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* Potential hormonal effects
* Potential hormonal effects
* Assessment of the potential for development of bacterial resistance
* Assessment of the potential for development of bacterial resistance

=== Pre-clinical Studies ===

The data in this section are pre-clinical, and therefore the reported biomedical findings may not hold true in humans. In light of the general consensus of findings which are that benzalkonium chloride has deleterious effects on multiple cell types and their function, it is highly unlikely that these pre-clinical findings will progress to human studies.

Experimental studies have found that benzalkonium chloride triggers an apoptotic mechanism at low concentrations and a necrotic process at higher concentrations.<ref>{{cite journal | last1 = Debbasch | first1 = C | last2 = Brignole | first2 = F | last3 = Pisella | first3 = P | last4 = Warnet | first4 = J | last5 = Rat | first5 = P | last6 = Baudouin | first6 = C | title = Quaternary Ammoniums and Other Preservatives’ Contribution in Oxidative Stress and Apoptosis on Chang Conjunctival Cells | journal = Invest. Ophthalmol. Vis. Sci. | volume = 42 | year = 2001 | doi = | pmid = 11222522 | issue = 3 | url = http://www.iovs.org/content/42/3/642.long | pages = 642–652 }}</ref>

In a 2009 experiemental study, benzalkonium chloride was shown to be less toxic to ocular structures than thiomersal, which is rarely still used in ophthalmic preparations, but more toxic than other preservatives commonly used.<ref>{{cite journal | last1 = Epstein | first1 = S P | last2 = Ahdoot | first2 = M | last3 = Marcus | first3 = E | last4 = Asbell | first4 = P A | title = Comparative Toxicity of Preservatives on Immortalized Corneal and Conjunctival Epithelial Cells | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958436/ | journal = J Ocul Pharmacol Ther. | volume = 25 | year = 2009 | doi = 10.1089/jop.2008.0098 | pmc = 2958436 | issue = 2 | pages= 113–119 }}</ref>

In a 2006 study on rats, benzalkonium chloride was found to “consistently and dramatically (alter) the corneoconjunctival surface as evaluated by slit-lamp examination, the fluorescein test, impression cytology, in vivo confocal microscopy, and histology".<ref>{{cite journal | last1 = Labbé | first1 = A | last2 = Pauly | first2 = A | last3 = Liang | first3 = H | last4 = Brignole-Baudouin | first4 = F | last5 = Martin | first5 = C | last6 = Warnet | first6 = J M | last7 = Baudouin | first7 = C | title = Comparison of toxicological profiles of benzalkonium chloride and polyquaternium-1: an experimental study | journal = J Ocul Pharmacol Ther. | volume = 22 | year = 2006 | doi = 10.1089/jop.2006.22.267| pmid = 16910868 | issue = 4 | pages= 267–78 }}</ref>

A 2012 study on mice found that benzalkonium chloride decreases tear production.<ref>{{cite journal | last1 = Sarkar | first1 = J | last2 = Chaudhary | first2 = S | last3 = Namavari | first3 = A | last4 = Ozturk | first4 = O | last5 = Chang | first5 = J | last6 = Yco | first6 = L | last7 = Snehal | first7 = S | last8 = Vishakha | first8 = K | last9 = Joelle | first9 = H | last10 = Sandeep | first10 = J | title = Corneal Neurotoxicity Due to Topical Benzalkonium Chloride | url = http://www.iovs.org/content/53/4/1792.full.pdf | journal = Invest Ophthalmol Vis Sci. | volume = 53 | year = 2012 | doi = 10.1167/iovs.11-8775 | pmid = 22410563 | issue = 4 | pages= 1792–802 }}</ref>

Experiemental studies have found that the effects of benzalkonium chloride are cumulative and dose-dependent.<ref>{{cite journal | last1 = De Saint Jean | first1 = M | last2 = Brignole | first2 = F | last3 = Bringuier | first3 = A F | last4 = Bauchet | first4 = A | last5 = Feldmann | first5 = G | last6 = Baudouin | first6 = C | title = Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells | journal = Invest. Ophthalmol. Vis. Sci. | volume = 40 | year = 1999 | doi = | pmid = 10067965 | issue = 3 | url = | pages = 619–30 }}</ref>

A 2012 experimental study reported that simultaneous ocular exposure to an inert antigen and benzalkonium chloride leads to a significant change in the systemic immune response to the administered antigen in mice.<ref>{{cite journal | last1 = Galletti | first1 = J. G. | last2 = Gabelloni | first2 = M. L. | last4 = Sabbione | first4 = F. | last3 = Morande | first3 = P. E. | last5 = Vermeulen | first5 = M. E. | last6 = Trevani | first6 = A. S. | last7 = Giordano | first7 = M. N. | title = Benzalkonium chloride breaks down conjunctival immunological tolerance in a murine model | journal = Mucosal Immunology | volume = [Epub ahead of print] | year = 2012 | doi = 10.1038/mi.2012.44 | pmid=22692451 | issue=1 | pages=24–34}}</ref>

A 2006 study investigating the nasal toxicity of benzalkonium chloride found ciliary loss, epithelial spongiosis, mucosal swelling, hyperemic subepithelium with increased mononuclears in lamina propria in rats.<ref>{{cite journal | author = Khan, M A | title = Effects of Phenol, Benzalkonium Chloride, Oxymetazoline, Tobacco and Formalin on Nasal Mucosa of Albino Rat | journal = J.Anat.Soc. India | volume = 55 | issue = 1 | pages = 60–66 | year = 2006 | pmid = | url = http://medind.nic.in/jae/t06/i1/jaet06i1p60.pdf | doi=}}</ref>

A 1996 experimental study on animal and human mucosa respiratory found that benzalkonium chloride is ciliostatic in vitro to rat, guinea pig, and human respiratory mucosa.<ref>{{cite journal | last1 = Joki | first1= S. | last2 = Saano | first2 = V. | last3 = Nuutinen | first3 = J. | last4 = Virta | first4 = P. | last5 = Karttunen | first5 = P. | last6 = Silvasti | first6 = M. | last7 = Toskala | first7 = E. | title = Effects of Some Preservative Agents on Rat and Guinea Pig Tracheal and Human Nasal Ciliary Beat Frequency | journal = American Journal of Rhinology | volume = 10 | issue = 3 | pages = 181–186 | year = 1996 | pmid = | url = http://www.ingentaconnect.com/content/ocean/ajr/1996/00000010/00000003/art00008 | doi=10.2500/105065896781794932}}</ref>

A 1997 study demonstrated that degenerative morphological changes in the nasal mucosa of rats were directly attributed to the benzalkonium chloride in topical nasal steroid sprays.<ref>{{cite journal | last1 = Berg | first1 = Ø. H. | last2 = Lie | first2 = K | last3 = Steinsvåg | first3 = S. K. | title = The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride | journal = Allergy | volume = 52 | issue = 6 | pages = 627–32 | year = 1997 | pmid = 9226056 | doi=10.1111/j.1398-9995.1997.tb01041.x}}</ref>

A 1982 study found that benzalkonium chloride was toxic to guinea pig ears. Solutions of 0.1% benzalkonium chloride instilled into the ears of guinea pigs produced damage to the vestibulum and cochlear and pathological changes to the tympanic cavity and the perilymphatic spaces of vestibulum and cochlea were found.<ref>{{cite journal | last1 = Aursnes | first1 = J | title = Ototoxic effect of quaternary ammonium compounds | journal = Acta Otolaryngol. | volume = 93 | issue = 5–6 | pages = 421–33 | year = 1982 | pmid = 6125078 | doi=}}</ref>

Experimental and animal tests have established some mutagenic effects of benzalkonium chloride.<ref>{{cite journal | last1 = Ferf | first1 = F | last2 = Mišík | first2 = M | last3 = Hoelzl | first3 = C | last4 = Uhl | first4 = M | last5 = Fuerhacker | first5 = M | last6 = Grillitsch | first6 = B | last7 = Parzefall | first7 = W | last8 = Nersesyan | first8 = A | last9 = Mičieta | first9 = K | last10 = Grummt | first10 = T | last11 = Ehrlich | first11 = V | last12 = Knasmüller | first12 = S | title = Benzalkonium chloride (BAC) and dimethyldioctadecyl-ammonium bromide (DDAB), two common quaternary ammonium compounds, cause genotoxic effects in mammalian and plant cells at environmentally relevant concentrations | url = http://mutage.oxfordjournals.org/content/22/6/363.long | journal = Mutagenesis | volume = 22 | year = 2007 | doi = 10.1093/mutage/gem027 | pmid=17656635 | issue=6 | pages=363–70}}</ref>

Animal studies have established the toxicity of benzalkonium chloride on the lung.<ref name="pmid15458722">{{cite journal |last1=Xue |first1=Y |last2=Hieda |first2=Y |last3=Kimura |first3=K |last4=Takayama |first4=K |last5=Fujihara |first5=J |last6=Tsujino |first6=Y |title=Kinetic characteristics and toxic effects of benzalkonium chloride following intravascular and oral administration in rats |journal=J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. |volume=811 |issue=1 |pages=53–8 |year=2004 |pmid=15458722 |doi=10.1016/j.jchromb.2004.03.075}}</ref><ref name="pmid18715840">{{cite journal |last1=Swiercz |first1=R |last2=Hałatek |first2=T |last3=Wasowicz |first3=W |last4=Kur |first4=B |last5=Grzelińska |first5=Z |last6=Majcherek |first6=W |title=Pulmonary irritation after inhalation exposure to benzalkonium chloride in rats |journal=Int J Occup Med Environ Health |volume=21 |issue=2 |pages=157–63 |year=2008 |pmid=18715840 |doi=10.2478/v10001-008-0020-1}}</ref><ref name="pmid24288119">{{cite journal |last1=Swiercz |first1=R |last2=Hałatek |first2=T |last3=Stetkiewicz |first3=J |last4=Wąsowicz |first4=W |last5=Kur |first5=B |last6=Grzelińska |first6=Z |last7=Majcherek |first7=W |title=Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride |journal=Int J Occup Med Environ Health |volume=26 |issue=4 |pages=647–56 |year=2013 |pmid=24288119 |doi=10.2478/s13382-013-0137-8}}</ref><ref name="pmid22188809">{{cite journal |last1=Larsen |first1=ST |last2=Verder |first2=H |last3=Nielsen |first3=GD |title=Airway effects of inhaled quaternary ammonium compounds in mice |journal=Basic Clin. Pharmacol. Toxicol. |volume=110 |issue=6 |pages=537–43 |year=2012 |pmid=22188809 |doi=10.1111/j.1742-7843.2011.00851.x}}</ref>


==See also==
==See also==

Revision as of 07:30, 28 November 2014

Benzalkonium chloride
Names
Other names
N-Alkyl-N-benzyl-N,N-dimethylammonium chloride; Alkyldimethylbenzylammonium chloride; ADBAC; BC50 BC80; Quaternary ammonium compounds; quats
Identifiers
ChEMBL
ChemSpider
EC Number
  • 264-151-6
KEGG
UNII
Properties
variable
Molar mass variable
Appearance 100% is white or yellow powder; gelatinous lumps; Solutions BC50 (50%) & BC80 (80%) are colorless to pale yellow solutions
Density 0.98 g/cm3
very soluble
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
3
0
0
Flash point 250 °C (482 °F; 523 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Benzalkonium chloride, also known as BZK, BKC, alkyldimethylbenzylammonium chloride and ADBAC, is a 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. The chemical is a heterogeneous mixture of alkylbenzyldimethylammonium chlorides of various even-numbered[2] alkyl chain lengths.

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 of benzalkonium chloride are extremely wide ranging,[3] 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.

Benzalkonium chloride is used in:

  • Pharmaceutical products such as eye, ear and nasal drops or sprays, as a preservative
  • Personal care products such as hand sanitizers, hygienic towelettes and wet wipes
  • Aftershave, deodorants, hair products and cosmetics
  • Skin antiseptics, such as Bactine, to protect scrapes and cuts
  • Throat lozenges[4] and mouthwashes, as a biocide
  • Spermicidal creams
  • Over-the-counter single-application treatments for herpes, cold-sores, and fever blisters, such as RELEEV and Viroxyn
  • Burn and ulcer treatment
  • Preoperative skin disinfectants
  • Soak solutions for surgical/dental instruments prior to high-level sterilisation
  • Laundry detergents and treatments
  • Softeners for textiles
  • Cleaners for floor and hard surfaces as a disinfectant
  • Spray disinfectants for hard surface sanitisation
  • Algaecide for clearing of algae, moss, lichens from paths, roof tiles, swimming pools, masonry and in horticultural greenhouse disinfection

An advantage of benzalkonium chloride not shared by ethanol-based antiseptics or hydrogen peroxide antiseptic is that benzalkonium chloride-based antiseptics do not cause a burning sensation when applied to broken skin.[citation needed]

Biological activity

The greatest biocidal activity is associated with the C12 dodecyl & C14 myristyl 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 with benzalkonium chloride as the active ingredient met the FDA performance standards, while Purell, a popular alcohol-based sanitizer, did not. The study, which was undertaken and reported by a leading US developer, manufacturer and marketer of topical antimicrobial pharmaceuticals based on quaternary ammonium compounds, found that their own benzalkonium chloride-based sanitiser performed better than alcohol-based hand sanitiser after repeated use.[5]

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 New Delhi metallo-beta-lactamase 1 and other antibiotic resistant bacteria.[citation needed]

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.[citation needed] Formulation techniques have been used to great effect in enhancing the virucidal activity of quaternary ammonium-based disinfectants such as Virucide 100 to typical healthcare infection hazards such as hepatitis and HIV.[citation needed] The use of appropriate excipients can also greatly enhance the spectrum, performance and detergency, and prevent deactivation under use conditions.[citation needed] Formulation can also help minimise deactivation of benzalkonium solutions in the presence of organic and inorganic contamination.[citation needed]

Toxicology

Benzalkonium chloride 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).[6]

RTECS lists the following acute toxicity data:[7]

Organism Route of Exposure Dose (LD50)
Rat Intravenous 13,900 µg/kg
Rat Oral 240 mg/kg
Rat Intraperitoneal 14,500 µg/kg
Rat Subcutaneous 400 mg/kg
Mouse Subcutaneous 64 mg/kg

Benzalkonium chloride is a human skin and severe eye irritant.[8] It is a suspected respiratory toxicant, immunotoxicant, gastrointestinal toxicant and neurotoxicant.[9][10][11]

Benzalkonium chloride formulations for consumer use are dilute solutions. Concentrated solutions are toxic to humans, causing corrosion/irritation to the skin and mucosa, and death if taken internally in sufficient volumes. In 1954, animal and human testing identified that 0.1% is the maximum concentration of benzalkonium chloride that does not produce primary irritation on intact skin or act as a sensitizer.[12]

The lung and kidney appear to be the target organs of benzalkonium chloride toxicity.[13]

A 2014 case study detailing the fatal ingestion of up to 240ml of 10% benzalkonium chloride in a 78 year-old male also includes a summary of the currently published case reports of benzalkonium chloride ingestion.[14] While the majority of cases were caused by confusion about the contents of containers, one case cites incorrect pharmacy dilution of benzalkonium chloride as the cause of poisoning of two infants.[15]

Safety

Benzalkonium chloride is frequently used as a preservative in topical ophthalmic preparations, both for its microbial efficacy and its ability to break cell junctions in the corneal epithelium, allowing medication to enter the ocular anterior chamber.[16]

Benzalkonium chloride is effective at exceptionally low concentrations; contact lens solutions typically contain exceptionally low (0.002% to 0.01%) concentrations of benzalkonium chloride for effective preservative action.[17] Swan (1944) found that repeated use of benzalkonium chloride at 10-fold higher concentrations of 1:5000 (0.02%) or stronger can denature corneal protein and cause damage to the eye.[18] Walter (1938) identified that concentrations of less than 0.1% benzalkonium chloride instilled into human eyes produced no adverse sensations, whereas concentrations of 0.1% or greater produced “burning and stinging reactions”.[19] Whitehill (1945) determined that the maximum non-irritating concentration of benzalkonium chloride in rabbit eyes is 0.05%.[20]

Benzalkonium chloride posseses surfactant properties, dissolving the lipid phase of the tear film. Intraocular benzalkonium chloride is highly toxic to the corneal endothelium in concentrations commonly used extraocularly.[21] Avoiding the use of benzalkonium chloride solutions while contact lenses are in place is discussed in the literature.[22][23] When administered via the anterior chamber or instilled at a concentration of 0.1%, benzalkonium chloride "...destroys the endothelium and causes irreversible corneal edema... At even higher concentrations (1–2%), benzalkonium (chloride) totally destroys the anterior segment of experimental animals in less than a week.”[24]

Penetration by benzalkonium chloride of the deeper ocular structures has been shown in rabbit eyes by Brignole-Baudouin et al. (2012): “BAK was shown to penetrate healthy eyes even after a short duration and was not only detected on the ocular surface structures, but also in deeper tissues, especially in sensitive areas involved in glaucoma pathophysiology, such as the trabecular meshwork and the optic nerve areas...".[25]

Although historically benzalkonium chloride has been ubiquitous as a preservative in ophthalmic preparations, its ocular toxicity and irritant properties,[26] in conjunction with consumer demand, have led pharmaceutical companies to increase production of preservative-free preparations, or to replace benzalkonium chloride with preservatives which are less harmful.

Many mass-marketed inhaler and nasal spray formulations contain benzalkonium chloride as a preservative, despite substantial evidence that it can adversely affect ciliary motion, mucociliary transport, nasal mucosal histology, human neutrophil function, and leukocyte response to local inflammation.[27] Although some studies have found no correlation between use of benzalkonium chloride in nasal sprays and drug-induced rhinitis,[28] others have found benzalkonium chloride in oxymetazoline nasal spray to worsen rhinitis medicamentosa in healthy volunteers after both long-term use[29][30] and short-term use.[31][32]

A 2001 literature review concluded that "without conclusive data regarding BKC and the possibility of harmful effects, the use of nasal formulations without BKC might be a reasonable alternative".[33] In 2004, a literature review revealed very limited data that demonstrated statistically significant safety concerns for benzalkonium chloride concentrations at or below 0.1%.[28]

A 2010 literature review supports the nasal toxicity of benzalkonium chloride and its role in drug-induced rhinitis and rhinitis medicamentosa.[34] In the United States, nasal steroid preparations that are free of benzalkonium chloride include budesonide, triamcinolone acetonide, dexamethasone, and Beconase and Vancenase aerosol inhalers.[27]

A 2006 clinical trial on 43 healthy volunteers found that benzalkonium chloride in the concentration used in nasal preparations impaired mucociliary clearance in healthy individuals after 3 weeks of use.[35]

As with antibiotics, the use of biocides at sub-inhibitory concentrations can potentially result in resistant organisms, and should be used at recommended dilutions and extended contact time to ensure effective disinfection. While resistance is rarely linked to disinfectant usage at low concentrations, a 2009 study suggested that when used in less than lethal concentrations, benzalkonium chloride solutions could result in increased resistance Pseudomonas aeruginosa, and an increase in resistance of the bacteria to the ciprofloxacin antibiotic, even though the bacterial colonies had not been previously exposed to the antibiotic.[36]

In 2011, a large clinical trial designed to evaluate the efficacy of hand sanitisers based on different active ingredients in preventing virus transmission amongst schoolchildren was re-designed to exclude sanitisers based on benzalkonium chloride due to safety concerns.[37]

Benzalkonium chloride has been in common use as a pharmaceutical preservative and antimicrobial since the 1940s. While early studies confirmed the corrosive and irritant properties of benzalkonium chloride, investigations into the adverse effects of, and disease states linked to, benzalkonium chloride have only surfaced during the past 30 years.

Benzalkonium chloride is classed as a Category III antiseptic active ingredient by the United States Food and Drug Administration. Ingredients are categorised as Category III when "available data are insufficient to classify as safe and effective, and further testing is required”. Benzalkonium chloride is excluded from the current United States Food and Drug Administration review of the safety and effectiveness of consumer antiseptics and topical antimicrobial over-the-counter drug products, meaning it will remain a Category III ingredient.[38] There is acknowledgement that more data are required on its safety, efficacy and effectiveness, especially with relation to:

  • Human pharmacokinetic studies, including information on its metabolites
  • Studies on animal absorption, distribution, metabolism, and excretion
  • Data to help define the effect of formulation on dermal absorption
  • Carcinogenicity
  • Studies on developmental and reproductive toxicology
  • Potential hormonal effects
  • Assessment of the potential for development of bacterial resistance

Pre-clinical Studies

The data in this section are pre-clinical, and therefore the reported biomedical findings may not hold true in humans. In light of the general consensus of findings which are that benzalkonium chloride has deleterious effects on multiple cell types and their function, it is highly unlikely that these pre-clinical findings will progress to human studies.

Experimental studies have found that benzalkonium chloride triggers an apoptotic mechanism at low concentrations and a necrotic process at higher concentrations.[39]

In a 2009 experiemental study, benzalkonium chloride was shown to be less toxic to ocular structures than thiomersal, which is rarely still used in ophthalmic preparations, but more toxic than other preservatives commonly used.[40]

In a 2006 study on rats, benzalkonium chloride was found to “consistently and dramatically (alter) the corneoconjunctival surface as evaluated by slit-lamp examination, the fluorescein test, impression cytology, in vivo confocal microscopy, and histology".[41]

A 2012 study on mice found that benzalkonium chloride decreases tear production.[42]

Experiemental studies have found that the effects of benzalkonium chloride are cumulative and dose-dependent.[43]

A 2012 experimental study reported that simultaneous ocular exposure to an inert antigen and benzalkonium chloride leads to a significant change in the systemic immune response to the administered antigen in mice.[44]

A 2006 study investigating the nasal toxicity of benzalkonium chloride found ciliary loss, epithelial spongiosis, mucosal swelling, hyperemic subepithelium with increased mononuclears in lamina propria in rats.[45]

A 1996 experimental study on animal and human mucosa respiratory found that benzalkonium chloride is ciliostatic in vitro to rat, guinea pig, and human respiratory mucosa.[46]

A 1997 study demonstrated that degenerative morphological changes in the nasal mucosa of rats were directly attributed to the benzalkonium chloride in topical nasal steroid sprays.[47]

A 1982 study found that benzalkonium chloride was toxic to guinea pig ears. Solutions of 0.1% benzalkonium chloride instilled into the ears of guinea pigs produced damage to the vestibulum and cochlear and pathological changes to the tympanic cavity and the perilymphatic spaces of vestibulum and cochlea were found.[48]

Experimental and animal tests have established some mutagenic effects of benzalkonium chloride.[49]

Animal studies have established the toxicity of benzalkonium chloride on the lung.[50][51][52][53]

See also

References

  1. ^ a b c C&L Inventory: Quaternary ammonium compounds, benzyl-C8–18-alkyldimethyl, chlorides
  2. ^ U.S. Environmental Protection Agency: Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC)
  3. ^ http://www.quatchem.com/industries-products/biocidal-raw-materials/benzalkonium-chloride/benzalkonium-chloride-applications/
  4. ^ Bradosol
  5. ^ Dyer, David; Gerenraich, Kenneth; Whams, Peter (1998). "Testing a New Alcohol-Free Hand Sanitizer to Combat Infection". AORN Journal Vol 68 Issue 2: 239–251. {{cite journal}}: Cite journal requires |journal= (help)CS1 maint: location (link)
  6. ^ Frank T. Sanders, ed. (August 2006). Reregistration Eligibility Decision for Alkyl Dimethyl Benzyl Ammonium Chloride (ADBAC) (PDF) (Report). U.S. Environmental Protection Agency Office of Prevention, Pesticides, and Toxic Substances. p. 114. Retrieved 2009-03-31.
  7. ^ "RTECS BO3150000 Ammonium, alkyldimethylbenzyl - , chloride".
  8. ^ Lewis R J Sr (2004). Sax's Dangerous Properties of Industrial Materials (11 ed.). Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. p. 104. doi:10.1002/0471701343.
  9. ^ "TOXNET Benzalkonium Chloride Compounds".
  10. ^ "Haz-Map Benzalkonium Chloride".
  11. ^ "NIOSH ICSC Benzalkonium Chloride".
  12. ^ Seymour Stanton Block (2001). Disinfection, sterilization, and preservation (5, illustrated ed.). Lippincott Williams & Wilkins. p. 311. ISBN 0-683-30740-1.
  13. ^ Xue, Y; Hieda, Y; Saito, Y; Nomura, T; Fujihara, J; Takayama, K; Kimura, K; Takeshita, H (2004). "Distribution and disposition of benzalkonium chloride following various routes of administration in rats". Toxicol. Lett. 148 (1–2): 113–23. doi:10.1016/j.toxlet.2003.12.068. PMID 15019095.
  14. ^ Spiller, Henry A (2014). "A Case of Fatal Ingestion of a 10% Benzalkonium Chloride Solution". J Forensic Toxicol Pharmacol. 3 (1). doi:10.4172/2325-9841.1000113.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ Gossel, T A (1994). Principles Of Clinical Toxicology, Third Edition (3, illustrated, revised ed.). CRC Press.
  16. ^ Chen, W; Li, Z; Hu, J; Zhang, Z; Chen, L (2011). "Corneal Alterations Induced by Topical Application of Benzalkonium Chloride in Rabbit". PLoS ONE. 6 (10:e26103). doi:10.1371/journal.pone.0026103.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ U.S. Patent 5,725,887, column 2, line 8
  18. ^ Swan, K. C., "Reactivity of the Ocular Tissues to Wetting Agents", Am. J. Ophthalmol., 27, 118 (1944),
  19. ^ Walter, C W (1938). The use of a mixture of coconut oil derivatives as a bactericide in the operating room (67 ed.). Surg., Gynec. & Obst. pp. 683–688.
  20. ^ Whitehill, A R (1945). "Evaluation of some liquid antiseptics". J Am Pharm Assoc, Sci. Ed. (Wash). 34: 219–221. doi:10.1002/jps.3030340810.
  21. ^ Liu H, Routley I, Teichmann KD (2001). "Toxic endothelial cell destruction from intraocular benzalkonium chloride". J Cataract Refract Surg. 27 (11): 1746–50. doi:10.1016/S0886-3350(01)01067-7. PMID 11709246.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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Further reading

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