Description
Benzalkonium chloride is a quaternary ammonium
mixture of alkyl, dimethyl and benzyl ammonium
chlorides.It is an irritant rather than a sensitizer,
but may cause contact dermatitis in nursing and
medical personnel. An unusual case was reported in a
farm worker who used a detergent containing benzalkonium
chloride to clean the piggery.
Chemical Properties
white or light yellow/grey solid, or colourless aqueous solution
Chemical Properties
Benzalkonium chloride occurs as a white or yellowish-white
amorphous powder, a thick gel, or gelatinous flakes. It is
hygroscopic, soapy to the touch, and has a mild aromatic odor
and very bitter taste.
Uses
benzalkonium chloride is a preservative with anti-microbial and deodorant properties. It can also be used as a surfactant. With continuous use, it may cause occasional allergic reactions.
Uses
Cationic surface active agent and germicide. Pharmaceutic aid (preservative). Algicide.
Uses
Benzalkonium chloride is a quaternary ammonium antiseptic and disinfectant with actions and uses similar to those of other cationic surfactants. It is used prior to surgical procedures or for minor wound care to reduce risks of infection. For most multidose aqueous nasal, ophthalmic and otic products, benzalkonium chloride is the preservative of choice.
Definition
ChEBI: A class of quaternary ammonium chloride salts in which the nitrogen is substituted by a benzyl group, two methyl groups and an even-numbered alkyl chain.
Production Methods
Benzalkonium chloride is formed by the reaction of a solution of Nalkyl-
N-methylbenzamine with methyl chloride in an organic
solvent suitable for precipitating the quaternary compound as it is
formed.
brand name
Roccal (Sterling Winthrop); Zephiran Chloride
(Sterling Winthrop).
Hazard
Highly toxic; poison.
Agricultural Uses
Biocide, Algaecide, Fungicide: Used as an algaecide to control slime mold, algae,
fish pathogens, and mollusks in ponds, canals and bodies of water. Also widely used in deodorants, detergents,
sanitizers and germicides for applications in food plants,
laundries, and operating rooms. Not listed for use in
EU countries
. Registered for use in the U.S. but not
California.
Pharmaceutical Applications
Benzalkonium chloride is a quaternary ammonium compound used
in pharmaceutical formulations as an antimicrobial preservative in
applications similar to other cationic surfactants, such as cetrimide.
In ophthalmic preparations, benzalkonium chloride is one of the
most widely used preservatives,at a concentration of
0.01–0.02% w/v. Often it is used in combination with other
preservatives or excipients, particularly 0.1% w/v disodium edetate,
to enhance its antimicrobial activity against strains of Pseudomonas.
In nasal, and otic formulations a concentration of
0.002–0.02% w/v is used, sometimes in combination with
0.002–0.005% w/v thimerosal. Benzalkonium chloride 0.01%
w/v is also employed as a preservative in small-volume parenteral
products. Benzalkonium chloride was also shown to enhance the
topical penetration of lorazepam.
Benzalkonium chloride is additionally used as a preservative in
cosmetics.
Trade name
AMMONYX®; ARQUAD DMMCB-75®;
BARQUAT® MB-50; BARQUAT® MB-80;
BAYCLEAN®; BIO-QUAT 50-24®; CATAMINE® AB;
CONSAN®; DRAPOLENE®; GARDIQUAT®-1450;
HYAMINE®-3500; INTEXAN® LB-50; KATAMINE®
AB; NEO GERM-I-TOL®; ONYX BTC; OSVAN;
RODALON®; SENTINEL®; TRITON® K-60;
VIKROL® RQ
Contact allergens
This quaternary ammonium cationic surfactant is a
mixture of alkyl, dimethyl, and benzyl ammonium
chlorides (-R). It is an irritant rather than a sensitizer,
but may cause allergic contact dermatitis from creams,
detergents/antiseptics, ophthalmic preparations, and in
nursing, veterinary, dental, and medical personnel. Its
presence was observed in plaster of Paris.
Mechanism of action
Rapid action, thought to effect the cytoplasmic membrane that controls cell permeability
Clinical Use
Alkylbenzyldimethylammonium chloride (Zephiran) is a mixtureof alkylbenzyldimethylammonium chlorides of the generalformula [C6H5CH2N(CH3)2R] Cl , where R represents amixture of alkyl chains beginning with C8H17 and extendingto higher homologues with C12H25, C14H29, and C16H33. The higher–molecular-weight homologues compose the majorfractions. Although variations in the physical and antimicrobialproperties exist between individual members of the mixture,they are of little importance in the chemistry of the overallproduct. Benzalkonium chloride occurs as a white gel thatis soluble in water, alcohol, and organic solvents. Aqueous solutionsare colorless, slightly alkaline, and very foamy.
Benzalkonium chloride is a detergent, an emulsifier, anda wetting agent. It is used as an antiseptic for skin and mucousmembranes in concentrations of 1:750 to 1:20,000. Forirrigation, 1:20,000 to 1:40,000 concentrations are used. Forstorage of surgical instruments, 1:750 to 1:5,000 concentrationsare used, with 0.5% NaNO3 added as a preservative.
Side effects
Clinically, benzalkonium chloride may cause eye irritation and is known to discolour soft contact lenses.
Benzalkonium chloride in eye drops has also been reported to cause punctate keratopathy and/or toxic
ulcerative keratopathy, especially in frequent or prolonged use or in conditions where the cornea is
compromised.
Safety
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.
Ototoxicity can occur when benzalkonium chloride is applied to
the ear and prolonged contact with the skin can occasionally
cause irritation and hypersensitivity. Benzalkonium chloride is also
known to cause bronchoconstriction in some asthmatics when used
in nebulizer solutions.
Toxicity experiments with rabbits have shown benzalkonium
chloride to be harmful to the eye in concentrations higher than that
normally used as a preservative. However, the human eye appears to
be less affected than the rabbit eye and many ophthalmic products
have been formulated with benzalkonium chloride 0.01% w/v as
the preservative.
Benzalkonium chloride is not suitable for use as a preservative in
solutions used for storing and washing hydrophilic soft contact
lenses, as the benzalkonium chloride can bind to the lenses and may
later produce ocular toxicity when the lenses are worn. Solutions
stronger than 0.03% w/v concentration entering the eye require
prompt medical attention.
Local irritation of the throat, esophagus, stomach, and intestine
can occur following contact with strong solutions (>0.1% w/v).
The fatal oral dose of benzalkonium chloride in humans is estimated
to be 1–3 g. Adverse effects following oral ingestion include
vomiting, collapse, and coma. Toxic doses lead to paralysis of the
respiratory muscles, dyspnea, and cyanosis.
LD
50 (mouse, oral): 150 mg/kg
LD
50 (rat, IP): 14.5 mg/kg
LD
50 (rat, IV): 13.9 mg/kg
LD
50 (rat, oral): 300 mg/kg
LD
50 (rat, skin): 1.42 g/kg
storage
Benzalkonium chloride is hygroscopic and may be affected by light,
air, and metals.
Solutions are stable over a wide pH and temperature range and
may be sterilized by autoclaving without loss of effectiveness.
Solutions may be stored for prolonged periods at room temperature.
Dilute solutions stored in polyvinyl chloride or polyurethane
foam containers may lose antimicrobial activity.
The bulk material should be stored in an airtight container,
protected from light and contact with metals, in a cool, dry place.
Incompatibilities
Incompatible with aluminum, anionic surfactants, citrates, cotton,
fluorescein, hydrogen peroxide, hypromellose,iodides, kaolin,
lanolin, nitrates, nonionic surfactants in high concentration,
permanganates, protein, salicylates, silver salts, soaps, sulfonamides,
tartrates, zinc oxide, zinc sulfate, some rubber mixes, and
some plastic mixes.
Benzalkonium chloride has been shown to be adsorbed to
various filtering membranes, especially those that are hydrophobic
or anionic.
Regulatory Status
Included in the FDA Inactive Ingredients Database (inhalations, IM
injections, nasal, ophthalmic, otic, and topical preparations).
Included in nonparenteral medicines licensed in the UK. It is also
included in the Canadian List of Acceptable Non-medicinal
Ingredients.
Pesticide Type
Fungicide; Algicide
