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PubMed2004

Sorption of phenol and 4-chlorophenol onto pumice treated with cationic surfactant.

In this study the sorption of phenol and 4-chlorophenol on pumice modified with the cationic surfactants hexadecyltrimethyl ammonium bromide (HDTMA) and benzyldimethyl tetradecylammonium chloride (BDTDA) was investigated. Experimental studies indicate that HDTMA-pumice and BDTDA-pumice have the capability to remove phenol and 4-chlorophenol from aqueous solution. The influence of initial concentration and adsorbent dosage was studied. The adsorption of phenol and 4-chlorophenol increased with increasing initial concentration and decreased with increasing amount of adsorbent used. The Freundlich adsorption isotherm was found to describe well the equilibrium adsorption data. The parameters of the Freundlich model have been determined using the adsorption data.

Adsorption↗
PubMed2006

Removal of phenol and 4-chlorophenol by surfactant-modified natural zeolite.

In this study the adsorption characteristics of phenol and 4-chlorophenol by surfactant-modified zeolite was investigated. Batch studies were performed to evaluate the effects of various experimental parameters such as contact time, adsorbent dose, initial concentration, and temperature on the removal of phenol and 4-chlorophenol. The sorption kinetics was tested for intraparticle diffusion, Elovich, and pseudo-second order reaction and rate constants of kinetic models were calculated. Equilibrium isotherms for the adsorption of phenol were analyzed by Freundlich, Langmuir, and Tempkin isotherm models. Freundlich isotherm was found to best represent the data for phenol and 4-chlorophenol adsorption.

Adsorption↗
PubMed2006

In vivo efficacy of an alcohol-based surgical hand disinfectant containing a synergistic combination of ethylhexylglycerin and preservatives.

Alcohol-based surgical hand disinfectants are widely available in healthcare settings. Some currently marketed alcohol-based products use active concentrations of antimicrobials to achieve the required efficacy, raising the risk for exposure to potentially irritating levels of antimicrobials. This study compares the in vitro and in vivo efficacy of an alcohol-based surgical hand preparation containing 70% ethanol and preservative levels of chlorhexidine gluconate (CHG) and benzalkonium chloride (BZK) in synergistic combination with ethylhexylglycerin (Surgicept) with a surgical hand disinfectant containing 61% ethanol and 1% CHG (Avagard). The in vivo efficacy of Surgicept and Avagard was evaluated in volunteers using the Tentative Final Monograph method of the Food and Drug Administration (FDA), and their prolonged effect against transient pathogens was compared using a pig skin model. Surgicept exceeded the FDA requirements for surgical hand antiseptic with mean log(10) reductions of 2.36, 3.3 and 3.54 in resident flora 1 min after initial application, and showed a persistent effect with mean log(10) reductions of 2.23, 2.73 and 3.3, 6h post application on days 1, 2 and 5, respectively. Surgicept showed a superior prolonged effect against transient bacteria compared with Avagard. Surgicept (70% alcohol and preservative levels of CHG and BZK) may provide similar in vivo efficacy as Avagard (61% ethanol and 1% CHG).

Administration, Cutaneous↗
PubMed2004

Application of the HPLC method for benzalkonium chloride determination in aerosol preparations.

Benzalkonium chloride (BAC) is a bacteriostatic agent used in the pharmaceutical industry as a preservative. BAC is a mixture of alkylbenzyldimethylammonium chlorides, the three most important of which being those with alkyl substituents C12, C14, C16 at the quaternary ammonium salt. The purpose of this study was to develop a method for determining benzalkonium chloride identity and content in aerosol preparations in which protein or steroid hormones are the active components. The high performance liquid chromatography (HPLC) method was used for this purpose. In the performed comparison of the influence of selected factors on the process of the separation of BAC homologues, a column with packing modified with cyan groups and mobile phase containing 0.075 M acetate buffer with acetonitrile (45:55), in an isocratic elution, was used for qualitative and quantitative determinations and for method validation. The developed method may be used for the assessment of the identity and content of BAC homologues in various pharmaceutical preparations. It is simple and it does not require particular sample preparation for the tests. It is characterized by good selectivity and high precision of the determinations.

Aerosols↗
PubMed2006

Rapid determination of total benzalkonium chloride content in ophthalmic formulation.

A simple and rapid reversed-phase HPLC method was developed for routine analysis of total benzalkonium chloride in ophthalmic formulations. The analysis involves simple sample preparation using the mobile phase as the diluent. The method uses a Waters SymmetryShield RP-18 (75 mm x 4.6 mm, 3.5 microm particle size) column and a mobile phase consisting of a mixture of methanol-potassium phosphate (pH 3.0; 7.5 mM) (68:32, v/v). Using these conditions, three major homologs of the benzalkonium chloride (C(12), C(14) and C(16)) were separated in less then 7 min. Furthermore, recoveries ranging from 97% to 99% at three levels of the label claim of total benzalkonium chloride content were obtained for different ophthalmic formulations. Data supporting the development and validation of this method are presented.

Anti-Infective Agents, Local↗
PubMed2005

Double-blind study on the effects of topical anesthesia on laryngeal secretions.

The application of topical anesthesia to the oropharynx is a common clinical practice during oral and nasal laryngoscopy. Clinically, questions have been raised about whether topical anesthesia alters laryngeal secretions, which distorts clinical impressions. A double-blind, placebo controlled design was employed to address this issue. Ten premenopausal women with healthy vocal folds and 10 premenopausal women with phonotraumatic lesions underwent oral videolaryngoscopic examinations on subsequent days under both anesthesia and placebo conditions, in counterbalanced order. Video segments were rated by three judges. Dependent variables were balling and pooling of secretions, as previously described in the literature. Statistical analyses failed to reveal any clear effect of topical anesthesia on either secretion balling or pooling for the collapsed data set, but one cannot exclude changes in individual cases. Moreover, there was no evidence that secretions were differentially affected by anesthesia across subject groups. Null results in this data set replicate and extend previously reported findings by other authors. An incidental but potentially interesting finding was that the order of treatment condition (anesthesia versus placebo first) seemed relevant for secretions: Subjects who received the anesthesia condition first tended to show more secretion balling in general, as compared with subjects who received the placebo condition first. Speculation is entertained regarding possible physiological pathways for these incidental findings, which could be relevant for some clinical practice.

4-Aminobenzoic Acid↗
PubMed2004

Use of heterotrophic CO2 assimilation as a measure of metabolic activity in planktonic and sessile bacteria.

We have examined whether assimilation of CO2 can be used as a measure of metabolic activity in planktonic and sessile heterotrophic bacteria. CO2 assimilation by environmental samples and pure cultures of heterotrophic bacteria was studied using 14CO2 and 13CO2 as tracers. Heterotrophic growth on complex organic substrates resulted in assimilation of CO2 into cell biomass by activated sludge, drinking water biofilm, and pure cultures of Escherichia coli ATCC 25922, Es. coli ATCC 13706, Rhodococcus ruber, Burkholderia sp., Bacillus circulans, Pseudomonas putida, Pseudomonas stutzeri, and Pseudomonas aeruginosa. Analysis of 13C-labelled phospholipid fatty acids (PLFAs) confirmed that heterotrophic bacteria may assimilate 13CO2 into cell macromolecules such as membrane lipids. All major PLFAs extracted from activated sludge and drinking water biofilm samples were enriched in 13C after incubation with CO2. Between 1.4% and 6.5% of the biomass produced by cultures of P. putida and a drinking water biofilm during growth in complex media was apparently derived from assimilation of CO2. Resting cells assimilated less CO2 compared to actively growing cells, and CO2 assimilation activity correlated with the amount of biomass produced during heterotrophic growth. The 14CO2 assimilation assay was evaluated as a tool to examine inhibitory effects of biocides on planktonic and sessile heterotrophs (biofilms). On the basis of 14CO2 assimilation activity, the minimum inhibitory concentration (MIC) of benzalkonium chloride was estimated to 21.1 and 127.2 mg l(-1) for planktonic and biofilm samples, respectively. The results indicate that assimilation of isotopically labelled CO2 can be used as a relatively simple measure of metabolic activity in heterotrophic bacteria. CO2 assimilation assays may be used to study the effects of antimicrobial agents on growth and survival of planktonic and sessile heterotrophic organisms.

Anti-Bacterial Agents↗
PubMed2004

Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions.

BACKGROUND: For most multiuse aqueous nasal, ophthalmic, and otic products, benzalkonium chloride (BKC) is the preservative of choice. The American College of Toxicology has concluded that BKC can be safely used as an antimicrobial agent at concentrations up to 0.1%. BKC has been in clinical use since 1935 and is contained in a wide variety of prescription and over-the-counter products. However, over the past several years there have been conflicting reports of damage to human nasal epithelia and/or exacerbation of rhinitis medicamentosa associated with intranasal products containing BKC. OBJECTIVE: We sought to review the published literature and determine whether there is sufficient, clinically significant data that would confirm that intranasal products containing BKC are likely to damage human nasal epithelia or exacerbate rhinitis medicamentosa. METHODS: A literature search was conducted for in vivo and in vitro studies that evaluated the effects of BKC on human nasal epithelia. RESULTS: A total of 18 studies (14 in vivo, 4 in vitro) were identified that evaluated short- and long-term exposure of concentrations of BKC in concentrations ranging from 0.00045% to 0.1%. Eight studies, including a 6-month and 1-year long-term treatment study, demonstrated no toxic effects associated with BKC, indicating that BKC was neither harmful to nasal tissue nor prone to exacerbate rhinitis medicamentosa. Furthermore, of the 10 studies that concluded that BKC resulted in degenerative changes in human nasal epithelia (eg, ciliary beat frequency, ciliary morphology, mucociliary clearance, epithelial thinning and/or destruction) or that BKC exacerbates rhinitis medicamentosa, only 2 (it was 2 according to the Results section) of these studies were supported by statistically significant differences between BKC and placebo or active control groups were compared. It is important to note that in both of these studies, the protocol incorporated the use or oxymetazoline in some or all of the subjects. Oxymetazoline is associated with rhinitis medicamentosa. CONCLUSION: Intranasal products containing the preservative BKC appear to be safe and well tolerated for both long- and short-term clinical use.

Administration, Intranasal↗
PubMed2004

Ileal VIP submucous neurons: confocal study of the area enlargement induced by myenteric denervation in weanling rats.

Vasoactive Intestinal Peptide (VIP) neurons are maturing during suckling and weaning periods and the neuropeptide VIP is thought to be neurotrophic during ontogenesis. We have previously demonstrated that suckling rats with myenteric ablation have significantly higher mitotic index and an increase on villus height and crypt depth 15 days after treatment. In the current study, we measured the area of VIP neurons of submucous plexus in the ileum of weanling rats, in which myenteric neurons were ablated by serosal application of benzalkonium chloride (BAC). The area of VIP immunoreactive cell bodies, reconstructed under confocal microscope, was significantly increased in response to denervation. This result suggests that the myenteric plexus may have an inhibitory role over submucous plexus in the normal intestine. The enhanced production of VIP may be correlated with the increased epithelial proliferation induced by denervation in a critical period of life, from suckling to weaning time.

Animals↗
PubMed2004

Surfactant and UV-B-induced damage of the cultured bovine lens.

PURPOSE: To evaluate in vitro methods for testing the toxicity of the surfactants, sodium dodecyl sulfate (SDS) and benzalkonium chloride (BAK), and Ultraviolet (UV)-B radiation to the bovine lens. METHODS: Lenses were dissected from bovine eyes--obtained from a local abattoir--and incubated in M199 culture medium at 37 degrees C, with 4% CO(2) and 96% air atmosphere. For the SDS and BAK experiments, the lenses (n = 153) were exposed directly to 0.001%, 0.01%, 0.1%, and 1.0% solutions for 15 min. These lenses were then rinsed five times each with saline and medium. Another group of lenses (n = 36) was irradiated with broadband UV-B at energy levels of 1.0 and 2.0 J/cm(2) (0.445 and 0.89 J/cm(2) in the biologically effective energy levels). For all of the above experiments, lens optical quality and cellular viability of lens epithelial cells were evaluated. RESULTS: The analysis of optical quality, using a scanning laser in vitro assay system, of exposed lenses treated with SDS and BAK at concentrations of 0.01%, 0.1%, and 1.0%, and with UV-B at energy levels of 0.445 and 0.89 J/cm(2) showed a dose- and time-dependent increase in back vertex distance (BVD) variability, indicating loss of sharp focus in comparison with control lenses. Both 0.001% SDS and 0.001% BAK-treated lenses did not show any optical damage until 8-days after exposure. Lenses treated with 0.01% SDS showed recovery from optical damage 6-days later after exposure. Optical damage was not shown immediately for UV-B-exposed lenses. The Alamar Blue assay data for SDS, BAK and UV-B-exposed lenses, except the 0.001% SDS treated lens group, showed also dose- and time-dependent decreases in cellular viability in comparison with the control lenses, and there was no cellular recovery during the entire culture period. Lenses treated with 0.001% SDS did not show biological damage until 8-days after exposure. It appears that cellular changes appeared earlier than optical changes. CONCLUSIONS: The findings suggest that cultured bovine lenses can be evaluated by assays that probe optical properties and cellular function after exposure to surfactants and UV-B irradiation, and that the optical and biological assay methods are valuable for in vitro mild ocular toxicity research.

Animals↗
PubMed2006

In vitro genotoxicity and cytotoxicity of benzalkonium chloride.

Benzalkonium chloride (BAC) acts as a preservative in numerous nasal preparations. Possible genotoxic and cytotoxic effects of BAC in human respiratory epithelial BEAS-2B cells should be investigated in vitro. Cell cultures were exposed for 2h to BAC in concentrations ranging from 0.002% to 0.05%. Methyl methanesulfonate served as positive control, PBS as negative control. The tail moment of single-cell gel-electrophoresis (SCGE) was used to assess BAC-induced DNA damage. Cell viability was measured by trypan blue dye exclusion staining. Additionally, the critical micellar concentration (CMC) of BAC in PBS was detected. The tail moment increased dose dependently with the maximum value at 0.02%, and declined for higher concentrations. Nearly all cells died at low BAC concentrations up to 0.01%. Above this concentration cell viability increased. The CMC of BAC in PBS was estimated to be 0.02%. BAC caused relevant DNA changes in respiratory epithelial cells in vitro at concentrations commonly employed in commercially available nasal preparations. Some of the exposed cells survived. In further studies it could be considered to look whether these cells would still be able to proliferate and possibly fix the damage that they have possibly accumulated into an actual mutation using for example the induction of micronuclei.

Benzalkonium Compounds↗
PubMed2004

Distribution and disposition of benzalkonium chloride following various routes of administration in rats.

Benzalkonium chloride (BZK) is a cationic surfactant used widely as a disinfectant, preservative and sanitizer in hospitals, at home and many public places. The toxicity of BZK is not well established although several human fatalities have been reported over the years. In this study, distribution and disposition of BZK following oral administration (PO) and intravascular (jugular vein (JV), femoral artery (FA), femoral vein (FV) and jugular artery (JA)) administration in rats were investigated along with pathological examinations. Toxic doses of 250 and 15 mg/kg of BZK were used for PO and intravascular administration, respectively. The fatal effects of BZK appeared soon in JV-, FV- or JA-rats, but took hours in PO or FA-rats. No rat receiving BZK via FA survived longer than 1 day. The PO-rats that aspirated BZK into their lungs had some systemic symptoms and higher blood and tissue concentrations of BZK. The blood BZK levels and kinetics were similar among the different routes of intravascular administration, but the lung and kidney levels were higher in JV-rats. Pathological examinations confirmed severe congestion and edema in the lungs and kidneys. These results suggest that (1) the toxic effects of BZK varied depending on the route of administration, (2) the degree of toxicity correlated with peak blood and tissue concentrations in orally dosed rats, (3) different toxicological progressions and manifestations were observed in FA- and JV-dosed rats even though these groups had similar blood concentration profiles, and (4) lung and kidney are reservoirs for BZK and considered to be the target organs of BZK.

Administration, Oral↗
PubMed2005

Effect of mechanical stress on biofilms challenged by different chemicals.

In this study a methodology was applied in order to ascertain the mechanical stability of biofilms, by using a stainless-steel (SS) rotating device immersed in a biological reactor where biofilms formed by Pseudomonas fluorescens were allowed to grow for 7 days at a Reynolds number of agitation of 2400. The biofilms developed with this system were characterised in terms of amount of total, extracellular and intracellular proteins and polysaccharides, amount of mass, metabolic activity and mechanical stability, showing that the biofilms were active, had a high content of extracellular constituents and an inherent mechanical stability. In order to assess the role of chemical agents on the mechanical stability, the biofilms were exposed to chemical agents followed by mechanical treatments by submission to increase Reynolds number of agitation. Seven different chemical agents were tested (two non-oxidising biocides, three surfactants and two oxidising biocides) and their effects on the biofilm mechanical stability were evaluated. The increase in the Reynolds number increased the biofilm removal, but total biofilm removal was not found for all the conditions tested. For the experiment without chemical addition (only mechanical treatment), the biofilm remaining on the surface was about 76%. The chemical treatment followed by the subsequent mechanical treatment did not remove all the biofilms from the surface. The biofilm remaining on the SS cylinder ranged from 3% to 62%, depending on the chemical treatment, showing that the chemical treatment is far from being a cause that induces massive biofilm detachment and even the synergistic chemical and mechanical treatments did not promote biofilm removal. Some chemical agents promoted an increase in the biofilm mechanical stability such as glutaraldehyde (GTA), benzalkonium chloride (BC), except for the lower concentration tested, and sodium dodecyl sulphate (SDS), except for the higher concentration tested. Treatments that promoted biofilm removal, to an extent similar to the control experiment (without chemical treatment), were BC, for the lower and the higher concentration of SDS. Cetyltrimethyl ammonium bromide (CTAB), ortho-phthalaldehyde (OPA), sodium hydroxide (NaOH) and sodium hypochlorite (SHC) promoted the weakening of the biofilm mechanical stability.

Bacterial Proteins↗
PubMed1999

Effects of multiple applications of benzalkonium chloride and nonoxynol 9 on the vaginal epithelium in the pigtailed macaque (Macaca nemestrina).

OBJECTIVE: Safe and effective vaginally applied microbicides could help to control the continuing spread of sexually transmitted diseases. STUDY DESIGN: This study used nonhuman primates to test the effects of multiple applications of nonoxynol 9, benzalkonium chloride, or a combination on vaginal flora and lower reproductive tract tissues. Fourteen monkeys (Macaca nemestrina) received daily vaginal applications of nonoxynol 9, benzalkonium chloride, or both for 3 to 4 days. Vaginal microflora and colposcopic observations were made at baseline and during and after completion of treatments. Cervical biopsy specimens were collected from a subset of animals. RESULTS: Cervical erythema and vaginal erythema were observed in all 3 treatment groups. Cervical papillae and epithelial disruption were present in both the nonoxynol 9 and the nonoxynol 9 plus benzalkonium chloride groups. Vaginal epithelial disruption was noted in both the benzalkonium chloride and the nonoxynol 9 plus benzalkonium chloride groups. Cervical biopsy specimens from each group revealed acute inflammatory infiltrates with occasional plasma cells and lymphoid follicles. Detection of most microorganisms, including viridans streptococci, decreased in the benzalkonium chloride and the nonoxynol 9 plus benzalkonium chloride groups. Detection of Lactobacillus species decreased in the benzalkonium chloride group. All microflora levels recovered after several days without microbicide use. CONCLUSIONS: Although nonoxynol 9 is currently the only microbicide approved for use as a spermicide in the United States, its repeated use may be detrimental to the epithelial tissues of the female reproductive tract. Benzalkonium chloride, currently approved for use in other countries, not only may damage epithelial tissues but also appears to reduce the population of potentially protective Lactobacillus species in the vagina.

Animals↗
PubMed1983

Effects of topical timolol on corneal endothelial cell morphology in vivo.

To determine the effect of topical timolol on corneal endothelial cell morphology in a randomized, controlled, double-masked study of 40 healthy human eyes, we photographed the central corneal endothelium with a contact specular microscope before and after two weeks of treatment with placebo (20 eyes), with 0.5% timolol with 0.01% benzalkonium chloride (ten eyes), or with 0.5% timolol without benzalkonium chloride (ten eyes). From the specular photomicrographs, we analyzed five morphologic cell characteristics by means of electronic digitizer and microcomputer--cell density, mean cell area, the coefficient of variation for cell area, mean cell perimeter and a new feature quantifying cell shape. Statistical analysis of the data showed that two weeks of exposure to topical timolol or its preservative had no significant effect on corneal endothelial cell morphology in young, healthy eyes in vivo.

Adult↗
PubMed1991

The effects of denatured sodium hyaluronate on the corneal endothelium in cats.

In an in vivo cat model, wide-field specular microscopy and scanning electron microscopy were used to observe whether heat-denatured sodium hyaluronate causes cell damage to the corneal endothelium. The endothelial cell toxicities of various drugs, including 0.01% benzalkonium chloride, 0.2% chlorhexidine digluconate, and 0.5% lidocaine, mixed with intact or untreated sodium hyaluronate were also investigated. Neither heat-denatured nor intact or untreated sodium hyaluronate alone had any adverse effect on the corneal endothelium in cats, whereas 0.01% benzalkonium chloride and 0.2% chlorhexidine digluconate, mixed with sodium hyaluronate, caused substantial endothelial morphologic changes, which resulted in corneal edema. By comparison, 0.5% lidocaine with sodium hyaluronate was found to have minimal effect on the corneal endothelium in cats. These findings indicate that some chemical contaminant with sodium hyaluronate, not heat-denatured sodium hyaluronate, induces an immediate onset of pseudophakic bullous keratopathy.

Animals↗
PubMed1999

The survival of herpes simplex virus in multidose office ophthalmic solutions.

PURPOSE: To determine the survival of herpes simplex virus type 1 (HSV-1) in several multidose ophthalmic solutions. METHODS: In three separate trials, 10 aliquots of 5 ml each of three common multidose topical ophthalmic solutions, sodium fluorescein, proparacaine, and nonpreserved artificial tears, were inoculated with 10(5), 10(4), and 10(3) pfu per ml of HSV-1. All samples were titered on A549 cells at various time points for surviving HSV-1. RESULTS: Herpes simplex virus type 1 was not recovered from the fluorescein and proparacaine solutions at 1 hour or any time thereafter, regardless of inoculation titer. Herpes simplex virus type 1 was recovered from the artificial tears up to 7 days. CONCLUSION: Unlike adenovirus, HSV-1 does not survive in preserved fluorescein and proparacaine multidose solutions; therefore, office transmission is highly unlikely.

Benzalkonium Compounds↗