| Benzalkonium chloride | |
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benzyl-dimethyl-tridecyl-azanium chloride |
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Other names
N-decyl-N-benzyl-N,N-dimethylammonium chloride (with n=10 for alkyl side chain) |
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| Identifiers | |
| CAS number | 8001-54-5 |
| ChemSpider | 8423 = |
| UNII | F5UM2KM3W7 |
| EC number | 264-151-6 |
| KEGG | D00857 |
| ATC code | D08, D09AA11, R02AA16 |
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| 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
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| Flash point | 250 °C |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| 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.
Contents |
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.
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.
The applications are extremely wide ranging, from disinfectant formulations, such as being an active ingredient in Dettol and Lysol brand products, to microbial corrosion inhibition in the oilfield sector, and a multi-surface mould, algae and moss remover.[3] It is used in:
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.
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 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. 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 Purell, 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.[4] 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 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 readily be 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.
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).[5] Benzalkonium chloride solutions of 10% or more are toxic to humans, causing irritation to the skin and mucosa, and death if taken internally.[6]
Several studies have identified allergic reactions to benzalkonium chloride by some individuals[7][8][9][10][11][12][13] but several studies have cast doubt on its reputation for other negative health effects.[14][15] It is still widely used in eyewashes, nasal 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[16] 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 medicamentosa. Although some studies have found no correlation between use of benzalkonium chloride in nasal sprays and rhinitis medicamentosa,[17] others have found benzalkonium chloride in oxymetazoline nasal spray to worsen rhinitis medicamentosa in healthy volunteers after both long-term use[18][19] and short-term use.[20]
Contact lens solutions typically contain 0.002% to 0.01% benzalkonium chloride.[21] K. C. Swan[22] 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.[23] [24]
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.[25]
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 aeruginosa to the ciprofloxacin antibiotic, even though the bacterial colonies had not been previously exposed to the antibiotic.[26]