylbenzyl ammonium chloride

Benzalkonium chloride

Benzyl(dodecyl)dimethylammonium chloride, benzyl(tetradecyldimethylammonium chloride

benzyl-C8-18-alkyldimethyl chloride

benzyl-decyl-dimethylazanium chloride

benzyl-decyl-dimethylazanium;chloride

benzyl-dimethyl-tridecyl-azanium chloride

N-benzyl-N,N-dimethyldecan-1-aminium chloride

Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides

quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides

Quaternary ammonium compounds, benzylcoco alkyldimethyl, chlorides

Other identifiers

50957-62-5

Other

CAS number

50957-62-5

Other

Deleted CAS number

51004-71-8

Other

CAS number

51004-71-8

Other

Deleted CAS number

51668-62-3

CAS number

51668-62-3

Deleted CAS number

612-140-00-5

Index Number

63449-41-2

Alkyl (C12-16) dimethylbenzyl ammonium chloride (ADBAC/BKC (C12-16))

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

EC Inventory, Other, Cosmetic Products Regulation, Annex III – Restricted Substances, Cosmetic Products Regulation, Annex V – Allowed Preservatives

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

Pre-Registration process, Other, Cosmetic Products Regulation, Annex III – Restricted Substances, Cosmetic Products Regulation, Annex V – Allowed Preservatives

Translated names

Alkil (C12-16) dimetilbenzil amonijev klorid (ADBAC/BKC (C12-16)) (hr)

Alkil (C12-16) dimetilbenzil amonio chloridas (ADBAC (C12-16)) (lt)

Alkil (C12-16) dimetilbenzilamonija hlorīds (ADBAC/BKC (C12-16)) (lv)

Alkil (C12-16)-chlorku dimetylobenzyloamonu (ADBAC/BKC (C12-16)) (pl)

Alkil (C12–16) dimetil-benzil-ammónium-klorid (ADBAC/BKC [C12–16]) (hu)

Alkil (C12–16) dimetilbenzil amonijev klorid (ADBAC/BKC (C12–16)) (sl)

Alkyl (C12-16) dimethylbenzyl ammonium chloride (ADBAC/BKC (C12-C16)) (mt)

Alkyl (C12-16) dimethylbenzyl ammonium chloride (ADBAC/BKC (C12-C16)) (no)

alkyl(C12-16)benzyldimetylamónium-chlorid [ADBAC/BKC (C12-C16)] (sk)

alkyl(C12-16)dimethylbenzylammoniumchlorid (ADBAC/BKC (C12-16)) (da)

Alkyl(C12-16)dimethylbenzylammoniumchlorid (ADBAC/BKC (C12-16)) (de)

alkyl(C12-16)dimethylbenzylammoniumchlorid (ADBAC/BKC (C12-C16)) (cs)

Alkyl(C12-16)dimethylbenzylammoniumchloride (ADBAC/BKC (C12-16)) (nl)

Alkyl(C12-16)dimetylbensylammoniumklorid (ADBAC/BKC (C12-C16)) (sv)

Alkyyli-(C12-16)-dimetyylibentsyyliammoniumkloridi (ADBAC/BKC (C12-16)) (fi)

C12–16-alküüldimetüülbensüülammooniumkloriid (ADBAC/BKC (C12–16)) (et)

Chlorure d’alkyl(C12-C16)diméthylbenzylammonium [ADBAC/BKC (C12-C16)] (fr)

Cloreto de alquil(C12-16)dimetilbenzilamónio (ADBAC/KBC C12-16) (pt)

Cloruro de C12-16-alquildimetilbencilamonio (ADBAC/BKC (C12-16)) (es)

Cloruro di alchil (C12-16) dimetilbenzilammonio (ADBAC/BKC (C12-C16)) (it)

Clorură de alchil (C12-16) dimetilbenzil amoniu [ADBAC/BKC (C12-C16)] (ro)

Χλωριούχο αλκυλο(C12-16)διμεθυλοβενζυλαμμώνιο (ADBAC/BKC (C12-C16)) (el)

Алкил(C12-16)диметилбензиламониев хлорид (ADBAC/BKC (C12-C16)) (bg)

CAS names

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

IUPAC names

Alkyl dimethyl benzyl ammonium chloride

benzyl-C12-16-alkyldimethyl, chlorides

Benzyl-dimethyl-tetradecyl azanium chloride

benzyl-dimethyl-tetradecylazanium chloride

dimethyl benzyl ammonium chloride

N-ALKYL(C12-16)-N,N-DIMETHYL-N-BENZYLAMMONIUM CHLORIDE

N-Alkyl-N,N-dimethyl-N-benzylammonium Chloride

N-benzyl-N,N-dimethyl-C12-16-(evennumbered)-alkyl-1-aminium chloride

N-Benzyl-N,N-dimethyltetradecan-1-aminium chloride

N-benzyl-N,N-dimethyltetradecan-1-aminium chloride

Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

Quaternary ammoniumcompounds, benzyl-C12-16-alkyldimethyl, chlorides

Other identifiers: 284043-23-8

CAS number: 284043-23-8

Deleted CAS number:39403-41-3

CAS number: 39403-41-3

Deleted CAS number: 63449-42-3

CAS number: 63449-42-3

Deleted CAS number: 68424-85-1

—————————————————————————————————-

EC/List no.: 270-325-2; CAS no.: 68424-85-1

CAS RN: 68424-85-1; Chemical Name: Quaternary ammonium compounds, benzyl-C12-16-alkyldimethyl, chlorides

Substance names and other identifiers