Oral Health Group
Feature

Mouthwashes and Their Use in Dentistry: A Review

March 9, 2021
by Frank Poppolo Deus; BSc; Aviv Ouanounou, BSc, MSc, DDS, FICD, FACD, FICO


Abstract
Mouthwashes are aqueous topical medications that function by rinsing and gargling inside of the mouth. There are multiple mouthwashes available over the counter and by prescription with a wide range of active ingredients that can be used as an adjunct to aid in the multifactorial management of complex oral conditions, including halitosis, gingivitis, periodontal disease, oral mucositis and even xerostomia among others. More recently, many mouthwashes have been implicated in the prophylactic treatment of potentially infected coronavirus disease 2019 (COVID-19) patients as a pre-procedural rinse. However, as with any drug, there is potential for adverse effects and misuse. The main objective of this review is to aid dental professionals in the selection of the appropriate type of mouthwash based on the oral pathological condition being treated, as well as the relevant factors to consider involving such decisions.

Throughout history humankind has recognized the importance of oral hygiene.1 Archeologists have uncovered toothpicks dating as far as 3000 B.C.1 It appears even the practice of mouth rinsing has been used by humans for more than 2000 years, originating from Chinese medicine.1,2 It was at the end of the 19th century that oral hygiene practice truly began to change when a dentist trained in microbiology, Willoughby D. Miller, published “Micro-organisms of the human mouth”.2,3 He created a worldwide promotion of tooth brushing and flossing to combat oral biofilm, and even suggested the use of antimicrobial mouthwash that contained phenolic compounds to combat gingival inflammation.2,3

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Bacteria present in the oral biofilm are implicated in the pathogenesis of oral diseases, such as dental caries, periodontal diseases such as gingivitis and periodontitis, and even halitosiss.4-6 Periodontal disease affects about 47.2% of adults aged 30 years and older, and 70.1% of adults aged 65 and older in the U.S.7 Thus, effective biofilm control is important for preventing these conditions.4-6 Manual or power tooth brushing is recommended as the primary means of reducing plaque and gingivitis;8 however, effective mechanical plaque control is time consuming and requires motivation and dexterity-related skills.4,5 This is why chemical plaque control utilizing antimicrobial agents is important to complement the results of mechanical oral hygiene measures.4,5 In dentistry, oral rinses containing antimicrobials function by chemomechanical action, and are used for both preventative and therapeutic purposes.4,5,9 Mouthwashes act as an ideal medium for all inaccessible areas in the mouth and are necessary in order to allow proper wound healing in situations where oral hygiene is difficult or compromised.2,5,10,11

Generally speaking, there are two types of mouthwash products: cosmetic and therapeutic.6,10 Cosmetic mouthwash lacks active ingredients that provide a true chemical or biological application, they may temporarily control bad breath by leaving a pleasant taste, but they do not kill the bacteria associated with it.6,10 Oppositely, therapeutic mouthwash does contain active ingredients, such as cetylpyridinium chloride (CPC), chlorhexidine (CHX), fluoride, and peroxide.6,10 In other words, cosmetic mouthwashes cannot act as an antimicrobial and lack the bacteriostatic and bacteriocidal benefits that are provided by therapeutic mouthwashes. When therapeutic mouthwash is prescribed by a clinician it is often short-term, and always evidence based for addressing specific conditions.6 When used correctly therapeutic mouthwashes have been clinically effective in reducing dental biofilm accumulation, as well as an adjunct in the treatment of halitosis and periodontal disease, such as gingivitis and periodontitis.1,2,4-6,8,9,12

The problem is that over-the-counter mouthwash is advertised as part of routine oral hygiene procedures, sometimes solely for cosmetic reasons, but actually contain active ingredients, thus should be considered therapeutic.6,12 In fact, 90% of used mouthwash products in the US contain at least one active ingredient.6 Depending on the concentration and active ingredient, some therapeutic mouthwashes do not actually target specific oral pathogens, this is dangerous because it may lead to cross-resistance and overgrowth of pathogenic bacteria.6 In other words, the effect of unsystematically utilized mouthwash may lead to a reduction in the clinical efficacy of antibiotics.6 This garners the importance for patients to use mouthwash only when indicated by a dental practitioner or health professional, regardless if it is over the counter. This paper will outline some of the most effective therapeutic mouthwashes and their active ingredients, as well as indications to maximize efficacy and treatment protocols.

CHLORHEXIDINE

Chemical features
CHX is constituted from two 4-chlorophenyl rings and two biguanide groups linked by a hexamethylene chain.11,12 It is the chlorine group attached to each phenol ring which give chlorhexidine its cationic activity.13 Its positive charge attracts it to the negatively charged surfaces in the oral cavity. These surfaces include mucous membranes, salivary pellicles on teeth, titanium surfaces, and various components of biofilm including bacteria, extracellular polysaccharides and glycoproteins.14 CHX often bonds on the bacterial surface to anionic compounds, such as lipopolysaccharides on Gram-negative bacteria and phosphate groups of teichoic acid on Gram-positive bacteria, as well as sulfate groups.15,17

Antimicrobial features
In dentistry, CHX products are available only by prescription.12,18 CHX mouthwashes used in dentistry function for both prophylactic and therapeutic purposes via chemomechanical action.9,19 For these applications, CHX is used at a concentration between 0.1-0.2% in order to obtain an ideal dosage of 18-20mg per application to maximize efficacy, while minimizing adverse drug reactions.5,11,18,17 (Table 1). It is considered the most potent chemotherapeutic mouthwash and gold standard for reducing S. mutans and plaque.9,19,20,21 Although, it appears that a CHX mouthwash concentration of 0.2% is significantly more effective in reducing supragingival plaque when compared to 0.12% and 0.06%.22

Table 1

CHX mouthwash and it’s use in dentistry.

CHX mouthwash and it’s use in dentistry.

Chlorhexidine has a rapid antimicrobial and antifungal activity, even at lower concentrations it maintains efficacy.23,24 Several studies have demonstrated that both a 0.2% and 0.12% CHX utilized with a 60s rinse, as indicated by the manufacturers, significantly inhibit the growth of C. albicans in vitro.25,26 Increasing the rinse time to 120s appeared to have no significant difference but decreasing it to 30s significantly worsened the efficacy of the mouthwash.27 CHX even appears to be more effective than azoles and fluconazole, likely due to the fact that biofilm antifungal assays showed resistance, whereas the CHX did not.28,27 Furthermore, CHX at 0.2% was even able to reduce the biofilm viability in vitro by 80%, which equates to the breakpoint for sessile minimum inhibitory concentration testing.28 C. albicans colonies are more frequently isolated from the tissue-fitting surfaces of acrylic resin dentures than from the corresponding mucosa, making Candida albicans‐associated denture stomatitis the most common type of denture stomatitis.29 In vivo studies have demonstrated that using 0.12 % CHX mouthwash to store acrylic dentures overnight for 8 hours significantly reduces the amount C. albicans colonies and may be used in the treatment of denture stomatitis.26

The action of CHX towards aerobic and anaerobic bacteria is diverse. It does not show the bactericidal activity against tuberculosis bacilli and it is inactive against spores of bacteria at room temperature but becomes active at elevated temperatures.15,25,28 CHX can devastate both DNA and RNA viruses, and inactivate the infectivity of lipophilic-enveloped viruses, such as Herpes simplex virus, Human immunodeficiency viruses, Influenza A, Parainfluenza, Hepatitis B and even Cytomegalovirus.15,25,28,29

Conventional uses in dentistry
Conventional CHX mouthwash at 0.1-0.2% concentrations have also exhibited significant antiplaque and anti-inflammatory effects on the gingiva and oral cavity.5,22,24,30,31-34 However, CHX mouthwash at 0.12% is most effective as a prophylaxis in preventing the development of gingivitis if the patient’s teeth were professionally scaled prior to its application to ensure a plaque-free dental surface.14 CHX mouthwash also acts as a prophylactic in periodontal and implant procedures.5,18 It may be used prior to oral surgery as well as afterwards, when mechanical maintenance may become difficult or even impossible due to pain and discomfort.2,4,5,18 Oral biofilm is the main etiologic factor for the development of periodontitis and peri-implantitis, and adversely affect the process of wound healing in the oral cavity.5,11,18 Therefore, a reduction of biofilm and maintaining bacterial levels to a minimum is critical in the re-establishment of clinically healthy gingival tissues, emphasizing the importance of CHX mouthwash in post-surgical procedures.5,11,18.34

CHX mouthwash is such an effective antimicrobial, that The American Dental Association recommends the use of chlorhexidine before and after any surgical procedure involving bone or in the field of oral and maxillofacial surgery.23,28,35 The use of CHX mouthwash at 0.12-0.2% significantly reduces the risk of developing alveolar osteitis (dry socket) and bacteremia following dental extractions and should be considered an adjunct to proper surgical technique.36-38 The American Association of Oral and Maxillofacial Surgeons (AAOMS) also recommends the use of CHX mouthwash in patients that will be undergoing extractions and are over the age of 55 with a risk for development of medication-related osteonecrosis of the jaw (MRONJ).39,40 In order to direct rational treatment guidelines, a staging system was implemented by the AAOMS in the following order: “at risk, stage 0, stage 1, stage 2, stage 3”.41,42 Antimicrobial rinses should be used in patients presenting with MRONJ stages 1-3, specifically recommending 0.12% CHX for stage 1 patients.39-41

Adverse Drug Reactions
Even at low concentrations CHX mouthwash can have some adverse drug reactions (ADRs) occur within therapeutic range, this has been recorded in concentrations ranging from 0.06% to 0.2%.5,24,25,28,42 Self-reported ADR’s experienced throughout 21-days of usage included: taste perturbation (loss of taste), numb feeling in tongue and mouth, painful tongue and mouth, desiccating/dry feeling, and subjective discolouration.24 Although “loss of taste” and “numb feeling” were significantly more frequent with the 0.12% and 0.2% concentration, no serious ADRs associated with CHX, such as erosion and ulceration of oral mucosa, were reported.22

In other instances, commonly reported ADRs involving chronic use of CHX mouthwash at therapeutic values included brownish discolouration of teeth, dental prosthesis, restorations and oral surfaces, increased calculus formation, and altered taste perception.5,18,20,25,28,44 Less frequently reported ADRs included superficial desquamation and irritation of oral mucosa, ulceration and erosion of oral mucosa, tooth aches, headaches, sialadenitis, and even parotid gland swelling.5,18,20,25,28,44 Nevertheless, CHX 0.12% and 0.2% is recommended for short-term use, and the risk of ADRs are present no matter the concentration; therefore, the potential for ADRs should be considered in the dental setting whenever chlorhexidine may be prescribed.2,4,18,24,44 Table 1 summarizes the clinical usages and recommended treatment of CHX.

CETYLPYRIDINIUM CHLORIDE

Chemical and Antimicrobial Features
CPC is cationic quaternary ammonium compound with antimicrobial surface-active properties, acting as a bactericidal on Gram-positive pathogens as well as fungi and yeasts.2,43,44 Its mechanism of action relies on the hydrophilic part of the CPC molecule interacting with the bacterial cell membrane, and because of its cationic nature, it interrupts the cell membrane leading to intracellular loss of cell components, disruption of cell metabolism, inhibition of cell growth, and finally cell death.2,43,44 CPC in mouthwash at a concertation ranging between 0.045-0.10% has been considered safe and effective by the FDA for the treatment of plaque-induced gingivitis.29,45

Conventional uses in Dentistry
Many studies have demonstrated that CPC in mouthwash reduces plaque accumulation and gingival inflammation due to its moderate plaque inhibitory activity, with lower concentration’s in the 0.05% range being used as an alternative to CHX in patients who develop ADRs such as mucosal irritation and stains.2,29,45,46 Research has demonstrated that CPC mouthrinses exhibit anti-plaque activity when used alone, as well as an adjunct to toothbrushing.45 CPC mouthrinse at a concentration of 0.07%, was effective in inhibiting ‘de novo’ plaque formation over a 3-day study where no-brushing prophylaxis was used.47 A more recent study evaluated the clinical efficacy of 0.07% and 0.075% CPC compared to a non-antibacterial mouthwash when used as an adjunct to toothbrushing twice a day for a duration of 6-weeks.46 The results indicated that both CPC-containing mouthwashes exhibited statistically significant reductions in all the gingivitis and plaque parameters evaluated compared to subjects that did not incorporate it in the oral hygiene protocol.48 Other trials with durations of 2-4 weeks also indicated significantly more plaque inhibition when they incorporated CPC mouthwash at 0.07% as an adjunct to the oral hygiene protocol.47

It appears that mouthrinses with CPC at 0.07% maintain their efficacy long-term.43,48,49 Studies have revealed that 6-month oral hygiene protocols that incorporated 0.07% CPC three times per day adjunctively to mechanical tooth cleaning significantly prevented plaque accumulation and reduced gingival inflammation, in comparison to placebo mouth rinse.43,48 Microbiological changes with CPC-containing mouthwash at 3 and 6 months include a significant decrease in total subgingival bacterial counts with no relevant changes in placebo group.45 These changes led to significant inter-group differences at 6 months, with no overgrowth of opportunistic species detected.47 P. gingivalis was significantly reduced at the 3-month interval and P. intermedia at the 3- and 6-month interval.45 Another study specifically indicated a two-to-threefold significant decrease in total anaerobic bacteria at 6 months in the CPC group compared to placebo rinse when used as an adjunct, with no negative shift observed in microbiota of dental plaque or saliva.50 Thus, the use of CPC-containing mouth rinses in addition to toothbrushing is effective in controlling dental plaque and gingivitis in short, intermediate and long-term circumstances.51

Considering CPC’s antimicrobial effects, CPC containing mouthwash can also be utilized in the management of halitosis.50,51 Halitosis is defined as unpleasant breath odor with an intensity beyond socially acceptable levels, which may affect personal relationships.52 It is a consequence of volatile molecules, which are a result of pathological or nonpathological processes.52 Intraoral halitosis makes up 90% of cases and affects roughly 50% of the population world-wide.52 Improvement in oral hygiene is often recommended in management; however, if a protocol with toothbrushing and tongue brushing in combination with fluoride-containing toothpaste is insufficient, then a 0.075% CPC mouthwash can be added as an adjunct to reduce oral malodour and red-complex pathogens.52-54

Adverse Drug Reactions
Although CPC is considered safe, there is still the possibility for users to experience mild ADRs within therapeutic range, i.e. side-effects, none of which are considered severe from a medical standpoint.29,45,51 The most commonly reported are staining of the teeth and tongue, with other less frequently reported objective side-effects including ulcerations and burning sensations.51 It appears staining of CPC is much less severe than that of CHX mouthrinses, although they share a similar dietary aetiology.29,51 This may be explained with the lower substantivity of CPC and its mono-cationic nature, which may also explain its lower anti-plaque efficacy compared with CHX.44,51 Irrespective of its higher initial retention, CPC is cleared from the oral cavity more rapidly than CHX.44,51 CPC’s therapeutic effect is present up to 90 minutes in the oral cavity, compared with 7 hours for CHX.51 In one long-term study, the side effects of 0.07% CPC mouthwash used daily over 6 months revealed no serious ADRs, with participants reporting increased tooth staining as the only significant side effect, occurring in 10.4% of participants.48 A similar study also involving daily use of 0.07% CPC over a duration of 6 months, also reported no significant ADRs.43 One out of 33 patients complained about altered taste perception, and two others complained about an itchy feeling when rinsing at the 3-month interval. Only 1 out of the 33 complained about tooth staining at the 6-month interval.45 This supports the idea that CPC could have longer adjunctive use for oral hygiene even with its apparently lower potency compared with that of CHX due to its rapid clearance and less serious ADRs at therapeutic range.51 Table 2 summarizes the adverse drug effects of CHX & CPC mouthwashes. Table 3 provides therapeutic over the counter mouthwashes and their uses in dentistry.

Table 2

CHX mouthwash and it’s use in dentistry.

CHX mouthwash and it’s use in dentistry.

Table 3

Therapeutic over the counter mouthwashes and their uses in dentistry.

Therapeutic over the counter mouthwashes and their uses in dentistry.

FLUORIDATED MOUTHWASHES
These mouthwashes comprise of fluoride in different forms, sodium fluoride (NaF) is most commonly used (Table 3).44,53 Dental caries is a serious problem worldwide, affecting 97% of the population during their lifetimes.54 Caries development is a multifactorial process which can cause destruction of the hard dental structures as a result of the weak acids produced during the process of bacterial carbohydrate fermentation.54 It is important to realize that the prevention of caries is more important than its treatment.55 Fluoridated mouthrinses make enamel resistant to acid attacks and promote remineralization of enamel with fluorapatite and fluor-hydroxyapatite acting as caries preventive agents.46,57-59 Fluoride mouthrinses are most effective for reduction of caries in permanent dentition in patients aged 6-18 years (children and adolescents) as well as in adult root caries.55,56 Prescription-strength 0.09% fluoride mouthrinse, is recommended at least once a week for high caries risk patients in those categories.55,56 However, fluoride mouthrinses are contraindicated for children younger than 6 years due to risk of ingestion.44m53 The weekly use of 0.2% NaF mouthwash, when incorporated as an adjunct to oral hygiene protocol, significantly reduced DMFT scores in elementary students where fluoridated water was below ADA recommendations of 0.7ppm by as much as 51.5% when compared to the control group which did not use the mouthrinse.57,57

Fluoride rinses are so effective at enamel remineralization, that the most common oral hygiene protocol recommended by orthodontists is a daily 0.05% sodium fluoride rinse in conjunction with fluoridated toothpaste to prevent development of incipient lesions.58,59 Demineralization around orthodontic brackets is a main disadvantage of orthodontic treatment, with white spot lesions (WSL) developing in roughly 50% subjects without a preventive method.62 Using a 250ppm fluoride rinse, equivalent to a 0.05% NaF, daily in addition to oral hygiene protocol significantly reduced the amount of WSL developing.62 Participants that did not incorporate fluoride mouthrinse had 2.6 times more WSL during the 2-year study period, and 47% of those participants developed at least one WSL, compared to 31% of participants who utilized the Fluoridated mouthwash.62 It appears that both 0.05% and 0.2% NaF mouthrinses perform equally well in reducing lesion demineralization when used alone.60 Short-term use of NaF mouthwash has even demonstrated a reduction in plaque S. mutans levels in vivo, and significantly prevented erosion in situ and in vitro when used as an adjunct with fluoridated toothpaste as well as alone.61

OXIDIZING MOUTHWASHES

Wound Healing effects
Oxygenating mouthwashes include active ingredients like hydrogen peroxide (H2O2), sodium peroxyborate and peroxycarbonate.44,62 They function by delivering nascent oxygen, which breaks apart debris and cause death of anaerobic microorganisms.44 Hydrogen peroxide at 1.5% is the most studied concentration in the form of a mouthrinse, when 1%-1.5% H2O2 was used as a daily mouthrinse it showed no adverse effects to soft tissue over a duration of 2 years.29,63 Low concentrations of hydrogen peroxide accelerate wound closure, and indirectly induce matrix metallopeptidase 1.64 Matrix metallopeptidase 1 enhances H2O2 pro-wound effects by degrading extracellular matrix proteins and allowing wound cells to migrate to the area of injury.64 Considering this and its antimicrobial effects may explain why in dentistry wound healing following gingival surgery is often enhanced with the use of topical H2O2.65 Topical hydrogen peroxide has also been recommended in the treatment of chronic recurrent oral aphthous ulcers significantly reducing pain within a day of application.66

All oxygenating mouthwashes have been recommended short-term to reduce the inflammatory symptoms of pericoronitis (Table 3), and as disinfectants in the oral cavity.62,67 In terms of gingival inflammation, H2O2 also demonstrated anti-inflammatory effects.63 1.5% H2O2 mouthwash significantly improved gingival index scores that were larger than 1 and significantly lowered the percentage of gingival bleeding sites; moreover, fluoridated H2O2 (1.5%) also significantly reduced gingivitis when used long-term as an adjunct to daily hygiene.62,63

Teeth whitening effects of H2O2
Whether over the counter or prescription, most teeth whitening agents contain some sort of hydrogen peroxide due to its ability to remove stains.68 The mechanism of action causes the H2O2 to break down into water and oxygen, this allows the oxygen to infiltrate into the tooth and release the pigmented molecule that was causing the stain, resulting in a whitened tooth.68 There has been much controversy with the use of hydrogen peroxide in dentistry, but it should be considered a safe product as long as it is used in a controlled matter, especially when used at lower concentrations.68,69 (Table 3). The anti-staining properties of H2O2 are so effective on extrinsic stains of teeth, that when 1.5% H2O2 mouthwash was used adjunctively following the application of 0.2% CHX mouthwash, there was a significant decrease in the staining of teeth without decreasing the efficacy of CHX, compared to the group that did not use H2O2.68,70

PRE-PROCEDURAL MOUTHRINSES AGAINST COVID-19
Coronaviruses in the family of Coronaviridae, are circulating among the human population at a global magnitude, often targeting the upper-respiratory system resulting in mild to moderate symptoms similar to that of the common cold.71,72 However, some coronaviruses are able to cause more aggressive illness, which may result in death.72,73 Most prevalent is the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).72 COVID-19 was first contracted in Wuhan, China, in December 2019 and on March 11, 2020 the World Health Organization (WHO) declared it a global pandemic.71-73 When COVID-19 is compared to other coronaviruses, it appears to be less lethal but more contagious.72 The high transmissibility of COVID-19 combined with the fact that asymptomatic and pre-symptomatic individuals are capable of unknowingly spreading the virus has resulted in a unique challenge for dentists who are required to work in the oral cavity daily.29,72 With high SARS-CoV-2 viral loads detected in saliva, antiseptic mouthwashes have been suggested as pre-procedural rinses before any oral procedures.29 SARS-CoV-2 is an enveloped virus, and as a result several active ingredients in these mouthwashes have been recommended based on their mechanism of action and antimicrobial effects.29,74

Chlorohexidine (CHX)
0.12% CHX mouthwash demonstrated it can reduce the viral concentration of enveloped, but not non-enveloped viruses, including that of the coronavirus (SARS-CoV-2).29,74,75 The protocol consisted of a pre-procedural rinse of 15mL for 30s by patients, which decreased the viral load in the saliva transiently for 2 hours after using the 0.12% CHX mouthwash, but it returned to baseline 2-4 hours post-mouthwash.75

Cetylpyridinium Chloride (CPC)
The antimicrobial effect of CPC is so effective, that it acts as an antiviral against susceptible and resistant strains of influenza virus by targeting and disrupting the viral envelope.29,76 CPC exhibits direct virucidal activity against Influenza A and B, through direct attack on the viral envelope, including oseltamivir-resistant virus, significantly reducing the duration and severity of cough and sore throat in infected patients.29,51,52,74 Due to its lysosomotropic mechanism of action, it has also been hypothesized to be effective against SARS-CoV-2.29,74

Hydrogen Peroxide (H2O2)
It appears that coronavirus 229E and other enveloped viruses are inactivated at concentrations of H2O2 around 0.5%.74 However, an in vitro study reported that 3% H2O2 inactivated adenovirus types 3 and 6, adeno-associated virus type 4, rhinoviruses 1A, 1B, and type 7, myxoviruses, influenza A and B, respiratory syncytial virus, strain long, and coronavirus strain 229E within 1-30 minutes.29

Povidone-Iodine (PVP-I)
PVP-I has a strong antimicrobial and higher virucidal activity compared to other antiseptic agents, including CHX.29,74 PVP-I’s mechanism of action occurs following the dissociation of the free iodine from polyvinylpyrrolidone, resulting in rapid penetration of iodine into the microbes and disruption of proteins through oxidation of nucleic acid structures causing microbial death.29 It is routinely used as a mouthrinse in Japan at 0.23% because it inactivates SARS-CoV, MERS-CoV, influenza virus A (H1N1), and rotavirus in vitro, with an equivalence of 70% ethanol in inactivating SARS-CoV at 0.23%.29,74

However, PVP-I relies heavily on the free iodine component, which is bound to a large polyvinylpyrrolidone molecule, acting as a carrier to deliver molecular iodine (I2) to target cells.77 In fact, it is the I2 content of PVP-I that is associated with its viricidal activity.77 This becomes even more important when one considers that Betadine (10% PVP-I) can only deliver a max of 3ppm of I2 out of 31,600ppm of total iodine.77,78 As a result, only the molecular iodine is a biocidal species of iodine, whereas the large amount of ‘non-active’ iodine augments the undesirable properties of PVP-I such as staining and toxicity.77-79

Recently, it appears a new generation of iodine-based antiseptics has been developed by ioTech International (Boca Raton, FL) to overcome the undesired compositional side effects of PVP-I.77,78 They have developed and patented a stable aqueous formulation of I2 that contains over 100 times the available I2 compared to PVP-I, while limiting the ‘non-active’ iodine to a few hundred ppm.77,78 This new product is available for prophylactic use as mouthwash, and is significantly more efficacious compared to traditional PVP-I.77,78 Moreover, it has significantly less ADRs compared to traditional PVP-I, including less potential for irritancy, mucosal staining, and less overall toxicity, while also having an increased shelf-life.77,78 In comparison to 1.5% hydrogen peroxide, 0.2% povidone, 0.12% chlorhexidine, a 100-ppm molecular iodine rinse demonstrated higher virucidal activity against coronaviruses and took as little as 30 seconds to inactivate alpha coronaviruses (229E) completely.77,80 Another study demonstrated that 25ppm molecular iodine mouthrinse completely inactivated Rhinovirus in 30 seconds, whereas a CHX mouthwash, Listerine, Scope, and Colgate total were completely ineffective.77,78 It appears that as a pre-procedural mouthrinse molecular iodine is the best choice to inactivate viruses and bacteria that may be exposed to dental workers as a result of aerosol generating procedures. Currently, ioTech offers a professional dental mouthrinse listed as “IORINSE RTU” and it is available for adults and children of 12 years of age and older.81 The manufactures recommend a 30mL rinse for 30 seconds twice a day, or as directed by a dental professional.81 Ultimately, more controlled trials should be conducted using molecular iodine in order to confirm what appears to be a clear superiority over conventional PVP-I mouthwashes.77

CDA approved over-the-counter mouthwashes containing essential oils
Even essential oils, eucalyptol 0.092%, menthol 0.042%, methyl salicylate 0.060%, and thymol 0.064% w/v may exhibit virucidal actions.74 With eucalyptol oil and thymol having significant antiviral properties towards herpes simplex virus at these concentrations it is believed they disrupt the viral envelope.74 Most CDA approved Listerine mouthwashes (excluding Listerine “Healthy white” and “smart rinse” variations) contain these active ingredients in similar concentrations, implicating a potential role against SARS-CoV-2, although studies have not been conducted.74,82

Suggested recommendations
Gargle and swish for 30 seconds in the oral cavity and an additional 30 seconds in the back of the throat with 15 mL of: 1.5%1 or 3% H2O2; 0.12% CHX; 0.05% CPC; or 9mL of 0.2%,0.4%, or 0.5% PVP-I.29

FINAL CLINICAL CONSIDERATIONS

Alcohol-Free Mouthwash
It is very important that when determining a mouthwash product, it be free of alcohol content due to the negative effects and risks posed for the development of cancer associated with the regular use of alcohol containing oral products.83,84 The twice a day usage of alcohol containing mouthwashes has demonstrated a systemic aldehyde exposure of 0.26µg/kg bodyweight/day on average, conforming to a lifetime cancer risk of 3E-6.84 Whereas, local acetaldehyde contents in the saliva have reached concentrations associated with DNA adduct formation and sister chromatid exchange in vitro, further emphasizing the importance of selecting an alcohol-free mouthwash.83,84 Other studies have determined that alcohol-containing mouthwashes are genotoxic to normal and dysplastic oral keratinocytes and induce extensive changes in gene expression, in vitro.85 This raises the possibility of an additional mechanism for the synergistic effects of alcohol and tobacco on oral mucosal changes in oral potentially malignant disorders (OPMD), and may explain the added risk of malignant transformation for patients who smoke and use alcohol-containing mouthwashes on a regular basis.85 Mouthwash users who smoke have an Odd Ratio (OR) of 9.15 for developing oral squamous cell carcinoma (OSCC) compared to an OR of 4.98 in former smokers and an OR of 5.12 in current alcohol drinkers.85 Rinsing with higher alcohol-content mouthwash has also been associated with earlier pain onset with a longer duration and intensity, especially if the patient is a non-drinker.86 Consistent exposure to alcohol may sensitize peripheral nerve-endings, leading to diminished response because ethanol destroys nervous tissue by extracting cholesterol and other lipids, further emphasizing the use of alcohol-free mouthwash whenever possible and especially in long-term use.83,86

Sodium Lauryl Sulphate
Sodium Lauryl Sulphate (SLS), an anionic surfactant, is the most commonly used foaming agent in dentifrices.87 SLS aids in the solubilization of flavouring agents and active dentifrice ingredients by promoting wetting of the tooth surfaces, which results in an improved cleaning action.87,88 However, recently SLS has been linked to adverse effects on the oral mucosa; most importantly, the local irritation of mucosa leading to desquamation.89 Patients who cannot rinse or spit out, such as bedridden patients, as well as patients who have undergone radiotherapy, chemotherapy, or those who experience sensitivity in the oral mucosa, should be advised to avoid products contains SLS as well as menthol, cinnamon, and peppermint oil.88,89 Instead, SLS free dentifrices and mouthwashes should be recommended. SLS has also been linked to contact allergic reactions, if you experience irritation or an allergic like reaction in the oral mucosa immediately discontinue the use of the product and switch to an SLS-free alternative.88,90

Natural Mouthwashes
Natural mouthwashes provide some benefits as well; however, no natural CDA approved mouthwashes, nor Tom’s of Maine, currently contain active antibacterial ingredients.91-97 Although they do contain xylitol, which is an established prophylaxis in the development of caries, they do not contain any listed active ingredients that provide antibacterial benefits to the soft tissue and gingiva.98 Box 1 summarizes some clinical considerations before using a mouthwash.

Box 1

CONCLUSION
Although 90% of used mouthwash products in the US contain at least one active ingredient, 60% of the U.S population used mouthwash weekly, and 33% daily.6 This garners a need for patient education and a more organized approach to the application of these products by both the patients and dental providers. Consumers should stop viewing mouthwashes as cosmetic products, but rather the drugs which they are. Before using any mouthwash, one should always read the instructions and ingredient list, and if in doubt always ask a dental professional, especially in order to best manage specific oral health conditions and concerns.6,12

Oral Health welcomes this original article.

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About the Author

Mr. Frank Poppolo Deus holds a Bachelor of Science in Biochemistry and is a third-year dental student at the faculty of Dentistry, University of Toronto.

 

 

 

Dr. Aviv Ouanounou is an assistant professor of Pharmacology & Preventive Dentistry at the Faculty of Dentistry, University of Toronto, and a clinical instructor and Treatment Plan Coordinator in the clinics. He is the recipient of the 2014-2015 Dr. Bruce Hord Master Teacher Award for excellence in teaching and the 2018-2019 National W.W. Wood Teaching Award for Excellence in Dental Education. He is a Fellow of the International College of Dentists, American College of Dentists and Pierre Fouchard Academy. Dr. Ouanounou maintains a private practice in Toronto and is the corresponding author for this article. Reach him at aviv.ouanounou@dentistry.utoronto.ca.


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