Chlorhexidine toxicity

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Examples of preservatives are phenylmercuric nitrate or acetate (0.002% w/v), chlorhexidine acetate (0.01 % w/v), thiomersal (0.01 % w/v) and benzalkorrium chloride (0.01 % w/v). Chlorocresol is too toxic to the comeal epithehum, but 8-hydroxyquinoline and thiomersal may be used in specific instances. The principal considerahon in relation to antimicrobial properties is the activity of the bactericide against Pseudomonas aeruginosa, a major source of serious nosocomial eye infections. Although benzal-konium chloride is probably the most active of the recommended preservatives, it cannot always be used because of its incompatibility with many compounds commonly used to treat eye diseases, nor should it be used to preserve eye-drops containing anaesthetics. Since benzalkonium chloride reacts with natural mbber, silicone or butyl rabber teats should be substituted. Since silicone mbber is permeable to water vapour, products should not be stored for more than 3 months after manufacture. As with all mbber components, the mbber teat should be pre-equilibrated with the preservative prior to... 

An alternative to most of these mechanisms is the existence of efficient efflux systems, so that toxic concentrations of the drug are not achieved. There are three major families of proton-dependent multidrug efflux systems (1) the major facilitator superfamily, (2) the small multidrug resistance family, and (3) the resistance/nodulation/cell division family (Paulsen et al. 1996). It should be emphasized that several of these systems are involved not with antibiotic efflux but with, for example, acriflavine, chlorhexidine, and crystal violet. An attempt is made only to outline a few salient features of the resistance/nodulation/cell division family that mediates antibiotic efflux, and these are given in Table 3.3 (Nikaido 1996). They consist of a transporter, a linker, and an outer membrane channel. 

Chlorhexidine, a bisbiguanide, has been demonstrated to be somewhat less toxic than benzalkonium chloride and thimerosal at clinically relevant concentrations [87,89,95,144,145]. This work was confirmed in a series of in vitro and in vivo experiments [137,146-148],... 

As an oral rinsing agent, to date chlorhexidine has not been reported to produce any toxic systemic effects. Since chlorhexidine is poorly absorbed in the oral cavity and gastrointestinal tract, little if any enters the bloodstream. A summary of chlorhexidine oral rinses is given in Table 42.1. 

Chlorhexidine Bis-biguanide Good antibacterial activity, low sensitizing potential and toxicity ... 

Chlorhexidine, Kitagawa and Oikawa successfully treated two patients with 0.02% chlorhexidine, natamycin, and debridement. No toxic effects were... 

Use of preserved tear substitutes with contact lenses is a concern because the preservatives may bind to the lens polymer, prolonging ocular retention and exposure, which may result in toxic or hypersensitivity reactions. BAK is more readily absorbed than are thimerosal and chlorhexidine in most hydrogel lenses. 

A wide range of substances that are toxic to the cornea may produce epithelial insult known as toxic keratitis. This terminology is generally reserved for mild superficial corneal irritation after contact with a harmful substance. Solutions foreign to the eye that commonly cause toxic keratitis include shampoos, lotions, and chlorinated pool water. Toxic corneal reactions have been reported from tonometer tips contaminated with 70% isopropyl alcohol or hydrogen peroxide that was not fully removed after disinfection of the probe. Irreversible corneal scarring has resulted from inadvertent ocular contamination with chlorhexidine gluconate, a skin cleanser used preop-eratively. The mistaken use of nonophthalmic products for eyedrops may result in various forms of corneal trauma. 

Chlorhexidine diglnconate is a biguanide surfactant with low toxicity, bnt it is a strong contact sensitizer. Its mncns-binding capacity hmits its nse it binds to hydrophilic (soft) contact lenses. BnUd-up of proteinaceous debris in lenses may greatly increase the binding of chlorhexidine to the lens. 

It was predicted that in an autoclaved solution containing 0.01% w/v chlorhexidine, the amount of 4-chloroaniline formed would be about 0.00003%. At these low concentrations there would be little likelihood of any toxic hazard as a result of the increase in 4-chloroaniline content in the autoclaved solution. 

Animal studies suggest that the acute oral toxicity of chlorhexidine is low, with little or no absorption from the gastrointestinal tract. However, although humans have consumed up to 2g of chlorhexidine daily for 1 week, without untoward symptoms, chlorhexidine is not generally used as an excipient in orally ingested formulations. 

Chlorhexidine has broad-spectrum antibacterial activity hut is not active against acid-fast bacteria, spores, or viruses. It has been used for such topical uses as preoperative. skin disinfection, wound irrigation, mouthwashes, and general sanitiration. Chlorhexidine is not absorbed through skin or mucous membranes and docs not cause systemic toxicity. 

Definition Salt of chlorhexidine and gluconic acid Formuia C22H30CI2N10 2C6H12O7 Properties Sol. > 50% in water m.w. 897.76 Toxicoiogy LD50 (oral, rat) 2 g/kg, (subcut., rat) 3320 mg/kg, (IV, rat) 24,200 pg/kg poison by IV route mod. toxic by ing. and subcut. routes may cause contact dermatitis mutagenic data TSCA listed... 

Chlorhexidine is another cationic agent which is used extensively in periodontal therapy to suppress Gram-negative plaque organisms since it is non-toxic, readily retained and is very effective at low concentrations even though it has a poor detergent capability. Structurally it is a substituted 1,6-bisguanidohexane which contains both hydrophilic and hydrophobic components. 

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