The action of three antiseptics/disinfectants against enveloped and non-enveloped viruses

The antiviral action of chloroxylenol, benzalkonium chloride and cetrimide/chlorhexidine was assessed against a range of enveloped and non-enveloped human viruses using a suspension test method. Viral suspensions of 10⁶–10⁷ pfu/TCID₅₀ or sfu were prepared in each of the antiseptic/ disinfectant solutions in the presence of a bovine serum/yeast extract mixture to simulate ‘dirty conditions’. During incubation, aliquots were removed at predetermined timepoints up to 10 min to assess the kinetics of inactivation. Results indicate that all products were effective in inactivating the enveloped viruses herpes simplex virus type 1 and human immunodeficiency virus type 1, whilst being ineffective in inactivating human coronavirus, also enveloped, and the non-enveloped viruses. The exception to this was the benzalkonium chloride-based product (Dettol Hospital Concentrate) which was active against the non-enveloped human coxsackie virus. Four antiseptic/disinfectant solutions with chloroxylenol, benzalkonium chloride, cetrimide/ chlorhexidme and povidone-iodine were also assessed for antiviral effect against human immunodeficiency virus in the presence of whole human blood. All four solutions proved to be effective within l min despite the cytotoxic nature of the compounds to the detection system.     

氯苯甲烷铵和噻吗心胺对人晶状体上皮细胞损伤作用的比较

目的 了解氯苯甲烷铵和噻吗心胺对人晶状体上皮细胞(LECs)的损伤作用.方法 将不同质量浓度氯苯甲烷铵和噻吗心胺作用于人LECs,观察细胞形态变化,并用MTY还原法检测细胞活性,ELISA法检测细胞上清液中所含白介素-1α和前列腺素E2的质量浓度.结果 氯苯甲烷铵和噻吗心胺在高质量浓度时直接导致细胞死亡,前者随稀释倍数增加细胞存活率升高,但对细胞的作用转为慢性炎性刺激;后者在稀释20倍时对细胞的炎性刺激最强,随稀释倍数的增加对细胞毒害作用减轻.结论 氯苯甲烷铵作为噻吗心胺滴眼液的防腐剂,是对人LECs造成损伤并刺激其强烈分泌IL-1α和PGE2等炎性介质的主要原因.     

Assessment of corneal epithelial integrity after acute exposure to ocular hypotensive agents preserved with and without benzalkonium chloride

The corneal toxicity of 2 intraocular pressure-lowering agents was compared in a rabbit cornea model with New Zealand White rabbits. Corneal epithelial morphology and cell size were assessed by in vivo confocal microscopy. Baseline microscopic examinations were performed on 1 eye of each animal. Two weeks later, the eyes were bathed for 3 min in travoprost 0.004% preserved without benzalkonium chloride (BAK) or latanoprost 0.005% preserved with 0.02% BAK; the eyes were then rinsed with balanced salt solution, and the corneas were again examined by confocal microscopy (n=4/group). A second group of animals was exposed to the medications through a dosing regimen of 1 drop/min (3 drops total) (n=4/group). In eyes treated with travoprost without BAK (3-min bath), superficial epithelial cells were similar to baseline, as indicated by their visible cell borders and bright nuclei. In contrast, the surface cells in eyes treated with latanoprost were significantly smaller and brighter and had less distinct borders. Surface cell size was significantly smaller as compared with baseline size and as compared with rabbits treated with travoprost without BAK for 3 min. Similar effects on corneal epithelial cell morphology were observed with the 1-drop/min dosing regimen. In this rabbit model, travoprost 0.004% preserved without BAK did not cause corneal epithelial toxicity; latanoprost 0.005% induced superficial cell loss, most likely caused by the presence of a relatively high concentration of BAK (0.02%).     

Comparison of the relative toxicity of travoprost 0.004% without benzalkonium chloride and latanoprost 0.005% in an immortalized human cornea epithelial cell culture system

The purpose of this study was to compare the relative toxicity of a new topical ophthalmic glaucoma medication, travoprost 0.004% without benzalkonium chloride (BAK), with that of commercially available latanoprost 0.005% (preserved with 0.02% BAK) in immortalized human corneal epithelial cells (HCEs). Tissue culture plates (96 well) containing HCEs were divided into 6 groups. Two groups served as negative controls (70% methanol and gentamicin). Another 2 groups—1 in corneal epithelial culture media and the other in a hydroxypropyl (HP)-Guar gellable lubricant eyedrop—served as live controls. The travoprost 0.004% without BAK and latanoprost 0.005% groups were exposed to 100 μL of the undiluted solutions. Cells were incubated for 25 min at 37°C. A live/dead assay was used to measure the effects of travoprost without BAK and of latanoprost on HCEs compared to 70% methanol and culture medium. Between the 2 glaucoma medications tested, travoprost 0.004% preserved without BAK showed significantly less toxicity on HCEs than did latanoprost 0.005%. This difference may have ramifications in terms of tolerability for patients who use these topical glaucoma drugs on a long-term basis.     

Preservation of resin–dentin interfaces treated with benzalkonium chloride adhesive blends

Reducing collagen degradation within hybrid layers may contribute to the preservation of adhesive interfaces. This study evaluated the stability of resin–dentin interfaces treated with benzalkonium chloride (BAC)‐modified adhesive blends and assessed collagen degradation in dentin matrices treated with BAC. The etch‐and‐rinse adhesive, Adper Single Bond Plus, modified with 0.5% and 1.0% BAC, was evaluated for microtensile bond strength (μTBS) and nanoleakage (NL) after 24 h and 1 yr. Thirty completely demineralized dentin beams from human molars were dipped for 60 s in deionized water (DW; control), or in 0.5% or 1.0% BAC, and then incubated in simulated body fluid (SBF). Collagen degradation was assessed by quantification of the dry mass loss and the amount of hydroxyproline (HYP) released from hydrolyzed specimens after 1 or 4 wk. Although all groups demonstrated a significant increase in NL after 1 yr, adhesive modified with 0.5% BAC showed stable bond strength after 1 yr (9% decrease) relative to the control (44% decrease). Significantly less HYP release and dry mass loss were observed for both 0.5% and 1.0% BAC relative to the control. This in vitro study demonstrates that BAC contributes to the preservation of resin–dentin bonds for up to 1 yr by reducing collagen degradation.     

Immediate and short-term effects of benzalkonium chloride on the human nasal mucosa in vivo

The in vivo effects of benzalkonium chloride, which is a preservative in most nasal sprays and drops, have been investigated in normal human volunteers. Saccharin clearance time was slightly prolonged 10 min after 0.02% benzalkonium chloride was applied, compared to that following 0.9% saline (n = 27, P = 0.04, Wilcoxon test). Sixty-five normal volunteers were randomly assigned to receive saline, fluticasone propionate aqueous nasal spray or placebo (which contained all the ingredients of fluticasone aqueous spray incl. 0.02% benzalkonium chloride, minus the fluticasone propionate) for 2 weeks, two puffs twice a day on a double-blind basis. Symptom scores, acoustic rhinometry, saccharin clearance time and ciliary beat frequency were measured immediately prior to this study and again at 2 weeks. Fifty-eight individuals completed the study with >80% compliance. There was no significant difference between the three groups in any of the variables tested. Benzalkonium chloride causes slight prolongation of mucociliary clearance shortly after application but has no detectable effect on nasal mucosal function after 2 weeks regular use.     

Benzalkonium chloride neutralizes the irritant effect of sodium dodecyl sulfate

When benzalkonium chloride (BKC), a cationic surfactant, is added to sodium dodecyl sulfate (SDS), an anionic surfactant, and used in patch testing, on the basis of their known physicochemical interaction, it is possible to predict that there will be a tendency towards a reduction in the expected irritant response when compared to SDS alone. The aim of this study was to investigate whether BKC could reduce the irritant response to SDS when applied after the SDS exposure. 54 non-atopic adult volunteers were recruited for the study. 20% SDS was applied for 2 h under occlusion. 1% BKC was then applied to the same site. Various controls, including SDS application followed by water for 2 h, were included. The irritant reaction was assessed at 24 h and 48 h. 40 of the 54 subjects had some reaction when SDS was applied for 2 h followed by either benzalkonium chloride or water control under occlusion. In comparison to water control, where BKC was applied after SDS, 20 of the 40 responders had a weaker reaction but only 4 had a stronger response. This study shows that BKC applied to skin exposed to SDS attenuates the resulting irritant reaction.     

Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen

Human peripheral blood-derived dendritic cells (DC) respond to a variety of chemical allergens by up-regulating expression of the co-stimulatory molecule CD86. It has been postulated that this measure might provide the basis for an in vitro alternative approach for the identification of skin sensitizing chemicals. We recently reported that DC, exposed in culture to the highest non-cytotoxic concentrations of various chemical allergens, displayed marginal up-regulation of membrane CD86 expression; the interpretation being that such changes were insufficiently sensitive for the purposes of hazard identification. For the work presented here, immature DC were derived from human monocytes and treated with the chemical allergens 2,4-dinitrobenzenesulfonic acid (DNBS), nickel sulfate (NiSO4), p-phenylenediamine (PPD), Bandrowski's base (BB), hydroquinone (HQ) and propyl gallate (PG) for 48 h at concentrations which induced both no to slight to moderate cytotoxicity. For comparison, DC were treated with the irritants sodium dodecyl sulfate (SDS), benzoic acid (BA), and benzalkonium chloride (BZC) at concentrations resulting in comparable levels of cytotoxicity. CD86 expression, as measured by flow cytometry, was consistently up-regulated (ranging from 162 to 386% control) on DC treated with concentrations of chemical allergens that induced approximately 10-15% cytotoxicity. The irritants BA and BZC did not induce up-regulation of CD86 expression when tested at concentrations that induced similar levels of cytotoxicity. SDS, however, up-regulated CD86 expression to 125-138% of control in 2/4 preparations when tested at concentrations which induced similar toxicity. Our results confirm that chemical allergens up-regulate CD86 expression on blood-derived DC and illustrate further that up-regulation of CD86 surface marker expression is more robust when DC are treated with concentrations of chemical allergen that induce slight to moderate cytotoxicity.     

Severe contact dermatitis as a result of an antiseptic bath oil

Siblings aged 7 and 5 years developed extensive truncal and flexural inflammation and desquamation unresponsive to standard eczema therapy. After delays in diagnosis, subsequent history revealed prior use of an antiseptic bath oil in a much stronger concentration than recommended. The case illustrates the severe irritant contact dermatitis that can arise following inadequate dilution of antiseptic bath oils, presumably as a result of skin contact with benzalkonium chloride and triclosan. Features that may direct attention to such irritant dermatitis are flexural predominance with superficial desquamation and rapid improvement after avoidance of exposure to the antiseptic solution.