Preservative Resistance
Philip A. Geis in Cosmetic Microbiology, 2020
If a microorganism is resistant to the antimicrobial activity of a chemical disinfectant, it is possible that it is also resistant to a preservative in a product formulation if the active ingredient is in both the disinfectant and preservative. For example, a strain of Pseudomonas aeruginosa has been found to be resistant to N-dodecylpyridinium iodide (P-12), whose structure is similar to that of a common disinfectant, cetylpyridinium chloride (71). Pseudomonas aeruginosa has been well known to survive and proliferate in solutions of benzalkonium chloride (72). Benzalkonium chloride and cetylpyridinium chloride are QACs. It is well known that Gram-negative bacteria are less susceptible to QACs than Gram-positive bacteria, and Pseudomonas spp. have generally high intrinsic resistance compared to other Gram-negative bacteria (44). In addition, Pseudomonas spp. may adapt to survive against higher concentrations of QACs (73). In addition to being active ingredients in disinfectants, benzalkonium chloride and cetylpyridinium chloride can be used as preservatives in product formulations. If a microbial isolate in the manufacturing equipment is resistant to the antimicrobial activity of a benzalkonium chloride or cetylpyridinium chloride disinfectant, they could contaminate a finished product. If a finished product contains either benzalkonium chloride or cetylpyridinium chloride as the preservative, the resistant isolate may survive and eventually proliferate in that formulation.
Allergic Contact Dermatitis to Ingredients other than the Active Drug
Anton C. de Groot in Monographs in Contact Allergy, 2021
In cases of allergic contact dermatitis from topical pharmaceuticals, the allergenic culprit may be either the active drug or one or more of the other components, for example vehicle ingredients, preservatives, antioxidants, fragrances or other chemicals present in the topical drug product. Such reactions to non-drug components are far from rare. In eye drops, for example, many allergic reactions have been reported to the preservatives thimerosal and benzalkonium chloride. In creams and ointments, especially those used for herpes simplex (acyclovir), fungal infections (ketoconazole), and in topical corticosteroids, propylene glycol was often found to be the allergenic culprit. It should be realized, though, that these chemicals tend to cause irritant patch test reactions, and there can be no doubt that a number of the ‘allergic’ reactions reported have, in fact, been false-positive.
Animal, Human, and in Vitro Test Methods for Predicting Skin Irritation
Francis N. Marzulli, Howard I. Maibach in Dermatotoxicology Methods: The Laboratory Worker’s Vade Mecum, 2019
One example of such an approach compared the irritant capabilities of the irritants benzalko-nium chloride, trichloroacetic acid, phenol, and hydrochloric acid in the human and in the Skintex (In Vitro International, Irvine, CA) dermal assay system (Bason et al., 1992). The Skintex system was fairly sensitive in its ability to predict the irritant potential of these compounds in humans (sensitivity 82%, specificity 71%, positive predictive value 82%) (Bason et al., 1992). Additionally, the in vivo dose-response curves for each of the four substances were compared to the in vitro dose-response curves, and correlation coefficients were calculated. The in vitro dose response for benzalkonium chloride (R2 = .987) and phenol (R2 = .994) were strikingly similar to those generated in vivo, possibly indicating that the mechanisms of action in vivo and in vitro are similar for these two compounds.
Neutralization of the eye and skin irritant benzalkonium chloride using UVC radiation
Published in Cutaneous and Ocular Toxicology, 2021
Manlong Xu, Jacob G. Sivak, David J. McCanna
Benzalkonium chloride (BAK) is a group of quaternary ammonium compounds that have an extremely wide range of applications, such as biocides, disinfectants, food additives, as well as preservatives in pharmaceutical and cosmetic products. Benzalkonium is composed by a positively charged nitrogen atom linked to a long alkyl chain (ranging from 8 to 18 carbon atoms) on one side, and a benzyl group on the other. The two last positions are occupied by methyl groups1. The key mechanism of BAK’s antimicrobial action is membrane destruction, which is effective against enveloped viruses (e.g. SARS-CoV, SARS-CoV-2), bacteria (Gram-negative and Gram-positive), filamentous fungi, yeasts and protozoa2,3. Because of BAK’s efficiency, stability and low cost, it has become a major non-alcohol-based active ingredient used for hospitals, food processing plants, and domestic household biocides4,5.
Lacrimal Gland Insufficiency in Aqueous Deficiency Dry Eye Disease: Recent Advances in Pathogenesis, Diagnosis, and Treatment
Published in Seminars in Ophthalmology, 2022
These have been the first line of management in patients with ADDE, regardless of the disease severity. They are known to improve the ocular surface lubrication, tear retention, tear osmolarity and TBUT and reduce the ocular surface staining. However, there are various types of artificial tears available which differ in its constituents.73,74 Preservatives such as benzalkonium chloride should be avoided as it causes stinging sensation and ocular surface toxicity with long-term use. The pH of the human tear is between 6.9 and 7.5. Any compound having a higher pH causes burning sensation upon instillation. These factors further worsen the pre-existing symptoms of a patient with DED. Current recommendations are that a preservative-free compound having a lower pH should be preferred. Due to the varied compositions, the drops need to be individualized in every patient.
Lactic acid, citric acid, and potassium bitartrate non-hormonal prescription vaginal pH modulator (VPM) gel for the prevention of pregnancy
Published in Expert Review of Clinical Pharmacology, 2022
Benzalkonium chloride is both a spermicide and bactericidal agent that has been in use since 1935, however it is not approved by the U.S. FDA for contraception [27]. In concentrations above 0.007% it has the ability to immobilize sperm [27]. Clinical studies assessing the efficacy of benzalkonium chloride as a contraceptive have resulted in 17 pregnancies in 1998 cases (Pearl Index 1.1) [27]. A further multicenter phase III trial assessing contraceptive efficacy, tolerance and acceptability showed out of 653 women who were using the product, 23 became pregnant (Pearl Index 1.4) [27]. Benzalkonium chloride is generally well tolerated with one or more side effects reported in 22.6% of women – resulting in a discontinuation rate of only 2.4% [27]. A recent phase IV study involving 151 women age 40 and above in France and Russia was completed but has not released results [28]. However, as benzalkonium chloride immobilizes sperm by rupturing the integrity of the plasma membrane, similar to other spermicides, its safety has been debated, with a rising amount of evidence suggesting these products can increase susceptibility to STIs [29]. This occurs due to the harmful effects spermicides can have on the lining of vaginal epithelium triggering inflammatory responses as well as disrupting the balance of vaginal microbiota [29].
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