Benzalkonium chloride, also known as
alkyldimethylbenzylammonium chloride and
ADBAC, is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered alkyl chain lengths. This product is a nitrogenous cationic surface-acting agent belonging to the quaternary ammonium group. It has three main categories of use; as a
biocideA biocide is a chemical substance or microorganism which can deter, render harmless, or exert a controlling effect on any harmful organism by chemical or biological means. Biocides are commonly used in medicine, agriculture, forestry, and industry...
, a cationic surfactant and phase transfer agent in the chemical industry.
Properties
Benzalkonium chloride is readily soluble in
ethanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
and
acetoneAcetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
. Although dissolution in water is slow, aqueous solutions are easier to handle and are preferred. Solutions should be neutral to slightly alkaline, with colour ranging from colourless to a pale yellow. Solutions foam profusely when shaken, have a bitter taste and a faint almond-like odour which is only detectable in concentrated solutions.
Availability
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
rheologyRheology is the study of the flow of matter, primarily in the liquid state, but also as 'soft solids' or solids under conditions in which they respond with plastic flow rather than deforming elastically in response to an applied force....
modifiers (
alcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s,
polyethylene glycolPolyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
s, etc.) to prevent increases in viscosity or gel formation under low temperature conditions.
Applications
The applications are extremely wide ranging, from disinfectant formulations, such as being an active ingredient in Dettol and Lysol brand products, to
microbial corrosionMicrobial corrosion, also called bacterial corrosion, bio-corrosion, microbiologically-influenced corrosion, or microbially-induced corrosion , is corrosion caused or promoted by microorganisms, usually chemoautotrophs...
inhibitionA corrosion inhibitor is a chemical compound that, when added to a liquid or gas, decreases the corrosion rate of a material, typically a metal or an alloy. The effectiveness of a corrosion inhibitor depends on fluid composition, quantity of water, and flow regime...
in the oilfield sector, and a multi-surface mould, algae and moss remover. It is used in:
- Pharmaceuticals such as leave-on skin antiseptics
- Antiseptic in Bactine
Bactine is the trademarked name of a range of topical first-aid treatments produced by Bayer. It includes a first aid liquid with active ingredients Benzalkonium chloride, an antiseptic, and lidocaine, a local anaesthetic. Bactine Liquid is a topical anesthetic , which means that it is used to numb...
to safely treat childhood scrapes and cuts.
- Advanced, next-generation hand sanitizers
- Hygienic towelettes and wet wipes
- Cosmetics such as eye and nasal drops, as a preservative
- Cleaners for floor and hard surfaces as a disinfectant
- High-level surgical instrument sterilizing and disinfection solutions
- Air and surface sprayable disinfectants
- Over-the-counter herpes cold sore and fever blister single-application treatments such as RELEEV and Viroxyn
- Algaecide
Benzalkonium chloride and other alcohol-free solutions are often used in preparations used for skin disinfection prior to use of syringes.
New generation, plant-derived versions are used in hand sanitizers that are more effective and safer than alcohol gels. As an antiseptic, it has the advantage of not burning when put on a wound, which is not the case with ethanol-based antiseptics or hydrogen peroxide. As the antiseptic in Bactine, benzalkonium chloride has been used safely for decades on childhood scrapes and cuts.
Biological activity
The greatest biocidal activity is associated with the C12-C14 alkyl derivatives. The mechanism of bactericidal/
microbicidalMicrobicides for sexually transmitted diseases, are pharmacologic agents and chemical substances that are capable of killing or destroying certain microorganisms that commonly cause human infection, for example the human immunodeficiency virus....
action is thought to be due to disruption of intermolecular interactions. This can cause dissociation of cellular membrane
lipid bilayerThe lipid bilayer is a thin membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around cells. The cell membrane of almost all living organisms and many viruses are made of a lipid bilayer, as are the membranes surrounding the cell nucleus...
s, which compromises cellular permeability controls and induces leakage of cellular contents. Other biomolecular complexes within the bacterial cell can also undergo dissociation.
EnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s, 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-positiveGram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria are generally more susceptible than
Gram-negativeGram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
. Activity is not greatly affected by pH, but increases substantially at higher temperatures and prolonged exposure times. In a 1998 study utilizing the FDA protocol, a non-alcohol sanitizer utilizing the active ingredient benzalkonium chloride met the FDA performance standards, while
PurellPurell is an instant hand sanitizer made of ethyl alcohol which claims to kill "99.99%" of most common germs that may cause illness in as little as 15 seconds. Its active ingredient is ethanol . It is used by wetting one's hands thoroughly with the product, then briskly rubbing one's hands together...
, a popular alcohol-based sanitizer, did not. The study found that a benzalkonium chloride-based sanitizer was the most favorable non-alcohol-based hand sanitizer. 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 NDM1 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. This technique has been used to improve virucidal activity of quaternary ammonium-based formulations to healthcare infection hazards such as
hepatitisHepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
,
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, etc. Quaternary ammonium formulations are now the disinfectants of choice for hospitals. This is on account of user and patient safety even on contact with treated surfaces and the absence of harmful fumes. Benzalkonium solutions for hospital use tend to be neutral to alkaline, non-corrosive on metal surfaces, non-staining, and safe to use on all washable surfaces.
The use of appropriate supporting
excipientAn excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or...
s can also greatly improve efficacy and detergency, and prevent deactivation under use conditions. Formulation requires great care, as benzalkonium solutions can readily be inactivated in the presence of organic and inorganic contamination. Solutions are incompatible with
soapIn chemistry, soap is a salt of a fatty acid.IUPAC. "" Compendium of Chemical Terminology, 2nd ed. . Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford . XML on-line corrected version: created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins. ISBN...
s, and must not be mixed with anionic surfactants.
Hard waterHard water is water that has high mineral content . Hard water has high concentrations of Ca2+ and Mg2+ ions. Hard water is generally not harmful to one's health but can pose serious problems in industrial settings, where water hardness is monitored to avoid costly breakdowns in boilers, cooling...
salts can also reduce biocidal activity. As with any disinfectant, it is recommended that surfaces are free from visible dirt and interfering materials for maximal disinfection performance by quaternary ammonium products.
Although hazardous levels are not likely to be reached under normal use conditions, benzalkonium and other detergents can pose a hazard to marine organisms. Quaternary ammonium disinfectants are effective at very low ppm levels, so excess use should be avoided.
Safety
ADBAC is highly toxic to fish (LC
50 = 280 μg ai/L), very highly toxic to aquatic invertebrates (LC
50 = 5.9 μg ai/L), moderately toxic to birds ( = 136 mg/kg-bw), and slightly toxic to mammals (LD
50 = 430 mg/kg-bw). Benzalkonium chloride solutions of 10% or more are toxic to humans, causing irritation to the skin and mucosa, and death if taken internally.
Several studies have identified allergic reactions to benzalkonium chloride by some individuals but several studies have cast doubt on its reputation for other negative health effects. It is still widely used in
eyewashEyewash is a fluid, commonly saline, used in the aid of rinsing of the eye. Eyewash may also describe the apparatus used to physically wash the eyes in the case that they may be contaminated by foreign materials or substances....
es,
nasal sprayNasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
s, hand and face washes,
mouthwashMouthwash or mouth rinse is a product used to enhance oral hygiene. Some manufacturers of mouthwash claim that antiseptic and anti-plaque mouth rinse kill the bacterial plaque causing cavities, gingivitis, and bad breath. Anti-cavity mouth rinse uses fluoride to protect against tooth decay...
es,
spermicidalSpermicide is a contraceptive substance that eradicates sperm, inserted vaginally prior to intercourse to prevent pregnancy. As a contraceptive, spermicide may be used alone. However, the pregnancy rate experienced by couples using only spermicide is higher than that of couples using other methods...
creams, and in various other cleaners, sanitizers, and disinfectants. Manufacturers of over-the-counter artificial tears and eye washes became concerned about chemical sensitivity from long-term daily use and have in some products substituted
EDTAEthylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand...
as a preservative. Some have packaged eye drops in single-use vials with no preservative for sensitive eyes. There has also been concern that long-term use of benzalkonium as a preservative in nasal sprays may cause swelling of mucosa and lead to
rhinitis medicamentosaRhinitis medicamentosa is a condition of rebound nasal congestion brought on by extended use of topical decongestants that work by constricting blood vessels in the lining of the nose.-Presentation:This condition typically occurs after 5 to 7 days of use of such medications...
. Although some studies have found no correlation between use of benzalkonium chloride in nasal sprays and
rhinitis medicamentosaRhinitis medicamentosa is a condition of rebound nasal congestion brought on by extended use of topical decongestants that work by constricting blood vessels in the lining of the nose.-Presentation:This condition typically occurs after 5 to 7 days of use of such medications...
, others have found benzalkonium chloride in oxymetazoline nasal spray to worsen
rhinitis medicamentosaRhinitis medicamentosa is a condition of rebound nasal congestion brought on by extended use of topical decongestants that work by constricting blood vessels in the lining of the nose.-Presentation:This condition typically occurs after 5 to 7 days of use of such medications...
in healthy volunteers after both long-term use and short-term use.
Contact lens solutions typically contain 0.002% to 0.01% benzalkonium chloride. K. C. Swan found that repeated use of benzalkonium chloride at concentrations of 1:5000 (0.02%) or stronger can denature corneal protein and cause irreversible damage to the eye. Swan also found that 0.04% to 0.05% solutions of benzalkonium chloride can cause punctures of the corneal epithelium. The disadvantages of using benzalkonium chloride solutions with contact lenses are also discussed in the literature.
A disinfectant containing benzalkonium chloride and the related compound
didecyldimethylammonium chlorideDidecyldimethylammonium chloride is an antiseptic/disinfectant, which is used in many biocidal applications. They cause disruption of intermolecular interactions and dissociation of lipid bilayers. They are Broad spectrum Bactericidal and Fungicidal.They can be used as Disinfectant Cleaner for...
(DDAC) has been identified as the most probable cause of birth defects and fertility problems in caged mice.
A 2009 study has found that benzalkonium chloride, when used in less than lethal concentrations, resulted in an increased resistance to the disinfectant solution, and a 256-fold increase in resistance of the bacteria
Pseudomonas aeruginosaPseudomonas aeruginosa is a common bacterium that can cause disease in animals, including humans. It is found in soil, water, skin flora, and most man-made environments throughout the world. It thrives not only in normal atmospheres, but also in hypoxic atmospheres, and has, thus, colonized many...
to the
ciprofloxacinCiprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
antibiotic, even though the bacterial colonies had not been previously exposed to the antibiotic.
See also
- Stearalkonium chloride
Stearalkonium chloride is a type of benzalkonium chloride which is used as an anti-static agent, a surfactant and an antimicrobial. It is an ingredient in some cosmetics and hair care products, particularly conditioners....
- Polyaminopropyl biguanide, an alternative preservative for contact lens solutions
Further reading
- Bernstein IL: Is the use of benzalkonium chloride as a preservative for nasal formulations a safety concern? J Allergy Clin Immunol 2000 Jan; 105(1 Pt 1): 39-44.
- Graf P: Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis and rhinitis medicamentosa. Clin Ther 1999 Oct; 21(10): 1749-55.
- Graf P, Hallen H, Juto JE: Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers. Clin Exp Allergy 1995 May; 25(5): 395-400.
External links