Next Article in Journal
Mechanical Differences between Men and Women during Overground Load Carriage at Self-Selected Walking Speeds
Next Article in Special Issue
Prevalence and Periodontal Conditions of Developmental Grooves in an Italian School of Dentistry and Dental Hygiene: A Cross-Sectional Study
Previous Article in Journal
“The Ugliness of It Seeps into Me”: Experiences of Vicarious Trauma among Female Psychologists Treating Survivors of Sexual Assault
Previous Article in Special Issue
Association between Healthy Lifestyle (Diet Quality, Physical Activity, Normal Body Weight) and Periodontal Diseases in Korean Adults
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJERPH
Volume 19
Issue 7
10.3390/ijerph19073926
ijerph-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

A Fresh Look at Mouthwashes—What Is Inside and What Is It For?

by
Dominik Radzki
1,2,*,
Marta Wilhelm-Węglarz
3,
Katarzyna Pruska
2,
Aida Kusiak
1 and
Iwona Ordyniec-Kwaśnica
3
1
Department of Periodontology and Oral Mucosa Diseases, Faculty of Medicine, Medical University of Gdańsk, 80-208 Gdańsk, Poland
2
Division of Molecular Bacteriology, Institute of Medical Biotechnology and Experimental Oncology, Intercollegiate Faculty of Biotechnology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
3
Department of Dental Prosthetics, Faculty of Medicine, Medical University of Gdańsk, 80-208 Gdańsk, Poland
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2022, 19(7), 3926; https://doi.org/10.3390/ijerph19073926
Submission received: 3 March 2022 / Revised: 21 March 2022 / Accepted: 22 March 2022 / Published: 25 March 2022
(This article belongs to the Special Issue Advances in Oral Health and Health Promotion Research)
Review Reports Versions Notes

Abstract

:
Mouthwashes are a very popular additional oral hygiene element and there are plenty of individual products, whose compositions are in a state of flux. The aim of our study was to investigate the compositions of mouthwashes and their functions, as well as to discuss their effectiveness in preventing and curing oral diseases and side effects. We searched for mouthwashes available on the market in Poland. We identified 241 individual mouthwash products. The extraction of compositions was performed and functions of the ingredients were assessed. Then, analysis was performed. The evaluation revealed that there are plenty of ingredients, but a typical mouthwash is a water–glycerine mixture and consists of additional sweetener, surfactant, preservative, and some colourant and flavouring agent, as well as usually having two oral health substances, anticaries sodium fluoride and antimicrobial essential oils. The effectiveness or side effects of several substances of mouthwashes were thoroughly discussed. We recommend not multiplying individual mouthwash products and their ingredients beyond medical or pharmaceutical necessity, especially without scientific proof.

1. Introduction

Since the disseminated change from hunter-gatherer to agrarian societies and agriculture development, dental caries have been observed to be more frequent. These are associated with the alteration in human diet and food preparation techniques: meals became more farinaceous, rich in simple sugars, soft and adherable. The more refined plant foods do not stimulate saliva flow so efficiently and do not ensure self-cleaning as their unrefined counterparts, which worsen buffering capacity and the remineralisation of enamel and support dental plaque accumulation [1,2,3,4]. With the development of modern healthcare and access to various foods, periodontal diseases related to vitamin C deficiency are almost forgotten, but the ineffective removal of dental plaque in association with chronic stress, inveterate smoking, diabetes, dyslipidemia, etc., may result in periodontitis, which affects a large part of the population worldwide [2,5,6,7,8]. Rising life expectancy generates other problems such as tissue degeneration as well as neoplasms and their treatment, which may result in hyposalivation, immunodeficiency or malnutrition with subsequent oral diseases [9,10,11,12]. Proper oral hygiene is the basis of keeping the oral cavity healthy. Brushing and flossing, as well as a suitable diet and hydration, are all necessary. Nevertheless, there are additional, adjuvant oral hygiene products to potentiate the effectiveness of oral hygiene, such as irrigators, tongue scrapers and mouthwashes.
Mouthwashes are a very popular additional oral hygiene element and there are plenty of individual products. There are two main types of mouthwash applications: preventive and therapeutic. A single product may possess a double function: antiplaque substances prevent as well as support the treatment of periodontal diseases, among others. It is not strictly associated with the concentration of active substances seen in mouthwashes, but with the duration of usage and of course with current health status. In prevention, long-term use is required, whereas in therapy, short-time use is usually sufficient. Another function is to provide relief in some conditions, in preoperative or postoperative management as well as in aesthetic dentistry (anti-stain and whitening effects).
Mouthwashes have been under study for a long time and their compositions are in a state of flux. A substance once considered to be promising may today be forgotten, while others are still the standard of prevention and therapy [13]. The aim of our study was to investigate the compositions of mouthwashes and their functions.

2. Materials and Methods

2.1. Definition of Mouthwashes

Mouthwashes (also called mouth rinses/mouthrinses, oral rinses or oral washes) are liquid, aqueous compositions mainly intended to prevent, relieve and cure oral conditions and maintain oral health (such as: dental caries, dental erosion, halitosis, gingivitis, periodontitis, mucositis, to reduce the oral microbiota, etc.). Our study is restricted to over-the-counter compositions. Saliva substitutes are not taken into account, as they are a group of special-purpose drugs, other than mouthwashes, used when own production of saliva is inadequate. However, indications of those two groups may overlap.
The mouthwashes were selected according to the following inclusion criteria:
  • Intended to prevent and cure oral conditions and maintain oral health;
  • Over-the-counter;
  • In one of the following forms:
    • An aqueous solution;
    • A concentrate to be diluted with water;
    • A tablet or powder to be dissolved in water.
The exclusion criteria were as follows:
  • Full composition not available;
  • Saliva substitutes;
  • Not recognised as cosmetic;
  • Containing antibiotics, antimycotics, steroids, parasympathomimetic saliva stimulants, topical local anaesthetics and other prescription drugs;
  • Orally taken, but not intended for oral health (e.g.,nitroglycerine)
  • Toothpastes, gels, powders, foams and similar;
  • With majority of coconut oil or other oils;
  • Homeopathics;
  • Tablets for chewing;
  • Intended to cure tonsillitis, pharyngitis and other conditions of the respiratory tract.

2.2. Search Strategy and Data Collection

We searched for mouthwashes available on the (online and traditional) market in Poland, including online stores, which may correspond to markets in other countries (trade names or ingredients may differ). The authors used browsing methods available to an average consumer. Search, identification and extraction of compositions were performed by two researchers (D.R. and M.W.W.) independently. Only readily available (package/website) data on the product’s composition were used in the study; we did not contact the producer to request missing data (e.g., concentration of fluorine). Subsequently, the lists of mouthwashes and their compositions were compared. In case of disagreement, the composition was checked and corrected. Then, the two lists were combined. The third researcher (K.P.) checked the fused list. As compositions may be changed by producers without notice, there may exist differences between declared and actual composition of a product. In our study, we worked with the assumption that the data provided by the producers is accurate. We only analysed products available on the market as of the time of conducting this study (November 2020–February 2022), and some of them may have since been discontinued.

2.3. Analysis

After identification and extraction of compositions, functions of all mouthwash ingredients were established and listed. Then, several groups of ingredients were distinguished according to their main functions. Among the groups, an analysis of frequency of substances was performed.

3. Results

3.1. Components and Their Functions

We focused on the chemistry and medical significance of the ingredients used in mouthwashes, with the exception of the majority of plant extracts (due to their number and very limited clinical research on herbal-based dentifrices [14]). Ingredients and their properties (in mouthwashes) were tabulated and presented in Table 1 (Ingredients of mouthwashes and their main functions therein). There is no certainty that an indicated property is observed in the mouthwashes, as for each composition there are many factors at play that may alter the characteristics of the substance. It appears that some of the components may present no effect (neither medical nor pharmaceutical) and are used only for marketing purposes. Their properties were mostly described in isolation; potential interactions were not explored. Potential of hydrogen, viscosity, electrical conductivity, the volume of mouthwash, concentration of each ingredient, mutually exclusive properties or synergies of ingredients, time of rinsing, chemical reactions between ingredients (e.g., between anions and cations or chelation), time of storage, etc., may result in some changes in properties.

3.2. Analysis of Mouthwash Components

We identified 241 individual mouthwash products according to the inclusion and exclusion criteria, of which 234 were aqueous solutions and 7 in the form of a tablet. The full composition of each mouthwash is presented in the supplementary material (Table S1). Among them, several groups were distinguished according to their main postulated functions (functions of substances from each group may overlap to some extent). We subdivided them as follows: oral health substances, solvents, surfactants and thickeners, sweeteners, plant (extracts, waters and oils), preservatives, colourants, flavouring or cooling agents, and others.
Among oral health substances, several groups were recognised. Fluorine compounds are present in 63.5% of all mouthwashes (individual products), and the most common compound is sodium fluoride (86.9% of mouthwashes containing fluorine compounds) with a concentration around 187–250 ppm of fluoride ions. Arginine as well as sodium bicarbonate are present in 1.2%, and aluminium lactate in 1.7%. Potassium compounds are present in 17.8% of them, and tetrapotassium pyrophosphate is the most common potassium compound, followed by potassium chloride and potassium nitrate. Zinc compounds are observed in 19.5% of all mouthwashes; zinc chloride and zinc citrate are the most common. Phosphorus and calcium compounds are present in 17.8%, among them tetrapotassium pyrophosphate, tetrasodium pyrophosphate and hydroxyapatite are the most common. Stannous compounds (chloride and fluoride) are in 1.7% of mouthwashes. Antimicrobial drugs are very common and present in 52.3% of mouthwashes, therein usually essential oils, cetylpyridinium chloride or chlorhexidine. Essential oils are present in 47.3% of mouthwashes and the most common compound derived from essential oils is menthol, seen in 78.9% of mouthwashes with essential oils. Chlorhexidine is in 20.7% of mouthwashes and the usual compound is chlorhexidine digluconate (98% of mouthwashes with chlorhexidine) at a concentration of 0.2% (26%).
Mouthwashes are composed of many other substances, not directly associated with medical benefits, but necessary in the creation of formulas. Ethanol, glycerine and propylene glycol are the most frequent solvents, except water, present in 10.8, 74.7 and 42.7% of all mouthwashes, respectively. Surfactants are in 92.5% of mouthwashes, and PEG-40 hydrogenated castor oil is the most frequent. Sweeteners (together with glycerine) are present in 96.7%, with saccharin, sorbitol and xylitol being the most common (apart from glycerine). Preservatives are found in 82.2%, with the majority being sodium benzoate. Colourants are added to 66% mouthwashes, while flavouring agents to 99.2%. Entire results and details are presented in Table 2.
A typical mouthwash on the market is a water–glycerine mixture, consisting of an additional sweetener (saccharin), surfactant (PEG-40 hydrogenated castor oil), preservative (sodium benzoate), some colourant and flavouring agent, as well as having two oral health substances, an anticaries compound (sodium fluoride, around 217–250 parts per million) and antimicrobial drug (essential oils).

4. Discussion

Selected ingredients found in mouthwashes and their uses in hygiene of the oral cavity are discussed below.

4.1. Sodium Bicarbonate

Sodium bicarbonate is also known as baking soda, bicarbonate of soda, and by the IUPAC name, sodium hydrogen carbonate. Sodium bicarbonate is a versatile substance; there are many general and medical uses of it. It is used in the treatment of metabolic acidosis and acid reflux, and as a mucolytic agent [84]. Sodium bicarbonate is a nonspecific antidote that is effective in the treatment of a variety of poisonings [85].
It is composed of a sodium cation (Na+) and a bicarbonate anion (HCO3−), which are normal constituents in the human body. The bicarbonate anion is the result of interconversion of water and carbon dioxide. Carbonic anhydrases (CAs) are a family of several zinc-dependent enzymes which increase the efficiency of bicarbonate anion formation. CAs maintain the excretion of carbon dioxide from the body as well as acid–base homeostasis [86]. Only one is isoenzyme of CAs, CA VI (called gustin), produces a secreted form of the bicarbonate anion. CA VI is produced by serous acinar cells of parotid and submandibular glands [87]. It is also detected in tears and milk [88]. Its primary function is to regulate pH in the oral cavity. Bicarbonate is the principal buffer of extracellular fluid (plasma and interstitial fluid) as well as saliva. When fermentation of carbohydrates in the oral cavity occurs, pH lowers (increasing concentration of H+), but is neutralised by the bicarbonate anion (by conversion to water and carbon dioxide) [84]. The supplementing of bicarbonate ions, introduced by rinsing with sodium bicarbonate solution, may be a sufficient refill of buffer capacity of saliva, when used regularly.
CA VI expression (both its concentration and activity) and bicarbonate anion concentration are supposed to be modified by various factors: genetic (single nucleotide polymorphism in the gene coding CA VI), chemical and a changed flow rate of saliva, etc. [89,90]. A mean CA VI concentration is significantly lower in the active caries group than in the caries-free group [89]. When the activity of CA VI is measured in the caries group, it is increased, but there is no increased ability of CA VI to buffer and buffering capacity of saliva is lower in the caries group [91]. Moreover, the ability of CA VI to buffer is more related to its concentration than its activity, but elevated CA VI concentrations in saliva do not necessarily indicate that the enzyme is active [92]. CA VI is a potential drug target for cariogenesis. Further studies are required.
A 1.26% (w/v) solution of sodium bicarbonate concentration is isotonic. Slightly hypotonic, 1% solution, can be used as a mild mouthwash to neutralise acids, moisturise, deodorise and decrease the number of bacteria [84]. A hypertonic solution of sodium bicarbonate facilitates osmotic movement of water from bacterial cells, resulting in shrinkage, plasmolysis and cell death [93]. Sodium bicarbonate in solution is able to disrupt biofilms without an antimicrobial effect, hypothetically by disrupting the exopolysaccharide matrix structure of dental plaque [94]. Hypernatremia after regular rinsing is unexpected if the product is not swallowed.
According to our study, some mouthwashes in tablets contain sodium bicarbonate. Nevertheless, therein sodium bicarbonate is just a component of effervescent salts (with citric acid or/and tartaric acid) [33]. After dissolution in water, neutralisation occurs—sodium bicarbonate through interaction with organic acids generates carbon dioxide and bicarbonate anions no longer exist. In addition, in our unpublished study, the pH of one of the tested products (Georganics Spearmint) was slightly acidic (pH 6.5; tablets dissolved in tap water pH 7.5). Therefore, we cannot consider those mouthwashes as a source of bicarbonate anions able to neutralise acidic pH of the oral cavity.

4.2. Essential Oils

Essential oils (EOs) are liquid, volatile, fragrant, limpid and coloured, soluble in lipids and organic solvents. EOs are derived from many plants and play an important role in protecting the plant, repelling predators and pests, as well as attracting pollinators. EOs consist of various compounds, predominantly monoterpenes (or monoterpenoids), sesquiterpenes, aromatic compounds (often phenylpropane derivatives, e.g., phenylpropanoids) and their derivatives: acids, alcohols, ketones and aldehydes, aliphatic hydrocarbons, acyclic esters or lactones, nitrogen- and sulphur-containing compounds, coumarins [95,96].
Essential oils contain a wide variety of secondary metabolites that exhibit antibacterial (bactericidal or bacteriostatic), antiviral and antifungal properties [95]. EOs or their components are regularly used in many dentifrices and mouthwashes due to their germicidal effects, resulting in a noticeable reduction of dental plaque, with anticaries [97] and antigingivitis potential [98]. They may also serve as preservatives. Antioxidant, anti-inflammatory, local anaesthetic and analgesic effects are other relevant properties [99,100]. Nevertheless, they play an important role in oral hygiene as fragrances.
EOs, as was said above, are composed of many substances, but only few of those show significant antimicrobial (antibacterial, antifungal and antiviral) [101] properties. The antimicrobial effects of EO components are not attributed to a unique mechanism, but rely on toxic effects on membrane structure and the entire cell. Due to their lipophilic character, they pass from the aqueous phase into membrane structures, which results in the disturbance of the cell membrane. Alteration of the membrane fatty acids, increased membrane fluidity and permeability, disturbance of membrane-embedded proteins, inhibition of respiration, alteration of ion transport processes and alteration of proton motive force are all observed. It is suggested that the cytoplasm is a secondary target. Compounds of EOs after penetration into cell plasma may interact with intracellular structures, which leads to cytoplasm coagulation, denaturation of several proteins and the loss of metabolites and ions, resulting in alterations in functionality. Most EOs have a more powerful effect on Gram-positive than Gram-negative bacteria, presumably due to differences in the cell membrane composition (presence of outer membrane in Gram-negative) and permeability to lipophilic substances [95,102,103].
Menthol, thymol, eucalyptol, eugenol and methyl salicylate (or EOs containing them) are regularly used in dentifrices and mouthwashes. There are several (clinical and microbiological) studies that demonstrated antibacterial effects of the mouthwashes containing EOs (ethanol and propane-1,2-diol based solutions). In spite of this, there is no evidence methyl salicylate in isolation possesses any antibacterial effect, but it is used as a fragrance, with anti-inflammatory effect [104]. Bisabolol possesses anti-inflammatory [105] and antimicrobial [106] activity. Menthol presents moderate antimicrobial (antibacterial) effects (Mentha piperita oil also shows antiviral and antifungal properties) [107]. Eucalyptol (1,8-cineole) [108,109], eugenol [110,111], and thymol [112] are effective antibacterial substances and present antibiofilm (inhibitory or disruptive) activity. Those substances also act as preservatives, to prevent foodborne pathogens in storage [113]. Antimicrobial components of EOs are usually used in complex compositions, with an expected wider antibacterial spectrum.
Moreover, there are plenty of other substances with antimicrobial activity derived from essential oils. Many of them are components of mouthwashes, both single compounds and essential oils. They are mainly used as a scent and there is no sufficient evidence that they act as antibacterial drugs intended for combating the oral microbiota (or even as preservatives), but there are such possibilities. Benzyl alcohol is mainly used as a fragrance and preservative [114,115] and only its derivative (2,4-dichlorobenzyl alcohol) is used as a mild oral and pharyngeal antiseptic. Limonene [99,116,117], linalool [99,117], citral [118] and cinnamal (cinnamaldehyde) [119] exhibit a non-negligible activity against oral pathogenic microorganisms. Geraniol [120] and anethole [121] also show some antimicrobial properties.
In our study, according to the established customs in (dental) studies and uses in cosmetics, we tabulated (in Table S1 and Table 2) EOs or their components in the following groups: 1. oral health substances (menthol, thymol, eucalyptol, methyl salicylate, additionally eugenol and bisabolol or EOs that are expected to contain a significant amount of them); 2. plant extracts, waters and oils (with potential various functions in mouthwashes; they are not under our study); 3. Preservatives (benzyl alcohol); or 4. aroma or cooling agents (every EO or its components tabulated in groups 1–3 may also act as a fragrance as well as every EO tabulated as an aroma may possess relevant antimicrobial properties).

4.3. Fluorine Compounds

Fluorine, specifically some compounds of fluorine, have become a principal agent in preventing dental caries. In mouthwashes, the most common compound of fluorine is sodium fluoride, others are calcium fluoride (uncertain solubility in mouthwashes), potassium fluoride, stannous fluoride (unstable in mouthwashes), monofluorophosphate, aluminium fluoride, fluorohydroxyapatite (as suspended nanoparticles), olaflur and nicomethanolhydrofluoride. The mechanism of action depends on their solubility and ability to release free fluoride anions. Cations may be responsible only for solubility (sodium fluoride) or confer additional properties (olaflur, stannous fluoride, aluminium fluoride). Sodium fluoride is a thoroughly researched compound: comprehensive and critical descriptions are commonly available, and its usage and benefits are well established, therefore we did not review them. Other fluorine compounds are relatively uncommon in mouthwashes. Nevertheless, we would like to describe one—stannous fluoride, a compound of fluorine that is potentially very useful in mouthwashes, but also very unstable.
Stannous fluoride, IUPAC tin (II) fluoride, shows a similar or slightly higher anticaries activity compared with non-stannous fluoride. Stannous fluoride mechanism of action in the prevention of caries is similar to sodium fluoride. Fluoride ions are deposed on the tooth surface as a layer of calcium fluoride. When the pH of saliva decreases, fluoride ions are released and can be incorporated into hydroxyapatite by substituting hydroxyl groups in hydroxyapatite, allowing the formation of fluorohydroxyapatite or fluorapatite, much more resistant to the acidic pH [122,123,124].
Stannous fluoride can be useful not only in the prevention of dental caries. Antibacterial effects of stannous fluoride were observed as well as its ability to prevent dental plaque formation resulting in antigingivitis property [125,126]. Stannous fluoride reduces calculus formation (by inhibition of calcium phosphate compound creation), halitosis (by reduction in volatile sulphur compound levels and antimicrobial activity) and dentinal hypersensitivity (by forming precipitates in the dentin tubules) [122,127,128,129,130]. Antimicrobial and anti-halitosis effects of stannous fluoride may be potentiated by content of zinc compounds, which are added to dentifrices as stabilisers protecting stannous from oxidation [129]. Stannous fluoride (as well as stannous chloride) can be useful in the prevention of enamel erosion [38,123]. When the demineralisation of enamel and dentin by extrinsic acids takes place, the organic matrix containing collagen is exposed. The exposed collagen can be degraded by endogenous (from dentin or saliva) collagenases, including matrix metalloproteinases (MMPs), which blocks its remineralisation. Stannous ions cause a direct inhibition of the MMPs, and the presence of both calcium and phosphate, with or without fluoride ions, promotes the remineralisation [67].
Those properties cannot be observed in commercial mouthwashes. The aqueous solution of stannous fluoride is unstable. Its ions are readily removed from solution by oxidation to stannic ions, by the formation of complex ions and by hydrolysis, thus becoming ineffective in desired therapeutic benefits [131]. (Stannous can be hydrolysed into SnOH+, Sn(OH)20 and Sn(OH)3−at low concentration, Sn2(OH)22+ and Sn(OH)42+ are predominant at higher concentration [132]).The instability of stannous fluoride in water depends on time; therefore, only a freshly made solution should be used [131,133]. When trying to obtain a stable solution of stannous fluoride, the majority or, ideally, all of the water should be replaced by another solvent. Recently, a water-free concentrated solution of stannous fluoride has been released; it has to be mixed with water immediately before use and should not be stored in dissolved form, according to the manual. Stannous fluoride (and stannous chloride) may be solubilised in such low levels of water compositions containing low-polar solvents (such as glycerine and propylene glycol), forming non-ionic molecular structures. Such compositions remain stable during storage, with fluoride and stannous ions being released from the non-ionic structure when in contact with water or saliva [134,135]. This may not be the case for mouthwashes in the form of aqueous solutions. It is, however, possible for this compound to be present in a viable product—in the form of tablets (or a water-free concentrate) intended for preparing a fresh aqueous solution before every use. There are also formulas of water-free glycerine-based gels [136].

4.4. Glycerine

Glycerol (commonly called glycerine or glycerin, IUPAC propane-1,2,3-triol) is one of the most prevalent ingredients of the mouthwashes, but to our knowledge there are not many scientific papers focusing on its biological effects. Glycerol acts as a solvent and increases the solubility of some components in water, therefore it can be a substitute (to some extent) of ethyl alcohol and can also be used in formulation with ethyl alcohol and water together [137,138]. It is commonly used as a lubricant and emollient, as it provides smoothness, but due to its hygroscopic properties which may cause desiccation [139].
Due to its sweet taste, it may serve as a sweetener and improve the taste of mouthwash by masking the unpleasant taste of some ingredients. Its taste may promote an increased flow of saliva, as other sweeteners do [140].
Dental erosion is one of the most reported side effects of mouthwashes. The erosive potential of some mouthwash ingredients not only depends on their pH, but also on their viscosity. Glycerine elevates the viscosity of solutions, resulting in the ability of the liquid to adhere to the tooth surface and potentiate erosive properties [141]. Other factors, such as salivary flow and buffering capacity, might influence the overall effect of mouthwashes on the enamel [142]. Glycerol used in the formulation of isopropanol-based surgical hand rubs decreases the bactericidal efficacy [143]—the impact of glycerol on antibacterial properties of mouthwashes should be investigated. An in vitro study revealed that glycerol affects the mucosa homeostasis (increasing epithelial thickness, proliferation and apoptosis) if glycerol concentration is above 42.5% and does not affect mucosal integrity. Affected homeostasis and increased proliferation may result in DNA damage accumulation and pose potential risks in long-term exposure [139]. Glycerine is also an ingredient in the liquid used in electronic cigarettes, with no toxicologically relevant effects [144].

4.5. Ethyl Alcohol

Ethyl alcohol (EtOH), IUPAC ethanol, commonly and inappropriately just alcohol, is used as a polar solvent in mouthwashes, as well as a solubiliser, stabiliser, flavouring agent and preservative. It also displays an antiseptic effect. EtOH enhances the effect of the essential oils and acts as an antiplaque adjuvant [145]. Usage of ethanol in mouthwashes is very controversial and currently there are not many individual mouthwash products containing this solvent, but they are very popular and time-honoured. Ethanol has been replaced by propylene glycol in most brands, but the ethanol-containing mouthwashes remain in production and used in high volumes.
Ethanol itself is not genotoxic, mutagenic or carcinogenic. Nevertheless, acetaldehyde (ACH), the first metabolite of EtOH, is a carcinogen [146,147] and it has been observed that ACH levels may play an important role in the carcinogenesis of alcohol in the oral cavity [148]. Ingested alcohol is metabolised in the liver via ACH to acetate (by alcohol and aldehyde dehydrogenases), then to carbon dioxide and water; ACH in this process is degraded very efficiently, resulting in no increased ACH concentration in the blood [147]. Aldehyde dehydrogenase is essential to ACH elimination [149]. ACH from ethanol can be produced locally in the gastrointestinal tract by its epithelial cells as well as its flora (bacterial and fungal) [146,148,150,151]. Acetaldehyde can also be produced directly from glucose through the pyruvate-bypass pathway (by pyruvate decarboxylase) [149].
For an individual microbiome and its ability to produce ACH, poor oral hygiene, dysbiotic microflora (independent risk factor for oropharyngeal cancer), smoking and drinking alcohol increase the production of ACH [146,147,148,152]. Severe leukoplakia and insufficient oral hygiene promote a dysbiotic, fungal microflora [146,153]. Mutagenic ACH concentration can be produced by Candida yeasts either from ethanol (via alcohol dehydrogenases) or glucose (via the pyruvate-bypass pathway) [146]. Other potent producers of ACH are Rothia mucilaginosa, Neisseria spp., Streptococcus spp. [152,154]. A role of bacteria in carcinogenesis relies on the expression of alcohol dehydrogenases and the lack of ability to produce functional acetaldehyde dehydrogenases. If the bacteria have the gene encoding acetaldehyde dehydrogenase, they may have no carcinogenic effect or even possess a protective role [152]. Generally, the oral microbiome has a very low or no aldehyde dehydrogenase activity [147,149]. Therefore, mutagenic ACH concentration may be observed locally in saliva; in lower ethanol concentrations (ranging from 0.5‰ to 2.5%), mutagenic ACH concentration is observed as well [147].
While the correlation between the use of EtOH-based mouthwashes (in the absence of other factors) and the occurrence of head and neck carcinomas is unclear due to contradicting results across many studies [148], the use of ethanol and tobacco (both in smoke and smokeless form) together have the synergistic effect of significantly increasing the probability of carcinoma; other risk factors may potentiate the effect [148,155,156]. The time of exposure to carcinogens is vital to induce carcinogenesis. Nevertheless, ethanol-based mouthwashes usually contain additional antiseptics such as chlorhexidine (CHX), which is proposed to reduce prolonged mutagenic concentration of ACH when other carcinogenic risk factors are absent [147,148].

4.6. Propylene Glycol

Propylene glycol (propanediol, IUPAC propane-1,2-diol) is ubiquitous in topical and systemic drugs as well as in many foods, one of the most prevalent ingredients of mouthwashes. Due to a controversy of using ethyl alcohol in mouthwashes, or its side effects such as mucosa irritation, it was replaced mostly by propylene glycol. It is a viscous, faintly sweet, colourless alcohol containing two hydroxyl functional groups. It has been used as an emollient and solvent, more efficient than glycerine: it dissolves such compounds as phenols, vitamins A and D and many local anaesthetics. It also serves as a preservative. It is comparable to ethanol as an antiseptic [157]. Propylene glycol is generally recognised as safe. To our knowledge, there is no study investigating the impact of regular use on the oral tissues and properties of saliva. Propylene glycol is also an ingredient in the liquid used in electronic cigarettes, with no toxicologically relevant effects observed [144].

4.7. PEGylated Oils

PEGylated oils are derivatives of polyethylene glycol (PEG)—products of the etherification and esterification of glycerides and fatty acids with ethylene oxide. PEGylated oils function as a surfactant (emulsifying or solubilizing agents) used in cosmetics. They may also be used as non-ionic surfactants in oral, topical and parenteral drug delivery systems. There are a large number of oils and multiple PEG chain lengths [158].
PEG-40 hydrogenated castor oil (trade name Cremophor RH 40) is often used in mouthwashes. It is a polyethylene glycol derivative of hydrogenated castor oil where an average PEG chain is 40. Castor oil triglycerides are primarily composed of ricinoleic acid residues, approximately 13% are other acids; therefore, pegylated castor oil is a rather complex mixture of structurally related molecules [158]. PEG-40 hydrogenated castor oil is the most used PEGylated oil in mouthwashes as well as in cosmetics. PEG-40 hydrogenated castor oil functions as an emulsion stabiliser and surfactant. It helps solubilise fragrances and fat-soluble vitamins and may enhance hydrophilic penetration [158]. It shows a moderate cytotoxic effect (a negative impact on keratinocyte viability), but no antibacterial properties [159].

4.8. Zinc Compounds

Zinc is an essential trace element and its deficiency results in various pathologies or potentiates them [160,161]. Zinc ions are necessary for the activity of over three hundred enzymes in the human body [162]. Zinc compounds have a variety of positive effects on oral health but are not common in mouthwashes. As shown in our study, the following compounds of zinc are used in mouthwashes: zinc acetate, zinc chloride, zinc citrate, zinc gluconate, zinc hydroxyapatite, zinc lactate, zinc pidolate and zinc sulphate.
Zinc ions present antibacterial properties and are used as an antiplaque agent. The antibacterial property is a result of targeting the cytoplasm and glycolytic enzymes and the inhibition of glycolysis [38]. Zinc ions promote remineralisation and prevent dentin demineralisation, and also reduce enamel solubility via incorporation into hydroxyapatite surfaces [38]. Volatile sulphur compounds (VSC), such as hydrogen sulphide, methyl mercaptan or dimethyl sulphide, are responsible for malodour. Zinc ions, by antibacterial effect on VSC-producing bacteria as well as by direct inhibition on some VSC (by converting hydrogen sulphide and methyl mercaptan into non-volatile zinc sulphides), may help in reducing halitosis [163,164,165]. They also reduce calculus formation, by crystal growth modification or inhibition [166].
Matrix metalloproteinases (MMPs), responsible for the degradation of extracellular matrix proteins (e.g., collagen), play a significant role in periodontitis or dentine erosion [67,167]. MMPs are zinc- and calcium-dependent enzymes [168]. Potentially, oral topical substitution or binding of zinc (and calcium) ions may result in decreased activity of MMPs. Inhibition of MMPs by stannous ions and benefits of stannous fluoride usage were observed [67,127], but a zinc-binding system may pose a risk. As was said above, zinc ions provide many benefits. In addition, zinc ions are required for the activity of an enzyme crucial for oral acid-base homeostasis (carbonic anhydrase VI) [169]. Moreover, systemic zinc deficiency may result in a high caries prevalence [170,171]. Zinc deficiency may also be involved in the pathogenesis of common oral mucosal diseases (such as erosive oral lichen planus, burning mouth syndrome, recurrent aphthous stomatitis and xerostomia), and zinc supplementation may be useful in the prevention and treatment [172].

4.9. Limitations of the Study

There are several limitations of our study. There is no certainty that every single mouthwash product on the market has been found. There is also no certainty that an indicated property of components is observed in some or all mouthwashes, as for each composition there are many factors at play that may alter the characteristics of the substance (such as pH, solvents, etc., as mentioned in Section 3.1). Another limitation may be the composition list provided by the producer on the package (or website); we have not performed chemical analysis and rely solely on the accuracy of the above.

5. Conclusions

Despite there being numerous mouthwashes and countless components, there is not enough information about many of them. We recommend not to multiply individual mouthwash products and their ingredients beyond medical (or pharmaceutical) necessity, especially without scientific proof.
Nowadays, there may be a great chance to provide novelties. Mouthwashes in the form of a tablet to prepare a fresh solution each time would help reduce plastic waste and take advantage of substances unstable in water solution, even when they are stored for months. Several well-known substances (such as sodium bicarbonate, stannous fluoride or filmogenic substances) have the potential for novel applications—those should be explored and the compounds possibly introduced in new mouthwash products. However, it is also vital to consider and study the long-term side effects of those substances.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/ijerph19073926/s1, Table S1: List of mouthwashes and their compositions.

Author Contributions

Conceptualization, D.R. and I.O.-K.; methodology, D.R.; validation, D.R., M.W.-W. and K.P.; formal analysis, D.R. and K.P.; investigation, D.R. and M.W.-W.; resources, D.R. and M.W.-W.; data curation, D.R., K.P. and M.W.-W.; writing—original draft preparation, D.R.; writing—review and editing, K.P. and D.R.; visualization, D.R. and K.P.; supervision, D.R., I.O.-K. and A.K.; project administration, D.R.; funding acquisition, I.O.-K. and A.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are contained within the article and Supplementary Materials.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Tayles, N.; Domett, K.; Halcrow, S. Can Dental Caries Be Interpreted as Evidence of Farming? The Asian Experience. Front. Oral Biol. 2009, 13, 162–166. [Google Scholar] [CrossRef] [PubMed]
  2. Forshaw, R. Dental Indicators of Ancient Dietary Patterns: Dental Analysis in Archaeology. Br. Dent. J. 2014, 216, 529–535. [Google Scholar] [CrossRef] [PubMed]
  3. Hancock, S.; Zinn, C.; Schofield, G. The Consumption of Processed Sugar- and Starch-Containing Foods, and Dental Caries: A Systematic Review. Eur. J. Oral Sci. 2020, 128, 467–475. [Google Scholar] [CrossRef] [PubMed]
  4. Schneider, H.-G.; Knieknecht, G.K. Die Bildung von Zahnbelägen in Abhängigkeit von Der Nahrungsaufnahme. Mol. Nutr. Food Res. 1986, 30, 31–37. [Google Scholar] [CrossRef]
  5. Tada, A.; Miura, H. The Relationship between Vitamin C and Periodontal Diseases: A Systematic Review. Int. J. Environ. Res. Public Health 2019, 16, 2472. [Google Scholar] [CrossRef] [Green Version]
  6. Coelho, J.M.F.; Miranda, S.S.; da Cruz, S.S.; Trindade, S.C.; de Passos-Soares, J.S.; de Cerqueira, E.M.M.; da Costa, M.C.N.; Figueiredo, A.C.M.G.; Hintz, A.M.; Barreto, M.L.; et al. Is There Association between Stress and Periodontitis? Clin. Oral Investig. 2020, 24, 2285–2294. [Google Scholar] [CrossRef]
  7. Scannapieco, F.A.; Gershovich, E. The Prevention of Periodontal Disease-An Overview. Periodontol. 2020, 84, 9–13. [Google Scholar] [CrossRef]
  8. Gomes-Filho, I.S.; Oliveira, M.T.; da Cruz, S.S.; de Cerqueira, E.M.M.; Trindade, S.C.; Vieira, G.O.; Couto Souza, P.H.; Adan, L.F.F.; Hintz, A.M.; de Passos-Soares, J.S.; et al. Periodontitis Is a Factor Associated with Dyslipidemia. Oral Dis. 2021, 28, 813–823. [Google Scholar] [CrossRef]
  9. Proctor, G.B.; Shaalan, A.M. Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva. J. Dent. Res. 2021, 100, 1201–1209. [Google Scholar] [CrossRef]
  10. Pulito, C.; Cristaudo, A.; Porta, C.L.; Zapperi, S.; Blandino, G.; Morrone, A.; Strano, S. Oral Mucositis: The Hidden Side of Cancer Therapy. J. Exp. Clin. Cancer Res. 2020, 39, 210. [Google Scholar] [CrossRef]
  11. Almhöjd, U.; Cevik-Aras, H.; Karlsson, N.; Chuncheng, J.; Almståhl, A. Stimulated Saliva Composition in Patients with Cancer of the Head and Neck Region. BMC Oral Health 2021, 21, 509. [Google Scholar] [CrossRef]
  12. Zhou, X.; Zhang, W.; Liu, X.; Zhang, W.; Li, Y. Interrelationship between Diabetes and Periodontitis: Role of Hyperlipidemia. Arch. Oral Biol. 2015, 60, 667–674. [Google Scholar] [CrossRef]
  13. Adams, D.; Addy, M. Mouthrinses. Adv. Dent. Res. 1994, 8, 291–301. [Google Scholar] [CrossRef]
  14. Saliasi, I.; Llodra, J.C.; Bravo, M.; Tramini, P.; Dussart, C.; Viennot, S.; Carrouel, F. Effect of a Toothpaste/Mouthwash Containing Leaf Extract on Interdental Gingival Bleeding: A Randomized Controlled Trial. Int. J. Environ. Res. Public Health 2018, 15, 2660. [Google Scholar] [CrossRef] [Green Version]
  15. Code of Federal Regulations. Title 21—Food and Drugs. Chapter I—Food and Drug Administration Department of Health and Human Services. Subchapter D—Drugs for Human Use. Part 355—Anticaries Drug Products for Over-The-Counter Human Use. Available online: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=355&showFR=1 (accessed on 2 February 2022).
  16. Bijle, M.N.; Abdalla, M.M.; Ashraf, U.; Ekambaram, M.; Yiu, C.K.Y. Enamel Remineralization Potential of Arginine-Fluoride Varnish in a Multi-Species Bacterial pH-Cycling Model. J. Dent. 2021, 104, 103528. [Google Scholar] [CrossRef]
  17. Bijle, M.N.; Ekambaram, M.; Yiu, C.K.Y. A Scoping Review on Arginine in Caries Prevention. J. Evid. Based. Dent. Pract. 2020, 20, 101470. [Google Scholar] [CrossRef]
  18. Lingström, P.; Fure, S.; Dinitzen, B.; Fritzne, C.; Klefbom, C.; Birkhed, D. The Release of Vitamin C from Chewing Gum and Its Effects on Supragingival Calculus Formation. Eur. J. Oral Sci. 2005, 113, 20–27. [Google Scholar] [CrossRef]
  19. Münchow, E.A.; Hamann, H.J.; Carvajal, M.T.; Pinal, R.; Bottino, M.C. Stain Removal Effect of Novel Papain- and Bromelain-Containing Gels Applied to Enamel. Clin. Oral Investig. 2016, 20, 2315–2320. [Google Scholar] [CrossRef]
  20. Schirrmeister, J.F.; Seger, R.K.; Altenburger, M.J.; Lussi, A.; Hellwig, E. Effects of Various Forms of Calcium Added to Chewing Gum on Initial Enamel Carious Lesions in Situ. Caries Res. 2007, 41, 108–114. [Google Scholar] [CrossRef]
  21. Yavuz, B.S.; Kargul, B. Comparative Evaluation of the Spectral-Domain Optical Coherence Tomography and Microhardness for Remineralization of Enamel Caries Lesions. Dent. Mater. J. 2021, 40, 1115–1121. [Google Scholar] [CrossRef]
  22. Lynch, R.J.M. Calcium Glycerophosphate and Caries: A Review of the Literature. Int. Dent. J. 2004, 54, 310–314. [Google Scholar] [CrossRef]
  23. Beiraghi, S.; Atkins, S.; Rosen, S.; Wilson, S.; Odom, J.; Beck, M. Effect of Calcium Lactate in Erosion and S. Mutans in Rats When Added to Coca-Cola. Pediatr. Dent. 1989, 11, 312–315. [Google Scholar]
  24. Atalay, S.; Jarocka-Karpowicz, I.; Skrzydlewska, E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidant 2019, 9, 21. [Google Scholar] [CrossRef] [Green Version]
  25. Cuba, L.F.; Salum, F.G.; Cherubini, K.; Figueiredo, M.A.Z. Cannabidiol: An Alternative Therapeutic Agent for Oral Mucositis? J. Clin. Pharm. Ther. 2017, 42, 245–250. [Google Scholar] [CrossRef] [Green Version]
  26. Franco, M.C.; Uehara, J.; Meroni, B.M.; Zuttion, G.S.; Cenci, M.S. The Effect of a Charcoal-Based Powder for Enamel Dental Bleaching. Oper. Dent. 2020, 45, 618–623. [Google Scholar] [CrossRef]
  27. Mhaske, S.P.; Ambiti, R.; Jagga, U.; Paul, U.; Shanmukappa, S.M.; Iska, D. Clinicomicrobiological Evaluation of 2% Chitosan Mouthwashes on Dental Plaque. J. Contemp. Dent. Pract. 2018, 19, 94–97. [Google Scholar] [CrossRef]
  28. Wheeler, T.T.; Hodgkinson, A.J.; Prosser, C.G.; Davis, S.R. Immune Components of Colostrum and Milk—A Historical Perspective. J. Mammary Gland Biol. Neoplasia 2007, 12, 237–247. [Google Scholar] [CrossRef]
  29. Fenyvesi, F.; Nguyen, T.L.P.; Haimhoffer, Á.; Rusznyák, Á.; Vasvári, G.; Bácskay, I.; Vecsernyés, M.; Ignat, S.-R.; Dinescu, S.; Costache, M.; et al. Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin. Materials 2020, 13, 3618. [Google Scholar] [CrossRef]
  30. Maheriya, M.P. Cyclodextrin: A Promising Candidate in Enhancing Oral Bioavailability of Poorly Water Soluble Drugs. MOJ Bioequiv. Bioavailab. 2017, 3, 34. [Google Scholar] [CrossRef] [Green Version]
  31. Lambert, R.J.W.; Hanlon, G.W.; Denyer, S.P. The Synergistic Effect of EDTA/antimicrobial Combinations on Pseudomonas Aeruginosa. J. Appl. Microbiol. 2004, 96, 244–253. [Google Scholar] [CrossRef]
  32. Dubray, C.; Maincent, P.; Milon, J.Y. From the Pharmaceutical to the Clinical: The Case for Effervescent Paracetamol in Pain Management. A Narrative Review. Curr. Med. Res. Opin. 2021, 37, 1039–1048. [Google Scholar] [CrossRef] [PubMed]
  33. Aslani, A.; Fattahi, F. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets. Adv. Pharm. Bull. 2013, 3, 217–225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Dhakad, A.K.; Pandey, V.V.; Beg, S.; Rawat, J.M.; Singh, A. Biological, Medicinal and Toxicological Significance of Eucalyptus Leaf Essential Oil: A Review. J. Sci. Food Agric. 2018, 98, 833–848. [Google Scholar] [CrossRef] [PubMed]
  35. Khazraei, H.; Shamsdin, S.A.; Zamani, M. In Vitro Cytotoxicity and Apoptotic Assay of Eucalyptus Globulus Essential Oil in Colon and Liver Cancer Cell Lines. J. Gastrointest. Cancer 2021, 11, 601. [Google Scholar] [CrossRef] [PubMed]
  36. Chaieb, K.; Hajlaoui, H.; Zmantar, T.; Kahla-Nakbi, A.B.; Rouabhia, M.; Mahdouani, K.; Bakhrouf, A. The Chemical Composition and Biological Activity of Clove Essential Oil, Eugenia Caryophyllata (Syzigium Aromaticum L. Myrtaceae): A Short Review. Phytother. Res. 2007, 21, 501–506. [Google Scholar] [CrossRef]
  37. Clerck, C.D.; Maso, S.D.; Parisi, O.; Dresen, F.; Zhiri, A.; Jijakli, M.H. Screening of Antifungal and Antibacterial Activity of 90 Commercial Essential Oils against 10 Pathogens of Agronomical Importance. Foods 2020, 9, 1418. [Google Scholar] [CrossRef]
  38. Rajendiran, M.; Trivedi, H.M.; Chen, D.; Gajendrareddy, P.; Chen, L. Recent Development of Active Ingredients in Mouthwashes and Toothpastes for Periodontal Diseases. Molecules 2021, 26, 2001. [Google Scholar] [CrossRef]
  39. Casale, M.; Moffa, A.; Vella, P.; Sabatino, L.; Capuano, F.; Salvinelli, B.; Lopez, M.A.; Carinci, F.; Salvinelli, F. Hyaluronic Acid: Perspectives in Dentistry. A Systematic Review. Int. J. Immunopathol. Pharmacol. 2016, 29, 572–582. [Google Scholar] [CrossRef]
  40. Ibrahim, S.A.; Elkot, R.A.; Soliman, H.E. Lactic Acid 5% Mouth Wash vs Kenalog in Orabase 0.1% for Treatment and Prophylaxis of Recurrent Aphthous Ulcer. J. Cosmet. Dermatol. 2020, 19, 964–969. [Google Scholar] [CrossRef]
  41. Sharquie, K.E.; Al-Tammimy, S.M.; Al-Mashhadani, S.; Hayani, R.K.; Al-Nuaimy, A.A. Lactic Acid 5 Percent Mouthwash Is an Effective Mode of Therapy in Treatment of Recurrent Aphthous Ulcerations. Dermatol. Online J. 2006, 12, 2. [Google Scholar] [CrossRef]
  42. Seifu, E.; Buys, E.M.; Donkin, E.F. Significance of the Lactoperoxidase System in the Dairy Industry and Its Potential Applications: A Review. Trends Food Sci. Technol. 2005, 16, 137–154. [Google Scholar] [CrossRef]
  43. Magacz, M.; Kędziora, K.; Sapa, J.; Krzyściak, W. The Significance of Lactoperoxidase System in Oral Health: Application and Efficacy in Oral Hygiene Products. Int. J. Mol. Sci. 2019, 20, 1443. [Google Scholar] [CrossRef] [Green Version]
  44. Kim, S.-Y.; Han, S.-D.; Kim, M.; Mony, T.J.; Lee, E.-S.; Kim, K.-M.; Choi, S.-H.; Hong, S.H.; Choi, J.W.; Park, S.J. Mentha Arvensis Essential Oil Exerts Anti-Inflammatory in LPS-Stimulated Inflammatory Responses via Inhibition of ERK/NF-κB Signaling Pathway and Anti-Atopic Dermatitis-like Effects in 2,4-Dinitrochlorobezene-Induced BALB/c Mice. Antioxidant 2021, 10, 1941. [Google Scholar] [CrossRef]
  45. Wu, Z.; Tan, B.; Liu, Y.; Dunn, J.; Martorell Guerola, P.; Tortajada, M.; Cao, Z.; Ji, P. Chemical Composition and Antioxidant Properties of Essential Oils from Peppermint, Native Spearmint and Scotch Spearmint. Molecules 2019, 24, 2825. [Google Scholar] [CrossRef] [Green Version]
  46. Kim, M.H.; Park, S.J.; Yang, W.M. Inhalation of Essential Oil from Mentha Piperita Ameliorates PM10-Exposed Asthma by Targeting IL-6/JAK2/STAT3 Pathway Based on a Network Pharmacological Analysis. Pharmaceuticals 2020, 14, 2. [Google Scholar] [CrossRef]
  47. Arruda, M.O.; Mendes, S.J.F.; Teixeira, S.A.; de Mesquita, L.S.S.; de Sousa Ribeiro, M.N.; de Galvão, S.S.L.; Muscará, M.N.; Fernandes, E.S.; Monteiro-Neto, V. The Hydroalcoholic Extract Obtained from Mentha Piperita L. Leaves Attenuates Oxidative Stress and Improves Survival in Lipopolysaccharide-Treated Macrophages. J Immunol. Res. 2017, 2017, 2078794. [Google Scholar] [CrossRef] [Green Version]
  48. Nair, B. Final Report on the Safety Assessment of Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water. Int. J. Toxicol. 2001, 20 (Suppl. 3), 61–73. [Google Scholar] [CrossRef]
  49. Snoussi, M.; Noumi, E.; Trabelsi, N.; Flamini, G.; Papetti, A.; De Feo, V. Mentha Spicata Essential Oil: Chemical Composition, Antioxidant and Antibacterial Activities against Planktonic and Biofilm Cultures of Vibrio spp. Strains. Molecules 2015, 20, 14402–14424. [Google Scholar] [CrossRef]
  50. Mentha Viridis (L.). Available online: https://www.gbif.org/species/2927178 (accessed on 2 February 2022).
  51. Degli Esposti, L.; Ionescu, A.C.; Brambilla, E.; Tampieri, A.; Iafisco, M. Characterization of a Toothpaste Containing Bioactive Hydroxyapatites and In Vitro Evaluation of Its Efficacy to Remineralize Enamel and to Occlude Dentinal Tubules. Materials 2020, 13, 2928. [Google Scholar] [CrossRef]
  52. Ionescu, A.C.; Esposti, L.D.; Iafisco, M.; Brambilla, E. Enamel Remineralization and Dentine Tubules Occlusion by Bioactive Formulations Based on Ion-Doped Nanohydroxyapatite and Precursor Nanoparticles. Res. Sq. 2021. (under consideration). [Google Scholar] [CrossRef]
  53. Jones, S.B.; West, N.X.; Nesmiyanov, P.P.; Krylov, S.E.; Klechkovskaya, V.V.; Arkharova, N.A.; Zakirova, S.A. The Antibacterial Efficacy of a Foam Mouthwash and Its Ability to Remove Biofilms. BDJ Open 2018, 4, 17038. [Google Scholar] [CrossRef] [PubMed]
  54. Zorina, O.A.; Petruhina, N.B.; M, A.Z.; Boriskina, O.A.; Tupicin, A.A.; Prohodnaja, V.A. Clinical and laboratory evaluation of the Elgydium Protection caries toothpaste effectiveness in patients with high intensity of dental caries. Stomatologiia 2019, 98, 21–24. [Google Scholar] [CrossRef] [PubMed]
  55. Guertin, P.A. How Safe Are Glycerin and Polyglycerin-10 as Key Ingredients in Personal Care Products. Clin. Pharmacol. Toxicol. Res. 1976, 2, 291. [Google Scholar]
  56. Park, S.; Mun, S.; Kim, Y.-R. Influences of Added Surfactants on the Water Solubility and Antibacterial Activity of Rosemary Extract. Food Sci. Biotechnol. 2020, 29, 1373–1380. [Google Scholar] [CrossRef]
  57. Burnett, C.L.; Bergfeld, W.F.; Belsito, D.V.; Hill, R.A.; Klaassen, C.D.; Liebler, D.C.; Marks, J.G., Jr.; Shank, R.C.; Slaga, T.J.; Snyder, P.W.; et al. Final Report of the Amended Safety Assessment of PVM/MA Copolymer and Its Related Salts and Esters as Used in Cosmetics. Int. J. Toxicol. 2011, 30, 128S–144S. [Google Scholar] [CrossRef]
  58. Elder, R.L. 7 Final Report on the Safety Assessment of Polyvinylpyrrolidone/Vinyl Acetate Copolymer. J. Am. Coll. Toxicol. 1983, 2, 141–159. [Google Scholar] [CrossRef]
  59. Martinotti, S.; Ranzato, E. Propolis: A New Frontier for Wound Healing? Burn. Trauma 2015, 3, 9. [Google Scholar] [CrossRef] [Green Version]
  60. Stojko, M.; Wolny, D.; Włodarczyk, J. Nonwoven Releasing Propolis as a Potential New Wound Healing Method—A Review. Molecules 2021, 26, 5701. [Google Scholar] [CrossRef]
  61. Hussain, A.I.; Anwar, F.; Chatha, S.A.S.; Jabbar, A.; Mahboob, S.; Nigam, P.S. Rosmarinus Officinalis Essential Oil: Antiproliferative, Antioxidant and Antibacterial Activities. Braz. J. Microbiol. 2010, 41, 1070–1078. [Google Scholar] [CrossRef] [Green Version]
  62. Cutillas, A.-B.; Carrasco, A.; Martinez-Gutierrez, R.; Tomas, V.; Tudela, J. Composition and Antioxidant, Antienzymatic and Antimicrobial Activities of Volatile Molecules from Spanish Salvia Lavandulifolia (Vahl) Essential Oils. Molecules 2017, 22, 1382. [Google Scholar] [CrossRef] [Green Version]
  63. Frydrysiak, E.; Kunicka-Styczyńska, A.; Śmigielski, K.; Frydrysiak, M. The Impact of Selected Essential Oils Applied to Non-Woven Viscose on Bacteria That Cause Lower Urinary Tract Infections-Preliminary Studies. Molecules 2021, 26, 6854. [Google Scholar] [CrossRef]
  64. El Euch, S.K.; Hassine, D.B.; Cazaux, S.; Bouzouita, N.; Bouajila, J. Salvia Officinalis Essential Oil: Chemical Analysis and Evaluation of Anti-Enzymatic and Antioxidant Bioactivities. S. Afr. J. Bot. 2019, 120, 253–260. [Google Scholar] [CrossRef]
  65. Dinel, A.-L.; Lucas, C.; Guillemet, D.; Layé, S.; Pallet, V.; Joffre, C. Chronic Supplementation with a Mix of Salvia Officinalis and Salvia Lavandulaefolia Improves Morris Water Maze Learning in Normal Adult C57Bl/6J Mice. Nutrients 2020, 12, 1777. [Google Scholar] [CrossRef]
  66. Palaia, G.; Tenore, G.; Tribolati, L.; Russo, C.; Gaimari, G.; Del Vecchio, A.; Romeo, U. Evaluation of Wound Healing and Postoperative Pain after Oral Mucosa Laser Biopsy with the Aid of Compound with Chlorhexidine and Sodium Hyaluronate: A Randomized Double Blind Clinical Trial. Clin. Oral Investig. 2019, 23, 3141–3151. [Google Scholar] [CrossRef] [Green Version]
  67. Cvikl, B.; Lussi, A.; Carvalho, T.S.; Moritz, A.; Gruber, R. Stannous Chloride and Stannous Fluoride Are Inhibitors of Matrix Metalloproteinases. J. Dent. 2018, 78, 51–58. [Google Scholar] [CrossRef]
  68. Green, A.; Crichard, S.; Ling-Mountford, N.; Milward, M.; Hubber, N.; Platten, S.; Gupta, A.K.; Chapple, I.L.C. A Randomised Clinical Study Comparing the Effect of Steareth 30 and SLS Containing Toothpastes on Oral Epithelial Integrity (desquamation). J. Dent. 2019, 80 (Suppl. 1), S33–S39. [Google Scholar] [CrossRef]
  69. Galovičová, L.; Borotová, P.; Valková, V.; Vukovic, N.L.; Vukic, M.; Terentjeva, M.; Štefániková, J.; Ďúranová, H.; Kowalczewski, P.Ł.; Kačániová, M. Thymus Serpyllum Essential Oil and Its Biological Activity as a Modern Food Preserver. Plants 2021, 10, 1416. [Google Scholar] [CrossRef]
  70. Borugă, O.; Jianu, C.; Mişcă, C.; Goleţ, I.; Gruia, A.T.; Horhat, F.G. Thymus Vulgaris Essential Oil: Chemical Composition and Antimicrobial Activity. J. Med. Life 2014, 7, 56–60. [Google Scholar]
  71. Pinto, L.; Bonifacio, M.A.; De Giglio, E.; Cometa, S.; Logrieco, A.F.; Baruzzi, F. Unravelling the Antifungal Effect of Red Thyme Oil (Thymus Vulgaris L.) Compounds in Vapor Phase. Molecules 2020, 25, 4761. [Google Scholar] [CrossRef]
  72. GasmiBenahmed, A.; Gasmi, A.; Arshad, M.; Shanaida, M.; Lysiuk, R.; Peana, M.; Pshyk-Titko, I.; Adamiv, S.; Shanaida, Y.; Bjørklund, G. Health Benefits of Xylitol. Appl. Microbiol. Biotechnol. 2020, 104, 7225–7237. [Google Scholar] [CrossRef]
  73. Xu, X.; Wang, N.; Wu, M.; Wang, J.; Wang, D.; Chen, Z.; Xie, J.; Ding, C.; Li, J. Programmed Antibacterial and Mineralization Therapy for Dental Caries Based on Zinc-Substituted Hydroxyapatite/ Alendronate-Grafted Polyacrylic Acid Hybrid Material. Colloids Surf. B Biointerfaces 2020, 194, 111206. [Google Scholar] [CrossRef] [PubMed]
  74. Hannig, C.; Basche, S.; Burghardt, T.; Al-Ahmad, A.; Hannig, M. Influence of a Mouthwash Containing Hydroxyapatite Microclusters on Bacterial Adherence in Situ. Clin. Oral Investig. 2013, 17, 805–814. [Google Scholar] [CrossRef] [PubMed]
  75. Falk, N.A. Surfactants as Antimicrobials: A Brief Overview of Microbial Interfacial Chemistry and Surfactant Antimicrobial Activity. J. Surfactants Deterg. 2019, 22, 1119–1127. [Google Scholar] [CrossRef] [PubMed]
  76. Kockisch, S.; Rees, G.D.; Young, S.A.; Tsibouklis, J.; Smart, J.D. A Direct-Staining Method to Evaluate the Mucoadhesion of Polymers from Aqueous Dispersion. J. Control. Release 2001, 77, 1–6. [Google Scholar] [CrossRef]
  77. Fallacara, A.; Baldini, E.; Manfredini, S.; Vertuani, S. Hyaluronic Acid in the Third Millennium. Polymers 2018, 10, 701. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  78. Rodu, B.; Russell, C.M. Performance of a Hydroxypropyl Cellulose Film Former in Normal and Ulcerated Oral Mucosa. Oral Surg. Oral Med. Oral Pathol. 1988, 65, 699–703. [Google Scholar] [CrossRef]
  79. Nguyen, K.T.; Tran, P.H.L.; Ngo, H.V.; Tran, T.T.D. Film-Forming Nanogels: Effects of Nanocarriers and Film-Forming Gel on the Sustained Release of Curcumin. Anticancer Agents Med. Chem. 2021, 21, 658–666. [Google Scholar] [CrossRef]
  80. Suharyani, I.; Fouad Abdelwahab Mohammed, A.; Muchtaridi, M.; Wathoni, N.; Abdassah, M. Evolution of Drug Delivery Systems for Recurrent Aphthous Stomatitis. Drug Des. Devel. Ther. 2021, 15, 4071–4089. [Google Scholar] [CrossRef]
  81. Aranaz, I.; Acosta, N.; Civera, C.; Elorza, B.; Mingo, J.; Castro, C.; Gandía, M.D.L.L.; Heras Caballero, A. Cosmetics and Cosmeceutical Applications of Chitin, Chitosan and Their Derivatives. Polymers 2018, 10, 213. [Google Scholar] [CrossRef] [Green Version]
  82. Rajaram, D.M.; Laxman, S.D. Buccal Mucoadhesive Films: A Review. Syst. Rev. Pharm. 2016, 8, 31–38. [Google Scholar] [CrossRef]
  83. Arnaud, T.M.S.; de Barros Neto, B.; Diniz, F.B. Chitosan Effect on Dental Enamel de-Remineralization: An In Vitro Evaluation. J. Dent. 2010, 38, 848–852. [Google Scholar] [CrossRef]
  84. Madeswaran, S.; Jayachandran, S. Sodium Bicarbonate: A Review and Its Uses in Dentistry. Indian J. Dent. Res. 2018, 29, 672. [Google Scholar] [CrossRef]
  85. Wax, P.M.; Haynes, A. Sodium Bicarbonate. In Goldfrank’s Toxicologic Emergencies, 11th ed.; Nelson, L.S., Howland, M., Lewin, N.A., Smith, S.W., Goldfrank, L.R., Hoffman, R.S., Eds.; McGraw Hill: New York, NY, USA, 2019. [Google Scholar]
  86. Lee, D.; Hong, J.H. The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs. Int. J. Mol. Sci. 2020, 21, 339. [Google Scholar] [CrossRef] [Green Version]
  87. Parkkila, S.; Kaunisto, K.; Rajaniemi, L.; Kumpulainen, T.; Jokinen, K.; Rajaniemi, H. Immunohistochemical Localization of Carbonic Anhydrase Isoenzymes VI, II, and I in Human Parotid and Submandibular Glands. J. Histochem. Cytochem. 1990, 38, 941–947. [Google Scholar] [CrossRef]
  88. Winum, J.-Y.; Montero, J.-L.; Vullo, D.; Supuran, C.T. Carbonic Anhydrase Inhibitors: Glycosylsulfanilamides Act as Subnanomolar Inhibitors of the Human Secreted Isoform VI. Chem. Biol. Drug Des. 2009, 74, 636–639. [Google Scholar] [CrossRef]
  89. Piekoszewska-Ziętek, P.; Szymański, K.; Olczak-Kowalczyk, D. Polymorphism in the CAVI Gene, Salivary Properties and Dental Caries. Acta Odontol. Scand. 2020, 78, 250–255. [Google Scholar] [CrossRef]
  90. De Cassia Rodrigues Picco, D.; Lopes, L.M.; Marques, M.R.; Line, S.R.P.; Parisotto, T.M.; dos Santos, M.N. Children with a Higher Activity of Carbonic Anhydrase VI in Saliva Are More Likely to Develop Dental Caries. Creces 2017, 51, 394–401. [Google Scholar] [CrossRef]
  91. De-Sousa, E.T.; Lima-Holanda, A.T.; Nobre-Dos-Santos, M. Carbonic Anhydrase VI Activity in Saliva and Biofilm Can Predict Early Childhood Caries: A Preliminary Study. Int. J. Paediatr. Dent. 2021, 31, 361–371. [Google Scholar] [CrossRef]
  92. Borghi, G.N.; Rodrigues, L.P.; Lopes, L.M.; Parisotto, T.M.; Steiner-Oliveira, C.; Nobre-Dos-Santos, M. Relationship among α Amylase and Carbonic Anhydrase VI in Saliva, Visible Biofilm, and Early Childhood Caries: A Longitudinal Study. Int. J. Paediatr. Dent. 2017, 27, 174–182. [Google Scholar] [CrossRef]
  93. Corral, L.G.; Post, L.S.; Montville, T.J. Antimicrobial Activity of Sodium Bicarbonate. J. Food Sci. 1988, 53, 981–982. [Google Scholar] [CrossRef]
  94. Pratten, J.; Wiecek, J.; Mordan, N.; Lomax, A.; Patel, N.; Spratt, D.; Middleton, A.M. Physical Disruption of Oral Biofilms by Sodium Bicarbonate: An In Vitro Study. Int. J. Dent. Hyg. 2016, 14, 209–214. [Google Scholar] [CrossRef]
  95. Nazzaro, F.; Fratianni, F.; De Martino, L.; Coppola, R.; De Feo, V. Effect of Essential Oils on Pathogenic Bacteria. Pharmaceuticals 2013, 6, 1451–1474. [Google Scholar] [CrossRef]
  96. Butnariu, M.; Sarac, I. Essential Oils from Plants. J. Biotechnol. Biomed. Sci. 2018, 1, 35–43. [Google Scholar] [CrossRef] [Green Version]
  97. Freires, I.A.; Denny, C.; Benso, B.; de Alencar, S.M.; Rosalen, P.L. Antibacterial Activity of Essential Oils and Their Isolated Constituents against Cariogenic Bacteria: A Systematic Review. Molecules 2015, 20, 7329–7358. [Google Scholar] [CrossRef]
  98. Van der Weijden, F.A.; Van der Sluijs, E.; Ciancio, S.G.; Slot, D.E. Can Chemical Mouthwash Agents Achieve Plaque/Gingivitis Control? Dent. Clin. N. Am. 2015, 59, 799–829. [Google Scholar] [CrossRef] [Green Version]
  99. Marchese, E.; D’onofrio, N.; Balestrieri, M.L.; Castaldo, D.; Ferrari, G.; Donsì, F. Bergamot Essential Oil Nanoemulsions: Antimicrobial and Cytotoxic Activity. Z. Naturforsch. C 2020, 75, 279–290. [Google Scholar] [CrossRef]
  100. Bakkali, F.; Averbeck, S.; Averbeck, D.; Idaomar, M. Biological Effects of Essential Oils—A Review. Food Chem. Toxicol. 2008, 46, 446–475. [Google Scholar] [CrossRef]
  101. Yadalam, P.K.; Varatharajan, K.; Rajapandian, K.; Chopra, P.; Arumuganainar, D.; Nagarathnam, T.; Sohn, H.; Madhavan, T. Antiviral Essential Oil Components Against SARS-CoV-2 in Pre-Procedural Mouth Rinses for Dental Settings During COVID-19: A Computational Study. Front. Chem. 2021, 9, 86. [Google Scholar] [CrossRef]
  102. Burt, S.A.; Reinders, R.D. Antibacterial Activity of Selected Plant Essential Oils against Escherichia Coli O157:H7. Lett. Appl. Microbiol. 2003, 36, 162–167. [Google Scholar] [CrossRef] [Green Version]
  103. Trombetta, D.; Castelli, F.; Sarpietro, M.G.; Venuti, V.; Cristani, M.; Daniele, C.; Saija, A.; Mazzanti, G.; Bisignano, G. Mechanisms of Antibacterial Action of Three Monoterpenes. Antimicrob. Agents Chemother. 2005, 49, 2474–2478. [Google Scholar] [CrossRef] [Green Version]
  104. Zhang, D.; Liu, R.; Sun, L.; Huang, C.; Wang, C.; Zhang, D.-M.; Zhang, T.-T.; Du, G.-H. Anti-Inflammatory Activity of Methyl Salicylate Glycosides Isolated from Gaultheria Yunnanensis (Franch.) Rehder. Molecules 2011, 16, 3875–3884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. Rocha, N.F.; Rios, E.R.; Carvalho, A.M.; Cerqueira, G.S.; Lopes, A.A.; Leal, L.K.; Dias, M.L.; de Sousa, D.P.; de Sousa, F.C. Anti-Nociceptive and Anti-Inflammatory Activities of (-)-α-Bisabolol in Rodents. Naunyn. Schmiedebergs. Arch. Pharmacol. 2011, 384, 525–533. [Google Scholar] [CrossRef] [PubMed]
  106. Zhandabayeva, M.A.; Kozhanova, K.K.; Boshkayeva, A.K.; Kataev, V.A.; Ustenova, G.O.; Gemejiyeva, N.G.; Iskakbayeva, Z.A. Determination of the Chemical Composition and Antimicrobial Activity of Lavatera Thuringiaca L. Medicinal Herb Material Extracted under Subcritical Conditions by the Liquid Carbon Dioxide Method. Int. J. Biomater. 2021, 2021, 7541555. [Google Scholar] [CrossRef] [PubMed]
  107. Singh, R.; Shushni, M.A.M.; Belkheir, A. Antibacterial and Antioxidant Activities of Mentha Piperita L. Arab. J. Chem. 2011, 8, 322–328. [Google Scholar] [CrossRef] [Green Version]
  108. Safaei-Ghomi, J.; Ahd, A.A. Antimicrobial and Antifungal Properties of the Essential Oil and Methanol Extracts of Eucalyptus Largiflorens and Eucalyptus Intertexta. Pharmacogn. Mag. 2010, 6, 172–175. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  109. Vijayakumar, K.; Manigandan, V.; Jeyapragash, D.; Bharathidasan, V.; Anandharaj, B.; Sathya, M. Eucalyptol Inhibits Biofilm Formation of and Its Mediated Virulence Factors. J. Med. Microbiol. 2020, 69, 1308–1318. [Google Scholar] [CrossRef]
  110. Ashrafudoulla, M.; Mizan, M.F.R.; Ha, A.J.; Park, S.H.; Ha, S.D. Antibacterial and Antibiofilm Mechanism of Eugenol against Antibiotic Resistance Vibrio Parahaemolyticus. Food Microbiol. 2020, 91, 103500. [Google Scholar] [CrossRef]
  111. Lahiri, D.; Nag, M.; Dutta, B.; Dey, S.; Mukherjee, D.; Joshi, S.J.; Ray, R.R. Antibiofilm and Anti-Quorum Sensing Activities of Eugenol and Linalool from OcimumTenuiflorum against Pseudomonas Aeruginosa Biofilm. J. Appl. Microbiol. 2021, 131, 2821–2837. [Google Scholar] [CrossRef]
  112. Kowalczyk, A.; Przychodna, M.; Sopata, S.; Bodalska, A.; Fecka, I. Thymol and Thyme Essential Oil-New Insights into Selected Therapeutic Applications. Molecules 2020, 25, 4125. [Google Scholar] [CrossRef]
  113. Ozogul, Y.; Kuley, E.; Ucar, Y.; Ozogul, F. Antimicrobial Impacts of Essential Oils on Food Borne-Pathogens. Recent Pat. Food Nutr. Agric. 2015, 7, 53–61. [Google Scholar] [CrossRef]
  114. Geier, J.; Ballmer-Weber, B.; Buhl, T.; Rieker-Schwienbacher, J.; Mahler, V.; Dickel, H.; Schubert, S.; IVDK. Is Benzyl Alcohol a Significant Contact Sensitizer? J. Eur. Acad. Dermatol. Venereol. 2022, 12, 17968. [Google Scholar] [CrossRef]
  115. Zhou, Q.; Shi, M.; Zhang, H.; Zhu, Z. Comparative Study of the Petal Structure and Fragrance Components of the Nymphaea Hybrid, a Precious Water Lily. Molecules 2022, 27, 408. [Google Scholar] [CrossRef]
  116. Sun, Y.; Chen, S.; Zhang, C.; Liu, Y.; Ma, L.; Zhang, X. Effects of Sub-Minimum Inhibitory Concentrations of Lemon Essential Oil on the Acid Tolerance and Biofilm Formation of Streptococcus Mutans. Arch. Oral Biol. 2018, 87, 235–241. [Google Scholar] [CrossRef]
  117. Benzaid, C.; Belmadani, A.; Tichati, L.; Djeribi, R.; Rouabhia, M. Effect of Citrus Aurantium L. Essential Oil on Growth, Biofilm Formation and Virulent Genes Expression. Antibiotics 2021, 10, 54. [Google Scholar] [CrossRef]
  118. Chaves-Quirós, C.; Usuga-Usuga, J.-S.; Morales-Uchima, S.-M.; Tofiño-Rivera, A.-P.; Tobón-Arroyave, S.-I.; Martínez-Pabón, M.-C. Assessment of Cytotoxic and Antimicrobial Activities of Two Components of Essential Oil. J. Clin. Exp. Dent. 2020, 12, e749–e754. [Google Scholar] [CrossRef]
  119. He, Z.; Huang, Z.; Jiang, W.; Zhou, W. Antimicrobial Activity of Cinnamaldehyde on Streptococcus Mutans Biofilms. Front. Microbiol. 2019, 10, 2241. [Google Scholar] [CrossRef] [Green Version]
  120. De Lira, M.H.P.; de Andrade Júnior, F.P.; Moraes, G.F.Q.; da Silva Macena, G.; de Oliveira Pereira, F.; Lima, I.O. Antimicrobial Activity of Geraniol: An Integrative Review. J. Essent. Oil Res. 2020, 32, 187–197. [Google Scholar] [CrossRef]
  121. Kwiatkowski, P.; Grygorcewicz, B.; Pruss, A.; Wojciuk, B.; Dołęgowska, B.; Giedrys-Kalemba, S.; Sienkiewicz, M.; Wojciechowska-Koszko, I. The Effect of Subinhibitory Concentrations of Trans-Anethole on Antibacterial and Antibiofilm Activity of Mupirocin Against Mupirocin-Resistant Staphylococcus Aureus Strains. Microb. Drug Resist. 2019, 25, 101. [Google Scholar] [CrossRef]
  122. Johannsen, A.; Emilson, C.G.; Johannsen, G.; Konradsson, K.; Lingström, P.; Ramberg, P. Effects of Stabilized Stannous Fluoride Dentifrice on Dental Calculus, Dental Plaque, Gingivitis, Halitosis and Stain: A Systematic Review. Heliyon 2019, 5, 1424–1429. [Google Scholar] [CrossRef] [Green Version]
  123. Konradsson, K.; Lingström, P.; Emilson, C.G.; Johannsen, G.; Ramberg, P.; Johannsen, A. Stabilized Stannous Fluoride Dentifrice in Relation to Dental Caries, Dental Erosion and Dentin Hypersensitivity: A Systematic Review. Am. J. Dent. 2020, 33, 95–105. [Google Scholar]
  124. Pajor, K.; Pajchel, L.; Kolmas, J. Hydroxyapatite and Fluorapatite in Conservative Dentistry and Oral Implantology—A Review. Materials 2019, 12, 2683. [Google Scholar] [CrossRef] [Green Version]
  125. Haraszthy, V.I.; Raylae, C.C.; Sreenivasan, P.K. Antimicrobial Effects of a Stannous Fluoride Toothpaste in Distinct Oral Microenvironments. J. Am. Dent. Assoc. 2019, 150, S14–S24. [Google Scholar] [CrossRef]
  126. Tinanoff, N.; Siegrist, B.; Lang, N.P. Safety and Antibacterial Properties of Controlled Release SnF2. J. Oral Rehabil. 1986, 13, 73–81. [Google Scholar] [CrossRef]
  127. Fiorillo, L.; Cervino, G.; Herford, A.S.; Laino, L.; Cicciù, M. Stannous Fluoride Effects on Enamel: A Systematic Review. Biomimetics 2020, 5, 41. [Google Scholar] [CrossRef]
  128. Seriwatanachai, D.; Triratana, T.; Kraivaphan, P.; Amaornchat, C.; Mateo, L.R.; Sabharwal, A.; Delgado, E.; Szewczyk, G.; Ryan, M.; Zhang, Y.-P. Effect of Stannous Fluoride and Zinc Phosphate Dentifrice on Dental Plaque and Gingivitis: A Randomized Clinical Trial with 6-Month Follow-Up. J. Am. Dent. Assoc. 2019, 150, S25–S31. [Google Scholar] [CrossRef]
  129. Myers, C.P.; Pappas, I.; Makwana, E.; Begum-Gafur, R.; Utgikar, N.; Alsina, M.A.; Fitzgerald, M.; Trivedi, H.M.; Gaillard, J.-F.; Masters, J.G.; et al. Solving the Problem with Stannous Fluoride: Formulation, Stabilization, and Antimicrobial Action. J. Am. Dent. Assoc. 2019, 150, S5–S13. [Google Scholar] [CrossRef]
  130. Mahmoodi, B.; Goggin, P.; Fowler, C.; Cook, R.B. Quantitative Assessment of Dentine Mineralization and Tubule Occlusion by NovaMin and Stannous Fluoride Using Serial Block Face Scanning Electron Microscopy. J. Biomed. Mater. Res. B Appl. Biomater. 2021, 109, 717–722. [Google Scholar] [CrossRef]
  131. Duckworth, R. Stannous Fluoride Dentifrices; University of Liverpool: Liverpool, UK, 1964. [Google Scholar]
  132. Séby, F.; Potin-Gautier, M.; Giffaut, E.; Donard, O.F.X. A Critical Review of Thermodynamic Data for Inorganic Tin Species. Geochim. Cosmochim. Acta 2001, 65, 3041–3053. [Google Scholar] [CrossRef]
  133. Denes, G.; Lazanas, G. Oxidation of SnF2 Stannous Fluoride in Aqueous Solutions. Hyperfine Interact. 1994, 90, 435–439. [Google Scholar] [CrossRef]
  134. Fisher, S.; Fruge, L.; Prencipe, M. Low Water Stannous Fluoride Plus Zinc Citrate Dentifrice with Improved Stability, Rheology, and Efficacy. U.S. Patent US9968803B2, 15 May 2018. [Google Scholar]
  135. Vemishetti, K.; Fruge, L.; Prencipe, M. Low Water Dentifrice Compositions. World Patent 2016178652:A1, 10 November 2016. [Google Scholar]
  136. Singh, P. Stannous Fluoride Gel with Improved Stand-Up. U.S. Patent GB2336537A, 27 October 1999. [Google Scholar]
  137. Huamán-Castilla, N.L.; Mariotti-Celis, M.S.; Martínez-Cifuentes, M.; Pérez-Correa, J.R. Glycerol as Alternative Co-Solvent for Water Extraction of Polyphenols from Carménère Pomace: Hot Pressurized Liquid Extraction and Computational Chemistry Calculations. Biomolecules 2020, 10, 474. [Google Scholar] [CrossRef] [Green Version]
  138. Kowalska, G.; Baj, T.; Kowalski, R.; Szymańska, J. Optimization of Glycerol-Water Extraction of Selected Bioactive Compounds from Peppermint and Common Nettle. Antioxidant 2021, 10, 817. [Google Scholar] [CrossRef] [PubMed]
  139. Kvalheim, S.F.; Xenaki, V.; Kvalheim, A.; Lie, S.-A.; Marthinussen, M.C.; Strand, G.V.; Costea, D.E. Effect of Glycerol on Reconstructed Human Oral Mucosa. Eur. J. Oral Sci. 2019, 127, 19–26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  140. Kusakabe, Y.; Shindo, Y.; Kawai, T.; Maeda-Yamamoto, M.; Wada, Y. Relationships between the Response of the Sweet Taste Receptor, Salivation toward Sweeteners, and Sweetness Intensity. Food Sci. Nutr. 2021, 9, 719–727. [Google Scholar] [CrossRef] [PubMed]
  141. Da Cunha, D.A.; Gondim, B.L.C.; Pereira, I.F.; Moreira, M.D.S.C.; Santiago, B.M.; Valença, A.M.G. PropriedadesFísico-Químicas, Apresentação de Rotulagem E AtividadeAntimicrobiana de ColutóriosInfantis. Rev. Odontociênc. 2015, 30, 17. [Google Scholar] [CrossRef] [Green Version]
  142. Crețescu, I.; Horhat, R.; Munteanu, O.; Capriță, R. Evaluation of Physical-Chemical Characteristics of Commercially Available Fluoride Mouth Rinses. Rom. J. Biophys. 2017, 27, 81–88. [Google Scholar]
  143. Suchomel, M.; Weinlich, M.; Kundi, M. Influence of Glycerol and an Alternative Humectant on the Immediate and 3-Hours Bactericidal Efficacies of Two Isopropanol-Based Antiseptics in Laboratory Experiments in Vivo according to EN 12791. Antimicrob. Resist. Infect. Control 2017, 6, 72. [Google Scholar] [CrossRef] [Green Version]
  144. Phillips, B.; Titz, B.; Kogel, U.; Sharma, D.; Leroy, P.; Xiang, Y.; Vuillaume, G.; Lebrun, S.; Sciuscio, D.; Ho, J.; et al. Toxicity of the Main Electronic Cigarette Components, Propylene Glycol, Glycerin, and Nicotine, in Sprague-Dawley Rats in a 90-Day OECD Inhalation Study Complemented by Molecular Endpoints. Food Chem. Toxicol. 2017, 109, 315–332. [Google Scholar] [CrossRef]
  145. Gandini, S.; Negri, E.; Boffetta, P.; La Vecchia, C.; Boyle, P. Mouthwash and Oral Cancer Risk Quantitative Meta-Analysis of Epidemiologic Studies. Ann. Agric. Environ. Med. 2012, 19, 173–180. [Google Scholar]
  146. Nieminen, M.T.; Salaspuro, M. Local Acetaldehyde—An Essential Role in Alcohol-Related Upper Gastrointestinal Tract Carcinogenesis. Cancers 2018, 10, 11. [Google Scholar] [CrossRef] [Green Version]
  147. Salaspuro, M. Local Acetaldehyde: Its Key Role in Alcohol-Related Oropharyngeal Cancer. VIS 2020, 36, 167–174. [Google Scholar] [CrossRef]
  148. Ustrell-Borràs, M.; Traboulsi-Garet, B.; Gay-Escoda, C. Alcohol-Based Mouthwash as a Risk Factor of Oral Cancer: A Systematic Review. Med. Oral Patol. Oral Cir. Bucal. 2020, 25, e1–e12. [Google Scholar] [CrossRef]
  149. Pavlova, S.I.; Jin, L.; Gasparovich, S.R.; Tao, L. Multiple Alcohol Dehydrogenases but No Functional Acetaldehyde Dehydrogenase Causing Excessive Acetaldehyde Production from Ethanol by Oral Streptococci. Microbiology 2013, 159, 1437–1446. [Google Scholar] [CrossRef] [Green Version]
  150. Yokoyama, S.; Takeuchi, K.; Shibata, Y.; Kageyama, S.; Matsumi, R.; Takeshita, T.; Yamashita, Y. Characterization of Oral Microbiota and Acetaldehyde Production. J. Oral Microbiol. 2018, 10, 1492316. [Google Scholar] [CrossRef] [Green Version]
  151. Salaspuro, M. Acetaldehyde and Gastric Cancer. J. Dig. Dis. 2011, 12, 51–59. [Google Scholar] [CrossRef]
  152. Pietrobon, G.; Tagliabue, M.; Stringa, L.M.; De Berardinis, R.; Chu, F.; Zocchi, J.; Carlotto, E.; Chiocca, S.; Ansarin, M. Leukoplakia in the Oral Cavity and Oral Microbiota: A Comprehensive Review. Cancers 2021, 13, 4439. [Google Scholar] [CrossRef]
  153. Gupta, V.; Abhisheik, K.; Balasundari, S.; Devendra, N.K.; Shadab, K.; Anupama, M. Identification of Using Different Culture Media and Its Association in Leukoplakia and Oral Squamous Cell Carcinoma. J. Oral Maxillofac. Pathol. 2019, 23, 28–35. [Google Scholar] [CrossRef]
  154. Amer, A.; Whelan, A.; Al-Hebshi, N.N.; Healy, C.M.; Moran, G.P. Acetaldehyde Production by Isolates from Patients with Oral Leukoplakia. J. Oral Microbiol. 2020, 12, 1743066. [Google Scholar] [CrossRef] [Green Version]
  155. Mello, F.W.; Melo, G.; Pasetto, J.J.; Silva, C.A.B.; Warnakulasuriya, S.; Rivero, E.R.C. The Synergistic Effect of Tobacco and Alcohol Consumption on Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Clin. Oral Investig. 2019, 23, 2849–2859. [Google Scholar] [CrossRef]
  156. Radzki, D.; Kusiak, A.; Ordyniec-Kwaśnica, I.; Bondarczuk, A. Human Papillomavirus and Leukoplakia of the Oral Cavity: A Systematic Review. Postepy Dermatol. Alergol. 2021, 38, 38. [Google Scholar] [CrossRef]
  157. Rowe, R.C.; Sheskey, P.J.; Quinn, M.E. (Eds.) Handbook of Pharmaceutical Excipients, 6th ed.; Pharmaceutical Press: London, UK, 2011; p. 592. [Google Scholar]
  158. Burnett, C.L.; Heldreth, B.; Bergfeld, W.F.; Belsito, D.V.; Hill, R.A.; Klaassen, C.D.; Liebler, D.C.; Marks, J.G., Jr.; Shank, R.C.; Slaga, T.J.; et al. Safety Assessment of PEGylated Oils as Used in Cosmetics. Int. J. Toxicol. 2014, 33, 13S–39S. [Google Scholar] [CrossRef]
  159. Müller, H.-D.; Eick, S.; Moritz, A.; Lussi, A.; Gruber, R. Cytotoxicity and Antimicrobial Activity of Oral Rinses In Vitro. Biomed. Res. Int. 2017, 2017, 4019723. [Google Scholar] [CrossRef]
  160. Zhang, Y.; Tian, Y.; Zhang, H.; Xu, B.; Chen, H. Potential Pathways of Zinc Deficiency-Promoted Tumorigenesis. Biomed. Pharmacother. 2021, 133, 110983. [Google Scholar] [CrossRef]
  161. Skalny, A.V.; Aschner, M.; Tinkov, A.A. Zinc. Adv. Food Nutr. Res. 2021, 96, 251–310. [Google Scholar] [CrossRef]
  162. Hou, R.; He, Y.; Yan, G.; Hou, S.; Xie, Z.; Liao, C. Zinc Enzymes in Medicinal Chemistry. Eur. J. Med. Chem. 2021, 226, 113877. [Google Scholar] [CrossRef]
  163. Fedorowicz, Z.; Aljufairi, H.; Nasser, M.; Outhouse, T.L.; Pedrazzi, V. Mouthrinses for the Treatment of Halitosis. Cochrane Database Syst. Rev. 2008, 4, CD006701. [Google Scholar] [CrossRef]
  164. Suzuki, N.; Nakano, Y.; Watanabe, T.; Yoneda, M.; Hirofuji, T.; Hanioka, T. Two Mechanisms of Oral Malodor Inhibition by Zinc Ions. J. Appl. Oral Sci. 2018, 26, e20170161. [Google Scholar] [CrossRef] [Green Version]
  165. Alzoman, H.; Alzahrani, A.; Alwehaiby, K.; Alanazi, W.; AlSarhan, M. Efficacy of Arabic Coffee and Black Tea in Reducing Halitosis: A Randomized, Double-Blind, Controlled, Crossover Clinical Trial. Healthcare 2021, 9, 250. [Google Scholar] [CrossRef]
  166. Uwitonze, A.M.; Ojeh, N.; Murererehe, J.; Atfi, A.; Razzaque, M.S. Zinc Adequacy Is Essential for the Maintenance of Optimal Oral Health. Nutrients 2020, 12, 949. [Google Scholar] [CrossRef] [Green Version]
  167. Lee, J.; Lee, J.-B.; Song, H.-Y.; Son, M.J.; Li, L.; Rhyu, I.-C.; Lee, Y.-M.; Koo, K.-T.; An, J.-S.; Kim, J.S.; et al. Diagnostic Models for Screening of Periodontitis with Inflammatory Mediators and Microbial Profiles in Saliva. Diagnostics 2020, 10, 820. [Google Scholar] [CrossRef]
  168. Lulińska, E.; Gibbon, A.; Kaczmarczyk, M.; Maciejewska-Skrendo, A.; Ficek, K.; Leońska-Duniec, A.; Wilk, M.; Leźnicka, K.; Michałowska-Sawczyn, M.; Humińska-Lisowska, K.; et al. Matrix Metalloproteinase Genes (MMP1, MMP10, MMP12) on Chromosome 11q22 and the Risk of Non-Contact Anterior Cruciate Ligament Ruptures. Genes 2020, 11, 766. [Google Scholar] [CrossRef]
  169. Carta, F.; Pothen, B.; Maresca, A.; Tiwari, M.; Singh, V.; Supuran, C.T. Carbonic Anhydrase Inhibitors: Inhibition of Cytosolic Carbonic Anhydrase Isozymes II and VII with Simple Aromatic Sulfonamides and Some Azo Dyes. Chem. Biol. Drug Des. 2009, 74, 196–202. [Google Scholar] [CrossRef] [PubMed]
  170. Cerklewski, F.L. Effect of Suboptimal Zinc Nutrition during Gestation and Lactation on Rat Molar Tooth Composition and Dental Caries. J. Nutr. 1981, 111, 1780–1783. [Google Scholar] [CrossRef] [PubMed]
  171. Atasoy, H.B.; Ulusoy, Z.I.A. The Relationship between Zinc Deficiency and Children’s Oral Health. Pediatr. Dent. 2012, 34, 383–386. [Google Scholar] [PubMed]
  172. Bao, Z.-X.; Yang, X.-W.; Shi, J.; Liu, L.-X. Serum Zinc Levels in 368 Patients with Oral Mucosal Diseases: A Preliminary Study. Med. Oral Patol. Oral Cir. Bucal 2016, 21, e335–e340. [Google Scholar] [CrossRef]
Table
Table 1. Ingredients of mouthwashes and their main functions therein.
Table 1. Ingredients of mouthwashes and their main functions therein.
Compound (In Alphabetical Order)Main Functions or Commentary
1,3-propanediolsolvent
2-bromo-2-nitropropane-1,3-diolpreservative
2-propanol (isopropyl alcohol)solvent, preservative
acesulfame K (potassium acesulfame)sweetener
acidulated phosphate fluorideanticaries mixture, consists of phosphoric acid, monosodium or disodium phosphate and sodium fluoride [15]
allantoinunknown, uncertain oral topical meaning (wound healing)
aluminium lactateastringent (causing shrinkage of the tissues, arrest of secretion, control of bleeding)
ammonium acryloyldimethyltaurate/VP copolymerthickener, emulsion stabilising, film former (2)
amyloglucosidase (amylase)an enzyme catalysing the hydrolysis of starch into sugars
anethole (^)fragrance
arginine anticaries protection, remineralisation (3) [16,17]
ascorbic acid (vitamin C vitamer)antioxidant, uncertain oral topical meaning (antiplaque, tartar control, anti-inflammatory) [18]
aspartamesweetener
benzoic acidpreservative
benzyl alcoholpreservative, fragrance
betaine (trimethylglycine, glycine betaine)uncertain (humectant)
BHTsee ‘butylated hydroxytoluene’
bifida ferment lysateuncertain (probiotic)
bisabolol (^)anti-inflammatory, antimicrobial (4), fragrance
bromelainanti-stain, dental plaque control [19]
buteth-3solvent
butylated hydroxytoluene (BHT)antioxidant
butylene glycolsolvent, humectant
caffeinefragrance
calcium fluorideanticaries protection, remineralisation (3)
calcium gluconateanticaries protection, remineralisation (3) [20]
calcium glycerophosphateanticaries protection, remineralisation (3) [21,22]
calcium lactateanticaries protection, remineralisation (3) [20,23]
cannabidiolanti-inflammatory, analgesic, antioxidant [24,25]
caprylyl glycolhumectant
caprylyl/capryl wheat bran/straw glycosidessurfactant (1)
caramelfragrance, pigment
carbomer (polyacrylic acid)thickener, emulsion stabilising, film former (2)
carvonefragrance
cellulose gum (carboxymethyl cellulose)thickener, emulsion stabilising, film former (2)
cetylpyridinium chlorideantimicrobial (4)
charcoal powderpigment, uncertain oral topical meaning (bleaching property not observed, anti-odour) [26]
chitosanfilm former (2), antiplaque [27]
chlorhexidine diacetate antimicrobial (4)
chlorhexidine digluconateantimicrobial (4)
chlorine dioxideantimicrobial (4)
chlorobutanolpreservative
chlorphenesinpreservative
cinnamal (cinnamaldehyde) (^)fragrance
citral (^)fragrance
citric acidbuffering, pH adjuster (acidifier), chelating, component of effervescent salts when in the form of a tablet or powder (see ‘effervescent salts’)
citronellolfragrance
CI (colour index), eg. Cl 42090pigment
cocamidopropyl betainesurfactant (1), thickener
colostrumantibacterial, consists of immune components such as lactoferrin, lysozyme, lactoperoxidase, complement [28]
copper gluconateuncertain (wound healing)
Cremophor RH 40see ‘PEG-40 hydrogenated castor oil’
cyclodextrinsolubiliser, uncertain oral topical meaning (anti-odour) [29,30]
dehydroacetic acidpreservative
diazolidinyl ureapreservative (formaldehyde releaser)
dichlorobenzyl alcoholantimicrobial (4)
diethylhexyl sodium sulfosuccinatesurfactant (1)
dipotassium glycyrrhizatesweetener
dipotassium oxalatedentin hypersensitivity treatment (oxalate ions by plugging dentinal tubules; potassium ions by nerve desensitisation)
disodium C12-14 pareth-2 sulfosuccinatesurfactant (1)
disodium EDTAchelating, preservative synergist [31]
disodium phosphatebuffering, pH adjuster (alkaliser), component of acidulated phosphate fluoride (see ‘acidulated phosphate fluoride’)
disodium pyrophosphatetartar control, buffering, chelating
effervescent saltsa powder mixture of sodium bicarbonate and citric acid or/and tartaric acid (in general), produce effervescence when mixed with water; provide quick production of solution, mask the unpleasant taste of many drugs [32,33]
epigallocatechin gallateantioxidant
essential oil of clovessee ‘Eugenia caryophyllus (caryophyllata) (clove/leaf/bud) oil’
ethanol (ethyl alcohol)solvent, antimicrobial (4)
ethyl lauroyl arginate HClpreservative
ethyl menthane carboxamidecooling agent
ethylhexylglycerinpreservative
ethylparabenpreservative
eucalyptol (^)antimicrobial (4), fragrance
Eucalyptus globulus (leaf) oilessential oil of blue gum, consists of i.a. eucalyptol (1,8-cineole)
(see ‘eucalyptol’) [34,35]
Eugenia caryophyllus (caryophyllata) (clove/leaf/bud) oil (essential oil of cloves)essential oil of clove, consists of i.a. eugenol (see ‘eugenol’) [36,37]
eugenol (^)antimicrobial (4), fragrance
flavouring agent (aroma)fragrance (composition is usually a trade secret)
fluorinolsee ‘nicotinyl alcohol HF’
fluorohydroxyapatiteanticaries protection, remineralisation (3)
fructosesweetener, humectant
fusel wheat bran/straw glycosidessurfactant (1), anti-foaming, solvent
gellan gumthickener, emulsion stabilising, film former (2)
geraniol (^)fragrance
gluconic acidchelating
glucose oxidasesee ‘modified lactoperoxidase system’, catalyser of the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone
glucose pentaacetatesee ‘modified lactoperoxidase system’, substrate (presumably) of glucose oxidase (see ‘glucose oxidase’)
glycerine (glycerol) (^)solvent, thickener, humectant, sweetener
glyceryl caprylatesurfactant (1), preservative
Glycyrrhiza glabra (Glycirrhizia glabra) root extractfragrance, anti-inflammatory, antimicrobial, ingredient of modified lactoperoxidase system (see ‘modified lactoperoxidase system’) [38]
hyaluronic acidwound healing (postoperative, gingivitis, periodontitis, ulcers), humectant, film former (2) [39]
hydrated silicathickener, emulsion stabilising
hydrochloric acidpH adjuster (acidifier)
hydrogen peroxideantimicrobial (4), teeth-whitening agent
hydrogenated castor oil (unidentified specimen)surfactant (1)
hydrogenated starch hydrolysatesweetener, humectant, thickener
hydrolysed hyaluronic acidwound healing, humectant, film former (2)
hydroxyapatite anticaries protection, remineralisation (3)
hydroxyethyl cellulosethickener, emulsion stabilising, film former (2)
hypothiocyaniteantimicrobial (4)
imidazolidinyl ureapreservative (formaldehyde releaser)
inulinsweetener (presumably), prebiotic
isomaltsweetener, humectant
Kolliphor RH 40see ‘PEG-40 hydrogenated castor oil’
lactic acidpreservative, pH adjuster (acidifier), fragrance enhancer, 5% mouthwash in treatment of recurrent aphthous ulcerations [40,41]
Lactobacillusa genus of bacteria, uncertain oral topical meaning (probiotic)
lactoferrinantimicrobial (4), ingredient of modified lactoperoxidase system (see ‘modified lactoperoxidase system’)
lactoperoxidasesee ‘lactoperoxidase system’ or ‘modified lactoperoxidase system’, catalyser of the oxidation of several substrates by hydrogen peroxide
lactoperoxidase systemantimicrobial (4), consists of lactoperoxidase, thiocyanate, hydrogen peroxide and oxidised product (hypothiocyanite
[see ‘hypothiocyanite’]) [42,43]
lactosesweetener, humectant
levulinic aciduncertain (preservative)
limonene (^)fragrance
linalool (^)fragrance
lysozymeantimicrobial (4)
macrogolglycerol hydroxystearatesee ‘PEG-40 hydrogenated castor oil’
magnesium aspartateunknown
magnesium stearateanticaking (mouthwashes in the form of powder)
magnesium sulphateuncertain (viscosity controlling)
maltodextrinsweetener
Mentha arvensis (leaf) oilessential oil of wild mint, consists of i.a. menthol (see ‘menthol’) [44]
Mentha piperita (leaf) oilessential oil of peppermint, consists of i.a. menthol (see ‘menthol’) [45,46]
Mentha piperita leaf extractextract of peppermint, consists of flavonoids, i.a. catechin; naringenin (antioxidants) (added to distinct from Mentha piperita oil) [47]
Mentha piperita waterfragrance (added to distinct from Mentha piperita oil) [48]
Mentha spicata (herb) oilessential oil of spearmint, consists of i.a. carvone (see ‘carvone’) and limonene (see ‘limonene’) (added to distinct from Mentha piperita oil and Mentha arvensis oil) [45,49]
Mentha viridis (leaf) oilMentha spicata subspecies (see ‘Mentha spicata’) (added to distinguish from Mentha piperita oil) [50]
menthol (^)antimicrobial (4), fragrance, cooling agent
menthol carboxamidefragrance, cooling agent
menthone glycerine acetalfragrance, cooling agent
menthyl lactatefragrance, cooling agent
menthyl nicotinatehumectant, unknown oral topical meaning, ester of niacin and menthol
methyl salicylate (^)anti-inflammatory, fragrance
methylisothiazolinonepreservative
methylparabenpreservative
Mg-Sr-carbonate hydroxyapatite conjugated with chitosananticaries protection, remineralisation (3); chitosan: film former (2) [51,52]
modified lactoperoxidase systemantimicrobial (4), consists of potassium thiocyanate, lactoperoxidase, glucose oxidase, glucose pentaacetate, lactoferrin, Glycirrhizia glabra root extract (check also ‘lactoperoxidase system’) [53]
neohesperidin di(hydro)chalconesweetener, fragrance enhancer
niacinamide (vitamin B3 vitamer)unknown
nicomethanol hydrofluoridesee ‘nicotinyl alcohol HF’
nicotinyl alcohol HF (fluorinol, nicomethanol hydrofluoride)anticaries protection, remineralisation (3) [54]
o-cymen-5-olpreservative
octenidine dihydrochloride (octenidine HCl)antimicrobial (4)
olafluranticaries protection, remineralisation (3)
panthenol (vitamin B5 vitamer)humectant, uncertain oral topical meaning (moisturiser, wound healing)
papainanti-stain, dental plaque control [19]
PEG-12 (polyethylene glycol)humectant, solvent
PEG-12 allyl etherunknown
PEG-12 dimethicone (polyether-group silicone polymer)surfactant (1), emollient
PEG-32 (polyethylene glycol)humectant, solvent
PEG-35 castor oilsurfactant (1)
PEG-40 hydrogenated castor oil (macrogolglycerol hydroxystearate, Cremophor RH 40, Kolliphor RH 40) (^)surfactant (1)
PEG-60 hydrogenated castor oilsurfactant (1)
PEG-8 (polyethylene glycol)humectant, solvent
pegylated hydrogenated castor oils (^)surfactant (1)
pentasodium triphosphatetartar control, buffering, chelating
pentylene glycolsolvent, humectant
phenethyl alcoholpreservative, fragrance
phenoxyethanolpreservative
phosphoric acidpH adjuster (acidifier), buffering, component of acidulated phosphate fluoride (see ‘acidulated phosphate fluoride’)
phthalimidoperoxycaproic acidteeth-whitening agent
poloxamer 188surfactant (1)
poloxamer 338surfactant (1)
poloxamer 407surfactant (1), anti-foaming, thickener
polycarbophilfilm former (2)
polyglycerin-10humectant [55]
polyglyceryl-10 lauratesurfactant (1)
polyglyceryl-10 myristatesurfactant (1) [56]
polyglyceryl-10 stearatesurfactant (1)
polyglyceryl-3 caprate/caprylate/succinatesurfactant (1)
polyglyceryl-4 capratesurfactant (1)
polyglyceryl-4 laurate/sebacatesurfactant (1)
polyglyceryl-5 oleatesurfactant (1)
polyglyceryl-6 caprylate/capratesurfactant (1)
polylysinepreservative (if ε-polylysine)
polysorbate 20 (Tween 20)surfactant (1)
polysorbate 80surfactant (1)
polyvinyl methyl ether/maleic acid copolymer (PVM/MA copolymer)film former (2), emulsion stabilising [57]
polyvinylpyrrolidone (PVP)surfactant (1), thickener, emulsion stabilising, film former (2)
polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA copolymer, VP/VA copolymer)film former (2), emulsion stabilising [58]
potassium chloridedentin hypersensitivity treatment (nerve desensitisation)
potassium citrate (tripotassium citrate)dentin hypersensitivity treatment (nerve desensitisation), buffering, chelating, pH adjuster (alkaliser)
potassium fluoride (KF)anticaries protection, remineralisation (3), dentin hypersensitivity treatment (nerve desensitisation)
potassium nitratedentin hypersensitivity treatment (nerve desensitisation)
potassium phosphate (monopotassium phosphate)buffering, uncertain oral topical meaning (nerve desensitisation)
potassium sorbatepreservative
potassium thiocyanatesee ‘thiocyanate’
propolis extractwound healing, antioxidant, antimicrobial (4) [59,60]
propylene glycol (^)solvent, antimicrobial (4)
propylparabenpreservative
PVM/MA copolymersee ‘polyvinyl methyl ether/maleic acid copolymer’
PVP/VA copolymersee ‘polyvinylpyrrolidone/vinyl acetate copolymer’
retinyl palmitate (vitamin A vitamer)antioxidant, uncertain oral topical meaning (wound healing)
Rosmarinus officinalis (leaf) oilessential oil of rosemary, consists of i.a. camphor, eucalyptol
(1,8-cineole) (see ‘eucalyptol’) [61]
saccharinsee ‘sodium saccharin’
Salvia lavandulaefolia (leaf) oilessential oil of Spanish sage, consists of i.a. camphor, borneol, α-thujone, eucalyptol (1,8-cineole) (see ‘eucalyptol’) [62,63]
Salvia officinalis oilessential oil of common sage, consists of i.a. camphor, α-thujone, eucalyptol (1,8-cineole) (see ‘eucalyptol’) [63,64,65]
sodium acrylates/methacryloylethyl phosphate copolymerfilm former (2)
sodium anisatepreservative
sodium ascorbyl phosphateantioxidant, a stable precursor of vitamin C
sodium benzoatepreservative
sodium benzotriazolyl butylphenol sulfonateUV light stabiliser
sodium bicarbonate (^)buffering, pH adjuster (alkaliser, mild), component of effervescent salts when in the form of a tablet or powder (see ‘effervescent salts’)
sodium C14-16 olefin sulfonatesurfactant (1)
sodium C14-17 alkyl sec sulfonatesurfactant (1)
sodium carbonatepH adjuster (alkaliser), buffering
sodium caseinateunknown
sodium chlorideuncertain (taste, viscosity controlling)
sodium citratesee ‘trisodium citrate’
sodium coco-sulphatesurfactant (1)
sodium cocoyl glutamatesurfactant (1)
sodium dehydroacetatepreservative
sodium ethylhexylglycerinsee ‘ethylhexylglycerin’
sodium ethylparabensee ‘ethylparaben’
sodium fluorideanticaries protection, remineralisation (3)
sodium gluconatechelating
sodium hexametaphosphatetartar control, chelating, emulsifier
sodium hyaluronatewound healing, humectant, film former (2) [66]
sodium hydroxidepH adjuster (alkaliser)
sodium hydroxymethylglycinatepreservative
sodium lactatebuffering, humectant
sodium lauroyl sarcosinatesurfactant (1)
sodium lauryl sulphate (sodium dodecyl sulphate)surfactant (1)
sodium levulinateuncertain (preservative)
sodium metabisulfitepreservative, antioxidant
sodium methyl cocoyl tauratesurfactant (1)
sodium methylparabensee ‘methylparaben’
sodium monofluorophosphate (SMFP)anticaries protection, remineralisation (3)
sodium myristoyl sarcosinatesurfactant (1)
sodium perboratepreservative, bleaching
sodium phosphate (monosodium phosphate)buffering, component of acidulated phosphate fluoride
(see ‘acidulated phosphate fluoride’)
sodium phytatechelating, preservative synergist
sodium propionatepreservative
sodium propylparabensee ‘propylparaben’
sodium saccharinsweetener
sodium sulfateuncertain (viscosity controlling)
sorbitolsweetener, humectant, thickener
stannous chlorideantimicrobial (4), anti-erosive, inhibitor of metalloproteinases [38,67]
stannous fluoride (^)anticaries protection, remineralisation (3), antiplaque, antimicrobial (4), tartar control, anti-odour, anti-erosive, inhibitor of metalloproteinases
steareth-30surfactant (1) [68]
steviasweetener
Stevia rebaudiana leaf extractsee ‘stevia’
steviosidethe main sweetener found in the stevia leaves (see ‘stevia’)
strontium acetatedentin hypersensitivity treatment (by plugging dentinal tubules)
sucralosesweetener
tannaseanti-stain
tartaric acidcomponent of effervescent salts when in the form of a tablet or powder (see ‘effervescent salts’)
tetrapotassium pyrophosphatetartar control, buffering, chelating
tetrasodium EDTAchelating, preservative synergist [31]
tetrasodium glutamate diacetatechelating
tetrasodium pyrophosphatetartar control, buffering, chelating
thiocyanatesee ‘lactoperoxidase system’ or ‘modified lactoperoxidase system’, substrate of lactoperoxidase (see ‘lactoperoxidase’)
thymol (^)antimicrobial (4), fragrance
Thymus serpillum (leaf) oilessential oil of wild thyme, consists of i.a. thymol (see ‘thymol’) [69]
Thymus vulgaris (flower/leaf) oilessential oil of common thyme, consists of i.a. thymol (see ‘thymol’) [70,71]
tocopheryl acetate (vitamin E vitamer)see ‘vitamin E’
tributyl citratesolvent
triclosanantimicrobial (4)
trisodium citrate (sodium citrate)buffering, chelating, pH adjuster (alkaliser)
ubiquinone (coenzyme Q)antioxidant
vitamin Eantioxidant, uncertain oral topical meaning (wound healing)
VP/VA copolymersee ‘polyvinylpyrrolidone/vinyl acetate copolymer’
watersolvent
xanthan gumthickener, emulsion stabilising, film former (2)
xylitol sweetener, anticaries protection, remineralisation (3), humectant [72]
zinc acetate (^)anti-odour, dental plaque control, tartar control
zinc chloride (^)anti-odour, dental plaque control, tartar control
zinc citrate (^)anti-odour, dental plaque control, tartar control
zinc gluconate (^)anti-odour, dental plaque control, tartar control
zinc hydroxyapatite (^)anticaries protection, remineralisation (3), anti-odour, dental plaque control, tartar control [73,74]
zinc lactate (^)anti-odour, dental plaque control, tartar control
zinc PCA (zinc pidolate) (^)anti-odour, dental plaque control, tartar control, humectant
zinc sulphate (^)anti-odour, dental plaque control, tartar control
(1) Surfactant (may act as a solubiliser, emulsifier, emulsion stabiliser, detergent, wetting agent, foaming agent/defoamer and may possess antimicrobial features) [75]; (2) mucoadhesive film former (filmogenic agents) (it is suggested that they may act as a moisturiser, as dressing for wounds, to prevent dental plaque and stain formation, to prevent demineralisation, as a barrier to relieve pain in oral lesions such as aphthous ulcers, to improving the delivery and retention of actives) [27,76,77,78,79,80,81,82,83]; (3) remineralisation agent (to remineralise the demineralised tooth surface in dental caries or erosion as well as to prevent demineralisation, also in dentin hypersensitivity to obturate the dentinal tubules); (4) antimicrobial agent (an oral antiseptic, it may act as a preservative); (^) means it is discussed in the subsequent text.
Table
Table 2. Analysis of selected mouthwash components.
Table 2. Analysis of selected mouthwash components.
GroupAmong All Mouthwashes (1)Within a Group (2)
n%Componentn%Componentn%
identified
specimens and their form		241100.0%aqueous solutions or concentrates23497.1%tablets etc. for making aqueous solutions72.9%
fluorine compounds15363.5%olaflur1811.8%nicotinyl alcohol HF32.0%
fluorohydroxyapatite21.3%sodium monofluorophosphate106.5%
sodium fluoride13386.9%potassium fluoride21.3%
stannous fluoride21.3%calcium fluoride10.7%
concentration of fluoride ions (ppm)15363.5%98–135159.8%187–25010266.7%
400–5001811.8%900–113685.2%
145010.7%N/A95.9%
arginine31.2%
sodium bicarbonate (3)31.2%
potassium compounds (4)4317.8%dipotassium oxalate24.7%potassium citrate37.0%
potassium fluoride24.7%potassium chloride1023.3%
potassium phosphate511.6%potassium nitrate920.9%
tetrapotassium pyrophosphate2046.5%
zinc compounds4719.5%zinc acetate510.6%zinc chloride1327.7%
zinc citrate1021.3%zinc gluconate817.0%
zinc hydroxyapatite24.3%zinc lactate612.8%
zinc PCA48.5%zinc sulphate12.1%
aluminium lactate41.7%
phosphorus and calcium compounds (5)4317.8%calcium gluconate12.3%calcium glycerophosphate49.3%
calcium lactate24.7%fluorohydroxyapatite24.7%
hydroxyapatite818.6%zinc hydroxyapatite24.7%
Mg-Sr-carbonate hydroxyapatite conjugated with chitosan24.7%tetrapotassium pyrophosphate2046.5%
disodium pyrophosphate24.7%tetrasodium pyrophosphate1637.2%
pentasodium triphosphate716.3%sodium hexametaphosphate49.3%
stannous compounds41.7%stannous chloride250.0%stannous fluoride250.0%
antimicrobial drugs (6)12652.3%chlorhexidine 5039.7%essential oils (7)11389.7%
cetylpyridinium chloride8466.7%octenidine HCl10.8%
dichlorobenzyl alcohol10.8%hydrogen peroxide21.6%
chlorine dioxide54.0%triclosan10.8%
essential oils11447.3%thymol (8)3026.3%menthol (9)9078.9%
eucalyptol (10)2824.6%methyl salicylate1815.8%
eugenol (11)2118.4%bisabolol76.1%
chlorhexidine compounds5020.7%digluconate4998.0%diacetate12.0%
concentration of chlorhexidine (%)5020.7%0.05612.0%0.0636.0%
0.0912.0%0.1510.0%
0.12714.0%0.21326.0%
N/A1530.0%
ethanol2610.8%
glycerine18074.7%
propylene glycol10342.7%
surfactants22392.5%PEG-40 hydrogenated castor oil11451.1%poloxamer 407 5524.7%
sodium lauryl sulphate2511.2%polyvinylpyrrolidone114.9%
polysorbate 204520.2%cocamidopropyl betaine135.8%
others (12)7835.0%
sweeteners23396.7%sorbitol8938.2%xylitol8737.3%
stevia (13)114.7%lactose10.4%
maltodextrin73.0%saccharin14461.8%
neohesperidin dichalcone31.3%aspartame10.4%
fructose10.4%hydrogenated starch hydrolysate135.6%
acesulfame K229.4%sucralose3916.7%
isomalt73.0%dipotassium glycyrrhizate20.9%
glycerine18077.3%
preservatives (14)19882.2%2-bromo-2-nitropropane-1,3-diol136.6%benzoic acid178.6%
benzyl alcohol2211.1%ethylhexylglycerine73.5%
lactic acid147.1%methylparaben3718.7%
phenoxyethanol115.6%potassium sorbate5728.8%
propylparaben2311.6%sodium benzoate12764.1%
others (12)3115.7%
colourants15966.0%
flavouring and cooling agents (15)23999.2%
(1) Among all mouthwashes (total number or percentage of mouthwashes containing indicated groups of ingredients among all mouthwashes); (2) within a group (expanded when a group consists of more than one element; total number or percentage of mouthwashes containing indicated ingredients within a particular group); (3) sodium bicarbonate (it is not counted if other components of effervescent salts are present and if the product is a mouthwash in the form of a tablet or powder to dissolve in water); (4) potassium compounds (except potassium sorbate, potassium thiocyanate, dipotassium glycyrrhizate, acesulfame K); (5) phosphorus and calcium compounds (except sodium ascorbylphosphate, sodium monofluorophosphate, sodium acrylates/methacryloylethyl phosphate copolymer); (6) antimicrobial drugs (except peptides and proteins, preservatives, ethanol and other alcohols, sodium bicarbonate, stannous compounds, zinc compounds, fluorine compounds); (7) essential oils (thymol, menthol, eucalyptol, eugenol, bisabolol or oils with an expected high concentration of them, not methyl salicylate); (8) thymol and/or Thymus serpillum (leaf) oil and/or Thymus vulgaris (flower/leaf) oil (counted once for one individual product, if more than one present); (9) menthol and/or Mentha arvensis (leaf) oil and/or Mentha piperita(leaf) oil (counted once for one individual product, if more than one present); (10) eucalyptol and/or Eucalyptus globulus (leaf) oil and/or Rosmarinus officinalis (leaf) oil and/or Salvia lavandulaefolia (leaf) oil and/or Salvia officinalis oil (counted once for one individual product, if more than one present); (11) eugenol and/or Eugenia caryophyllus (caryophyllata) (clove/leaf/bud) oil (essential oil of cloves) (counted once for one individual product, if more than one present); (12) others (according to Table 1 and Table S1); (13) stevia and/or stevioside and/or Stevia rebaudianaleaf extract; (14) preservatives (antimicrobial agents except ethanol and other alcohols, essential oils, chlorhexidine, cetylpyridinium chloride, propolis extract, lactoferrin, dichlorobenzyl alcohol, hydrogen peroxide, lactoperoxidase system, lysozyme, octenidine dihydrochloride, chlorine dioxide, triclosan); (15) flavouring and cooling agents (counted with essential oils); N/A—not available.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Radzki, D.; Wilhelm-Węglarz, M.; Pruska, K.; Kusiak, A.; Ordyniec-Kwaśnica, I. A Fresh Look at Mouthwashes—What Is Inside and What Is It For? Int. J. Environ. Res. Public Health 2022, 19, 3926. https://doi.org/10.3390/ijerph19073926

AMA Style

Radzki D, Wilhelm-Węglarz M, Pruska K, Kusiak A, Ordyniec-Kwaśnica I. A Fresh Look at Mouthwashes—What Is Inside and What Is It For? International Journal of Environmental Research and Public Health. 2022; 19(7):3926. https://doi.org/10.3390/ijerph19073926

Chicago/Turabian Style

Radzki, Dominik, Marta Wilhelm-Węglarz, Katarzyna Pruska, Aida Kusiak, and Iwona Ordyniec-Kwaśnica. 2022. "A Fresh Look at Mouthwashes—What Is Inside and What Is It For?" International Journal of Environmental Research and Public Health 19, no. 7: 3926. https://doi.org/10.3390/ijerph19073926

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop