Benzalkonium chloride

Structural formula
	General structural formula of the cation with the counterion chloride
General
Surname	Benzalkonium chloride
other names	Alkylbenzyldimethylammonium chloride; Benzyldimethylalkylammonium chloride; BAC; N -alkyl- N -benzyl- N , N -dimethylammonium chloride; BENZALKONIUM CHLORIDE ( INCI ) ;
Molecular formula	C 9 H 13 ClNR (R = C 8 H 17 to C 18 H 37 )
Brief description	white, almost odorless mass
External identifiers / databases
EC number	616-786-9
ECHA InfoCard	100.132.452
Wikidata	Q55261298
Drug information
ATC code	D08 AJ01 ; D09 AA11 ; R02 AA16 ;
properties
Molar mass	variable
Physical state	firmly
Melting point	40 ° C
solubility	very light in water (4000 g l −1 at 20 ° C)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 302 + 312-314-400
	P: 273-280-305 + 351 + 338-310
Toxicological data	1.25 mg l −1 ( LC 50 , fish , 96 h , median value) ; 0.102 mg l −1 ( LC 50 , crustaceans , 48 h , median value) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Benzalkonium chloride is a mixture of alkylbenzyldimethylammonium chlorides (ABDAC), the alkyl part of which consists of C ₈ to C ₁₈ chains. It is an active ingredient known above all for its disinfecting and preserving properties and belongs to the quaternary ammonium compounds .

use

Benzalkonium chloride acts against bacteria , fungi , yeasts and algae and to a lesser extent also antiviral. It is contained in many disinfectants and cleaning agents from well-known manufacturers ( e.g. Sagrotan ) for surface disinfection. Benzalkonium chloride is also used to disinfect laundry.

Benzalkonium chloride is also a component of many algicides , e.g. B. for swimming pools.

The medical use extends to the application for skin and mucous membrane disinfection (for example prophylaxis against infections with skin fungi , antiseptic treatment of inflammatory symptoms in the mouth and throat).

Due to its surface-active properties, benzalkonium chloride attacks the cell membrane of the sperm , making sperm immobile. It is therefore also used for local contraception .

Benzalkonium chloride is used pharmaceutically in low concentrations for the preservation of nose and eye drops . Benzalkonium chloride reduces the stability of the tear film and can cause dry eyes with long-term use. It attacks the cornea of the eye down to the deeper cell layers and can lead to corneal damage. Occasionally, allergies to benzalkonium chloride occur. If a tear replacement fluid preserved with benzalkonium chloride is dripped into the eye and, some time afterwards, eye drops containing another drug, this active ingredient can penetrate the cornea faster and deeper than usual. This can lead to undesired enhancement of the effect and increased side effects .

Biological importance

Benzalkonium chloride accumulates in the cell membranes of living organisms and can thus impair the function of the cell membrane. The disinfecting effect of this group of compounds is based on this. The cation of benzalkonium chloride is eliminated well in sewage treatment plants and has a very high removal rate from the liquid phase of the treated wastewater.

safety instructions

Benzalkonium chloride (BAC) is the most common and longest-running preservative in eye drops. It has a relatively high cell toxicity. Even low concentrations lead to cytological and histological changes in eye tissue. The half-life in the corneal and conjunctival epithelium is 20 hours. It remains in the deeper conjunctival tissue with a half-life of 11 hours and can possibly be enriched there with repeated application per day. The cell-damaging effect has been comprehensively proven by in-vitro , in-vivo and clinical studies. Damage includes chronic inflammation, fibrosis , cell loss, and structural changes to the conjunctiva and cornea. Studies reveal that damage to the lens ( cataract ), trabecular meshwork ( glaucoma ) and retina (macular holes) is attributed to benzalkonium chloride. The European approval authority and the German Ophthalmological Society have long known the harmful effects of this preservative. Further studies are considered useful. A switch to preservative-free eye drops in single-dose containers (EDO) or to preservatives that are less harmful to cells to protect eye health is required by responsible bodies. The German Ophthalmological Society warns against benzalkonium chloride, but puts the damage into perspective with short-term and infrequent use. Treatment with eye drops containing benzalkonium chloride for glaucoma is not recommended because of the poor chances of success in a trabeculectomy, which is often necessary later in the course of the disease .

Contact dermatitis was observed from a concentration of one percent . The assessment of the allergy relevance is generally difficult; In the case of test groups, deliberate sensitization could hardly be achieved, due to the lack of general dissemination there are only few empirical values.

literature

KK Huber-van der Velden, H. Thieme, M. Eichhorn: Morphological changes due to preservatives in eye drops. In: The ophthalmologist. 109, 2012, pp. 1077-1081, doi : 10.1007 / s00347-012-2639-3 .
EM Messmer: Preservatives in ophthalmology. In: The ophthalmologist. 109, 2012, pp. 1064-1070, doi : 10.1007 / s00347-012-2638-4 .
German Ophthalmological Society (DOG): Be careful with eye drops: Preservatives can lead to dry eyes . Press archive 2013.
H. Thieme, KK van der Velden: Preservatives from the perspective of glaucoma surgery. In: The ophthalmologist. 109, 2012, pp. 1073-1076, doi : 10.1007 / s00347-012-2642-8 .

Web links

Reports on the toxicity of benzalkonium chloride from the European Medicines Agency , which is responsible for the authorization and monitoring of medicinal products

Individual evidence

↑ Entry on BENZALKONIUM CHLORIDE in the CosIng database of the EU Commission, accessed on December 28, 2019.
↑ ^a ^b ^c ^d ^e ^f ^g Entry on alkylbenzyldimethylammonium chloride in the GESTIS substance database of the IFA , accessed on December 29, 2019(JavaScript required) .
↑ Entry on Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 29, 2019. Manufacturers or distributors can expand the harmonized classification and labeling .
↑ Martina Scholz: In vitro permeation studies of hydrophilic and lipophilic drugs on ocular tissues and cell cultures , dissertation, 2003, section 3.2.2.1
^ Association of Austrian Environmental Advice Centers (2010), accessed on July 16, 2012: Swimming pool in autumn and winter - How to overwinter your private swimming pool in the most environmentally friendly way possible (PDF file; 2.48 MB) .
↑ Oliver Gans et al. (2005): Basics for risk assessment for quaternary ammonium compounds (PDF file; 1.22 MB) . Federal Environment Agency , Vienna.

[CosIng-1] Entry on BENZALKONIUM CHLORIDE in the CosIng database of the EU Commission, accessed on December 28, 2019.

[GESTIS-2] ↑ ^a ^b ^c ^d ^e ^f ^g Entry on alkylbenzyldimethylammonium chloride in the GESTIS substance database of the IFA , accessed on December 29, 2019(JavaScript required) .

[CLP_100.058.301-3] Entry on Quaternary ammonium compounds, benzyl-C8-18-alkyldimethyl, chlorides in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on December 29, 2019. Manufacturers or distributors can expand the harmonized classification and labeling .

[4] Martina Scholz: In vitro permeation studies of hydrophilic and lipophilic drugs on ocular tissues and cell cultures , dissertation, 2003, section 3.2.2.1

[5] Association of Austrian Environmental Advice Centers (2010), accessed on July 16, 2012: Swimming pool in autumn and winter - How to overwinter your private swimming pool in the most environmentally friendly way possible (PDF file; 2.48 MB) .

[6] Oliver Gans et al. (2005): Basics for risk assessment for quaternary ammonium compounds (PDF file; 1.22 MB) . Federal Environment Agency , Vienna.