benzalkonium chloride

Benzalkonium chloride
IUPAC name	benzyl-dimethyl-tridecyl-azanium chloride
Identifiers
CAS number	8001-54-5 Y
PubChem	8753
EC number	264-151-6
SMILES	[Cl-].c1ccccc1C[N+](C)(CCCCCCCCCCCC)C
InChI	1/C21H38N.ClH/c1-4-5-6-7-8-9-10-11-12-16-19-22(2,3)20-21-17-14-13-15-18-21;/h13-15,17-18H,4-12,16,19-20H2,1-3H3;1H/q+1;/p-1
InChI key	JBIROUFYLSSYDX-REWHXWOFAE
ChemSpider ID	8423
Properties
Molecular formula	variable
Molar mass	variable
Appearance	white or yellow powder; gelatinous lumps; colorless solution
Density	0.98 g/cm3
Solubility in water	very soluble
Hazards
EU classification	C, N [1]
R-phrases	R21/22, R34, R50 [1]
S-phrases	S36/37/39, S45, S61 [1]
NFPA 704	0 1 0
Flash point	250 °C
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Benzalkonium chloride, also known as alkyldimethylbenzylammonium chloride and ADBAC, is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered^[2] 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 biocide, a cationic surfactant and phase transfer agent in the chemical industry.

Properties

Benzalkonium chloride is readily soluble in ethanol and acetone. 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 rheology modifiers (alcohols, polyethylene glycols, etc.) to prevent increases in viscosity or gel formation under low temperature conditions.

Applications

The applications are extremely wide ranging, from disinfectant formulations to microbial corrosion inhibition in the oilfield sector.^[3] It is used in pharmaceuticals such as leave-on skin antiseptics, hygienic towelettes, and wet wipes, Lysol and ethanol-free solutions are often used in preparations used for skin disinfection prior to use of syringes.^{[citation needed]} Its use as a preservative in cosmetics such as eye and nasal drops attests. There have been reports of allergic reactions associated with continuous, long-term use in sensitive users, especially on mucous membranes. 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.

Biological activity

The greatest biocidal activity is associated with the C12-C14 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 rapidly 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. Activity is not greatly affected by pH, but increases substantially at higher temperatures and prolonged exposure times.

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 hepatitis, HIV, 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 excipients can also greatly improve efficacy and detergency, and prevent deactivation under use conditions. Formulation requires great care as benzalkonium solutions can be readily inactivated in the presence of organic and inorganic contamination. Solutions are incompatible with soaps, and must not be mixed with anionic surfactants. Hard water 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

Please help improve this article by expanding it. Further information might be found on the talk page. (February 2007)

ADBAC is highly toxic to fish (LC₅₀ = 280 μg ai/L), very highly toxic to aquatic invertebrates (LC₅₀ = 5.9 μg ai/L), moderately toxic to birds (LD₅₀ = 136 mg/kg-bw), and slightly toxic to mammals (LD₅₀ = 430 mg/kg-bw).^[4] Benzalkonium chloride solutions of 10% or more are toxic to humans, causing irritation to the skin and mucosa, and death if taken internally.^[5]

Benzalkonium chloride is an allergen^{[6][7][8][9][10][11][12]} and several studies have cast doubt on its reputation for safety.^[13][14] Some products have been reformulated in light of this research, but it is still widely used in eyewashes, nose sprays, hand and face washes, mouthwashes, spermicidal 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 EDTA as a preservative. Some have packaged eye drops in single-use vials with no preservative^[15] for sensitive eyes. There has also been concern that long-term use of benzalkonium as a preservative in nose sprays may cause swelling of mucosa and lead to rhinitis medicamentosa.

Contact lens solutions typically contain 0.002% to 0.01% benzalkonium chloride.^[16] K. C. Swan^[17] found that repeated use of benzalkonium chloride at concentrations of 1:5000 (0.02%) or stronger can denature corneal protein and cause irreversable 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 lens are also discussed in the literature.^{[18] [19]}

A disinfectant containing benzalkonium chloride and the related compound didecyldimethylammonium chloride (DDAC) has been identified as the most probable cause of birth defects and fertility problems in caged mice.^[20]

See also

• Stearalkonium chloride, the benzalkonium chloride in which n=18

References

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

• Nasal Saline Sprays - The Additives May Be the Problem
• Chemical Database